胰腺癌治疗进展英文课件

Pancreatic CancerEpidemiology n2019-46,420 new cases in USAn2019-39,590 deathsn4th most common cancer killern2nd most common GI cancer killer(colon#1)Pancreatic CancerEpidemiology1 1Pancreatic CancerEpidemiology New Cancer Deaths,United States,2019.New Cancer Deaths,United States,2019.Pancreatic CancerEpidemiology2 2Pancreatic CancerEpidemiology Incidence increasing 1%yearlyPancreatic CancerEpidemiology3 3Pancreatic CancerEpidemiology n85%of new cases are advancednLocally advanced:blood vessels(Stage III)nDistant spread to liver,lungs (Stage IV)Pancreatic CancerEpidemiology4 4Late Presentation-Poor SurvivalHowlander et al,SEER Cancer Statistics Review 2019.American Cancer Society,Cancer Facts&Figures 2019.StageIIIIIIIVPercent at diagnosis60%45%30%15%0%Late Presentation-Poor Survi5 5Late Presentation-Poor SurvivalHowlander et al,SEER Cancer Statistics Review 2019.American Cancer Society,Cancer Facts&Figures 2019.24181260Median Survival(mos)StageIIIIIIIV0Even“early”stage diseaseis advancedLate Presentation-Poor Survi6 6No Surgery No Surgery If.If.nnMajor blood vessels involved Major blood vessels involved(Stage III)(Stage III)nnDistant metastases(Stage IV)Distant metastases(Stage IV)nnSome Stage III may be Some Stage III may be exceptionsexceptionsNo Surgery If.7 7Pancreatic ResectionDistal Pancreatectomy (no Appleby)Whipple operation(Pancreaticoduodenectomy)(Pancreaticoduodenectomy)Pancreatic ResectionDistal Pan8 8Standard Whipple Standard Whipple 9 9Standard WhippleRoux-en-Yrarely doneStandard WhippleRoux-en-Y1010Pylorus Preserving Whipple Cure rate is same with each.Most resections arePylorus PreservingWhipplesPylorus Preserving Whipple 1111Pylorus Preserving WhipplePylorus Preserving Whipple1212Factors Influencing Survival Factors Influencing Survival 1313182 consecutive patients underwent a Whipple for pancreatic cancer between 1987 and 2019.Patients from 1987-2019 were compared with those from 2019-2019.Study Design182 consecutive patients under1414ResultsResults1515SurvivalBiological factors related to tumornDifferentiationnNodal involvementnPerineural invasionnResection marginsSurvivalBiological factors rel1616Degree of Tumor DifferentiationActuarial survival estimate for patients with well,Actuarial survival estimate for patients with well,moderately,and poorly differentiated adenocarcinoma of moderately,and poorly differentiated adenocarcinoma of the pancreas(P.001).the pancreas(P.001).50%50%(1987-2019)Degree of Tumor Differentiatio1717Lymph NodesNegativeNegativePositivePositive28%28%22%22%Actuarial survival for node-negative(solid line)Actuarial survival for node-negative(solid line)and node-positive(dotted line)patients with and node-positive(dotted line)patients with adenocarcinoma of the pancreas undergoing a adenocarcinoma of the pancreas undergoing a pancreaticoduodenectomy(P.001).pancreaticoduodenectomy(P.001).38%38%(1987-2019)Lymph NodesNegativePositive28%1818Perineural InvasionNegativeNegativePositivePositive36%36%13%13%Actuarial survival for patients with Actuarial survival for patients with adenocarcinoma of the pancreas undergoing adenocarcinoma of the pancreas undergoing pancreaticoduodenectomy(P.001).pancreaticoduodenectomy(P.001).36%36%(1987-2019)Perineural InvasionNegativePos1919Resection MarginsNegativeNegativePositivePositive27%27%Biologic features of the tumors themselves Biologic features of the tumors themselves are the primary determinants of prognosis!are the primary determinants of prognosis!27%27%157 pts157 pts(1987-2019)R0R0R1R1Resection MarginsNegativePosit202027.4%27.4%40.9%40.9%76.4%76.4%All 182 PtsAll 182 PtsSurvival for Entire CohortSurvival for Entire CohortAll 182 PtsAll 182 Pts(1987-2019)27.4%40.9%76.4%All 182 PtsSurv2121胰腺癌治疗进展英文课件2222350 ml EBL350 ml EBL475 ml EBL475 ml EBL35.5%35.5%15.8%15.8%Blood Loss Influences Survival350 ml EBL475 ml EBL35.5%15.8%2323Adjuvant TherapyTreatment given after resection Effort to eradicate any remaining microscopic tumorAll pts in USA receive chemotherapy after resection!Some in USA also get radiation Adjuvant TherapyTreatment give2424Cancer may involve HA,PV,superior mesentericvein or arteryUNRESECTABLECancer may UNRESECTABLE2525Criteria for ResectionCriteria for ResectionWhy not resect the Why not resect the involved blood vessels?involved blood vessels?Criteria for ResectionWhy not 2626Criteria for ResectionCriteria for ResectionThose with vessel invasion have Those with vessel invasion have Those with vessel invasion have extensive tumor with microscopic extensive tumor with microscopic extensive tumor with microscopic spread that cannot be removed spread that cannot be removed spread that cannot be removed completelycompletelycompletelyNot seen on preop scans,but Not seen on preop scans,but Not seen on preop scans,but experience tells us its thereexperience tells us its thereexperience tells us its thereIf we resect Stage III tumors,the If we resect Stage III tumors,the If we resect Stage III tumors,the cancer comes back quicklycancer comes back quicklycancer comes back quicklyCriteria for ResectionThose wi2727“Downstaging”of PaCan Pts given chemotherapy 6-12 mosn We try to kill the microscopic tumor firstn Re-evaluation by CT,CA19-9n Resection then possible in somen First reported by our group(2019)n Now more widely done in USASo.“Downstaging”of PaCaSo.2828Effect of Chemotherapy on TumorTumor:4.4 x 3.8cmTumor:4.4 x 3.8cmPV invasion(+)PV invasion(+)Tumor:2.8 x 2.5cm(57%reduction)Tumor:2.8 x 2.5cm(57%reduction)PV invasion(-)PV invasion(-)BeforeBeforeAfterAfterEffect of Chemotherapy on Tumo2929Initial scan shows SMA involvement6 mos scan looks similarBut patient felt well and CA19-9 fell from 840 to normal.Arch Surg.2019;146(7):836-843.Donahue TR,Reber HA et alWhen/Whether to Operate?CT ImagingInitial scan shows SMA involve3030PVPVSMASMASVSVSMVSMVIMVIMVLRVLRVLGALGASASAHAHAPancreasPancreasAdrenalAdrenalPVSMASVSMVIMVLRVLGASAHAPancrea3131Downstaging of PaCa Survival25+survivors 5-17 yearsObserved five-year survival rate:28%Observed five-year survival rate:28%13 more close to 5 yrs with no recurrence Possible five year survival rate:53%Possible five year survival rate:53%Downstaging of PaCa25+survivo3232Adjuvant TherapyTreatment given after surgery (Whipple/distal)Effort to eradicate any remaining microscopic tumorStandard approachAdjuvant TherapyTreatment give3333Neoadjuvant TherapyTreatment given Treatment given beforebefore surgery in surgery in pts with resectable disease pts with resectable disease (Stage I and II)(Stage I and II)Some in USA recommend this Some in USA recommend this instead of surgery firstinstead of surgery firstAdvantages and disadvantages Advantages and disadvantages Neoadjuvant TherapyTreatment g3434Theoretical AdvantagesAlmost all pts have micrometastatic disease at diagnosis 1 cm-28%have metastases1 cm-28%have metastases2 cm-73%2 cm-73%3 cm-94%3 cm-94%So almost all pts So almost all pts couldcould benefit.benefit.Iacobuzio-Donahue et al 2019 CellTheoretical AdvantagesAlmost a3535Theoretical AdvantagesIf given after surgery,up to 25%If given after surgery,up to 25%may not be treated at all.may not be treated at all.If given before,more likely to be If given before,more likely to be physically fit and able to tolerate physically fit and able to tolerate treatment treatment Or treatment may start late if there Or treatment may start late if there were complicationswere complicationsTheoretical AdvantagesIf given3636Effect of Adjuvant Treatment Delay on SurvivalEffect of Adjuvant Treatment Delay on SurvivalIacobuzio-Donahue et al 2019 CellAvoid Treatment Delay After SurgeryAvoid Treatment Delay After Surgery70%40%Effect of Adjuvant Treatment D3737Theoretical Advantages of Neoadjuvant TherapyIdentify pts unlikely to benefit from surgery During 2-3 mo treatment,up to During 2-3 mo treatment,up to 20%pts show metastases.20%pts show metastases.or develop poor performance.or develop poor performance status status Theoretical Advantages of Neoa3838Is This an Advantage?Is this good or bad?GoodGood.They are spared surgery that They are spared surgery that would not have helped.would not have helped.ororBadBad.They missed their chance for.They missed their chance for resection and possible cure.resection and possible cure.Is This an Advantage?Is this g3939Neoadjuvant Therapy So why has it not become the So why has it not become the standard approach?standard approach?Several reasons are givenSeveral reasons are givenChemotherapy today has little Chemotherapy today has little effect in most ptseffect in most ptsNeoadjuvant Therapy So why has4040Neoadjuvant Therapy At most,1/3 of pts respond to At most,1/3 of pts respond to neoadjuvant treatment.neoadjuvant treatment.So 2/3 would delay resection by 2-3 So 2/3 would delay resection by 2-3 months,without effective treatment months,without effective treatment during that time.during that time.Disease could progressDisease could progressNeoadjuvant Therapy At most,4141Neoadjuvant Therapy Although today Chemotherapy has Although today Chemotherapy has little effect in most pts.little effect in most pts.nThis could change with more effective This could change with more effective neoadjuvant regimens.neoadjuvant regimens.nOr with the ability to selectively choose a Or with the ability to selectively choose a regimen specific for the molecular regimen specific for the molecular features of each tumorfeatures of each tumorNeoadjuvant Therapy Although t4242Neoadjuvant RadioTherapy Radiation Therapy(RTx)of unclear Radiation Therapy(RTx)of unclear value in most ptsvalue in most ptsnRTx definitely decreases RTx definitely decreases locallocal recurrencerecurrence of cancerof cancernBut it does But it does notnot increase survival in most.increase survival in most.nMost pts die of distant disease(liver,Most pts die of distant disease(liver,lung,peritoneal)even when local lung,peritoneal)even when local recurrence is lowrecurrence is lownSo neoadjuvant RTx also is not So neoadjuvant RTx also is not done by most USA surgeonsdone by most USA surgeonsNeoadjuvant RadioTherapy Radi4343Surgery in USA-2019Further major surgical advances unlikelyMortality rate 1%;morbidity still highImproved outcomes likely to come from more effective drugs in combination with surgeryNeoadjuvant therapy will be used moreMore downstaging with better drugs Surgery in USA-2019Further ma4444David Geffen School of Medicine at UCLA 1955-2019David Geffen School of Medicin4545Ronald Reagan UCLA Medical CenterOpened June 2019Ronald Reagan UCLA Medical Cen4646Howard A.Reber,MDHoward A.Reber,MDProfessor of SurgeryProfessor of SurgeryUCLA School of MedicineUCLA School of MedicinePancreatic Cancer Surgical Approach in the USA-2019Agi Hirshberg Center for Pancreatic Diseasesat UCLAHoward A.Reber,MDPancreatic 4747 Thank you拯畏怖汾关炉烹霉躲渠早膘岸缅兰辆坐蔬光膊列板哮瞥疹傻俘源拯割宜跟三叉神经痛-治疗三叉神经痛-治疗 拯畏怖汾关炉烹霉躲渠早膘岸缅兰辆坐蔬光膊列板哮瞥疹48 拯畏怖汾关炉烹霉躲渠早膘岸缅兰辆坐蔬光膊列板哮瞥疹傻俘源拯割宜跟三叉神经痛-治疗三叉神经痛-治疗 拯畏怖汾关炉烹霉躲渠早膘岸缅兰辆坐蔬光膊列板哮瞥疹49