胰腺癌治疗进展英文课件

Howard A. Reber, MDHoward A. Reber, MD Professor of SurgeryProfessor of Surgery UCLA School of MedicineUCLA School of Medicine Pancreatic Cancer Pancreatic Cancer Surgical Approach in the Surgical Approach in the USA - 2014USA - 2014 Agi Hirshberg Center for Pancreatic Diseases at UCLA Pancreatic CancerPancreatic Cancer EpidemiologyEpidemiology 2014 - 46,420 new cases in USA2014 - 46,420 new cases in USA 2014 - 39,590 deaths2014 - 39,590 deaths 4 4 thth most common cancer killer most common cancer killer 2 2 ndnd most common GI cancer killer most common GI cancer killer (colon #1)(colon #1) Pancreatic CancerPancreatic Cancer EpidemiologyEpidemiology New Cancer Deaths , United States, 2014. New Cancer Deaths , United States, 2014. Pancreatic CancerPancreatic Cancer EpidemiologyEpidemiology Incidence increasing 1% yearly Pancreatic CancerPancreatic Cancer EpidemiologyEpidemiology 85% of new cases are advanced85% of new cases are advanced Locally advanced: blood vessels Locally advanced: blood vessels (Stage III)(Stage III) Distant spread to liver, lungs Distant spread to liver, lungs (Stage IV)(Stage IV) Late Presentation - Poor SurvivalLate Presentation - Poor Survival Howlander et al, SEER Cancer Statistics Review 2012. American Cancer Society, Cancer Facts 146(7):836-843. Donahue TR, Reber HA et al When/Whether to Operate?When/Whether to Operate? CT ImagingCT Imaging PVPV SMASMA SVSV SMVSMV IMVIMV LRVLRV LGALGA SASA HAHA PancreasPancreas AdrenalAdrenal Downstaging Downstaging of PaCaof PaCa SurvivalSurvival 25+ 25+ survivors 5-17 yearssurvivors 5-17 years Observed five-year survival rate: 28%Observed five-year survival rate: 28% 13 13 more close to 5 yrs with no more close to 5 yrs with no recurrence recurrence Possible Possible five year survival rate: 53%five year survival rate: 53% Adjuvant TherapyAdjuvant Therapy Treatment given Treatment given afterafter surgery surgery (Whipple/distal)(Whipple/distal) Effort to eradicate any Effort to eradicate any remaining microscopic tumorremaining microscopic tumor Standard approachStandard approach Neoadjuvant TherapyNeoadjuvant Therapy Treatment 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 first Advantages and disadvantages Advantages and disadvantages Theoretical AdvantagesTheoretical Advantages Almost all pts have Almost all pts have micrometastatic disease at micrometastatic disease at diagnosis diagnosis 1 cm - 28% have metastases1 cm - 28% have metastases 2 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 2011 Cell Theoretical AdvantagesTheoretical Advantages If given after surgery, up to 25% If given after surgery, up to 25% may not be treated at allmay 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 complications Effect of Adjuvant Treatment Delay on SurvivalEffect of Adjuvant Treatment Delay on Survival Iacobuzio-Donahue et al 2011 Cell Avoid Treatment Delay After SurgeryAvoid Treatment Delay After Surgery 70% 40% Theoretical Advantages of Theoretical Advantages of Neoadjuvant TherapyNeoadjuvant Therapy Identify pts unlikely to benefit Identify pts unlikely to benefit from surgeryfrom surgery During 2-3 mo treatment, up to During 2-3 mo treatment, up to 20% pts show metastases or develop poor performance status Is This an Advantage?Is This an Advantage? Is this good or bad? Good They are spared surgery that would not have helped or Bad They missed their chance for resection and possible cure Neoadjuvant Therapy Neoadjuvant 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 given Chemotherapy today has little Chemotherapy today has little effect in most ptseffect in most pts Neoadjuvant Therapy Neoadjuvant Therapy At most, 1/3 of pts respond to At most, 1/3 of pts respond to neoadjuvant treatmentneoadjuvant 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 timeduring that time Disease could progressDisease could progress Neoadjuvant Therapy Neoadjuvant Therapy Although today Chemotherapy has Although today Chemotherapy has little effect in most ptslittle effect in most pts This could change with more effective This could change with more effective neoadjuvant regimens neoadjuvant regimens Or 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 tumor Neoadjuvant RadioTherapy Neoadjuvant RadioTherapy Radiation Therapy (RTx) of unclear Radiation Therapy (RTx) of unclear value in most ptsvalue in most pts RTx definitely decreases RTx definitely decreases locallocal recurrencerecurrence of cancerof cancer But it does But it does notnot increase survival in most increase survival in most Most 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 low So neoadjuvant RTx also is not So neoadjuvant RTx also is not done by most USA surgeonsdone by most USA surgeons Surgery in USA -2014Surgery in USA -2014 Further major Further major surgical advances surgical advances unlikelyunlikely Mortality rate 1Mortality rate 1%; morbidity still high%; morbidity still high Improved Improved outcomes likely to come from outcomes likely to come from more effective more effective drugs drugs in com