RT for BTC can be classified into adjuvant therapy after surgery or therapy for inoperable cases. While no randomized control trial has been conducted, a meta-analysis revealed that patients with extrahepatic cholangiocarcinoma treated with adjuvant RT show a significantly lower mortality rate than patients treated with surgery alone . Data in the Surveillance Epidemiology and End Result database also suggest that palliative RT prolongs survival in patients with extrahepatic cholangiocarcinoma . In these reports, the outcomes of the treatment were reported in detail, but detailed information on RT use has not been provided and there are few reports on patterns of RT practice. We therefore decided to evaluate the practice of RT for BTC at Japanese radiation oncology centers, with the goal of assisting with development of randomized clinical trials. JROSG has conducted similar surveys and successfully determined the general patterns of RT practice for several other cancers in Japan [5, 6]. Of the 31 responding institutions, 43% treated fewer than 10 patients over the period covered by the survey. Surprisingly, none of the patients were treated with an investigational protocol, clearly indicating a need for a prospective multicenter study to determine a standard therapeutic approach.
The results of the study showed that CT-based treatment planning was used for approximately 90% of the patients. Previous nationwide surveys of the structural characteristics of radiation oncology in Japan found that only 329 (45%) of 726 facilities in 2003 and 407 (57%) of 712 facilities in 2005 used CT-based treatment planning [7, 8]. These results suggest that three-dimensional conformal RT planning became mainstream during the survey period or that patients with BTC received RT more frequently in facilities with advanced equipment.
We examined the variations in RT use (modality, total dose, or RT fields) according to the purpose of RT or BTC subsites. Some analyses have suggested that there is a dose–response relationship for treatment of BTC and have stressed the importance of dose escalation [9, 10]. However, many patients with EBRT included in this survey were treated with a total dose of 50 or 50.4 Gy (~40%) and only 13% of the patients received a total dose ≥60 Gy. These data indicate that use of sufficient doses for EBRT for tumors in the hepatic hilum and liver regions was severely restricted by technical difficulties with the delivery of high doses to these regions while sparing surrounding organs, including the liver, duodenum, stomach, and spinal cord, even though most institutions used CT-based treatment planning. Recently, IMRT has emerged as a sophisticated technique for treatment of tumors, including BTC, in areas at risk of recurrence, while sparing adjacent normal tissue from high-dose irradiation . However, only two patients were treated with IMRT for EBRT during the survey period.
ILBT can also be used for dose escalation in a region at risk [9, 12] since it has the advantage of allowing delivery of a sufficient dosage to a target focus while reducing the effect of irradiation on surrounding tissues. Theoretically, a combination of ILBT and EBRT can enhance the beneficial effects of RT, with fewer adverse effects than those incurred with EBRT alone. In fact, ILBT with EBRT entailed a significantly higher EQD2 dose than EBRT alone in our study cohort. While 42% of the institutions performed ILBT, only 14% of all patients received ILBT combined with EBRT, indicating that this treatment modality was used only in selected cases because the effect of ILBT is limited to the area surrounding the lumen of the biliary tract and improvement in local control can therefore be expected only for small tumors .
The optimal radiation field for BTC remains to be defined. The majority of relapses after resection with curative intent occur at the primary tumor site , which suggests that it may be reasonable to limit RT to the primary tumor (bed). Only 23% of the patients included in this survey received radiation to the tumor (bed) as well as the regional lymph nodes, regardless of the lymph node status. Although limiting the radiation field to the tumor (bed) has tended to become prevalent in Japan, the definition of clinical target volume included regional lymph nodes as well as the tumor (bed) in a recent meta-analysis of 14 selected papers with detailed information on adjuvant RT after surgery , as well as in many reports on unresectable BTC published since 2000 [14–17]. Collectively, these findings indicate that the radiation field for BTC is not yet standardized due to the lack of a large randomized control trial and that additional studies investigating the optimal radiation field should be conducted.
The study presented here showed that chemotherapy is frequently administered in combination with RT (47% of all patients). Chemotherapy was most often administered during RT, followed by after RT. Several trials have examined the efficacy of adjuvant chemoradiation after surgery  or of chemoradiation for unresectable cases . The National Comprehensive Cancer Network (NCCN) reported that most CCRT for BTC involved the use of 5-FU, and that CCRT with gemcitabine is not recommended due to the limited experience with and potential toxicity of this treatment. However, the use of CCRT combined with gemcitabine-containing regimens increased in Japan during the period covered by the current survey, which suggests that additional studies should be undertaken to establish the optimal sequencing of RT and chemotherapy with drugs such as gemcitabine. For chemotherapy for advanced BTC, the recent randomized control phase III ABC-02 study showed that a combination of gemcitabine and cisplatin improved overall and progression-free survival by 30% over gemcitabine alone . Based on these results, the combination of gemcitabine and cisplatin can now be considered to be the standard of care as first-line chemotherapy for patients with advanced or metastatic BTC. In Japan, however, oral anticancer drugs such as TS-1 or UFT also tend to be used as adjuvant chemotherapy after RT, and only two patients in the current study were treated with a combination of gemcitabine and cisplatin after RT.