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High-Dose Intensity Modulated Radiation Therapy (IMRT) Using a Simultaneous Integrated Boost (SIB) Method Combined With Temozolomide (TMZ) for Malignant Gliomas
Poster Viewing Abstracts S249
Volume 87 Number 2S Supplement 2013 registered with pre-RT mPET so as to facilitate correlations. Failures were assigned to be within a said volume if it contained >50% of the lesion bulk. All patients received concurrent and adjuvant temozolomide. After a median post-RT span of 18 months, 54 failures were noted. After excluding 5 distant failures, 49 cases of non-distant failure (NDF) were analyzed. Results: Ratio of volume means of TVT2F:PV1.4 was 3.3 (47.5 cc vs 14.3 cc; 95% CI of difference 31.39 / 35.01, p < 0.0001). The ratios TVGd:PV1.8 and TVGd:PV2 were 0.9 (4.8 cc vs 5.3 cc; 95% CI of difference -1.03 / 0.03, p Z 0.0489) and 1.6 (4.8 cc vs 1.9 cc; 95% CI of difference 2.63 / 3.16, p < 0.0001), respectively. Volumes PV1.4 and TVT2F both contained 100% of subsequent NDFs. Other pre-RT volumes TVGd, PV1.8 and PV2 contained 75.5%, 79.6%, and 71.4% of NDFs, respectively. Conclusions: The mPET volume PV1.4 was able to predict 100% of NDFs despite being significantly smaller than the MRI volume TVT2F. The mPET volumes PV1.8 and PV2 were comparable to contrast enhanced MRI volume TVGd. Author Disclosure: S.P. Susheela: None. S. Revannasiddaiah: None. G. Mallarajapatna: None. S. Muzumder: None. K. Kallur: None. R.S. Bilimagga: None. M. Rastogi: None. M. Hassan V: None. M. Gupta: None. A. Basavalingaiah: None.
2117 High-Dose Intensity Modulated Radiation Therapy (IMRT) Using a Simultaneous Integrated Boost (SIB) Method Combined With Temozolomide (TMZ) for Malignant Gliomas K. Nakamatsu, Y. Nishimura, and I. Tachibana; Kinki University Faculty of Medicine, Osaka-Sayama City, Japan Purpose/Objective(s): Due to the low a/b ratio of malignant gliomas, hypo-fractionated radiation therapy with a high dose fraction size of >2 Gy may be effective for malignant gliomas. We have adopted a SIB protocol of a total dose of 70 Gy with a fraction size of 2.5 Gy to gross tumor volume (GTV) since 2000. Since 2008, TMZ was combined with IMRT. Clinical results of IMRT using a SIB method combined with TMZ for malignant gliomas were compared with a similar IMRT method without TMZ, retrospectively. Materials/Methods: Between 2008 and 2012, 29 patients with histologically proven malignant gliomas treated with TMZ were enrolled in this study (TMZ group) and those of 15 malignant gliomas treated without TMZ before 2008 (historical control) were compared. The TMZ group included 22 patients with glioblastoma (GBM), 7 patients with grade 3 glioma (G3). The historical control group included 8 patients with GBM, and 7 patients with G3. All patients in the TMZ group received TMZ at 75 mg/m2 (100 mg-120 mg/body) from the first day of IMRT for 42 days. The planning CT and MRI T2 weighted image were fused for all patients. IMRT was performed with 4MV or 6MV using 5 or 7 fields. GTV was defined as a contrast enhanced lesion on the pre-operative MRI T1-weighted image or contrast-enhanced CT. Clinical target volume (CTV) was defined as the GTV plus a 2-cm margin. The margin was modified to be expanded to include the edema beyond 2 cm from the GTV or to be shrunken to the anatomical defense such as intracerebral fissures or tentorium cerebelli. A total dose of 70 Gy/fraction size of 2.5 Gy/39 days was given to GTV plus 5 mm margin, and 56 Gy/fraction size of 2.0 Gy/39 days to the surrounding area of CTV plus 5 mm margin. Results: IMRT of a planned dose of 70 Gy could be delivered safely without acute toxicity for all patients in the both group. The 4-year survival rates for the TMZ group and the historical control group were 44% and 20% without statistical significance, respectively. The 2-year local rates for the corresponding groups were 24% and 7%, respectively. Even in the TMZ group, most of the tumors recurred from the GTV area. In the both groups, no brain necrosis with neurological symptom was observed. Conclusions: Our high dose fraction size IMRT with TMZ for malignant gliomas showed a better survival rate than the historical control without TMZ. However, the local recurrence rate was still high even in the TMZ group. Based on this analysis, a new prospective study of IMRT using 3 Gy
fraction to a total dose of 84 Gy to GTV for GBM combined with TMZ is undergoing at our institution. Author Disclosure: K. Nakamatsu: None. Y. Nishimura: None. I. Tachibana: None.
2118 Reirradiation of Recurrent Gliomas S. Oh, J.M. Gales, C.A. Reddy, E.S. Murphy, J.S. Yu, J.H. Suh, and S.C. Chao; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): The aim of this study was to evaluate overall survival, progression free survival, and toxicity of patients with relapsed gliomas after a second course of radiation therapy (RT). Materials/Methods: Between 1999 and 2012, a total of 49 patients with relapsed gliomas were reirradiated (1 patient with pilocytic astrocytoma, 6 patients with low grade glioma, 12 patients with anaplastic astrocytoma, and 30 patients with glioblastoma). Eighteen patients were female and 31 patients were male. Thirty-two patients received external beam radiation therapy and 17 patients received stereotactic radiosurgery. The median age at primary diagnosis of the tumor was 44 years (range, 4-64 years). Median KPS at diagnosis was 90 (range, 50-100) and median KPS at reirradiation was 80 (range, 50-100). Median initial RT dose was 60 Gy (range, 50.4-61.2 Gy), and median reirradiation RT dose was 30 Gy (range, 15 Gy-60 Gy). Patients were evaluated in follow-up by clinical investigators with MRI every three months after reirradiation until death. Results: Median interval between reirradiation was 21.9 months (mos) (range, 2.6-138.4 mos). All patients completed the planned reirradiation. Median follow-up was 11 mos (range, 2.6-61.2 mos). At the time of analysis, 43 patients (87.8%) have progressed and 32 patients (65.3%) have died. Median progression-free survival was 3.8 mos (range, 0-52 mos). Median overall survival was 14.1 mos (range, 3-60 mos). The median PFS and OS for pilocytic astrocytoma, low grade gliomas, anaplastic astrocytoma, and glioblastoma were 2.0 mos and 2.6 mos, 6.7 mos and not reached, 3.4 mos and 14.2 mos, and 3.6 mos and 12.9 mos, respectively. Fourteen patients had no central nervous system (CNS) toxicity (28.6%). 27 patients had grade 1 CNS toxicity (55.1%). Four patients had grade 2 CNS toxicity (8.2%). Four patients had grade 3 CNS toxicity (8.2%). No grade 4 or 5 CNS toxicity was observed. Conclusions: Overall, reirradiation of gliomas was well tolerated with minimal toxicity. Reirradiation techniques should be studied in a prospective manner to determine the best treatment for these patients. Author Disclosure: S. Oh: None. J.M. Gales: None. C.A. Reddy: None. E.S. Murphy: None. J.S. Yu: None. J.H. Suh: None. S.C. Chao: None.
2119 Hypofractionated Stereotactic Radiation Therapy (HFSRT) With Concurrent Chemotherapy (CTX) in Patients With Newly Diagnosed Poor Prognosis GBM: Early Results J.C. Ye, M. Yondorf, S.C. Pannullo, J.A. Boockvar, T.H. Schwartz, P.E. Stieg, B. Parashar, D. Nori, K.C. Chao, and A. Wernicke; New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY Purpose/Objective(s): HFSRT with concurrent CTX is well tolerated in patients with recurrent and newly diagnosed resected small GBM (max dimension 5 cm and volume <60 cc) in young patients with good KPS. This study reports the initial experience on the feasibility and efficacy of HFSRT with concurrent CTX for patients with GBM who carry an especially poor prognosis in light of unresectable disease or a poor function status. Materials/Methods: Twelve patients (7 men and 5 women) with GBM and RTOG RPA class V-VI underwent maximally safe resection or biopsy (when considered inoperable), followed by HFSRT between 2011 and 2013. HFSRT was given with dose painting in 6 treatments over 2 weeks. Prescribed dose was 6 x 6 Gy to contrast-enhancing tumor + 5 mm margin (CTV1) and 6 x 4 Gy to FLAIR hypersignal + 2 cm (CTV2). Additional 5
Volume 87 Number 2S Supplement 2013 registered with pre-RT mPET so as to facilitate correlations. Failures were assigned to be within a said volume if it contained >50% of the lesion bulk. All patients received concurrent and adjuvant temozolomide. After a median post-RT span of 18 months, 54 failures were noted. After excluding 5 distant failures, 49 cases of non-distant failure (NDF) were analyzed. Results: Ratio of volume means of TVT2F:PV1.4 was 3.3 (47.5 cc vs 14.3 cc; 95% CI of difference 31.39 / 35.01, p < 0.0001). The ratios TVGd:PV1.8 and TVGd:PV2 were 0.9 (4.8 cc vs 5.3 cc; 95% CI of difference -1.03 / 0.03, p Z 0.0489) and 1.6 (4.8 cc vs 1.9 cc; 95% CI of difference 2.63 / 3.16, p < 0.0001), respectively. Volumes PV1.4 and TVT2F both contained 100% of subsequent NDFs. Other pre-RT volumes TVGd, PV1.8 and PV2 contained 75.5%, 79.6%, and 71.4% of NDFs, respectively. Conclusions: The mPET volume PV1.4 was able to predict 100% of NDFs despite being significantly smaller than the MRI volume TVT2F. The mPET volumes PV1.8 and PV2 were comparable to contrast enhanced MRI volume TVGd. Author Disclosure: S.P. Susheela: None. S. Revannasiddaiah: None. G. Mallarajapatna: None. S. Muzumder: None. K. Kallur: None. R.S. Bilimagga: None. M. Rastogi: None. M. Hassan V: None. M. Gupta: None. A. Basavalingaiah: None.
2117 High-Dose Intensity Modulated Radiation Therapy (IMRT) Using a Simultaneous Integrated Boost (SIB) Method Combined With Temozolomide (TMZ) for Malignant Gliomas K. Nakamatsu, Y. Nishimura, and I. Tachibana; Kinki University Faculty of Medicine, Osaka-Sayama City, Japan Purpose/Objective(s): Due to the low a/b ratio of malignant gliomas, hypo-fractionated radiation therapy with a high dose fraction size of >2 Gy may be effective for malignant gliomas. We have adopted a SIB protocol of a total dose of 70 Gy with a fraction size of 2.5 Gy to gross tumor volume (GTV) since 2000. Since 2008, TMZ was combined with IMRT. Clinical results of IMRT using a SIB method combined with TMZ for malignant gliomas were compared with a similar IMRT method without TMZ, retrospectively. Materials/Methods: Between 2008 and 2012, 29 patients with histologically proven malignant gliomas treated with TMZ were enrolled in this study (TMZ group) and those of 15 malignant gliomas treated without TMZ before 2008 (historical control) were compared. The TMZ group included 22 patients with glioblastoma (GBM), 7 patients with grade 3 glioma (G3). The historical control group included 8 patients with GBM, and 7 patients with G3. All patients in the TMZ group received TMZ at 75 mg/m2 (100 mg-120 mg/body) from the first day of IMRT for 42 days. The planning CT and MRI T2 weighted image were fused for all patients. IMRT was performed with 4MV or 6MV using 5 or 7 fields. GTV was defined as a contrast enhanced lesion on the pre-operative MRI T1-weighted image or contrast-enhanced CT. Clinical target volume (CTV) was defined as the GTV plus a 2-cm margin. The margin was modified to be expanded to include the edema beyond 2 cm from the GTV or to be shrunken to the anatomical defense such as intracerebral fissures or tentorium cerebelli. A total dose of 70 Gy/fraction size of 2.5 Gy/39 days was given to GTV plus 5 mm margin, and 56 Gy/fraction size of 2.0 Gy/39 days to the surrounding area of CTV plus 5 mm margin. Results: IMRT of a planned dose of 70 Gy could be delivered safely without acute toxicity for all patients in the both group. The 4-year survival rates for the TMZ group and the historical control group were 44% and 20% without statistical significance, respectively. The 2-year local rates for the corresponding groups were 24% and 7%, respectively. Even in the TMZ group, most of the tumors recurred from the GTV area. In the both groups, no brain necrosis with neurological symptom was observed. Conclusions: Our high dose fraction size IMRT with TMZ for malignant gliomas showed a better survival rate than the historical control without TMZ. However, the local recurrence rate was still high even in the TMZ group. Based on this analysis, a new prospective study of IMRT using 3 Gy
fraction to a total dose of 84 Gy to GTV for GBM combined with TMZ is undergoing at our institution. Author Disclosure: K. Nakamatsu: None. Y. Nishimura: None. I. Tachibana: None.
2118 Reirradiation of Recurrent Gliomas S. Oh, J.M. Gales, C.A. Reddy, E.S. Murphy, J.S. Yu, J.H. Suh, and S.C. Chao; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): The aim of this study was to evaluate overall survival, progression free survival, and toxicity of patients with relapsed gliomas after a second course of radiation therapy (RT). Materials/Methods: Between 1999 and 2012, a total of 49 patients with relapsed gliomas were reirradiated (1 patient with pilocytic astrocytoma, 6 patients with low grade glioma, 12 patients with anaplastic astrocytoma, and 30 patients with glioblastoma). Eighteen patients were female and 31 patients were male. Thirty-two patients received external beam radiation therapy and 17 patients received stereotactic radiosurgery. The median age at primary diagnosis of the tumor was 44 years (range, 4-64 years). Median KPS at diagnosis was 90 (range, 50-100) and median KPS at reirradiation was 80 (range, 50-100). Median initial RT dose was 60 Gy (range, 50.4-61.2 Gy), and median reirradiation RT dose was 30 Gy (range, 15 Gy-60 Gy). Patients were evaluated in follow-up by clinical investigators with MRI every three months after reirradiation until death. Results: Median interval between reirradiation was 21.9 months (mos) (range, 2.6-138.4 mos). All patients completed the planned reirradiation. Median follow-up was 11 mos (range, 2.6-61.2 mos). At the time of analysis, 43 patients (87.8%) have progressed and 32 patients (65.3%) have died. Median progression-free survival was 3.8 mos (range, 0-52 mos). Median overall survival was 14.1 mos (range, 3-60 mos). The median PFS and OS for pilocytic astrocytoma, low grade gliomas, anaplastic astrocytoma, and glioblastoma were 2.0 mos and 2.6 mos, 6.7 mos and not reached, 3.4 mos and 14.2 mos, and 3.6 mos and 12.9 mos, respectively. Fourteen patients had no central nervous system (CNS) toxicity (28.6%). 27 patients had grade 1 CNS toxicity (55.1%). Four patients had grade 2 CNS toxicity (8.2%). Four patients had grade 3 CNS toxicity (8.2%). No grade 4 or 5 CNS toxicity was observed. Conclusions: Overall, reirradiation of gliomas was well tolerated with minimal toxicity. Reirradiation techniques should be studied in a prospective manner to determine the best treatment for these patients. Author Disclosure: S. Oh: None. J.M. Gales: None. C.A. Reddy: None. E.S. Murphy: None. J.S. Yu: None. J.H. Suh: None. S.C. Chao: None.
2119 Hypofractionated Stereotactic Radiation Therapy (HFSRT) With Concurrent Chemotherapy (CTX) in Patients With Newly Diagnosed Poor Prognosis GBM: Early Results J.C. Ye, M. Yondorf, S.C. Pannullo, J.A. Boockvar, T.H. Schwartz, P.E. Stieg, B. Parashar, D. Nori, K.C. Chao, and A. Wernicke; New York Presbyterian Hospital/Weill Cornell Medical College, New York, NY Purpose/Objective(s): HFSRT with concurrent CTX is well tolerated in patients with recurrent and newly diagnosed resected small GBM (max dimension 5 cm and volume <60 cc) in young patients with good KPS. This study reports the initial experience on the feasibility and efficacy of HFSRT with concurrent CTX for patients with GBM who carry an especially poor prognosis in light of unresectable disease or a poor function status. Materials/Methods: Twelve patients (7 men and 5 women) with GBM and RTOG RPA class V-VI underwent maximally safe resection or biopsy (when considered inoperable), followed by HFSRT between 2011 and 2013. HFSRT was given with dose painting in 6 treatments over 2 weeks. Prescribed dose was 6 x 6 Gy to contrast-enhancing tumor + 5 mm margin (CTV1) and 6 x 4 Gy to FLAIR hypersignal + 2 cm (CTV2). Additional 5