Central nervous system (CNS) relapse affects 5% of diffuse large B‐cell lymphoma (DLBCL) patients and portends a poor prognosis. Prophylactic intravenous high‐dose methotrexate (HD‐MTX) is frequently employed to reduce this risk, but there is limited evidence supporting this practice. We conducted a multicenter retrospective study to determine the CNS relapse risk with HD‐MTX in DLBCL patients aged 18–70 years treated in Alberta, Canada between 2012 and 2019. Provincial guidelines recommended HD‐MTX for patients at high‐risk of CNS relapse based upon CNS‐IPI score, double‐hit lymphoma, or testicular involvement. Among 906 patients with median follow‐up 35.3 months (range 0.29–105.7), CNS relapse occurred in 1.9% with CNS‐IPI 0–1, 4.9% with CNS‐IPI 2–3, and 12.2% with CNS‐IPI 4–6 (p < .001). HD‐MTX was administered to 115/326 (35.3%) high‐risk patients, of whom 96 (83.5%) had CNS‐IPI score 4–6, 45 (39.1%) had double‐hit lymphoma, and four (3.5%) had testicular lymphoma. The median number of HD‐MTX doses was two (range 1–3). Central nervous system relapse risk was similar with versus without HD‐MTX (11.2% vs. 12.2%, p = .82) and comparable to previous reports of high‐risk patients who did not receive CNS prophylaxis (10–12%). In multivariate and propensity score analyses, HD‐MTX demonstrated no association with CNS relapse, progression‐free survival, or overall survival. This study did not demonstrate a benefit of prophylactic HD‐MTX in this high‐risk patient population. Further study is required to determine the optimal strategy to prevent CNS relapse in DLBCL.
Given the safety and potential benefits of intravenous ascorbic acid (AA) administration in cancer patients, there is merit in further exploring this therapeutic concept. In this review, we discuss the potential benefits of intravenous AA administration on colorectal cancer and we specifically focus on its effect on glycolysis in mutant and wild type RAS. We perform a PubMed and Ovid MEDLINE search using ascorbic acid, intravenous vitamin C, KRAS mutation, BRAF mutation and colorectal cancer (CRC) as keywords. At the cellular level, colorectal cancer cells undergo a metabolic shift called the Warburg effect to allow for more glucose absorption and utilization of glycolysis. This shift also allows AA to enter which leads to a disruption in the Warburg effect and a shutdown of the downstream KRAS pathway in mutated KRAS colon cancer cells. At the clinical level, AA is associated with tumour regression in advanced disease and improved tolerability and side effects of standard therapy. Based on these findings, we conclude that further clinical trials are needed on a larger scale to examine the therapeutic benefits of AA in colon cancer.
Gastric cancer remains a disease with a dismal prognosis. Extensive efforts to find targetable disease drivers in gastric cancer were implemented to improve patient outcomes. Beyond anti-HER2 therapy, MET pathway seems to be culprit of cancer invasiveness with MET-overexpressing tumors having poorer prognosis. Tyrosine kinase inhibitors targeting the HGF/MET pathway were studied in MET-positive gastric cancer, but no substantial benefit was proven. Some patients responded in early phase trials but later developed resistance. Others failed to show any benefit at all. Etiologies of resistance may entail inappropriate patient selection with a lack of MET detection standardization, tumor alternative pathways, variable MET amplification, and genetic variation. Optimizing MET detection techniques and better understanding the MET pathway, as well as tumor bypass mechanisms, are an absolute need to devise means to overcome resistance using targeted therapy alone, or in combination with other synergistic agents to improve outcomes of patients with MET-positive GC.
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