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BACKGROUND: The appropriate surgical approach for pancreatic ductal adenocarcinoma (PDAC) is determined by the tumor's relation to the porto-mesenteric axis. Although the extent and location of lymphadenectomy is dependent on the type of resection, a pancreatoduodenectomy (PD), distal pancreatectomy (DP), or total pancreatectomy (TP) are considered equivalent oncologic operations for pancreatic neck tumors. Therefore, we aimed to assess differences in histopathological and oncological outcomes for surgical approaches in the treatment of pancreatic neck tumors. METHODS: Patients with resected PDAC located in the pancreatic neck were identified from the National Cancer Database (2004-2020). Patients with metastatic disease were excluded. Furthermore, patients with 90-day mortality and R2-resections were excluded from the multivariable Cox-regression analysis. RESULTS: Among 846 patients, 58% underwent PD, 25% DP, and 17% TP with similar R0-resection rates (p = 0.722). Significant differences were observed in nodal positivity (PD:44%, DP:34%, TP:57%, p < 0.001) and mean-number of examined lymph nodes (PD:17.2 ± 10.4, DP:14.7 ± 10.5, TP:21.2 ± 11.0, p < 0.001). Furthermore, inadequate lymphadenectomy (< 12 nodes) was observed in 30%, 44%, and 19% of patients undergoing PD, DP, and TP, respectively (p < 0.001). Multivariable analysis yielded similar overall survival after DP (HR:0.83, 95%CI:0.63-1.11), while TP was associated with worse survival (HR:1.43, 95%CI:1.08-1.89) compared to PD. CONCLUSION: While R0-rates are similar amongst all approaches, DP is associated with inadequate lymphadenectomy which may result in understaging disease. However, this had no negative influence on survival. In the premise that an oncological resection of the pancreatic neck tumor is feasible with a partial pancreatectomy, no benefit is observed by performing a TP.
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Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Masculino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Feminino , Estudos Retrospectivos , Pancreatectomia/métodos , Idoso , Pessoa de Meia-Idade , Pancreaticoduodenectomia/métodos , Pancreaticoduodenectomia/mortalidade , Excisão de Linfonodo , Estudos de CoortesRESUMO
BACKGROUND: Surgical subspecialty training aims to meet the needs of practicing surgeons and their communities. This study investigates career preparedness of Complex General Surgical Oncology (CGSO) fellowship graduates, identifies factors associated with practice readiness, and explores potential opportunities to improve the current training model. METHODS: The Society of Surgical Oncology partnered with the National Cancer Institute to conduct a 36-question survey of CGSO fellowship graduates from 2012 to 2022. RESULTS: The overall survey response rate was 38% (221/582) with a slight male predominance (63%). Forty-six percent of respondents completed their fellowship after 2019. Factors influencing fellowship program selection include breadth of cancer case exposure (82%), mentor influence (66%), and research opportunities (38%). Overall, graduates reported preparedness for practice; however, some reported unpreparedness in research (18%) and in specific clinical areas: thoracic (43%), hyperthermic intraperitoneal chemotherapy (HIPEC) (15%), and hepato-pancreato-biliary (15%) surgery. Regarding technical preparedness, 70% reported being "very prepared". Respondents indicated lack of preparedness in robotic (63%) and laparoscopic (33%) surgery approaches. Suggestions for training improvement included increased autonomy and case volumes, program development, and research infrastructure. Current practice patterns by graduates demonstrated discrepancies between ideal contracts and actual practice breakdowns, particularly related to the practice of general surgery. CONCLUSIONS: This study of CGSO fellowship graduates demonstrates potential gaps between trainee expectations and the realities of surgical oncology practice. Although CGSO fellowship appears to prepare surgeons for careers in surgical oncology, there may be opportunities to refine the training model to better align with the needs of practicing surgical oncologists.
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Internato e Residência , Oncologia Cirúrgica , Humanos , Masculino , Feminino , Bolsas de Estudo , Inquéritos e Questionários , Educação de Pós-Graduação em MedicinaRESUMO
OBJECTIVE: This study aimed to analyze post-recurrence progression in context of recurrence sites and assess implications for post-recurrence treatment. BACKGROUND: Most patients with resected pancreatic ductal adenocarcinoma (PDAC) recur within two years. Different survival outcomes for location-specific patterns of recurrence are reported, highlighting their prognostic value. However, a lack of understanding of post-recurrence progression and survival remains. METHODS: This retrospective analysis included surgically treated PDAC patients at the NYU-Langone Health (2010-2021). Sites of recurrence were identified at time of diagnosis and further follow-up. Kaplan-Meier curves, log-rank test, and Cox-regression analyses were applied to assess survival outcomes. RESULTS: Recurrence occurred in 57.3% (196/342) patients with a median time to recurrence of 11.3 months (95%CI:12.6 to 16.5). First site of recurrence was local in 43.9% patients, liver in 23.5%, peritoneal in 8.7%, lung in 3.6%, while 20.4% had multiple sites of recurrence. Progression to secondary sites was observed in 11.7%. Only lung involvement was associated with significantly longer survival after recurrence compared to other sites (16.9 months vs. 8.49 months, P=0.003). In local recurrence, 21 (33.3%) patients were alive after one year without progression to secondary sites. This was associated with a CA19-9 of <100U/ml at time of primary diagnosis (P=0.039), nodal negative disease (P=0.023), and well-moderate differentiation (P=0.042) compared to patients with progression. CONCLUSION: Except for lung recurrence, post-recurrence survival after PDAC resection is associated with poor survival. A subset of patients with local-only recurrence do not quickly succumb to systemic spread. This is associated with markers for favorable tumor biology, making them candidates for potential curative re-resections when feasible.
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INTRODUCTION: There is no consensus regarding the role of primary tumor resection for patients with metastatic pancreatic neuroendocrine tumors (panNET). We assessed surgical treatment patterns and evaluated the survival impact of primary tumor resection in patients with metastatic panNET. METHODS: Patients with synchronous metastatic nonfunctional panNET in the National Cancer Database (2004-2016) were categorized based on whether they underwent primary tumor resection. We used logistic regressions to assess associations with primary tumor resection. We performed survival analyses with Kaplan-Meier survival functions, log-rank test, and Cox proportional hazard regression within a propensity score matched cohort. RESULTS: In the overall cohort of 2613 patients, 68% (n = 839) underwent primary tumor resection. The proportion of patients who underwent primary tumor resection decreased over time from 36% (2004) to 16% (2016, p < 0.001). After propensity score matching on age at diagnosis, median income quartile, tumor grade, size, liver metastasis, and hospital type, primary tumor resection was associated with longer median overall survival (OS) (65 vs. 24 months; p < 0.001) and was associated with lower hazard of mortality (HR: 0.39, p < 0.001). CONCLUSION: Primary tumor resection was significantly associated with improved OS, suggesting that, if feasible, surgical resection can be considered for well-selected patients with panNET and synchronous metastasis.
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Neoplasias Hepáticas , Segunda Neoplasia Primária , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/secundário , Análise de Sobrevida , Neoplasias Pancreáticas/cirurgiaRESUMO
BACKGROUND: With each succession along the surgical career pathway, from medical school to faculty, the percentage of those who identify as underrepresented in medicine (URiM) decreases. We sought to evaluate the demographic trend of surgical fellowship applicants, matriculants, and graduates over time. STUDY DESIGN: The Electronic Residency Application Service and the Graduate Medical Education Survey for general surgery fellowships in colorectal surgery, surgical oncology, pediatric surgery, thoracic surgery, and vascular surgery were retrospectively analyzed (2005 to 2020). The data were stratified by race and gender, descriptive statistics were performed, and time series were evaluated. Race/ethnicity groups included White, Asian, other, and URiM, which is defined as Black/African American, Hispanic/Latino(a), Alaskan or Hawaiian Native, and Native American. RESULTS: From 2005 to 2020, there were 5,357 Electronic Residency Application Service applicants, 4,559 matriculants, and 4,178 graduates to surgery fellowships. Whites, followed by Asians, represented the highest percentage of applicants (62.7% and 22.3%, respectively), matriculants (65.4% and 23.8% respectively), and graduates (65.4% and 24.0%, respectively). For URiMs, the applicants (13.4%), matriculants (9.1%), and graduates (9.1%) remained significantly low (p < 0.001). When stratified by both race and gender, only 4.6% of the applicants, 2.7% of matriculants, and 2.4% of graduates identified as both URiM and female compared to White female applicants (20.0%), matriculants (17.9%), and graduates (16.5%, p < 0.001). CONCLUSIONS: Significant disparities exist for URiMs in general surgery subspecialty fellowships. These results serve as a call to action to re-examine and improve the existing processes to increase the number of URiMs in the surgery subspecialty fellowship training pathway.
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Bolsas de Estudo , Internato e Residência , Criança , Humanos , Feminino , Estados Unidos , Estudos Retrospectivos , Grupos Minoritários , Educação de Pós-Graduação em MedicinaRESUMO
BACKGROUND: Time to treatment (TTT) varies widely for patients with gastric cancer. We aimed to evaluate relationships between time to treatment, overall survival (OS), and other surgical outcomes in patients with stage I-III gastric cancer. METHODS: We identified patients with clinical stage I-III gastric cancer who underwent curative-intent gastrectomy within the National Cancer Database (2006-2015) and grouped them by treatment sequence: neoadjuvant chemotherapy or surgery upfront. We defined TTT as weeks from diagnosis to treatment initiation (neoadjuvant chemotherapy or definitive surgical procedure, respectively). Survival differences were assessed by Kaplan-Meier estimate, Cox proportional hazard regression, and log rank test. RESULTS: Among the 22,846 patients with stage I-III gastric cancer, most (56%) received surgery upfront. Median TTT was 5 weeks (IQR 4-7) and 6 weeks (IQR 3-9) for patients in the neoadjuvant and surgery upfront groups, respectively. In the neoadjuvant group, increasing TTT was significantly associated with increasing median OS up to TTT of 5 weeks, with no change in median OS when TTT was > 5 weeks. In the surgery group, increasing TTT was significantly associated with increasing median OS up to 6 weeks; however, increasing TTT between 14 and 21 weeks was associated with decreasing median OS. CONCLUSIONS: The relationship between time to treatment and survival outcomes is non-linear. Among patients who underwent surgery upfront, the relationship between time to treatment and OS was bimodal, suggesting that deferring definitive surgery, up to 14 weeks, is not associated with worse OS or oncologic outcomes. The relationship between time to treatment and overall survival among patients was bimodal, suggesting that deferring definitive surgery up to 14 weeks is not associated with worse OS.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Estadiamento de Neoplasias , Terapia Neoadjuvante/métodos , Quimioterapia Adjuvante , Estimativa de Kaplan-Meier , Estudos RetrospectivosRESUMO
Preoperative localization of nonpalpable breast lesions using a radar reflector surgical guidance system has become commonplace, but the clinical utility of this emerging technology in the musculoskeletal system has not yet been well established. The system components include a console, a handpiece, an implanted radiofrequency reflector that works as a lesion marker, and an infrared light-emitting probe to guide the surgeon. The reflector can be deployed to localize small nonpalpable nodules within the subcutaneous fat as well as lesions within the deeper soft tissues. It can also be used for lymph nodes and foreign bodies. Localization can be performed both before and after treatment. The objective of this article is to describe the potential applications and our technique and initial experience for radar reflector localization within the musculoskeletal system.
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Neoplasias da Mama , Sistema Musculoesquelético , Cirurgia Assistida por Computador , Humanos , Feminino , Radar , Mastectomia Segmentar/métodos , Cirurgia Assistida por Computador/métodosRESUMO
OBJECTIVE: To evaluate long-term oncologic outcomes of patients with stage IV pancreatic ductal adenocarcinoma and to identify survival benchmarks for comparison when considering resection in these patients. BACKGROUND: Highly selected cohorts of patients with liver-oligometastatic pancreas cancer have reported prolonged survival after resection. The long-term impact of surgery in this setting remains undefined because of a lack of appropriate control groups. METHODS: We identified patients with clinical stage IV pancreatic ductal adenocarcinoma with synchronous liver metastases within our cancer registry. We estimated overall survival (OS) among various patient subgroups using the Kaplan-Meier method. To mitigate immortal time bias, we analyzed long-term outcomes of patients who survived beyond 12 months (landmark time) from diagnosis. RESULTS: We identified 241 patients. Median OS was 7 months (95% CI, 5-9), both overall and for patients with liver-only metastasis (n=144). Ninety patients (38% of liver only; 40% of whole cohort) survived at least 12 months; those who received chemotherapy in this subgroup had a median OS of 26 months (95% CI, 17-39). Of these patients, those with resectable or borderline resectable primary tumors and resectable liver-only metastasis (n=9, 4%) had a median OS of 39 months (95% CI, 13-NR). CONCLUSIONS: The 4% of our cohort that were potentially eligible for surgery experienced a prolonged survival compared with all-comers with stage IV disease. Oncologic outcomes of patients undergoing resection of metastatic pancreas cancer should be assessed in the context of the expected survival of patients potentially eligible for surgery and not relative to all patients with stage IV disease.
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Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Benchmarking , Neoplasias Hepáticas/secundário , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: Adherence to evidence-based guidelines for gastric cancer is low, particularly at the hospital level, despite a strong association with improved overall survival (OS). We aimed to evaluate patterns of hospital and regional adherence to National Comprehensive Cancer Network guidelines for gastric cancer. METHODS: Using the National Cancer Database (2004-2015), we identified patients with stage I-III gastric cancer. Hospital-level guideline adherence was calculated by dividing the patients who received guideline adherent care by the total patients treated at that hospital. OS was estimated for each hospital. Associations between adherence, region, and survival were compared using mixed-effects, hierarchical regression. RESULTS: Among 576 hospitals, the median hospital guideline adherence rate was 25% (range 0-76%) and varied significantly by region (p = 0.001). Adherence was highest in the Middle Atlantic (29%) and lowest in the East South Central region (19%); hospitals in the New England, Middle Atlantic, and East North Central regions were more likely to be guideline adherent than those in the East South Central region (all p < 0.05), after adjusting for patient and hospital mix. Most (35%) of the adherence variation was attributable to the hospital. Median 2-year OS varied significantly by region. After adjusting for hospital and patient mix, hazard of mortality was 17% lower in the Middle Atlantic (hazard ratio 0.82, 95% confidence interval 0.74-0.90) relative to the East South Central region, with most of the variation (54%) attributable to patient-level factors. CONCLUSIONS: Hospital-level guideline adherence for gastric cancer demonstrated significant regional variation and was associated with longer OS, suggesting that efforts to improve guideline adherence should be directed toward lower-performing hospitals.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , HospitaisRESUMO
OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.
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Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Adulto , Humanos , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/cirurgia , Biópsia de Linfonodo Sentinela , Estudos de Coortes , Melanoma/cirurgia , Melanoma/tratamento farmacológico , Excisão de Linfonodo , Estudos RetrospectivosRESUMO
Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.
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Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Excisão de Linfonodo , Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/tratamento farmacológicoRESUMO
Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive dermal-based sarcoma. Metastatic potential is extremely low, primarily in the setting of fibrosarcomatous transformation. DFSP is characterized by a t(17;22) (q22;q13) translocation that results in active PDGFB signaling. Surgical resection with negative margins (typically including the underlying fascia) is the potentially curative treatment. Delayed wound closure should be considered for cases requiring extensive resection or tissue rearrangement. Tyrosine kinase inhibitors, such as imatinib, have shown response rates of 50% to 60% in patients with locally advanced or metastatic disease. Radiation can be useful for residual or recurrent diseases.
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Dermatofibrossarcoma , Neoplasias Cutâneas , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/genética , Dermatofibrossarcoma/terapia , Humanos , Mesilato de Imatinib , Margens de Excisão , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapiaRESUMO
INTRODUCTION: Surgery is an option for symptom palliation in patients with metastatic gastric cancer. Operative outcomes after palliative interventions are largely unknown. Herein, we assess the trends of surgical palliation use for patients with gastric cancer and describe outcomes of patients undergoing surgical palliation compared to nonsurgical palliation. METHODS: Patients with clinical Stage IV gastric cancer in the National Cancer Database (2004-2015) who received surgical or nonsurgical palliation were selected. We identified factors associated with palliative surgery. Survival differences were assessed by Kaplan-Meier estimate, Cox proportional hazard regression, and log rank test. RESULTS: Six thousand eight hundred twenty nine patients received palliative care for gastric cancer. Most patients (87%, n = 5944) received nonsurgical palliation: 29% radiation therapy, 57% systemic treatment, and 14% pain management. The number of patients receiving palliative care increased between 2004 and 2015; however, use of surgical palliation declined significantly (22% in 2004, 8% in 2015; P < 0.001). Median overall survival (OS) for the cohort was 5.65 mo (95% confidence interval 5.45-5.85); 1-year and 2-year OS were 24% and 9%, respectively. Older age at diagnosis and diagnosis between 2004 and 2006 were significantly associated with undergoing surgical palliation. Patients who underwent surgical palliation had significantly shorter median OS and a 20% higher hazard of mortality than those who received nonsurgical palliation. CONCLUSIONS: Patients with metastatic gastric cancer experience very short survival. While palliative surgery is used infrequently, the observed association with shorter median OS underscores the importance of careful patient selection. Palliative surgery should be offered judiciously and expectations about outcomes clearly established.
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Neoplasias Gástricas , Humanos , Estimativa de Kaplan-Meier , Manejo da Dor , Cuidados Paliativos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND: Diagnostic laparoscopy (DL) is a key component of staging for locally advanced gastric adenocarcinoma (GA). We hypothesized that utilization of DL varied between safety net (SNH) and affiliated tertiary referral centers (TRCs). METHODS: Patients diagnosed with primary GA eligible for DL were identified from the US Safety Net Collaborative database (2012-2014). Clinicopathologic factors were analyzed for association with use of DL and findings on DL. Overall survival (OS) was analyzed by Kaplan-Meier method. RESULTS: Among 233 eligible patients, 69 (30%) received DL, of which 24 (35%) were positive for metastatic disease. Forty percent of eligible SNH patients underwent DL compared to 21.5% at TRCs. Lack of insurance was significantly associated with decreased use of DL (OR 0.48, p < 0.01), while African American (OR 6.87, p = 0.02) and Asian race (OR 3.12, p ≤ 0.01), signet ring cells on biopsy (OR 3.14, p < 0.01), and distal tumors (OR 1.62, p < 0.01) were associated with increased use. Median OS of patients with a negative DL was better than those without DL or a positive DL (not reached vs. 32 vs. 12 months, p < 0.005, Figure 1). CONCLUSIONS: Results from DL are a strong predictor of OS in GA; however, the procedure is underutilized. Patients from racial minority groups were more likely to undergo DL, which likely accounts for higher DL rates among SNH patients.
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Adenocarcinoma , Laparoscopia , Neoplasias Gástricas , Adenocarcinoma/patologia , Hospitais , Humanos , Laparoscopia/métodos , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
PURPOSE: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. METHODS: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. RESULTS: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. CONCLUSION: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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Inibidores de Checkpoint Imunológico , Melanoma , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Ipilimumab/uso terapêutico , Melanoma/patologia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: National Comprehensive Cancer Network guidelines recommend resection and adjuvant chemotherapy for patients with locally advanced duodenal adenocarcinoma. Outcomes after systemic treatment in this rare malignancy have not been well studied. We examined utilization patterns of systemic treatment and compared overall survival of patients receiving neoadjuvant therapy, surgery alone, and adjuvant therapy. METHODS: Patients with stage 0 to III duodenal adenocarcinoma undergoing curative-intent surgery were identified within the National Cancer Database from 2006 to 2015. Outcomes, including median overall survival and 30- and 90-day mortality, were compared based on treatment sequence (neoadjuvant, adjuvant, or surgery alone). Propensity score matching on likelihood of receiving systemic treatment and landmark analysis were performed to mitigate bias. RESULTS: Of the 2,956 patients meeting inclusion criteria, most patients with known clinical stage had locally advanced disease (72%), of which 53% received systemic therapy (8% neoadjuvant, 45% adjuvant). After landmark analysis on the propensity matched cohort, patients with locally advanced disease who received systemic treatment had longer median overall survival compared to patients who underwent surgery alone (49 vs 40 months, P = .018) and a 20% lower hazard of mortality (hazard ratio 0.80, 95% confidence interval 0.69-0.93, P = .003). Patients who received neoadjuvant and adjuvant therapy had similar survival outcomes. CONCLUSION: Adjuvant therapy was underutilized in patients with National Comprehensive Cancer Network guideline indications, despite an association with longer median overall survival and decreased hazard of mortality. Neoadjuvant therapy, although rarely used, had similar survival to adjuvant therapy. Given its other potential benefits, systemic treatment in the neoadjuvant setting may be a reasonable option in adequately selected patients with clinically advanced duodenal adenocarcinoma.
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Adenocarcinoma , Neoplasias Duodenais , Adenocarcinoma/patologia , Quimioterapia Adjuvante , Neoplasias Duodenais/patologia , Neoplasias Duodenais/terapia , Humanos , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
Survival outcomes in melanoma and their association with mutations in the telomerase reverse transcriptase gene TERT promoter remain uncertain. In addition, few studies have examined whether these associations are affected by a nearby common germline polymorphism or vary on the basis of melanoma histopathological subtype. We analyzed 408 primary tumors from a prospective melanoma cohort for somatic TERT-124[C>T] and TERT-146[C>T] mutations, the germline polymorphism rs2853669, and BRAFV600 and NRASQ61 mutations. We tested the associations between these variants and clinicopathologic factors and survival outcomes. TERT-124[C>T] was associated with thicker tumors, ulceration, mitoses (>0/mm2), nodular histotype, and CNS involvement. In a multivariable model controlling for the American Joint Committee on Cancer stage, TERT-124[C>T] was an independent predictor of shorter recurrence-free survival (hazard ratio = 2.58, P = 0.001) and overall survival (hazard ratio = 2.47, P = 0.029). Patients with the germline variant and TERT-124[C>T]-mutant melanomas had significantly shorter recurrence-free survival than those lacking either or both sequence variants (P < 0.04). The impact of the germline variant appeared to be more pronounced in superficial spreading than in nodular melanoma. No associations were found between survival and TERT-146[C>T], BRAF, or NRAS mutations. These findings strongly suggest that TERT-124[C>T] mutation is a biomarker of aggressive primary melanomas, an effect that may be modulated by rs2853669.
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Melanoma , Telomerase , Humanos , Melanoma/patologia , Mutação , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas , Telomerase/genética , Telomerase/metabolismo , Melanoma Maligno CutâneoRESUMO
BACKGROUND AND OBJECTIVES: Adherence to evidence-based guidelines in gastric cancer is low. We aimed to evaluate adherence to National Comprehensive Cancer Network (NCCN) Guidelines for gastric cancer at both patient- and hospital-levels and examine associations between guideline adherence and treatment outcomes, including overall survival (OS). METHODS: We applied stage-specific, annual NCCN Guidelines (2004-2015) to patients with gastric cancer treated with curative-intent within the National Cancer Database and compared characteristics of patients who did and did not receive guideline-adherent care. Hospitals were evaluated by guideline adherence rate. We identified associations with OS through multivariable Cox regression. RESULTS: Of 37 659 patients included, 32% received NCCN Guideline-adherent treatment. OS was significantly associated with both guideline adherence (51 months for patients receiving guideline-adherent treatment vs. 22 for patients receiving nonadherent treatment, p < 0.001). Treatment at a hospital with higher adherence was associated with longer OS (21 months for patients treated at lowest adherence quartile hospitals vs. 37 months at highest adherence quartile hospitals, p < 0.001), regardless of type of treatment received. CONCLUSIONS: Guideline-adherent treatment was strongly associated with longer median OS. Guideline adherence should be used as a benchmark for focused quality improvement for physicians taking care of patients with gastric cancer and institutions at large.