irradiation of stem cell niches in the periventricular and sub granular zones in gbm : A Prospective study Akram K S, Monica I, Deepa J, Kesava R, Fayaz Ahmed S, Vijaya Krishna E, Pavan Kumar L, Deepthi V, Suresh P, Naidu KVJR Department of Radiation Oncology, Nizam’s Institute of Medical Sciences, Hyderabad, India

BACKGROUND Glioblastoma one of the most common malignant primary tumors of the brain, is very aggressive, tends to infiltrate diffusely into surrounding brain tissues. The current standard of care combines surgery and radiotherapy with concurrent and adjuvant chemotherapy treatment.With this multi-modality approach, the median survival is only around 14 months with early recurrences primarily found in the brain. Recent preclinical and clinical data provide convincing evidence that GBMs are organized hierarchically with small number of cancer stem cells (CSCs), which have the unique ability to self-renew and exhibit multi-lineage potency while their progeny lack these features. According to the cancer stem cell hypothesis, all CSCs need to be eliminated in order to cure cancer. The normal tissue stem cells niche in the brain may be a reservoir for CSCs from where they initiate and repopulate a tumor and that irradiation of the potential cancer stem cell niches in the brain would improve survival.

OBJECTIVES Various investigators have included csc niches areas invariably to include entire periventricular zone including the subgranular layer of the hippocampus or only a 3-5mm strip along the lateral wall of lateral ventricles during radiotherapy. We conducted a prospective study of patients of Glioblastomae multiformae to study the effect of radiation doses of ≥ 50 Gy delivered to the potential stem cell niches.

MATERIALS & METHODS Following maximal safe resection, patients of GBM were planned for radiation therapy to a total dose of 60 Gy @ 2 Gy per fraction. The CTV was contoured to include the preoperative tumor with 1- 1.5cm margin, peritumoral edema and potential stem cell niches. The periventricular zone (PVZ) was contoured as a 5 mm margin around the ventricles including the subgranular layer (SGL) of the hippocampus.

SVZ CONTOURING Sub ventricular zone (SVZ) is contoured as 5 mm expansion along the lateral margin of the lateral ventricles on axial planning CT SCAN fused with MRI SCAN.

SGL CONTOURING The SGL of hippocampus was contoured as per RTOG contouring atlas.

MATERIALS & METHODS The ipsilateral PVZ was planned to receive ≥50Gy respecting adjacent critical structure tolerance doses. All patients received concurrent chemotherapy with Temozolomide (TMZ) 75 mg/m2/day during radiation. Adjuvant chemotherapy was planned with TMZ 150-200 mg/m2/day for 1st 5days,4th weekly for 6-12 cycles. Survival was analyzed and correlated with doses to ipsilateral PVZ, SVZ and SGL. Statistical analysis was done using SPSS v 19.0.

Site group as per classification scheme suggested by Jaffri et al RESULTS A total of 40 patients were included in the study. Mean age was 45 years (range 11 to 70). Follow up was available for 33 patients . Mean doses to ipsilateral PVZ, SVZ and SGL were 56, 58 and 52 Gy respectively. Mean doses to contralateral PVZ and SVZ were 47 and 48 Gy respectively. Median survival as per Kaplan Meier estimates was 14 months. Mean ipsilateral SVZ dose of ≥58 Gy was significant for overall survival (p=0.05). Mean and minimum doses to ipsilateral PVZ and SGL did not show any significant correlation. 35% 37.5% Site group as per classification scheme suggested by Jaffri et al Group I - 46% (18) Group II - 11.5% (5) Group III - 36% (14) Group IV - 2.5% (1) Multifocal – 4% (2)

CONCLUSIONS An ipsilateral SVZ mean dose of ≥58 Gy was associated with improved overall survival. Mean dose to the entire ipsilateral PVZ including the SGL did not show any correlation with survival in these group of patients. Including the ipsilateral SVZ in the CTV to receive the doses of ≥58 Gy could potentially improve outcomes in GBM. However these findings need confirmation in a larger trial accounting for various prognostic factors in Glioblastomae multiformae. REFERENCES Barmani et al, Patrick Evers et al Tejpal Gupta et al, Linda Chen et al Percy Lee et al, Nazia F. Jafri et al CONTACT INFORMATION: k.syedakram@gmail.com