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589 poster Radiotherapy plus concomitant temozolomide in glioblastoma multiforme and anaplastic astrocytoma: preliminary data
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36 Gy. The median interval between surgery and the start of RT was 28 days (range 10-40).Chemotherapy was used on only four patients (% 29). The median follow-up was 31 months (6-52 months)
Conclusion: Medulloblastoma is a highly malignant cerebellar tumor of children and less frequently seen at adults. The prognosis has improved significantly in recent decades, in parallel with the improvement in neurosurgical techniques and the use of postoperative radiotherapy. Although chemotherapy may be useful and well tolerated, radiotherapy remains the mainstay adjuvant treatment. 587 poster Clinical results of proton beam therapy for skull base chordoma
~ , K. Tokuuye ~, T. Okumura 2, S. Sugahara 3, K. Kagei , M. Hata 1, K. Ohara 3, K. Tsubol-4, T. Hashimoto I , Y. Akine ~ I University of Tsukuba, Proton Medical Research Center, Ibaraki, Japan 21baraki Prefectural Central Hospital, Department of Radiology, Ibaraki, Japan 3University of Tsukuba, Department of Radiation Oncology, Ibaraki, Japan 4University of Tsukuba, Department of Neurosurgery, Ibaraki, Japan Background: Proton beam therapy can deliver higher dose to the tumor because of better dose distribution compared with conventional radiotherapy. The aim of this study was to evaluate clinical results of proton beam therapy for patients with skull base chordoma.
Methods and Materials: Thirteen patients with pathologically confirmed chordoma in the skull base who were treated using proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were analyzed. The patients' ages ranged from 14 to 74 years (median 61 years). The median preoperative tumor volume was 27.4 mL (range 3.3-88.4 mL). The median total tumor dose of 72.0 Gy (range 63.0-95.0 Gy) was delivered in 20-38 fractions (median 33 fractions). Five patients of the 13 were irradiated combining 6.0-24.0 Gy of X-rays in 2.0 Gy per fraction. The patients were followed-up for a median period of 69.3 months (range 14.6-123.4 months). Results: Of the 13 patients, 6 suffered from recurrence; all of them had Ioco-regional recurrence and none had disseminated or metastatic diseases. Seven patients died: 3 by chordoma, 1 by radiation-induced brain necrosis, and 3 by intercurrent diseases. The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors less than 30 mL (60.0% vs. 0% at 5 years). The local control rate for the patients who underwent partial or subtotal tumor removal as the latest surgery was not better than that for those who underwent biopsy only. Local control rate for the seven patients who had tumors less than 30 mL with no prior treatment was 83.3% at 5 years. Conclusions: Proton beam therapy is an effective modality for patients with skull base chordoma, especially for those with small tumors. For a patient having a tumor less than 30 mL with no prior treatment, biopsy without tumor removal appears appropriate before proton beam therapy.
Posters
588 poster
3-D conformal radiotherapy in children with low-grade brain tumours A. Skowronska-Gardas, M. Chojnacka, K. Pedziwiatr Centre of Oncology, Radiotherapy, Warszawa, Poland Purpose: 3-D CRT is a treatment of choice for children with partially resected or nonoperable low-grade tumours. In our department, due to neurosurgeons preference, the accepted policy was to deliver RT only to patients with recurrent craniopharyngioma or low-grade astrocytoma. Results of conformal RT in children with localised, low-grade brain tumours are presented. Material and methods: In 1997-2001, 20 children, age 3.518 years with low-grade brain tumours (8 craniopharyngioma and 12 astrocytoma) were treated with conformal radiotherapy techniques. In craniopharyngioma group, all patients were irradiated due to recurrent tumour, after multiples surgeries, and were seriously handicapped before RT onset. Patients with astrocytoma were treated after partial surgery (3) or biopsy only (9) and chemotherapy as well (7). Details of radiotherapy techniques will be presented. Results: All patients with craniopharyngioma are living with no recurrence (7) or with stable disease (1). We did not •observe radiotherapy-related complications. Four patients with astrocytoma died, due to progressive disease (3) or complications after chemotherapy (1). Two are living with dissemination, and 6 with stable disease. Late complications of radiotherapy were not observed. Conclusions: 3-D CRT for children with craniopharyngioma should be applied early in the treatment and follow limited surgical resection to diminish the severe toxicity of repeated surgery. For patients with astrocytoma conformal radiotherapy is treatment of choice when total or subtotal resection of tumour is not possible. The risk of complications related to RT is relatively low. 589 poster
Radiotherapy plus concomitant temozolomide in glioblastoma multiforme and anaplastic astrocytoma: preliminary data A. D'Amico I, V. Solarino 1, S. Maluta ~, L. Cristoforf, P. luzzolino 3, L. Vivenza 3
~HospitaI-University, Radiotherapy, Verona, Italy 2Hospital-University, Neurosurgery, Verona, Italy 3Hospital-University, Pathology, Verona, Italy Objectives: This phase II study, approved by the Ethical Committee of Azienda Ospedaliera of assess the response rate of the (RT+TMZ), the safety profile of the quality of life of patients undergoing this
Verona, is aimed to combined regimen association and the combined therapy.
Patients and Methods: The inclusion criteria were as follows: prior histologic confirmation of glioblastoma, gliosarcoma, anaplastic astrocytoma or anaplastic mixed oligoastrocytoma; all patients underwent macroscopic surgical resection; age > 18 years; Kamofsky Performance Status > 60%; ANC > 1500/mm 3, platelet > 100000/mm 3, hemoglobin > 8g/dl; life expectancy greater than 3 months; informed consent obtained. From June 2002 to November 2003, twenty patients have been enrolled at the Radiotherapy Dept. of Ospedale Maggiore of Verona. In the fase II study, 20 patients affected by GBM (19 pts = 95%) and AA (1 pt = 5%) received Temozolomide (75 mg/mq) daily for 6 weeks combined with synchronous postoperative radiotherapy (60 Gy, 2 Gy per fraction, 5 days a week).
Posters
Results: All the patients concluded the combined treatment without toxicity of radiotherapy (nausea, vomiting, headache or fatigue) and without toxicity of chemotherapy (myelotoxicity). The patients evaluable with NMR postradiotherapy (after 30 days from the end of RT) are 14 (70%) and none of these shows relapse. All these patients will be treated with adjuvant chemotherapy administered bi-weekly (150 mg/mq/day for 7 consecutive days of every alternating week, for six months). This part of the study is ongoing and further data will be communicated. Conclusions: This treatment is well tolerated. The quality of life is good. 590 poster
Gamma knife radiosurgery for intracranial metastatic melanoma: an analysis of survival and prognostic factors
M. Koc ~, J. McGregor 2, J.Grecula ~, C.J. Bauer 1, N.Gupta ~, R.A. Gahbauer 1 ~The Ohio State University Arthur G. James Cancer Hospital and Research Institute, Radiation Oncology, Columbus, OH, USA 2The Ohio State University Arthur G. James Cancer Hospital and Research Institute, Neurosurgery, Columbus, OH, USA Objective of this study was to evaluate retrospectively the effectiveness of gamma knife radiosurgery (GKS) for intracranial metastatic melanoma and to identify prognostic factors related to survival. Twenty-six patients with intracranial metastases (72 lesions) from melanoma underwent GKS. In 14 patients (54%) whole-brain radiotherapy (WBRT) was performed as part of the initial treatment, and in 12 patients (38%) immunotherapy and/or chemotherapy was given after GKS. The median tumor volume for GKS-treated lesions was 1.72 cm 3. The median prescribed radiation dose was 18 Gy (range 8-22 Gy) typically prescribed to the isodose at the tumor margin. Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival. Overall median survival was 6 months after GKS, and 1-year survival was 25%. The median survival from the onset of brain metastases was 9 months and from the original diagnosis of melanoma was 50 months (range 4-160 months). There were no major acute or late GKS complications. In univariate testing, the Karnofsky score equal to or higher than 90% (p<0.01, log-rank test), supratentorial localization (p<0.001, log-rank test), intracranial tumor volume less than l c m 3 (p<0.02, log-rank test), and absence of neurological signs or symptoms before GKS (p<0.003, log-rank test) were significant favorable factors for survival. In multivariate regression analyses, the most important predictors associated with increased survival were a KPS > 90 (p< 0.023), female sex (p< 0.004), supratentorial localization (p< 0.01), and absence of neurological symptoms (p< 0.008). Radiosurgery is a noninvasive, safe, and effective treatment option for patients with single or multiple intracranial metastases from melanoma. Female sex, Karnofsky score > 90, supratentorial localization and lack of symptoms before the GKS were good independent predictors of survival.
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591 poster
Radiotherapy with concomitant and sequential temozolomide compared with radiotherapy with sequential temozolomide in the treatment of glioblastoma multiforme
V. De Sanctis ~, M.F. Ostf, V. Donato ~, M. Valeriani 2, M. Salvati J, S. Del Bufalo ~, G. Mazzarella ~, G. Minnitf, V. Tombolini 2, R. Maurizi E n r i d ~University La Sapienza, Roma, Radiotherapy Oncology, Department of Radiology, Rome, Italy 2University of L'Aquila, L "Aquila, Department of Radiotherapy, Radiotherapy Oncology, L "Aquila, Italy 3University La Sapienza, Roma, Department Neurosurgery, Rome, Italy The purpose of this study was to evaluate the activity, measured in terms of overall survival (OS), of the oral alkylating chemotherapy agent temozolomide (TMZ) concomitant and sequential to radiotherapy (RT) in adult patients with newly-diagnosed glioblastoma muitiforme (GBM) after surgery. This study was performed at the Department of Radiotherapy of University La Sapienza of Rome and at Department of Radiotherapy of University of Aquila, Italy. We compared these data with results of a phase II study conducted at Department of Radiotherapy of University of Rome in which patients, after surgery, were treated with RT alone and sequential TMZ.
Patients and methods: Thirty-four patients with newly histologically confirmed GBM were enrolled into this trial from March 2000 and is actually ongoing. The median age at diagnosis was 61 years (range 33-78 years). 8 patients were less than 50 years old, 17 had a Karnofsky performance status more than 70 before radiotherapy. 20 patients underwent a gross total tumor resection, 11 a subtotal tumor resection and 3 only a biopsy. RT was delivered with Linear Accelerator (6 MEV energy) using immobilization systems and personalized blocks or multileaf collimator, 2 Gy per fraction once daily, 5 days per week, 30-40 days after surgery. The total dose of RT delivered was in the range 6066 Gy. TMZ (75 mg/m2/day per 7 days/wk) was orally administered to patients concomitantly with RT (1 hour before RT in a fasting state). TMZ was administered 28 days after the end of RT according to the schedule of 200 mg/m2/day per 5 days every 28 days until tolerance and/or progressive disease. Patients enrolled in the trial RT alone and adjuvant TMZ (between November 1999 and April 2002) were 17, with a median age at diagnosis of 61 years (range 37-80). This group is well matched for prognostic factors considered. RT delivered was in the range 60-66 Gy, TMZ was administered with the schedule 200 mg/m2/day per 5 days every 28 days until tolerance and/or progressive disease. Results: Treatment was well tolerated, with 4% of grade 3-4 WHO hematological toxicity in the patients of the 2 groups. We did not find any statistical significance among prognostic factors considered in the unvaried analysis using Kaplan Meier method and log-rank test. In the group of patients treated with RT and concomitant TMZ the actuarial OS is 90% at 6 months, 67% at 12 months, 25% at 18 months with a median survival of 10 months (range 2-26). In the group of patients treated with adjuvant TMZ the actuarial OS was 76% at 6 months, 51% at 12 months, 26% at 18 months with a median survival of 12 months (range 2-29). There was no difference between the actuarial survivals of the 2 groups. Conclusions: Although not randomised, our data confirm that TMZ is safe and effective as first line treatment either in a concomitant schedule with RT as in adjuvant schedule alone.
36 Gy. The median interval between surgery and the start of RT was 28 days (range 10-40).Chemotherapy was used on only four patients (% 29). The median follow-up was 31 months (6-52 months)
Conclusion: Medulloblastoma is a highly malignant cerebellar tumor of children and less frequently seen at adults. The prognosis has improved significantly in recent decades, in parallel with the improvement in neurosurgical techniques and the use of postoperative radiotherapy. Although chemotherapy may be useful and well tolerated, radiotherapy remains the mainstay adjuvant treatment. 587 poster Clinical results of proton beam therapy for skull base chordoma
~ , K. Tokuuye ~, T. Okumura 2, S. Sugahara 3, K. Kagei , M. Hata 1, K. Ohara 3, K. Tsubol-4, T. Hashimoto I , Y. Akine ~ I University of Tsukuba, Proton Medical Research Center, Ibaraki, Japan 21baraki Prefectural Central Hospital, Department of Radiology, Ibaraki, Japan 3University of Tsukuba, Department of Radiation Oncology, Ibaraki, Japan 4University of Tsukuba, Department of Neurosurgery, Ibaraki, Japan Background: Proton beam therapy can deliver higher dose to the tumor because of better dose distribution compared with conventional radiotherapy. The aim of this study was to evaluate clinical results of proton beam therapy for patients with skull base chordoma.
Methods and Materials: Thirteen patients with pathologically confirmed chordoma in the skull base who were treated using proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were analyzed. The patients' ages ranged from 14 to 74 years (median 61 years). The median preoperative tumor volume was 27.4 mL (range 3.3-88.4 mL). The median total tumor dose of 72.0 Gy (range 63.0-95.0 Gy) was delivered in 20-38 fractions (median 33 fractions). Five patients of the 13 were irradiated combining 6.0-24.0 Gy of X-rays in 2.0 Gy per fraction. The patients were followed-up for a median period of 69.3 months (range 14.6-123.4 months). Results: Of the 13 patients, 6 suffered from recurrence; all of them had Ioco-regional recurrence and none had disseminated or metastatic diseases. Seven patients died: 3 by chordoma, 1 by radiation-induced brain necrosis, and 3 by intercurrent diseases. The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors less than 30 mL (60.0% vs. 0% at 5 years). The local control rate for the patients who underwent partial or subtotal tumor removal as the latest surgery was not better than that for those who underwent biopsy only. Local control rate for the seven patients who had tumors less than 30 mL with no prior treatment was 83.3% at 5 years. Conclusions: Proton beam therapy is an effective modality for patients with skull base chordoma, especially for those with small tumors. For a patient having a tumor less than 30 mL with no prior treatment, biopsy without tumor removal appears appropriate before proton beam therapy.
Posters
588 poster
3-D conformal radiotherapy in children with low-grade brain tumours A. Skowronska-Gardas, M. Chojnacka, K. Pedziwiatr Centre of Oncology, Radiotherapy, Warszawa, Poland Purpose: 3-D CRT is a treatment of choice for children with partially resected or nonoperable low-grade tumours. In our department, due to neurosurgeons preference, the accepted policy was to deliver RT only to patients with recurrent craniopharyngioma or low-grade astrocytoma. Results of conformal RT in children with localised, low-grade brain tumours are presented. Material and methods: In 1997-2001, 20 children, age 3.518 years with low-grade brain tumours (8 craniopharyngioma and 12 astrocytoma) were treated with conformal radiotherapy techniques. In craniopharyngioma group, all patients were irradiated due to recurrent tumour, after multiples surgeries, and were seriously handicapped before RT onset. Patients with astrocytoma were treated after partial surgery (3) or biopsy only (9) and chemotherapy as well (7). Details of radiotherapy techniques will be presented. Results: All patients with craniopharyngioma are living with no recurrence (7) or with stable disease (1). We did not •observe radiotherapy-related complications. Four patients with astrocytoma died, due to progressive disease (3) or complications after chemotherapy (1). Two are living with dissemination, and 6 with stable disease. Late complications of radiotherapy were not observed. Conclusions: 3-D CRT for children with craniopharyngioma should be applied early in the treatment and follow limited surgical resection to diminish the severe toxicity of repeated surgery. For patients with astrocytoma conformal radiotherapy is treatment of choice when total or subtotal resection of tumour is not possible. The risk of complications related to RT is relatively low. 589 poster
Radiotherapy plus concomitant temozolomide in glioblastoma multiforme and anaplastic astrocytoma: preliminary data A. D'Amico I, V. Solarino 1, S. Maluta ~, L. Cristoforf, P. luzzolino 3, L. Vivenza 3
~HospitaI-University, Radiotherapy, Verona, Italy 2Hospital-University, Neurosurgery, Verona, Italy 3Hospital-University, Pathology, Verona, Italy Objectives: This phase II study, approved by the Ethical Committee of Azienda Ospedaliera of assess the response rate of the (RT+TMZ), the safety profile of the quality of life of patients undergoing this
Verona, is aimed to combined regimen association and the combined therapy.
Patients and Methods: The inclusion criteria were as follows: prior histologic confirmation of glioblastoma, gliosarcoma, anaplastic astrocytoma or anaplastic mixed oligoastrocytoma; all patients underwent macroscopic surgical resection; age > 18 years; Kamofsky Performance Status > 60%; ANC > 1500/mm 3, platelet > 100000/mm 3, hemoglobin > 8g/dl; life expectancy greater than 3 months; informed consent obtained. From June 2002 to November 2003, twenty patients have been enrolled at the Radiotherapy Dept. of Ospedale Maggiore of Verona. In the fase II study, 20 patients affected by GBM (19 pts = 95%) and AA (1 pt = 5%) received Temozolomide (75 mg/mq) daily for 6 weeks combined with synchronous postoperative radiotherapy (60 Gy, 2 Gy per fraction, 5 days a week).
Posters
Results: All the patients concluded the combined treatment without toxicity of radiotherapy (nausea, vomiting, headache or fatigue) and without toxicity of chemotherapy (myelotoxicity). The patients evaluable with NMR postradiotherapy (after 30 days from the end of RT) are 14 (70%) and none of these shows relapse. All these patients will be treated with adjuvant chemotherapy administered bi-weekly (150 mg/mq/day for 7 consecutive days of every alternating week, for six months). This part of the study is ongoing and further data will be communicated. Conclusions: This treatment is well tolerated. The quality of life is good. 590 poster
Gamma knife radiosurgery for intracranial metastatic melanoma: an analysis of survival and prognostic factors
M. Koc ~, J. McGregor 2, J.Grecula ~, C.J. Bauer 1, N.Gupta ~, R.A. Gahbauer 1 ~The Ohio State University Arthur G. James Cancer Hospital and Research Institute, Radiation Oncology, Columbus, OH, USA 2The Ohio State University Arthur G. James Cancer Hospital and Research Institute, Neurosurgery, Columbus, OH, USA Objective of this study was to evaluate retrospectively the effectiveness of gamma knife radiosurgery (GKS) for intracranial metastatic melanoma and to identify prognostic factors related to survival. Twenty-six patients with intracranial metastases (72 lesions) from melanoma underwent GKS. In 14 patients (54%) whole-brain radiotherapy (WBRT) was performed as part of the initial treatment, and in 12 patients (38%) immunotherapy and/or chemotherapy was given after GKS. The median tumor volume for GKS-treated lesions was 1.72 cm 3. The median prescribed radiation dose was 18 Gy (range 8-22 Gy) typically prescribed to the isodose at the tumor margin. Univariate and multivariate analyses were used to determine significant prognostic factors affecting survival. Overall median survival was 6 months after GKS, and 1-year survival was 25%. The median survival from the onset of brain metastases was 9 months and from the original diagnosis of melanoma was 50 months (range 4-160 months). There were no major acute or late GKS complications. In univariate testing, the Karnofsky score equal to or higher than 90% (p<0.01, log-rank test), supratentorial localization (p<0.001, log-rank test), intracranial tumor volume less than l c m 3 (p<0.02, log-rank test), and absence of neurological signs or symptoms before GKS (p<0.003, log-rank test) were significant favorable factors for survival. In multivariate regression analyses, the most important predictors associated with increased survival were a KPS > 90 (p< 0.023), female sex (p< 0.004), supratentorial localization (p< 0.01), and absence of neurological symptoms (p< 0.008). Radiosurgery is a noninvasive, safe, and effective treatment option for patients with single or multiple intracranial metastases from melanoma. Female sex, Karnofsky score > 90, supratentorial localization and lack of symptoms before the GKS were good independent predictors of survival.
$259
591 poster
Radiotherapy with concomitant and sequential temozolomide compared with radiotherapy with sequential temozolomide in the treatment of glioblastoma multiforme
V. De Sanctis ~, M.F. Ostf, V. Donato ~, M. Valeriani 2, M. Salvati J, S. Del Bufalo ~, G. Mazzarella ~, G. Minnitf, V. Tombolini 2, R. Maurizi E n r i d ~University La Sapienza, Roma, Radiotherapy Oncology, Department of Radiology, Rome, Italy 2University of L'Aquila, L "Aquila, Department of Radiotherapy, Radiotherapy Oncology, L "Aquila, Italy 3University La Sapienza, Roma, Department Neurosurgery, Rome, Italy The purpose of this study was to evaluate the activity, measured in terms of overall survival (OS), of the oral alkylating chemotherapy agent temozolomide (TMZ) concomitant and sequential to radiotherapy (RT) in adult patients with newly-diagnosed glioblastoma muitiforme (GBM) after surgery. This study was performed at the Department of Radiotherapy of University La Sapienza of Rome and at Department of Radiotherapy of University of Aquila, Italy. We compared these data with results of a phase II study conducted at Department of Radiotherapy of University of Rome in which patients, after surgery, were treated with RT alone and sequential TMZ.
Patients and methods: Thirty-four patients with newly histologically confirmed GBM were enrolled into this trial from March 2000 and is actually ongoing. The median age at diagnosis was 61 years (range 33-78 years). 8 patients were less than 50 years old, 17 had a Karnofsky performance status more than 70 before radiotherapy. 20 patients underwent a gross total tumor resection, 11 a subtotal tumor resection and 3 only a biopsy. RT was delivered with Linear Accelerator (6 MEV energy) using immobilization systems and personalized blocks or multileaf collimator, 2 Gy per fraction once daily, 5 days per week, 30-40 days after surgery. The total dose of RT delivered was in the range 6066 Gy. TMZ (75 mg/m2/day per 7 days/wk) was orally administered to patients concomitantly with RT (1 hour before RT in a fasting state). TMZ was administered 28 days after the end of RT according to the schedule of 200 mg/m2/day per 5 days every 28 days until tolerance and/or progressive disease. Patients enrolled in the trial RT alone and adjuvant TMZ (between November 1999 and April 2002) were 17, with a median age at diagnosis of 61 years (range 37-80). This group is well matched for prognostic factors considered. RT delivered was in the range 60-66 Gy, TMZ was administered with the schedule 200 mg/m2/day per 5 days every 28 days until tolerance and/or progressive disease. Results: Treatment was well tolerated, with 4% of grade 3-4 WHO hematological toxicity in the patients of the 2 groups. We did not find any statistical significance among prognostic factors considered in the unvaried analysis using Kaplan Meier method and log-rank test. In the group of patients treated with RT and concomitant TMZ the actuarial OS is 90% at 6 months, 67% at 12 months, 25% at 18 months with a median survival of 10 months (range 2-26). In the group of patients treated with adjuvant TMZ the actuarial OS was 76% at 6 months, 51% at 12 months, 26% at 18 months with a median survival of 12 months (range 2-29). There was no difference between the actuarial survivals of the 2 groups. Conclusions: Although not randomised, our data confirm that TMZ is safe and effective as first line treatment either in a concomitant schedule with RT as in adjuvant schedule alone.