Radiation Oncology for Liver Tumors

The SCCA Proton Therapy Center, located at UW Medicine's Northwest Hospital & Medical Center.

Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells. Radiation therapy uses machines to externally deliver beams of radiation into the body and toward the tumor. Radiation therapy is designed to accurately target tumors and to avoid the surrounding normal, healthy tissue as much as possible. All forms of radiation treatments are non-invasive, painless, and given in an outpatient setting, typically five days a week (Monday through Friday), with each treatment lasting only a few minutes.

Two state-of-the-art forms of radiation therapy are available to patients at UW Medicine/SCCA: stereotactic body radiation therapy and proton beam therapy. If radiation therapy is considered a treatment option for your cancer, your radiation oncologist will determine the form of radiation that is most appropriate for you.

Stereotactic Body Radiation Therapy (SBRT)

SBRT is designed to non-invasively deliver very high (ablative) doses of radiation accurately over a short period of time with minimal side effects. SBRT uses advanced computer and imaging technology to focus many beams of photon radiation to deliver high doses of radiation with millimeter accuracy in order to ablate or kill tumors. As opposed to conventional radiation therapy that is delivered over several weeks, SBRT is delivered over 3 to 5 treatments over the course of 1 or 1½ weeks.

Proton Beam Therapy

Proton therapy is a special type of radiation, called heavy-charged particle radiation, that delivers less radiation to healthy tissues and organ around tumors. For liver cancers, proton therapy may allow safe delivery of high doses of radiation to tumors while better sparing surrounding normal liver tissue, stomach, bowel, kidneys and the heart. This may increase the chances of controlling tumors while reducing the side effects and complications often associated with radiation therapy. The SCCA Proton Therapy Center​ on UW Medicine’s Northwest Hospital & Medical Center campus, the only proton therapy center in the Pacific Northwest, now offers proton therapy as a treatment option for liver cancer patients.

Meet our Team

Radiation Oncology

Smith Apisarnthanarax, M.D.
The SCCA Proton Therapy Center, located at UW Medicine's Northwest Hospital & Medical Center. Dr. Smith Apisarnthanarax, radiation oncologist, in lab coat.

At low doses, radiation is used to image the internal anatomy of patients, such as in X-ray films or CT scans. When radiation is used therapeutically to treat cancer, higher doses at higher energies are used to damage and kill cancer cells. In general, therapeutic doses of radiation generate reactive oxygen species (free radicals) by ionization of water that damage the DNA of cancerous cells. When these cells attempt to divide and proliferate, they accumulate DNA defects over time that ultimately result in their death, which partly explains why it often takes weeks to months to detect significant treatment responses in tumors.

Radiation therapy is a form of cancer treatment that involves many team members to accurately and safely deliver therapeutic doses of radiation to patients. The radiation oncologist (physician) determines the need and indication for radiation therapy, prescribes the dose of radiation needed, and defines the area where the radiation should be delivered (tumor) or avoided (surrounding normal tissues). Dosimetrists are specially trained to generate and optimize the treatment planning of the radiation with the aid of sophisticated computer software and in conjunction with medical physicists. Radiation therapists are technologists who are specially trained to execute the actual delivery of the radiation under the directives of the physician and radiation treatment plans. Registered nurses and/or nurse practitioners and physician assistants may also be involved in caring for patients during and after treatment.

After patients are evaluated by the physician, patients undergo a planning procedure called a CT simulation where images are taken of the treatment area of interest. These images are transferred to a treatment planning software where the radiation treatment plan is generated to map out where the radiation is delivered for each individual patient (a "blueprint" of the radiation is designed). Depending on the complexity of the treatment plan, it may take anywhere from 1 - 2 weeks for the radiation treatment plan to be created and tested for quality assurance before treatments begin.

At the University of Washington Medical Center (UWMC)/Seattle Cancer Care Alliance (SCCA), we offer two general forms of radiation: photon (stereotactic body radiation therapy or SBRT) and proton radiation therapy. The form of radiation patients receive will be determined by the radiation oncologist and is dependent on many factors, including but not limited to: tumor location, tumor size, baseline liver function, and history of prior liver-directed therapies.

At the University of Washington Medical Center (UWMC)/Seattle Cancer Care Alliance (SCCA), we offer two state-of-the-art forms of radiation therapy: stereotactic body radiation therapy and proton beam therapy.

Stereotactic Body Radiation Therapy (SBRT)

Historically, radiation therapy has been delivered over a few to several weeks where a small amount of radiation is given with each treatment (conventional fractionation). With highly conformal radiation delivery and modern imaging, stereotactic body radiation therapy (SBRT) becomes a potential treatment option for appropriate patients where ablative or near-ablative doses of radiation are delivered to the tumor over a short period of time, typically in 3 - 5 treatments over 1 to 1½​ weeks.

SBRT has been used to treat primary liver cancers (hepatocellular carcinoma) and secondary liver cancers (tumors that have metastasized to the liver) for over a decade.1-8 Liver SBRT is generally well tolerated with preserved quality of life4 and results in excellent tumor local control of greater than 80 - 90% at 1 to 2 years.2,5-8 An example of a liver SBRT treatment is shown below:

liver-SBRT-uw-medicine.jpg
Liver SBRT given to a patient with hepatocellular carcinoma over 5 treatments. The color wash represents radiation dose being delivered to the liver. The cooler hues (blues) represent the lower doses of radiation and the hotter hues (yellow, red) show the higher doses of radiation. This illustrates the ability of SBRT to deliver high doses of radiation to the tumor while significantly sparing the liver from radiation.


Proton Radiation Therapy

The normal liver tissues are considered sensitive to the effects of radiation therapy. Therefore, in some cases, a special kind of radiation called proton beam therapy (PBT) may be useful and appropriate. PBT uses heavy charged particles (protons) to deliver high doses of radiation to liver tumors. As opposed to photons where there is also some degree of exit dose through the body, protons can be designed to stop at a certain depth within the body (called the Bragg peak), at which point zero radiation dose is delivered (no exit dose). This results in the potential advantage to spare more normal tissues that surround the tumor, most notably the normal liver around the tumor, and allows for higher doses of radiation to be delivered safely to the tumor.

PBT has been used to treat liver cancers for over two decades, primarily in Asia, and has been demonstrated to be safe and effective.9,10 It is increasingly being utilized in the United States with similar outcomes and tumor local control over 90% at 2 years.11-13 At the SCCA Proton Therapy Center, the only proton center in the Pacific Northwest region, PBT is now an available treatment option for patients with liver cancer. Although which patients should receive PBT is still being understood, the following types of patients may benefit the most from PBT:

  • Patients with tumors that are large and peripherally or centrally located within the liver.14
  • Patients with severely decompensated liver function.
  • Patients with tumors and livers that have previously received external beam radiation or internal radiation (radioembolization).

An example of a liver PBT treatment is shown below:

liver-protein-beam-therapy-uw-medicine.jpg
Liver PBT given to a patient with bulky hepatocellular carcinoma over 15 treatments. The color wash represents radiation dose being delivered to the liver. The cooler hues (blues) represent the lower doses of radiation and the hotter hues (yellow, red) show the higher doses of radiation. Due to the large size of the liver tumor, a photon-based radiation plan would not have been feasible or safe to deliver.

References

  1. Bujold A, Massey CA, Kim JJ, et al: Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma.​ J Clin Oncol 31:1631-9, 2013
  2. Chang DT, Swaminath A, Kozak M, et al: Stereotactic body radiotherapy for colorectal liver metastases: a pooled analysis. ​Cancer 117:4060-9, 2011
  3. Klein J, Dawson LA: Hepatocellular carcinoma radiation therapy: review of evidence and future opportunities.​ Int J Radiat Oncol Biol Phys 87:22-32, 2013
  4. Klein J, Dawson LA, Jiang H, et al: Prospective Longitudinal Assessment of Quality of Life for Liver Cancer Patients Treated With Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 93:16-25, 2015
  5. Lee MT, Kim JJ, Dinniwell R, et al: Phase I study of individualized stereotactic body radiotherapy of liver metastases. J Clin Oncol 27:1585-91, 2009
  6. Rusthoven KE, Kavanagh BD, Cardenes H, et al: Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 27:1572-8, 2009
  7. Sanuki N, Takeda A, Oku Y, et al: Stereotactic body radiotherapy for small hepatocellular carcinoma: a retrospective outcome analysis in 185 patients. ​Acta Oncol 53:399-404, 2014
  8. Wahl DR, Stenmark MH, Tao Y, et al: Outcomes After Stereotactic Body Radiotherapy or Radiofrequency Ablation for Hepatocellular Carcinoma.​ J Clin Oncol 34:452-9, 2016
  9. Matsuzaki Y, Osuga T, Chiba T, et al: New, effective treatment using proton irradiation for unresectable hepatocellular carcinoma. Intern Med 34:302-4, 1995
  10. Mizumoto M, Okumura T, Hashimoto T, et al: Proton beam therapy for hepatocellular carcinoma: a comparison of three treatment protocols.​ Int J Radiat Oncol Biol Phys 81:1039-45, 2011
  11. Bush DA, Kayali Z, Grove R, et al: The safety and efficacy of high-dose proton beam radiotherapy for hepatocellular carcinoma: a phase 2 prospective trial. Cancer 117:3053-9, 2011
  12. Bush DA, Smith JC, Slater JD, et al: Randomized Clinical Trial Comparing Proton Beam Radiation Therapy with Transarterial Chemoembolization for Hepatocellular Carcinoma: Results of an Interim Analysis.​ Int J Radiat Oncol Biol Phys 95:477-82, 2016
  13. Hong TS, Wo JY, Yeap BY, et al: Multi-Institutional Phase II Study of High-Dose Hypofractionated Proton Beam Therapy in Patients With Localized, Unresectable Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. ​J Clin Oncol 34:460-8, 2016
  14. Gandhi SJ, Liang X, Ding X, et al: Clinical decision tool for optimal delivery of liver stereotactic body radiation therapy: Photons versus protons. Pract Radiat Oncol 5:209-18, 2015

Despite careful radiation treatment planning and sophisticated radiation techniques (stereotactic body radiation therapy, proton beam therapy), risk of liver injury from radiation therapy still exists. Researchers within the departments of Radiation Oncology and Radiology are focused on decreasing this risk while not compromising tumor control through personalized radiation therapy approaches. Modern radiation therapy has traditionally focused on precise targeting of the tumor and delivering higher doses of radiation to the tumor. Our team is focused on taking modern radiation therapy a step further by not only delivering higher doses to liver tumors, but also decreasing radiation away from the healthy liver tissue to increase the safety of radiation therapy to the liver.

Functional Liver Avoidance Radiation Therapy

The concept of diverting radiation away from the healthiest regions of the liver requires the ability to image functional and non-functional liver tissue. Our team of researchers is actively investigating the use of [99mTc] sulfur colloid SPECT/CT scans to image livers in liver cancer patients to better understand how to select which patients are the most appropriate for radiation treatments as well as to create radiation treatment plans that are able to avoid functional liver tissue while still delivering high doses to the tumor.

total-liver-function-uw-medicine.jpg

Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients.1 We have shown that there may be distinct normal liver phenotypes in patients with cirrhosis with differing degrees of global and spatial liver function (shown above). In addition, we have developed an imaging metric​​​--total liver function--that assesses the degree and volume of functioning liver that appears to be highly predictive of clinical outcomes.

Differential-hepatic-avoidance-radiation-therapy.jpg

Differential hepatic avoidance radiation therapy: proof of concept in hepatocellular carcinoma patients.2 We have demonstrated the feasibility of altering the way radiation therapy is delivered by leveraging information gained from sulfur colloid SPECT/CT scans. By imaging the portions of the liver that are the most highly functional, we are able to differentially divert radiation dose away from healthy liver tissue (see above). We hypothesize that doing so will lead to improved clinical outcomes in liver cancer patients with cirrhosis by decreasing the risk of treatment-related liver injury while maintaining high rates of tumor control.

At UW Medicine, we have a prospective clinical trial open for enrollment that is designed to further understand the utility of these functional liver imaging scans in the treatment of liver cancers.

References

  1. Bowen SR, Chapman TR, Borgman J, et al: Measuring total liver function on sulfur colloid SPECT/CT for improved risk stratification and outcome prediction of hepatocellular carcinoma patients. EJNMMI Res 6:57, 2016
  2. Bowen SR, Saini J, Chapman TR, et al: Differential hepatic avoidance radiation therapy: Proof of concept in hepatocellular carcinoma patients. Radiother Oncol 115:203-10, 2015​