Preoperative Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain. METHODS: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy. Adults with rectal cancer that had been clinically staged as T2 node-positive, T3 node-negative, or T3 node-positive who were candidates for sphincter-sparing surgery were eligible to participate. The primary end point was disease-free survival. Noninferiority would be claimed if the upper limit of the two-sided 90.2% confidence interval of the hazard ratio for disease recurrence or death did not exceed 1.29. Secondary end points included overall survival, local recurrence (in a time-to-event analysis), complete pathological resection, complete response, and toxic effects. RESULTS: From June 2012 through December 2018, a total of 1194 patients underwent randomization and 1128 started treatment; among those who started treatment, 585 were in the FOLFOX group and 543 in the chemoradiotherapy group. At a median follow-up of 58 months, FOLFOX was noninferior to chemoradiotherapy for disease-free survival (hazard ratio for disease recurrence or death, 0.92; 90.2% confidence interval [CI], 0.74 to 1.14; P = 0.005 for noninferiority). Five-year disease-free survival was 80.8% (95% CI, 77.9 to 83.7) in the FOLFOX group and 78.6% (95% CI, 75.4 to 81.8) in the chemoradiotherapy group. The groups were similar with respect to overall survival (hazard ratio for death, 1.04; 95% CI, 0.74 to 1.44) and local recurrence (hazard ratio, 1.18; 95% CI, 0.44 to 3.16). In the FOLFOX group, 53 patients (9.1%) received preoperative chemoradiotherapy and 8 (1.4%) received postoperative chemoradiotherapy. CONCLUSIONS: In patients with locally advanced rectal cancer who were eligible for sphincter-sparing surgery, preoperative FOLFOX was noninferior to preoperative chemoradiotherapy with respect to disease-free survival. (Funded by the National Cancer Institute; PROSPECT ClinicalTrials.gov number, NCT01515787.).

Common variation in a long non-coding RNA gene modulates variation of circulating TGF-ß2 levels in metastatic colorectal cancer patients (Alliance).

BACKGROUND: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous blood collected at baseline. A robust rank-based method was used to assess the statistical significance of each variant and protein pair against a strict genome-wide level. A given pQTL was tested for validation in two external datasets of prostate (CALGB 90401) and pancreatic cancer (CALGB 80303) patients. Bioinformatics analyses were conducted to further establish biological bases for these findings. RESULTS: The final analysis was carried out based on data from 540,021 common typed genetic variants and 23 protein markers from 869 genetically estimated European patients with mCRC. Correcting for multiple testing, the analysis discovered a novel cis-pQTL in LINC02869, a long non-coding RNA gene, for circulating TGF-ß2 levels (rs11118119; AAF = 0.11; P-value < 1.4e-14). This finding was validated in a cohort of 538 prostate cancer patients from CALGB 90401 (AAF = 0.10, P-value < 3.3e-25). The analysis also validated a cis-pQTL we had previously reported for VEGF-A in advanced pancreatic cancer, and additionally identified trans-pQTLs for VEGF-R3, and cis-pQTLs for CD73. CONCLUSIONS: This study has provided evidence of a novel cis germline genetic variant that regulates circulating TGF-ß2 levels in plasma of patients with advanced mCRC and prostate cancer. Moreover, the validation of previously identified pQTLs for VEGF-A, CD73, and VEGF-R3, potentiates the validity of these associations.

Evaluation of Culture Conducive to Academic Success by Gender at a Comprehensive Cancer Center.

INTRODUCTION: The primary objective of this study was to determine whether workplace culture in academic oncology differed by gender, during the COVID-19 pandemic. MATERIALS AND METHODS: We used the Culture Conducive to Women's Academic Success (CCWAS), a validated survey tool, to investigate the academic climate at an NCI-designated Cancer Center. We adapted the CCWAS to be applicable to people of all genders. The full membership of the Cancer Center was surveyed (total faculty = 429). The questions in each of 4 CCWAS domains (equal access to opportunities, work-life balance, freedom from gender bias, and leadership support) were scored using a 5-point Likert scale. Median score and interquartile ranges for each domain were calculated. RESULTS: A total of 168 respondents (men = 58, women = 106, n = 4 not disclosed) submitted survey responses. The response rate was 39% overall and 70% among women faculty. We found significant differences in perceptions of workplace culture by gender, both in responses to individual questions and in the overall score in the following domains: equal access to opportunities, work-life balance, and leader support, and in the total score for the CCWAS. CONCLUSIONS: Our survey is the first of its kind completed during the COVID-19 pandemic at an NCI-designated Cancer Center, in which myriad factors contributed to burnout and workplace challenges. These results point to specific issues that detract from the success of women pursuing careers in academic oncology. Identifying these issues can be used to design and implement solutions to improve workforce culture, mitigate gender bias, and retain faculty.

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.

Dietary fat in relation to all-cause mortality and cancer progression and death among people with metastatic colorectal cancer: Data from CALGB 80405 (Alliance)/SWOG 80405.

Data on diet and survival among people with metastatic colorectal cancer are limited. We examined dietary fat in relation to all-cause mortality and cancer progression or death among 1149 people in the Cancer and Leukemia Group B (Alliance)/Southwest Oncology Group (SWOG) 80405 trial who completed a food frequency questionnaire at initiation of treatment for advanced or metastatic colorectal cancer. We examined saturated, monounsaturated, total and specific types (n-3, long-chain n-3 and n-6) of polyunsaturated fat, animal and vegetable fats. We hypothesized higher vegetable fat intake would be associated with lower risk of all-cause mortality and cancer progression. We used Cox proportional hazards regression to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Over median follow-up of 6.1 years (interquartile range [IQR]: 5.3, 7.2 y), we observed 974 deaths and 1077 events of progression or death. Participants had a median age of 59 y; 41% were female and 86% identified as White. Moderate or higher vegetable fat was associated with lower risk of mortality and cancer progression or death (HRs comparing second, third and fourth to first quartile for all-cause mortality: 0.74 [0.62, 0.90]; 0.75 [0.61, 0.91]; 0.79 [0.63, 1.00]; P trend: .12; for cancer progression or death: 0.74 [0.62, 0.89]; 0.78 [0.64, 0.95]; 0.71 [0.57, 0.88]; P trend: .01). No other fat type was associated with all-cause mortality and cancer progression or death. Moderate or higher vegetable fat intake may be associated with lower risk of cancer progression or death among people with metastatic colorectal cancer.

Physical activity in recurrent colon cancer: Cancer and Leukemia Group B/SWOG 80702 (Alliance).

BACKGROUND: One in three patients with stage III colon cancer will experience tumor recurrence. It is uncertain whether physical activity during and after postoperative chemotherapy for stage III colon cancer improves overall survival after tumor recurrence. METHODS: A prospective cohort study nested within a randomized multicenter trial of patients initially diagnosed with stage III colon cancer who experienced tumor recurrence (N = 399) was conducted. Postoperative physical activity before tumor recurrence was measured. Physical activity energy expenditure was quantified via metabolic equivalent task hours per week (MET-h/week). The primary end point was overall survival after tumor recurrence. Multivariable flexible parametric survival models estimated relative and absolute effects with two-sided hypothesis tests. RESULTS: Compared with patients expending <3.0 MET-h/week of physical activity (comparable to <1.0 h/week of brisk walking), patients with ≥18.0 MET-h/week of physical activity (comparable to 6 h/week of brisk walking) had a 33% relative improvement in overall survival time after tumor recurrence (hazard ratio, 0.67; 95% CI, 0.42-0.96). The overall survival rate at 3 years after tumor recurrence was 61.3% (95% CI, 51.8%-69.2%) with <3.0 MET-h/week of physical activity and 72.2% (95% CI, 63.1%-79.6%) with ≥18 MET-h/week of physical activity (risk difference, 10.9 percentage points; 95% CI, 1.2-20.8 percentage points). CONCLUSIONS: Higher postoperative physical activity is associated with improved overall survival after tumor recurrence in patients initially diagnosed with stage III colon cancer. These data may be relevant to patients who, despite optimal postoperative medical therapy, have a high risk of tumor recurrence.

Phase III Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection for Colon Cancer: An Intergroup Trial of the ECOG-ACRIN Cancer Research Group (E1292).

BACKGROUND: Studies suggest that adjuvant chemotherapy should be initiated at the earliest possible time. The Eastern Cooperative Oncology Group (ECOG) and Intergroup evaluated the effect of perioperative fluorouracil (5-FU) on overall survival (OS) for colon cancer. PATIENTS AND METHODS: This phase III trial randomized patients to receive continuous infusional 5-FU for 7 days starting within 24 h after curative resection (arm A) or no perioperative 5-FU (arm B). Patients with Dukes' B3 and C disease received adjuvant chemotherapy per standard of care. The primary endpoint of the trial was overall survival in patients with Dukes' B3 and C disease. The secondary objective was to determine whether a week of perioperative infusion would affect survival in patients with Dukes' B2 colon cancer with no additional chemotherapy. RESULTS: From August 1993 to May 2000, 859 patients were enrolled and 855 randomized (arm A: 427; arm B: 428). The trial was terminated early due to slow accrual. The median follow-up is 15.4 years (0.03-20.3 years). Among patients with Dukes' B3 and C disease, there was no statistically significant difference in OS [median 10.3 years (95% CI 8.4, 13.2) for perioperative chemotherapy and 9.3 years (95% CI 5.7, 12.3) for no perioperative therapy, one-sided log-rank p = 0.178, HR = 0.88 (95% CI 0.66, 1.16)] or disease-free survival (DFS). For patients with Dukes' B2 disease, there was also no significant difference in OS (median 16.1 versus 12.9 years) or DFS. There was no difference between treatment arms in operative complications. One week of continuous infusion of 5-FU was tolerable; 18% of arm A patients experienced grade 3 or greater toxicity.

NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

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.

Sexual function remains persistently low in women after treatment for colorectal cancer and anal squamous cell carcinoma.

BACKGROUND: Women diagnosed with colorectal cancer (CRC) or anal squamous cell carcinoma (ASCC) are at high risk of sexual dysfunction after treatment, yet little is known about recovery and risk factors for chronic dysfunction. AIM: We aimed to describe sexual function and sexual activity among women who underwent definitive treatment for CRC or ASCC, examine relationships between time since treatment completion and sexual function, and explore factors associated with desire and changes in sexual desire over time. METHODS: As part of a prospective cohort study of patients with gastrointestinal cancer at the University of California San Francisco, female-identifying participants who finished definitive treatment for CRC or ASCC completed the Female Sexual Function Index (FSFI) at 6- to 12-month intervals. We used multivariable linear mixed models to explore factors associated with the FSFI desire subscale. OUTCOMES: Outcomes were rates of sexual activity, proportion at risk for sexual dysfunction (FSFI score <26.55), total FSFI score, and FSFI desire subscale. RESULTS: Among the 97 cancer survivors who completed at least 1 FSFI, the median age was 59 years, the median time since treatment end was 14 months, and 87% were menopausal. Fifty-five women (57%) had a history of colon cancer; 21 (22%), rectal cancer; and 21 (22%), ASCC. An additional 13 (13%) had a current ostomy. Approximately half the women were sexually active (n = 48, 49%). Among these 48 sexually active women, 34 (71%) had FSFI scores indicating risk for sexual dysfunction. Among the 10 sexually active women who completed a FSFI ≥2 years since end of treatment, the median total score was 22.6 (IQR, 15.6-27.3). None of the evaluated characteristics were associated with desire (age, tumor site, treatment, menopause status, or ostomy status). CLINICAL IMPLICATIONS: Consistent with prior studies, we found low desire scores after treatment for CRC or ASCC, with little recovery over time, suggesting that patients should not expect an eventual rebound of sexual function. STRENGTHS AND LIMITATIONS: Strengths of our study include longitudinal data and use of the validated FSFI. Women with ASCC composed 22% of our cohort, allowing for insight into this rare disease group. Limitations of this study include the small sample size, particularly for longitudinal analyses, and the enrollment of patients at variable times since treatment end. CONCLUSION: We observed a high prevalence of sexual health concerns, including low desire, after the treatment of CRC and ASCC that persisted for years after treatment was completed.

Barriers and confidence among colorectal and prostate cancer survivors participating in two behavioral intervention studies.

PURPOSE: Exercise and healthy diet are key components of cancer survivorship. We sought to explore perceived barriers to engaging in healthy diet and exercise, and whether these barriers change throughout remote-based behavioral interventions. METHODS: Smart Pace (SP) and Prostate 8 (P8) were two 12-week pilot randomized controlled trials (RCTs) among 42 colorectal cancer (CRC) survivors and 76 prostate cancer (PC) survivors, respectively, that encouraged participants to implement exercise (both) and healthy diet (P8 only) through text messaging and wearable fitness monitors; P8 also included web materials. Participants completed surveys on perceived barriers and confidence in their ability to implement healthy behaviors at enrollment and 12 weeks; P8 also included a 52-week assessment. RESULTS: At enrollment, CRC survivors commonly reported a lack of discipline/willpower (36%), time (33%), and energy (31%); PC survivors often reported a lack of knowledge about healthy dietary behaviors (26%). Not having anyone with whom to exercise with was a common barrier among both groups (21% in CRC, 20% in PC). Among the intervention groups in both studies, various enrollment barriers (overall, functional/psychological disability, aversiveness, excuses, and inconveniences) were associated with change in behavior over time. CONCLUSIONS: Among CRC and PC survivors, there are multiple potential barriers related to motivation, time, social support, and lack of knowledge, that can be addressed and overcome to improve healthy behaviors. Tailoring lifestyle interventions to participants' individual barriers and confidence is needed to promote and sustain behavior change long-term.

Quality of life among colorectal cancer survivors participating in a pilot randomized controlled trial of a web-based dietary intervention with text messages.

PURPOSE: We aimed to estimate the effect of a 12-week web-based dietary intervention with text messages on quality of life (QoL) among colorectal cancer (CRC) survivors. METHODS: Between 2017 and 2018, 50 CRC survivors were randomized (1:1) to receive a 12-week web-based dietary intervention with daily text messages or wait-list control. Health-related QoL was assessed using the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and colorectal quality of life module (QLQ-CR29) at baseline, 12, and 24 weeks. Within- and between-group mean changes in health-related QoL with 95% confidence intervals (CI) were calculated for both arms. RESULTS: Compared to the controls, participants receiving the intervention had an improvement in emotional functioning (mean change: 14.3; 95% CI: 3.0, 25.6) at 12 weeks and social functioning (mean change: 13.8; 95% CI: 2.1, 25.5) at 24 weeks. A decrease of fatigue from baseline was also observed in the intervention arm (mean change: - 9.1; 95% CI: - 17.1, - 1.1) at 24 weeks. No other changes in QoL scores were associated with the intervention. CONCLUSION: CRC survivors randomized to receive a web-based dietary intervention with text messages experienced higher emotional and social functioning. Further study with a larger population may be warranted. TRIAL REGISTRATION: clinicaltrials.gov, NCT02965521. Registered 16 November 2016, https://clinicaltrials.gov/ct2/keydates/NCT02965521.

Genome-wide association studies of survival in 1520 cancer patients treated with bevacizumab-containing regimens.

Germline variants might predict cancer progression. Bevacizumab improves overall survival (OS) in patients with advanced cancers. No biomarkers are available to identify patients that benefit from bevacizumab. A meta-analysis of genome-wide association studies (GWAS) was conducted in 1,520 patients from Phase III trials (CALGB 80303, 40503, 80405 and ICON7), where bevacizumab was randomized to treatment without bevacizumab. We aimed to identify genes and single nucleotide polymorphisms (SNPs) associated with survival independently of bevacizumab treatment or through interaction with bevacizumab. A cause-specific Cox model was used to test the SNP-OS association in both arms combined (prognostic), and the effect of SNPs-bevacizumab interaction on OS (predictive) in each study. The SNP effects across studies were combined using inverse variance. Findings were tested for replication in advanced colorectal and ovarian cancer patients from The Cancer Genome Atlas (TGCA). In the GWAS meta-analysis, patients with rs680949 in PRUNE2 experienced shorter OS compared to patients without it (P = 1.02 × 10-7 , hazard ratio [HR] = 1.57, 95% confidence interval [CI] 1.33-1.86), as well as in TCGA (P = .0219, HR = 1.58, 95% CI 1.07-2.35). In the GWAS meta-analysis, patients with rs16852804 in BARD1 experienced shorter OS compared to patients without it (P = 1.40 × 10-5 , HR = 1.51, 95% CI 1.25-1.82) as well as in TCGA (P = 1.39 × 10-4 , HR = 3.09, 95% CI 1.73-5.51). Patients with rs3795897 in AGAP1 experienced shorter OS in the bevacizumab arm compared to the nonbevacizumab arm (P = 1.43 × 10-5 ). The largest GWAS meta-analysis of bevacizumab treated patients identified PRUNE2 and BARD1 (tumor suppressor genes) as prognostic genes of colorectal and ovarian cancer, respectively, and AGAP1 as a potentially predictive gene that interacts with bevacizumab with respect to patient survival.

Phase I prospective trial of TAS-102 (trifluridine and tipiracil) and radioembolization with 90Y resin microspheres for chemo-refractory colorectal liver metastases.

BACKGROUND: Extrahepatic disease progression limits clinical efficacy of Yttrium-90 (90Y) radioembolization (TARE) for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). Trifluridine and tipiracil (TAS-102) has overall survival benefit for patients with refractory mCRC and may be a radiosensitizer. METHODS: Sequential lobar TARE using 90Y resin microspheres in combination with TAS-102 in 28-day cycles were used to treat adult patients with bilobar liver-dominant chemo-refractory mCRC according to 3 + 3 dose escalation design with a 12-patient dose expansion cohort. Study objectives were to establish safety and determine maximum tolerated dose (MTD) of TAS-102 in combination with TARE. RESULTS: A total of 21 patients (14 women, 7 men) with median age of 60 years were enrolled. No dose limiting toxicities were observed. Treatment related severe adverse events included cytopenias (10 patients, 48%) and radioembolization-induced liver disease (2 patients, 10%). Disease control rate in the liver lobes treated with TARE was 100%. Best observed radiographic responses were partial response for 4 patients (19%) and stable disease for 12 patients (57%). CONCLUSIONS: The combination of TAS-102 and TARE for patients with liver-dominant mCRC is safe and consistently achieves disease control within the liver. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02602327 (first posted 11/11/2015).

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.

Quality of life of colorectal cancer survivors participating in a pilot randomized controlled trial of physical activity trackers and daily text messages.

PURPOSE: There are over 1.3 million colorectal cancer (CRC) survivors in the USA, many of whom report lower health-related quality of life (HRQoL) years after treatment. This study aimed to explore the effect of digital health tools on HRQoL in CRC survivors. METHODS: We conducted a two-arm, randomized controlled trial of 42 subjects who had completed treatment for CRC. Participants in the intervention arm received a Fitbit Flex™ and daily text messages for 12 weeks. HRQoL was assessed as a secondary endpoint in both arms at enrollment and 12 weeks using the Medical Outcomes Study Short Form Survey (SF-36) and the Functional Assessment of Cancer Therapy-Colorectal (FACT-C). Survey score changes from enrollment to 12 weeks were compared between the two arms using independent t tests, and scores at enrollment and 12 weeks were compared using paired t tests. RESULTS: An increase in the FACT-C functional well-being subscale was observed in individuals in the intervention arm pre- to post-intervention (median difference, 2; interquartile range (IQR), 1, 4; P = .02). Although the between-group comparison was not statistically significant, no change in the functional well-being subscale was observed in the control arm (median difference, 0; IQR, 1, 1; P = .71). No other measures of HRQoL appeared to differ within arm across time points or between arms. CONCLUSION: A 12-week digital physical activity intervention may improve functional well-being among CRC survivors. Larger randomized studies are needed to determine if digital health tools improve functional well-being among CRC survivors and if this improvement can be sustained over time. TRIAL REGISTRATION: NCT02966054; registration date, November 17, 2016.

Racial differences in survival and response to therapy in patients with metastatic colorectal cancer: A secondary analysis of CALGB/SWOG 80405 (Alliance A151931).

BACKGROUND: The objective of this study was to evaluate the association between self-identified race and overall survival (OS), progression-free survival (PFS), and response to therapy among patients enrolled in the randomized Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial. METHODS: Patients with advanced or metastatic colorectal cancer who were enrolled in the CALGB/SWOG 80405 trial were identified by race. On the basis of covariates (treatment arm, KRAS status, sex, age, and body mass index), each Black patient was exact matched with a White patient. The association between race and OS and PFS was examined using a marginal Cox proportional hazard model for matched pairs. The interaction between KRAS status and race was tested in the model. The association between race and response to therapy and adverse events were examined using a marginal logistic regression model. RESULTS: In total, 392 patients were matched and included in the final data set. No difference in OS (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.73-1.16), PFS (HR, 0.97; 95% CI, 0.78-1.20), or response to therapy (odds ratio [OR], 1.00; 95% CI, 0.65-1.52) was observed between Black and White patients. Patients with KRAS mutant status (HR, 1.31; 95% CI, 1.02-1.67), a performance statusscore of 1 (reference, a performance status of 0; HR, 1.49; 95% CI, 1.18-1.88), or ≥3 metastatic sites (reference, 1 metastatic site; HR, 1.67; 95% CI, 1.22-2.28) experienced worse OS. Black patients experienced lower rates and risk of grade ≥3 fatigue (6.6% vs 13.3%; OR, 0.46; 95% CI, 0.24-0.91) but were equally likely to be treated with a dose reduction (OR, 1.09; 95% CI, 0.72-1.65). CONCLUSIONS: No difference in OS, PFS, or response to therapy was observed between Black patients and White patients in an equal treatment setting of the CALGB/SWOG 80405 randomized controlled trial. LAY SUMMARY: Despite improvements in screening and treatment, studies have demonstrated worse outcomes in Black patients with colorectal cancer. The purpose of this study was to determine whether there was a difference in cancer-specific outcomes among Black and White patients receiving equivalent treatment on the CALGB/SWOG 80405 randomized clinical trial. In this study, there was no difference in overall survival, progression-free survival, or response to therapy between Black and White patients treated on a clinical trial. These findings suggest that access to care and differences in treatment may be responsible for racial disparities in colorectal cancer.

Cabozantinib in Patients with Advanced and Progressing Hepatocellular Carcinoma.

BACKGROUND: Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma. METHODS: A total of 707 patients were randomly assigned in a 2:1 ratio to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival. Secondary end points were progression-free survival and the objective response rate. RESULTS: At the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group and in 36% in the placebo group. The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%). CONCLUSIONS: Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group. (Funded by Exelixis; CELESTIAL ClinicalTrials.gov number, NCT01908426 .).

Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer focuses on systemic therapy options for the treatment of metastatic colorectal cancer (mCRC), because important updates have recently been made to this section. These updates include recommendations for first-line use of checkpoint inhibitors for mCRC, that is deficient mismatch repair/microsatellite instability-high, recommendations related to the use of biosimilars, and expanded recommendations for biomarker testing. The systemic therapy recommendations now include targeted therapy options for patients with mCRC that is HER2-amplified, or BRAF V600E mutation-positive. Treatment and management of nonmetastatic or resectable/ablatable metastatic disease are discussed in the complete version of the NCCN Guidelines for Colon Cancer available at NCCN.org. Additional topics covered in the complete version include risk assessment, staging, pathology, posttreatment surveillance, and survivorship.