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The German GPOH-HD 95 Trial on Pediatric Hodgkin's Disease: 10 Year Results and Analysis of Treatment Failures
Proceedings of the 50th Annual ASTRO Meeting Conclusions: This multi-modal approach combining viral lysis, apoptosis-inducing gene therapy, and radiation therapy could have great impact in achieving complete local tumor control, reducing radiation dose and associated treatment morbidities, and improving the clinical outcome for patients with high risk locally advanced prostate cancer. Author Disclosure: J.A. Jimenez, None; Y. Mohammadi, None; S. Ko, None; P.A.S. Johnstone, None; C. Kao, None; T.A. Gardner, None.
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A Prospective Phase I/II Study using Proton Beam Radiation to Deliver 82GyE to Men with Localized Prostate Cancer: Preliminary Results of ACR 0312
A. L. Zietman1, K. Bae2, J. J. Coen1, J. D. Slater3, M. Lunt3, W. U. Shipley1, C. Rossi3 1 Massachusetts General Hospital, Boston, MA, 2American College of Radiology, Philadelphia, WV, 3Loma Linda University Medical Center, Loma Linda, CA
Purpose/Objective(s): To assess the safety and efficacy of dose-escalation in localized prostate cancer using proton beam monotherapy. Materials/Methods: A prospective study enrolled 85 men with localized prostate cancer at two sites, the MGH and LLUMC. Patients had T1-2a tumors and a PSA of \15ng. All were treated with opposed lateral proton beams delivering 82GyE total dose in 2GyE daily fractions. CTV1 to 50Gy included the prostate and seminal vesicles with a 1cm margin (0.5cm posteriorly) and CTV2 for a further 32GyE was the prostate GTV alone. The primary endpoints were late rectal and GU late morbidity as assessed by RTOG/EORTC criteria. Secondary endpoints include PSA failure and local failure. 84 patients were eligible for analysis. Results: The median follow-up is 23 months and no patient has died. Rates of grade 1, 2, and 3, acute GU/GI toxicity were 50%, 14%, 1%, respectively. Twenty-one patients (25%) have experienced grade 2 late GU/GI toxicity, six (7%) have had grade 3, and one (1%) had grade 4 (hemorrhagic cystitis and rectal ulcer). The actuarial risk of grade 3+ toxicity at 2 years is 6.1%. Insufficient time has elapsed to assess the secondary endpoints. Conclusions: Dose escalation to 82Gy can be given to the prostate using proton beam with acceptable morbidity. The late morbidity profile is similar to that seen in the RTOG 9406 IMRT study subgroups which used 2Gy per fraction but to lower total doses. Additional cautious dose-escalation may be possible using more advanced proton beam techniques such as intensity modulation to better define the maximum tolerable dose. Author Disclosure: A.L. Zietman, Ismar Medical, D. Speakers Bureau/Honoraria; K. Bae, None; J.J. Coen, None; J.D. Slater, None; M. Lunt, None; W.U. Shipley, None; C. Rossi, None.
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The German GPOH-HD 95 Trial on Pediatric Hodgkin’s Disease: 10 Year Results and Analysis of Treatment Failures
U. Ruehl Private, retired, Berlin, Germany Purpose/Objective(s): Aim of the GPOH-HD 95 trial was to evaluate whether consolidating radiotherapy (cRT) is mandatory for patients in clinical complete remission (CR) following induction chemotherapy (CTx). Materials/Methods: Children (\18 years) were treated according to low, medium, and high risk factors (stage, B-symptoms, extranodal extension) within 3 different treatment groups (TG 1-3) with 2, 4, or 6 cycles of combination chemotherapy. cRT was withheld in cases with CR. Involved areas with partial remission (PR) .75% were treated with 20 Gy, \75% with 30 Gy, remaining bulk .50 ml to 35Gy. Modified involved field RT was meticulously controlled by the Trial Coordination Center. Results: 1018 eligible patients from 7 European countries were registered between 1995 and 2001 (median follow-up 69 months), 899 are in continuous CR, 119 events occurred (38 early progressions, 64 relapses, 12 second malignancies), 13 pts died. Overall survival at 10 years is 95% for all pts, 99% for TG1 (stage I/IIA), 97% for TG2, 90% for TG3 (advanced disease). Disease free survival (DFS) for the low risk group (408 pts) is 94% (21 events), no difference between the 114 pts without cRT (CTx a` CR, 4 events) and the 281 pts with cRT (CTx a` PR, 13 events). For the intermediate and high risk groups (TG 2+3) DFS is 91% when PR was followed by cRT, in cases with CR and no cRT the incidence of relapse is significantly higher (DFS 69%, p = 0.0001). However, there is no difference in survival between the two groups since for pts with relapse an effective rescue treatment is available. One can estimate that by this trial 194 pts (20%) have been spared potential long term toxicity of RT while due to additional relapses in the no cRT group 13 pts more needed intensive treatment for rescue (1%); overall survival however is identical. Risk factors for treatment failure are stage of disease, extranodal extension, unfavourable histology, male gender, and protocol violations. Sites of relapse are different for irradiated and unirradiated pts. The rate of second cancers is increasing. Conclusions: Results of the HD95 trial continue to be excellent at 10 years. Only in pts with advanced disease, are relapse rates higher when cRT is omitted after achieving a CR with CTx; however, the total failure rate is low and has no impact on survival. The potential gain by reducing radiation dose and volume with respect to treatment induced long term toxicity might be considerable for the young patients. Author Disclosure: U. Ruehl, None.
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Conformal Radiation Therapy for Pediatric Ependymoma: The St. Jude Experience
T. E. Merchant, F. A. Boop, F. H. Laningham, A. Gajjar, L. E. Kun, R. A. Sanford St. Jude Children’s Research Hospital, Memphis, TN Purpose/Objective(s): Successful therapy for ependymoma requires aggressive surgical intervention and radiation therapy administered using methods which minimize the risk of side effects. The purpose of this study was to report the outcome for 153 children treated at our institution. Materials/Methods: Between July 1997 and December 2007, 153 pediatric patients (median age 2.9 ± 0.4 years) with localized ependymoma received conformal or intensity-modulated radiation therapy at St. Jude Children’s Research Hospital. Doses of 59.4 (n = 131) or 54.0Gy (n = 22) were administered to the post-operative tumor bed using a 10mm clinical target volume and 3-5 mm
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A Prospective Phase I/II Study using Proton Beam Radiation to Deliver 82GyE to Men with Localized Prostate Cancer: Preliminary Results of ACR 0312
A. L. Zietman1, K. Bae2, J. J. Coen1, J. D. Slater3, M. Lunt3, W. U. Shipley1, C. Rossi3 1 Massachusetts General Hospital, Boston, MA, 2American College of Radiology, Philadelphia, WV, 3Loma Linda University Medical Center, Loma Linda, CA
Purpose/Objective(s): To assess the safety and efficacy of dose-escalation in localized prostate cancer using proton beam monotherapy. Materials/Methods: A prospective study enrolled 85 men with localized prostate cancer at two sites, the MGH and LLUMC. Patients had T1-2a tumors and a PSA of \15ng. All were treated with opposed lateral proton beams delivering 82GyE total dose in 2GyE daily fractions. CTV1 to 50Gy included the prostate and seminal vesicles with a 1cm margin (0.5cm posteriorly) and CTV2 for a further 32GyE was the prostate GTV alone. The primary endpoints were late rectal and GU late morbidity as assessed by RTOG/EORTC criteria. Secondary endpoints include PSA failure and local failure. 84 patients were eligible for analysis. Results: The median follow-up is 23 months and no patient has died. Rates of grade 1, 2, and 3, acute GU/GI toxicity were 50%, 14%, 1%, respectively. Twenty-one patients (25%) have experienced grade 2 late GU/GI toxicity, six (7%) have had grade 3, and one (1%) had grade 4 (hemorrhagic cystitis and rectal ulcer). The actuarial risk of grade 3+ toxicity at 2 years is 6.1%. Insufficient time has elapsed to assess the secondary endpoints. Conclusions: Dose escalation to 82Gy can be given to the prostate using proton beam with acceptable morbidity. The late morbidity profile is similar to that seen in the RTOG 9406 IMRT study subgroups which used 2Gy per fraction but to lower total doses. Additional cautious dose-escalation may be possible using more advanced proton beam techniques such as intensity modulation to better define the maximum tolerable dose. Author Disclosure: A.L. Zietman, Ismar Medical, D. Speakers Bureau/Honoraria; K. Bae, None; J.J. Coen, None; J.D. Slater, None; M. Lunt, None; W.U. Shipley, None; C. Rossi, None.
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The German GPOH-HD 95 Trial on Pediatric Hodgkin’s Disease: 10 Year Results and Analysis of Treatment Failures
U. Ruehl Private, retired, Berlin, Germany Purpose/Objective(s): Aim of the GPOH-HD 95 trial was to evaluate whether consolidating radiotherapy (cRT) is mandatory for patients in clinical complete remission (CR) following induction chemotherapy (CTx). Materials/Methods: Children (\18 years) were treated according to low, medium, and high risk factors (stage, B-symptoms, extranodal extension) within 3 different treatment groups (TG 1-3) with 2, 4, or 6 cycles of combination chemotherapy. cRT was withheld in cases with CR. Involved areas with partial remission (PR) .75% were treated with 20 Gy, \75% with 30 Gy, remaining bulk .50 ml to 35Gy. Modified involved field RT was meticulously controlled by the Trial Coordination Center. Results: 1018 eligible patients from 7 European countries were registered between 1995 and 2001 (median follow-up 69 months), 899 are in continuous CR, 119 events occurred (38 early progressions, 64 relapses, 12 second malignancies), 13 pts died. Overall survival at 10 years is 95% for all pts, 99% for TG1 (stage I/IIA), 97% for TG2, 90% for TG3 (advanced disease). Disease free survival (DFS) for the low risk group (408 pts) is 94% (21 events), no difference between the 114 pts without cRT (CTx a` CR, 4 events) and the 281 pts with cRT (CTx a` PR, 13 events). For the intermediate and high risk groups (TG 2+3) DFS is 91% when PR was followed by cRT, in cases with CR and no cRT the incidence of relapse is significantly higher (DFS 69%, p = 0.0001). However, there is no difference in survival between the two groups since for pts with relapse an effective rescue treatment is available. One can estimate that by this trial 194 pts (20%) have been spared potential long term toxicity of RT while due to additional relapses in the no cRT group 13 pts more needed intensive treatment for rescue (1%); overall survival however is identical. Risk factors for treatment failure are stage of disease, extranodal extension, unfavourable histology, male gender, and protocol violations. Sites of relapse are different for irradiated and unirradiated pts. The rate of second cancers is increasing. Conclusions: Results of the HD95 trial continue to be excellent at 10 years. Only in pts with advanced disease, are relapse rates higher when cRT is omitted after achieving a CR with CTx; however, the total failure rate is low and has no impact on survival. The potential gain by reducing radiation dose and volume with respect to treatment induced long term toxicity might be considerable for the young patients. Author Disclosure: U. Ruehl, None.
171
Conformal Radiation Therapy for Pediatric Ependymoma: The St. Jude Experience
T. E. Merchant, F. A. Boop, F. H. Laningham, A. Gajjar, L. E. Kun, R. A. Sanford St. Jude Children’s Research Hospital, Memphis, TN Purpose/Objective(s): Successful therapy for ependymoma requires aggressive surgical intervention and radiation therapy administered using methods which minimize the risk of side effects. The purpose of this study was to report the outcome for 153 children treated at our institution. Materials/Methods: Between July 1997 and December 2007, 153 pediatric patients (median age 2.9 ± 0.4 years) with localized ependymoma received conformal or intensity-modulated radiation therapy at St. Jude Children’s Research Hospital. Doses of 59.4 (n = 131) or 54.0Gy (n = 22) were administered to the post-operative tumor bed using a 10mm clinical target volume and 3-5 mm
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