Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab. METHODS: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response. CONCLUSION: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024.

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Ten-Year Update of a Randomized, Prospective Trial of Conventional Fractionated Versus Moderate Hypofractionated Radiation Therapy for Localized Prostate Cancer.

PURPOSE: The previously published single institution randomized prospective trial failed to show superiority in the 5-year biochemical and/or clinical disease failure (BCDF) rate with moderate hypofractionated intensity-modulated radiation therapy (H-IMRT) versus conventionally fractionated IMRT (C-IMRT). We now present 10-year disease outcomes using updated risk groups and definitions of biochemical failure. METHODS: Men with protocol-defined intermediate- and high-risk prostate adenocarcinoma were randomly assigned to receive C-IMRT (76 Gy in 38 fractions) or H-IMRT (70.2 Gy in 26 fractions). Men with high-risk disease were all prescribed 24 months of androgen deprivation therapy (ADT) and had lymph node irradiation. Men with intermediate risk were prescribed 4 months of ADT at the discretion of the treating physician. The primary endpoint was cumulative incidence of BCDF. We compared disease outcomes and overall mortality by treatment arm, with sensitivity analyses for National Comprehensive Cancer Network (NCCN) risk group adjustment. RESULTS: Overall, 303 assessable men were randomly assigned to C-IMRT or H-IMRT. The median follow-up was 122.9 months. Per updated NCCN risk classification, there were 28 patients (9.2%) with low-risk, 189 (62.4%) with intermediate-risk, and 86 (28.4%) with high-risk prostate cancer. The arms were equally balanced for clinicopathologic factors, except that there were more black patients in the C-IMRT arm (17.8% v 7.3%; P = .02). There was no difference in ADT use (P = .56). The 10-year cumulative incidence of BCDF was 25.9% in the C-IMRT arm and was 30.6% in the H-IMRT arm (hazard ratio, 1.31; 95% CI, 0.82 to 2.11). The two arms also had similar cumulative 10-year rates of biochemical failure, prostate cancer-specific mortality, and overall mortality; however, the 10-year cumulative incidence of distant metastases was higher in the H-IMRT arm (rate difference, 7.8%; 95% CI, 0.7% to 15.1%). CONCLUSION: H-IMRT failed to demonstrate superiority compared with C-IMRT in long-term disease outcomes.

Clustered Microcysts at Breast US: Outcomes and Updates for Appropriate Management Recommendations.

Background Clustered microcysts are common, especially in perimenopausal women, and are seen in up to 6% of US examinations. However, there are limited published data on appropriate assessment and management recommendations for clustered microcysts on breast US images. Purpose To determine outcomes of lesions identified as clustered microcysts on breast US images to help guide appropriate management recommendations. Materials and Methods Lesions classified as clustered microcysts at breast US were retrospectively identified in women at two hospitals (a large tertiary care academic hospital and a National Comprehensive Cancer Network-designated comprehensive cancer center) within one metropolitan health system from 2005 through 2015. If US-guided tissue sampling was performed, results were obtained from the pathology or cytology reports. If sampling was not performed, only lesions with at least 24 months of imaging follow-up or any imaging follow-up with interval resolution or decrease in size were included in the study. Data were evaluated using standard statistics, Fisher exact tests, and Wilcoxon rank sum tests. Results A total of 189 women (median age, 52 years [interquartile range, 46-59 years]) with 196 lesions classified as clustered microcysts on US images were included in this study. During the surveillance period of at least 24 months and at tissue diagnosis, malignancy was not found in any of the 196 lesions (0%) (95% confidence interval: 0.0%, 1.9%). A total of 158 of 196 (80%) lesions were followed with imaging, and 38 of 196 (20%) lesions underwent percutaneous sampling. During the follow-up period, 28 of 158 (18%) lesions spontaneously resolved, 13 of 158 (8%) decreased in size, and one of 158 lesions (0.6%) increased at 18-month follow-up but then became stable. One hundred sixteen of 158 lesions (73%) demonstrated no change at follow-up imaging, 38 of 196 (19%) lesions underwent percutaneous sampling, and 38 of 38 (100%) revealed benign results. Conclusion No malignancies were identified in this series. These results further support the existing literature that lesions characterized as clustered microcysts demonstrate a very low risk of malignancy and can be classified as benign. Biopsy may be safely avoided. © RSNA, 2020 See also the editorial by Berg in this issue.

Adherence to postresection colorectal cancer surveillance at National Cancer Institute-designated Comprehensive Cancer Centers.

Guidelines recommend surveillance after resection of colorectal cancer (CRC), but rates of adherence to surveillance are variable and have not been studied at National Cancer Institute (NCI)-designated Comprehensive Cancer Centers. The aim of this study was to determine rates of adherence to standard postresection CRC surveillance recommendations including physician visits, carcinoembryonic antigen (CEA), computed tomography (CT), and colonoscopy after CRC resection at three NCI-designated centers. Data on patients with resected CRC from 2010 to 2017 were reviewed. Adherence to physician visits was defined as having at least two visits within 14 months after surgical resection. CEA adherence was defined as having at least four CEA levels drawn within 14 months. CT and colonoscopy adherence were defined as completing each between 10 and 14 months from surgical resection. Chi-square test and logistic regression analyses were performed for overall adherence and adherence to individual components. A total of 241 CRC patients were included. Overall adherence was 23%. While adherence to physician visits was over 98%, adherence to CEA levels, CT, and colonoscopy were each less than 50%. Center was an independent predictor of adherence to CEA, CT, and/or colonoscopy. Stage III disease predicted CT adherence, while distance traveled of 40 miles or less predicted colonoscopy adherence. Overall adherence to postresection CRC guideline-recommended care is low at NCI-designated centers. Adherence rates to surveillance vary by center, stage, and distance traveled for care. Understanding factors associated with adherence is critical to ensure CRC patients benefit from postresection surveillance.

Implementation of a comprehensive cancer control program at the worksite: year one summary report.

The worksite is an ideal forum for cancer risk assessment. We describe here the baseline characteristics of a large cohort. Participants completed surveys that assessed a variety of risk factors and behavioral mediators. Personalized feedback letters identified cancer risks. A total of 4395 surveys were received. Cancer prevalence was 6.5% (range, 4.3% to 11.2%). The most common risk factors were lack of exercise (41%; 32% to 68%), obesity (28%; 24% to 39%), and smoking (14%; 13% to 32%). Cardiovascular risk was also common (25%; 15% to 48%). Screening was fair to good for all cancers except colon cancer. The perceived risk for cancer was less than that for cardiovascular disease (P < 0.0001). Most smokers were in the pre-contemplation phase, whereas action/maintenance phases predominated for breast and colon cancer screening. Modifiable cancer risk factors can be identified in the majority of workers. Inaccurate risk perception is an important target for future interventions.