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1.
JAMA Oncol ; 8(9): 1263-1270, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35834226

RESUMEN

Importance: National guidelines endorse treatment with neoadjuvant therapy for borderline resectable pancreatic ductal adenocarcinoma (PDAC), but the optimal strategy remains unclear. Objective: To compare treatment with neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) with or without hypofractionated radiation therapy with historical data and establish standards for therapy in borderline resectable PDAC. Design, Setting, and Participants: This prospective, multicenter, randomized phase 2 clinical trial conducted from February 2017 to January 2019 among member institutions of National Clinical Trials Network cooperative groups used standardized quality control measures and included 126 patients, of whom 70 (55.6%) were registered to arm 1 (systemic therapy; 54 randomized, 16 following closure of arm 2 at interim analysis) and 56 (44.4%) to arm 2 (systemic therapy and sequential hypofractionated radiotherapy; all randomized before closure). Data were analyzed by the Alliance Statistics and Data Management Center during September 2021. Interventions: Arm 1: 8 treatment cycles of mFOLFIRINOX (oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2) over 46 hours, administered every 2 weeks. Arm 2: 7 treatment cycles of mFOLFIRINOX followed by stereotactic body radiotherapy (33-40 Gy in 5 fractions) or hypofractionated image-guided radiotherapy (25 Gy in 5 fractions). Patients without disease progression underwent pancreatectomy, which was followed by 4 cycles of treatment with postoperative FOLFOX6 (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; bolus fluorouracil, 400 mg/m2; and infusional fluorouracil, 2400 mg/m2 over 46 hours). Main Outcomes and Measures: Each treatment arm's 18-month overall survival (OS) rate was compared with a historical control rate of 50%. A planned interim analysis mandated closure of either arm for which 11 or fewer of the first 30 accrued patients underwent margin-negative (R0) resection. Results: Of 126 patients, 62 (49%) were women, and the median (range) age was 64 (37-83) years. Among the first 30 evaluable patients enrolled to each arm, 17 patients in arm 1 (57%) and 10 patients in arm 2 (33%) had undergone R0 resection, leading to closure of arm 2 but continuation to full enrollment in arm 1. The 18-month OS rate of evaluable patients was 66.7% (95% CI, 56.1%-79.4%) in arm 1 and 47.3% (95% CI 35.8%-62.5%) in arm 2. The median OS of evaluable patients in arm 1 and arm 2 was 29.8 (95% CI, 21.1-36.6) months and 17.1 (95% CI, 12.8-24.4) months, respectively. Conclusions and Relevance: This randomized clinical trial found that treatment with neoadjuvant mFOLFIRINOX alone was associated with favorable OS in patients with borderline resectable PDAC compared with mFOLFIRINOX treatment plus hypofractionated radiotherapy; thus, mFOLFIRINOX represents a reference regimen in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02839343.


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/radioterapia , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Femenino , Fluorouracilo/uso terapéutico , Humanos , Irinotecán/uso terapéutico , Leucovorina/uso terapéutico , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Oxaliplatino/uso terapéutico , Páncreas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/radioterapia , Estudios Prospectivos , Neoplasias Pancreáticas
2.
J Clin Oncol ; 39(36): 4009-4019, 2021 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-34752136

RESUMEN

PURPOSE: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/efectos adversos , Fluorouracilo/uso terapéutico , Oxaliplatino/efectos adversos , Oxaliplatino/uso terapéutico , Adenocarcinoma/complicaciones , Adenocarcinoma/mortalidad , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias Colorrectales/mortalidad , Femenino , Fluorouracilo/farmacología , Humanos , Masculino , Persona de Mediana Edad , Oxaliplatino/farmacología , Pronóstico , Tasa de Supervivencia , Factores de Tiempo
3.
Ther Adv Med Oncol ; 13: 17588359211020547, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34262614

RESUMEN

BACKGROUND: Benchmarking international cancer survival differences is necessary to evaluate and improve healthcare systems. Our aim was to assess the potential regional differences in outcomes among patients with metastatic colorectal cancer (mCRC) participating in international randomized clinical trials (RCTs). DESIGN: Countries were grouped into 11 regions according to the World Health Organization and the EUROCARE model. Meta-analyses based on individual patient data were used to synthesize data across studies and regions and to conduct comparisons for outcomes in a two-stage random-effects model after adjusting for age, sex, performance status, and time period. We used mCRC patients enrolled in the first-line RCTs from the ARCAD database, which provided enrolling country information. There were 21,509 patients in 27 RCTs included across the 11 regions. RESULTS: Main outcomes were overall survival (OS) and progression-free survival (PFS). Compared with other regions, patients from the United Kingdom (UK) and Ireland were proportionaly over-represented, older, with higher performance status, more frequently male, and more commonly not treated with biological therapies. Cohorts from central Europe and the United States (USA) had significantly longer OS compared with those from UK and Ireland (p = 0.0034 and p < 0.001, respectively), with median difference of 3-4 months. The survival deficits in the UK and Ireland cohorts were, at most, 15% at 1 year. No evidence of a regional disparity was observed for PFS. Among those treated without biological therapies, patients from the UK and Ireland had shorter OS than central Europe patients (p < 0.001). CONCLUSIONS: Significant international disparities in the OS of cohorts of mCRC patients enrolled in RCTs were found. Survival of mCRC patients included in RCTs was consistently lower in the UK and Ireland regions than in central Europe, southern Europe, and the USA, potentially attributed to greater overall population representation, delayed diagnosis, and reduced availability of therapies.

4.
Prehosp Disaster Med ; 36(1): 74-78, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33198837

RESUMEN

OBJECTIVE: The primary goal of this study was to determine if ultrasound (US) use after brief point-of-care ultrasound (POCUS) training on cardiac and lung exams would result in more paramedics correctly identifying a tension pneumothorax (TPTX) during a simulation scenario. METHODS: A randomized controlled, simulation-based trial of POCUS lung exam education investigating the ability of paramedics to correctly diagnose TPTX was performed. The US intervention group received a 30-minute cardiac and lung POCUS lecture followed by hands-on US training. The control group did not receive any POCUS training. Both groups participated in two scenarios: right unilateral TPTX and undifferentiated shock (no TPTX). In both scenarios, the patient continued to be hypoxemic after verified intubation with pulse oximetry of 86%-88% and hypotensive with a blood pressure of 70/50. Sirens were played at 65 decibels to mimic prehospital transport conditions. A simulation educator stated aloud the time diagnoses were made and procedures performed, which were recorded by the study investigator. Paramedics completed a pre-survey and post-survey. RESULTS: Thirty paramedics were randomized to the control group; 30 paramedics were randomized to the US intervention group. Most paramedics had not received prior US training, had not previously performed a POCUS exam, and were uncomfortable with POCUS. Point-of-care US use was significantly higher in the US intervention group for both simulation cases (P <.001). A higher percentage of paramedics in the US intervention group arrived at the correct diagnosis (77%) for the TPTX case as compared to the control group (57%), although this difference was not significantly different (P = 0.1). There was no difference in the correct diagnosis between the control and US intervention groups for the undifferentiated shock case. On the post-survey, more paramedics in the US intervention group were comfortable with POCUS for evaluation of the lung and comfortable decompressing TPTX using POCUS (P <.001). Paramedics reported POCUS was within their scope of practice. CONCLUSIONS: Despite being novice POCUS users, the paramedics were more likely to correctly diagnose TPTX during simulation after a brief POCUS educational intervention. However, this difference was not statistically significant. Paramedics were comfortable using POCUS and felt its use improved their TPTX diagnostic skills.


Asunto(s)
Servicios Médicos de Urgencia , Neumotórax , Técnicos Medios en Salud , Humanos , Neumotórax/diagnóstico por imagen , Neumotórax/terapia , Sistemas de Atención de Punto , Ultrasonografía
5.
Clin Colorectal Cancer ; 12(3): 179-87, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23810482

RESUMEN

PURPOSE: To compare long-term outcomes between men and women in a large cohort of clinical trial participants with early-stage colon cancer, specifically by examining whether the prognostic effect of sex varies based on age, stage of disease, and type of adjuvant therapy received. METHODS: A pooled analysis of individual patient data from 33,345 patients with colon cancer enrolled in 24 phase III studies of various adjuvant systemic therapies was conducted. Chemotherapy consisted of (1) fluorouracil (5-FU), (2) 5-FU variations, (3) 5-FU plus oxaliplatin, (4) 5-FU plus irinotecan, or (5) oral fluoropyrimidine-based regimens. The primary endpoint was disease-free survival; secondary endpoints included overall survival and time to recurrence. Stratified Cox models were used to assess the effect of sex on outcomes. Multivariate models were used to assess adjusted effects and to explore the interaction among sex and other factors. RESULTS: A total of 18,244 (55%) men and 15,101 (45%) women were included. In the entire cohort, the median age was 61 years; 91% (24,868) were white; 31% (10,347) and 69% (22,964) had stage I/II and III disease, respectively. Overall, men had inferior prognoses when compared with women for time to recurrence (hazard ratio [HR] 1.05 [95% CI, 1.01-1.09]) and other endpoints after adjusting for age, stage, and treatment. Sex was not a predictive factor of treatment efficacy (P for interaction between sex and treatment when adjusting for age and stage were .40, .67, and .77 for disease-free survival, overall survival, and time to recurrence, respectively). In exploratory analyses, worse outcomes in men were more prominent in the older patients when adjusting for stage and treatment (HR 1.08 in age ≤ 65 years vs. HR 1.18 in age > 65 years; interaction P = .016 for disease-free survival). The stage of disease and type of adjuvant regimen did not modify the prognostic value of sex. CONCLUSIONS: Sex is a modest independent prognostic marker for patients with early-stage colon cancer, particularly in older patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Colon/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Quimioterapia Adyuvante , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Irinotecán , Leucovorina/administración & dosificación , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino , Pronóstico , Factores Sexuales , Tasa de Supervivencia , Adulto Joven
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