胰腺癌治療進展英文

1、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 ne

2、w 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,,Inci

3、dence 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,Howland

4、er 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

5、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 vesse

6、ls involved (Stage III)Distant metastases (Stage IV) Some Stage III may be exceptions,Pancreatic Resection,Distal Pancreatectomy (no Appleby)Whipple operation (Pancreaticoduodenectomy),Standard Whipple,,,,S

7、tandard 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

8、 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 tumorDifferentia

9、tionNodal involvementPerineural invasionResection margins,Degree of Tumor Differentiation,,,Actuarial survival estimate for patients with well, moderately, and poorly differentiated adenocarcinoma of the pancreas (P&l

10、t;.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 pancreatic

11、oduodenectomy (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%,(198

12、7-2005),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 Entir

13、e 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

14、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?,Crit

15、eria 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 it’s thereIf we resect Stage III tumors, the

16、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 (

17、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

18、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,,D

19、ownstaging 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

20、 (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 i

21、nstead 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

22、..,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 ma

23、y 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,Ident

24、ify 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 spar

25、ed 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 givenChemother

26、apy 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

27、 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

28、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 p

29、ts die of distant disease (liver, lung, peritoneal) even when local recurrence is lowSo neoadjuvant RTx also is not done by most USA surgeons,,Surgery in USA -2014,Further major surgical advances unlikelyMortality rate

30、 <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,David Geffen School of Medicin

31、e at UCLA 1955 - 2014,,,Ronald Reagan UCLA Medical Center,Opened June 2008,Howard A. Reber, MDProfessor of SurgeryUCLA School of Medicine,Pancreatic Cancer Surgical Approach in the USA - 2014,Agi Hirshberg Center f