Ali Raza Khaki, MD

All Publications

• Association of Tumor Mutational Burden and Microsatellite Instability With Response and Outcomes in Patients With Urothelial Carcinoma Treated With Immune Checkpoint Inhibitor. Clinical genitourinary cancer Bakaloudi, D. R., Talukder, R., Makrakis, D., Diamantopoulos, L., Enright, T., Leary, J. B., Patgunarajah, U., Thomas, V. M., Swami, U., Agarwal, N., Jindal, T., Koshkin, V. S., Brown, J. R., Barata, P., Murgić, J., Miletić, M., Johnson, J., Zakharia, Y., Hui, G., Drakaki, A., Duran, I., Buznego, L. A., Barrera, R. M., Castañeda, D. M., Rey-Cárdenas, M., Castellano, D., Nguyen, C. B., Park, J. J., Alva, A., McKay, R. R., Stewart, T. F., Epstein, I. B., Bellmunt, J., Wright, J. L., Gupta, S., Grivas, P., Khaki, A. R. 2024; 22 (6): 102198

  Abstract

  Microsatellite Instability (MSI) and Tumor Mutational Burden (TMB) are associated with immune checkpoint inhibitor (ICI) efficacy. We examined the association between TMB and MSI status with survival in patients with urothelial carcinoma (UC) treated with ICI.Patients from 15 institutions were treated with ICI monotherapy. Primary endpoint was overall survival and secondary endpoints included observed response rate (ORR), and progression-free (PFS) calculated from ICI initiation. TMB was analyzed as dichotomous (≥10 vs. <10 mut/Mb) and continuous variable.We identified 411 patients: 203 were treated with ICI 1L/upfront; 104 with 2 + L. For the 1L/upfront: median [m] OS was numerically longer in patients with TMB ≥10 versus TMB <10: mOS 35 versus 26 months (HR = 0.6) and with MSI-H and MSI-S (mOS NR vs. 22 months), though neither association was statistically significant. A statistically significant association was found between TMB (continuous variable) and OS (HR = 0.96, P = .01). For 2 + L: mOS was numerically longer in patients with TMB ≥10 versus TMB <10: (20 vs. 12 months; HR = 0.9); mOS was 12 and 17 months for patients with MSI-H and MSI-S, respectively. Eighty-nine patients received maintenance avelumab (mAV): mOS was longer in patients with TMB ≥10 versus TMB <10: 61 versus 17 months; (HR = 0.2, P = .02) and with MSI-H and MSI-S (NR vs. 24 months).Although not reaching statistical significance in several subsets, patients with high TMB and MSI-H had numerically longer OS with ICI, especially with mAV. Further validation is needed.

  View details for DOI 10.1016/j.clgc.2024.102198

  View details for PubMedID 39241315

• An assessment of the direct and indirect costs of bladder cancer preceding and following a cystectomy: a real-world evidence study. Journal of medical economics Tkacz, J., Ireland, A., Agatep, B., Ellis, L., Balaji, H., Khaki, A. R. 2024: 1-14

  Abstract

  Introduction: To estimate the direct and indirect costs of bladder cancer prior to and following cystectomy in a U.S. sample of patients.Methods: This retrospective, observational analysis of de-identified patients with bladder cancer utilized the MarketScan Commercial Claims & Encounters and Health & Productivity Management databases. Adult patients with bladder cancer plus ≥ 1 claim for partial or radical cystectomy between 10/1/2015 - 12/31/20 (date of the cystectomy=index date) and who were continuously enrolled for 6 months pre- (baseline) and post-index (follow-up) were included in the sample. All-cause total healthcare costs and indirect costs associated with short-term and long-term disability (STD and LTD) employer claims were assessed during each of the 6-month baseline and follow-up periods.Results: The study included N=142 patients; mean age 56±6 years, 76% (male), and 42% had a baseline Deyo-Charlson Comorbidity Index ≥ 2. Baseline mean total all-cause direct healthcare costs were $51,473 ± $48,560 (median: $36,202), and $99,524±86,839 (median: $75,444) during follow-up. At baseline, 32% of patients had ≥ 1 STD claim, equating to a mean 134±303hours lost and $2,353 ± $6,445 in total payments per patient. Follow up STD claims increased 23.4% equating to a mean 218±324hours lost and $3,679 ± $7,795 per patient. Patient LTD claims increased from baseline to follow-up (1% to 3%), with post-cystectomy LTD claims resulting in 574±490hours lost, and $1,636 ± $1,429 in total payments. Over 85% of the population had a cystectomy related complication, the most common were genitourinary-related (47.9%) and infection/sepsis (33.1%).Conclusions: Cystectomy was associated with complications and decreased work productivity post-surgery. Findings may aid to inform decisions regarding cystectomy vs. bladder preservation approaches, and underscores an ongoing need to further develop bladder preservation therapies within the bladder cancer treatment landscape.

  View details for DOI 10.1080/13696998.2024.2382639

  View details for PubMedID 39028539

• Characterizing the authorship of phase 3 randomized clinical trials in oncology, 1960-2023 Warner, J., Bakow, B. R., Brown, A. J., Choe, J., Fan, E., Ganta, T., Glover, M., Hadfield, M., Hilton, C., Khaki, A., Kothari, S., Lythgoe, M., Nagpal, S., Nguyen, R., Noyd, D. H., Bin Riaz, I., Rooney, M., Sethi, T., Singhi, E., Rubinstein, S. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402551

• Safety, efficacy, and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced or metastatic ovarian cancer: Results from a multi-center multi-country phase 1/2a expansion cohort Khaki, A., Razak, A., Laurie, S. A., Hwang, C., Diep, A. N., Schmidt, M., Vold, R., Majeed, S., Glatt, D. M., Krystal, J. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557401421

• Safety, efficacy, and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced neuroendocrine cancers: Results from a multi-center multi-country phase 1/2a expansion cohort. Rasco, D. W., Razak, A., Khaki, A., Spira, A. I., Hwang, C., Diep, A. N., Schmidt, M., Vold, R., Majeed, S., Glatt, D. M. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557401100

• Mind the gap: Estimating the opportunity lost due to the gap between FDA and EMA cancer drug approvals. Gage, S., Eteshola, E., Hadfield, M., Hamze, D., Khaki, A., Mishra, S., Rooney, M., Masse, G., Hilal, T., Jain, S., Rubinstein, S., Lythgoe, M., Warner, J. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557402505

• Response and outcomes with immune checkpoint inhibitor (ICI) in patients (pts) with urothelial carcinoma (UC) and subtype histology (SH) Rafailia Bakaloudi, D., Makrakis, D., Talukder, R., Nikolaos Diamantopoulos, L., Jindal, T., Nguyen, C. B., Hobeika, C., Thomas, V., Johnson, J., Marmolejo Castaneda, D., Korolewicz, J., Zakopoulou, R., Hui, G., Barata, P. C., Alonso Buznego, L., Brown, J. R., Stewart, T. F., Epstein, I. B., Khaki, A., Grivas, P. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001275557401223

• Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. European journal of nuclear medicine and molecular imaging Song, H., Leonio, M. I., Ferri, V., Duan, H., Aparici, C. M., Davidzon, G., Franc, B. L., Moradi, F., Shah, J., Bergstrom, C. P., Fan, A. C., Shah, S., Khaki, A. R., Srinivas, S., Iagaru, A. 2024

  Abstract

  PURPOSE: Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617.METHODS: In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean±SD: 1.8±0.6h, range 1.1-4.9h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates.RESULTS: 56 patients (means age 76.2±8.1 years, range: 60-93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~12min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0-15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had>30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P=0.008) and PSA-PFS (median 6 months vs. 1 months, P<0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS.CONCLUSION: We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1-2h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

  View details for DOI 10.1007/s00259-024-06718-6

  View details for PubMedID 38635050

• The 2023 European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: A Critical Appraisal. European urology Hensley, P. J., Choudhury, A., Khaki, A. R., Grivas, P., Kamat, A. M. 2023

  View details for DOI 10.1016/j.eururo.2023.10.010

  View details for PubMedID 37919189

• Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: a COVID-19 and cancer consortium (CCC19) cohort study. eLife Nagaraj, G., Vinayak, S., Khaki, A. R., Sun, T., Kuderer, N. M., Aboulafia, D. M., Acoba, J. D., Awosika, J., Bakouny, Z., Balmaceda, N. B., Bao, T., Bashir, B., Berg, S., Bilen, M. A., Bindal, P., Blau, S., Bodin, B. E., Borno, H. T., Castellano, C., Choi, H., Deeken, J., Desai, A., Edwin, N., Feldman, L. E., Flora, D. B., Friese, C. R., Galsky, M. D., Gonzalez, C. J., Grivas, P., Gupta, S., Haynam, M., Heilman, H., Hershman, D. L., Hwang, C., Jani, C., Jhawar, S. R., Joshi, M., Kaklamani, V., Klein, E. J., Knox, N., Koshkin, V. S., Kulkarni, A. A., Kwon, D. H., Labaki, C., Lammers, P. E., Lathrop, K. I., Lewis, M. A., Li, X., Lopes, G. d., Lyman, G. H., Makower, D. F., Mansoor, A. H., Markham, M. J., Mashru, S. H., McKay, R. R., Messing, I., Mico, V., Nadkarni, R., Namburi, S., Nguyen, R. H., Nonato, T. K., O'Connor, T. L., Panagiotou, O. A., Park, K., Patel, J. M., Patel, K. G., Peppercorn, J., Polimera, H., Puc, M., Rao, Y. J., Razavi, P., Reid, S. A., Riess, J. W., Rivera, D. R., Robson, M., Rose, S. J., Russ, A. D., Schapira, L., Shah, P. K., Shanahan, M. K., Shapiro, L. C., Smits, M., Stover, D. G., Streckfuss, M., Tachiki, L., Thompson, M. A., Tolaney, S. M., Weissmann, L. B., Wilson, G., Wotman, M. T., Wulff-Burchfield, E. M., Mishra, S., French, B., Warner, J. L., Lustberg, M. B., Accordino, M. K., Shah, D. P. 2023; 12

  Abstract

  Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 -1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 - 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 - 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 - 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 - 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 - 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 - 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L. Warner; P30-CA046592 to Christopher R. Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K. Shah and Dimpy P. Shah; and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01 -CCE) and P30-CA054174 for Dimpy P. Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical Trial Number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

  View details for DOI 10.7554/eLife.82618

  View details for PubMedID 37846664

• Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors. Journal of the National Cancer Institute El Zarif, T., Nassar, A. H., Pond, G. R., Zhuang, T. Z., Master, V., Nazha, B., Niglio, S., Simon, N., Hahn, A. W., Pettaway, C. A., Tu, S. M., Abdel-Wahab, N., Velev, M., Flippot, R., Buti, S., Maruzzo, M., Mittra, A., Gheeya, J., Yang, Y., Rodriguez, P. A., Castellano, D., de Velasco, G., Roviello, G., Antonuzzo, L., McKay, R. R., Vincenzi, B., Cortellini, A., Hui, G., Drakaki, A., Glover, M., Khaki, A. R., El-Am, E., Adra, N., Mouhieddine, T. H., Patel, V., Piedra, A., Gernone, A., Davis, N. B., Matthews, H., Harrison, M. R., Kanesvaran, R., Giudice, G. C., Barata, P., Farolfi, A., Lee, J. L., Milowsky, M. I., Stahlfeld, C., Appleman, L., Kim, J. W., Freeman, D., Choueiri, T. K., Spiess, P. E., Necchi, A., Apolo, A. B., Sonpavde, G. P. 2023

  Abstract

  Treatment options for penile squamous cell carcinoma (PeCa) are limited. We sought to investigate clinical outcomes and safety profiles of patients with PeCa receiving immune checkpoint inhibitors (ICIs).This retrospective study included patients with locally advanced or metastatic PeCa receiving ICIs during 2015-2022 across 24 centers in the United States, Europe, and Asia. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Objective response rates (ORRs) were determined per RECIST 1.1 criteria. Treatment-related adverse events (trAEs) were graded per the Common Terminology Criteria for Adverse Events v5.0. Two-sided statistical tests were used for comparisons.Among 92 patients, 8 were Asian (8.7%), 6 (6.5%) were Black, and 24 (29%) were Hispanic/Latinx. Median age was 62 (inter-quartile range: 53 to 70) years. 83 (90%) had metastatic PeCa, and 74 (80%) received ≥2nd line treatment. Most patients received pembrolizumab monotherapy (n = 26, 28%), combination nivolumab/ipilimumab +/- multi-targeted tyrosine kinase inhibitors (n = 23, 25%), nivolumab (n = 16, 17%) or cemiplimab (n = 15, 16%) monotherapies. Median OS and PFS were 9.8 (95% CI: 7.7-12.8) months and 3.2 (95% CI: 2.5-4.2) months, respectively. ORR was 13% (n = 11/85) in the overall cohort and 35% (n = 7/20) in patients with lymph node-only metastases. Visceral metastases, ECOG performance status ≥1, and higher Neutrophil/Lymphocyte ratio (NLR) were associated with worse OS. TrAEs occurred in 29% (n = 27) and 9.8% (n = 9) were grade ≥3.ICIs are active in a subset of patients with PeCa. Future translational studies are warranted to identify patients more likely to derive clinical benefit from ICIs.

  View details for DOI 10.1093/jnci/djad155

  View details for PubMedID 37563779

• Implications of Contact Days in the Treatment of Relapsed Refractory Diffuse Large B-Cell Lymphoma. The oncologist Bojanini, L., Gupta, N., Khaki, A. R. 2023

  View details for DOI 10.1093/oncolo/oyad204

  View details for PubMedID 37432278

• Role of Underlying Liver Pathology in the Development of Immune-Related Hepatitis: A Case-Control Study. Targeted oncology Storm, E. M., Makrakis, D., Lin, G. I., Talukder, R., Bakaloudi, D. R., Shah, E. E., Liou, I. W., Hockenbery, D., Grivas, P., Khaki, A. R. 2023

  Abstract

  BACKGROUND: Immune-related hepatitis (irH) is a serious immune-related adverse event (IRAE) that may result in morbidity, immune checkpoint inhibitor (ICI) therapy interruption and, rarely, mortality. The impact of underlying liver pathology, including liver metastasis, on the incidence of irH remains poorly understood.OBJECTIVES: We hypothesized that the presence of underlying liver pathology increased the risk of irH in patients with cancer treated with ICI.PATIENTS AND METHODS: We conducted a retrospective case-control study of irH in patients with cancer receiving first ICI treatment from 2016-2020. Provider documented cases of ≥ grade 2 irH were identified and control matched in a 2:1 ratio based on age, sex, time of ICI initiation, and follow-up time. Conditional logistic regression was used to estimate the relationship between irH and liver metastasis at ICI initiation.RESULTS: Ninety-seven cases of irH were identified, 29% of which had liver metastases at time of ICI initiation. Thirty-eight percent of patients developed grade 2, 47% grade 3, and 14% grade 4 irH. When adjusted for covariates/confounders, the presence of liver metastasis was associated with increased odds of irH (aOR 2.79 95% CI 1.37-5.66, p = 0.005). The presence of liver metastases did not correlate with irH grade or rate of irH recurrence after ICI rechallenge.CONCLUSIONS: Presence of liver metastases increased the odds of irH in patients with first-time ICI therapy. Limitations include the retrospective nature, moderate sample size, possible selection bias and confounding. Our findings are hypothesis-generating and warrant external validation as well as tissue and circulating biomarker exploration.

  View details for DOI 10.1007/s11523-023-00980-8

  View details for PubMedID 37358780

• Response and Outcomes of Maintenance Avelumab After Platinum-Based Chemotherapy (PBC) in Patients With Advanced Urothelial Carcinoma (aUC): "Real World" Experience. Clinical genitourinary cancer Bakaloudi, D. R., Talukder, R., Lin, G. I., Makrakis, D., Diamantopoulos, L. N., Tripathi, N., Agarwal, N., Zakopoulou, R., Bamias, A., Brown, J. R., Pinato, D. J., Korolewicz, J., Jindal, T., Koshkin, V. S., Murgić, J., Miletić, M., Frobe, A., Johnson, J., Zakharia, Y., Drakaki, A., Rodriguez-Vida, A., Rey-Cárdenas, M., Castellano, D., Buznego, L. A., Duran, I., Carballeira, C. C., Barrera, R. M., Marmorejo, D., McKay, R. R., Stewart, T., Gupta, S., Ruplin, A. T., Yu, E. Y., Khaki, A. R., Grivas, P. 2023

  Abstract

  Platinum-based chemotherapy (PBC) followed by avelumab switch maintenance in nonprogressors is standard first line (1L) treatment for advanced urothelial carcinoma (aUC). We describe clinical features and outcomes in a "real-world' cohort treated with avelumab maintenance for aUC.This was a retrospective cohort study of patients (pts) who received 1L switch maintenance avelumab after no progression on PBC for aUC. We calculated progression-free survival (PFS) and overall survival (OS) from initiation of maintenance avelumab. We also described OS and PFS for specific subsets using Cox regression and observed response rate (ORR).A total of 108 pts with aUC from 14 sites treated with maintenance avelumab were included. There was a median of 6 weeks1-30 from end of PBC to avelumab initiation; median follow-up time from avelumab initiation was 8.8 months (1-42.7). Median [m]PFS was 9.6 months (95%CI 7.5-12.1) and estimated 1-year OS was 72.5%. CR/PR (vs. SD) to 1L PBC (HR = 0.33, 95% CI 0.13-0.87) and ECOG PS 0 (vs. ≥1), (HR = 0.15, 95% CI 0.05-0.47) were associated with longer OS. The presence of liver metastases was associated with shorter PFS (HR = 2.32, 95% CI 1.17-4.59). ORR with avelumab maintenance was 28.7% (complete response 17.6%, partial response 11.1%), 29.6% stable disease, 26.9% progressive disease as best response (14.8% best response unknown).Results seem relatively consistent with findings from JAVELIN Bladder100 trial and recent "real world" studies. Prior response to platinum-based chemotherapy, ECOG PS 0, and absence of liver metastases were favorable prognostic factors. Limitations include the retrospective design, lack of randomization and central scan review, and possible selection/confounding biases.

  View details for DOI 10.1016/j.clgc.2023.06.008

  View details for PubMedID 37414620

• Patient-reported distress at a cancer center during the COVID-19 pandemic. Scientific reports Shah, M. P., Rosenthal, S. W., Roy, M., Khaki, A. R., Hernandez-Boussard, T., Ramchandran, K. 2023; 13 (1): 9581

  Abstract

  Assessments of health-related quality of life (HRQOL) are conducted by health systems to improve patient-centered care. Studies have shown that the COVID-19 pandemic poses unique stressors for patients with cancer. This study investigates change in self-reported global health scores in patients with cancer before and during the COVID-19 pandemic. In this single-institution retrospective cohort study, patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) at a comprehensive cancer center before and during the COVID-19 pandemic were identified. Surveys were analyzed to assess change in the global mental health (GMH) and global physical health (GPH) scores at different time periods (pre-COVID: 3/1/5/2019-3/15/2020, surge1: 6/17/2020-9/7/2020, valley1: 9/8/2020-11/16/2020, surge2: 11/17/2020-3/2/2021, and valley2: 3/3/2021-6/15/2021). A total of 25,192 surveys among 7209 patients were included in the study. Mean GMH score for patients before the COVID-19 pandemic (50.57) was similar to those during various periods during the pandemic: surge1 (48.82), valley1 (48.93), surge2 (48.68), valley2 (49.19). Mean GPH score was significantly higher pre-COVID (42.46) than during surge1 (36.88), valley1 (36.90), surge2 (37.33) and valley2 (37.14). During the pandemic, mean GMH (49.00) and GPH (37.37) scores obtained through in-person were similar to mean GMH (48.53) and GPH (36.94) scores obtained through telehealth. At this comprehensive cancer center, patients with cancer reported stable mental health and deteriorating physical health during the COVID-19 pandemic as indicated by the PROMIS survey. Modality of the survey (in-person versus telehealth) did not affect scores.

  View details for DOI 10.1038/s41598-023-36025-3

  View details for PubMedID 37311790

  View details for PubMedCentralID 7450263

• Renal cell carcinoma with metastasis to the pancreas: Genomic signatures and clinical outcomes Glover, M., Chiang, R. S., Hoerner, C. R., Khan, O. A., Kao, C., Shah, S., Srinivas, S., Fan, A. C., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002374

• Assessment of price variation in colorectal cancer screening procedures at US hospitals. Paranjpe, I., Sharma, P., Wei, C., Puram, V., Kamat, S., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003371

• Outcomes with immune checkpoint inhibitors (ICI) in patients (pts) with MTAP alterations (alt) in advanced urothelial carcinoma (aUC). Talukder, R., Bakaloudi, D., Lin, G., Enright, T., Leary, J., Makrakis, D., Tripathi, N., Agarwal, N., Jindal, T., Koshkin, V. S., Brown, J. R., Johnson, J., Zakharia, Y., Park, J. J., Alva, A., Barrera, R., Drakaki, A., Barata, P. C., Khaki, A., Grivas, P. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772001062

• Sarcomatoid Urothelial Carcinoma Is Associated With Limited Response to Neoadjuvant Chemotherapy and Poor Oncologic Outcomes After Radical Cystectomy. Clinical genitourinary cancer Sekar, R. R., Diamantopoulos, L. N., Bakaloudi, D. R., Khaki, A. R., Grivas, P., Winters, B. R., Vakar-Lopez, F., Tretiakova, M. S., Psutka, S. P., Holt, S. K., Gore, J. L., Lin, D. W., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Schweizer, M. T., Cheng, H. H., Yu, E. Y., True, L. D., Montgomery, R. B., Wright, J. L. 2023

  Abstract

  To examine oncologic outcomes and response to neoadjuvant chemotherapy (NAC) in patients with sarcomatoid urothelial carcinoma (SUC) treated with radical cystectomy (RC).We retrospectively queried our institutional database (2003-18) and Surveillance, Epidemiology, and End Results (SEER)-Medicare (2004-2015) for patients with cT2-4, N0-2, M0 SUC and conventional UC (CUC) treated with RC. Clinicopathologic characteristics were described using descriptive statistics (t test, χ2-test and log-rank-test for group comparison). Overall (OS) and recurrence-free-survival (RFS) after RC were estimated with the Kaplan Meier method and associations with OS were evaluated with Cox proportional hazards models.We identified 38 patients with SUC and 287 patients with CUC in our database, and 190 patients with SUC in SEER-Medicare. In the institutional cohort, patients with SUC versus CUC had higher rates of pT3/4 stage (66% vs. 35%, P < 0.001), lower rates of ypT0N0 (6% vs. 35%, P = .02), and worse median OS (17.5 vs. 120 months, P < .001). Further, patients with SUC in the institutional versus SEER-Medicare cohort had similar median OS (17.5 vs. 21 months). In both cohorts, OS was comparable between patients with SUC undergoing NAC+RC vs. RC alone (17.5 vs. 18.4 months, P = .98, institutional cohort; 24 vs. 20 months, P = .56, SEER cohort). In Cox proportional hazards models for the institutional RC cohort, SUC was independently associated with worse OS (HR 2.3, CI 1.4-3.8, P = .001).SUC demonstrates poor pathologic response to NAC and worse OS compared with CUC, with no OS benefit associated with NAC. A unique pattern of rapid abdominopelvic cystic recurrence was identified.

  View details for DOI 10.1016/j.clgc.2023.03.015

  View details for PubMedID 37150667

• Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study. medRxiv : the preprint server for health sciences Nagaraj, G., Vinayak, S., Khaki, A. R., Sun, T., Kuderer, N. M., Aboulafia, D. M., Acoba, J. D., Awosika, J., Bakouny, Z., Balmaceda, N. B., Bao, T., Bashir, B., Berg, S., Bilen, M. A., Bindal, P., Blau, S., Bodin, B. E., Borno, H. T., Castellano, C., Choi, H., Deeken, J., Desai, A., Edwin, N., Feldman, L. E., Flora, D. B., Friese, C. R., Galsky, M. D., Gonzalez, C. J., Grivas, P., Gupta, S., Haynam, M., Heilman, H., Hershman, D. L., Hwang, C., Jani, C., Jhawar, S. R., Joshi, M., Kaklamani, V., Klein, E. J., Knox, N., Koshkin, V. S., Kulkarni, A. A., Kwon, D. H., Labaki, C., Lammers, P. E., Lathrop, K. I., Lewis, M. A., Li, X., de Lima Lopes, G., Lyman, G. H., Makower, D. F., Mansoor, A. H., Markham, M. J., Mashru, S. H., McKay, R. R., Messing, I., Mico, V., Nadkarni, R., Namburi, S., Nguyen, R. H., Nonato, T. K., O'Connor, T. L., Panagiotou, O. A., Park, K., Patel, J. M., Patel, K. G., Peppercorn, J., Polimera, H., Puc, M., Rao, Y. J., Razavi, P., Reid, S. A., Riess, J. W., Rivera, D. R., Robson, M., Rose, S. J., Russ, A. D., Schapira, L., Shah, P. K., Shanahan, M. K., Shapiro, L. C., Smits, M., Stover, D. G., Streckfuss, M., Tachiki, L., Thompson, M. A., Tolaney, S. M., Weissmann, L. B., Wilson, G., Wotman, M. T., Wulff-Burchfield, E. M., Mishra, S., French, B., Warner, J. L., Lustberg, M. B., Accordino, M. K., Shah, D. P. 2023

  Abstract

  Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations.This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity.1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 - 1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 - 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 - 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 - 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 - 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 - 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 - 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status.Using one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients.

  View details for DOI 10.1101/2023.03.09.23287038

  View details for PubMedID 37205429

  View details for PubMedCentralID PMC10187350

• Biomarkers of response to enfortumab vedotin (EV) in patients (pts) with advanced urothelial carcinoma (aUC): Analysis of the UNITE study. Jindal, T., Kilari, D., Alhalabi, O., Nizam, A., Khaki, A., Basu, A., Barata, P. C., Bilen, M., Shah, S., Zakharia, Y., Milowsky, M. I., Bellmunt, J., Emamekhoo, H., Davis, N. B., Grivas, P., Gupta, S., Hoimes, C. J., Campbell, M. T., Alva, A., Koshkin, V. S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200479

• Homologous recombination repair (HRR) mutation concordance between liquid biopsy (LB) and tumor tissue by NGS in a real-world prostate cancer (PC) database. Shen, J., Wang, L., Khaki, A., Jimenez, R. E., Mauer, E., Stoppler, M., Chao, C. Y., Kohli, M. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200343

• Response and outcomes of maintenance avelumab after platinum-based chemotherapy (PBC) in patients (pts) with advanced urothelial carcinoma (aUC): "Real world" experience. Bakaloudi, D., Talukder, R., Makrakis, D., Agarwal, N., Tripathi, N., Bamias, A., Zakopoulou, R., Brown, J., Korolewicz, J., Fulgenzi, C. M., Jindal, T., Murgic, J., Frobe, A., Johnson, J., Drakaki, A., Rodriguez-Vida, A., Rey-Cardenas, M., Buznego, L., Khaki, A., Grivas, P. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200501

• Outcomes with immune checkpoint inhibitor (ICI) therapy in patients with FGFR2/3 alterations in advanced urothelial carcinoma (aUC). Talukder, R., Bakaloudi, D., Makrakis, D., Tripathi, N., Agarwal, N., Jindal, T., Koshkin, V. S., Johnson, J., Zakharia, Y., Brown, J., Rey-Cardenas, M., Castellano, D., Alva, A., Zakopoulou, R., Korolewicz, J., Drakaki, A., Barata, P. C., Grivas, P., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200507

• Phase 2 open label study of durvalumab with neoadjuvant chemotherapy in variant histology bladder cancer. Khaki, A., Fan, A. C., Shah, S., Parikh, D., Chien, J., Moore, K., Ruiz, S., Haas, D., Fakhoury, L., Del Toro, N., Baker, P., O'Brien, A., Srinivas, S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001098050200553

• Adjuvant checkpoint inhibitor trials: Is disease-free survival an appropriate endpoint? Journal of cancer policy Khaki, A. R., Lythgoe, M. P., Prasad, V. 2023; 35: 100402

  View details for DOI 10.1016/j.jcpo.2023.100402

  View details for PubMedID 36639103

• Geriatric assessment in the older adult with genitourinary cancer: A narrative review. Frontiers in oncology Singhal, S., Marwell, J. G., Khaki, A. R. 2023; 13: 1124309

  Abstract

  Genitourinary (GU) cancers including bladder, prostate, and kidney cancers affect older adults with a higher prevalence compared to younger adults. GU cancer treatment is associated with poorer outcomes in older adults compared to their younger counterparts. To better identify and support older adults receiving cancer care, oncologic societies recommend the use of a geriatric assessment (GA) to guide management. However, little is known about the implementation and usefulness of the GA in older adults with GU cancers. We performed a narrative review to investigate the utility of the GA in older adults with GU cancers and propose strategies to optimize the real-world use of the GA. Here, we describe a framework to incorporate GA into the routine cancer care of older adults with GU cancers and provide several implications for future research.

  View details for DOI 10.3389/fonc.2023.1124309

  View details for PubMedID 36816955

• Use of Machine Learning and Lay Care Coaches to Increase Advance Care Planning Conversations for Patients With Metastatic Cancer. JCO oncology practice Gensheimer, M. F., Gupta, D., Patel, M. I., Fardeen, T., Hildebrand, R., Teuteberg, W., Seevaratnam, B., Asuncion, M. K., Alves, N., Rogers, B., Hansen, J., DeNofrio, J., Shah, N. H., Parikh, D., Neal, J., Fan, A. C., Moore, K., Ruiz, S., Li, C., Khaki, A. R., Pagtama, J., Chien, J., Brown, T., Tisch, A. H., Das, M., Srinivas, S., Roy, M., Wakelee, H., Myall, N. J., Huang, J., Shah, S., Lee, H., Ramchandran, K. 2022: OP2200128

  Abstract

  Patients with metastatic cancer benefit from advance care planning (ACP) conversations. We aimed to improve ACP using a computer model to select high-risk patients, with shorter predicted survival, for conversations with providers and lay care coaches. Outcomes included ACP documentation frequency and end-of-life quality measures.In this study of a quality improvement initiative, providers in four medical oncology clinics received Serious Illness Care Program training. Two clinics (thoracic/genitourinary) participated in an intervention, and two (cutaneous/sarcoma) served as controls. ACP conversations were documented in a centralized form in the electronic medical record. In the intervention, providers and care coaches received weekly e-mails highlighting upcoming clinic patients with < 2 year computer-predicted survival and no prior prognosis documentation. Care coaches contacted these patients for an ACP conversation (excluding prognosis). Providers were asked to discuss and document prognosis.In the four clinics, 4,968 clinic visits by 1,251 patients met inclusion criteria (metastatic cancer with no prognosis previously documented). In their first visit, 28% of patients were high-risk (< 2 year predicted survival). Preintervention, 3% of both intervention and control clinic patients had ACP documentation during a visit. By intervention end (February 2021), 35% of intervention clinic patients had ACP documentation compared with 3% of control clinic patients. Providers' prognosis documentation rate also increased in intervention clinics after the intervention (2%-27% in intervention clinics, P < .0001; 0%-1% in control clinics). End-of-life care intensity was similar in intervention versus control clinics, but patients with ≥ 1 provider ACP edit met fewer high-intensity care measures (P = .04).Combining a computer prognosis model with care coaches increased ACP documentation.

  View details for DOI 10.1200/OP.22.00128

  View details for PubMedID 36395436

• Treatment Rechallenge With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma. Clinical genitourinary cancer Makrakis, D., Bakaloudi, D. R., Talukder, R., Lin, G. I., Diamantopoulos, L. N., Jindal, T., Vather-Wu, N., Zakharia, Y., Tripathi, N., Agarwal, N., Dawsey, S., Gupta, S., Lu, E., Drakaki, A., Liu, S., Zakopoulou, R., Bamias, A., Fulgenzi, C. M., Cortellini, A., Pinato, D., Barata, P., Grivas, P., Khaki, A. R., Koshkin, V. S. 2022

  Abstract

  To examine patient and disease characteristics, toxicity, and clinical outcomes for patients with advanced urothelial carcinoma (aUC) who are rechallenged with immune checkpoint inhibitor (ICI)-based therapy.In this retrospective cohort, we included patients treated with ICI for aUC after having prior ICI treatment. Endpoints included the evaluation of radiographic response and disease control rates with first and second ICI courses, outcomes based on whether there was a change in ICI class (anti-PD-1 vs. anti-PD-L1), and assessment of the reasons for ICI discontinuation.We identified 25 patients with aUC from 9 institutions who received 2 separate ICI courses. ORR with first ICI and second ICI were 39% and 13%, respectively. Most patients discontinued first ICI due to progression (n = 19) or treatment-related toxicity (n = 4). Thirteen patients received non-ICI treatment between the first and second ICI, and 12 patients changed ICI class (anti-PD-1 vs. anti-PD-L1) at rechallenge. Among 10 patients who changed ICI class, 8 (80%) had progressive disease as best response with second ICI, while among 12 patients re-treated with the same ICI class, only 3 (25%) had progressive disease as best response at the time of rechallenge. With second ICI, most patients discontinued treatment due to progression (n = 18) or patient preference (n = 2).A proportion of patients with aUC rechallenged with ICI-based regimens may achieve disease control, supporting clinical trials in that setting, especially with ICI-based combinations. Future studies are needed to validate our results and should also focus on identifying biomarkers predictive of benefit with ICI rechallenge.

  View details for DOI 10.1016/j.clgc.2022.11.003

  View details for PubMedID 36481176

• Racial diversity and reporting in United States Food and Drug Administration registration trials for thoracic malignancies from 2006-2020. Cancer investigation Chiang, R. S., Desai, A., Glover, M. J., Hui, G., Ramchandran, K. J., Wakelee, H., Lythgoe, M. P., Khaki, A. R. 2022: 1-6

  Abstract

  There is significant racial disparity in thoracic malignancies in terms of epidemiology and outcomes. We analyzed race reporting and racial diversity in the registration trials of drugs approved by the FDA for thoracic malignancies from 2006-2020. We found a significant under-representation of non-white participants in FDA drug registration trials in thoracic malignancies. Furthermore, though almost all trials report some race information, FDA guidelines are not universally followed. There is a disproportionate disease burden of lung cancer in under-represented race communities, and clinical trials should prioritize racial diversity and inclusion efforts.

  View details for DOI 10.1080/07357907.2022.2131808

  View details for PubMedID 36197034

• Demographics, Outcomes, and Risk Factors for Patients with Sarcoma and COVID-19: A CCC19-Registry Based Retrospective Cohort Study. Cancers Wagner, M. J., Hennessy, C., Beeghly, A., French, B., Shah, D. P., Croessmann, S., Vilar-Compte, D., Ruiz-Garcia, E., Ingham, M., Schwartz, G. K., Painter, C. A., Chugh, R., Fecher, L., Park, C., Zamulko, O., Trent, J. C., Subbiah, V., Khaki, A. R., Tachiki, L., Nakasone, E. S., Loggers, E. T., Labaki, C., Saliby, R. M., McKay, R. R., Ajmera, A., Griffiths, E. A., Puzanov, I., Tap, W. D., Hwang, C., Tejwani, S., Jhawar, S. R., Hayes-Lattin, B., Wulff-Burchfield, E., Kasi, A., Reuben, D. Y., Nagaraj, G., Joshi, M., Polimera, H., Kulkarni, A. A., Esfahani, K., Kwon, D. H., Paoluzzi, L., Bilen, M. A., Durbin, E. B., Grivas, P., Warner, J. L., Davis, E. J., COVID-19 and Cancer Consortium 2022; 14 (17)

  Abstract

  BACKGROUND: Patients with sarcoma often require individualized treatment strategies and are likely to receive aggressive immunosuppressive therapies, which may place them at higher risk for severe COVID-19. We aimed to describe demographics, risk factors, and outcomes for patients with sarcoma and COVID-19.METHODS: We performed a retrospective cohort study of patients with sarcoma and COVID-19 reported to the COVID-19 and Cancer Consortium (CCC19) registry (NCT04354701) from 17 March 2020 to 30 September 2021. Demographics, sarcoma histologic type, treatments, and COVID-19 outcomes were analyzed.RESULTS: of 281 patients, 49% (n = 139) were hospitalized, 33% (n = 93) received supplemental oxygen, 11% (n = 31) were admitted to the ICU, and 6% (n = 16) received mechanical ventilation. A total of 23 (8%) died within 30 days of COVID-19 diagnosis and 44 (16%) died overall at the time of analysis. When evaluated by sarcoma subtype, patients with bone sarcoma and COVID-19 had a higher mortality rate than patients from a matched SEER cohort (13.5% vs 4.4%). Older age, poor performance status, recent systemic anti-cancer therapy, and lung metastases all contributed to higher COVID-19 severity.CONCLUSIONS: Patients with sarcoma have high rates of severe COVID-19 and those with bone sarcoma may have the greatest risk of death.

  View details for DOI 10.3390/cancers14174334

  View details for PubMedID 36077869

• Association of the Time to Immune Checkpoint Inhibitor (ICI) Initiation and Outcomes With Second Line ICI in Patients With Advanced Urothelial Carcinoma. Clinical genitourinary cancer Talukder, R., Makrakis, D., Lin, G. I., Diamantopoulos, L. N., Dawsey, S., Gupta, S., Carril-Ajuria, L., Castellano, D., de Kouchkovsky, I., Jindal, T., Koshkin, V. S., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Tripathi, N., Agarwal, N., Vather-Wu, N., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Cortellini, A., Fulgenzi, C. A., Pinato, D. J., Nelson, A., Hoimes, C. J., Gupta, K., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Murgic, J., Frobe, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Lu, E., Kumar, V., Lorenzo, G. D., Joshi, M., Isaacsson-Velho, P., Buznego, L. A., Duran, I., Moses, M., Barata, P., Sonpavde, G., Wright, J. L., Yu, E. Y., Montgomery, R. B., Hsieh, A. C., Grivas, P., Khaki, A. R. 2022

  Abstract

  BACKGROUND: Early progression on first-line (1L) platinum-based therapy or between therapy lines may be a surrogate of more aggressive disease and poor outcomes in advanced urothelial carcinoma (aUC), but its prognostic role regarding immune checkpoint inhibitor (ICI) response and survival is unclear. We hypothesized that shorter time until start of second-line (2L) ICI would be associated with worse outcomes in aUC.PATIENTS AND METHODS: We performed a retrospective multi-institution cohort study in patients with aUC treated with 1L platinum-based chemotherapy, who received 2L ICI. Patients receiving switch maintenance ICI were excluded. We defined time to 2L ICI therapy as the time between the start of 1L platinum-based chemotherapy to the start of 2L ICI and categorized patients a priori into 1 of 3 groups: less than 3 months versus 3-6 months versus more than 6 months. We calculated overall response rate (ORR) with 2L ICI, progression-free survival (PFS) and overall survival (OS) from the start of 2L ICI. ORR was compared among the 3 groups using multivariable logistic regression, and PFS, OS using cox regression. Multivariable models were adjusted for known prognostic factors.RESULTS: We included 215, 215, and 219 patients in the ORR, PFS, and OS analyses, respectively, after exclusions. ORR difference did not reach statistical significance between patients with less than 3 months versus 3-6 months versus more than 6 months to 2L ICI. However, PFS (HR 1.64; 95% CI 1.02-2.63) and OS (HR 1.77; 95% CI 1.10-2.84) was shorter among those with time to 2L ICI less than 3 months compared to those who initiated 2L ICI more than 6 months.CONCLUSION: Among patients with aUC treated with 2L ICI, time to 2L ICI less than 3 months was associated with lower, but not significantly different ORR, but shorter PFS and OS compared to 2L ICI more than 6 months. This highlights potential cross resistance mechanisms between ICI and platinum-based chemotherapy.

  View details for DOI 10.1016/j.clgc.2022.08.006

  View details for PubMedID 36155169

• Immune related liver toxicity and potential risk factors: A case-control study Storm, E. M., Makraki, D., Lin, G. I., Kennedy, L. C., Shah, E. E., Phipps, A. I., Liou, I. W., Hockenbery, D., Grivas, P., Khaki, A. R. AMER ASSOC CANCER RESEARCH. 2022

  View details for Web of Science ID 000892509505258

• Association Between Sites of Metastasis and Outcomes With Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma. Clinical genitourinary cancer Makrakis, D., Talukder, R., Lin, G. I., Diamantopoulos, L. N., Dawsey, S., Gupta, S., Carril-Ajuria, L., Castellano, D., de Kouchkovsky, I., Koshkin, V. S., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Tripathi, N., Agarwal, N., Vather-Wu, N., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Cortellini, A., Fulgenzi, C. A., Pinato, D. J., Nelson, A., Hoimes, C. J., Gupta, K., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Murgic, J., Frobe, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Lu, E., Kumar, V., Lorenzo, G. D., Joshi, M., Isaacsson-Velho, P., Buznego, L. A., Duran, I., Moses, M., Jang, A., Barata, P., Sonpavde, G., Yu, E. Y., Montgomery, R. B., Grivas, P., Khaki, A. R. 2022

  Abstract

  BACKGROUND: Sites of metastasis have prognostic significance in advanced urothelial carcinoma (aUC), but more information is needed regarding outcomes based on metastatic sites in patients treated with immune checkpoint inhibitors (ICI). We hypothesized that presence of liver/bone metastases would be associated with worse outcomes with ICI.METHODS: We identified a retrospective cohort of patients with aUC across 26 institutions, collecting demographics, clinicopathological, treatment, and outcomes information. Outcomes were compared with logistic (observed response rate; ORR) and Cox (progression-free survival; PFS, overall survival; OS) regression between patients with/without metastasis beyond lymph nodes (LN) and those with/without bone/liver/lung metastasis. Analysis was stratified by 1st or 2nd+ line.RESULTS: We identified 917 ICI-treated patients: in the 1st line, bone/liver metastases were associated with shorter PFS (Hazard ratio; HR: 1.65 and 2.54), OS (HR: 1.60 and 2.35, respectively) and lower ORR (OR: 0.48 and 0.31). In the 2nd+ line, bone/liver metastases were associated with shorter PFS (HR: 1.71 and 1.62), OS (HR: 1.76 and 1.56) and, for bone-only metastases, lower ORR (OR: 0.29). In the 1st line, LN-confined metastasis was associated with longer PFS (HR: 0.53), OS (HR:0.49) and higher ORR (OR: 2.97). In the 2nd+ line, LN-confined metastasis was associated with longer PFS (HR: 0.47), OS (HR: 0.54), and higher ORR (OR: 2.79); all associations were significant.CONCLUSION: Bone and/or liver metastases were associated with worse, while LN-confined metastases were associated with better outcomes in patients with aUC receiving ICI. These findings in a large population treated outside clinical trials corroborate data from trial subset analyses.

  View details for DOI 10.1016/j.clgc.2022.06.001

  View details for PubMedID 35778337

• Use of systemic cancer treatments based on a validated survival prediction model in metastatic cancer. Roy, M., Gensheimer, M. F., Chang, D., Singhal, S., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680302618

• Cancer Therapy Approval Timings, Review Speed, and Publication of Pivotal Registration Trials in the US and Europe, 2010-2019. JAMA network open Lythgoe, M. P., Desai, A., Gyawali, B., Savage, P., Krell, J., Warner, J. L., Khaki, A. R. 2022; 5 (6): e2216183

  Abstract

  Importance: Ensuring patients have access to safe and efficacious medicines in a timely manner is an essential goal for regulatory agencies, one which has particular importance in oncology because of the substantial unmet need for new therapies. The 2 largest regulatory agencies, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have pivotal global roles, and their recommendations and approvals are frequently followed by other national regulators.Objective: To compare market authorization dates for new oncology therapies approved in the US and Europe over the past decade and to examine and contrast the regulatory activities of the FDA and EMA in the approval of new cancer medicines.Design, Setting, and Participants: This cross-sectional study reviewed the FDA and EMA regulatory databases to identify new oncology therapies approved in both the US and Europe from 2010 to 2019, and characterization of the timings of regulatory activities. Statistical analysis was performed from January to April 2022.Main Outcomes and Measures: Regulatory approval date, review time, submission of market authorization application, accelerated approval or conditional marketing authorization status and proportion of approvals prior to peer-reviewed publication of pivotal trial results.Results: In total, 89 new concomitant oncology therapies were approved in the US and Europe from 2010 to 2019. The FDA approved 85 oncology therapies (95%) before European authorization and 4 therapies (5%) after. The median (IQR) delay in market authorization for new oncology therapies in Europe was 241 (150-370) days compared with the US. The median (IQR) review time was 200 (155-277) days for the FDA and 426 (358-480) days for the EMA. Sixty-four new licensing applications (72%) were submitted to the FDA first, compared with 21 (23%) to the EMA. Thirty-five oncology therapies (39%) were approved by the FDA prior to pivotal study publication, whereas only 8 (9%) by the EMA.Conclusion and Relevance: In this cross-sectional study, new oncology therapies were approved earlier in the US than Europe. The FDA received licensing applications sooner and had shorter review times. However, more therapies were approved prior to licensing study publication, leaving uncertainty for practitioners regarding clinical utility and safety of newly approved therapies.

  View details for DOI 10.1001/jamanetworkopen.2022.16183

  View details for PubMedID 35687337

• Using real-world data to assess variations in cost and healthcare utilization for patients diagnosed with bladder cancer. Boehmer, L., Khaki, A., Carthon, B., Davis, N. B., Washington, S. L., Goltz, H., Lucas, L., Mangir, C. LIPPINCOTT WILLIAMS & WILKINS. 2022: E18815

  View details for Web of Science ID 000863680303947

• Patient-reported distress at a cancer center during the COVID-19 pandemic. Shah, M. P., Rosenthal, S., Roy, M., Khaki, A., Hernandez-Boussard, T., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2022: E18644

  View details for Web of Science ID 000863680303793

• Reducing inpatient mortality in patients with cancer through multidisciplinary review and targeted interventions. Shah, M. P., Garrigues, S. K., Khaki, A., Hansen, J., Divi, V., Blayney, D. W. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300580

• Re: Pembrolizumab Monotherapy for the Treatment of High-risk Non-muscle-invasive Bladder Cancer Unresponsive to BCG (KEYNOTE-057): An Open-label, Single-arm, Multicentre, Phase 2 Study EUROPEAN UROLOGY Parikh, D. A., Kaki, A., Williams, S. B. 2022; 81 (4): 429-430

  View details for DOI 10.1016/j.ejso.2020.06.024

  View details for Web of Science ID 000834990100028

• Association of renal cell carcinoma (RCC) metastatic to pancreas with a distinct molecular profile and immune cell population. Chiang, R. S., Ashok, A., Mauer, E., Barrett, A., Hoerner, C. R., Khan, O. A., Kao, C., Shah, S., Srinivas, S., Fan, A. C., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1200/JCO.2022.40.6_suppl.366

  View details for Web of Science ID 000771008900370

• Association of time to second-line (2L) immune-checkpoint inhibitors (ICI) and outcomes with ICIs in patients (pts) with advanced urothelial carcinoma (aUC). Makrakis, D., Talukder, R., Dawsey, S., Carril, L., Stewart, T. F., Morales-Barrera, R., Park, J. J., Fulgenzi, C., Murgic, J., Vather-Wu, N., de Kouchkovsky, I., Devitt, M., Di Lorenzo, G., Gupta, K., Tripathi, N., Zakopoulou, R., Tripathi, A., Lu, E., Grivas, P., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1200/JCO.2022.40.6_suppl.505

  View details for Web of Science ID 000771008900512

• Long-term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer. Golla, V., Shan, Y., Farran, E., Vu, K., Stewart, C. A., Khaki, A., Keegan, K. A., Kamat, A. M., Tyler, D. S., Freedland, S. J., Williams, S. B. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for DOI 10.1200/JCO.2022.40.6_suppl.455

  View details for Web of Science ID 000771008900462

• Geriatric risk factors for serious COVID-19 outcomes among older adults with cancer: a cohort study from the COVID-19 and Cancer Consortium. The Lancet. Healthy longevity Elkrief, A., Hennessy, C., Kuderer, N. M., Rubinstein, S. M., Wulff-Burchfield, E., Rosovsky, R. P., Vega-Luna, K., Thompson, M. A., Panagiotou, O. A., Desai, A., Rivera, D. R., Khaki, A. R., Tachiki, L., Lynch, R. C., Stratton, C., Elias, R., Batist, G., Kasi, A., Shah, D. P., Bakouny, Z., Cabal, A., Clement, J., Crowell, J., Dixon, B., Friese, C. R., Fry, S. L., Grover, P., Gulati, S., Gupta, S., Hwang, C., Khan, H., Kim, S. J., Klein, E. J., Labaki, C., McKay, R. R., Nizam, A., Pennell, N. A., Puc, M., Schmidt, A. L., Shahrokni, A., Shaya, J. A., Su, C. T., Wall, S., Williams, N., Wise-Draper, T. M., Mishra, S., Grivas, P., French, B., Warner, J. L., Wildes, T. M., COVID-19 and Cancer Consortium 2022

  Abstract

  Background: Older age is associated with poorer outcomes of SARS-CoV-2 infection, although the heterogeneity of ageing results in some older adults being at greater risk than others. The objective of this study was to quantify the association of a novel geriatric risk index, comprising age, modified Charlson comorbidity index, and Eastern Cooperative Oncology Group performance status, with COVID-19 severity and 30-day mortality among older adults with cancer.Methods: In this cohort study, we enrolled patients aged 60 years and older with a current or previous cancer diagnosis (excluding those with non-invasive cancers and premalignant or non-malignant conditions) and a current or previous laboratory-confirmed COVID-19 diagnosis who reported to the COVID-19 and Cancer Consortium (CCC19) multinational, multicentre, registry between March 17, 2020, and June 6, 2021. Patients were also excluded for unknown age, missing data resulting in unknown geriatric risk measure, inadequate data quality, or incomplete follow-up resulting in unknown COVID-19 severity. The exposure of interest was the CCC19 geriatric risk index. The primary outcome was COVID-19 severity and the secondary outcome was 30-day all-cause mortality; both were assessed in the full dataset. Adjusted odds ratios (ORs) and 95% CIs were estimated from ordinal and binary logistic regression models.Findings: 5671 patients with cancer and COVID-19 were included in the analysis. Median follow-up time was 56 days (IQR 22-120), and median age was 72 years (IQR 66-79). The CCC19 geriatric risk index identified 2365 (41·7%) patients as standard risk, 2217 (39·1%) patients as intermediate risk, and 1089 (19·2%) as high risk. 36 (0·6%) patients were excluded due to non-calculable geriatric risk index. Compared with standard-risk patients, high-risk patients had significantly higher COVID-19 severity (adjusted OR 7·24; 95% CI 6·20-8·45). 920 (16·2%) of 5671 patients died within 30 days of a COVID-19 diagnosis, including 161 (6·8%) of 2365 standard-risk patients, 409 (18·5%) of 2217 intermediate-risk patients, and 350 (32·1%) of 1089 high-risk patients. High-risk patients had higher adjusted odds of 30-day mortality (adjusted OR 10·7; 95% CI 8·54-13·5) than standard-risk patients.Interpretation: The CCC19 geriatric risk index was strongly associated with COVID-19 severity and 30-day mortality. Our CCC19 geriatric risk index, based on readily available clinical factors, might provide clinicians with an easy-to-use risk stratification method to identify older adults most at risk for severe COVID-19 as well as mortality.Funding: US National Institutes of Health National Cancer Institute Cancer Center.

  View details for DOI 10.1016/S2666-7568(22)00009-5

  View details for PubMedID 35187516

• Re: Pembrolizumab Monotherapy for the Treatment of High-risk Non-muscle-invasive Bladder Cancer Unresponsive to BCG (KEYNOTE-057): An Open-label, Single-arm, Multicentre, Phase 2 Study. European urology Parikh, D. A., Khaki, A. R., Williams, S. B. 2022

  View details for DOI 10.1016/j.eururo.2022.01.016

  View details for PubMedID 35131115

• Long term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer. Urologic oncology Golla, V., Shan, Y., Farran, E. J., Stewart, C. A., Vu, K., Yu, A., Khaki, A. R., Parikh, D. A., Swanson, T. A., Keegan, K. A., Kamat, A. M., Tyler, D. S., Freedland, S. J., Williams, S. B. 2022

  Abstract

  Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC).We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models.A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781).The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.

  View details for DOI 10.1016/j.urolonc.2022.01.007

  View details for PubMedID 35168881

• Determinants of prognosis in metastatic urothelial carcinoma: a review of the literature JOURNAL OF CANCER METASTASIS AND TREATMENT Hui, G., Khaki, A., Grivas, P. 2022; 8

  View details for DOI 10.20517/2394-4722.2022.04

  View details for Web of Science ID 000911216100034

• Considerations in the reliability and fairness audits of predictive models for advance care planning Frontiers in Digital Health Lu, J., Sattler, A., Wang, S., Khaki, A. R., Callahan, A., Fleming, S., Fong, R., Ehlert, B., Li, R., Shieh, L., Ramchandran, K., Gensheimer, M., Chobot, S., Pfohl, S., Li, S., Shum, K., Parikh, N., Desai, P., Seevaratnam, B., Hanson, M., Smith, M., Xu, Y., Gokhale, A., Lin, S., Shah, N. 2022: 943768

  View details for DOI 10.3389/fdgth.2022.943768

• Immunotherapy for Urothelial Carcinoma: Focus on Clinical Utility of Nivolumab. OncoTargets and therapy Chiang, R. S., Glover, M. J., Khaki, A. R., Srinivas, S. 2022; 15: 1259-1269

  Abstract

  Over the past decade, the emergence of immune checkpoint inhibitors has brought about significant change to the treatment landscape of bladder cancer. Nivolumab is an immune checkpoint inhibitor that has shown favorable results resulting in FDA approval for treatment of platinum-refractory locally advanced or metastatic urothelial carcinoma. More recently, it was the first (and only) immune checkpoint inhibitor to receive FDA approval for the treatment of urothelial carcinoma in the adjuvant setting after radical surgery. Multiple trials are now actively underway to further understand the nuances in which immune checkpoint inhibitors such as nivolumab can be beneficial. In this review, we explore the development of nivolumab in terms of its mechanism of action, its growing indications in the treatment of urothelial carcinoma, and potential future directions for clinical trials.Immune checkpoint inhibitors are a promising treatment for bladder cancer, but further work is needed to continue to improve outcomes for patients.

  View details for DOI 10.2147/OTT.S369043

  View details for PubMedID 36275184

• Response and Outcomes to Immune Checkpoint Inhibitors in Advanced Urothelial Cancer Based on Prior Intravesical Bacillus Calmette-Guerin. Clinical genitourinary cancer Talukder, R., Makrakis, D., Diamantopoulos, L. N., Carril-Ajuria, L., Castellano, D., De Kouchkovsky, I., Koshkin, V. S., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Santos, V. S., Agarwal, N., Jain, J., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Grant, M., Lythgoe, M. P., Pinato, D. J., Nelson, A., Hoimes, C. J., Shreck, E., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Murgic, J., Frobe, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Kumar, V., Lorenzo, G. D., Joshi, M., Velho, P. I., Buznego, L. A., Duran, I., Moses, M., Barata, P., Sonpavde, G., Yu, E. Y., Wright, J. L., Grivas, P., Khaki, A. R. 1800

  Abstract

  BACKGROUND: Immune checkpoint inhibitors (ICI) improve overall survival (OS) in patients with locally advanced, unresectable, or metastatic urothelial carcinoma (aUC), but response rates can be modest. We compared outcomes between patients with and without prior intravesical Bacillus Calmette-Guerin (BCG), who received ICI for aUC, hypothesizing that prior intravesical BCG would be associated with worse outcomes.PATIENTS AND METHODS: We performed a retrospective cohort study across 25 institutions in US and Europe. We compared observed response rate (ORR) using logistic regression; progression-free survival (PFS) and OS using Kaplan-Meier and Cox proportional hazards. Analyses were stratified by treatment line (first line/salvage) and included multivariable models adjusting for known prognostic factors.RESULTS: A total of 1026 patients with aUC were identified; 614, 617, and 638 were included in ORR, OS, PFS analyses, respectively. Overall, 150 pts had history of prior intravesical BCG treatment. ORR to ICI was similar between those with and without prior intravesical BCG exposure in both first line and salvage settings (adjusted odds radios 0.55 [P= .08] and 1.65 [P= .12]). OS (adjusted hazard ratios 1.05 [P= .79] and 1.13 [P= .49]) and PFS (adjusted hazard ratios 1.12 [P= .55] and 0.87 [P= .39]) were similar between those with and without intravesical BCG exposure in first line and salvage settings.CONCLUSION: Prior intravesical BCG was not associated with differences in response and survival in patients with aUC treated with ICI. Limitations include retrospective nature, lack of randomization, presence of selection and confounding biases. This study provides important preliminary data that prior intravesical BCG exposure may not impact ICI efficacy in aUC.

  View details for DOI 10.1016/j.clgc.2021.12.012

  View details for PubMedID 35078711

• Efficacy of enfortumab vedotin in advanced urothelial cancer: Analysis from the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study. Cancer Koshkin, V. S., Henderson, N., James, M., Natesan, D., Freeman, D., Nizam, A., Su, C. T., Khaki, A. R., Osterman, C. K., Glover, M. J., Chiang, R., Makrakis, D., Talukder, R., Lemke, E., Olsen, T. A., Jain, J., Jang, A., Ali, A., Jindal, T., Chou, J., Friedlander, T. W., Hoimes, C., Basu, A., Zakharia, Y., Barata, P. C., Bilen, M. A., Emamekhoo, H., Davis, N. B., Shah, S. A., Milowsky, M. I., Gupta, S., Campbell, M. T., Grivas, P., Sonpavde, G. P., Kilari, D., Alva, A. S. 2021

  Abstract

  BACKGROUND: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials.METHODS: UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator-assessed for patients with at least 1 post-baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy.RESULTS: The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression-free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06).CONCLUSIONS: In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate < 30 mL/min and significant comorbidities.LAY SUMMARY: Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real-world setting, and support the use of this drug in broader patient populations.

  View details for DOI 10.1002/cncr.34057

  View details for PubMedID 34882781

• Disparity of Race Reporting in FDA Drug Approvals for Urinary System Cancers from 2006 to 2021. BJU international Glover, M., Hui, G., Chiang, R., Savage, P., Krell, J., Julve, M., Grivas, P., Lythgoe, M., Khaki, A. R. 2021

  Abstract

  BACKGROUND: Significant racial disparity exists in urinary system cancers (urothelial carcinoma [UC] and renal cell carcinoma [RCC]), in terms of epidemiology, access to therapy and outcomes. We analyzed racial diversity and race reporting in FDA drug registration trials for UC and RCC.METHOD: All FDA pivotal registration trials between 2006-2021 for both UC and RCC were identified. The trials were analyzed to check for compliance with current FDA recommendations for race reporting. Additional information on participant recruitment and race was obtained to assess representation based on cancer type.RESULTS: From 2006-2021 there were 30 new drug registrations for the management of urinary systems cancers, of which 16 in RCC and 14 in UC. Overall, 70% of these trials reported data on racial representation, however, only 43% reported data stratified into five categories as recommended by the FDA.CONCLUSION: We found a significant under-representation of non-white participants in FDA drug registration clinical trials in UC and RCC. Race reporting is inconsistent and FDA guidelines are not being universally followed. Considering the disproportionate disease burden in UC and RCC, clinical trials should prioritize recruiting a diverse population of participants.

  View details for DOI 10.1111/bju.15629

  View details for PubMedID 34748278

• Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19. JAMA network open Schmidt, A. L., Tucker, M. D., Bakouny, Z., Labaki, C., Hsu, C., Shyr, Y., Armstrong, A. J., Beer, T. M., Bijjula, R. R., Bilen, M. A., Connell, C. F., Dawsey, S. J., Faller, B., Gao, X., Gartrell, B. A., Gill, D., Gulati, S., Halabi, S., Hwang, C., Joshi, M., Khaki, A. R., Menon, H., Morris, M. J., Puc, M., Russell, K. B., Shah, N. J., Sharifi, N., Shaya, J., Schweizer, M. T., Steinharter, J., Wulff-Burchfield, E. M., Xu, W., Zhu, J., Mishra, S., Grivas, P., Rini, B. I., Warner, J. L., Zhang, T., Choueiri, T. K., Gupta, S., McKay, R. R. 2021; 4 (11): e2134330

  Abstract

  Importance: Androgen deprivation therapy (ADT) has been theorized to decrease the severity of SARS-CoV-2 infection in patients with prostate cancer owing to a potential decrease in the tissue-based expression of the SARS-CoV-2 coreceptor transmembrane protease, serine 2 (TMPRSS2).Objective: To examine whether ADT is associated with a decreased rate of 30-day mortality from SARS-CoV-2 infection among patients with prostate cancer.Design, Setting, and Participants: This cohort study analyzed patient data recorded in the COVID-19 and Cancer Consortium registry between March 17, 2020, and February 11, 2021. The consortium maintains a centralized multi-institution registry of patients with a current or past diagnosis of cancer who developed COVID-19. Data were collected and managed using REDCap software hosted at Vanderbilt University Medical Center in Nashville, Tennessee. Initially, 1228 patients aged 18 years or older with prostate cancer listed as their primary malignant neoplasm were included; 122 patients with a second malignant neoplasm, insufficient follow-up, or low-quality data were excluded. Propensity matching was performed using the nearest-neighbor method with a 1:3 ratio of treated units to control units, adjusted for age, body mass index, race and ethnicity, Eastern Cooperative Oncology Group performance status score, smoking status, comorbidities (cardiovascular, pulmonary, kidney disease, and diabetes), cancer status, baseline steroid use, COVID-19 treatment, and presence of metastatic disease.Exposures: Androgen deprivation therapy use was defined as prior bilateral orchiectomy or pharmacologic ADT administered within the prior 3 months of presentation with COVID-19.Main Outcomes and Measures: The primary outcome was the rate of all-cause 30-day mortality after COVID-19 diagnosis for patients receiving ADT compared with patients not receiving ADT after propensity matching.Results: After exclusions, 1106 patients with prostate cancer (before propensity score matching: median age, 73 years [IQR, 65-79 years]; 561 (51%) self-identified as non-Hispanic White) were included for analysis. Of these patients, 477 were included for propensity score matching (169 who received ADT and 308 who did not receive ADT). After propensity matching, there was no significant difference in the primary end point of the rate of all-cause 30-day mortality (OR, 0.77; 95% CI, 0.42-1.42).Conclusions and Relevance: Findings from this cohort study suggest that ADT use was not associated with decreased mortality from SARS-CoV-2 infection. However, large ongoing clinical trials will provide further evidence on the role of ADT or other androgen-targeted therapies in reducing COVID-19 infection severity.

  View details for DOI 10.1001/jamanetworkopen.2021.34330

  View details for PubMedID 34767021

• Outcomes of Patients with COVID-19 from a Specialized Cancer Care Emergency Room. Cancer investigation Nath, S. S., Yadav, N. U., Derkach, A., Perez-Johnston, R., Tachiki, L., Maguire, K., Babar, A., Maloy, M. A., Klotz, A., Jee, J., Taur, Y., Chawla, S., Babady, E., Khaki, A. R., Madeleine, M. M., Grivas, P., Henning, D. J., Aaltonen, L., Lyman, G. H., Groeger, J. 2021: 1-9

  Abstract

  PURPOSE: Our goal was to identify discrete clinical characteristics associated with safe discharge from an emergency department/urgent care for patients with a history of cancer and concurrent COVID-19 infection during the SARS-CoV-2 pandemic and prior to widespread vaccination.PATIENTS AND METHODS: We retrospectively analyzed 255 adult patients with a history of cancer who presented to Memorial Sloan Kettering Cancer Center (MSKCC) urgent care center (UCC) from March 1, 2020 to May 31, 2020 with concurrent COVID-19 infection. We evaluated associations between patient characteristics and 30-day mortality from initial emergency department (ED) or urgent care center (UCC) visit and the absence of a severe event within 30days. External validation was performed on a retrospective data from 29 patients followed at Fred Hutchinson Cancer Research Center that presented to the local emergency department. A late cohort of 108 additional patients at MSKCC from June 1, 2020 to January 31, 2021 was utilized for further validation.RESULTS: In the MSKCC cohort, 30-day mortality and severe event rate was 15% and 32% respectively. Using stepwise regression analysis, elevated BUN and glucose, anemia, and tachypnea were selected as the main predictors of 30-day mortality. Conversely, normal albumin, BUN, calcium, and glucose, neutrophil-lymphocyte ratio <3, lack of (severe) hypoxia, lack of bradycardia or tachypnea, and negative imaging were selected as the main predictors of an uneventful course as defined as a Lack Of a Severe Event within Thirty Days (LOSETD). Utilizing this information, we devised a tool to predict 30-day mortality and LOSETD which achieved an area under the operating curve (AUC) of 79% and 74% respectively. Similar estimates of AUC were obtained in an external validation cohort. A late cohort at MSKCC was consistent with the prior, albeit with a lower AUC.CONCLUSION: We identified easily obtainable variables that predict 30-day mortality and the absence of a severe event for patients with a history of cancer and concurrent COVID-19. This has been translated into a bedside tool that the clinician may utilize to assist disposition of this group of patients from the emergency department or urgent care setting.

  View details for DOI 10.1080/07357907.2021.1985134

  View details for PubMedID 34709102

• Racial diversity and reporting in FDA registration trials for thoracic malignancies from 2006 to 2020 Chiang, R. S., Glover, M., Hui, G., Desai, A., Wakelee, H. A., Lythgoe, M., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.135

  View details for Web of Science ID 000707130200134

• Association of prior local therapy and outcomes with PD(L)1 inhibitor in advanced urothelial cancer. BJU international Makrakis, D., Talukder, R., Diamantopoulos, L. N., Carril-Ajuria, L., Castellano, D., De Kouchkovsky, I., Koshkin, V. S., Park, J. J., Alva, A., Bilen, M. A., Stewart, T. F., McKay, R. R., Santos, V. S., Agarwal, N., Jain, J., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Grant, M., Lythgoe, M. P., Pinato, D. J., Nelson, A., Hoimes, C. J., Shreck, E., Gartrell, B. A., Sankin, A., Tripathi, A., Zakopoulou, R., Bamias, A., Murgic, J., Frobe, A., Rodriguez-Vida, A., Drakaki, A., Liu, S., Kumar, V., Di Lorenzo, G., Joshi, M., Isaacsson-Velho, P., Buznego, L. A., Duran, I., Moses, M., Barata, P., Sonpavde, G., Yu, E. Y., Wright, J. L., Grivas, P., Khaki, A. R. 2021

  Abstract

  OBJECTIVES: To compare clinical outcomes with anti-PD(L)1 immune checkpoint inhibitors (ICIs) in patients with advanced urothelial carcinoma (aUC) who have vs have not undergone radical surgery (RS) or radiation (RT) prior to developing metastatic disease.PATIENTS AND METHODS: We performed a retrospective cohort study collecting clinicopathological, treatment and outcomes data for patients with aUC receiving ICIs across 25 institutions. We compared outcomes (observed response rate [ORR], progression-free survival [PFS], overall survival [OS]) between patients with vs without prior RS, and by type of prior locoregional treatment (RS vs RT vs no locoregional treatment). Patients with de novo advanced disease were excluded. Analysis was stratified by treatment line (first [1st ] & second or greater [2nd+ ]). Logistic regression was used to compare ORR; Kaplan-Meier analysis and Cox regression for PFS and OS. Multivariable models were adjusted for known prognostic factors.RESULTS: We included 562 patients (1st line: 342 and 2nd+ : 220). There was no difference in outcomes based on prior locoregional treatment among those treated with 1st line ICI. In the 2nd+ line, prior RS was associated with higher ORR (adjusted odds ratio [aOR] 2.61 [95% CI 1.19-5.74]), longer OS (adjusted hazard ratio [aHR] 0.61 [95% CI 0.42-0.88]) and PFS (aHR 0.63 [95% CI 0.45-0.89]) vs no prior RS. This association remained significant when the type of prior locoregional treatment (RS and RT) was modeled separately.CONCLUSION: Prior RS prior to developing advanced disease was associated with better outcomes in patients with aUC treated with ICI in the 2nd+ , but not in the 1st line setting. While further validation is needed, our findings can have implications on prognostic estimates in clinical discussions and benchmarking for clinical trials. Limitations include retrospective nature, lack of randomization, possible selection and confounding biases.

  View details for DOI 10.1111/bju.15603

  View details for PubMedID 34597472

• Patients' perception of meaning of life and needed support before and after cancer treatment initiation Roy, M., Rosenthal, S., Shah, M., Khaki, A., Hernandez-Boussard, T., Ramchandran, K. SPRINGER. 2021: S156-S157

  View details for Web of Science ID 000712224700339

• Association of treatment type with patient-reported quality of life in cancer distress screening Roy, M., Rosenthal, S., Shah, M. P., Khaki, A., Bozkurt, S., Seto, T., Blayney, D. W., Hernandez-Boussard, T., Ramchandran, K. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2020.39.28_suppl.178

  View details for Web of Science ID 000707130200177

• Use of Second-line Immunotherapy in Control Arms of Randomized Clinical Trials in Kidney Cancer: A Systematic Review. JAMA network open Sharp, J., Khaki, A. R., Prasad, V. 2021; 4 (9): e2124728

  Abstract

  Importance: Immunotherapy (anti-programmed death ligand 1 antibodies) is associated with improved survival rates in advanced kidney cell carcinoma (KCC) after progression on first-line tyrosine kinase inhibitor (TKI) treatment. It is unknown whether and to what degree patients in the control arm receive postprotocol immunotherapy in trials comparing combination immunotherapy regimens with TKI in first-line advanced KCC.Objective: To characterize the proportion of patients in the control arm who received postprotocol immunotherapy in trials comparing combination immunotherapy regimens with TKI in first-line advanced KCC.Evidence Review: A search of PubMed was conducted to identify randomized clinical trials of combination immunotherapy compared with TKI in first-line advanced KCC between January 1, 2015, and February 28, 2021. Combination immunotherapy was defined as an anti-programmed death ligand 1 agent and an additional agent. Search terms included renal cell cancer and first-line and were filtered by the type clinical trial. All English-language trials of combination immunotherapy compared with a TKI were included. The trials and their protocols and supplements were analyzed to determine the proportion of patients in the control arm receiving postprotocol immunotherapy.Findings: A total of 106 articles met search criteria and were screened. A total of 6 trials and 3 published updates of trial results were included in the systematic review. Of 2565 patients assigned to control arm groups, 2069 (81%) were no longer on TKI at last data cutoff. Of patients in the control arm who discontinued TKI, 932 (45%) received postprotocol immunotherapy. Of patients in the control arm receiving any type of postprotocol therapy, 66.4% received immunotherapy.Conclusions and Relevance: This systematic review found that the proportion of patients in the control arm receiving postprotocol immunotherapy is low in randomized clinical trials of first-line combination immunotherapy regimens for advanced KCC. Appropriate use of postprotocol therapy is essential to answering the question of whether a combination or sequential treatment strategy with immunotherapy is superior.

  View details for DOI 10.1001/jamanetworkopen.2021.24728

  View details for PubMedID 34570209

• Immunotherapy in Patients With Poor Performance Status: The Jury Is Still Out on This Special Population. JCO oncology practice Khaki, A. R., Glisch, C., Petrillo, L. A. 2021: OP2100397

  View details for DOI 10.1200/OP.21.00397

  View details for PubMedID 34297600

• Clinical and Virologic Characteristics and Outcomes of Coronavirus Disease 2019 at a Cancer Center. Open forum infectious diseases Yoke, L. H., Lee, J. M., Krantz, E. M., Morris, J., Marquis, S., Bhattacharyya, P., So, L., Riedo, F. X., Simmons, J., Khaki, A. R., Cheng, G., Greninger, A. L., Pergam, S. A., Waghmare, A., Ogimi, C., Liu, C. 2021; 8 (6): ofab193

  Abstract

  Background: High morbidity and mortality have been observed in patients with cancer and coronavirus disease 2019 (COVID-19); however, there are limited data on antimicrobial use, coinfections, and viral shedding.Methods: We conducted a retrospective cohort study of adult patients at the Seattle Cancer Care Alliance diagnosed with COVID-19 between February 28, 2020 and June 15, 2020 to characterize antimicrobial use, coinfections, viral shedding, and outcomes within 30 days after diagnosis. Cycle threshold values were used as a proxy for viral load. We determined viral clearance, defined as 2 consecutive negative results using severe acute respiratory syndrome coronavirus 2 reverse-transcription polymerase chain reaction results through July 30, 2020.Results: Seventy-one patients were included with a median age of 61 years; 59% had a solid tumor. Only 3 patients had documented respiratory bacterial coinfection. Empiric antibiotics for pneumonia were prescribed more frequently early in the study period (February 29-March 28, 2020; 12/34) compared to the later period (March 29-June 15, 2020; 2/36) (P = .002). The median number of days from symptom onset to viral clearance was 37 days with viral load rapidly declining in the first 7-10 days after symptom onset. Within 30 days of diagnosis, 29 (41%) patients were hospitalized and 12 (17%) died. Each additional comorbidity was associated with 45% lower odds of days alive and out of hospital in the month following diagnosis in adjusted models.Conclusions: Patients at a cancer center, particularly those with multiple comorbidities, are at increased risk of poor outcomes from COVID-19. Prolonged viral shedding is frequently observed among cancer patients, and its implications on transmission and treatment strategies warrant further study.

  View details for DOI 10.1093/ofid/ofab193

  View details for PubMedID 34183982

• Efficacy of anti-PD(L)1 therapy for patients (Pts) with advanced urothelial carcinoma (aUC) with primary resistance to platinum-based chemotherapy (PC). Stewart, T. F., Kotha, N. V., Dzimitrowicz, H., Makrakis, D., Khaki, A., Simon, N. I., Nelson, A., Freeman, D., Rose, T. L., Beck, W., Chawla, N., Pal, S. K., Kilari, D., Milowsky, M. I., Apolo, A. B., Grivas, P., Zhang, T., Sonpavde, G. P., McKay, R. R. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e16515

  View details for Web of Science ID 000708120302216

• Outcomes of patients (pts) with advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs): Associations with age, race, sex and smoking history. Makrakis, D., Talukder, R., Carril, L., de Kouchkovsky, I., Park, J. J., Bilen, M., McKay, R. R., Agarwal, N., Zakharia, Y., Devitt, M. E., Pinato, D., Hoimes, C. J., Gartrell, B., Tripathi, A., Bamias, A., Drakaki, A., Murgic, J., Di Lorenzo, G., Grivas, P., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e16526

  View details for Web of Science ID 000708120302226

• Time intervals between US Food and Drug Administration (FDA) and European Medicines Agency (EMA) new cancer therapy approvals. Lythgoe, M., Krell, J., Warner, J., Desai, A., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.1575

  View details for Web of Science ID 000708120600274

• Demographics, outcomes, and risk factors for patients (Pts) with sarcoma and COVID-19: A multi-institutional cohort analysis. Wagner, M. J., Ingham, M., Painter, C., Chugh, R., Trent, J. C., Subbiah, V., Khaki, A., Tachiki, L., Loggers, E., Labaki, C., Mckay, R. R., Griffiths, E. A., Thornton, K., Kasi, A., Hwang, C., Chen, J., Halfdanarson, T., Reuben, D. Y., Park, C., Davis, E. J. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.11523

  View details for Web of Science ID 000708120606060

• Code status and outcomes in patients with cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) registry analysis. Loggers, E., Wulff-Burchfield, E., Subbiah, I., Khaki, A., Egan, P., Farmakiotis, D., Phull, H., Nakasone, E., Labaki, C., Yu, P., Joshi, M., Griffiths, E. A., Wise-Draper, T., Jani, C., Thakkar, A., Puc, M., Hwang, C., Mavromatis, B. H., Shah, D. P., Warner, J. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.12035

  View details for Web of Science ID 000708120606146

• Utilization of Systemic Therapy in Patients With Cancer Near the End of Life in the Pre- Versus Postimmune Checkpoint Inhibitor Eras. JCO oncology practice Khaki, A. R., Chennupati, S., Fedorenko, C., Li, L., Sun, Q., Grivas, P., Ramsey, S. D., Schwartz, S. M., Shankaran, V. 2021: OP2001050

  Abstract

  PURPOSE: Systemic therapy use in the last 30 days of life (DOL) for patients with advanced cancer is a low-value medical practice. We hypothesized that systemic therapy use in the last 30 DOL increased after approval of antiprogrammed cell death protein 1 immune checkpoint inhibitors (ICIs) and has contributed to increased health care utilization and spending.METHODS: We investigated the change in prevalence of any systemic therapy use in the last 30 DOL among patients with advanced solid tumors in the 4 years before and after antiprogrammed cell death protein 1 ICI approval in 2014. We used cases from the Western Washington Cancer Surveillance System linked to commercial and Medicare insurance. We calculated the difference in prevalence between the pre- and post-ICI periods. We also calculated the annual prevalence of any systemic therapy and ICI use in the last 30 DOL and measured health care utilization (emergency department visits and hospitalizations) and costs during the last 30 DOL.RESULTS: Eight thousand eight hundred seventy-one patients (median age 73 years) were included; 34% and 66% in the pre-and post-ICI period, respectively. Systemic therapy use in the last 30 DOL was lower in the post-ICI versus pre-ICI period (12.4% v 14.4%; difference -2.0% [95% CI, -3.5 to -0.5]). The annual prevalence of systemic therapy use in the last 30 DOL also declined, although ICI use rose. Patients treated with ICIs in last 30 DOL had more emergency department visits, hospitalizations, and higher costs.CONCLUSION: Systemic therapy use in the last 30 DOL was lower in the period after ICI approval. However, ICI use rose over time and had higher utilization and costs in the last 30 DOL. Systemic therapy use in the last 30 DOL warrants monitoring, especially as more ICI indications are approved.

  View details for DOI 10.1200/OP.20.01050

  View details for PubMedID 34010026

• Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors. Scientific reports Michailidou, D., Khaki, A. R., Morelli, M. P., Diamantopoulos, L., Singh, N., Grivas, P. 2021; 11 (1): 9029

  Abstract

  Patients with cancer treated with immune checkpoint inhibitors (ICIs) develop immune related adverse events (irAEs), however biomarkers are lacking. We hypothesized that clinicopathologic and laboratory factors would be associated with irAE risk and overall survival (OS) in this population. In a retrospective study of patients treated with ICIs we collected clinicopathologic, laboratory, irAEs and outcomes data. The association between baseline blood biomarkers, clinicopathologic features and irAEs was assessed by logistic regression adjusting for age, sex, smoking, cancer type, performance status, concomitant other systemic therapy, history of autoimmune disease (AD), chronic infection and pre-existing systemic steroid use (regardless of dose). Optimal cutoff values of biomarkers were identified by recursive partitioning analysis. 470 patients were identified; 156 (33%) developed irAEs, which were associated with baseline absolute lymphocyte count>2.6k/ul (adjusted [a]OR: 4.30), absolute monocyte count>0.29k/ul(aOR: 2.34) and platelet count>145k/ul (aOR: 2.23), neutrophil to lymphocyte ratio (NLR)≤5.3 (aOR: 2.07) and monocyte to lymphocyte ratio (MLR)≤0.73 (aOR: 2.96), as well as platelet to lymphocyte ratio≤534 (aOR: 5.05). Patients with pre-existing AD (aOR: 2.57), family history of AD (aOR: 5.98), and ICI combination (aOR: 2.00) had higher odds of irAEs. Baseline NLR≤5.3 (aHR: 0.68), MLR≤0.73 (aHR: 0.43), PLT>145 (aHR: 0.48) and PLR≤534 (aHR: 0.48) were associated with longer OS. irAEs were associated with autoimmune history, ICI combination and baseline laboratory measurements. Lower NLR, MLRand PLR may have favorable prognostic value. Our hypothesis-generating findings require validation in larger prospective studies.

  View details for DOI 10.1038/s41598-021-88307-3

  View details for PubMedID 33907229

• Cost-effectiveness analysis of neoadjuvant immune checkpoint inhibition vs. cisplatin-based chemotherapy in muscle invasive bladder cancer. Urologic oncology Khaki, A. R., Shan, Y., Nelson, R. E., Kaul, S., Gore, J. L., Grivas, P., Williams, S. B. 2021

  Abstract

  BACKGROUND: Multiple single-arm clinical trials showed promising pathologic complete response rates with neoadjuvant immune checkpoint inhibitors (ICIs) in muscle-invasive bladder cancer. We conducted a cost-effectiveness analysis comparing neoadjuvant ICIs with cisplatin-based chemotherapy (CBC).METHODS: We applied a decision analytic simulation model with a health care payer perspective to compare neoadjuvant ICIs vs. CBC. For the primary analysis we compared pembrolizumab with ddMVAC. We performed a secondary analysis with gemcitabine/cisplatin as CBC and exploratory analyses with atezolizumab or nivolumab/ipilimumab as ICI. We input pathologic complete response rates from trials or meta-analysis and costs from average sales price. Outcomes of interest included costs, 2-year recurrence-free survival (RFS), and incremental cost-effectiveness ratio (ICER) of cost per 2-year RFS. A threshold analysis estimated a price reduction for ICI to be cost-effective and one-way and probabilistic sensitivity analyses were performed.RESULTS: The incremental cost of pembrolizumab compared with ddMVAC was $8,041 resulting in an incremental improvement of 1.5% in 2-year RFS for an ICER of $522,143 per 2-year RFS. A 21% reduction in cost of pembrolizumab would render it more cost-effective with an ICER of $100,000 per 2-year RFS. GC required an 89% pembrolizumab cost reduction to achieve an ICER of $100,000 per 2-year RFS. Atezolizumab appeared to be more cost-effective than ddMVAC.CONCLUSIONS: ICIs were not cost-effective as neoadjuvant therapies, except when atezolizumab was compared with ddMVAC. Randomized clinical trials, larger sample sizes and longer follow-up are required to better understand the value of ICIs as neoadjuvant treatments.

  View details for DOI 10.1016/j.urolonc.2021.03.004

  View details for PubMedID 33766465

• Early Bone Metastases are Associated with Worse Outcomes in Metastatic Urothelial Carcinoma. Bladder cancer (Amsterdam, Netherlands) Nelson, A. A., Cronk, R. J., Lemke, E. A., Szabo, A., Khaki, A. R., Diamantopoulos, L. N., Grivas, P., Nezami, B. G., MacLennan, G. T., Zhang, T., Hoimes, C. J. 2021; 7 (1): 33-42

  Abstract

  Outcomes of patients with metastatic urothelial carcinoma (mUC) with early bone metastases (eBM) vs no early bone metastases (nBM) have not thoroughly been described in the age of immuno-oncology.To compare survival and other clinical outcomes in patients with eBM and nBM.We used a multi-institutional database of patients with mUC treated with systemic therapy. Demographic, metastatic site, treatment patterns, and clinical outcomes were recorded. Wilcoxon rank-sum, chi-square tests were performed. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed.We identified 270 pts, 67% men, mean age 69±11 years. At metastatic diagnosis, 27% had≥1 eBM and were more likely to have de novo vs. recurrent metastases (42% vs 19%, p < 0.001). Patients with eBM had shorter overall survival (OS) vs. those with nBM, (6.1 vs 13.7 months, p < 0.0001). On multivariable analysis, eBM independently associated with higher risk of death, HR = 2.52 (95% CI: 1.75-3.63, p < 0.0001). OS was shorter for patients with eBM who received initial immune checkpoint inhibitor vs platinum-based chemotherapy, (1.6 vs 9.1 months, p = 0.02). Patients with eBM received higher opioid analgesic doses compared to patients with nBM and received quantitatively more palliative radiation.Patients with mUC and eBM have poorer outcomes, may benefit less from anti-PD-1/PD-L1 therapy and represent an unmet need for novel therapeutic interventions. Dedicated clinical trials, biomarker validation to assist in patient selection, as well as consensus on reporting of non-measurable disease are required.

  View details for DOI 10.3233/BLC-200377

  View details for PubMedID 38993215

  View details for PubMedCentralID PMC11181800

• Perioperative Immunotherapy in Muscle-invasive Bladder Cancer. European urology oncology Tripathi, A., Khaki, A. R., Grivas, P. 2021

  Abstract

  Immune checkpoint inhibitors (ICIs) have already been approved for the treatment of metastatic urothelial carcinoma and are now being investigated for perioperative treatment of muscle-invasive bladder cancer (MIBC). Ongoing trials are assessing ICIs as monotherapy and in combination with other treatments. Early data are promising, and long-term survival data are awaited to confirm the potential of ICIs in MIBC.

  View details for DOI 10.1016/j.euo.2021.01.004

  View details for PubMedID 33642222

• Association between sites of metastases (mets) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC). Makrakis, D., Diamantopoulos, L., Koshkin, V. S., Alva, A., Bilen, M., Stewart, T., Santos, V., Jain, J., Morales-Barrera, R., Devitt, M. E., Carril-Ajuria, L., Nelson, A., Sankin, A., Zakopoulou, R., Pinato, D., Frobe, A., Joshi, M., Sonpavde, G., Grivas, P., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.445

  View details for Web of Science ID 000636801500447

• Efficacy of enfortumab vedotin in advanced urothelial cancer: Retrospective analysis of the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) Study. Koshkin, V. S., Sun Yilun, Freeman, D., Osterman, C. K., Su, C., Natesan, D., Khaki, A., Makrakis, D., Jain, J., Olsen, A., Basu, A., Barata, P. C., Zakharia, Y., Bilen, M., Emamekhoo, H., Davis, N. B., Milowsky, M., Kilari, D., Sonpavde, G., Alva, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.443

  View details for Web of Science ID 000636801500445

• Immune checkpoint inhibitors (ICI) in advanced upper tract and lower tract urothelial carcinoma (UC): A comparison of outcomes. Esagian, S. M., Khaki, A., Carril-Ajuria, L., Park, J. J., Bilen, M., Stewart, T., Santos, V., Jain, J., Morales-Barrera, R., Devitt, M., Hoimes, C. J., Shreck, E., Tripathi, A., Zakopoulou, R., Rodriguez-Vida, A., Drakaki, A., Kumar, V., Msaouel, P., Koshkin, V. S., Petros, G. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.406

  View details for Web of Science ID 000636801500409

• Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT). Tucker, M. D., Schmidt, A., Hsu, C., Shyr, Y., Armstrong, A. J., Bakouny, Z., Chapman, C., Dawsey, S., Gartrell, B., Halabi, S., Joshi, M., Khaki, A., Menon, H., Puc, M., Sharifi, N., Shaya, J., Wulff-Burchfield, E., Zhang, T., Gupta, S., McKay, R. R., CCC19 Prostate Canc Working Grp LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.39

  View details for Web of Science ID 000636801500090

• Racial diversity and reporting in FDA registration trials for genitourinary (GU) cancers from 2006-20. Lythgoe, M., Julve, M., Krell, J., Savage, P., Grivas, P., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.22

  View details for Web of Science ID 000636801500073

• Association between prior radical surgery (RS) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC). Makrakis, D., Castellano, D., de Kouchkov, I., Park, J. J., Bilen, M., Agarwal, N., Zakharia, Y., Morales-Barrera, R., Devitt, M. E., Nelson, A., Gartrell, B. A., Tripathi, A., Bamias, A., Rodriguez-Vida, A., Liu, S., McKay, R. R., Alonso Buznego, L., Murgic, J., Grivas, P., Khaki, A. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.444

  View details for Web of Science ID 000636801500446

• Cost-effectiveness analysis of neoadjuvant immune checkpoint inhibition (ICI) versus cisplatin-based chemotherapy (CBC) in muscle-invasive bladder cancer (MIBC). Khaki, A., Shan, Y., Nelson, R., Kaul, S., Gore, J. L., Grivas, P., Williams, S. B. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.6_suppl.419

  View details for Web of Science ID 000636801500422

• Patterns and timing of perioperative blood transfusion and association with outcomes after radical cystectomy. Urologic oncology Diamantopoulos, L. N., Sekar, R. R., Holt, S. K., Khaki, A. R., Miller, N. J., Gadzinski, A., Nyame, Y. A., Vakar-Lopez, F., Tretiakova, M. S., Psutka, S. P., Gore, J. L., Lin, D. W., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Schweizer, M. T., Cheng, H. H., Yu, E. Y., True, L. D., Montgomery, R. B., Grivas, P., Wright, J. L. 2021

  Abstract

  BACKGROUND: Perioperative blood transfusion (PBT) has been associated with worse outcomes across tumor types, including bladder cancer. We report our institutional experience with PBT utilization in the setting of radical cystectomy (RC) for patients with bladder cancer, exploring whether timing of PBT receipt influences perioperative and oncologic outcomes.METHODS: Consecutive patients with bladder cancer treated with RC were identified. PBT was defined as red blood cell transfusion during RC or the postoperative admission. Clinicopathologic and peri and/or postoperative parameters were extracted and compared between patients who did and did not receive PBT using Mann Whitney U Test, chi-square, and log-rank test. Overall (OS) and recurrence-free survival (RFS) were estimated with the Kaplan Meier method. Univariate/multivariate logistic and Cox proportional hazards regression were used to identify variables associated with postoperative and oncologic outcomes, respectively.RESULTS: The cohort consisted of 747 patients (77% men; median age 67 years). Median follow-up was 61.5 months (95% CI 55.8-67.2) At least one postoperative complication (90-day morbidity) occurred in 394 (53%) patients. Median OS and RFS were 91.8 months (95% CI: 76.0-107.6) and 66.0 months (95% CI: 48.3-83.7), respectively. On multivariate analysis, intraoperative, but not postoperative, BT was independently associated with shorter OS (HR: 1.74, 95% CI: 1.32-2.29) and RFS (HR: 1.55, 95%CI: 1.20-2.01), after adjusting for relevant clinicopathologic variables. PBT (intra- or post- operative) was significantly associated with prolonged postoperative hospitalization ≥10 days.CONCLUSIONS: Intraoperative BT was associated with inferior OS and RFS, and PBT overall was associated with prolonged hospitalization following RC. Further studies are needed to validate this finding and explore potential causes for this observation.

  View details for DOI 10.1016/j.urolonc.2021.01.009

  View details for PubMedID 33551249

• Characteristics and outcomes of SARS-CoV-2 infection in patients with invasive breast cancer (BC) from the COVID-19 and cancer consortium (CCC19) cohort study Khaki, A., Shah, D. P., Lustberg, M. B., Accordino, M. K., Stover, D. G., Nagaraj, G., Rivera, D. R., Perez, E. A., Tolaney, S. M., Peppercorn, J., Grivas, P., Warner, J. L., Painter, C. A., Lopes, G., Peters, S., Thompson, M. A., Choueiri, T. K., Rini, B. I., Lyman, G. H., Kuderer, N. M., Vinayak, S. AMER ASSOC CANCER RESEARCH. 2021

  View details for Web of Science ID 000618737701094

• Outcomes of Patients with Sarcoma and COVID-19 Infection: A Single Institution Cohort Analysis. Cancer investigation Wagner, M. J., Pollack, S. M., Cranmer, L. D., Thompson, M. J., Maxwell, S. n., Wright, S. n., Khaki, A. R., Madeleine, M. M., Grivas, P. n., Kuderer, N. M., Lyman, G. H., Loggers, E. T. 2021: 1–11

  Abstract

  Outcomes for patients (pts) with sarcoma and COVID-19 are unknown. This is a single institution retrospective study of adults with sarcoma and COVID-19. Ten pts [median age 60 (range 24-69)] were identified. Five were hospitalized; two died from COVID-19 complications; another died from sarcoma. Time between last systemic treatment dose and COVID-19 diagnosis was 6-41 days in pts who died. 5 underwent prior radiation (RT); time between RT and COVID-19 diagnosis was 20-62 days for pts who died. All three pts with WBC differential data (2 died) were lymphopenic. Efforts to capture outcomes for a larger cohort are urgently needed.

  View details for DOI 10.1080/07357907.2021.1903914

  View details for PubMedID 33720792

• Gender Differences in Faculty Rank and Subspecialty Choice among Academic Medical Oncologists. Cancer investigation Graham, L. S., Sokolova, A. O., Khaki, A. R., Wu, Q. V., Davidson, N. E. 2021; 39 (1): 21–24

  Abstract

  Gender parity within academic oncology is important. We hypothesized that gender differences exist in subspecialty choice and academic rank among medical oncologists. We performed a cross-sectional study of adult medical oncologists at the top 15 cancer centers. Gender, rank, subspecialty (breast, thoracic, gastrointestinal, and genitourinary) and board certification year were recorded. 570 medical oncologists were identified (60% men; 40% women). More women practice breast oncology (OR 3.1, p < 0.001), but less practice genitourinary oncology (OR 0.37, p < 0.001). 22% of women were full professors vs 34% of men (OR 0.55, p = 0.001). Gender differences persist in academic adult medical oncology.

  View details for DOI 10.1080/07357907.2020.1846191

  View details for PubMedID 33131319

• Loose Regulatory Standards Portend a New Era of Imprecision Oncology. Cancer investigation Khaki, A. R. 2021: 1–4

  Abstract

  Precision oncology has revolutionized the therapeutic landscape of oncology and is a goal for cancer drug development. However, lenient drug approvals by the United States Food and Drug Administration under the auspices of precision oncology are setting up this therapeutic approach to fail. In this commentary, I review two recent FDA drug approvals (pembrolizumab for tumor mutation burden-high solid tumors and olaparib for castration-resistant prostate cancer with deleterious homologous recombination repair mutations) where the FDA indication is broader than the studied population. I explain how these broad approvals stray from principles of precision oncology and can cause harm to patients.

  View details for DOI 10.1080/07357907.2020.1851705

  View details for PubMedID 33290099

• A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors. European urology oncology Khaki, A. R., Li, A. n., Diamantopoulos, L. N., Miller, N. J., Carril-Ajuria, L. n., Castellano, D. n., De Kouchkovsky, I. n., Koshkin, V. n., Park, J. n., Alva, A. n., Bilen, M. A., Stewart, T. n., Santos, V. n., Agarwal, N. n., Jain, J. n., Zakharia, Y. n., Morales-Barrera, R. n., Devitt, M. n., Nelson, A. n., Hoimes, C. J., Shreck, E. n., Gartrell, B. A., Sankin, A. n., Tripathi, A. n., Zakopoulou, R. n., Bamias, A. n., Rodriguez-Vida, A. n., Drakaki, A. n., Liu, S. n., Kumar, V. n., Lythgoe, M. P., Pinato, D. J., Murgic, J. n., Fröbe, A. n., Joshi, M. n., Isaacsson Velho, P. n., Hahn, N. n., Alonso Buznego, L. n., Duran, I. n., Moses, M. n., Barata, P. n., Galsky, M. D., Sonpavde, G. n., Yu, E. Y., Shankaran, V. n., Lyman, G. H., Grivas, P. n. 2021

  Abstract

  While immune checkpoint inhibitors (ICIs) are approved in the first-line (1L) setting for cisplatin-unfit patients with programmed death-ligand 1 (PD-L1)-high tumors or for platinum (cisplatin/carboplatin)-unfit patients, response rates remain modest and outcomes vary with no clinically useful biomarkers (except for PD-L1).We aimed to develop a prognostic model for overall survival (OS) in patients receiving 1L ICIs for advanced urothelial cancer (aUC) in a multicenter cohort study.Patients treated with 1L ICIs for aUC across 24 institutions and five countries (in the USA and Europe) outside clinical trials were included in this study.We used a stepwise, hypothesis-driven approach using clinician-selected covariates to develop a new risk score for patients receiving ICIs in the 1L setting. Demographics, clinicopathologic data, treatment patterns, and OS were collected uniformly. Univariate Cox regression was performed on 18 covariates hypothesized to be associated with OS based on published data. Variables were retained for multivariate analysis (MVA) if they correlated with OS (p < 0.2) and were included in the final model if p < 0.05 on MVA. Retained covariates were assigned points based on the beta coefficient to create a risk score. Stratified median OS and C-statistic were calculated.Among 984 patients, 357 with a mean age of 71 yr were included in the analysis, 27% were female, 68% had pure UC, and 13% had upper tract UC. Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases were significant prognostic factors on MVA and were included in the risk score. C index for new 1L risk score was 0.68 (95% confidence interval 0.65-0.71). Limitations include retrospective nature and lack of external validation.We developed a new 1L ICI risk score for OS based on data from patients with aUC treated with ICIs in the USA and Europe outside of clinical trials. The score components highlight readily available factors related to tumor biology and treatment response. External validation is being pursued.With multiple new treatments under development and approved for advanced urothelial carcinoma, it can be difficult to identify the best treatment sequence for each patient. The risk score may help inform treatment discussions and estimate outcomes in patients treated with first-line immune checkpoint inhibitors, while it can also impact clinical trial design and endpoints. TAKE  HOME MESSAGE: A new risk score was developed for advanced urothelial carcinoma treated with first-line immune checkpoint inhibitors. The score assigned Eastern Cooperative Oncology Group performance status ≥2, albumin <3.5 g/dl, neutrophil:lymphocyte ratio >5, and liver metastases each one point, with a higher score being associated with worse overall survival.

  View details for DOI 10.1016/j.euo.2020.12.006

  View details for PubMedID 33423945

• Immune checkpoint inhibitors in advanced upper and lower tract urothelial carcinoma: a comparison of outcomes. BJU international Esagian, S. M., Khaki, A. R., Diamantopoulos, L. N., Carril-Ajuria, L. n., Castellano, D. n., De Kouchkovsky, I. n., Park, J. J., Alva, A. n., Bilen, M. A., Stewart, T. F., McKay, R. R., Santos, V. S., Agarwal, N. n., Jain, J. n., Zakharia, Y. n., Morales-Barrera, R. n., Devitt, M. E., Nelson, A. n., Hoimes, C. J., Shreck, E. n., Gartrell, B. A., Sankin, A. n., Tripathi, A. n., Zakopoulou, R. n., Bamias, A. n., Rodriguez-Vida, A. n., Drakaki, A. n., Liu, S. n., Kumar, V. n., Lythgoe, M. P., Pinato, D. J., Murgic, J. n., Fröbe, A. n., Joshi, M. n., Isaacsson Velho, P. n., Hahn, N. n., Alonso Buznego, L. n., Duran, I. n., Moses, M. n., Barata, P. n., Galsky, M. D., Sonpavde, G. n., Yu, E. Y., Msaouel, P. n., Koshkin, V. S., Grivas, P. n. 2021

  Abstract

  To compare clinical outcomes between patients with locally advanced (unresectable) or metastatic urothelial carcinoma (aUC) in the upper and lower urinary tract receiving immune checkpoint inhibitors (ICIs).We performed a retrospective cohort study collecting clinicopathological, treatment, and outcome data for patients with aUC receiving ICIs from 2013 to 2020 across 24 institutions. We compared the objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) between patients with upper and lower tract UC (UTUC, LTUC). Uni- and multivariable logistic and Cox regression were used to assess the effect of UTUC on ORR, OS, and PFS. Subgroup analyses were performed stratified based on histology (pure, mixed) and line of treatment (first line, subsequent line).Out of a total of 746 eligible patients, 707, 717, and 738 were included in the ORR, OS, and PFS analyses, respectively. Our results did not contradict the hypothesis that patients with UTUC and LTUC had similar ORRs (24% vs 28%; adjusted odds ratio [aOR] 0.73, 95% confidence interval [CI] 0.43-1.24), OS (median 9.8 vs 9.6 months; adjusted hazard ratio [aHR] 0.93, 95% CI 0.73-1.19), and PFS (median 4.3 vs 4.1 months; aHR 1.01, 95% CI 0.81-1.27). Patients with mixed-histology UTUC had a significantly lower ORR and shorter PFS vs mixed-histology LTUC (aOR 0.20, 95% CI 0.05-0.91 and aHR 1.66, 95% CI 1.06-2.59), respectively).Overall, patients with UTUC and LTUC receiving ICIs have comparable treatment response and outcomes. Subgroup analyses based on histology showed that those with mixed-histology UTUC had a lower ORR and shorter PFS compared to mixed-histology LTUC. Further studies and evaluation of molecular biomarkers can help refine patient selection for immunotherapy.

  View details for DOI 10.1111/bju.15324

  View details for PubMedID 33556233

• Early Bone Metastases are Associated with Worse Outcomes in Metastatic Urothelial Carcinoma BLADDER CANCER Nelson, A. A., Cronk, R. J., Lemke, E. A., Szabo, A., Khaki, A. R., Diamantopoulos, L. N., Grivas, P., Nezami, B., MacLennan, G. T., Zhang, T., Hoimes, C. J. 2021; 7 (1): 33–42

  View details for DOI 10.3233/BLC-200377

  View details for Web of Science ID 000631422000004

• Utilization of COVID-19 treatments and clinical outcomes among patients with cancer: A COVID-19 and Cancer Consortium (CCC19) cohort study. Cancer discovery Rivera, D. R., Peters, S., Panagiotou, O. A., Shah, D. P., Kuderer, N. M., Hsu, C., Rubinstein, S. M., Lee, B. J., Choueiri, T. K., de Lima Lopes, G., Grivas, P., Painter, C. A., Rini, B. I., Thompson, M. A., Arcobello, J., Bakouny, Z., Doroshow, D. B., Egan, P. C., Farmakiotis, D., Fecher, L. A., Friese, C. R., Galsky, M. D., Goel, S., Gupta, S., Halfdanarson, T. R., Halmos, B., Hawley, J. E., Khaki, A. R., Lemmon, C. A., Mishra, S., Olszewski, A. J., Pennell, N. A., Puc, M. M., Revankar, S. G., Schapira, L., Schmidt, A., Schwartz, G. K., Shah, S. A., Wu, J. T., Xie, Z., Yeh, A. C., Zhu, H., Shyr, Y., Lyman, G. H., Warner, J. L. 2020

  Abstract

  Among 2,186 US adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality, and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. While observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through prospective controlled trials inclusive of this population.

  View details for DOI 10.1158/2159-8290.CD-20-0941

  View details for PubMedID 32699031

• Sarcomatoid urothelial carcinoma: Oncologic outcomes from a tertiary center and SEER-Medicare data. Sekar, R., Diamantopoulos, L., Khaki, A., Vakar-Lopez, F., Tretiakova, M. S., Psutka, S. P., Holt, S. K., Gore, J. L., Schade, G. R., Lin, D. W., Hsieh, A., Lee, J., Yezefski, T., Schweizer, M., Cheng, H. H., Yu, E. Y., True, L. D., Montgomery, R. B., Grivas, P., Wright, J. L. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368306189

• Perioperative blood transfusion and postoperative outcomes in patients undergoing radical cystectomy for bladder cancer. Diamantopoulos, L., Sekar, R., Khaki, A., Miller, N., Gadzinski, A., Psutka, S. P., Gore, J. L., Schade, G. R., Lin, D. W., Tretiakova, M. S., Vakar-Lopez, F., True, L. D., Hsieh, A., Cheng, H. H., Yu, E. Y., Schweizer, M., Yezefski, T., Montgomery, R. B., Grivas, P., Wright, J. L. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368306169

• Emerging clinical phenotype of bone metastatic urothelial cancer (mUC): Association of early osseous metastases (EOM) and outcomes. Nelson, A., Cronk, R., Szabo, A., Lemke, E., Giever, T. A., Burfeind, J. D., Kilari, D., Riese, M., Bylow, K. A., Diamantopoulos, L., Khaki, A., Wright, M., MacLennan, G., Draves, M., Goolamier, G., Rosey, S., Calaway, A., Grivas, P., Ponsky, L., Hoimes, C. J. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368306165

• Plasmacytoid urothelial carcinoma: response to chemotherapy and oncologic outcomes. Bladder cancer (Amsterdam, Netherlands) Diamantopoulos, L. N., Khaki, A. R., Grivas, P., Gore, J. L., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Yu, E. Y., Schweizer, M. T., Cheng, H. H., Psutka, S. P., Lin, D. W., Tretiakova, M. S., Vakar-Lopez, F., Montgomery, R. B., Wright, J. L. 2020; 6 (1): 71-81

  Abstract

  Plasmacytoid urothelial carcinoma is a rare bladder cancer variant with scarce data on outcomes and prognostic factors.We report our institutional experience with this histology to determine response to neoadjuvant chemotherapy, definitive surgery and survival.We conducted a retrospective chart review of consecutive patients with plasmacytoid, as well as conventional urothelial carcinoma (for comparison) seen in our institution (2007 - 2018). Baseline characteristics, clinicopathologic and treatment data were captured. T-test, chi-squared and log-rank test was used for group comparison. Kaplan Meier method was used for estimation of overall survival and Cox regression for identification of prognostic factors.64 patients with plasmacytoid and 418 with conventional urothelial histology were identified; 53% of those with plasmacytoid presented with cT3/4 stage and 67% underwent extirpative surgery. Patients with plasmacytoid histology had higher rates of pT3/4 (65% vs. 28%), nodal disease (37% vs. 16%) and positive surgical margins (23% vs. 5%) compared to urothelial group (p < 0.01), as well as higher incidence of post-operative recurrence (47% vs. 29%, p = 0.05) and lower ypT0N0 rates after neoadjuvant chemotherapy (10% vs. 33%, p = 0.03). Plasmacytoid histology was associated with lower median overall survival compared to conventional urothelial (24 vs. 154 months, p < 0.01).Plasmacytoid urothelial carcinoma frequently presented with advanced stage at diagnosis and extirpative surgery, poor pathologic response to neoadjuvant chemotherapy, and inferior outcomes, when compared to conventional urothelial. Prospective trials evaluating upfront cystectomy versus preoperative chemotherapy and/or novel treatments should be considered.

  View details for DOI 10.3233/blc-190258

  View details for PubMedID 34109262

  View details for PubMedCentralID PMC8186525

• Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet (London, England) Kuderer, N. M., Choueiri, T. K., Shah, D. P., Shyr, Y. n., Rubinstein, S. M., Rivera, D. R., Shete, S. n., Hsu, C. Y., Desai, A. n., de Lima Lopes, G. n., Grivas, P. n., Painter, C. A., Peters, S. n., Thompson, M. A., Bakouny, Z. n., Batist, G. n., Bekaii-Saab, T. n., Bilen, M. A., Bouganim, N. n., Larroya, M. B., Castellano, D. n., Del Prete, S. A., Doroshow, D. B., Egan, P. C., Elkrief, A. n., Farmakiotis, D. n., Flora, D. n., Galsky, M. D., Glover, M. J., Griffiths, E. A., Gulati, A. P., Gupta, S. n., Hafez, N. n., Halfdanarson, T. R., Hawley, J. E., Hsu, E. n., Kasi, A. n., Khaki, A. R., Lemmon, C. A., Lewis, C. n., Logan, B. n., Masters, T. n., McKay, R. R., Mesa, R. A., Morgans, A. K., Mulcahy, M. F., Panagiotou, O. A., Peddi, P. n., Pennell, N. A., Reynolds, K. n., Rosen, L. R., Rosovsky, R. n., Salazar, M. n., Schmidt, A. n., Shah, S. A., Shaya, J. A., Steinharter, J. n., Stockerl-Goldstein, K. E., Subbiah, S. n., Vinh, D. C., Wehbe, F. H., Weissmann, L. B., Wu, J. T., Wulff-Burchfield, E. n., Xie, Z. n., Yeh, A. n., Yu, P. P., Zhou, A. Y., Zubiri, L. n., Mishra, S. n., Lyman, G. H., Rini, B. I., Warner, J. L. 2020

  Abstract

  Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness.In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing.Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57-76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53-2·21), male sex (1·63, 1·07-2·48), smoking status (former smoker vs never smoked: 1·60, 1·03-2·47), number of comorbidities (two vs none: 4·50, 1·33-15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11-7·18), active cancer (progressing vs remission: 5·20, 2·77-9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79-4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07-0·84) or the US-Midwest (0·50, 0·28-0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality.Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments.American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

  View details for DOI 10.1016/S0140-6736(20)31187-9

  View details for PubMedID 32473681

• Plasmacytoid Urothelial Carcinoma: Response to Chemotherapy and Oncologic Outcomes BLADDER CANCER Diamantopoulos, L. N., Khaki, A., Grivas, P., Gore, J. L., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T., Yu, E. Y., Schweizer, M. T., Cheng, H. H., Psutka, S. P., Lin, D. W., Tretiakova, M. S., Vakar-Lopez, F., Montgomery, R. B., Wright, J. L. 2020; 6 (1): 71–81

  View details for DOI 10.3233/BLC-190258

  View details for Web of Science ID 000523301600008

• Impact of performance status on treatment outcomes: A real-world study of advanced urothelial cancer treated with immune checkpoint inhibitors. Cancer Khaki, A. R., Li, A. n., Diamantopoulos, L. N., Bilen, M. A., Santos, V. n., Esther, J. n., Morales-Barrera, R. n., Devitt, M. n., Nelson, A. n., Hoimes, C. J., Shreck, E. n., Assi, H. n., Gartrell, B. A., Sankin, A. n., Rodriguez-Vida, A. n., Lythgoe, M. n., Pinato, D. J., Drakaki, A. n., Joshi, M. n., Isaacsson Velho, P. n., Hahn, N. n., Liu, S. n., Alonso Buznego, L. n., Duran, I. n., Moses, M. n., Jain, J. n., Murgic, J. n., Baratam, P. n., Barata, P. n., Tripathi, A. n., Zakharia, Y. n., Galsky, M. D., Sonpavde, G. n., Yu, E. Y., Shankaran, V. n., Lyman, G. H., Grivas, P. n. 2020; 126 (6): 1208–16

  Abstract

  Immune checkpoint inhibitors (ICIs) represent an appealing treatment for patients with advanced urothelial cancer (aUC) and a poor performance status (PS). However, the benefit of ICIs for patients with a poor PS remains unknown. It was hypothesized that a poor Eastern Cooperative Oncology Group (ECOG) PS (≥2 vs 0-1) would correlate with shorter overall survival (OS) in patients receiving ICIs.In this retrospective cohort study, clinicopathologic, treatment, and outcome data were collected for patients with aUC who were treated with ICIs at 18 institutions (2013-2019). The overall response rate (ORR) and OS were compared for patients with an ECOG PS of 0 to 1 and patients with an ECOG PS ≥ 2 at ICI initiation. The association between a new ICI in the last 30 and 90 days of life (DOL) and death location was also tested.Of the 519 patients treated with ICIs, 395 and 384 were included in OS and ORR analyses, respectively, with 26% and 24% having a PS ≥ 2. OS was higher in those with a PS of 0 to 1 than those with a PS ≥ 2 who were treated in the first line (median, 15.2 vs 7.2 months; hazard ratio [HR], 0.62; P = .01) but not in subsequent lines (median, 9.8 vs 8.2 months; HR, 0.78; P = .27). ORRs were similar for patients with a PS of 0 to 1 and patients with a PS ≥ 2 in both lines. Of the 288 patients who died, 10% and 32% started ICIs in the last 30 and 90 DOL, respectively. ICI initiation in the last 30 DOL was associated with increased odds of death in a hospital (odds ratio, 2.89; P = .04).Despite comparable ORRs, ICIs may not overcome the negative prognostic role of a poor PS, particularly in the first-line setting, and the initiation of ICIs in the last 30 DOL was associated with hospital death location.

  View details for DOI 10.1002/cncr.32645

  View details for PubMedID 31829450

  View details for PubMedCentralID PMC7050422

• Histological Subtypes and Response to PD-1/PD-L1 Blockade in Advanced Urothelial Cancer: A Retrospective Study. The Journal of urology Miller, N. J., Khaki, A. R., Diamantopoulos, L. N., Bilen, M. A., Santos, V. n., Agarwal, N. n., Morales-Barrera, R. n., Devitt, M. n., Nelson, A. n., Hoimes, C. J., Shreck, E. n., Assi, H. n., Gartrell, B. A., Sankin, A. n., Rodriguez-Vida, A. n., Lythgoe, M. n., Pinato, D. J., Drakaki, A. n., Joshi, M. n., Isaacsson Velho, P. n., Hahn, N. n., Liu, S. n., Alonso Buznego, L. n., Duran, I. n., Moses, M. n., Jain, J. n., Murgic, J. n., Barata, P. n., Tripathi, A. n., Zakharia, Y. n., Galsky, M. D., Sonpavde, G. n., Yu, E. Y., Lyman, G. H., Grivas, P. n. 2020; 204 (1): 63–70

  Abstract

  Urinary tract cancer can be pure urothelial carcinoma, pure nonurothelial carcinoma or variant urothelial carcinoma (defined here as mixed urothelial carcinoma). Little is known regarding outcomes for patients with variant urothelial carcinoma receiving immune checkpoint inhibitors. We hypothesized that variant urothelial carcinoma does not compromise immune checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.We performed a retrospective cohort study across 18 institutions. Demographic, clinicopathological, treatment and outcomes data were collected for patients with advanced urothelial carcinoma who received immune checkpoint inhibitors. Patients were divided into pure vs variant urothelial carcinoma subgroups, with variant urothelial carcinoma further divided by type of variant (ie squamous, neuroendocrine etc). We compared overall response rate using univariate and multivariate logistic regression and progression-free survival and overall survival using Kaplan-Meier and univariate and multivariate Cox proportional hazards.Overall 519 patients were identified, with 395, 406 and 403 included in overall response rate, overall survival and progression-free survival analyses, respectively. Overall response rate to immune checkpoint inhibitors between patients with pure vs variant urothelial carcinoma was comparable (28% vs 29%, p=0.90) without significant differences for individual subtypes vs pure urothelial carcinoma. Median overall survival for patients with pure urothelial carcinoma was 11.0 months vs 10.1 months for variant urothelial carcinoma (p=0.60), but only 4.6 months for patients with neuroendocrine features (9 patients, HR 2.75, 95% CI 1.40-5.40 vs pure urothelial carcinoma, p=0.003). Median progression-free survival was 4.1 months for pure vs 5.2 months for variant urothelial carcinoma (p=0.43) and 3.7 months for neuroendocrine features (HR 1.87, 95% CI 0.92-3.79 vs pure urothelial carcinoma, p=0.09).Overall response rate to immune checkpoint inhibitors was comparable across histological types. However, overall survival was worse for patients with tumors containing neuroendocrine features. Variant urothelial carcinoma should not exclude patients from receiving immune checkpoint inhibitors.

  View details for DOI 10.1097/JU.0000000000000761

  View details for PubMedID 31971495

  View details for PubMedCentralID PMC7289665

• Use of Real-World Electronic Health Records to Estimate Risk, Risk Factors, and Disparities for COVID-19 in Patients With Cancer. JAMA oncology Desai, A. n., Khaki, A. R., Kuderer, N. M. 2020

  View details for DOI 10.1001/jamaoncol.2020.5461

  View details for PubMedID 33300955

• Response to Neoadjuvant Chemotherapy and Survival in Micropapillary Urothelial Carcinoma: Data From a Tertiary Referral Center and the Surveillance, Epidemiology, and End Results (SEER) Program. Clinical genitourinary cancer Diamantopoulos, L. N., Holt, S. K., Khaki, A. R., Sekar, R. R., Gadzinski, A. n., Nyame, Y. A., Vakar-Lopez, F. n., Tretiakova, M. S., Psutka, S. P., Gore, J. L., Lin, D. W., Schade, G. R., Hsieh, A. C., Lee, J. K., Yezefski, T. n., Schweizer, M. T., Cheng, H. H., Yu, E. Y., True, L. D., Montgomery, R. B., Grivas, P. n., Wright, J. L. 2020

  Abstract

  Micropapillary urothelial carcinoma (MPC) is a rare urothelial carcinoma variant with conflicting data guiding clinical practice. In this study, we explored oncologic outcomes in relation to neoadjuvant chemotherapy (NAC) in a retrospective cohort of patients with MPC, alongside data from Surveillance, Epidemiology, and End Results (SEER)-Medicare.We retrospectively identified patients with MPC or conventional urothelial carcinoma (CUC) without any variant histology undergoing radical cystectomy (RC) in our institution (2003-2018). SEER-Medicare was also queried to identify patients diagnosed with MPC (2004-2015). Clinicopathologic data and treatment modalities were extracted. Overall survival (OS) was estimated with the Kaplan-Meier method. Mann-Whitney-Wilcoxon and chi-square tests were used for comparative analysis and Cox regression for identifying clinical covariates associated with OS.Our institutional database yielded 46 patients with MPC and 457 with CUC. In SEER-Medicare, 183 patients with MPC were identified, and 63 (34%) underwent RC. In the institutional cohort, patients with MPC had significantly higher incidence of cN+ (17% vs. 8%), pN+ stage (30% vs. 17%), carcinoma-in-situ (43% vs. 25%), and lymphovascular invasion (30% vs. 16%) at RC versus those with CUC (all P < .05). Pathologic complete response (ypT0N0) to NAC was 33% for MPC and 35% for CUC (P = .899). Median OS was lower for institutional MPC versus CUC in univariate analysis (43.6 vs. 105.3 months, P = .006); however, MPC was not independently associated with OS in the multivariate model. Median OS was 25 months in the SEER MPC cohort for patients undergoing RC, while NAC was not associated with improved OS in that group.Pathologic response to NAC was not significantly different between MPC and CUC, while MPC histology was not an independent predictor of OS. Further studies are needed to better understand biological mechanisms behind its aggressive features as well as the role of NAC in this histology variant.

  View details for DOI 10.1016/j.clgc.2020.10.002

  View details for PubMedID 33160889

• Comparison of Health Care Utilization at the End of Life Among Patients With Cancer in Alberta, Canada, Versus Washington State. JCO oncology practice Khaki, A. R., Xu, Y. n., Cheung, W. Y., Li, L. n., Fedorenko, C. n., Grivas, P. n., Ramsey, S. n., Shankaran, V. n. 2020; 16 (12): e1543–e1552

  Abstract

  Aggressive care at the end of life (EOL) can lead to unnecessary suffering and health care costs for patients with cancer. Despite geographic proximity and cultural similarities, we hypothesize that EOL care is more intense in the United States multipayer system versus the Canadian single-payer system. We compared health care utilization at EOL among patients with cancer in Alberta, Canada, with those in Washington state in the United States.Adult patients with American Joint Committee on Cancer stage II to IV solid tumors who died between 2014 and 2016 in Alberta and between 2015 and 2017 in Washington were identified from regional population-based cancer registries linked to treatment and hospitalization records (Alberta) and health claims from major regional insurance plans (Washington). The proportion of patients receiving chemotherapy and having multiple emergency department (ED) visits, or intensive care unit (ICU) admissions in the last 30, 60, and 90 days of life (DOL) in Alberta and Washington were determined and compared using two-sample z-test and multivariable logistic regression (α = .006 after Bonferroni correction).Of patients, 11,177 in Alberta and 12,807 in Washington were included. Patients were similar in age (median, 71 v 72 year), with more patients in Washington with no comorbidities. More patients in Washington were treated with chemotherapy (12.6% v 6.6%; adjusted OR [aOR], 2.74), had multiple ED visits (16.2% v 12.1%; aOR, 1.40), and ICU admissions (23.7% v 3.9%; aOR, 14.27) in the last 30 DOL. Utilization was also higher in Washington in the last 60 and 90 DOL and among those with stage IV disease and those age 65 years and older.Utilization of chemotherapy, ED visits, and ICU admissions near EOL was higher in Washington versus Alberta. Future studies to characterize drivers of aggressive EOL care may help improve cancer care for patients in the United States and Canada.

  View details for DOI 10.1200/OP.20.00217

  View details for PubMedID 32804586

  View details for PubMedCentralID PMC7735039

• Immunotherapy-based combination strategies for advanced urothelial cancer: A long quest. Cancer Khaki, A. R., Agarwal, N. n., Pal, S. K., Grivas, P. n. 2020; 126 (20): 4446–50

  Abstract

  Despite longer survival with immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1), metastatic urothelial carcinoma remains lethal. There is an unmet need to further improve the efficacy of these agents. In their phase 2 trial, Zhang et al. evaluated the combination of pembrolizumab (a PD-1 inhibitor) plus acalabrutinib (a novel agent inhibiting an enzyme considered relevant to immunotherapy resistance) based on strong rationale but did not demonstrate clinical benefit compared with pembrolizumab alone. Future trials that examine such promising rational combinations may be able to evaluate selected patients based on validated biomarkers to optimize benefit in an endless pursuit of personalizing therapies.

  View details for DOI 10.1002/cncr.33068

  View details for PubMedID 32757318

• Untangling the Multidisciplinary Care Web: Streamlining Care Through an Immune-Related Adverse Events (IRAE) Tumor Board. Targeted oncology Kennedy, L. C., Wong, K. M., Kamat, N. V., Khaki, A. R., Bhatia, S. n., Thompson, J. A., Grivas, P. n. 2020; 15 (4): 541–48

  Abstract

  Immune-related adverse events (IRAEs) are becoming increasingly common as the use of immune checkpoint inhibitors expands into more tumor types and treatment settings. Although the majority of IRAEs are mild and can be managed in the outpatient setting by the medical oncologist, severe IRAEs can be life threatening and often require complex care coordination among multiple providers. These providers include a variety of non-oncology specialists who have interest and expertise in managing IRAEs. Multiple systems-based solutions have been proposed in the literature, but these need to be tailored to the needs and resources of each practice setting. In this article, we highlight the challenges of IRAE care by presenting an illustrative case from our institution. We then describe the format and structure of the IRAE Tumor Board established at the University of Washington/Seattle Cancer Care Alliance/Fred Hutchinson Cancer Research Center. Finally, we discuss how this tumor board attempts to address clinical issues related to complex IRAE presentations and provide IRAE education.

  View details for DOI 10.1007/s11523-020-00739-5

  View details for PubMedID 32710246

  View details for PubMedCentralID PMC7489785

• Central Nervous System Metastasis in Patients With Urothelial Carcinoma: Institutional Experience and a Comprehensive Review of the Literature. Clinical genitourinary cancer Diamantopoulos, L. N., Khaki, A. R., Sonpavde, G. P., Venur, V. A., Yu, E. Y., Wright, J. L., Grivas, P. n. 2020; 18 (3): e266–e276

  Abstract

  Central nervous system (CNS) metastasis in patients with urothelial carcinoma (UC) is uncommon and poorly understood. We aimed to explore the clinical behavior and outcomes of this unique patient population.We performed a retrospective analysis of patients with UC and CNS metastasis, treated in our institution (2006-2018), along with an exploratory patient-point meta-analysis of a similar patient population derived from a comprehensive literature review. Data regarding diagnosis, management, and outcomes were extracted. Overall survival, time to CNS metastasis (TTCM), and residual survival (RS) from CNS involvement to death were calculated (Kaplan-Meier method). Cox regression was used for testing key clinicopathologic associations.We identified 20 "institutional" and 154 "literature" patients with adequate data granularity for analysis. Median TTCM was 17.7 (institutional cohort) and 10 (literature cohort) months. Most patients who developed CNS metastases had previous non-CNS metastasis (15/20 [75%] and 103/154 [67%], respectively). CNS lesions without previous history of metastasis were identified in 5/20 (25%) and 33/154 (21%) cases and those patients had a shorter TTCM. CNS lesions in the absence of known UC history were also documented in 18/154 (12%) literature cases. Multifocal CNS disease was associated with shorter RS in both cohorts in univariate, but not multivariate, analysis.We observed a variability in disease presentation and course, with a subset of patients showing an early predilection for CNS insult, potentially reflecting a diverse underlying biology. Genomic profiling studies, elucidating the molecular landscape, and driving future treatments should be considered in this setting.

  View details for DOI 10.1016/j.clgc.2019.11.008

  View details for PubMedID 32178979

  View details for PubMedCentralID PMC7272305

• Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis LANCET GLOBAL HEALTH Di Tanna, G., Khaki, A., Theron, G., McCarthy, K., Cox, H., Mupfumi, L., Trajman, A., Zijenah, L., Mason, P., Durovni, R., Bara, W., Hoelscher, M., Clowes, P., Mangu, C., Chanda, D., Pym, A., Mwaba, P., Cobelens, F., Nicol, M. P., Dheda, K., Churchyard, G., Fielding, K., Metcalfe, J. Z., Bandason, T. 2019; 7 (2): E191–E199

  Abstract

  Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF.We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394.Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68-1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65-1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60-0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I2<20% for the primary outcome).Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact.US National Institutes of Health.

  View details for DOI 10.1016/S2214-109X(18)30458-3

  View details for Web of Science ID 000456441300022

  View details for PubMedID 30683238

  View details for PubMedCentralID PMC6366854

• Clinical Risk During the Evaluation of Genomic Risk for Hormone-Sensitive Breast Cancer: Ignoring Valuable Data. Journal of the National Comprehensive Cancer Network : JNCCN Khaki, A. R., Gadi, V. K., Prasad, V. n. 2019; 17 (12): 1456–58

  View details for DOI 10.6004/jnccn.2019.7363

  View details for PubMedID 31805524

• Association of Renin and Aldosterone With Ethnicity and Blood Pressure: The Multi-Ethnic Study of Atherosclerosis AMERICAN JOURNAL OF HYPERTENSION Rifkin, D. E., Khaki, A. R., Jenny, N. S., McClelland, R. L., Budoff, M., Watson, K., Ix, J. H., Allison, M. A. 2014; 27 (6): 801–10

  Abstract

  Although variations in plasma renin activity (PRA) and aldosterone have been examined in whites and blacks, the association of these hormones with blood pressure in multiethnic populations has not been described.We measured PRA and aldosterone in 1,021 participants in the Multi-Ethnic Study of Atherosclerosis not taking antihypertensives and examined the association between ethnicity and PRA/aldosterone and the association between PRA/aldosterone with systolic blood pressure (SBP).Average age was 62 (SD = 9) years, and 49% of participants were women. Median PRA was 0.51 (interquartile range (IQR) = 0.29-0.87) ng/ml/hour, and median aldosterone was 12.6 (IQR = 9.1-17.1) ng/dl. After age and sex adjustment, compared with whites, blacks had 28% lower PRA and 17.4% lower aldosterone, and Hispanics had 20.1% higher PRA but similar aldosterone levels. After multivariable adjustment, compared with whites, only Hispanic ethnicity independently associated with higher PRA (0.18ng/ml/hour; 95% confidence interval (CI) = 0.06-0.31). Blacks had lower aldosterone (-1.7ng/dl; 95% CI = -3.2 to -0.2) compared with whites. After multivariable adjustment, PRA was associated with lower SBP in whites (-3.2mm Hg; 95% CI = -5.2 to -1.2 per standardized unit PRA), Chinese (-3.5mm Hg; 95% CI = -6.2 to -0.80 per standardized unit), and Hispanics (-2.3mm Hg; 95% CI = -4.1 to -0.6 per standardized unit) but not blacks. Aldosterone was associated with higher SBP only in Hispanics (2.5mm Hg; 95% CI = 0.4-4.5 per SD).Compared with whites, blacks have lower aldosterone and Hispanics have higher PRA. Aldosterone had significant associations with higher SBP in Hispanics compared with other groups, a finding that may suggest a different mechanism of hypertension.

  View details for DOI 10.1093/ajh/hpt276

  View details for Web of Science ID 000336527400006

  View details for PubMedID 24436325

  View details for PubMedCentralID PMC4017931