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Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection

Analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation

Radiochemotherapie bei Patienten mit extrahepatischen und hilären Gallengangskarzinomen nach inkompletter Resektion oder Inoperabilität

Evaluierung von Effektivität, Toxizität und Rezidivmustern nach postoperativer oder primärer Radiochemotherapie

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Abstract

Background

The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease.

Patients and methods

From 2003–2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38–80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups.

Results

Patients at high risk (9  times R1 resection, 1  pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups.

Conclusion

Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials.

Zusammenfassung

Hintergrund

Evaluierung von Effektivität, Toxizität und Rezidivmustern nach kombinierter Radiochemotherapie bei Patienten mit extrahepatischen und hilären Gallengangskarzinomen (Klatskin-Tumoren) nach inkompletter Resektion oder Inoperabilität.

Patienten und Methoden

Im Zeitraum von 2003 bis 2010 wurden in unserer Institution 25 Patienten mit nichtmetastasierten extrahepatischen und hilären Gallengangskarzinomen mittels Radiotherapie und kombinierter Radiochemotherapie postoperativ (10 Patienten, 9 Patienten mit R1-Resektion) oder im Falle einer Inoperabilität (15 Patienten) behandelt. Das mediane Alter lag bei 63 Jahren (Spanne 38–80 Jahre). Von den Patienten waren 20 männlich und 5 weiblich. Die median applizierte Dosis betrug in beiden Patientengruppen 45 Gy.

Ergebnisse

Patienten mit hohem Rezidivrisiko (9 -mal R1-Resektion, 1 -mal Lymphangiosis) nach kurativ intendierter Resektion hatten eine mediane Zeitdauer von 8,7 Monaten bis zur Krankheitsprogression und ein mittleres Gesamtüberleben von 23,2 Monaten (6 von 10 Patienten waren zum Zeitpunkt der Analyse noch unter Beobachtung). Patienten, die aufgrund eines inoperablen Tumors eine kombinierte Radiochemotherapie erhielten, hatten eine vergleichbar schlechte Prognose mit einem progressionsfreien Überleben von 7,1 Monaten und einem Gesamtüberleben von 12 Monaten. In beiden Patientengruppen kam es im Verlauf überwiegend zu einem systemischen Progress (hepatisch, peritoneal). Es traten in beiden Gruppen keine höhergradigen Toxizitäten auf.

Schlussfolgerung

Eine kombinierte Radiochemotherapie mit Gemcitabin wird gut toleriert und kann sicher bei Patienten mit extrahepatischen und hilären Gallengangskarzinomen sowohl in der primären als auch in der postoperativen Situation bei erhöhtem Rezidivrisiko eingesetzt werden. Zukünftige Studien sollten eine weitere Dosiseskalation hinsichtlich der systemischen Therapie als auch der radiotherapeutischen Behandlungsmöglichkeiten prüfen, da die Prognose des vorgestellten Kollektivs weiterhin verbesserungswürdig ist.

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Author’s contributions

DH, JD, SC, SR, TW and KL were responsible for patient treatment and care. DH collected the patients’ data, performed all statistical analyses and wrote the manuscript. KH made substantial contributions to collecting the patients’ data.

SR, KJ, BG, PS, MWB, TW and JD contributed to the analysis of data and revised the manuscript. SEC conceived the study, helped to write and finalized the manuscript. All authors helped with the interpretation of the data, read and approved the final manuscript.

Conflict of interest

The corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    D. Habermehl, K. Lindel, S. Rieken, K. Haase, T. Welzel, J. Debus & S.E. Combs

  2. Institute of Pathology, University of Heidelberg, Heidelberg, Germany

    B. Goeppert & P. Schirmacher

  3. Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany

    M.W. Büchler

Authors
  1. D. Habermehl
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  2. K. Lindel
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  3. S. Rieken
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  4. K. Haase
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  5. B. Goeppert
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  6. M.W. Büchler
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  7. P. Schirmacher
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  8. T. Welzel
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  9. J. Debus
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  10. S.E. Combs
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Correspondence to D. Habermehl.

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Habermehl, D., Lindel, K., Rieken, S. et al. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection. Strahlenther Onkol 188, 795–801 (2012). https://doi.org/10.1007/s00066-012-0099-y

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