Purpose Alterations in DNA damage response and repair (DDR) genes are associated with increased mutation load and improved clinical outcomes in platinum-treated metastatic urothelial carcinoma. We examined the relationship between DDR alterations and response to PD-1/PD-L1 blockade. Methods Detailed demographic, treatment response, and long-term outcome data were collected on patients with metastatic urothelial carcinoma treated with atezolizumab or nivolumab who had targeted exon sequencing performed on pre-immunotherapy tumor specimens. Presence of DDR alterations was correlated with best objective response per Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free and overall survival. Results Sixty patients with urothelial cancer enrolled in prospective trials of anti-PD-1/PD-L1 antibodies met inclusion criteria. Any DDR and known or likely deleterious DDR mutations were identified in 28 (47%) and 15 (25%) patients, respectively. The presence of any DDR alteration was associated with a higher response rate (67.9% v 18.8%; P < .001). A higher response rate was observed in patients whose tumors harbored known or likely deleterious DDR alterations (80%) compared with DDR alterations of unknown significance (54%) and in those whose tumors were wild-type for DDR genes (19%; P < .001). The correlation remained significant in multivariable analysis that included presence of visceral metastases. DDR alterations also were associated with longer progression-free and overall survival. Conclusion DDR alterations are independently associated with response to PD-1/PD-L1 blockade in patients with metastatic urothelial carcinoma. These observations warrant additional study, including prospective validation and exploration of the interaction between tumor DDR alteration and other tumor/host biomarkers of immunotherapy response.

Our findings provide additional support for the National Comprehensive Cancer Network (NCCN) guidelines that categorize TNT as a viable treatment strategy for rectal cancer. Our data suggest that TNT facilitates delivery of planned systemic therapy. Long-term follow-up will determine if this finding translates into improved survival. In addition, given its high CR rate, TNT may facilitate nonoperative treatment strategies aimed at organ preservation.

This largest Western series to evaluate the utility of preoperative inflammatory markers in patients with HCC found that only PLR was associated with RFS and OS and that albumin was associated with MVI.

Guidelines recommend vaccination starting 12 months after autologous hematopoietic stem cell transplant (aHCT), but there is varying practice for patients on maintenance therapy, with some centers not immunizing at all. Because of decreased vaccine rates among the general population causing loss of herd immunity, we aimed to establish the safety and efficacy of revaccinating multiple myeloma patients on lenalidomide maintenance (LM). Of the 122 patients who were vaccinated after aHCT between 2010 and 2014 at Memorial Sloan Kettering Cancer Center, 91 (75%) were on LM. Vaccine responses were defined by increases between pre- and postvaccination titers. Reponses varied by vaccine type with 76% responding to pertussis, 70% diphtheria, 60% tetanus, 71% Haemophilus influenzae, and 58% pneumococcal. All patients retained minimal levels of polio immunity, but 27% responded with increased titers. Fewer patients received hepatitis A and B, but of those who did, 30% responded to hepatitis A and 40% to hepatitis B. No differences were seen in rates of response for those on LM at time of vaccination compared with those who were not. There were no vaccine-related adverse effects. Reimmunization with inactivated vaccines in patients on LM is therefore both safe and effective, offering this population immunity to vaccine-preventable diseases.

Cyst size stability at the 5-year time point did not preclude future growth, cross-over to resection, or carcinoma development. Patients who were stable at 5 years had a nearly 3-fold higher risk of developing cancer compared with the general population and should continue long-term surveillance.

Understanding the molecular and phenotypic profile of colorectal cancer (CRC) in West Africa is vital to addressing the regions rising burden of disease. Tissue from unselected Nigerian patients was analyzed with a multigene, next-generation sequencing assay. The rate of microsatellite instability is significantly higher among Nigerian CRC patients (28.1%) than patients from The Cancer Genome Atlas (TCGA, 14.2%) and Memorial Sloan Kettering Cancer Center (MSKCC, 8.5%, P < 0.001). In microsatellite-stable cases, tumors from Nigerian patients are less likely to have APC mutations (39.1% vs. 76.0% MSKCC P < 0.001) and WNT pathway alterations (47.8% vs. 81.9% MSKCC, P < 0.001); whereas RAS pathway alteration is more prevalent (76.1% vs. 59.6%, P = 0.03). Nigerian CRC patients are also younger and more likely to present with rectal disease (50.8% vs. 33.7% MSKCC, P < 0.001). The findings suggest a unique biology of CRC in Nigeria, which emphasizes the need for regional data to guide diagnostic and treatment approaches for patients in West Africa.

In this manuscript, we demonstrate that hepatic arterial infusion chemotherapy (HAIC) may provide comparable survival to resection for patients with liver-limited intrahepatic cholangiocarcinoma (IHC) and lymph node metastases (LNM). HAIC is an attractive form of liver-directed therapy and can be offered with lower morbidity and mortality risk than liver resection, while also providing adequate disease control for traditionally unresectable patients.Moreover, this manuscript bridges the translational connection between genomics and clinical care by analyzing the next generation sequencing (NGS) data for this cohort of patients, treated with both modalities. Patients with N1 disease and high-risk alterations, which included mutations in KRAS and TP53, and deletions in CDKN2A and CDKN2B, had significantly worse prognosis, regardless of treatment. Conversely, mutations in IDH1 and IDH2 as well as FGFR2 fusion events, had no association with survival. Our results support the routine use of NGS in all patients with IHC, which may provide valuable insights into which patients are unlikely to derive benefit from any form of liver-directed therapy Research.

BackgroundColorectal cancer (CRC) is the third most common cancer worldwide. Mortality for CRC is improving in high income countries, but in low and middle income countries, rates of disease and death from disease are rising. In Sub‐Saharan Africa, the ratio of CRC mortality to incidence is the highest in the world. This study investigated the nature of CRC treatment currently being offered and received in Nigeria.MethodsBetween April 2013 and October 2017, a prospective study of consecutively diagnosed cases of CRC was conducted. Patient demographics, clinical features, and treatment recommended and received was recorded for each case. Patients were followed during the study period every 3 months or until death.ResultsThree hundred patients were included in our analysis. Seventy‐one percent of patients received a recommended surgical operation. Of those that didn't undergo surgery as recommended, 37% cited cost as the main reason, 30% declined due to personal reasons, and less than 5% absconded or were lost to follow up. Approximately half of patients (50.5%) received a chemotherapy regimen when it was recommended, and 4.1% received radiotherapy when this was advised as optimal treatment. With therapy, the median overall survival for patients diagnosed with stage III and stage IV CRC was 24 and 10.5 months respectively. Overall, we found significantly better median survival for patients that received the recommended treatment (25 vs 7 months; P < .01).ConclusionsA number of patients were unable to receive the recommended treatment, reflecting some of the burden of untreated CRC in the region. Receiving the recommended treatment was associated with a significant difference in outcome. Improved healthcare financing, literacy, training, access, and a better understanding of tumor biology will be necessary to address this discrepancy.