In a previous study, we reported that the combination of HAI via the reservoir system and RT for patients with HCC plus MVI led to improved outcomes [26–28]. In this study, we analyzed the clinical outcomes of patients with HCC with MVI treated by the combination of one-shot CDDP administered via HAI plus RT. The median OS and PFS times were 8.6 and 3.2 months, respectively. The ORR, evaluated 1.4 months after HAI, was 16% for the main tumor, and 59% for tumor in the MVI. There were no severe adverse events that ended the study for any of the patients. Nineteen of 32 patients received additional systemic therapy. These results seemed well tolerated and showed immediate and favorable control of MVI. Since we did not use the implanted reservoir system in this study, there were no adverse events associated with an implanted port and catheter which we reported in previous study with reservoir system.
HCC is a leading cause of cancer-related death worldwide, and the prognosis of patients with unresectable HCC with major MVI is extremely poor [1,2]. Systemic chemotherapy, such as atezo+beva, is effective for advanced HCC [10,23] and for HCC with Vp. However, the prognosis remains poor, with 67% of patients alive 6 months after the initiation of treatment with atezo+beva [24,25]. Kudo et al. reported that MVI is a factor leading to poor outcomes in patients with advanced HCC because MVI rapidly worsens flow in the portal vein and leads to liver failure and portal hypertension .
Many studies have reported the efficacy of HAI for treating patients with HCC with the portal vein tumor thrombus (PVTT). This HAI regimen was based on 5-fuluolouracil (5-FU) and cisplatin (FP), and infused repeatedly via an implanted catheter and port which called reservoir system. The prospective SILIUS study, which compared sorafenib and HAI with low-dose FP did not show better results than those of the patients treated with sorafenib; however, the subgroup analysis of patients with HCC with Vp4 showed a better outcome than that of patients treated with sorafenib . Fujino et al. reported that the combination of HAI with 5-FU based regimen and RT showed better ORR for patients with HCC with PVTT than with HAI without RT . Kodama et al. compared the combination of HAI and RT for patients with HCC with PVTT and sorafenib without RT and found respective median OS times of 9.9 vs. 5.3 months . Kawaoka et al. compared the outcomes of the patients treated with 5-FU regimen administered by HAI and one-shot CDDP administered by HAI, and showed a comparison of the ORR and median OS time (9.1 vs. 8.6 months), but there was no statically significant difference . Kosaka et al. reported that the OS and PFS of 5-FU via HAI and RT for patients with HCC with Vp4 were 12.1 and 4.2 months, respectively, with 19.6% ORR for the main tumor, and 51% ORR for tumor in the MVI . However, there are some problems related to the implanted reservoir system [26,29–31]. Each type of HAI and RT therapy showed a rapid effect for MVI; on the other hand, there was insufficient overall control of the HCC, especially with large intrahepatic volumes over half of the liver or extrahepatic metastasis. Thus, we should consider the rapid initiation of systemic chemotherapy in patients with such advanced HCC.
The current first choice of systemic chemotherapy is atezo+beva [10,23]. The median OS of this combination therapy was 19.2 months, which was longer than the median OS of 13.6 months for the sorafenib group . However, the subgroup analysis reported that the prognosis of the HCC patients with Vp4 remains poor, the median OS of the Vp4 patients treated with atezo+beva was7.6 months and that with sorafenib was 5.5 months . In addition, the median time of response to atezo+beva was 2.8 months after initiation, and approximately 20% of patients were nonresponders . These timelapse of atezo+beva might increase the risk to improve the MVI and reduce the liver preservation function.
Above all, we suggest that the combination of HAI and RT is important for the rapid control of MVI and as a bridging therapy to systemic chemotherapy. In particular, one-shot CDDP via HAI combined with RT should be a good therapeutic option because problems related to the reservoir system cannot occur.
This study has limitations. It was a retrospective single-arm study with a small number of patients. Accumulation of sample cases and further studies such as prospective, multi-arm studies, in addition to systemic reviews, should be considered. We hope that the results of our study warrant further studies.