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Adjuvant radiochemotherapy vs. chemotherapy alone in gastric cancer: a meta-analysis

Adjuvante Radiochemotherapie vs. alleinige Chemotherapie beim Magenkarzinom: Eine Metaanalyse

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Abstract

Background

As an adjuvant therapeutic strategy in advanced gastric cancer, both adjuvant chemotherapy (CTx) and postoperative radiochemotherapy (RCTx) can be considered. Both approaches have been shown to improve overall survival compared to resection alone. Several prospective randomized trials have compared the two postoperative concepts.

Methods

We performed a literature search to identify prospective randomized trials which compared adjuvant chemotherapy to adjuvant radiochemotherapy in patients with advanced gastric cancer. As effect sizes, we extracted hazard ratios (HR) as well as event rates from the included trials for the endpoints overall survival, disease-free survival and locoregional control.

Results

We identified seven studies that enrolled 1807 patients overall. Combined radiochemotherapy showed no significant improvement of overall survival in comparison to chemotherapy alone (HR = 0.93; 95%CI: 0.82–1.06; p = 0.28). For disease-free survival (HR = 0.86; 95%CI: 0.76–0.98; p = 0.023) and locoregional control (odds ratio [OR] = 0.56; 95%CI: 0.42–0.75; p = <0.001) we detected significant advantages from the addition of radiation to chemotherapy. A subgroup analysis demonstrated an improvement in survival when the radiochemotherapy protocol was not de-intensified.

Conclusions

Adjuvant chemotherapy or radiochemotherapy demonstrate similar oncologic efficacy and therapy-associated toxicity. Individual patient characteristics should therefore determine the therapeutic approach in a multidisciplinary discussion. Irradiation added to standard-dose chemotherapy possibly results in a survival benefit.

Zusammenfassung

Hintergrund

Als adjuvante Therapiestrategie beim fortgeschrittenen Magenkarzinom kommen sowohl die adjuvante Chemotherapie (CTx) als auch die postoperative Radiochemotherapie (RCTx) in Frage. Für beide Ansätze konnte eine Verbesserung des Gesamtüberlebens im Vergleich zur alleinigen Operation gezeigt werden. Mehrere prospektive, randomisierte Studien haben die beiden postoperativen Konzepte miteinander verglichen.

Methoden

Wir führten eine Literaturrecherche zur Identifikation von prospektiven, randomisierten Studien durch, die bei Patienten mit einem fortgeschrittenen Magenkarzinom eine CTx mit einer RCTx verglichen. Als Effektschätzer wurden die „Hazard Ratios“ (HR) sowie die Ereignisraten aus den eingeschlossenen Studien für die Endpunkte Gesamtüberleben, krankheitsfreies Überleben und lokoregionäre Kontrolle extrahiert.

Ergebnisse

Es wurden sieben Studien identifiziert, die insgesamt 1807 Patienten einschlossen. Eine kombinierte RCTx zeigte keine signifikante Verbesserung des Gesamtüberlebens im Vergleich der alleinigen CTx (HR = 0,93; 95 %-Konfidenzintervall [KI] 0,82–1,06; p = 0,28). Hinsichtlich des krankheitsfreien Überlebens (HR = 0,86; 95 %-KI 0,76–0,98; p = 0,023) und lokaler Tumorkontrolle (Odds Ratio [OR] = 0,56; 95 %-KI 0,42–0,75; p = <0,001) konnten klare statistische Vorteile der Addition von Strahlentherapie zur Chemotherapie detektiert werden. Eine Subgruppenanalyse zeigte einen Überlebensvorteil, wenn die RCTx nicht deintensiviert appliziert wurde.

Schlussfolgerung

Adjuvante CTx und RCTx zeigen ähnliche onkologische Effektivität und therapieassoziierte Toxizität, sodass die individuelle Patientencharakteristik die Therapieentscheidung im Rahmen einer multidisziplinären Diskussion bestimmen sollte. Möglicherweise resultiert aus der Strahlentherapie zusammen mit der volldosierten Chemotherapie ein Überlebensvorteil.

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Authors and Affiliations

  1. Department of Radiation Oncology, Heinrich Heine University, Moorenstr. 5, 40225, Dusseldorf, Germany

    Christiane Matuschek,  Jan Haussmann,  Edwin Bölke,  Bálint Tamaskovics,  Freddy-Joel Djiepmo Njanang,  Klaus Orth,  Peter Arne Gerber &  Wilfried Budach

  2. Division of Biostatistics and Bioinformatics, Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Kai Kammers M.Sc., Ph.D.

  3. Vincere Cancer Center, Scottsdale, AZ, USA

    Bahar Anooshar MD

  4. Department of Surgery, St. Marien Krankenhaus Ratingen, Ratingen, Germany

    Matthias Peiper

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  1. Christiane Matuschek
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  2. Jan Haussmann
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Contributions

C. Matuschek and J. Haussmann contributed equally to the manuscript. E. Bölke and W. Budach had the idea, coordinated the work, and wrote parts of the manuscript. E. Bölke did the literature research, prepared the data for analysis, and wrote parts of the manuscript. K. Kammers and J. Haussmann did the statistical analysis. C. Matuschek, J. Haussmann, K. Orth, and M. Peiper wrote parts of the manuscript. J. Haussmann contributed significantly to the discussion on the interpretation of the results. C. Matuschek, J. Haussmann, and P.A. Gerber prepared the figures and tables and wrote parts of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Edwin Bölke.

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Conflict of interest

C. Matuschek, J. Haussmann, E. Bölke, B. Tamaskovics, F.-J. Djiepmo Njanang, K. Orth, M. Peiper, P.A. Gerber, B. Anooshar, K. Kammers, and W. Budach declare that they have no competing interests.

Ethical standards

The authors did not conduct any studies with human or animal participants for this article. As for other studies cited in this article, information on ethical guidelines may be found in the respective sources.

Additional information

This work was presented in parts at the Annual ASCO (American Society of Clinical Oncology) meeting in Chicago 2018.

Christiane Matuschek and Jan Haussmann contributed equally to this work.

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Matuschek, C., Haussmann, J., Bölke, E. et al. Adjuvant radiochemotherapy vs. chemotherapy alone in gastric cancer: a meta-analysis. Strahlenther Onkol 195, 695–706 (2019). https://doi.org/10.1007/s00066-019-01431-y

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  • DOI: https://doi.org/10.1007/s00066-019-01431-y

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