Pancreatic cancer: What defines resectabilityWhat …

1 Pancreatic cancer : what defines resectabilityWhat defines resectability and the role for surgery Douglas B. EvansFor the Multidisciplinary PancreaticFor the Multidisciplinary Pancreatic cancer Study GroupThe University of TexasyM. D. Anderson cancer CenterHouston, TexasSeptember 20, 2008 Multidisciplinary Clinical Working GroupSurgeryMedical OncologyJi Abbpyg pPeter PistersJeff LeeJason FlemingNi k V thJim AbbruzzeseRobert WolffGauri VaradhacharyMike FischRadiation OncologyChris CraneSunil KrishnanNick VautheyEddie AbdallaMike FischMilind JavleDavid FogelmanPrajnan DasDiagnostic ImagingEric TammPathologyHuamin WangGastroenterologyJeffrey H. LeeManoop BhutaniChusilp CharnsangavejLisa LanoPriya BhosalegGregg StaerkelManoop BhutaniAparna BalachandranStage-specific survivalMonths From DxAll I, : Pancreatic cancer Program Database 1991-2007, N = 4,395 Katz MHG, Hwang RF, et al. TNM staging of Pancreatic adenocarcinoma.

2 CA cancer J Clin. 2008;58(2):111-25. Intraoperative Assessment of Resectability Inaccurateaccu ate Incomplete gross resection provides no survival benefit compared to chemoradiation without surgerySMA Margin(Retroperitoneal/uncinate)(Retrope ritoneal/uncinate)? Complete Resection? Complete ResectionR StatusR DesignationGross ResectionMicroscopic MarginR0completenegativeR0completenegati veR1completepositiveR2incompletepositive Exocrine Pancreas. InGreene FL, Page DL, Fleming ID, et al., eds. AJCC CStiMl ChiIL S i2002157164 AJCC cancer Staging Manual. Chicago, IL: Springer, 2002. pp. (Retroperitoneal) Margin AJCC cancer Staging Manual 6thEditionAJCC cancer Staging Manual 6 EditionRP marginSMVSMASMAPVPVSMASMVSYNOPTIC REPORTS pecimen: PancreaticoduodenectomyTumor Diagnosis: DUCTAL ADENOCARCINOMAD egree of Differentiation: ModerateThe tumor size is cm in diameterExtrapancreatic extension presentExtrapancreatic extension presentLymphovascular presentPerineural invasion presentSMA margin uninvolvedwith distance of 18mm to inked marginBile duct margin uninvolvedPancreatic transection margin uninvolvedProximal stomach or duodenum margin uninvolvedDistal duodenum or jejunum margin uninvolvedDistal duodenum or jejunum margin uninvolvedRegional Lymph Nodes: Total number involved: 3 Total number examined: 30, including hepatic artery and periaortic (P t Ad B)(Parts A and B)Vessels removed: None statedFinal pTNM Staging (AJCC 6th edition).

3 PT3 Tumor extends beyond the pancreaspyppN1 Regional lymph node metastasispMX Distant metastasis cannot be assessed739559 DefinitionsResectable: no extension to celiac, CHA, SMApatent SMV-PV confluencestage I, II (T1-3, Nx, M0)Locally Advanced: celiac, SMA encasement (>1800)celiac, SMA encasement ( 180)stage III (T4, Nx, M0)Borderline:Borderline:arterial abutment (<1800)stage III (minimal T4)stage III (minimal T4)Varadhachary GR, et al. Ann Surg Oncol. 2006;13(8):1035-46 Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46 ResectableBorderline ResectableBorderline ResectableLocally AdvancedCourtesy of R Wolff, MDSMVSMASdiNOYESS urrounding perineural plexusNOYESR esection LowHighoperative riskgIf resect, is the resection UsuallyUsually notcomplete (R0)Resectable adenocarcinoma of the Pancreatic headSMVSMASMATK itts 527268 Resectable tumor, RRHAR esectable : likely to require venous resectionSMVSMAR esectable : likely to require venous resectionBorderline ResectableSMAV aradhachary GR, et al.

4 Ann Surg Oncol. 2006;13(8):1035-46 Katz MHG, et al. J Am Coll Surg. 2008;206(5):833-46 Locally Advanced (Stage III)SMVSMAL ocally Advanced (Stage III)Celiac encasementSMA encasementDefinitions: SSO/AHPBA CCResectable: no extension to celiac, CHA, SMA, SMV-PV flconfluencestage I, II (T1-3, Nx, M0)Borderline:a) venous abutment or encasement (with )(option for reconstruction)b) arterial abutment (<1800)Locally Advanced: celiac SMA encasement (> 1800)celiac, SMA encasement (> 1800)stage III (T4, Nx, M0)Imaging Template for Pancreatic Cancerggp Tumor size and location Tumor and veins relationship SMV, portal vein and splenic veinportal vein and splenic vein Tumor and arteries relationship SMA, celiac axis common hepatic arteryceliac axis, common hepatic artery Presence or absence of distant metastasesli er l ng peritone mmetastases liver, lung, peritoneumMDACC M ltidi i liPti CSt d GMDACC Multidisciplinary Pancreatic cancer Study GroupMDACC Classification System for yBorderline Resectable Disease Type A: Anatomically borderlineresectable tumor(tumor abuts artery for <1800)(y) Type B: Indeterminantextrapancreatic metastasis Type C: Patient of marginalperformance statusKatz MHG, et al.

5 J Am Coll Surg. 2008;206(5):833-46 Treatment of Borderline Resectable Pancreatic CancerUnderlying hypothesis / assumption1. Neoadjuvant treatment sequencing used to: select those with favorable biologyttdihi lllt M1 di treat radiographically occult M1 disease enhance the chance of a complete (R0, R1) resectionR1) resection 2 Outcome for R1 different than R2 (iebetter)2. Outcome for R1 different than R2 (ie, better)Accurate Pathology and Multimodality TherapyPancreaticoduodenectomy: Ductal Adenocarcinoma M D Anderson (N = 360)VariableNo. PtsMed Surp moR111 moR16022 Maj CompNo2632701R111 s9 32 2 Ann Surg 2001 Raut, Ann Surg 2007;246:52-60 Local Failure (All pts): 8% The Importance of Neoadjuvant TherapyPancreaticoduodenectomy: Ductal AdenocarcinomaPancreaticoduodenectomy: Ductal Adenocarcinoma M D Anderson (N = 360)Preoperative TherapyR1 ResectionpyYES13%NO19%Raut, Ann Surg 2007;246:52-60 LlFil (Allt)8%Local Failure (All pts): 8% Borderline Resectable PC MDACC Treatment ApproachTreatment phaseBreak ~ 6 wksCTXgem comboChemo-XRTR estagingDropoutRestagingDropoutORClassif icationStaging CTDropoutDropoutClassification as BorderlineStaging CTKatz MHG, et al.

6 J Am Coll Surg. 2008;206(5):833-46 Rates of Resection Path Response SurvivalRates of Resection, Path Response, Survival160 Patients with Borderline Resectable PCNo. of Patients (%)Median Survival (Mos)p*MDACC TypeTotalResectedPath Resp. IIb III IVAll PtsResectedUnresectedTypeIIb, III, IVA84 (53)32 (38)19 (59) (28)22 (50)13 (59)1629120 001B44 (28)22 (50)13 (59) (20)12 (38)5 (42) (41)37 (56) *p: comparison of median survival between resected and unresected patients of each typeKatz MHG, et al. J Am Coll Surg. 2008;206(5):833-46 Final path:R0 Rev saph vein graftLymph nodes: 0/24 CHAdividedSpl ACHA hidividedbile ductPVSpl Vsaph veinpatch492495 SMVS ummaryLocal tumor resectability is best determined by Local tumor resectability is best determined by high quality CT (exploratory surgery is out-dated)dated) Resectable tumors may be treated with upfront surgery or a neoadjuvant approachBdlitbltb tt td Borderline resectable tumors are best treated with upfront systemic therapy/chemoradiation Locally advanced tumors, as defined by arterial encasement, are not resectable and surgery is ,gynot a realistic treatment optio