The Role of Radiation therapy for Intra- and Extrahepatic Biliary Cancers

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The Role of Radiation therapy for Intra- and Extrahepatic Biliary Cancers. C h ristopher H. Crane , M.D. Program Director, GI Section Department of Radiation Oncology . Outline. Liver XRT in the stereotactic era Organ motion management Image guidance (IGRT): CT, CBCT - PowerPoint PPT Presentation

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The Role of Radiation therapy for Intra- and Extrahepatic Biliary CancersChristopher H. Crane, M.D.Program Director, GI Section Department of Radiation Oncology

1Outline Liver XRT in the stereotactic eraOrgan motion managementImage guidance (IGRT): CT, CBCTNeoadjuvant surgeryFunctional imaging TC-99 SpectHigh dose XRT resultsIntrahepatic Cholangiocarcinoma2Outline contExtrahepatic biliary cancer AHBPA consensus guidelines (pending)AdjuvantLocally advanced unresectable3Intrahepatic

Gallbladder

Extrahepatic - Hilar

Extrahepatic - PeriampullaryIntrahepatic Cholangiocarcinoma: High Dose Stereotactic Radiation approaches

4Challenges of High Dose Liver XRTTumor delineation Sparing (often diseased) liverProximity of duodenum, stomach colonOrgan motion Respiratory motionDay to day differences

5Mechanisms of hepatic failure liver tumorsHV / IVC occlusion - hepatic congestion liver ischemia liver failurePV occlusion liver ischemia Obstruction of the main bile ductsBiliary sepsis6

BuddChiari syndrome = tumor related mortality7RPM System Tracks Breathing Motion during CT

marker block with IR-reflecting dotsTargeting the tumor:4D-CT Treatment Simulation

Feedback Guided Gated Breath-hold (FGBH)

Patient to voluntarily holds their breath within the gate (visual feedback helps this process)Turn the beam on when the patient is holding their breath in the gate.CBCT or CT-on-rails can be done during FGBHs

10Daily CT vs Simulation CT with IVC

Daily CT Simulation

11CBCT vs Sim CT

Sim CT

CBCTUnresectable 14 cm IHC -Before XRT

13

Stereotactic IMRT treatment100Gy/25x

75Gy/25fxStomachMax 55Gy14

3 months post therapy15IHCA near stomach: 67.5Gy/15fx - IMRT

Stomach/Tumor interface

NPONPO16Neoadjuvant SurgeryLaparoscopic/open Alloderm PlacementYoon, et al, PRO, 9/201317Sometimes the bowel is too closeColon, duodenum, stomach are dose limiting

duodenum0 cmtumorCourtesy Tom Aloia18AlloDerm Envelope

Courtesy Tom Aloia19Open AlloDerm Spacer Placement

Courtesy Tom Aloia20

duodenumcolon3 cmEnvelopeEnvelopetumor21

Unresectable Intrahepatic Cholangio near Stomach22

100Gy/25x

75Gy/25fxIMRT after Alloderm Placement23

100Gy/25x

75Gy/25fxIMRT after Alloderm Placement24

100Gy/25x

75Gy/25fxIMRT after Alloderm Placement25

6 wk follow-up scan26

Pre vs post XRT scan27

99mTc-sulfur colloid SPECT functional treatment planning in patients with hepatoma 28IMRT vs Protons IMRT- better bowel sparingsharper edge (penumbra) Protons + Charged particles better liver sparingdont exit, but high dose volume larger

29Limitations of IMRT / Liver Primaries

Exit dose=Must be less than 20-30Gy

Inadequate Doses for Tumor Cure

(in Larger Tumors)

25Gy /15fx31

MDACC/ MGH Phase II Study Primary Hepatic Tumors2009-0556P-01 supported trial in collaboration with MGH2cm from the hilumN=54 accrued, 35 IHCCa 1 in-field progressionNo significant toxicity

32MGH/MDACC Phase IIPreliminary data35 patients w IHCCa accrued from 4/2010 to present15 fractionsPeripheral - 67.5 GyE(Central (within 2 cm porta hepatis) 58 GyE 33MGH/MDACC TolerabilityNo Gr.3/4 eventsNo RILDNo Radiation-induced biliary strictures34ResultsOS is 58% at 2 years. 1-yr 2-yrOS 69% 58%PFS 41% 28%

1 local tumor progression LC >90%3580y/0 with HCC Proton 67.5CGE/15fx

1/3/13 5/14/13 , 11/20/13

36

Unpublished, 6/2013MDACC Conventional doses**Crane IRJOBP, 2002MS- NR >30mo2 yr OS- 58%MS- 11mo2 yr OS- 9%MGH/MDACC:Preliminary dataHigh dose Proton Therapy37Unresectable Cholangioca-liver confined-no cirrhosis or CPC A-up to 2 satellite lesions-12 cm or lessStratify:Largest tumor > 6 cm-satellite y/nGem/Cis x 4Liver Directed Radiation TherapyFollowed by maintenance Gem/Cis x 4Gem/Cis x 4Re-staging AND Randomizationafter cycle 3Radiation Planning during cycle 4RTOG 1320 Phase III TrialHong, PI, Activation 201438SummaryAblative Radiation Therapy for IHCTumor control is dose relatedProton therapy = higher doses in selected casesExtremely well toleratedLC 90-100%Inoperable patients: Curative treatment option?2yOS > 50%5yOS- need more FUPossibly comparable to surgeryLimitations Proximity to bowelMetastatic disease control

39Intrahepatic

Gallbladder

Extrahepatic - Hilar

Extrahepatic - PeriampullaryBiliary Tract Tumors

40

Jarnagin, et al 98, (8) 21 AUG 2003MSKCC Results Initial site of recurrenceHilar Cholangiocarcinoma- 60% of rec LRR

76 pts with HCA24% R+ resections25% LN+10% Adjuvant therapyCTX- 6 ptsCXRT- 2ptsRecurrence41% local24% regional 36% distant13% DM + LRR60% of rec LRR

41Unresectable Hilar cholangiocarcinomasNon-operative treatmentNeoadjuvant CXRT / TransplantChemoradiation +/- brachytherapy

42History of EHBT - TransplantationEarly results (1990s) of hepatic transplant poorConsidered a contraindication5-yr OS *17% , **23%47% local / remnant tumor recurrenceMayo neoadjuvant CXRT , transplant protocol

* Penn, Surgery 1991**Meyer, Transplantation, 200043

Gastroenterology Volume 143, Issue 1 2012 88 - 98.e3Efficacy of Neoadjuvant Chemoradiation, Followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers

5 yr OS from presentation53%5 yr OS from transplant65%25% dropout44Results of palliative EBRT + brachytherapy:Long term OS is possible

Ghafoori, et al, IJROBP 2011MS 10-14.6mo45Resected Hilar cholangiocarcinomasAdjuvant treatment46

Nakeeb: Ann Surg, Volume 224(4).October 1996.463-475

Adjuvant Radiation TreatmentEHBT JHU (1996)Post-operative radiation therapy did not provide a benefit *only 16 patients curatively resected + CXRTIrradiated pts: more hepatic or HA invasion47

Nakeeb: Ann Surg, Volume 224(4).October 1996.463-475

Adjuvant Radiation TreatmentEHBTPost-operative radiation therapy did not provide a benefit

JHUMDACCCXRT of particular benefit in high-risk patientsBorghero Y, Crane et al Ann Surg Onc 2008*Irradiated pts: more hepatic or HA invasion*Irradiated pts: all R+ or N+48

Improved survival in resected biliary malignanciesNakeeb , et al Surgery Volume 132, Issue 4 2002 555 - 564MCW results: Improved OS with CXRTResected EHBT (n=90) (2002)48% received (C)XRTMVA:CXRT improved OSHR 3.1 p