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426 poster Temozolomide enhances radiation treatment efficacy in brain metastases: a randomized phase II study
Posters
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bone metastasis. Plain radiography and bone scintigraphy have been routinely used and currently frequency of CT or MRI have increased for diagnosis and evaluation of the metastatic bone tumors. In this study, we aimed to find what proportion of patients with the metastatic bone tumors had advantage from CT or MRI findings in determination of radiation field in addition to the simple radiography. Methods & Materials : The total of 545 cases of palliative radiotherapy was given to 473 patients with metastatic bone tumors between January 1996 and December 1998. CT or MRI was checked for 247 cases in 213 patients and CT or MRI findings of 146 cases in 143 patients among these were evaluated. The treated bone was spine in 132 cases, pelvis in 6, sternum in 3, femur in 2, humerus, tibia, skull in a case each. We compared the extent of metastatic bone tumors in the plain radiography and CR or MRI. Results: Among the cases of symptomatic spine metastasis, 32.5% (43 cases) were diagnosed with CT or MRI but not with plain radiography. Soft tissue extension of the metastatic bone tumors measured in CT/MRI films was less than 1.0 cm in 47 cases, 1.0 - 1.9 cm in 46, 2.0- 2.9 cm in 19, 3.03.9 cm in t2, and 4 cm or more in 8. Soft tissue extension in tumors other than spine was less than 1.0 cm in 3 cases, 1.0- 1.9 cm in 5, 2.0- 2.9 cm in 2, 3.0- 3.9 cm in I, and 4 cm or more in 3. Thus we could have a high chance of geographic miss in 33%(39/121) of metastatic tumors in the spine and 50%(6/12) of tumors in other bone if we use 2 cm margin of the normal tissue from the tumor extent of simple radiography. But error chance in longitudinal direction was not substantial because tumor extension measured in CT or MRI in longitudinal direction was less than 1.0 cm in 11 cases, 1.0- 1.9 cm in 1, and 4 cm or more in 2. Conclusion: We can avoid geographic miss in simulation for the metastatic bone tumors in at least 30% of cases with using CT or MRI findings in addition to the simple radiography. It should, however, be soon determined who could gain maximal benefit from CT/MRI at the moment of diagnosis of metastatic bone tumor. 426
poster
Temozolomide enhances radiation treatment efficacy in brain metastases: a randomized phase II study D. Antonadou, M. Paraskevaides, N. Co/iarakis, G. Sarris, P. Karageorgis, N. Throuva/as Hellenic Group C/inica/ Radiation Onco/ogy, Pireus, Greece Background:Metastases to the brain occur in 25%-35% of all cancer patients. Most ~of these present as multiple metastases rather than as a single metastasis. In these cases, radiation treatment (XRT) remains the most effective recourse, but despite high initial response rates it shows a modest gain in survival. Temozolomide (TMZ) is an oral cytotoxic agent that crosses the blood-brain barrier. Purpose:We conducted a randomized study to evaluate the efficacy and safety of concurrent administration of TMZ and XRT in patients with previously untreated brain metastases. Methods:Eligible patients were randomly allocated to treatment with TMZ 75mg/m2 daily during conventional XRT 2Gy/5 days/week for a total dose of 40 Gy or to XRT alone (control). In the TMZ + XRT group, 200mg/m ~ TMZ were administered one month post XRT for 5 consecutive days every 28 days for 6 cycles. The primary endpoint was radiological response as assessed by CT scan or MRI and neurological symptom evaluation at 2 months post XRT. Results:To date, 38 pts have been enrolled. The groups did not differ significantly in primary tumour site, age, gender and performance status. No grade 3 toxicity occured. Thus far, 28 patients have been evaluated for response by radiological assessment (15 in the TMZ+XRT group and 13 in the XRT only [control] group). There were 7 complete and 3 partial responses in the TMZ+XRT arm versus 2 complete and 5 partial responses in the control arm (CR:p=0.038, PR:p=0.410). Neurological evaluation showed amelioration in 12 pts in the TMZ+XRT group versus 7 patients in the control group (p=0.05) Conclusion:These preliminary results indicate that combined treatment with TMZ+XRT is well tolerated and enhances XRT efficacy in brain metastases. 427
poster
Prognostic factors by radiotherapy used for the treatment of metastatic brain tumors from lung cancer A. Kate 1, K. Kinbara 1, K. Watai 1, S. Takebayashi 1, S. Matsubara 1, K. Watanabe 2 1yokohama City Universityity University Medical Center, Radiology, Yokohama, Japan 2yokohama Citizeh Hospital, Respiratory medicine, Yokohama, Japan Purpose: Radiotherapy is often used for the treatment of metastatic brain
tumors from lung cancer. It is a palliative therapy in many cases, and there are many different procedures. We researched for the prognostic factors by radiotherapy used for metastatic brain tumors from lung cancer. Materials and methods: From 1988 to 1998, 132 patients of brain metastatic tumors from lung cancer underwent radiotherapy. Generally, it started for the whole brain on two left-to-right opposed portals of 6MV X-ray. The survival periods were counted from the first day of radiotherapy by the Kaplan-Meier method. Log-rank test was used for the monovarLate analysis, and Cox's proportional regression hazard model for the multivariate analysis. Thirteen factors were evaluated. They consisted of age, sex, total irradiation dose, period of radiotherapy, the number of metastatic brain tumors, Performance status(PS) before radiotherapy, improvement of PS through radiotherapy, duration from definite diagnosis of lung cancer till the occurrence of metastatic brain tumors, initial response, radiotherapy procedure, control of the primary lesions, metastatic tumors of other organs and pathological findings. Results: The monovariate analysis showed that initial response, radiotherapy procedure, PS before radiotherapy and control of the primary lesions were significant prognostic factors. It showed that sex and metastatic tumors of other organs were likely to be marginally significant as well. Meanwhile, the multivariate analysis showed that initial response, PS before radiotherapy, control of the primary lesions and pathological findings were significant prognostic factors, and that radiotherapy procedure, improvement of PS through radiotherapy, metastatic tumors of other organs and duration till the occurrence of metaststic brain tumors were likely to be marginally significant. Initial responses were as follows: complete response, 26 cases(19.7%); partial response, 50 cases(37.9%); no change, 42 cases(31.8%); and progressive disease, 14 cases(10.6%). Overall 1- and 2-year survival rates were 16.7% and 8.9% respectively. Conclusion: Scalable significant prognostic factors before radiotherapy were control of the primary lesions, metastatic tumors of other organs, PS before radiotherapy and duration till the occurrence of metastatic brain tumors. We thought that open head surgery and radiosurgery should also be considered as a strategy for good prognosis.
MELANOMA 428
poster
Ruthenium-106-brachytherapy in combination with transpupillary thermotherapy of choroidal melanoma M. Ehrhardt 1, H. Schneider2, R. Guthoff2, R. Fietkau 1 1Dept. of Radiotherapy, 2Dept. of Ophtalmology, University of Restock, Germany Purpose: it is to evaluate the efficacy of transpupitlary thermotherapy (TTT) as a coplementary method to Ru-106-brachytherapy (Ru-BT) for treatment of choroidal melanoma. Methods: experience with 170 patients with choroidal melanoma treated by Ru-BT has shown, that tumors with a height of >6 mm regressed insufficient. Therefore in this situation or in case of tumor location at posterior pole Ru-BT is supplemented by TTT since 1997. Ru+BT dose at least 100 Gy at apex of the tumor and at most 1000 Gy scleral contact dose completed by diode laser (810 nm) expositioin time 60-90 sec including the tumor area with a safety distance of 500 pm. Results: 20 patients were treated with a mean follow-up period of 14 months. All tumors exhibited a reduction of tumor height without renewed tumor progression. The combined therapy showed quicker tumor regression thatn Ru-BT alone. Side effects were minimal. By the described method also tumors with a height of >6mm are sufficiently to be treated. Conclusions: in view of the quicker tumor regression under combined therapy dependent on position and extend of the tumor TTT seems to be an effective adjuvant method for the treatment of choroidal melanoma. Greater number of patients and longer follow-up are necessary relating for long-term and side effects. 429
poster
Malignant melanoma - a review of cases in 25-year period in Ibadan. T.N. E/ume/u, A. Adenipekun University College Hospital, Radiotherapy, /badan, Nigeria Purpose: To study malignant Melanoma trend in our environment inview of rising incidence in parts of the world. Methods: Record of all histologically confirmed Malignant Melanoma cases seen between January 1974 and December 1998 in the University College Hospital, lbadan were retrieved via the Hospital Cancer Registry, the
S 1] 1
bone metastasis. Plain radiography and bone scintigraphy have been routinely used and currently frequency of CT or MRI have increased for diagnosis and evaluation of the metastatic bone tumors. In this study, we aimed to find what proportion of patients with the metastatic bone tumors had advantage from CT or MRI findings in determination of radiation field in addition to the simple radiography. Methods & Materials : The total of 545 cases of palliative radiotherapy was given to 473 patients with metastatic bone tumors between January 1996 and December 1998. CT or MRI was checked for 247 cases in 213 patients and CT or MRI findings of 146 cases in 143 patients among these were evaluated. The treated bone was spine in 132 cases, pelvis in 6, sternum in 3, femur in 2, humerus, tibia, skull in a case each. We compared the extent of metastatic bone tumors in the plain radiography and CR or MRI. Results: Among the cases of symptomatic spine metastasis, 32.5% (43 cases) were diagnosed with CT or MRI but not with plain radiography. Soft tissue extension of the metastatic bone tumors measured in CT/MRI films was less than 1.0 cm in 47 cases, 1.0 - 1.9 cm in 46, 2.0- 2.9 cm in 19, 3.03.9 cm in t2, and 4 cm or more in 8. Soft tissue extension in tumors other than spine was less than 1.0 cm in 3 cases, 1.0- 1.9 cm in 5, 2.0- 2.9 cm in 2, 3.0- 3.9 cm in I, and 4 cm or more in 3. Thus we could have a high chance of geographic miss in 33%(39/121) of metastatic tumors in the spine and 50%(6/12) of tumors in other bone if we use 2 cm margin of the normal tissue from the tumor extent of simple radiography. But error chance in longitudinal direction was not substantial because tumor extension measured in CT or MRI in longitudinal direction was less than 1.0 cm in 11 cases, 1.0- 1.9 cm in 1, and 4 cm or more in 2. Conclusion: We can avoid geographic miss in simulation for the metastatic bone tumors in at least 30% of cases with using CT or MRI findings in addition to the simple radiography. It should, however, be soon determined who could gain maximal benefit from CT/MRI at the moment of diagnosis of metastatic bone tumor. 426
poster
Temozolomide enhances radiation treatment efficacy in brain metastases: a randomized phase II study D. Antonadou, M. Paraskevaides, N. Co/iarakis, G. Sarris, P. Karageorgis, N. Throuva/as Hellenic Group C/inica/ Radiation Onco/ogy, Pireus, Greece Background:Metastases to the brain occur in 25%-35% of all cancer patients. Most ~of these present as multiple metastases rather than as a single metastasis. In these cases, radiation treatment (XRT) remains the most effective recourse, but despite high initial response rates it shows a modest gain in survival. Temozolomide (TMZ) is an oral cytotoxic agent that crosses the blood-brain barrier. Purpose:We conducted a randomized study to evaluate the efficacy and safety of concurrent administration of TMZ and XRT in patients with previously untreated brain metastases. Methods:Eligible patients were randomly allocated to treatment with TMZ 75mg/m2 daily during conventional XRT 2Gy/5 days/week for a total dose of 40 Gy or to XRT alone (control). In the TMZ + XRT group, 200mg/m ~ TMZ were administered one month post XRT for 5 consecutive days every 28 days for 6 cycles. The primary endpoint was radiological response as assessed by CT scan or MRI and neurological symptom evaluation at 2 months post XRT. Results:To date, 38 pts have been enrolled. The groups did not differ significantly in primary tumour site, age, gender and performance status. No grade 3 toxicity occured. Thus far, 28 patients have been evaluated for response by radiological assessment (15 in the TMZ+XRT group and 13 in the XRT only [control] group). There were 7 complete and 3 partial responses in the TMZ+XRT arm versus 2 complete and 5 partial responses in the control arm (CR:p=0.038, PR:p=0.410). Neurological evaluation showed amelioration in 12 pts in the TMZ+XRT group versus 7 patients in the control group (p=0.05) Conclusion:These preliminary results indicate that combined treatment with TMZ+XRT is well tolerated and enhances XRT efficacy in brain metastases. 427
poster
Prognostic factors by radiotherapy used for the treatment of metastatic brain tumors from lung cancer A. Kate 1, K. Kinbara 1, K. Watai 1, S. Takebayashi 1, S. Matsubara 1, K. Watanabe 2 1yokohama City Universityity University Medical Center, Radiology, Yokohama, Japan 2yokohama Citizeh Hospital, Respiratory medicine, Yokohama, Japan Purpose: Radiotherapy is often used for the treatment of metastatic brain
tumors from lung cancer. It is a palliative therapy in many cases, and there are many different procedures. We researched for the prognostic factors by radiotherapy used for metastatic brain tumors from lung cancer. Materials and methods: From 1988 to 1998, 132 patients of brain metastatic tumors from lung cancer underwent radiotherapy. Generally, it started for the whole brain on two left-to-right opposed portals of 6MV X-ray. The survival periods were counted from the first day of radiotherapy by the Kaplan-Meier method. Log-rank test was used for the monovarLate analysis, and Cox's proportional regression hazard model for the multivariate analysis. Thirteen factors were evaluated. They consisted of age, sex, total irradiation dose, period of radiotherapy, the number of metastatic brain tumors, Performance status(PS) before radiotherapy, improvement of PS through radiotherapy, duration from definite diagnosis of lung cancer till the occurrence of metastatic brain tumors, initial response, radiotherapy procedure, control of the primary lesions, metastatic tumors of other organs and pathological findings. Results: The monovariate analysis showed that initial response, radiotherapy procedure, PS before radiotherapy and control of the primary lesions were significant prognostic factors. It showed that sex and metastatic tumors of other organs were likely to be marginally significant as well. Meanwhile, the multivariate analysis showed that initial response, PS before radiotherapy, control of the primary lesions and pathological findings were significant prognostic factors, and that radiotherapy procedure, improvement of PS through radiotherapy, metastatic tumors of other organs and duration till the occurrence of metaststic brain tumors were likely to be marginally significant. Initial responses were as follows: complete response, 26 cases(19.7%); partial response, 50 cases(37.9%); no change, 42 cases(31.8%); and progressive disease, 14 cases(10.6%). Overall 1- and 2-year survival rates were 16.7% and 8.9% respectively. Conclusion: Scalable significant prognostic factors before radiotherapy were control of the primary lesions, metastatic tumors of other organs, PS before radiotherapy and duration till the occurrence of metastatic brain tumors. We thought that open head surgery and radiosurgery should also be considered as a strategy for good prognosis.
MELANOMA 428
poster
Ruthenium-106-brachytherapy in combination with transpupillary thermotherapy of choroidal melanoma M. Ehrhardt 1, H. Schneider2, R. Guthoff2, R. Fietkau 1 1Dept. of Radiotherapy, 2Dept. of Ophtalmology, University of Restock, Germany Purpose: it is to evaluate the efficacy of transpupitlary thermotherapy (TTT) as a coplementary method to Ru-106-brachytherapy (Ru-BT) for treatment of choroidal melanoma. Methods: experience with 170 patients with choroidal melanoma treated by Ru-BT has shown, that tumors with a height of >6 mm regressed insufficient. Therefore in this situation or in case of tumor location at posterior pole Ru-BT is supplemented by TTT since 1997. Ru+BT dose at least 100 Gy at apex of the tumor and at most 1000 Gy scleral contact dose completed by diode laser (810 nm) expositioin time 60-90 sec including the tumor area with a safety distance of 500 pm. Results: 20 patients were treated with a mean follow-up period of 14 months. All tumors exhibited a reduction of tumor height without renewed tumor progression. The combined therapy showed quicker tumor regression thatn Ru-BT alone. Side effects were minimal. By the described method also tumors with a height of >6mm are sufficiently to be treated. Conclusions: in view of the quicker tumor regression under combined therapy dependent on position and extend of the tumor TTT seems to be an effective adjuvant method for the treatment of choroidal melanoma. Greater number of patients and longer follow-up are necessary relating for long-term and side effects. 429
poster
Malignant melanoma - a review of cases in 25-year period in Ibadan. T.N. E/ume/u, A. Adenipekun University College Hospital, Radiotherapy, /badan, Nigeria Purpose: To study malignant Melanoma trend in our environment inview of rising incidence in parts of the world. Methods: Record of all histologically confirmed Malignant Melanoma cases seen between January 1974 and December 1998 in the University College Hospital, lbadan were retrieved via the Hospital Cancer Registry, the