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1.
Cancer Treat Rev ; 129: 102795, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38972133

RESUMO

Melanoma metabolism can be reprogrammed by activating BRAF mutations. These mutations are present in up to 50% of cutaneous melanomas, with the most common being V600E. BRAF mutations augment glycolysis to promote macromolecular synthesis and proliferation. Prior to the development of targeted anti-BRAF therapies, these mutations were associated with accelerated clinical disease in the metastatic setting. Combination BRAF and MEK inhibition is a first line treatment option for locally advanced or metastatic melanoma harboring targetable BRAF mutations. This therapy shows excellent response rates but these responses are not durable, with almost all patients developing resistance. When BRAF mutated melanoma cells are inhibited with targeted therapies the metabolism of those cells also changes. These cells rely less on glycolysis for energy production, and instead shift to a mitochondrial phenotype with upregulated TCA cycle activity and oxidative phosphorylation. An increased dependence on glutamine utilization is exhibited to support TCA cycle substrates in this metabolic rewiring of BRAF mutated melanoma. Herein we describe the relevant core metabolic pathways modulated by BRAF inhibition. These adaptive pathways represent vulnerabilities that could be targeted to overcome resistance to BRAF inhibitors. This review evaluates current and future therapeutic strategies that target metabolic reprogramming in melanoma cells, particularly in response to BRAF inhibition.

2.
Am J Clin Oncol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38937882

RESUMO

OBJECTIVES: Melanoma survival has greatly improved with the advent of immunotherapy, but unequal access to these medications may exist due to nonmedical patient factors such as insurance status, educational background, and geographic proximity to treatment. METHODS: We used the National Cancer Database to assess patients with nonmetastatic cutaneous melanoma who underwent surgical resection and sentinel lymph node biopsy (SLNB) with tumor involvement from 2015 to 2020. We evaluated rates of adjuvant immunotherapy among this patient population based on patient, tumor, and facility variables, including insurance status, socioeconomic status, pathologic stage (IIIA-IIID), and treatment facility type and volume. RESULTS: Adjuvant immunotherapy was associated with improved survival for stage III melanoma, with a slight increase in 5-year OS for stage IIIA (87.9% vs. 85.9%, P=0.044) and a higher increase in stages IIIB-D disease (70.3% vs. 59.6%, P<0.001). Receipt of adjuvant immunotherapy was less likely for patients who were older, low socioeconomic status, or uninsured. Low-volume and community cancer centers had higher rates of adjuvant immunotherapy overall for all stage III patients, whereas high-volume and academic centers used adjuvant immunotherapy much less often for stage IIIA patients compared with those in stages IIIB-D. CONCLUSIONS: Our results demonstrate inconsistent use of adjuvant immunotherapy among patients with stage III melanoma despite a significant association with improved survival. Notably, there was a lower use of adjuvant immunotherapy in patients of lower SES and those treated at high-volume centers. Equity in access to novel standards of care represents an opportunity to improve outcomes for patients with melanoma.

3.
Cancers (Basel) ; 16(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38927900

RESUMO

BACKGROUND: Survival data on patients with locally advanced rectal cancer (LARC) undergoing non-operative management (NOM) in a real-world setting are lacking. METHODS: We analyzed LARC patients from the National Cancer Database with the following features: treated between 2010 and 2020, age 18-65 years, Charlson comorbidity index (CCI) ≤ 1, received neoadjuvant multiagent chemotherapy plus radiation ≥ 45 Gray, and underwent surgery or NOM. Patients were stratified into two groups: (A) clinical T1-3 tumors with positive nodes (cT1-3N+) and (B) clinical T4 tumors, N+/- (cT4N+/-). We performed a comparative analysis of overall survival (OS) with NOM versus surgery by the Kaplan-Meier method and propensity score matching. Additionally, a multivariable analysis explored the association between NOM and OS. RESULTS: NOM exhibited significantly lower OS than surgery in both groups. In cT1-3N+ patients, NOM resulted in a 5-year OS of 73.9% (95% confidence interval [CI] = 69.7-77.6%) versus 84.5% (95% CI = 83.6-85.3%) with surgery (p < 0.001). In the cT4N+/- group, NOM yielded a 5-year OS of 44.5% (95% CI = 37.0-51.8%) versus 72.5% (95% CI = 69.9-74.8%) with surgery (p < 0.001). Propensity score matching and multivariable analyses revealed similar conclusions. CONCLUSION: Patients with LARC undergoing NOM versus surgery in real-world settings appear to have inferior survival.

4.
Surgery ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38851901

RESUMO

BACKGROUND: Characteristics of children with impaired development who have acute appendicitis are not well described in the literature. METHODS: We reviewed the National Surgical Quality Improvement Program-Pediatric and the multicenter Pediatric Health Information System for patients with acute appendicitis. Comparisons for demographics, clinical outcomes, and hospital charges between children with impaired development versus neurotypical children were made using independent t test or Wilcoxon rank sum tests. The multivariable logistic regression model estimated the odds of complicated acute appendicitis in impaired development patients. Based on correlation analyses, hierarchical linear modeling was used to examine the extent to which impaired development influenced resource use. RESULTS: Patients with impaired development were younger, had higher comorbidities, and were more commonly male sex. In the National Surgical Quality Improvement Program-Pediatric database, impaired development was associated with higher rates of complicated acute appendicitis (33.6% vs 27.5, P < .001), particularly in older children, and higher usage of computed tomography at National Surgical Quality Improvement Program-Pediatric hospitals (23.1% vs 15.1%, P < .001). In the Pediatric Health Information System database, the adjusted odds of complicated acute appendicitis were significantly higher in patients with impaired development (1.20 [1.09-1.31]), low childhood opportunity level (1.39 [95% confidence interval: 1.31-1.47]), and Black race (1.25 [1.17-1.33]). Hierarchical adjusted linear modeling showed that impaired development was associated with significantly higher hospital charges (9% increase). CONCLUSION: Management of acute appendicitis in children with impaired development remains a challenge to clinicians, as evidenced by the higher rate of perforated appendicitis in older children, diagnostic computed tomography use at National Surgical Quality Improvement Program-Pediatric hospitals, postoperative computed tomography use, and increased costs.

5.
J Gastrointest Surg ; 28(7): 1062-1066, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38653337

RESUMO

BACKGROUND: The optimal surgical option in patients with multifocal hepatocellular carcinoma (MHCC) is an area of active research. The preference varies based on geographic variations and institutional policies. We sought to determine long-term outcomes in patients with MHCC based on surgical treatment-liver transplant (LT) vs resection (LR). METHODS: We performed a retrospective analysis of the National Cancer Database (2004-2015) and identified patients with MHCC within Milan criteria. Patients with α-fetoprotein ≥ 1000 ng/mL and those who underwent ablation were excluded. The primary outcome measure was long-term survival in patients undergoing LT vs LR. The secondary aim of our study was to determine clinicodemographic factors associated with the receipt of LT and LR. RESULTS: A total of 1546 patients were included, of whom 1211 received LT and 335 underwent LR. Patients who were non-Hispanic White (70.8% vs 54.9%; P < .01), privately insured (53.7% vs 36.7%; P < .01), and treated at academic centers (85.4% vs 71.6%; P < .01) were more likely to receive an LT. Multivariable Cox analysis revealed LT was associated with improved survival compared with LR (hazard ratio, 0.34; 95% CI, 0.28-0.42). CONCLUSION: We described clinical and sociodemographic differences in LT and LR patients and found LT to be associated with a decreased mortality risk compared with LR. The study's findings should be interpreted in the context of several limitations, including the selection of MHCC criteria within Milan criteria.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Transplante de Fígado/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Hepatectomia/métodos , Hepatectomia/estatística & dados numéricos , Idoso , Taxa de Sobrevida , Resultado do Tratamento , Modelos de Riscos Proporcionais
6.
Am J Clin Oncol ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587336

RESUMO

BACKGROUND: Immune checkpoint inhibitors are a promising new therapy for advanced Merkel Cell Carcinoma (MCC). We investigated real-world utilization and survival outcomes of first-line immunotherapies in a contemporary cohort. METHODS: Using the National Cancer Database (NCDB), we identified 759 patients with MCC between 2015 and 2020 with stage IV disease and known status of first-line systemic therapy. Univariable and multivariable analyses were used to determine predictors of immunotherapy usage. Overall survival (OS) was compared for patients receiving immunotherapy, chemotherapy, or no systemic therapies. RESULTS: We identified 759 patients meeting our inclusion criteria: 329 patients received immunotherapy, 161 received chemotherapy, and 269 received no systemic therapy. Adjusting for demographic, clinical, and facility factors, high facility volume significantly predicted first-line immunotherapy use (OR 1.99; P=0.017). Median OS was 16.2, 12.3, and 8.7 months, among patients who received immunotherapy, chemotherapy, or no systemic therapy, respectively (P<0.001). On Cox multivariable survival analysis, first-line immunotherapy treatment (HR=0.79, P=0.041) and treatment at high-volume centers (HR=0.58, P=0.004) were associated with improved OS. CONCLUSIONS: Consistent with clinical trial results, first-line immunotherapy associated with improvement in median overall survival for patients with stage IV MCC, significantly outperforming chemotherapy in this real-world cohort. Treatment at high-volume centers associated with first-line immunotherapy utilization suggesting that familiarity with this rare disease is important to achieving optimal outcomes for metastatic MCC.

7.
J Surg Oncol ; 129(6): 1113-1120, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38333997

RESUMO

INTRODUCTION: The management of T2 multifocal hepatocellular carcinoma (MHCC) is controversial, and the comparative impact of liver resection (LR) versus tumor ablation (TA) on survival continues to be debated. The aim of our study was to examine short- and long-term survival for LR and TA in a nationally representative cohort. We hypothesized that patients who underwent LR would have improved survival. METHODS: We utilized the National Cancer Database (2004-2015) to identify patients diagnosed with non-metastatic T2 MHCC. Kaplan-Meier survival curves were generated to compare 10-year overall survival (OS) between LR and TA patients. Kaplan-Meier analysis with stratification was also performed based on lymphovascular invasion, resection margin status, and Charlson-Deyo score. Cox proportional hazard models were used in multivariable analyses. RESULTS: A total of 1225 patients met the inclusion criteria. 991 patients received LR, and 234 received TA. The majority of patients were male, White, and older than ≥60 years old. Clinicodemographic characteristics were generally similar between LR and TA patients. Among patients who underwent LR, 84% had negative margins, and 17% had lymphovascular invasion. Mortality at 30 days was significantly higher among LR patients compared to TA patients (5.4% vs 0.0%, p < 0.001), with those having a Charlson-Deyo score ≥2 facing the highest risk at 7.3%. Nevertheless, 10-year OS for the LR cohort was 27.5% (95% confidence interval [CI]: 24.4%-30.8%) versus 14.7% (95% CI: 9.8%-20.7%, p < 0.001) for TA patients. In stratified analysis, survival benefit was statistically significant only among those with negative resection margin, no lymphovascular invasion, and Charlson-Deyo score ≤1. In multivariable Cox analysis, LR was independently associated with improved survival compared to TA (hazard ratio: 0.80; 95% CI = 0.67-0.95). CONCLUSION: LR poses a higher long-term survival benefit than TA. Prospective studies are warranted to confirm these findings. Although our study patients are a highly selected group of multifocal T2 patients, it gives us a good insight into the fact that LR provides better outcomes if a transplant option is unavailable.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Masculino , Feminino , Hepatectomia/mortalidade , Hepatectomia/métodos , Pessoa de Meia-Idade , Idoso , Taxa de Sobrevida , Estudos Retrospectivos , Seguimentos
8.
Am J Clin Oncol ; 47(5): 239-245, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38251734

RESUMO

BACKGROUND: In 2011, immunotherapy and targeted therapy revolutionized melanoma treatment. However, inequities in their use may limit the benefits seen by certain patients. METHODS: We performed a retrospective review of patients in the National Cancer Database for patients with stage IV melanoma from 2 time periods: 2004-2010 and 2016-2020, distinguishing between those who received systemic therapy and those who did not. We investigated the rates and factors associated with treatment omission. We employed Kaplan-Meier analysis to explore the impact of treatment on overall survival. RESULTS: A total of 19,961 patients met the inclusion criteria: 7621 patients were diagnosed in 2004-2010 and 12,340 patients in 2016-2020, of whom 54.9% and 28.3% did not receive systemic treatment, respectively. The rate of "no treatment" has decreased to a plateau of ∼25% in 2020. Median overall survival was improved with treatment in both time periods (2004-2010: 8.8 vs. 5.6 mo [ P <0.05]; and 2016-2020: 25.9 vs. 4.3 mo [ P <0.05]). Nonmedical factors associated with the omission of treatment in both periods included low socioeconomic status, Medicaid or no health insurance, and treatment at low-volume centers. In the period from 2016 to 2020, patients treated at nonacademic programs were also less likely to receive treatment. CONCLUSIONS: Systemic therapies significantly improve survival for patients with metastatic melanoma, but significant disparities exist with their receipt. Local efforts are needed to ensure all patients benefit from these revolutionary treatments.


Assuntos
Disparidades em Assistência à Saúde , Melanoma , Humanos , Melanoma/terapia , Melanoma/mortalidade , Melanoma/patologia , Melanoma/tratamento farmacológico , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Idoso , Estados Unidos , Neoplasias Cutâneas/terapia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Adulto , Taxa de Sobrevida
9.
HPB (Oxford) ; 26(3): 370-378, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38042732

RESUMO

OBJECTIVES: We used a novel combined analysis to evaluate various factors associated with failure to undergo surgery in non-metastatic pancreatic cancer. METHODS: We identified rates of surgery and reasons for surgical attrition from clinical trials, which studied neoadjuvant therapy in resectable pancreatic cancer. Next, we queried the National Cancer Database (NCDB) for Stage I-III, T1-3 pancreatic adenocarcinoma patients. We investigated the rates and factors associated with the receipt of surgery. Finally, we evaluated variable importance predicting the receipt of surgery. RESULTS: In clinical trials, 25-30 % of patients did not undergo surgery, mostly due to disease progression. In the NCDB, the overall surgical rate was only 49 %, but increased to 67 % in a curated cohort meant to mirror clinical trial patients. Patients treated at low-volume institutions (OR = 0.64, 95 % CI: 0.61-0.67) and who were uninsured (OR = 0.56, 95 % CI: 0.52-0.62) and Medicaid-insured (OR = 0.67, 95 % CI: 0.64-0.71) were less likely to receive potentially curative surgery. CONCLUSION: We have identified a realistic target surgery rate of 70%-75 % in potentially-resectable pancreatic cancer. While attrition to pancreatic cancer surgery is mostly due to tumor biology, our study identified the most important non-medical barriers, such as facility volume and insurance, affecting pancreatic cancer surgery.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Estados Unidos , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Terapia Neoadjuvante , Progressão da Doença
10.
Crit Rev Oncol Hematol ; 193: 104193, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37926375

RESUMO

We reviewed phase II and III trials beginning after 2010 studying preoperative therapy in melanoma (61 trials). Compared to standard adjuvant treatment, neoadjuvant immune checkpoint inhibitors (ICIs) show improved outcomes with approximately 70-80% recurrence free survival at 2 years. Several biomarkers demonstrate predictive value for pathological response (higher PD-L1 expression) and survival (IFN-γ signatures, CD8 + cell density). A number of 'non-standard' treatment mechanisms are being studied in combination with ICI therapies such as TLR-9 agonists, and anti-LAG3 checkpoint inhibitors, which show promise for alternative therapy options in the neoadjuvant setting. Finally, trials for advanced unresectable melanomas show improved survival compared to definitive systemic treatment when upfront systemic therapies lead to resectability. To conclude, in the preoperative setting for melanoma, ICIs have potential to improve outcomes for patients, and will likely change the standard treatment approach for advanced resectable disease.


Assuntos
Melanoma , Humanos , Melanoma/tratamento farmacológico , Terapia Neoadjuvante , Imunoterapia
11.
J Surg Oncol ; 129(3): 509-516, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37985362

RESUMO

BACKGROUND AND OBJECTIVES: There is no consensus guidelines on the best timing to perform Sentinel lymph node biopsy (SLNB) in high-risk melanoma patients. We aimed to understand the impact of surgical timing on nodal upstaging in patients with cutaneous melanoma. METHODS: We queried the National Cancer Database from 2004 to 2018 for patients with T2-T4, N0, M0 melanomas, who underwent melanoma excision and nodal surgery. We included patients who underwent surgery within 2-19 weeks postdiagnosis. We aimed to determine the association of surgical delay (weeks) with nodal positivity. RESULTS: A total of 53 355 patients were included, of whom 20.9% had positive lymph nodes. Patients underwent surgery at a median of 5 (4-7) weeks after diagnosis. The rate of positive nodes increased with increased weeks to surgery (line of best-fit slope = 0.38). Multivariable regression analysis identified an association between time to surgery and nodal positivity (2.4% increased risk per week, p < 0.05). Our analysis showed significantly increased likelihood of nodal positivity beginning 9 weeks after diagnosis (odds ratio [OR] = 1.3, p < 0.05). Furthermore, patients with T2-3 tumors had a significant increase in nodal positivity with increased time to surgery (OR = 1.03 per week, p < 0.001). However, no significant trend in nodal positivity was identified for patients with T4 melanomas (OR = 1.01 per week, p = 0.596). CONCLUSION: Surgery within 9 weeks of melanoma diagnosis was not associated with increased likelihood of nodal positivity. These data can guide clinical conversations regarding the importance of surgical timing for melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Excisão de Linfonodo
12.
J Surg Oncol ; 129(4): 804-812, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38018361

RESUMO

BACKGROUND AND OBJECTIVES: Sentinel lymph node biopsy (SLNB) is an area of debate in the management of lentigo maligna melanoma (LMM). The utility of SLNB and its prognostic value in LMM have not yet been studied with large databases. METHODS: We performed a retrospective review of the National Cancer Database (2012-2020) and the Surveillance, Epidemiology, and End Results (2010-2019) database for patients with cutaneous nonmetastatic LMM with Breslow thickness >1.0 mm. Multivariable logistic regression identified factors associated with SLNB performance and sentinel lymph node (SLN) positivity. Univariable and multivariable analyses assessed overall survival (OS) and melanoma-specific survival (MSS) based on SLNB performance and SLN status. RESULTS: Compared to other melanoma subtypes, LMM had lower rates of SLNB (66.6% vs. 80.0%-84.0%) and SLN positivity (11.3% vs. 18.6%-34.2%). Compared to patients who did not undergo SLNB, SLN status was significantly associated with improved OS in patients with SLN positive (HR = 0.64 [0.55-0.76]) and SLN negative (HR = 0.68 [0.49-0.94]), and worse MSS only in patients with positive SLN (HR = 3.93, p < 0.05). CONCLUSION: The improved OS associated with SLNB likely implies surgical selection bias. Analysis of MSS confirms appropriate patient selection and suggests important prognostic value associated with SLN status. These results support continued SLNB for LMM patients according to standard guidelines.


Assuntos
Sarda Melanótica de Hutchinson , Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Biópsia de Linfonodo Sentinela , Melanoma/patologia , Neoplasias Cutâneas/patologia , Sarda Melanótica de Hutchinson/cirurgia , Sarda Melanótica de Hutchinson/patologia , Prognóstico , Estudos Retrospectivos , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Linfonodos/patologia
13.
Surgery ; 175(2): 251-257, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37981548

RESUMO

BACKGROUND: The surgical management of 1- to 2-cm neuroendocrine tumors of the appendix is an area of debate. We analyzed the clinical outcomes of appendectomy and compared them to right hemicolectomy. METHODS: We queried the National Cancer Database to identify patients treated for 1- to 2-cm ANETs from 2004 to 2018. Patients were stratified by surgical approach (appendectomy vs. hemicolectomy). Multivariable models were used to identify factors associated with the choice of surgical approach and the association between surgical approach and overall survival. RESULTS: Of the 3,189 patients we included, 1,573 (49.3%) underwent right hemicolectomy and 1,616 (50.7%) appendectomy. The appendectomy rate increased from 37.7% in 2004 to 58.9% in 2018. On multivariable analysis, patients with grade 2 and 3 tumors were less likely to undergo appendectomy alone (odds ratio = 0.41, 95% confidence interval = 0.26-0.66). Longer travel distance was associated with a higher likelihood of undergoing appendectomy (odds ratio = 2.52, 95% confidence interval = 1.15-5.51). After adjusting for tumor grade, appendectomy alone had similar survival to hemicolectomy (hazard ratio = 1.03, 95% confidence interval = 0.67-1.59). CONCLUSION: In this updated analysis of the National Cancer Database, right hemicolectomy was not associated with improved overall survival compared to appendectomy alone for 1- to 2-cm neuroendocrine tumors of the appendix. Although patients with grade 2 or 3 tumors are more likely to undergo right hemicolectomy, this procedure may not improve their treatment or overall outcome.


Assuntos
Neoplasias do Apêndice , Tumores Neuroendócrinos , Humanos , Apendicectomia/métodos , Neoplasias do Apêndice/cirurgia , Neoplasias do Apêndice/patologia , Modelos de Riscos Proporcionais , Colectomia/métodos , Estudos Retrospectivos
14.
Surgery ; 174(3): 618-625, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37391325

RESUMO

BACKGROUND: Surgery is the only potentially curative treatment for non-metastatic upper gastrointestinal cancers. We analyzed patient and provider characteristics associated with non-surgical management. METHODS: We queried the National Cancer Database for patients with upper gastrointestinal cancers from 2004 to 2018 who underwent surgery, refused surgery, or for whom surgery was contraindicated. Multivariate logistic regression identified factors associated with surgery being refused or contraindicated, and Kaplan-Meier curves assessed survival. RESULTS: We identified 249,813 patients based on our selection criteria-86.3% had surgery, 2.4% refused, and for 11.3%, surgery was contraindicated. Median overall survival was 48.2 months for patients who underwent surgery versus 16.3 and 9.4 months for the refusal and contraindicated groups. Medical and non-medical factors predicted both surgery refusals and contraindications, such as increasing age (odds ratio = 1.07 and 1.03, respectively, P < .001), Black race (odds ratio = 1.72 and 1.45, P < .001), comorbidities (Charlson-Deyo score 2+, odds ratio = 1.18 and 1.66, P < .001), low socioeconomic status (odds ratio = 1.70 and 1.40, P < .001), no health insurance (odds ratio = 3.26 and 2.34, P < .001), community cancer programs (odds ratio = 1.43 and 1.40, P < .001), low volume facilities (odds ratio = 1.82 and 1.52, P < .001), and stage 3 disease (odds ratio = 1.51 and 6.50, P < .001). On subset analysis (excluding patients age >70, Charlson-Deyo score 2+, and stage 3 cancer), non-medical predictors of both outcomes were similar. CONCLUSION: Refusal of and medical contraindications for surgery profoundly impact overall survival. The same factors (ie, race, socioeconomic status, hospital volume, and hospital type) predict these outcomes. These findings suggest variation and potential bias that may exist between physicians and patients discussing cancer surgery.


Assuntos
Neoplasias Gastrointestinais , Humanos , Adenocarcinoma , População Negra , Neoplasias Gastrointestinais/economia , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etnologia , Neoplasias Gastrointestinais/cirurgia , Seguro Saúde , Classe Social , Atitude do Pessoal de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Recusa do Paciente ao Tratamento , Preconceito , Hospitais/estatística & dados numéricos
15.
J Gastrointest Surg ; 27(9): 1913-1924, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37340108

RESUMO

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines recommend adjuvant chemotherapy (AC) within 6-8 weeks of surgical resection for patients with stage III colon cancer. However, postoperative complications or prolonged surgical recovery may affect the receipt of AC. The aim of this study was to assess the utility of AC for patients with prolonged postoperative recovery. METHODS: We queried the National Cancer Database (2010-2018) for patients with resected stage III colon cancer. Patients were categorized as having either normal or prolonged length of stay (PLOS: >7 days, 75th percentile). Multivariable Cox proportional hazard regression and logistic regressions were used to identify factors associated with overall survival and receipt of AC. RESULTS: Of the 113,387 patients included, 30,196 (26.6%) experienced PLOS. Of the 88,115 (77.7%) patients who received AC, 22,707 (25.8%) initiated AC more than 8 weeks after surgery. Patients with PLOS were less likely to receive AC (71.5% vs. 80.0%, OR: 0.72, 95%CI=0.70-0.75) and displayed inferior survival (75 vs. 116 months, HR: 1.39, 95%CI=1.36-1.43). Receipt of AC was also associated with patient factors such as high socioeconomic status, private insurance, and White race (p<0.05 for all). AC within and after 8 weeks of surgery was associated with improved survival for patients with both normal LOS and PLOS (normal LOS: <8 weeks HR: 0.56, 95% CI: 0.54-0.59, >8 weeks HR: 0.68, 95% CI: 0.65-0.71; PLOS: <8 weeks HR: 0.51, 95% CI: 0.48-0.54, >8 weeks HR: 0.63, 95% CI 0.60-0.67). AC was associated with significantly improved survival if initiated up to 15 weeks postoperatively (normal LOS: HR: 0.72, 95%CI=0.61-0.85; PLOS: HR: 0.75, 95%CI=0.62-0.90), and very few patients (<3.0%) initiated AC beyond this time. CONCLUSION: Receipt of AC for stage III colon cancer may be affected by surgical complications or otherwise prolonged recovery. Timely and even delayed AC (>8 weeks) are both associated with improved overall survival. These findings highlight the importance of delivering guideline-based systemic therapies, even after complicated surgical recovery.


Assuntos
Neoplasias do Colo , Humanos , Modelos de Riscos Proporcionais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Neoplasias do Colo/patologia , Quimioterapia Adjuvante , Período Pós-Operatório , Complicações Pós-Operatórias/tratamento farmacológico , Estadiamento de Neoplasias , Estudos Retrospectivos
16.
Br J Dermatol ; 189(4): 419-426, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37290803

RESUMO

BACKGROUND: Melanomas < 0.8 mm in Breslow depth have less than a 5% risk for nodal positivity. Nonetheless, nodal positivity is prognostic for this group. Early identification of nodal positivity may improve the outcomes for these patients. OBJECTIVES: To determine the degree to which ulceration and other high-risk features predict sentinel lymph node (SLN) positivity for very thin melanomas. METHODS: The National Cancer Database was reviewed from 2012 to 2018 for patients with melanoma with Breslow thickness < 0.8 mm. Data were analysed from 7 July 2022 through to 25 February 2023. Patients were excluded if data regarding their ulceration status or SLN biopsy (SLNB) performance were unknown. We analysed patient, tumour and health system factors for their effect on SLN positivity. Data were analysed using χ2 tests and logistic regressions. Overall survival (OS) was compared by Kaplan-Meier analyses. RESULTS: Positive nodal metastases were seen in 876 (5.0%) patients who underwent SLNB (17 692). Factors significantly associated with nodal positivity on multivariable analysis include lymphovascular invasion [odds ratio (OR) 4.5, P < 0.001], ulceration (OR 2.6, P < 0.001), mitoses (OR 2.1, P < 0.001) and nodular subtype (OR 2.1, P < 0.001). Five-year OS was 75% and 92% for patients with positive and negative SLN, respectively. CONCLUSIONS: Nodal positivity has prognostic significance for very thin melanomas. In our cohort, the rate of nodal positivity was 5% overall in these patients who underwent SLNB. Specific tumour factors (e.g. lymphovascular invasion, ulceration, mitoses, nodular subtype) were associated with higher rates of SLN metastases and should be used to guide clinicians in choosing which patients will benefit from SLNB.


Assuntos
Melanoma , Linfonodo Sentinela , Neoplasias Cutâneas , Humanos , Metástase Linfática/patologia , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/patologia , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Prognóstico , Estudos Retrospectivos , Melanoma Maligno Cutâneo
18.
Ann Surg Oncol ; 30(7): 4207-4216, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37046129

RESUMO

OBJECTIVES: We used a novel combined analysis to evaluate various factors associated with failure to surgical resection in non-metastatic gastric cancer. METHODS: We identified factors associated with the receipt of surgery in publicly available clinical trial data for gastric cancer and in the National Cancer Database (NCDB) for patients with stages I-III gastric adenocarcinoma. Next, we evaluated variable importance in predicting the receipt of surgery in the NCDB. RESULTS: In published clinical trial data, 10% of patients in surgery-first arms did not undergo surgery, mostly due to disease progression and 15% of patients in neoadjuvant therapy arms failed to reach surgery. Effects related to neoadjuvant administration explained the increased attrition (5%). In the NCDB, 61.7% of patients underwent definitive surgery. In a subset of NCDB patients resembling those enrolled in clinical trials (younger, healthier, and privately insured patients treated at high-volume and academic centers) the rate of surgery was 79.2%. Decreased likelihood of surgery was associated with advanced age (OR 0.97, p < 0.01), Charlson-Deyo score of 2+ (OR 0.90, p < 0.01), T4 tumors (OR 0.39, p < 0.01), N+ disease (OR 0.84, p < 0.01), low socioeconomic status (OR 0.86, p = 0.01), uninsured or on Medicaid (OR 0.58 and 0.69, respectively, p < 0.01), low facility volume (OR 0.64, p < 0.01), and non-academic cancer programs (OR 0.79, p < 0.01). CONCLUSION: Review of clinical trials shows attrition due to unavoidable tumor and treatment factors (~ 15%). The NCDB indicates non-medical patient and provider characteristics (i.e., age, insurance status, facility volume) associated with attrition. This combined analysis highlights specific opportunities for improving potentially curative surgery rates.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Estados Unidos , Humanos , Neoplasias Gástricas/cirurgia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Medicaid , Terapia Neoadjuvante , Pessoas sem Cobertura de Seguro de Saúde
20.
HPB (Oxford) ; 25(2): 239-251, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36411233

RESUMO

BACKGROUND: We described trends and disparities in utilization of systemic chemotherapy in metastatic hepato-pancreato-biliary (HPB) cancers. METHODS: We queried the National Cancer Database for metastatic HPB cancers [hepatocellular carcinoma (HCC), biliary tract cancers (BTC), pancreatic adenocarcinoma (PDAC)]. We used multivariable analysis to examine the factors associated with utilization of systemic chemotherapy. We utilized marginal structural logistic models to estimate the effect of health insurance, facility type, or facility volume on utilization of systemic chemotherapy. RESULTS: We identified 162,283 patients with metastatic HPB cancers: 23,923 (14.7%) had HCC, 26,766 (16.5%) had BTC, and 111,594 (68.8%) had PDAC. A total of 37.2% patients with HCC, 55.6% with BTC, and 56.4% with PDAC received chemotherapy. Age ≥70 years and Charlson-Deyo score ≥2 were associated with lower likelihood of receiving chemotherapy across all cancers. Patients with private health insurance had higher receipt of chemotherapy. Receiving treatment at academic facilities had no effect on the receipt of chemotherapy. Treatment of patients with HCC or PDAC at high-volume facilities resulted in higher receipt of chemotherapy. CONCLUSION: A significant proportion of patients with metastatic HPB cancers do not receive systemic chemotherapy. Several disparities in administration of chemotherapy for metastatic HPB cancers exist.


Assuntos
Adenocarcinoma , Neoplasias do Sistema Biliar , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Idoso
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