胰腺癌治疗进展英文

Howard A. Reber, MDProfessor of SurgeryUCLA School of Medicine,Pancreatic Cancer Surgical Approach in the USA - 2014,Agi Hirshberg Center for Pancreatic Diseasesat UCLA,Pancreatic CancerEpidemiology,2014 - 46,420 new cases in USA2014 - 39,590 deaths4th most common cancer killer2nd most common GI cancer killer (colon #1),Pancreatic CancerEpidemiology,New Cancer Deaths , United States, 2014.,Pancreatic CancerEpidemiology,Incidence increasing 1% yearly,Pancreatic CancerEpidemiology,85% of new cases are advancedLocally advanced: blood vessels (Stage III)Distant spread to liver, lungs (Stage IV),Late Presentation - Poor Survival,Howlander et al, SEER Cancer Statistics Review 2012.American Cancer Society, Cancer Facts & Figures 2013.,Stage,I,II,III,IV,Percent at diagnosis,60%,45%,30%,15%,0%,Late Presentation - Poor Survival,Howlander et al, SEER Cancer Statistics Review 2012.American Cancer Society, Cancer Facts & Figures 2013.,24,18,12,6,0,Median Survival (mos),Stage,I,II,III,IV,0,Even “early”stage diseaseis advanced,No Surgery,If.Major blood vessels involved (Stage III)Distant metastases (Stage IV) Some Stage III may be exceptions,Pancreatic Resection,Distal Pancreatectomy (no Appleby)Whipple operation (Pancreaticoduodenectomy),Standard Whipple,Standard Whipple,Roux-en-Yrarely done,Pylorus Preserving Whipple,Cure rate is same with each. Most resections arePylorus PreservingWhipples,Pylorus Preserving Whipple,Factors Influencing Survival,182 consecutive patients underwent a Whipple for pancreatic cancer between 1987 and 2005. Patients from 1987-1995 were compared with those from 1996-2005.,Study Design,Results,Survival,Biological factors related to tumorDifferentiationNodal involvementPerineural invasionResection margins,Degree of Tumor Differentiation,Actuarial survival estimate for patients with well, moderately, and poorly differentiated adenocarcinoma of the pancreas (P.001).,50%,(1987-2005),Lymph Nodes,Negative,Positive,28%,22%,Actuarial survival for node-negative (solid line) and node-positive (dotted line) patients with adenocarcinoma of the pancreas undergoing a pancreaticoduodenectomy (P.001).,38%,(1987-2005),Perineural Invasion,Negative,Positive,36%,13%,Actuarial survival for patients with adenocarcinoma of the pancreas undergoing pancreaticoduodenectomy (P.001).,36%,(1987-2005),Resection Margins,Negative,Positive,27%,Biologic features of the tumors themselves are the primary determinants of prognosis!,27%,157 pts,(1987-2005),R0,R1,27.4%,40.9%,76.4%,All 182 Pts,Survival for Entire Cohort,All 182 Pts,(1987-2005),350 ml EBL,475 ml EBL,35.5%,15.8%,Blood Loss Influences Survival,Adjuvant Therapy,Treatment given after resection Effort to eradicate any remaining microscopic tumorAll pts in USA receive chemotherapy after resection!Some in USA also get radiation,Cancer may involve HA, PV, superior mesentericvein or artery,UNRESECTABLE,Criteria for Resection,Why not resect the involved blood vessels?,Criteria for Resection,Those with vessel invasion have extensive tumor with microscopic spread that cannot be removed completelyNot seen on preop scans, but experience tells us its thereIf we resect Stage III tumors, the cancer comes back quickly,“Downstaging” of PaCa,Pts given chemotherapy 6-12 mos We try to kill the microscopic tumor first Re-evaluation by CT, CA19-9 Resection then possible in some First reported by our group (1998) Now more widely done in USA,So.,Effect of Chemotherapy on Tumor,Tumor: 4.4 x 3.8cmPV invasion (+),Tumor: 2.8 x 2.5cm (57% reduction)PV invasion (-),Before,After,Initial scan shows SMA involvement,6 mos scan looks similar,But patient felt well and CA19-9 fell from 840 to normal.,Arch Surg. 2011;146(7):836-843. Donahue TR, Reber HA et al,When/Whether to Operate?CT Imaging,PV,SMA,SV,SMV,IMV,LRV,LGA,SA,HA,Pancreas,Adrenal,Downstaging of PaCa Survival,25+ survivors 5-17 yearsObserved five-year survival rate: 28%13 more close to 5 yrs with no recurrence Possible five year survival rate: 53%,Adjuvant Therapy,Treatment given after surgery (Whipple/distal)Effort to eradicate any remaining microscopic tumorStandard approach,Neoadjuvant Therapy,Treatment given before surgery in pts with resectable disease (Stage I and II)Some in USA recommend this instead of surgery firstAdvantages and disadvantages,Theoretical Advantages,Almost all pts have micrometastatic disease at diagnosis 1 cm - 28% have metastases2 cm - 73%3 cm - 94%So almost all pts could benefit.,Iacobuzio-Donahue et al 2011 Cell,Theoretical Advantages,If given after surgery, up to 25% may not be treated at all.If given before, more likely to be physically fit and able to tolerate treatment Or treatment may start late if there were complications,Effect of Adjuvant Treatment Delay on Survival,Iacobuzio-Donahue et al 2011 Cell,Avoid Treatment Delay After Surgery,70%,40%,Theoretical Advantages of Neoadjuvant Therapy,Identify pts unlikely to benefit from surgery During 2-3 mo treatment, up to 20% pts show metastases . . or develop poor performance status,Is This an Advantage?,Is this good or bad? Good. They are spared surgery that would not have helped. orBad. They missed their chance for resection and possible cure.,Neoadjuvant Therapy,So why has it not become the standard approach?Several reasons are givenChemotherapy today has little effect in most pts,Neoadjuvant Therapy,At most, 1/3 of pts respond to neoadjuvant treatment.So 2/3 would delay resection by 2-3 months, without effective treatment during that time.Disease could progress,Neoadjuvant Therapy,Although today Chemotherapy has little effect in most pts.This could change with more effective neoadjuvant regimens. Or with the ability to selectively choose a regimen specific for the molecular features of each tumor,Neoadjuvant RadioTherapy,Radiation Therapy (RTx) of unclear value in most ptsRTx definitely decreases local recurrence of cancerBut it does not increase survival in most.Most pts die of dis