Disparities in Clinical Trial Enrollment and Reporting in Rectal Cancer: A Systematic Review and Demographic Comparison to the National Cancer Database.

BACKGROUND: Cancer care guidelines based on clinical trial data in homogenous populations may not be applicable to all rectal cancer patients. The aim of this study was to evaluate whether patients enrolled in rectal cancer clinical trials (CTs) are representative of United States (U.S.) rectal cancer patients. METHODS: Prospective rectal cancer CTs from 2010 to 2019 in the United States were systematically reviewed. In trials with multiple arms reporting separate demographic variables, each arm was considered a separate CT group in the analysis. Demographic variables considered in the analysis were age, sex, race/ethnicity, facility location throughout the United States, rural vs urban geography, and facility type. Participant demographics from trial and the National Cancer Database (NCDB) participants were compared using chi-squared goodness of fit and one-sample t-test where applicable. RESULTS: Of 50 CT groups identified, 42 (82%) studies reported mean or median age. Trial participants were younger compared to NCDB patients (P < .001 all studies). All but three trials had fewer female patients than NCDB (48.2% female, P < .001). Less than half the CT groups reported on race or ethnicity. Eighteen out of 22 trials (82%) had a smaller percentage of Black patients and 4 out of 8 (50%) trials had fewer Hispanic or Spanish origin patients than the NCDB. No CTs reported comorbidities, socioeconomic factors, or education. CT primary sites were largely at academic centers and in urban areas. CONCLUSION: The present study supports the need for improved demographic representation and transparency in rectal cancer clinical trials.

Primary Colorectal Tumor Location and Predictors for Metastasis to the Brain.

Introduction Although rectal cancer is thought to have a higher rate of metastasis to the brain compared with colon cancer, there is limited and contradictory data on the subject. This study aims to determine the prevalence of brain metastasis for colon and rectal cancers (CRC), and to explore associations and predictors of brain metastasis (BM). Methods The 2010-2016 National Cancer Database (NCDB) was queried for patients with stage IV CRC. Patients with missing data on site of metastasis and primary tumor location were excluded. Chi-square test was used for categorical data and multivariate logistic regression analysis was performed to evaluate the predictors of BM. Results Of 108,540 stage IV CRC patients, the prevalence of BM was 1.21% from the right colon, 1.29% from the left colon, and 1.59% from the rectal adenocarcinoma (p<0.001). The presence of lung, bone, and liver metastases were the strongest predictors for BM. Bone and lung metastases increased the odds for BM by 3.87 (95% CI: 3.36-4.46) and 3.38 (95% CI: 3.01-3.80), respectively while the presence of liver metastasis decreased odds for BM by 55% (OR: 0.45; 95% CI: 0.40-0.50). On multivariate analysis, primary tumor location was not predictive of BM. Discussion This study helps to characterize the prevalence and associations of BM from CRC using the NCDB. The correlation between BM and bone and lung metastases, along with negative association of liver metastasis further supports the hypothesis of systemic transmission of tumor cells. Further identification of predictors and correlations with BM may help guide surveillance among patients with advanced CRC.

Factors Associated with Receipt of Adjuvant Chemotherapy in Stage II Colon Cancer.

BACKGROUND: The benefits of chemotherapy in stage II colon cancer remain unclear, but it is recommended for high-risk stage II disease. Which patients receive chemotherapy and its impact on survival remains undetermined. METHODS: The National Cancer Database was surveyed between 2004 and 2016 for stage II colon cancer patients. Patients were categorized as high- or average-risk as defined by the National Comprehensive Cancer Network. The demographic characteristics of high- and average-risk patients who did and did not receive chemotherapy were compared using univariate and multivariable analyses. The survival of high- and average-risk patients was compared based on receipt of chemotherapy with Cox hazard ratios and Kaplan-Meier curves. RESULTS: Overall, 84,424 patients met the inclusion criteria. A total of 34,868 patients were high-risk and 49,556 were average-risk. In high-risk patients, the risk factors for not receiving chemotherapy included increasing age, distance from the treatment facility, Charlson-Deyo score, and lack of insurance. In average-risk patients, factors associated with receipt of chemotherapy were decreasing age, distance from the treatment facility, Charlson-Deyo score, and non-academic association of the treatment facility. In both, chemotherapy was significantly associated with increased survival on the Kaplan-Meier curve. In the Cox hazard ratio, only high-risk patients benefited from chemotherapy (hazard ratio 1.183, confidence interval 1.116-1.254). CONCLUSIONS: Factors associated with not receiving chemotherapy in high-risk stage II colon cancers included increasing age, medical comorbidities, increasing distance from the treatment facility, and lack of insurance. Chemotherapy is associated with improved overall survival in high-risk patients.

Sarcopenia in Patients With Rectal Adenocarcinoma: An Opportunity for Preoperative Rehabilitation.

BACKGROUND: Sarcopenia, defined as low skeletal muscle mass, affects up to 60% of rectal adenocarcinoma patients receiving neoadjuvant chemoradiation (NACRT), with negative impact on patient outcomes. Identifying modifiable risk factors may decrease morbidity and mortality. METHODS: A retrospective review of rectal cancer patients from a single academic center from 2006 to 2020 was performed. Sixty-nine patients with pre- and post-NACRT CT imaging were included. Skeletal muscle index (SMI) was calculated as total L3 skeletal muscle divided by height squared. Sarcopenia thresholds were 52.4 cm2/m2 for men and 38.5 cm2/m2 for women. Student T-test, chi-square test, multivariable regression, and multivariable Cox hazard analysis were performed. RESULTS: 62.3% of patients lost SMI from pre- to post-NACRT imaging, with a mean change of -7.8% (±19.9%). Eleven (15.9%) patients were sarcopenic at presentation, increasing to 20 (29.0%) following NACRT. Mean SMI decreased from 49.0 cm2/m2 (95% CI: 42.0 cm2/m2-56.0 cm2/m2) to 38.2 cm2/m2 (95% CI: 33.6 cm2/m2-42.9 cm2/m2) (P = .003). Pre-NACRT sarcopenia correlated with post-NACRT sarcopenia (OR 20.6, P = .002). Percent decrease in SMI was associated with a 5% increased mortality risk. CONCLUSION: The presence of sarcopenia at diagnosis and its association with post-NACRT sarcopenia suggests an opportunity for a high-impact intervention.

Could meeting the standards of the National Accreditation Program for Rectal Cancer in the National Cancer Database improve patient outcomes?

AIM: The National Accreditation Program for Rectal Cancer (NAPRC) was developed to improve rectal cancer patient outcomes in the United States. The NAPRC consists of a set of process and outcome measures that hospitals must meet in order to be accredited. We aimed to assess the potential of the NAPRC by determining whether achievement of the process measures correlates with improved survival. METHODS: The National Cancer Database was used to identify patients undergoing curative proctectomy for non-metastatic rectal cancer from 2010 to 2014. NAPRC process measures identified in the National Cancer Database included clinical staging completion, treatment starting <60 days from diagnosis, carcinoembryonic antigen level measured prior to treatment, tumour regression grading and margin assessment. RESULTS: There were 48 669 patients identified with a mean age of 62 ± 12.9 years and 61.3% of patients were men. The process measure completed most often was assessment of proximal and distal margins (98.4%) and the measure completed least often was the serum carcinoembryonic antigen level prior to treatment (63.8%). All six process measures were completed in 23.6% of patients. After controlling for age, gender, comorbidities, annual facility resection volume, race and pathological stage, completion of all process measures was associated with a statistically significant mortality decrease (Cox hazard ratio 0.88, 95% CI 0.81-0.94, P < 0.001). CONCLUSION: Participating institutions provided complete datasets for all six process measures in less than a quarter of patients. Compliance with all process measures was associated with a significant mortality reduction. Improved adoption of NAPRC process measures could therefore result in improved survival rates for rectal cancer in the United States.

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy.

BACKGROUND: While neoadjuvant combined modality therapy (NA-CMT) is beneficial for most patients with locally advanced rectal cancer some patients may experience disease progression during treatment. The purpose of this study is to identify characteristics associated with progression during NA-CMT. METHODS: A single institution retrospective review of patients with stage II-III rectal cancer receiving NA-CMT was conducted from 2008-2019. Patients with incomplete or unknown NA-CMT treatment and those who received chemotherapy in addition to NA-CMT were excluded. Initial staging MRI was compared to post-operative pathology to determine progression. Definitions: responders (complete response or regression) and non-responders (stable disease or progression). RESULTS: 156 patients were included: 25 (16.1%) complete responders, 79 (50.6%) had evidence of regression, 34 (21.8%) were stable non-responders, and 18 (11.5%) were progressors. Those who progressed had worse overall survival. Factors associated with non-responders included black race (OR 4.5, 95% CI: 1.10-18.7) and increasing distance from the anal verge (OR 1.2, 95% CI: .2-2.9). Distance from the anal verge was determined via MRI. Recurrence was significantly more common among non-responders (15, 30.61%) when compared to responders (14, 13.46%), P = .012. CONCLUSION: Patients who progress despite NA-CMT have overall worse survival compared to patients who do respond. While this study failed to identify modifiable or predictive risk factors for progression, the multivariate logistic regression model suggests that race and tumor biology may play a role in progression. Future studies should focus on early identification of patients who may not benefit from NA-CMT in an effort to develop alternative treatment algorithms.

The impact of a "Residents as Teachers" Workshop at one year follow-up.

INTRODUCTION: "Residents as Teachers" (RaT) Workshops have been implemented in many General Surgery residency programs to improve resident teaching ability. The aim of this project was to assess whether there was significant degradation of teaching skills and knowledge one year after a RaT workshop. METHODS: A 4-h interactive workshop was delivered at an academic general surgery residency program. Pre- and post-workshop assessments evaluated participants' knowledge and confidence regarding teaching skills and they were re-evaluated one-year later. RESULTS: On a 5-point Likert scale, residents improved confidence and self-perception following the workshop was stable after one year. A decrease was found in the resident's perception of the education-related training received and scores on the knowledge-based questions. CONCLUSION: The confidence residents obtained from single-day RaT workshop was maintained at one year, but the knowledge was not. Resident perception of their educational training may benefit from more frequent reinforcement.

Lymph node yield after rectal resection is a predictor of survival among patients with node-negative rectal adenocarcinoma.

BACKGROUND: Pathologic review of at least 12 lymph nodes is recommended by the American Joint Committee on Cancer following surgical resection of rectal cancer. However, implications of lymph node yield on prognosis are unclear. This study evaluates the impact of lymph node yield on survival among pathologic node-negative patients who received appropriate neoadjuvant chemoradiation. METHODS: The National Cancer Database from 2010 to 2016 was queried for clinical stage II and III rectal adenocarcinoma with neoadjuvant chemoradiation, resection of the primary tumor, negative surgical margins, and pN0M0 pathologic stage. Data were analyzed with χ2, student's t test, or Mann-Whitney U test as appropriate. Propensity score matching controlled for clinicodemographic variation. Survival was estimated with Kaplan-Meier curves and Cox hazards analysis. RESULTS: Inadequate lymph node yield (1-11 nodes on pathology) led to a 29% increased risk of mortality compared to adequate lymph node yield (≥12 nodes on pathology). Among patients with an incomplete pathologic complete response to neoadjuvant therapy, 5-year survival was estimated to be 73% for inadequate lymph node yield and 78% for adequate lymph node yield (P = .002). Among patients with a complete pathologic response, 5-year survival estimated to be 82% for inadequate lymph node yield and 90% for adequate lymph node yield (P = .006). Among patients with inadequate lymph node yield and complete pathologic response, 5-year survival improved with the use of adjuvant chemotherapy (90.4%), compared to those without adjuvant chemotherapy (78.5%, P < .001). CONCLUSION: These findings suggest an inadequate lymph node yield can negatively impact survival, despite negative nodal status and a pathologic complete response to neoadjuvant therapy.

General Surgery Residents' Retention of Knowledge After an Anorectal Skills Workshop.

INTRODUCTION: Studies have demonstrated suboptimal resident exposure to anorectal pathology. A workshop was developed at an academic general surgery residency. This study assesses durability of learning from the workshop. METHODS: Thirty-six residents participated in a skills laboratory addressing diagnosis and management of anorectal complaints. The skills laboratory was broken into didactic and hand-on skills stations. Residents completed pre-, post- and 6-mo after workshop assessments to evaluate knowledge and confidence. Knowledge and confidence-based scores pre-, post- and 6-mo after workshop were compared. RESULTS: Scores demonstrated retention of information. Knowledge-based question median scores improved from 63.2% pre-workshop to 73.7% post-workshop and 76.3% at 6 mo (P = 0.0005). Median confidence scores improved from 31 pre-workshop to 40 post-workshop, and were stable at 6 mo (P = 0.0001). CONCLUSIONS: Knowledge and confidence gained from an anorectal skills workshop was stable or improved at 6 mo. These results suggest that an anorectal curriculum is effective at improving general surgery resident background knowledge and confidence when managing anorectal complaints.

Neoadjuvant radiation above NCCN guidelines for rectal cancer is associated with age under 50 and early clinical stage.

INTRODUCTION: Recent data suggest patients with early-onset rectal cancer (EORC) receive neoadjuvant radiation above recommended doses without oncologic benefit. The use of excessive radiation may lead to worse outcomes and patient harm. We sought to evaluate predictors of aggressive neoadjuvant radiation (A-XRT) use in EORC patients and compare this to late-onset rectal cancer (LORC) patients. METHODS: The National Cancer Database from 2004 to 2014 was queried for rectal adenocarcinoma patients undergoing surgical resection. Patients with stage 0 or IV disease, positive margins, and incomplete data were excluded. Standard neoadjuvant radiation (S-XRT) was based upon NCCN guidelines: 25-50.4 Gray for stage II/III patients and none for stage I. Excess radiation was considered A-XRT. Patients diagnosed at age < 50 years were labeled EORC; those ≥ 50 years were LORC. Categorical data were analyzed with chi-square test. Logistic regression was used to analyze clinicodemographic associations with A-XRT. RESULTS: 45,403 patients were included: 7999 (17.6%) EORC and 37,404 (82.4%) LORC. Multivariable logistic regression demonstrated that A-XRT use among stage I patient was associated with male gender, age under 50, urban location, mucinous histology, and poor tumor differentiation. Among stage II and III patients, A-XRT use was associated with male gender, age under 50, higher education and income, and urban location. Cox hazards did not demonstrate a significant association of A-XRT use with survival. CONCLUSION: Our data reaffirm that EORC patients more frequently receive A-XRT and that use is based on demographic features independent of tumor characteristics. Reasons for A-XRT, particularly in EORC patients, should be clarified to promote adherence to guidelines and minimize patient harm.

Predictors of curative-intent oncologic management among patients with stage IV rectal cancer.

BACKGROUND: Management of stage IV rectal adenocarcinoma is categorized into curative and palliative-intent strategies. The aim of this study is to determine the incidence of and associations with curative-intent treatment in stage IV rectal cancer. METHODS: The National Cancer Database from 2010 to 2016 was queried for patients with stage IV rectal adenocarcinoma and were grouped into curative-intent and non-curative management. Multivariable logistic regression was used to predict use of curative-intent management. RESULTS: 16,862 patients were included in this study: 4886 (30.0%) curative-intent and 11,975 (71.0%) non-curative. Multivariable regression demonstrated curative intent was associated with young age, female gender, white race, private insurance, mucinous histology and anaplastic grade. CONCLUSION: Use of curative intent oncologic management among patients with stage IV rectal adenocarcinoma is influenced by age, tumor biology and location of metastatic disease. Association with gender and insurance imply the presence of disparity in the delivery of cancer care among this patient population.

Evaluation of Demographics and Management of Rectal Cancer by Age Group: A Retrospective Propensity Matched Cohort Analysis of the National Cancer Database.

Background Data suggests there are demographic and biological differences in colon cancer between young and typical-onset patients. However, it is unclear if these differences persist in rectal cancer patients, exclusive of colon cancer. This is a retrospective review of a large national database to evaluate age-based differences in demographics, tumor features, and treatment among patients with rectal adenocarcinoma. Methods The National Cancer Database from 2004-2014 was queried for rectal adenocarcinoma. Patients were grouped by age at diagnosis: early-onset, defined as <40 years, mid-onset 40-49, and late-onset ≥50. Propensity matching controlled for demographic variation among cohorts. Pairwise Chi-square with Bonferroni correction was used for analysis. Results Thirty thousand nine hundred seventy-eight patients were included: 1,249 (4%) early-onset, 4,156 (13%) middle-onset, and 25,573 (83%) late-onset. Significant differences existed between all three cohorts in nearly all demographic and pathologic metrics. Control for demographic variation revealed early-onset and middle-onset cohorts differed only with respect to the stage at presentation, while early-onset and late-onset cohorts differed more significantly on the basis of stage, histology, and oncologic management. Conclusion The demographic differences observed demonstrate that patients under 50 should not be considered one cohort. Propensity matching led to a decrease in tumor trait differences among cohorts, suggesting that demographics other than age drive variation in tumor biology. Young patients received more aggressive management, implying the presence of an age bias. Age-based screening is likely insufficient and may exclude the rising proportion of young patients at risk for disease, while age-based management may lead to under- or overtreatment of patients at either end of the age spectrum.

Intimate Partner Violence Among Surgeons: We are Not Immune.

OBJECTIVE: The incidence and risk factors for IPV are not well-studied among surgeons. We sought to fill this gap in knowledge by surveying surgeons to estimate the incidence and identify risk factors associated with IPV. SUMMARY OF BACKGROUND DATA: An estimated 36.4% of women and 33.6% of men in the United States have experienced IPV. Risk factors include low SES, non-White ethnicity, psychiatric disorders, alcohol and drug abuse, and history of childhood abuse. Families with higher SES are not exempt from IPV, yet there is very little data examining incidence and risk factors among these populations. METHODS: An anonymous online survey targeting US-based surgeons was distributed through 4 major surgical societies. Demographics, history of abuse, and related factors were assessed. Chi-square analysis and multivariable logistic regression were utilized to evaluate for potential risk factors of IPV. RESULTS: Eight hundred eighty-two practicing surgeons and trainees completed the survey, of whom 536 (61%) reported experiencing some form of behavior consistent with IPV. The majority of respondents were women (74.1%, P = 0.004). Emotional abuse was most common (57.3%), followed by controlling behavior (35.6%), physical abuse (13.1%), and sexual abuse (9.6%).History of mental illness, [odds ratio (OR) 2.32, P < 0.001], alcohol use (frequent/daily OR 1.76, P = 0.035 and occasional OR 1.78, P = 0.015), childhood physical abuse (OR 1.96, P = 0.020), childhood emotional abuse (OR 1.76, P = 0.008), and female sex (OR 1.46, P = 0.022) were associated with IPV. CONCLUSIONS: As the first national study of IPV among surgeons, this analysis demonstrates surgeons experience IPV and share similar risk factors to the general population.

Where is the leak in the surgeon pipeline?

INTRODUCTION: In order to care for an increasingly diverse population, the surgical workforce must improve in gender, racial, and ethnic diversity. We aim to identify deficiencies in the surgical pipeline. METHODS: Data from the United States Census, Bureau of Labor Statistics, and Association of American Medical Colleges were collected from 2004 to 2018, and evaluated for changing population over time. RESULTS: Women comprise 51% of the population, 32% of surgeons, and representation is increasing at a rate of 0.4% per year. 13% of the population and 6% of surgeons are black, and representation is decreasing at a rate of -0.1% per year. Hispanics represent 18% of the population, 6% of surgeons, and representation is increasing at a rate of 0.04% per year. CONCLUSIONS: While the proportion of women and Hispanic surgeons is slowly increasing, the proportion of black surgeons is decreasing. Recruitment methods need to be focused to improve surgical workforce diversity.

Primary tumor location impacts survival in colorectal cancer patients after resection of liver metastases.

BACKGROUND AND OBJECTIVES: Right-sided colon cancers (R-CC) are associated with worse outcomes compared to left-sided colon cancers (L-CC). We hypothesize that R-CC with synchronous liver metastases who undergo resection of primary and metastatic sites have worse survival and that survival will vary significantly among R-CC, L-CC, and rectal cancer (ReC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016 was used to identify colorectal cancer patients with liver metastases who underwent surgical resection of both primary and metastatic disease. Survival was analyzed by multivariate Cox regression. RESULTS: A total of 2275 patients were included; 38% R-CC, 46% L-CC, and 16% ReC. R-CC primary tumors tended to be larger than 5 cm, higher grade, and mucinous (all P < .001). Compared to patients with R-CC, both L-CC and ReC had improved overall (HR 0.72; P < .001; HR 0.75, P = .006) and disease-specific (HR 0.71, P < .001; HR 0.73, P = .008) survival. There was no difference in survival between L-CC and ReC. CONCLUSIONS: Patients with R-CC have significantly worse survival than L-CC or ReC. This provides additional evidence that R-CC tumors are fundamentally different from L-CC and ReC tumors. Future studies should determine factors responsible for this disparity, and identify targeted treatment based on primary tumor location.

Sarcopenia is associated with worse overall survival in patients with anal squamous cell cancer.

BACKGROUND AND OBJECTIVES: Sarcopenia is associated with poor long-term outcomes in many gastrointestinal cancers, but its role in anal squamous cell carcinoma (ASCC) is not defined. We hypothesized that patients with sarcopenic ASCC experience worse long-term outcomes. METHODS: A retrospective review of patients with ASCC treated at an academic medical center from 2006 to 2017 was performed. Of 104 patients with ASCC, 64 underwent PET/computed tomography before chemoradiation and were included in the analysis. The skeletal muscle index was calculated as total L3 skeletal muscle divided by height squared. Sarcopenia thresholds were 52.4 cm2 /m2 for men and 38.5 cm2 /m2 for women. Cox regression analysis was performed to assess overall and progression-free survival. RESULTS: Twenty-five percent of the patients were sarcopenic (n = 16). Demographics were similar between groups. There was no difference in the clinical stage or comorbidities between groups. On multivariate analysis, factors associated with worse overall survival were male gender (hazard ratio [HR] 3.7, P = .022) and sarcopenia (HR 3.6, P = .019). Male gender was associated with worse progression-free survival (HR 2.6, P = .016). CONCLUSIONS: Sarcopenia is associated with worse overall survival in patients with anal cancer. Further studies are indicated to determine if survival can be improved with increased attention to nutritional status in sarcopenic patients.

Force Comparison of Commercially Available Transfascial Suture Passers.

BACKGROUND: Transfascial suture passers (TSPs) are a commonly used surgical tool available in a wide array of tip configurations. We assessed the insertion force of various TSPs in an ex vivo porcine model. METHODS: Uniform sections of porcine abdominal wall were secured to a 3D-printed platform. Nine TSPs were passed through the abdominal wall both without and with prolene suture under the following scenarios: abdominal wall only and abdominal wall plus underlay ePTFE or composite ePTFE/polypropylene mesh. Insertion forces were recorded in Newton (N). RESULTS: When passed without suture through the abdominal wall, smaller diameter TSPs required less insertional force (1.50 ± 0.17 N vs 9.68 ± 1.50 N [ P = 0.00072]). Through composite mesh, the solid tipped TSPs required less force than hollow tipped ones (3.87 ± 0.25 N vs 7.88 ± 0.20 N [ P = 0.00026]). Overall, smaller diameter TSPs required less force than the larger TSPs when passed through ePTFE empty (Gore 2.95 ± 0.83 N vs Carter-Thomason 16.07 ± 2.10 N [ P = .0005]) or with suture (Gore 8.37 ± 2.59 N vs Carter-Thomason 19.12 ± 1.10 N [ P = .003]). CONCLUSIONS: Diameter plays the greatest role in the force required for TSP penetration. However, when passed through underlay mesh or while holding suture, distal tip shape, the mechanism of suture holding, and shaft diameter all contribute to the forces necessary for penetration. These factors should be considered when choosing a TSP for intraoperative use.