Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8þ) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3 0 region of BRCA2 (c.7914þ) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR ¼ 1.78; 95% confidence interval (CI), 1.25-2.52; P ¼ 0.001], as well as elevated risk of Gleason 8þ prostate cancer (HR ¼ 3.11; 95% CI, 1.63-5.95; P ¼ 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR ¼ 2.83; 95% CI, 1.71-4.68; P ¼ 0.00004) and elevated risk of Gleason 8þ prostate cancer (HR ¼ 4.95; 95% CI, 2.12-11.54; P ¼ 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer.Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
Background. There are still few data on the activity and safety of cetuximab-based salvage chemotherapy after immunotherapy (SCAI) in patients with squamous cell cancer of the head and neck (SCCHN). Materials and Methods. Retrospective study of patients with SCCHN who received cetuximab-based SCAI after PD1 or PDL1 (PD(L)1) inhibitors. Overall response rate (ORR) and disease control rate (DCR) with SCAI and with last chemotherapy before immunotherapy (LCBI) by RECIST 1.1, percentage change from baseline in target lesions (PCTL), progression-free survival (PFS), overall survival (OS), treatment compliance and toxicity were evaluated. Results. Between March 2016 and November 2019, 23 patients were identified. SCAI consisted of cetuximabbased combinations (3wkCDDP-5FU-Cetuximab (n=2), wkPaclitaxel-Cetuximab (n=17), wkCDDP-Cetuximab (n=2), wkCBDCA-Paclitaxel-Cetuximab (n=2)). ORR was 56.5% (11 partial response (PR), 2 complete response (CR)). DCR was 78.3%. Among 13 objective responders, median best PCTL was-53.5% (range:-30% to-100%). Median OS and PFS were 12m and 6m, respectively. In 10 patients receiving LCBI, ORR to LCBI was 40%, while ORR to SCAI achieved 60%. In LCBI-treated patients median PFS with LCBI was 8m and median PFS and OS with SCAI were 7m and 12m, respectively. Reduced dose intensity of the chemotherapy and cetuximab components occurred in 82.6% and 52.2% of the patients. Grade 1 or 2 AEs occurred in all patients. Grade 3 or 4 AEs developed in 65%, being grade 3 in all of them except in one patient (grade 4 neutropenia). There were no treatment-related deaths. Conclusion. Cetuximab-based salvage chemotherapy after PD(L)1 inhibitors associated with high response rates and deep tumor reductions with a manageable safety profile. Subsequent lines of therapy may explain the long survival achieved in our series. These results invite to design studies to elucidate the best therapeutic sequence in patients with SCCHN in the immunotherapy era. The Oncologist 2021;9999:• • Implications for Practice: Cetuximab-based salvage chemotherapy (SCAI) achieved high response rates in patients with R/M SCCHN after progression to PD1/PDL1 inhibitors. Objective response rate was higher and progression-free survival was comparable to that of chemotherapy administered before immunotherapy (IO). In most patients, SCAI consisted of weekly, welltolerated regimens. These observations have implications for current practice due to the limited evidence to date in SCCHN and the scant therapeutic options in this disease, and invite to elucidate which may be the best treatment sequence for head and neck cancer patients in the IO era.
Renal cell cancer has been rarely reported as a cause of gastric or esophageal metastases. They usually present with gastrointestinal bleeding and most cases have been managed surgically or endoscopically. We report the case of a 38-year-old man with a 4-year history of metastatic renal cell carcinoma admitted to the emergency room with melena and anemia. At endoscopy, three esophageal polypoid lesions (middle and distal thirds) and a 7 cm mass in the gastric fundus were identified. Biopsy revealed esophageal mucosa infiltrated by renal cell carcinoma. Radiotherapy was administered (30 Gy in 10 fractions), followed by pazopanib, with excellent tolerance and without new bleeding episodes. Computed tomography scan showed complete disappearance of the esophageal and fundic lesions at 3 months follow-up. Twenty-four months after being initiated on pazopanib, there is no radiological evidence of disease. This is the first reported case showing complete remission of gastric and esophageal metastases after treatment with radiotherapy and pazopanib.
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