Resection of Noncontrast-Enhancing Regions Deteriorated the Immunotherapeutic Efficacy of HSPPC-96 Vaccination in Treating Glioblastoma

Surgical resection remains a first-line therapy for glioblastoma multiforme (GBM). Increased extent of resection (EOR) of noncontrast-enhancing regions in T2-weighted MRI images (T2-EOR) provides a survival benefit for GBM patients receiving standard radio/chemotherapy. However, whether it also improves immunotherapeutic outcomes remains unclear. We calculated the T2-EOR by comparing the preoperative and postoperative MRI T2 hyperintensity outside the enhancing tumour and correlated the T2-EOR with immunological and clinical outcomes from our published early-phase trial of heat shock protein peptide complex-96 (HSPPC-96) vaccination in treating a cohort of 19 patients with newly diagnosed GBMs (NCT02122822). Patients with higher T2-EOR exhibited shorter progression-free survival (PFS) (HR 11.29, p=0.002) and overall survival (OS) (HR 6.5, p=0.003) times than patients with lower T2-EOR. T2-EOR was negatively correlated with the levels of tumour specific immune response (TSIR) post-vaccination (R=-0.725, p<0.001) and absolute TSIR increase from pre- to post-vaccination (R=-0.679, p=0.001). Multivariate Cox regression models revealed that higher T2-EOR represented an independent risk factor for PFS (HR 19.85, p=0.0068) and OS (HR 21.24, p=0.0185) in this patient cohort. Taken together, increased T2-EOR deteriorated immunotherapeutic outcomes by suppressing TSIR, suggesting the potential of T2-EOR as an early biomarker for predicting the immunotherapeutic efficacy of HSPPC-96 vaccination.