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Long-term follow-up of a prospective trial of pre-operative external-beam radiation and post-operative brachytherapy for retroperitoneal sarcoma. LA Mikula, PF Ridgway, CN Catton, JJ Jones, B O’Sullivan, MA Ko, CJ Swallow University of Toronto
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Long-term follow-up of a prospective trial of pre-operativeexternal-beam radiationand post-operative brachytherapyfor retroperitoneal sarcoma LA Mikula, PF Ridgway, CN Catton, JJ Jones, B O’Sullivan, MA Ko, CJ Swallow University of Toronto Mount Sinai Hospital & Princess Margaret Hospital Toronto, Canada
Retroperitoneal SarcomaPrincess Margaret Hospitaln=45 resected patients, 1975-1988 OS Local Relapse-Free Survival Distant relapse-Free Survival Catton, O’Sullivan et al, Int J Rad Oncol Biol Phys 1994; 29:1005.
Treatment Schema • Patients with RPS referred to Princess Margaret Hospital, Toronto, June 1996-April 2003 • Inclusion criteria: resectable disease & no mestastases; signed informed consent Pre-operative XRT: 45 Gy/5 weeks 4-6 weeks Surgery Post-operative brachytherapy (BT): 25 Gy (0.5Gy/hr, depth 0.5cm)
RPS n=83 incurable n=12 refused therapy n=2 trial recent resection n=14 n=55 mets n=5 resection pre-op death n=4 n=46 BT n=2 pre-op XRT n=40 no RT n=2 BT and post-op XRT n=2 + BT n=19 - BT n=21 XRT = external beam radiation therapy BT = post-operative brachytherapy Jones et al, Ann Surg Onc 2002,9,346
Pre-operative External Beam Radiation • Conformal planning using 3D techniques • Shielding of contralateral kidney; liver
Post-operative Brachytherapy • Single plane of 3-8 afterloading BT catheters placed on the surgical bed with 1cm spacing • Planar implant dose of 0.5 Gy/hr, depth 0.5cm • Afterloading iridium-192 pulsed dose rate BT unit • BT initiated once GI function returned (7-14 days post-op)
Outcomes & Follow-up • Follow-up: clinic visit + CT scan every 6 months x5 years, then anually • Minimum follow-up 48 months • Outcomes: • Survival • Disease recurrence • Toxicity: Radiation Therapy Oncology Group scores • Pre-operative toxicity • Acute post-operative toxicity (within 3 months) • Late toxicity (3 months to 1 year post-op) Jones et al, Ann Surg Onc 2002,9,346
Pre-Operative Toxicity:40 patients treated with pre-op XRT • All patients had a maximum RTOG score of ≤ 2 • Acute toxicity scores related to upper and lower GI symptoms … • … except for one patient who developed cystitis Jones et al, Ann Surg Onc 2002,9,346
Acute Post-operative Toxicity:46 resected patients 4 life- threatening 0 none 1 mild 2 medical therapy 3 hospital admission 5 death n= 15 8 5 11 6 1 4/6 had BT Hepatic failure Jones et al, Ann Surg Onc 2002,9,346
Modified Late Toxicity(3-12 months post-op) 0 none 1 mild 2 medical therapy 5 death 3 hospital admission 4 life- threatening 36 1 1 1 1 2 n= 2 late complications of duodenal perforation 6/6 had BT Jones et al, Ann Surg Onc 2002,9,346
Clinicopathologic Features:Pre-op XRT + Surgery • N=40 • Male 15, female 25 • Median age 58 yrs (range 41-75) • Primary presentation of RPS = 29 (72%) • Referred with recurrent disease = 11 (28%) • Tumour characteristics: • Median size 19cm (range 4-40cm) • 55% high grade • 70% liposarcoma
Treatment Characteristics • Patients who completed pre-op XRT & surgery: • Median pre-op XRT dose = 45 Gy (range 45-57 Gy) • Median BT dose = 23 Gy (range 7.5-25 Gy) • All resections were grossly complete • 97% had resection of contiguous structures • No patients received adjunctive chemotherapy
Status at Last Follow-Up • Median follow-up 89 months (7.4 years) • No patients lost to follow-up • 4 patients recurred and were re-resected • At last follow-up: • 25 alive and disease-free (62.5%) • 3 alive with recurrent disease (7.5%) • 9 dead of disease (22.5%) • 3 dead of other causes (7.5%)
Overall Survival (n=40) 5yr OS 10yr OS 75% 63% median OS not reached at median 89 mos. f/u (months)
Recurrence-Free Survival (n=40) 5yr RFS 10yr RFS 69% 52% median RFS ≈ 120 mos. median 89 mnths f/u
OS BT (n=19) vs no BT (n=21) 5yr OS 10yr OS 80% 80% Log Rank: p=0.27 5yr OS 10yr OS 68% 54% Median not reached median OS not reached
RFS BT (n=19) vs no BT (n=21) 5yr RFS: 75% 10yr RFS:-- 5yr RFS 10yr RFS 61% 47% Log Rank: p=0.58 No BT: median RFS not reached BT: median RFS ≈ 106 mnths
OS in High-Grade Tumours (n=22) 5yr RFS 10yr RFS 68% --- Log Rank: p=0.68 No BT, n=10 BT, n=12 5yr RFS 10yr RFS 58% 47% No BT: median OS not reached BT: median OS ≈ 116 mnths
Prospective Trials of Combined Radiation + Resection for RPS
Historical vs. Current Data OS Local Relapse-Free Survival Catton, O’Sullivan et al, Int J Rad Oncol Biol Phys 1994; 29:1005.
Conclusions • Pre-operative XRT was well tolerated • Brachytherapy to the upper abdomen was associated with significant toxicity • Pre-operative XRT and aggressive surgical resection shows promise in improving local control and long-term survival in RPS
Intent-to-treat Analysis • For all 55 patients entered into the trial: 2-year OS 73% • For 46 patients resected with curative intent: 2-year OS 88%