RESUMEN
OBJECTIVE: We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome. SUMMARY BACKGROUND DATA: Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation. METHODS: Pancreatic samples were collected at the time of resection from 109 patients. Samples included tumor tissue (control, n=20; IPMN, n=20; PDAC, n=19) and pancreatic cyst fluid (IPMN, n=30; SCA, n=10; MCN, n=10). Assessment of bacterial DNA by quantitative PCR and 16S ribosomal RNA gene sequencing was performed. Downstream analyses determined the relative abundances of individual taxa between groups and compared intergroup diversity. Whole-genome sequencing data from 140 patients with PDAC in the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) were analyzed to validate findings. RESULTS: Sequencing of pancreatic tissue yielded few microbial reads regardless of diagnosis, and analysis of pancreatic tissue showed no difference in the abundance and composition of bacterial taxa between normal pancreas, IPMN, or PDAC groups. Low-grade dysplasia (LGD) and high-grade dysplasia (HGD) IPMN were characterized by low bacterial abundances with no difference in tissue composition and a slight increase in Pseudomonas and Sediminibacterium in HGD cyst fluid. Decontamination analysis using the CPTAC database confirmed a low-biomass, low-diversity intrinsic pancreatic microbiome that did not differ by pathology. CONCLUSIONS: Our analysis of the pancreatic microbiome demonstrated very low intrinsic biomass that is relatively conserved across diverse neoplastic conditions and thus unlikely to drive malignant transformation.
RESUMEN
ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma (PDAC) is highly lethal with up to 80% of resected patients experiencing disease recurrence within 2 years (Watanabe, Nakamura, Kimura et al in Int J Mol Sci 23(19):11521, 2022). Cross-sectional imaging and serum tumor markers are used for monitoring post-operative recurrence; however, both have significant limitations (Edland, Tjensvoll, Oltedal et al in Mol Oncol 17:1857-1870, 2023). Circulating tumor DNA (ctDNA) has emerged as a valuable prognostic tool to measure molecular residual disease (MRD) and predict recurrence in solid tumors (Watanabe, Nakamura, Kimura et al in Int J Mol Sci 23(19):11521, 2022). In this study, we evaluated the feasibility of a personalized, tumor-informed ctDNA assay to detect recurrence prior to standard surveillance tools in patients with PDAC. PATIENTS AND METHODS: After Institutional Review Board (IRB) approval (Pro00106870), we assessed serial ctDNA measurements (n = 177) from 35 patients with resectable PDAC treated by either upfront resection or neoadjuvant chemotherapy. Plasma samples (median 4 ml, interquartile range 0.6-5.9 ml) were isolated from blood collected in EDTA tubes and banked at diagnosis, during neoadjuvant therapy if applicable, on the day of surgery, and every 2-3 months postoperatively. A tumor-informed assay (Signatera™, Natera, Inc.) that tracks up to 16 individual-specific, somatic single nucleotide variants in the corresponding patient's plasma samples were used for ctDNA detection. Survival was calculated using Kaplan-Meier curves, and significance was determined with the log-rank test. RESULTS: Personalized ctDNA assays were successfully designed for all patients (with 32/35 patients having 16-plex assays). Median follow-up from initial treatment was 13 months (range 1-26 months; Table 1). ctDNA-positivity at any time point was observed in 40% (14/35) of patients. During the follow-up period, 18 patients (51%) developed radiographic evidence of recurrence after a median of 9 months of follow-up (range 1-26 months). At the time of radiographic recurrence, 50% (9/18) of patients were ctDNA-positive. During the immediate postoperative period (up to 9 weeks post-surgery), RFS and OS were significantly inferior in patients who were ctDNA-positive versus ctDNA-negative (RFS 97 versus 297 days, p < 0.001; OS 110 versus 381 days, p < 0.001; Fig. 1). Table 1 Cohort demographics (N = 35); patient demographics, tumor characteristics, and survival Gender (%) Female 17 (49%) Male 18 (51%) Median age (IQR) 70 years (65-75 years) Neoadjuvant treatment (%) 11 (31%) Median sample plasma volume (IQR) 4.0 mL (0.6-5.9 mL) Median follow-up (range) 13 months (1-26 months) Median initial CA 19-9 in U/mL (IQR) 56 (18-160) Median tumor size in cm (IQR) 2.5 (1.8-3.3) Median number of positive lymph nodes (IQR) 1 (0-3) Median recurrence-free survival 9.4 months Median overall survival N/A (not reached) Fig. 1 a Overview plot showing longitudinal ctDNA status, treatment regimen, and clinical outcomes for each patient (N = 35); median follow-up from the start of the neoadjuvant therapy/surgery was 13 months (range 1-26 months); ctDNA at any time point was 40% (14/35); out of the 35 patients, 18 (51%) developed radiographic evidence of recurrence (median RFS: 9 months), and of these 18 patients with clinical recurrence, 9 (50%) were ctDNA-positive and the remaining ctDNA-negative; notably, all ctDNA-negative patients with recurrence had suboptimal plasma volume available for ctDNA analysis; b, c Kaplan-Meier estimates representing the association of ctDNA status with (b) RFS and (c) OS, at MRD time point (9 weeks post-surgery) DISCUSSION: Our study demonstrates the feasibility of tumor-informed ctDNA-based MRD testing in resectable PDAC and shows that MRD detected by ctDNA within the immediate postoperative period portends a dismal prognosis. This information is valuable for both patients and clinicians in setting prognostic expectations.
Asunto(s)
Adenocarcinoma , ADN Tumoral Circulante , Neoplasias Pancreáticas , Humanos , Masculino , Femenino , Lactante , Neoplasias Pancreáticas/cirugía , ADN Tumoral Circulante/genética , Adenocarcinoma/cirugía , Recurrencia Local de Neoplasia/patología , Pronóstico , Biomarcadores de Tumor/genéticaRESUMEN
INTRODUCTION: Desmoid tumors (DTs) are rare, fibroblastic cell proliferations that can exhibit locally aggressive behavior but lack metastatic potential. Initial management has traditionally involved upfront resection; however, contemporary guidelines and expert panels have increasingly advocated for prioritizing active surveillance strategies. METHODS: A single-institution, retrospective chart review identified all patients diagnosed with a primary DT at any site from 2007 to 2020. The primary outcome was the initial management strategy over time. Secondary outcomes included treatment-free survival (TFS) and time to treatment (TTT) for those undergoing active surveillance, as well as recurrence-free survival (RFS) and time to recurrence for those undergoing resection. RESULTS: Overall, 103 patients were included, with 68% female and a median follow-up of 44 months [24-74]. The most common tumor locations included the abdominal wall (27%), intra-abdominal/mesenteric (25%), chest wall (19%), and extremity (10%). Initial management included resection (60%), systemic therapy (20%), active surveillance (18%), and cryoablation (2%). Rates of surgical resection significantly decreased (p < 0.001) over time, from 69.6% prior to 2018 to 29.2% after 2018. For those treated with upfront resection, 5-year RFS was 41.2%, and for patients undergoing initial active surveillance, TFS was 66.7% at 2 years, with a median TTT of 4 months [4-10]. CONCLUSIONS: This single-institution cohort at a tertiary medical center spanning over a decade demonstrates the transition to active surveillance for initial management of DTs, and highlights salient metrics in the era of surveillance. This trend mirrors recommended treatment strategies by expert panels and consensus guidelines.
RESUMEN
BACKGROUND: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical cholecystectomy for pathologic stage T1B gallbladder cancer. METHODS: The National Cancer Database (NCDB) was queried for patients with pathologic T1B gallbladder cancer diagnosed from 2004 to 2018. Patients were stratified by surgical management. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Altogether, 950 patients were identified with pathologic T1B gallbladder cancer: 187 (19.7 %) receiving simple and 763 (80.3 %) radical cholecystectomy. Median OS was 89.5 (95 % CI 62.5-137) and 91.4 (95 % CI 75.9-112) months for simple and radical cholecystectomy, respectively (log-rank p = 0.55). Receipt of simple cholecystectomy was not associated with greater hazard of mortality compared to radical cholecystectomy (HR 1.23, 95 % CI 0.95-1.59, p = 0.12). DISCUSSION: In this analysis, we report comparable outcomes with simple cholecystectomy among patients with pathologic T1B gallbladder cancer. These findings suggest that highly selected patients, such as those with R0 resection and imaging at low risk for residual disease and/or nodal metastasis, may not benefit from extended resection; however, radical cholecystectomy remains standard of care until prospective validation can be achieved.
Asunto(s)
Carcinoma in Situ , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/patología , Estadificación de Neoplasias , Estudios Retrospectivos , Colecistectomía , Escisión del Ganglio Linfático , Carcinoma in Situ/patologíaRESUMEN
BACKGROUND: Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry. PATIENTS AND METHODS: Patients with clinical stage I-III ICC < 3 cm diagnosed 2010-2018 who underwent resection, ablation, or RT were identified in the National Cancer Database. Overall survival (OS) was compared using Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 545 patients, 297 (54.5%) underwent resection, 114 (20.9%) ablation, and 134 (24.6%) RT. Median OS was similar between resection and ablation [50.5 months, 95% confidence interval (CI) 37.5-73.9; 39.5 months, 95% CI 28.7-58.4, p = 0.14], both exceeding that of RT (20.9 months, 95% CI 14.1-28.3). RT patients had high rates of stage III disease (10.4% RT vs. 1.8% ablation vs. 11.8% resection, p < 0.001), but the lowest rates of chemotherapy utilization (9.0% RT vs. 15.8% ablation vs. 38.7% resection, p < 0.001). In multivariable analysis, resection and ablation were associated with reduced mortality compared with RT [hazard ratio (HR) 0.44, 95% CI 0.33-0.58 and HR 0.53, 95% CI 0.38-0.75, p < 0.001, respectively]. CONCLUSION: Resection and ablation were associated with improved survival in patients with ICC < 3 cm compared with RT. Acknowledging confounders, anatomic constraints of ablation, limitations of available data, and need for prospective study, these results favor ablation in small ICC where resection is not feasible.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Estudios Prospectivos , Colangiocarcinoma/radioterapia , Colangiocarcinoma/cirugía , Hepatectomía , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/patología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Resection remains the cornerstone of curative-intent treatment for biliary tract cancers (BTCs). However, recent randomized data also support a role for adjuvant chemotherapy (AC). This study aimed to characterize trends in the use of AC and subsequent outcomes in gallbladder cancer and cholangiocarcinoma (CCA). METHODS: The National Cancer Database (NCDB) was queried for patients with resected, localized BTC from 2010 to 2018. Trends in AC were compared among BTC subtypes and stages of disease. Multivariable logistic regression was used to identify factors associated with receipt of AC. Survival analysis was performed with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: The study identified 7039 patients: 4657 (66%) with gallbladder cancer, 1159 (17%) with intrahepatic CCA (iCCA), and 1223 (17%) with extrahepatic CCA (eCCA). Adjuvant chemotherapy was administered to 2172 (31%) patients, increasing from 23% in 2010 to 41% in 2018. Factors associated with AC included female sex, year of diagnosis, private insurance, care at an academic center, higher education, eCCA (vs iCCA), positive margins, and stage II or III disease (vs stage I). Alternatively, increasing age, higher comorbidity score, gallbladder cancer (vs iCCA), and farther travel distance for treatment were associated with reduced odds of AC. Overall, AC was not associated with a survival advantage. However, subgroup analysis showed that AC was associated with a significant reduction in mortality among patients with eCCA. CONCLUSIONS: Among the patients with resected BTC, those who received AC were in the minority. In the context of recent randomized data and evolving recommendations, emphasis on guideline concordance with a focus on at-risk populations may improve outcomes.
Asunto(s)
Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colangiocarcinoma , Neoplasias de la Vesícula Biliar , Humanos , Femenino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/cirugía , Neoplasias de la Vesícula Biliar/patología , Neoplasias del Sistema Biliar/tratamiento farmacológico , Neoplasias del Sistema Biliar/cirugía , Neoplasias del Sistema Biliar/patología , Colangiocarcinoma/patología , Quimioterapia Adyuvante , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/patologíaRESUMEN
OBJECTIVES: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA). METHODS: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods. RESULTS: Of 2140 patients, 1877 (87.7%) underwent resection and 263 (12.3%) underwent ablation, with median tumor sizes of 5.5 and 3 cm, respectively. Overall, resection was associated with greater median OS (41.2 months (95% confidence interval [95% CI]: 37.6-46.2) vs. 28 months (95% CI: 15.9-28.6) on univariable analysis (p < 0.0001). There was no significant difference on multivariable analysis (p = 0.42); however, there was a significant interaction between tumor size and management. On subgroup analysis of patients with tumors <3 cm, there was no difference in OS between resection versus ablation. However, ablation was associated with increased mortality for tumors ≥3 cm. CONCLUSION: Although resection is associated with improved OS for tumors ≥3 cm, we observed no difference in survival between management strategies for tumors < 3 cm. Ablation may be an alternative therapeutic strategy for small iCCA, particularly in patients at risk for high surgical morbidity.
Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Estudios Retrospectivos , Neoplasias de los Conductos Biliares/patología , Colangiocarcinoma/patología , Hepatectomía/métodos , Conductos Biliares Intrahepáticos/patologíaRESUMEN
BACKGROUND: Optimal management of stage II/III gastric cancer requires multidisciplinary care, often necessitating treatment at more than one facility. We aimed to determine patterns of "fragmented" care and its impact on outcomes, including concordance with National Comprehensive Cancer Network (NCCN) guidelines and overall survival. METHODS: The 2006-2016 National Cancer Database was queried for patients with clinical stage II/III gastric adenocarcinoma who received preoperative therapy in addition to surgery. Patients were stratified based on whether surgery and chemotherapy/chemoradiation were performed at one versus multiple facilities (termed "coordinated" and "fragmented" care, respectively). Multivariable logistic regression was performed to identify factors associated with fragmented care. Survival was compared using Kaplan-Meier and Cox proportional hazards methods. RESULTS: Overall, 2033 patients met study criteria: 1043 (51.3%) received coordinated care and 990 (48.7%) fragmented care. There was no significant difference in time to surgery or pathologic upstaging by care structure. On adjusted analysis, factors associated with receipt of fragmented care included increasing age and distance traveled to the treating facility. Factors associated with coordinated care included metropolitan residence and treatment at academic and high-volume centers. Fragmented care was associated with a reduction in guideline-preferred perioperative chemotherapy (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.63-0.97, p = 0.02) and increased mortality (HR 1.16, 95% CI 1.00-1.34, p = 0.05). CONCLUSIONS: For patients with stage II/III gastric cancer, fragmented care is associated with inferior outcomes, including a reduction in preferred perioperative treatment and survival. Further work is needed to ensure equitable outcomes among patients as complex cancer care becomes more regionalized.
Asunto(s)
Neoplasias Gástricas , Neoplasias Testiculares , Quimioradioterapia/métodos , Humanos , Masculino , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been associated with dysplastic progression; however, the cause and composition of this inflammation remains poorly characterized. We sought to comprehensively profile immune cell infiltration using parallel spatial transcriptomic and flow cytometric techniques. METHODS: Twelve patients with resected IPMN exhibiting both high-grade dysplasia (HGD) and low-grade dysplasia (LGD) were selected for spatial transcriptomics (NanoString GeoMx). Immune (CD45+), epithelial (PanCK+), and stromal (SMA+) compartments were analyzed separately using the GeoMx NGS Pipeline. An additional 11 patients resected for IPMN of varying degrees of dysplasia underwent immunophenotyping using flow cytometry (DURAClone IM). RESULTS: Spatial transcriptomics revealed that T cells represent the dominant immune cell within IPMN stroma, which was confirmed by flow cytometry (56%). Spatial profiling found that the T-cell infiltrate was significantly higher in regions of LGD compared with HGD (62% vs. 50%, p = 0.038). Macrophages were the only other immune cell type with > 10% abundance, yet conversely, were generally more abundant in regions of HGD compared to LGD (19% vs. 11%, p = 0.058). Correspondingly, immune cells within regions of HGD demonstrated transcriptional upregulation of genes associated with macrophage activity including secretion (CXCL1) and phagocytosis (C1QA, C1S, C4B). CONCLUSIONS: IPMN immune infiltrate is primarily composed of T cells and macrophages. Regions of HGD appear to be relatively deplete of T cells and show a trend toward macrophage enrichment compared with regions of LGD.
Asunto(s)
Adenocarcinoma Mucinoso , Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Humanos , Hiperplasia/patología , Inmunofenotipificación , Inflamación/patología , Macrófagos/patología , Neoplasias Intraductales Pancreáticas/genética , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Linfocitos TRESUMEN
INTRODUCTION: Both neo-adjuvant chemoradiation therapy (NACRT) and neo-adjuvant chemotherapy (NAC), in addition to surgical resection of gastric cardia cancer, improves survival outcomes. We assessed whether NACRT or NAC had superior overall survival (OS) and relative survival (RS) outcomes using the National Cancer Database (NCDB). METHODS: The NCDB from 2006 to 2014 was reviewed to identify non-metastatic adult gastric cardia cancer patients who underwent surgical resection and received NACRT or NAC. Advanced statistical models were applied to assess survival outcomes. RESULTS: Of the 5,371 patients included, 4,520 (84.2%) were male, the mean age was 61.2 years (SD 10.0), 4,229 (78.7%) underwent NACRT, and 1,142 (21.3%) underwent NAC. NACRT patients more often had an R0 resection compared to NAC (91.4 vs. 86.6%, p < 0.001, respectively). Univariate 5-year OS rates were 40.0% (95% CI 38.2-41.8) for NACRT and 40.1% (37.0-43.6) for NAC (p = 0.302). No differences in OS for NAC vs. NACRT were found after multivariable analysis (hazard ratio [HR] 0.95, 95% CI 0.86-1.05, p = 0.290). There were no survival differences after stepwise, propensity score, RS analyses, nor after near-far-matching (HR 0.94, 95% CI 0.82-1.07, p = 0.332). CONCLUSIONS: NAC or NACRT yield the same survival outcome for patients with resectable gastric cardia cancer. These data support the need for randomized controlled trials comparing the 2 regimens head-to-head.
Asunto(s)
Adenocarcinoma/terapia , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Cardias/cirugía , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Terapia Combinada , Bases de Datos Factuales , Esofagectomía , Femenino , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Radioterapia Adyuvante , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía , Análisis de Supervivencia , Resultado del Tratamiento , Estados UnidosRESUMEN
PURPOSE: While the importance of lymphadenectomy is well-established for patients with resectable pancreatic cancer, its direct impact on survival in relation to other predictive factors is still ill-defined. METHODS: The National Cancer Data Base 2006-2015 was queried for patients with resected pancreatic adenocarcinoma (stage IA-IIB). Patients were dichotomized into the following two groups, those with 1-14 resected lymph nodes and those with ≥ 15. Optimal number of resected lymph nodes and the effect of lymphadenectomy on survival were assessed using various statistical modeling techniques. Mediation analysis was performed to differentiate the direct and indirect effect of lymph node resection on survival. RESULTS: A total of 21,912 patients were included; median age was 66 years (IQR 59-73), 48.9% were female. Median number of resected lymph nodes was 15 (IQR 10-22), 10,163 (46.4%) had 1-14 and 11,749 (53.6%) had ≥ 15 lymph nodes retrieved. Lymph node positivity increased by 4.1% per lymph node up to eight examined lymph nodes, and by 0.6% per lymph node above eight. Five-year overall survival was 17.9%. Overall survival was better in the ≥ 15 lymph node group (adjusted HR 0.91, CI 0.88-0.95, p < 0.001). On a continuous scale, survival improved with increasing LNs collected. Patients who underwent adjuvant chemotherapy and were treated at high-volume centers had improved overall survival compared with their counterparts (adjusted HR 0.59, CI 0.57-0.62, p < 0.001; adjusted HR 0.86, CI 0.83-0.89, p < 0.001, respectively). Mediation analysis revealed that lymphadenectomy had only 18% direct effect on improved overall survival, while 82% of its effect were mediated by other factors like treatment at high-volume hospitals and adjuvant chemotherapy. DISCUSSION: While higher number of resected lymph nodes increases lymph node positivity and is associated with better overall survival, most of the observed survival benefit is mediated by chemotherapy and treatment at high-volume centers.
Asunto(s)
Hospitales de Alto Volumen , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Antineoplásicos/uso terapéutico , Quimioterapia Adyuvante , Bases de Datos Factuales , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugíaRESUMEN
BACKGROUND: For many cancer types, survival is improved when patients receive management at treatment centers that encounter high numbers of patients annually. This correlation may be more important with less common malignancies such as sarcoma. Existing evidence, however, is limited and inconclusive as to whether facility volume may be associated with survival in soft tissue sarcoma. QUESTIONS/PURPOSES: The purpose of this study was to examine the association between facility volume and overall survival in patients with soft tissue sarcoma of the extremities. In investigating this aim, we sought to (1) examine differences in the treatment characteristics of high- and low-volume facilities; (2) estimate the 5-year survival by facility volume; and (3) examine the association between facility volume and of traveling a further distance to a high-volume center and overall survival when controlling for confounding factors. METHODS: The largest sarcoma patient registry to date is contained within the National Cancer Database (NCDB) and captures > 70% of new cancer diagnoses annually. We retrospectively analyzed 25,406 patients with soft tissue sarcoma of the extremities in the NCDB from 1998 through 2012. Patients were stratified based on per-year facility sarcoma volume and we used univariate comparisons and multivariate proportional hazards analyses to correlate survival measures with facility volume and various other patient-, tumor-, and treatment-related factors. First, we evaluated long-term survival for all variables using the Kaplan-Meier method with statistical comparisons based on the log-rank test. Multiple patient, tumor, and treatment characteristics were compared between the two facility-volume groups and then included them in the multivariate proportional hazards model. Of the 25,406 patients analyzed, 3310 were treated at high-volume centers (≥ 20 patients annually) and 22,096 were treated at low-volume centers. Patient demographics were generally not different between both patient cohorts, although patients treated at high-volume centers were more likely to have larger and higher grade tumors (64% versus 56% size ≥ 5 cm, 28% versus 14% undifferentiated grade, p < 0.001). RESULTS: When controlling for patient, tumor, and treatment characteristics in a multivariate proportional hazards analysis, patients treated at high-volume facilities had an overall lower risk of mortality than those treated at low-volume centers (hazard ratio, 0.81 [0.75-0.88], p < 0.001). Patients treated at high-volume centers were also less likely to have positive margins (odds ratio [OR], 0.59 [0.52-0.68], p < 0.001) and in patients who received radiation, those treated at high-volume centers were more likely to have radiation before surgery (40.5% versus 21.7%, p < 0.001); there was no difference in the type of surgery performed (resection versus amputation) (OR, 1.01 [0.84-1.23], p = 0.883). CONCLUSIONS: With the largest patient cohort to date, this database review suggests that certain patients with soft tissue sarcoma of the extremities, particularly those with large high-grade tumors, may benefit from treatment at high-volume centers. Further investigation is necessary to help improve the referral of appropriate patients to high-volume sarcoma centers and to increase the treatment capacity of and access to such centers. LEVEL OF EVIDENCE: Level III, therapeutic study.
Asunto(s)
Hospitales de Alto Volumen , Sarcoma/cirugía , Neoplasias de los Tejidos Blandos/cirugía , Femenino , Accesibilidad a los Servicios de Salud , Hospitales de Bajo Volumen , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Derivación y Consulta , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Sarcoma/mortalidad , Sarcoma/patología , Neoplasias de los Tejidos Blandos/mortalidad , Neoplasias de los Tejidos Blandos/patología , Factores de Tiempo , Transporte de Pacientes , Resultado del Tratamiento , Carga Tumoral , Estados UnidosRESUMEN
BACKGROUND: Pancreatic acinar cell carcinoma (pACC) is a rare malignancy and surgical utilization has been historically low in these patients. Contemporary outcomes for this patient population remain unknown. METHODS: The 1998-2012 National Cancer Data Base was queried for baseline characteristics in patients with pACC. Patients with potentially operable disease (stage I/II) were grouped by surgical resection. Multivariable logistic regression was used to predict factors associated with resection. Survival was estimated using Kaplan-Meier analysis. A proportional hazards model identified factors associated with overall survival. RESULTS: 980 patients were identified. Mean age at diagnosis was 64 years. Tumors were more common in men (68%), white patients (88%), and within the pancreatic head (57%). Thirty-four percent of patients with localized disease failed to undergo resection. Five-year survival was higher among patients who underwent resection (42% vs. 9%, p < 0.001). In patients with resectable disease, male sex, older age, black race, tumors within the pancreatic head, lower grade tumors and treatment at non-academic centers are associated with failure to undergo surgery. CONCLUSION: Patients with localized pACC have increased survival after resection. However, in this contemporary analysis, resection continues to be underutilized and new efforts to increase resection rates should be undertaken.
Asunto(s)
Mal Uso de los Servicios de Salud/estadística & datos numéricos , Pancreatectomía/estadística & datos numéricos , Neoplasias Pancreáticas/cirugía , Sistema de Registros , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología , Neoplasias PancreáticasAsunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/secundario , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: In the United States, race and socioeconomic status are well known predictors of adverse outcomes in several different cancers. Existing evidence suggests that race and socioeconomic status may impact survival in soft tissue sarcoma (STS). We investigated the National Cancer Database (NCDB), which contains several socioeconomic and medical variables and contains the largest sarcoma patient registry to date. Our goal was to determine the impact of race, ethnicity and socioeconomic status on patient survival in patients with soft tissue sarcoma of the extremities (STS-E). METHODS: We retrospectively analyzed 14,067 STS-E patients in the NCDB from 1998 through 2012. Patients were stratified based on race, ethnicity and socioeconomic status. Univariate and multivariate analyses were used to correlate specific outcomes and survival measures with these factors. Then, long-term survival between groups was evaluated using the Kaplan-Meier (KM) method with comparisons based on the log-rank test. Multiple variables were analyzed between two groups. RESULTS: Of the 14,067 patients analyzed, 84.9% were white, 11% were black and 4.1% were Asian. Black patients were significantly more likely (7.18% vs 5.65% vs 4.47%) than white or Asian patients to receive amputation (p = 0.027). Black patients were also less likely to have either an above-median education level or an above-median income level (p < 0.001). In addition, black patients were more likely to be uninsured (p < 0.001) and more likely to have a higher Charleson Comorbidity Score than white or Asian patients. Tumors were larger in size upon presentation in black patients than in white or Asian patients (p < 0.001). Black patients had significantly poorer overall survival than did white or Asian patients (p < 0.001) with a KM 5-year survival of 61.4% vs 66.9% and 69.9% respectively, and a 24% higher independent likelihood of dying in a multivariate analysis. CONCLUSION: This large database review reveals concerning trends in black patients with STS-E. These include larger tumors, poorer resources, a greater likelihood of amputation, and poorer survival than white and Asian patients. Future studies are warranted to help ensure adequate access to effective treatment for all patients.
Asunto(s)
Extremidades/patología , Grupos de Población , Sarcoma/epidemiología , Adulto , Anciano , Comorbilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Sarcoma/etnología , Sarcoma/mortalidad , Sarcoma/patología , Factores Socioeconómicos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although surgery remains the cornerstone of gastric cancer therapy, the use of radiation therapy (RT) is increasingly being employed to optimize outcomes. We sought to assess outcomes following use of RT for the treatment of gastric adenocarcinoma. METHODS: Using the National Cancer Data Base (NCDB) from 1998 to 2012, all patients with resected gastric adenocarcinoma were identified. Patients were stratified into four groups based on preoperative therapy: RT alone, chemotherapy only, chemoradiotherapy (CRT), and no preoperative therapy. Overall survival was estimated using multivariate Cox proportional hazards model. Adjusted secondary outcomes include margin positivity, lymph node harvest, LOS, 30-day readmission and mortality. RESULTS: A total of 10 019 patients met study criteria. In the unadjusted analysis, patients undergoing CRT compared to chemotherapy alone had fewer positive margins (7.9% vs 15.9%; P < 0.001), increased negative LNs (54.6% vs 37.7%; P < 0.001) with reduced LN retrieval (mean: 13.5 vs 19.6; P < 0.01). After multivariate adjustment, there was no survival benefit to any preoperative therapy; however, preoperative RT/CRT remained associated with decreased LN retrieval. CONCLUSIONS: The results support previous reports on preoperative RT resulting in decreased margin positivity. This study highlights the need to reconsider practice guidelines regarding appropriate lymphadenectomy in the setting of preoperative RT given reduced LN retrieval.
Asunto(s)
Adenocarcinoma/terapia , Unión Esofagogástrica/cirugía , Escisión del Ganglio Linfático , Terapia Neoadyuvante , Radioterapia Adyuvante , Neoplasias Gástricas/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Quimioradioterapia Adyuvante , Bases de Datos Factuales , Esofagectomía , Femenino , Gastrectomía , Humanos , Masculino , Márgenes de Escisión , Persona de Mediana Edad , North Carolina/epidemiología , Guías de Práctica Clínica como Asunto , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: The prognosis of metastatic gastric cancer (GC) remains dismal, with a median survival of 10 months. Historically, primary tumor resection was not thought to confer any survival benefit. Although high-level data exist guiding treatment of metastatic GC for patients in the East, no such data exist for Western patients despite inherent ethnic differences in GC biology. METHODS: The 2006-2012 National Cancer Database was queried for adult patients with metastatic gastric adenocarcinoma. Patients were classified into those who underwent primary tumor resection and chemotherapy (PTRaC) and those who received chemotherapy only. Groups were propensity score matched, and survival was compared using advanced statistical modeling. RESULTS: A total of 7026 patients met the inclusion criteria: 6129 (87%) patients were treated with chemotherapy alone and 897 (13%) patients were treated with PTRaC. After multivariable adjustment, patients who underwent PTRaC had a significantly better overall survival (OS) than patients who received systemic therapy only (HR, 0.60; 95% CI, 0.56-0.64; p < 0.001). Following full bipartite propensity score-adjusted analysis, 2-year OS for patients who received chemotherapy only was 12.6% (95% CI, 11.7-13.5%), whereas it was 34.2% (95% CI, 31.3-37.5%) for patients who underwent PTRaC (HR for resection: 0.52; 95% CI, 0.47-0.57; p < 0.001). CONCLUSION: Our data suggest that there exists a subset of patients with metastatic GC for which PTRaC may improve OS. As significant uncertainty still remains, our results support the need for further prospective trials investigating the influence of palliative gastrectomy on survival among Western patients.