Session IV: Radiation Therapy to the Liver

Left to right: Yilun Koethe, MD, RPVI, Moderator: Bruno Odisio, MD, and
Jennifer Wo, MD

Session IV featured panelists exploring the role of radiation therapy to the liver for patients with cholangiocarcinoma (CCA). Jennifer Wo, MD, Massachusetts General Hospital and Harvard Medical School, presented “Radiation Therapy for Cholangiocarcinoma: An Evolving Role.” Dr Wo first discussed adjuvant radiation for biliary tract cancers (BTCs). The use of radiation in the adjuvant setting is controversial in CCA because of the lack of high-quality data.¹ Dr Wo summarized select clinical trial data, including the SWOG S0809 study, which was a single-arm phase 2 study of patients with extrahepatic CCA or gallbladder cancer that investigated gemcitabine/capecitabine therapy followed by chemoradiation.² In this study, patients with R0 or R1 disease had a 2-year estimated overall survival (OS) of 65%²; in addition, OS was not significantly different between these 2 groups of patients.² Although not preferred, guidelines list fluoropyrimidine-based chemoradiation as an option following surgery in patients with R0 and R1 disease in extrahepatic CCA, gallbladder cancer, and intrahepatic CCA.¹ Dr Wo also discussed radiation therapy in patients with unresectable intrahepatic CCA. Currently, the standard of care for unresectable intrahepatic CCA is chemotherapy; however, liver stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiotherapy are emerging treatment options.¹ These are sophisticated radiotherapy techniques that use multiple noncoplanar beams or arcs to deliver highly conformal radiotherapy in ablative radiotherapy doses.¹ In a study conducted at MD Anderson Cancer Center, ablative radiotherapy doses led to substantial prolonged survival in patients with inoperable intrahepatic CCA compared with survival reported in patients receiving surgical resection.³ The dose of radiotherapy was a prognostic factor for increased survival, and biologically effective doses (BEDs) >80.5 Gy had higher 3-year OS and 3-year local control rates compared with that seen with BEDs <80.5 Gy.³ In the metastatic setting, a National Cancer Database study evaluated 2201 patients with metastatic intrahepatic CCA.⁴ A total of 2093 patients were treated with chemotherapy alone and 104 patients were treated with liver-directed treatment that consisted of either surgery or radiotherapy.² Baseline characteristics indicated that patients treated with chemotherapy alone were more likely to have larger primary tumors and lung metastasis, and were less likely to have distant lymph node metastasis.⁴ In addition, patients who received chemotherapy plus liver-directed therapy had a better median OS, 16.7 months, versus 8.3 months for those who received chemotherapy alone.⁴

Yilun Koethe, MD, RPVI, Oregon Health & Science University, discussed radioembolization in CCA. Effective curative treatment options are currently lacking for patients with intrahepatic CCA, as <10% of patients survive >5 years regardless of the treatment regimen received.⁵ Surgical resection remains the gold standard of care; however, many patients are not candidates for surgery due to their tumor location, stage of disease at presentation, or co-occurring comorbidities.⁵ New advanced liver-directed therapies, including transarterial radioembolization (TARE), hepatic arterial infusion pumps, and SBRT, can improve survival and downstage to surgical resection, and can be curative in select patients who are poor candidates for surgery.⁵ TARE delivers yttrium-90 (Y90) intraarterially to target the liver mass.⁵ Y90 segmentectomy is often performed for localized disease, <2 segments; whereas Y90 lobectomy is performed in unilobar disease with the goal of disease control and contralateral lobar hypertrophy as a potential bridge to surgery.⁵ As first-line therapy, TARE offers 19 to 24 months’ survival with <10% complication rate as demonstrated in 3 prospective, phase 2, single-arm clinical trials.^6,7 Additional prospective, randomized, controlled trials are needed to compare TARE with other treatment options, but Dr Koethe concluded it may be more effective than systemic therapy alone.⁵ To make TARE safe for patients with intrahepatic CCA, careful patient selection and segmental/lobar strategies should be used if possible.⁵ To be candidates, patients should have an Eastern Cooperative Oncology Group performance status <2, total bilirubin <2, peripheral lesions rather than infiltrative lesions, and locally advanced disease.⁵ The timing of TARE treatment depends on the goals of therapy, and currently there is no standard approach regarding when to use TARE in patients with intrahepatic CCA.⁵ Using TARE as first-line therapy may be more effective than its use in subsequent lines of therapy, as some studies suggest non–first-line use of TARE may result in worse outcomes.⁸ Careful patient selection and the use of newer ablative dosing strategies can improve the efficacy of TARE in patients with CCA.⁵ In general, TARE may be a more effective therapeutic option compared with transarterial chemoembolization (TACE) and ablation because TACE often has higher rates of complication, and ablation is limited to patients with small tumors who are likely good candidates for surgery.⁵

References

1. Wo J. Radiation therapy for cholangiocarcinoma: an evolving role. Presented at: 5th Anniversary Cholangiocarcinoma Summit, October 19-21, 2023; Scottsdale, Arizona.
2. Ben-Josef E, Guthrie KA, El-Khoueiry AB, et al. SWOG S0809: a phase II intergroup trial of adjuvant capecitabine and gemcitabine followed by radiotherapy and concurrent capecitabine in extrahepatic cholangiocarcinoma and gallbladder carcinoma. J Clin Oncol. 2015;33(24):2617-2622.
3. Tao R, Krishnan S, Bhosale PR, et al. Ablative radiotherapy doses lead to a substantial prolongation of survival in patients with inoperable intrahepatic cholangiocarcinoma: a retrospective dose response analysis. J Clin Oncol. 2016;34(3):219-226.
4. Sebastian NT, Tan Y, Miller ED, et al. Association of liver-directed local therapy with overall survival in adults with metastatic intrahepatic cholangiocarcinoma. JAMA Netw Open. 2019;2(9):e1911154.
5. Koethe Y. Radioembolization in cholangiocarcinoma. Presented at: 5th Anniversary Cholangiocarcinoma Summit, October 19-21, 2023; Scottsdale, Arizona.
6. Edeline J, Touchefeu Y, Guiu B, et al. Radioembolization plus chemotherapy for first-line treatment of locally advanced intrahepatic cholangiocarcinoma: a phase 2 clinical trial. JAMA Oncol. 2020;6(1):51-59.
7. Kis B, Shridhar R, Mhaskar R, et al. Radioembolization with yttrium-90 glass microspheres as a first-line treatment for unresectable intrahepatic cholangiocarcinoma—-a prospective feasibility study. J Vasc Interval Radiol. 2023;34(9):1547-1555.
8. Gupta AN, Gordon AC, Gabr A, et al. Yttrium-90 radioembolization of unresectable intrahepatic cholangiocarcinoma: long-term follow-up for a 136-patient cohort. Cardiovasc Intervent Radios. 2022;45(8):1117-1128.