Impact of neoadjuvant therapy on nodal harvest in clinical stage III rectal cancer: Establishing optimum cut-offs by disease response.

INTRODUCTION: A minimum lymph node harvest (LNH) of 12 is the current standard for appropriate nodal staging in resectable rectal cancer. However, the rise of neoadjuvant chemoradiation (NCRT) and total neoadjuvant therapy (TNT) has been associated with decreasing number of LNH. We hypothesize that as tumor response to neoadjuvant therapy increases, the optimum for LNH to achieve appropriate nodal staging should decrease. METHODS: Patients with clinical stage III rectal adenocarcinoma who underwent NCRT/TNT followed by resection were identified from the National Cancer Database. A JoinPoint regression analysis was used to determine the LNH for each tumor regression grade (TRG) category beyond which the rate of positive nodes does not significantly change. RESULTS: Thirteen thousand four hundred and twenty-six patients met inclusion criteria. Of these, 2406 (17.9%) achieved TRG 0 or ypT0 and 8210 (61.2%) achieved ypN0. Collectively, 2043 patients (15.2%) were reported to have a pathologic complete response (ypT0 ypN0). Positive pathologic nodes were found in 15%, 23%, 31%, 54%, and 53% as ypT stage increased from ypT0 to ypT4, respectively. Similarly, ypN+ rates were 15%, 36%, 41%, and 55% in TRG 0-3. No JoinPoint was identified for TRG 0, whereas inflection points were found at 6-10 nodes for TRG1 (p = 0.002) and TRG 2 (p = 0.016), and at 11-15 nodes for TRG 3. CONCLUSION: The benchmark of retrieving 12 nodes in resectable stage III rectal cancer is not consistently achieved after NCRT/TNT. We demonstrate that the LNH requirement to establish accurate pathologic nodal staging can vary depending on the tumor response to neoadjuvant therapies.

Which Treatment for Which Patient: Rectal Cancer Management After PROSPECT Trial.

Determining treatment options for patients with locally advanced rectal cancer after the PROSPECT trial data readout adds an important level to the decision-making process.

Functional quality of life among newly diagnosed young adult colorectal cancer survivors compared to older adults: results from the ColoCare Study.

PURPOSE: Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18-39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. METHODS: Participants were grouped by age (years) as follows: 18-39 (YA), 40-49, 50-64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. RESULTS: Participants (N = 1590) were n = 81 YAs, n = 196 aged 40-49, n = 627 aged 50-64, and n = 686 aged 65 + . Average physical function was better among YAs than participants aged 50-64 (p = 0.010) and 65 + (p < 0.001), and average social function was worse among YAs than aged 65 + (p = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40-49 OR = 0.13, 95%CI = 0.06-0.29; aged 50-64 OR = 0.10, 95%CI = 0.05-0.21; aged 65 + OR = 0.07, 95%CI = 0.04-0.15) and role dysfunction (aged 40-49 OR = 0.36, 95%CI = 0.18-0.75; aged 50-64 OR = 0.41, 95%CI = 0.22-0.78; aged 65 + OR = 0.32, 95%CI = 0.17-0.61). Participants aged 40-49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19-0.93). CONCLUSION: YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. TRIAL REGISTRATION: NCT02328677, registered December 2014.

Associations of combined physical activity and body mass index groups with colorectal cancer survival outcomes.

BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes. METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m2) was categorized into 'normal weight', 'overweight', and 'obese'. Patients were further classified into combined physical activity and BMI groups. Cox-proportional hazard models with Firth correction were computed to assess associations [hazard ratio (HR), 95% profile HR likelihood confidence interval (95% CI) between individual and combined physical activity and BMI groups with overall and disease-free survival in colorectal cancer patients. RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk of death or recurrence (HR: 1.41 (95% CI: 0.99-2.06), p = 0.03; HR: 1.49 (95% CI: 1.02-2.21) and HR: 1.51 (95% CI: 1.02-2.26), p = 0.04, respectively). 'Not-highly active' patients had worse disease-free survival outcomes, regardless of their BMI, compared to 'highly active/normal weight' patients. 'Not-highly active/obese' patients had a 3.66 times increased risk of death or recurrence compared to 'highly active/normal weight' patients (HR: 4.66 (95% CI: 1.75-9.10), p = 0.002). Lower activity thresholds yielded smaller effect sizes. CONCLUSION: Physical activity and BMI were individually associated with disease-free survival among colorectal cancer patients. Physical activity seems to improve survival outcomes in patients regardless of their BMI.

Return to intended oncologic therapy after colectomy for stage III colon adenocarcinoma: Does surgical approach matter?

AIM: Return to intended oncologic treatment (RIOT) is an important paradigm for surgically resected cancers requiring multimodal treatment. Benefits of minimally invasive colectomy (MIC) may allow earlier initiation of adjuvant chemotherapy (ACT) and have associated survival benefits. We sought to determine if operative approach affects RIOT timing in resected stage III colon cancer. METHODS: NCDB identified pathological stage III colon adenocarcinoma patients who underwent resection and received ACT. Propensity score matching and kernel density estimation compared operative approaches and conversion impact on intervals to RIOT. RESULTS: A total of 15,132 open colectomies (OC) versus 14,107 MIC were included. MIC patients had two-days shorter median length of stay (LOS) (4 vs. 6 days; p < 0.001), one-week shorter median time to RIOT (6 vs. 7 weeks; p = 0.015) comparing 12,867 matched pairs. There was no difference in time interval to RIOT between the LC versus RC, converted MIC vs. OC groups. MIC was a favourable predictor of earlier RIOT (HR 1.14 [1.07-1.22]; p < 0.001). CONCLUSION: MIC in stage III colon cancer is associated with a shorter time to RIOT when compared to OC. Since timely initiation of ACT may influence cancer outcome, MIC may be oncologically preferable. Prospective studies are needed to assess RIOT and survival outcomes in stage III colon cancer.

BRAF Mutations Are Associated with Poor Survival Outcomes in Advanced-stage Mismatch Repair-deficient/Microsatellite High Colorectal Cancer.

BACKGROUND: Mismatch repair-deficient (MMR-D)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) is a unique disease entity with growing interest given the rise of young-onset CRC. Given its heterogeneous behavior and potential for highly effective treatment outcomes, we sought to identify the clinical and molecular features that offer prognostic value for MMR-D CRC. MATERIALS/METHODS: This was a retrospective cohort study of patients with metastatic CRC with MMR-D or microsatellite instability in a real-world database. Overall survival (OS) was determined by the date of metastatic disease to date of death with stratification made based on factors including BRAF and RAS mutation status, age, and MMR protein loss type. RESULTS: There were 1101 patients in the study. Patients with BRAF mutations had worse OS compared with patients with wild-type BRAF with a median survival of 18.9 months versus 33.2 months (hazard ratio [HR] 1.52, 95% confidence interval [CI]: 1.25-1.86, P < .001). Patients with age >50 were found to have decreased OS versus age ≤50 with a median survival of 21.4 months versus 38.7 months (HR 1.66, 95% CI: 1.33-2.07, P < .001). BRAF mutations and age >50 remained significant predictors of OS in multivariate analysis. CONCLUSION: BRAF mutations and age >50 are associated with worse survival outcomes for patients with MMR-D mCRC. RAS mutations and specific MMR alterations are not associated with survival outcomes.

Phase I Study of Lenvatinib and Capecitabine with External Radiation Therapy in Locally Advanced Rectal Adenocarcinoma.

BACKGROUND: Neoadjuvant chemoradiation with fluoropyrimidine followed by surgery and adjuvant chemotherapy has been the standard treatment of locally advanced stages II and III rectal cancer for many years. There is a high risk for disease recurrence; therefore, optimizing chemoradiation strategies remains an unmet need. Based on a few studies, there is evidence of the synergistic effect of VEGF/PDGFR blockade with radiation. METHODS: In this phase I, dose-escalation and dose-expansion study, we studied 3 different dose levels of lenvatinib in combination with capecitabine-based chemoradiation for locally advanced rectal cancer. RESULTS: A total of 20 patients were enrolled, and 19 were eligible for assessment of efficacy. The combination was well tolerated, with an MTD of 24 mg lenvatinib. The downstaging rate for the cohort and the pCR was 84.2% and 37.8%, respectively. Blood-based protein biomarkers TSP-2, VEGF-R3, and VEGF correlated with NAR score and were also differentially expressed between response categories. The NAR, or neoadjuvant rectal score, encompasses cT clinical tumor stage, pT pathological tumor stage, and pN pathological nodal stage and provides a continuous variable for evaluating clinical trial outcomes. CONCLUSION: The combination of lenvatinib with capecitabine and radiation in locally advanced rectal cancer was found to be safe and tolerable, and potential blood-based biomarkers were identified. CLINICAL TRIAL REGISTRATION: NCT02935309.

Management of Malignant Small Bowel Obstruction: Is Intestinal Bypass Effective Palliation?

BACKGROUND/PURPOSE: Malignant small bowel obstruction (mSBO) is a common consequence of advanced malignancies. Surgical consultation is common, however data on the outcomes following an operation are lacking. We investigated a specific operative approach-intestinal bypass-to determine the outcomes associated with this intervention. METHODS: Patients with a preoperative diagnosis of mSBO who underwent intestinal bypass between 2015 and 2021 were included. Isolated colonic obstruction was excluded as was gastric outlet obstruction. Perioperative and postoperative outcomes were measured, including complications, overall survival, return to oral intake, and return to intended oncologic therapy. Patients were additionally grouped as to whether the operation was performed as elective or as inpatient. RESULTS: Overall, 55 patients were identified, with a mean age of 61.2 ± 14 years. The most common primary malignancy was colorectal cancer (65.5%) and 80% of patients had a preoperative diagnosis of metastatic disease. Small bowel to colon was the most common bypass procedure (51%). Severe complications occurred in 25.5% of patients with three in-hospital mortalities (5.5%). Survival rates at 30, 90, and 180 days were 91%, 80%, and 62%, respectively. The majority of patients were discharged to home (85.5%) and were tolerating an oral diet (74.6%). Twenty-seven patients (49.1%) returned to some form of oncologic treatment. CONCLUSIONS: Patients with mSBO face a potentially terminal condition. In this study, approximately 75% of patients who underwent intestinal bypass were able to regain the ability to eat, and 49% returned to oncologic therapy. Although retrospective, these data suggest the approach is efficacious for palliation of this difficult sequela of advanced cancer.

Neoadjuvant rectal score is prognostic for survival: A population-based propensity-matched analysis.

INTRODUCTION: Neoadjuvant rectal (NAR) score may serve as a surrogate short-term endpoint for overall survival (OS) in clinical trials. This study aims to test the NAR score using a large, national cancer registry. METHODS: National Cancer Database patients with clinical stage II/III rectal adenocarcinoma (RAC) treated with neoadjuvant chemoradiation (CRT) followed by surgery were selected and divided into low-, intermediate-, and high-NAR subgroups. OS outcomes were analyzed using Kaplan-Meier and logistic regression models. RESULTS: A total of 12 452 patients were selected, of which 5071 (40.7%) were in clinical stage II and 7381 (59.3%) were in clinical stage III; 15.2% had pathologic complete response. The mean NAR score was 10.01 ± 10.61. Six thousand nine hundred and forty-one (55.7%) did not receive adjuvant chemotherapy (AC) and were propensity-matched across NAR subgroups (966 in each group). A significant difference in 5-year OS between low-, intermediate-, and high-NAR groups was observed (85% vs. 76% vs. 68%; p < 0.001). Five thousand five hundred and eleven (44.3%) received AC and 1045 triplets were propensity-matched per NAR groups. A significant difference was again observed for 5-year OS (93% vs. 88% vs. 75%; p < 0.001). Logistic regression confirmed NAR strata as a significant predictor of 5-year OS. CONCLUSION: NAR score, as a neoadjuvant response measure, is a strong predictor of 5-year OS, regardless of AC receipt in a heterogenous population of locally advanced RAC patients.

Malignant colon polyps: predicting lymph node metastasis following endoscopic excision.

AIM: The risk of lymph node metastasis (LNM) of malignant colon polyps (MCPs) is partly estimated by histologic features of the sampled polyp. However, the routinely available histologic data is limited to tumor grade and status of lymphovascular invasion (LVI). METHODS: The NCDB for colon cancer 2004-2018 was utilized. Patients with pT1Nx adenocarcinoma arising in a polyp and undergoing partial colectomy with ≥ 12 retrieved nodes were selected. NCDB 2004-2017 was used as a training cohort to develop two scoring systems based on a multivariable regression for predictors of LNM including clinical characteristics, grade, and LVI: a nomogram scoring system (NSS) and a simplified scoring system (SSS). These models were internally validated using NCDB 2018 to calculate precision metrics for each model. RESULTS: Six thousand sixty-nine patients were selected in the training cohort. 64.5% of MCPs were in the sigmoid, and LNM rate was 11.2%. Multivariable regression identified younger age, females, hindgut location, higher grade, and LVI as significant predictors of LNM. LNM risk was 1.2% when all unfavorable predictors were absent and exceeded 10% when NSS > 70 or SSS ≥ 3. In the 2018 validation cohort, 723 patients were scored per NSS and SSS, and the negative predictive value for both was 96%. CONCLUSION: Estimating LNM risk in MCPs by applying clinical characteristics along with limited histologic data can help inform decision-making when considering formal oncologic resection. The NSS and SSS demonstrated comparable predictability of LNM among pT1Nx MCPs. The models require external validation and may be strengthened by incorporating additional endoscopic and pathologic characteristics.

Endoscopic Feature and Response Reproducibility in Tumor Assessment after Neoadjuvant Therapy for Rectal Adenocarcinoma.

BACKGROUND: The watch-and-wait approach may be safe for selected rectal cancer patients who achieve a complete clinical response after neoadjuvant treatment. Endoscopic examination is critical in determining completeness of tumor response but has not been systematically studied. METHODS: Two cross-sectional surveys, each containing endoscopic photos of rectal cancers treated with neoadjuvant therapy, were distributed to surgeons. The first survey assessed the reproducibility of eight endoscopic criteria using 41 unique endoscopic photos. The percentage of surgeons selecting each of the prespecified endoscopic criteria for each photo was calculated to determine the reproducibility of endoscopic criteria in assessing treatment and tumor response grade across multiple surgeons. The second survey included endoscopic pairs of pre- and post-neoadjuvant treatment photos of 17 patients. The surgeons were assigned a tumor response grade (clinical complete response [cCR], near complete clinical response [nCR], incomplete [iCR] clinical response), and percentages of correct diagnostic assignment were calculated. RESULTS: The findings showed significant inter- and intra-surgeon variation in the selection of predefined endoscopic features used to grade tumor response as well as significant inter- and intra-surgeon variation in the selection of the tumor response grade (cCR, nCR, or iCR). However, individual endoscopic features and tumor response grades clustered together, suggesting consistency in tumor response interpretation. Surgeons were more accurate in identifying patients with a complete response (82%) than in identifying patients with an incomplete response (68%). CONCLUSIONS: Despite inter- and intra-surgeon variation, endoscopic features were well-selected in terms of tumor response grade, suggesting consistency in endoscopic interpretation. Surgeons tended to underestimate the degree of tumor response, identifying complete responses more accurately than incomplete responses.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

How Big Is Too Big?: The Effect of Defect Size on Postoperative Complications of Vertical Rectus Abdominis Flap Reconstruction.

BACKGROUND: The vertical rectus abdominis myocutaneous (VRAM) flap has been frequently used for perineal reconstruction given the high potential for wound complications associated with direct closure of this area. However, the relationship between defect size and postoperative complications remains undefined. METHODS: A retrospective chart review of the last 20 years for VRAM flaps was performed. Defect size, age, body mass index (BMI), cause of defect, sex, radiation, and flap donor laterality were recorded. Complications of infection, partial flap loss, total flap loss, minor wounds, treated nonoperatively, and major wound, which required reoperation, were analyzed with respect to defect size. Descriptive statistics were used to summarize the demographic and clinical characteristics of the included patients. Associations were assessed using binary logistic regression analysis, and difference in means for compared groups was assessed using the independent samples t test. P values were set at 5% for all comparisons. RESULTS: There were 65 patients with VRAM flaps identified during the review period. Mean defect size was 204.71 cm2. Mean age was 63.97, and mean BMI was 27.18. History of prior radiation was noted in 90.77% of patients (n = 59). When adjusted for age and BMI, mean defect area was significantly different for patients with minor or major wounds. Larger perineal defects were associated with increased risk of major wound complications (odds ratio, 1.012; 95% confidence interval, 1.003-1.022). CONCLUSIONS: The vertical rectus abdominis flap has been a workhorse flap for perineal reconstruction. Defect size does not affect risk of partial flap necrosis, complete flap loss, infection, abdominal fascial dehiscence, ventral hernia, or seroma, which supports the utility of VRAM flap for perineal reconstruction. Larger perineal defects are associated with increased risk for major wound complications, which required reoperation, regardless of age or BMI. Future studies should be performed to determine if there is a maximum defect size cutoff that limits the utility of VRAM flap reconstruction or to develop a predictive model to assess the risk of major wound complications based on defect size.

Pretreatment CT and PET radiomics predicting rectal cancer patients in response to neoadjuvant chemoradiotherapy.

BACKGROUND: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T). MATERIALS AND METHODS: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET. RESULTS: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1-3; 91% accuracy in predicting TRG 0-1 vs. TRG 2-3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores. CONCLUSION: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.

Preoperative Radiographic Assessment Predicts Incomplete Cytoreduction in Patients with Low Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for patients with low-grade mucinous adenocarcinoma (LGMA) is most effective when complete cytoreduction is achieved. We externally validated two radiographic scoring systems to predict resectability and assessed radiographic response to systemic chemotherapy (SCT). METHODS: Patients with LGMA who received preoperative SCT followed by CRS/HIPEC from 2013 to 2016 were identified. CT scans were graded by six physicians using the simplified radiologic score (SRS) and simplified preoperative assessment of appendiceal tumor (SPAAT) systems. Positive and negative predictive values (PPV, NPV) were calculated by comparing to completeness of cytoreduction. Inter-rater agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: Twenty-four patients had preoperative SCT followed by CRS/HIPEC. Thirteen patients underwent incomplete CRS and 11 patients complete CRS. Scoring of the preoperative CT had a PPV of complete cytoreduction of 75% and 66.7% for SRS and SPAAT, respectively. NPV was 83.4% and 88.9% for SRS and SPAAT, respectively. ICC for the preoperative SRS and SPAAT score was 0.826 (95% confidence interval [CI]: 0.720-0.910] and 0.788 [0.667-0.888). Comparison of CT scans before and after SCT recorded an increase in calculated scores in 45.8% (SRS) and 50% (SPAAT) of patients. CONCLUSIONS: External validation of two radiographic scoring systems to predict complete cytoreduction showed that inter-rater agreement for both systems was good. Both scoring systems predicted incomplete cytoreduction. Applying a systematic approach to preoperative imaging review is recommended to improve treatment selection by minimizing morbidity associated with incomplete CRS and help to set patient expectations.

Repeat Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Is Not Associated with Prohibitive Complications: Results of a Multiinstitutional Retrospective Study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is offered to select patients with peritoneal metastases. In instances of recurrence/progression, a repeat CRS/HIPEC may be considered. The perioperative morbidity and the potential oncologic benefits are not well described. PATIENTS AND METHODS: We performed a retrospective analysis of a multiinstitutional database to assess the perioperative outcomes following repeat CRS/HIPEC (repeat). Kaplan-Meier and Cox estimates were used to assess survival. RESULTS: In the entire cohort, 2157 patients were analyzed, with 158 (7.3%) in the repeat cohort. The rate of complete cytoreduction was 89.8% versus 83.0% in initial versus repeat groups. The overall incidence of major complications was similar (26.3% vs. 30.7%); however, reoperation was more common in the repeat group. Perioperative outcomes such as length of stay and nonhome discharge were not significantly different. For the entire cohort, 5-year overall survival (OS) was 56.0% in the initial group and 59.5% in the repeat group. In patients with only appendiceal cancer, we observed a 5-year OS of 64.0% in the initial group compared with 67.3% in the repeat cohort. For patients with appendiceal cancer who developed a recurrence/progression, median OS was 36 months in the no repeat operation group compared with 73 months for those that did. Multivariable regression demonstrated that completeness of cytoreduction and tumor grade were associated with OS, but repeat operation was not. CONCLUSIONS: Repeat CRS/HIPEC is not associated with prohibitive risk. Survival is possibly improved, and therefore, repeat operation should be considered in selected patients with recurrent or progressive disease.

Magnetic Resonance Guided Radiotherapy for Rectal Cancer: Expanding Opportunities for Non-Operative Management.

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide, and the incidence is increasing among younger patients. 30% of these malignancies arise in the rectum. Patients with rectal cancer have historically been managed with preoperative radiation, followed by radical surgery, and adjuvant chemotherapy, with permanent colostomies in up to 20% of patients. Beginning in the early 2000s, non-operative management (NOM) of rectal cancer emerged as a viable alternative to radical surgery in select patients. Efforts have been ongoing to optimize neoadjuvant therapy for rectal cancer, thereby increasing the number of patients potentially eligible to forgo radical surgery. Magnetic resonance guided radiotherapy (MRgRT) has recently emerged as a treatment modality capable of intensifying preoperative radiation therapy for rectal cancer patients. This technology may also predict which patients will achieve a complete response to preoperative therapy, thereby allowing for more appropriate selection of patients for NOM. The present work seeks to illustrate the potential role MRgRT could play in personalizing rectal cancer treatment thus expanding the role of NOM in rectal cancer.

Modeling precision genomic-based radiation dose response in rectal cancer.

Aim: Genomic-based risk stratification to personalize radiation dose in rectal cancer. Patients & methods: We modeled genomic-based radiation dose response using the previously validated radiosensitivity index (RSI) and the clinically actionable genomic-adjusted radiation dose. Results: RSI of rectal cancer ranged from 0.19 to 0.81 in a bimodal distribution. A pathologic complete response rate of 21% was achieved in tumors with an RSI <0.31 at a minimal genomic-adjusted radiation dose of 29.76 when modeling RxRSI to the commonly prescribed physical dose of 50 Gy. RxRSI-based dose escalation to 55 Gy in tumors with an RSI of 0.31-0.34 could increase pathologic complete response by 10%. Conclusion: This study provides a theoretical platform for development of an RxRSI-based prospective trial in rectal cancer.

Value of adding dynamic contrast-enhanced MRI visual assessment to conventional MRI and clinical assessment in the diagnosis of complete tumour response to chemoradiotherapy for rectal cancer.

PURPOSE: To determine if DCE-MRI adds diagnostic value to the combined use of T2WI and DWI-MRI in the determination of clinical complete response (cCR) after neoadjuvant treatment (NAT) in patients with locally advanced rectal cancer. METHODS AND MATERIALS: In this IRB-approved, HIPAA-compliant retrospective study, response was assessed using a 5-point confidence score by T2WI and DWI-MRI only ('standard MRI'), then with addition of DCE-MRI. Review of digital rectal exams and endoscopy notes produced a clinical overall response score. The reference standard was CR by histopathology or cCR determined after a minimum of 18 months' follow-up. Diagnostic accuracy and ROC curves were calculated for standard MRI and added DCE-MRI (to detect complete or good response), for clinical evaluation (to detect CR) and for MRI and clinical methods combined. RESULTS: Of 65 patients undergoing NAT, 20 had cCR (31%). Sensitivity, specificity and area under the ROC (AUC) were 0.55, 0.87 and 0.69 for clinical evaluation; 0.42, 0.77 and 0.66 for standard MRI, and 0.53, 0.76 and 0.68 for added DCE-MRI, respectively. Combined clinical evaluation and standard MRI with DCE-MRI resulted in the highest specificity of 0.96 and highest AUC of 0.72. CONCLUSION: For the assessment of cCR after neoadjuvant therapy using clinical and multi-sequence MRI reading strategies, the addition of DCE-MRI increased specificity and PPV, but not significantly. KEY POINTS: • The addition of dynamic contrast-enhanced MRI to standard MRI, including DWI-MRI, may not significantly improve accuracy of response assessment in rectal cancer treatment. • Clinical assessment consisting of digital rectal examination and endoscopy is the most accurate standalone test to assess response to chemoradiotherapy in rectal cancer. • Combining MRI using DWI and DCE with the clinical assessment may potentially improve the accuracy for response assessment in rectal cancer.