Publisher Correction:Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence (Nature Genetics, (2018), 50, 4, (487-492), 10.1038/s41588-018-0071-6)

In the HTML version of the article originally published, the figures for Supplementary Figures 1–15 were incorrect and did not match the correct figures in the PDF of Supplementary Text and Figures. The error has been corrected in the HTML version of the article

Safety of Nivolumab Added to Chemoradiation Therapy Platforms for Intermediate and High-Risk Locoregionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504

PURPOSE: Programmed death-1 immune checkpoint blockade improves survival of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but the benefits of addition to (chemo)radiation for newly diagnosed patients with HNSCC remain unknown. METHODS AND MATERIALS: We evaluated the safety of nivolumab concomitant with 70 Gy intensity modulated radiation therapy and weekly cisplatin (arm 1), every 3-week cisplatin (arm 2), cetuximab (arm 3), or alone for platinum-ineligible patients (arm 4) in newly diagnosed intermediate- or high-risk locoregionally advanced HNSCC. Patients received nivolumab from 2 weeks prior to radiation therapy until 3 months post-radiation therapy. The primary endpoint was dose-limiting toxicity (DLT). If ≤2 of the first 8 evaluable patients experienced a DLT, an arm was considered safe. Secondary endpoints included toxicity and feasibility of adjuvant nivolumab to 1 year, defined as all 7 additional doses received by ≥4 of the first 8 evaluable patients across arms. RESULTS: Of 39 patients (10 in arms 1, 3, 4 and 9 in arm 2), 72% had T3-4 tumors, 85% had N2-3 nodal disease, and 67% had \u3e10 pack-years of smoking. There were no DLTs in arms 1 and 2, 1 in arm 3 (mucositis), and 2 in arm 4 (lipase elevation and mucositis in 1 and fatigue in another). The most common grade ≥3 nivolumab-related adverse events were lipase increase, mucositis, diarrhea, lymphopenia, hyponatremia, leukopenia, fatigue, and serum amylase increase. Adjuvant nivolumab was feasible as defined in the protocol. CONCLUSIONS: Concomitant nivolumab with the 4 tested regimens was safe for patients with intermediate- and high-risk HNSCC, and subsequent adjuvant nivolumab was feasible as defined (NCT02764593)

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study

BACKGROUND: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. METHODS: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. RESULTS: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. CONCLUSIONS: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. FUNDING: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. CLINICAL TRIAL NUMBER: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701

Cetuximab in the Treatment of Rheumatoid Arthritis

Members of the epidermal growth factor receptor (EGFR) family and their associated ligands are commonly expressed by synovial cells, and may be involved in the synovial hyperplasia seen in rheumatoid arthritis and its disease progression. This family of receptors is also expressed in cancer cells, and EGFR targeted therapy is now a mainstay of anticancer therapy. Cetuximab (Erbitux) is a monoclonal antibody directed against the EGFR extracellular receptor that has received Food and Drug Administration approval for the treatment of colorectal cancer as well as head and neck cancer. We report a case of a 61-year-old woman with an extensive history of rheumatoid arthritis requiring multiple therapies, who experienced a surprising remission of her disease and its symptoms while being treated with cetuximab for her head and neck cancer. The case as well as possible mechanisms of action are discussed. Further clinical investigations are clearly warranted

Exanetide and Pancreatic Cancer: A Case Report and Review of Relevant Literature

Introduction: Pancreatic cancer is the 4th most common cause of cancer death in the United States, and is associated with a 5 year survival rate of 5%. In recent years, epidemiological studies have raised the concern about a link between the use of antidiabetic drugs that act along the glucagon-like peptide pathway and the development of pancreatic cancer.  Additionally, pre-clinical studies have suggested that GLP-1 pathway agents may promote the malignant progression of pancreatic intraepithelial (PanIN). Exenatide, which is a glucagon-like peptide -1 agonist (GLP-1), is among the most commonly used agents in this class. Case presentation: The patient described in this case report presented with stage IV pancreatic cancer 5 years after the initiation of exanetide.  The patient and her husband raised the question of an association between exanetide and her cancer. Unfortunately, her cancer was refractory to gemcitabine based therapy, and she succumbed to her disease shortly after diagnosis.Conclusion:There is limited evidence to establish a link between this class of antidiabetic medication and pancreatic cancer. While there are preclinical studies that demonstrate a mechanism by which GLP-1 pathway drugs cause chronic pancreatitis and promotion of pancreatic oncogenesis, epidemiological studies are conflicting.  However, most of these studies had a fairly brief follow up period ( 5 years), and the process of oncogenesisis likely to be protracted over several years. This case, occurring 5 years after the initiation of the agent, highlights the need for longer epidemiological studies. As of 2007, over 700,000 patients had already used exanetide. Given the high usage of these medications and the poor prognosis associated with pancreatic cancer, any association is important. Long term clinical studies, and preclinical studies that explore the question of associated deleterious somatic mutations in this population are indicated