Clinical Presentation Patterns and Survival Outcomes of Hispanic Patients with Gastric Cancer
Background: Hispanic patients have a higher incidence of gastric cancer when compared to non-Hispanics. Outlining clinicodemographic characteristics and assessing the impact of ethnicity on stage-specific survival may identify opportunities to improve gastric cancer care for this population. Methods: Patients with gastric cancer in the US Safety Net Collaborative (2012-2014) were retrospectively reviewed. Demographics, clinicopathologic characteristics, operative details, and outcomes were compared between Hispanic and non-Hispanic patients. Early onset gastric cancer was defined as age <50 years. Kaplan-Meier and Cox proportional-hazards models were used to identify the impact of ethnicity on disease-specific survival (DSS). Results: Seven hundred and ninety-seven patients were included, of which 219 (28%) were Hispanic. Hispanic patients were more likely to seek care at safety-net hospitals (66 vs 39%) and be uninsured (36 vs 17%), and less likely to have a primary care provider (PCP) (46 vs 75%; all P<0.05). Hispanic patients were twice as likely to present with early onset gastric cancer (28 vs 15%) and were more frequently diagnosed in the emergency room (54 vs 37%) with both abdominal pain and weight loss (44 vs 31%; all P <0.05). Treatment paradigms, operative outcomes, and DSS were similar between Hispanic and non-Hispanic patients when accounting for cancer stage. Cancer stage, pathologically positive nodes, and negative surgical margins were independently associated with DSS. Conclusions: A diagnosis of gastric cancer must be considered in previously healthy Hispanic patients who present to the emergency room with both abdominal pain and weight loss. Fewer than 50% of Hispanic patients have a PCP, indicating poor outpatient support. Efforts to improve outpatient support and screening may improve gastric cancer outcomes in this vulnerable population.
Deep learning and pathomics analyses reveal cell nuclei as important features for mutation prediction of BRAF-mutated melanomas
Image-based analysis as a method for mutation detection can be advantageous in settings when tumor tissue is limited or unavailable for direct testing. Here, we utilize two distinct and complementary machine learning methods of analyzing whole slide images (WSI) for predicting mutated BRAF. In the first method, WSI of melanomas from 256 patients were used to train a deep convolutional neural network (CNN) in order to develop a fully automated model that first selects for tumor-rich areas (Area Under the Curve AUC=0.96) then predicts for mutated BRAF (AUC=0.71). Saliency mapping was performed and revealed that pixels corresponding to nuclei were the most relevant to network learning. In the second method, WSI were analyzed using a pathomics pipeline that first annotates nuclei and then quantifies nuclear features, demonstrating that mutated BRAF nuclei were significantly larger and rounder nuclei compared to BRAF WT nuclei. Lastly, we developed a model that combines clinical information, deep learning, and pathomics that improves the predictive performance for mutated BRAF to AUC=0.89. Not only does this provide additional insights on how BRAF mutations affect tumor structural characteristics, machine learning-based analysis of WSI has the potential to be integrated into higher order models for understanding tumor biology.
Rare presentation of inflammatory myofibroblastic tumor in a failed renal allograft
Inflammatory myofibroblastic tumors (IMT) are rare, mesenchymal tumors that can occur in any anatomic location. IMTs have a variable clinical course but usually require wide surgical excision to prevent local recurrence. There have been limited case reports of IMT occurring in solid organ transplant recipients. Herein we report on a case of IMT presenting in a failed renal allograft. A 53-year-old male awaiting re-transplant presented with pain and a palpable mass in his allograft. Imaging demonstrated an infiltrative soft tissue mass encasing the renal hilum. Percutaneous biopsy demonstrated a myofibroblastic proliferation with myxoid background and no high-grade features. The tumor cells were diffusely positive for anaplastic lymphoma kinase-1 (ALK-1) and had a Ki-67 proliferation index of 10%. These findings were consistent with a diagnosis of IMT. A transplant nephrectomy was performed with wide margins to achieve an R0 resection. Pathology on the resection specimen confirmed an IMT that measured 6.5 cm x 6.3 cm. The patient has no evidence of local recurrence at 6-months follow-up and has been relisted for a second kidney transplant.
Training Paradigms in Hepato-Pancreatico-Biliary Surgery: an Overview of the Different Fellowship Pathways
Hepato-pancreatico-biliary (HPB) surgery, and the training of HPB surgeons, has evolved significantly over the last several decades. The current state of training in HPB surgery in North America is defined through three main pathways: the Complex General Surgical Oncology (CGSO) ACGME fellowship, the American Society of Transplant Surgeons (ASTS) fellowship, and the Americas Hepatopancreaticobiliary Association (AHPBA) fellowship. These fellowships offer variable experiences in pancreas, liver, and biliary cases, and each pathway offers a unique perspective on HPB surgery. The CGSO ACGME, ASTS, and AHPBA fellowships represent decades of work by the three major surgical leadership stakeholders to improve and ensure quality training of future HPB surgeons. The best care is provided by the HPB surgeon who has been trained to understand the importance of all available treatment options within the context of a multidisciplinary setting. The three fellowship pathways are outlined in this paper with the nuances and variations characteristic of the different training programs highlighted.
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/UNASSIGNED: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.
Correction to: The Devil's in the Details: Discrepancy Between Biopsy Thickness and Final Pathology in Acral Melanoma
Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis
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/METHODS: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%, pÂ = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, pÂ = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, pÂ = 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.
Optimization of an automated tumor-infiltrating lymphocyte algorithm for improved prognostication in primary melanoma
Tumor-infiltrating lymphocytes (TIL) have potential prognostic value in melanoma and have been considered for inclusion in the American Joint Committee on Cancer (AJCC) staging criteria. However, interobserver discordance continues to prevent the adoption of TIL into clinical practice. Computational image analysis offers a solution to this obstacle, representing a methodological approach for reproducibly counting TIL. We sought to evaluate the ability of a TIL-quantifying machine learning algorithm to predict survival in primary melanoma. Digitized hematoxylin and eosin (H&E) slides from prospectively enrolled patients in the NYU melanoma database were scored for % TIL using machine learning and manually graded by pathologists using Clark's model. We evaluated the association of % TIL with recurrence-free survival (RFS) and overall survival (OS) using Cox proportional hazards modeling and concordance indices. Discordance between algorithmic and manual TIL quantification was assessed with McNemar's test and visually by an attending dermatopathologist. In total, 453 primary melanoma patients were scored using machine learning. Automated % TIL scoring significantly differentiated survival using an estimated cutoff of 16.6% TIL (log-rank Pâ€‰<â€‰0.001 for RFS; Pâ€‰=â€‰0.002 for OS). % TIL was associated with significantly longer RFS (adjusted HRâ€‰=â€‰0.92 [0.84-1.00] per 10% increase in % TIL) and OS (adjusted HRâ€‰=â€‰0.90 [0.83-0.99] per 10% increase in % TIL). In comparison, a subset of the cohort (nâ€‰=â€‰240) was graded for TIL by melanoma pathologists. However, TIL did not associate with RFS between groups (Pâ€‰>â€‰0.05) when categorized as brisk, nonbrisk, or absent. A standardized and automated % TIL scoring algorithm can improve the prognostic impact of TIL. Incorporation of quantitative TIL scoring into the AJCC staging criteria should be considered.
Surgical resection of early stage hepatocellular carcinoma improves patient survival at safety net hospitals
BACKGROUND AND OBJECTIVES/OBJECTIVE:Surgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs). METHODS:Patients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012-2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan-Meier and Cox proportional-hazards models were used to identify the effect of surgery on overall (OS). RESULTS:A total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; pâ€‰<â€‰.05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well-differentiated tumors (23% vs. 2%; pâ€‰<â€‰.05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS. CONCLUSIONS:Although SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.
Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis
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/OBJECTIVE: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:= .001) were also prognostic factors for recurrence-free survival. CONCLUSION/CONCLUSIONS: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.