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Introduction: We aimed to determine the prevalence and landscape of germline mutations among patients with young onset pancreatic ductal adenocarcinoma (PDAC) as well as their influence in prognosis. Methods: Patients from two cohorts were studied, the High Risk Cohort (HRC) which included 584 PDAC patients who received genetic counseling at MD Anderson Cancer Center and a General Cohort (GC) with 233 metastatic PDAC patients. We defined germline DNA sequencing on 13 known pancreatic cancer susceptibility genes. The prevalence and landscape of mutations was determined and clinical characteristics including survival were analyzed. Results: A total of 409 patients underwent genetic testing (277 from HRC and 132 from GC). As expected, the HRC had higher prevalence of germline mutations compared to the GC: 17.3% vs 6.81%. The most common mutations in both cohorts were in BRCA1/2 and mismatch repair (MMR) genes. Patients younger than 60 years old had significantly higher prevalence of germline mutations in both the HRC (OR: 1.93 +/−1.03–3.70, P: 0.039) and GC (4.78 +/−1.10–32.95, P: 0.036). Furthermore, PDAC patients with germline mutations in the GC had better overall survival than patients without mutations (HR= 0.44, 95% CI of HR: 0.25–0.76, p: 0.030). Discussion Germline mutations are highly prevalent in patients with PDAC of early-onset and can be predictive of better outcomes. Considering emerging screening strategies for relatives carrying susceptibility genes as well as impact on therapy choices, genetic counseling and testing should be encouraged in PDAC patients, particularly those of young onset.

Key Points Cold agglutinin syndrome is one of the rare immune-related adverse events of nivolumab. Rituximab should be considered for treatment of nivolumab-induced cold agglutinin syndrome.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454‐489.