- Email: [email protected]
Stereotactic Ablative Radiation Therapy for the Treatment of Oligometastatic Prostate Cancer
E248
International Journal of Radiation Oncology Biology Physics
B. Clarisse,11 J.L. Habrand,1 A.E. Dugue,11 and F. Joly12; 1Dept. of Radiation Oncology, Centre Franc¸ois Baclesse, Caen, France, 2Dept. of Radiation Oncology, Centre Oscar Lambret, Lille, France, 3Centre Hospitalier et Re´gional Universitaire, Henry S. Kaplan Center, Clinique d’Oncologie et de Radiothe´rapie, Tours, France, 4Dept. of Radiation Oncology, Centre Leon Berard, Lyon, France, 5Dept. of Medical Oncology, Hoˆpital Foch, Suresnes, France, 6Dept. of Medical Oncology, Institut Gustave Roussy, Villejuif, France, 7Institut Gustave Roussy, Villejuif, France, 8Dept. of Radiation Oncology, Centre Eugene Marquis, Rennes, France, 9Dept. of Radiation Oncology, Hopital Saint-Louis, AP-HP, Paris, France, 10Dept. of Radiation Oncology, Hoˆpital Henri Mondor, Cre´teil, France, 11Dept. of Clinical Research, Centre Franc¸ois Baclesse, Caen, France, 12Dept. of Medical Oncology, Centre Franc¸ois Baclesse, Caen, France
Author Disclosure: E. Meyer: None. D. Pasquier: None. G. Bernadou: None. G. Calais: None. C. Carrie: None. D. Stefan: None. C. Theodore: None. L. Albiges: Consultant; Novartis, Pfizer, Sanofi, Amgen, BristolMyers Squibb, Bayer. A. Bossi: None. P. Maroun: None. R. De Crevoisier: None. C. Hennequin: None. J. Lagrange: None. F. Lesaunier: None. J. Grellard: None. B. Clarisse: None. J. Habrand: None. A.E. Dugue: None. F. Joly: None.
Purpose/Objective(s): Renal cell carcinoma is radioresistant to conventional radiation therapy. However, by delivering high dose per fraction, SRT can improve local control of treated metastases. The purpose of this study was to determine the efficacy of SRT for mRCC. Materials/Methods: Data from patients (pts) treated for oligometastatic or oligoprogressive mRCC in 6 French referral centers were retrospectively collected. Local progression free survival (LPFS) for lesions and progression free survival (PFS) and overall survival (OS) for pts were assessed. Results: A total of 194 pts and 259 metastases from various sites were treated. SRT was delivered as exclusive treatment in 64 pts and concomitantly with systemic therapy in 130. Overall, median gross tumor volume (GTV) and planning target volume (PTV) were 13 and 17 cm3. Fourteen percent of lesions were treated with SRT for reirradiation after failing of conventional radiation therapy. Delivered doses were heterogeneous, ranged from 8 to 60 Gy in 1 to 11 fractions, and median biologically effective dose for a/b Z 7 (BED7) was 54 Gy (13 e 180). Complete, partial and stable local control was achieved in 17%, 38% and 36% of treated lesions. After a median follow up of 13 months (mo), 36 local relapses were observed and LPFS was 17 mos (95% CI 15 e 25). In multivariate analysis, higher PTV and higher BED7 were associated with longer LPFS (HR 0.98, each). Median PTV, BED7, and LPFS for treated lesions according to metastatic sites are listed in the following Table 1. Abstract 2603; Table 1. Treated metastases (n)
Median PTV cm3 (range)
Brain (122) 5 (0.1 e 83) Bone (89) 27 (2 e 96) Kidney (6) 10 (2 e 17) Adrenal gland (7) 34 (23 e 40) Liver (6) NA Lymph nodes (7) 44 (9 e 98) Lung (18) 17 (2 e 69) Pancreas (2) 55 (17 e 94) Soft tissues (2) NA NA : not available - NR : not reached
Median BED7 Gy (range) 53 49 95 67 106 73 180 46 110
(13 e 83) (13 e 110) (52 e 180) (65 e 110) (87 e 180) (43 e 110) (97 e 180) (40 e 52) (110 e 110)
Median LPFS mo (95% CI) 14 (12 e 26) 15 (13 e 18) 16 (16 e NR) 28 (10 e NR) 34 (14 e NR) 42 (42 e NR) NR NR NR
No event was observed during follow-up for lung, pancreas and soft tissues metastases. BED was the only factor independently linked to brain metastases LPFS (HR 0.97) and no prognostic factor was found for bone lesions. Six grade 3-4 toxicities were reported corresponding to oesomediastinal fistula, intratumoral hemorrhage of brain metastases, intracranial hypertension for 2 pts, convulsion and pain. Thirty-three pts received a second course of SRT for distant limited progression. Median PFS, OS, and delay to introduce or change systemic therapy were 8, 29 and 13 mo. Conclusion: SRT is safe and efficient for local control of metastases from RCC but a consensus is necessary to homogenize dose and fractionation. SRT seems also interesting for systemic control in case of limited progression of mRCC, permitting a prolonged PFS and to delay modification of anticancer drug.
2604 Stereotactic Ablative Radiation Therapy for the Treatment of Oligometastatic Prostate Cancer P.T. Tran,1 N. Radwan,1 A.E. Ross,1 D. Reyes,1 J.L. Wright,1 D. Song,1 C. Deville, Jr,1 T.L. DeWeese,2 M. Carducci,1 E.M. Schaeffer,3 K. Pienta,1 and M. Eisenberger1; 1Johns Hopkins Medicine, Baltimore, MD, 2 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 3 Northwestern University, Chicago, IL Purpose/Objective(s): Local ablative treatment to limited metastatic or oligometastatic patients can result in long term disease-free survival in colorectal and sarcoma patients. The importance of consolidating all macroscopic tumor deposits in prostate cancer in the modern era is an unanswered question. Stereotactic ablative radiation (SABR) is highly focused, high-dose radiation that is ideally suited for treatment of oligometastatic patients. Here we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative SABR at a single institution. Materials/Methods: Records of all men with OPC, defined as up to 5 metastases (bone, lymph nodes and viscera) diagnosed on imaging (bone scan, CT, MRI or PET), who underwent consolidative SABR at our institution were reviewed. Demographic, pathologic, clinical and concurrent-adjuvant therapy data were collected from our IRB approved departmental prostate cancer radiation therapy registry. SABR was delivered in 1-5 fractions of 5-18 Gy using linear accelerator or robotic stereotactic technology. Kaplan-Meier method was used to assess local progression-free survival (LPFS), biochemical progression-free survival (bPFS; nadir+2) and distant progression-free survival (DPFS). Results: In total, 46 OPC patients were identified with 16 (35%) of those men presenting as synchronous OPC undergoing complete consolidation of primary and all metastatic sites. The remaining 30 men had recurrent or metachronous OPC. Median and mean follow-up was 27 and 33 weeks, respectively. The majority of men (36/46 or 78%) had hormone sensitive prostate cancer (HSPC) at the time of SABR with the remaining (10/46 or 22%) having castration resistant prostate cancer (CRPC). Most men were treated with concurrent hormonal therapy (37/46 or 81%). In total consolidative SABR was delivered to 92 metastases: 71 bone (77%), 18 nodal (20%) and 3 (3%) visceral metastases. Overall LPFS at 1-year was 75% and 100% for SABR biologically effective doses >40. The bPFS and DPFS at 1-year were 72.7% and 73.5%, respectively. Crude Grade 1 and 2 acute toxicity were low at 30% and 5%, respectively, with no Grade 3 or higher acute toxicity. Conclusion: Consolidative SABR in men with OPC is feasible and well tolerated. The heterogeneity and small size of our series limits interpretation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggests this approach is worthy of further prospective study. More definitive conclusions await the completion and reporting of prospective randomized studies such as the Belgian STOMP trial and our Baltimore ORIOLE trial. Author Disclosure: P.T. Tran: Research Grant; Astellas-Medivation. Rad Onc Study Section; RSNA. N. Radwan: None. A.E. Ross: Research Grant; Merck. D. Reyes: None. J.L. Wright: None. D. Song: None. C. Deville: None. T.L. DeWeese: None. M. Carducci: Chair; ECOGACRIN. E.M. Schaeffer: None. K. Pienta: None. M. Eisenberger: None.
International Journal of Radiation Oncology Biology Physics
B. Clarisse,11 J.L. Habrand,1 A.E. Dugue,11 and F. Joly12; 1Dept. of Radiation Oncology, Centre Franc¸ois Baclesse, Caen, France, 2Dept. of Radiation Oncology, Centre Oscar Lambret, Lille, France, 3Centre Hospitalier et Re´gional Universitaire, Henry S. Kaplan Center, Clinique d’Oncologie et de Radiothe´rapie, Tours, France, 4Dept. of Radiation Oncology, Centre Leon Berard, Lyon, France, 5Dept. of Medical Oncology, Hoˆpital Foch, Suresnes, France, 6Dept. of Medical Oncology, Institut Gustave Roussy, Villejuif, France, 7Institut Gustave Roussy, Villejuif, France, 8Dept. of Radiation Oncology, Centre Eugene Marquis, Rennes, France, 9Dept. of Radiation Oncology, Hopital Saint-Louis, AP-HP, Paris, France, 10Dept. of Radiation Oncology, Hoˆpital Henri Mondor, Cre´teil, France, 11Dept. of Clinical Research, Centre Franc¸ois Baclesse, Caen, France, 12Dept. of Medical Oncology, Centre Franc¸ois Baclesse, Caen, France
Author Disclosure: E. Meyer: None. D. Pasquier: None. G. Bernadou: None. G. Calais: None. C. Carrie: None. D. Stefan: None. C. Theodore: None. L. Albiges: Consultant; Novartis, Pfizer, Sanofi, Amgen, BristolMyers Squibb, Bayer. A. Bossi: None. P. Maroun: None. R. De Crevoisier: None. C. Hennequin: None. J. Lagrange: None. F. Lesaunier: None. J. Grellard: None. B. Clarisse: None. J. Habrand: None. A.E. Dugue: None. F. Joly: None.
Purpose/Objective(s): Renal cell carcinoma is radioresistant to conventional radiation therapy. However, by delivering high dose per fraction, SRT can improve local control of treated metastases. The purpose of this study was to determine the efficacy of SRT for mRCC. Materials/Methods: Data from patients (pts) treated for oligometastatic or oligoprogressive mRCC in 6 French referral centers were retrospectively collected. Local progression free survival (LPFS) for lesions and progression free survival (PFS) and overall survival (OS) for pts were assessed. Results: A total of 194 pts and 259 metastases from various sites were treated. SRT was delivered as exclusive treatment in 64 pts and concomitantly with systemic therapy in 130. Overall, median gross tumor volume (GTV) and planning target volume (PTV) were 13 and 17 cm3. Fourteen percent of lesions were treated with SRT for reirradiation after failing of conventional radiation therapy. Delivered doses were heterogeneous, ranged from 8 to 60 Gy in 1 to 11 fractions, and median biologically effective dose for a/b Z 7 (BED7) was 54 Gy (13 e 180). Complete, partial and stable local control was achieved in 17%, 38% and 36% of treated lesions. After a median follow up of 13 months (mo), 36 local relapses were observed and LPFS was 17 mos (95% CI 15 e 25). In multivariate analysis, higher PTV and higher BED7 were associated with longer LPFS (HR 0.98, each). Median PTV, BED7, and LPFS for treated lesions according to metastatic sites are listed in the following Table 1. Abstract 2603; Table 1. Treated metastases (n)
Median PTV cm3 (range)
Brain (122) 5 (0.1 e 83) Bone (89) 27 (2 e 96) Kidney (6) 10 (2 e 17) Adrenal gland (7) 34 (23 e 40) Liver (6) NA Lymph nodes (7) 44 (9 e 98) Lung (18) 17 (2 e 69) Pancreas (2) 55 (17 e 94) Soft tissues (2) NA NA : not available - NR : not reached
Median BED7 Gy (range) 53 49 95 67 106 73 180 46 110
(13 e 83) (13 e 110) (52 e 180) (65 e 110) (87 e 180) (43 e 110) (97 e 180) (40 e 52) (110 e 110)
Median LPFS mo (95% CI) 14 (12 e 26) 15 (13 e 18) 16 (16 e NR) 28 (10 e NR) 34 (14 e NR) 42 (42 e NR) NR NR NR
No event was observed during follow-up for lung, pancreas and soft tissues metastases. BED was the only factor independently linked to brain metastases LPFS (HR 0.97) and no prognostic factor was found for bone lesions. Six grade 3-4 toxicities were reported corresponding to oesomediastinal fistula, intratumoral hemorrhage of brain metastases, intracranial hypertension for 2 pts, convulsion and pain. Thirty-three pts received a second course of SRT for distant limited progression. Median PFS, OS, and delay to introduce or change systemic therapy were 8, 29 and 13 mo. Conclusion: SRT is safe and efficient for local control of metastases from RCC but a consensus is necessary to homogenize dose and fractionation. SRT seems also interesting for systemic control in case of limited progression of mRCC, permitting a prolonged PFS and to delay modification of anticancer drug.
2604 Stereotactic Ablative Radiation Therapy for the Treatment of Oligometastatic Prostate Cancer P.T. Tran,1 N. Radwan,1 A.E. Ross,1 D. Reyes,1 J.L. Wright,1 D. Song,1 C. Deville, Jr,1 T.L. DeWeese,2 M. Carducci,1 E.M. Schaeffer,3 K. Pienta,1 and M. Eisenberger1; 1Johns Hopkins Medicine, Baltimore, MD, 2 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 3 Northwestern University, Chicago, IL Purpose/Objective(s): Local ablative treatment to limited metastatic or oligometastatic patients can result in long term disease-free survival in colorectal and sarcoma patients. The importance of consolidating all macroscopic tumor deposits in prostate cancer in the modern era is an unanswered question. Stereotactic ablative radiation (SABR) is highly focused, high-dose radiation that is ideally suited for treatment of oligometastatic patients. Here we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative SABR at a single institution. Materials/Methods: Records of all men with OPC, defined as up to 5 metastases (bone, lymph nodes and viscera) diagnosed on imaging (bone scan, CT, MRI or PET), who underwent consolidative SABR at our institution were reviewed. Demographic, pathologic, clinical and concurrent-adjuvant therapy data were collected from our IRB approved departmental prostate cancer radiation therapy registry. SABR was delivered in 1-5 fractions of 5-18 Gy using linear accelerator or robotic stereotactic technology. Kaplan-Meier method was used to assess local progression-free survival (LPFS), biochemical progression-free survival (bPFS; nadir+2) and distant progression-free survival (DPFS). Results: In total, 46 OPC patients were identified with 16 (35%) of those men presenting as synchronous OPC undergoing complete consolidation of primary and all metastatic sites. The remaining 30 men had recurrent or metachronous OPC. Median and mean follow-up was 27 and 33 weeks, respectively. The majority of men (36/46 or 78%) had hormone sensitive prostate cancer (HSPC) at the time of SABR with the remaining (10/46 or 22%) having castration resistant prostate cancer (CRPC). Most men were treated with concurrent hormonal therapy (37/46 or 81%). In total consolidative SABR was delivered to 92 metastases: 71 bone (77%), 18 nodal (20%) and 3 (3%) visceral metastases. Overall LPFS at 1-year was 75% and 100% for SABR biologically effective doses >40. The bPFS and DPFS at 1-year were 72.7% and 73.5%, respectively. Crude Grade 1 and 2 acute toxicity were low at 30% and 5%, respectively, with no Grade 3 or higher acute toxicity. Conclusion: Consolidative SABR in men with OPC is feasible and well tolerated. The heterogeneity and small size of our series limits interpretation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggests this approach is worthy of further prospective study. More definitive conclusions await the completion and reporting of prospective randomized studies such as the Belgian STOMP trial and our Baltimore ORIOLE trial. Author Disclosure: P.T. Tran: Research Grant; Astellas-Medivation. Rad Onc Study Section; RSNA. N. Radwan: None. A.E. Ross: Research Grant; Merck. D. Reyes: None. J.L. Wright: None. D. Song: None. C. Deville: None. T.L. DeWeese: None. M. Carducci: Chair; ECOGACRIN. E.M. Schaeffer: None. K. Pienta: None. M. Eisenberger: None.