Patients with unresectable IHCC may be eligible for local-regional therapy, systemic chemotherapy, and best supportive care. Local-regional therapies for these patients include RT, transarterial chemoembolization, and radiofrequency ablation, but few studies to date have evaluated their efficacy in patients with unresectable IHCC. To our knowledge, this is the first study to assess the outcomes of CCRT in patients with stage IVa/IVb IHCC. We found that the combination of XP chemotherapy and external beam RT was well tolerated and resulted in prolonged PFS and OS compared with XP alone. CCRT outcomes have been reported in patients with extrahepatic cholangiocarcinoma
[17, 18, 23, 24], and CCRT did not significantly enhance benefits, compared with RT alone, in patients with unresectable extrahepatic biliary cancer
. Prospective randomized trials are therefore needed to confirm the benefits of CCRT in patients with advanced-stage unresectable biliary tract cancer.
A recent retrospective study showed that external beam RT prolonged survival and relieved the symptoms of jaundice in patients with early-stage but unresectable IHCC, with a median OS of 9.5 months and a 1-year OS rate of 38.5%
. However, CCRT may be more beneficial than loco-regional RT alone for patients with advanced-stage unresectable IHCC, including those with distant metastases. The CCRT group in our study, which included 11 patients (44%) with extrahepatic metastases, had better outcomes than the group receiving XP alone. Because of the small number of patients, however, we could not analyze the prognostic factors, such as distant metastasis, associated with OS and PFS.
Although systemic chemotherapy has been reported superior to best supportive care
[11, 12], a standard chemotherapy regimen has not yet been established in patients with advanced, unresectable IHCC, because of the lack of randomized, prospective trials
. A recent phase III randomized controlled trial showed that the combination of gemcitabine and cisplatin (GP chemotherapy) was highly effective in patients with locally advanced or metastatic biliary tract cancer, including in patients with recurrent disease after resection
. Because on a few patients in our center received GP chemotherapy, we analyzed patients treated with XP chemotherapy. In phase II trials, XP chemotherapy was shown to be an active and well-tolerated first-line regimen in patients with advanced biliary tract cancer
XP has also shown good radio-sensitizing activity in patients with gastrointestinal malignancies
. Our findings indicated that CCRT may be better option for patients with advanced-stage unresectable IHCC than systemic chemotherapy alone. The better outcomes observed with XP-CCRT may have been because of the synergistic effects of RT and systemic chemotherapy. Moreover, except for neutropenia, the frequencies of treatment-related toxicity and >3 grade toxicity (24% vs. 10.4%, p = 0.174) were not significantly higher in the XP-CCRT than in the XP group, despite the former group receiving more cycles of chemotherapy as well as RT. These findings indicate that XP-CCRT is safe for patients with advanced-stage, unresectable IHCC.
This study had several limitations, including the small number of patients and its retrospective design. Thus, selection bias is inevitable. Moreover, the RT method and total dose differed among patients in the XP-CCRT group. Nevertheless, the significant improvements in PFS and OS observed with CCRT suggest the need for randomized prospective clinical trials comparing the different chemotherapy regimens (e.g., GP vs. XP) in combination with RT.