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.

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 ).

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.

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.

Diet, weight management, physical activity and Ovarian & Breast Cancer Risk in women with BRCA1/2 pathogenic Germline gene variants: systematic review.

INTRODUCTION: Women with pathogenic germline gene variants in BRCA1 and/or BRCA2 are at increased risk of developing ovarian and breast cancer. While surgical and pharmacological approaches are effective for risk-reduction, it is unknown whether lifestyle approaches such as healthful dietary habits, weight management, and physical activity may also contribute to risk-reduction. We conducted a systematic review of evidence related to dietary habits, weight status/change, and physical activity on ovarian and breast cancer risk among women with BRCA1/2 pathogenic variants. METHODS: We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to October 3, 2019. We identified 2775 records and included 21. RESULTS: There is limited evidence related to these factors and ovarian cancer risk. For breast cancer risk, evidence suggests higher diet quality, adulthood weight-loss of ≥10 pounds, and activity during adolescence and young-adulthood may be linked with decreased risk. Higher meat intake and higher daily energy intake may be linked with increased risk. CONCLUSIONS: There is not enough evidence to suggest tailored recommendations for dietary habits or weight management among women with BRCA1/2 pathogenic variants compared to the general population for ovarian and breast cancer risk-reduction, and physical activity recommendations should remain the same.

Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features.

The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.

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.

Timing of Surgical Resection for Curative Colorectal Cancer with Liver Metastasis.

PURPOSE AND DESIGN: Optimal surgical strategy for resectable synchronous colorectal cancer with liver metastasis (SCRLM) remains a therapeutic dilemma. Multiple retrospective studies including several meta-analyses have been published since 2001 to help facilitate the decision making process and identify the optimal surgical approach. Controversy limits the generalization of available data to draw conclusions. A review of available literature on appropriate surgical timing may alleviate confusion among physicians and promote a more evidence based approach. RESULTS AND CONCLUSION: Current evidence supports the feasibility, safety, and equivalent oncological outcomes of simultaneous curative resection of stage IV colorectal cancer with liver metastasis in appropriately selected patients.

Assessment of Ileostomy Output Using Telemedicine: A Feasibility Trial.

BACKGROUND: Ileostomies are a routine part of the care of patients with rectal cancer, but are associated with significant risk for dehydration, readmission, and acute kidney injury. Telemedicine has proven beneficial in decreasing readmission in chronic medical illnesses, but its utility in patients with an ileostomy is not well studied. OBJECTIVE: The purpose of this study was to evaluate the feasibility of televideoconferencing in the assessment of ileostomy output. DESIGN: An institutional review board-approved, prospective clinical trial was conducted at a single institution from November 2014 through December 2015. SETTINGS: The study was conducted in a single, large academic medical center. PATIENTS: Patients >18 years of age undergoing surgery with plans for ileostomy were eligible. INTERVENTIONS: Televideoconference assessments of ileostomy output and the need for medical intervention were conducted during the postoperative stay and compared with in-person assessment. MAIN OUTCOME MEASURES: The primary end point of the trial was the feasibility of using teleconferencing to assess the need for medical intervention, defined as 90% agreement between telemedicine and in-person assessments. Secondary end points included patient/provider satisfaction, and correlative studies examined dehydration events and readmission. RESULTS: Twenty-seven patients underwent 44 teleconferencing assessments of ileostomy output. Compared with in-person treatment decisions, there was a 95% match (95% CI, 85%-99%). The readmission rate for the study participants was 31%, and 18% experienced dehydration events. Both patients and faculty responded favorably to surveys regarding the use of telemedicine in the perioperative period. LIMITATIONS: The study is limited by its in-hospital use of technology and small sample size. CONCLUSIONS: Televideoconference evaluation is a feasible, reliable means of assessing ileostomy output with high patient and physician acceptance. Our pilot study provides rationale for further study in the postdischarge setting for patients with ileostomies. The incorporation of televideoconference assessment within a teledischarge program may enable early intervention to improve patient outcomes. See Video Abstract at http://links.lww.com/DCR/A455.

Comparative effectiveness of primary tumor resection in patients with stage IV colon cancer.

BACKGROUND: Although the safety of combination chemotherapy without primary tumor resection (PTR) in patients with stage IV colon cancer has been established, questions remain regarding a potential survival benefit with PTR. The objective of this study was to compare mortality rates in patients who had colon cancer with unresectable metastases who did and did not undergo PTR. METHODS: An observational cohort study was conducted among patients with unresectable metastatic colon cancer identified from the National Cancer Data Base (2003-2005). Multivariate Cox regression analyses with and without propensity score weighting (PSW) were performed to compare survival outcomes. Instrumental variable analysis, using the annual hospital-level PTR rate as the instrument, was used to account for treatment selection bias. To account for survivor treatment bias, in situations in which patients might die soon after diagnosis from different reasons, a landmark method was used. RESULTS: In the total cohort, 8641 of 15,154 patients (57%) underwent PTR, and 73.8% of those procedures (4972 of 6735) were at landmark. PTR was associated with a significant reduction in mortality using Cox regression (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.44-0.47) or PSW (HR, 0.46; 95% CI, 0. 44-0.49). However, instrumental variable analysis revealed a much smaller effect (relative mortality rate, 0.91; 95% CI, 0.87-0.96). Although a smaller benefit was observed with the landmark method using Cox regression (HR, 0.6; 95% CI, 0.55-0.64) and PSW (HR, 0.59; 95% CI, 0.54-0.64), instrumental variable analysis revealed no survival benefit (relative mortality rate, 0.97; 95% CI, 0.87-1.06). CONCLUSIONS: Among patients with unresectable metastatic colon cancer, after adjustment for confounder effects, PTR was not associated with improved survival compared with systemic chemotherapy; therefore, routine noncurative PTR is not recommended. Cancer 2017;123:1124-1133. © 2016 American Cancer Society.

An international randomised trial of celecoxib versus celecoxib plus difluoromethylornithine in patients with familial adenomatous polyposis.

BACKGROUND AND AIM: Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any. METHODS: The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria. RESULTS: 112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02). CONCLUSIONS: CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number N01-CN95040.

A Prospective Six Sigma Quality Improvement Trial to Optimize Universal Screening for Genetic Syndrome Among Patients With Young-Onset Colorectal Cancer.

BACKGROUND: Improving the quality of health care is a national priority, and providing patient-centered care is one of the 6 key areas for quality improvement. In the setting of patients with young-onset colorectal cancer (CRC), appropriate genetic workup and testing for potential underlying inherited CRC syndromes is fundamental to patient-centered care. Lynch syndrome (LS) is the most common of these inherited syndromes, and current recommendations from the NCCN and other professional societies advocate universal screening for LS among young patients with CRC. However, practical implementation of these guidelines often falls short. METHODS: We conducted a prospective quality improvement intervention trial to optimize universal screening for LS in young (age <50 years) patients, involving 356 eligible patients during the 12-month preintervention period and 299 patients during the postintervention. RESULTS: Applying the Six Sigma conceptual framework, we demonstrated a significant increase in use of tumor-based molecular testing and subsequent confirmatory germline mutation testing for LS. This led to identification of more patients to be managed as having LS and of more first- and second-degree relatives to benefit from the testing results. CONCLUSIONS: This study demonstrated the successful application of a quality improvement conceptual framework for the universal adoption of molecular biomarker testing in patients with cancer, and for improving adherence to NCCN Clinical Practice Guidelines in Oncology for CRC Screening. As molecular and genetic testing is becoming increasingly common, we present a prototype study for improving the adoption of molecular studies and the provision of guideline-based patient-centered care.

Postoperative chemotherapy use after neoadjuvant chemoradiotherapy for rectal cancer: Analysis of Surveillance, Epidemiology, and End Results-Medicare data, 1998-2007.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by tumor resection and postoperative chemotherapy is the standard of care for patients with clinical stage II or III adenocarcinoma of the rectum. Significant variation exists in the receipt of postoperative chemotherapy after resection in this population. The objective of this study was to determine the demographic and clinicopathologic factors associated with the initiation of postoperative chemotherapy in elderly patients with rectal cancer and to identify potential targets for reducing treatment variation. METHODS: A retrospective cohort study was performed of patients with rectal cancer ages 66 to 80 years who received neoadjuvant chemoradiotherapy and underwent radical resection in the Surveillance, Epidemiology, and End Results-linked Medicare database (1998-2007). Multivariate logistic regression was used to assess chemotherapy use in relation to patient, tumor, and treatment response characteristics. RESULTS: Among 1492 patients who met the study criteria, 61.5% received adjuvant therapy with 5-fluorouracil. Pathologic stage was the strongest determinant of whether patients received postoperative chemotherapy (48.3% of patients with stage I disease, 59.6% of patients with stage II disease, and 77.6% of patients with stage III disease). Increasing age and postoperative readmission also were associated significantly with a decreased rate of adjuvant therapy initiation. CONCLUSIONS: Although standard treatment guidelines for locally advanced rectal cancer include postoperative chemotherapy for all patients after neoadjuvant chemoradiotherapy and radical resection, greater than 1 in 3 patients failed to receive adjuvant therapy. Despite the absence of established evidence, treatment decisions appear to be influenced by the findings at surgical pathology.

Impact of ileostomy-related complications on the multidisciplinary treatment of rectal cancer.

BACKGROUND: Radical resection is the primary treatment for rectal cancer. When anastomosis is possible, a temporary ileostomy is used to decrease morbidity from a poorly healed anastomosis. However, ileostomies are associated with complications, dehydration, and need for a second operation. We sought to evaluate the impact of ileostomy-related complications on the treatment of rectal cancer. METHODS: We conducted a retrospective study of patients who underwent sphincter-preserving surgery between January 2005 and December 2010 at a tertiary cancer center. The primary outcome was the overall rate of ileostomy-related complications. Secondary outcomes included complications related to ileostomy status, ileostomy closure, anastomotic complications at primary resection, rate of stoma closure, and completion of adjuvant chemotherapy assessed by multivariate logistic regression. RESULTS: Of 294 patients analyzed, 32% (n = 95) were women. Two hundred seventy-one (92%) received neoadjuvant chemoradiation. The median tumor distance from the anal verge was 7 cm (interquartile range 5-10 cm). Two hundred eighty-one (96%) underwent stoma closure at a median of 7 months (interquartile range 5.4-8.3 months). The most common complication related to readmission was dehydration (n = 32-11%). Readmission within 60 days of primary resection was associated with delay in initiating adjuvant chemotherapy (odds ratio 3.01, 95% confidence interval 1.42-6.38, p = 0.004). CONCLUSIONS: Diverting ileostomies created during surgical treatment of rectal cancers are associated with morbidity; however, this is balanced against the risk of anastomosis-related morbidity at rectal resection. Given the potential benefit of fecal diversion, patient-oriented interventions to improve ostomy management, particularly during adjuvant chemotherapy, can be expected to yield marked benefits.

Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience.

BACKGROUND: We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC). METHODS: We retrospectively evaluated all patients with CRC treated with IORT at our institution from 2001 to 2010. IORT was delivered using high-dose-rate brachytherapy (median 12.5-Gy). We analyzed factors associated with postoperative morbidity, local control (LC), and overall survival (OS). RESULTS: One hundred patients were evaluated with 70% received IORT for recurrent tumors. R0 resection rate was 58%. Postoperative Grade ≥3 complications (33%) were independently associated with transfusions ≥3 units packed red blood cells (P = 0.016) and body mass index (BMI) ≥35 (P = 0.0499). Eighty-two patients underwent external beam radiation therapy (EBRT) before IORT. Five-year LC was 94%, for primary and 56%, for recurrent tumors, respectively (P = 0.007). Microscopic positive (R1) margins were not associated with LC (P = 0.316). BMI ≥30 (P = 0.048) and post-discharge complications (P = 0.041) were independent risk factors for worse LC. Median post-IORT OS was 67.7 (95% CI 51.1-84.3) months for all patients. CONCLUSION: For patients with primary or recurrent locally advanced CRC, treatment with radical surgery and IORT achieved excellent LC outcomes irrespective of microscopic margin status. IORT may be indicated for tumors suspected to have close or positive microscopic margins.

Patient-reported disease knowledge and educational needs in Lynch syndrome: findings of an interactive multidisciplinary patient conference.

BACKGROUND: Patients with Lynch Syndrome, the most common hereditary colorectal cancer syndrome, benefit from genetic education and family counseling regarding diagnostic testing and cancer surveillance/prevention recommendations. Although genetic counseling is currently the most common venue where such education and counseling takes place, little is known about the level of disease knowledge and education needs as directly reported by patients and families with Lynch Syndrome. Furthermore, experiences with forums for larger-scale knowledge transfer have been limited in the current literature. METHODS: We conducted a one-day interactive multidisciplinary patient conference, designed to complement individual genetic counseling for updating disease knowledge, supportive networking and needs assessment among Lynch Syndrome patients and their family members. The patient conference was designed utilizing the conceptual framework of action research. Paired pre- and post-conference surveys were administered to 44 conference participants anonymously to assess patient-reported disease knowledge and education needs. RESULTS: A multidisciplinary team of expert providers utilized a variety of educational formats during the one-day conference. Four main focus areas were: genetic testing, surveillance/prevention, living with Lynch Syndrome, and update on research. Thirty-two participants (73%) completed the pre-conference, and 28 (64%) participants completed the post-conference surveys. Nineteen respondents were affected and the remaining were unaffected. The scores of the disease-knowledge items significantly increased from 84% pre- to 92% post-conference (p = 0.012). Patients reported a high level of satisfaction and identified further knowledge needs in nutrition (71%), surveillance/prevention options (71%), support groups (36%), cancer risk assessment (32%), active role in medical care (32%), and research opportunities (5%). CONCLUSION: Our experience with a dedicated patient education conference focused on Lynch Syndrome demonstrated that such an educational format is effective for updating or reinforcing disease knowledge, for identifying patient-reported unmet educational needs, as well as for peer-support.

Long-term results of weekly/daily cisplatin-based chemoradiation for locally advanced squamous cell carcinoma of the anal canal.

BACKGROUND: Weekly or daily cisplatin and 5-fluorouracil (5-FU)-based chemoradiation was evaluated for patients with locally advanced squamous cell carcinoma (SCC) of the anal canal treated at a single institution over a 20-year period. METHODS: A retrospective, single-institution analysis was conducted of patients receiving concurrent 5-FU/cisplatin and radiotherapy for locally advanced SCC from 1989 to 2009. Endpoints included clinical complete response rate, local recurrence rate, colostomy-free survival, disease-free survival (DFS), overall survival, and treatment-related toxicity. RESULTS: A total of 197 patients were evaluable. The majority had American Joint Committee on Cancer stage II (41%) or stage III (46%) disease; most were T2 (44%) or T3 (27%); bulky nodal disease (N2-N3) was noted in 24% of patients. Patients received weekly (20 mg/m2) or daily (4 mg/m2) cisplatin during radiotherapy. Median radiation dose was 55 Gy. Clinical complete response was observed in 185 patients (94%). After a median follow-up of 8.6 years, local recurrence rate was 11%. Sixteen patients (8%) developed distant metastases. The 5-year DFS was 81%, the 5-year overall survival was 86%, and the 5-year colostomy-free survival was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-year DFS (P = .02, 95% confidence interval = 1.17-2.01) and distant metastases (P = .046, 95% confidence interval = 1.09-2.13). Increased T-stage correlated with the necessity for salvage surgery (P = .01). CONCLUSIONS: The combination of weekly/daily cisplatin and 5-FU-based chemotherapy with concurrent radiotherapy is an effective regimen, and our long-term results indicate that cisplatin is an alternative to mitomycin C and may be considered for the treatment of locally advanced SCC of the anal canal.