Prognostic Factors and Treatment Patterns in the Management of Giant Cell Glioblastoma.
BACKGROUND: There is a lack of literature guiding treatment of giant cell glioblastoma (gcGBM), a rare subtype of glioblastoma (GBM). We used a national hospital-based registry to explore treatment patterns and outcomes associated with gcGBM.METHODS: Adult patients (age 18+) diagnosed with gcGBM or GBM between 2004-2014 were identified from the National Cancer Database (NCDB). Chi-squared analysis and Wilcoxon rank sum testing were used to compare characteristics between the gcGBM and GBM cohorts. Kaplan-Meier statistics, univariable and multivariable Cox regression, and propensity score matching were used to evaluate association between patient, tumor and treatment factors and survival outcomes. Correlation analysis was used to evaluate historical trends in the treatment of gcGBM. Landmark analysis allowed for accounting of immortal time.RESULTS: In total, 683 patients with gcGBM were identified. Patients with gcGBM had improved survival compared to patients with GBM (15.5 months from landmark vs 11.7, p < 0.001). Increased age (p < 0.001) was associated with worse survival while being of female sex (p = 0.023) and having a median income of higher than $63,000 (p = 0.004) predisposed patients to improved outcomes. Patients receiving trimodal therapy (biopsy and/or surgery, radiotherapy, and chemotherapy) experienced better outcomes compared to those receiving either biopsy and/or surgery only or biopsy and/or surgery and radiotherapy without systemic therapy (median survival 17.55 months vs 6.68 months; p < 0.001).CONCLUSION: gcGBM has favorable prognosis compared with GBM and should be aggressively managed with trimodal therapy. Prospective studies on gcGBM are warranted to better characterize gcGBM treatment outcomes.
View details for PubMedID 31009783
- The Burden of Mental Health Disorders Among Elderly Patients with Gastrointestinal Malignancies ELSEVIER SCIENCE INC. 2019: E30–E31
- Definitive Radiotherapy with or Without Cisplatin for Cervical Cancer in Older Women ELSEVIER SCIENCE INC. 2019: E11
Adjuvant treatment and survival in older women with triple negative breast cancer: A Surveillance, Epidemiology, and End Results analysis.
The breast journal
Patients with triple negative breast cancer were identified using the Surveillance, Epidemiology, and End Results database. Competing risks analysis was used to assess the cumulative incidence of breast cancer-specific mortality (BCSM). Multivariable Fine-Gray regression was used to identify predictors of BCSM. Women age 70+ (n=4221) were less likely to receive chemotherapy and radiation treatment (P<0.0001) and had higher BCSM compared to younger women (P<0.0001). There were no differences in BCSM in patients who received adjuvant treatment (P=0.10). Stage II patients derived the greatest relative and absolute benefit from adjuvant treatment. Age was not a significant predictor of BCSM.
View details for DOI 10.1111/tbj.13251
View details for PubMedID 30925635
- National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma GYNECOLOGIC ONCOLOGY 2019; 152 (3): 599–604
Physiological motion of the optic chiasm and its impact on stereotactic radiosurgery dose.
The British journal of radiology
Avoidance of radiation-induced optic neuropathy (RION) from stereotactic radiosurgery (SRS) requires precise anatomical localization; however, no prior studies have characterized the physiologic motion of the optic chiasm. We measured the extent of chiasm motion and its impact on SRS dose.In this cross-sectional study, serial magnetic resonance imaging was performed in multiple planes in 11 human subjects without optic pathway abnormalities to determine chiasm motion across time. Subsequently, the measured displacement was applied to the hypothetical chiasm dose received in 11 patients treated with SRS to a perichiasmatic lesion.On sagittal images, the average anteroposterior chiasm displacement was 0.51 mm (95 % confidence interval [CI] 0.27 - 0.75 mm), and the average superior-inferior displacement was 0.48 mm (95% CI 0.22 - 0.74 mm). On coronal images, the average superior-inferior displacement was 0.42 mm (95% CI 0.13 - 0.71 mm), and the average lateral displacement was 0.75 mm (95% CI 0.42 - 1.08 mm). In 11 patients who underwent SRS to a perichiasmatic lesion, the average displacements increased the maximum chiasm dose (Dmax) by a mean of 14 % (range 6 - 23 %; p < 0.001).Average motion of the optic chiasm was approximately 0.50 - 0.75 mm, which increased chiasm Dmax by a mean of 14 %. In the occasional patient with higher-than-average chiasm motion in a region of steep dose gradient, the increase in chiasm Dmax and risk of RION could be even larger. Similarly, previously reported chiasm dose constraints may underestimate the true dose received during radiosurgery.To limit the risk of RION, clinicians may consider adding a 0.50 - 0.75 mm expansion to the chiasm avoidance structure.
View details for PubMedID 31067077
National patterns of care and cancer-specific outcomes of adjuvant treatment in patients with serous and clear cell endometrial carcinoma.
OBJECTIVES: To investigate outcomes of adjuvant therapy for serous and clear cell endometrial carcinoma, as prior studies are limited by sample size and/or patient heterogeneity. National guidelines permit substantial variations in treatment, suggesting the need for additional data.METHODS: Patients with FIGO stages I-III serous or clear cell uterine carcinoma who underwent at least total hysterectomy were identified in SEER-Medicare. Adjuvant external beam radiation, brachytherapy, and chemotherapy were determined using SEER fields and Medicare claims. The primary outcome was death from endometrial cancer (cancer-specific mortality [CSM]) evaluated using Gray's test (univariable analysis, UVA) and Fine-Gray regression (multivariable analysis, MVA).RESULTS: A total of 1789 patients (1437 serous, 352 clear cell) were identified. In stages I-II patients (n = 1188), brachytherapy was significant for survival in UVA (P = 0.03) and MVA (P = 0.02). Additionally, in the subset with serous histology (n = 947), chemotherapy was also significant in UVA (P = 0.002) and approached significance in MVA (P = 0.05). The 4-year CSM for stages I-II serous cancers was 25% without brachytherapy or chemotherapy, 15% with one, and 9% with both (P ≤ 0.05 for all pairwise comparisons). In stage III patients (n = 601), chemotherapy was significant in UVA (P = 0.002) and MVA (P = 0.006). Most (81%) patients underwent lymph node dissection, which predicted lower CSM in stage III (P = 0.001) but not stages I-II patients.CONCLUSIONS: Our results suggest brachytherapy benefits stages I-II serous/clear cell cancers, chemotherapy benefits stage III serous/clear cell cancers, and both chemotherapy and brachytherapy benefit stages I-II serous cancers.
View details for PubMedID 30551884
- Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis CANCER 2018; 124 (23): 4486–94
Survival of patients with head and neck cancer treated with definitive radiotherapy and concurrent cisplatin or concurrent cetuximab: A Surveillance, Epidemiology, and End Results-Medicare analysis.
BACKGROUND: Cisplatin and cetuximab are both systemic therapies commonly used in combination with radiation (RT) for the definitive treatment of head and neck cancers, but their comparative efficacy is unclear.METHODS: Patients with locoregionally advanced (American Joint Committee on Cancer stage III-IVB) squamous cell carcinomas of the oropharynx, larynx, or hypopharynx were identified in the Surveillance, Epidemiology, and End Results-Medicare database. Patients received either cisplatin or cetuximab concurrent with RT, as determined by Medicare claims. The primary study outcome was head and neck cancer-specific mortality (CSM) analyzed with competing risks. Filtering, propensity score matching, and multivariable Fine-Gray regression were used to adjust for differences between the cisplatin and cetuximab cohorts, including age, comorbidity, and cycles of systemic therapy received.RESULTS: The total cohort consisted of 1395 patients, of whom 786 (56%) received cisplatin and 609 (44%) received cetuximab; the median follow-up was 3.5 years in the patients who remained alive. In the cetuximab cohort, CSM was significantly higher than in the cisplatin cohort (39% vs 25% at 3 years; P < .0001). In the matched cohorts (n = 414), the adjusted hazard ratio of CSM for cetuximab was 1.65 (95% confidence interval, 1.30-2.09; P < .0001) relative to cisplatin, corresponding to an absolute difference of approximately 10% in both CSM and overall survival at 3 years. Cetuximab was associated with less dysphagia, more dermatitis, and a similar incidence of mucositis.CONCLUSIONS: In this sizeable, national patient population, treatment with cetuximab was associated with significantly higher CSM than cisplatin. These results suggest that cisplatin may be the preferred chemotherapeutic agent in this setting. Cancer 2018;124:000-000.
View details for PubMedID 30332498
Comparative Effectiveness and Toxicity of Cetuximab or Cisplatin With Concurrent Radiation for Locoregionally Advanced Squamous Cell Carcinoma of The Head And Neck: A Population-Based Analysis
ELSEVIER SCIENCE INC. 2018: E16
View details for Web of Science ID 000432447200037
Gene expression-based discovery of atovaquone as a STAT3 inhibitor and anticancer agent
2016; 128 (14): 1845-1853
The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is frequently activated inappropriately in a wide range of hematological and solid cancers, but clinically-available therapies targeting STAT3 are lacking. Using a computational strategy to identify compounds opposing the gene expression signature of STAT3, we discovered atovaquone (Mepron™), an FDA-approved anti-microbial, to be a potent STAT3 inhibitor. We show that, at drug concentrations routinely achieved clinically in human plasma, atovaquone inhibits STAT3 phosphorylation, the expression of STAT3 target genes, and the viability of STAT3-dependent hematological cancer cells. These effects were also observed with atovaquone treatment of primary blasts isolated from patients with acute myelogenous leukemia or acute lymphocytic leukemia. Atovaquone is not a kinase inhibitor, but instead rapidly and specifically downregulates cell-surface expression of glycoprotein 130 (gp130), which is required for STAT3 activation in multiple contexts. The administration of oral atovaquone to mice inhibited tumor growth and prolonged survival in a murine model of multiple myeloma. Finally, in patients with acute myelogenous leukemia treated with hematopoietic stem cell transplantation, extended use of atovaquone for Pneumocystis prophylaxis was associated with improved relapse-free survival. These findings establish atovaquone as a novel, clinically-accessible STAT3 inhibitor with evidence of anti-cancer efficacy in both animal models and humans.
View details for DOI 10.1182/blood-2015-07-660506
View details for Web of Science ID 000385737900012
View details for PubMedID 27531676
View details for PubMedCentralID PMC5054697
- Brachytherapy boost and cancer-specific mortality in favorable high-risk and other high-risk prostate cancer. AMER SOC CLINICAL ONCOLOGY. 2016
Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer
JOURNAL OF CONTEMPORARY BRACHYTHERAPY
2016; 8 (1): 1-6
Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or T1c, Gleason 6, PSA > 20 ng/ml).We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors.EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022).Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined "favorable high-risk" category may be used to personalize therapy for men with high-risk disease.
View details for DOI 10.5114/jcb.2016.58080
View details for Web of Science ID 000372138300001
View details for PubMedID 26985191
View details for PubMedCentralID PMC4793071