Radiation Therapy for Liver Malignancies

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Radiation Therapy for Liver Malignancies

• June Chan, MD
• Assistant Professor, Radiation Oncology
• University of Michigan/Providence Cancer Center
• Advances in Hepatobiliary and Pancreatic Diseases
• November 2, 2013

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Overview

• Liver malignancies
• Background
• Rationale for local therapy
• Radiation Techniques
• 3D Conformal
• Stereotactic Body Radiation Therapy (SBRT)
• Local Radiation Therapy for
• Liver Metastases
• Hepatocellular Carcinoma (HCC)

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Local Radiation for Cancer in the Liver
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Limitations of RT for Liver Cancer

• Most cancers involving liver relate to metastatic
  disease (GI, breast, lung)
• Role for local RT for systemic disease?
• Low tolerance of liver to radiation
• Whole liver 30-33 Gy
• Tumor control 60 Gy

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Rationale for Local Therapies with Metastatic
Liver Disease

• Better systemic therapies have improved long term
  survival
• Improved imaging and targeting allow for dose
  escalation
• Oligometastases may behave differently than
  diffuse metastases

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Local Treatment Options for Malignant Liver
Disease

• Surgical resection
• Radiofrequency ablation (RFA)
• Fractionated Radiation
• 3D conformal
• Stereotactic body radiation therapy (SBRT)

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Fractionated Radiation

• Small doses (1.8-3 Gy) of radiation given daily
  Monday through Friday, over 2-8 weeks
• Cancer cells are deficient in repair of DNA
  damage, while normal tissues can repair the daily
  damages caused by radiation treatment

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Fractionated Therapy for Liver

• Radiation doses that the liver can safely receive
  is related to the volume of liver being treated
• Whole liver can receive 30 Gy
• 2/3 can receive 50 Gy
• 1/3 can receive 70 Gy
• Higher doses are associated with higher
  probability of local control

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3D Conformal Radiation

• Treatment based on 3D anatomic information (with
  CT, MRI and PET)
• Improved target definition with 3D reconstruction
  of targets/organs
• Non-parallel beams result in more conformal
  radiation fields

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Stereotactic Body Radiation Therapy (SBRT)

• Very accurately localized, high-dose (10-20 Gy
  per fraction) radiotherapy to target discrete
  tumor masses in the body (extracranial locations)
• Ablates tissue in high dose region
• Typically given in a hypofractionated regimen
  (1-5 treatments), two fractions per week
• Reduced dose to surrounding normal structures
• Dose escalation to tumor

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Liver SBRT
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Techniques of Radiation Planning
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Stereotactic Radiation Requirements

• Accurate imaging to define the target in 3D
• CT
• MRI
• PET
• Reducing motion effects from breathing
• Abdominal compression
• Breath hold techniques
• Tracking or gating
• Localization during treatment
• Fiducial markers
• Cone beam CT (CBCT) imaging

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SBRT Target Delineation

• Treatment planning CT scan is fused with
  diagnostic study (PET/CT, MRI, CT)
• Target is expanded to ensure adequate coverage
  accounting for day to day variability
• 5mm axial, 8mm cranio-caudal

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CT simulation

• Methods of diaphragmatic motion control
• ABC breath hold (if tolerated) scan on
  expiration
• Abdominal compression
• If not tolerated, 4D CT to create integrated
  target volume

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Fiducials for targeting lesions
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Cone Beam CT Alignment
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Radiation Toxicity to the Liver
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Hepatic Radiation Toxicity

• Commonly called radiation hepatitis but more
  accurate term is radiationinduced liver disease
  (RILD)
• Histopathologically similar to veno-occlusive
  disease
• Symptoms include painful hepatomegaly, anicteric
  ascites
• Time frame is usually 3 weeks to 3 months after
  completing course of RT

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Potential Side Effects of Treatment

• Late
• RILD (0.9)
• Small bowel damage/ obstruction (lt1)
• Secondary Malignancy (lt0.5)

• Acute
• Fatigue
• Nausea
• Abdominal Pain

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Normal Liver Constraints

• Average volume of the liver is 2000cc
• Surgical data shows that up to 75-80 of liver
  can be safely resected
• Whole liver tolerance RTOG/UM 30/33Gy
• Fractionated RT
• Whole liver can receive 30 Gy
• 2/3 can receive 50 Gy
• 1/3 can receive 70 Gy
• SBRT
• gt 700cc or 35 should be kept below
• 3 fractions 15 Gy (5 Gy/fx)
• 5 fractions 20 Gy (4 Gy/fx)

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Liver Metastases
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Liver Metastases

• The liver is the most common organ location for
  metastatic involvement
• In the US, metastases are far more common than
  primary liver tumors
• Primary sites
• colorectal, breast, lung, pancreas, gastric,
  renal cell, ovarian, bladder, melanoma

EA 2012
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Surgery for Liver Metastases

• Surgery plays an important role in treatment of
  liver metastases
• Large body of literature demonstrate that
  metastectomies can be done safely with long term
  survival rates
• Cures can be achieved in the setting of
  metastatic disease

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Surgical Resection of Liver Metastases
25-46 (5 yr)
20-28 (10 yr)
45-64 (3 yr)
Timmerman et al., Ca Cancer J Clin, 2009
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Radiation Therapy for Liver Metastases

• If not a candidate for surgical resection,
  different radiation techniques, with different
  goals, can be used
• Whole liver radiation for palliation of liver
  pain
• Standard fractionated XRT
• Stereotactic techniques (SBRT)

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Radiation Dosing

• 2 yr local control
• gt54 Gy 89.3
• 36-53.9 Gy 54
• lt36 Gy 8.1
• McCammon et al. IJROBP 2009
• SBRT dosing
• Two Fractions per week
• 3 fractions x 20 Gy/Fx 60 Gy
• 5 fractions x 10 Gy/Fx 50 Gy

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SBRT for Liver Metastases
57-82 (2 yr)
37-50 (2 yr)
Doses 20-60Gy 1-5 fractions
Timmerman et al., Ca Cancer J Clin, 2009
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Primary Liver Cancer

• Hepatocellular Carcinoma (HCC)

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Hepatocellular Carcinoma (HCC)

• Since radiation can be effective for metastatic
  liver lesions, can it be used for primary
  hepatocellular carcinoma?

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HCC Background

• 5th most common malignancy worldwide
• Relatively uncommon in US, but incidence
  increasing since 1990s
• Primary therapy is resection of liver or
  transplant but only a minority of patients
  present with resectable disease

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Liver Resection for HCC
35-73 (3yrs)
Taefi et al. Cochrane Library 2013
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Radiation Therapy for HCC

• Historically limited due to
• Low tolerance of the liver to high radiation
  doses
• Overall poor underlying liver function (cirrhosis
  and/or hepatitis)

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Fractionated RT for HCC
Doses 30-66Gy 1.5-3 Gy/fx
60-80 (1 yr LC)
35-72 (1 yr OS)
Feng, M et al. Seminars of Radiation Oncology 2011
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SBRT Control Rates for HCC
65-100 1yr LC
48-93 1yr OS

• Feng, M et al. Seminars of Radiation Oncology 2011

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Summary

• Local liver RT (SBRT) achieves excellent local
  control for both metastatic lesions and primary
  hepatocellular carcinoma
• Future prospective trials are needed to assess
  SBRT vs. other local modalities and potentially
  in combination with other modalities

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Emerging Techniques

• Radioembolization for primary or metastatic liver
  disease
• Injection of micron-sized radioisotopes via
  percutaneous transarterial techniques
  (preferential dosing to tumor)
• Example yttrium-90/TheraSphere
• CT guided brachytherapy
• Placement of radioactive seeds into liver
• Can be used for large tumors (10cm)