Understanding the Impact of Population and Cancer Type on Tumor Mutation Burden Scores: A Comprehensive Whole-Exome Study in Cancer Patients From India.

PURPOSE: The purpose of this study was to understand the impact of population diversity and geographic variation on tumor mutation burden (TMB) scores across cancers and its implication on stratification of patients for immune checkpoint inhibitor (ICI) therapy. MATERIALS AND METHODS: This retrospective study used whole-exome sequencing (WES) to profile 1,233 Indian patients with cancer across 30 different cancer types and to estimate their TMB scores. A WES-based pipeline was adopted, along with an indigenously developed strategy for arriving at true somatic mutations. A robust unsupervised machine learning approach was used to understand the distribution of TMB scores across different populations and within the population. RESULTS: The results of the study showed a biphasic distribution of TMB scores in most cancers, with different threshold scores across cancer types. Patients with cancer in India had higher TMB scores compared with the Caucasian patients. We also observed that the TMB score value at 90th percentile (predicting high efficacy to ICI) was high in four different cancer types (sarcoma, ovary, head and neck, and breast) in the Indian cohort as compared with The Cancer Genome Atlas or public cohort. However, in lung and colorectal cancers, the TMB score distribution was similar between the two population cohorts. CONCLUSION: The findings of this study indicate that it is crucial to benchmark both cancer-specific and population-specific TMB distributions to establish a TMB threshold for each cancer in various populations. Additional prospective studies on much larger population across different cancers are warranted to validate this observation to become the standard of care.

Short-Term Surgical Outcomes of Standard and Lateral Video Endoscopic Inguinal Lymphadenectomy: A Multinational Retrospective Study.

Background: Video endoscopic inguinal lymphadenectomy (VEIL) is a minimally invasive technique that gives superior surgical outcomes than open inguinal lymphadenectomy (IL) for treating lymph node metastasis in penile, vulvar, and skin cancers. This study compared surgical outcomes obtained with two different approaches of VEIL, standard VEIL and lateral VEIL (L-VEIL), in cancer patients. Methods: Sixty-two patients who underwent standard VEIL (n = 15) or L-VEIL (n = 47) for treatment of lymph node metastasis were evaluated retrospectively from three centers in Brazil, Egypt, and India. Primary endpoint analyzed was conversion rate to open IL in the two groups, and the secondary endpoints included operative time, estimated blood loss, nodal yield, nodal positivity, postoperative drain duration, and postoperative complications. Results: The conversion rate to open IL was higher in L-VEIL compared with VEIL group (2% vs. 0%). Significantly lesser blood loss was reported with L-VEIL compared with VEIL (mean difference: 3.63 mL; P = .01). Postoperative drain duration was significantly lower with L-VEIL (-4.34 days; P < .05) than VEIL. The L-VEIL group had a higher number of lymph nodes without infiltration (mean difference: -0.48; P = .02). Operative time, nodal yield, nodal positivity, and hospitalization duration were similar in both groups. Postoperative complications were higher in the L-VEIL versus VEIL group (35 vs. 11 cases). Lymphedema events were significantly higher with L-VEIL in comparison with VEIL (38.8% vs. 16.7%; P = .03). Among patients with penile cancer, no significant difference was observed in outcomes obtained with VEIL and L-VEIL. Conclusion: As L-VEIL and VEIL approaches lead to comparable surgical outcomes, surgeons may choose either of these as per their convenience.