291 results on '"Coit DG"'
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2. A prospective evaluation of the utility of 2-deoxy-2-[(18) F]fluoro-D-glucose positron emission tomography and computed tomography in staging locally advanced gastric cancer.
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Smyth E, Schöder H, Strong VE, Capanu M, Kelsen DP, Coit DG, Shah MA, Smyth, Elizabeth, Schöder, Heiko, Strong, Vivian E, Capanu, Marinela, Kelsen, David P, Coit, Daniel G, and Shah, Manish A
- Abstract
Background: The aim of this study was to examine prospectively the utility of adding preoperative [(18) F]fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) to routine CT, endoscopic ultrasound (EUS), and laparoscopic staging of localized gastric cancer.Methods: Patients with locally advanced gastric/gastroesophageal cancer were screened for 2 institutional review board-approved Memorial Sloan-Kettering Cancer Center neoadjuvant chemotherapy protocols. Locally advanced disease was defined as T3 or T4, or lymph node-positive, based on EUS and high-resolution CT scan. All patients underwent both standard FDG-PET/CT and laparoscopy with cytological examination of washings. The sensitivity and specificity of FDG-PET/CT for the identification of metastatic disease not seen on CT was determined. An economic model using Medicare/Medicaid reimbursement charges was developed to assess the cost-effectiveness of these interventions.Results: A total of 113 patients were enrolled from 2003 to 2010. All patients were assessed as having locally advanced disease by CT/EUS. FDG uptake in the primary tumor was associated with male sex, proximal tumors, and nondiffuse Lauren's subtype. 31 (27%) patients had occult metastatic disease detected by PET/CT (n = 11, 10%) and/or laparoscopy (n = 21, 19%), with a single overlap. Economic modeling suggests that the addition of FDG-PET/CT to the standard staging evaluation of patients with locally advanced gastric cancer resulted in an estimated cost savings of ∼US $13,000 per patient.Conclusions: FDG-PET/CT identifies occult metastatic lesions in approximately 10% of patients with locally advanced gastric cancer. Because of reduced morbidity from fewer futile surgeries and lower patient care costs, PET/CT should be considered as a component of the standard staging algorithm for localized gastric cancer. [ABSTRACT FROM AUTHOR]- Published
- 2012
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3. Prospective impact of tumor grade assessment in biopsies on tumor stage and prognostic grouping in gastroesophageal adenocarcinoma: Relevance of the seventh edition American Joint Committee on Cancer Staging Manual revision.
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Dikken JL, Coit DG, Klimstra DS, Rizk NP, van Grieken N, Ilson D, and Tang LH
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- 2012
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4. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases.
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Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, Cascinelli N, Cochran AJ, Coit DG, Eggermont AM, Johnson T, Kirkwood JM, Leong SP, McMasters KM, Mihm MC Jr, Morton DL, Ross MI, Sondak VK, Balch, Charles M, and Gershenwald, Jeffrey E
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- 2010
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5. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis.
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Tanvetyanon T, Robinson LA, Schell MJ, Strong VE, Kapoor R, Coit DG, and Bepler G
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- 2008
6. Staging laparoscopy in the management of gastric cancer: a population-based analysis.
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Karanicolas PJ, Elkin EB, Jacks LM, Atoria CL, Strong VE, Brennan MF, and Coit DG
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- 2011
7. Patient metabolic profile defined by liver and muscle 18 F-FDG PET avidity is independently associated with overall survival in gastric cancer.
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Vitiello GA, Jayaprakasam VS, Tang LH, Schattner MA, Janjigian YY, Ku GY, Maron SB, Schoder H, Larson SM, Gönen M, Datta J, Coit DG, Brennan MF, and Strong VE
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- Humans, Male, Aged, Female, Positron Emission Tomography Computed Tomography, Prognosis, Muscles pathology, Liver, Metabolome, Albumins, Retrospective Studies, Radiopharmaceuticals, Fluorodeoxyglucose F18, Stomach Neoplasms pathology
- Abstract
Background: PET-CT-based patient metabolic profiling is a novel concept to incorporate patient-specific metabolism into gastric cancer care., Methods: Staging PET-CTs, demographics, and clinicopathologic variables of gastric cancer patients were obtained from a prospectively maintained institutional database. PET-CT avidity was measured in tumor, liver, spleen, four paired muscles, and two paired fat areas in each patient. The liver to rectus femoris (LRF) ratio was defined as the ratio of SUV
mean of liver to the average SUVmean of the bilateral rectus femoris muscles. Kaplan-Meier and Cox-proportional hazards models were used to identify the impact of LRF ratio on OS., Results: Two hundred and one patients with distal gastroesophageal (48%) or gastric (52%) adenocarcinoma were included. Median age was 65 years, and 146 (73%) were male. On univariate analysis, rectus femoris PET-CT avidity and LRF ratio were significantly associated with overall survival (p < 0.05). LRF ratio was significantly higher in males, early-stage cancer, patients with an ECOG 0 or 1 performance status, patients with albumin > 3.5 mg/dL, and those with moderately differentiated tumor histology. In multivariable regression, gastric cancer stage, albumin, and LRF ratio were significant independent predictors of overall survival (LRF ratio HR = 0.73 (0.56-0.96); p = 0.024). Survival curves showed that the prognostic impact of LRF was associated with metastatic gastric cancer (p = 0.009)., Conclusions: Elevated LRF ratio, a patient-specific PET-CT-based metabolic parameter, was independently associated with an improvement in OS in patients with metastatic gastric cancer. With prospective validation, LRF ratio may be a useful, host-specific metabolic parameter for prognostication in gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)- Published
- 2024
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8. Immediate Lymphatic Reconstruction with Vascularized Omentum Lymph Node Transplant: Reducing the Risk of Both Painful Contracture and Lymphedema.
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Brown S, Kokosis G, Graziano FD, Haran O, Smith-Montes E, Zivanovic O, Ariyan CE, Coit DG, Coriddi M, Mehrara BJ, and Dayan JH
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Patients undergoing extensive lymph node dissection and radiation are at high risk for not only lymphedema but also painful contracture. In a standard lymphadenectomy, immediate lymphatic reconstruction using a lymphovenous bypass is effective in reconstructing the lymphatic defect. However, a more aggressive nodal clearance leaves the patient with a large cavity and skeletonized neurovascular structures, often resulting in severe contracture, pain, cosmetic deformity, and venous stricture. Adjuvant radiotherapy to the nodal bed can lead to severe and permanent disability despite physical therapy. Typically, these patients are referred to us after the fact, where surgery will rarely restore the patient to normal function. In an effort to avoid lymphedema and contracture, we have been reconstructing both the lymphatic and soft tissue defect during lymphadenectomy, using vascularized omentum lymphatic transplant (VOLT). A total of 13 patients underwent immediate reconstruction with VOLT at the time of axillary (n = 8; 61.5%) or groin (n = 5; 38.5%) dissection. No postoperative complications were observed. The mean follow-up time was 15.1 ± 12.5 months. Only one lower extremity patient developed mild lymphedema (11% volume differential), with excellent scores in validated patient-reported outcomes. All patients maintained full range of motion with no pain. None of the 13 patients required a compression garment. Immediate lymphatic reconstruction with VOLT is a promising procedure for minimizing the risk of lymphedema and contracture in the highest risk patients undergoing particularly extensive lymph node dissection and radiotherapy., Competing Interests: Babak J. Mehrara, MD, is the recipient of investigator-initiated research awards from Regeneron, Atyr, Integra, and Pfizer and royalty payments from PureTech, and he is a consultant for Mediflix. Joseph H. Dayan, MD, is a paid consultant for the Stryker Corporation, has intellectual property rights with Elucida Oncology and equity interest in Welwaze Medical, LLC, and has a royalty agreement with Springer Publishers for Multimodal Management of Upper and Lower Extremity Lymphedema. Dr. Ariyan has participated in Ad Boards for Merck and Iovance and holds stock in Pfizer. All the other authors have no financial interest to declare in relation to the content of this article. This research was supported in part by the NIH through R01 HL111130 and R01CA278599 awarded to Babak J. Mehrara, MD and the Cancer Center Support Grant P30 CA008748 that supports the research infrastructure at Memorial Sloan Kettering Cancer Center., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)
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- 2024
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9. Population-Based Validation of the MIA and MSKCC Tools for Predicting Sentinel Lymph Node Status.
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Olofsson Bagge R, Mikiver R, Marchetti MA, Lo SN, van Akkooi ACJ, Coit DG, Ingvar C, Isaksson K, Scolyer RA, Thompson JF, Varey AHR, Wong SL, Lyth J, and Bartlett EK
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- Male, Humans, Middle Aged, Aged, Female, Sentinel Lymph Node Biopsy, Australia, Sentinel Lymph Node, Melanoma, Skin Neoplasms
- Abstract
Importance: Patients with melanoma are selected for sentinel lymph node biopsy (SLNB) based on their risk of a positive SLN. To improve selection, the Memorial Sloan Kettering Cancer Center (MSKCC) and Melanoma Institute Australia (MIA) developed predictive models, but the utility of these models remains to be tested., Objective: To determine the clinical utility of the MIA and MSKCC models., Design, Setting, and Participants: This was a population-based comparative effectiveness research study including 10 089 consecutive patients with cutaneous melanoma undergoing SLNB from the Swedish Melanoma Registry from January 2007 to December 2021. Data were analyzed from May to August 2023., Main Outcomes and Measures,: The predicted probability of SLN positivity was calculated using the MSKCC model and a limited MIA model (using mitotic rate as absent/present instead of count/mm2 and excluding the optional variable lymphovascular invasion) for each patient. The operating characteristics of the models were assessed and compared. The clinical utility of each model was assessed using decision curve analysis and compared with a strategy of performing SLNB on all patients., Results: Among 10 089 included patients, the median (IQR) age was 64.0 (52.0-73.0) years, and 5340 (52.9%) were male. The median Breslow thickness was 1.8 mm, and 1802 patients (17.9%) had a positive SLN. Both models were well calibrated across the full range of predicted probabilities and had similar external area under the receiver operating characteristic curves (AUC; MSKCC: 70.8%; 95% CI, 69.5-72.1 and limited MIA: 69.7%; 95% CI, 68.4-71.1). At a risk threshold of 5%, decision curve analysis indicated no added net benefit for either model compared to performing SLNB for all patients. At risk thresholds of 10% or higher, both models added net benefit compared to SLNB for all patients. The greatest benefit was observed in patients with T2 melanomas using a threshold of 10%; in that setting, the use of the nomograms led to a net reduction of 8 avoidable SLNBs per 100 patients for the MSKCC nomogram and 7 per 100 patients for the limited MIA nomogram compared to a strategy of SLNB for all., Conclusions and Relevance: This study confirmed the statistical performance of both the MSKCC and limited MIA models in a large, nationally representative data set. However, decision curve analysis demonstrated that using the models only improved selection for SLNB compared to biopsy in all patients when a risk threshold of at least 7% was used, with the greatest benefit seen for T2 melanomas at a threshold of 10%. Care should be taken when using these nomograms to guide selection for SLNB at the lowest thresholds.
- Published
- 2024
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10. Clinical and molecular characteristics of early-onset vs average-onset esophagogastric cancer.
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Lumish MA, Walch H, Maron SB, Chatila W, Kemel Y, Maio A, Ku GY, Ilson DH, Won E, Li J, Joshi SS, Gu P, Schattner MA, Laszkowska M, Gerdes H, Jones DR, Sihag S, Coit DG, Tang LH, Strong VE, Molena D, Stadler ZK, Schultz N, Janjigian YY, and Cercek A
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- Humans, Female, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Cardia metabolism, Esophagogastric Junction metabolism, Esophagogastric Junction pathology, Retrospective Studies, Esophageal Neoplasms epidemiology, Esophageal Neoplasms genetics, Stomach Neoplasms diagnosis, Stomach Neoplasms epidemiology, Stomach Neoplasms genetics, Adenocarcinoma epidemiology, Adenocarcinoma genetics, Carcinoma, Signet Ring Cell metabolism, Carcinoma, Signet Ring Cell pathology
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Background: The rate of esophagogastric cancer is rising among individuals under 50 years of age. It remains unknown whether early-onset esophagogastric cancer represents a unique entity. This study investigated the clinical and molecular characteristics of early-onset and average-onset esophagogastric cancer ., Methods: We reviewed the Memorial Sloan Kettering Cancer Center gastric, esophageal, and gastroesophageal junction cancer database. Associations between baseline characteristics and tumor and germline molecular alterations were compared between those with early-onset and average-onset esophagogastric cancer using Fisher exact tests and the Benjamini-Hochberg method for multiple-hypothesis correction., Results: We included 1123 patients with early-onset esophagogastric cancer (n = 219; median age = 43 years [range = 18-49 years]) and average-onset esophagogastric cancer (n = 904; median age = 67 years [range = 50-94 years]) treated between 2005 and 2018. The early-onset group had more women (39% vs 28%, P = .002). Patients with early-onset esophagogastric cancer were more likely to have a gastric primary site (64% vs 44%, P < .0001). The signet ring cell and/or diffuse type was 3 times more common in the early-onset esophagogastric cancer group (31% vs 9%, P < .0001). Early-onsite tumors were more frequently genomically stable (31% vs 18%, P = .0002) and unlikely to be microsatellite instability high (2% vs 7%, P = .003). After restricting to adenocarcinoma and signet ring cell and/or diffuse type carcinomas, we observed no difference in stage (P = .40) or overall survival from stage IV diagnosis (median = 22.7 vs 22.1 months, P = .78)., Conclusions: Our study supported a preponderance of gastric primary disease sites, signet ring histology, and genomically stable molecular subtypes in early-onset esophagogastric cancer. Our findings highlight the need for further research to define the underlying pathogenesis and strategies for early detection and prevention., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2024
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11. Clinical Utility of Melanoma Sentinel Lymph Node Biopsy Nomograms.
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Drebin HM, Hosein S, Kurtansky NR, Nadelmann E, Moy AP, Ariyan CE, Bello DM, Brady MS, Coit DG, Marchetti MA, and Bartlett EK
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- Humans, Sentinel Lymph Node Biopsy, Nomograms, Lymphatic Metastasis pathology, Lymph Nodes pathology, Retrospective Studies, Melanoma pathology, Sentinel Lymph Node pathology, Skin Neoplasms surgery, Skin Neoplasms pathology
- Abstract
Background: For patients with melanoma, the decision to perform sentinel lymph node biopsy (SLNB) is based on the estimated risk of lymph node metastasis. We assessed 3 melanoma SLNB risk-prediction models' statistical performance and their ability to improve clinical decision making (clinical utility) on a cohort of melanoma SLNB cases., Study Design: Melanoma patients undergoing SLNB at a single center from 2003 to 2021 were identified. The predicted probabilities of sentinel lymph node positivity using the Melanoma Institute of Australia, Memorial Sloan Kettering Cancer Center (MSK), and Friedman nomograms were calculated. Receiver operating characteristic and calibration curves were generated. Clinical utility was assessed via decision curve analysis, calculating the net SLNBs that could have been avoided had a given model guided selection at different risk thresholds., Results: Of 2,464 melanoma cases that underwent SLNB, 567 (23.0%) had a positive sentinel lymph node. The areas under the receiver operating characteristic curves for the Melanoma Institute of Australia, MSK, and Friedman models were 0.726 (95% CI, 0.702 to 0.750), 0.720 (95% CI, 0.697 to 0.744), and 0.721 (95% CI, 0.699 to 0.744), respectively. For all models, calibration was best at predicted positivity rates below 30%. The MSK model underpredicted risk. At a 10% risk threshold, only the Friedman model would correctly avoid a net of 6.2 SLNBs per 100 patients. The other models did not reduce net avoidable SLNBs at risk thresholds of ≤10%., Conclusions: The tested nomograms had comparable performance in our cohort. The only model that achieved clinical utility at risk thresholds of ≤10% was the Friedman model., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)
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- 2024
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12. Perioperative versus total neoadjuvant chemotherapy in gastric cancer.
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Yang J, Greally M, Strong VE, Coit DG, Chou JF, Capanu M, Maron SB, Kelsen DP, Ilson DH, Janjigian YY, and Ku GY
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Background: Perioperative chemotherapy is standard of care management for locally advanced gastric cancer (GC), but a substantial proportion of patients do not complete adjuvant therapy due to postoperative complications and prolonged recovery. Administration of all chemotherapy prior to surgery in the form of total neoadjuvant therapy (TNT) may optimize complete delivery of systemic therapy., Methods: We performed a retrospective review of GC patients who had surgery at Memorial Sloan Kettering Cancer Center (MSKCC) from May 2014 to June 2020., Results: One hundred and forty-nine patients were identified; 121 patients received perioperative chemotherapy and 28 patients received TNT. TNT was chosen if patients had interim radiographic and/or clinical response to treatment. Baseline characteristics were well-balanced between the two group except for chemotherapy regimen; more TNT patients received FLOT compared to the perioperative group (79% vs. 31%). There was no difference in the proportion of patients who completed all planned cycles, but TNT patients received a higher proportion of cycles containing all chemotherapy drugs (93% vs. 74%, P<0.001). Twenty-nine patients (24%) in the perioperative group did not receive intended adjuvant therapy. There was no significant difference in hospital length of stay or surgical morbidity. The overall distribution of pathologic stage was similar between the two groups. Fourteen percent of TNT patients and 5.8% of perioperative patients achieved a pathologic complete response (P=0.6). There was no significant difference in recurrence free survival (RFS) or overall survival (OS) between the TNT and perioperative groups [24-month OS rate 77% vs. 85%, HR 1.69 (95% CI: 0.80-3.56)]., Conclusions: Our study was limited by a small TNT sample size and biases inherent to a retrospective analysis. TNT appears to be feasible in a select population, without any increase in surgical morbidity., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-23-4/coif). VS reported receiving speaking honoraria from Merck. SBM reported receiving honoraria from Natera, Bicara, Novartis, Basilea, Elevation Oncology, and Daiichi Sankyo, research-associated travel from AstraZeneca, grant support from the Conquer Cancer Foundation outside the submitted work, and owning stock in Calithera. DHI reported receiving consulting fees from Merck, AstraZeneca, Bristol-Myers Squibb, Astellas, Roche, Taiho, Macrogenics, Bayer, Daiichi Sankyo, and Eli Lilly. YYJ reported receiving research funding from the National Cancer Institute, the US Department of Defense, Cycle for Survival, Fred’s Team, RGENIX, Bayer, Genentech/Roche, Bristol-Myers Squibb, Eli Lilly, and Merck, consulting fees from Amerisource, Ask-Gene Pharma, Arcus Biosciences, Basilea, Geneos, GlaxoSmithKline, Imedex, Lynx Health, Mersana, Michael J. Hennessy, Paradigm Medical, PeerView, Phanes, RGENIX, Bayer, Bristol-Myers Squibb, Eli Lilly, Merck, Merck Serono, Daiichi Sankyo, Pfizer, Imugene, Zymeworks, Seagen, Silverback, and AstraZeneca, and having stock options in RGENIX outside the submitted work. GYK reported receiving grants from Adaptimmune, AstraZeneca, BMS, CARsgen, Eli Lilly, I-Mab, Merck, Oncolys, Pieris, Zymeworks, and Daiichi Sankyo, and receiving consulting fees from/served on Advisory Boards for AstraZeneca, BMS, I-Mab, Merck, and Pieris. The other authors have no conflicts of interest to declare., (2023 Journal of Gastrointestinal Oncology. All rights reserved.)
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- 2023
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13. Are the MIA and MSKCC nomograms useful in selecting patients with melanoma for sentinel lymph node biopsy?
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Hosein S, Drebin HM, Kurtansky NR, Olofsson Bagge R, Coit DG, Bartlett EK, and Marchetti MA
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- Humans, Female, Sentinel Lymph Node Biopsy, Nomograms, Lymphatic Metastasis pathology, Patient Selection, ROC Curve, Australia, Lymph Nodes pathology, Melanoma surgery, Melanoma pathology, Breast Neoplasms pathology
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Background and Methods: The Melanoma Institute of Australia (MIA) and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms were developed to help guide sentinel lymph node biopsy (SLNB) decisions. Although statistically validated, whether these prediction models provide clinical benefit at National Comprehensive Cancer Network guideline-endorsed thresholds is unknown. We conducted a net benefit analysis to quantify the clinical utility of these nomograms at risk thresholds of 5%-10% compared to the alternative strategy of biopsying all patients. External validation data for MIA and MSKCC nomograms were extracted from respective published studies., Results: The MIA nomogram provided added net benefit at a risk threshold of 9% but net harm at 5%-8% and 10%. The MSKCC nomogram provided added net benefit at risk thresholds of 5% and 9%-10% but net harm at 6%-8%. When present, the magnitude of net benefit was small (1-3 net avoidable biopsies per 100 patients)., Conclusion: Neither model consistently provided added net benefit compared to performing SLNB for all patients., Discussion: Based on published data, use of the MIA or MSKCC nomograms as decision-making tools for SLNB at risk thresholds of 5%-10% does not clearly provide clinical benefit to patients., (© 2023 Wiley Periodicals LLC.)
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- 2023
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14. Survival of Locally Advanced MSI-high Gastric Cancer Patients Treated With Perioperative Chemotherapy: A Retrospective Cohort Study.
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Vos EL, Maron SB, Krell RW, Nakauchi M, Fiasconaro M, Capanu M, Walch HS, Chatila WK, Schultz N, Ilson DH, Janjigian YY, Ku GY, Yoon SS, Coit DG, Vanderbilt CM, Tang LH, and Strong VE
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- Humans, Microsatellite Instability, Retrospective Studies, Prognosis, Disease-Free Survival, Chemotherapy, Adjuvant, Stomach Neoplasms drug therapy, Stomach Neoplasms surgery
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Objective: To evaluate the efficacy of chemotherapy in patients with microsatellite instability (MSI)-high gastric cancer., Background: Although MSI-high gastric cancer is associated with a superior prognosis, recent studies question the benefit of perioperative chemotherapy in this population., Methods: Locally advanced gastric adenocarcinoma patients who either underwent surgery alone or also received neoadjuvant, perioperative, or adjuvant chemotherapy between 2000 and 2018 were eligible. MSI status, determined by next-generation sequencing or mismatch repair protein immunohistochemistry, was determined in 535 patients. Associations among MSI status, chemotherapy administration, overall survival (OS), disease-specific survival, and disease-free survival were assessed., Results: In 535 patients, 82 (15.3%) had an MSI-high tumor and ∼20% better OS, disease-specific survival, and disease-free survival. Grade 1 (90%-100%) pathological response to neoadjuvant chemotherapy was found in 0 of 40 (0%) MSI-high tumors versus 43 of 274 (16%) MSS. In the MSI-high group, the 3-year OS rate was 79% with chemotherapy versus 88% with surgery alone ( P =0.48). In the MSS group, this was 61% versus 59%, respectively ( P =0.96). After multivariable interaction analyses, patients with MSI-high tumors had superior survival compared with patients with MSS tumors whether given chemotherapy (hazard ratio=0.53, 95% confidence interval: 0.28-0.99) or treated with surgery alone (hazard ratio=0.15, 95% confidence interval: 0.02-1.17)., Conclusions: MSI-high locally advanced gastric cancer was associated with superior survival compared with MSS overall, despite worse pathological chemotherapy response. In patients with MSI-high gastric cancer who received chemotherapy, the survival rate was ∼9% worse compared with surgery alone, but chemotherapy was not significantly associated with survival., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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15. Risk prediction model of peritoneal seeding in advanced gastric cancer: A decision tool for diagnostic laparoscopy.
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Kubo N, Cho H, Lee D, Yang H, Kim Y, Khalayleh H, Yoon HM, Ryu KW, Hanna GB, Coit DG, Hakamada K, and Kim YW Professor
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- Male, Female, Humans, Neoplasm Staging, Retrospective Studies, Peritoneum pathology, Nomograms, Stomach Neoplasms diagnosis, Stomach Neoplasms surgery, Stomach Neoplasms pathology, Laparoscopy
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Background: Selective diagnostic laparoscopy in gastric cancer patients at high risk of peritoneal metastasis is essential for optimal treatment planning. In this study available clinicopathologic factors predictive of peritoneal seeding in advanced gastric cancer (AGC) were identified, and this information was translated into a clinically useful tool., Methods: Totally 2833 patients underwent surgery for AGC between 2003 and 2013. The study identified clinicopathologic factors associated with the risk of peritoneal seeding for constructing nomograms using a multivariate logistic regression model with backward elimination. A nomogram was constructed to generate a numerical value indicating risk. Accuracy was validated using bootstrapping and cross-validation., Results: The proportion of seeding positive was 12.7% in females and 9.6% in males. Of 2833 patients who underwent surgery for AGC, 300 (10.6%) were intraoperatively identified with peritoneal seeding. Multivariate analysis revealed the following factors associated with peritoneal seeding: high American Society of Anesthesiologists score, fibrinogen, Borrmann type 3 or 4 tumors, the involvement of the middle, anterior, and greater curvature, cT3 or cT4cN1 or cN2 or cN3, cM1, and the presence of ascites or peritoneal thickening or plaque or a nodule on the peritoneal wall on computed tomography. The bootstrap analysis revealed a robust concordance between mean and final parameter estimates. The area under the ROC curve for the final model was 0.856 (95% CI, 0.835-0.877), which implies good performance., Conclusions: This nomogram provides effective risk estimates of peritoneal seeding from gastric cancer and can facilitate individualized decision-making regarding the selective use of diagnostic laparoscopy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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16. Current evidence does not support Mohs micrographic surgery or staged excision as equivalent to wide excision for primary cutaneous melanoma.
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Huerta T, Swetter SM, Nehal KS, Coit DG, Bichakjian CK, and Durham AB
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- Humans, Mohs Surgery, Neoplasm Recurrence, Local surgery, Melanoma, Cutaneous Malignant, Skin Neoplasms surgery, Melanoma surgery
- Abstract
Competing Interests: Conflicts of interest None disclosed.
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- 2023
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17. Distinct Differences in Gastroesophageal Junction and Gastric Adenocarcinoma in 2194 Patients: In Memory of Rebecca A. Carr, February 24, 1988-January 19, 2021.
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Nakauchi M, Vos EL, Carr RA, Barbetta A, Tang LH, Gonen M, Russo A, Janjigian YY, Yoon SS, Sihag S, Rusch VW, Bains MS, Jones DR, Coit DG, Molena D, and Strong VE
- Abstract
Objective: We sought to compare gastroesophageal junction (GEJ) cancer and gastric cancer (GC) and identify clinicopathological and oncological differences., Summary Background Data: GEJ cancer and GC are frequently studied together. Although the treatment approach for each often differs, clinico-pathological and oncological differences between the 2 have not been fully evaluated., Methods: We retrospectively identified patients with GEJ cancer or GC who underwent R0 resection at our center between January 2000 and December 2016. Clinicopathological characteristics, disease-specific survival (DSS), and site of first recurrence were compared., Results: In total, 2194 patients were analyzed: 1060 (48.3%) with GEJ cancer and 1134 (51.7%) with GC. Patients with GEJ cancer were younger (64 vs 66 years; P < 0.001), more often received neoadjuvant treatment (70.9% vs 30.2%; P < 0.001), and had lower pathological T and N status. Five-year DSS was 62.2% in patients with GEJ cancer and 74.6% in patients with GC ( P < 0.001). After adjustment for clinicopathological factors, DSS remained worse in patients with GEJ cancer (hazard ratio, 1.78; 95% confidence interval, 1.40-2.26; P < 0.001). The cumulative incidence of recurrence was approximately 10% higher in patients with GEJ cancer ( P < 0.001). The site of first recurrence was more likely to be hematogenous in patients with GEJ cancer (60.1% vs 31.4%; P < 0.001) and peritoneal in patients with GC (52.9% vs 12.5%; P < 0.001)., Conclusions: GEJ adenocarcinoma is more aggressive, with a higher incidence of recurrence and worse DSS, compared with gastric adenocarcinoma. Distinct differences between GEJ cancer and GC, especially in patterns of recurrence, may affect evaluation of optimal treatment strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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18. Risk of Lymph Node Metastasis in T1b Gastric Cancer: An International Comprehensive Analysis from the Global Gastric Group (G3) Alliance.
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Vos EL, Nakauchi M, Gönen M, Castellanos JA, Biondi A, Coit DG, Dikken JL, D'ugo D, Hartgrink H, Li P, Nishimura M, Schattner M, Song KY, Tang LH, Uyama I, Vardhana S, Verhoeven RHA, Wijnhoven BPL, and Strong VE
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- Humans, Female, Male, Lymphatic Metastasis, Retrospective Studies, Lymph Node Excision, Stomach Neoplasms surgery, Stomach Neoplasms pathology
- Abstract
Objective: We sought to define criteria associated with low lymph node metastasis risk in patients with submucosal (pT1b) gastric cancer from 3 Western and 3 Eastern countries., Summary Background Data: Accurate prediction of lymph node metastasis risk is essential when determining the need for gastrectomy with lymph node dissection following endoscopic resection. Under present guidelines, endoscopic resection is considered definitive treatment if submucosal invasion is only superficial, but this is not routinely assessed., Methods: Lymph node metastasis rates were determined for patient groups defined according to tumor pathological characteristics. Clinicopathological predictors of lymph node metastasis were determined by multivariable logistic regression and used to develop a nomogram in a randomly selected subset that was validated in the remainder. Overall survival was compared between Eastern and Western countries., Results: Lymph node metastasis was found in 701 of 3166 (22.1%) Eastern and 153 of 560 (27.3%) Western patients. Independent predictors of lymph node metastasis were female sex, tumor size, distal stomach location, lymphovascular invasion, and moderate or poor differentiation. Patients fulfilling the National Comprehensive Cancer Network guideline criteria, excluding the requirement that invasion not extend beyond the superficial submucosa, had a lymph node metastasis rate of 8.9% (53/594). Excluding moderately differentiated tumors lowered the rate to 3.4% (10/296). The nomogram's area under the curve was 0.690. Regardless of lymph node status, overall survival was better in Eastern patients., Conclusions: The lymph node metastasis rate was lowest in patients with well differentiated tumors that were ≤3 cm and lacked lymphovascular invasion. These criteria may be useful in decisions regarding endoscopic resection as definitive treatment for pT1b gastric cancer., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2023
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19. A Novel Microbiome Signature in Gastric Cancer: A Two Independent Cohort Retrospective Analysis.
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Abate M, Vos E, Gonen M, Janjigian YY, Schattner M, Laszkowska M, Tang L, Maron SB, Coit DG, Vardhana S, Vanderbilt C, and Strong VE
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- Cohort Studies, Computational Biology, Humans, Retrospective Studies, Microbiota, Stomach Neoplasms genetics, Stomach Neoplasms pathology
- Abstract
Objective: The microbiome is hypothesized to have a significant impact on cancer development. In gastric cancer (GC), Helicobacter pylori is an established class I carcinogen. However, additional organisms in the intratumoral microbiome play an important role in GC pathogenesis and progression. In this study, we characterize the full spectrum of the microbes present within GC and identify distinctions among molecular subtypes., Methods: A microbiome bioinformatics pipeline that is generalizable across multiple next-generation sequencing platforms was developed. Microbial profiles for alpha diversity and enrichment were generated for 2 large, demographically distinct cohorts: (1) internal Memorial Sloan Kettering Cancer Center (MSKCC) and (2) The Cancer Genome Atlas (TCGA) cohorts. A total of 520 GC samples were compared with select tumor-adjacent nonmalignant samples. Microbiome differences among the GC molecular subtypes were identified., Results: Compared with nonmalignant samples, GC had significantly decreased microbial diversity in both MSKCC and TCGA cohorts ( P <0.05). Helicobacter , Lactobacillus , Streptococcus , Prevotella , and Bacteroides were significantly more enriched in GC samples when compared with nonmalignant tissue ( P <0.05). Microsatellite instability-high GC had distinct microbial enrichment compared with other GC molecular subtypes., Conclusion: Distinct patterns of microbial diversity and species enrichment were identified in patients with GC. Given the varied spectrum of disease progression and treatment response of GC, understanding unique microbial signatures will provide the landscape to explore key microbial targets for therapy., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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20. Fifty years of progress in surgical oncology: Melanoma.
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Coit DG and Ariyan CE
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- Humans, Immunotherapy methods, Melanoma drug therapy, Melanoma genetics, Melanoma surgery, Skin Neoplasms drug therapy, Skin Neoplasms genetics, Skin Neoplasms surgery, Surgical Oncology
- Abstract
This paper outlines the scientific and clinical advances in the treatment of melanoma over the past 50 years. Among the highlights of progress, the dominant themes include evidence-based reduction in the extent and morbidity of surgical procedures in patients with local or regional melanoma without compromising end results, and the introduction of effective systemic therapy, specifically targeted therapy matched to patients based on specific tumor mutations, and immune checkpoint blockade. Management of advanced disease has also changed dramatically, due to improved understanding of the genomic variability of the disease as well as continuing improvements in imaging., (© 2022 Wiley Periodicals LLC.)
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- 2022
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21. Fifty years of progress in gastric cancer.
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Coit DG and Strong VE
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- Humans, Randomized Controlled Trials as Topic, Stomach Neoplasms pathology
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As with every human malignancy, the diagnosis, staging, and treatment of patients with gastric cancer have undergone enormous evidence-based change over the last 50 years, largely as a result of increasingly rapid developments in technology and science. Some of the changes in clinical practice have derived from prospective randomized controlled trials (RCTs), whereas others have come from study of meticulously maintained prospective databases, which define the disease's natural history over time, and occasionally from in-depth analysis of a single patient with an unexpectedly good or poor outcome. Herein we summarize the more important changes in gastric cancer management and the data supporting those changes., (© 2022 Wiley Periodicals LLC.)
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- 2022
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22. Validation of the Memorial Sloan Kettering Gastric Cancer Post-Resection Survival Nomogram: Does It Stand the Test of Time?
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Nakauchi M, Court CM, Tang LH, Gönen M, Janjigian YY, Maron SB, Molena D, Coit DG, Brennan MF, and Strong VE
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- Esophagogastric Junction pathology, Humans, Neoadjuvant Therapy, Neoplasm Staging, Prognosis, Nomograms, Stomach Neoplasms surgery
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Background: The Memorial Sloan Kettering Cancer Center (MSK) nomogram combined both gastroesophageal junction (GEJ) and gastric cancer patients and was created in an era from patients who generally did not receive neoadjuvant chemotherapy. We sought to reevaluate the MSK nomogram in the era of multidisciplinary treatment for GEJ and gastric cancer., Study Design: Using data on patients who underwent R0 resection for GEJ or gastric cancer between 2002 and 2016, the C-index of prediction for disease-specific survival (DSS) was compared between the MSK nomogram and the American Joint Committee on Cancer (AJCC) 8th edition staging system after segregating patients by tumor location (GEJ or gastric cancer) and neoadjuvant treatment. A new nomogram was created for the group for which both systems poorly predicted prognosis., Results: During the study period, 886 patients (645 gastric and 241 GEJ cancer) underwent up-front surgery, and 999 patients (323 gastric and 676 GEJ) received neoadjuvant treatment. Compared with the AJCC staging system, the MSK nomogram demonstrated a comparable C-index in gastric cancer patients undergoing up-front surgery (0.786 vs 0.753) and a better C-index in gastric cancer patients receiving neoadjuvant treatment (0.796 vs 0.698). In GEJ cancer patients receiving neoadjuvant chemotherapy, neither the MSK nomogram nor the AJCC staging system performed well (C-indices 0.647 and 0.646). A new GEJ nomogram was created based on multivariable Cox regression analysis and was validated with a C-index of 0.718., Conclusions: The MSK gastric cancer nomogram's predictive accuracy remains high. We developed a new GEJ nomogram that can effectively predict DSS in patients receiving neoadjuvant treatment., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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23. Outcomes and Molecular Features of Brain Metastasis in Gastroesophageal Adenocarcinoma.
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Tsai C, Nguyen B, Luthra A, Chou JF, Feder L, Tang LH, Strong VE, Molena D, Jones DR, Coit DG, Ilson DH, Ku GY, Cowzer D, Cadley J, Capanu M, Schultz N, Beal K, Moss NS, Janjigian YY, and Maron SB
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- Female, Humans, Male, Mutation, Prognosis, Retrospective Studies, Adenocarcinoma pathology, Brain Neoplasms secondary
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Importance: Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis., Objectives: To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival., Design, Setting, and Participants: In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021. Genomic data were derived from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets clinical sequencing platform., Exposures: Treatment with BrM resection and/or radiotherapy., Main Outcomes and Measures: Overall survival after BrM diagnosis., Results: Sixty-eight patients (median age at diagnosis, 57.4 years [IQR, 49.8-66.4 years]; 59 [86.8%] male; 55 [85.9%] White) participated in the study. A total of 57 (83.8%) had primary tumors in the distal esophagus or gastroesophageal junction. Median time from initial diagnosis to BrM diagnosis was 16.9 months (IQR, 8.5-27.7 months). Median survival from BrM diagnosis was 8.7 months (95% CI, 5.5-11.5 months). Overall survival was 35% (95% CI, 25%-48%) at 1 year and 24% (95% CI, 16%-37%) at 2 years. In a multivariable analysis, an Eastern Cooperative Oncology Group performance status of 2 or greater (hazard ratio [HR], 4.66; 95% CI, 1.47-14.70; P = .009) and lack of surgical or radiotherapeutic intervention (HR, 7.71; 95% CI, 2.01-29.60; P = .003) were associated with increased risk of all-cause mortality, whereas 3 or more extracranial sites of disease (HR, 1.85; 95% CI, 0.64-5.29; P = .25) and 4 or more BrMs (HR, 2.15; 95% CI, 0.93-4.98; P = .07) were not statistically significant. A total of 31 patients (45.6%) had ERBB2 (formerly HER2 or HER2/neu)-positive tumors, and alterations in ERBB2 were enriched in BrM relative to primary tumors (8 [47.1%] vs 7 [20.6%], P = .05), as were alterations in PTPRT (7 [41.2%] vs 4 [11.8%], P = .03)., Conclusions and Relevance: This study suggests that that a notable proportion of patients with BrM from GEA achieve survival exceeding 1 and 2 years from BrM diagnosis, a more favorable prognosis than previously reported. Good performance status and treatment with combination surgery and radiotherapy were associated with the best outcomes. ERBB2 positivity and amplification as well as PTPRT alterations were enriched in BrM tissue compared with primary tumors; therefore, further study should be pursued to identify whether these variables represent genomic risk factors for BrM development.
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- 2022
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24. Phase II Trial Evaluating Esophageal Anastomotic Reinforcement with a Biologic, Degradable, Extracellular Matrix after Total Gastrectomy and Esophagectomy.
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Vos EL, Nakauchi M, Capanu M, Park BJ, Coit DG, Molena D, Yoon SS, Jones DR, and Strong VE
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- Anastomotic Leak etiology, Anastomotic Leak prevention & control, Constriction, Pathologic etiology, Extracellular Matrix, Humans, Anastomosis, Surgical adverse effects, Anastomosis, Surgical methods, Esophageal Neoplasms surgery, Esophagectomy adverse effects, Gastrectomy adverse effects
- Abstract
Background: A biologic, degradable extracellular matrix (ECM) has been shown to support esophageal tissue remodeling, which could reduce the risk of anastomotic leak following total gastrectomy and esophagectomy. We evaluated the safety and efficacy of reinforcing the anastomosis with ECM in reducing anastomotic leak as compared to a matched cohort., Study Design: In this single-center, nonrandomized phase II trial, gastric or esophageal adenocarcinoma patients undergoing total gastrectomy or esophagectomy were recruited from November 2013 through December 2018. ECM was surgically wrapped circumferentially around the anastomosis. Anastomotic leak was assessed clinically and by contrast study and defined as clinically significant if requiring invasive treatment (grade 3 or higher). Anastomotic stenosis, other adverse events, symptoms, and dysphagia score were collected by standardized forms at regular follow-up visits at approximately postoperative days (POD) 21 and 90. Patients receiving ECM were compared to a cohort matched for surgery type and age., Results: ECM placement was not feasible in 9 of 75 patients (12%), resulting in 66 patients receiving ECM. Total gastrectomy was performed in 50 patients (76%) and esophagectomy in 16 (24%). Clinically significant anastomotic leak was diagnosed in 6 of 66 patients (9.1%) (3/50 [6.0%] after gastrectomy, 3/16 [18.8%] after esophagectomy); this rate did not differ from that in the matched cohort (p = 0.57). Stenosis requiring invasive treatment occurred in 8 patients (12.5%), and 10 patients (15.6%) reported not being able to eat a normal diet at POD 90. No adverse events related to ECM were reported., Conclusions: Esophageal anastomotic reinforcement after total gastrectomy or esophagectomy with a biologic, degradable ECM was mostly feasible and safe, but was not associated with a statistically significant decrease in anastomotic leak., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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25. Defining and Targeting Esophagogastric Cancer Genomic Subsets With Patient-Derived Xenografts.
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Moy RH, Walch HS, Mattar M, Chatila WK, Molena D, Strong VE, Tang LH, Maron SB, Coit DG, Jones DR, Hechtman JF, Solit DB, Schultz N, de Stanchina E, and Janjigian YY
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- Genomics, Heterografts, Humans, Phosphatidylinositol 3-Kinases metabolism, Xenograft Model Antitumor Assays, Esophageal Neoplasms drug therapy, Stomach Neoplasms drug therapy
- Abstract
Purpose: Comprehensive genomic profiling has defined key oncogenic drivers and distinct molecular subtypes in esophagogastric cancer; however, the number of clinically actionable alterations remains limited. To establish preclinical models for testing genomically driven therapeutic strategies, we generated and characterized a large collection of esophagogastric cancer patient-derived xenografts (PDXs)., Materials and Methods: We established a biobank of 98 esophagogastric cancer PDX models derived from primary tumors and metastases. Clinicopathologic features of each PDX and the corresponding patient sample were annotated, including stage at diagnosis, treatment history, histology, and biomarker profile. To identify oncogenic DNA alterations, we analyzed and compared targeted sequencing performed on PDX and parent tumor pairs. We conducted xenotrials in genomically defined models with oncogenic drivers., Results: From April 2010 to June 2019, we implanted 276 patient tumors, of which 98 successfully engrafted (35.5%). This collection is enriched for PDXs derived from patients with human epidermal growth factor receptor 2-positive esophagogastric adenocarcinoma (62 models, 63%), the majority of which were refractory to standard therapies including trastuzumab. Factors positively correlating with engraftment included advanced stage, metastatic origin, intestinal-type histology, and human epidermal growth factor receptor 2-positivity. Mutations in TP53 and alterations in receptor tyrosine kinases ( ERBB2 and EGFR ), RAS/PI3K pathway genes, cell-cycle mediators ( CDKN2A and CCNE1 ), and CDH1 were the predominant oncogenic drivers, recapitulating clinical tumor sequencing. We observed antitumor activity with rational combination strategies in models established from treatment-refractory disease., Conclusion: The Memorial Sloan Kettering Cancer Center PDX collection recapitulates the heterogeneity of esophagogastric cancer and is a powerful resource to investigate mechanisms driving tumor progression, identify predictive biomarkers, and develop therapeutic strategies for molecularly defined subsets of esophagogastric cancer., Competing Interests: Daniela MolenaHonoraria: Bristol Myers Squibb/Pfizer, MerckConsulting or Advisory Role: Johnson & Johnson, UroGen pharma, Boston Scientific, AstraZeneca/MedImmune Steven B. MaronStock and Other Ownership Interests: Calithera BiosciencesConsulting or Advisory Role: Natera, Basilea, Daichi Sankyo, Bicara Therapeutics, NovartisResearch Funding: Roche/Genentech (Inst), Guardant Health (Inst)Travel, Accommodations, Expenses: Bayer David R. JonesConsulting or Advisory Role: Merck, AstraZeneca Jaclyn F. HechtmanEmployment: NeoGenomics LaboratoriesStock and Other Ownership Interests: NeoGenomics LaboratoriesHonoraria: WebMD, Illumina, BayerConsulting or Advisory Role: Cor2Ed, Axiom Healthcare Strategies, BayerResearch Funding: Bayer, Lilly, Boehringer Ingelheim David B. SolitThis author is a member of the JCO Precision Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Stock and Other Ownership Interests: Scorpion Therapeutics, Vividion Therapeutics, Fore BiotherapeuticsConsulting or Advisory Role: Pfizer, Lilly, BridgeBio Pharma, Scorpion Therapeutics, Vividion Therapeutics, Syros Pharmaceuticals Yelena Y. JanjigianStock and Other Ownership Interests: RgenixConsulting or Advisory Role: Pfizer, Merck, Bristol Myers Squibb, Merck Serono, Daiichi Sankyo, Rgenix, Bayer, Imugene, AstraZeneca, Lilly, Zymeworks, Basilea Pharmaceutical, Michael J. Hennessy Associates, Paradigm, Seattle GeneticsResearch Funding: Bayer (Inst), Rgenix (Inst), Bristol Myers Squibb (Inst), Merck (Inst), Lilly (Inst), NCI (Inst), Department of Defense (Inst), Cycle for Survival (Inst), Fred's Team (Inst), Genentech/Roche (Inst)Other Relationship: Clinical Care Options, Axis Medical Education, Research to PracticeNo other potential conflicts of interest were reported.
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- 2022
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26. Assessment of Frailty Can Guide Decision Making for Utilization of Sentinel Lymph Node Biopsy in Patients with Thick Melanoma.
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Sharma AS, Flynn JR, Panageas KS, Shahrokni A, Tin AL, Bello DM, Ariyan CE, Brady MS, Coit DG, and Bartlett EK
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- Decision Making, Humans, Prognosis, Retrospective Studies, Sentinel Lymph Node Biopsy, Frailty, Melanoma surgery, Sentinel Lymph Node surgery, Skin Neoplasms surgery
- Abstract
Background: Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated., Objective: We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma., Methods: Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included. Frailty was assessed using the Memorial Sloan Kettering Frailty Index (MSK FI), a composite score of functional status and medical comorbidities. Five-year melanoma-specific survival (MSS) and overall survival (OS) were estimated using Cox regression, and predictors of OS were identified using competing risk models., Results: MSS did not differ between patients who did (n = 451) or did not undergo SLNB (n = 179) [63.2% vs. 65.0%, p = 0.14]; however, omission of SLNB was associated with decreased 5-year OS (29% vs. 44%, p < 0.001). In a multivariable competing risk model, selection for SLNB omission was an independent predictor of death from non-melanoma causes (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.2-2.3, p < 0.001). After incorporation of the MSK FI score into the multivariable model in this subset, MSK FI (HR 2.4, 95% CI 1.5-4.1, p < 0.001), but not SLNB omission, was an independent predictor of poorer OS., Conclusion: We observed worse OS in patients with thick melanoma selected not to undergo SLNB, which was attributed to death due to non-melanoma causes. Formal assessment of frailty may provide an objective prognostic measure to guide selective use of SLNB in these patients., (© 2021. Society of Surgical Oncology.)
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- 2021
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27. Association of Obesity with Worse Operative and Oncologic Outcomes for Patients Undergoing Gastric Cancer Resection.
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Nakauchi M, Vos EL, Tang LH, Gonen M, Janjigian YY, Ku GY, Ilson DH, Maron SB, Yoon SS, Brennan MF, Coit DG, and Strong VE
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- Body Mass Index, Gastrectomy adverse effects, Humans, Obesity complications, Retrospective Studies, Treatment Outcome, Stomach Neoplasms complications, Stomach Neoplasms surgery
- Abstract
Background: How obesity has an impact on operative and oncologic outcomes for gastric cancer patients is unclear, and the influence of obesity on response to neoadjuvant chemotherapy (NAC) has not been evaluated., Methods: Patients who underwent curative gastrectomy for primary gastric cancer between 2000 and 2018 were retrospectively identified. After stratification for NAC, operative morbidity, mortality, overall survival (OS), and disease-specific survival (DSS) were compared among three body mass index (BMI) categories: normal BMI (< 25 kg/m
2 ), mild obesity (25-35 kg/m2 ), and severe obesity (≥ 35 kg/m2 )., Results: During the study period, 984 patients underwent upfront surgery, and 484 patients received NAC. Tumor stage did not differ among the BMI groups. However, the rates of pathologic response to NAC were significantly lower for the patients with severe obesity (10% vs 40%; p < 0.001). Overall complications were more frequent among the obese patients (44.3% for obese vs 24.9% for normal BMI, p < 0.001). Intraabdominal infections were also more frequent in obese patients (13.9% for obese vs 4.7% for normal BMI, p = 0.001). In the upfront surgery cohort, according to the BMI, OS and DSS did not differ, whereas in the NAC cohort, severe obesity was independently associated with worse OS [hazard ratio (HR) 1.87; 95% confidence interval (CI) 1.01-3.48; p = 0.047] and disease-specific survival (DSS) (HR 2.08; 95% CI 1.07-4.05; p = 0.031)., Conclusion: For the gastric cancer patients undergoing curative gastrectomy, obesity was associated with significantly lower rates of pathologic response to NAC and more postoperative complications, as well as shorter OS and DSS for the patients receiving NAC., (© 2021. Society of Surgical Oncology.)- Published
- 2021
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28. Outcomes of Neoadjuvant Chemotherapy for Clinical Stages 2 and 3 Gastric Cancer Patients: Analysis of Timing and Site of Recurrence.
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Nakauchi M, Vos E, Tang LH, Gonen M, Janjigian YY, Ku GY, Ilson DH, Maron SB, Yoon SS, Brennan MF, Coit DG, and Strong VE
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- Chemotherapy, Adjuvant, Gastrectomy, Humans, Neoplasm Recurrence, Local drug therapy, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Retrospective Studies, Neoadjuvant Therapy, Stomach Neoplasms drug therapy, Stomach Neoplasms pathology, Stomach Neoplasms surgery
- Abstract
Background: This study aimed to analyze timing and sites of recurrence for patients receiving neoadjuvant chemotherapy for gastric cancer. Neoadjuvant chemotherapy followed by surgical resection is the standard treatment for locally advanced gastric cancer in the West, but limited information exists as to timing and patterns of recurrence in this setting., Methods: Patients with clinical stage 2 or 3 gastric cancer treated with neoadjuvant chemotherapy followed by curative-intent resection between January 2000 and December 2015 were analyzed for 5-year recurrence-free survival (RFS) as well as timing and site of recurrence., Results: Among 312 identified patients, 121 (38.8%) experienced recurrence during a median follow-up period of 46 months. The overall 5-year RFS rate was 58.9%, with RFS rates of 95.8% for ypT0N0, 81% for ypStage 1, 77.4% for ypStage 2, and 22.9% for ypStage 3. The first site of recurrence was peritoneal for 49.6%, distant (not peritoneal) for 45.5%, and locoregional for 11.6% of the patients. The majority of the recurrences (84.3%) occurred within 2 years. Multivariate analysis showed that ypT4 status was an independent predictor for recurrence within 1 year after surgery (odds ratio, 2.58; 95% confidence interval, 1.10-6.08; p = 0.030)., Conclusions: The majority of the recurrences for patients with clinical stage 2 or 3 gastric cancer who received neoadjuvant chemotherapy and underwent curative resection occurred within 2 years. After neoadjuvant chemotherapy, pathologic T stage was a useful risk predictor for early recurrence., (© 2021. Society of Surgical Oncology.)
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- 2021
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29. Prevalence of Germline Alterations on Targeted Tumor-Normal Sequencing of Esophagogastric Cancer.
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Ku GY, Kemel Y, Maron SB, Chou JF, Ravichandran V, Shameer Z, Maio A, Won ES, Kelsen DP, Ilson DH, Capanu M, Strong VE, Molena D, Sihag S, Jones DR, Coit DG, Tuvy Y, Cowie K, Solit DB, Schultz N, Hechtman JF, Offit K, Joseph V, Mandelker D, Janjigian YY, and Stadler ZK
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Esophageal Neoplasms epidemiology, Female, Humans, Male, Middle Aged, Prevalence, Whole Genome Sequencing methods, Esophageal Neoplasms genetics, Germ-Line Mutation genetics, Whole Genome Sequencing statistics & numerical data
- Abstract
Importance: Among patients with esophagogastric cancers, only individuals who present with known features of heritable cancer syndromes are referred for genetic testing. Broader testing might identify additional patients with germline alterations., Objectives: To examine the prevalence of likely pathogenic or pathogenic (LP/P) germline alterations among patients with esophagogastric cancer and to assess associations between germline variant prevalence and demographic and clinicopathologic features., Design, Setting, and Participants: This cross-sectional study was performed at a tertiary referral cancer center from January 1, 2014, to December 31, 2019, in 515 patients with esophagogastric cancer who consented to tumor and blood sequencing., Main Outcomes and Measures: Presence or absence of LP/P variants in up to 88 genes associated with cancer predisposition syndromes as identified by targeted sequencing (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets)., Results: Among 515 patients (median age, 59 years; range, 18-87 years; 368 [71.5%] male; 398 [77.3%] White), 243 (47.2%) had gastric cancer, 111 (21.6%) had gastroesophageal junction (GEJ) cancer, and 161 (31.3%) had esophageal cancer. A total of 48 patients with gastric cancer (19.8%), 16 (14.4%) with GEJ cancer, and 17 (10.6%) with esophageal cancer had LP/P germline variants. The number of LP/P variants in high- and moderate-penetrance genes was significantly higher in patients with gastric cancer (29 [11.9%]; 95% CI, 8.1%-16.7%) vs patients with esophageal cancer (8 [5.0%]; 95% CI, 2.2%-9.6%; P = .03), and the difference was greater for high-penetrance germline alterations in patients with gastric cancer (25 [10.3%]; 95% CI, 6.8%-14.8%) vs in patients with esophageal cancer (3 [1.9%]; 95% CI, 0.38%-5.3%; P = .001). The most frequent high- and moderate-penetrance LP/P alterations were in BRCA1/2 (14 [2.7%]), ATM (11 [2.1%]), CDH1 (6 [1.2%]), and MSH2 (4 [0.8%]). Those with early-onset disease (≤50 years of age at diagnosis) were more likely to harbor an LP/P germline variant (29 [21.0%]; 95% CI, 14.5%-28.8%) vs those with late-onset disease (patients >50 years of age at diagnosis) (52 [13.8%]; 95% CI, 10.5%-17.7%; P = .046). ATM LP/P variants occurred in 6 patients (4.3%; 95% CI, 1.6%-9.1%) with early-onset esophagogastric cancer vs 5 (1.3%; 95% CI, 0.4%-3.1%; P = .08) of those with late-onset esophagogastric cancer., Conclusions and Relevance: These results suggest that pathogenic germline variants are enriched in gastric and early-onset esophagogastric cancer and that germline testing should be considered in these populations. The role of ATM alterations in esophagogastric cancer risk warrants further investigation.
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- 2021
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30. Comparison of Long- and Short-term Outcomes in 845 Open and Minimally Invasive Gastrectomies for Gastric Cancer in the United States.
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Nakauchi M, Vos E, Janjigian YY, Ku GY, Schattner MA, Nishimura M, Gonen M, Coit DG, and Strong VE
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- Gastrectomy, Humans, Length of Stay, Minimally Invasive Surgical Procedures, Retrospective Studies, Treatment Outcome, United States epidemiology, Laparoscopy, Robotic Surgical Procedures, Stomach Neoplasms surgery
- Abstract
Background: Few Western studies have evaluated the long-term oncologic outcomes of minimally invasive surgery (MIS) approaches to gastrectomy for gastric cancer. This study aimed to compare the outcomes between minimally invasive and open gastrectomies and between laparoscopic and robotic gastrectomies at a high-volume cancer center in the United States., Methods: The study analyzed data for all patients undergoing curative gastrectomy for gastric adenocarcinoma from January 2007 to June 2017. Postoperative complications and disease-specific survival (DSS) were compared between surgical approaches., Results: The median follow-up period for the 845 patients in this study was 38.5 months. The stage-stratified 5-year DSS did not differ significantly between open surgery (n = 534) and MIS (n = 311). The MIS approach resulted in significantly fewer complications, as confirmed by adjusted comparison (odds ratio [OR], 0.70; range, 0.49-1.00; p = 0.049). After adjustment, the two groups did not differ in terms of DSS (hazard ratio [HR], 0.83; range, 0.55-1.25; p = 0.362). The robotic operations (n = 190) had fewer conversions to open procedure (p = 0.010), a shorter operative time (212 vs 240 min; p < 0.001), more dissected nodes (27 vs 22; p < 0.001), fewer Clavien-Dindo grade ≥3 complications (5.8% vs 13.2%; p = 0.023), and a shorter postoperative stay (5 vs 6 days; p = 0.045) than the laparoscopic operations (n = 121). The DSS rate did not differ between the laparoscopic and robotic groups., Conclusion: The study findings demonstrated the long-term survival and oncologic equivalency of MIS gastrectomy and the open approach in a Western cohort, supporting the use of MIS at centers that have adequate experience with appropriately selected patients.
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- 2021
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31. Therapeutic Implications of Detecting MAPK-Activating Alterations in Cutaneous and Unknown Primary Melanomas.
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Shoushtari AN, Chatila WK, Arora A, Sanchez-Vega F, Kantheti HS, Rojas Zamalloa JA, Krieger P, Callahan MK, Betof Warner A, Postow MA, Momtaz P, Nair S, Ariyan CE, Barker CA, Brady MS, Coit DG, Rosen N, Chapman PB, Busam KJ, Solit DB, Panageas KS, Wolchok JD, and Schultz N
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Drug Resistance, Neoplasm genetics, Female, Gain of Function Mutation, Humans, Immune Checkpoint Inhibitors pharmacology, Immune Checkpoint Inhibitors therapeutic use, Ipilimumab pharmacology, Ipilimumab therapeutic use, Kaplan-Meier Estimate, MAP Kinase Signaling System genetics, Male, Melanoma genetics, Melanoma mortality, Melanoma secondary, Middle Aged, Neoplasms, Unknown Primary genetics, Neoplasms, Unknown Primary immunology, Neoplasms, Unknown Primary mortality, Nivolumab pharmacology, Nivolumab therapeutic use, Prognosis, Programmed Cell Death 1 Receptor antagonists & inhibitors, Prospective Studies, Retrospective Studies, Skin Neoplasms genetics, Skin Neoplasms immunology, Skin Neoplasms mortality, Time Factors, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols pharmacology, Melanoma drug therapy, Mitogen-Activated Protein Kinases genetics, Neoplasms, Unknown Primary drug therapy, Skin Neoplasms drug therapy
- Abstract
Purpose: Cutaneous and unknown primary melanomas frequently harbor alterations that activate the MAPK pathway. Whether MAPK driver detection beyond BRAF V600 is clinically relevant in the checkpoint inhibitor era is unknown., Experimental Design: Patients with melanoma were prospectively offered tumor sequencing of 341-468 genes. Oncogenic alterations in 28 RTK-RAS-MAPK pathway genes were used to construct MAPK driver groups. Time to treatment failure (TTF) was determined for patients who received first-line programmed cell death protein 1 (PD-1) monotherapy, nivolumab plus ipilimumab, or subsequent genomically matched targeted therapies. A Cox proportional hazards model was constructed for TTF using driver group and clinical variables., Results: A total of 670 of 696 sequenced melanomas (96%) harbored an oncogenic RTK-RAS-MAPK pathway alteration; 33% had ≥1 driver. Nine driver groups varied by clinical presentation and mutational burden. TTF of PD-1 monotherapy ( N = 181) varied by driver, with worse outcomes for NRAS Q61 and BRAF V600 versus NF1 or other alterations (median 4.2, 7.5, 22, and not reached; P < 0.0001). Driver group remained significant, independent of tumor mutational burden and clinical features. TTF did not vary by driver for nivolumab plus ipilimumab ( N = 141). Among 172 patients with BRAF V600 wild-type melanoma who progressed on checkpoint blockade, 27 were treated with genomically matched therapy, and eight (30%) derived clinical benefit lasting ≥6 months., Conclusions: Targeted capture multigene sequencing can detect oncogenic RTK-RAS-MAPK pathway alterations in almost all cutaneous and unknown primary melanomas. TTF of PD-1 monotherapy varies by mechanism of ERK activation. Oncogenic kinase fusions can be successfully targeted in immune checkpoint inhibitor-refractory melanoma., (©2021 American Association for Cancer Research.)
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- 2021
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32. Outcome of 1000 Patients With Gastrointestinal Stromal Tumor (GIST) Treated by Surgery in the Pre- and Post-imatinib Eras.
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Cavnar MJ, Seier K, Curtin C, Balachandran VP, Coit DG, Yoon SS, Crago AM, Strong VE, Tap WD, Gönen M, Antonescu CR, Brennan MF, Singer S, and DeMatteo RP
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Female, Gastrointestinal Stromal Tumors mortality, Humans, Male, Middle Aged, Retrospective Studies, Survival Rate, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Gastrointestinal Stromal Tumors drug therapy, Gastrointestinal Stromal Tumors surgery, Imatinib Mesylate therapeutic use
- Abstract
Objective: To characterize the results of surgery for gastrointestinal stromal tumor (GIST) in the pre and post-imatinib eras at a single institution and to identify current prognostic clinicopathologic factors., Background: Imatinib has radically changed the management of GIST, yet the magnitude of impact on outcome across the spectrum of GIST presentation and relevance of historical prognostic factors are not well defined., Methods: We retrospectively analyzed 1000 patients who underwent surgery for GIST at our institution from 1982 to 2016. Patients were stratified by presentation status as primary tumor only (PRIM), primary with synchronous metastasis (PRIM + MET), or metachronous recurrence/metastases (MET), and also imatinib era (before and after it became available). Cox proportional-hazard models and Kaplan-Meier methods were used to model and estimate overall survival (OS) and recurrence-free survival (RFS)., Results: OS was longer in the imatinib era compared with the pre-imatinib era in each presentation group, including in Miettinen high-risk primary tumors. Among PRIM patients from the pre-imatinib era, tumor site, size, and mitotic rate were independently associated with OS and RFS on multivariate analysis. PRIM patients in the imatinib era who received imatinib (neoadjuvant and/or adjuvant) had higher risk tumors, but after adjusting for treatment, only size >10 cm remained independently prognostic of RFS [hazard ratio (HR) 3.85, 95% confidence interval (CI) 2.00-7.40, P < 0.0001) and OS (HR 3.37, 95% CI 1.60-7.13, P = 0.001)]., Conclusions: Patients treated in the imatinib era had prolonged OS across all presentations. In the imatinib era, among site, size, and mitotic rate, high-risk features were associated with treatment with the drug, but only size >10 cm correlated with outcome. Imatinib should still be prescribed for patients with high-risk features., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2021
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33. Longitudinal Analysis of Quality-of-Life Recovery After Gastrectomy for Cancer.
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Hu Y, Vos EL, Baser RE, Schattner MA, Nishimura M, Coit DG, and Strong VE
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- Humans, Postoperative Period, Surveys and Questionnaires, Gastrectomy, Quality of Life, Stomach Neoplasms surgery
- Abstract
Objective: The purpose of this study was to identify factors associated with quality-of-life recovery after gastrectomy., Methods: Patients anticipated to undergo gastric cancer resection were invited to complete the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and STO22 surveys in the preoperative setting and at 0-1.5 months (early), > 1.5-6 months (intermediate), and > 6-18 months (late) following resection. Quality-of-life recovery was measured as paired differences between pre- and postoperative results. Multivariable linear regression identified factors associated with preoperative quality of life and degree of change following resection., Results: Across 393 participants, response rates at the intermediate and late postoperative time points were 58% (n = 228) and 71% (n = 277), respectively. Relative to baseline, median global health scale decreased in the early (- 15.1 pts, p < 0.001) and intermediate (- 3.6 pts, p = 0.02) time points, but recovered by the late time point (+ 1.2 pts, p = 0.411). Relative to distal/subtotal gastrectomy, proximal/total gastrectomy was associated with worse recovery in both the early and late time points. Surgical complications were associated with worse early recovery. Patients who presented with locally advanced tumors (T3-T4) had lower preoperative quality-of-life scores, and more readily recovered to baseline after surgery. A minimally invasive approach was not associated with postoperative recovery., Conclusions: Most patients recover to baseline within 1 year following major gastrectomy, and recovery is easier with more limited resections. Patients with locally advanced tumors tend to have poorer baseline quality of life, which may improve following resection.
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- 2021
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34. Sentinel Lymph Node Biopsy for T1b Melanoma: Balancing Prognostic Value and Cost.
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Hu Y, Briggs A, Gennarelli RL, Bartlett EK, Ariyan CE, Coit DG, and Brady MS
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- Aged, Humans, Lymph Node Excision, Medicare, Prognosis, Retrospective Studies, Sentinel Lymph Node Biopsy, United States, Melanoma surgery, Sentinel Lymph Node surgery, Skin Neoplasms surgery
- Abstract
Background: The purpose of this study is to report the additional prognostic information and cost associated with sentinel lymph node biopsy (SLNB) for patients with T1b melanoma., Patients and Methods: An institutional database was queried for patients with T1b melanoma (0.8-1.0 mm or < 0.8 mm with ulceration) with at least 5 years of follow-up. Results of SLNB, completion lymphadenectomy (CLND), recurrence, and melanoma-specific survival (MSS) were assessed. Institutional costs of melanoma care were converted to Medicare proportional dollars. A Markov model was created to estimate long-term costs., Results: Among the total 392 patients, 238 underwent SLNB. Median follow-up was 10.5 years. SLNB was positive in 19 patients (8.0%). Patients who underwent SLNB had higher 10-year nodal recurrence-free survival (98.6% vs. 91.2%, p < 0.001) but not MSS (94.4% vs. 93.2%, p = 0.55). Ulceration (HR 4.7, p = 0.022) and positive sentinel node (HR 11.5, p < 0.001) were associated with worse MSS. Estimates for 5-year costs reflect a fourfold increase in total costs of care associated with SLNB. However, a treatment plan that forgoes adjuvant therapy for resected stage IIIA melanoma but offers systemic therapy for a node-basin recurrence would nullify the additional cost of SLNB., Conclusions: SLNB is prognostic for T1b melanoma. Its impact on the overall cost of melanoma care is intimately tied to systemic therapy in the adjuvant and recurrent settings.
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- 2020
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35. Performance of the American College of Surgeons NSQIP Surgical Risk Calculator for Total Gastrectomy.
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Vos EL, Russo AE, Hohmann A, Yoon SS, Coit DG, Ko CY, and Strong VE
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- Female, Gastrectomy statistics & numerical data, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications etiology, Risk Factors, Stomach Neoplasms surgery, United States, Gastrectomy adverse effects, Risk Assessment
- Abstract
Background: To encourage implementation of the American College of Surgeons (ACS) NSQIP Risk Calculator for total gastrectomy for gastric cancer, its predictive performance for this specific procedure should be validated. We assessed its discriminatory accuracy and goodness of fit for predicting 12 adverse outcomes., Study Design: Data were collected on all patients with gastric cancer who underwent total gastrectomy with curative intent at Memorial Sloan Kettering Cancer Center between 2002 and 2017. Preoperative risk factors from the electronic medical record were manually inserted into the ACS-NSQIP Risk Calculator. Predictions for adverse outcomes were compared with observed outcomes by Brier scores, c-statistics, and Hosmer-Lemeshow p value., Results: In a total of 452 patients, the predicted rate of all complications (29%) was lower than the observed rate (45%). Brier scores varied between 0.017 for death and 0.272 for any complication. C-statistics were moderate (0.7-0.8) for death and renal failure, good (0.8-0.9) for cardiac complication, and excellent (≥0.9) for discharge to nursing or rehabilitation facility. Hosmer-Lemeshow p value found poor goodness of fit for pneumonia only., Conclusions: For adverse outcomes after total gastrectomy with curative intent in gastric cancer patients, performance of the ACS-NSQIP Risk Calculator is variable. Its predictive performance is best for cardiac complications, renal failure, death, and discharge to nursing or rehabilitation facility., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2020
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36. Cost-Benefit Implication of Gene Expression Profiling and Adjuvant Therapy in Stage IIIA Melanoma.
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Hu Y, Briggs A, Marchetti MA, Ariyan CE, Coit DG, and Bartlett EK
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- Adult, Antibodies, Monoclonal, Humanized economics, Antineoplastic Agents, Immunological economics, Female, Humans, Male, Markov Chains, Medicare economics, Melanoma mortality, Melanoma pathology, Melanoma therapy, Neoplasm Staging, Skin Neoplasms mortality, Skin Neoplasms pathology, Skin Neoplasms therapy, Survival Rate, United States, Chemotherapy, Adjuvant economics, Cost-Benefit Analysis, Gene Expression Profiling, Melanoma genetics, Skin Neoplasms genetics
- Abstract
Background: Indiscriminate use of adjuvant therapy in stage IIIA melanoma is controversial. We sought to model the clinical impact and cost of implementing a gene expression profile (GEP) test to guide adjuvant therapy., Study Design: A Markov decision-analysis model was created to represent resected stage IIIA melanoma with 3 treatment options: observation (OBS), adjuvant pembrolizumab for all patients (ALL), and selective adjuvant therapy (SEL). In the SEL option, only high-risk patients based on GEP stratification were treated with pembrolizumab. Cost of adjuvant therapy was normalized to reflect Medicare reimbursement schedules. The primary outcome was cost per mortality avoided at 10 years., Results: Model projections for 10-year overall survival were 68% for OBS, 73% for SEL, and 76% for ALL. The estimated incremental cost-per-mortality-avoided (compared to OBS) was $2.1 million for SEL and $2.4 million for ALL. These translate to costs of $583.0K and $697.1K per life-year for the SEL and ALL strategies, respectively., Conclusions: Routine adjuvant pembrolizumab for stage IIIA melanoma is costly, and risk-stratification by GEP only marginally improves the value of therapy., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)
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- 2020
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37. Gene Expression Profile-Based Risk Modeling to Select Patients With Melanoma Who Can Avoid Sentinel Lymph Node Biopsy: Are We There Yet?
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Bartlett EK, Marchetti MA, and Coit DG
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- 2020
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38. Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies.
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Vos EL, Salo-Mullen EE, Tang LH, Schattner M, Yoon SS, Gerdes H, Markowitz AJ, Mandelker D, Janjigian Y, Offitt K, Coit DG, Stadler ZK, and Strong VE
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- Adult, Carcinoma, Signet Ring Cell diagnosis, Cohort Studies, Endoscopy, Digestive System, Female, Humans, Male, Middle Aged, Minimally Invasive Surgical Procedures, Patient Selection, Stomach Neoplasms diagnosis, Stomach Neoplasms surgery, Antigens, CD genetics, Cadherins genetics, Carcinoma, Signet Ring Cell genetics, Carcinoma, Signet Ring Cell surgery, Gastrectomy, Germ-Line Mutation genetics, Stomach Neoplasms genetics
- Abstract
Importance: CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer., Objectives: To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy., Design, Setting, and Participants: This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution., Interventions: Genetic counseling, esophagogastroduodenoscopy, and possible total gastrectomy., Main Outcomes and Measures: CDH1 variant classification, family cancer history, findings of signet ring cell carcinoma at esophagogastroduodenoscopy and surgery, postoperative events and weight changes, and follow-up., Results: Of 181 individuals with CDH1 germline variants (mean [SD] age at time of testing, 44 [15] years; 126 [70%] female), 165 harbored a pathogenic or likely pathogenic variant. Of these patients, 101 underwent open (n = 58) or minimally invasive (n = 43) total gastrectomy. Anastomotic leaks that required drainage were infrequent (n = 3), and median long-term weight loss was 20% (interquartile range [IQR], 10%-23%). In those undergoing minimally invasive operations, more lymph nodes were retrieved (median, 28 [IQR, 20-34] vs 15 [IQR, 9-19]; P < .001) and the hospital stay was 1 day shorter (median, 6 [IQR, 5-7] vs 7 [IQR, 6-7] days; P = .04). Signet ring cell cancer was identified in the surgical specimens of 85 of 95 patients (89%) with a family history of gastric cancer and 4 of 6 patients (67%) who lacked a family history. Among the latter 6 patients, 4 had a personal or family history of lobular breast cancer, including 2 with signet ring cell cancer. Of the 16 patients with pathogenic or likely pathogenic CDH1 variants who presented with locally advanced or metastatic gastric cancer, 3 (19%) had no family history of gastric cancer or personal or family history of lobular breast cancer., Conclusions and Relevance: Total gastrectomy may be warranted for patients with pathogenic or likely pathogenic CDH1 variants and a family history of gastric or lobular breast cancer and may be appropriate for those without a family history. A minimally invasive approach is feasible and may be preferred for selected patients.
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- 2020
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39. Nodal and systemic recurrence following observation of a positive sentinel lymph node in melanoma.
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Bartlett EK, Lee AY, Spanheimer PM, Bello DM, Brady MS, Ariyan CE, and Coit DG
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Databases, Factual, Female, Follow-Up Studies, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Melanoma mortality, Melanoma surgery, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local surgery, Retrospective Studies, Sentinel Lymph Node surgery, Sentinel Lymph Node Biopsy, Skin Neoplasms mortality, Skin Neoplasms surgery, Survival Analysis, Watchful Waiting, Young Adult, Melanoma pathology, Neoplasm Recurrence, Local pathology, Sentinel Lymph Node pathology, Skin Neoplasms pathology
- Abstract
Background: Two RCTs found no survival benefit for completion lymphadenectomy after positive sentinel lymph node biopsy compared with observation with ultrasound in patients with melanoma. Recurrence patterns and regional control are not well described for patients undergoing observation alone., Methods: All patients with a positive sentinel node biopsy who did not have immediate completion lymphadenectomy were identified from a single-institution database (1995-2018). First recurrences were classified as node only, local and in-transit (LCIT) only, LCIT and nodal, or systemic. Regional control and factors associated with recurrence survival were analysed., Results: Median follow-up was 33 months. Of 370 patients, 158 (42·7 per cent) had a recurrence. The sites of first recurrence were node only (13·2 per cent), LCIT only (11·9 per cent), LCIT and nodal (3·5 per cent), and systemic (13·8 per cent). The 3-year postrecurrence melanoma-specific survival rate was 73 (95 per cent c.i. 54 to 86) per cent for patients with node-only first recurrence, and 51 (31 to 68) per cent for those with initial systemic recurrence. In multivariable analysis, ulceration in the primary lesion (hazard ratio (HR) 2·53, 95 per cent c.i. 1·27 to 5·04), disease-free interval 12 months or less (HR 2·38, 1·28 to 4·35), and systemic (HR 2·57, 1·16 to 5·65) or LCIT and nodal (HR 2·94, 1·11 to 7·79) first recurrence were associated significantly with decreased postrecurrence survival. Maintenance of regional control required therapeutic lymphadenectomy in 13·0 per cent of patients during follow-up., Conclusion: Observation after a positive sentinel lymph node biopsy is associated with good regional control, permits assessment of the time to and pattern of recurrence, and spares lymphadenectomy-related morbidity in patients with melanoma., (Published by John Wiley & Sons Ltd.)
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- 2020
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40. Prognostic Gene Expression Profiling in Cutaneous Melanoma: Identifying the Knowledge Gaps and Assessing the Clinical Benefit.
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Grossman D, Okwundu N, Bartlett EK, Marchetti MA, Othus M, Coit DG, Hartman RI, Leachman SA, Berry EG, Korde L, Lee SJ, Bar-Eli M, Berwick M, Bowles T, Buchbinder EI, Burton EM, Chu EY, Curiel-Lewandrowski C, Curtis JA, Daud A, Deacon DC, Ferris LK, Gershenwald JE, Grossmann KF, Hu-Lieskovan S, Hyngstrom J, Jeter JM, Judson-Torres RL, Kendra KL, Kim CC, Kirkwood JM, Lawson DH, Leming PD, Long GV, Marghoob AA, Mehnert JM, Ming ME, Nelson KC, Polsky D, Scolyer RA, Smith EA, Sondak VK, Stark MS, Stein JA, Thompson JA, Thompson JF, Venna SS, Wei ML, and Swetter SM
- Subjects
- Consensus, Consensus Development Conferences as Topic, Humans, Melanoma genetics, Melanoma pathology, Melanoma therapy, Neoplasm Staging, Prognosis, Sentinel Lymph Node Biopsy standards, Skin Neoplasms genetics, Skin Neoplasms pathology, Skin Neoplasms therapy, Clinical Decision-Making methods, Gene Expression Profiling standards, Melanoma diagnosis, Practice Guidelines as Topic, Skin Neoplasms diagnosis
- Abstract
Importance: Use of prognostic gene expression profile (GEP) testing in cutaneous melanoma (CM) is rising despite a lack of endorsement as standard of care., Objective: To develop guidelines within the national Melanoma Prevention Working Group (MPWG) on integration of GEP testing into the management of patients with CM, including (1) review of published data using GEP tests, (2) definition of acceptable performance criteria, (3) current recommendations for use of GEP testing in clinical practice, and (4) considerations for future studies., Evidence Review: The MPWG members and other international melanoma specialists participated in 2 online surveys and then convened a summit meeting. Published data and meeting abstracts from 2015 to 2019 were reviewed., Findings: The MPWG members are optimistic about the future use of prognostic GEP testing to improve risk stratification and enhance clinical decision-making but acknowledge that current utility is limited by test performance in patients with stage I disease. Published studies of GEP testing have not evaluated results in the context of all relevant clinicopathologic factors or as predictors of regional nodal metastasis to replace sentinel lymph node biopsy (SLNB). The performance of GEP tests has generally been reported for small groups of patients representing particular tumor stages or in aggregate form, such that stage-specific performance cannot be ascertained, and without survival outcomes compared with data from the American Joint Committee on Cancer 8th edition melanoma staging system international database. There are significant challenges to performing clinical trials incorporating GEP testing with SLNB and adjuvant therapy. The MPWG members favor conducting retrospective studies that evaluate multiple GEP testing platforms on fully annotated archived samples before embarking on costly prospective studies and recommend avoiding routine use of GEP testing to direct patient management until prospective studies support their clinical utility., Conclusions and Relevance: More evidence is needed to support using GEP testing to inform recommendations regarding SLNB, intensity of follow-up or imaging surveillance, and postoperative adjuvant therapy. The MPWG recommends further research to assess the validity and clinical applicability of existing and emerging GEP tests. Decisions on performing GEP testing and patient management based on these results should only be made in the context of discussion of testing limitations with the patient or within a multidisciplinary group.
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- 2020
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41. Performance of Gene Expression Profile Tests for Prognosis in Patients With Localized Cutaneous Melanoma: A Systematic Review and Meta-analysis.
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Marchetti MA, Coit DG, Dusza SW, Yu A, McLean L, Hu Y, Nanda JK, Matsoukas K, Mancebo SE, and Bartlett EK
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- Biopsy, Humans, Melanoma genetics, Melanoma pathology, Melanoma therapy, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Prognosis, Skin pathology, Skin Neoplasms genetics, Skin Neoplasms pathology, Skin Neoplasms therapy, Gene Expression Profiling instrumentation, Melanoma diagnosis, Neoplasm Recurrence, Local diagnosis, Reagent Kits, Diagnostic, Skin Neoplasms diagnosis
- Abstract
Importance: The performance of prognostic gene expression profile (GEP) tests for cutaneous melanoma is poorly characterized., Objective: To systematically assess the performance of commercially available GEP tests in patients with American Joint Committee on Cancer (AJCC) stage I or stage II disease., Data Sources: For this systematic review and meta-analysis, comprehensive searches of PubMed/MEDLINE, Embase, and Web of Science were conducted on December 12, 2019, for English-language studies of humans without date restrictions., Study Selection: Two reviewers identified GEP external validation studies of patients with localized melanoma. After exclusion criteria were applied, 7 studies (8%; 5 assessing DecisionDx-Melanoma and 2 assessing MelaGenix) were included., Data Extraction and Synthesis: Data were extracted using an adaptation of the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS-PF). When feasible, meta-analysis using random-effects models was performed. Risk of bias and level of evidence were assessed with the Quality in Prognosis Studies tool and an adaptation of Grading of Recommendations Assessment, Development, and Evaluation., Main Outcomes and Measures: Proportion of patients with or without melanoma recurrence correctly classified by the GEP test as being at high or low risk., Results: In the 7 included studies, a total of 1450 study participants contributed data (age and sex unknown). The performance of both GEP tests varied by AJCC stage. Of patients tested with DecisionDx-Melanoma, 623 had stage I disease (6 true-positive [TP], 15 false-negative, 61 false-positive, and 541 true-negative [TN] results) and 212 had stage II disease (59 TP, 13 FN, 78 FP, and 62 TN results). Among patients with recurrence, DecisionDx-Melanoma correctly classified 29% with stage I disease and 82% with stage II disease. Among patients without recurrence, the test correctly classified 90% with stage I disease and 44% with stage II disease. Of patients tested with MelaGenix, 88 had stage I disease (7 TP, 15 FN, 15 FP, and 51 TN results) and 245 had stage II disease (59 TP, 19 FN, 95 FP, and 72 TN results). Among patients with recurrence, MelaGenix correctly classified 32% with stage I disease and 76% with stage II disease. Among patients without recurrence, the test correctly classified 77% with stage I disease and 43% with stage II disease., Conclusions and Relevance: The prognostic ability of GEP tests among patients with localized melanoma varied by AJCC stage and appeared to be poor at correctly identifying recurrence in patients with stage I disease, suggesting limited potential for clinical utility in these patients.
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- 2020
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42. Hereditary diffuse gastric cancer: updated clinical practice guidelines.
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Blair VR, McLeod M, Carneiro F, Coit DG, D'Addario JL, van Dieren JM, Harris KL, Hoogerbrugge N, Oliveira C, van der Post RS, Arnold J, Benusiglio PR, Bisseling TM, Boussioutas A, Cats A, Charlton A, Schreiber KEC, Davis JL, Pietro MD, Fitzgerald RC, Ford JM, Gamet K, Gullo I, Hardwick RH, Huntsman DG, Kaurah P, Kupfer SS, Latchford A, Mansfield PF, Nakajima T, Parry S, Rossaak J, Sugimura H, Svrcek M, Tischkowitz M, Ushijima T, Yamada H, Yang HK, Claydon A, Figueiredo J, Paringatai K, Seruca R, Bougen-Zhukov N, Brew T, Busija S, Carneiro P, DeGregorio L, Fisher H, Gardner E, Godwin TD, Holm KN, Humar B, Lintott CJ, Monroe EC, Muller MD, Norero E, Nouri Y, Paredes J, Sanches JM, Schulpen E, Ribeiro AS, Sporle A, Whitworth J, Zhang L, Reeve AE, and Guilford P
- Subjects
- Humans, Neoplastic Syndromes, Hereditary, Stomach Neoplasms
- Abstract
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that is characterised by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, although pathogenic variants in CTNNA1 occur in a minority of families with HDGC. In this Policy Review, we present updated clinical practice guidelines for HDGC from the International Gastric Cancer Linkage Consortium (IGCLC), which recognise the emerging evidence of variability in gastric cancer risk between families with HDGC, the growing capability of endoscopic and histological surveillance in HDGC, and increased experience of managing long-term sequelae of total gastrectomy in young patients. To redress the balance between the accessibility, cost, and acceptance of genetic testing and the increased identification of pathogenic variant carriers, the HDGC genetic testing criteria have been relaxed, mainly through less restrictive age limits. Prophylactic total gastrectomy remains the recommended option for gastric cancer risk management in pathogenic CDH1 variant carriers. However, there is increasing confidence from the IGCLC that endoscopic surveillance in expert centres can be safely offered to patients who wish to postpone surgery, or to those whose risk of developing gastric cancer is not well defined., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
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- 2020
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43. Trends in Completion Lymph Node Dissection for Patients with Melanoma.
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Bartlett EK and Coit DG
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- Humans, Lymph Node Excision, Melanoma surgery, Sentinel Lymph Node
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- 2020
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44. Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation: A Retrospective Cohort Study.
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Cassidy MR, Lefkowitz RA, Long N, Qin LX, Kirane A, Sbaity E, Hameed M, Coit DG, Brennan MF, Singer S, and Crago AM
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- Adult, Aged, Disease Progression, Female, Fibromatosis, Aggressive mortality, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Retrospective Studies, Tumor Burden, Fibromatosis, Aggressive diagnostic imaging, Magnetic Resonance Imaging methods
- Abstract
Objective: The aim of this study was to identify predictors of desmoid progression during observation., Summary of Background Data: Untreated desmoids can grow, remain stable, or regress, but reliable predictors of behavior have not been identified., Methods: Primary or recurrent desmoid patients were identified retrospectively from an institutional database. In those managed with active observation who underwent serial magnetic resonance imaging (MRIs) with T2-weighted sequences, baseline tumor size was recorded, and 2 radiologists independently estimated the percentage of tumor volume showing hyperintense T2 signal at baseline. Associations of clinical or radiographic characteristics with progression-free survival (PFS; by RECIST) were evaluated by Cox regression and Kaplan-Meier statistics., Results: Among 160 patients with desmoids, 72 were managed with observation, and 37 of these had serial MRI available for review. Among these 37 patients, median age was 35 years and median tumor size was 4.7 cm; all tumors were extra-abdominal (41% in abdominal wall). Although PFS was not associated with size, site, or age, it was strongly associated with hyperintense T2 signal in ≥90% versus <90% of baseline tumor volume (as defined by the "test" radiologist; hazard ratio = 11.3, P = 0.003). For patients in the ≥90% group (n = 20), 1-year PFS was 55%, compared with 94% in the <90% group (n = 17). The percentage of baseline tumor volume with hyperintense T2 signal defined by a validation radiologist correlated with results of the test radiologist (ρ = 0.75)., Conclusion: The percent tumor volume characterized by hyperintense T2 signal is associated with desmoid progression during observation and may help distinguish patients who would benefit from early intervention from those who may be reliably observed.
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- 2020
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45. Survival Outcomes After Metastasectomy in Melanoma Patients Categorized by Response to Checkpoint Blockade.
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Bello DM, Panageas KS, Hollmann T, Shoushtari AN, Momtaz P, Chapman PB, Postow MA, Callahan MK, Wolchok JD, Brady MS, Coit DG, and Ariyan CE
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological pharmacology, CTLA-4 Antigen antagonists & inhibitors, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Immune Checkpoint Inhibitors pharmacology, Ipilimumab pharmacology, Male, Melanoma mortality, Melanoma pathology, Middle Aged, Nivolumab pharmacology, Programmed Cell Death 1 Receptor antagonists & inhibitors, Prospective Studies, Retrospective Studies, Skin Neoplasms mortality, Skin Neoplasms pathology, Survival Rate, Treatment Outcome, Young Adult, Antineoplastic Agents, Immunological therapeutic use, Immune Checkpoint Inhibitors therapeutic use, Ipilimumab therapeutic use, Melanoma drug therapy, Melanoma surgery, Metastasectomy methods, Nivolumab therapeutic use, Skin Neoplasms drug therapy, Skin Neoplasms surgery
- Abstract
Introduction: Checkpoint inhibitors have improved outcomes in metastatic melanoma, with 4-year overall survival (OS) of 46% for anti-PD-1 alone or 53% in combination with anti-CTLA-4. However, the median progression free survival is 6.9 and 11.5 months, respectively. Many who progress have gone on to alternative treatments, including surgery, yet the outcome of patients selected for surgery after checkpoint blockade remains unclear., Methods: Patients who were treated with checkpoint blockade from 2003 to 2017, followed by metastasectomy, were identified from a prospectively maintained institutional melanoma database. Response to immunotherapy was assessed at the time of surgery. Patients were categorized as having responding, isolated progressing, or multiple progressing lesions., Results: Of the 237 total patients identified, 208 (88%) had stage IV disease, and 29 (12%) had unresectable stage III disease at the start of immunotherapy. Median OS following first resection was 21 months. Median follow-up among survivors was 23 months. Complete resection at the first operation (n = 87, 37%) was associated with improved survival compared with patients with incomplete resection (n = 150, 63%) [median OS not reached (NR) vs. 10.8 months, respectively; 95% CI: 7.3, 14.8; p < 0.0001]. Patients resected for an isolated progressing or responding tumor had a longer median survival compared with those with multiple progressing lesions (NR vs. 7.8 months, 95% CI: 6.2, 11.2; p < 0.0001)., Conclusions: Patients selected for surgical resection following checkpoint blockade have a relatively favorable survival, especially if they had a response to immunotherapy and undergo complete resection of isolated progressing or responding disease.
- Published
- 2020
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46. NCCN Guidelines Insights: Uveal Melanoma, Version 1.2019.
- Author
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Rao PK, Barker C, Coit DG, Joseph RW, Materin M, Rengan R, Sosman J, Thompson JA, Albertini MR, Boland G, Carson Iii WE, Contreras C, Daniels GA, DiMaio D, Durham A, Fields RC, Fleming MD, Galan A, Gastman B, Grossman K, Guild V, Johnson D, Karakousis G, Lange JR, Margolin K, Nath S, Olszanski AJ, Ott PA, Ross MI, Salama AK, Skitzki J, Swetter SM, Wuthrick E, McMillian NR, and Engh A
- Subjects
- Brachytherapy standards, Education, Medical, Continuing, Eye Enucleation standards, Humans, Medical Oncology education, Medical Oncology methods, Melanoma diagnosis, Melanoma pathology, Oncologists education, Tumor Burden, Uveal Neoplasms diagnosis, Uveal Neoplasms pathology, Medical Oncology standards, Melanoma therapy, Neoplasm Recurrence, Local prevention & control, Practice Guidelines as Topic, Uveal Neoplasms therapy
- Abstract
The NCCN Guidelines for Uveal Melanoma include recommendations for staging, treatment, and follow-up of patients diagnosed with uveal melanoma of the choroid or ciliary body. In addition, because distinguishing between uveal melanoma and benign uveal nevi is in some cases difficult, these guidelines also contain recommendations for workup of patients with suspicious pigmented uveal lesions, to clarify the tests needed to distinguish between those who should have further workup and treatment for uveal melanoma versus those with uncertain diagnosis and low risk who should to be followed and later reevaluated. These NCCN Guidelines Insights describe recommendations for treatment of newly diagnosed nonmetastatic uveal melanoma in patients who have already undergone a complete workup.
- Published
- 2020
- Full Text
- View/download PDF
47. High neutrophil-to-lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD-1 inhibitor monotherapy.
- Author
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Bartlett EK, Flynn JR, Panageas KS, Ferraro RA, Sta Cruz JM, Postow MA, Coit DG, and Ariyan CE
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Immunological adverse effects, Disease-Free Survival, Female, Humans, Kaplan-Meier Estimate, Lymphocyte Count, Lymphocytes drug effects, Male, Melanoma immunology, Melanoma mortality, Melanoma pathology, Middle Aged, Neoplasm Staging, Neutrophils drug effects, Programmed Cell Death 1 Receptor immunology, Antineoplastic Agents, Immunological administration & dosage, Melanoma drug therapy, Prognosis, Programmed Cell Death 1 Receptor antagonists & inhibitors
- Abstract
Background: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor survival in patients with cancer, including those who receive immunotherapies. The authors sought to investigate NLR as a biomarker of treatment outcomes in patients with melanoma who were treated with PD-1 inhibition., Methods: Patients undergoing initial treatment with PD-1 inhibitor monotherapy for stage IV melanoma at a single center from 2012 to 2015 were included. Clinical characteristics and the NLR at baseline and before subsequent treatment cycles were collected. The time to treatment failure (TTF) and overall survival (OS) were evaluated using Kaplan-Meier and landmark analyses., Results: Among 224 study patients, 63 (28%) had a baseline NLR ≥5. The baseline NLR was significantly associated with Eastern Cooperative Oncology Group performance status and the number of involved metastatic sites. With a median follow-up of 39 months in survivors, a baseline NLR ≥5 was independently associated with shorter OS (hazard ratio, 2.0; 95% CI, 1.3-2.9) and TTF (hazard ratio, 1.7; 95% CI, 1.2-2.4). An NLR increase ≥30% during the first 2 cycles of treatment was associated with worse OS (median, 47 vs 13.5 months; P < .001) and a trend toward shorter TTF (12.8 vs 5.9 months; P = .05). A combined baseline NLR ≥5 and an NLR increase ≥30% identified a small cohort with markedly shortened OS (median, 5.8 months) and TTF (median, 1.8 months)., Conclusions: Elevated baseline NLR and an increased NLR early during treatment are prognostic for TTF and OS in patients who have melanoma treated with PD-1 inhibitor monotherapy. Combined, these biomarkers can widely risk-stratify patients for treatment failure and survival., (© 2019 American Cancer Society.)
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- 2020
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48. Adrenal Metastasectomy in the Presence and Absence of Extraadrenal Metastatic Disease.
- Author
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Russo AE, Untch BR, Kris MG, Chou JF, Capanu M, Coit DG, Chaft JE, D'Angelica MI, Brennan MF, and Strong VE
- Subjects
- Adrenal Gland Neoplasms mortality, Adrenal Gland Neoplasms secondary, Aged, Disease-Free Survival, Female, Follow-Up Studies, Humans, Kidney Neoplasms pathology, Liver Neoplasms pathology, Male, Middle Aged, Prognosis, Prospective Studies, Sarcoma pathology, Skin Neoplasms pathology, Survival Rate trends, United States epidemiology, Adrenal Gland Neoplasms surgery, Adrenalectomy methods, Laparoscopy methods, Metastasectomy methods
- Abstract
Objective: To determine if there are differences in overall survival (OS) or event-free survival (EFS) in patients with and without concomitant extra-adrenal metastases undergoing adrenal metastasectomy., Background: There is growing interest in the use of local therapies in patients with oligometastatic disease. Previously published series have indicated that long-term survival is possible with resection. Adrenalectomy has been used to treat adrenal metastases in select patients., Methods: Patients who underwent adrenal metastasectomy from 1994 to 2015 were identified from a prospectively maintained institutional database of adrenalectomy patients, excluding adrenalectomies due to tumor extension or for palliation. Sites of disease, treatment history, and survival data were extracted from chart review., Results: One hundred seventy-four patients were included. Tumor histology included 68 nonsmall cell lung cancer, 34 renal cancer, 18 colorectal cancer, 11 melanoma cancer, 10 hepatocellular cancer, 8 sarcoma cancer, and 25 other cancers. The median follow-up among survivors was 5.2 (1-21) years. OS at 3 and 5 years was 50% and 40%, respectively. Patients with (n = 83) and without (n = 91) extra-adrenal metastases did not differ with respect to age, adrenal tumor size, or margin status. Median OS (3.3 years for patients with concomitant extra-adrenal metastases and 3.0 years for patients with isolated adrenal metastases; P = 0.816) and EFS (9.39 vs 9.59 months; P = 0.87) were similar. Factors negatively associated with OS included adrenal tumor size (P < 0.01), renal primary versus other (P < 0.01), and adrenal margin status (P < 0.01)., Conclusions: In selected patients undergoing adrenal metastasectomy, there were no significant differences in OS or EFS between patients with and without concomitant extra-adrenal metastases.
- Published
- 2019
- Full Text
- View/download PDF
49. The Changing Kinetics of Advanced Melanoma.
- Author
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Coit DG
- Subjects
- Disease Progression, Humans, Kinetics, Recurrence, Melanoma, Skin Neoplasms
- Published
- 2019
- Full Text
- View/download PDF
50. Intratumoral Immune Response to Gastric Cancer Varies by Molecular and Histologic Subtype.
- Author
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Kim TS, da Silva E, Coit DG, and Tang LH
- Subjects
- Adenocarcinoma genetics, Adenocarcinoma pathology, Adenocarcinoma virology, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Databases, Factual, Female, Genetic Heterogeneity, Genetic Predisposition to Disease, Herpesvirus 4, Human isolation & purification, Humans, Male, Microsatellite Instability, Middle Aged, Phenotype, Programmed Cell Death 1 Receptor analysis, Retrospective Studies, Stomach Neoplasms genetics, Stomach Neoplasms pathology, Stomach Neoplasms virology, Young Adult, Adenocarcinoma immunology, Lymphocytes, Tumor-Infiltrating immunology, Macrophages immunology, Stomach Neoplasms immunology, Tumor Escape, Tumor Microenvironment
- Abstract
Immune checkpoint inhibition is effective in a subset of patients with advanced gastric cancer. Genomic profiling has revealed the heterogeneity of gastric adenocarcinomas, but the immune microenvironment and predictors of immunotherapy response remain poorly understood. We aimed to better characterize the underlying immune response to gastric cancer. Retrospective review of a prospectively maintained institutional database was performed to identify patients who underwent curative intent resection of gastric adenocarcinoma from 2006 to 2016. Tumors were classified according to modified TCGA subtype: Epstein-Barr virus (EBV)-associated, microsatellite instability (MSI)-high, intestinal as a surrogate for chromosomal instability, diffuse as a surrogate for genomically stable. Tumor-infiltrating leukocytes were measured using immunohistochemistry. Forty-three patients were identified: 6 EBV, 11 MSI, 14 intestinal, 12 diffuse. The most prevalent tumor-infiltrating leukocytes were CD8 T lymphocytes and CD68 macrophages, comprising 15% and 13% of all tumor cells. EBV and MSI tumors were the most infiltrated, harboring 30% to 50% T cells and 20% macrophages. Intestinal tumors contained fewer T cells but disproportionately more macrophages. Diffuse tumors were the least infiltrated. Programmed cell death protein 1 was most frequently expressed in intestinal tumors, whereas 70% of EBV and MSI tumors expressed programmed death-ligand 1. We herein demonstrate a heterogenous immune response to gastric cancer, which varies by tumor subtype and has implications for future immunotherapy trials. Checkpoint inhibition is unlikely to be effective as single-agent therapy against intestinal and diffuse tumors lacking prominent T-cell infiltration or substantial programmed death-ligand 1 expression.
- Published
- 2019
- Full Text
- View/download PDF
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