Combined M anagement of Retroperiton Retroperiton neal Sarcoma neal Sarcoma Carol J. Swallow Department of S Surgical Oncology Princess Margaret and Princess Margaret and d Mount Sinai Hospitals d Mount Sinai Hospitals University y of Toronto Charles Catton, Brian O’Sullivan, Pete er Chung, Martin Blackstein, David Hogg, Abha Gupta, Korosh Khalili, Sangeet Gha ai, Rita Kandel, David Howarth, Ilan Weinreb Lynn Mikula, Julia Jones, Michael Ko, Rya Lynn Mikula Julia Jones Michael Ko Rya an Heisler Paul Ridgway Rebecca Gladdy an Heisler, Paul Ridgway, Rebecca Gladdy l 50 th Anniversary Conference Princess Margaret Hospital Toronto, Canada a October 17, 2008
Presentation Freque ency by Primary Site PMH Sarcoma D atabase 1989-1997 (n= 1282) 10% Site of Soft Tissue Sarcoma Site of Soft Tissue Sarcoma 10% Extremity and Trunk Viscera Viscera Head and Neck Retroperitoneum p 15% 15% 65%
Overall Sur Overall Sur rvival after Resection rvival after Resection by Primary Site e of Soft Tissue Sarcoma PMH PMH PMH ’75-’90 Catton, O’Sullivan et al., d Oncol Biol Phys 1994; 29:1005. Int J Ra
Combined Mana agement of RPS g • Scope of pro • Scope of pro blem blem • Work-up • Resection tec chnique • Adjuvant rad • Adjuvant rad iation iation – rationale – morbidity bidit • Long term on ncologic outcomes
R t Retroperitoneal Sarc it l S coma: The Challenge! Th Ch ll !
Retroperitoneal Sarcoma: The Challenge
When I was a fellow*… “If it’s resectable, take it out!” *circa 1993-95, MSKCC
There is a better ma anagement strategy • lymphoma • asymptomatic be enign PNST • metastatic carcin noma Think first, cut late er • paraganglioma paraganglioma • PNET etc. • Soft Tissue Tum • Soft Tissue Tum mour mour
Approach to the Re etroperitoneal Mass • often asymptomatic o e asy p o a c • increasingly incidental • usually non urgent • usually non-urgent • broad differential • avoid diagnostic laparot tomy
Approach to the Re Approach to the Re etroperitoneal Mass etroperitoneal Mass Reasons to Biops sy Percutaneously • diagnosis unclear from clinical presentation and clinical presentation and imaging AND treatment will be altered will be altered • neoadjuvant treatment planned planned
Resection: Cornerstone of RPS Treatment
Retroperitoneal Retroperitoneal l Sarcoma: Outcome in l Sarcoma: Outcome in Resect ted Patients 1975 - 1990 n = 45 n 45 5 yr 5 yr patients 10 yr 100 80 80 ntage of p 60 40 40 percen 20 0 Survival LR Relapse Distant Relapse Free Free * *complete gross resection rate was 43% l t ti t 43% Catton, O’Sullivan et al., Int J Rad Oncol Biol Phys 1994; 29:1005.
Catton, O’Sullivan et al., Int J Rad Oncol Biol Phys 1994; 29:1005.
4 = Lewis, 1998 MSKCC, n=231 10 = Stoeckle, 2001 FSG, n=94 30 = Heslin, 1997 MSKCC, n=198 , , * Chiappa et al., JSO 2006; 93:456. + Yin Lu et al., CMJ 2007; 120:1047. # van Dalen et al., EJSO 2006; 33:234. 8 = Gronchi, 2004 Milano, n=167 * + +# 9 = Singer 1995 DFCI n=83 9 = Singer, 1995 DFCI, n=83 +# #
Strategies to imp prove local control I. Surgical Technique I Surgical Technique • pre-surgical plannin ng • intraoperative/ posto operative care • en bloc resection of adherent viscera II. Radiation delivery y Protect normal struc Protect normal struc ctures; escalate dose ctures; escalate dose • removable implant ts • pre-operative RT • IORT boost • brachytherapy boo ost
RPS Combined Treatm ment Protocol Surgical Technique – PM ec que MH series ’96-’00 se es 96 00 Structures resected d Percent en bloc with tumou en bloc with tumou ur ur (n 46) (n= 46) Psoas/iliacus 63% Large bowel Large bowel 63% 63% Kidney/adrenal 63% Chest wall/diaphrag Chest wall/diaphrag gm gm 31% 31% Liver 31% Pancreas Pancreas 19% 19% Stomach 19% S l Spleen 19% 19% Small bowel 12%
Technical Optimization of Resection
Technical Optimization of Resection
Randomized trials of local ma Randomized trials of local ma anagement of extremity STS anagement of extremity STS Author Institute Tri al Local Control Rosenberg (1982) NCI Rosenberg (1982) NCI Am Am mp vs mp vs 100% 100% Sx x + EBRT 85% Pisters (1996) Pisters (1996) MSKCC MSKCC Sx Sx x vs x vs 71% 71% Sx x +BRT 84% Yang (1998) NCI Sx x vs 75% Sx x + EBRT 99% O’Sullivan (2000) NCIC-CTG Pre e-op EBRT 93% Po ost-op EBRT 93% Eilber (1990) UCLA Pre e-op RT+ IV dox 92% pre pre e op RT +IA dox e-op RT +IA dox 93% 93%
* Catton, O’Sullivan et al., Int J Rad Oncol Biol Phys 1994; 29:1005.
Strategies to imp prove local control I. Surgical Technique I Surgical Technique • pre-surgical plannin ng • intraoperative/ posto operative care • en bloc resection of adherent viscera II. Radiation delivery y Protect normal struc Protect normal struc ctures; escalate dose ctures; escalate dose • removable implant ts • pre-operative RT • IORT boost • brachytherapy boo ost
Rationale for PreOperat tive Radiotherapy for RPS preop postop
Preoperative Radiation fo r Retroperitoneal Sarcoma: Complex Complex x Planning x Planning
Management of E Extremity Sarcoma Stage II & III: Pre e- vs Post- Op RT NCIC SR-2 Trial NCIC SR 2 Trial O’Sullivan et al, Lancet 2002: 359:2235
Initial R esults of a Trial of Pr Initial R esults of a Trial of Pr re-operative External B eam re-operative External B eam R adiation Therapy and Post-o operative B rachytherapy for R etroperitone eal Sarcom a Julia J. Jones, C harles N . C atton, Brian O ’Sullivan, Jean C outure, R yan L. H eisler, R R ita A. Kandel, C arol J. Sw allow U niversity of Toronto Sarcom a G rou p, Princess M argaret H ospital and M ount Sinai H ospital, T M t Si i H it l T T Toronto, O N , C anada t O N C d Jone es et al, Ann Surg Oncol 2002: 9:346
PMH Protocol of Combin ned Modality Treatment (XRT + SR + BRT) for Re etroperitoneal Sarcoma Pretreatment t Assessment • pathological and imaging review • differential renal diff ti l l scan (if indicated) (if i di t d) • CT Abdomen/Pe lvis • CT Chest
Combined Modality ( (XRT + SR + BRT) for Retroperiton neal Sarcoma Treatmen Treatmen nt Schema nt Schema • pre-op XRT 45- 50 Gy pre-op XRT 45- 50 Gy y/25 (5 weeks) y/25 (5 weeks) • 4 - 6 week wait • total gross resection + total gross resection + catheter placement catheter placement • > 5 day wait • +/- pulsed dose rate B / pu sed dose a e BRT to max 70 Gy o a 0 Gy
Management of patients w with retroperitoneal sarcoma at Princess Marga aret Hospital, Toronto between June 199 96 and October 2000. R RPS RPS R n n=83 trial trial incurable incurable refused refused recent t n=55 n=12 therapy n=2 resection n=14 mets resection pre-op death n=5 n=46 n=4 BT BT pre-op XRT XRT no RT BT an nd post-op n=2 n=40 n=2 XR RT n=2 + BT + BT - BT - BT XRT = = external beam radiation therapy n=19 n=21 BT = post-operative brachytherapy
Pre-opera ative XRT RTOG acute to RTOG acute to oxicity scores oxicity scores ad a maximum score ≤ 2 • All patients (n=40) ha • Acute toxicity scores Acute toxicity scores s related to upper and lower s related to upper and lower GI symptoms excep pt for one patient • One patient develope ed cystitis
Intra-operative p placement of b brachytherapy c h th catheters th t
Brachytherapy cath Brachytherapy cath heter exit sites heter exit sites
• Iridium192 pulsed dose rate BT unit p • dose rate 0.5 Gy/hr, depth of 0.5 cm • median dose 25 Gy, area 50 cm 2
Acute post-ope erative toxicity scale an nd scores 4 0 1 2 3 5 life- none mild medical ho ospital death threatening therapy ad mission n= n= 15 15 8 5 8 5 11 6 1 11 6 1 4/6 had BT H Hepatic failure ti f il
Modified la ate toxicity scale an nd scores 0 0 1 1 2 2 5 5 3 3 4 4 none mild medical death h hospital life- therapy ad dmission threatening 36 1 1 1 1 2 n= 2 late complications of duo odenal perforation 6/6 had BT
• OS at 2 yrs (n=55) = OS at 2 yrs (n 55) 73% • OS at 2 yrs (n=46) = 88% • RFS at 2 yrs (n=46) = 80% 80%
Phase II Trial of Com mbined Management Overall Survival in pa Overall Survival in pa atients who completed atients who completed preoperative XRT a and resection, n=40 5yr OS S 10yr OS 75% 75% 63% 63% Rx’d 06/96 to10/00 median OS not reached at median OS not reached at f/u to 08/07 median 89 mos. f/u no BT, n=21 BT, n=19 (months) Versus historical PMH control in resected patie ents: 5 yr OS 57%, 10 yr OS 20% Mikula et al., 2008
Phase II Trial of Com mbined Management Recurrence-Free Su urvival in patients who p completed preoperative XRT and resection, n=40 no BT, n=21 BT, n=19 5yr R 5y RFS 10yr RFS S 0y S 69% % 52% medi ian RFS ≈ 120 mos. medi di i ian 89 mos. f/u 89 f/ Versus historical PMH control in resected patie ents: 5 yr RFS 45%, 10 yr RFS 17% Mikula et al., 2008
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