Stereotactic Body Radiation Therapy after Chemotherapy for Unresectable Perihilar Cholangiocarcinoma: The STRONG Trial, a Phase I Safety and Feasibility Study

Rogier Baak, François E J A Willemssen, Yvette van Norden, Ferry A L M Eskens, Maaike T W Milder, Ben J M Heijmen, Bas Groot Koerkamp, Dave Sprengers, Lydi M J W van Driel, Heinz-Josef Klümpen, Wilhelm den Toom, Merel S Koedijk, Jan N M IJzermans, Alejandra Méndez Romero, Rogier Baak, François E J A Willemssen, Yvette van Norden, Ferry A L M Eskens, Maaike T W Milder, Ben J M Heijmen, Bas Groot Koerkamp, Dave Sprengers, Lydi M J W van Driel, Heinz-Josef Klümpen, Wilhelm den Toom, Merel S Koedijk, Jan N M IJzermans, Alejandra Méndez Romero

Abstract

Background: In unresectable pCCA, the standard of care is palliative chemotherapy. We investigated the feasibility and safety of adding stereotactic body radiation therapy (SBRT) after chemotherapy.

Methods: Patients with unresectable pCCA, stage T1-T4N0-N1M0, ECOG 0-1, having finished 6-8 cycles of cisplatin and gemcitabine without disease progression were eligible. SBRT was planned in 15 fractions of 3.0-4.5 Gy. The primary endpoints were feasibility (defined as completing SBRT as planned) and toxicity, evaluated within 3 months after SBRT (CTCAE v4.03). A conventional "3 + 3" design was used, corresponding to a sample size of 6 patients. Dose-limiting toxicity (DLT) was defined as grade ≥ 4 hepatobiliary or grade ≥ 3 gastrointestinal toxicity. The secondary endpoints, measured from the start of radiotherapy, were local control, progression-free survival, overall survival, and quality of life (QoL). ClinicalTrials.gov identifier: NCT03307538.

Results: Six patients were enrolled between November 2017 and March 2020. SBRT was delivered as planned. All patients were treated with 60Gy (15 × 4.0Gy). No SBRT-related DLT was observed. The most common grade ≥ 3 toxicity was cholangitis (n = 5). The median follow-up was 14 months. The 12-month local control rate was 80%. We observed no substantial changes in QoL.

Conclusion: In patients with unresectable pCCA with stable disease after palliative chemotherapy, adding SBRT is feasible and safe. The observed local control merits an additional evaluation of effectiveness.

Keywords: chemotherapy; perihilar cholangiocarcinoma; stereotactic body radiation therapy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Patients with unresecectable pCCA referred from Erasmus Medical Center during the inclusion period for the STRONG-trial. Of the 6 patients included in the trial, 3 patients were referred from another hospital after chemotherapy and were not included in this overview.
Figure 2
Figure 2
Efficacy endpoints: Local control from the start of radiotherapy (A), local control from the start of chemotherapy (B), overall survival from the start of radiotherapy (C), and overall survival from the start of chemotherapy (D).
Figure 3
Figure 3
Quality of life, median score at each evaluation. QLQ-C30 “global health status” (A), EORTC QLQ-C30 “fatigue” (B), EuroQol-5D-5L “health today” score (C), and QLQ-BIL21 “pain” (D). The number of patients who responded is shown underneath each follow-up point.

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