Introduction: High-grade glioma (HGG) usually follows a short but variable clinical course with survival ranging between a few weeks to a few years. All patients follow the same course of treatment so this heterogeneity in response is poorly understood. We now aimed to determine the relationship between responses to treatment for patients with the ALT versus those with non-ALT HGGs
Methods: One hundred and thirty five glioblastomas prospectively collected with informed consent following neurosurgery in New Zealand. Tumours were analyzed for TMM using Southern blot or ALT associated PML bodies (APBs). The presence of macrophages/activated microglia was determined by immunohistochemistry for CD163 and MGMT expression
Results: 13/35 (37%) ALTs contained MGMT positive CD163 positive non-malignant cells. For the non-ALTs the proportion was similar with about one third of tumours containing significant numbers of CD163 positive cells. The presence of macrophages in the Non-Alt GBMs group greatly affected the extent of resection making total/near total resection possible in only half of them comparing 78% in their absences. The presence of ALT TMM associated with a longer survival but surprisingly with no significant response to temozolomide treatment. Patients with the ALT phenotype did not respond to temozolomide, with median survival of 17.5 months for surgery + radiotherapy and 20.3 months for those who also received additional temozolomide, with ALT tumours 50% survived irrespective of treatment.
Patients with non-ALT HGG responded significantly to TMZ, particularly in the absence of CD163 expressing cells (P = 0.002).
Conclusions: By the conclusion ALT TMM is associated with more frequent total surgical resections and a better long-term survival rate in spite of a resistance to TMZ. In the Non-Alt group the presence of macrophages has an adverse effect on ability to obtain a total resection and response to TMZ resulting in lower median survival with no LTS.
Patient Care: better understanding of GBMs and response to treatment.
Learning Objectives: treatment of GBMs could be individualized