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Saïd C Azoury,1 Norma Elizabeth Farrow,2 Qing L Hu,2 Kevin C Soares,1 Caitlin W Hicks,1 Faris Azar,1 Nelson Rodriguez-Unda,3 Katherine E Poruk,1 Peter Cornell,1 Karen K Burce,1 Carisa M Cooney,3 Hien T Nguyen,1 Frederic E Eckhauser1 1Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA; 2School of Medicine, Johns Hopkins University, Baltimore, MD, USA; 3Department of Plastic and Reconstructive Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA Abstract: Surgical site infections (SSIs) complicate the postoperative course of a significant proportion of general abdominal surgical patients and are associated with excessive health care costs. SSIs increase postoperative morbidity and mortality, and may require hospital admission, intravenous antibiotics, and even surgical reintervention. Risks associated with SSIs are related to both host and perioperative factors. However, a vast majority of these infections are preventable. More recently, quality initiative programs such as American College of Surgeons National Surgical Quality Improvement Program are expanding their roles to help better monitor adherence to improvement measures. Indeed, standardizing preoperative antibiotic prophylaxis timing is perhaps the most persuasive example and this has been integral to reducing postoperative SSI rates. Herein, the authors provide an update on the epidemiology, risk factors, identification, and management of wound infections following abdominal surgery. Keywords: surgical site infection, diagnosis, treatment, prevention

Objective: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma., Summary Background Data: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization., Methods: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics., Results: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients., Conclusions: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The outcomes associated with receipt of adjuvant radiation in patients after surgery for MPM are poorly understood., Objective: The objective of this study was to use 2 registries to compare the outcomes of patients receiving adjuvant radiation or no radiation after definitive surgery for pathologic stage I-III MPM., Methods: Patients with resected pathologic stage I-III MPM were identified from the Duke University registry (1996-2016) and National Cancer Database (NCDB) (2004-2015). The primary outcome was overall survival. Propensity score-matched and landmark subgroup analyses were performed., Results: A total of 212 institutional and 1615 NCDB patients met criteria. In both cohorts, patients who underwent radiation were more likely to have margin-negative resection and more advanced pathologic stage. At a landmark time of 4.4 and 4.7 months from surgery, Duke [hazard ratio (HR) 1.14; 95% confidence interval (CI) 0.62-2.11] and NCDB patients (HR 0.97; 95% CI 0.81-1.17) who received adjuvant radiation did not experience improved survival compared to those who did not receive radiation in multivariable analysis. Duke patients who received radiation had similar incidence of recurrence and time to both overall recurrence and ipsilateral recurrence (HR 0.87; 95% CI 0.43-1.77) compared to those who did not. Duke patients experienced 100 grade 1/2, 21 grade 3/4, and one grade 5 toxicity events during radiation., Conclusions: In this dual registry analysis of patients with resected stage I-III MPM, the receipt of adjuvant hemithoracic radiation was not associated with improved survival compared to no radiation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Stereotactic body radiation therapy (SBRT) is used to treat stage I non-small cell lung cancer (NSCLC) in nonsurgical candidates, although guidelines specify that inoperability be determined in multidisciplinary fashion. We characterized NSCLC patients treated with SBRT undergoing thoracic surgical evaluation (TSUe) and quantified TSUe's impact on time to treatment, receipt of diagnostic staging procedures, and health care costs., Methods: Adults with newly diagnosed NSCLC undergoing SBRT were identified in the MarketScan all-payer claims database (2014-2018). TSUe was defined as an outpatient encounter with a thoracic surgeon or multispecialty group. Time to treatment and total costs in the 6 months preceding treatment were examined using multivariable regression by receipt of TSUe, adjusting for demographic and clinical factors., Results: Of 1894 patients, 36.3% (n = 687) underwent TSUe. Compared with patients without TSUe, these patients were younger (mean age, 73.6 vs 76.3 years) and more likely to undergo invasive biopsy/staging procedures (90% vs 82%) or pulmonary function testing (80.6% vs 69.5%). Patients undergoing TSUe had a median time to treatment of 64 days (interquartile range, 43-98 days), compared with 44 days (interquartile range, 29-70 days) for no TSUe. Adjusted time to treatment was 43% longer (incident rate ratio, 1.43; 95% CI, 1.32-1.54; P < .001) with TSUe. Patients undergoing TSUe also incurred 30% higher costs (adjusted cost ratio, 1.30; 95% CI, 1.20-1.41; P < .001)., Conclusions: Among patients with early-stage NSCLC undergoing SBRT as primary treatment, a minority are evaluated by a thoracic surgeon. Because they have a longer time to treatment, more invasive diagnostic procedures, and higher costs, this represents a targetable gap to make workup protocols more efficient., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Completion lymph node dissection (CLND) for microscopic lymph node metastases has been replaced by observation; however, CLND is standard for clinically detectable nodal metastases (cLN). CLND has high morbidity, which may be reduced by excision of only the cLN (precision lymph node dissection [PLND]). We hypothesized that same-basin recurrence risk would be low after PLND., Methods: Retrospective review at four tertiary care hospitals identified patients who underwent PLND. The primary outcome was 3-year cumulative incidence of isolated same-basin recurrence., Results: Twenty-one patients underwent PLND for cLN without synchronous distant metastases. Reasons for forgoing CLND included patient preference (n = 11), comorbidities (n = 5), imaging indeterminate for distant metastases (n = 2), partial response to checkpoint blockade (n = 1), or not reported (n = 2). A median of 2 nodes (range: 1-6) were resected at PLND, and 68% contained melanoma. Recurrence was observed in 33% overall. Only 1 patient (5%) developed an isolated same-basin recurrence. Cumulative incidences at 3 years were 5.0%, 17.3%, and 49.7% for isolated same-basin recurrence, any same-basin recurrence, and any recurrence, respectively. Complications from PLND were reported in 1 patient (5%)., Conclusions: These pilot data suggest that PLND may provide adequate regional disease control with less morbidity than CLND. These data justify prospective evaluation of PLND in select patients., (© 2022 Wiley Periodicals LLC.)

Background: Although adult guidelines are often applied to children, age-specific surgical margins have not been defined for pediatric melanoma., Procedure: Patients &lt;20 years of age with invasive, cutaneous melanoma were identified using the 2004-2016 National Cancer Database and categorized as undergoing wide (&gt;1 cm) or narrow (≤1 cm) excision. Unadjusted overall survival (OS) was compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models were used to estimate the effect of excision margin on OS after adjustment for available covariates., Results: In total, 2081 patients met study criteria: 1338 (64.3%) patients underwent wide excision whereas 743 (35.7%) underwent narrow excision. Unadjusted OS was improved in the narrow-excision group (log-rank p = .01), which was consistent among patients with thicker (&gt;1 mm) and thinner (≤1 mm) tumors. After adjustment for patient and tumor characteristics, we found no evidence of a difference in OS for patients who underwent narrow excision compared to patients who underwent wide excision (adjusted hazard ratio 0.57, 95% confidence interval 0.32-1.01, p = .053). There was no interaction between excision margin width and Breslow depth (p = .85), indicating that the effect of excision margin width on OS does not differ based on Breslow depth., Conclusions: In this analysis, wide excision (&gt;1 cm) does not appear to be associated with improved survival in children with melanoma regardless of tumor characteristics. Although further studies are needed to define optimal excision margins in pediatric melanoma, this study suggests that more narrow margins (≤1 cm) may be acceptable., (© 2022 Wiley Periodicals LLC.)

Background Many hospitalized patients are not administered prescribed doses of pharmacologic venous thromboembolism prophylaxis. Methods and Results In this cluster-randomized controlled trial, all adult non-intensive care units (10 medical, 6 surgical) in 1 academic hospital were randomized to either a real-time, electronic alert-triggered, patient-centered education bundle intervention or nurse feedback intervention to evaluate their effectiveness for reducing nonadministration of venous thromboembolism prophylaxis. Primary outcome was the proportion of nonadministered doses of prescribed pharmacologic prophylaxis. Secondary outcomes were proportions of nonadministered doses stratified by nonadministration reasons (patient refusal, other). To test our primary hypothesis that both interventions would reduce nonadministration, we compared outcomes pre- versus postintervention within each cohort. Secondary hypotheses were tested comparing the effectiveness between cohorts. Of 11 098 patient visits, overall dose nonadministration declined significantly after the interventions (13.4% versus 9.2%; odds ratio [OR], 0.64 [95% CI, 0.57-0.71]). Nonadministration decreased significantly ( P <0.001) in both arms: patient-centered education bundle, 12.2% versus 7.4% (OR, 0.56 [95% CI, 0.48-0.66]), and nurse feedback, 14.7% versus 11.2% (OR, 0.72 [95% CI, 0.62-0.84]). Patient refusal decreased significantly in both arms: patient-centered education bundle, 7.3% versus 3.7% (OR, 0.46 [95% CI, 0.37-0.58]), and nurse feedback, 9.5% versus 7.1% (OR, 0.71 [95% CI, 0.59-0.86]). No differential effect occurred on medical versus surgical units. The patient-centered education bundle was significantly more effective in reducing all nonadministered ( P =0.03) and refused doses ( P =0.003) compared with nurse feedback (OR, 1.28 [95% CI, 1.0-1.61]; P =0.03 for interaction). Conclusions Information technology strategies like the alert-triggered, targeted patient-centered education bundle, and nurse-focused audit and feedback can improve venous thromboembolism prophylaxis administration. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03367364.

Background: We previously reported results from a phase 1 study testing intratumoral recombinant poliovirus, lerapolturev, in 12 melanoma patients. All 12 patients received anti-PD-1 systemic therapy before lerapolturev, and 11 of these 12 patients also received anti-PD-1 after lerapolturev. In preclinical models lerapolturev induces intratumoral innate inflammation that engages antitumor T cells. In the current study, prelerapolturev and postlerapolturev tumor biopsies and blood were evaluated for biomarkers of response., Methods: The following analyses were performed on tumor tissue (n=11): (1) flow cytometric assessment of immune cell density, (2) NanoString Digital Spatial profiling of protein and the transcriptome, and (3) bulk RNA sequencing. Immune cell phenotypes and responsiveness to in vitro stimulation, including in vitro lerapolturev challenge, were measured in peripheral blood (n=12)., Results: Three patients who received anti-PD-1 therapy within 30 days of lerapolturev have a current median progression-free survival (PFS) of 2.3 years and had higher CD8+T cell infiltrates in prelerapolturev tumor biopsies relative to that of 7 patients with median PFS of 1.6 months and lower CD8+T cell infiltrates in prelerapolturev tumor biopsies. In peripheral blood, four patients with PFS 2.3 years (including three that received anti-PD-1 therapy within 30 days before lerapolturev and had higher pretreatment tumor CD8+T cell infiltrates) had significantly higher effector memory (CD8+, CCR7-, CD45RA-) but lower CD8+PD-1+ and CD4+PD-1+ cells compared with eight patients with median PFS 1.6 months. In addition, pretreatment blood from the four patients with median PFS 2.3 years had more potent antiviral responses to in vitro lerapolturev challenge compared with eight patients with median PFS 1.6 months., Conclusion: An inflamed pretreatment tumor microenvironment, possibly induced by prior anti-PD-1 therapy and a proficient peripheral blood pretreatment innate immune response (antiviral/interferon signaling) to lerapolturev was associated with long term PFS after intratumoral lerapolturev in a small cohort of patients. These findings imply a link between intratumoral T cell inflammation and peripheral immune function., Trial Registration Number: NCT03712358., Competing Interests: Competing interests: GMB reports clinical trial funding from Istari Oncology, Delcath, Oncosec Medical, Replimune, and Checkmate Pharmaceuticals paid to Duke University. AnS receives research funding paid to the institution from Bristol Myers Squibb, Immunocore, Merck, Pfizer Advisory roles; and has served on advisory boards for Array, Novartis, Iovance, and Regeneron. MCB, DDB and MG are paid consultants of Istari Oncology, Inc. and MG and DDB are scientific advisors for Istari Oncology; DDB and MG hold equity in Istari Oncology. MCB, DDB, MG and SKN own intellectual property related to this research, which has been licensed to Istari Oncology. Duke University (Licensor of PVSRIPO) has a financial interest in Istari Oncology. All other authors declare they have no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients., Methods: Flow cytometry was performed on fresh tumor draining lymph nodes (LN). Paraffin slides from a separate cohort underwent NanoString Digital Spatial Profiling (DSP)®. After staining with fluorescent markers for CD20 (B cells), CD3 (T cells), CD11c (antigen presenting cells) and a nuclear marker (tumor) was performed, regions of interest (ROI) were selected based on the location of B cell regions (B cell follicles). A panel of 68 proteins was then analyzed from the ROIs., Results: B cell percentage trended higher in patients with tumor in LN (n=3) compared to patients with nSLN (n=10) by flow cytometry. B cell regions from a separate cohort of patients with tumor in the (pSLN) (n=8) vs. no tumor (nSLN) (n=16) were examined with DSP. Within B cell regions of the SLN, patients with pSLN had significantly higher expression of multiple activation markers including Ki-67 compared to nSLN patients. Among 4 patients with pSLN, we noted variability in arrangement of B cell follicles which were either surrounding the tumor deposit or appeared to be infiltrating the tumor. The B cell follicle infiltrative pattern was associated with prolonged recurrence free survival., Conclusion: These data suggest a role for B cell follicles in coordinating effective adaptive immune responses in melanoma when low volume metastatic disease is present in tumor draining LN., (Copyright © 2022 Therien, Beasley, Rhodin, Farrow, Tyler, Boczkowski, Al-Rohil, Holl and Nair.)

Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients., Competing Interests: Competing interests: ZE: Advisory boards: Array, Pfizer, OncoSec, Regeneron, Genentech, Novartis, Natera. Research funding: Novartis, Pfizer, Boehringer-Ingelheim. JFT: Advisory boards: BMS Australia, MSD Australia, GSK, Provectus Inc. Travel support: GSK, Provectus Inc and Novartis. TJH: Research funding: Genentech, SkylineDX. EKB: Research funding: SkylineDx, Honorarium: Excite International inc. DEG: Honoraria: BMS, Novartis, Q biotics. GK; Advisory Board: Merck. AVA: Advisory Boards: Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Pierre Fabre, Provectus, Sanofi, Sirius Medical, 4SC Research funding: Amgen, Merck-Pfizer. JV: Speaker: Caste Biosciences. GB: Research funding: Istari Oncology, Delcath, Oncosec Medical, Replimune, Checkmate Pharmaceuticals. ROB: Advisory boards: Amgen, BD/BARD, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche and Sanofi Genzyme. Research funding: Bristol-Myers Squibb, SkyLineDx. Speaker honorarium: Roche and Pfizer. Shareholder in SATMEG Ventures AB. NIK: Advisory boards: Bristol-Myers Squibb, AstraZeneca, Regeneron, Array, Immunocore, Merck, Incyte, Jounce Therapeutics,Pfizer,Novartis, Nektar,Castle Biosciences, Instil Bio. Research funding: Bristol-Myers Squibb, Merck, Novartis, Celgene, Replimune, Amgen, Regneron, HUYA, GlaxoSmithKline Stocks: Bellicum Pharmaceuticals, Amarin Corporation, Asensus Surgical., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Standard of care for resectable pancreatic cancer is a combination of surgical resection (SR) and multiagent chemotherapy (MCT). We aim to determine whether SR or MCT is associated with superior survival for patients receiving only single-modality therapy., Methods: Patients with stage I-IIb pancreatic head adenocarcinoma who received either MCT or SR were identified in the NCDB (2013-2015). Following a piecewise approach to estimating hazards over the course of follow-up, conditional overall survival (OS) at 30, 60, and 90 days after treatment initiation was estimated using landmark analyses., Results: 3103 patients received MCT alone (60.3%) and 2043 underwent SR alone (39.7%). SR had an OS disadvantage at 30 (HR 3.99, 95% CI 3.12-5.11) and 60 days (HR 1.85, 95% CI 1.4-2.45), but an OS advantage after 90 days (HR 0.59, 95% CI 0.55-0.64). In a landmark analysis conditioned on 90 days survival post treatment initiation, median OS was improved for SR (17.0 vs. 12.2 months, p < 0.0001); SR improved 3-year OS by 21.3% (p < 0.05), despite patients being older (median 72 vs. 67 years, p < 0.0001) with higher Charlson-Deyo comorbidity scores (≥2: 11.2 vs. 8.6%, p = 0.006)., Conclusion: For patients with resectable pancreatic cancer, SR is associated with superior long-term survival compared to MCT., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Importance: Pulmonary rehabilitation (PR) after exacerbation of chronic obstructive pulmonary disease (COPD) is effective in reducing COPD hospitalizations and mortality while improving health-related quality of life, yet use of PR remains low. Estimates of the cost-effectiveness of PR in this setting could inform policies to improve uptake., Objective: To estimate the cost-effectiveness of participation in PR after hospitalization for COPD., Design, Setting, and Participants: This economic evaluation estimated the cost-effectiveness of participation in PR compared with no PR after COPD hospitalization in the US using a societal perspective analysis. A Markov microsimulation model was developed to estimate the cost-effectiveness in the US health care system with a lifetime horizon, 1-year cycle length, and a discounted rate of 3% per year for both costs and outcomes. Data sources included published literature from October 1, 2001, to April 1, 2021, with the primary source being an analysis of Medicare beneficiaries living with COPD between January 1, 2014, and December 31, 2015. The analysis was designed and conducted from October 1, 2019, to December 15, 2021. A base case microsimulation, univariate analyses, and a probabilistic sensitivity analysis were performed., Interventions: Pulmonary rehabilitation compared with no PR after COPD hospitalization., Main Outcomes and Measures: Net cost in US dollars, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio., Results: Among the hypothetical cohort with a mean age of 76.9 (age range, 60-92) years and 58.6% women, the base case microsimulation from a societal perspective demonstrated that PR resulted in net cost savings per patient of $5721 (95% prediction interval, $3307-$8388) and improved quality-adjusted life expectancy (QALE) (gain of 0.53 [95% prediction interval, 0.43-0.63] years). The findings of net cost savings and improved QALE with PR did not change in univariate analyses of patient age, the Global Initiative for Obstructive Lung Disease stage, or number of PR sessions. In a probabilistic sensitivity analysis, PR resulted in net cost savings and improved QALE in every one of 1000 samples and was the dominant strategy in 100% of simulations at any willingness-to-pay threshold. In a 1-way sensitivity analysis of total cost, assuming completion of 36 sessions, a single PR session would remain cost saving to $171 per session and had an incremental cost-effectiveness ratio of $884 per session for $50 000/QALY and $1597 per session for $100 000/QALY., Conclusions and Relevance: In this economic evaluation, PR after COPD hospitalization appeared to result in net cost savings along with improvement in QALE. These findings suggest that stakeholders should identify policies to increase access and adherence to PR for patients with COPD.

Background: We hypothesized that the ratio of positive lymph nodes to total assessed lymph nodes (LNR) is an indicator of cancer burden in esophageal adenocarcinoma and may identify patients who may most benefit from AC., Objective: The aim of this study was to discern whether there is a threshold LNR above which AC is associated with a survival benefit in this population., Methods: The 2004-2015 National Cancer Database was queried for patients who underwent upfront, complete resection of pT1-4N1-3M0 esophageal adenocarcinoma. The primary outcome, overall survival, was examined using multivariable Cox proportional hazards models employing an interaction term between LNR and AC., Results: A total of 1733 patients were included: 811 (47%) did not receive AC whereas 922 (53%) did. The median LNR was 20% (interquartile range 9-40). In a multivariable Cox model, the interaction term between LNR and receipt of AC was significant (P = 0.01). A plot of the interaction demonstrated that AC was associated with improved survival beyond a LNR of about 10%-12%. In a sensitivity analysis, the receipt of AC was not associated with improved survival in patients with LNR <12% (hazard ratio 1.02; 95% confidence interval 0.72-1.44) but was associated with improved survival in those with LNR ≥12% (hazard ratio 0.65; 95% confidence interval 0.50-0.79)., Conclusions: In this study of patients with upfront, complete resection of node-positive esophageal adenocarcinoma, AC was associated with improved survival for LNR ≥12%. LNR may be used as an adjunct in multidisciplinary decision-making about adjuvant therapies in this patient population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In 2014, technetium-99m tilmanocept (TcTM) replaced technetium-99m sulfur colloid (TcSC) as the standard lymphoscintigraphy (LS) mapping agent in melanoma patients undergoing sentinel lymph node biopsy (SLNB). The aim of this study was to examine differences in mapping time, intra-operative identification of sentinel lymph node (SLN), and false negative rate (FNR) between patients who underwent SLNB with TcTM compared to TcSC., Methods: Patients who underwent SLNB between 2010 and 2018 were retrospectively identified. Patient demographic, tumor, and imaging data was stratified by receipt of TcSC (n = 258) or TcTM (n = 133). Student's t test and χ 2 test were used to compare characteristics and outcomes., Results: Both cohorts were similar in demographic, primary tumor characteristics, and total number of SLN identified (TcTM 3.56 vs. TcSC 3.28, p = 0.244). TcTM was associated with significantly shorter LS mapping times (51.8 vs. 195.1 min, p < 0.01). There was no significant difference in the number of patients with positive SLN (TcTM 11.3 vs. TcSC 17.4%, p = 0.109) and the FNR was similar between both groups (TcTM 25% vs. TcSC 22%)., Conclusion: TcTM was associated with significantly shorter LS mapping time while identifying similar numbers of SLN. Our results support further study to ensure similar FNR and oncologic outcomes between agents., (© 2021 Wiley Periodicals LLC.)

Background: Laparoscopic surgery has become standard of care in high-income countries but is rarely accessible in low- and middle-income countries (LMICs). This study assessed experience with laparoscopy and attitudes toward a low-cost laparoscopic system among surgeons in sub-Saharan Africa., Methods: A survey assessing current laparoscopic practice and feedback on a low-cost laparoscopic system was administered to attendees of the College of Surgeons of East, Central, and Southern Africa (COSECSA) Scientific Conference between December 4 and December 6, 2019 in Kampala, Uganda., Results: Fifty-six surgeons from 14 countries participated. A majority were male (n = 46, 82%) general surgeons (n = 37, 66%) from tertiary/teaching hospitals (n = 36, 64%). For those with training in laparoscopy (n = 33, 59%), 22 (67%) reported less than 1 year of training and over half (n = 17, 52%) reported 1 month or less. Overall, a minority (n = 21, 38%) used laparoscopy in current practice, with 57% (n = 12) of those performing laparoscopy less than once per week. The most common laparoscopic surgeries performed were cholecystectomy (n = 15), diagnostic laparoscopy (n = 14), and appendectomy (n = 12). Few surgeons were performing more complex cases (n = 5). Barriers to laparoscopy included poor access to training equipment (n = 34, 61%), mentors (n = 33, 59%), laparoscopic equipment (n = 31, 55%), equipment maintenance (n = 25, 45%), access to consumable supplies (n = 21, 38%), and cost (n = 31, 55%). Fifty-two participants (93%) were interested in increasing their use of laparoscopy; the majority felt that a low-cost laparoscope (n = 52, 93%) and lift retractor for gasless laparoscopy (n = 46, 82%) would serve an unmet need in their practice., Conclusions: While the use of laparoscopy is currently limited in COSECSA countries, there is a significant interest among surgeons to increase implementation. A low-cost, durable laparoscopic system was viewed as a potential solution to the current barriers and could improve implementation in LMICs., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

BACKGROUND Low-dose chest CT (LDCT) is the only effective screening test for lung cancer. Annual lung cancer screening (LCS) is recommended by the US Preventive Services Task Force (USPSTF) for individuals at high risk for primary lung neoplasm. METHODS We retrospectively identified patients receiving LCS from January 2016 through March 2018 whose residential addresses were within our health center's county. We estimated driving distance from the patient's address to our health center and obtained sociodemographic characteristics from the electronic health record (EHR). The census-tract-level LCS-eligible population size was estimated, and their population characteristics determined via US Census Bureau, Centers for Disease Control and Prevention (CDC), and Behavioral Risk Factor Surveillance System (BRFSS) data. The Cochran-Mantel-Haenszel test was used to determine differences amongst the LCS-eligible and LCS-enrolled populations. Multivariable regression was used to determine the effects of sociodemographic characteristics on LCS eligibility. RESULTS There was modest correlation between census-tract-level LCS-eligible population size and LCS enrollment ( r = 0.68, P < .001). 5.9% (364/6185) of the estimated LCS-eligible population in our county received LCS, with census-tract LCS rates ranging from 1.5% to 12.5%. Nonwhite race status (Hispanic and African American) was associated with decreased likelihood of LCS enrollment compared to White race (OR = 95% CI, 0.765 [0.61, 0.95] and 0.031 [0.008, 0.124], respectively). Older age, Medicaid, and uninsured statuses were positively correlated with LCS eligibility ( P ≤ .01). LIMITATIONS This analysis comprises a single county. Other LCS facilities within our health system in neighboring counties, as well as individuals receiving LCS outside of our health system, are not captured. CONCLUSIONS The uptake of LCS remains low, with disproportionately lower screening rates amongst Hispanic and African American populations. Medicaid and uninsured patients in our community are also more likely to be LCS-eligible. These populations may be targets for interventions aimed at increasing LCS awareness and uptake., (©2021 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

Background: Although sentinel lymph node (SLN) biopsy is a standard procedure used to identify patients at risk for melanoma recurrence, it fails to risk-stratify certain patients accurately. Because processes in SLNs regulate anti-tumor immune responses, the authors hypothesized that SLN gene expression may be used for risk stratification., Methods: The Nanostring nCounter PanCancer Immune Profiling Panel was used to quantify expression of 730 immune-related genes in 60 SLN specimens (31 positive [pSLNs], 29 negative [nSLNs]) from a retrospective melanoma cohort. A multivariate prediction model for recurrence-free survival (RFS) was created by applying stepwise variable selection to Cox regression models. Risk scores calculated on the basis of the model were used to stratify patients into low- and high-risk groups. The predictive power of the model was assessed using the Kaplan-Meier and log-rank tests., Results: During a median follow-up period of 6.3 years, 20 patients (33.3%) experienced recurrence (pSLN, 45.2% [14/31] vs nSLN, 20.7% [6/29]; p = 0.0445). A fitted Cox regression model incorporating 12 genes accurately predicted RFS (C-index, 0.9919). Improved RFS was associated with increased expression of TIGIT (p = 0.0326), an immune checkpoint, and decreased expression of CXCL16 (p = 0.0273), a cytokine important in promoting dendritic and T cell interactions. Independent of SLN status, the model in this study was able to stratify patients into cohorts at high and low risk for recurrence (p < 0.001, log-rank)., Conclusions: Expression profiles of the SLN gene are associated with melanoma recurrence and may be able to identify patients as high or low risk regardless of SLN status, potentially enhancing patient selection for adjuvant therapy.

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., (© 2021 American Cancer Society.)

Background: While programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) antagonists have improved the prognosis for many patients with melanoma, around 60% fail therapy. PVSRIPO is a non-neurovirulent rhinovirus:poliovirus chimera that facilitates an antitumor immune response following cell entry via the poliovirus receptor CD155, which is expressed on tumor and antigen-presenting cells. Preclinical studies show that oncolytic virus plus anti-PD-1 therapy leads to a greater antitumor response than either agent alone, warranting clinical investigation., Methods: An open-label phase I trial of intratumoral PVSRIPO in patients with unresectable melanoma (American Joint Committee on Cancer V.7 stage IIIB, IIIC, or IV) was performed. Eligible patients had disease progression on anti-PD-1 and V-raf murine sarcoma viral oncogene homolog B (BRAF)/mitogen activated protein kinase kinase (MEK) inhibitors (if BRAF mutant). The primary objective was to characterize the safety and tolerability of PVSRIPO. Twelve patients in four cohorts received a total of 1, 2 or 3 injections of PVSRIPO monotherapy, with 21 days between injections., Results: PVSRIPO injections were well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported. All adverse events (AEs) were grade (G) 1 or G2 (G1 pruritus most common at 58%); all but two PVSRIPO-treatment related AEs were localized to the injected or adjacent lesions (n=1 G1 hot flash, n=1 G1 fatigue). Four out of 12 patients (33%) achieved an objective response per immune-related response criteria (two observations, 4 weeks apart), including 4/6 (67%) who received three injections. In the four patients with in-transit disease, a pathological complete response (pCR) was observed in two (50%) patients. Following study completion, 11/12 patients (92%) reinitiated immune checkpoint inhibitor-based therapy, and 6/12 patients (50%) remained without progression at a median follow-up time of 18 months., Conclusion: Intratumoral PVSRIPO was well tolerated. Despite the limited number of PVSRIPO treatments relative to the overall lesion burden (67% patients>5 lesions), intratumoral PVSRIPO showed promising antitumor activity, with pCR in injected as well as non-injected lesions in select patients., Trial Registration Number: NCT03712358., Competing Interests: Competing interests: SKN owns intellectual property related to this research, which has been licensed to Istari Oncology, Inc. DDB and MG have financial interest in Istari Oncology, Inc. Duke University (Licensor of PVSRIPO) has a financial interest in Istari Oncology, Inc., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown., Study Design: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma-specific mortality were compared., Results: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86)., Conclusions: SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Older patients are often considered high-risk surgical candidates for locally advanced esophageal cancer, and the benefit of surgery in this population is unclear. This national analysis examines the effect of age on esophagectomy outcomes and compares surgery versus chemoradiation in older patients., Methods: The National Cancer Database was used to identify patients with clinical stage II to III esophageal adenocarcinoma undergoing surgery or definitive chemoradiation between 2004 and 2015. Restricted cubic splines were used to examine the relationship between age and survival after esophagectomy, and maximally selected rank statistics were used to identify an age at which survival worsened. We used Cox proportional hazard models including an interaction term between age and treatment to compare overall survival, as well as survival of patients receiving esophagectomy versus definitive chemoradiation., Results: Of 17,495 patients, 11,680 underwent esophagectomy and 5815 received chemoradiation. Survival after esophagectomy worsened with increasing age and decreased considerably after age 73 (hazard ratio = 1.05, 95% confidence interval, 1.04-1.06, per increasing year after 73 versus hazard ratio = 1.01, 95% confidence interval, 1.00-1.01, per increasing year to 73; both P < .001). Chemoradiation was increasingly used over surgery as age increased. The interaction between age and treatment was significant, and a graph of this interaction demonstrated a survival benefit for surgery over chemoradiation at most ages, including octogenarians., Conclusions: Survival worsens with age after esophagectomy for locally advanced esophageal cancer. However, esophagectomy is associated with improved survival compared with definitive chemoradiation at most ages, including octogenarians. Esophagectomy may be considered over chemoradiation for patients who can tolerate surgery regardless of age., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Induction therapy for patients with cT2N0M0 esophageal cancer is controversial. We performed a retrospective cohort analysis of the National Cancer Database to examine the patterns of use of induction therapy for this population., Methods: The National Cancer Database was queried for patients with cT2N0M0 esophageal cancer who underwent esophagectomy (2004-2015). Patients were stratified by upfront surgery or induction therapy. Overall survival was analyzed and a multivariable logistic regression performed to identify factors associated with receipt of induction therapy., Results: Overall 2540 patients met study criteria: 1177 (46%) received upfront esophagectomy and 1363 (53%) received induction therapy. Patients receiving induction therapy were more likely to be younger, male, without comorbidities, privately insured, and treated at a nonacademic center. These patients were also less likely to be treated in highest volume surgery centers. In multivariable regression, factors independently associated with receipt of induction therapy included later year of diagnosis, increasing tumor size, and increasing tumor grade. Factors associated with upfront esophagectomy included advancing age, comorbidities, lack of insurance, geographic location, and highest volume centers. The receipt of induction chemotherapy was not associated with a survival benefit compared with no induction therapy., Conclusions: Several patient-, treatment center-, and tumor-related factors are associated with receipt of induction therapy for cT2N0M0 esophageal cancer, although induction therapy is not associated with a survival benefit. Further inquiry into these differences and the potential benefit or lack thereof of induction therapy should be conducted to provide more equitable and appropriate care for patients with esophageal cancer., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: In melanoma patients, microscopic tumor in the sentinel lymph-node biopsy (SLN) increases the risk of distant metastases, but the transition from tumor in the SLN to metastatic disease remains poorly understood., Methods: Fluorescent staining for CD3, CD20, CD11c, and DNA was performed on SLN tissue and matching primary tumors. Regions of interest (ROI) were then chosen geometrically (e.g., tumor) or by fluorescent cell subset markers (e.g., CD11c). Each ROI was further analyzed using NanoString Digital Spatial Profiling high-resolution multiplex profiling. Digital counts for 59-panel immune-related proteins were collected and normalized to account for system variation and ROI area., Results: Tumor regions of SLNs had variable infiltration of CD3 cells among patients. The patient with overall survival (OS) > 8 years had the most CD11c- and CD3-expressing cells infiltrating the SLN tumor region. All patients had CD11c (dendritic cell, DC) infiltration into the SLN tumor region. Selecting ROI by specific cell subtype, we compared protein expression of CD11c cells between tumor and non-tumor/normal tissue SLN regions. Known markers of DC activation such as CD86, HLA-DR, and OX40L were lowest on CD11c cells within SLN tumor for the patient with OS < 1 year and highest on the patient with OS > 8 years., Conclusion: We demonstrate the feasibility of profiling the protein expression of CD11c cells within the SLN tumor. Identifying early regulators of melanoma control when the disease is microscopically detected in the SLN is beneficial and requires follow-up studies in a larger cohort of patients.

Background: Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care., Objectives: To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients., Methods: Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017., Results: Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8-97] years; 53% female, 83% white), 66% presented with stage 0-2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0-259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05-1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00-3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07-1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38-3.80; P = .001) were also prognostic factors for recurrence-free survival., Conclusion: In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.

Background: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS)., Methods: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes., Results: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013)., Conclusions: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.

Introduction: Since 2011, encouraging clinical trial results have led to approval of multiple new therapies for advanced melanoma, but the impact of these therapies outside of trial populations is largely unknown. This study examines use of novel therapies and survival in contemporary patients with melanoma., Methods: Stage I-IV melanoma patients were identified in the 2004-2015 National Cancer Database and grouped into historic (2004-2010) and contemporary (2011-2015) cohorts. Overall survival (OS) was compared using Kaplan-Meier and Cox proportional hazard modeling adjusting for patient, tumor, and facility characteristics., Results: Of 268,668 patients, 136,828 were classified as historic and 131,840 as contemporary. Among all stages, immunotherapy utilization was significantly higher among contemporary patients (5.3% vs. 5.1%, p = 0.006). Adjusted OS was improved in the contemporary cohort (hazard ratio [HR]: 0.90 p < 0.001). There was no difference in OS among stage I/II patients between groups (HR: 0.99, p = 0.63), while OS was significantly improved for contemporary stage III/IV patients (HR: 0.85, p < 0.001). Among stage III/IV patients who received immunotherapy, OS was improved for the contemporary cohort (HR: 0.87, p = 0.014)., Conclusions: Adjusted overall survival for contemporary melanoma patients is improved. This effect is driven by improvements for those with advanced stage disease, particularly those that received immunotherapy and BRAF/MEK targeted therapies.

Background: Multiple adjuvant therapies for melanoma have been approved since 2015 based on randomized trials demonstrating improvements in recurrence-free survival (RFS) with adjuvant therapy after surgical resection of high-risk disease. Inclusion criteria for these trials required performance of a completion lymph node dissection (CLND) for positive sentinel lymph node (pSLN) disease., Objective: We aimed to describe current practice for adjuvant therapies in patients with pSLN without CLND (active surveillance [AS]), and to evaluate recurrence in these patients., Methods: Melanoma patients with pSLN between 2016 and 2019 were identified at two institutions. Demographic information, disease and treatment characteristics, and recurrence details were reviewed retrospectively. Patients were stratified by recurrence and patient-, treatment- and tumor-related characteristics were compared using Fisher's exact test and t test for categorical and continuous variables, respectively., Results: Overall, 245 SLN biopsies were performed, of which 36 (14.7%) were pSLN. Of 36 pSLN, 4 underwent CLND and 32 underwent AS, of whom 22 (68.8%) received adjuvant therapy with the anti-programmed death-1 (PD1) inhibitor nivolumab (16/22), anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab (3/22), or BRAF/MEK inhibitors (3/22). At a median follow up of 13.3 months, 7/32 (21.9%) patients on AS recurred, including 4/22 (18.2%) who received adjuvant therapy and 3/10 (30.0%) who did not. Tumor ulceration was significantly associated with recurrence. While not significant, acral lentiginous subtype appeared more common among those with recurrence., Conclusion: The majority (68.8%) of patients with pSLN managed without CLND were treated with adjuvant therapy. The 1-year RFS for patients managed with adjuvant therapy without CLND was 82%, which is similar to modern adjuvant therapy trials requiring CLND.

Purpose: We hypothesized that initial biopsy may understage acral lentiginous melanoma (ALM) and lead to undertreatment or incomplete staging. Understanding this possibility can potentially aid surgical planning and improve primary tumor staging., Methods: A retrospective review of primary ALMs treated from 2000 to 2017 in the US Melanoma Consortium database was performed. We reviewed pathology characteristics of initial biopsy, final excision specimens, surgical margins, and sentinel lymph node biopsy (SLNB)., Results: We identified 418 primary ALMs (321 plantar, 34 palmar, 63 subungual) with initial biopsy and final pathology results. Median final thickness was 1.8 mm (range 0.0-19.0). There was a discrepancy between initial biopsy and final pathology thickness in 180 (43%) patients with a median difference of 1.6 mm (range 0.1-16.4). Final T category was increased in 132 patients (32%), including 47% of initially in situ, 32% of T1, 39% of T2, and 28% of T3 lesions. T category was more likely to be increased in subungual (46%) and palmar (38%) melanomas than plantar (28%, p = 0.01). Among patients upstaged to T2 or higher, 71% had ≤ 1-cm margins taken. Among the 27 patients upstaged to T1b or higher, 8 (30%) did not have a SLNB performed, resulting in incomplete initial staging., Conclusions: In this large series of ALMs, final T category was frequently increased on final pathology. A high index of suspicion is necessary for lesions initially in situ or T1 and consideration should be given to performing additional punch biopsies, wider margin excisions, and/or SLNB.

Introduction: Isolated limb infusion (ILI) is a minimally-invasive procedure for delivering high-dose regional chemotherapy to treat melanoma in-transit metastases confined to a limb. The aim of this international multi-centre study was to identify predictive factors for toxicity and response., Methods: Data of 687 patients who underwent a first ILI for melanoma in-transit metastases confined to the limb between 1992 and 2018 were collected at five Australian and four US tertiary referral centres., Results: After ILI, predictive factors for increased limb toxicity (Wieberdink grade III/IV limb toxicity, n = 192, 27.9%) were: female gender, younger age, procedures performed before 2005, lower limb procedures, higher melphalan dose, longer drug circulation and ischemia times, and increased tissue hypoxia. No patient experienced grade V toxicity (necessitating amputation). A complete response (n = 199, 28.9%) was associated with a lower stage of disease, lower burden of disease (BOD) and thinner Breslow thickness of the primary melanoma. Additionally, an overall response (combined complete and partial response, n = 441, 64.1%) was associated with female gender, Australian centres, procedures performed before 2005, lower limb procedures and lower actinomycin-D doses. On multivariate analysis, higher melphalan dose remained a predictive factor for toxicity, while lower stage of disease and lower BOD remained predictive factors for overall response., Conclusion: ILI is safe and effective to treat melanoma in-transit metastases. Predictive factors for toxicity and response identified in this study will allow improved patient selection and optimization of intra-operative parameters to increase response rates, while keeping toxicity low., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Patients with unresectable cutaneous, subcutaneous, or nodal melanoma metastases are often candidates for injectable therapies, which are attractive for ease of intralesional delivery to superficial metastases and limited systemic toxicity profiles. Injectable or intralesional therapies can be part of multifaceted treatment strategies to kill tumor directly or to alter the tumor so as to make it more sensitive to systemic therapy. Talimogene laherparepvec is the only Food and Drug Administration-approved injectable therapy currently in wide clinical use in the United States, although ongoing trials are evaluating novel intralesional agents as well as combinations with systemic therapies, particularly checkpoint inhibitors., Competing Interests: Disclosure The authors have no disclosures related to this work. To the best of the authors’ knowledge, this review contains no material previously published or written by another person except where due references are made. There was no funding provided for this work., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To examine guideline concordance across a national sample and determine the relationship between socioeconomic factors, use of recommended postoperative adjuvant therapy, and outcomes for patients with resected pN1 or pN2 non-small cell lung cancer., Methods: All margin-negative pT1-3 N1-2 M0 non-small cell lung cancers treated with lobectomy or pneumonectomy without induction therapy in the National Cancer Database between 2006 and 2013 were included. Use of guideline-concordant adjuvant treatment, defined as chemotherapy for pN1 disease and chemotherapy with or without radiation for pN2 disease, was examined. Multivariable regression models were developed to determine associations of clinical factors with guideline adherence. Survival was estimated using Kaplan-Meier and Cox proportional hazard analyses., Results: Of 13,462 patients, 10,113 had pN1 disease and 3349 had pN2 disease. Guideline-concordant adjuvant therapy was used in 6844 (67.7%) patients with pN1 disease and 2622 (78.3%) patients with pN2 disease. After multivariable adjustment, insurance status, older age, pneumonectomy, readmission, and longer postoperative stays were associated with lower likelihood of guideline concordance. Conversely, increased education level, later year of diagnosis, and greater nodal stage were associated with greater concordance. Overall, patients treated with guideline-concordant therapy had superior survival (5-year survival: 51.6 vs 36.0%; hazard ratio, 0.66; 95% confidence interval, 0.62-0.70, P < .001)., Conclusions: Socioeconomic factors, including insurance status and geographic region, are associated with disparities in use of adjuvant therapy as recommended by National Comprehensive Cancer Network guidelines. These disparities significantly impact patient survival. Future work should focus on improving access to appropriate adjuvant therapies among the under insured and socioeconomically disadvantaged., (Copyright © 2019 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON)., Patients and Methods: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used., Results: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively., Conclusions: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

Background: Chemotherapy improves outcomes in patients with resectable gastric cancer. Minimally invasive gastrectomy (MIS) rates are increasing, though the impact of MIS on postoperative chemotherapy remains uncertain. This study examines the impact of MIS vs open gastrectomy (OG) on utilization of adjuvant chemotherapy for high-risk gastric cancer., Methods: Patients in the National Cancer Database who underwent resection for high-risk gastric adenocarcinoma between 2010 and 2015 were included. Patients were stratified by surgical approach (MIS vs OG) and analyzed using multivariable regression modeling. Primary endpoints were utilization of and time to initiation of adjuvant chemotherapy., Results: Overall, 23 071 patients were included; 16 595 (71.9%) underwent OG and 6476 (28.1%) underwent MIS. After adjusting for patient and tumor characteristics, MIS was not associated with increased use of adjuvant chemotherapy (odds ratio [OR]: 1.027, 95% confidence interval [CI]: 0.95 to 1.11, P = .50), and time to initiation of chemotherapy was similar (-2% change, 95% CI: -5% to +1%, P = .27). MIS was associated with shorter hospital stays (-1 day). Thirty-day readmission rates, 90-day mortality, and overall survival were similar between groups., Conclusions: In this study, while MIS for gastric adenocarcinoma was associated with shorter hospital stays and comparable survival, it was not associated with improved utilization or time to initiation of adjuvant chemotherapy., (© 2020 Wiley Periodicals, Inc.)

In the original article, there is an error in the funding information. The correct funding information is as follows.

Background: Approximately 38% of patients with colorectal cancer will develop isolated liver metastases. Sidedness of colon tumor is identified in non-metastatic and unresected metastatic cancers as predictive of survival, yet its dedicated analysis in resected liver metastases is minimal. Our primary aim was to assess whether left-sided primary tumors improve prognosis in stage IV cancer patients undergoing curative-intent liver metastasectomy; it was hypothesized that it would., Methods: This is a retrospective, observational cohort study from 1996 to 2016 in a single tertiary-care facility. Survival from diagnosis was calculated via Kaplan-Meier method and compared between the right and left sides via log-rank analysis., Results: Median survival differs significantly between colorectal tumors of the right and left origins after hepatic metastasectomy in 612 patients. In patients with right-sided tumors, median survival from diagnosis was 4.5 years (IQR 4.1-5.3), and 6.3 years (IQR 5.6-6.9) in those with left tumors (HR 1.5, 95% CI 1.38-1.60, p < 0.001)., Conclusion: As in studies on earlier-stage or unresected metastatic disease, tumor sidedness is an important prognostic factor in patient survival with liver metastasectomy. Clinical risk scores should include side of primary tumor. Further work is needed to determine the molecular basis for this difference., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The National Comprehensive Cancer Network guidelines recommend consideration of surgery for clinical T4a esophageal adenocarcinoma. There are limited data on the outcomes of patients with T4a adenocarcinoma treated with surgery vs definitive chemoradiation, however., Methods: The National Cancer Database was used to identify patients from 2010-2015 with clinical T4aN0-3M0 esophageal adenocarcinoma, and grouped by receipt of surgery (with or without perioperative therapy) or definitive, concurrent chemoradiation. Patients receiving incomplete definitive therapy or with missing survival information were excluded. Overall survival was evaluated with Kaplan-Meier and Cox proportional hazard analyses., Results: Of 182 patients in the study, 85 (47%) underwent esophagectomy and 97 (53%) underwent chemoradiation. In the surgery cohort, 79 patients (93%) received perioperative chemotherapy. Unadjusted and multivariable analyses demonstrated a significant survival benefit associated with surgery compared with definitive chemoradiotherapy (adjusted hazard ratio 0.32; 95% confidence interval 0.21, 0.50). A 1:1 propensity score-matched analysis of 63 patient pairs also revealed a significant overall survival benefit with surgery compared with chemoradiotherapy alone (hazard ratio 0.26; 95% confidence interval 0.16, 0.43)., Conclusions: In this national analysis, surgery for cT4a esophageal adenocarcinoma was associated with improved outcomes when compared with definitive chemoradiation. Surgery should be considered for medically fit patients with cT4aN0-3M0 esophageal adenocarcinoma., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Nodal observation is safe for patients with microscopic melanoma metastasis in a sentinel lymph node (LN). Complete LN dissection (CLND) remains the standard of care for patients with clinically evident LN (cLN) metastases, even though about 40% have only one pathologic LN (pLN). We sought to identify clinical features associated with having one pLN among patients with cLNs., Methods: Patients at three melanoma centers who underwent CLND for cLNs were identified. Clinicopathologic and imaging characteristics associated with one pLN were determined by multivariable logistic regression and classification tree analysis., Results: Of 190 patients, 90 (47.4%) had one pLN and 100 (52.6%) had more than one pLN. By multivariable logistic regression, extremity versus truncal primary (odds ratio [OR] 2.15, p = 0.012), axillary versus superficial inguinal location (OR 3.89, p = 0.009), and preoperative cross-sectional imaging demonstrating more than one versus one cLN (OR 17.1, p < 0.001) were associated with more than one pLN. The negative predictive value for additional pathologic nodal disease of preoperative imaging was 70.9%, increasing to 74.4% for positron emission tomography/computed tomography. In the subgroup of patients with one cLN, the classification tree identified two groups with < 10% risk of additional pLNs: (1) Breslow thickness > 6.55 mm (n = 17); and (2) if unknown primary or Breslow thickness ≤ 6.55 mm, then LN diameter > 1.8 cm in the inguinal location (n = 22)., Conclusion: The majority of patients with one cLN from melanoma by preoperative imaging will harbor no additional pathologic nodes on CLND. Safety of nodal observation after clinical nodal excision in these patients, particularly in an era of effective adjuvant therapies, deserves prospective evaluation.

Background: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma located on a limb. The current international multicenter study evaluated the perioperative and long-term oncologic outcomes for patients who underwent ILI for stage 3B or 3C melanoma., Methods: Patients undergoing a first-time ILI for stage 3B or 3C melanoma (American Joint Committee on Cancer [AJCC] 7th ed) between 1992 and 2018 at five Australian and four United States of America (USA) tertiary referral centers were identified. The primary outcome measures included treatment response, in-field (IPFS) and distant progression-free survival (DPFS), and overall survival (OS)., Results: A total of 687 first-time ILIs were performed (stage 3B: n = 383, 56%; stage 3C; n = 304, 44%). Significant limb toxicity (Wieberdink grade 4) developed in 27 patients (3.9%). No amputations (grade 5) were performed. The overall response rate was 64.1% (complete response [CR], 28.9%; partial response [PR], 35.2%). Stable disease (SD) occurred in 14.5% and progressive disease (PD) in 19.8% of the patients. The median follow-up period was 47 months, with a median OS of 38.2 months. When stratified by response, the patients with a CR or PR had a significantly longer median IPFS (21.9 vs 3.0 months; p < 0.0001), DPFS (53.6 vs 12.7 months; p < 0.0001), and OS (46.5 vs 24.4 months; p < 0.0001) than the nonresponders (SD + PD)., Conclusion: This study is the largest to date reporting long-term outcomes of ILI for locoregionally metastatic melanoma. The findings demonstrate that ILI is effective and safe for patients with stage 3B or 3C melanoma confined to a limb. A favorable response to ILI is associated with significantly longer IFPS, DPFS, and OS.

There has been a rapid increase in adjuvant therapies approved for treatment following surgical resection of stages III/IV melanoma. We review current indications for adjuvant therapy, which currently includes a heterogenous group of stages III and IV patients with melanoma. We describe several pivotal clinical trials of systemic immune therapies, targeted immune therapies, and adjuvant vaccine strategies. Finally, we discuss the evidence for selecting the most appropriate treatment regimen(s) for the individual patient., (© 2018 Wiley Periodicals, Inc.)