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 Christopher H. Crane, M.D. Program Director, GI Section Department of Radiation Oncology

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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

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

Page 1: The Role of Radiation therapy for Intra- and Extrahepatic Biliary Cancers

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!