Correspondence (reply): In Reply

The focus of our review has been on the present clinical practice based on scientific evidence; therefore, promising but currently still experimental treatment approaches have not been discussed in detail (1). In addition, all studies on the molecular and targeted treatment of CCA (particularly EGFR-directed antibodies) have unfortunately not yet been successful. More recently, the BINGO study, a joint study of the Working Group of Internal Oncology (Arbeitsgemeinschaft Internistische Onkologie, AIO), evaluating gemcitabine and oxaliplatin with and without cetuximab, did not reveal any relevant improvement in progression-free survival (6.1 months with cetuximab and 5.5 months without cetuximab) (2). Data from the PiCCA study, an AIO-associated study, which only included KRAS wild-type patients for treatment with gemcitabine and cisplatin with and without panitumumab, are not yet available. As with other tumor entities, there is a reasonable expectation, as described by Dr. Tsamaloukas, that treatment-relevant target structures for CCA may be identified by using the latest sequencing techniques. Whether these eventually will be mutations of the isocitrate dehydrogenase 1 and 2 genes will have to be confirmed in clinical studies.

Radiation therapy based on the intra-arterial injection of the beta emitter Yttrium-90—which is encapsulated in microspheres in the case of selective internal radiation therapy (SIRT)—enables local tumor control in arterially hypervascular liver tumors. Therefore, this procedure represents a treatment option for some patients with intrahepatic cholangiocarcinoma (iCCA) too. Due to the lack of randomized and controlled trials, its integration with the treatment algorithm for iCCA is not possible, especially not as an alternative treatment option or as a further treatment after systemic chemotherapy. The available monocentric and non-controlled cohort studies with 24 to 46 patients of Mouli et al. (3), Ibrahim et al. and Saxena et al. (4) showed in summary that SIRT can be performed safely, provided proper patient selection (stabile general condition with ECOG ≤ 2, bilirubin serum levels < 2 mg/dL). Especially—and this is also indicated by the data published to date—local tumor control can be achieved in patients with a single, peripheral intrahepatic focal lesion. In this respect we agree with Ezziddin et al. that SIRT for iCCA may be a clinically relevant treatment option for some patients which should be evaluated by an interdisciplinary tumor board As already mentioned in our review, prospective randomized clinical trials will have to be conducted to evaluate the actual value of this treatment, especially in combination with systemic treatments.