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Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus

Long-term outcome

Radio(chemo)therapie beim lokal fortgeschrittenem Plattenepithelkarzinom des Ösophagus

Langzeitergebnisse

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Abstract

Purpose

The purpose of this work is to report the long-term outcomes of three-dimensional conformal radio(chemo)therapy in the curative management of esophageal squamous cell carcinoma (ESCC).

Patients and methods

A retrospective analysis of patients treated with radio(chemo)therapy between 1988 and 2011 at Klinikum rechts der Isar, Technische Universität München was performed. In all, 168 patients received radio(chemo)therapy for ESCC in curative intention. The median follow-up time was 91 months (range 1–212 months). There were 128 men and 40 women with a median age of 63 years. Selection criteria for radio(chemo)therapy were unfit for surgery and/or unresectable primary tumor (n = 146, 87 %) or patients’ choice (n = 22, 13 %). The majority of the patients received a combination of cisplatin and 5-fluorouracil chemotherapy with 54 Gy in 30 fractions of radiotherapy.

Results

The median overall survival (OS) was 20 months (95 % confidence interval 17–23 months). The OS at 2 and 5 years for the whole cohort was 41 ± 4 % and 22 ± 3 %, respectively. Forty patients (24 %) suffered an in-field recurrence. The most common acute nonhematologic toxicity >grade 2 was dysphagia in 35 % of the patients. Acute hematologic toxicity > grade 2 was recorded in 14 % of the patients. There was no grade 5 toxicity observed during the study. Poor ECOG performance status (0–1 vs. 2–3, HR = 1.70, p = 0.002) and weight loss ≥ 10 % before the start of therapy (HR = 1.99, p = 0.001) were among the factors significantly associated with poor OS in multivariate analysis.

Conclusion

Three-dimensional conformal definitive radio(chemo)therapy is well tolerated and leads to long-term survival in more than 20 % of patients with advanced disease and/or contraindication to surgery. However, 24 % in-field recurrence remains a major concern. Prospective trials are warranted to assess if a well-tailored conformal radiochemotherapy can improve the local control and obviate the need for surgical resection in patients with good general condition and potentially resectable tumors.

Zusammenfassung

Hintergrund

Ziel dieser Arbeit war es, die Langzeitergebnisse von Patienten mit einem Plattenepithelkarzinom des Ösophagus (ESCC), die mit dreidimensional konformaler Radio(chemo)therapie in kurativer Absicht behandelt wurden, zu berichten.

Patienten und Methoden

Durchgeführt wurde eine retrospektive Analyse von Patienten, die zwischen 1988 und 2011 am Klinikum rechts der Isar, Technische Universität München, mit einer Radio(chemo)therapie behandelt wurden. In kurativer Intention erhielten 168 ESCC-Patienten eine Radio(chemo)therapie. Die mediane Nachbeobachtungszeit betrug 91 Monate (Intervall 1–212 Monate). Die Kohorte bestand aus 128 männlichen und 40 weiblichen Patienten mit einem medianen Alter von 63 Jahren. Die Selektionskriterien für eine Radio(chemo)therapie waren "ungeeignet für eine Operation" und/oder nichtresezierbarer Primärtumor (n = 146, 87 %) oder "Entscheidung des Patienten" (n = 22, 13 %). Die Mehrheit der Patienten erhielt eine Kombination aus einer Cisplatin- und 5-Fluorouracil-Chemotherapie mit einer 54-Gy-Bestrahlung in 30 Fraktionen.

Ergebnisse

Das mediane Gesamtüberleben (OS) lag bei 20 Monaten (95 %-Konfidenzintervall 17–23 Monate). Das 2- und 5-Jahres-OS für die gesamte Kohorte betrug jeweils 41 ± 4% und 22 ± 3%. Bei 40 Patienten (24%) trat nach der Behandlung ein In-field-Rezidiv auf. Die häufigste nichthämatologische akute Nebenwirkung der Behandlung >Grad 2 war Dysphagie in 35 % der Patienten. Akute hämatologische Nebenwirkungen >Grad 2 traten in 14 % der Patienten auf. In der Gesamtdauer der Studie wurden keine Grad-5-Nebenwirkungen beobachtet. Ein schlechter ECOG-Performance-Status (0–1 vs. 2–3, HR = 1,70; p = 0,002) und ein Gewichtsverlust ≥ 10 % vor Beginn der Therapie (HR = 1,99; p = 0,001) waren Faktoren, die in der multivariaten Analyse signifikant mit einem schlechterem OS assoziiert waren.

Schlussfolgerung

Eine dreidimensional konformale definitive Radio(chemo)therapie wird gut toleriert und führt in über 20 % der Patienten mit fortgeschrittenem Stadium und/oder Kontraindikationen für eine Operation zu einem verbesserten Langzeitüberleben. Eines der größten Probleme bleibt dennoch eine In-field-Rezidivrate von 24 %. Prospektive Studien sind notwendig, um zu beurteilen, ob eine optimal geplante, konformale Radiochemotherapie bei Patienten mit gutem Allgemeinzustand und potentiell resezierbarem Tumor die Lokalrezidivrate verbessern kann und eine Alternative zu einer chirurgischen Resektion darstellt.

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Authors and Affiliations

  1. Department of Radiation Oncology, Klinikum rechts der Isar, Technische Universität München, München, Germany

    Arif Deniz Ordu M.D., Hans Geinitz M.D., Lisa Felicia Deymann, Vera Scherer, Stephanie E. Combs M.D. &  Khashayar Fakhrian M.D.

  2. Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodø, and Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway

    Carsten Nieder M.D.

  3. Department of Radiation Oncology, Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria

    Hans Geinitz M.D.

  4. Department of Radiation Oncology, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Hölkeskampring 40, 44625, Herne, Germany

    Philipp Günther Kup M.D. &  Khashayar Fakhrian M.D.

  5. Department of Radiation Oncology, Sankt Josef Hospital Bochum, Universitätsklinikum der Ruhr-Universität Bochum, Gudrunstraße 56, Bochum, 44791, Germany

    Khashayar Fakhrian M.D.

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  1. Arif Deniz Ordu M.D.
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Correspondence to Khashayar Fakhrian M.D..

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Conflict of interest

A.D. Ordu, C. Nieder, H. Geinitz, P.G. Kup, L.F. Deymann, V. Scherer, S.E. Combs, and K. Fakhrian state that there are no conflicts of interest.

The accompanying manuscript does not include studies on humans or animals.

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Ordu, A., Nieder, C., Geinitz, H. et al. Radio(chemo)therapy for locally advanced squamous cell carcinoma of the esophagus. Strahlenther Onkol 191, 153–160 (2015). https://doi.org/10.1007/s00066-014-0779-x

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