Health care disparities among octogenarians and nonagenarians with stage II and III rectal cancer.

BACKGROUND: Octogenarians and nonagenarians with stage II/III rectal adenocarcinomas are underrepresented in the randomized trials that have established the standard-of-care therapy of preoperative chemoradiation followed by definitive resection (ie, chemoradiation and then surgery [CRT+S]). The purpose of this study was to evaluate the impact of therapies on overall survival (OS) for patients with stage II/III rectal cancers and determine predictors of therapy within the National Cancer Data Base (NCDB). METHODS: In the NCDB, patients who were 80 years old or older and had clinical stage II/III rectal adenocarcinoma from 2004 to 2013 were queried. Kaplan-Meier analysis, log-rank testing, logistic regression, Cox proportional hazards regression, interaction effect testing, and propensity score-matched analysis were conducted. RESULTS: The criteria were met by 2723 patients: 14.9% received no treatment, 29.7% had surgery alone, 5.0% underwent short-course radiation and then surgery (RT+S), 45.3% underwent CRT+S, and 5.1% underwent surgery and then chemoradiation (S+CRT). African American race and residence in a less educated county were associated with not receiving treatment. Male sex, older age, worsening comorbidities, and receiving no treatment or undergoing surgery alone were associated with worse OS. There was no statistical difference in OS between RT+S, S+CRT, and CRT+S. Interaction testing found that CRT+S improved OS independently of age, comorbidity status, sex, race, and tumor stage. In the propensity score-matched analysis, CRT+S was associated with improved OS in comparison with surgery alone. CONCLUSIONS: A significant portion of octogenarians and nonagenarians with stage II/III rectal adenocarcinomas do not receive treatment. African American race and living in a less educated community are associated with not receiving therapy. This series suggests that CRT+S is a reasonable strategy for elderly patients who can tolerate therapy. Cancer 2017;123:4325-36. © 2017 American Cancer Society.

Dosimetric Factors Related to Radiation Necrosis After 5-Fraction Radiosurgery for Patients With Resected Brain Metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs. METHODS AND MATERIALS: From 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator-based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic. RESULTS: Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm3, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not. CONCLUSIONS: To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning.

Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: analysis of the national cancer data base.

BACKGROUND: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation (CRT) in the National Cancer Data Base (NCDB). METHODS: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis (UVA) was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. RESULTS: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n=498, 46.8%) and HPV- (n=565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR: 0.60, 95% CI: 0.38-0.96; P=0.034). However, for women, HPV infection did not significantly influence survival (HR: 1.47, 95% CI: 0.96-2.25; P=0.074). CONCLUSIONS: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.

TNFRSF10C copy number variation is associated with metastatic colorectal cancer.

BACKGROUND: Genetic markers for distant metastatic disease in patients with colorectal cancer (CRC) are not well defined. Identification of genetic alterations associated with metastatic CRC could help to guide systemic and local treatment strategies. We evaluated the association of tumor necrosis factor receptor superfamily member 10C (TNFRSF10C) copy number variation (CNV) with distant metastatic disease in patients with CRC using The Cancer Genome Atlas (TCGA). METHODS: Genetic sequencing data and clinical characteristics were obtained from TCGA for all available patients with CRC. There were 515 CRC patient samples with CNV and clinical outcome data, including a subset of 144 rectal adenocarcinoma patient samples. Using the TCGA CRC dataset, CNV of TNFRSF10C was evaluated for association with distant metastatic disease (M1 vs. M0). Multivariate logistic regression analysis with odds ratio (OR) using a 95% confidence interval (CI) was performed adjusting for age, T stage, N stage, adjuvant chemotherapy, gender, microsatellite instability (MSI), location, and surgical margin status. RESULTS: TNFRSF10C CNV in patients with CRC was associated with distant metastatic disease [OR 4.81 (95% CI, 2.13-10.85) P<0.001] and positive lymph nodes [OR 18.83 (95% CI, 8.42-42.09)]; P<0.001) but not MSI (OR P=0.799). On multivariate analysis, after adjusting for pathologic T stage, N stage, adjuvant chemotherapy, gender, and MSI, TNFRSF10C CNV remained significantly associated with distant metastatic disease (OR P=0.018). Subset analysis revealed that TNFRSF10C CNV was also significantly associated with distant metastatic disease in patients with rectal adenocarcinoma (OR P=0.016). CONCLUSIONS: TNFRSF10C CNV in patients with CRC is associated with distant metastatic disease. With further validation, such genetic profiles could be used clinically to support optimal systemic treatment strategies versus more aggressive local therapies in patients with CRC, including radiation therapy for rectal adenocarcinoma.

Cholangiocarcinoma size on magnetic resonance imaging versus pathologic specimen: Implications for radiation treatment planning.

PURPOSE: The accuracy of abdominal magnetic resonance imaging (MRI) in measuring gross tumor volume in patients with resectable cholangiocarcinoma (CC) is unknown. CC is a highly difficult tumor to visualize and treatment with dose-escalated radiation therapy requires clear tumor delineation. We aim to investigate the concordance between imaging and pathologic size in patients with resected CC to determine the usefulness of MRI for image guided treatment modalities. METHODS AND MATERIALS: The records of 51 patients with resected CC who underwent preoperative MRI were evaluated. Each preoperative MRI was individually reviewed by a diagnostic radiologist (P.M.), who was blinded to pathologic measurements. A combination of dynamic multiphase contrast-enhanced T1- and T2-weighted images, original imaging reports, and pathologic reports were reviewed for greatest tumor dimensions. A general linear regression model was used to examine the outcome MRI minus pathology using MRI report, T1-weighted measurement, or T2-weighted measurement. A multivariable regression model was fit to assess the association of other factors with pathologic underestimation. RESULTS: The median age was 69 years. Eleven tumors were categorized distal/extrahepatic, 17 hilar, and 23 intrahepatic CC. The median tumor size on pathology report was 3.00 cm (range, 0.3-19). The median tumor size from the MRI report was 3 cm (range, 0.80-16.20) and median tumor size on independent radiological review was 3 cm (range, 0.90-17) on the T1-weighted and 3 cm (range, 0.90-17) on the T2-weighted MRI sequences. When compared with pathologic tumor size, the MRI report dimension was found to underestimate tumor size by 4.1 mm (P = .04). On multivariable analysis, pathologic size underestimation was influenced by increasing tumor size (slope, -0.20; P < .001); however, underestimation was not affected by tumor location or MRI sequence. CONCLUSIONS: MRI underestimates tumor size, which was more pronounced with larger tumors, but not influenced by tumor location. The potential for gross tumor volume underestimation should be considered when planning highly conformal radiation therapy treatment of CC.