Dr. Vitzthum is a radiation oncologist and clinical assistant professor of radiation oncology at Stanford University School of Medicine. He specializes in the treatment of gastrointestinal and thoracic cancers. He also has a clinical and research interest in oligometastatic cancer, which is cancer that has metastasized to a limited number of sites beyond its origin.
He began his career in biomedical engineering and is passionate about integrating new technologies to advance patient care.
Dr. Vitzthum delivers treatment personalized to each patient’s condition, overall health, and goals. He believes clear communication between doctor and patient is vital to help patients make informed care decisions.
His research interests include clinical trial development, survivorship, and predictive modeling to personalize patient treatment. He is especially interested in pursuing research that can address unmet clinical needs.
Dr. Vitzthum has received research support through the Radiological Society of North America, the American Society of Clinical Oncology’s Conquer Cancer Foundation, and the UCSD Altman Clinical and Translational Research Institute. His work has appeared in International Journal of Radiation Oncology Biology Physics, Annals of Oncology, JAMA Oncology, Clinical Cancer Research, and other publications.
He is a member of the American College of Radiation Oncology, American Society for Radiation Oncology, American Society of Clinical Oncology, and Radiologic Society of North America.
Dr. Vitzthum is also interested in improving access to high-quality cancer care for under-served populations domestically and abroad.
- Radiation Oncology
- Gastrointestinal Cancers
- Lung Cancers
- Stereotactic Body Radiotherapy
Honors & Awards
Roentgen Research Award, RSNA (2020)
Endowed Young Investigator Award, American Society of Clinical Oncology (2019)
Resident Research Grant, RSNA (2019)
Alpha Omega Alpha Medical Honor Society, University of Minnesota (2014)
Dean's Merit Scholarship, University of Minnesota Medical School (2010-2015)
Medical Education: University of Minnesota School of Medicine (2015) MN
Board Certification: American Board of Radiology, Radiation Oncology (2021)
Residency: UCSD Radiation Oncology Residency Program (2020) CA
Internship: Hennepin County Medical Center Transitional Year Residency (2016) MN
MR Guided Focused Ultrasound vs Radiotherapy for Palliative Pain Tx in Bone Metastases
This is a prospective, single-center, randomized study directly comparing outcomes after MR guided high intensity focused ultrasound (MR HIFU) or external beam radiation therapy (EBRT) treatment of painful bone metastases.
Stanford is currently not accepting patients for this trial. For more information, please contact Brittney Williams, 650-497-8588.
Early Outcomes and Toxicity with Concurrent Chemotherapy and Hypofractionated Radiation Therapy in Patients with Non-Small Cell Lung Cancer
LIPPINCOTT WILLIAMS & WILKINS. 2022: S44
View details for Web of Science ID 000847787800093
Dosimetric Predictors of Local Control after Stereotactic Ablative Radiotherapy (SABR) for Lung Tumors: A Secondary Analysis of a Phase II Prospective Trial of Individualized SABR (iSABR)
LIPPINCOTT WILLIAMS & WILKINS. 2022: S16
View details for Web of Science ID 000847787800034
Rectosigmoid Cancer-Rectal Cancer or Sigmoid Cancer?
American journal of clinical oncology
OBJECTIVES: We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR).MATERIALS AND METHODS: We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using chi2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis.RESULTS: One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage (P<0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6%, P=0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF (P=0.05).CONCLUSIONS: Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.
View details for DOI 10.1097/COC.0000000000000931
View details for PubMedID 35848736
Isolated Nodal Recurrence After Definitive Stereotactic Ablative Radiotherapy for Non-Small Cell Lung Cancer.
Practical radiation oncology
Stereotactic ablative radiotherapy (SABR) results in high rates of primary tumor control for early-stage non-small cell lung cancer (NSCLC). For patients with isolated hilar or mediastinal nodal recurrences (INR) after SABR, the optimal salvage treatment strategy is unclear. The purpose of this study is to determine the rate of INR after SABR for early-stage NSCLC and to describe patterns of care and treatment outcomes after salvage therapy.This retrospective cohort study included 342 patients with Stage T1-3N0M0 NSCLC treated with definitive SABR from 2003-2018. We evaluated the incidence of INR and baseline factors between patients who did and did not experience INR. Among patients who experienced INR, we described treatment patterns and outcomes including overall (OS) and progression free survival (PFS) from the time of nodal failure using the Kaplan-Meier method.With a median follow-up of 3.3 years, the 3-year INR rate was 10.6% (6.6% -13.4%). Among the 34 patients experiencing INR, the 3-year rates of OS and PFS were 39.3% (24.4 - 63.3%) and 26.7% (14.1 - 50.3%), respectively. The 34 patients with INR were treated with RT alone (26.7 %), concurrent chemoradiotherapy (CRT) (43.3 %), chemotherapy alone (13.3%), or observation (16.7%). CRT had the best survival outcomes with a 3-year OS and PFS of 81.5% (61.1 - 100.0%) and 63.9% (40.7 - 100.0%), respectively. Of the patients treated with salvage RT or CRT, 14.3% experienced grade 3 toxicity with no patients having grade 4+ toxicity.INR occurred in approximately 10% of patients treated with SABR for early-stage NSCLC. The highest rates of OS an PFS among patients with INR were observed in those treated with salvage chemoradiotherapy.
View details for DOI 10.1016/j.prro.2022.06.013
View details for PubMedID 35858658
Neoadjuvant therapy in the post-German rectal trial era: making sense in the absence of consensus.
Practical radiation oncology
Trimodality therapy per the German Rectal trial has led to excellent locoregional outcomes for locally advanced rectal cancer. Recent efforts have shifted towards improving distant control and health-related quality of life in this disease. To this end, total neoadjuvant therapy has become an increasingly used approach where most, if not all, chemotherapy is delivered prior to surgery to improve compliance and to address micrometastases early. To avoid surgical morbidity, a "watch-and-wait" approach, in which total mesorectal excision is deferred, has also been studied for patients who achieve a clinical complete response after chemoradiation. These two concurrent treatment trends have raised many points of uncertainty in what used to be a relatively straightforward neoadjuvant treatment paradigm. We discuss here our approach to neoadjuvant therapy for locally advanced rectal cancer, based on the data we currently have and through shared decision-making with patients to help them select the treatment that best aligns with their preferences and values.
View details for DOI 10.1016/j.prro.2022.06.010
View details for PubMedID 35803535
Evaluating High-Dimensional Machine Learning Models to Predict Hospital Mortality Among Older Patients With Cancer.
JCO clinical cancer informatics
2022; 6: e2100186
Older hospitalized cancer patients face high risks of hospital mortality. Improved risk stratification could help identify high-risk patients who may benefit from future interventions, although we lack validated tools to predict in-hospital mortality for patients with cancer. We evaluated the ability of a high-dimensional machine learning prediction model to predict inpatient mortality and compared the performance of this model to existing prediction indices.We identified patients with cancer older than 75 years from the National Emergency Department Sample between 2016 and 2018. We constructed a high-dimensional predictive model called Cancer Frailty Assessment Tool (cFAST), which used an extreme gradient boosting algorithm to predict in-hospital mortality. cFAST model inputs included patient demographic, hospital variables, and diagnosis codes. Model performance was assessed with an area under the curve (AUC) from receiver operating characteristic curves, with an AUC of 1.0 indicating perfect prediction. We compared model performance to existing indices including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score.We identified 2,723,330 weighted emergency department visits among older patients with cancer, of whom 144,653 (5.3%) died in the hospital. Our cFAST model included 240 features and demonstrated an AUC of 0.92. Comparator models including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score achieved AUCs of 0.58, 0.62, and 0.71, respectively. Predictive features of the cFAST model included acute conditions (respiratory failure and shock), chronic conditions (lipidemia and hypertension), patient demographics (age and sex), and cancer and treatment characteristics (metastasis and palliative care).High-dimensional machine learning models enabled accurate prediction of in-hospital mortality among older patients with cancer, outperforming existing prediction indices. These models show promise in identifying patients at risk of severe adverse outcomes, although additional validation and research studying clinical implementation of these tools is needed.
View details for DOI 10.1200/CCI.21.00186
View details for PubMedID 35671416
Characterization of Metastatic Non-Small Cell Lung Cancer and Oligometastatic Incidence in an Era of Changing Treatment Paradigms.
International journal of radiation oncology, biology, physics
Due to the limitations of current staging systems and evolving definitions, there are limited data on oligometastatic non-small cell lung cancer (NSCLC) epidemiology. The purpose of this study is to evaluate metastatic disease burden and the incidence of oligometastatic disease using recent clinical trial edibility criteria.A cohort of patients with metastatic NSCLC, diagnosed from 2016 to 2019, were randomly sampled from a curated tumor registry. Definitions for oligometastatic disease were obtained from relevant clinical trials. The Stanford Cancer Institute Research Database (SCIRDB) was used to identify baseline patient factors, systemic and local therapy, extent and location of metastatic lesions, and survival outcomes.Among 120 patients presenting with metastatic NSCLC, the majority had de novo metastatic disease (75%) with a median of 4 metastatic lesions involving 3 organ systems. 37.5% would have been eligible for at least one oligometastatic trial with 28.3% meeting criteria for MDACC, 20.0% for NRG-LU002, 6.7% for SINDAS and 16.7% for SABR-COMET. By adding malignant pleural effusions (MPE) and early progression as exclusionary criteria, only 54.1% of patients with ≤3 synchronous metastases were eligible for consideration of local therapy. Early progression on systemic therapy was associated with worse survival (10.0 vs. 42.4 months, p < 0.001), whereas presence of MPE was not. Of those tumors identified as oligometastatic, 44.4% received local therapy and 28.9% underwent ablative therapy to all sites. There was a trend towards greater overall survival (44.4 vs 24.9 months, p=0.055) and progression free survival (8.0 vs. 5.4 months, p=0.06) in patients meeting eligibility for at least one oligometastatic trial.Around 48% of patients with metastatic NSCLC had ≤3 metastases at presentation and 28% met clinical trial criteria for oligometastatic disease. Future research is needed to better define the oligometastatic state and identify patients most likely to benefit from local therapy.
View details for DOI 10.1016/j.ijrobp.2022.04.050
View details for PubMedID 35654305
Validation of NRG Oncology's prognostic nomograms for oropharyngeal cancer in the Veterans Affairs database.
BACKGROUND: To test whether nomograms developed by NRG Oncology for oropharyngeal squamous cell carcinoma (OPSCC) patients could be validated in an independent population-based sample.METHODS: The authors tested nomograms for estimating progression-free survival (PFS) and overall survival (OS) in patients from the Veterans Health Administration with previously untreated locoregionally advanced OPSCC, diagnosed between 2008 and 2017, managed with definitive radiotherapy with or without adjuvant systemic therapy. Covariates were age, performance status, p16 status, T/N category, smoking history, education history, weight loss, marital status, and anemia. We used multiple imputation to handle missing data and performed sensitivity analyses on complete cases. Validation was assessed via Cox proportional hazards models, log-rank tests, and c-indexes.RESULTS: A total of 4007 patients met inclusion criteria (658 patients had complete data). Median follow-up time was 3.20 years, with 967 progression events and 471 noncancer deaths. Each risk score was associated with poorer outcomes per unit increase (PFS score, hazard ratio [HR], 1.42 [1.37-1.47]; OS score, HR, 1.40 [1.34-1.45]). By risk score quartile, 2-year PFS estimates were 89.2%, 78.5%, 65.8%, and 48.3%; OS estimates were 92.6%, 83.6%, 73.9%, and 51.3%, respectively (P < .01 for all comparisons). C-indices for models of PFS and OS were 0.65 and 0.67, for all patients, respectively (0.69 and 0.73 for complete cases). The nomograms slightly overestimated PFS and OS in the overall cohort but exhibited high agreement in complete cases.CONCLUSIONS: NRG nomograms were effective for predicting PFS and OS for patients with OPSCC, supporting their broader applicability in the OPSCC population undergoing definitive radiotherapy.
View details for DOI 10.1002/cncr.34141
View details for PubMedID 35194791
Jumping to conclusions: Misdiagnosing radiation induced sarcoma as recurrent breast cancer.
2022; 84: 110-112
Radiation therapy (RT) induced chondrosarcoma is a rare but important potential complication seen in cancer patients treated with radiation. Although uncommon, these patients tend to have a poor prognosis, so early detection and complete resection are the crucial steps towards survival. We present the case of an 81-year-old breast cancer patient who was treated with RT to the left chest wall. Eight years later, she presented with a growing left chest wall mass, initially thought to represent local breast cancer recurrence. Imaging demonstrated a well-defined mass arising from the left pectoralis major muscle. The mass was excised, and pathology demonstrated chondrosarcoma. We discuss the clinical and radiologic aspects of RT-induced sarcomas with attention to the very rare chondrosarcoma. The aim of this report is to provide a succinct but relevant summary of the diagnostic considerations for RT-induced sarcoma supported by information about epidemiology, clinical diagnostic criteria, and radiation biology to expedite patient workup and ultimately improve patient outcomes.
View details for DOI 10.1016/j.clinimag.2022.01.014
View details for PubMedID 35176572
Bias Reduction through Analysis of Competing Events (BRACE) Correction to Address Cancer Treatment Selection Bias in Observational Data.
Clinical cancer research : an official journal of the American Association for Cancer Research
BACKGROUND: Cancer treatments can paradoxically appear to reduce the risk of non-cancer mortality in observational studies, due to residual confounding. Here we introduce a method, Bias Reduction through Analysis of Competing Events (BRACE), to reduce bias in the presence of residual confounding.METHODS: BRACE is a novel method for adjusting for bias from residual confounding in proportional hazards models. Using standard simulation methods, we compared BRACE vs. Cox proportional hazards regression in the presence of an unmeasured confounder. We examined estimator distributions, bias, mean squared error (MSE), and coverage probability. We then estimated treatment effects of high vs. low intensity treatments in 36,630 prostate cancer, 4,069 lung cancer, and 7,117 head/neck cancer patients, using the Veterans Affairs database. We analyzed treatment effects on cancer-specific mortality (CSM), non-cancer mortality (NCM), and overall survival (OS), using conventional multivariable Cox and propensity score (adjusted using inverse probability weighting) models, vs. BRACE-adjusted estimates.RESULTS: In simulations with residual confounding, BRACE uniformly reduced both bias and MSE. In the absence of bias, BRACE introduced bias toward the null, albeit with lower MSE. BRACE markedly improved coverage probability, but with a tendency toward overcorrection for effective but non-toxic treatments. For each clinical cohort, more intensive treatments were associated with significantly reduced hazards for CSM, NCM, and OS. BRACE attenuated OS estimates, yielding results more consistent with findings from randomized trials and meta-analyses.CONCLUSIONS: BRACE reduces bias and MSE when residual confounding is present and represents a novel approach to improve treatment effect estimation in non-randomized studies.
View details for DOI 10.1158/1078-0432.CCR-21-2468
View details for PubMedID 35140122
- Phase II trial of organ preservation program using short-course radiation and folfoxiri for rectal cancer (SHORT-FOX) LIPPINCOTT WILLIAMS & WILKINS. 2022
Temporal Trends and Predictors of Opioid Use Among Older Patients With Cancer.
American journal of clinical oncology
OBJECTIVES: While opioids represent a cornerstone of cancer pain management, the timing and patterns of opioid use in the cancer population have not been well studied. This study sought to explore longitudinal trends in opioid use among Medicare beneficiaries with nonmetastatic cancer.MATERIALS AND METHODS: Within a cohort of 16,072 Medicare beneficiaries ≥66 years old diagnosed with nonmetastatic cancer between 2007 and 2013, we determined the likelihood of receiving a short-term (0 to 6mo postdiagnosis), intermediate-term (6 to 12mo postdiagnosis), long-term (1 to 2y postdiagnosis), and high-risk (morphine equivalent dose ≥90mg/day) opioid prescription after cancer diagnosis. Multivariable logistic regression models were used to identify patient and cancer risk factors associated with these opioid use endpoints.RESULTS: During the study period, 74.6% of patients received an opioid prescription, while only 2.66% of patients received a high-risk prescription. Factors associated with use varied somewhat between short-term, intermediate-term, and long-term use, though in general, patients at higher risk of receiving an opioid prescription after their cancer diagnosis were younger, had higher stage disease, lived in regions of higher poverty, and had a history of prior opioid use. Prescriptions for high-risk opioids were associated with individuals living in regions with lower poverty.CONCLUSIONS: Temporal trends in opioid use in cancer patients depend on patient, demographic, and tumor characteristics. Overall, understanding these correlations may help physicians better identify patient-specific risks of opioid use and could help better inform future evidence-based, cancer-specific opioid prescription guidelines.
View details for DOI 10.1097/COC.0000000000000888
View details for PubMedID 35019879
Impacts of an Opioid Safety Initiative on United States Veterans Undergoing Cancer Treatment.
Journal of the National Cancer Institute
There is limited research on how the opioid epidemic and consequent risk reduction policies have impacted pain management among cancer patients. The purpose of this study is to analyze how an Opioid Safety Initiative (OSI) implemented at the Veteran's Health Administration (VHA) affected opioid prescribing patterns and opioid-related toxicity.We performed an interrupted time series analysis of 42,064 opioid-naïve patients treated at the VHA for prostate, lung, breast, and colorectal cancer from 2011-2016. Segmented regression was used to evaluate the impact of the OSI on the incidence of any new opioid prescriptions, high-risk prescriptions, persistent use, and pain-related ED visits. We compared the cumulative incidence of adverse opioid events including an opioid related admission or diagnosis of misuse before and after the OSI. All statistical tests were 2-sided.The incidence of new opioid prescriptions was 26.7% (95% CI = 25.0-28.4%) in 2011 and increased to 50.6% (95% CI = 48.3-53.0%) by 2013 prior to OSI implementation (monthly rate of change: +3.3%, 95% CI = 1.3-4.2%, p < .001). After the OSI, there was a decrease in the monthly rate of change for new prescriptions (-3.4%, 95% CI = -3.9 - -2.9%, p < .001). The implementation of the OSI was associated with a decrease in the monthly rate of change of concomitant benzodiazepines and opioid prescriptions (-2.5%, 95% CI = -3.2 - -1.8%, p < .001), no statistically significant change in high-dose opioids (-1.2%, 95% CI = -3.2-0.9%, p = .26), a decrease in persistent opioid use (-5.7%, 95% CI = -6.8 - -4.7%, p < .001), and an increase in pain-related ED visits (+3.0%, 95% CI = 1.0-5.0%, p = .003). The OSI was associated with a decreased incidence of opioid-related admissions (3-year cumulative incidence: 0.9% [95% CI = 0.7-1.0%] vs. 0.5% [95% CI = 0.4-0.6%], p < .001) and no statistically significant change in the incidence of opioid misuse (3-year cumulative incidence: 1.2% [95% CI = 1.0-1.3%] vs. 1.2% [1.1-1.4%], p = .77).The OSI was associated with a relative decline in the rate of new, persistent, and certain high-risk opioid prescribing as well as a slight increase in the rate of pain-related ED visits. Further research on patient-centered outcomes is required to optimize opioid prescribing policies for patients with cancer.
View details for DOI 10.1093/jnci/djac017
View details for PubMedID 35078240
IMRT and SBRT Treatment Planning Study for the First Clinical Biology-Guided Radiotherapy System.
Technology in cancer research & treatment
2022; 21: 15330338221100231
Purpose: The first clinical biology-guided radiation therapy (BgRT) system-RefleXionTM X1-was installed and commissioned for clinical use at our institution. This study aimed at evaluating the treatment plan quality and delivery efficiency for IMRT/SBRT cases without PET guidance. Methods: A total of 42 patient plans across 6 cancer sites (conventionally fractionated lung, head, and neck, anus, prostate, brain, and lung SBRT) planned with the EclipseTM treatment planning system (TPS) and treated with either a TrueBeam or Trilogy were selected for this retrospective study. For each Eclipse VMAT plan, 2 corresponding plans were generated on the X1 TPS with 10mm jaws (X1-10mm) and 20mm jaws (X1-20mm) using our institutional planning constraints. All clinically relevant metrics in this study, including PTV D95%, PTV D2%, Conformity Index (CI), R50, organs-at-risk (OAR) constraints, and beam-on time were analyzed and compared between 126 VMAT and RefleXion plans using paired t-tests. Results: All but 3 planning metrics were either equivalent or superior for the X1-10mm plans as compared to the Eclipse VMAT plans across all planning sites investigated. The Eclipse VMAT and X1-10mm plans generally achieved superior plan quality and sharper dose fall-off superior/inferior to targets as compared to the X1-20mm plans, however, the X1-20mm plans were still considered acceptable for treatment. On average, the required beam-on time increased by a factor of 1.6 across all sites for X1-10mm compared to X1-20mm plans. Conclusions: Clinically acceptable IMRT/SBRT treatment plans were generated with the X1 TPS for both the 10mm and 20mm jaw settings.
View details for DOI 10.1177/15330338221100231
View details for PubMedID 35579876
- Progression Versus Radiation Treatment Changes After Stereotactic Ablative Radiation Therapy of a Liver Metastasis PRACTICAL RADIATION ONCOLOGY 2022; 12 (1): 1-2
Pulmonary Hemorrhage in Patients Treated With Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents
ELSEVIER SCIENCE INC. 2021: E423
View details for Web of Science ID 000715803800868
Pulmonary Hemorrhage in Patients Treated with Thoracic Stereotactic Ablative Radiotherapy and Anti-Angiogenic Agents
LIPPINCOTT WILLIAMS & WILKINS. 2021: S105
View details for Web of Science ID 000701779700169
IMRT Treatment Planning Study for the First Clinical Biology-guided Radiotherapy System
LIPPINCOTT WILLIAMS & WILKINS. 2021: S137-S138
View details for Web of Science ID 000701779700218
Treatment Patterns for Isolated Nodal Recurrences in Non-Small Cell Lung Cancer After Definitive Stereotactic Ablative Radiotherapy
LIPPINCOTT WILLIAMS & WILKINS. 2021: S109
View details for Web of Science ID 000701779700174
Evaluating the clinical trends and benefits of low-dose computed tomography in lung cancer patients.
BACKGROUND: Despite guideline recommendations, utilization of low-dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real-world effect of LDCT utilization on lung cancer outcomes remain limited.METHODS: We identified patients diagnosed with non-small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer-specific mortality (CSM) was evaluated using Fine-Gray regression with non-cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening.RESULTS: Among 4664 patients, mean age was 67.8 with 58-month median follow-up, 95% CI=[7-71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%-6.6%, mean=1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46-3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21-0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42-0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non-Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely.CONCLUSIONS: Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT-screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority.
View details for DOI 10.1002/cam4.4229
View details for PubMedID 34528761
Trimodality Versus Bimodality Therapy in Patients With Locally Advanced Esophageal Carcinoma: Commentary on the American Society of Clinical Oncology Practice Guidelines.
Practical radiation oncology
In the recent guideline statement from the American Society of Clinical Oncology, experts reviewed relevant literature and provided treatment recommendations for multimodality treatment approaches. The guidelines recommend either preoperative concurrent neoadjuvant chemoradiotherapy (CRT) or perioperative chemotherapy for locally advanced adenocarcinoma and either preoperative CRT followed by esophagectomy or definitive CRT for squamous cell carcinoma. Whether radiation can be omitted in patients with adenocarcinoma or whether surgery can be omitted in patients with squamous cell carcinoma is a subject of ongoing debate and clinical trials.
View details for DOI 10.1016/j.prro.2021.05.004
View details for PubMedID 34353757
Pancreatic Stereotactic Body Radiation Therapy with or without Hypofractionated Elective Nodal Irradiation.
International journal of radiation oncology, biology, physics
PURPOSE/OBJECTIVES: Pancreatic stereotactic body radiation therapy (SBRT) is limited to gross tumor without elective coverage for subclinical disease. Given a better understanding of recurrence patterns, we hypothesized that the addition of elective nodal irradiation (ENI) to pancreatic SBRT would be tolerable and would decrease locoregional progression.MATERIALS/METHODS: We conducted a retrospective 1:2 propensity-matched cohort study to compare toxicity and locoregional progression among patients treated with pancreatic SBRT with or without ENI. In the SBRT+ENI cohort, an elective target volume was delineated per RTOG guidelines and treated to 25 Gy in 5 fractions alongside 40 Gy in 5 fractions to gross disease. The primary outcome was the cumulative incidence of locoregional progression, with death as a competing risk.RESULTS: Among 135 candidate controls treated with SBRT alone, 100 were propensity-matched to 50 patients treated with SBRT+ENI. All patients completed SBRT. Median potential radiographic follow-up was 28 months. The incidence of late and serious acute toxicity were similar between matched cohorts. However, SBRT+ENI was associated with a statistically significant increase in acute grade 1-2 nausea (60% vs. 20%, p<0.001). The 24-month cumulative incidences of locoregional progression with and without ENI were 22.6% (95% confidence interval [CI]: 10.0-35.1%) vs. 44.6% (95% CI: 34.8-54.4%, multivariable-adjusted hazard ratio 0.39, 95% CI 0.18-0.87, p=0.021). This was stable in sensitivity analyses of uniform prescription dose, multiagent chemotherapy, and resectability. There were fewer peripancreatic (0% vs. 7%), porta hepatis (2% vs. 7%), and peri-aortic/aortocaval (5% vs. 12%) recurrences after SBRT+ENI, but no difference in survival.CONCLUSIONS: Pancreatic SBRT+ENI was tolerable and did not increase late or serious acute toxicity relative to a matched cohort undergoing SBRT alone, but did increase acute grade 1-2 nausea. The addition of ENI to SBRT was associated with decreased locoregional progression but not improved survival. Further studies are warranted to determine if ENI offers meaningful benefit.
View details for DOI 10.1016/j.ijrobp.2021.07.1698
View details for PubMedID 34348171
- Impact of the VA opioid safety initiative on pain management for cancer patients. LIPPINCOTT WILLIAMS & WILKINS. 2021
Microstructural injury to corpus callosum and intra-hemispheric white matter tracts correlate with attention and processing speed decline after brain radiation.
International journal of radiation oncology, biology, physics
The corpus callosum (CC) and intra-hemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention/processing speed decline post-radiotherapy in primary brain tumor patients.On a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and MRI/diffusion-weighted imaging pre-radiotherapy, and 3-, 6-, and 12-months post-radiotherapy. CC (subregions; total) and IHWM tracts (left/right without CC; total) were autosegmented; tumor/tumor bed/edema were censored. Biomarkers included: volume changes (cc); mean diffusivity (MD, higher values indicate WM injury); fractional anisotropy (FA, lower values indicate WM injury). Reliable-change indices measured changes in attention (WAIS-IV digits-forward; D-KEFS-Trail-Making visual-scanning) and processing speed (WAIS-IV coding; D-KEFS-Trail-Making number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between 1) mean radiation dose and biomarkers (volume, MD, FA); 2) imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons.Processing speed declined at 6 months (number-sequencing, letter-sequencing; p<0.04). Seizures and anti-epileptic drug therapy were associated with lower visual-scanning attention reliable-change indices at 6 months (p=0.039). Higher radiation dose correlated with smaller mid-anterior CC volume (p=0.023), lower FA in posterior CC, anterior CC, and total CC (all p<0.03), and higher MD in anterior CC (p=0.012). Smaller mid-anterior CC and left IHWM volume correlated with worse processing speed (coding, letter-sequencing, number-sequencing, all p<0.03). Higher FA in right, left, and total IHWM correlated with better coding scores (all p<0.01). Lower FA in total IHWM (p=0.009) was associated with worse visual-scanning attention scores. Higher FA in mid-posterior CC (p=0.029) correlated with better digits-forward attention scores.The CC demonstrated radiation dose-dependent atrophy and WM injury. Microstructural injury within the CC and IHWM was associated with attention/processing speed decline after radiotherapy. These areas represent possible avoidance regions for preservation of attention/processing speed.
View details for DOI 10.1016/j.ijrobp.2020.12.046
View details for PubMedID 33412257
End of treatment cone-beam computed tomography (CBCT) is predictive of radiation response and overall survival in oropharyngeal squamous cell carcinoma.
Radiation oncology (London, England)
2021; 16 (1): 147
Image guidance in radiation oncology has resulted in significant improvements in the accuracy and precision of radiation therapy (RT). Recently, the resolution and quality of cone beam computed tomography (CBCT) for image guidance has increased so that tumor masses and lymph nodes are readily detectable and measurable. During treatment of head and neck squamous cell carcinoma (HNSCC), on-board CBCT setup imaging is routinely obtained; however, this CBCT imaging data is not utilized to predict patient outcomes. Here, we analyzed whether changes in CBCT measurements obtained during a course of radiation therapy correlate with responses on routine 3-month follow-up diagnostic imaging and overall survival (OS).Patients with oropharyngeal primary tumors who received radiation therapy between 2015 and 2018 were included. Anatomical measurements were collected of largest nodal conglomerate (LNC) at CT simulation, end of radiation treatment (EOT CBCT), and routine 3-month post-RT imaging. At each timepoint anteroposterior (AP), mediolateral (ML) and craniocaudal (CC) measurements were obtained and used to create a 2-dimensional (2D) maximum.CBCT data from 64 node positive patients were analyzed. The largest nodal 2D maximum and CC measurements on EOT CBCT showed a statistically significant correlation with complete response on 3-month post-RT imaging (r = 0.313, p = 0.02 and r = 0.318, p = 0.02, respectively). Furthermore, patients who experienced a 30% or greater reduction in the CC dimension had improved OS (Binary Chi-Square HR 4.85, p = 0.028).Decreased size of pathologic lymph nodes measured using CBCT setup imaging during a radiation course correlates with long term therapeutic response and overall survival of HNSCC patients. These results indicate that CBCT setup imaging may have utility as an early predictor of treatment response in oropharyngeal HNSCC.
View details for DOI 10.1186/s13014-021-01871-w
View details for PubMedID 34372887
Racial, Ethnic, and Socioeconomic Discrepancies in Opioid Prescriptions Among Older Patients With Cancer.
JCO oncology practice
Minority race and lower socioeconomic status are associated with lower rates of opioid prescription and undertreatment of pain in multiple noncancer healthcare settings. It is not known whether these differences in opioid prescribing exist among patients undergoing cancer treatment.This observational cohort study involved 33,872 opioid-naive patients of age > 65 years undergoing definitive cancer treatment. We compared rates of new opioid prescriptions by race or ethnicity and socioeconomic status controlling for differences in baseline patient, cancer, and treatment factors. To evaluate downstream impacts of opioid prescribing and pain management, we also compared rates of persistent opioid use and pain-related emergency department (ED) visits.Compared with non-Hispanic White patients, the covariate-adjusted odds of receiving an opioid prescription were 24.9% (95% CI, 16.0 to 33.9, P < .001) lower for non-Hispanic Blacks, 115.0% (84.7 to 150.3, P < .001) higher for Asian-Pacific Islanders, and not statistically different for Hispanics (-1.0 to 14.0, P = .06). There was no significant association between race or ethnicity and persistent opioid use or pain-related ED visits. Patients living in a high-poverty area had higher odds (53.9% [25.4 to 88.8, P < .001]) of developing persistent use and having a pain-related ED visit (39.4% [16.4 to 66.9, P < .001]).For older patients with cancer, rates of opioid prescriptions and pain-related outcomes significantly differed by race and area-level poverty. Non-Hispanic Black patients were associated with a significantly decreased likelihood of receiving an opioid prescription. Patients from high-poverty areas were more likely to develop persistent opioid use and have a pain-related ED visit.
View details for DOI 10.1200/OP.20.00773
View details for PubMedID 33534647
Validation of an oncology-specific opioid risk calculator in cancer survivors.
BACKGROUND: Clinical guidelines recommend that providers risk-stratify patients with cancer before prescribing opioids. Prior research has demonstrated that a simple cancer opioid risk score might help identify to patients with cancer at the time of diagnosis with a high likelihood of long-term posttreatment opioid use. This current project validates this cancer opioid risk score in a generalizable, population-based cohort of elderly cancer survivors.METHODS: This study identified 44,932 Medicare beneficiaries with cancer who had received local therapy. Longitudinal opioid use was ascertained from Medicare Part D data. A risk score was calculated for each patient, and patients were categorized into low-, moderate-, and high-risk groups on the basis of the predicted probability of persistent opioid use. Model discrimination was assessed with receiver operating characteristic curves.RESULTS: In the study cohort, 5.2% of the patients were chronic opioid users 1 to 2years after the initiation of cancer treatment. The majority of the patients (64%) were at low risk and had a 1.2% probability of long-term opioid use. Moderate-risk patients (33% of the cohort) had a 5.6% probability of long-term opioid use. High-risk patients (3.5% of the cohort) had a 75% probability of long-term opioid use. The opioid risk score had an area under the receiver operating characteristic curve of 0.869.CONCLUSIONS: This study found that a cancer opioid risk score could accurately identify individuals with a high likelihood of long-term opioid use in a large, generalizable cohort of cancer survivors. Future research should focus on the implementation of these scores into clinical practice and how this could affect prescriber behavior and patient outcomes.LAY SUMMARY: A novel 5-question clinical decision tool allows physicians treating patients with cancer to accurately predict which patients will persistently be using opioid medications after completing therapy.
View details for DOI 10.1002/cncr.33410
View details for PubMedID 33378556
Comparison of Hematologic Toxicity and Bone Marrow Compensatory Response in Head and Neck vs. Cervical Cancer Patients Undergoing Chemoradiotherapy
FRONTIERS IN ONCOLOGY
2020; 10: 1179
Background: Hematologic toxicity is a critical problem limiting treatment delivery in cancer patients undergoing concurrent chemoradiotherapy. However, the extent to which anatomic variations in radiation dose limit chemotherapy delivery is poorly understood. A unique natural experiment arises in patients with head and neck and cervical cancer, who frequently undergo identical chemotherapy but receive radiation to different regions of the body. Comparing these cohorts can help elucidate to what extent hematologic toxicity is attributable to marrow radiation as opposed to chemotherapy. Methods: In this longitudinal cohort study, we compared hematologic toxicity and bone marrow compensatory response in 148 patients (90 cervix, 58 head/neck) undergoing chemoradiotherapy with concurrent weekly cisplatin 40 mg/m2. We used linear mixed effect models to compare baseline and time-varying peripheral cell counts and hemoglobin levels between cohorts. To assess bone marrow compensatory response, we measured the change in metabolically active bone marrow (ABM) volume on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Results: We observed greater reductions in log-transformed lymphocyte, platelet, and absolute neutrophil counts (ANC) for cervix compared to head/neck cancer patients (fixed effects for time-cohort interaction [95% CI]: lymphocytes, -0.06 [-0.09, -0.031]; platelets,-0.028 [-0.051, -0.0047]; ANC, -0.043 [-0.075, -0.011]). Mean ANC nadirs were also lower for cervical vs. head/neck cancer cohorts (2.20 vs. 2.85 × 103 per μL, p < 0.01). Both cohorts exhibited reductions in ABM volume within the radiation field, and increases in ABM volume in out-of-field areas, indicating varying compensatory response to radiation injury. Conclusions: Cervical cancer patients had faster decreases in ANC, lymphocyte, and platelet counts, and lower ANC nadirs, indicating a significant effect of pelvic irradiation on acute peripheral blood cell counts. Both cohorts exhibited a compensatory response with increased out-of-field bone marrow activity.
View details for DOI 10.3389/fonc.2020.01179
View details for Web of Science ID 000558484800001
View details for PubMedID 32793487
View details for PubMedCentralID PMC7385402
- Managing Cancer Pain During the Opioid Epidemic-Balancing Caution and Compassion JAMA ONCOLOGY 2020; 6 (7): 1103–4
Predicting Persistent Opioid Use, Abuse, and Toxicity Among Cancer Survivors.
Journal of the National Cancer Institute
2020; 112 (7): 720–27
BACKGROUND: Although opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse.METHODS: Within a cohort of 106732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique.RESULTS: The rate of persistent opioid use in cancer survivors was 8.3% (95% CI=8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI=2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI=2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC=0.87), and admission for opioid abuse or toxicity (AUC=0.78).CONCLUSION: This study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients.
View details for DOI 10.1093/jnci/djz200
View details for PubMedID 31754696
- Challenge of Directly Comparing Imaging-Based Diagnoses Made by Machine Learning Algorithms With Those Made by Human Clinicians JOURNAL OF CLINICAL ONCOLOGY 2020; 38 (16): 1868-+
Tobacco smoking and death from prostate cancer in US veterans
PROSTATE CANCER AND PROSTATIC DISEASES
2020; 23 (2): 252–59
Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC.This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses.The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p < 0.001), and had more advanced disease stage (stage IV disease current: 5.3%, never: 4.3%; p < 0.04). The 10-year incidence of PCSM was 5.2%, 4.8%, and 4.5% for current, past, and never smokers, respectively. On competing risk regression, current smoking was associated with increased PCSM (subdistribution hazard ratio: 1.14, 95% confidence interval: (1.05-1.24), p = 0.002), whereas past smoking was not. Hierarchical regression suggests that this increased risk was partially attributable to tumor characteristics.Smoking at the time of diagnosis is associated with a higher risk of dying from PC as well as other causes of death. In contrast, past smoking was not associated with PCSM suggesting that smoking may be a modifiable risk factor. PC diagnosis may be an important opportunity to discuss smoking cessation.
View details for DOI 10.1038/s41391-019-0178-6
View details for Web of Science ID 000534552900005
View details for PubMedID 31624316
African-American men with low-risk prostate cancer treated with radical prostatectomy in an equal-access health care system: implications for active surveillance
PROSTATE CANCER AND PROSTATIC DISEASES
There is concern that African-American men (AA) with low-risk prostate cancer may present with more aggressive disease and thus may not be candidates for active surveillance (AS). However, it is uncertain if poorer outcomes are due to disparities in access to medical care rather than true biological differences.Observational cohort study of patients diagnosed with low-risk PC-Gleason score ≤6, clinical tumor stage ≤2A, and prostate specific antigen (PSA) level ≤10-at US Department of Veterans Affairs between January 1, 2001 and October 31, 2015 and treated with radical prostatectomy. Outcomes included upgrading to Gleason Grade Group 2 (GG2), GG ≥ 3, PSA recurrence, pathologic tumor stage ≥3, positive surgical margins, and all-cause mortality.A total of 2857 men (AA: 835 White: 2022) with a median follow-up of 7.1 years. Overall, there was no significant difference between AA and White men in upgrading to GG ≥ 3 (RR = 1.18, p = 0.43), tumor stage ≥3 (RR = 0.95, p = 0.74), positive surgical margins (RR = 1.14, p = 0.20), PSA recurrence (SHR = 1.26, p = 0.06), and all-cause mortality (SHR = 1.26, p = 0.16). However, there was a significant increase in upgrading for AA to GG2 (RR = 1.49, p < 0.01).There was no significant difference in most adverse pathologic outcomes between AA and White patients. However, GG2 upgrading was more common in AA men. The implication is that AA may need to undergo additional evaluation, such as a biopsy MRI, before initiating AS. Whether the increase in GG2 upgrading will lead to poorer long-term clinical outcomes such as metastasis and PCSM also requires further investigation.
View details for DOI 10.1038/s41391-020-0230-6
View details for Web of Science ID 000528293600001
View details for PubMedID 32327702
Survival of African American and non-Hispanic white men with prostate cancer in an equal-access health care system.
2020; 126 (8): 1683-1690
African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity.A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015.AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P < .001) and lower high school graduation rates (83% for AA men vs 88% for NHW men; P < .001). At the time of diagnosis, AA men were younger (median age, 63.0 years vs 66.0 years; P < .001) and had a higher prostate-specific antigen level (median, 6.7 ng/mL vs 6.2 ng/mL; P < .001), but were less likely to have Gleason score 8 to 10 disease (18.8% among AA men vs 19.7% among NHW men; P < .001), a clinical T classification ≥3 (2.2% vs 2.9%; P < .001), or distant metastatic disease (2.7% vs 3.1%; P = 0.01). The 10-year PC-specific mortality rate was slightly lower for AA men (4.4% vs 5.1%; P = .005), which was confirmed in multivariable competing-risk analysis (subdistribution hazard ratio, 0.85; 95% CI, 0.78-0.93; P < .001).AA men diagnosed with PC in the VA health system do not appear to present with more advanced disease or experience worse outcomes compared with NHW men, in contrast to national trends, suggesting that access to care is an important determinant of racial equity.
View details for DOI 10.1002/cncr.32666
View details for PubMedID 31984482
Risk of Pelvic Fracture With Radiation Therapy in Older Patients
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2020; 106 (3): 485–92
Older patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality.This observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population.The 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture.IMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.
View details for DOI 10.1016/j.ijrobp.2019.10.006
View details for Web of Science ID 000510861900009
View details for PubMedID 31610251
Associations among statins, preventive care, and prostate cancer mortality
PROSTATE CANCER AND PROSTATIC DISEASES
2020; 23 (3): 475–85
Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information.We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model.The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p < 0.001) and PSA (76 vs. 67%, p < 0.001). In the model which excluded screening, prediagnosis statin users had improved PCSM (SHR 0.90, 95% CI 0.84-0.97; p = 0.004) and ACM (HR 0.96, 95% CI 0.93-0.99; p = 0.02). However, after including cholesterol and PSA screening rates, prediagnosis statin users and nonusers showed no differences in PCSM (SHR 0.98, 95% CI 0.91-1.06; p = 0.59) or ACM (HR 1.02, 95% CI 0.98-1.05; p = 0.25).We found that statin users tend to have more screening than nonusers. When we considered screening utilization, we observed no relationship between statin use before a prostate cancer diagnosis and prostate cancer mortality.
View details for DOI 10.1038/s41391-020-0207-5
View details for Web of Science ID 000511538100001
View details for PubMedID 32029930
Predictive classifier for intensive treatment of head and neck cancer.
This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer.This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS).Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011).LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.
View details for DOI 10.1002/cncr.33212
View details for PubMedID 33017867
Selection of Head and Neck Cancer Patients for Intensive Therapy
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
2020; 106 (1): 157–66
Previous studies have found that patients with head and neck cancer (HNC) with a higher relative hazard for recurrence versus competing mortality (ω+ ratio) are more likely to benefit from intensive therapy. Nomograms to predict this ratio (ω scores) can be useful to guide clinical management; however, comorbidity and other risk factors are frequently lacking from trial samples.In this study of 7117 US veterans, we evaluated the ability of a ω score nomogram developed from clinical trial data to stratify patients with HNC treated with radiation therapy by their relative risk of cancer progression versus competing mortality. We then fit generalized competing event models to determine the effect of comorbidity and other covariates on the ω+ ratio.The ω score was effective in stratifying patients with HNC according to their risk for cancer recurrence relative to competing mortality, especially among patients aged >70 years. Patients with ω score ≥0.80 were more likely to receive intensive therapy compared with patients with a ω score <0.80 (66 vs. 54%; P < .001). On multivariable generalized competing event regression, T2-4 category (relative hazard ratio [RHR], 1.08; 95% confidence interval [CI], 1.01-1.16), N2-3 category (RHR, 1.07; 95% CI, 1.01-1.15), and being employed (RHR, 1.11; 95% CI, 1.03-1.20) were associated with increased ω+ ratio, and increasing age (RHR, 0.83; 95% CI, 0.78-0.89), Charlson comorbidity index ≥2 (RHR, 0.85; 95% CI, 0.79-0.91), being a current smoker (RHR, 0.90; 95% CI, 0.84-0.96), and lower body mass index (RHR, 0.89; 95% CI, 0.84-0.95) were associated with a decreased ω+ ratio.The ω scores are effective in stratifying patients with HNC and are correlated with the intensity of treatment given. The ω scores incorporating comorbidity and other risk factors could help identify patients with HNC most likely to benefit from intensive therapy.
View details for DOI 10.1016/j.ijrobp.2019.09.011
View details for Web of Science ID 000502338300030
View details for PubMedID 31580929
Cost-effectiveness Analysis of Stereotactic Ablative Radiotherapy in Patients with Oligometastatic Cancer.
International journal of radiation oncology, biology, physics
The SABR-COMET phase 2 randomized clinical trial found that stereotactic ablative radiotherapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of the addition of SABR compared to standard therapy alone among cancer patients with oligometastatic disease.We constructed a Markov model to simulate treatment with stereotactic ablative radiotherapy or standard therapy among patients with oligometastatic cancers. The model derived transition probabilities from SABR-COMET clinical trial data to estimate risks of toxicity, disease progression and survival. Healthcare costs and health utilities were estimated from the literature. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty. Cost-effectiveness was estimated from both the health care sector and societal perspectives with an incremental cost-effectiveness ratio (ICER) defined as dollars per quality-adjusted life year (QALY). An ICER less than $100,000/QALY was considered cost-effective. One-way and probabilistic sensitivity analyses were used to examine model uncertainty.The addition of SABR increased total costs by $54,260 (health care sector perspective) or $72,799 (societal perspective) and improved effectiveness by 1.88 QALYs compared with standard therapy, leading to an ICER of $28,906/QALY (health care sector perspective) or $38,783/QALY (societal perspective). The model was modestly sensitive to assumptions about tumor progression, though the model was not sensitive to assumptions about survival or cost of treatment. Probabilistic sensitivity analyses demonstrated that SABR was the cost-effective treatment option 99.8% (health care sector perspective) or 98.7% (societal perspective) of the time.The addition of SABR increased costs and improved quality adjusted survival, overall leading to a cost-effective treatment strategy for patients with oligometastatic cancer.
View details for DOI 10.1016/j.ijrobp.2020.09.045
View details for PubMedID 33002541
Combined Androgen Blockade in Localized Prostate Cancer Treated With Definitive Radiation Therapy
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
2019; 17 (12): 1497-+
The addition of androgen deprivation therapy to radiation therapy (RT) improves survival in patients with intermediate- and high-risk prostate cancer (PCa), but it is not known whether combined androgen blockade (CAB) with a gonadotropin-releasing hormone agonist (GnRH-A) and a nonsteroidal antiandrogen improves survival over GnRH-A monotherapy.This study evaluated patients with intermediate- and high-risk PCa diagnosed in 2001 through 2015 who underwent RT with either GnRH-A alone or CAB using the Veterans Affairs Informatics and Computing Infrastructure. Associations between CAB and prostate cancer-specific mortality (PCSM) and overall survival (OS) were determined using multivariable regression with Fine-Gray and multivariable Cox proportional hazards models, respectively. For a positive control, the effect of long-term versus short-term GnRH-A therapy was tested.The cohort included 8,423 men (GnRH-A, 4,529; CAB, 3,894) with a median follow-up of 5.9 years. There were 1,861 deaths, including 349 resulting from PCa. The unadjusted cumulative incidences of PCSM at 10 years were 5.9% and 6.9% for those receiving GnRH-A and CAB, respectively (P=.16). Compared with GnRH-A alone, CAB was not associated with a significant difference in covariate-adjusted PCSM (subdistribution hazard ratio [SHR], 1.05; 95% CI, 0.85-1.30) or OS (hazard ratio, 1.02; 95% CI, 0.93-1.12). For high-risk patients, long-term versus short-term GnRH-A therapy was associated with improved PCSM (SHR, 0.74; 95% CI, 0.57-0.95) and OS (SHR, 0.82; 95% CI, 0.73-0.93).In men receiving definitive RT for intermediate- or high-risk PCa, CAB was not associated with improved PCSM or OS compared with GnRH alone.
View details for DOI 10.6004/jnccn.2019.7335
View details for Web of Science ID 000500944300010
View details for PubMedID 31805534
Nomogram to Predict the Benefit of Intensive Treatment for Locoregionally Advanced Head and Neck Cancer.
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE: Previous studies indicate the benefit of therapy depends on patients' risk for cancer recurrence relative to non-cancer mortality (omega ratio). We sought to test the hypothesis that head and neck cancer (HNC) patients with a higher omega ratio selectively benefit from intensive therapy.EXPERIMENTAL DESIGN: We analyzed 2688 patients with stage III-IVB HNC undergoing primary radiation therapy (RT) with or without systemic therapy on three phase III trials (RTOG 9003, RTOG 0129, and RTOG 0522). We used generalized competing event regression to stratify patients according to omega ratio, and compared the effectiveness of intensive therapy as a function of predicted omega ratio (i.e., omega score). Intensive therapy was defined as treatment on an experimental arm with altered fractionation (AFX) and/or multiagent concurrent systemic therapy. A nomogram was developed to predict patients' omega score based on tumor, demographic, and health factors. Analysis was by intention-to-treat.RESULTS: Decreasing age, improved performance status, higher body mass index, node positive status, P16 negative status, and oral cavity primary predicted a higher omega ratio. Patients with omega score ≥ 0.80 were more likely to benefit from intensive treatment (5-year OS, 70.0% vs. 56.6%; HR 0.73, 95% CI 0.57-0.94; P=0.016) than those with a omega score < 0.80 (5-year OS, 46.7% vs. 45.3%; HR 1.02, 95% CI 0.92-1.14; P=0.69;P=0.019 for interaction). In contrast, the effectiveness of intensive therapy did not depend on risk of progression.CONCLUSION: HNC patients with a higher omega score selectively benefit from intensive treatment. A nomogram was developed to help select patients for intensive therapy.
View details for DOI 10.1158/1078-0432.CCR-19-1832
View details for PubMedID 31420360
Reducing prolonged chemoradiation treatment times for cervical cancer.
BMJ open quality
2019; 8 (3): e000516
Prolonged total treatment times (TTTs) beyond 56 days are associated with worse outcomes for cervical cancer treated with radiation therapy. We reviewed treatment times in a cohort of 24 consecutive patients treated with definitive chemoradiation (CRT) at our institution and found that only 14 patients (58.3%) completed treatment in less than or equal to 56 days. The primary objectives of this institutional quality improvement initiative were to identify sources for delays in treatment completion and to implement effective measures in an effort to minimise prolonged TTT. Pareto plot and process mapping were used to identify and resolve root causes of prolonged treatment. The Plan-Do-Study-Act method was then implemented to reduce treatment duration. Post-intervention treatment times were prospectively evaluated in 81 subsequent patients treated with definitive CRT. Process mapping identified inefficiencies with scheduling, staggered treatments and inadequate patient and staff education. Institutional changes were implemented, heavily utilising oncology nurses' skill set in staff re-education and care coordination. Our workflow was redesigned to reduce/eliminate treatment delays. These interventions led to a significant improvement in the percentage of patients meeting the goal TTT compared with the pre-intervention cohort (85.2% vs 58.3%, p<0.01), and results were sustainable in additional 47 patients prospectively followed subsequently, potentially making a positive impact on their treatment outcomes.
View details for DOI 10.1136/bmjoq-2018-000516
View details for PubMedID 31637317
Prognostic Role of p16 in Nonoropharyngeal Head and Neck Cancer
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
2018; 110 (12): 1393–99
Previous studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC).Using the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided.In multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05).Our findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.
View details for DOI 10.1093/jnci/djy072
View details for Web of Science ID 000455209700014
View details for PubMedID 29878161
View details for PubMedCentralID PMC6292787
Comparison of Comorbidity and Frailty Indices in Patients With Head and Neck Cancer Using an Online Tool
JCO CLINICAL CANCER INFORMATICS
2018; 2: 1–9
Comorbidity is an independent predictor of mortality and treatment tolerance in head and neck cancer and should be considered with regard to treatment intensification. Multiple previously validated models can be used to evaluate comorbidity and propensity to benefit from intensive treatment, but they have not been directly compared.An online tool was developed and used to calculate the Charlson Comorbidity Index (CCI), Adult Comorbidity Evaluation-27 (ACE-27), Cumulative Illness Rating Scale for Geriatrics (CIRS-G), Geriatric 8 (G8), Cancer and Aging Research Group (CARG), and Generalized Competing Event (GCE) scores. To assess interrater variability, five evaluators independently calculated scores on a retrospective cohort of 20 patients. Correlation between models as well as age and performance status were calculated from a cohort of 40 patients.The GCE and G8 models had an excellent (intraclass correlation coefficient and Fleiss' kappa ≥ 0.75) degree of interrater agreement. The CCI, ACE-27, CIRS-G, and CARG had a good (intraclass correlation coefficient and Fleiss' kappa 0.6-0.74) degree of interrater agreement. There was statistically significant correlation between models, especially with the CCI, ACE-27, and CIRS-G indices. Increased age was correlated with an increased CCI score and having moderate to severe comorbidity was correlated with the ACE-27 model. Except for the G8 model, the comorbidity indices were not associated with Eastern Cooperative Oncology Group performance status.We developed an online tool to calculate indices of comorbidity in patients with head and neck cancer with a high degree of reproducibility. Comorbidity is not strongly correlated with performance status and should be independently evaluated in patients.
View details for DOI 10.1200/CCI.18.00082
View details for Web of Science ID 000462336800001
View details for PubMedID 30652602
Optimism bias' in contemporary national clinical trial network phase III trials: are we improving?
ANNALS OF ONCOLOGY
2018; 29 (10): 2135–39
Previous studies have found that overestimating treatment effects (i.e. 'optimism bias') leads to underpowered clinical trials. The prevalence of 'optimism bias' in contemporary National Clinical Trials Network (NCTN) cancer clinical trials is unknown.We conducted a systematic review of NCTN phase III randomized trials published from January 2007 to January 2017. We compared the hypothesized versus observed treatment effects in each trial, and examined whether trial-related factors were correlated with the study results. We also reviewed the methods of each protocol to assess whether a rationale for the hypothesized effect size was provided.We identified 161 clinical trials, of which 130 were eligible for analysis. Original protocols could not be located for 8 trials (5.0%). Twenty-eight trials (21.5%) observed a statistically significant difference in the primary end point favoring the experimental treatment. The median ratio of observed-to-expected hazard ratios among trials that observed a statistically significant effect on the primary end point was 1.07 (range: 0.33-1.28) versus 1.32 (range: 0.86-2.02) for trials that did not, compared with 1.34 and 1.86, respectively, for National Cancer Institute (NCI) trials published between 1955 and 2006. An effect size at least as large as the one projected in the protocol trials was observed in 9.8% of trials, compared with 17% of NCI trials published from 1955 to 2006. Most trials (64.6%) provided no rationale to support the magnitude of the proposed treatment effect in the protocol.Despite a reduction in 'optimism bias' compared with previous eras, most contemporary NCTN phase III trials failed to establish statistically significant benefits of new cancer therapies. Better rationalization of proposed effect sizes in research protocols is needed.
View details for DOI 10.1093/annonc/mdy340
View details for Web of Science ID 000455165100018
View details for PubMedID 30412223
View details for PubMedCentralID PMC6454418
- The role of p16 as a biomarker in nonoropharyngeal head and neck cancer. Oncotarget 2018; 9 (70): 33247–48
Generalized Competing Event Models Can Reduce Cost and Duration of Cancer Clinical Trials
JCO CLINICAL CANCER INFORMATICS
2018; 2: 1–12
Generalized competing event (GCE) models improve stratification of patients according to their risk of cancer events relative to competing causes of mortality. The potential impact of such methods on clinical trial power and cost, however, is uncertain. We sought to test the hypothesis that GCE models can reduce estimated clinical trial cost in elderly patients with cancer.Patients with nonmetastatic head and neck (n = 9,677), breast (n = 22,929), or prostate cancer (n = 51,713) were sampled from the SEER-Medicare database. Using multivariable Cox proportional hazards models, we compared risk scores for all-cause mortality (ACM) and cancer-specific mortality (CSM) with GCE-based risk scores for each disease. We applied a cost function to estimate the cost and duration of clinical trials with a primary end point of overall survival in each population and in high-risk subpopulations. We conducted sensitivity analyses to examine model uncertainty.For the purpose of enriching subpopulations, GCE models reduced estimated clinical trial cost compared with Cox models of ACM and CSM in all disease sites. The relative cost reductions with GCE models compared with ACM and CSM models, respectively, were -68.4% and -14.4% in prostate cancer, -38.8% and -18.3% in breast cancer, and -17.1% and -4.1% in head and neck cancer. Cost savings in breast and prostate cancers were on the order of millions of dollars. The GCE model also reduced relative clinical trial duration compared with CSM and ACM models for all disease sites. The optimal risk score cutoff for clinical trial enrollment occurred near the top tertile for all disease sites.GCE models have significant potential to improve clinical trial efficiency and reduce cost, with a potentially large impact in prostate and breast cancers.
View details for DOI 10.1200/CCI.17.00124
View details for Web of Science ID 000461551600001
View details for PubMedID 30652559
Head and Neck Soft Tissue Sarcomas Treated with Radiation Therapy.
2016; 8 (2): 6165
Head and neck soft tissue sarcomas (HNSTSs) are rare and heterogeneous cancers in which radiation therapy (RT) has an important role in local tumor control (LC). The purpose of this study was to evaluate outcomes and patterns of treatment failure in patients with HNSTS treated with RT. A retrospective review was performed of adult patients with HNSTS treated with RT from January 1, 1998, to December 31, 2012. LC, locoregional control (LRC), disease-free survival (DFS), overall survival (OS), and predictors thereof were assessed. Forty-eight patients with HNSTS were evaluated. Five-year Kaplan-Meier estimates of LC, LRC, DFS, and OS were 87, 73, 63, and 83%, respectively. Angiosarcomas were found to be associated with worse LC, LRC, DFS, and OS. Patients over the age of 60 had lower rates of DFS. HNSTSs comprise a diverse group of tumors that can be managed with various treatment regimens involving RT. Angiosarcomas have higher recurrence and mortality rates.
View details for DOI 10.4081/rt.2016.6165
View details for PubMedID 27441072
View details for PubMedCentralID PMC4935821
Study of Na+/H+ exchange-mediated pHi regulations in neuronal soma and neurites in compartmentalized microfluidic devices.
Integrative biology : quantitative biosciences from nano to macro
2010; 2 (1): 58-64
Regulation of intracellular pH (pH(i)) in neurons is crucial to maintain their physiological function. In the current study, newly-developed polydimethylsiloxane (PDMS) microfluidic devices were used to independently investigate pH(i) regulation in neuronal soma and neurites. Embryonic cortical neurons were cultured in PDMS microfluidic devices with soma growing in one chamber (seeded) and neurites extending through a set of perpendicular microchannels into the opposite parallel chamber (non-seeded). Neurons in the microchambers were characterized by the vital dye calcein-red, polarized mitochondria, and expression of neuronal specific beta-tubulin (type-III), axonal Tau-1 protein, dendritic microtubule associated protein (MAP-2), and Na(+)/H(+) exchanger isoform 1 (NHE-1). Neurites exhibited higher resting pH(i) than soma (7.16 +/- 0.09 vs. 6.90 +/- 0.15). The neurites had a proton extrusion rate 3.7-fold faster than in soma following NH(4)Cl prepulse-mediated acidification (p < 0.05). The difference in the pH(i) regulation rates between neurites and soma can be accounted for by the larger surface area to volume ratio in the neurites. Interestingly, pharmacological inhibition of NHE-1 activity blocked the pH(i) regulation in soma and in neurites by approximately 70% (p < 0.05). Taken together, our study demonstrated that the microfluidic devices provide a useful tool to study neuronal pH(i) regulation in soma and their neurites. We conclude that NHE-1 plays an important role in regulation of pH(i) in both compartments.
View details for DOI 10.1039/b918440f
View details for PubMedID 20473413
View details for PubMedCentralID PMC2875691
Global engineering education initiative through student organization.
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual Conference
2009; 2009: 2022-4
Engineering is becoming a more globally aware discipline that is revolutionizing the way individuals interact internationally. Engineering World Health (EWH) - Madison Chapter is a student-initiated organization that has developed opportunities to facilitate both local and global engineering education. Through EWH - Madison Chapter student-initiated activities, this organization has developed an interface between Traditional, Technical, and Translational education mediums. This study attests to the development of global engineering programs in the context of biomedical applications.
View details for DOI 10.1109/IEMBS.2009.5334420
View details for PubMedID 19964768