NCCN Guidelines® Insights: Rectal Cancer, Version 3.2024.

The determination of an optimal treatment plan for an individual patient with rectal cancer is a complex process. In addition to decisions relating to the intent of rectal cancer surgery (ie, curative or palliative), consideration must also be given to the likely functional results of treatment, including the probability of maintaining or restoring normal bowel function/anal continence and preserving genitourinary functions. Particularly for patients with distal rectal cancer, finding a balance between curative-intent therapy while having minimal impact on quality of life can be challenging. Furthermore, the risk of pelvic recurrence is higher in patients with rectal cancer compared with those with colon cancer, and locally recurrent rectal cancer is associated with a poor prognosis. Careful patient selection and the use of sequenced multimodality therapy following a multidisciplinary approach is recommended. These NCCN Guidelines Insights detail recent updates to the NCCN Guidelines for Rectal Cancer, including the addition of endoscopic submucosal dissection as an option for early-stage rectal cancer, updates to the total neoadjuvant therapy approach based on the results of recent clinical trials, and the addition of a "watch-and-wait" nonoperative management approach for clinical complete responders to neoadjuvant therapy.

Colon Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of cancer death in the United States. Management of disseminated metastatic CRC involves various active drugs, either in combination or as single agents. The choice of therapy is based on consideration of the goals of therapy, the type and timing of prior therapy, the mutational profile of the tumor, and the differing toxicity profiles of the constituent drugs. This manuscript summarizes the data supporting the systemic therapy options recommended for metastatic CRC in the NCCN Guidelines for Colon Cancer.

Relationships Among Physical Activity, Sleep, and Cancer-related Fatigue: Results From the International ColoCare Study.

BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.

Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.

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.

Risk factors and health behaviors associated with loneliness among cancer survivors during the COVID-19 pandemic.

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies.

Impact of Social Determinants of Health on Outcomes Following Resection for Hepatocellular Carcinoma.

BACKGROUND: We sought to determine the impact of social determinants of health (SDoH) on outcomes of patients undergoing resection for hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Patients with HCC in the National Cancer Database who underwent resection from 2009 to 2018 were identified. SDoH associated with length of stay (LOS), 30-day readmission, and 30-day mortality were analyzed using regression analyses adjusted for confounding variables. RESULTS: Among 9235 patients, the median age (range) was 65.0 (18-90) years, 72.1% were male, and 57.9% were White. A total of 3% were uninsured, 11.1% had Medicaid, 21% resided in regions with a median household income within the lowest quartile of the US population, and 27.0% resided in regions within the lowest quartile of education level. The odds for having longer LOS were lower among patients with the highest regional education level compared with those with the lowest level [odds ratio (OR) 0.86, 95% confidence interval (CI) 0.77-0.97]. The risk of readmission was lower among patients with Medicare (OR 0.52; 95% CI 0.33-0.81), Medicaid (OR 0.52; 95% CI 0.31-0.87), or private insurance (OR 0.56; 95% CI 0.35-0.88) compared with uninsured patients. Thirty-day overall mortality was less likely among patients with Medicare (OR 0.45; 95% CI 0.27-0.75), Medicaid (OR 0.53; 95% CI 0.30-0.93), or private insurance (OR 0.40; 95% CI 0.24-0.66), and among patients with high regional income (OR 0.58; 95% CI 0.44-0.77). CONCLUSIONS: Adjusted regression analyses identified SDoH that were associated with HCC outcomes. Increased awareness of how SDoH relate to outcomes may inform strategies that attempt to account for these associations and improve patient outcomes.

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.

Anal Carcinoma, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology.

This discussion summarizes the NCCN Clinical Practice Guidelines for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. A multidisciplinary approach including physicians from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology is necessary. Primary treatment of perianal cancer and anal canal cancer are similar and include chemoradiation in most cases. Follow-up clinical evaluations are recommended for all patients with anal carcinoma because additional curative-intent treatment is possible. Biopsy-proven evidence of locally recurrent or persistent disease after primary treatment may require surgical treatment. Systemic therapy is generally recommended for extrapelvic metastatic disease. Recent updates to the NCCN Guidelines for Anal Carcinoma include staging classification updates based on the 9th edition of the AJCC Staging System and updates to the systemic therapy recommendations based on new data that better define optimal treatment of patients with metastatic anal carcinoma.

Peritoneal metastases from primary appendiceal and colorectal carcinomas demonstrate distinct molecular identities on comprehensive tumor analysis.

BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

Lymph node metastases in young patients with gastrointestinal stromal tumor: A nationwide analysis.

BACKGROUND: Children, adolescents, and young adults (CAYA) (age ≤39 years) with GIST have high rates of LNM, but their clinical relevance is undefined. This study analyzed the impact of LNM on overall survival (OS) for CAYA with GIST. METHODS: The National Cancer Database was queried for patients with resected GIST and pathologic nodal staging data from 2004-2019. Factors associated with LNM were identified. Survival was assessed stratified by presence of LNM. RESULTS: Of 4420 patients with GIST, 238 were CAYA (5.4%). When compared to older adults, CAYA more often had small intestine primaries (51.8% vs. 36.6%, p < 0.0001), T4 tumors (30.7% vs. 24.5%, p = 0.0275) and pN1 disease (11.3% vs. 4.7%, p < 0.0001). Within a multivariable Cox proportional hazards regression model adjusting for age, comorbid disease, mitotic rate, tumor size, and primary site, LNM were associated with increased hazard of death for older adults (hazard ratio [HR]: 1.83; confidence interval [CI]: 1.35-2.42; p < 0.0001), but not CAYA (HR: 3.38; CI: 0.50-14.08; p = 0.13). For CAYA, only high mitotic rate predicted mortality (HR: 4.68; CI: 1.41-18.37: p = 0.02). CONCLUSIONS: LNM are more commonly identified among CAYA with resected GIST who undergo lymph node evaluations, but do not appear to impact OS as observed in older adults. High mitotic rate remains a predictor of poor outcomes for CAYA with GIST.

Trajectories and risk factors of fatigue following colorectal cancer diagnosis.

AIM: This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups. METHOD: Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups. RESULTS: Among 1615 participants (57% men, 86% non-Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II-IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05). CONCLUSION: A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.

Segmental bile duct resection versus pancreatoduodenectomy for middle and distal third bile duct cancer. A systematic review and meta-analysis of comparative studies.

INTRODUCTION: Data regarding oncologic outcomes of segmental bile duct resection (SBDR) versus pancreatoduodenectomy (PD) for bile duct cancers (BDC) are conflicting. We compared SBDR and PD for BDC utilizing pooled data analysis. MATERIALS AND METHODS: A comprehensive PRISMA 2020 systematic review was performed. Studies comparing SBDR with PD for BDC were included. Pooled mean differences (MD), odds ratios (OR), and risk ratios (RR) with 95% confidence intervals (CI) were calculated. Subgroup analyses were performed. Study quality, bias, heterogeneity, and certainty were analyzed. RESULTS: Twelve studies from 2004 to 2021 were included, comprising 533 SBDR and 1,313 PD. SBDR was associated with positive proximal duct margins (OR 1.56; CI 1.11-2.18; P = .01), and distal duct margins (OR 43.25; CI 10.38-180.16; P < .01). SBDR yielded fewer lymph nodes (MD -6.93 nodes; CI -9.72-4.15; P < .01) and detected fewer nodal metastases (OR 0.72; CI 0.55-0.94; P = .01). SBDR portended less perioperative morbidity (OR 0.31; CI 0.21-0.46; P < .01), but not mortality (OR 0.52; CI 0.20-1.32; P = .17). SBDR was associated with locoregional recurrences (OR 1.88; CI 1.01-3.53; P = .02), and lymph node recurrences (OR 2.13; CI 1.42-3.2; P = .04). SBDR yielded decreased 5-year OS (OR 0.75; CI 0.65-0.85; P < .01). CONCLUSIONS: Despite decreased perioperative morbidity, SBDR appears to provide inferior oncologic control for BDC.

The pancreatic cancer immune tumor microenvironment is negatively remodeled by gemcitabine while TGF-ß receptor plus dual checkpoint inhibition maintains antitumor immune cells.

Pancreatic ductal adenocarcinoma (PDA) tumors have a highly immunosuppressive desmoplastic tumor microenvironment (TME) where immune checkpoint inhibition (ICI) therapy has been exceptionally ineffective. Transforming growth factor-ß (TGF-ß) receptor activation leads to cancer and immune cell proliferation and phenotype, and cytokine production leading to tumor progression and worse overall survival in PDA patients. We hypothesized that TGF-ß receptor inhibition may alter PDA progression and antitumor immunity in the TME. Here, we used a syngeneic preclinical murine model of PDA to explore the impact of TGF-ß pathway inhibitor galunisertib (GAL), dual checkpoint immunotherapy (anti-PD-L1 and CTLA-4), the chemotherapy gemcitabine (GEM), and their combinations on antitumor immune responses. Blockade of TGF-ß and ICI in immune-competent mice bearing orthotopically injected murine PDA cells significantly inhibited tumor growth and was accompanied by antitumor M1 macrophage infiltration. In contrast, GEM treatment resulted in increased PDA tumor growth, decreased antitumor M1 macrophages, and decreased cytotoxic CD8+ T cell subpopulation compared to control mice. Together, these findings demonstrate the ability of TGF-ß inhibition with GAL to prime antitumor immunity in the TME and the curative potential of combining GAL with dual ICI. These preclinical results indicate that targeted inhibition of TGF-ß may enhance the efficacy of dual immunotherapy in PDA. Optimal manipulation of the immune TME with non-ICI therapy may enhance therapeutic efficacy.

Factors associated with changes in exercise behaviors during the COVID-19 pandemic.

PURPOSE: There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined changes in exercise behaviors since the pandemic and identified characteristics associated with these changes among cancer patients. METHODS: Cancer patients (n = 1,210) completed a survey from August to September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into three groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. RESULTS: One-third of the patients reported a decreased amount of regular exercise, while 10% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired and have poor health status and psychosocial stressors such as disruptions in daily life while less likely to be former smokers (all p < 0.05). In contrast, patients who exercised more were younger, had stage IV diagnosis, and also reported disruptions in daily life (all p < 0.05). Patients who were living in rural areas were also more likely not to experience changes in exercise habits (all p < 0.05), although rural-urban status was not identified as a strong predictor. CONCLUSION: A significant proportion of cancer patients experienced changes in exercise habits, especially exercising less, during the first 6 months of the COVID-19 pandemic. Age, employment status, tumor stage, health status, smoking status, and psychosocial factors were associated with changes in exercise behaviors. Our results highlight the importance of promoting physical activity guidelines for cancer survivorship during the COVID-19 pandemic and may help improve the identification of cancer patients susceptible to exercising less.

Lymph Node Metastases in Gastrointestinal Stromal Tumors: an Uncommon Event.

BACKGROUND: Lymph node (LN) metastases are uncommon among gastrointestinal stromal tumors (GISTs), and their presence has not been utilized in disease prognostication. This study was designed to examine factors associated with GIST nodal metastases and their impact on survival. PATIENTS AND METHODS: Patients undergoing surgical resection of GIST with nodal evaluation were selected from the National Cancer Database. Logistic regression was utilized to evaluate factors associated with LN metastases. Survival was assessed for patients with and without nodal involvement and Cox regression was used to evaluate the impact of LN metastases while adjusting for other prognostic factors. RESULTS: Out of 5018 patients, 301 (6.0%) had LN involvement. Nodal metastases occurred most frequently among tumors of the stomach (49.5%), followed by the small bowel (43.2%), colorectum (6.0%), and esophagus (1.3%). On multivariable analysis, male sex (OR 1.34), high mitotic rate (OR 2.10), tumor size (OR 1.02), and a primary tumor located in the small bowel (OR 1.36) were all significantly associated with nodal metastases. LN metastases were significantly associated with decreased overall survival (OS) for tumors arising in the small bowel (log-rank p < 0.01) and the colorectum (log-rank p < 0.01). Within a multivariable model adjusting for established prognostic factors, LN metastases remained independently associated with decreased survival (HR 1.60, p < 0.001). CONCLUSIONS: For GISTs, LN metastases occur more often in males and were associated with tumor size and mitotic activity. Nodal involvement is associated with decreased survival, independent of other well-established prognostic factors.

Association of Sugar Intake with Inflammation- and Angiogenesis-Related Biomarkers in Newly Diagnosed Colorectal Cancer Patients.

Evidence suggests a positive association between sugar intake and colorectal cancer (CRC) outcomes. We sought to investigate inflammation and angiogenesis as underlying mechanisms behind increased sugar intake and worse CRC outcomes. Pre-surgery serum samples were obtained from 191 patients diagnosed with primary invasive stage I-IV CRC. Biomarkers of inflammation (CRP, SAA, IL-6, IL-8, MCP-1, TNFα) and angiogenesis (VEGFA, VEGFD, sICAM-1 and sVCAM-1) were analyzed (Meso-Scale-Discovery). Fructose, glucose, sucrose, and total sugar intake (calories/day, % total calories) were assessed by FFQ. Pearson's correlation and multiple linear regression analyses were performed. Patients were on average 64 years old, 64% were male, the majority was diagnosed with stage II-III (58%) cancers, and 67% were either overweight or obese. Among normal-weight individuals (BMI <25 kg/m2), we observed a significant inverse association between VEGFD and any type of sugar intake in cal/day (sucrose: p = 0.01, glucose and fructose: p < 0.001) and MCP-1 and fructose intake (p = 0.05). The magnitude of reduction in VEGF ranged between -1.24 for sucrose to 4.49 for glucose intake, and -2.64 for fructose intake for MCP-1 levels. Sugar intake was associated with some inflammation or angiogenesis biomarkers, among CRC patients; differences were observed by adiposity that warrant further investigation.Supplemental data for this article is available online at at 10.1080/01635581.2021.1957133.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Anal cancer: current standards in care and recent changes in practice.

Answer questions and earn CME/CNE The management of squamous cell carcinomas of the anal canal has evolved from surgery as first-line treatment to curative chemoradiation, with surgery reserved for salvage. Significant progress has been made in understanding how to most effectively deliver chemotherapy and reduce toxicity through advancements in radiation delivery. The purpose of this article is to review the multimodality approach to the diagnosis and management of anal cancer based on a review of the published data and in light of available guidelines.

Visceral angiosarcoma: A nationwide analysis of treatment factors and outcomes.

BACKGROUND AND OBJECTIVES: Visceral angiosarcoma is rare and aggressive, accounting for 2% of soft tissue sarcomas. Using a national data set, we examine determinants of outcomes for patients presenting with this rare disease. METHODS: The 2004-2015 National Cancer Database was queried for patients with visceral angiosarcoma. Trends in treatment and outcomes were examined. Factors affecting overall survival (OS) were assessed with log-rank and Cox regression. RESULTS: Eight hundred and ninety-three patients with visceral angiosarcoma were identified (median age 65 years, male [63%], Charlson comorbidity index <1 [86%]). Tumor size was <5 cm in 20.7%, and 34.2% were moderate/high grade. Median OS was 3.8 months (95% CI: 3.4-4.4). By multivariate analysis, increased tumor grade and size, and liver/biliary origin demonstrated worse OS while surgery, radiation, and systemic chemotherapy demonstrated improved OS (all p < 0.001). Survival was similar between patients achieving R0 resection and those with R1/2 resection receiving chemotherapy by Kaplan-Meier analysis. CONCLUSIONS: Visceral angiosarcomas are rare tumors with poor outcomes. Liver/biliary origin, higher tumor grade, and larger tumor size demonstrate worse outcomes. While R0 resection remains the mainstay of treatment, patients with R1/R2 resection have improved survival with addition of chemotherapy. Consideration should be made for multimodal therapy in these patients.

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.