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.

Colorectal surveillance outcomes from an institutional longitudinal cohort of lynch syndrome carriers.

Objective: Lynch Syndrome (LS) carriers have a significantly increased risk of developing colorectal cancer (CRC) during their lifetimes. Further stratification of this patient population may help in identifying additional risk factors that predispose to colorectal carcinogenesis. In most LS patients CRC may arise from adenomas, although an alternative non-polypoid carcinogenesis pathway has been proposed for PMS2 carriers. Using data from our institutional LS cohort, our aim was to describe our current colorectal screening outcomes with a focus on the incidence of adenomas in the context of different MMR genotypes and patient demographics such as gender, race, and ethnicity. Design: We collected demographics, genetic, colonoscopy, and pathology results from a total of 163 LS carriers who obtained regular screening care at MD Anderson Cancer Center. Data were extracted from the electronic health records into a REDCap database for analysis. Logistic regressions were performed to measure the association between MMR variants and the likelihood of adenomas, advanced adenomas, and CRC. Then, we analyzed the cumulative incidences of these outcomes for the first 36 months following enrollment using Kaplan-Meier incidence curves, and Cox proportional hazard regressions. Results: On multivariate analysis, age (≥45 years old) was associated with an increased risk of developing adenomas (P=0.034). Patients with a prior or active cancer status were less likely to develop adenomas (P=0.015), despite of the lack of association between surgical history with this outcome (P=0.868). We found no statistically significant difference in likelihood of adenoma development between MLH1 and MSH2/EPCAM, MSH6, and PMS2 carriers. Moreover, we observed no statistically significant difference in the likelihood of advanced adenomas or CRC for any measured covariates. On Cox proportional hazard, compared to MLH1 carriers, the incidence of adenomas was highest among MSH2/EPCAM carriers during for the first 36-months of follow-up (P<0.001). We observed a non-statistically significant trend for Hispanics having a higher and earlier cumulative incidence of adenomas compared to non-Hispanics (P=0.073). No MMR carrier was more likely to develop advanced adenomas. No difference in the incidence of CRC by MMR gene (P=0.198). Conclusion: Screening recommendations for CRC in LS patients should be based on specific MMR variants and should also be tailored to consider patient demographics.

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 ).

Colorectal cancer during pregnancy or postpartum: Case series and literature review.

Background: Colorectal cancer in young adults is on the rise. This rise combined with delayed childbearing increases the likelihood of colorectal cancer diagnosed during pregnancy or in the postpartum period. Methods: Electronic health records were used to identify individuals with colorectal cancer in pregnancy or the postpartum period from 1 August 2007 to 1 August 2019. Results: Forty-two cases were identified. Median age at diagnosis was 33 years. Most (93%) were diagnosed in an advanced stage (III or IV) and had left-sided colorectal cancer tumors (81%). Molecular analysis was completed in 18 (43%) women with microsatellite status available in 40 (95%). The findings were similar to historical controls. Sixty percent were diagnosed in the postpartum period. Common presenting symptoms were rectal bleeding and abdominal pain. Conclusion: Currently there is no consensus recommendation regarding how to manage colorectal cancer during pregnancy. Given the overlapping symptoms with pregnancy, patients often present with advanced disease. We encourage all health care professionals caring for pregnant women to fully evaluate women with persistent gastrointestinal symptoms to rule out colorectal cancer.

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.

Intraoperative Radiation After Pelvic Short Course Radiation-Based Total Neoadjuvant Therapy for Patients With Rectal Adenocarcinoma at High Risk for Local Recurrence.

BACKGROUND: Short course radiation-based total neoadjuvant therapy can improve disease-free survival for patients with high-risk locally advanced rectal cancer. Tumors that involve or threaten the circumferential resection margin have a particularly high risk of local recurrence. Intraoperative radiation therapy enables treatment escalation at the threatened or involved margin at the time of surgery. PATIENTS AND METHODS: Patients with rectal adenocarcinoma treated with preoperative short course radiotherapy-based total neoadjuvant therapy and intraoperative radiation at the time of surgery were identified. All patients had a threatened or involved circumferential resection margin on magnetic resonance imaging at the time of diagnosis. Treatment details, radiation toxicities, postoperative complications and oncologic outcomes were recorded. RESULTS: Ten patients received intraoperative radiation after short course radiation-based total neoadjuvant therapy. All patients had an involved or threatened circumferential resection margin, 60% had extramural venous invasion, and 60% had positive lateral pelvic lymph nodes. Seven patients had negative surgical margins (≥ 2 mm), and 3 patients had an R1 resection with radial margins < 2 mm. The median [IQR] length of hospitalization after surgery was 11 [7-14] days. Three patients required readmission and 2 patients required reoperation due to complications including anastamotic leak and abscess. With a median follow up of 19.5 months postoperatively, no patient developed a pelvic recurrence, and 6 patients developed distant recurrences. CONCLUSIONS: The use of intraoperative radiation after a short course radiotherapy-based neoadjuvant therapy is safe and feasible. Further data are needed to determine whether the addition of intraoperative radiation improves local recurrence rates over preoperative radiation alone.

Benchmarking Outcomes for Definitive Treatment of Young-Onset, Locally Advanced Rectal Cancer.

PURPOSE: There has been an increase in the incidence of rectal cancer diagnosed in young adults (age < 50 years). We evaluated outcomes among young adults treated with pre-operative long course chemoradiation (CRT) and total mesorectal excision (TME). METHODS: The medical records of 219 patients, age 18-49, with non-metastatic, cT3-4, or cN1-2 rectal adenocarcinoma treated from 2000 to 2017 were reviewed for demographic and treatment characteristics, as well as pathologic and oncologic outcomes. The Kaplan-Meier test, log-rank test, and Cox regression analysis were used to evaluate survival outcomes. RESULTS: The median age at diagnosis was 44 years. CRT followed by TME and post-operative chemotherapy was the most frequent treatment sequence (n = 196), with FOLFOX (n = 115) as the predominant adjuvant chemotherapy. There was no difference in sex, stage, MSS/pMMR, or pCR by age (< 45 years [n = 111] vs. ≥ 45 years [n = 108]). The 5-year rates of DFS were 77.2% for all patients, 69.8% for age < 45 years and 84.7% for age ≥ 45 years (P = .01). The 5-year rates of OS were 89.6% for all patients, 85.1% for patients with age < 45 years and 94.3% for patients with age ≥ 45 years (P = .03). Age ≥ 45 years was associated with a lower risk of disease recurrence or death on multivariable Cox regression analysis (HR = 0.55, 95% CI 0.31-0.97, P = .04). CONCLUSION: Among young adults, patients with age < 45 years had lower rates of DFS and OS, compared to those with age ≥ 45 years. These outcomes could serve as a benchmark by which to evaluate newer treatment approaches.

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer.

Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome. Methods: From 2008-2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate. Results: Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24-18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84-5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8-258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1-4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced. Conclusions: The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT00745134.

Healthy Moves to Improve Lifestyle Behaviors of Cancer Survivors and Their Spouses: Feasibility and Preliminary Results of Intervention Efficacy.

Spouses offer a primary source of support and may provide critical assistance for behavior change. A diet-exercise intervention previously found efficacious in improving cancer survivors' lifestyle behaviors was adapted to utilize a couples-based approach. The aims were to test the feasibility of this couples-based (CB) intervention and compare its efficacy to the same program delivered to the survivor-only (SO). Twenty-two survivor-spouse couples completed baseline assessments and were randomized to the CB or SO interventions. The study surpassed feasibility benchmarks; 91% of survivors and 86% of spouses completed a 6-month follow-up. Survivors and spouses attended 94% and 91% of sessions, respectively. The SO survivors showed significant improvements on the 30-s chair stand and arm curl tests, weight, and fruit and vegetable (F and V) consumption. The CB survivors showed significant improvements on the 6-min walk and 2-min step tests, body weight, and fat and F and V consumption. Improvement in the 30-s chair stand and arm curl tests was significantly better for SO survivors. The SO spouses showed no significant changes in outcome measures, but the CB spouses showed significant improvements in moderate-to-strenuous physical activity, weight, and fat and F and V consumption. Weight loss was significantly greater in CB spouses compared to SO spouses. Findings demonstrate feasibility, warranting further investigation of CB approaches to promote lifestyle change among cancer survivors and spouses.

CEA as a blood-based biomarker in anal cancer.

BACKGROUND: The clinical utility of a blood-based biomarker in squamous cell carcinoma of the anus (SCCA) is unknown. We analyzed carcinoembryonic antigen (CEA), a commonly employed assay for patients with colorectal adenocarcinoma, as a serum biomarker for patients with biopsy-proven SCCA. MATERIALS AND METHODS: Medical records from 219 patients with biopsy-proven SCCA at the University of Texas MD Anderson Cancer Center were reviewed under an IRB-approved protocol from 2013 to 2020 to assess for correlations between CEA levels and corresponding clinical and pathologic characteristics. RESULTS: The mean CEA among subgroups by clinical status at the time of presentation to our institution was highest among those patients with metastatic SCCA to visceral organs (M-V, 20.7 ng/mL), however this finding was not statistically significant by ANOVA (p = .74). By clinical subgroup, the percentage of patients with an abnormally elevated CEA was highest in those patients with metastatic disease to lymph nodes (M-L, 41.2%) followed by recurrent/unresectable SCCA (36.8%), and metastatic SCCA to visceral organs (M-V, 35.2%), and was statistically significant between groups (Fisher's exact test p = .02). Using RECIST criteria for tumor progression and disease response, the mean change in CEA for patients with progression was an increase in 19 ng/mL, compared to a change of -7.3 ng/mL in those with disease response (p = .004). We likewise assessed whether CEA levels were associated with survival outcomes for all patients with metastatic SCCA, and found no correlation between CEA and likelihood for survival in a ROC analysis (multivariate, age-adjusted analysis for CEA cutoff of 8, HR = 1.01, 95% CI 0.52-1.96). CONCLUSIONS: Despite interesting patterns of abnormally high CEA in SCCA patients with advanced disease, and correlation of increased CEA with disease progression (and conversely decreased CEA with disease response), CEA is not associated with survival outcomes in SCCA, and is not a clinically relevant biomarker in this disease.

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.

Health and lifestyle behaviors in colorectal cancer survivors with and without Lynch syndrome.

Lynch syndrome (LS), a hereditary cancer syndrome, accounts for approximately 3% of colorectal cancers (CRC). Positive health behaviors and surveillance are preventive strategies, but research on whether recommended behavioral guidelines are followed by individuals with LS is limited. Additional health education and promotion could be beneficial to the improved survivorship of CRC survivors. Explore health and lifestyle behaviors in CRC survivors with and without LS. We conducted a case-control study of CRC survivors with and without LS using a mailed questionnaire. Recruitment was conducted via patient registries at The University of Texas MD Anderson Cancer Center (cases n = 33; controls n = 75) and through social media (cases n = 42). CRC survivors with and without LS in our study had substantially lower smoking prevalence (5.5% and 2.7%) compared to national prevalence (18.0%). However, they had higher levels of alcohol consumption (36.8% and 10.3% for male and female LS survivors, respectively, and 35.8% and 22.0% for male and female sporadic survivors, respectively) compared to national prevalence of 13.88% for males and 6.02% for females. Both groups of CRC survivors participate in negative health behaviors that impact survivorship. More research is needed to examine the relationship between personal engagement in preventive behaviors and patient-provider relationships to improve health behaviors and explore strategies for intervention. Additionally, better health education and lifestyle change recommendations would promote and reinforce positive health outcomes in the CRC population and especially in LS survivors.

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.

A Phase II Study of Capecitabine/Oxaliplatin With Concurrent Radiotherapy in Locally Advanced Squamous Cell Carcinoma of the Anal Canal.

INTRODUCTION: Squamous cell carcinoma of the anal canal (SCCA) presents a rising incidence in the United States. Standard of care for locally advanced disease is comprised of infusional 5-fluorouracil with mitomycin C or cisplatin concurrent with radiation therapy (RT). We designed this trial to evaluate the efficacy and safety of a more convenient regimen composed of capecitabine and oxaliplatin. PATIENTS AND METHODS: This was a single-arm, phase II trial, with treatment-naive stage II to IIIB (TX,1-4NxM0) SCCA patients. The regimen was composed of capecitabine (825 mg/m2 twice per day for 5 days) and oxaliplatin (50 mg/m2 weekly) during weeks 1 through 6, concurrent with RT (XELOX-XRT; group 1). After the first 11 patients, the study was amended to omit chemotherapy during the third and sixth weeks (group 2). The primary objective was 3-year time to treatment failure (TTF) and safety. Secondary objectives were complete response (CR) rate, locoregional control, colostomy-free survival (CFS), and overall survival (OS). RESULTS: Twenty patients were enrolled. Seven patients of group 1 (63%) developed Grade 3 toxicity, which reduced to 22% in Group 2. No Grade 4 toxicities were noted. The median RT dose was 55 Gy. CR occurred in 100% of the 19 patients evaluable for response at 12 to 14 weeks. After a median follow-up of 47.6 months, 2 patients had local recurrence and 1 had distant recurrence. Three-year TTF was 90.0%, with similar rates between groups 1 and 2 (respectively, 90.9% vs. 88.8%, P = .984). Three-year CFS was 90.0%. The median OS has not been reached. CONCLUSION: The XELOX-XRT regimen is safe, with promising efficacy, and should be explored in larger trials for the treatment of locally advanced SCCA.

Energy balance related lifestyle factors and risk of endometrial and colorectal cancer among individuals with lynch syndrome: a systematic review.

Lifestyle factors related to energy balance, such as excess body weight, poor diet, and physical inactivity, are associated with risk of sporadic endometrial cancer (EC) and colorectal cancer (CRC). There are limited data on energy balance-related lifestyle factors and EC or CRC risk among individuals with lynch syndrome, who are at extraordinarily higher risk of developing EC or CRC. We conducted a systematic review of evidence related to weight status, weight change, dietary habits, and physical activity on EC and CRC risk among individuals with lynch syndrome. Findings are reported narratively. We searched Medline, EMBASE, CENTRAL, PubMed, and clinicaltrials.gov up to June 14th, 2018. In total, 1060 studies were identified and 16 were included. Three studies were related to EC and 13 to CRC. Overall, evidence suggests that weight status/weight change may not be associated with EC risk and multivitamin and folic-acid supplementation may be associated with decreased EC risk. Early-adulthood overweight/obese weight-status and adulthood weight-gain may be associated with increased CRC risk, whereas multivitamin supplementation, tea and high fruit intake, and physical activity may be associated with decreased CRC risk. Current evidence proposes that recommendations related to weight, some dietary habits, and physical activity recommended for the general public are also relevant to individuals with lynch syndrome. More research is needed, specifically prospective cohorts and randomized controlled trials, to determine if tailored recommendations are needed among individuals with lynch syndrome.