- Email: [email protected]
Long-Term Quality of Life of Retroperitoneal Sarcoma Patients Treated With Preoperative Radiation Therapy and Surgery
Volume 96 Number 2S Supplement 2016 diagnosis was 4.1 (IQR, 2.5-7.1). Table 1 shows that increasing NLR, when subcategorized into quintiles, correlates with higher risk of relapse/ refractory disease (P Z 0.02, chi square). A receiver operator curve (ROC) analysis was then applied to determine the NLR cutoff value of 6.5, which optimally identified the risk of relapse. On univariate analysis, NLR > 6.5 was significantly associated with relapse/refractory disease (HR: 3.39, 95% CI: 1.69d6.94, P Z 0.0007). 5 year PFS for patients with NLR > 6.5 was 81.2% as opposed to 93.6% in the remainder of patients (P Z 0.0003). On multivariate analysis, even after adjusting for bulky disease, NLR > 6.5 remained a significant, independent predictor of progression (HR: 2.22, 95% CI: 1.08d4.68, P Z 0.03). Conclusion: In this cohort of stage I and II HL patients, pre-treatment NLR above a threshold is significantly associated with increased risk of relapse or refractory disease and predicts for worse PFS. If validated, pre-treatment NLR could be an effective, low cost screening test that, in conjunction with other clinical parameters, could be used to identify patients at highest risk of progression. Author Disclosure: J. Reddy: None. J.R. Gunther: None. B. Dabaja: None. M. Akhtari: None. G.V. Martin: None. P.K. Allen: None. B.J. Aktinson: None. G.L. Smith: None. C.C. Pinnix: None. S.A. Milgrom: None. Z. Abou Yehia: None. E.M. Osborne: None. M. Fanale: None.
49 Phase 1 Trial of Preoperative Image Guided Intensity Modulated Proton Radiation Therapy (IMPT) With Simultaneously Integrated Boost to the High Risk Margin for Retroperitoneal Sarcomas T.F. DeLaney,1,2 Y.L.E. Chen,1 J.A. Adams,3 S. Hickey,3 D. Wang,4 E.H. Baldini,5 K. Bernstein,3 B.Y. Yeap,6 S.M. Hahn,7 G.P. Nielsen,3 E. Choy,8 J.T. Mullen,9 and S.S. Yoon10; 1Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 2Harvard Medical School, Boston, MA, 3Massachusetts General Hospital, Boston, MA, 4Rush University Medical Center, Chicago, IL, 5Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 6Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 8Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, 9Department of Surgery, Massachusetts General Hospital, Boston, MA, 10Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): To conduct a phase I/II trial with photon IMRT and proton IMPT arms to selectively escalate retroperitoneal sarcoma (RPS) preoperative radiation dose to a tumor volume (CTV2) judged by the treating surgeon and radiation oncologist to be at high risk for positive margins, aiming to reduce the risk of LR. We report the proton IMPT phase I study arm. Materials/Methods: Patients > 18 years with primary or locally recurrent RPS were treated with preoperative IMPT, 50.4 GyRBE/28 fractions, to CTV1 (GTV and adjacent tissues at risk of subclinical disease) with simultaneous integrated boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15, 2.20, and 2.25 GyRBE respectively. Phase I study primary objective was determination of the MTD of radiation to CTV2, which would then be further tested in the follow-on phase II study. Results: Eleven patients were accrued to increasing protocol IMPT dose levels without acute dose limiting toxicities (DLTs) preventing dose escalation to MTD. Acute toxicity was generally mild with no radiation interruptions. No unexpected perioperative morbidity was noted. Eight months postoperatively, one patient developed hydronephrosis treated by stent; that ureter, dissected off tumor, had received 57.5 GyRBE preoperatively. Retained ureters were subsequently constrained to 50.4 GyRBE without further problem. With 18-month median follow-up, there were no LRs. Conclusion: IMPT dose escalation to CTV2 to 63 GyRBE was achieved without acute DLT; phase II IMPT study will accrue to that dose. Parallel IMRT phase I arm is currently accruing. Ureters undergoing high dose
Oral Scientific Sessions
S23
radiation/surgery are at risk for hydroureter; our future studies will constrain retained ureter(s) to 50.4 GyRBE to avoid ureteral stricture. Author Disclosure: T.F. DeLaney: Honoraria; UpToDate, Oakstone Medical Publishing. Consultant; Gerston Lehman Consulting. Advisory Board; Amgen. Y.E. Chen: None. J.A. Adams: None. S. Hickey: None. D. Wang: None. E.H. Baldini: None. K. Bernstein: None. B.Y. Yeap: None. S.M. Hahn: None. G.P. Nielsen: None. E. Choy: None. J.T. Mullen: None. S.S. Yoon: None.
50 Long-Term Quality of Life of Retroperitoneal Sarcoma Patients Treated With Preoperative Radiation Therapy and Surgery P. Wong,1 Z. Kassam,2,3 C. Swallow,4,5 R. Gladdy,4,5 P. Chung,3 B. O’Sullivan,6 J.G. Ringash,6 and C.N. Catton3; 1Hopital Notre-Dame du CHUM, Montreal, QC, Canada, 2Stronach Regional Cancer Center, Newmarket, ON, Canada, 3Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 4Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 5Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, 6Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada Purpose/Objective(s): The management of retroperitoneal sarcomas (RPS) may include preoperative radiotherapy (RT) and surgery. As RPS often requires multi-visceral resection, combined treatment of RPS can be associated with substantial toxicity as radiation sensitive organs may be affected by pre-op RT. We aimed to examine how these treatments related toxicities affect patient quality of life (QOL). Materials/Methods: In a cross-sectional study, 25 primary RPS patients treated with preoperative IMRT from 2004-2012 were recruited and assessed for QOL (EORTC QLQ-C30) and to determine RT and surgery related toxicities (CTCAE V.4). Baseline and prospective QOL was available for 11 patients. In the other 14 patients cross-sectional data alone were obtained at different time-points during their follow-up (4-week, 6month, 1-year, 3-year, 5-year, and 10 year post-IMRT). Unless stated otherwise, all scores refer to the global domain. Results: Ten female and 15 male patients with a median age of 56 (38-80) were treated with IMRT to a median dose of 50.4 Gy (41.4-50.4). The median maximum dimension was 13.4cm (5.7-28) and the majority (17/ 25) were liposarcomas. The median time from completion of RT to RPS surgery was 9.4 weeks (5-17.4). Of the 11 patients who completed baseline QOL assessments, their compliance at 4-week, 6-month, 1-year and 3-year post-RT were 80%, 100%, 90%, and 100%. Mean pre-RT QOL was 48.5 (standard deviation (SD) 19.3). At 4-weeks post-RT, mean QOL was 57.5 (SD: 23.7) however, the mean diarrhea symptom scale increased from baseline (85 vs. 18.1, P < 0.001). Correspondingly, 54% of patients had gastrointestinal toxicities (32% G1, 56% G2 and 8% G3) by the end of RT. Regression slope analysis suggested that QOL significantly (P Z 0.002) improved over the first 3 years. The number of toxicities was significantly (P Z 0.002) associated with QOL over time. Clinically important improvement (>10 points) from baseline was observed at 1-year (68.6, SD: 18.4). At 3-year post-RT, 88% of patients had chronic RT and/or surgery related toxicities of which 30% were Grade 3 toxicities. RPS patients who survived at least 3 years had significantly better QOL (mean: 67.2, P Z 0.007 Mann-Whitney Test) relative to the full group at diagnosis. QOL changed little (mean: 0.31 point/month; SD: 0.36) after 3 years (n Z 10). RT dose, tumor size, patient age, and gender were not associated with 3-year QOL scores. Conclusion: Treatment toxicities seem to contribute to QOL recovery during the first 3-years. The number of toxicities a patient had was significantly associated with QOL. Despite patients having on average 2.5 treatment-related chronic toxicities, QOL at 3-years was better than at diagnosis. Author Disclosure: P. Wong: None. Z. Kassam: None. C. Swallow: None. R. Gladdy: None. P. Chung: None. B. O’Sullivan: None. J.G. Ringash: None. C.N. Catton: None.
49 Phase 1 Trial of Preoperative Image Guided Intensity Modulated Proton Radiation Therapy (IMPT) With Simultaneously Integrated Boost to the High Risk Margin for Retroperitoneal Sarcomas T.F. DeLaney,1,2 Y.L.E. Chen,1 J.A. Adams,3 S. Hickey,3 D. Wang,4 E.H. Baldini,5 K. Bernstein,3 B.Y. Yeap,6 S.M. Hahn,7 G.P. Nielsen,3 E. Choy,8 J.T. Mullen,9 and S.S. Yoon10; 1Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, 2Harvard Medical School, Boston, MA, 3Massachusetts General Hospital, Boston, MA, 4Rush University Medical Center, Chicago, IL, 5Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 6Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 8Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA, 9Department of Surgery, Massachusetts General Hospital, Boston, MA, 10Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): To conduct a phase I/II trial with photon IMRT and proton IMPT arms to selectively escalate retroperitoneal sarcoma (RPS) preoperative radiation dose to a tumor volume (CTV2) judged by the treating surgeon and radiation oncologist to be at high risk for positive margins, aiming to reduce the risk of LR. We report the proton IMPT phase I study arm. Materials/Methods: Patients > 18 years with primary or locally recurrent RPS were treated with preoperative IMPT, 50.4 GyRBE/28 fractions, to CTV1 (GTV and adjacent tissues at risk of subclinical disease) with simultaneous integrated boost to CTV2 to doses of 60.2, 61.6, and 63.0 GyRBE in 28 fractions of 2.15, 2.20, and 2.25 GyRBE respectively. Phase I study primary objective was determination of the MTD of radiation to CTV2, which would then be further tested in the follow-on phase II study. Results: Eleven patients were accrued to increasing protocol IMPT dose levels without acute dose limiting toxicities (DLTs) preventing dose escalation to MTD. Acute toxicity was generally mild with no radiation interruptions. No unexpected perioperative morbidity was noted. Eight months postoperatively, one patient developed hydronephrosis treated by stent; that ureter, dissected off tumor, had received 57.5 GyRBE preoperatively. Retained ureters were subsequently constrained to 50.4 GyRBE without further problem. With 18-month median follow-up, there were no LRs. Conclusion: IMPT dose escalation to CTV2 to 63 GyRBE was achieved without acute DLT; phase II IMPT study will accrue to that dose. Parallel IMRT phase I arm is currently accruing. Ureters undergoing high dose
Oral Scientific Sessions
S23
radiation/surgery are at risk for hydroureter; our future studies will constrain retained ureter(s) to 50.4 GyRBE to avoid ureteral stricture. Author Disclosure: T.F. DeLaney: Honoraria; UpToDate, Oakstone Medical Publishing. Consultant; Gerston Lehman Consulting. Advisory Board; Amgen. Y.E. Chen: None. J.A. Adams: None. S. Hickey: None. D. Wang: None. E.H. Baldini: None. K. Bernstein: None. B.Y. Yeap: None. S.M. Hahn: None. G.P. Nielsen: None. E. Choy: None. J.T. Mullen: None. S.S. Yoon: None.
50 Long-Term Quality of Life of Retroperitoneal Sarcoma Patients Treated With Preoperative Radiation Therapy and Surgery P. Wong,1 Z. Kassam,2,3 C. Swallow,4,5 R. Gladdy,4,5 P. Chung,3 B. O’Sullivan,6 J.G. Ringash,6 and C.N. Catton3; 1Hopital Notre-Dame du CHUM, Montreal, QC, Canada, 2Stronach Regional Cancer Center, Newmarket, ON, Canada, 3Radiation Medicine Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, 4Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, 5Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, 6Department of Radiation Oncology, Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada Purpose/Objective(s): The management of retroperitoneal sarcomas (RPS) may include preoperative radiotherapy (RT) and surgery. As RPS often requires multi-visceral resection, combined treatment of RPS can be associated with substantial toxicity as radiation sensitive organs may be affected by pre-op RT. We aimed to examine how these treatments related toxicities affect patient quality of life (QOL). Materials/Methods: In a cross-sectional study, 25 primary RPS patients treated with preoperative IMRT from 2004-2012 were recruited and assessed for QOL (EORTC QLQ-C30) and to determine RT and surgery related toxicities (CTCAE V.4). Baseline and prospective QOL was available for 11 patients. In the other 14 patients cross-sectional data alone were obtained at different time-points during their follow-up (4-week, 6month, 1-year, 3-year, 5-year, and 10 year post-IMRT). Unless stated otherwise, all scores refer to the global domain. Results: Ten female and 15 male patients with a median age of 56 (38-80) were treated with IMRT to a median dose of 50.4 Gy (41.4-50.4). The median maximum dimension was 13.4cm (5.7-28) and the majority (17/ 25) were liposarcomas. The median time from completion of RT to RPS surgery was 9.4 weeks (5-17.4). Of the 11 patients who completed baseline QOL assessments, their compliance at 4-week, 6-month, 1-year and 3-year post-RT were 80%, 100%, 90%, and 100%. Mean pre-RT QOL was 48.5 (standard deviation (SD) 19.3). At 4-weeks post-RT, mean QOL was 57.5 (SD: 23.7) however, the mean diarrhea symptom scale increased from baseline (85 vs. 18.1, P < 0.001). Correspondingly, 54% of patients had gastrointestinal toxicities (32% G1, 56% G2 and 8% G3) by the end of RT. Regression slope analysis suggested that QOL significantly (P Z 0.002) improved over the first 3 years. The number of toxicities was significantly (P Z 0.002) associated with QOL over time. Clinically important improvement (>10 points) from baseline was observed at 1-year (68.6, SD: 18.4). At 3-year post-RT, 88% of patients had chronic RT and/or surgery related toxicities of which 30% were Grade 3 toxicities. RPS patients who survived at least 3 years had significantly better QOL (mean: 67.2, P Z 0.007 Mann-Whitney Test) relative to the full group at diagnosis. QOL changed little (mean: 0.31 point/month; SD: 0.36) after 3 years (n Z 10). RT dose, tumor size, patient age, and gender were not associated with 3-year QOL scores. Conclusion: Treatment toxicities seem to contribute to QOL recovery during the first 3-years. The number of toxicities a patient had was significantly associated with QOL. Despite patients having on average 2.5 treatment-related chronic toxicities, QOL at 3-years was better than at diagnosis. Author Disclosure: P. Wong: None. Z. Kassam: None. C. Swallow: None. R. Gladdy: None. P. Chung: None. B. O’Sullivan: None. J.G. Ringash: None. C.N. Catton: None.