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Reirradiation of Thoracic Cancers with Intensity Modulated Proton Therapy
222
International Journal of Radiation Oncology Biology Physics
RTOG 0915 was open, and closed on April 15; 2015 after accruing a total of 98 patients. All patients received planned SBRT treatment. Median follow-up was 27 months. In follow-up; 10 patients were lost to follow-up; 1 was in arm 1 and 9 in arm 2. Baseline patient and tumor characteristics were balanced between both arms. Thirteen (27%) patients on arm 1 and 16 (33%) patients on arm 2 experienced RTOG grade 3 AEs; there were no grade 4 AEs. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no differences in OS or PFS survival, log-rank PZ.44 and .99, respectively. OS at 2 years was 71% (95% CI; 55-82%) for arm 1 and 61% (95% CI; 44-78%) for arm 2. PFS at 2 years was 63% (95% CI; 46-75%) for arm 1 and 51% (95% CI; 34-65%) for arm 2. Conclusion: This randomized phase 2 study demonstrated that 30 Gy in one fraction was equivalent to 60 Gy in three fractions in terms of toxicity, progression-free survival, and overall survival. Author Disclosure: A.K. Singh: None. J. Gomez Suescun: None. K.L. Stephans: None. J.A. Bogart: None. T. Lili: None. H. Malhotra: None. G.M. Videtic: None. A. Groman: None.
Author Disclosure: J.C. Ho: None. Q. Nguyen: None. H. Li: None. P.K. Allen: None. X. Zhang: None. X. Zhu: None. D.R. Gomez: None. S.H. Lin: Research Grant; Genentech, Peregrine Pharmaceuticals, STCube Pharmaceuticals, Hitachi, Elekta. Honoraria; AstraZeneca, ProCure, US Oncology. M.T. Gillin: None. R.U. Komaki: None. Z. Liao: None. S.M. Hahn: None. J.Y. Chang: None.
5 Reirradiation of Thoracic Cancers with Intensity Modulated Proton Therapy J.C. Ho,1 Q.N. Nguyen,1 H. Li,2 P.K. Allen,1 X. Zhang,2 X.R. Zhu,2 D.R. Gomez,1 S.H. Lin,1 M.T. Gillin,2 R.U. Komaki,1 Z. Liao,1 S.M. Hahn,1 and J.Y. Chang1; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2 Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Reirradiation of thoracic malignancies is a treatment challenge, with concerns for toxicity and inability to deliver definitive doses. Given the unique physical characteristic of the Bragg peak, intensity modulated proton therapy (IMPT) potentially can deliver a higher radiation dose to tumor while minimizing dose to normal critical tissue, compared to photon or passive scattering proton therapy. Here, we report our reirradiation experience with the use of IMPT for thoracic malignancies. Materials/Methods: Between 2011 and 2016, 27 consecutive patients who received IMPT for reirradiation of thoracic malignancies with definitive intent were enrolled in prospectively registered clinical trials, and were retrospectively analyzed. Patients were included if they received a prior thoracic radiation course delivered with curative intent. All patients underwent 4D CT-based simulation and motion analysis and individualized tumormotion dose-uncertainty analysis. Patients also had 4D CT resimulation during treatment. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). Patients received IMPT for recurrence of thoracic cancer (93%) or sequentially after a course of thoracic stereotactic ablative radiation therapy (7%), to a median dose of 66 EQD2 Gy (range 43.2 e 84 Gy). Results: Twenty-two patients (81%) were treated for nonesmall cell lung cancer. The median time to reirradiation was 29.5 months. At a median follow-up for all patients of 11.2 months (25.9 months for those still alive), the median overall survival (OS) was 18.0 months, with a 1-year OS of 54%. Four patients (15%) experienced an in-field local failure (LF), with 1-year and 2-year freedom from LF rates of 78%. The 1-year freedom from local-regional relapse (LRR) and 1-year progression-free survival (PFS) rates were 61% and 51%, respectively. Patients who received 66 EQD2 Gy or higher had improved rates of 1-year freedom from LF (100% vs 49%, PZ.013), 1-year freedom from LRR (84% vs 23%, PZ.035), and 1-year PFS (76% vs 14%, PZ.050). Higher original T stage at diagnosis, squamous histology, and higher recurrent tumor volume were associated with worse OS. Reirradiation was well tolerated, with only 2 patients (7%) experiencing late grade 3 pulmonary toxicity, and none with grade 3 or higher esophagitis. There were no grade 4-5 toxicities. Conclusion: These data represent the first and largest series of patients treated with IMPT for definitive reirradiation of thoracic cancers. They demonstrate that IMPT can provide durable local control with minimal toxicity in patients who can have extended survival, and also suggest that higher doses may improve outcomes. IMPT appears to be a safe and effective option for the reirradiation of thoracic cancers.
6 Individualizing Radiation Dose in Locally Advanced NoneSmall Cell Lung Cancer Patients Using Pretreatment Serum MicroRNA Signatures S. Jolly,1 Y. Sun,2 P.G. Hawkins,1 N. Bi,3 J.W.D. Hearn,4 M.M. Matuszak,1 M. Tewari,5 T.S. Lawrence,1 R. K. Ten Haken,1 F.M. Kong,6 and M. Schipper2; 1Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 2Department of Biostatistics, University of Michigan, Ann Arbor, MI, 3Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 4University of Michigan, Ann Arbor, MI, 5 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 6 Department of Radiation Oncology, Indiana University, Indianapolis, IN Purpose/Objective(s): While high radiation (RT) doses of 100 Gy10 in early stage nonesmall cell lung cancer (NSCLC) have shown high tumor control, the randomized phase 3 RTOG 0617 trial showed no benefit to escalating dose to 74 Gy (88.8 Gy10) in locally advanced (LA) NSCLC. However, results from RTOG 0617 stand in contrast to other data supporting dose escalation, and it is possible that there is heterogeneity regarding who may benefit. Serum microRNAs (miRNAs) have shown promise as prognostic biomarkers for some cancer populations. However, little is known about their clinical utility in inoperable NSCLC treated with RT. We sought to identify which patients may benefit from high-dose radiation therapy (RT) by combining pre-treatment miRNA measurements with clinical factors to develop a predictive signature. Materials/Methods: Eighty-three patients with LA NSCLC treated with definitive RT with or without chemotherapy were recruited in prospective NSCLC trials. Serum was collected pretreatment. MiRNA profiles were analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) arrays, which contained 84 miRNA panels. Elastic net Cox regression was used to select miRNAs predictive of overall survival, which was the primary endpoint. We combined these predictive miRNAs with baseline clinical factors to generate a predictive score and evaluated the effect of RT dose on survival according to this score. Full crossvalidation and multivariate Cox regression was used to confirm the interaction between radiation dose and predictive score. We also evaluated the effect of RT dose according to predictive score on the secondary endpoints of local progression and distant metastasis using multivariate Cox regression. Results: Median age was 66 yrs; 84% had stage III disease; Median GTV dose was 68.4 Gy. Elastic net Cox regression identified 8 predictive miRNAs, which were combined with clinical factors to generate a predictive score. For patients with a low predictive score, high RT dose was associated with improved overall survival (HR for death 0.28; 95% CI 0.14 to 0.56), whereas there was no significant dose effect in patients with a high predictive score (HR 0.91; 95% CI 0.44 to 1.91). The interaction between predictive score and RT dose remained significant on multivariate analysis (P Z 2.72E-10). Findings were similar for local progression and distant metastasis, with the interaction between predictive score and RT dose remaining significant on multivariate analysis (PZ.03). Conclusion: We developed and cross-validated a predictive score combining 8 circulating miRNAs with baseline clinical factors for LA-NSCLC treated with RT. Our data suggest this signature may allow pretreatment stratification of patients according to whether they are likely to benefit from RT dose-escalated treatment. Additional studies are warranted to further validate these findings. Author Disclosure: S. Jolly: None. Y. Sun: None. P.G. Hawkins: None. N. Bi: None. J.W. Hearn: None. M.M. Matuszak: None. M. Tewari: None. T.S. Lawrence: None. R.K. Ten Haken: None. F.M. Kong: None. M. Schipper: None.
International Journal of Radiation Oncology Biology Physics
RTOG 0915 was open, and closed on April 15; 2015 after accruing a total of 98 patients. All patients received planned SBRT treatment. Median follow-up was 27 months. In follow-up; 10 patients were lost to follow-up; 1 was in arm 1 and 9 in arm 2. Baseline patient and tumor characteristics were balanced between both arms. Thirteen (27%) patients on arm 1 and 16 (33%) patients on arm 2 experienced RTOG grade 3 AEs; there were no grade 4 AEs. Thoracic grade 3 AEs were experienced by 8 (16%) patients on arm 1 and 6 (12%) patients on arm 2. There were no differences in OS or PFS survival, log-rank PZ.44 and .99, respectively. OS at 2 years was 71% (95% CI; 55-82%) for arm 1 and 61% (95% CI; 44-78%) for arm 2. PFS at 2 years was 63% (95% CI; 46-75%) for arm 1 and 51% (95% CI; 34-65%) for arm 2. Conclusion: This randomized phase 2 study demonstrated that 30 Gy in one fraction was equivalent to 60 Gy in three fractions in terms of toxicity, progression-free survival, and overall survival. Author Disclosure: A.K. Singh: None. J. Gomez Suescun: None. K.L. Stephans: None. J.A. Bogart: None. T. Lili: None. H. Malhotra: None. G.M. Videtic: None. A. Groman: None.
Author Disclosure: J.C. Ho: None. Q. Nguyen: None. H. Li: None. P.K. Allen: None. X. Zhang: None. X. Zhu: None. D.R. Gomez: None. S.H. Lin: Research Grant; Genentech, Peregrine Pharmaceuticals, STCube Pharmaceuticals, Hitachi, Elekta. Honoraria; AstraZeneca, ProCure, US Oncology. M.T. Gillin: None. R.U. Komaki: None. Z. Liao: None. S.M. Hahn: None. J.Y. Chang: None.
5 Reirradiation of Thoracic Cancers with Intensity Modulated Proton Therapy J.C. Ho,1 Q.N. Nguyen,1 H. Li,2 P.K. Allen,1 X. Zhang,2 X.R. Zhu,2 D.R. Gomez,1 S.H. Lin,1 M.T. Gillin,2 R.U. Komaki,1 Z. Liao,1 S.M. Hahn,1 and J.Y. Chang1; 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 2 Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Reirradiation of thoracic malignancies is a treatment challenge, with concerns for toxicity and inability to deliver definitive doses. Given the unique physical characteristic of the Bragg peak, intensity modulated proton therapy (IMPT) potentially can deliver a higher radiation dose to tumor while minimizing dose to normal critical tissue, compared to photon or passive scattering proton therapy. Here, we report our reirradiation experience with the use of IMPT for thoracic malignancies. Materials/Methods: Between 2011 and 2016, 27 consecutive patients who received IMPT for reirradiation of thoracic malignancies with definitive intent were enrolled in prospectively registered clinical trials, and were retrospectively analyzed. Patients were included if they received a prior thoracic radiation course delivered with curative intent. All patients underwent 4D CT-based simulation and motion analysis and individualized tumormotion dose-uncertainty analysis. Patients also had 4D CT resimulation during treatment. All doses were recalculated to an equivalent dose in 2-Gy fractions (EQD2). Patients received IMPT for recurrence of thoracic cancer (93%) or sequentially after a course of thoracic stereotactic ablative radiation therapy (7%), to a median dose of 66 EQD2 Gy (range 43.2 e 84 Gy). Results: Twenty-two patients (81%) were treated for nonesmall cell lung cancer. The median time to reirradiation was 29.5 months. At a median follow-up for all patients of 11.2 months (25.9 months for those still alive), the median overall survival (OS) was 18.0 months, with a 1-year OS of 54%. Four patients (15%) experienced an in-field local failure (LF), with 1-year and 2-year freedom from LF rates of 78%. The 1-year freedom from local-regional relapse (LRR) and 1-year progression-free survival (PFS) rates were 61% and 51%, respectively. Patients who received 66 EQD2 Gy or higher had improved rates of 1-year freedom from LF (100% vs 49%, PZ.013), 1-year freedom from LRR (84% vs 23%, PZ.035), and 1-year PFS (76% vs 14%, PZ.050). Higher original T stage at diagnosis, squamous histology, and higher recurrent tumor volume were associated with worse OS. Reirradiation was well tolerated, with only 2 patients (7%) experiencing late grade 3 pulmonary toxicity, and none with grade 3 or higher esophagitis. There were no grade 4-5 toxicities. Conclusion: These data represent the first and largest series of patients treated with IMPT for definitive reirradiation of thoracic cancers. They demonstrate that IMPT can provide durable local control with minimal toxicity in patients who can have extended survival, and also suggest that higher doses may improve outcomes. IMPT appears to be a safe and effective option for the reirradiation of thoracic cancers.
6 Individualizing Radiation Dose in Locally Advanced NoneSmall Cell Lung Cancer Patients Using Pretreatment Serum MicroRNA Signatures S. Jolly,1 Y. Sun,2 P.G. Hawkins,1 N. Bi,3 J.W.D. Hearn,4 M.M. Matuszak,1 M. Tewari,5 T.S. Lawrence,1 R. K. Ten Haken,1 F.M. Kong,6 and M. Schipper2; 1Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, 2Department of Biostatistics, University of Michigan, Ann Arbor, MI, 3Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 4University of Michigan, Ann Arbor, MI, 5 Department of Internal Medicine, University of Michigan, Ann Arbor, MI, 6 Department of Radiation Oncology, Indiana University, Indianapolis, IN Purpose/Objective(s): While high radiation (RT) doses of 100 Gy10 in early stage nonesmall cell lung cancer (NSCLC) have shown high tumor control, the randomized phase 3 RTOG 0617 trial showed no benefit to escalating dose to 74 Gy (88.8 Gy10) in locally advanced (LA) NSCLC. However, results from RTOG 0617 stand in contrast to other data supporting dose escalation, and it is possible that there is heterogeneity regarding who may benefit. Serum microRNAs (miRNAs) have shown promise as prognostic biomarkers for some cancer populations. However, little is known about their clinical utility in inoperable NSCLC treated with RT. We sought to identify which patients may benefit from high-dose radiation therapy (RT) by combining pre-treatment miRNA measurements with clinical factors to develop a predictive signature. Materials/Methods: Eighty-three patients with LA NSCLC treated with definitive RT with or without chemotherapy were recruited in prospective NSCLC trials. Serum was collected pretreatment. MiRNA profiles were analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) arrays, which contained 84 miRNA panels. Elastic net Cox regression was used to select miRNAs predictive of overall survival, which was the primary endpoint. We combined these predictive miRNAs with baseline clinical factors to generate a predictive score and evaluated the effect of RT dose on survival according to this score. Full crossvalidation and multivariate Cox regression was used to confirm the interaction between radiation dose and predictive score. We also evaluated the effect of RT dose according to predictive score on the secondary endpoints of local progression and distant metastasis using multivariate Cox regression. Results: Median age was 66 yrs; 84% had stage III disease; Median GTV dose was 68.4 Gy. Elastic net Cox regression identified 8 predictive miRNAs, which were combined with clinical factors to generate a predictive score. For patients with a low predictive score, high RT dose was associated with improved overall survival (HR for death 0.28; 95% CI 0.14 to 0.56), whereas there was no significant dose effect in patients with a high predictive score (HR 0.91; 95% CI 0.44 to 1.91). The interaction between predictive score and RT dose remained significant on multivariate analysis (P Z 2.72E-10). Findings were similar for local progression and distant metastasis, with the interaction between predictive score and RT dose remaining significant on multivariate analysis (PZ.03). Conclusion: We developed and cross-validated a predictive score combining 8 circulating miRNAs with baseline clinical factors for LA-NSCLC treated with RT. Our data suggest this signature may allow pretreatment stratification of patients according to whether they are likely to benefit from RT dose-escalated treatment. Additional studies are warranted to further validate these findings. Author Disclosure: S. Jolly: None. Y. Sun: None. P.G. Hawkins: None. N. Bi: None. J.W. Hearn: None. M.M. Matuszak: None. M. Tewari: None. T.S. Lawrence: None. R.K. Ten Haken: None. F.M. Kong: None. M. Schipper: None.