Outcomes of rectal cancer patients who refuse surgery after incomplete clinical response to neoadjuvant therapy.

BACKGROUND AND OBJECTIVES: Total 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. METHODS: A 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. RESULTS: One 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. CONCLUSION: A 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.

Integrating Academic and Community Cancer Care and Research through Multidisciplinary Oncology Pathways for Value-Based Care: A Review and the City of Hope Experience.

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.

National postoperative and oncologic outcomes after pelvic exenteration for T4b rectal 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.

Health-related quality of life and oncologic outcomes after surgery in older adults with colorectal cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Impact of Surgical Resection on Survival Outcomes After Chemoradiotherapy in Anal Adenocarcinoma.

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.

Rationale, development, and design of the Altering Intake, Managing Symptoms (AIMS) dietary intervention for bowel dysfunction in rectal cancer survivors.

PURPOSE: Bowel 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. METHODS: The 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. CONCLUSIONS: The 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.

A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy.

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.

Wireless Monitoring Program of Patient-Centered Outcomes and Recovery Before and After Major Abdominal Cancer Surgery.

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.

Impact of RAS and BRAF mutations on carcinoembryonic antigen production and pattern of colorectal metastases.

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.

Accuracy of computed tomography in nodal staging of colon cancer patients.

AIM: To predict node-positive disease in colon cancer using computed tomography (CT). METHODS: American Joint Committee on Cancer stage I-III colon cancer patients who underwent curavtive-intent colectomy between 2007-2010 were identified at a single comprehensive cancer center. All patients had preoperative CT scans with original radiology reports from referring institutions. CT images underwent blinded secondary review by a surgeon and a dedicated abdominal radiologist at our institution to identify pericolonic lymph nodes (LNs). Comparison of outside CT reports to our independent imaging review was performed in order to highlight differences in detection in actual clinical practice. CT reviews were compared with final pathology. Results of the outside radiologist review, secondary radiologist review, and surgeon review were compared with the final pathologic exam to determine sensitivity, specificity, positive and negative predictive values, false positive and negative rates, and accuracy of each review. Exclusion criteria included evidence of metastatic disease on CT, rectal or appendiceal involvement, or absence of accompanying imaging from referring institutions. RESULTS: From 2007 to 2010, 64 stageI-III colon cancer patients met the eligibility criteria of our study. The mean age of the cohort was 68 years, and 26 (41%) patients were male and 38 (59%) patients were female. On final pathology, 26 of 64 (40.6%) patients had node-positive (LN+) disease and 38 of 64 (59.4%) patients had node-negative (LN-) disease. Outside radiologic review demonstrated sensitivity of 54% (14 of 26 patients) and specificity of 66% (25 of 38 patients) in predicting LN+ disease, whereas secondary radiologist review demonstrated 88% (23 of 26) sensitivity and 58% (22 of 38) specificity. On surgeon review, sensitivity was 69% (18 of 26) with 66% specificity (25 of 38). Secondary radiology review demonstrated the highest accuracy (70%) and the lowest false negative rate (12%), compared to the surgeon review at 67% accuracy and 31% false negative rate and the outside radiology review at 61% accuracy and 46% false negative rate. CONCLUSION: CT LN staging of colon cancer has moderate accuracy, with administration of NCT based on CT potentially resulting in overtreatment. Active search for LN+ may improve sensitivity at the cost of specificity.

Successful sphincter-sparing surgery for all anal fistulas.

PURPOSE: This study was designed to evaluate the success of a sphincter-sparing treatment algorithm for patients with anal fistulas. METHODS: All patients with anal fistulas presenting to a single surgeon from 1999 to 2004 were retrospectively reviewed. Patients were treated according to a sphincter-sparing algorithm that utilized three operative approaches: subcutaneous fistulotomy, seton placement followed by fibrin glue, and/or seton placement followed by rectal advancement flap. Data analyzed included: age, gender, type of fistula, operative intervention, treatment success, and functional results. RESULTS: A total of 137 patients with anal fistulas were evaluated (age range, 23-74 years). Fistula etiology was cryptoglandular in 116 (85 percent), inflammatory bowel disease in 9 (7 percent), HIV in 3 (2 percent), and miscellaneous in 9 (7 percent). A subcutaneous fistulotomy was possible in 38 patients (28 percent), and all of these patients healed. The remaining 99 patients (72 percent) with transsphincteric fistulas underwent staged procedures: 89 patients (65 percent) underwent seton placement followed by fibrin glue closure (55 healed, 62 percent success rate), 9 patients had seton placement followed by flap (9 healed, 100 percent success rate), and 1 patient had seton placement alone. Of the 34 patients with fibrin glue failure, retreatment with glue was successful in 8 of 14 (57 percent success rate). The remaining 20 patients who declined glue retreatment and the 6 patients who failed glue retreatment underwent flap (26 healed, 100 percent success rate). All fistulas healed with an average of two operations per patient, and fecal continence was maintained in all patients. CONCLUSIONS: By using staged operative procedures without any division of anal sphincter muscle, all fistulas healed with excellent functional results. A sphincter-sparing approach can successfully treat all anal fistulas.

The "cost" of operative training for surgical residents.

HYPOTHESIS: There is an increase in the amount of time required to perform an operation when the procedure involves training a surgical resident. This increased time does not translate into a financial burden for the hospital. DESIGN: Retrospective review of prospectively collected data. During the study period, surgeons and residents were blinded to the study's intent. We compared the operative times of academic surgeons performing 4 common surgical procedures before and after the introduction of a postgraduate year 3 resident into a community teaching hospital. Between January 1, 2001, and June 30, 2002, 4 academic surgeons performed operations without a resident in a community hospital that was recently integrated into a tertiary medical center system. During that period, surgeons operated alone (hernia surgery) or assisted one another (laparoscopic cholecystectomy, colectomy, and carotid endarterectomy). From July 1, 2002, through March 31, 2003, these same 4 surgeons were assisted by a postgraduate year 3 resident on similar procedures. SETTING: Community hospital recently integrated into a tertiary medical center system. PARTICIPANTS: Four experienced academic surgeons operating in the community setting and patients undergoing 1 of 4 surgical procedures (inguinal hernia repair, laparoscopic cholecystectomy, partial colectomy, or carotid endarterectomy) from January 1, 2001, through March 31, 2003. INTERVENTION: The introduction of a postgraduate year 3 surgical resident rotation into a community hospital in which the same academic surgeons had been performing operations without a resident for 18 months. MAIN OUTCOME MEASURES: Mean operating time with and without a postgraduate year 3 resident participating in 4 common surgical procedures. Result For the 4 procedures studied, there was a significant increase in the operative time required to complete such procedures. CONCLUSIONS: There is an increased time cost associated with the operative training of surgical residents. This "cost" primarily impacts the attending surgeon.

Fibrin glue for anal fistulas: long-term results.

PURPOSE: The aim of this study was to evaluate the long-term success and complication rate of fibrin-glue treatment of anal fistulas. METHODS: Patients with an anal fistula presenting to a single surgeon over a three-year period were enrolled in this study. At their first operation, all 48 patients (26-72 years old) underwent anoscopy, biopsy, destruction of the internal gland, and placement of a draining seton. Approximately two months later after preoperative bowel preparation, the seton was removed, the internal opening closed with a single suture, and fibrin glue instilled by way of the external opening to seal the fistula tract. Patients were followed closely to document the results of treatment and any complications. Long-term follow-up was done by telephone interview. RESULTS: Cause of the anal fistula was cryptoglandular in 36 (75 percent) patients, Crohn's disease in 5 (10 percent), and miscellaneous in 7 (15 percent). Median follow-up was 22 months (range, 6-46 months). After a single treatment with fibrin glue, 29 (60 percent) fistulas closed. Retreatment with fibrin glue brought the successful number of fistula tracts closed to 33 (69 percent). The 15 (29 percent) patients who failed either one or two treatments with fibrin glue were successfully treated with either fistulotomy or advancement flap. Bowel function and fecal incontinence were not altered by the fibrin-glue treatment. In one patient who failed fibrin glue, the fibrin-glue treatment may have created a more complicated fistula tract. Late recurrences (>6 months) occurred in three (6 percent) patients, two of whom were successfully retreated with fibrin glue. CONCLUSIONS: Fibrin-glue treatment of anal fistulas is successful in up to 69 percent of patients if initial failures are retreated. This sphincter-saving technique is associated with minimal complications and no functional detriment. Late recurrences are unusual.