The prognostic impact of tumor deposits in colorectal cancer: More than just N1c.

BACKGROUND: The identification of tumor deposits (TD) currently plays a limited role in staging for colorectal cancer (CRC) aside from N1c lymph node designation. The objective of this study was to determine the prognostic impact, beyond American Joint Committee on Cancer N1c designation, of TDs among patients with primary CRC. METHODS: Patients who had resected stage I-III primary CRC diagnosed between 2010 and 2019 were identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. Cancer-specific survival (CSS) stratified by TD status and lymph node (N) status was calculated using the Kaplan-Meier method and multivariable Cox proportional hazards regression analyses. RESULTS: In total, 147,783 patients with primary CRC were identified. TDs were present in 15,444 patients (10.5%). The presence of TDs was significantly associated with adverse tumor characteristics, including advanced pathologic stage, nodal status, and metastasis status. The presence of TDs was associated with worse CSS (hazard ratio [HR], 3.12; 95% confidence interval [CI], 3.02-3.22), as it was for each given N category (e.g., N2a and TD-negative [HR, 2.50; 95% CI, 2.37-2.64] vs. N2a and TD-positive [HR, 3.75; 95% CI, 3.49-4.03]). The presence of multiple TDs was also associated with decreased CSS for each given N category compared with a single TD (e.g. N2a with one TD [HR, 3.09; 95% CI, 2.65-3.61] vs. N2a with two or more TDs [HR, 4.32; 95% CI, 3.87-4.82]). CONCLUSIONS: TDs were identified as an independent predictor of a worse outcome in patients with CRC. The presence of TDs confers distinctly different CSS and provides important prognostic information among patients with CRC and warrants further investigation as a unique variable in future iterations of CRC staging.

Para-aortic Lymph Node Dissection for Colorectal Cancer: Predicting Pathologic Lymph Node Positivity and Optimizing Outcomes.

INTRODUCTION: In colorectal cancer, the presence of para-aortic lymph nodes (PALN) indicates extraregional disease. Appropriately selecting patients for whom PALN dissection will provide oncologic benefit remains challenging. This study identified factors to predict survival among patients undergoing PALN dissection for colorectal cancer. METHODS: An institutional database was queried for patients who underwent curative-intent resection of clinically positive PALN for colorectal cancer between 2007 and 2020. Preoperative radiologic images were reviewed, and patients who did and did not have positive PALN on final pathology were compared. Survival analysis was performed to evaluate the impact of pathologically positive PALN on recurrence-free (RFS) and overall survival (OS). RESULTS: Of 74 patients who underwent PALN dissection, 51 had PALN metastasis at the time of primary tumor diagnosis, whereas 23 had metachronous PALN disease. Preoperative chemotherapy ± radiotherapy was given in 60 cases (81.1%), and 28 (37.8%) had pathologically positive PALN. Independent factors associated with positive PALN pathology included metachronous PALN disease and pretreatment and posttreatment radiographically abnormal PALN. On multivariable analysis, pathologically positive PALN was significantly associated with decreased RFS (hazard ratio 3.90) and OS (HR 4.49). Among patients with pathologically positive PALN, well/moderately differentiated histology was associated with better OS, and metachronous disease trended toward an association with better OS. CONCLUSIONS: Pathologically positive PALN are associated with poorer RFS and OS after PALN dissection for colorectal cancer. Clinicopathologic factors may predict pathologic PALN positivity. Curative-intent surgery may provide benefit, especially in patients with well-to-moderately differentiated primary tumors and possibly metachronous PALN disease.

The Learning Curve for Robotic Lateral Pelvic Lymph Node Dissection for Rectal Cancer: A View From the West.

BACKGROUND: Lateral pelvic lymph node dissection is performed for selected patients with rectal cancer with persistent lateral nodal disease after neoadjuvant therapy. This technique has been slow to be adopted in the West because of concerns regarding technical difficulty. This is the first report on the learning curve for lateral pelvic lymph node dissection in the United States or Europe. OBJECTIVE: This study aimed to analyze the learning curve associated with robotic lateral pelvic lymph node dissection. DESIGN: Retrospective observational cohort. SETTING: Tertiary academic cancer center. PATIENTS: Consecutive patients from 2012 to 2021. INTERVENTION: All patients underwent robotic lateral pelvic lymph node dissection. MAIN OUTCOME MEASURES: The primary end points were the learning curves for the maximum number of nodes retrieved and urinary retention, which was evaluated with simple cumulative sum and 2-sided Bernoulli cumulative sum charts. RESULTS: Fifty-four procedures were included. A single-surgeon learning curve (n = 35) and an institutional learning curve are presented in the analysis. In the single-surgeon learning curve, a turning point marking the end of a learning phase was detected at the 12th procedure for the number of retrieved nodes and at the 20th procedure for urinary retention. In the institutional learning curve analysis, 2 turning points were identified at the 13th procedure, indicating progressive improvements for the number of retrieved nodes, and at the 27th procedure for urinary retention. No sustained alarm signals were detected at any time point. LIMITATIONS: The retrospective nature, small sample size, and the referral center nature of the reporting institution may limit generalizability. CONCLUSIONS: In a setting of institutional experience with robotic colorectal surgery, including beyond total mesorectal excision resections, the learning curve for robotic lateral pelvic lymph node dissection is acceptably short. Our results demonstrate the feasibility of the acquisition of this technique in a controlled setting, with sufficient case volume and proctoring to optimize the learning curve. See Video Abstract. LA CURVA DE APRENDIZAJE DE LA DISECCIN ROBTICA DE LOS GANGLIOS LINFTICOS PLVICOS LATERALES EN EL CNCER DE RECTO UNA VISIN DESDE OCCIDENTE: ANTECEDENTES:La disección lateral de los ganglios linfáticos pélvicos se realiza en pacientes seleccionados con cáncer de recto con enfermedad ganglionar lateral persistente tras el tratamiento neoadyuvante. La adopción de esta técnica en Occidente ha sido lenta debido a la preocupación por su dificultad técnica. Éste es el primer informe sobre la curva de aprendizaje de la disección de los ganglios linfáticos pélvicos laterales en EE.UU. o Europa.OBJETIVO:El objetivo de este estudio fue analizar la curva de aprendizaje asociada a la disección robótica de los ganglios linfáticos pélvicos laterales.DISEÑO:Cohorte observacional retrospectiva.LUGAR:Centro oncológico académico terciario.PACIENTES:Pacientes consecutivos desde 2012 al 2021.INTERVENCIÓN:Todos los pacientes fueron sometieron a disección robótica de ganglios linfáticos pélvicos laterales.PRINCIPALES MEDIDAS DE RESULTADO:Los criterios de valoración primarios fueron las curvas de aprendizaje tomando en cuenta el mayor número de ganglios recuperados y la retención urinaria que fueron evaluados con gráficos de suma acumulativa simple y de suma acumulativa de Bernoulli de dos caras.RESULTADOS:Fueron incluidos 54 procedimientos. En el análisis se presentan una curva de aprendizaje de un solo cirujano (n = 35) y una curva de aprendizaje institucional. En la curva de aprendizaje de un solo cirujano, se detectó un punto de inflexión que marcaba el final de una fase de aprendizaje en el duodécimo procedimiento para el número de ganglios extraídos y en el vigésimo para la retención urinaria. En el análisis de la curva de aprendizaje institucional, se identificaron dos puntos de inflexión en las intervenciones 13.ª y 26.ª, que indicaron mejoras progresivas en el número de ganglios extraídos, y en la 27.ª en la retención urinaria. No se detectaron señales de alarma sostenidas en ningún momento.LIMITACIONES:La naturaleza retrospectiva, el pequeño tamaño de la muestra y la naturaleza de centro de referencia de la institución informante que pueden limitar la capacidad de generalizarse.CONCLUSIONES:En un entorno de experiencia institucional con cirugía robótica colorrectal incluyendo más allá de las resecciones TME, la curva de aprendizaje para la disección robótica de ganglios linfáticos pélvicos laterales es aceptablemente corta. Nuestros resultados demuestran la viabilidad de la adquisición de esta técnica en un entorno controlado, con un volumen de casos suficiente y una supervisión que puede optimizar la curva de aprendizaje. (Traducción-Dr. Osvaldo Gauto ).

Early Postoperative Prediction of Complications and Readmission After Colorectal Cancer Surgery Using an Artificial Neural Network.

BACKGROUND: Early predictors of postoperative complications can risk-stratify patients undergoing colorectal cancer surgery. However, conventional regression models have limited power to identify complex nonlinear relationships among a large set of variables. We developed artificial neural network models to optimize the prediction of major postoperative complications and risk of readmission in patients undergoing colorectal cancer surgery. OBJECTIVE: This study aimed to develop an artificial neural network model to predict postoperative complications using postoperative laboratory values and compare the accuracy of models to standard regression methods. DESIGN: This retrospective study included patients who underwent elective colorectal cancer resection between January 1, 2016, and July 31, 2021. Clinical data, cancer stage, and laboratory data from postoperative days 1 to 3 were collected. Complications and readmission risk models were created using multivariable logistic regression and single-layer neural networks. SETTING: National Cancer Institute-Designated Comprehensive Cancer Center. PATIENTS: Adult patients with colorectal cancer. MAIN OUTCOME MEASURES: The accuracy of predicting postoperative major complications, readmissions, and anastomotic leaks using the area under the receiver operating characteristic curve. RESULTS: Neural networks had larger areas under the curve for predicting major complications compared to regression models (neural network 0.811; regression model 0.724, p < 0.001). Neural networks also showed an advantage in predicting anastomotic leak ( p = 0.036) and readmission using postoperative day 1 to 2 values ( p = 0.014). LIMITATIONS: Single-center, retrospective design limited to cancer operations. CONCLUSIONS: In this study, we generated a set of models for the early prediction of complications after colorectal surgery. The neural network models provided greater discrimination than the models based on traditional logistic regression. These models may allow for early detection of postoperative complications as early as postoperative day 2. See the Video Abstract . PREDICCIN POST OPERATORIA TEMPRANA DE COMPLICACIONES Y REINGRESO DESPUS DE LA CIRUGA DE CNCER COLORRECTAL MEDIANTE UNA RED NEURONAL ARTIFICIAL: ANTECEDENTES:Los predictores tempranos de complicaciones postoperatorias pueden estratificar el riesgo de los pacientes sometidos a cirugía de cáncer colorrectal. Sin embargo, los modelos de regresión convencionales tienen un poder limitado para identificar relaciones no lineales complejas entre un gran conjunto de variables. Desarrollamos modelos de redes neuronales artificiales para optimizar la predicción de complicaciones postoperatorias importantes y riesgo de reingreso en pacientes sometidos a cirugía de cáncer colorrectal.OBJETIVO:El objetivo de este estudio fue desarrollar un modelo de red neuronal artificial para predecir complicaciones postoperatorias utilizando valores de laboratorio postoperatorios y comparar la precisión de estos modelos con los métodos de regresión estándar.DISEÑO:Este estudio retrospectivo incluyó a pacientes que se sometieron a resección electiva de cáncer colorrectal entre el 1 de enero de 2016 y el 31 de julio de 2021. Se recopilaron datos clínicos, estadio del cáncer y datos de laboratorio del día 1 al 3 posoperatorio. Se crearon modelos de complicaciones y riesgo de reingreso mediante regresión logística multivariable y redes neuronales de una sola capa.AJUSTE:Instituto Nacional del Cáncer designado Centro Oncológico Integral.PACIENTES:Pacientes adultos con cáncer colorrectal.PRINCIPALES MEDIDAS DE RESULTADO:Precisión de la predicción de complicaciones mayores postoperatorias, reingreso y fuga anastomótica utilizando el área bajo la curva característica operativa del receptor.RESULTADOS:Las redes neuronales tuvieron áreas bajo la curva más grandes para predecir complicaciones importantes en comparación con los modelos de regresión (red neuronal 0,811; modelo de regresión 0,724, p < 0,001). Las redes neuronales también mostraron una ventaja en la predicción de la fuga anastomótica ( p = 0,036) y el reingreso utilizando los valores del día 1-2 postoperatorio ( p = 0,014).LIMITACIONES:Diseño retrospectivo de un solo centro limitado a operaciones de cáncer.CONCLUSIONES:En este estudio, generamos un conjunto de modelos para la predicción temprana de complicaciones después de la cirugía colorrectal. Los modelos de redes neuronales proporcionaron una mayor discriminación que los modelos basados en regresión logística tradicional. Estos modelos pueden permitir la detección temprana de complicaciones posoperatorias tan pronto como el segundo día posoperatorio. (Traducción-Dr. Mauricio Santamaria ).

Do resected colorectal cancer patients need early chest imaging? Impact of clinicopathologic characteristics on time to development of pulmonary metastases.

BACKGROUND AND OBJECTIVES: For patients with colorectal cancer (CRC), the lung is the most common extra-abdominal site of distant metastasis. However, practices for chest imaging after colorectal resection vary widely. We aimed to identify characteristics that may indicate a need for early follow-up imaging. METHODS: We retrospectively reviewed charts of patients who underwent CRC resection, collecting clinicopathologic details and oncologic outcomes. Patients were grouped by timing of pulmonary metastases (PM) development. Analyses were performed to investigate odds ratio (OR) of PM diagnosis within 3 months of CRC resection. RESULTS: Of 1600 patients with resected CRC, 233 (14.6%) developed PM, at a median of 15.4 months following CRC resection. Univariable analyses revealed age, receipt of systemic therapy, lymph node ratio (LNR), lymphovascular and perineural invasion, and KRAS mutation as risk factors for PM. Furthermore, multivariable regression showed neoadjuvant therapy (OR: 2.99, p < 0.001), adjuvant therapy (OR: 6.28, p < 0.001), LNR (OR: 28.91, p < 0.001), and KRAS alteration (OR: 5.19, p < 0.001) to predict PM within 3 months post-resection. CONCLUSIONS: We identified clinicopathologic characteristics that predict development of PM within 3 months after primary CRC resection. Early surveillance in such patients should be emphasized to ensure timely identification and treatment of PM.

Germline Cancer Risk Profiles of Patients With Young-Onset Colorectal Cancer: Findings From a Prospective Universal Germline Testing and Telegenetics Program.

BACKGROUND: Colorectal cancer is being increasingly diagnosed in people younger than 50 years. An inheritable cancer predisposition has been reported in 22% of the young-onset cases. Assessment of germline risk is critical for personalized cancer care. OBJECTIVE: The study aimed to implement universal germline cancer risk assessment and testing and to define the germline cancer risk profiles of patients presenting with young-onset disease. DESIGN: This is a prospective cohort study. SETTINGS: This study was conducted at a tertiary-referral academic medical center. PATIENTS: This study included newly diagnosed patients presenting to surgical clinics between September 2019 and February 2021 who were treated on a standardized care pathway including the universal germline risk assessment. INTERVENTIONS: Patients received educational material on young-onset disease, genetic testing, and insurance coverage followed by genetic counseling (either remotely by telegenetics or in person). Consenting patients were assessed on a 47-gene common hereditary cancer panel. MAIN OUTCOME MEASURES: The primary outcome was a proportion of patients with identifiable germline cancer predisposition. RESULTS: Among 500 patients with colorectal cancer, 185 (37%) were 50 years of age or younger (median: 44). A family history was absent for the majority of patients (123; 67%), and in 15 patients, tumors (8.1%) were deficient in DNA mismatch repair. Germline testing was completed in 130 patients (70%); the remainder were pending (7%), deceased (1%), or declined (22%). Pathogenic germline mutations were identified in 25 of 130 (19%) patients: 12 in mismatch repair genes and 13 in other genes. A variant of uncertain significance was found in 23 (18%) patients. Importantly, a pathogenic germline mutation was identified in 12% of the patients without a family history (versus 32% with; p = 0.015) and in 13% of those with proficient mismatch repair colorectal cancers (versus 71% if deficient; p < 0.001). LIMITATIONS: The study is limited by its implementation at a single tertiary academic institution. CONCLUSIONS: One in 5 patients with young-onset disease harbored germline cancer predisposition. This detection rate, coupled with a high level of interest and acceptance from patients and feasibility of implementation, supports universal germline cancer risk assessment in this patient population. See Video Abstract at http://links.lww.com/DCR/B925 . PERFILES DE RIESGO DE CNCER DE LNEA GERMINAL DE PACIENTES CON CNCER COLORRECTAL DE INICIO JOVEN HALLAZGOS DE UN PROGRAMA UNIVERSAL PROSPECTIVO DE PRUEBAS DE LNEA GERMINAL Y TELEGENTICA: ANTECEDENTES:El cáncer colorrectal se diagnostica cada vez más en personas menores de 50 años. Se ha informado una predisposición hereditaria al cáncer en el 22 % de los casos de aparición temprana. La evaluación del riesgo de la línea germinal es fundamental para la atención personalizada del cáncer.OBJETIVO:Implementar la evaluación y las pruebas universales de riesgo de cáncer de línea germinal, y definir los perfiles de riesgo de cáncer de línea germinal de los pacientes que presentan una enfermedad de aparición temprana.DISEÑO:Un estudio de cohorte prospectivo.AJUSTE:Un centro médico académico de referencia terciaria.PACIENTES:Los pacientes recién diagnosticados que se presentaron en clínicas quirúrgicas entre Septiembre de 2019 y Febrero de 2021 fueron tratados en una vía de atención estandarizada que incluye una evaluación de riesgo de línea germinal universal.INTERVENCIÓN:Los pacientes recibieron material educativo sobre enfermedades de aparición temprana, pruebas genéticas y cobertura de seguro, seguido de asesoramiento genético (ya sea a distancia por telegenética o en persona). Los pacientes que dieron su consentimiento fueron evaluados en un panel de cánceres hereditarios comunes de 47 genes.MEDIDA DE RESULTADO PRINCIPAL:Proporción de pacientes con predisposición identificable al cáncer de línea germinal.RESULTADOS:Entre 500 pacientes con cáncer colorrectal, 185 (37%) tenían 50 años o menos (mediana: 44). No había antecedentes familiares en la mayoría (123, 67%) y 15 tumores (8,1%) eran deficientes en la reparación del desajuste de ácido desoxirribonucleico. La prueba de línea germinal se completó en 130 pacientes (70%); el resto estaban pendientes (7%), fallecidos (1%) o declinados (22%). Se identificaron mutaciones patogénicas de la línea germinal en 25 (de 130, 19%) pacientes: 12 en genes de reparación de errores de emparejamiento y 13 en otros genes. Se encontró una variante de significado incierto en 23 (18%) pacientes. Es importante señalar que se identificó una mutación germinal patogénica en el 12% de los pacientes sin antecedentes familiares (frente al 32% con; p = 0,015) y en el 13% de aquellos con cánceres colorrectales competentes en la reparación de errores de emparejamiento (frente al 71% si eran deficientes; p < 0,001).LIMITACIÓN:Implementado en una sola institución académica terciaria.CONCLUSIÓN:Uno de cada cinco pacientes con enfermedad de inicio joven albergaba predisposición al cáncer de línea germinal. Esta tasa de detección, junto con un alto nivel de interés y aceptación por parte de los pacientes y la viabilidad de la implementación, respaldan la evaluación universal del riesgo de cáncer de línea germinal en esta población de pacientes. Consulte el Video Resumen en http://links.lww.com/DCR/B925 . (Traducción-Dr. Yesenia Rojas-Khalil ).

Impact of cumulative operative time on postoperative complication risk in simultaneous resections of colorectal liver metastases and primary tumors.

BACKGROUND: Simultaneous resection of colorectal liver metastases (CLM) and primary colorectal cancers (CRC) is nuanced without firm rules for selection. This study aimed to identify factors associated with morbidity after simultaneous resection. METHODS: Using a prospective database, patients undergoing simultaneous CLM-CRC resection from 1/1/2017-7/1/2020 were analyzed. Regression modeling estimated impact of colorectal resection type, Kawaguchi-Gayet (KG) hepatectomy complexity, and perioperative factors on 90-day complications. RESULTS: Overall, 120 patients underwent simultaneous CLM-CRC resection. Grade≥2 complications occurred in 38.3% (n = 46); these patients experienced longer length of stay (median LOS 7.5 vs. 4, p < 0.001) and increased readmission (39% vs. 1.4%, p < 0.001) compared to patients with zero or Grade 1 complications. Median OR time was 298 min. Patients within highest operative time quartile (>506 min) had higher grade≥2 complications (57%vs. 23%, p = 0.04) and greater than 4-fold increased odds of grade≥2 morbidity (OR 4.3, 95% CI (Confidence Interval) 1.41-13.1, p = 0.01). After adjusting for Pringle time, KG complexity and colorectal resection type, increasing operative time was associated with grade≥2 complications, especially for resections in highest quartile of operative time (OR 7.28, 95% CI 1.73-30.6, p = 0.007). CONCLUSION: In patients undergoing simultaneous CLM-CRC resection, prolonged operative time is independently associated with grade≥2 complications. Awareness of cumulative operative time may inform intraoperative decision-making by surgical teams.

High Rate of Positive Circumferential Resection Margin in Colon Cancer: A National Appraisal and Call for Action.

OBJECTIVE: To identify rates of positive circumferential resection margin (CRM) for colon cancer surgery in the US. SUMMARY BACKGROUND DATA: CRM is one of the most important determinants of local control in colorectal cancers. The extent to which CRM involvement exists after colon cancer surgery is unknown. METHODS: Colon cancer cases with resection 2010 to 2015 were identified from the National Cancer Data Base. Adjusting for patient and tumor characteristics, comparisons were made between cases with CRM > 1 mm (negative margin) and those with margin involved with tumor or ≤ 1 mm (positive margin, CRM+). Hospital-level analysis was performed, examining observed-to-expected CRM+ rates. RESULTS: In total, 170,022 cases were identified: 150,291 CRM- and 19,731 CRM+ (11.6%). Pathologic T-category was the greatest predictor of CRM+, with higher rates in pT4(25.8%), pT4A(24.7%), and pT4B(31.5%) versus pT1(4.5%), pT2(6.3%) and pT3 (10.9%, P < 0.001). Within pT4 patients, predictors of CRM+ included signet-ring histology (38.1% vs 26.7% nonmucinous, and 26.9% mucinous adenocarcinoma, P < 0.001), removing < 12 lymph nodes (36.5% vs 26.1% >12, P < 0.001), community facilities (32.7%) versus academic/research (23.6%, P < 0.001), year (30.1% 2010 vs 22.6% 2015, P < 0.001), and hospital volume (24.5% highest quartile vs 32.7% lowest, P < 0.001). Across 1288 hospitals, observed-to-expected ratios for CRM+ ranged from 0 to 7.899; 429 facilities had higher than expected rates. CONCLUSIONS: Overall rate of CRM+ in US colon cancer cases is high. Variation exists across hospitals, with higher than expected rates in many facilities. Although biology is a major influencing factor, CRM+ rates represent an area for multidisciplinary improvement in quality of colon cancer care.

Magnetic Resonance Imaging Directed Surgical Decision Making for Lateral Pelvic Lymph Node Dissection in Rectal Cancer After Total Neoadjuvant Therapy (TNT).

OBJECTIVE: Lateral pelvic lymph node (LPLN) metastases are an important cause of preventable local failure in rectal cancer. The aim of this study was to evaluate clinical and oncological outcomes following magnetic resonance imaging (MRI)-directed surgical selection for lateral pelvic lymph node dissection (LPLND) after total neoadjuvant therapy (TNT). METHODS: A retrospective consecutive cohort analysis was performed of rectal cancer patients with enlarged LPLN on pretreatment MRI. Patients were categorized as LPLND or non-LPLND. The main outcomes were lateral local recurrence rate, perioperative and oncological outcomes and factors associated with decision making for LPLND. RESULTS: A total of 158 patients with enlarged pretreatment LPLN and treated with TNT were identified. Median follow-up was 20 months (interquartile range 10-32). After multidisciplinary review, 88 patients (56.0%) underwent LPLND. Mean age was 53 (SD±12) years, and 54 (34.2%) were female. Total operative time (509 vs 429 minutes; P =0.003) was greater in the LPLND group, but median blood loss ( P =0.70) or rates of major morbidity (19.3% vs 17.0%) did not differ. LPLNs were pathologically positive in 34.1%. The 3-year lateral local recurrence rates (3.4% vs 4.6%; P =0.85) did not differ between groups. Patients with LPLNs demonstrating pretreatment heterogeneity and irregular margin (odds ratio, 3.82; 95% confidence interval: 1.65-8.82) or with short-axis ≥5 mm post-TNT (odds ratio 2.69; 95% confidence interval: 1.19-6.08) were more likely to undergo LPLND. CONCLUSIONS: For rectal cancer patients with evidence of LPLN metastasis, the appropriate selection of patients for LPLND can be facilitated by a multidisciplinary MRI-directed approach with no significant difference in perioperative or oncologic outcomes.

Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution.

BACKGROUND: Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. METHODS: Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan-Meier method. RESULTS: A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. CONCLUSIONS: Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

Prognosis for Poorly Differentiated, High-Grade Rectal Neuroendocrine Carcinomas.

INTRODUCTION: Rectal neuroendocrine carcinomas (rNECs) are poorly characterized and, given their aggressive nature, optimal management is not well-established. We therefore sought to describe clinicopathologic traits, treatment details, and survival patterns for patients with rNECs. METHODS: Patients captured in the National Cancer Database (NCDB; 2004-2016) with rNECs managed with observation, chemotherapy, or proctectomy ± chemotherapy were considered for analysis. RESULTS: The inclusion criteria were met by 777 patients. Mean age was 62.4 years, 45% were male, 80% were Caucasian, 40% presented with lymph nodes metastases, and 49% presented with distant metastases. Chemotherapy and surgical resection were administered in 72 and 19% of cases, respectively. Median overall survival (OS) was 0.83 years (1 year, 41%; 3 years, 13%; 5 years, 10%). During the study interval, 659 (85%) patients died, with a median follow-up of 0.79 years. On multivariable analysis, age ≥60 years, male sex, and distant metastases were associated with worse survival; surgical resection and administration of chemotherapy were associated with a reduced risk of death. Among non-metastatic patients treated with surgical resection, administration of chemotherapy was protective, while a positive lymph node ratio (LNR) ≥42% (median value) was associated with an increased risk of death. There was no difference in the number of examined lymph nodes between LNR cohorts. CONCLUSIONS: Patients with rNECs experience dismal survival outcomes, including those with non-metastatic disease treated with curative-intent surgical resection. Neoadjuvant therapy can serve as a useful biologic test, and surgical resection should be judiciously employed.

Quality and Location of the Surgical Episode Mediate a Large Proportion of Socioeconomic-Based Survival Disparities in Patients with Resected Stage I-III Colon Cancer.

INTRODUCTION: Lower socioeconomic status (SES) is associated with shorter overall survival (OS) in patients with locoregional colon cancer. We aimed to estimate: (1) the proportion of SES-based OS disparities mediated by disparities in the quality and location of surgical treatment in patients with resected stage I-III colon cancer and (2) the relative importance of components of surgical quality. PATIENTS AND METHODS: We examined patients ages 18-80 years with resected stage I-III colon adenocarcinoma using the 2010-2016 National Cancer Database. SES was defined at the zip code level. Inverse odds weighting mediation analysis was used to estimate the proportion mediated (PM) for nine treatment quality-related and facility-related factors and composite PMs in models including all nine mediators. Models compared high SES patients with each lower SES stratum. RESULTS: Among 171,009 patients, 5-year OS increased from 70.4% in low SES patients to 78.1% in high SES. When high SES patients were compared with low, lower-middle, and upper-middle SES patients, PM ranges among lower SES strata were: minimally invasive surgery 16.0-16.6%, lymph nodes examined 7.7-9.6%, positive margins 3.8-6.5%, length of stay 16.7-28.1%, readmissions insignificant to 3.7%, treatment at > 1 CoC facility 2.7-3.1%, facility type insignificant to 7.3%, facility volume 2.9-8.2%, and adjusted facility 90-day mortality rates 33.2-42.8%. Composite PMs were 76.9% (95% CI 61.3%, 92.4%) for low SES, 68.7% (95% CI 56.4%, 81.1%) for lower-middle SES, and 60.9% (95% CI 43.1%, 78.6%) for upper-middle SES. CONCLUSIONS: These data suggest that improving the quality of the surgical episode for disadvantaged patients undergoing resection for locoregional colon cancer could decrease SES-based survival disparities by over half.

What is the Risk for Peritoneal Metastases and Survival Afterwards in T4 Colon Cancers?

BACKGROUND: Patients with T4 colon adenocarcinomas have an increased risk of peritoneal metastases (PM) but the histopathologic risk factors for its development are not well-described. OBJECTIVE: The purpose of this study was to determine factors associated with PM, time to recurrence, and survival after recurrence among patients with T4 colon cancer. PATIENTS AND METHODS: Patients with pathologic T4 colon cancer who underwent curative resection from 2005 to 2017 were identified from a prospectively maintained institutional database and classified by recurrence pattern: (a) none - 68.8%; (b) peritoneal only - 7.9%; (c) peritoneal and extraperitoneal - 9.9%; and (d) extraperitoneal only - 13.2%. Associations between PM development and patient, primary tumor, and treatment factors were assessed. RESULTS: Overall, 151 patients were analyzed, with a median follow-up of 66.2 months; 27 patients (18%) developed PM (Groups B and C) and 20 (13%) patients recurred at non-peritoneal sites only (Group D). Median time to developing metastases was shorter for Groups B and C compared with Group D (B and C: 13.7 months; D: 46.7 months; p = 0.022). Tumor deposits (TDs) and nodal stage were associated with PM (p < 0.05), and TDs (p = 0.048) and LVI (p = 0.015) were associated with additional extraperitoneal recurrence. Eleven (41%) patients with PM underwent salvage surgery, and median survival after recurrence was associated with the ability to undergo cytoreduction (risk ratio 0.20, confidence interval 0.06-0.70). CONCLUSION: PM risk after resection of T4 colon cancer is independently associated with factors related to lymphatic spread, such as N stage and TDs. Well-selected patients can undergo cytoreduction with long-term survival. These findings support frequent postoperative surveillance and aggressive early intervention, including cytoreduction.

Is neoadjuvant therapy an alternative strategy to immediate surgery in locally perforated colon cancer?

BACKGROUND: Perforations are a rare but serious complication of colorectal cancer. The current standard of treatment is emergent surgery followed by adjuvant chemotherapy. The concern with this approach is not only the uncertainty of achieving a R0 resection but also potential injury to adjacent vessels, nerves and ureters due to inflamed tissue planes. A subset of this patient population with a contained perforation who are clinically stable may have superior oncological outcomes with local sepsis control, neoadjuvant therapy followed by radical resection. The aim of this study is to report on the pre-operative safety profile for neoadjuvant therapy in the setting of an abscess from colon cancer perforation and the short-term oncological surgical quality outcomes. METHODS: In this retrospective observational study, all consecutive perforated colon cancer receiving neoadjuvant therapy from Jan 2010 to Dec 2019 were included. RESULTS: There were 21 patients that met the inclusion criteria. The most common symptom at presentation was abdominal pain (71.4%) and most common site of perforation was sigmoid colon (61.9%). Local sepsis control was achieved with a combination of radiological or surgical drainage, diverting ostomy and/or intravenous antibiotics. Thirteen patients had long-course chemoradiation and eight patients had neoadjuvant chemotherapy. Of these, 13 (61.9%) had tumour regression, with one patient having a pathological complete response. All patients achieved a R0 resection. CONCLUSIONS: In a small subset of patients with colon cancer perforation, this study has demonstrated the potential safe usage of neoadjuvant therapy first before radical surgery to achieve a clear resection margin.

Fertility discussions in young adult stage III colorectal cancer population: a single-center institution experience.

PURPOSE: Colorectal cancer (CRC) is a malignancy that usually occurs in older age individuals. However, CRC cases in young adults are on the rise, and this increase is expected to continue. Young adult CRC requires the healthcare team to familiarize themselves with the unique needs of this population, including concerns about treatment-related infertility. We performed a retrospective review to determine how often our patients, 18-39 years old (yo), had discussions regarding fertility preservation prior to starting stage III CRC treatment. METHODS: Our electronic health record was utilized to identify adult patients < 40 yo with a stage III CRC diagnosis during 1/1/2015-9/1/2019. Fertility preservation discussions were determined by searching the patient's EHR chart. Progress notes from the medical oncology, surgery, and/or radiation oncology teams were reviewed. Additionally, notes from our fertility specialist's team were reviewed when consulted. RESULTS: One hundred and three patients met criteria. Patients were 21-39 yo at diagnosis (median age of 34 yo). Fifty-two percent were male while the remaining 48% were female. Forty-six percent had stage III colon cancer while 54% had stage III rectal cancer. Search terms and progress notes were utilized to determine if discussions were documented. Fertility discussions were documented in 73% of cases while 27% of patients lacked documentation regarding fertility. CONCLUSION: Our results show that most of our young adult stage III CRC population participate in fertility preservation discussions. However, in order to capture all patients, we recognize that a more formal approach is warranted. We additionally recommend these discussions occur with all patients of child-bearing age.

The Pelvis-First Approach for Robotic Proctectomy in Patients with Redundant Abdominal Colon.

BACKGROUND: Robotic surgery is increasingly performed for low rectal cancer.1 A redundant sigmoid colon makes retraction and pelvic dissection challenging. We present a 'pelvis-first' approach to robotic proctectomy where pelvic dissection occurs prior to colonic mobilization. METHODS: A 26-year-old woman was diagnosed with a clinical T3N1 rectal adenocarcinoma at 3 cm from the anal verge. The patient had Lynch syndrome, with a germline mutation in the PMS2 gene. A near-complete clinical response was observed after neoadjuvant chemoradiation (NCRT), and the patient wished to delay surgery and permanent colostomy. Additional FOLFOX was administered and led to a complete clinical response. After 2.5 months of watchful delay of surgery, the tumor regrew, and the patient then underwent robotic abdominoperineal resection (APR). RESULTS: Initial exploration revealed a highly redundant sigmoid colon. A pelvis-first approach was undertaken. The colon was left tethered and outside of the pelvis during the pelvic dissection. The levator ani was divided transabdominally. Vascular dissection and left colon mobilization were completed after pelvic dissection.2 The specimen was removed transanally, obviating the need for abdominal incision. An end colostomy was created laparoscopically, and the perineum was closed primarily after omental flap. The patient recovered without complications. CONCLUSIONS: The 'pelvis-first' approach to proctectomy is advantageous for patients with a highly redundant sigmoid colon. Transabdominal division of the levator ani during APR ensures excellent circumferential margin. Although Lynch syndrome-associated rectal cancer can show excellent response to NCRT,3 patients undergoing watchful delay of surgery require close monitoring and prompt triggering of salvage proctectomy when tumor regrowth is observed.4,5.

Complex General Surgical Oncology Fellowship Applicants: Trends over Time and the Impact of Board Certification Eligibility.

BACKGROUND: Complex general surgical oncology (CGSO) fellowships recently obtained Accreditation Council for Graduate Medical Education (ACGME) accreditation and board certification eligibility. We aimed to characterize the applicant pool and identify factors predictive of matching into our program. METHODS: We conducted a retrospective review of CGSO fellowship applications to a major cancer center from 2008 to 2018. Data were analyzed for trends over time, including a comparison of pre- versus post-American Board of Surgery (ABS) certification eligibility. RESULTS: A total of 846 applications were reviewed. Most applicants (86.2%) trained in a US residency program; 58.4% performed ≥ 1 research year during residency; 29.6% had a dual degree. Fewer applicants (34.5%) were female, a trend which did not change over time. Post-ABS, applicants were more likely to complete ≥ 1 year between residency and fellowship (20.9% versus 13.2%, p = 0.003), to be in practice at the time of application (12.2% versus 6.6%, p = 0.005), and to reapply (5.5% versus 1.0%, p < 0.001). Post-ABS applicants listed more peer-reviewed publications (8 [interquartile range (IQR) 4, 15] versus 5 [IQR 2, 10]; p < 0.001). On multivariable analysis, factors associated with matching into our program included: US allopathic medical school graduation [odds ratio (OR) 4.6, 95% confidence interval (CI) 1.8-11.7], Alpha Omega Alpha (AOA) Honor Medical Society distinction (OR 2.7, 95% CI 1.6-4.7), dual degree (OR 2.0, 95% CI 1.1-3.4), and performance of a clinical/research rotation at our institution (OR 4.9, 95% CI 2.2-10.7). CONCLUSIONS: After establishment of CGSO board certification eligibility, applicants were more likely to apply while in practice and to reapply. A number of factors, including having a dual degree and rotating at our institution, were associated with matriculation.

Determining the Safety and Efficacy of Enhanced Recovery Protocols in Major Oncologic Surgery: An Institutional NSQIP Analysis.

BACKGROUND: Enhanced-recovery (ER) protocols are increasingly being utilized in surgical practice. Outside of colorectal surgery, however, their feasibility, safety, and efficacy in major oncologic surgery have not been proven. This study compared patient outcomes before and after multispecialty implementation of ER protocols at a large, comprehensive cancer center. METHODS: Surgical cases performed from 2011 to 2016 and captured by an institutional NSQIP database were reviewed. Following exclusion of outpatient and emergent surgeries, 2747 cases were included in the analyses. Cases were stratified by presence or absence of ER compliance, defined by preoperative patient education and electronic medical record order set-driven opioid-sparing analgesia, goal-directed fluid therapy, and early postoperative diet advancement and ambulation. RESULTS: Approximately half of patients were treated on ER protocols (46%) and the remaining on traditional postoperative (TP) protocols (54%). Treatment on an ER protocol was associated with decreased overall complication rates (20% vs. 33%, p < 0.0001), severe complication rates (7.4% vs. 10%, p = 0.010), and median hospital length of stay (4 vs. 5 days, p < 0.0001). There was no change in readmission rates (ER vs. TP, 8.6% vs. 9.0%, p = 0.701). Subanalyses of high magnitude cases and specialty-specific outcomes consistently demonstrated improved outcomes with ER protocol adherence, including decreased opioid use. CONCLUSIONS: This assessment of a large-scale ER implementation in multispecialty major oncologic surgery indicates its feasibility, safety, and efficacy. Future efforts should be directed toward defining the long-term oncologic benefits of these protocols.

Detection of Pathogenic Germline Variants Among Patients With Advanced Colorectal Cancer Undergoing Tumor Genomic Profiling for Precision Medicine.

BACKGROUND: Genomic profiling of colorectal cancer aims to identify actionable somatic mutations but can also discover incidental germline findings. OBJECTIVE: The purpose of this study was to report the detection of pathogenic germline variants that confer heritable cancer predisposition. DESIGN: This was a retrospective study. SETTINGS: The study was conducted at a tertiary-referral institution. PATIENTS: Between 2012 and 2015, 1000 patients with advanced cancer underwent targeted exome sequencing of a 202-gene panel. The subgroup of 151 patients with advanced colorectal cancer who underwent matched tumor-normal (blood) sequencing formed our study cohort. INTERVENTIONS: Germline variants in 46 genes associated with hereditary cancer predisposition were classified according to a defined algorithm based on in silico predictions of pathogenicity. Patients with presumed pathogenic variants were examined for type of mutation, as well as clinical, pedigree, and clinical genetic testing data. MAIN OUTCOME MEASURES: We measured detection of pathogenic germline variants. RESULTS: A total of 1910 distinct germline variants were observed in 151 patients. After filtering, 15 pathogenic germline variants (9.9%) were found in 15 patients, arising from 9 genes of varying penetrance for colorectal cancer (APC (n = 2; 13%), ATM (n = 1; 6%), BRCA1 (n = 2; 13%), CDH1 (n = 2; 13%), CHEK2 (n = 4; 27%), MSH2 (n = 1; 7%), MSH6 (n = 1; 7%), NF2 (n = 1; 7%), and TP53 (n = 1; 7%)). Patients with pathogenic variants were diagnosed at a younger age than those without (median, 45 vs 52 y; p = 0.03). Of the 15 patients, 7 patients (46.7%) with variants in low/moderate- penetrant genes for colorectal cancer would likely have not been tested based on clinical and pedigree criteria, where 2 harbored clinically actionable variants (CDH1 and NF2, 28.5% of 7). LIMITATIONS: This study was limited by its small sample size and advanced-stage patients. CONCLUSIONS: Tumor-normal sequencing can incidentally discover clinically unsuspected germline variants that confer cancer predisposition in 9.9% of patients with advanced colorectal cancer. Precision medicine should integrate clinical cancer genetics to inform and interpret the actionability of germline variants and to provide follow-up care to mutation carriers. See Video Abstract at http://links.lww.com/DCR/A906.

Who Should Get Lateral Pelvic Lymph Node Dissection After Neoadjuvant Chemoradiation?

BACKGROUND: Despite the use of neoadjuvant chemoradiation and total mesorectal excision for rectal cancer, lateral pelvic lymph node recurrence is still an important problem. OBJECTIVE: This study aimed to determine the indication for lateral pelvic lymph node dissection in post neoadjuvant chemoradiation rectal cancer. DESIGN: This is a retrospective analysis of a prospectively collected institutional database. SETTINGS: This study was conducted at a tertiary care cancer center from January 2006 through December 2017. PATIENTS: Patients who had rectal cancer with suspected lateral pelvic lymph node metastasis, who underwent total mesorectal excision with lateral pelvic lymph node dissection, were included. MAIN OUTCOME MEASURES: The primary outcome measured was pathologic lateral pelvic lymph node positivity. INTERVENTIONS: The associations between lateral pelvic lymph node size on post-neoadjuvant chemoradiation imaging and pathologic lateral pelvic lymph node positivity and recurrence outcomes were evaluated. RESULTS: A total of 64 patients were analyzed. The mean lateral pelvic lymph node size before and after neoadjuvant chemoradiation was 12.6 ± 9.5 mm and 8.5 ± 5.4 mm. The minimum size of positive lateral pelvic lymph node was 5 mm on post neoadjuvant chemoradiation imaging. Among 13 (20.3%) patients who had a <5 mm lateral pelvic lymph node after neoadjuvant chemoradiation, none were pathologically positive. Among 51 (79.7%) patients who had a ≥5 mm lateral pelvic lymph node after neoadjuvant chemoradiation, 33 patients (64.7%) were pathologically positive. Five-year overall survival and disease-specific survival were higher in the histologic lateral pelvic lymph node negative group than in the lateral pelvic lymph node positive group (overall survival 79.6% vs 61.8%, p = 0.122; disease-specific survival 84.5% vs 66.2%, p= 0.088). After a median 39 months of follow-up, there were no patients in the <5 mm group who died of cancer. There were no lateral compartment recurrences in the entire cohort. LIMITATIONS: Being a single-center retrospective study may limit generalizability. CONCLUSIONS: Post-neoadjuvant chemoradiation lateral pelvic lymph node size ≥5 mm was strongly associated with pathologic positivity. No patients with size <5 mm had pathologically positive lymph nodes. Following lateral pelvic lymph node dissection, no patients with a positive lateral pelvic lymph node developed lateral compartment recurrence. Therefore, patients who have rectal cancer with clinical evidence of lateral pelvic lymph node metastasis and post-neoadjuvant chemoradiation lateral pelvic lymph node size ≥5 mm should be considered for lateral pelvic lymph node dissection at the time of total mesorectal excision. See Video Abstract at http://links.lww.com/DCR/B3. ¿QUIéN DEBE RECIBIR LINFADENECTOMíA PéLVICA LATERAL DESPUéS DE LA QUIMIORRADIACIóN NEOADYUVANTE?: A pesar del uso de quimiorradiación neoadyuvante y la escisión total de mesorectao para el cáncer de recto, la recurrencia en los ganglios linfáticos pélvicos laterales sigue siendo un problema importante. OBJETIVO: Determinar la indicación para la disección de los ganglios linfáticos pélvicos laterales en el cáncer rectal post quimiorradiación neoadyuvante. DISEÑO:: Análisis retrospectivo de la base de datos institucional prospectivamente recopilada. ESCENARIO: Centro de cáncer de atención terciaria, de enero de 2006 hasta diciembre de 2017. PACIENTES: Pacientes con cáncer de recto con sospecha de metástasis en los ganglios linfáticos pélvicos laterales, que se sometieron a escisión total mesorectal con disección de los ganglios linfáticos pélvicos laterales. PRINCIPALES MEDIDAS DE RESULTADOS: Positividad de ganglios linfáticos pélvicos laterales en histopatología. INTERVENCIONES: Se evaluaron las asociaciones entre el tamaño de los ganglios linfáticos pélvicos laterales en imagenología postquimiorradiación neoadyuvante y la positividad y recurrencia en los ganglios linfáticos pélvicos laterales en histopatología. RESULTADOS: Se analizaron un total de 64 pacientes. La media del tamaño de los ganglios linfáticos pélvicos laterales antes y después de la quimiorradiación neoadyuvante fue de 12.6 ± 9.5 mm y 8.5 ± 5.4 mm, respectivamente. El tamaño mínimo de los ganglios linfáticos pélvicos laterales positivos fue de 5 mm en las imágenes postquimiorradiación neoadyuvante. Entre 13 (20.3%) pacientes que tenían <5 mm de ganglio linfático lateral pélvico después de la quimiorradiación neoadyuvante; ninguno fue positivo en histopatología. Entre 51 (79.7%) pacientes con ganglio linfático pélvico lateral ≥ 5 mm después de la quimiorradiación neoadyuvante; 33 pacientes (64.7%) fueron positivos en histopatología. La supervivencia general a 5 años y la supervivencia específica de la enfermedad fueron mayores en el grupo histológico de ganglio linfático pélvico lateral negativo que en el grupo de ganglio linfático pélvico lateral positivo (Supervivencia general 79.6% vs 61.8%, p = 0.122; Supervivencia específica de la enfermedad 84.5% vs 66.2%, p = 0.088). Después de una mediana de seguimiento de 39 meses, no hubo pacientes en el grupo de <5 mm que hayan fallecido por cáncer. No hubo recurrencias en el compartimento lateral en toda la cohorte. LIMITACIONES: Al ser un estudio retrospectivo en un solo centro puede limitar la generalización. CONCLUSIONES: El tamaño de los ganglios linfáticos pélvicos laterales postquimiorradiación neoadyuvante ≥ 5 mm se asoció fuertemente con la positividad histopatológica. Ningún paciente con tamaño <5 mm tuvo ganglios linfáticos histopatológicamente positivos. Después de la disección de los ganglios linfáticos pélvicos laterales, ningún paciente con ganglios linfáticos pélvicos laterales positivos desarrolló recurrencia del compartimiento lateral. Por lo tanto, los pacientes con cáncer rectal con evidencia clínica de metástasis en los ganglios linfáticos pélvicos laterales y tamaño de ganglios linfáticos pélvicos laterales postquimiorradiación neoadyuvante ≥ 5 mm deben considerarse para disección de los ganglios linfáticos pélvicos laterales en el momento de la escisión total de mesorrecto. Vea el Abstract en video en http://links.lww.com/DCR/B3.