pancreatic cancer: chemoradiation

Download pancreatic cancer: chemoradiation

If you can't read please download the document

Post on 02-Nov-2014

56 views

Category:

Health & Medicine

1 download

Embed Size (px)

DESCRIPTION

What would you recommend as first line therapy for a 68 y/o woman with local pancreatic cancer and no metastatic disease with ECOG-1? Chemoradiation: Rachna Shroff, MD Surgical Resection: Yongyut Sirivatanauksorn, MD

TRANSCRIPT

  • 1. PREOPERATIVE THERAPYFOR RESECTABLEPANCREATIC CANCERR AC H N A S H ROF F , MD , MSA S S I S T A N T P ROF E S SOR ,D E P T OF GI ME D I CA L ONCOLOGYM. D . A N D E R SON CA NCE R CE N T E RR S H ROF F@MD A N D E R SON .ORGA U B HO 2 0 1 4

2. PANCREATIC CANCER SURVIVAL BYSTAGE/TREATMENTn 5-yr OS (%)Median OS(Mos.)Adjusted HR(95% CI)Resectable -> OR 2736 24.6 19.3Resectable -> No OR 3644 2.9 8.4 2.24 (2.07 2.43)Stage III or IV 68521 0.8 4.2 4.16 (3.86 4.48)Billimoria, Ann Surg 2007 3. LOCAL DISEASE STAGINGPotentiallyResectableBorderlineResectable*LocallyAdvancedSMV-PV T-V-I < 180T-V-I 180 and / orreconstructable occlusionUnreconstructableOcclusionSMA No T-V-I T-V-I < 180 T-V-I 180CHA No T-V-IReconstructableshort-segmentT-V-I of any degreeUnreconstructableCeliacTrunkNo T-V-I T-V-I < 180 T-V-I 180*, Intergroup Definition; T-V-I: tumor-vessel interface 4. CONKO-001Oettle, JAMA 2007DFS with surgery alone: DISMALDFS with postoperative gemcitabine: BETTER 5. EVIDENCE IN SUPPORT OF ADJUVANTTHERAPYTrial Year n Treatment arm Control armMedian OS (mos)(treatment v. control)Systemic gemcitabine +/- CXRT is standard postoperative therapypGITSG 1985 435-FU-basedchemoradiation followedby maintenance 5-FUObservation 21.0 v. 10.9 0.03EORTC 1999 1145-FU-basedchemoradiationObservation 17.1 v. 12.6 NSESPAC-1 2001 541 Chemotherapy No chemotherapy 19.7 v. 14.0 < 0.01Chemoradiation No chemoradiation 15.5 v. 16.1 NSESPAC-1 2004 289 Chemotherapy No chemotherapy 20.1 v. 15.5 < 0.01Chemoradiation No chemoradiation 15.9 v. 17.9 0.05CONKO 2008 368 Gemcitabine Observation 22.8 v. 20.2 0.005RTOG97-042008 388Gemcitabine, 5-FU-basedchemoradiation,Gemcitabine5-FU, 5-FU-basedchemoradiation, 5-FU20.5 v. 16.9 NS 6. Oettle, JAMA 2007CONKO-0013-year DFS: 24%DFS with adjuvant therapy for the best of the bestLets face it: also pretty dismal.Median age: 61Median PS: 80Postop CA 19-9:< 2.5 ULNMedian time torandomization: 3weeksMost rec in year 1-2 7. RATIONALE FOR NEOADJUVANTTHERAPY Provides immediate therapy for subclinical mets All resected patients get multimodality therapy Patient selection for surgery Oncologic issues Performance status Enhancement of R0 resection 8. OCCULT MICROSCOPIC METASTASESRapid recurrence common following radical resection +/- postop therapy due toexisting disease that is not dealt with surgicallyVan den Broeck, E J Surg Onc 2009 9. ADJUVANT VS. NEOADJUVANTTHERAPYRecovery4-8 weeksS CTX +/- CXRT (~6 months)Presentation with PDACOR SDropoutS CTX +/- CXRT on/off protocol (2 6 months) S ORThe goal is eradication of microscopic disease local and distant 10. Series (Year) N Margin Status %Median OS(Mos.)pJohns Hopkins(2006)1175R1/R2 42 14< 0.0001R0 58 20University of Leeds- UK (2006)26R1 85 110.01R0 15 37ESPAC -1 (2001) 541R1 19 110.006R0 81 17University ofNaples - Italy(2000)75R1/R2 20 90.001R0 80 26Rush-Presbyterian-St. Luke's (1999)75R1 29 80.01R0 71 17MGH (1993) 72R1/R2 51 120.05R0 49 20At least macroscopically complete resection is critical to OS 11. WHAT IS RESECTABLE PANCREATICCANCER? Absence ofextrapancreaticdisease Tissue planebetween tumor andSMA/CA Patent SMV-PVconfluence231TVACriteria yield high rates of microscopically complete (R0) resection 12. Concordance Coefficient 0.07 (95% CI: 0.02 0.13)The SMA margin distance is routinely overestimated by preoperative CTOverestimated UnderestimatedRADIOLOGY:PATHOLOGY 13. SMA margin distance measured histopathologically followingSMA MarginDistanceNpancreaticoduodenectomy(n = 194)Preop CXRT(n = 147)Initial Surgery(n = 47)p*Positive 8 3 (2) 5 (11)0.011mm 40 28 (19) 12 (26)>1mm < 1cm 72 53 (36) 19 (40)1cm 66 57 (39) 9 (19)Preop CXRT associated with longer SMA margin distance even though include all patientswith borderline resectable disease* Not recorded in 8 patients 14. TIME TO LOCAL RECURRENCENeoadjuvantLocal recurrence from dartmouthGreer, JACS 2008NeodjuvantP = 0.03AdjuvantPreoperative CXRT prolongs time to LR 15. DISEASE-FREE SURVIVALP = 0.0030 12 24 36 48 60 72 84 96100806040200CXRT, > 1mmInitial Surgery, > 1mmCXRT,