Disparities in Outcomes following Resection of Locally Advanced Rectal Cancer.

Surgical margins following rectal cancer resection impact oncologic outcomes. We examined the relationship between margin status and race, ethnicity, region of care, and facility type. Patients undergoing resection of a stage II-III locally advanced rectal cancer (LARC) between 2004 and 2018 were identified through the National Cancer Database. Inverse probability of treatment weighting (IPTW) was performed, with margin positivity rate as the outcome of interest, and race/ethnicity and region of care as the predictors of interest. In total, 58,389 patients were included. After IPTW adjustment, non-Hispanic Black (NHB) patients were 12% (p = 0.029) more likely to have margin positivity than non-Hispanic White (NHW) patients. Patients in the northeast were 9% less likely to have margin positivity compared to those in the south. In the west, NHB patients were more likely to have positive margins than NHW patients. Care in academic/research centers was associated with lower likelihood of positive margins compared to community centers. Within academic/research centers, NHB patients were more likely to have positive margins than non-Hispanic Other patients. Our results suggest that disparity in surgical management of LARC in NHB patients exists across regions of the country and facility types. Further research aimed at identifying drivers of this disparity is warranted.

Watch and Wait for Near-Complete Responders-A Word of Caution.

This Viewpoint discusses the establishment of a cutoff point as the watch and wait approach is increasingly used in patients with locally advanced rectal cancer.

Factors Associated With Performing IPAA After Total Colectomy for Ulcerative Colitis.

BACKGROUND: IPAA is considered the procedure of choice for restorative surgery after total colectomy for ulcerative colitis. Previous studies have examined the rate of IPAA within individual states but not at the national level in the United States. OBJECTIVE: This study aimed to assess the rate of IPAA after total colectomy for ulcerative colitis in a national population and identify factors associated with IPAA. DESIGN: This was a retrospective cohort study. SETTINGS: This study was performed in the United States. PATIENTS: Patients who were aged 18 years or older and who underwent total colectomy between 2009 and 2019 for a diagnosis of ulcerative colitis were identified within a commercial database. This database excluded patients with public insurance, including all patients older than 65 years with Medicare. MAIN OUTCOME MEASURES: The primary outcome was IPAA. Multivariable logistic regression was used to assess the association between covariates and the likelihood of undergoing IPAA. RESULTS: In total, 2816 patients were included, of whom 1414 (50.2%) underwent IPAA, 928 (33.0%) underwent no further surgery, and 474 (16.8%) underwent proctectomy with end ileostomy. Younger age, lower comorbidities, elective case, and laparoscopic approach in the initial colectomy were significantly associated with IPAA but socioeconomic status was not. LIMITATIONS: This retrospective study included only patients with commercial insurance. CONCLUSIONS: A total of 50.2% of patients who had total colectomy for ulcerative colitis underwent IPAA, and younger age, lower comorbidities, and elective cases are associated with a higher rate of IPAA placement. This study emphasizes the importance of ensuring follow-up with colorectal surgeons to provide the option of restorative surgery, especially for patients undergoing urgent or emergent colectomies. See Video Abstract . FACTORES ASOCIADOS CON LA REALIZACIN DE ANASTOMOSIS ANALBOLSA ILEAL DESPUS DE UNA COLECTOMA TOTAL POR COLITIS ULCEROSA: ANTECEDENTES:La anastomosis ileo-anal se considera el procedimiento de elección para la cirugía reparadora tras la colectomía total por colitis ulcerosa. Estudios previos han examinado la tasa de anastomosis ileo-anal dentro de los estados individuales, pero no a nivel nacional en los Estados Unidos.OBJETIVO:Evaluar la tasa de anastomosis bolsa ileal-anal después de la colectomía total para la colitis ulcerosa en una población nacional e identificar los factores asociados con la anastomosis bolsa ileal-anal.DISEÑO:Se trata de un estudio de cohortes retrospectivo.LUGAR:Este estudio se realizó en los Estados Unidos.PACIENTES:Los pacientes que tenían ≥18 años de edad que se sometieron a colectomía total entre 2009 y 2019 para un diagnóstico de colitis ulcerosa fueron identificados dentro de una base de datos comercial. Esta base de datos excluyó a los pacientes con seguro público, incluidos todos los pacientes >65 años con Medicare.MEDIDAS DE RESULTADO PRINCIPALES:El resultado primario fue la anastomosis ileal bolsa-anal. Se utilizó una regresión logística multivariable para evaluar la asociación entre las covariables y la probabilidad de someterse a una anastomosis ileal.RESULTADOS:En total, se incluyeron 2.816 pacientes, de los cuales 1.414 (50,2%) se sometieron a anastomosis ileo-anal, 928 (33,0%) no se sometieron a ninguna otra intervención quirúrgica y 474 (16,8%) se sometieron a proctectomía con ileostomía terminal. La edad más joven, las comorbilidades más bajas, el caso electivo, y el abordaje laparoscópico en la colectomía inicial se asociaron significativamente con la anastomosis ileal bolsa-anal, pero no el estatus socioeconómico.LIMITACIONES:Este estudio retrospectivo incluyó sólo pacientes con seguro comercial.CONCLUSIONES:Un 50,2% de los pacientes se someten a anastomosis ileo-anal y la edad más joven, las comorbilidades más bajas y los casos electivos se asocian con una mayor tasa de colocación de anastomosis ileo-anal. Esto subraya la importancia de asegurar el seguimiento con cirujanos colorrectales para ofrecer la opción de cirugía reparadora, especialmente en pacientes sometidos a colectomías urgentes o emergentes. (Traducción-Dr. Yolanda Colorado ).

Prediction of Pathologic Complete Response for Rectal Cancer Based on Pretreatment Factors Using Machine Learning.

BACKGROUND: Pathologic complete response after neoadjuvant therapy is an important prognostic indicator for locally advanced rectal cancer and may give insights into which patients might be treated nonoperatively in the future. Existing models for predicting pathologic complete response in the pretreatment setting are limited by small data sets and low accuracy. OBJECTIVE: We sought to use machine learning to develop a more generalizable predictive model for pathologic complete response for locally advanced rectal cancer. DESIGN: Patients with locally advanced rectal cancer who underwent neoadjuvant therapy followed by surgical resection were identified in the National Cancer Database from years 2010 to 2019 and were split into training, validation, and test sets. Machine learning techniques included random forest, gradient boosting, and artificial neural network. A logistic regression model was also created. Model performance was assessed using an area under the receiver operating characteristic curve. SETTINGS: This study used a national, multicenter data set. PATIENTS: Patients with locally advanced rectal cancer who underwent neoadjuvant therapy and proctectomy. MAIN OUTCOME MEASURES: Pathologic complete response defined as T0/xN0/x. RESULTS: The data set included 53,684 patients. Pathologic complete response was experienced by 22.9% of patients. Gradient boosting showed the best performance with an area under the receiver operating characteristic curve of 0.777 (95% CI, 0.773-0.781), compared with 0.684 (95% CI, 0.68-0.688) for logistic regression. The strongest predictors of pathologic complete response were no lymphovascular invasion, no perineural invasion, lower CEA, smaller size of tumor, and microsatellite stability. A concise model including the top 5 variables showed preserved performance. LIMITATIONS: The models were not externally validated. CONCLUSIONS: Machine learning techniques can be used to accurately predict pathologic complete response for locally advanced rectal cancer in the pretreatment setting. After fine-tuning a data set including patients treated nonoperatively, these models could help clinicians identify the appropriate candidates for a watch-and-wait strategy. See Video Abstract . EL CNCER DE RECTO BASADA EN FACTORES PREVIOS AL TRATAMIENTO MEDIANTE EL APRENDIZAJE AUTOMTICO: ANTECEDENTES:La respuesta patológica completa después de la terapia neoadyuvante es un indicador pronóstico importante para el cáncer de recto localmente avanzado y puede dar información sobre qué pacientes podrían ser tratados de forma no quirúrgica en el futuro. Los modelos existentes para predecir la respuesta patológica completa en el entorno previo al tratamiento están limitados por conjuntos de datos pequeños y baja precisión.OBJETIVO:Intentamos utilizar el aprendizaje automático para desarrollar un modelo predictivo más generalizable para la respuesta patológica completa para el cáncer de recto localmente avanzado.DISEÑO:Los pacientes con cáncer de recto localmente avanzado que se sometieron a terapia neoadyuvante seguida de resección quirúrgica se identificaron en la Base de Datos Nacional del Cáncer de los años 2010 a 2019 y se dividieron en conjuntos de capacitación, validación y prueba. Las técnicas de aprendizaje automático incluyeron bosque aleatorio, aumento de gradiente y red neuronal artificial. También se creó un modelo de regresión logística. El rendimiento del modelo se evaluó utilizando el área bajo la curva característica operativa del receptor.ÁMBITO:Este estudio utilizó un conjunto de datos nacional multicéntrico.PACIENTES:Pacientes con cáncer de recto localmente avanzado sometidos a terapia neoadyuvante y proctectomía.PRINCIPALES MEDIDAS DE VALORACIÓN:Respuesta patológica completa definida como T0/xN0/x.RESULTADOS:El conjunto de datos incluyó 53.684 pacientes. El 22,9% de los pacientes experimentaron una respuesta patológica completa. El refuerzo de gradiente mostró el mejor rendimiento con un área bajo la curva característica operativa del receptor de 0,777 (IC del 95%: 0,773 - 0,781), en comparación con 0,684 (IC del 95%: 0,68 - 0,688) para la regresión logística. Los predictores más fuertes de respuesta patológica completa fueron la ausencia de invasión linfovascular, la ausencia de invasión perineural, un CEA más bajo, un tamaño más pequeño del tumor y la estabilidad de los microsatélites. Un modelo conciso que incluye las cinco variables principales mostró un rendimiento preservado.LIMITACIONES:Los modelos no fueron validados externamente.CONCLUSIONES:Las técnicas de aprendizaje automático se pueden utilizar para predecir con precisión la respuesta patológica completa para el cáncer de recto localmente avanzado en el entorno previo al tratamiento. Después de realizar ajustes en un conjunto de datos que incluye pacientes tratados de forma no quirúrgica, estos modelos podrían ayudar a los médicos a identificar a los candidatos adecuados para una estrategia de observar y esperar. (Traducción-Dr. Ingrid Melo ).

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.To assess long-term risk of local tumor regrowth, we report updated organ preservation rate and oncologic outcomes of the OPRA trial (ClinicalTrials.gov identifier: NCT02008656). Patients with stage II/III rectal cancer were randomly assigned to receive induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT). Patients who achieved a complete or near-complete response after finishing treatment were offered watch-and-wait (WW). Total mesorectal excision (TME) was recommended for those who achieved an incomplete response. The primary end point was disease-free survival (DFS). The secondary end point was TME-free survival. In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years.

Exploring Stakeholders' Perspectives on Implementing Universal Germline Testing for Colorectal Cancer: Findings From a Clinical Practice Survey.

PURPOSE: New guidelines recommend considering germline genetic testing for all patients with colorectal cancer (CRC). However, there is a lack of data on stakeholders' perspectives on the advantages and barriers of implementing universal germline testing (UGT). This study assessed the perspectives of members of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer (CGA-IGC) regarding the implementation of UGT for patients with CRC, including readiness, logistics, and barriers. METHODS: A cross-sectional survey was sent to 317 active members of CGA-IGC. The survey included sections on demographics, clinical practice specialty, established institutional practices for testing, and questions pertaining to support of and barriers to implementing UGT for patients with CRC. RESULTS: Eighty CGA-IGC members (25%) participated, including 42 genetic counselors (53%) and 14 gastroenterologists (18%). Forty-seven (59%) reported an academic medical center as their primary work setting, and most participants (56%) had more than 10 years of clinical practice. Although most participants (73%) supported UGT, 54% indicated that changes in practice would be required before adopting UGT, and 39% indicated that these changes would be challenging to implement. There was support for both genetics and nongenetics providers to order genetic testing, and a majority (57%) supported a standardized multigene panel rather than a customized gene panel. Key barriers to UGT implementation included limited genetics knowledge among nongenetics providers, time-consuming processes for obtaining consent, ordering tests, disclosing results, and lack of insurance coverage. CONCLUSION: This study demonstrates wide support among hereditary GI cancer experts for implementation of UGT for patients with CRC. However, alternative service delivery models using nongenetics providers should be considered to address the logistical barriers to UGT implementation, particularly the growing demand for genetic testing.

"Free-Floating Anus": A Flap-Free Approach for Definitive Excision of Circumferential Giant Condyloma Acuminata.

Giant condyloma acuminata (GCA), or Buschke-Löwenstein tumor, is a rare exophytic cauliflower-like growth in the anogenital region. The spectrum of treatment options is wide, ranging from the application of topical ointments to the performance of an abdominoperineal resection. Currently, wide local excision is the most common approach and may entail the creation of a protective loop ileostomy or implementation of flaps or grafts that facilitate closure. We describe a unique surgical approach for the management of circumferential GCA void of the use a protective loop ileostomy, flaps, or grafts. Our report highlights that the implementation of a radical, circumferential, wide excision resulting in "free-floating anus" and healing via secondary intention can ultimately lead to excellent functional and cosmetic results and therefore may be considered a minimally invasive surgical option for patients afflicted with a large, circumferential GCA.

Estimating Risk of Locoregional Failure and Overall Survival in Anal Cancer Following Chemoradiation: A Machine Learning Approach.

BACKGROUND: Optimal treatment of anal squamous cell carcinoma (ASCC) is definitive chemoradiation. Patients with persistent or recurrent disease require abdominoperineal resection (APR). Current models for predicting need for APR and overall survival are limited by low accuracy or small datasets. This study sought to use machine learning (ML) to develop more accurate models for locoregional failure and overall survival for ASCC. METHODS: This study used the National Cancer Database from 2004-2018, divided into training, validation, and test sets. We included patients with stage I-III ASCC who underwent chemoradiation. Our primary outcomes were need for APR and 3-year overall survival. Random forest (RF), gradient boosting (XGB), and neural network (NN) ML-based models were developed and compared with logistic regression (LR). Accuracy was assessed using area under the receiver operating characteristic curve (AUROC). RESULTS: APR was required in 5.3% (1,015/18,978) of patients. XGB performed best with AUROC of 0.813, compared with 0.691 for LR. Tumor size, lymphovascular invasion, and tumor grade showed the strongest influence on model predictions. Mortality was 23.6% (7,988/33,834). AUROC for XGB and LR were similar at 0.766 and 0.748, respectively. For this model, age, radiation dose, sex, and insurance status were the most influential variables. CONCLUSIONS: We developed and internally validated machine learning-based models for predicting outcomes in ASCC and showed higher accuracy versus LR for locoregional failure, but not overall survival. After external validation, these models may assist clinicians with identifying patients with ASCC at high risk of treatment failure.

New Opportunities for Minimizing Toxicity in Rectal Cancer Management.

Advances in multimodal management of locally advanced rectal cancer (LARC), consisting of preoperative chemotherapy and/or radiotherapy followed by surgery with or without adjuvant chemotherapy, have improved local disease control and patient survival but are associated with significant risk for acute and long-term morbidity. Recently published trials, evaluating treatment dose intensification via the addition of preoperative induction or consolidation chemotherapy (total neoadjuvant therapy [TNT]), have demonstrated improved tumor response rates while maintaining acceptable toxicity. In addition, TNT has led to an increased number of patients achieving a clinical complete response and thus eligible to pursue a nonoperative, organ-preserving, watch and wait approach, thereby avoiding toxicities associated with surgery, such as bowel dysfunction and stoma-related complications. Ongoing trials using immune checkpoint inhibitors in patients with mismatch repair-deficient tumors suggest that this subgroup of patients with LARC could potentially be treated with immunotherapy alone, sparing them the toxicity associated with preoperative treatment and surgery. However, the majority of rectal cancers are mismatch repair-proficient and less responsive to immune checkpoint inhibitors and require multimodal management. The synergy noted in preclinical studies between immunotherapy and radiotherapy on immunogenic tumor cell death has led to the design of ongoing clinical trials that explore the benefit of combining radiotherapy, chemotherapy, and immunotherapy (mainly of immune checkpoint inhibitors) and aim to increase the number of patients eligible for organ preservation.

Current chemoprevention approaches in Lynch syndrome and Familial adenomatous polyposis: a global clinical practice survey.

Background: International chemoprevention preferences and approaches in Lynch syndrome (LS) and APC-associated polyposis, including Familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) have not been previously explored. Aim: To describe current chemoprevention strategies for patients with LS or FAP/AFAP (referred to collectively as FAP) practiced by members of four international hereditary cancer societies through administration of a survey. Results: Ninety-six participants across four hereditary gastrointestinal cancer societies responded to the survey. Most respondents (91%, 87/96) completed information regarding their demographics and practice characteristics relating to hereditary gastrointestinal cancer and chemoprevention clinical practices. Sixty-nine percent (60/87) of respondents offer chemoprevention for FAP and/or LS as a part of their practice. Of the 75% (72/96) of survey respondents who were eligible to answer practice-based clinical vignettes based off of their responses to ten barrier questions regarding chemoprevention, 88% (63/72) of those participants completed at least one case vignette question to further characterize chemoprevention practices in FAP and/or LS. In FAP, 51% (32/63) would offer chemoprevention for rectal polyposis, with sulindac - 300 mg (18%, 10/56) and aspirin (16%, 9/56) being the most frequently selected options. In LS, 93% (55/59) of professionals discuss chemoprevention and 59% (35/59) frequently recommend chemoprevention. Close to half of the respondents (47%, 26/55) would recommend beginning aspirin at time of commencement of the patient's first screening colonoscopy (usually at age 25yrs). Ninety-four percent (47/50) of respondents would consider a patient's diagnosis of LS as an influential factor for aspirin use. There was no consensus on the dose of aspirin (≤100 mg, >100 mg - 325 mg or 600 mg) to offer patients with LS and there was no agreement on how other factors, such as BMI, hypertension, family history of colorectal cancer, and family history of heart disease, would affect the recommendation for aspirin use. Possible harm among older patients (>70 years) was identified as the most common reason to discourage aspirin use. Conclusion: Although chemoprevention is widely discussed and offered to patients with FAP and LS by an international group of hereditary gastrointestinal cancer experts, there is significant heterogeneity in how it is applied in clinical practice.