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1.
Clin Case Rep ; 12(3): e8604, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38449895

RESUMEN

Although endometriosis is a common condition, both extrapelvic endometriosis and endometriosis associated malignancy (EAM) are rare. We describe the first reported case of a patient with Müllerian-type carcinosarcoma arising in gastric endometriosis.

3.
Clin Cancer Res ; 30(2): 450-461, 2024 01 17.
Artículo en Inglés | MEDLINE | ID: mdl-37943631

RESUMEN

PURPOSE: This study sought to identify ß-catenin targets that regulate desmoid oncogenesis and determine whether external signaling pathways, particularly those inhibited by sorafenib (e.g., PDGFRß), affect these targets to alter natural history or treatment response in patients. EXPERIMENTAL DESIGN: In vitro experiments utilized primary desmoid cell lines to examine regulation of ß-catenin targets. Relevance of results was assessed in vivo using Alliance trial A091105 correlative biopsies. RESULTS: CTNNB1 knockdown inhibited hypoxia-regulated gene expression in vitro and reduced levels of HIF1α protein. ChIP-seq identified ABL1 as a ß-catenin transcriptional target that modulated HIF1α and desmoid cell proliferation. Abrogation of either CTNNB1 or HIF1A inhibited desmoid cell-induced VEGFR2 phosphorylation and tube formation in endothelial cell co-cultures. Sorafenib inhibited this activity directly but also reduced HIF1α protein expression and c-Abl activity while inhibiting PDGFRß signaling in desmoid cells. Conversely, c-Abl activity and desmoid cell proliferation were positively regulated by PDGF-BB. Reduction in PDGFRß and c-Abl phosphorylation was commonly observed in biopsy samples from patients after treatment with sorafenib; markers of PDGFRß/c-Abl pathway activation in baseline samples were associated with tumor progression in patients on the placebo arm and response to sorafenib in patients receiving treatment. CONCLUSIONS: The ß-catenin transcriptional target ABL1 is necessary for proliferation and maintenance of HIF1α in desmoid cells. Regulation of c-Abl activity by PDGF signaling and targeted therapies modulates desmoid cell proliferation, thereby suggesting a reason for variable biologic behavior between tumors, a mechanism for sorafenib activity in desmoids, and markers predictive of outcome in patients.


Asunto(s)
Productos Biológicos , Fibromatosis Agresiva , Humanos , Fibromatosis Agresiva/tratamiento farmacológico , Fibromatosis Agresiva/genética , beta Catenina/genética , beta Catenina/metabolismo , Sorafenib/farmacología , Transducción de Señal
4.
Ann Surg Open ; 4(1): e260, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37600898

RESUMEN

Background: Surgeon productivity is measured in relative value units (RVUs). The feasibility of attaining RVU productivity targets requires surgeons to have enough allocated block time to generate RVUs. However, it is unknown how much block time is required for surgeons to attain specific RVU targets. We aimed to estimate the effect of surgeon and practice environment characteristics (SPECs) on block time needed to attain fixed RVU targets. Methods: We computationally simulated individual surgeons' annual caseloads under a variety of SPECs in the following way. First, empirical case data were sampled from ACS NSQIP in accordance with surgeon specialty, case-mix complexity, and RVU target. Surgeons' operating schedules were then constructed according to the block length, turnover time, and scheduling flexibility of the practice environment. These 6 SPECs were concurrently varied over their ranges for a 6-way sensitivity analysis. Results: Annual operating schedules for 60,000,000 surgeons were simulated. The number of blocks required to attain RVU targets varied significantly with surgeon specialty and increased with increased case-mix complexity, increased turnover time, and decreased scheduling flexibility. Intraspecialty variation in block requirement with variation in environmental characteristics exceeded interspecialty variation with fixed environmental characteristics. Multivariate linear models predicted block utilization across surgical specialties with consideration for the stated factors. An online tool is shared with which to apply these results to one's particular practice. Conclusions: Block time required to attain RVU targets varies widely with SPECs; intraspecialty variation exceeds interspecialty variation. The feasibility of attaining RVU targets requires alignment between targets and allocated operating time with consideration for surgical specialty and other practice conditions.

5.
JAMA Oncol ; 9(9): 1245-1254, 2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37471075

RESUMEN

Importance: Personalized treatment approaches for patients with oligometastatic colorectal liver metastases are critically needed. We previously defined 3 biologically distinct molecular subtypes of colorectal liver metastases: (1) canonical, (2) immune, and (3) stromal. Objective: To independently validate these molecular subtypes in the phase 3 New EPOC randomized clinical trial. Design, Setting, and Participants: This retrospective secondary analysis of the phase 3 New EPOC randomized clinical trial included a bi-institutional discovery cohort and multi-institutional validation cohort. The discovery cohort comprised patients who underwent hepatic resection for limited colorectal liver metastases (98% received perioperative chemotherapy) from May 31, 1994, to August 14, 2012. The validation cohort comprised patients who underwent hepatic resection for liver metastases with perioperative chemotherapy (fluorouracil, oxaliplatin, and irinotecan based) with or without cetuximab from February 26, 2007, to November 1, 2012. Data were analyzed from January 18 to December 10, 2021. Interventions: Resected metastases underwent RNA sequencing and microRNA (miRNA) profiling in the discovery cohort and messenger RNA and miRNA profiling with microarray in the validation cohort. Main Outcomes and Measures: A 31-feature (24 messenger RNAs and 7 miRNAs) neural network classifier was trained to predict molecular subtypes in the discovery cohort and applied to the validation cohort. Integrated clinical-molecular risk groups were designated based on molecular subtypes and the clinical risk score. The unique biological phenotype of each molecular subtype was validated using gene set enrichment analyses and immune deconvolution. The primary clinical end points were progression-free survival (PFS) and overall survival (OS). Results: A total of 240 patients were included (mean [range] age, 63.0 [56.3-68.0] years; 151 [63%] male), with 93 in the discovery cohort and 147 in the validation cohort. In the validation cohort, 73 (50%), 28 (19%), and 46 (31%) patients were classified as having canonical, immune, and stromal metastases, respectively. The biological phenotype of each subtype was concordant with the discovery cohort. The immune subtype (best prognosis) demonstrated 5-year PFS of 43% (95% CI, 25%-60%; hazard ratio [HR], 0.37; 95% CI, 0.20-0.68) and OS of 63% (95% CI, 40%-79%; HR, 0.38; 95% CI, 0.17-0.86), which was statistically significantly higher than the canonical subtype (worst prognosis) at 14% (95% CI, 7%-23%) and 43% (95% CI, 32%-55%), respectively. Adding molecular subtypes to the clinical risk score improved prediction (the Gönen and Heller K for discrimination) from 0.55 (95% CI, 0.49-0.61) to 0.62 (95% CI, 0.57-0.67) for PFS and 0.59 (95% CI, 0.52-0.66) to 0.63 (95% CI, 0.56-0.70) for OS. The low-risk integrated group demonstrated 5-year PFS of 44% (95% CI, 20%-66%; HR, 0.38; 95% CI, 0.19-0.76) and OS of 78% (95% CI, 44%-93%; HR, 0.26; 95% CI, 0.08-0.84), superior to the high-risk group at 16% (95% CI, 10%-24%) and 43% (95% CI, 32%-52%), respectively. Conclusions and Relevance: In this prognostic study, biologically derived colorectal liver metastasis molecular subtypes and integrated clinical-molecular risk groups were highly prognostic. This novel molecular classification warrants further study as a possible predictive biomarker for personalized systemic treatment for colorectal liver metastases. Trial Registration: isrctn.org Identifier: ISRCTN22944367.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , MicroARNs , Humanos , Masculino , Persona de Mediana Edad , Femenino , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Oxaliplatino , Fluorouracilo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , MicroARNs/genética , MicroARNs/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
7.
NPJ Precis Oncol ; 6(1): 72, 2022 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-36241710

RESUMEN

Personalized treatment approaches for patients with limited liver metastases from colorectal cancer are critically needed. By leveraging three large, independent cohorts of patients with colorectal liver metastases (n = 336), we found that a proliferative subtype associated with elevated CIN70 scores is linked to immune exclusion, increased metastatic proclivity, and inferior overall survival in colorectal liver metastases; however, high CIN70 scores generate a therapeutic vulnerability to DNA-damaging therapies leading to improved treatment responses. We propose CIN70 as a candidate biomarker to personalize systemic treatment options for patients with metastatic colorectal cancer. These findings are potentially broadly applicable to other human cancers.

9.
JCO Precis Oncol ; 6: e2100337, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35188804

RESUMEN

PURPOSE: Current surveillance imaging and tumor markers lack sensitivity for the early detection of recurrence in GI cancers. This study critically evaluates the current literature on the role of sequential measurement of circulating tumor DNA (ctDNA) before and after curative resection in informing recurrence. METHODS: A systematic search using a predefined, registered protocol was conducted for studies published between January 2010 and May 2020. Included studies described patients with GI cancers treated with curative-intent surgical resection and measurement of ctDNA both before and after surgery. Patients were divided into three groups on the basis of the presence or absence of ctDNA at these time points. The primary outcome was recurrence-free survival (RFS). RESULTS: The search yielded 3,873 articles; five met the inclusion criteria and collectively evaluated 57 patients. Pooled median RFS was 62 months (interquartile range 19 to not reached). Although median RFS was not reached in group 1 (- to -) or group 2 (+ to -), median RFS in group 3 (+ to +) was 15 months (interquartile range 9.6-60.4 months). Cox hazard ratio was 4.46 (95% CI, 1.17 to 16.99; P = .028) between group 1 and group 2, and 10.47 (95% CI, 2.91 to 37.74; P < .001) between group 2 and group 3. CONCLUSION: Detectable ctDNA, either preoperatively or postoperatively, and its persistence after curative surgery are associated with a greater risk of recurrence and decreased RFS in GI cancers. Thus, perioperative measurement of ctDNA may be a useful postoperative risk stratification tool and guide additional therapies.


Asunto(s)
Ácidos Nucleicos Libres de Células , ADN Tumoral Circulante , Neoplasias Gastrointestinales , Biomarcadores de Tumor/genética , ADN Tumoral Circulante/genética , Neoplasias Gastrointestinales/diagnóstico , Humanos , Pronóstico
10.
Ann Surg Oncol ; 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34988836

RESUMEN

BACKGROUND: Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma. METHODS: This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS2, adverse events, quality of life, and financial toxicity. DISCUSSION: This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

11.
Ann Surg Oncol ; 28(8): 4433-4443, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33420565

RESUMEN

BACKGROUND: The authors hypothesized that cytoreductive surgery (CRS, comprising gastrectomy combined with metastasectomy) in addition to systemic chemotherapy (SC) is associated with a better survival than chemotherapy alone for patients with metastatic gastric adenocarcinoma (MGA). METHODS: Patients with MGA who received SC between 2004 and 2016 were identified using the National Cancer Database (NCDB). Nearest-neighbor 1:1 propensity score-matching was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those who survived longer than 90 days. RESULTS: The study identified 29,728 chemotherapy-treated patients, who were divided into the following four subgroups: no surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248), and CRS (n = 620) with median OS periods of 8.6, 10.9, 14.8, and 16.3 months, respectively (p < 0.001). Compared with the patients who underwent NS, the patients who had CRS were younger (58.9 ± 13.4 vs 62.0 ± 13.1 years), had a lower proportion of disease involving multiple sites (4.6% vs 19.1%), and were more likely to be clinically occult (cM0 stage: 59.2% vs 8.3%) (p < 0.001 for all). The median OS for the propensity-matched patients who underwent CRS (n = 615) was longer than for those with NS (16.4 vs 9.3 months; p < 0.001), including in those with clinical M1 stage (n = 210). In the Cox regression model using the matched data, the hazard ratio for CRS versus NS was 0.56 (95% confidence interval [CI], 0.49-0.63). In the immortal-matched cohort, the corresponding median OS was 17.0 versus 9.5 months (p < 0.001). CONCLUSIONS: In addition to SC, CRS may be associated with an OS benefit for a selected group of MGA patients meriting further prospective investigation.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Procedimientos Quirúrgicos de Citorreducción , Gastrectomía , Humanos , Estimación de Kaplan-Meier , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía
12.
Cancer Discov ; 11(2): 308-325, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33234578

RESUMEN

The one-year and median overall survival (mOS) rates of advanced gastroesophageal adenocarcinomas (GEA) are ∼50% and <12 months, respectively. Baseline spatial and temporal molecular heterogeneity of targetable alterations may be a cause of failure of targeted/immunooncologic therapies. This heterogeneity, coupled with infrequent incidence of some biomarkers, has resulted in stalled therapeutic progress. We hypothesized that a personalized treatment strategy, applied at first diagnosis then serially over up to three treatment lines using monoclonal antibodies combined with optimally sequenced chemotherapy, could contend with these hurdles. This was tested using a novel clinical expansion-platform type II design with a survival primary endpoint. Of 68 patients by intention-to-treat, the one-year survival rate was 66% and mOS was 15.7 months, meeting the primary efficacy endpoint (one-sided P = 0.0024). First-line response rate (74%), disease control rate (99%), and median progression-free survival (8.2 months) were superior to historical controls. The PANGEA strategy led to improved outcomes warranting a larger randomized study. SIGNIFICANCE: This study highlights excellent outcomes achieved by individually optimizing chemotherapy, biomarker profiling, and matching of targeted therapies at baseline and over time for GEA. Testing a predefined treatment strategy resulted in improved outcomes versus historical controls. Therapeutic resistance observed in correlative analyses suggests that dual targeted inhibition may be beneficial.This article is highlighted in the In This Issue feature, p. 211.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Adenocarcinoma/secundario , Adulto , Anciano , Anciano de 80 o más Años , Chicago , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida , Supervivencia sin Progresión , Neoplasias Gástricas/patología , Resultado del Tratamiento
13.
Proc Natl Acad Sci U S A ; 117(36): 22423-22429, 2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32848073

RESUMEN

Metastases are the cause of the vast majority of cancer deaths. In the metastatic process, cells migrate to the vasculature, intravasate, extravasate, and establish metastatic colonies. This pattern of spread requires the cancer cells to change shape and to navigate tissue barriers. Approaches that block this mechanical program represent new therapeutic avenues. We show that 4-hydroxyacetophenone (4-HAP) inhibits colon cancer cell adhesion, invasion, and migration in vitro and reduces the metastatic burden in an in vivo model of colon cancer metastasis to the liver. Treatment with 4-HAP activates nonmuscle myosin-2C (NM2C) (MYH14) to alter actin organization, inhibiting the mechanical program of metastasis. We identify NM2C as a specific therapeutic target. Pharmacological control of myosin isoforms is a promising approach to address metastatic disease, one that may be readily combined with other therapeutic strategies.


Asunto(s)
Acetofenonas/farmacología , Actomiosina/metabolismo , Citoesqueleto , Metástasis de la Neoplasia/fisiopatología , Actinas/metabolismo , Animales , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Neoplasias Colorrectales/metabolismo , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Femenino , Células HCT116 , Humanos , Ratones , Ratones Desnudos
14.
Ann Surg Oncol ; 27(Suppl 3): 911-915, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32424589

RESUMEN

BACKGROUND: The COVID-19 pandemic has overlapped with the scheduled interview periods of over 20 surgical subspecialty fellowships, including the Complex General Surgical Oncology (CGSO) fellowships in the National Resident Matching Program and the Society of Surgical Oncology's Breast Surgical Oncology fellowships. We outline the successful implementation of and processes behind a virtual interview day for CGSO fellowship recruitment after the start of the pandemic. METHODS: The virtual CGSO fellowship interview process at the University of Chicago Medicine and NorthShore University Health System was outlined and implemented. Separate voluntary, anonymous online secure feedback surveys were email distributed to interview applicants and faculty interviewers after the interview day concluded. RESULTS: Sixteen of 20 interview applicants (80.0%) and 12 of 13 faculty interviewers (92.3%) completed their respective feedback surveys. Seventy-five percent (12/16) of applicants and all faculty respondents (12/12) stated the interview process was 'very seamless' or 'seamless'. Applicants and faculty highlighted decreased cost, time savings, and increased efficiency as some of the benefits to virtual interviewing. CONCLUSIONS: Current circumstances related to the COVID-19 pandemic require fellowship programs to adapt and conduct virtual interviews. Our report describes the successful implementation of a virtual interview process. This report describes the technical steps and pitfalls of organizing such an interview and provides insights into the experience of the interviewer and interviewee.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Becas , Entrevistas como Asunto/métodos , Selección de Personal/tendencias , Neumonía Viral/epidemiología , Especialidades Quirúrgicas , Oncología Quirúrgica/educación , Interfaz Usuario-Computador , Betacoronavirus , COVID-19 , Chicago , Becas/métodos , Becas/organización & administración , Becas/tendencias , Humanos , Innovación Organizacional , Pandemias , Evaluación de Programas y Proyectos de Salud , SARS-CoV-2 , Especialidades Quirúrgicas/clasificación , Especialidades Quirúrgicas/educación
15.
J Gastrointest Surg ; 24(7): 1686-1691, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32285338

RESUMEN

INTRODUCTION: Among surgeons worldwide, a concern with the use of minimally invasive techniques has been raised due to a proposed risk of viral transmission of the coronavirus disease of 2019 (COVID-19) with the creation of pneumoperitoneum. Due to this proposed concern, we sought to collect the available data and evaluate the use of laparoscopy and the risk of COVID-19 transmission. METHODS: A literature review of viral transmission in surgery and of the available literature regarding the transmission of the COVID-19 virus was performed. We additionally reviewed surgical society guidelines and recommendations regarding surgery during this pandemic. RESULTS: Few studies have been performed on viral transmission during surgery, but to date there is no study that demonstrates or can suggest the ability for a virus to be transmitted during surgical treatment whether open or laparoscopic. There is no societal consensus on limiting or restricting laparoscopic or robotic surgery; however, there is expert consensus on the modification of standard practices to minimize any risk of transmission. CONCLUSIONS: Despite very little evidence to support viral transmission through laparoscopic or open approaches, we recommend making modifications to surgical practice such as the use of smoke evacuation and minimizing energy device use among other measures to minimize operative staff exposure to aerosolized particles.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/transmisión , Laparoscopía , Pandemias/prevención & control , Neumonía Viral/prevención & control , Neumonía Viral/transmisión , COVID-19 , Humanos , Control de Infecciones , Selección de Paciente , Procedimientos Quirúrgicos Robotizados , SARS-CoV-2
16.
J Am Coll Surg ; 231(2): 281-288, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32278725

RESUMEN

Hospitals have severely curtailed the performance of nonurgent surgical procedures in anticipation of the need to redeploy healthcare resources to meet the projected massive medical needs of patients with coronavirus disease 2019 (COVID-19). Surgical treatment of non-COVID-19 related disease during this period, however, still remains necessary. The decision to proceed with medically necessary, time-sensitive (MeNTS) procedures in the setting of the COVID-19 pandemic requires incorporation of factors (resource limitations, COVID-19 transmission risk to providers and patients) heretofore not overtly considered by surgeons in the already complicated processes of clinical judgment and shared decision-making. We describe a scoring system that systematically integrates these factors to facilitate decision-making and triage for MeNTS procedures, and appropriately weighs individual patient risks with the ethical necessity of optimizing public health concerns. This approach is applicable across a broad range of hospital settings (academic and community, urban and rural) in the midst of the pandemic and may be able to inform case triage as operating room capacity resumes once the acute phase of the pandemic subsides.


Asunto(s)
Infecciones por Coronavirus/prevención & control , Toma de Decisiones/ética , Transmisión de Enfermedad Infecciosa/prevención & control , Recursos en Salud/provisión & distribución , Control de Infecciones/organización & administración , Pandemias/prevención & control , Selección de Paciente/ética , Neumonía Viral/prevención & control , Servicio de Cirugía en Hospital/ética , Betacoronavirus , COVID-19 , Chicago/epidemiología , Infecciones por Coronavirus/epidemiología , Eficiencia Organizacional , Humanos , Neumonía Viral/epidemiología , Riesgo , SARS-CoV-2 , Triaje/ética
17.
JAMA Netw Open ; 3(2): e1921290, 2020 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-32058557

RESUMEN

Importance: Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value. Objective: To evaluate the coprimary end points of margin-negative (R0) resection rates and pathologic response grades (PRGs) of gFOLFIRINOX therapy among patients with locally advanced gastroesophageal adenocarcinoma. Design, Setting, and Participants: This single-group phase 2 trial, conducted at 2 academic medical centers from February 2014 to March 2019, enrolled 36 evaluable patients with locally advanced adenocarcinoma of the esophagus, gastroesophageal junction, and gastric body. Data analysis was conducted in May 2019. Interventions: Patients received biweekly gFOLFIRINOX (fluorouracil, 2400 mg/m2 over 46 hours; oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2 for UGT1A1 genotype 6/6, 135 mg/m2 for UGT1A1 genotype 6/7, or 90 mg/m2 for UGT1A1 genotype 7/7; and prophylactic peg-filgastrim, 6 mg) for 4 cycles before and after surgery. Patients with tumors positive for ERBB2 also received trastuzumab (6-mg/kg loading dose, then 4 mg/kg). Main Outcomes and Measures: Margin-negative resection rate and PRG. Results: A total of 36 evaluable patients (27 [78%] men; median [range] age, 66 [27-85] years; 10 [28%] with gastric body cancer; 24 [67%] with intestinal-type tumors; 6 [17%] with ERBB2-positive tumors; 19 [53%] with UGT1A1 genotype 6/6; 16 [44%] with genotype 6/7; and 1 [3%] with genotype 7/7) were enrolled. Of these, 35 (97%) underwent surgery; 1 patient (3%) died after completing neoadjuvant chemotherapy while awaiting surgery. Overall, R0 resection was achieved in 33 of 36 patients (92%); 2 patients (6%) with linitis plastica achieved R1 resection. Pathologic response grades 1, 2, and 3 occurred in 13 patients (36%), 9 patients (25%), and 14 patients (39%), respectively, and PRG 1 was observed in 11 of 24 intestinal-type tumors (46%). Median disease-free survival was 30.1 months (95% CI, 15.0 months to not reached), and median overall survival was not reached (95% CI, 8.3 months to not reached). There were no differences in outcomes by UGT1A1 genotype group. A total of 38 patients, including 2 (5%) with antral tumors, were evaluable for toxic effects. Grade 3 or higher adverse events occurring in 5% or more of patients during the perioperative cycles included diarrhea (7 patients [18%]; 3 of 19 patients [16%] with genotype 6/6; 2 of 16 patients [13%] with genotype 6/7; 2 of 3 patients [67%] with genotype 7/7), anemia (2 patients [5%]), vomiting (2 patients [5%]), and nausea (2 patients [5%]). Conclusions and Relevance: In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02366819.


Asunto(s)
Glucuronosiltransferasa/genética , Neoplasias Gástricas , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Femenino , Fluorouracilo , Genotipo , Humanos , Irinotecán , Leucovorina , Masculino , Persona de Mediana Edad , Oxaliplatino , Tomografía de Emisión de Positrones , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia
18.
J Gastrointest Oncol ; 11(6): 1399-1407, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33457009

RESUMEN

BACKGROUND: We explored the safety and efficacy of ablative doses of stereotactic body radiation therapy (SBRT) for unresectable pancreatic cancer. METHODS: This phase I/II trial included patients with unresectable pancreatic cancer previously treated with any number of cycles of induction chemotherapy. Patients were enrolled according to a 3+3 dose escalation design at 10, 12.5, and 15 Gy ×3, with subsequent patients at the maximally tolerated dose (MTD). Treatment was delivered to gross tumor delineated with MRI fusion using image-guidance to fiducial markers. Dose-limiting toxicity (DLT) was defined as grade 3+ toxicity within 30 days. Secondary endpoints included late gastrointestinal (GI) toxicity, freedom from local failure (FFLF), and survival. RESULTS: Fifteen patients received a median 10 cycles of chemotherapy. There were no DLTs, and the MTD was 15 Gy ×3. Thirty-day toxicity included grade 2 nausea (46%) and grade 2 diarrhea (7%). Median survival after SBRT was 12.8 months (23 months after diagnosis) and median relapse-free survival was 7 months. At 1-year, FFLF was 80%. Four patients had grade 3+ GI bleeding after 30 days (median 6 months). Grade 3+ GI bleeding was associated with tumor volume (P=0.01), heterogeneity of dose within the planning target volume (PTV) (V120, P=0.03), and duodenal dose (V26-30 Gy, P<0.2). CONCLUSIONS: This aggressive SBRT regimen demonstrated limited 30-day morbidity, a moderate degree of local control, and a moderate risk for late GI bleeding. Further work is necessary to define the most appropriate hypofractionated radiation therapy (RT) regimen in the ablative dose range.

19.
Cancer ; 126(2): 281-292, 2020 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-31639217

RESUMEN

BACKGROUND: Metastasectomy of isolated colorectal liver metastases (CRLM) requires significant clinical expertise and may not be readily available or offered. The authors hypothesized that hospitals that treat a greater percentage of patients from higher income catchment areas are more likely to perform metastasectomies regardless of patient or tumor characteristics. METHODS: Using the National Cancer Data Base, the authors classified facilities into facility income quartiles (FIQs) based on the percentage of patients from the wealthiest neighborhoods (by zip code). Quartile 1 included facilities with <2.1% of the patients residing within the highest income zip codes, quartile 2 included facilities with 2.2% to 15.6% of patients residing within the highest income zip codes, quartile 3 included facilities with 15.7% to 40.2% of patients residing within the highest income zip codes, and quartile 4 included facilities with 40.3% to 90.5% of patients residing within the highest income ZIP codes. Patient, tumor, and facility characteristics were analyzed using a multivariate logistic regression to identify associations between metastasectomy and FIQ. RESULTS: Patients with CRLM were more likely to undergo metastasectomy at facilities in the highest FIQ compared with the lowest FIQ (18% vs 11% in FIQ4; P = .001). This trend was not observed in the resection of primary tumors for nonmetastatic CRLM (rates of 95% vs 93%; P = .94). After adjusting for individual insurance status, distance traveled, zip code-level individual income, tumor, and host, patients who were treated at the highest FIQ facilities were found to be more likely to undergo metastasectomy (odds ratio, 1.29; 95% CI, 1.02-1.72 [P = .03]). CONCLUSIONS: Metastasectomy for CRLM is more likely to occur at facilities that serve a greater percentage of patients from high-income catchment areas, regardless of individual patient characteristics. This disparity uniquely affects those patients with advanced cancers for which specialized expertise for therapy is necessary.


Asunto(s)
Adenocarcinoma/cirugía , Neoplasias Colorrectales/patología , Disparidades en Atención de Salud/estadística & datos numéricos , Renta/estadística & datos numéricos , Neoplasias Hepáticas/cirugía , Metastasectomía/estadística & datos numéricos , Características de la Residencia/estadística & datos numéricos , Adenocarcinoma/secundario , Anciano , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Disparidades en Atención de Salud/economía , Hospitales/estadística & datos numéricos , Humanos , Neoplasias Hepáticas/secundario , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Estados Unidos
20.
Ann Surg Oncol ; 27(2): 511-517, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31571057

RESUMEN

BACKGROUND: The optimal surgical approach to the resection of gastoesophageal junction cancer is unknown. A comprehensive literature search was conducted to further compare the esophageal and gastric approaches to gastroesophageal junction cancer. METHODS: A systematic review of the literature from January 1990 to May 2018 was performed to determine whether an esophageal or gastric surgical approach offers better perioperative and oncologic outcomes. RESULTS: A total of 179 abstracts were identified and after excluding publications for non-English language, primary focus on neoadjuvant and/or adjuvant treatment, lack of comparison of surgical approaches or not addressing morbidity, mortality, or survival-related outcomes, a total of 14 nonrandomized, comparative studies were reviewed in detail. CONCLUSIONS: The proximal and distant extent of the tumor based on Siewert type classification greatly influences choice of operation. Overall survival rates and surgical outcomes are comparable, and surgical approach should be dictated by patient factors.


Asunto(s)
Neoplasias Esofágicas/mortalidad , Esofagectomía/mortalidad , Unión Esofagogástrica/cirugía , Gastrectomía/mortalidad , Neoplasias Gástricas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Unión Esofagogástrica/patología , Humanos , Atención Perioperativa , Pronóstico , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Tasa de Supervivencia
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