ABSTRACT
BACKGROUND: Total neoadjuvant therapy in rectal cancer may increase pathological complete response rates, potentially allowing for a nonoperative approach. OBJECTIVE: The objective of this study was to identify patient and tumor characteristics that predict a complete response following total neoadjuvant therapy. DESIGN: This was a retrospective cohort study. SETTINGS: This study was conducted at a university-based National Cancer Institute-designated Comprehensive Cancer Center. PATIENTS: The patients include those with stage 2 or 3 rectal adenocarcinoma. INTERVENTIONS: Interventions included total neoadjuvant therapy, total mesorectal excision, and nonoperative management. MAIN OUTCOME MEASURES: Complete response was defined as either patients with a clinical complete response undergoing nonoperative management who remained cancer-free or patients undergoing surgery with a pathological complete response. RESULTS: Among 102 patients, median age was 54 years, 69% were male, median carcinoembryonic antigen level was 3.0 ng/mL, and the median distance of the tumor above the anorectal ring was 3 cm. Thirty-eight (37%) patients had a complete response, including 15 of 18 (83%) nonoperative patients who remained cancer free at a median of 22 months (range, 7-48 months) and 23 of 84 (27%) patients who underwent surgery and had a pathological complete response. The incomplete response group consisted of 61 patients who underwent initial surgery and 3 nonoperative patients with regrowth. There were no differences in gender, T-stage, or tumor location between groups. Younger age (median, 49 vs 55 years), normal carcinoembryonic antigen (71% vs 41%), clinical node-negative (24% vs 9%), smaller tumors (median 3.9 vs 5.4 cm), and wild-type p53 (79% vs 47%) and SMAD4 (100% vs 81%) were more likely to have a complete response (all p < 0.05). LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSIONS: In patients with rectal cancer treated with total neoadjuvant therapy, more than one-third will achieve a pathological complete response or sustained clinical complete response with nonoperative management, making oncological resection superfluous in these patients. Smaller, wild-type p53 and SMAD4, and clinically node-negative cancers are predictive features of a complete response. See Video Abstract at http://links.lww.com/DCR/B889 . CNCER DE RECTO PREDICTORES CLNICOS Y MOLECULARES DE UNA RESPUESTA COMPLETA A LA TERAPIA NEOADYUVANTE TOTAL: ANTECEDENTES:La terapia neoadyuvante total en el cáncer de recto puede aumentar las tasas de respuesta patológica completa y permitir potencialmente un enfoque no quirúrgico.OBJETIVO:El objetivo fue identificar las características tanto del paciente y del tumor que logren predecir una respuesta completa después de la terapia neoadyuvante total.DISEÑO:Este fue un estudio de cohorte retrospectivo.AJUSTES:Este estudio se realizó en un Centro Integral de Cáncer designado por el Instituto Nacional del Cáncer con sede universitaria.PACIENTES:Los pacientes incluyen aquellos con adenocarcinoma de recto en estadio 2 o 3.INTERVENCIONES:Terapia neoadyuvante total, escisión total del mesorrecto, manejo conservador no quirúrgico.PRINCIPALES MEDIDAS DE RESULTADO:La respuesta completa se definió como pacientes con una respuesta clínica completa sometidos a tratamiento no quirúrgico que permanecieron libres de cáncer o pacientes sometidos a cirugía con una respuesta patológica completa.RESULTADOS:Entre 102 pacientes, la mediana de edad fue de 54 años, el 69% fueron hombres, la mediana del nivel de antígeno carcinoembrionario fue de 3.0 ng/ml y la mediana de la distancia del tumor por encima del anillo anorrectal fue de 3 cm. Thirty-eight (37%) pacientes tuvieron una respuesta completa que incluyó a 15 de 18 (83%) pacientes con manejo no operatorio y que permanecieron libres de cáncer en una mediana de 22 meses (rango 7- 48 meses) y 23 de 84 (27%) pacientes que fueron sometidos a cirugía y tuvieron una respuesta patológica completa. El grupo de respuesta incompleta consistió en 61 pacientes que fueron sometidos inicialmente a cirugía y 3 pacientes no quirúrgicos con recrecimiento. No se encontró diferencias de género, estadio T o ubicación del tumor entre los grupos. Edad más joven (mediana 49 frente a 55), antígeno carcinoembrionario normal (71% frente a 41%), ganglios clínicos negativos (24% frente a 9%), tumores más pequeños (mediana de 3,9 frente a 5,4 cm) y p53 de tipo salvaje (79 % vs 47%) y SMAD4 (100% vs 81%) tenían más probabilidades de tener una respuesta completa (todos p < 0,05).LIMITACIONES:Este fue un estudio retrospectivo y con un tamaño de muestra pequeño.CONCLUSIONES:En pacientes con cáncer de recto tratados con terapia neoadyuvante total, más de un tercio logrará una respuesta patológica completa o una respuesta clínica completa sostenida con manejo no operatorio, logrando que la resección oncológica sea superflua en estos pacientes. Los cánceres más pequeños, clínicamente con ganglios negativos, con p53 de tipo salvaje y SMAD4, son características predictoras de una respuesta completa. Consulte Video Resumen en http://links.lww.com/DCR/B889 . (Traducción-Dr. Osvaldo Gauto ).
Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Female , Humans , Male , Middle Aged , Adenocarcinoma/therapy , Adenocarcinoma/pathology , Carcinoembryonic Antigen , Neoplasm Staging , Rectal Neoplasms/therapy , Retrospective Studies , Tumor Suppressor Protein p53ABSTRACT
PURPOSE: Intraoperative hyperglycemia is associated with infectious complications in general surgery patients. This study aimed to determine if the use of lactated Ringer's (LR) carrier solution during hyperthermic intraperitoneal chemotherapy (HIPEC) would lower the incidence of intraoperative hyperglycemia and improve postoperative outcomes when compared with a standard 1.5% dextrose peritoneal dialysate carrier solution. PATIENTS AND METHODS: This is a retrospective cohort study of 134 patients who underwent HIPEC at the University of Colorado. Perioperative glucose levels and outcomes were compared between patients who were perfused with 1.5% dextrose peritoneal dialysate carrier solution (n = 68) versus LR carrier solution (n = 66). RESULTS: The study population consisted of patients undergoing HIPEC for appendiceal (50%), colorectal (34%), mesothelioma (8%), and ovarian cancer (5%). Intraoperative severe hyperglycemia (glucose ≥ 180 mg/dL) was significantly more common among patients perfused with a dextrose-containing carrier solution versus those perfused with LR (88% vs. 21%; p < 0.001). Patients in the dextrose cohort had significantly more severe complications (39% vs. 12%; p = 0.034), infectious complications (35% vs. 15%; p = 0.011), and organ space infections (18% vs. 5%: p = 0.026) than the LR cohort. On multivariable analysis, dextrose-containing carrier solution was significantly associated with an increased risk of postoperative infectious complications (HR 5.16; p = 0.006). CONCLUSIONS: Intraoperative hyperglycemia is common when dextrose-containing carrier solution is used during HIPEC, and severe intraoperative hyperglycemia is strongly associated with an increased risk for infectious of complications following HIPEC. LR carrier solution should be routinely used to reduce intraoperative hyperglycemia and its associated risks.
