Background and ObjectivesTotal mesorectal excision (TME) remains the standard of care for patients with rectal cancer who have an incomplete response to total neoadjuvant therapy (TNT). A minority of patients will refuse curative intent resection. The aim of this study is to examine the outcomes for these patients.MethodsA retrospective cohort study of stage 1-3 rectal adenocarcinoma patients who underwent neoadjuvant chemoradiation therapy or TNT at a single institution. Patients either underwent TME, watch-and-wait protocol, or if they refused TME, were counseled and watched (RCW). Clinical outcomes and resource utilization were examined in each group.ResultsOne hundred seventy-one patients (Male 59%) were included with a median surveillance of 43 months. Twenty-nine patients (17%) refused TME and had shortened overall survival (OS). Twelve patients who refused TME converted to a complete clinical response (cCR) on subsequent staging with a prolonged OS. 92% of these patients had a near cCR at initial staging endoscopy. Increased physician visits and testing was utilized in RCW and WW groups.ConclusionA significant portion of patients convert to cCR and have prolonged OS. Lengthening the time to declare cCR may be considered in select patients, such as those with a near cCR at initial endoscopic staging.

1 University of Massachusetts Chan Medical School–Baystate Health, Springfield, Massachusetts 2 City of Hope, Duarte, California Funding/Support: None reported. Financial Disclosure: None reported. All specific references to Current Procedural Terminology codes and descriptions are © 2022 American Medical Association. All rights reserved. Current Procedural Terminology is a registered trademark of the American Medical Association. Correspondence: Kelly M. Tyler, M.D., University of Massachusetts Chan Medical School–Baystate Health, 749 Chestnut St S3608, Springfield, MA 01199. E-mail: [email protected]

Stefanou, Amalia J. M.D.1; Sentovich, Stephen M. M.D., M.B.A.2; Peters, Walter R. M.D., M.B.A.3; On behalf of the Healthcare Economics Committee of the American Society of Colon and Rectal Surgeons Author Information

As the US transitions from volume- to value-based cancer care, many cancer centers and community groups have joined to share resources to deliver measurable, high-quality cancer care and clinical research with the associated high patient satisfaction, provider satisfaction, and practice health at optimal costs that are the hallmarks of value-based care. Multidisciplinary oncology care pathways are essential components of value-based care and their payment metrics. Oncology pathways are evidence-based, standardized but personalizable care plans to guide cancer care. Pathways have been developed and studied for the major medical, surgical, radiation, and supportive oncology disciplines to support decision-making, streamline care, and optimize outcomes. Implementing multidisciplinary oncology pathways can facilitate comprehensive care plans for each cancer patient throughout their cancer journey and across large multisite delivery systems. Outcomes from the delivered pathway-based care can then be evaluated against individual and population benchmarks. The complexity of adoption, implementation, and assessment of multidisciplinary oncology pathways, however, presents many challenges. We review the development and components of value-based cancer care and detail City of Hope's (COH) academic and community-team-based approaches for implementing multidisciplinary pathways. We also describe supportive components with available results towards enterprise-wide value-based care delivery.

Tyler, Kelly M. M.D.1; Baucom, Rebeccah B. M.D.2; Patel, Jitesh A. M.D., M.B.A.3; Sentovich, Stephen M. M.D., M.B.A.4; On behalf of the Healthcare Economics Committee of the American Society of Colon and Rectal SurgeonsAuthor Information

52 Background: Older adults with cancer often have age-associated vulnerabilities and challenges, especially during hospitalization. Geriatric assessment (GA) can help identify such vulnerabilities, generate recommendations, and guide the choice of interventions. Recently, GA-driven interventions have been shown to decrease chemotherapy toxicity among older adults with cancer in the outpatient setting. However, few studies have examined its role in the inpatient setting. Our purpose was to evaluate the feasibility of GA-driven interventions among hospitalized older adults with cancer. Methods: Hospitalized patients, age 75+, with a solid tumor malignancy were eligible. Each patient completed a GA while hospitalized at T1 (Timepoint 1) and one-month post discharge T2 (Timepoint 2). An Advanced Practice Nurse (APN) reviewed the T1 GA, provided targeted care utilizing GA results and implemented interventions based on predefined triggers built into the GA’s various domains. An APN also completed follow-up visits by phone at 1 week and 1 month post discharge. The primary outcome was feasibility, defined as the percentage of participants who received GA-guided interventions and was pre-specified as successful if > 80% were given recommendations. A secondary outcome of the study was to capture unplanned readmissions within 1 month post discharge. Results: Between 9/19/2017 and 5/3/2019, 49 patients were eligible and 40 were enrolled, an 82% participation rate. The median age was 80.5 years (range 75-88), 58% male, 63% Non-Hispanic white, 18% Hispanic, 15% Asian, 70% > a high school education, 73% married/partner, and 48% had stage IV cancer. Most common cancer types: GI (28%), GU (23%), lung (20%). All 40 patients (100%) had ≥ 1 predefined trigger in the GA generating interventions and completed ≥ 2 follow-up visits with the APN. In total, 857 interventions were recommended, and the mean number of interventions generated per patient was 11. The top 4 interventions were Occupational Therapy/Physical Therapy (n = 66), Social Work (n = 52), Nutrition (n = 39), and Pharmacy (n = 36). Overall 89% of GA-guided interventions were implemented. Unplanned hospital readmission was low with only one patient readmitted within 30 days (3%). Conclusions: Among hospitalized adults over age 75 with cancer, using GA to identify vulnerability, and provide GA-driven multidisciplinary interventions is feasible. Further studies are warranted to examine the impact of GA-driven interventions on outcomes among hospitalized older adults with cancer.

Background and Objectives Studies reporting outcomes after pelvic exenteration for rectal cancer are limited. The objective of this study was to evaluate early postoperative and oncologic outcomes in a national multi-institutional cohort. Methods Using the National Cancer Database (NCDB), which collects data from over 1500 commission on cancer (CoC)-accredited hospitals, we analyzed patients undergoing pelvic exenteration for T4b rectal adenocarcinoma. Results There were 1367 pelvic exenterations performed in 552 hospitals. Median age was 60 years, the majority of patients (n = 831; 60.8%) were female. Neoadjuvant radiation was used only in 57%; 24.3% of resections had positive margins. Following exenteration, 30-day mortality rate, 90-day mortality rate, and readmission rates were: 1.8%, 4.4%, and 7.4%. Age >= 60 years and higher Charlson-Deyo comorbidity index were independently associated with increased 90-day mortality (P < .001). Overall survival (OS) was 50 months. After adjustment of significant covariates, negative margin status (adjusted HR, 0.6, 95% CI, 0.5-0.8; P < .001) and receipt of perioperative radiation or chemoradiation (adjusted HR, 0.5; 95% CI, 0.4-0.6; P < .001) were significantly associated with decreased risk of death. Only 71% of the patients received perioperative radiation. Conclusions Pelvic exenterations are being performed safely in Coc-accredited hospitals. However, up to one fourth of patients undergo resections with positive margins or are subject to underutilization of perioperative radiation therapy. Increased use of radiation may increase negative margin resections and improve patient outcomes.

Data regarding changes in functional status and health-related quality of life (HRQOL) before and after surgery are lacking. We identified colorectal cancer patients from the SEER-Medicare Health Outcomes Survey (MHOS) linked database to evaluate the association between HRQOL and survival. HRQOL survey data captured physical/mental health, activities of daily living (ADLs), and medical comorbidities. Patients who underwent surgery with HRQOL surveys prior to cancer diagnosis and ≥ 1 year after diagnosis were selected. Patient, disease, and HRQOL measures were analyzed in regard to overall survival (OS), disease-specific survival (DSS), and non-DSS. Of 590 patients included, 55% were female, 75% were Caucasian, and 83% had colonic primary. Disease extent was localized for 52%, regional for 41%, and distant for 7%. Median OS was 83 months. Decreased OS was independently associated with age ≥ 75 (HR 1.7, p < 0.0001), male sex (HR 1.4, p = 0.011), advanced disease (regional—HR 2.0, p < 0.0001; distant—HR 7.0, p < 0.0001), and decreased mental HRQOL (HR 1.4, p = 0.005). Decreased DSS was independently associated with advanced disease (regional—HR 4.1, p < 0.0001; distant—HR 16.5, p < 0.0001) and rectal primary (HR 1.6, p = 0.047). Decreased non-DSS was independently associated with age ≥ 75 (HR 2.2, p < 0.0001), male sex (HR 1.4, p = 0.03), decreased mental HRQOL (HR 1.4, p = 0.02), and increased comorbidities (HR 1.4, p = 0.04). The potential overall survival benefit of oncologic surgery is diminished by declines in physical and mental health. Early identification of older surgical patients at risk for functional and HRQOL declines may improve survival following colorectal cancer surgery.

BACKGROUND:Anal adenocarcinoma is a rare malignancy with a poor prognosis, and no randomized data are available to guide management. Prior retrospective analyses offer differing conclusions on the benefit of surgical resection after chemoradiotherapy (CRT) in these patients. We used the National Cancer Database (NCDB) to analyze survival outcomes in patients undergoing CRT with and without subsequent surgical resection.METHODS:Patients with adenocarcinoma of the anus diagnosed in 2004 through 2015 were identified using the NCDB. Patients with metastatic disease and survival <90 days were excluded. We analyzed patients receiving CRT and stratified by receipt of surgical resection. Logistic regression was used to evaluate predictors of use of surgery and to form a propensity score-matched cohort. Overall survival (OS) was compared between treatment strategies using Cox proportional hazards regression.RESULTS:We identified 1,747 patients with anal adenocarcinoma receiving CRT, of whom 1,005 (58%) received surgery. Predictors of increased receipt of surgery included age <65 years, private insurance, overlapping involvement of the anus and rectum, N0 disease, and external-beam radiation dose ≥4,000 cGy. With a median follow-up of 3.5 years, 5-year OS was 61.1% in patients receiving CRT plus surgery compared with 39.8% in patients receiving CRT alone (log-rank P<.001). In multivariate analysis, surgery was associated with significantly improved OS (hazard ratio, -0.59; 95% CI, 0.50-0.68; P<.001). This survival benefit persisted in a propensity score-matched cohort (log-rank P<.001).CONCLUSIONS:In the largest series of anal adenocarcinoma cases to date, treatment with CRT followed by surgery was associated with a significant survival benefit compared with CRT alone in propensity score-matching analysis. Our findings support national guideline recommendations of neoadjuvant CRT followed by resection for patients with anal adenocarcinoma.

141 Background: Rectal cancer survivors often experience persistent long-term effects of treatment. Functional deficits, such as bowel dysfunction, are associated with poor quality of life (QOL). There is a lack of evidence-based interventions to address bowel dysfunction symptoms in rectal cancer survivors. The purpose of this abstract is to describe the development and design of the Altering Intake, Managing Symptoms (AIMS) intervention to manage bowel dysfunction in rectal cancer survivors. Methods: Survivors with stage I-III rectosigmoid colon or rectal cancer who are 6 months post-treatment, > 21 years, and English-speaking are eligible to participate. The AIMS intervention is a ten (30-40 minute) session, 4 month, telephone-based intervention delivered by trained health coaches. Outcome measures are assessed at baseline, 4 and 6 months, and include the MSKCC Bowel Function Tool, the COH-QOL-CRC, and adherence to cancer survivorship diet guidelines. Results: Based on the Chronic Care Self-Management Model (CCM), the AIMS intervention applies social cognitive theory to improve self-efficacy and self-management of bowel symptoms by coaching survivors to modify their diets to attenuate symptoms and enhance diet quality. Motivational interviewing-based behavioral approaches are applied, such as goal setting, self-monitoring, identification of barriers, and problem-solving. Monitoring of diet health involves review of 24 hour dietary recalls in conjunction with food and symptom diaries to promote survivor-directed behavior change resulting in improved bowel health. Conclusions: The AIMS intervention is among the first and few to address diet behavior changes for symptom management in rectal cancer survivors. It has the potential to positively impact the quality of long-term rectal cancer survivorship by integrating classic behavior change theories for cancer symptom management. Findings from the study will inform the design and development of future multi-institutional Phase II and III randomized trials. Clinical trial information: NCT03063918.

PurposeBowel dysfunction is a common, persistent long-term effect of treatment for rectal cancer survivors. Survivors often use dietary modifications to maintain bowel control. There are few evidence-based interventions to guide survivors on appropriate diet modifications for bowel symptom management. The purpose of this paper is to describe the development and design of the Altering Intake, Managing Symptoms (AIMS) intervention to support bowel dysfunction management in rectal cancer survivors.MethodsThe AIMS intervention is a ten-session, telephone-based diet behavior change intervention delivered by trained health coaches. It uses dietary recall, participant-completed food and symptom diaries, and health coaching guided by motivational interviewing to promote bowel symptom management and improved diet quality. Based on the Chronic Care Self-Management Model (CCM), the AIMS Intervention is designed to improve self-efficacy and self-management of bowel symptoms by coaching survivors to appropriately modify their diets through goal setting, self-monitoring, and problem-solving. The intervention targets survivors with stage I-III rectosigmoid colon/rectum cancer who are 6 months post-treatment, 21 years and older, and English-speaking.ConclusionsThe design and development process described in this paper provides an overview and underscores the potential of the AIMS intervention to positively impact the quality of long-term survivorship for rectal cancer survivors. An ongoing pilot study will inform the design and development of future multi-site Phase II and III randomized trials.

Manchio, Jeffrey V. M.D.; Sentovich, Stephen M. M.D., M.B.A.; Peters, Walter R. M.D., M.B.A. Author Information

Importance A combined subjective and objective wireless monitoring program of patient-centered outcomes can be carried out in patients before and after major abdominal cancer surgery. Objective To conduct a proof-of-concept pilot study of a wireless, patient-centered outcomes monitoring program before and after major abdominal cancer surgery. Design, Setting, and Participants In this proof-of-concept pilot study, patients wore wristband pedometers and completed online patient-reported outcome surveys (symptoms and quality of life) 3 to 7 days before surgery, during hospitalization, and up to 2 weeks after discharge. Reminders via email were generated for all moderate to severe scores for symptoms and quality of life. Surgery-related data were collected via electronic medical records, and complications were calculated using the Clavien-Dindo classification. The study was carried out in the inpatient and outpatient surgical oncology unit of one National Cancer Institute–designated comprehensive cancer center. Eligible patients were scheduled to undergo curative resection for hepatobiliary and gastrointestinal cancers, were English speaking, and were 18 years or older. Twenty participants were enrolled over 4 months. The study dates were April 1, 2015, to July 31, 2016. Main Outcomes and Measures Outcomes included adherence to wearing the pedometer, adherence to completing the surveys (MD Anderson Symptom Inventory and EuroQol 5-dimensional descriptive system), and satisfaction with the monitoring program. Results This study included a final sample of 20 patients (median age, 55.5 years [range, 22-74 years]; 15 [75%] female) with evaluable data. Pedometer adherence (88% [17 of 20] before surgery vs 83% [16 of 20] after discharge) was higher than survey adherence (65% to 75% [13 of 20 and 15 of 20] completed). The median number of daily steps at day 7 was 1689 (19% of daily steps at baseline), which correlated with the Comprehensive Complication Index, for which the median was 15 of 100 (r = −0.64, P < .05). Postdischarge overall symptom severity (2.3 of 10) and symptom interference with activities (3.5 of 10) were mild. Pain (4.4 of 10), fatigue (4.7 of 10), and appetite loss (4.0 of 10) were moderate after surgery. Quality-of-life scores were lowest at discharge (66.6 of 100) but improved at week 2 (73.9 of 100). While patient-reported outcomes returned to baseline at 2 weeks, the number of daily steps was only one-third of preoperative baseline. Conclusions and Relevance Wireless monitoring of combined subjective and objective patient-centered outcomes can be carried out in the surgical oncology setting. Preoperative and postoperative patient-centered outcomes have the potential of identifying high-risk populations who may need additional interventions to support postoperative functional and symptom recovery.

BACKGROUND:This was a first in-human, open-label, dose-escalation phase I study conducted to evaluate the maximum tolerated dose (MTD), safety, and efficacy of the combination of oral binimetinib and FOLFOX.MATERIALS AND METHODS:Patients with metastatic colorectal cancer (mCRC) who progressed on prior standard therapies received twice daily binimetinib continuously or intermittently with FOLFOX. Dose-limiting toxicities (DLTs) were assessed in the first 2 cycles of study treatment. Pharmacokinetic (PK) analysis of 5-FU and oxaliplatin was performed at the MTD in an expanded 6 patient cohort.RESULTS:Twenty-six patients were enrolled and assessed for safety. In the dose-escalation phase, no DLTs were noted in all binimetinib dosing schedules and the MTD of binimetinib in with FOLFOX was 45 mg orally twice daily. There were no significant differences in the PKs of 5-FU or oxaliplatin with or without binimetinib. Continuous dosing of binimetinib produced SD at 2 months in 9 of 13 evaluable patients and a median PFS of 3.5 months. Nine of 10 patients had PD at 2 months on the intermittent arm.CONCLUSIONS:Oral binimetinib and FOLFOX has a manageable toxicity profile and showed some evidence of antitumor activity in heavily pretreated mCRC patients.

679 Background: Pre-clinical studies have shown that the combination of MEK inhibitors and 5-FU improves antitumor activity and that MEK inhibition overcomes both 5FU and platinum resistance. This phase I study was conducted to determine the maximum tolerated dose (MTD) of the combination MEK162 and FOLFOX. Methods: Patients (pts) with metastatic colon or rectal cancer who progressed or failed prior 5FU, irinotecan, oxaliplatin and anti-EGFR therapy (in cases of RAS wild type tumors) received twice daily MEK162 in combination with every-2-week FOLFOX. Two dose levels of MEK162 (30mg and 45mg) were investigated in a standard 3 + 3 escalation design in combination with standard doses of FOLFOX without bolus 5-FU. Dose limiting toxicity (DLT) was defined as any treatment-related grade (G) 3 or 4 non-hematological toxicity (with the exception of G3 diarrhea or vomiting < 48 hrs) or G 4 neutropenia or thrombocytopenia within the first 2 cycles (4 weeks) of the treatment. Limited pharmacokinetic (PK) analysis of 5FU, oxaliplatin and MEK162 was performed at the MTD level. Results: 16 pts were enrolled (median age (range) 53 yrs (49-78); 11 men; ECOG 0/1 in 9/7 patients). No DLT was noted on the study. The MTD of MEK162 was 45 mg PO BID. An additional 6 pts (for a total of 12) were enrolled at the MTD for PK analysis and none of them developed DLT defining toxicities. A median of 8 cycles (range 1-19) was administered. Treatment-related ≥ grade 3 toxicities included anaphylaxis due to oxaliplatin (n = 1), CPK elevation (n = 2), neutropenia (n = 1), peripheral neuropathy (n = 3), thrombocytopenia (n = 1), retinal vascular disorder (n = 1), and acneiform rash (n = 1). 10 pts had SD at 2 months (m) by radiographic assessment, 5 of whom with stabilizations of > 5 months (5-10 months). There were no significant differences in the PKs of 5FU or oxaliplatin when administered with or without MEK162. Conclusions: The combination of MEK162 and FOLFOX has a manageable toxicity profile and promising antitumor activity in heavily pretreated metastatic colorectal cancer patients. Clinical trial information: NCT02041481.

AIM: To investigate the impact of RAS and BRAF mutations on the pattern of metastatic disease and carcinoembryonic antigen (CEA) production.METHODS: In this retrospective study, we investigated the impact of RAS and BRAF mutational status on pattern of metastatic disease and CEA production. Only patients presenting with a newly diagnosed metastatic colorectal cancer (CRC) were included. Patients' characteristics, primary tumor location, site of metastatic disease and CEA at presentation were compared between those with and without RAS and BRAF mutations.RESULTS: Among 174 patients, mutations in KRAS, NRAS and BRAF were detected in 47%, 3% and 6% respectively. RAS mutations (KRAS and NRAS) were more likely to be found in African American patients (87% vs 13%; P value = 0.0158). RAS mutations were associated with a higher likelihood of a normal CEA (<5 ng/mL) at presentation. BRAF mutations were more likely to occur in females. We were not able to confirm any association between mutational status and site of metastatic disease at initial diagnosis.CONCLUSION: No association was found between RAS and BRAF mutations and sites of metastatic disease at the time of initial diagnosis in our cohort. Patients with RAS mutations were more likely to present with CEA levels <5 ng/mL. These findings may have clinical implications on surveillance strategies for RAS mutant patients with earlier stages of CRC.

542 Background: Serial CEA testing is recommended in the surveillance of patients with resected stage II-IV colorectal cancer. However, the sensitivity of CEA in identifying metastatic disease has not been evaluated in the settings of RAS mutant (MT) and RAS/BRAF wild-type tumors (WT). In order to evaluate the impact of RAS mutational status on CEA production, we retrospectively evaluated a single-institute metastatic colorectal cancer (mCRC) population. Methods: We retrospectively reviewed, in a single center, all cases with mCRC with known RAS mutational status based on next generation sequencing (ONCO44 and ONCO48). These assays identify clinically relevant mutations in BRAF, KRAS, and NRAS. Additional eligibility criteria included the availability of CEA levels and imaging studies at first diagnosis of mCRC. Patient demographics, primary tumor location and sites of metastatic disease at 1 st diagnosis were captured. CEA levels were stratified as normal or elevated based on a cut point of 5ng/ml. Results: 139 mCRC patients satisfied the eligibility criteria (75 RAS-MT, 59 RAS/BRAF-WT, and 5 BRAF-MT). BRAF-MT patients were excluded from the analysis due to their small sample size. Patients with RAS/BRAF-WT tumors were more likely to present with metastatic disease to the liver, but this did not reach statistical significance (p = 0.056). There was no difference in the incidence of normal CEA at presentation in RAS-MT (30%) and RAS/BRAF-WT (28%) cohorts. CEA production was dependent on the pattern of metastatic disease. Elevated CEA was associated with the presence of liver metastases versus no metastases among RAS-MT (92% vs 47% p <.0001) and RAS/BRAF-WT patients (82% vs 50% p = 0.0101). RAS status did not impact the likelihood of CEA production within the hepatic metastases and non-hepatic metastases groups. Conclusions: RAS status does not appear to influence CEA production in patients with mCRC. CEA elevations are highly associated with liver metastases and are less prevalent in patients without hepatic involvement. These findings confirm the limited predictive value of CEA for non-hepatic recurrence, irrespective of RAS status.

Dumitra, Sinziana MD; Sun, Virginia PhD; Ruel, Nora H.; Lee, Byrne MD, FACS; Woo, Yanghee MD; Melstrom, Laleh G. MD, FACS; Melstrom, Kurt MD, FACS; Sentovich, Stephen MD, FACS; Singh, Gagandeep MD; Fong, Yuman MD, FACS Author Information

Postoperative adjuvant chemotherapy improves survival and reduces the rate of recurrence for patients with stage III colon cancer and may also improve survival in some subgroups of patients with stage II colon cancer. The recommended chemotherapeutic regimens, FOLFOX [Folinic acid (leucovorin) + 5-Fluorouracil (5-FU) + Oxaliplatin (Eloxatin)] or CapeOx (capecitabine + oxaliplatin), are more effective than past regimens, but also have more side effects. Since 5-year survival rates are improved 20–25 % with adjuvant therapy, all patients with stage III colon cancer should be evaluated for postoperative chemotherapy. For rectal cancer, neoadjuvant chemoradiotherapy is recommended for all clinical stage II and III disease to decrease recurrence. In addition, all clinical and/or histologic stage II and III rectal cancers should be considered for adjuvant chemotherapy. This chapter will review the indications, data, and outcomes for adjuvant therapy for colon and rectal cancer.