Cs-131 brachytherapy for patients with recurrent glioblastoma combined with bevacizumab avoids radiation necrosis while maintaining local control.

PURPOSE: Re-irradiation of recurrent glioblastoma (GBM) may delay further recurrence but re-irradiation increases the risk of radionecrosis (RN). Salvage therapy should focus on balancing local control (LC) and toxicity. We report the results of using intraoperative Cesium-131 (Cs-131) brachytherapy for recurrent GBM in a population of patients who also received bevacizumab. METHODS AND MATERIALS: Twenty patients with recurrent GBM underwent maximally safe neurosurgical resection with Cs-131 brachytherapy between 2010 and 2015. Eighty Gy was prescribed to 0.5 cm from the surface of the resection cavity. All patients previously received adjuvant radiotherapy and temozolomide, and received bevacizumab before or after salvage brachytherapy. Seven of 20 (35%) tumors were multiply recurrent and had been previously salvaged with external beam radiotherapy. Patients received MRI scans every 2 months monitored for recurrence, progression, and RN. RESULTS: Median tumor diameter was 4.65 cm (range, 1.2-6.3 cm). Median number of seeds pace was 41 (range, 20-74) with total seed activity 96.8U (range, 41.08-201.3U). At a median followup of 19 months, crude LC was 85% and median overall survival was 9 months (range, 5-26 months). There were two postoperative wound infections (10%), three seizures (15%), and 0% incidence of RN. CONCLUSIONS: Our study demonstrates that while LC and survival are similar to other studies of postoperative external beam radiotherapy, no RN occurred in any of these patients, including 7 multiply re-irradiated patients. Of interest, there were patients with multiple recurrences whose survival extended beyond 20 months. These findings suggest that the use of highly conformal Cs-131 brachytherapy is a promising treatment for patients with recurrent GBM with minimal risk of development of RN.

Omission of Adjuvant Radiotherapy in the Elderly Breast Cancer Patient: Missed Opportunity?

PURPOSE: We used the National Cancer Data Base to analyze practice patterns of adjuvant breast radiotherapy (RT) in elderly patients to see if a difference in overall survival (OS) could be detected. Additionally, we investigated factors that affected OS in these patients. PATIENTS AND METHODS: Women aged ≥ 65 years with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative pathologic T1-T2N0M0 invasive breast cancer measuring up to 3 cm who were treated with breast conservation and adjuvant endocrine therapy without adjuvant chemotherapy were identified and stratified by use of adjuvant RT. Multivariable Cox proportional hazards modeling was used to examine the association of treatment and mortality adjusting for demographic, socioeconomic, and clinicopathologic factors. Kaplan-Meier analysis was used to estimate overall 5-year survival in patients who did or did not receive adjuvant RT, and to compare those groups. RESULTS: A total of 61,395 patients with a median follow-up of 48.7 months (range, 0-107 months) were identified. On Cox regression analysis, improved OS was associated with treatment at an academic facility, younger age, higher income level, lower Charlson-Deyo comorbidity index, and receipt of adjuvant RT (all P < .05). The overall 5-year survival rate was 93.0% (95% confidence interval 92.7-93.3) in the adjuvant RT group and 83.6% (95% confidence interval 82.5-84.7) in the nonadjuvant RT group (P < .0001). CONCLUSION: Improved survival is associated with the receipt of adjuvant RT for older women with early-stage hormone receptor-positive HER2-negative breast cancer who received adjuvant endocrine therapy. However, there are many limitations inherent to a retrospective database study such as ours, so the findings should be taken with caution.

Role of Postoperative Radiotherapy in Pathologic Stage IIIA (N2) Non-Small Cell Lung Cancer in a Prospective Nationwide Oncology Outcomes Database.

INTRODUCTION: The role of postoperative radiotherapy (PORT) in the treatment of pathologic stage IIIA (N2) NSCLC remains controversial. We investigated practice patterns and outcomes for these patients in a prospectively maintained nationwide oncology outcomes database. METHODS: Patients with known histologic features of pathologic stage IIIA (N2) NSCLC who underwent an operation with negative margins and received adjuvant multiagent chemotherapy from 2004 to 2013 were identified from the National Cancer Data Base and stratified by the use of PORT. Multivariable logistic regression modeling was used to examine factors associated with receiving PORT, and multivariable proportional hazards regression was used to examine the association of treatment and mortality, adjusting for demographic, socioeconomic and clinicopathologic factors. Landmark analysis and covariate balancing propensity score (CBPS) weighting were also explored to account for immortal time bias and nonrandomization. RESULTS: A total of 2691 patients were identified, with a median follow-up of 32.32 months. In multivariable analysis, improved overall survival was associated with multiple factors, including younger age, female sex, lower Charlson-Deyo comorbidity index, histologic type (with squamous cell being better than adenocarcinoma), smaller tumor size, lower pathologic T stage, surgical procedure (with pneumonectomy or lobectomy being better than sublobar resection), and receipt of PORT (all p < 0.05). Before landmark analysis, the hazard ratio (HR) showed an overall survival benefit for patients receiving PORT (adjusted HR = 0.83, 95% CI [confidence interval]: 0.72-0.95; p = 0.008). This benefit remained significant after CBPS weighting (HR = 0.81, 95% CI: 0.70-0.94, p = 0.005), almost significant after landmark analysis (adjusted HR = 0.84, 95% CI: 0.69-1.007, p = 0.059), and significant after landmark analysis with CBPS weighting (HR = 0.77, 95% CI: 0.63-0.94, p = 0.009). Median survival past landmark time was 27.43 months in the PORT group and 25.86 months in the non-PORT group. Factors significantly associated with receiving PORT were facility location, facility type, Charlson-Deyo comorbidity index, and grade (all p < 0.05). CONCLUSIONS: Improved survival is associated with receipt of PORT for patients with pathologic stage IIIA (N2) NSCLC treated with complete resection and multiagent chemotherapy.

Addition of Surgery After Radiation Significantly Improves Survival in Stage IIIB Non-small Cell Lung Cancer: A Population-Based Analysis.

OBJECTIVES: Limited work, either retrospective or prospective, has been done to investigate whether or not there is a cause-specific mortality (CSM) or all-cause mortality (ACM) benefit to adding surgery following neoadjuvant treatment for Stage IIIB NSCLC. METHODS: We extracted patients with Stage IIIB NSCLC from the Survival, Epidemiology, and End Results Program (SEER) database treated from 2004 to 2012 with either radiation alone or radiation followed by surgery. Other variables extracted were age, sex, race, and tumor location. The impact of patient and treatment variables on CSM and ACM was explored using Cox multivariable regression analysis. RESULTS: A total of 14,065 patients were extracted from the SEER database. On multivariable analysis, even after adjustment for age, gender, race, and site, radiation followed by surgery was associated with a reduction in cause-specific mortality compared to radiation alone (adjusted HR 0.46; 95 % CI 0.41, 0.52; p < 0.0001). Median overall survival was 11 months in the radiotherapy alone arm versus 29 months in the radiotherapy plus surgery arm (p < 0.0001 by log-rank test). After adjustment for these same factors, radiation followed by surgery was also associated with a reduction in all-cause mortality compared with radiation alone (adjusted HR 0.47; 95 % CI 0.42, 0.52; p < 0.0001). Median cause-specific survival was 12 months in the radiotherapy alone arm versus 33 months in the radiotherapy plus surgery arm (p < 0.0001 by log-rank test). DISCUSSION: In the SEER database, there appears to be both a CSM and ACM benefit to adding surgery following radiation for Stage IIIB NSCLC.

Evaluation of Outcomes in Patients With Carcinoma of the Cervix Treated With Concurrent Radiation and Cisplatin Versus Cisplatin/5-FU Compared With Radiation Alone.

OBJECTIVES: The objective of this study was to compare outcomes for patients with cervical cancer treated with radiation concurrently with cisplatin, cisplatin/5-fluorouracil (5-FU), or without chemotherapy. MATERIALS AND METHODS: We reviewed the records of eligible patients with locoregionally confined, stage IB1 through IVA, intact cervical cancer who were treated at Northwestern Memorial Hospital. All patients underwent definitive radiotherapy with combined external beam radiation-the majority with extended-field (62%)-and received low-dose rate brachytherapy. RESULTS: A total of 236 patients were included: 99 had no concurrent chemotherapy, 95 were treated with concurrent cisplatin, and 42 were treated with cisplatin/5-FU. For all patients treated with or without chemotherapy, overall survival at 5 and 10 years was 64% and 59%, respectively. Patients treated with chemotherapy had a superior recurrence-free survival rate of 69% at 5 years versus 49% in patients who did not receive chemotherapy (P=0.09). Twenty-six percent of patients treated with cisplatin alone, 31% of patients treated with cisplatin/5-FU, and 45% of patients who did not receive chemotherapy experienced a disease recurrence. Adenosquamous histology conferred a higher rate of recurrence as compared with adenocarcinoma and squamous cell histologies (54% vs. 34%, respectively; P=0.05). CONCLUSIONS: Cisplatin-based concurrent chemoradiotherapy showed a trend toward improved recurrence-free survival survival in the definitive treatment of nonmetastatic cervical cancer. The addition of 5-FU to cisplatin did not appear to significantly impact survival or recurrence-free survival. Adenosquamous histology was associated with a higher risk of recurrence as compared with other histologic subtypes.

Characterization of antigenic variants of hepatitis C virus in immune evasion.

BACKGROUND: Antigenic variation is an effective way by which viruses evade host immune defense leading to viral persistence. Little is known about the inhibitory mechanisms of viral variants on CD4 T cell functions. RESULTS: Using sythetic peptides of a HLA-DRB1*15-restricted CD4 epitope derived from the non-structural (NS) 3 protein of hepatitis C virus (HCV) and its antigenic variants and the peripheral blood mononuclear cells (PBMC) from six HLA-DRB1*15-positive patients chronically infected with HCV and 3 healthy subjects, the in vitro immune responses and the phenotypes of CD4+CD25+ cells of chronic HCV infection were investigated. The variants resulting from single or double amino acid substitutions at the center of the core region of the Th1 peptide not only induce failed T cell activation but also simultaneously up-regulate inhibitory IL-10, CD25-TGF-ß+ Th3 and CD4+IL-10+ Tr1 cells. In contrast, other variants promote differentiation of CD25+TGF-ß+ Th3 suppressors that attenuate T cell proliferation. CONCLUSIONS: Naturally occuring HCV antigenic mutants of a CD4 epitope can shift a protective peripheral Th1 immune response into an inhibitory Th3 and/or Tr1 response. The modulation of antigenic variants on CD4 response is efficient and extensive, and is likely critical in viral persistence in HCV infection.