Shibata, David

ABSTRACTBackgroundPrior studies have documented that patients with colorectal cancer (CRC) are at an increased risk of cardiovascular disease (CVD).ObjectivesTo examine coronary artery calcium (CAC) as a marker of subclinical atherosclerosis and its association with major adverse cardiovascular events (MACE) in patients with CRC across the cancer treatment trajectory.MethodsAdults with newly diagnosed CRC were enrolled in the prospective ColoCare study from 2017 to 2024. CAC was measured from routine diagnostic computed tomography (CT) and positron emission tomography‐CT scans at CRC diagnosis until 5 years post‐diagnosis. Atherosclerosis was defined as the presence of CAC. We used multivariable‐adjusted Fine and Gray models to assess the association between CAC and MACE risk, accounting for competing risks.ResultsAmong 300 CRC patients, the most common CVD risk factors at cancer diagnosis were hypertension (37%), hyperlipidemia (24%), and diabetes (14%). During follow‐up (median = 5.3 years), 75 (25%) individuals experienced MACE: stroke (3%), new/worsening HF (9%), HF exacerbation requiring hospitalization (2%), coronary revascularization (3%), and death (19%). Among individuals with imaging at baseline (n = 101), 37 (36.6%) had CAC, and statins were not prescribed in 11 (55.0%) patients with moderate/high CAC. For those with serial imaging (n = 61), 31.1% showed worsening CAC and 3% developed new CAC. Baseline CAC conferred a higher risk of MACE (HR = 4.79; 95% CI: 1.05–21.75, p = 0.04) after accounting for cancer‐related deaths as a competing risk.ConclusionsSubclinical atherosclerosis and MACE are common among patients with CRC. Integrating CAC from routine cancer imaging can identify patients who may benefit from cardio‐preventive treatment.

Multigene panel testing has allowed for the detection of a growing number of inherited pathogenic/likely pathogenic variants in people at high risk of cancer, including endometrial cancer (EC). Hereditary syndromes associated with EC include Lynch syndrome, PTEN hamartoma tumor syndrome, and Peutz-Jeghers syndrome. This manuscript provides the latest recommendations from the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal, Endometrial, and Gastric on the screening and management of EC in patients at high risk for these syndromes, as well as the advantages and limitations of multigene panel testing. This manuscript also describes recent updates to these guidelines regarding de-implementation of colon cancer screening in individuals with CHEK2 pathogenic/likely pathogenic variants, based on the most up-to-date evidence regarding the association between CHEK2 pathogenic/likely pathogenic variants and colon cancer risk.

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.

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.

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.

AbstractBackground and ObjectivesPublished data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP).MethodsCTP was performed, including next‐generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB).ResultsOne 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.ConclusionsDespite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

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.

Background National studies have reported racial and socioeconomic disparities in gastric cancer (GC) care. The current study evaluated adequate lymph node (LN) assessment (≥16 LNs) during resection for GC within a healthcare system servicing a socioeconomically disparate, mostly non-White population in the Southeast United States. Methods A retrospective cohort study of patients undergoing resection for GC between 2003-2019 was performed. Factors associated with adequate LN assessment including patient and tumor characteristics were analyzed. Results Among 202 patients, adequate LN assessment was performed in 97 (48%) patients. On univariable analysis, younger age, non-White race, lower Charlson Comorbidity Index (CCI), Medicaid or no insurance, D1+/D2 lymphadenectomy, clinical evidence of regional LN metastases, total gastrectomy, and receipt of neoadjuvant therapy were associated with adequate LN assessment. On multivariable analysis, non-White race (OR 2.79, 95% CI 1.38-5.65), CCI <4 (OR 2.14, 95% CI 1.15-3.96), and D1+/D2 lymphadenectomy (OR 3.63, 95% CI 1.96-6.74) were the only factors independently associated with adequate LN evaluation. Conclusions In the current study, non-White race, independent of socioeconomics, was significantly associated with adequate LN assessment. Future work is necessary to improve standardization and achieve higher rates of adequate LN assessment for all patients during resection for GC.

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.

The NCCN Guidelines for Rectal Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with rectal cancer. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines. These updates include clarifying the definition of rectum and differentiating the rectum from the sigmoid colon; the total neoadjuvant therapy approach for localized rectal cancer; and biomarker-targeted therapy for metastatic colorectal cancer, with a focus on new treatment options for patients with BRAF V600E– or HER2 amplification–positive disease.