Factors Associated With Adjuvant Chemotherapy Noncompliance and Survival in Older Adults With Stage III Colon Cancer.

BACKGROUND: Standard management of stage III colon cancer includes surgical resection and adjuvant chemotherapy. Despite improved overall survival with adjuvant chemotherapy in stage III colon cancer, it is reportedly underused in older adults. To date, no contemporary national analysis of adjuvant chemotherapy use and its impact on older adults with stage III colon cancer exists. OBJECTIVE: This study aimed to assess the current use of adjuvant chemotherapy in older adults with stage III colon cancer and determine factors associated with noncompliance. DESIGN: Retrospective cohort study. SETTINGS: Conducted using the National Cancer Database. PATIENTS: This study included patients aged 65 years and older undergoing curative resection for stage III colon adenocarcinomas, 2010-2017. MAIN OUTCOME MEASURES: Adjuvant chemotherapy use, factors associated with adjuvant chemotherapy use, and overall survival with and without adjuvant chemotherapy in older adults with pathologic stage III disease. RESULTS: Of 64,608 patients included, 64.3% received adjuvant chemotherapy. Adjuvant chemotherapy was significantly independently associated with improved 1-, 3-, and 5-year overall survival vs no adjuvant chemotherapy (92.8%, 75.3%, 62.4% vs 70.8%, 46.6%, 32.7%; HR 0.475; 95% CI, 0.459-0.492; p <0.001). Compared with the no adjuvant chemotherapy cohort, patients who received adjuvant chemotherapy were younger, female, and less comorbid ( p < 0.001). Factors associated with adjuvant chemotherapy noncompliance included advancing age, lower annual income, open approach, longer length of stay, pathologic stage IIIA, and fewer than 12 lymph nodes. LIMITATIONS: Administrative data source with inherent risks of bias, coding errors, and limitations in the fields available for analysis. CONCLUSIONS: Adjuvant chemotherapy significantly improved overall survival but was only used in 64.3% of older adults with stage III colon cancer. Adjuvant chemotherapy noncompliance was seen in the most vulnerable and highest-risk patients, including those with greater comorbidity, lower income, and patients who received open surgery. See Video Abstract at http://links.lww.com/DCR/C125 . FACTORES ASOCIADOS CON EL INCUMPLIMIENTO DE LA QUIMIOTERAPIA ADYUVANTE Y LA SUPERVIVENCIA EN ADULTOS MAYORES CON CNCER DE COLON EN ESTADIO III: ANTECEDENTES: El tratamiento estándar de oro del cáncer de colon en estadio III incluye la resección quirúrgica y la quimioterapia adyuvante. A pesar de la mejora de la supervivencia general con la quimioterapia adyuvante en el cáncer de colon en estadio III, se reporta que se utiliza poco en los adultos mayores. Hasta la fecha, no existe ningún análisis nacional actual, sobre el uso de quimioterapia adyuvante y su impacto en adultos mayores con cáncer de colon en etapa III.OBJETIVO: Evaluar el uso actual de quimioterapia adyuvante en adultos mayores con cáncer de colon en estadio III y determinar los factores asociados con el incumplimiento.DISEÑO: Estudio de cohorte retrospectivo.AJUSTES: Realizado y utilizando la Base de Datos Nacional de Cáncer.PACIENTES: Pacientes de 65 años o más sometidos a resección curativa por adenocarcinomas de colon en estadio III de 2010-2017.PRINCIPALES MEDIDAS DE RESULTADO: Uso de quimioterapia adyuvante, factores asociados con el uso de quimioterapia adyuvante y supervivencia general con y sin quimioterapia adyuvante en adultos mayores con enfermedad en estadio patológico III.RESULTADOS: De 64.608 pacientes incluidos, el 64,3% recibió quimioterapia adyuvante. La quimioterapia adyuvante se asoció de forma significativa e independiente con una mejor supervivencia general a 1, 3 y 5 años frente a ninguna quimioterapia adyuvante (92,8 %, 75,3 %, 62,4 % frente a 70,8 %, 46,6 %, 32,7 %; respectivamente, HR 0,475, 95 % IC 0,459-0,492, p < 0,001). En comparación con la cohorte sin quimioterapia adyuvante, los pacientes que recibieron quimioterapia adyuvante eran más jóvenes, mujeres y con menos comorbilidad. (p < 0,001). Los factores asociados con el incumplimiento de la quimioterapia adyuvante incluyeron edad avanzada (OR 0,857, IC del 95 % 0,854-0,861), ingresos anuales más bajos (OR 0,891, IC del 95 % 0,844-0,940), abordaje abierto (0,730, IC del 95 % 0,633-0,842), mayor duración de la estancia (OR 0,949, IC 95% 0,949-0,954) y estadio patológico IIIA (0,547, IC 95% 0,458-0,652) y <12.LIMITACIONES: Fuente de datos administrativos con riesgos inherentes de sesgo, errores de codificación y limitaciones en los campos disponibles para el análisis.CONCLUSIONES: La quimioterapia adyuvante mejoró significativamente la supervivencia general, pero solo se utilizó en el 64,3 % de los adultos mayores con cáncer de colon en estadio III. El incumplimiento de la quimioterapia adyuvante se observó en los pacientes más vulnerables y de mayor riesgo, incluidos aquellos con mayor comorbilidad, menores ingresos y pacientes que recibieron cirugía abierta. Consulte Video Resumen en http://links.lww.com/DCR/C125 . (Traducción-Dr. Fidel Ruiz Healy ).

A Randomized Controlled Trial Examining the Impact of an Anorectal Surgery Multimodal Enhanced Recovery Program on Opioid Use.

BACKGROUND: Anorectal cases may be a common gateway to the opioid epidemic. Opioid reduction is inherent in enhanced recovery after surgery (ERAS) protocols, but little work has evaluated ERAS in these cases. OBJECTIVE: To determine if ERAS could reduce postoperative opioid utilization in ambulatory anorectal surgery without sacrificing patient pain or satisfaction. METHODS: A randomized controlled trial assigned ambulatory anorectal patients to ERAS (experimental) or routine care (surgeon's choice) for pain management (control) over 30-days postoperatively. Primary outcome was overall days of opioid use. Secondary outcomes included pain and satisfaction scores over multiple time points and new persistent opioid use. The Visual Analog Scale, Functional Pain Scale, and EQ-5D-3L measured patient-reported pain and satisfaction. Univariate analysis compared outcomes overall and at individual time points. Two-way mixed ANOVA evaluated pain and satisfaction measures between groups and over time. RESULTS: Thirty-two patients were randomized into each arm (64 total). The control group consumed significantly more opioids after discharge (median 121.3MME vs 23.5MME, P < 0.001). Significantly more control patients requested additional narcotics (P  =  0.004), made unplanned calls (P = 0.009), and had unplanned clinic visits (P = 0.003). The control group had significantly more days on opioids (mean 14.4 vs 2.2, P < 0.001). Three control patients (9.4%) versus no experimental patients had new persistent opioid use. The mean global health, EQ5D-3L, Visual Analog Scale, and Functional Pain scores were comparable between groups over time. CONCLUSIONS: An ERAS protocol in ambulatory anorectal surgery is feasible, and resulted in reduced opioid use, and healthcare utilization, with no difference in pain or patient satisfaction. This challenges the paradigm that extended opioids are needed for effective postoperative pain management.

A national evaluation of the use and survival impact of adjuvant chemotherapy in Stage II colon cancer from the national cancer database.

AIM: Stage II colon cancers are a heterogeneous category, with controversy over use of adjuvant chemotherapy (AC). Patients with high-risk features may benefit from AC to improve overall survival (OS). Current guidelines do not routinely recommend AC in low-risk cases, but the actual use and benefit on OS in this cohort have not been fully examined on a national scale. We aimed to evaluate the use and impact of AC on OS in low-risk Stage II colon cancer. METHODS: The national cancer database was reviewed for Stage II colon cancers undergoing curative resection (2010-2015). Cases with preoperative radio-chemotherapy or high-risk features were excluded. Cases were stratified into 'AC' and 'no AC' cohorts, and then propensity score matched. Kaplan-Meier and Cox regression analysed OS. The main outcome measures were the incidence and impact of AC on OS in low-risk Stage II colon cancer. RESULTS: Of 39 926 patients evaluated, 8.2% (n = 3275) received AC. Matching resulted in 3275 cases per cohort. AC significantly improved 1-, 3- and 5-year OS versus no AC (P = 0.0017). The 5-year absolute risk reduction was 2.6%, relative risk reduction 12%, with a number needed to treat of 38. In the Cox model, AC remained significantly associated with increased OS (hazard ratio 0.816; 95% CI 0.713-0.934; P < 0.003). CONCLUSIONS: From this dataset, AC was associated with improved OS in low-risk Stage II disease. These findings from a large-scale sample question current guidelines and the need for better risk stratification. Further study with more robust variables is warranted to determine AC best practices.

Predictors of Positive Circumferential Resection Margin in Rectal Cancer: A Current Audit of the National Cancer Database.

BACKGROUND: Positive circumferential resection margin is a predictor of local recurrence and worse survival in rectal cancer. National programs aimed to improve rectal cancer outcomes were first created in 2011 and continue to evolve. The impact on circumferential resection margin during this time frame has not been fully evaluated in the United States. OBJECTIVE: The purpose of this study was to determine the incidence and predictors of positive circumferential resection margin after rectal cancer resection, across patient, provider, and tumor characteristics. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted using the National Cancer Database, 2011-2016. PATIENTS: Adults who underwent proctectomy for pathologic stage I to III rectal adenocarcinoma were included. MAIN OUTCOME MEASURES: Rate and predictors of positive circumferential resection margin, defined as resection margin ≤1 mm, were measured. RESULTS: Of 52,620 cases, circumferential resection margin status was reported in 90% (n = 47,331) and positive in 18.4% (n = 8719). Unadjusted analysis showed that patients with positive circumferential resection margin were more often men, had public insurance and shorter travel, underwent total proctectomy via open and robotic approaches, and were treated in Southern and Western regions at integrated cancer networks (all p < 0.001). Multivariate analysis noted that positive proximal and/or distal margin on resected specimen had the strongest association with positive circumferential resection margin (OR = 15.6 (95% CI, 13.6-18.1); p < 0.001). Perineural invasion, total proctectomy, robotic approach, neoadjuvant chemoradiation, integrated cancer network, advanced tumor size and grade, and Black race had increased risk of positive circumferential resection margin (all p < 0.050). Laparoscopic approach, surgery in North, South, and Midwest regions, greater hospital volume and travel distance, lower T-stage, and higher income were associated with decreased risk (all p < 0.028). LIMITATIONS: This was a retrospective cohort study with limited variables available for analysis. CONCLUSIONS: Despite creation of national initiatives, positive circumferential resection margin rate remains an alarming 18.4%. The persistently high rate with predictors of positive circumferential resection margin identified calls for additional education, targeted quality improvement assessments, and publicized auditing to improve rectal cancer care in the United States. See Video Abstract at http://links.lww.com/DCR/B584. PREDICTORES PARA UN MARGEN POSITIVO DE RESECCIN CIRCUNFERENCIAL EN EL CNCER DE RECTO UNA AUDITORA VIGENTE DE LA BASE DE DATOS NACIONAL DE CANCER: ANTECEDENTES:El margen positivo de resección circunferencial es un predictor de recurrencia local y peor sobrevida en el cáncer de recto. Los programas nacionales destinados a mejorar los resultados del cáncer de recto se crearon por primera vez en 2011 y continúan evolucionando. La repercusión del margen de resección circunferencial durante este período de tiempo no se ha evaluado completamente en los Estados Unidos.OBJETIVO:Determinar la incidencia y los predictores para un margen positivo de resección circunferencial posterior a la resección del cáncer de recto, según las características del paciente, el proveedor y el tumor.DISEÑO:Estudio de cohorte retrospectivo.AMBITO:Base de datos nacional de cáncer, 2011-2016.PACIENTES:Adultos que se sometieron a proctectomía por adenocarcinoma de recto con un estadío por patología I-III.PRINCIPALES VARIABLES EVALUADAS:Tasa y predictores para un margen positivo de resección circunferencial, definido como margen de resección ≤ 1 mm.RESULTADOS:De 52,620 casos, la condición del margen de resección circunferencial se informó en el 90% (n = 47,331) y positivo en el 18.4% (n = 8,719). El análisis no ajustado mostró que los pacientes con margen positivo de resección circunferencial se presentó con mayor frecuencia en hombres, tenían un seguro social y viajes más cortos, se operaron de proctectomía total abierta y robótica, y fueron tratados en las regiones del sur y el oeste en redes integradas de cáncer (todos p <0,001). El análisis multivariado destacó que el margen proximal y / o distal positivo de la pieza resecada tenía la asociación más fuerte con el margen postivo de resección circunferencial (OR 15,6; IC del 95%: 13,6-18,1, p <0,001). La invasión perineural, la proctectomía total, el abordaje robótico, la quimioradioterapia neoadyuvante, la red de cáncer integrada, el tamaño y grado del tumor avanzado y la raza afroamericana tenían un mayor riesgo de un margen de una resección positiva circunferencial (todos p <0,050). El abordaje laparoscópico, la cirugía en las regiones Norte, Sur y Medio Oeste, un mayor volumen hospitalario y distancia de viaje, estadio T más bajo y mayores ingresos se asociaron con una disminución del riesgo (todos p <0,028).LIMITACIONES:Estudio de cohorte retrospectivo con variables limitadas disponibles para análisis.CONCLUSIONES:A pesar del establecimiento de iniciativas nacionales, la tasa de margen positivo de resección circunferencial continúa siendo alarmante, 18,4%. El índice continuamente elevado junto a los predictores de un margen positivo de resección circunferencial hace un llamado para una mayor educación, evaluaciones específicas de mejora de la calidad y difusión de las auditorías para mejorar la atención del cáncer de recto en los Estados Unidos. Vea el resumen de video en http://links.lww.com/DCR/B584. Consulte Video Resumen en http://links.lww.com/DCR/B584.

N1c colon cancer and the use of adjuvant chemotherapy: a current audit of the National Cancer Database.

AIM: Colorectal cancer staging has evolved to define N1c as the presence of tumour deposits without concurrent positive lymph nodes. Work to date reports poor prognosis in N1c colon cancer, with Stage III categorization and adjuvant chemotherapy (AC) recommended. No study has yet evaluated the prevalence, treatment compliance or treatment-related outcomes on a national scale. We aimed to evaluate the prevalence of N1c colon cancer, use, outcomes and factors associated with AC in the USA. METHOD: The National Cancer Database was reviewed for N1cM0 colon adenocarcinomas that underwent resection from 2010 to 2016. Cases were stratified into 'AC' or 'no AC' cohorts. The Kaplan-Meier method was used to estimate overall survival (OS) and compare the AC and no AC cohorts using the log-rank test. Multivariable logistic regression identified factors associated with AC. The main outcome measures were the prevalence and factors associated with AC use and its impact in N1c disease. RESULTS: Of the 5684 (1.59% of 357 752) colon adenocarcinomas that were N1c, 55% (n = 3071) received AC. AC significantly improved 1-, 3- and 5-year OS compared with no AC (96.2%, 80%, 67.4% and 72.9%, 48.5%, 33.8%, respectively; P < 0.001). Compared with the no AC group, AC patients were younger, had less comorbidity, were of the male gender and received minimally invasive surgery at an academic treatment centre (all P < 0.05). Socioeconomic and procedural factors significantly impacted the use of AC. CONCLUSION: In the USA, AC is underutilized in N1c colon cancer despite significantly improved OS. Socioeconomic and procedural factors associated with AC were identified, highlighting disparities in AC use and opportunities to improve oncological outcomes and survival.

Obesity and Inflammatory Factors in the Progression of Early-Onset Colorectal Cancer.

Metabolic dysfunction associated with obesity leads to a chronic pro-inflammatory state with systemic effects, including the alteration of macrophage metabolism. Tumor-associated macrophages have been linked to the formation of cancer through the production of metabolites such as itaconate. Itaconate downregulates peroxisome proliferator-activated receptor gamma as a tumor-suppressing factor and upregulates anti-inflammatory cytokines in M2-like macrophages. Similarly, leptin and adiponectin also influence macrophage cytokine expression and contribute to the progression of colorectal cancer via changes in gene expression within the PI3K/AKT pathway. This pathway influences cell proliferation, differentiation, and tumorigenesis. This work provides a review of obesity-related hormones and inflammatory mechanisms leading to the development and progression of early-onset colorectal cancer (EOCRC). A literature search was performed using the PubMed and Cochrane databases to identify studies related to obesity and EOCRC, with keywords including 'EOCRC', 'obesity', 'obesity-related hormones', 'itaconate', 'adiponectin', 'leptin', 'M2a macrophage', and 'microbiome'. With this concept of pro-inflammatory markers contributing to EOCRC, increased use of chemo-preventative agents such as aspirin may have a protective effect. Elucidating this association between obesity-related, hormone/cytokine-driven inflammatory effects with EOCRC may help lead to new therapeutic targets in preventing and treating EOCRC.

National disparities in use of minimally invasive surgery for rectal cancer in older adults.

BACKGROUND: Minimally invasive surgery (MIS) is safe and improves outcomes in older persons with rectal cancer but may be underutilized. As older persons are the largest surgical population, investigation of the current use and factors impacting MIS use is warranted. Our goal is to investigate the trends and disparities that affect utilization of MIS in older persons with rectal cancer. METHODS: The National Cancer Database was reviewed for persons 65 years and older who underwent curative resection for rectal adenocarcinoma from 2010 to 2017. Cases were stratified by surgical approach (open or MIS [laparoscopic or robotic]). Univariate analysis compared patient and provider demographics across approaches. Multivariate analysis investigated variables associated with MIS use. Main outcome measures were trends and factors associated with MIS use in older persons. RESULTS: Of 31,910 patients analyzed, 51.9% (n = 16,555) were open and 48.1% (n = 15,355) MIS. The MIS cohort was 66.7% (n = 10,236) laparoscopic and 33.3% (n = 5119) robotic. MIS increased from 29% in 2010 (n = 1197; 25% laparoscopic, 4% robotic) to 65% in 2017 (n = 2382; 35% laparoscopic, 30% robotic), likely from annual increases in robotics (OR 1.24/year, p < 0.0001). In the unadjusted analysis, there were significant differences in MIS use by age, race, comorbidity, socioeconomic status, and facility type. In multivariate analysis, patients with advancing age (OR 0.93, p < 0.001), major comorbidity (OR 0.75, p < 0.001), total proctectomy (OR0.78, p < 0.001), and advanced pathologic stage (OR 0.51, p < 0.001) were less likely to undergo MIS. CONCLUSION: Nationwide, less than half of rectal cancer cases in older persons were performed with MIS, despite steady robotic growth. Patient and facility factors impacted MIS use. Further work on regionalizing rectal cancer care and ensuring equitable MIS access and training could improve utilization.