BIOM-15. METASTATIC BIFOCAL GERMINOMA: A CASE HIGHLIGHTING DRAMATIC EARLY RADIOLOGICAL RESPONSE TO STEROIDS AND REBOUND FOLLOWING DISCONTINUATION, AND THE UTILITY OF CIRCULATING MIR-371A-3P QUANTIFICATION AND VINBLASTINE MONOTHERAPY PRIOR TO DEFINITI

Abstract BACKGROUND In Europe, bifocal germinoma is diagnosed based on typical age (>8-10y), symptoms (diabetes insipidus), radiological appearances, and serum/CSF AFP/HCG markers below thresholds. A 12yo male presented with 4-month headaches, 3-month polyuria/polydipsia, visual and somnolence/memory issues. Weight=71.1kg; height=166cm. MRI head/spine revealed hydrocephalus and 19×14×15mm (volume=2.09cm3) enhancing pineal lesion with nodular suprasellar and septum-pellucidum soft tissue. CSF positive for malignant cells. Serum/CSF AFP/HCG markers below thresholds. Metastatic bifocal germinoma diagnosed. Dexamethasone (8mg/day=4.4mg/m2/day) commenced for raised pressure. Proton referral (craniospinal-irradiation) made, but 8 weeks to expected start; hence, external-ventricular-drain (EVD) placed and weekly vinblastine commenced (PMIDs:32642701/34520101). METHODS Serum/CSF placental-alkaline-phosphatase (PLAP) and miR-371a-3p measured at diagnosis and CSF longitudinally. MRI performed at d9+d19 post-vinblastine. RESULTS. At diagnosis, CSF miR-371a-3p PCR positive (raw-Cq=18.64) (PMID:37386046); serum miR-371a-3p and serum/CSF PLAP all negative. In follow-up, CSF miR-371a-3p levels fell with weekly vinblastine, consistent with treatment response; PLAP remained non-informative. Repeat CSF cytology after two vinblastine doses was negative. D9 MRI showed reduction in tumour size/enhancement [pineal lesion 13×7×12mm (0.57cm3) from 19×14×15mm] and reduced ventricular size. Dexamethasone switched to maintenance-dose hydrocortisone (10mg+5mg+2.5mg=9.7mg/m2/day). D19 MRI, however, showed increased tumour volume again (pineal=17×10×14mm; 1.25cm3), albeit less than at diagnosis, with CSF miR-371a-3p down to raw-Cq=26.92 (>300-fold reduction from diagnosis). EVD removed and septostomy performed; biopsy confirmed germinoma only (<5% cells) with >95% inflammatory cells (lymphocytes/macrophages). Vinblastine continued until protons without further tumour-associated comorbidity; MRI pre-protons showed pineal 10×10×12mm (0.63cm3; partial-remission) and post-protons complete-remission. Conclusion. Early radiological response to dexamethasone, with rebound on maintenance hydrocortisone, presumably secondary to lymphocytic re-infiltration of tumour (PMID:18000859). Reassuringly, circulating miR-371a-3p was informative for germinoma diagnosis (confirmed by biopsy) and treatment response. Weekly vinblastine useful bridge to definitive radiotherapy, explored in upcoming MonoGerm trial.