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Radiation Therapy for Liver Malignancies

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. Overview. Liver malignancies Background Rationale for local therapy

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Radiation Therapy for Liver Malignancies

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  1. 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

  2. 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)

  3. Local Radiation for Cancer in the Liver

  4. 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+

  5. 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

  6. Local Treatment Options for Malignant Liver Disease Surgical resection Radiofrequency ablation (RFA) Fractionated Radiation: 3D conformal Stereotactic body radiation therapy (SBRT)

  7. 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

  8. 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

  9. 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

  10. 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

  11. Liver SBRT

  12. Techniques of Radiation Planning

  13. 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

  14. 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

  15. 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

  16. Cone Beam CT Alignment

  17. Radiation Toxicity to the Liver

  18. Hepatic Radiation Toxicity • Commonly called radiation “hepatitis” but more accurate term is “radiation–induced 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

  19. Potential Side Effects of Treatment Acute Fatigue Nausea Abdominal Pain Late RILD (0.9%) Small bowel damage/ obstruction (<1%) Secondary Malignancy (<0.5%)

  20. 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: > 700cc or 35% should be kept below: 3 fractions: 15 Gy (5 Gy/fx) 5 fractions: 20 Gy (4 Gy/fx)

  21. Liver Metastases

  22. 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

  23. 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

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

  25. 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) 27 27

  26. Radiation Dosing 2 yr local control >54 Gy: 89.3% 36-53.9 Gy: 54% <36 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

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

  28. Primary Liver Cancer Hepatocellular Carcinoma (HCC)

  29. Hepatocellular Carcinoma (HCC) Since radiation can be effective for metastatic liver lesions, can it be used for primary hepatocellular carcinoma?

  30. 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

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

  32. 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)

  33. 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

  34. SBRT Control Rates for HCC 65-100% 1yr LC 48-93% 1yr OS Feng, M et al. Seminars of Radiation Oncology 2011

  35. 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

  36. 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)

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