Leveraging machine learning for integrative analysis of T-cell receptor repertoires in colorectal cancer: Insights into MAIT cell dynamics and risk assessment.

This study investigates the T-cell receptor (TCR) repertoires in colorectal cancer (CRC) patients by analyzing three distinct datasets: one bulk sequencing dataset of 205 patients with various tumor stages, all newly diagnosed at Sheba Medical Center between 2017 and 2022, with minimal recruitment in 2014 and 2016, and two (public) single-cell sequencing datasets of 10 and 12 patients. Despite the significant variability in the TCR repertoire and the low likelihood of sequence overlap, our analysis reveals an interesting set of TCR sequences across these data. Notably, we observe elevated presence of mucosal-associated invariant T (MAIT) cells in both metastatic and non-metastatic patients.

Mitochondrial DNA lineages determine tumor progression through T cell reactive oxygen signaling.

Mitochondrial DNA (mtDNA) is highly polymorphic, and host mtDNA variation has been associated with altered cancer severity. To determine the basis of this mtDNA-cancer association, we analyzed conplastic mice with the C57BL/6J (B6) nucleus but two naturally occurring mtDNA lineages, and , where mitochondria generate more oxidative phosphorylation (OXPHOS)-derived reactive oxygen species (mROS). In a cardiac transplant model, Foxp3+ T regulatory (Treg) cells supported long-term allograft survival, whereas Treg cells failed to suppress host T effector (Teff) cells, leading to acute rejection.

Duration of immunotherapy in dMMR/MSI-H metastatic colorectal cancer patients.

Background: Immune checkpoint blockade (ICB) has revolutionized treatment of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). However, there is no evidence on the optimal treatment duration. We aimed to compare outcomes of different immunotherapy durations.

Omission of 5-Fluorouracil Bolus From Multidrug Regimens for Advanced Gastrointestinal Cancers: A Multicenter Cohort Study.

Background: 5-Fluorouracil (5-FU) is a major component of gastrointestinal cancer treatments. In multidrug regimens such as FOLFOX, FOLFIRI, and FOLFIRINOX, 5-FU is commonly administered as a bolus followed by an infusion. However, the pharmacologic rationale for incorporating the 5-FU bolus in these regimens is unclear, and there are other effective regimens for gastrointestinal cancers that do not include the bolus.

Extremely high peritoneal cancer index in colorectal peritoneal metastases demonstrates safety and overall survival benefit in selected patients undergoing cytoreductive surgery and heated intraperitoneal chemotherapy.

Background: Colorectal peritoneal metastases are a devastating consequence of colorectal cancer (CRC) with extremely poor prognosis. Patients that can undergo complete cytoreduction by cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) have a markedly improved overall survival. Traditionally, patients with extremely high peritoneal cancer index (PCI), PCI >20, are not offered CRS/HIPEC.

Exogenous Insulin Therapy Is Associated with the Risk of Advanced Colorectal Adenoma in Patients with Diabetes Mellitus.

Background/aims: Exogenous insulin therapy increases systemic exposure to insulin which may promote the development of colorectal neoplasia. We sought to evaluate the association between exogenous insulin therapy and the incidence of advanced adenoma in type 2 diabetes mellitus.

Methods: A retrospective cohort study was conducted from January 1, 2007, to January 1, 2018, in a regional health system serving the United States Philadelphia metropolitan area, Central New Jersey, and South Central Pennsylvania.

Immunotherapy in mismatch repair-deficient metastatic colorectal cancer - Outcome and novel predictive markers.

Background: This study aims to assess predictive markers for response to immunotherapy in dMMR/MSI-H metastatic colorectal cancer (mCRC) patients.

Materials And Methods: A study using two prospective cohorts from MD Anderson Cancer Center and Sheba Medical Center of consecutive patients with dMMR/MSI-H mCRC that were treated with immunotherapy between 2014-2022. Primary outcome was progression-free survival (PFS) and secondary outcome was overall response rate (ORR).

Role of the microbiota in response to and recovery from cancer therapy.

Our understanding of how the microbiota affects the balance between response to and failure of cancer treatment by modulating the tumour microenvironment and systemic immune system has advanced rapidly in recent years. Microbiota-targeting interventions in patients with cancer are an area of intensive investigation. Promisingly, phase I-II clinical trials have shown that interventions such as faecal microbiota transplantation can overcome resistance to immune checkpoint blockade in patients with melanoma, improve therapeutic outcomes in treatment-naive patients and reduce therapy-induced immunotoxicities.

Early Systemic Anti-neoplastic Treatment Post SARS-CoV-2 Infection in Patients with Breast Cancer.

Introduction: It is unclear how soon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection it is safe to resume systemic anti-neoplastic treatment in patients with cancer. We assessed the risk of admissions or postponed treatment cycle in vaccinated patients with breast cancer receiving early systemic anti-neoplastic treatment following SARS-CoV-2 infection.

Methods: This was a retrospective cohort study conducted during Omicron SARS-CoV-2 outbreak in Israel, January-July 2022.

Tumor Differentiation as a Prognostic Marker in Clinically Staged T1bN0 Esophageal Adenocarcinoma.

Current guidelines recommend that clinically staged T1N0 esophageal cancers are to be referred to surgery or endoscopic resection. Using the National Cancer Database, we identified 733 individuals with clinically staged T1N0 esophageal carcinoma, who underwent upfront surgery and did not receive any prior treatment. We assessed upstaging, which was defined as ≥ T2 disease or positive lymph nodes.

Combination Treatment of Intratumoral Vidutolimod, Radiosurgery, Nivolumab, and Ipilimumab for Microsatellite Stable Colorectal Carcinoma With Liver Metastases.

Introduction: Microsatellite stable metastatic colorectal cancer (MSS mCRC) is largely refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response.

Patients And Methods: In this phase I single-institution study, patients with MSS mCRC were treated with a priming dose of s.

Fecal Microbiota Transplantation as a Cancer Therapeutic.

For decades, cancer research and treatment focused on the cellular level, viewing cancer as a genetic disease of cell transformation. In the era of chemotherapy and radiotherapy, studies from the second half of the 19th century suggesting an association between the microbiota and cancer were almost neglected. The main focus of the field was limited to identification of specific viruses and bacteria that may serve as direct carcinogens leading to the recognition of 7 viruses (i.

Pelvic Peritonectomy Poorly Affects Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Metastases.

Background: Constraints of pelvic anatomy render complete cytoreduction (CRS) challenging. The aim of this study is to investigate the impact of pelvic peritonectomy during CRS/HIPEC on colorectal peritoneal metastasis (CRPM) patients' outcomes.

Methods: This is a retrospective analysis of a prospectively maintained CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) database.

Natural History and Management of Small-Bowel Obstruction in Patients After Cytoreductive Surgery and Intraperitoneal Chemotherapy.

Background: Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis.

Methods: This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392).

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Elderly is Safe and Effective.

Introduction: An increasing proportion of elderly patients (EP) are undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). They have increased comorbidities and perioperative risk. Current literature is deficient in describing the outcomes of EP undergoing CRS/HIPEC.

Outcomes of Stable Lung Colorectal Metastases on Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Background: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have demonstrated benefit in patients with colorectal peritoneal metastases (CRPM). Traditionally, extraperitoneal disease is considered a contraindication to CRS/HIPEC. Stable lung metastases in patients with colorectal cancer often have an indolent course, while the presence of untreated peritoneal metastases poorly affects short-term survival.

Serological response to a third booster dose of BNT162b2 COVID-19 vaccine among seronegative cancer patients.

Background And Aim: The BNT162b2 COVID-19 vaccine (Pfizer/BioNTech), given as a two-dose series, 3 weeks apart, elicits a serological response in 84-98% of patients with cancer, even if administered while undergoing anticancer treatments. Herein, we report the impact of a third (booster) dose of BNT162b2, delivered 6 months following the second vaccine dose.

Methods: This pilot study included four patients with cancer who were seronegative after two vaccine doses, and received a third (booster) dose of BNT162b2 at 6 months following the second vaccine dose.

Validation of the Enriching New-Onset Diabetes for Pancreatic Cancer Model: A Retrospective Cohort Study Using Real-World Data.

Objectives: The Enriching New-onset Diabetes for Pancreatic Cancer (END-PAC) model identified patients at high-risk for pancreatic ductal adenocarcinoma (PDAC) more than 6 months before diagnosis. The current study aimed to validate the END-PAC model using a large, state-mandated health care provider database.

Methods: A retrospective cohort study of patients older than 50 years that had a diagnosis of new-onset diabetes (NOD) between 2006 and 2015.

Single-Fraction Celiac Plexus Radiosurgery: A Preliminary Proof-of-Concept Phase 2 Clinical Trial.

Background: Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate.

Benefit for single-agent adjuvant chemotherapy in elderly patients with locally advanced gastric adenocarcinoma.

Background: Current NCCN guidelines exclude the possibility of using single-agent adjuvant chemotherapy in locally advanced gastric adenocarcinoma, while allowing doublet chemotherapy. However, single-agent adjuvant chemotherapy is a valid treatment option in other gastrointestinal malignancies, preferred for elderly and/or frail patients. The current study used a nationwide oncology database to assess the benefit of single-agent adjuvant chemotherapy, specifically in the elderly population.