the role of radiation therapy for intra- and extrahepatic biliary cancers
DESCRIPTION
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 PresentationTRANSCRIPT
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The Role of Radiation therapy for Intra- and Extrahepatic Biliary
Cancers
Christopher H. Crane, M.D.Program Director, GI Section
Department of Radiation Oncology
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Outline
• Liver XRT in the stereotactic era• Organ motion management• Image guidance (IGRT): CT, CBCT• Neoadjuvant surgery• Functional imaging TC-99 Spect
• High dose XRT results– Intrahepatic Cholangiocarcinoma
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Outline – con’t
• Extrahepatic biliary cancer AHBPA consensus guidelines – (pending)– Adjuvant– Locally advanced unresectable
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IntrahepaticGallbladder
Extrahepatic - Hilar
Extrahepatic - Periampullary
Intrahepatic Cholangiocarcinoma: High Dose Stereotactic Radiation approaches
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Challenges of High Dose Liver XRT
• Tumor delineation • Sparing (often diseased) liver• Proximity of duodenum, stomach colon• Organ motion
– Respiratory motion– Day to day differences
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Mechanisms of hepatic failure – liver tumors
• HV / IVC occlusion - hepatic congestion – liver ischemia – liver failure
• PV occlusion – liver ischemia • Obstruction of the main bile ducts
– Biliary sepsis
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Budd–Chiari syndrome = tumor related mortality
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RPM System Tracks Breathing Motion during CT
marker block with IR-reflecting dots
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Targeting the tumor:4D-CT Treatment Simulation
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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
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Daily CT vs Simulation CT with IVC
Daily CT Simulation
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CBCT vs Sim CT
Sim CTCBCT
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Unresectable 14 cm IHC -Before XRT
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Stereotactic IMRT treatment
100Gy/25x
75Gy/25fxStomachMax 55Gy
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3 months post therapy
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IHCA near stomach: 67.5Gy/15fx - IMRT
Stomach/Tumor interface
NPONPO
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Neoadjuvant Surgery
Laparoscopic/open Alloderm Placement
Yoon, et al, PRO, 9/2013
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Sometimes the bowel is too closeColon, duodenum, stomach are dose limiting
duodenum
0 cm
tumor
Courtesy Tom Aloia
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AlloDerm® Envelope
Courtesy Tom Aloia
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Open AlloDerm® Spacer Placement
Courtesy Tom Aloia
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duodenum
colon
3 cm
Envelope
Envelope
tumor
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Unresectable Intrahepatic Cholangio near Stomach
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100Gy/25x
75Gy/25fx
IMRT after Alloderm Placement
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100Gy/25x
75Gy/25fx
IMRT after Alloderm Placement
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100Gy/25x
75Gy/25fx
IMRT after Alloderm Placement
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6 wk follow-up scan
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Pre vs post XRT scan
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99mTc-sulfur colloid SPECT functional treatment planning in patients with
hepatoma
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IMRT vs Protons
• IMRT- better bowel sparing– sharper edge (penumbra)
• Protons + Charged particles– better liver sparing– don’t exit, but high dose volume larger
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Limitations of IMRT / Liver Primaries
“Exit dose”=Must be less than 20-30Gy
Inadequate Doses for Tumor Cure
(in Larger Tumors)
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25Gy /15fx
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MDACC/ MGH Phase II Study Primary Hepatic Tumors2009-0556
• P-01 supported trial in collaboration with MGH• <12 cm hepatic primary tumors
– 58 CGE / 15 fractions for central tumors– 67.5 CGE / 15 fractions for tumors >2cm from the
hilum• N=54 accrued, 35 IHCCa • 1 in-field progression• No significant toxicity
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MGH/MDACC Phase IIPreliminary data
• 35 patients w IHCCa accrued from 4/2010 to present
• 15 fractions– Peripheral - 67.5 GyE– (Central (within 2 cm porta hepatis) – 58 GyE
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MGH/MDACC Tolerability
• No Gr.3/4 events• No RILD• No Radiation-induced biliary strictures
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Results
• OS is 58% at 2 years. 1-yr 2-yr
• OS 69% 58%• PFS 41% 28%
1 local tumor progression – LC >90%
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80y/0 with HCC – Proton 67.5CGE/15fx
1/3/13 5/14/13 , 11/20/13
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PHASE II CHOLANGIOMAS
Overall Survival from Protons Start (months)
0 12 24 36 48
0%
20%
40%
60%
80%
100%
Unpublished, 6/2013
MDACC Conventional
doses*
*Crane IRJOBP, 2002
MS- NR >30mo2 yr OS- 58%MS- 11mo2 yr OS- 9%
MGH/MDACC: Preliminary data
High dose Proton
Therapy
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Unresectable Cholangioca-liver confined
-no cirrhosis or CPC A
-up to 2 satellite lesions
-12 cm or less
Stratify:- Largest tumor > 6
cm- -satellite y/n
Gem/Cis x 4
Liver Directed Radiation Therapy
Followed by maintenance Gem/Cis x 4
Gem/Cis x 4
Re-staging AND Randomization
after cycle 3Radiation
Planning during cycle 4
RTOG 1320 – Phase III Trial
Hong, PI, Activation 2014
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SummaryAblative Radiation Therapy for IHC
• Tumor control is dose related• Proton therapy = higher doses in selected cases
– Extremely well tolerated• LC 90-100%• Inoperable patients: Curative treatment option?
– 2yOS > 50%– 5yOS- need more FU– Possibly comparable to surgery
• Limitations – Proximity to bowel– Metastatic disease control
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Intrahepatic
Gallbladder
Extrahepatic - Hilar Extrahepatic - Periampullary
Biliary Tract Tumors
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Jarnagin, et al 98, (8) 21 AUG 2003
MSKCC Results – Initial site of recurrenceHilar Cholangiocarcinoma- 60% of rec LRR
76 pts with HCA• 24% R+ resections• 25% LN+• 10% Adjuvant therapy
– CTX- 6 pts– CXRT- 2pts
• Recurrence– 41% local– 24% regional – 36% distant– 13% DM + LRR
• 60% of rec LRR
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Unresectable Hilar cholangiocarcinomasNon-operative treatment
• Neoadjuvant CXRT / Transplant• Chemoradiation +/- brachytherapy
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History of EHBT - Transplantation
• Early results (1990’s) of hepatic transplant poor• Considered a contraindication
• 5-yr OS *17% , **23%• 47% local / remnant tumor recurrence
• Mayo– neoadjuvant CXRT , transplant protocol
* Penn, Surgery 1991**Meyer, Transplantation, 2000
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Gastroenterology Volume 143, Issue 1 2012 88 - 98.e3
Efficacy of Neoadjuvant Chemoradiation, Followed by Liver Transplantation, for Perihilar Cholangiocarcinoma at 12 US Centers
5 yr OS from presentation
53%
5 yr OS from transplant
65%
25% dropout
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Results of palliative EBRT + brachytherapy:Long term OS is possible
Ghafoori, et al, IJROBP 2011
MS 10-14.6mo
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Resected Hilar cholangiocarcinomasAdjuvant treatment
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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 + CXRT• Irradiated pts: more hepatic or HA invasion
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Nakeeb: Ann Surg, Volume 224(4).October 1996.463-475
Adjuvant Radiation TreatmentEHBT
“Post-operative radiation therapy did not provide a benefit…”
Overall SurvivalCXRT vs Surg alone
Ove
rall
Sur
viva
l
P = NS
Months
CXRT
Surgery alone
543210
1.0
.8
.5
.3
0.0
95% CI42 mo ( 26 - 59)
38 mo (29 - 48)
JHU MDACC
“CXRT of particular benefit in high-risk patients”
Borghero Y, Crane et al Ann Surg Onc 2008
*Irradiated pts: more hepatic or HA invasion
*Irradiated pts: all R+ or N+
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Improved survival in resected biliary malignanciesNakeeb , et al Surgery Volume 132, Issue 4 2002 555 - 564
MCW results: Improved OS with CXRTResected EHBT (n=90) (2002)
• 48% received (C)XRT• MVA:
– CXRT improved OS– HR 3.1 p<0.08
• More recent era outcomes improved with multimodality therapy p<0.05
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R0: MS 18.4 vs 20mo, p=NSTodoroki et al. IJROBP 46(3);581-587: 2000
Adjuvant CXRT - Improved Survival (2000)R+ tumors
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Thank You!