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Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B–C hepatocellular carcinoma

Kombinierte stereotaktische Körperstamm-Strahlentherapie und transarterielle Chemoembolisation als Erstlinientherapie beim hepatozellulären Karzinom im BCLC-Stadium B–C

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Abstract

Purpose

We retrospectively evaluated the efficacy and safety of stereotactic body radiotherapy (SBRT) combined with trans-arterial chemoembolization (TACE) as initial therapy in Barcelona Clinic Liver Cancer (BCLC) system stage B–C hepatocellular carcinoma (HCC).

Patients and methods

Seventy-two patients received a single dose of TACE followed by SBRT 4 weeks later. All patients had tumor sizes ≥5 cm, at least 700 ml of disease-free liver, Child–Pugh (CP) score ≤ B7 and tumor nodules ≤5. SBRT dose, ranging from 6 × 5–8 Gy or 5–10 × 4 Gy, was individualized according to normal tissue constraints. No subsequent scheduled treatment was delivered unless disease progression was observed. Local control (LC), overall survival (OS), progression-free survival (PFS), response rate (RR), and toxicity were evaluated.

Results

The patients’ characteristics were: median age 60 years (range 28–87 years); CP score A/B (n = 68/4); BCLC stage B/C (n = 51/21); solitary/multifocal (n = 37/35); portal vein invasion (n = 18). The median tumor size and GTV were 11.2 cm (range 5.0–23.6 cm) and 751 cm3 (range 41–4009 cm3), respectively. The median equivalent dose in 2 Gy per fraction (EQD2, α/β = 10) was 37.3 Gy2 (range, 28–72 Gy2). The median follow-up time was 16.8 months (range, 3–96 months). The objective RR was 68% and the 1‑year LC rate was 93.6% (95% CI, 87.6–100%). The median OS was 19.8 months (95% CI, 11.6–30.6 months). SBRT-related grade 3 or higher adverse gastrointestinal events and treatment-related death occurred in three (2.8%) and one patient (1.4%) respectively. No patient developed classical radiation-induced liver injury.

Conclusion

Our experience suggests that combined TACE and SBRT can be a safe and effective initial therapy for BCLC stage B–C HCC with appropriate patient selection. Further prospective trials are warranted.

Zusammenfassung

Zielsetzung

Wir bewerteten retrospektiv Wirksamkeit und Sicherheit der stereotaktischen Körperstamm-Strahlentherapie (SBRT) in Kombination mit transarterieller Chemoembolisation (TACE) als Erstlinientherapie für Leberzellkarzinome (HCC) im Stadium B–C nach dem Barcelona-Klinik-Leberkrebs(BCLC)-System.

Patienten und Methoden

Es bekamen 72 Patienten eine einzige TACE-Anwendung gefolgt von einer SBRT 4 Wochen später. Alle Patienten hatten ≥5 cm, mindestens 700 ml tumorfreie Leber, einen Child-Pugh-Score (CP) ≤ B7 und Läsionen ≤ 5. Die SBRT-Dosen im Bereich von 6 × 5–8 Gy oder 5–10 × 4 Gy wurden bezüglich notwendiger Einschränkungen im Normalgewebe individualisiert. Eine weitere Behandlung wurde nur bei entsprechender Progression der Erkrankung durchgeführt. Der primäre Endpunkt war die lokale Kontrolle (LK). Sekundäre Endpunkte umfassten Gesamtüberleben (GS), progressionsfreies Überleben (PFÜ), Ansprechrate (AR) und Toxizität.

Ergebnisse

Patientenmerkmale waren: mittleres Alter 60 Jahre (Spanne 28–87 Jahre); CP-Score A/B (n = 68/4); BCLC-Stadium B/C (n = 51/21); solitär/multifokal (n = 37/35); Pfortaderinvasion (n = 18). Mittlere Tumorgröße und GTV betrugen 11,2 cm (Spanne 5,0–23,6 cm) bzw. 751 cm3 (Spanne 41–4009 cm3). Die mittlere Äquivalentdosis in 2 Gy pro Fraktion (EQD2, α/β = 10) betrug 37,3 Gy2 (Spanne 28–72 Gy2). Die mittlere Nachbeobachtungszeit war 16,8 Monate (Spanne 3–96 Monate). Die Ziel-AR betrug 68 % und die 1‑Jahres-LK 93,6 % (95 %-Konfidenzintervall [KI] 87,6–100 %). Das mediane GS lag bei 19,8 Monaten (95 %-KI 11,6–30,6 Monate). SBRT-induzierte Nebenwirkungen vom Grad 3 oder höher traten bei 3 Patienten (2,8 %) bzw. behandlungsbedingte Todesfälle bei 1 Patienten (1,4 %) auf. Kein Patient entwickelte eine klassische strahleninduzierte Leberschädigung.

Schlussfolgerungen

Unsere Erfahrung zeigt, dass bei entsprechender Patientenauswahl die Kombination von TACE und SBRT eine sichere und effektive Erstlinientherapie für das HCC im BCLC-Stadium B–C sein kann. Prospektive Studien sind gerechtfertigt.

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Authors and Affiliations

  1. Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, China

    C. L. Chiang, Mark K. H. Chan, Cynthia S. Y. Yeung, Connie H. M. Ho, Francis A. S. Lee, Venus W. Y. Lee & Frank C. S. Wong

  2. Department of Clinical Oncology, University of Hong Kong, Hong Kong, China

    C. L. Chiang

  3. Department of Clinical Oncology, University of Hong Kong-Shenzhen Hospital, Hong Kong, China

    C. L. Chiang

  4. Department of Radiation Oncology, Universitatsklinikum Schleswig-Holstein, Kiel, Germany

    Mark K. H. Chan & Oliver Blanck

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C.L. Chiang, M.K.H. Chan, C.S.Y. Yeung, C.H.M. Ho, F.A.S. Lee, V.W.Y. Lee, F.C.S. Wong, and O. Blanck declare that they have no competing interests.

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66_2018_1391_MOESM1_ESM.tif

Supplementary material Fig. S1: Comparison of CT images before and after TACE and SBRT. a Baseline axial images, b Baseline coronal images, c Axial images 6 months post treatment, d Coronal images 6 months post treatment

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Chiang, C.L., Chan, M.K.H., Yeung, C.S.Y. et al. Combined stereotactic body radiotherapy and trans-arterial chemoembolization as initial treatment in BCLC stage B–C hepatocellular carcinoma. Strahlenther Onkol 195, 254–264 (2019). https://doi.org/10.1007/s00066-018-1391-2

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