A blueprint for creating an early-onset colorectal cancer program based on experiences from 7 clinical centers across the United States and Canada.

Background: The incidence of individuals diagnosed with colorectal cancer under the age of 50, often referred to as early-onset colorectal cancer (EOCRC), has risen worldwide. The EOCRC patients have unique needs; however, there are no clear guidelines on how to address them. The objective of the present study was to propose a blueprint for EOCRC program development and implementation.

Long-Term Outcomes of Patients Undergoing Two-Stage Hepatectomy For Extensive Colorectal Liver Metastasis Treated With Perioperative Hepatic Artery and Systemic Chemotherapy.

Objective: This study analyzed outcomes and clinical differences between patients who completed or failed TSH (cTSH or fTSH), and evaluated predictive factors for cTSH.

Background: Two-stage hepatectomy (TSH) is a well-recognized treatment for extensive colorectal liver metastases (CRLM).

Methods: A retrospective review of a prospective database identified patients who underwent TSH for extensive CRLM not amenable to a single resection.

Clinicopathologic Characteristics and Clinical Outcomes of Patients with Testicular Mesothelioma.

Background: Mesothelioma of the tunica vaginalis testes (testicular mesothelioma [TM]) is a rare tumor, comprising less than 5% of mesotheliomas. Surgical intervention is the current standard of care, whereas the role of systemic therapies remains undefined.

Methods: We retrospectively reviewed 36 patients with pathologically confirmed TM treated at Memorial Sloan Kettering Cancer Center (MSK) between January 1996 to May 2023.

Hepatic Artery Infusion Chemotherapy Compared to Transarterial Radioembolization For Unresectable Colorectal Liver Metastases.

Objective: This study evaluates outcomes for patients with unresectable colorectal liver metastases (CRLM) undergoing hepatic artery infusion chemotherapy (HAI) and transarterial radioembolization (TARE).

Summary Background Data: The most common liver-directed therapies for unresectable CRLM include HAI and TARE.

Methods: In this retrospective cohort study, patients with unresectable CRLM treated with HAI at one high-volume center were compared with patients treated with TARE at five other institutions.

Development of Second Malignancies Following Chemotherapy With or Without Radiation Therapy for the Treatment of Locally Advanced Rectal Cancer.

Purpose: We sought to identify factors associated with second pelvic malignancies (SPM), as well as second nonpelvic malignancies (SNPM), after chemotherapy with or without radiation therapy (RT) for locally advanced rectal cancer (LARC).

Methods And Materials: Patients diagnosed with stage II-III LARC. Cumulative incidence of second malignancies was analyzed using a 2-year landmark analysis with death as a competing risk.

The value of MRI and flexible sigmoidoscopy in detecting tumor regrowth in watch and wait rectal cancer patients undergoing active surveillance after total neoadjuvant therapy.

Aim: Patients with locally advanced rectal cancer may avoid surgery if they develop a clinical complete response (cCR) to total neoadjuvant therapy (TNT). During surveillance, detection of local regrowth can be challenging. The ability of MRI to predict local regrowth is uncertain, especially when it differs from endoscopic findings.

Induction of a mismatch repair deficient genotype by tailored chemical mutagenesis in experimental models of cancer.

Mismatch repair deficient (MMRd) tumors harbor thousands of somatic mutations enriched for insertion-deletion (indels) conferring high sensitivity to immunotherapy. We sought to reproduce this phenotype using mutagenic agents to engineer an MMRd genotype in immunoresistant cells. The combination of temozolomide (TMZ) and cisplatin led to a rapid accumulation of a high mutational load enriched for indels in murine cell lines resulting from the epigenetic loss of Msh2.

Nonoperative Management of Mismatch Repair-Deficient Tumors.

Background: Among patients with mismatch repair-deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this approach can be extended to all early-stage dMMR solid tumors, regardless of tumor site, is unknown.

Methods: We conducted a phase 2 study in which patients with stage I, II, or III dMMR solid tumors that were amenable to curative-intent surgery were treated with neoadjuvant dostarlimab, a programmed cell death 1 (PD-1) blocking agent, for 6 months.

Entering the Era of Multidimensional Prognostication for Personalized Risk Assessment in Stage III Colon Cancer.

In the article that accompanies this editorial, Gallois et al. investigate the added value of transcriptomic signatures incorporating tumoral, stromal and immune features to refine the prognosis assessment of stage III colon cancer after resection. If prospectively validated, these findings pave the way for a personalized adjuvant strategy and possibly omission of adjuvant treatment for patients with very low risk disease or therapeutic intensification for high risk disease.

Radioimmunotherapy for peritoneal carcinomatosis: Preclinical proof of concept to clinical translation.

Peritoneal carcinomatosis (PC), characterized by the dissemination of metastatic tumor cells throughout the peritoneal cavity from several gastrointestinal and gynecological malignancies, has significantly compromised patient survival. The standard of care is cytoreductive surgery with or without intraperitoneal chemotherapy. However, surgical resection often leaves behind microscopic or clinically occult disease due to the complex anatomy of the peritoneum, where intraperitoneal chemotherapy and systemic chemotherapy have shown limited success.

Utilizing Patient Input in Rectal Cancer Trial Design.

Background: The treatment of locally advanced rectal cancer now includes "watch-and-wait" (WW) management for patients who exhibit a clinical complete response (cCR) to total neoadjuvant therapy (TNT). We assessed patients' knowledge and preferences regarding WW with the goal of incorporating patient input into clinical trial design.

Methods: Rectal cancer patients in advocacy groups (COLONTOWN/Rectalburgh and Fight CRC) were surveyed regarding perceptions about treatment strategies, tolerable risks of treatment failure, and preferences on clinical trial design.

A Phase Two, Single-Arm, Open-Label Study With Dostarlimab Monotherapy in Participants With Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer (AZUR-1).

Background: Colorectal cancer (CRC) had the second highest cancer mortality worldwide in 2020; nearly a third of CRCs were rectal cancers (RC). A recent study demonstrated that dostarlimab, an immune-checkpoint inhibitor, was highly effective in treating mismatch repair deficient (dMMR) locally advanced RC as all included patients had a clinical complete response (cCR) without radiation or chemotherapy. This study's objective is to evaluate the efficacy and safety of dostarlimab monotherapy in patients with previously untreated locally advanced dMMR RC.

Paired primary-metastasis patient-derived organoids and mouse models identify phenotypic evolution and druggable dependencies of peritoneal metastasis from appendiceal cancer.

Peritoneal carcinomatosis is a common yet deadly manifestation of gastrointestinal cancers, with few effective treatments. To identify targetable determinants of peritoneal metastasis, we focused on appendiceal adenocarcinoma (AC), a gastrointestinal cancer that metastasizes almost exclusively to the peritoneum. Current treatments are extrapolated from colorectal cancer (CRC), yet AC has distinct genomic alterations, mucinous morphology and peritoneum restricted metastatic pattern.

Minimum Requirements to Safely Establish and Sustain New Hepatic Arterial Infusion Pump Programs: An International Expert Perspective.

Hepatic arterial infusion (HAI) pump chemotherapy is an effective therapy for colorectal liver metastases and intrahepatic cholangiocarcinoma. In the setting of recent reports suggesting favorable outcomes in these diseases with HAI, there has been a surge in interest in this treatment worldwide, prompting the opening of many new HAI programs. While significant technical expertise is required for pump implantation, this alone is insufficient to open a safe and sustainable HAI program, and numerous other factors must be considered prior to the first pump implantation.

Adjuvant Cytotoxic Chemotherapy may not be Associated with a Survival Advantage for Resected Intrahepatic Cholangiocarcinoma.

Background: Randomized data suggest improved survival with adjuvant chemotherapy for biliary tract cancers; however, subset analyses of intrahepatic cholangiocarcinoma (IHC) show limited survival benefit. This study evaluated the impact of adjuvant chemotherapy on recurrence patterns and overall survival (OS) in patients with resected IHC.

Methods: Patients who underwent curative-intent resection for IHC were identified within a bi-institutional dataset and the National Cancer Database (NCDB).

Correlation Between Grade of Clinical Response to Neoadjuvant Therapy for Rectal Cancer and Oncologic Outcomes in the Era of Watch-and-Wait.

Background: The watch-and-wait strategy provides an opportunity to pursue nonoperative management in rectal cancer patients with clinical complete response after neoadjuvant therapy. The management of those with near-complete response remains controversial.

Objective: We assessed the oncologic outcomes of patients managed by watch-and-wait versus total mesorectal excision according to clinical response to neoadjuvant therapy.

MOUNTAINEER-03 phase III study design: first-line mFOLFOX6 + tucatinib + trastuzumab for HER2+ metastatic colorectal cancer.

Patients diagnosed with metastatic colorectal cancer (mCRC) have a poor prognosis with survival ranging 2-3 years. The prevalence of human epidermal growth factor receptor 2 (HER2) amplification is approximately 3-4% in mCRC and increases up to 8% in patients with // wild-type (WT) CRC tumors. Tucatinib is a highly selective HER2-directed tyrosine kinase inhibitor that, in combination with trastuzumab, has demonstrated clinically meaningful activity in patients with chemotherapy-refractory, HER2-positive (HER2+), WT mCRC in the MOUNTAINEER trial.

Differences in Ancestry and Presence of Gastric Precursor Lesions in Individuals With Young- and Average-Onset Gastric Cancer.

Background: There has been a paradoxical rise in young-onset gastric cancer (YOGC), defined as gastric cancer (GC) diagnosed before age 50. Precursor lesions may contribute to pathogenesis, though their role in progression to different histologic subtypes is unclear. The impact of self-reported race is also poorly characterized and may be unreliable as a proxy for genetic differences.

Predictors of Recurrence in Nonmetastatic Appendiceal Epithelial Cancers: An Updated Single-Center Experience Over 25 Years.

Background: Appendiceal epithelial tumors are rare and encompass a broad set of adenocarcinoma histologies, including mucinous (mAC), colonic-type (cAC), and goblet cell (GCA) adenocarcinomas. It has previously been reported that nodal disease predicted recurrence in patients with nonmetastatic appendiceal adenocarcinomas, supporting diagnostic laparoscopy with right hemicolectomy for staging and assessment for risk of recurrence. In this update, we sought to identify predictors of nodal disease on initial diagnostic pathology in nonmetastatic adenocarcinomas.

Analysis of Shared Variants between Cancer Biospecimens.

Purpose: Mutational data from multiple solid and liquid biospecimens of a single patient are often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence.

Experimental Design: Utilizing 8,000 patient tumors from The Cancer Genome Atlas across 33 cancer types, we estimated the background rates of co-occurrence of mutations between discrete pairs of samples across cancers and by cancer type.

Fertility outcomes post immune checkpoint inhibitor exposure.

Harrold et al. evaluate the fertility impact of checkpoint inhibitor blockade (ICB), demonstrating that unlike in utero exposure, post-exposure conception appears to result in uncomplicated pregnancies and healthy progeny. They demonstrate contemporaneous monitoring of temporal female hormonal fluctuations before, on, and post ICB exposure and prior to successful embryo implantation.