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Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma

Verbesserte onkologische Ergebnisse mit Chemoradiotherapie gefolgt von einer Operation beim nichtresezierbaren intrahepatischen Cholangiokarzinom

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Abstract

Purpose

To investigate the ability of chemoradiotherapy (CRT) to down-stage unresectable intrahepatic cholangiocarcinoma (IHCC) to resectable lesions, as well as the factors associated with achieving such down-staging.

Methods

The study cohort comprised 120 patients diagnosed with stage I–IVA IHCC between 2001 and 2012. Of these patients, 56 underwent surgery and 64 received CRT as their initial treatment. The rate of curative resections for patients who received CRT was assessed, and the locoregional failure-free survival (LRFFS) and overall survival (OS) rates of these patients were compared to those of patients who underwent CRT alone.

Results

Median follow-up was 36 months. A partial response after CRT was observed in 25% of patients, whereas a biologic response (a >70% decrease of CA19-9) was observed in 35%. Eight patients (12.5%) received curative resection after CRT and showed significantly improved LRFFS and OS compared to those treated with CRT alone (3-year LRFFS: 50 vs. 15.7%, respectively, p = 0.03; 3‑year OS: 50 vs. 11.2%, respectively, p = 0.012); these rates were comparable to those of patients who received initial surgery. Factors associated with curative surgery after CRT were gemcitabine administration, higher radiotherapy dose (biological effective dose ≥55 Gy with α/β = 10), and a >70% reduction of CA19-9.

Conclusion

Upfront CRT could produce favorable outcomes by converting unresectable lesions to resectable tumors in selected patients. Higher radiotherapy doses and gemcitabine-based chemotherapy yielded a significant reduction of CA19-9 after CRT; patients with these characteristics had a greater chance of curative resection and improved OS.

Zusammenfassung

Zielsetzung

Untersuchung der Fähigkeit der Radiochemotherapie (CRT), unauffällige intrahepatische Cholangiokarzinome (IHCC) auf resezierbare Läsionen herunterzustufen sowie der Faktoren, die mit dem Erreichen einer solchen Herabstufung verbunden sind.

Methoden

Die Studienkohorte umfasste 120 Patienten mit einem zwischen 2001 und 2012 diagnostizieren IHCC im Stadium I–IVA. Von diesen wurden 56 Patienten operiert und 64 erhielten als erste Behandlung eine CRT. Die Rate kurativer Resektionen für Patienten mit CRT wurde ermittelt und mit der lokoregionären versagensfreien (LRFFS) und der Gesamtüberlebensrate (OS) von Patienten verglichen, die ausschließlich einer CRT unterzogen wurden.

Ergebnisse

Die mediane Nachbeobachtungszeit betrug 36 Monate. Eine partielle Reaktion nach CRT wurde bei 25 % der Patienten beobachtet, eine biologische Reaktion (a >70 %-Reduktion von CA19-9) hingegen bei 35 %. Eine kurative Resektion nach CRT erhielten 8 Patienten (12,5 %). Sie zeigten signifikant verbesserte LRFFS und OS gegenüber denen, die ausschließlich mit CRT behandelt wurden (3-jährige LRFFS: 50 vs. 15,7 %, p = 0,03; 3‑jährige OS: 50 vs. 11,2 %, p = 0,012); diese Raten waren vergleichbar mit denen von Patienten mit initialer Operation. Faktoren, die mit einer kurativen Operation nach CRT assoziiert wurden, waren Gemcitabin-Verabreichung, höhere Strahlentherapiedosis (biologisch wirksame Dosis ≥55 Gy mit α/β = 10) und eine >70 %-Reduktion von CA19-9.

Schlussfolgerung

Eine CRT im Voraus kann durch die Umwandlung von nichtresezierbaren Läsionen in resezierbare Tumoren bei ausgewählten Patienten günstige Ergebnisse erzielen. Höhere Strahlentherapiedosen und eine gemcitabinbasierte Chemotherapie ergab eine signifikante Reduktion von CA19-9 nach CRT; Patienten mit diesen Eigenschaften hatten eine größere Chance auf kurative Resektion und ein verbessertes OS.

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Acknowledgements

This study was supported by a grant of the Korean Health Technology R&D Project (A121982), Ministry of Health & Welfare, Republic of Korea.

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Authors and Affiliations

  1. Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 120-752, Seoul, Korea (Republic of)

    Yeona Cho MD, Tae Hyung Kim MD & Jinsil Seong MD, PhD

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  1. Yeona Cho MD
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  2. Tae Hyung Kim MD
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  3. Jinsil Seong MD, PhD
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Corresponding author

Correspondence to Jinsil Seong MD, PhD.

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Conflict of interest

Y. Cho, T. Hyung Kim, and J. Seong declare that they have no competing interests.

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Cho, Y., Kim, T.H. & Seong, J. Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma. Strahlenther Onkol 193, 620–629 (2017). https://doi.org/10.1007/s00066-017-1128-7

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