High‐grade gliomas in patients with prior systemic malignancies

Abstract

BACKGROUND The current study was conducted to characterize the impact of a prior malignancy on the diagnosis, treatment, and outcome of high‐grade glioma. METHODS A retrospective study of 21 patients with a histologic diagnosis of glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO) after a prior diagnosis of solid tumor or hematologic malignancy was conducted. Glioma histology (GBM vs. AA/AO), patient age (≤ 60 years vs. > 60 years), and extent of resection (biopsy vs. subtotal vs. complete) were evaluated for their prognostic influence. RESULTS Of the 21 patients studied, 17 had GBM, 3 had AA, and 1 patient had high‐grade AO. There were 25 systemic carcinomas diagnosed in 21 patients (18 solid tumors including breast carcinoma, prostate carcinoma, and melanoma and 7 hematologic malignancies). The glioma occurred within a previous radiation field in only three patients, two of whom had solid tumors and one of whom had a childhood hematologic malignancy. Surgical resection was the initial treatment for the brain tumor in 17 patients, and the majority of patients received radiation therapy and adjuvant chemotherapy. Four patients who initially were misdiagnosed as having brain metastases received whole brain radiation therapy as their initial treatment, thereby compromising optimal care. The overall median survival for all the patients in the current study was 14 months (range, 1–44 months) from the time of brain tumor diagnosis. The extent of resection was found to be the only prognostic variable that was associated with survival (P = 0.03). CONCLUSIONS Secondary glioma may occur in patients as a consequence of therapy for a prior malignancy, but most often represents a sporadic event. The outcome and recommended treatment are identical to those for patients with primary gliomas. Accurate diagnosis is essential; neuroimaging often is suggestive of a primary brain tumor and should initiate surgical intervention so that histopathology can be obtained early and appropriate treatment instituted. Cancer 2002;94:3219–24. © 2002 American Cancer Society. DOI 10.1002/cncr.10595

Temozolomide and oral VP‐16 for children and young adults with recurrent or treatment‐induced malignant gliomas

“…Treatment with conventional chemotherapy has not proven effective [1,2], and more innovative approaches such as high-dose chemotherapy with stem cell rescue [3] and stereotactic radiosurgery [4] have resulted in only modest success. Children and young adults with secondary (i.e., treatment-related) high-grade gliomas or transformation from low-grade to higher-grade lesions also fare poorly [5][6][7].Temozolomide is a recently developed alkylating agent which has proven activity against pediatric and adult central nervous system (CNS) malignancies [8][9][10][11]. Despite initial enthusiasm about temozolomide for children with brain tumors, in a recent phase II study of this agent for children with recurrent CNS malignancies, only 12% of children with relapsed or progressive high-grade gliomas responded to therapy [12].…”

Comprehensive molecular characterization of pediatric treatment-induced high-grade glioma: A distinct entity despite disparate etiologies with defining molecular characteristics and potential therapeutic targets

“…The highest cumulative incidence of TIHGG is in survivors of medulloblastoma, ependymoma, and leukemia 1 . TIHGG represents a rare but significant cause of late mortality in survivors of childhood cancer 2 , as few therapeutic options are available at diagnosis 3, 4 . Genomic analysis of TIHGG has been restricted to only a few small cohorts, but early evidence suggests that, in comparison with de novo pediatric high-grade gliomas (pHGG), TIHGG may be enriched for recurrent copy-number alterations and for amplification of PDGFRA and other potential activators of the MAP kinase pathway 5, 6 .…”

Current Studies of Immunotherapy on Glioblastoma

“…The net balance is that CNS immune surveillance still occurs. In spite of these apparently local as well as global aberrations in cellular immunity, most of the glioblastoma patients are generally not systemically immune compromised prior to the growth of their tumor [12,17]. It is therefore likely that tumorassociated immunosuppressive factors will similarly affect clinical attempts to augment antitumor responses.…”