Predictive Impact of Tumor Mutational Burden on Real-World Outcomes of First-Line Immune Checkpoint Inhibition in Metastatic Melanoma.

PURPOSE: The choice of threshold and reliability of high tumor mutational burden (TMB) to predict outcomes and guide treatment choice for patients with metastatic melanoma receiving first-line immune checkpoint inhibitor (ICI) therapy in the real world is not well known. METHODS: Using a deidentified nationwide (US-based) melanoma clinicogenomic database, we identified a real-world cohort of patients with metastatic melanoma (N = 497) who received first-line monotherapy anti-PD-1 (n = 240) or dual anti-PD-1 and anti-CTLA-4 ICI (n = 257) and had a tissue-based comprehensive genomic profiling test TMB score. RESULTS: TMB-high (TMB-H; ≥10 mutations per megabase [muts/Mb], n = 352, 71%) was independently predictive of superior real-world progression-free survival and overall survival versus TMB-low (<10 mut/Mb, n = 145, 29%) in both mono ICI (hazard ratio [HR], 0.45 [95% CI, 0.32 to 0.63]; P < .001; HR, 0.61 [95% CI, 0.41 to 0.90]; P = .01, respectively) and dual ICI (HR, 0.67 [95% CI, 0.49 to 0.90]; P = .009; HR, 0.61 [95% CI, 0.42 to 0.88]; P = .007, respectively) patients. Dual ICI offered no significant advantage in BRAFwt patients and unexpectedly demonstrated greatest benefit in the TMB 10-19 mut/Mb group, identifying a TMB-very high (≥20 mut/Mb, n = 247, 50%) BRAFmut patient subgroup for whom mono ICI may be preferable. CONCLUSION: TMB-H predicts superior outcomes on ICI while coassessment of BRAF status and TMB may inform first-line regimen choice.

Current usage of pembrolizumab in triple negative breast cancer (TNBC).

INTRODUCTION: The use of immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 pathway has changed the landscape in the treatment of triple negative breast cancer (TNBC). The ICI pembrolizumab in combination with chemotherapy now forms a standard of care for the treatment of advanced PD-L1 positive TNBC and as part of neoadjuvant therapy for high-risk early-stage disease. Evidence in this space is rapidly advancing. AREAS COVERED: This review aims to highlight the evolving role of immunotherapy in TNBC management and to discuss current challenges. The studies in this review were searched from PubMed and ClinicalTrials.gov. EXPERT OPINION: The KEYNOTE-522 trial demonstrated that the addition of peri-operative pembrolizumab to neoadjuvant chemotherapy improves patient outcomes in early-stage TNBC. However, critical questions remain including how to select which patients truly gain benefit from the addition of pembrolizumab; the optimal duration of therapy, and the optimal adjuvant therapy depending on pathologic response.

Total 5-mm port approach: a feasible technique for both elective and emergency laparoscopic cholecystectomy.

BACKGROUND: The laparoscopic approach is considered the standard of care for cholecystectomy. Attempts to minimize incisions with single site and natural orifice approaches have shown promise but also have limitations. Technological advances have facilitated decreased port size, which may have a variety of benefits. The aim of this study was to determine the feasibility of an all 5-mm port approach for patients undergoing both elective and emergency laparoscopic cholecystectomy. METHODS: A consecutive series of laparoscopic cholecystectomies at three different hospitals using all 5-mm ports was prospectively evaluated. Recorded outcomes included operative findings, procedural difficulties, the need to extend the umbilical incision during extraction, operative time, length of stay and post-operative complications. RESULTS: A total of 101 patients were included and all had a successful cholecystectomy without the need for additional ports. The umbilical incision was extended for gallbladder extraction in 29 (29%) patients. Eight (8%) patients experienced minor post-operative complications and there were no major complications. Cholangiography was performed in 98% of cases and three patients underwent successful common bile duct exploration without requiring additional ports. In a small number of cases, there was difficulty with the quality of the view through the 5-mm laparoscope but this was rectified by removing old or damaged laparoscopes from the circulating stock. CONCLUSION: This study demonstrates that laparoscopic cholecystectomy using all 5-mm ports is both feasible and safe, and is comparable to published outcomes after conventional laparoscopic cholecystectomy. Further work is needed to determine whether this approach can also improve short- and long-term outcomes.

Laparoscopic ventral hernia repair using only 5-mm ports.

BACKGROUND: The technique of laparoscopic ventral hernia repair has been evolving since it was first described over 20 years ago. We report a new technique where polyester mesh was back loaded through a 5-mm port site, coming into contact with the skin. This avoids the need for any 10-12-mm ports. METHODS: A prospective database of laparoscopic ventral hernia repairs was examined. A single surgeon performed 344 laparoscopic ventral hernia repairs using this technique over 60 months. Follow-up was conducted by both clinical and independent phone review. SURGICAL TECHNIQUE: Laparoscopic access was achieved via a 5-mm optical port, adding two, or occasionally three, 5-mm extra ports. Hernia contents were reduced and the extra-peritoneal fat excised; 5-mm tooth graspers were placed through the lateral port and then in a retrograde fashion through the uppermost port. The port was removed, and the mesh pulled back into the abdominal cavity and positioned with a minimum of 3-cm overlap. The mesh was fixed using absorbable tacks and sutures. RESULTS: Most patients had primary umbilical hernias. There was one case of mesh infection due to enteric organisms. This occurred in a patient undergoing repair of a stoma site hernia, resulting from a Hartmann's procedure for perforated diverticulitis. There was no other evidence of acute or chronic mesh infection despite cutaneous contact with the mesh. In this series, there was an overall hernia recurrence rate of 2.4%. CONCLUSION: Laparoscopic ventral hernia repair using only 5-mm ports is a safe, effective technique with no extra risk of infection.