Clinical, Prognostic, and Survival Implications of Vitamin B12 Levels in Cancer Patients Following Chemo- or Radiotherapy

Cancer is widely accepted as a metabolic disease. Cancer treatment with chemotherapy and radiotherapy has significant toxicity that can impair prognosis and survival. Vitamin B12 is a cofactor in one-carbon metabolism essential for DNA synthesis and genomic stability. It has been proposed as a potential biomarker for cancer prognosis and survival, but its trends after chemotherapy or radiotherapy remain ambiguous. This systematic review investigated the potential of vitamin B12 levels as biomarkers in patients with cancer and whether levels, and changes after chemotherapy or radiotherapy, are connected with clinical outcomes, cancer prognosis, and survival. This systematic review followed the 2020 PRISMA guidelines. PubMed, ScienceDirect, Europe PMC, Directory of Open Access Journals (DOAJ), and HubMed were searched using combinations of terms related to vitamin B12, cancer, chemotherapy, radiotherapy, prognosis, and survival, supplemented by MeSH terms in PubMed. Observational studies (2005-2025) in adult cancer patients reporting vitamin B12 changes after chemotherapy/radiotherapy or their clinical, prognostic, or survival associations were included. Two reviewers independently screened records; quality was assessed using the Newcastle-Ottawa Scale for case-control/cohort studies and the JBI Critical Appraisal Checklist for cross-sectional studies. Due to heterogeneity, findings were synthesized narratively rather than meta-analytically. Of 1,074 records identified, eight studies representing seven distinct cohorts (1,477 patients) met inclusion criteria: one case-control, six cohort, and one cross-sectional study, spanning lung, breast, oesophageal, colorectal, hepatic, cervical cancers and diffuse large B-cell lymphoma. Seven studies evaluated chemotherapy and one, radiotherapy. Earlier chemotherapy studies generally showed no significant or only modest changes in vitamin B12 levels during or after treatment. However, a recent prospective study from Gaza demonstrated a significant decrease in serum vitamin B12 following chemotherapy, accompanied by increased methylmalonic acid and homocysteine, suggesting worsening functional vitamin B12 status. The same cohort demonstrated an association between worsening functional vitamin B12 status and chemotherapy-induced peripheral neuropathy. In contrast, the single radiotherapy study found significantly lower vitamin B12 levels and impaired cobalamin status 6-12 years after pelvic radiotherapy, with 20% of survivors meeting deficiency criteria. Lower baseline vitamin B12 was associated with greater anxiety severity during chemotherapy in one study, while another found lower baseline levels associated with significantly better overall survival and time to progression. In conclusion, chemotherapy does not appear to consistently alter circulating vitamin B12 levels, although recent evidence suggests it may be associated with a significant decline in vitamin B12 and worsening functional status in some populations. Pelvic radiotherapy may cause long-term vitamin B12 deficiency. While vitamin B12 status may hold clinical and prognostic value in some cancers, the limited number of studies and heterogeneity in the current literature preclude firm conclusions. Further high-quality prospective studies incorporating functional vitamin B12 biomarkers are needed to clarify the relationship between cancer therapy, vitamin B12 status, and clinical outcomes before routine clinical use can be recommended.