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The HD 12 panel of the German Hodgkin lymphoma study group (GHSG) - a quality assurance program based on a multidisciplinary panel reviewing all patients’ imaging
Proceedings of the 43rd Annual ASTRO Meeting
received 3 to 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The study was also devised to determine the relevance of the International Prognostic Index (IPI) to patients with early-stage NHL. Materials and Methods: 145 consecutive patients with stage I-II intermediate grade NHL who received consolidative radiotherapy following CHOP chemotherapy between 1990 and 1999 and had a minimal follow-up of one year were included in this study. The median age was 56 years (range 21-94). 104 patients (71%) had stage I disease and 80 (55%) had extranodal disease. Only 16 patients (11%) had B symptoms. The pre-chemotherapy largest tumor diameter measured up to 5 cm in 96 patients (66%), ⬎5-10 cm in 17 patients (12%), more than 10 cm in 9 patients (6%), and was not specified for 23 patients (16%). 124 patients (86%) had a low-risk IPI score (0-1 risk factor). The median number of cycles of CHOP was 4 (range 3-9). 139 patients (96%) received 3 to 6 cycles of CHOP. Following chemotherapy, 128 patients (88%) achieved a complete response (CR) or an uncertain CR (uCR) and 9 (6%) obtained a partial response (PR). The median radiation dose was 36 Gy (range 10.8-55.0 Gy) and in 108 patients (74%) the dose ranged between 30 Gy and 36 Gy. Involved-field radiotherapy was used in 124 patients (92%) and extended-field in 9 patients (6%). The median follow-up was 41 months. Survival analysis was performed using the Kaplan-Meier method and differences between subgroups were calculated by log-rank test. Results: Twenty-six patients (18%) relapsed. Of those, 21 experienced a systemic relapse without a local failure component and 4 patients had a concurrent local failure at the time of their systemic relapse. One patient experienced a relapse in a site adjacent to the treatment field. None of the patients relapsed in the radiation field alone. When all the relapses with a local component were considered, the actuarial 5-year local control was 98%. The 5-year actuarial local control was above 95% at all dose ranges (30.0-30.6 Gy, 30.7-36.0 Gy, 36.1-40.0 Gy, ⬎40 Gy). For the whole group, the actuarial 5-year freedom from relapse, progression-free survival and overall survival were 80%, 75% and 85%, respectively. The only factor indicative of an increased risk of relapse was an intermediate IPI score. The subgroup of patients with a low-risk IPI (0 to 1 risk factor) had a 5-year actuarial freedom from progression of 83% compared to 72% for patients with an intermediate risk IPI (2-3 risk factors) (p⫽0.04). Age above 60 years (p⫽0.001) and intermediate risk IPI score (p⫽0.02) were independently prognostic for decreased survival (step-wise Cox regression model). Other factors such as stage, nodal/extranodal location, LDH level, presence of B symptoms, tumor size (0-5 cm, ⬎5-10 cm, ⬎10 cm), number of cycles of chemotherapy (3, 4, 5-9), response to CHOP (CR/uCR, PR), radiation dose (ⱕ36 Gy, ⬎36 Gy) and field extent (involved-field vs extended field) failed to predict for relapse or decreased survival. Conclusion: Low dose involved-field radiotherapy in the range of 30 to 36 Gy provides excellent local control in patients treated with standard CHOP chemotherapy for early-stage NHL. Keeping the radiation dose below 36 Gy allows effective treatment without significant morbidity. Additionally, this study documents the relevance of the IPI score to patients with early-stage NHL treated with combined modality.
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The HD 12 Panel of the German Hodgkin Lymphoma Study Group (GHSG) - A Quality Assurance Program Based on a Multidisciplinary Panel Reviewing All Patients’ Imaging
H.T. Eich1, S. Staar1, A. Gossmann2, A. Engert3, J. Franklin3, B. Krug2, V. Diehl3, R.P. Mu¨ ller1 1 Department of Radiotherapy, University of Cologne, Cologne, Germany, 2Department of Radiology, University of Cologne, Cologne, Germany, 3Medical Oncology, University of Cologne, Cologne, Germany Purpose: The HD 12 protocol is a multicentric prospective randomized trial of the GHSG for advanced stages of Hodgkin⬘s disease. Beside a randomization for different intensities of chemotherapy (CTX) using the BEACOPP-schema, the indication and efficiency of additive radiotherapy (RT) to bulky and/or areas with residual disease is tested in a randomized setting. Materials and Methods: All study participants are asked to sent all diagnostic imaging as well as written protocol forms (initial status, after 4 and 8 cycles of CTX) of their HD 12-patients to the reference center. Here, a multidisciplinary panel of radiologists, radiotherapists and medical oncologists reviews without knowledge of the randomized treatment arm the diagnostic imaging with comparison to the documentation forms. For patients with poor response to CTX, the panel may recommend RT independent of the randomization. Additionally, the panel also evaluates the quality of computed tomography scans (CT) in this multicenter study. Since 7/1999, a total of 2607 CT of 371 pts. (head/neck 28%, chest 39%, abdomen 33%) have been evaluated. Results: There were 744 (29%) conventional CT and 1863 (71%) helical CT. 42% of all CT were performed in non-university hospitals, 28% in university hospitals, and 30% in private institutions. According to imaging quality the contrast enhancement was good in 77%, moderate in 15%, and poor in 8%. Helical CT showed a significantly higher contrast enhancement and imaging quality than conventional CT (p⬍0.001). CT-imaging from university hospitals was evaluated superior than that from other institutions (p⬍0.001). Compared to the written disease documentation by the study centers, the panel defined different extensions of disease in 814/2607 CT. These diagnostic findings would result in a change of stage in 17/371 pts. (5%). After CTX 167/371 pts. (45%) showed residual disease (⬎1.5 cm), and for 53/371 pts. (14%) the panel recommended additional RT independently from the randomization arm. Conclusion: Patients with Hodgkin”s disease receive high quality of imaging, especially CT. A central independent multidisciplinary panel may increase significantly quality assurance for these study patients.
2266
Clinical Stage I & II Diffuse Large-Cell Lymphoma: Results of Combined Modality Therapy and Prognostic Factor Analysis
M.K. Gospodarowicz1, R.W. Tsang1, W. Wells1, M. Pintilie1, D. Hodgson1, B. Patterson3, M. Crump2 1 Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 2Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 3Pathology, Princess Margaret Hospital, Toronto, ON, Canada Purpose: To review the long term results of therapy of stage I and II diffuse large-cell (DLC) and immunoblastic lymphomas managed with combined modality therapy (CMT).
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received 3 to 6 cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The study was also devised to determine the relevance of the International Prognostic Index (IPI) to patients with early-stage NHL. Materials and Methods: 145 consecutive patients with stage I-II intermediate grade NHL who received consolidative radiotherapy following CHOP chemotherapy between 1990 and 1999 and had a minimal follow-up of one year were included in this study. The median age was 56 years (range 21-94). 104 patients (71%) had stage I disease and 80 (55%) had extranodal disease. Only 16 patients (11%) had B symptoms. The pre-chemotherapy largest tumor diameter measured up to 5 cm in 96 patients (66%), ⬎5-10 cm in 17 patients (12%), more than 10 cm in 9 patients (6%), and was not specified for 23 patients (16%). 124 patients (86%) had a low-risk IPI score (0-1 risk factor). The median number of cycles of CHOP was 4 (range 3-9). 139 patients (96%) received 3 to 6 cycles of CHOP. Following chemotherapy, 128 patients (88%) achieved a complete response (CR) or an uncertain CR (uCR) and 9 (6%) obtained a partial response (PR). The median radiation dose was 36 Gy (range 10.8-55.0 Gy) and in 108 patients (74%) the dose ranged between 30 Gy and 36 Gy. Involved-field radiotherapy was used in 124 patients (92%) and extended-field in 9 patients (6%). The median follow-up was 41 months. Survival analysis was performed using the Kaplan-Meier method and differences between subgroups were calculated by log-rank test. Results: Twenty-six patients (18%) relapsed. Of those, 21 experienced a systemic relapse without a local failure component and 4 patients had a concurrent local failure at the time of their systemic relapse. One patient experienced a relapse in a site adjacent to the treatment field. None of the patients relapsed in the radiation field alone. When all the relapses with a local component were considered, the actuarial 5-year local control was 98%. The 5-year actuarial local control was above 95% at all dose ranges (30.0-30.6 Gy, 30.7-36.0 Gy, 36.1-40.0 Gy, ⬎40 Gy). For the whole group, the actuarial 5-year freedom from relapse, progression-free survival and overall survival were 80%, 75% and 85%, respectively. The only factor indicative of an increased risk of relapse was an intermediate IPI score. The subgroup of patients with a low-risk IPI (0 to 1 risk factor) had a 5-year actuarial freedom from progression of 83% compared to 72% for patients with an intermediate risk IPI (2-3 risk factors) (p⫽0.04). Age above 60 years (p⫽0.001) and intermediate risk IPI score (p⫽0.02) were independently prognostic for decreased survival (step-wise Cox regression model). Other factors such as stage, nodal/extranodal location, LDH level, presence of B symptoms, tumor size (0-5 cm, ⬎5-10 cm, ⬎10 cm), number of cycles of chemotherapy (3, 4, 5-9), response to CHOP (CR/uCR, PR), radiation dose (ⱕ36 Gy, ⬎36 Gy) and field extent (involved-field vs extended field) failed to predict for relapse or decreased survival. Conclusion: Low dose involved-field radiotherapy in the range of 30 to 36 Gy provides excellent local control in patients treated with standard CHOP chemotherapy for early-stage NHL. Keeping the radiation dose below 36 Gy allows effective treatment without significant morbidity. Additionally, this study documents the relevance of the IPI score to patients with early-stage NHL treated with combined modality.
2265
The HD 12 Panel of the German Hodgkin Lymphoma Study Group (GHSG) - A Quality Assurance Program Based on a Multidisciplinary Panel Reviewing All Patients’ Imaging
H.T. Eich1, S. Staar1, A. Gossmann2, A. Engert3, J. Franklin3, B. Krug2, V. Diehl3, R.P. Mu¨ ller1 1 Department of Radiotherapy, University of Cologne, Cologne, Germany, 2Department of Radiology, University of Cologne, Cologne, Germany, 3Medical Oncology, University of Cologne, Cologne, Germany Purpose: The HD 12 protocol is a multicentric prospective randomized trial of the GHSG for advanced stages of Hodgkin⬘s disease. Beside a randomization for different intensities of chemotherapy (CTX) using the BEACOPP-schema, the indication and efficiency of additive radiotherapy (RT) to bulky and/or areas with residual disease is tested in a randomized setting. Materials and Methods: All study participants are asked to sent all diagnostic imaging as well as written protocol forms (initial status, after 4 and 8 cycles of CTX) of their HD 12-patients to the reference center. Here, a multidisciplinary panel of radiologists, radiotherapists and medical oncologists reviews without knowledge of the randomized treatment arm the diagnostic imaging with comparison to the documentation forms. For patients with poor response to CTX, the panel may recommend RT independent of the randomization. Additionally, the panel also evaluates the quality of computed tomography scans (CT) in this multicenter study. Since 7/1999, a total of 2607 CT of 371 pts. (head/neck 28%, chest 39%, abdomen 33%) have been evaluated. Results: There were 744 (29%) conventional CT and 1863 (71%) helical CT. 42% of all CT were performed in non-university hospitals, 28% in university hospitals, and 30% in private institutions. According to imaging quality the contrast enhancement was good in 77%, moderate in 15%, and poor in 8%. Helical CT showed a significantly higher contrast enhancement and imaging quality than conventional CT (p⬍0.001). CT-imaging from university hospitals was evaluated superior than that from other institutions (p⬍0.001). Compared to the written disease documentation by the study centers, the panel defined different extensions of disease in 814/2607 CT. These diagnostic findings would result in a change of stage in 17/371 pts. (5%). After CTX 167/371 pts. (45%) showed residual disease (⬎1.5 cm), and for 53/371 pts. (14%) the panel recommended additional RT independently from the randomization arm. Conclusion: Patients with Hodgkin”s disease receive high quality of imaging, especially CT. A central independent multidisciplinary panel may increase significantly quality assurance for these study patients.
2266
Clinical Stage I & II Diffuse Large-Cell Lymphoma: Results of Combined Modality Therapy and Prognostic Factor Analysis
M.K. Gospodarowicz1, R.W. Tsang1, W. Wells1, M. Pintilie1, D. Hodgson1, B. Patterson3, M. Crump2 1 Radiation Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 2Medical Oncology, Princess Margaret Hospital, Toronto, ON, Canada, 3Pathology, Princess Margaret Hospital, Toronto, ON, Canada Purpose: To review the long term results of therapy of stage I and II diffuse large-cell (DLC) and immunoblastic lymphomas managed with combined modality therapy (CMT).
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