Deborah R. Smith

Clinical and molecular characteristics of gliosarcoma and modern prognostic significance relative to conventional glioblastoma

Gliosarcoma is a rare histopathologic variant of glioblastoma traditionally associated with a poor prognosis. While gliosarcoma may represent a distinct clinical entity given its unique histologic composition and molecular features, its relative prognostic significance remains uncertain. While treatment of gliosarcoma generally encompasses the same standardized approach used in glioblastoma, supporting evidence is limited given its rarity. Here, we characterized 32 cases of gliosarcoma and retrospectively evaluated survival relative to 451 glioblastoma patients diagnosed during the same era within the same institution. Overall, we identified 22 primary gliosarcomas, representing 4.7% of WHO Grade IV primary glioblastomas, and 10 secondary gliosarcomas. With median age of 62, patients were predominately Caucasian (87.5%) and male (65.6%). Tumors with available molecular profiling were primarily MGMT-unmethylated (87.5%), IDH-1-preserved (100%) and EGFR wild-type (100%). Interestingly, while no significant median survival difference between primary gliosarcoma and glioblastoma was observed across the entire cohort (11.0 vs. 14.8 months, p = 0.269), median survival was worse for gliosarcoma specifically among patients who received modern temozolomide-based (TMZ) chemoradiotherapy (11.0 vs. 17.3 months, p = 0.006). Matched-pair analysis also trended toward worse median survival among gliosarcomas (11.0 vs. 19.6 months, log-rank p = 0.177, Breslow p = 0.010). While adjuvant radiotherapy (HR 0.206, p = 0.035) and TMZ-based chemotherapy (HR 0.531, p = 0.000) appeared protective, gliosarcoma emerged as a significantly poor prognostic factor on multivariate analysis (HR 3.27, p = 0.012). Collectively, our results suggest that gliosarcoma may still portend worse prognosis even with modern trimodality therapy.

The success of NRG-GBM-RPA: biomarker-based classification, where to next?

Glioblastoma (GBM) is an aggressive primary brain tumor in which outcomes are poor (1). Treatment for GBM had been limited until 2005 with the seminal study by Stupp and colleagues in which the addition of concurrent and adjuvant temozolomide (TMZ) to adjuvant radiotherapy improved median overall survival (mOS) by approximately 2.5 months (2). Since then, radiation therapy with TMZ has been the backbone for management of GBM in the postoperative setting. Initially developed in 1993, the recursive partitioning analysis (RPA) was created to prognosticate patients with high-grade gliomas (including anaplastic astrocytoma and GBM) (3). This classification was further modified and verified in GBM patients treated with radiation and TMZ (1,4).

Koebner phenomenon: Consideration when choosing fractionation for breast irradiation

A 62-year-old woman with a remote medical history of psoriasis initially presented with a palpable right breast mass. She underwent right breast ultrasound that revealed a hypoechoic mass at 10:30, 6 cm from the nipple, that measured 1.7 × 2.1 × 2.1 cm. Biopsy of the mass revealed invasive ductal carcinoma. Subsequent breast magnetic resonance imaging scans confirmed the right breast cancer, but also revealed a suspicious left breast region at 1:00. Biopsy of the left breast mass revealed a radial scar. The patient was evaluated by both breast and plastic surgery physicians and subsequently underwent right partial mastectomy and sentinel lymph node biopsy and excisional biopsy for the radial scar followed by bilateral oncoplastic breast reduction. Final pathology showed right breast multifocal invasive ductal carcinoma, grade 3, with no involved sentinel nodes, and left breast ductal carcinoma in situ. The patient’s postoperative course was complicated by bilateral seromas requiring drainage as well as bilateral breast cellulitis treated with antibiotics. She was evaluated by the radiation oncology department, and the decision was made to delay starting radiation to allow adequate wound healing. In the interim, she was started on Anastrazole 1 mg. The patient was assessed weekly, and eventually radiation was begun on the right breast, with the left side delayed to allow for further healing. The patient was treated in the prone position with hypofractionated whole breast radiation therapy (WBRT) of 42.56 Gy in 16 fractions with a 10 Gy boost to the right breast starting November 21. She completed treatment on December 21 without treatment breaks. During the second week of treatment, using daily Hydrophor and topical hydrocortisone as needed, the patient developed grade 1 erythema and pruritus of the right breast. After her leftsided seroma drainage resolved, she started adjuvant hypofractionated WBRT of 42.56 Gy in 16 fractions to the left breast on January 5, which she completed on January 27 without treatment breaks. During the second week of treatment, the patient developed grade 1 erythema of the left breast. Her right breast erythema improved with mild hyperpigmentation. The patient was seen for routine follow-up on March 1 approximately 1 month after completing her left breast radiation course. The patient noted that the erythema in her left breast was resolving (Fig 1a); however, over the course of the following few days, she noted a new rash on her right breast (Fig 2a) in the distribution of her radiation field (Fig 2b), along with similar rashes in her right inguinal region (Fig 1b) and her left wrist. The patient’s psoriasis had been inactive for more than 5 years. She was seen by her dermatologist, who suspected Koebner phenomenon. The patient underwent biopsy of the right inguinal rash; Conflicts of interest: None. * Corresponding author. Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032. E-mail address: dph2119@cumc.columbia.edu (D.P. Horowitz). 1 C.-C.W. and S.W. contributed equally to this work. Advances in Radiation Oncology (2018) 3, 108–110