69P Transferrin saturation shows high prevalence of iron deficiency in cancer patients under adjuvant and neo-adjuvant treatment

Abstract

Background: Pathogenic BRCA1/2 mutations currently serve as the main biomarker of homologous recombination deficiency (HRD) for PARP inhibitor (PARPi) selection, which have also been reported to correlate with the efficacy of platinum (Pt) chemotherapy. However, patients without BRCA1/2 alterations can also present HRD phenotype through other mechanisms and might benefit from PARPi or Pt chemotherapy.Methods: HRD score of tumor samples from 199 patients (Cohort I: ovarian, breast, pancreatic, prostate, and uterine cancers) were evaluated by targeted next-generation sequencing (NGS) (GeneseeqPrimeÒ HRD). A cohort of 416 independent solid tumor patients (Cohort II) were further analyzed for exploring HRD score distribution, while another cohort of 84 high-grade serous ovarian cancer patients (Cohort III) who received Pt chemotherapy were analyzed for investigating the predictive value of HRD score in treatment efficacy.Results: HRD score, combining loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale station transitions (LST), of Cohort I ranges from 0 to 107, 32% of which harbor BRCA1/2-deficiency (pathogenic mutations with LOH, 2 pathogenic mutations, or homozygous deletion). HRD score 38 was defined as HRDpositive that accounts for approximately 95% of the BRCA1/2-deficient cases. In Cohort II, 14% of them were BRCA1/2-deficient with a median HRD score of 67 which was significantly higher than that of the BRCA1/2-sufficient ones (28; p<0.001). In BRCA1/2-wildtype subgroup, 37% of patients have HRD scores38 (51%, 42%, and 8% for ovarian, breast, and pancreatic cancers). In Cohort III, patients with a platinumfree interval (PFI) of over 6 months (Pt-sensitive) have significantly higher HRD scores than Pt-resistant patients (median: 55 vs 34, p¼0.04). In BRCA1/2-wildtype patients, a significantly longer PFS was observed when HRD38 than those with HRD<38 (median: 17.8 vs 11.8 months, p¼0.04).Conclusions: Our study reported an HRD evaluation pipeline based on targeted NGS in diverse cancer types, and HRD38 was chosen to define HRD-positive status, which correlates with better clinical outcomes of Pt-chemotherapy.

Iron deficiency screening is a key issue in chronic inflammatory diseases: A call to action

“…In the recent CARENFER study, among cancer patients with ID as defined by the ESMO criteria, TSAT was <20% in 85.8% of patients with neoadjuvant treatment, 90.1% with adjuvant therapy, and 88.6% with metastatic treatment [10, 97]. This indicates that TSAT <20% as the sole criterion for defining ID in cancer patients had high sensitivity regardless of the disease stage.…”