Purpose: Survival is currently prolonged in WHO grade II glioma (GIIG). Although exceptionally described, long-term survivors may develop second primary cancers outside the central nervous system (CNS). Here, a consecutive series explored the association between non-CNS cancers (nCNSc) and GIIG in patients who underwent glioma resection.

Methods: Inclusion criteria were adult patients operated for a GIIG who experienced nCNSc following cerebral surgery.

Results: Nineteen patients developed nCNSc after GIIG removal (median time 7.3 years, range 0.6-17.3 years), including breast cancers (n = 6), hematological cancers (n = 2), liposarcomas (n = 2), lung cancers (n = 2), kidney cancers (n = 2), cardia cancers (n = 2), bladder cancer (n = 1), prostate cancer (n = 1) and melanoma (n = 1). The mean extent of GIIG resection was 91.68 ± 6.39%, with no permanent neurological deficit. Fifteen oligodendrogliomas and 4 IDH-mutated astrocytomas were diagnosed. Adjuvant treatment was administrated in 12 patients before nCNSc onset. Moreover, 5 patients underwent reoperation. The median follow-up from initial GIIG surgery was 9.4 years (range 2.3-19.9 years). Nine patients (47%) died in this period. The 7 patients who deceased from the second tumor were significantly older at nCNSc diagnosis than the 2 patients who died from the glioma (p = 0.022), with a longer time between GIIG surgery and the occurrence of nCNSc (p = 0.046).

Conclusion: This is the first study investigating the combination between GIIG and nCNSc. Because GIIG patients are living longer, the risk to experience second neoplasm and to die from it is increasing, especially in older patients. Such data may be helpful for tailoring the therapeutic strategy in neurooncological patients developing several cancers.