Selective Internal Radiation Therapy and Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma with Portal Vein Tumour Thrombosis
The patient was a 63-year-old male diagnosed with hepatocellular carcinoma (HCC) in April 2013, presenting with two lesions – 7.7 and 3.5 cm in segment 4 and segment 8, respectively. He underwent two rounds of transarterial chemoembolization (TACE) in May and June 2013, with good response. In September 2013, he underwent hepatic wedge resection for both lesions.
What was the patient’s history of present illness?
In January 2015, the patient developed a recurrent tumour in segment 4, with tumour thrombus in the right portal vein and main portal vein. Liver function tests were intact. The patient was asymptomatic, had no other underlying disease and assessed to have ECOG performance status score of 0.
How was the patient managed?
Selective internal radiation therapy (SIRT) was oﬀered to the patient. The work-up angiography demonstrated that the main feeding artery to the tumour thrombus was from the medial branch of right hepatic artery (RHA).
In February 2015, the patient underwent SIRT, with a total dose of 1.99 GBq to the selective branch to the tumour thrombus and proximal right hepatic artery (RHA). Bremsstrahlung scan showed good radioactivity at the tumour and tumour thrombus. No complication was observed.
What was the patient’s clinical course during the treatment?
At 1 month post-SIRT, CT scan demonstrated partial necrosis, and MRI at 3 months post-SIRT showed complete necrosis of the tumour and tumour thrombus in the right portal vein. Alpha-fetoprotein (AFP) level went down from 391 to 50, and liver function tests were normal. However, a residual lesion enhancing tumour thrombus in the main portal vein was detected.
An angiogram identiﬁed a small arterial feeder from the proximal RHA (which was not included in the SIRT) supplying the residual viable tumour in the main portal vein. Upon discussion with the patient, TACE with lipiodol + mitomycin C + 5-fluorouracil were infused into the small feeding artery. Upon consultation with the radiation oncologist, a CT simulation image-guided stereotactic body radiation therapy (SBRT) was completed in July 2015, delivering a total of 54 Gy in 30 fractions. MRI at 2 months post-SBRT showed complete necrosis of tumour thrombus.
In December 2016, the patient developed a new recurrent tumour at segment 8. Liver function tests were normal, and he was assessed to have an ECOG score of 0. A second round of SIRT was performed in February 2017 via the RHA and right inferior phrenic artery, with a dose 1.1 GBq and 0.1 GBq, respectively. No complication was noted. MRI at 1 month and 3 months post-SIRT showed complete necrosis of the tumour. AFP level went down from 1175 to 8.
In November 2017, MRI revealed no evidence of active disease or liver deterioration. In February 2018, however, liver MRI showed new enlarged hepatoduodenal node, suggesting nodal metastasis. A chest CT scan showed an inﬁltrative mass near the lower thoracic oesophagus, suggesting metastasis. He developed dyspnoea, pleural eﬀusion, and ascites. The patient passed away in March 2018.
Achieving complete remission in HCC with main portal vein tumour thrombosis (PVTT) is rare and the prognosis is often poor. And yet, in this patient, two rounds of radioembolization with SIR-Spheres® microspheres combined with TACE and SBRT, extended survival by a total of 37 months. The treatment was well tolerated, without complications.
There is no internationally accepted consensus or guidelines for the treatment of HCC with PVTT, but expert groups, including the Barcelona Clinic Liver Cancer staging system, the European Association for the Study of Liver Disease, the American Association for the Study of Liver Disease, and the Asian Paciﬁc Association for the Study of the Liver recommend chemotherapy with sorafenib for patients with PVTT.1-4 However, in recent years, there have been several reports supporting the use of various modalities, either as a monotherapy or in combination, with promising outcomes that are, unfortunately, diﬃcult to compare owing to the lack of well-designed parallel studies.5,6
SIRT enables the administration of therapeutic doses of radiation directly to the hepatic tumour through the injection of microspheres laden with yttrium-90 into the hepatic artery or its branch. SIRT relies on the principle that tumours >0.5 cm obtain its blood supply through the hepatic artery while normal liver is primarily perfused via the portal vein, thereby delivering intense local radiation to the tumour whilst sparing the rest of the liver. Several peer-reviewed publications have established the benefits of SIRT in HCC, including in patients who were previously resected or have progressed after TACE.
As SIRT does not cause ischaemia, it can be performed in patients with PVTT. A systematic review of 14 clinical studies and three abstracts from conferences including 722 patients has reported promising outcomes (median time to progression, 5.6 months; median disease control rate, 74.3%; median survival time, 9.7 months), suggesting that SIRT may be an eﬀective option for treating HCC with PVTT.7 In this patient, the ﬁrst round of SIRT in 2015, in which we selectively implanted a high dose of SIRT to the tumour thrombus, achieved complete necrosis of the tumour and tumour thrombus in the right portal vein. For the residual viable tumour in the main portal vein, however, the vascular anatomy did not favour a repeat SIRT due to the high risk of reﬂux. Hence, at this point, a combination of TACE and external radiation was administered.
TACE + SBRT
Traditionally, TACE is contraindicated for the treatment of HCC with PVTT due to the potential risk of hepatic insufficiency resulting from ischaemia. Similarly, as the liver is highly radiosensitive, there have been concerns surrounding the hepatotoxicity of external radiotherapy. However, technological advancements in the field of radiotherapy, including image-guided SBRT, has enabled the precise delivery of high-dose radiation to liver tumours, with maximal normal-tissue sparing eﬀect. When performed together, TACE increases the eﬃciency of radiotherapy by enhancing radiosensitivity, and lipiodol uptake after TACE may be used as a tumour-targeting guide to enable a more precise RT.8 A number of studies have demonstrated favourable response and survival rates with radiotherapy after TACE.9-11 In this patient, this combination therapy achieved complete necrosis of the tumour thrombus and 17 months of remission.
Further palliation and prolonging survival with SIRT in patients with recurrent tumours is well described.12 In this patient, repeat SIRT was recommended given the good response obtained previously, and was able to, once again, achieve complete tumour necrosis. The patient underwent remission for another 13 months.
This report describes a multimodal approach to managing HCC with PVTT, successfully extending survival to 37 months after the ﬁrst SIRT. As has been reported elsewhere, combining liver-directed treatments as necessary to achieve a complete response is imperative to improving survival.13 This is particularly important in managing HCC with PVTT, which is associated with poor prognosis.