Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

Intraoperative Localization Using an Implanted Radar Reflector Facilitates Resection of Non-Palpable Trunk and Extremity Sarcoma.

BACKGROUND: Resecting non-palpable soft tissue tumors presents a unique challenge, particularly with recurrent disease in which surrounding tissue has been surgically manipulated and often irradiated. SAVI SCOUT® is a radar-based localization device that was developed for breast tumor localization and was recently FDA-approved for localization of soft tissue tumors. Application of this technology to soft tissue sarcoma has not been previously reported. METHODS: We assembled a single-institution retrospective case series of patients with trunk and extremity sarcomas resected by five sarcoma surgeons using SAVI SCOUT® from December 2018 to May 2020. Reflectors were placed preoperatively using image-guidance, and the radar detector was used intraoperatively to localize the target lesion. Clinical variables were abstracted from the electronic medical record including treatment history, pathology, and early oncologic outcomes. Using a focused review, we compared margin status and recurrence rates with previously published cohorts. RESULTS: Ten SAVI SCOUT®-localized sarcoma resections were performed. Eight were for locally recurrent disease, of which seven (83%) had prior radiation. The remaining lesions became non-palpable after neoadjuvant chemotherapy. SAVI SCOUT® facilitated resection in all cases with a margin-negative resection rate (77%) comparable to prior cohorts. In this high-risk population with a median follow-up of 14 months, only one patient recurred locally 7.5 months after SAVI SCOUT®-localized resection, requiring re-resection. CONCLUSION: SAVI SCOUT® technology facilitated resection of non-palpable recurrent sarcoma of the trunk and extremities in all ten cases attempted. In a high-risk patient population, the pattern of recurrence has been primarily distant with one instance of local tumor recurrence.

Utility of Taking Additional Margins When Performing Breast-Conserving Surgery with Intraoperative Radiation Therapy for Early Breast Cancer.

INTRODUCTION: Intraoperative radiation therapy (IORT) is an alternative to external beam radiation therapy (EBRT) after lumpectomy, in which radiation is delivered before the final margin analysis. Practices vary regarding excision of close or positive margins pre- and post-IORT. MATERIALS AND METHODS: In a retrospective cohort of women with hormone receptor-positive, clinically node-negative breast cancer undergoing lumpectomy with IORT and selective EBRT at our institution from 2011 to 2015, we compared the impact of pre- and post-IORT margin excisions on in-breast tumor recurrence. Additional pre-IORT margins were taken at surgical team discretion. Re-excisions post-IORT were performed for positive/close margins. We describe rate of invasive or in situ malignancy in additional pre-IORT and post-IORT re-excised specimens and compare IBTR using Chi-squared tests. RESULTS: There were 195 cases in 193 women (2 bilateral breast cancer). Pre-IORT, ≥1 additional margin was obtained in 139 (71%). The final margin on the initial lumpectomy was positive in 13 (9%) and ≤2 mm in 72 (52%). Additional pre-IORT margins contained in situ/invasive cancer in 16 (12%). Thirty-one patients (16%) underwent post-IORT re-excision and nine (29%) contained invasive/in situ malignancy. Twenty-three (12%) received EBRT. In 45.6-month mean follow-up, 13 had IBTR (7%) with no difference by additional pre-IORT margin excision (5 vs. 11%, p = 0.150), post-IORT margin re-excision (10 vs. 6%, p = 0.464), or EBRT (0 vs. 8%, p = 0.172). Adjuvant endocrine therapy was associated with lower IBTR (4 vs. 17%, p = 0.003). CONCLUSIONS: Taking additional pre-IORT margins and re-excising close/positive margins post-IORT improved margin clearance rates but had an unclear effect on IBTR. Adjuvant endocrine therapy significantly reduced IBTR.

Update on BRAF and MEK inhibition for treatment of melanoma in metastatic, unresectable, and adjuvant settings.

INTRODUCTION: Selective inhibition of the MAPK pathway with BRAF and MEK inhibitors has emerged as a key component of the treatment of BRAF-mutant unresectable/locally advanced metastatic melanoma. AREAS COVERED: Current data are presented on the efficacy and safety of BRAFi + MEKi combination therapy (dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib) from phase I, II, and III trials in the unresectable/locally advanced metastatic setting, as well as neoadjuvant and adjuvant applications. The theoretical basis, pre-clinical findings, clinical trial results and current ongoing clinical studies of combined BRAF/MEK inhibition with immunotherapy, also known as 'triplet therapy,' are also explored. EXPERT OPINION: Combination therapy with BRAF and MEK inhibitors dramatically improves response rates, progression-free survival and overall survival in patients with BRAF-mutant metastatic melanoma compared to historical treatments such as chemotherapy. Some serious adverse effects, including cutaneous squamous cell carcinoma, are attenuated with combination therapy, while less severe and reversible effects including pyrexia, left ventricular dysfunction, and ocular events can be more common with combination therapy. Existing data are insufficient to recommend triplet therapy, or a particular treatment sequence, with respect to BRAF and MEK inhibitors and immune therapies, though results from multiple ongoing trials are anticipated.

Implementation of telehealth is associated with improved timeliness to kidney transplant waitlist evaluation.

Introduction The United States Department of Veterans Affairs (VA) National Transplant Program has made efforts to improve access by introducing Web-based referrals and telehealth. The aims of this study were to describe the programmatic implementation and evaluate the effectiveness of new technology on the timeliness to kidney transplant evaluation at a VA medical centre. Methods Between 1 January 2009 and 31 May 2016, 835 patients were approved for evaluation. Monthly data were summarized as: number of applications, median days to evaluation, and median percentage of evaluations that occurred within 30 days. Temporal trends were analysed using non-parametric comparisons of medians between three eras: Pre Web-based submission, Web-based submission, and Web-based submission with videoconference (VC) telehealth. Results The number of applications did not vary between eras ( p = 0.353). The median time to evaluation and the median percentage of patients with appointments within 30 days improved significantly in the Web-based submission with VC era when compared with the Web-based and Pre Web-based eras (37 vs. 260 and 116 days, respectively, p < 0.001; 100% vs. 8% and 0%, respectively, p < 0.001). Discussion We have been able to markedly improve the timeliness to kidney transplant waitlist evaluation with the addition of telehealth.

Identifying Futile Interfacility Surgical Transfers.

Surgeons perceive that some surgical transfers are futile, but the incidence and risk factors of futile transfer are not quantified. Identifying futile interfacility transfers could save cost and undue burdens to patients and families. We sought to describe the incidence and factors associated with futile transfers. We conducted a retrospective cohort study from 2009 to 2013 including patients transferred to a tertiary referral center for general or vascular surgical care. Futile transfers were defined as resulting in death or hospice discharge within 72 hours of transfer without operative, endoscopic, or radiologic intervention. One per cent of patient transfers were futile (27/1696). Characteristics of futile transfers included older age, higher comorbidity burden and illness severity, vascular surgery admission, Medicare insurance, and surgeon documentation of end-stage disease as a factor in initial decision-making. Among futile transfers, 82 per cent were designated as do not resuscitate (vs 9% of nonfutile, P < 0.01), and 59 per cent received a palliative care consult (vs 7%, P < 0.01). A small but salient proportion of transferred patients undergo deliberate care de-escalation and early death or hospice discharge without intervention. Efforts to identify such patients before transfer through improved communication between referring and accepting surgeons may mitigate burdens of transfer and facilitate more comfortable deaths in patients' local communities.

Unnecessary Transfers for Acute Surgical Care: Who and Why?

Interhospital transfers for acute surgical care occur commonly, but without clear guidelines or protocols. Transfers may subject patients and delivery systems to significant burdens without clear clinical benefit. The incidence and factors associated with unnecessary transfers are not well described. We conducted a retrospective cohort study of patient transfers within a regional referral network to a tertiary center for nontrauma acute surgical care from 2009 to 2013. Clinically unnecessary transfers were defined as transfers that resulted in no intervention (operation, endoscopy, or interventional radiology procedure) and discharge to home within 72 hours. We performed bivariate and multivariate logistic regression analyses. The study population included 2177 patient transfers, 19 per cent of which were determined to be clinically unnecessary. After adjustment, clinically unnecessary transfers were more commonly performed for patient request (odds ratio = 2.52, 95% confidence interval = 1.60-3.99), continuity of care (1.87, 1.44-2.42), and care by urologic (1.50, 1.06-2.13) and vascular services (1.44, 1.03-2.01). Patients with higher comorbidity and severity of illness scores were less likely to have unnecessary transfers. The burden of unnecessary transfers could be mitigated by identifying appropriate transfer candidates through mutually developed guidelines, interfacility collaboration, and increased use of remote care to provide surgical subspecialty consultation and maintain continuity.