Clinical and genomic features in patients with second primary glioblastoma following first primary renal cell carcinoma

Abstract

Purpose To explore the potential pathogenesis and clinical features of second primary glioblastoma (spGBM) following first primary renal cell carcinoma (fpRCC). Methods Patients with spGBM after fpRCC were enrolled from our institution and the SEER dataset. Sanger sequencing, whole genome sequencing, and immunehistochemistry were used to detect molecular biomarkers. Results Four and 122 cases from our institution and the SEER dataset, respectively, were collected with an overall median age of 69 years at spGBM diagnosis following fpRCC. The median interval time between fpRCC and spGBM was 50.7 months and 4 years, for the four and 122 cases respectively. The median overall survival time was 11.2 and 6.0 months for the two datasets. In addition, spGBM patients of younger age (< 75 years) or shorter interval time (< 1 year) had favorable prognosis (p = 0.081 and 0.05, respectively). Moreover, the spGBM cases were molecularly classified as TERT only paired with TP53 mutation, PIK3CA mutation, EGFR alteration, low tumor mutation burden, and stable microsatellite status. Conclusions This is the first study to investigate the pathogenesis and clinical features of spGBM following spRCC. We found that spGBMs are old-age related, highly malignant, and have short survival time. Moreover, they might be misdiagnosed and treated as brain metastases from RCC. Thus, the incidence of spGBMs after fpRCC is underestimated. Further studies are needed to investigate the underlying molecular mechanisms and clinical biomarkers for the development of spGBM following fpRCC.

Letter to the Editor regarding “Clear-cell renal cell carcinoma and glioblastoma multiforme coexistence: Double primary malignancy, does it have a causal relationship?”

“…[2] Different patterns of coincidental RCC and GBM have been reported, including both synchronous and metachronous presentations. [2,4,[8][9][10][11] Although no clear relationship between these two cancers has been elucidated, it has been suggested that they may cooccur due to therapeutic side effects, underlying genetic syndromes, or as an unfortunate coincidence.…”

“…[8,11] However, Zhang et al were not able to confidently attribute GBM development to any specific therapeutic measure incurred during treatment for RCC, as none of the described patients received cranial radiotherapy, and the pharmacotherapy between patients was inconsistent. [11] In addition, Kim et al's description of an RCC occurring in a patient with existing GBM does not show a relationship between GBM treatment and RCC;…”

“…It has been suggested RCC and GBM may occur in the same patient as part of genetic syndromes, although there is no clear evidence as to which genes, alleles, or mutations are responsible. [10,11] Simanjuntak et al implicate genetic syndromes, such as Li-Fraumeni syndrome, neurofibromatosis, and VHL, as possibly being involved. [10] Notably, VHL is an established predisposition to developing RCC, although it does not seem to play a role in GBM.…”

“…[ 2 , 10 ] We have subsequently identified two case reports not described by Simanjuntak et al ., a recently reported case series/database analysis including 126 cases of RCC followed by GBM, and an investigation of malignancies in long-term survivors (LTS) of GBM that describes one RCC arising in a patient with an existing GBM diagnosis. [ 4 , 8 , 9 , 11 ] A brief overview of all cases is found in Table 1 .…”

“…hypothesize the average higher age of GBM and the molecular profiles of these tumors (TERT positive) are likely responsible for the worse outcomes. [ 11 ] Kim et al . report a case series of malignancies occurring in LTS of GBM.…”