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Stereotactic radiosurgery with whole brain radiation therapy improves survival in patients with brain metastases: report of radiation therapy oncology group phase III study 95–08
Proceedings of the 44th Annual ASTRO Meeting
49 days). Patients in arm 3 received radiation only at 70 Gy/35 fractions for 49 days. Patients with a neck node ⱖ3 cm or with multiple neck nodes underwent a neck dissection 8 weeks after completion of therapy. After excluding 30 patients from the study, 517 remained for analysis (173 in arm 1, 172 in arm 2, and 172 in 3). Sixty eight percent of the 517 patients had supraglottic cancer. Pretreatment patient and tumor characteristics were very similar in the 3 treatment arms. Results: At 2 years, LFS for the patients treated with concomitant chemotherapy and radiotherapy was significantly better than for patients treated with radiotherapy alone (p ⫽ 0.018). The LPR was significantly greater in arm 2 compared with arms 1 and 3. The number of laryngectomies at 2 years was 43, 21, and 49 for the induction, concomitant and radiotherapy arms respectively. Loco-regional control at 2 years for patients in arm 2 (78%) was significantly better than either arm 1 (61%), or arm 3 (56%), p ⬍ 0.01. Ten patients in the study died of treatment toxicity; 5 died in the induction chemotherapy arm and 5 died in the concomitant chemotherapy and radiation arm. Acute grade 4 and 5 toxicity was 31%, 21%, and 5% in treatment arms 1, 2, and 3 respectively (⬍0.0001). Late grade 4 and 5 toxicity was 9%, 8% and 10% in the 3 arms (not significant). Overall survival was very similar for the patients in the 3 treatment arms (⬵75% at 2 years). Conclusions: Concomitant chemotherapy and radiotherapy was superior for LPR and loco-regional control compared with induction chemotherapy followed by radiotherapy and compared to radiotherapy alone. Patients on concomitant treatment had a superior LFS compared to patients treated with radiation alone. There was no significant difference between induction chemotherapy and radiotherapy alone using these criteria. Better local control with the concomitant treatment arm did not improve survival.
Plenary 5
Stereotactic Radiosurgery with Whole Brain Radiation Therapy Improves Survival in Patients with Brain Metastases: Report of Radiation Therapy Oncology Group Phase III Study 95-08
P.W. Sperduto1, C. Scott2, D. Andrews3, M.C. Schell4, A. Flanders3, M. Werner-Wasik3, W. Demas5, J.K. Ryu6, L.E. Gaspar7, J. Bahary8, L. Souhami9, M. Rotman10, W.J. Curran3 1 Methodist Hospital, Minneapolis, Minneapolis, MN, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3Thomas Jefferson University, Philadelphia, PA, 4University of Rochester, Rochester, NY, 5Akron City Hospital, Akron, OH, 6 University of California–Davis, Sacramento, CA, 7Wayne State University, Detroit, MI, 8Notre Dame Hospital, Montreal, AB, Canada, 9McGill University, Montreal, AB, Canada, 10SUNY–Brooklyn, Brooklyn, NY Purpose/Objective: To determine if stereotactic radiosurgery (SRS) after conventional whole brain radiation therapy (WBRT) improves overall survival when compared to WBRT alone in patients with 1-3 brain metastases. Secondary objectives include a comparison of sites of recurrence and cause of death. Materials/Methods: Between 1/96 and 6/01, 333 patients from 34 institutions were randomized to receive WBRT ⫹ SRS or WBRT alone. The WBRT was given at 250cGy/fraction to 3750 cGy in 3 weeks. The SRS dose was based on tumor size and was delivered within one week of completion of WBRT. The study was designed to detect a 50% improvement in median survival time (MST) with 80% statistical power for all patients and a 75% improvement in MST in patients with solitary metastases. Central radiology review of local control and salvage therapy analyses will be presented. Results: There was a statistically significant survival advantage with WBRT ⫹ SRS for the following patients: solitary brain metastases (MST 6.5 vs 4.9 months, p⫽0.04), RPA class I (MST 11.6 vs 9.6 months, p⫽0.05), age ⬍ 50 (9.9 vs 8.3 months, p⫽0.04) and patients with non-small cell lung cancer or any squamous cell carcinoma (5.9 vs 3.9 months, p⫽0.05). Also, patients with initial KPS of 90-100 appeared to benefit (10.2 vs 7.4 months) without reaching statistical significance (p⫽0.07). Furthermore, all patients in the WBRT ⫹ SRS group were more likely to have a stable or improved performance status (KPS) at 3 months (50% vs 33%, p⫽0.02) and at 6 months (43% vs 27%, p⫽0.03). There was no significant difference in cause of death but there was a significant difference in local control as reported by the treating institution (82% vs 71% at one year for WBRT ⫹ SRS vs WBRT alone, respectively (p⫽0.01). Toxicities were comparable between the two treatment groups. Conclusions: WBRT ⫹ SRS provided a survival advantage compared to WBRT alone in each of the following patient categories: 1) solitary brain metastasis; 2) RPA class I ; 3) age ⬍ 50; 4) non-small cell lung cancer or any squamous cell carcinoma. Furthermore, all subsets of patients in the WBRT ⫹ SRS group were more likely to have a stable or improved performance status than those in the WBRT alone group. Systemic disease remained the primary cause of death (⬎2/3) in both groups and improved systemic therapies are needed.
1
Functional Consequences of Radiation (RT)-Induced Perfusion Changes in Patients with Left-Sided Breast Cancer
L.B. Marks1, R.G. Prosnitz1, P.M. Hardenbergh1, S. Borges-Neto2, T. Wong2, D. Hollis3, A. Tisch1, S. Zhou1, M. Blazing4 1 Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 2Department of Radiology, Duke University Medical Center, Durham, NC, 3Department of Statistics, Duke University Medical Center, Durham, NC, 4 Department of Cardiology, Duke University Medical Center, Durham, NC Purpose/Objective: Our group has previously demonstrated that incidental cardiac RT during therapy for left-sided breast cancer results in a dose-dependent reduction in regional cardiac perfusion. (Hardenbergh IJROBP 49:1023-1028, 2001) We herein assess whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. Materials/Methods: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function following RT for left-sided breast cancer. The median age was 57 (range 33-82). Patients had pre-RT SPECT perfusion scans to assess regional perfusion, regional wall motion, and ejection fraction. Patients were imaged 30-60 minutes following the resting IV injection of approximately 25-40 millicuries of technesium-99m sestamibi or Tetrofosmin. Projection data were acquired and images were reconstructed using clinical techniques. Post-RT perfusion scans (6, 12, 18, 24, and 36 months post-RT) were compared to the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. The severity/extent of regional perfusion defects were scored using
3
49 days). Patients in arm 3 received radiation only at 70 Gy/35 fractions for 49 days. Patients with a neck node ⱖ3 cm or with multiple neck nodes underwent a neck dissection 8 weeks after completion of therapy. After excluding 30 patients from the study, 517 remained for analysis (173 in arm 1, 172 in arm 2, and 172 in 3). Sixty eight percent of the 517 patients had supraglottic cancer. Pretreatment patient and tumor characteristics were very similar in the 3 treatment arms. Results: At 2 years, LFS for the patients treated with concomitant chemotherapy and radiotherapy was significantly better than for patients treated with radiotherapy alone (p ⫽ 0.018). The LPR was significantly greater in arm 2 compared with arms 1 and 3. The number of laryngectomies at 2 years was 43, 21, and 49 for the induction, concomitant and radiotherapy arms respectively. Loco-regional control at 2 years for patients in arm 2 (78%) was significantly better than either arm 1 (61%), or arm 3 (56%), p ⬍ 0.01. Ten patients in the study died of treatment toxicity; 5 died in the induction chemotherapy arm and 5 died in the concomitant chemotherapy and radiation arm. Acute grade 4 and 5 toxicity was 31%, 21%, and 5% in treatment arms 1, 2, and 3 respectively (⬍0.0001). Late grade 4 and 5 toxicity was 9%, 8% and 10% in the 3 arms (not significant). Overall survival was very similar for the patients in the 3 treatment arms (⬵75% at 2 years). Conclusions: Concomitant chemotherapy and radiotherapy was superior for LPR and loco-regional control compared with induction chemotherapy followed by radiotherapy and compared to radiotherapy alone. Patients on concomitant treatment had a superior LFS compared to patients treated with radiation alone. There was no significant difference between induction chemotherapy and radiotherapy alone using these criteria. Better local control with the concomitant treatment arm did not improve survival.
Plenary 5
Stereotactic Radiosurgery with Whole Brain Radiation Therapy Improves Survival in Patients with Brain Metastases: Report of Radiation Therapy Oncology Group Phase III Study 95-08
P.W. Sperduto1, C. Scott2, D. Andrews3, M.C. Schell4, A. Flanders3, M. Werner-Wasik3, W. Demas5, J.K. Ryu6, L.E. Gaspar7, J. Bahary8, L. Souhami9, M. Rotman10, W.J. Curran3 1 Methodist Hospital, Minneapolis, Minneapolis, MN, 2Radiation Therapy Oncology Group, Philadelphia, PA, 3Thomas Jefferson University, Philadelphia, PA, 4University of Rochester, Rochester, NY, 5Akron City Hospital, Akron, OH, 6 University of California–Davis, Sacramento, CA, 7Wayne State University, Detroit, MI, 8Notre Dame Hospital, Montreal, AB, Canada, 9McGill University, Montreal, AB, Canada, 10SUNY–Brooklyn, Brooklyn, NY Purpose/Objective: To determine if stereotactic radiosurgery (SRS) after conventional whole brain radiation therapy (WBRT) improves overall survival when compared to WBRT alone in patients with 1-3 brain metastases. Secondary objectives include a comparison of sites of recurrence and cause of death. Materials/Methods: Between 1/96 and 6/01, 333 patients from 34 institutions were randomized to receive WBRT ⫹ SRS or WBRT alone. The WBRT was given at 250cGy/fraction to 3750 cGy in 3 weeks. The SRS dose was based on tumor size and was delivered within one week of completion of WBRT. The study was designed to detect a 50% improvement in median survival time (MST) with 80% statistical power for all patients and a 75% improvement in MST in patients with solitary metastases. Central radiology review of local control and salvage therapy analyses will be presented. Results: There was a statistically significant survival advantage with WBRT ⫹ SRS for the following patients: solitary brain metastases (MST 6.5 vs 4.9 months, p⫽0.04), RPA class I (MST 11.6 vs 9.6 months, p⫽0.05), age ⬍ 50 (9.9 vs 8.3 months, p⫽0.04) and patients with non-small cell lung cancer or any squamous cell carcinoma (5.9 vs 3.9 months, p⫽0.05). Also, patients with initial KPS of 90-100 appeared to benefit (10.2 vs 7.4 months) without reaching statistical significance (p⫽0.07). Furthermore, all patients in the WBRT ⫹ SRS group were more likely to have a stable or improved performance status (KPS) at 3 months (50% vs 33%, p⫽0.02) and at 6 months (43% vs 27%, p⫽0.03). There was no significant difference in cause of death but there was a significant difference in local control as reported by the treating institution (82% vs 71% at one year for WBRT ⫹ SRS vs WBRT alone, respectively (p⫽0.01). Toxicities were comparable between the two treatment groups. Conclusions: WBRT ⫹ SRS provided a survival advantage compared to WBRT alone in each of the following patient categories: 1) solitary brain metastasis; 2) RPA class I ; 3) age ⬍ 50; 4) non-small cell lung cancer or any squamous cell carcinoma. Furthermore, all subsets of patients in the WBRT ⫹ SRS group were more likely to have a stable or improved performance status than those in the WBRT alone group. Systemic disease remained the primary cause of death (⬎2/3) in both groups and improved systemic therapies are needed.
1
Functional Consequences of Radiation (RT)-Induced Perfusion Changes in Patients with Left-Sided Breast Cancer
L.B. Marks1, R.G. Prosnitz1, P.M. Hardenbergh1, S. Borges-Neto2, T. Wong2, D. Hollis3, A. Tisch1, S. Zhou1, M. Blazing4 1 Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 2Department of Radiology, Duke University Medical Center, Durham, NC, 3Department of Statistics, Duke University Medical Center, Durham, NC, 4 Department of Cardiology, Duke University Medical Center, Durham, NC Purpose/Objective: Our group has previously demonstrated that incidental cardiac RT during therapy for left-sided breast cancer results in a dose-dependent reduction in regional cardiac perfusion. (Hardenbergh IJROBP 49:1023-1028, 2001) We herein assess whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. Materials/Methods: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function following RT for left-sided breast cancer. The median age was 57 (range 33-82). Patients had pre-RT SPECT perfusion scans to assess regional perfusion, regional wall motion, and ejection fraction. Patients were imaged 30-60 minutes following the resting IV injection of approximately 25-40 millicuries of technesium-99m sestamibi or Tetrofosmin. Projection data were acquired and images were reconstructed using clinical techniques. Post-RT perfusion scans (6, 12, 18, 24, and 36 months post-RT) were compared to the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. The severity/extent of regional perfusion defects were scored using
3