ABSTRACT
BACKGROUND: Patients with chronic kidney disease are commonly excluded from clinical trials. The impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer has not been previously studied. OBJECTIVE: This study aimed to investigate the impact of chronic kidney disease on outcomes in patients with locally advanced rectal cancer. DESIGN: This is a multi-institutional, retrospective cohort study. SETTINGS: This study was conducted at academic and community cancer centers participating in the Canadian Health Outcomes Research Database Consortium Rectal Cancer Database. PATIENTS: Consecutive patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation before curative-intent surgery from 2005 to 2013 were selected. MAIN OUTCOME MEASURES: Disease-free survival, overall survival, pathologic complete response, and neoadjuvant chemotherapy/radiotherapy completion rate were the primary outcomes measured. RESULTS: A total of 1254 patients were included. Median age was 62, and 29%/69% had clinical stage II and III disease. Median estimated creatinine clearance was 93 mL/min, with 11% <60 mL/min (n = 136). There was no significant difference in the completion rate of neoadjuvant chemotherapy (82% vs 85%, p = 0.36) or radiotherapy (93% vs 95%, p = 0.45) between patients with and without chronic kidney disease. Patients with chronic kidney disease were less likely to receive adjuvant chemotherapy (63% vs 77%, p < 0.01). On multivariate analysis, patients with chronic kidney disease had decreased disease-free survival (HR, 1.37; 95% CI, 1.03-1.82; p = 0.03) but not overall survival (HR, 1.23; 95% CI, 0.88-1.75; p = 0.23) or pathologic complete response (OR, 0.83; 95% CI, 0.50-1.39; p = 0.71). LIMITATIONS: This study was limited by its retrospective design and by limited events for overall survival analysis. CONCLUSIONS: In patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation, baseline chronic kidney disease was associated with less use of adjuvant chemotherapy and decreased disease-free survival. Chronic kidney disease was not independently associated with neoadjuvant chemotherapy/radiotherapy completion rate, pathologic complete response, or overall survival. These data suggest that patients with locally advanced rectal cancer with chronic kidney disease may have distinct outcomes and, accordingly, the results of landmark clinical trials may not be generalizable to this population. See Video Abstract at http://links.lww.com/DCR/B694. LA REPERCUSIN DE LA ENFERMEDAD RENAL CRNICA EN PACIENTES CON CNCER DE RECTO LOCALMENTE AVANZADO TRATADOS CON QUIMIORRADIOTERAPIA NEOADYUVANTE: ANTECEDENTES:Los pacientes con enfermedad renal crónica generalmente se excluyen de los ensayos clínicos. La repercusión de la enfermedad renal crónica en el desenlace en pacientes con cáncer de recto localmente avanzado no se ha estudiado previamente.OBJETIVO:Investigar la repercusión de la enfermedad renal crónica en los desenlaces en pacientes con cáncer de recto localmente avanzado.DISEÑO:Estudio de cohorte retrospectivo multiinstitucional.ESCENARIO:Centros oncológicos académicos y comunitarios que participan en la base de datos de cáncer rectal del consorcio CHORD.PACIENTES:Pacientes consecutivos con cáncer de recto localmente avanzado, tratados con quimiorradioterapia neoadyuvante, previa a la cirugía con intención curativa del 2005 al 2013.PRINCIPALES VARIABLES EVALUADAS:Sobrevida libre de enfermedad, sobrevida global, respuesta patológica completa, tasa de conclusión de quimioterapia / radioterapia neoadyuvante.RESULTADOS:Se incluyeron 1254 pacientes. El promedio de edad fue de 62, y el 29% / 69% tenían enfermedad en estadio clínico II y III, respectivamente. El promedio de la depuración de creatinina estimada fue de 93 mililitros / minuto, con un 11% <60 mililitros / minuto (n = 136). No hubo diferencias significativas en la tasa de conclusión de la quimioterapia neoadyuvante (82% vs 85%, p = 0,36) o radioterapia (93% vs 95%, p = 0,45) entre pacientes con y sin enfermedad renal crónica. Los pacientes con enfermedad renal crónica tenían menos probabilidades de recibir quimioterapia adyuvante (63% contra el 77%, p <0,01). En el análisis multivariado, los pacientes con enfermedad renal crónica tenían una sobrevida libre de enfermedad menor (HR 1,37, IC 95% 1,03-1,82, p = 0,03) pero no en la sobrevida global (HR 1,23, IC 95% 0,88-1,75, p = 0,23) o respuesta patológica completa (OR 0,83, IC 95% 0,50-1,39, p = 0,71).LIMITACIONES:Diseño retrospectivo y acontecimientos limitados para el análisis de sobrevida global.CONCLUSIONES:En pacientes con cáncer de recto localmente avanzado tratados con quimiorradioterapia neoadyuvante, la enfermedad renal crónica de base se asoció con un menor uso de quimioterapia adyuvante y una menor sobrevida libre de enfermedad. La enfermedad renal crónica no se asoció de forma independiente con la tasa de conclusión de la quimioterapia / radioterapia neoadyuvante, la respuesta patológica completa o la sobrevida global. Estos datos sugieren que los pacientes con cáncer de recto localmente avanzado con enfermedad renal crónica pueden tener resultados distintos y, en consecuencia, los resultados de los ensayos clínicos de referencia pueden no ser generalizables a esta población. Consulte Video Resumen en http://links.lww.com/DCR/B694.
Subject(s)
Neoadjuvant Therapy/methods , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Renal Insufficiency, Chronic/complications , Adult , Aged , Aged, 80 and over , Canada/epidemiology , Chemoradiotherapy/methods , Disease-Free Survival , Female , Humans , Male , Metabolic Clearance Rate , Middle Aged , Neoplasm Staging/methods , Outcome Assessment, Health Care , Rectal Neoplasms/pathology , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/physiopathology , Retrospective Studies , Severity of Illness IndexABSTRACT
OBJECTIVES: Use of adjuvant chemotherapy (AC) following neoadjuvant chemoradiation (nCRT) is controversial in rectal cancer (RC). We assessed a multi-institutional database to determine if there was benefit from AC for pathologic stage II RC patients and whether the addition of oxaliplatin to fluoropyrimidine (OXAC) therapy impacted outcomes. MATERIALS AND METHODS: We included patients who underwent nCRT and had pathologic stage II (ypT3/4 ypN0) tumors. Disease-free survival and overall survival were assessed. Multivariate Cox models adjusting for age, sex, Eastern Cooperative Oncology Group, high-risk features (pT4, poor differentiation, <12 nodes removed, lymphovascular/perineural invasion, or obstruction/perforation), and clinical stage were constructed. RESULTS: Of 485 patients, 73.6% received AC, of which 25.5% received OXAC. Patients receiving AC were younger (median age 61 vs. 64; P=0.003) and had higher rates of total mesorectal excision (81.5% vs. 78.9%; P=0.049), but had similar high-risk features, performance status, clinical stage, margin status, preoperative carcinoembryonic antigen, and nCRT regimen. In univariate analysis, overall survival was improved with fluoropyrimidine AC compared with no AC or OXAC (P=0.049), but not disease-free survival (P=0.33). In multivariate analysis, any AC, fluoropyrimidine AC, or OXAC did not improve outcomes. After stratifying patients by the presence of high-risk features, elevated carcinoembryonic antigen, margin status, or preoperative clinical stage, we did not identify a group with improved outcomes following AC. CONCLUSIONS: In this multi-institutional cohort of yp stage II RC patients, we failed to identify a group that derives benefit from AC following nCRT. The addition of oxaliplatin did not appear to improve outcomes when compared with fluoropyrimidine alone.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemoradiotherapy , Chemotherapy, Adjuvant/mortality , Neoplasm Recurrence, Local/drug therapy , Postoperative Care , Rectal Neoplasms/drug therapy , Salvage Therapy , Aged , Cohort Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Neoplasm Staging , Prognosis , Rectal Neoplasms/pathology , Rectal Neoplasms/therapy , Survival RateABSTRACT
A 44-year-old woman presented with lower abdominal pain and bilateral ovarian masses on ultrasound. Exploratory laparotomy revealed extensive peritoneal and intra-abdominal disease and an abnormal appendix. Bilateral salpingo-oophorectomy, infracolic omentectomy, ileocolic resection and primary anastomosis were performed. Final pathology revealed a primary appendiceal adenocarcinoma, poorly differentiated, of signet ring cell type. CT scan postoperatively revealed gross residual disease. The patient was treated with FOLFOX chemotherapy combined with bevacizumab. Repeat CT scan showed a decrease in residual disease and the patient clinically improved. After her treatment has been continued for 13 months, she remains clinically well and her CT scan shows sustained disease stability. Disseminated appendiceal carcinoma is generally considered to be refractory to 5-FU-based chemotherapy and, to our knowledge, this is the first reported case of a patient with appendiceal adenocarcinoma demonstrating clinical benefit and sustained stability of disease with combination chemotherapy plus bevacizumab.
