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Perioperative chemotherapy vs. neoadjuvant chemoradiation in gastroesophageal junction adenocarcinoma

A population-based evaluation of the Munich Cancer Registry

Perioperative Chemotherapie vs. neoadjuvante Radiochemotherapie bei Adenokarzinomen des gastroösophagealen Übergangs

Eine populationsbasierte Untersuchung des Münchner Tumorregisters

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Abstract

Background

To date, it remains unclear whether locally advanced adenocarcinoma of the gastroesophageal junction (AEG) should be treated with neoadjuvant chemoradiation (nCRT), analogous to esophageal cancer, or with perioperative chemotherapy (pCT), analogous to gastric cancer. The purpose of this study was to analyze the data of the Munich Cancer Registry (MCR) and to compare pCT and nCRT in AEG patients.

Patients and methods

A total of 2,992 AEG patients, treated between 1998 and 2014, were included in the study. Baseline and tumor parameters as well as overall survival (OS) and tumor recurrence were compared between 56 patients undergoing nCRT and 64 patients undergoing pCT with UICC stage II/III cancer. In addition, uni- and multivariate analyses using Cox regression models were performed to evaluate the effect of tumor characteristics and treatment regimens on OS.

Results

In patients with UICC stage II/III AEG treated with either nCRT or pCT, no significant differences were seen for baseline and tumor characteristics. While there was a significantly higher cumulative incidence of locoregional treatment failure after pCT (32.8%; 95% CI: 18.0–48.4%) compared with nCRT (7.4%; 95% CI: 2.3–16.5%; p = 0.007), there was no significant difference for distant treatment failure (52.9%; 95% CI: 35.4–67.7% and 38.4%; 95% CI: 23.7–52.9%; p = 0.347). When analyzing the whole cohort, patients who received pCT were younger (58.3 years vs. 63.0 years; p = 0.016), had a higher chance of complete tumor resection (81% vs. 67%; p = 0.033), more resected lymph nodes (p = 0.036), and fewer lymph node metastases (p = 0.038) compared with patients who received nCRT. Nevertheless, there was still a strong trend toward a higher incidence of local treatment failure after pCT (25.8%; 95% CI: 14.7–38.3% vs. 12.6%; 95% CI: 5.5–22.8%; p = 0.053). Comparable to the results for patients with UICC stage II/III, no difference was seen for the incidence of distant treatment failure. When excluding patients with UICC stage IV cancer, no significant difference was found for OS.

Conclusion

For UICC stage II/III carcinoma, nCRT was associated with an improved locoregional tumor control compared with pCT, while no further significant differences were seen between nCRT and pCT for UICC stage II/III AEG. Moreover, there was a strong trend toward improved locoregional tumor control after nCRT when analyzing all patients treated with nCRT or pCT, despite these patients having higher risk factors.

Zusammenfassung

Hintergrund

Bis heute ist nicht eindeutig geklärt, ob lokal fortgeschrittene Adenokarzinome des gastroösophagealen Übergangs (AEG) wie Ösophaguskarzinome mit neoadjuvanter Radiochemotherapie (nCRT) oder wie Magenkarzinome mit perioperativer Chemotherapie zu behandeln sind. In dieser Arbeit wird die Effektivität beider Verfahren anhand der Daten des Münchner Tumorregisters verglichen.

Material und Methoden

Ausgewertet wurden Daten von 2992, zwischen 1998 und 2014 behandelten, Patienten mit AEG. Patientencharakteristika, Tumorparameter, Gesamtüberleben (OS) und Rezidivraten von 56 (nCRT) bzw. 64 Patienten (pCT) mit AEG in den UICC-Stadien II und III wurden miteinander verglichen. Zusätzlich erfolgten uni- und multivariate Analysen mithilfe eines Cox-Regressions-Modells, um den Einfluss von Tumorcharakteristika und Behandlungsprotokollen auf das OS zu untersuchen.

Ergebnisse

Bei den AEG im UICC-Stadium II und III zeigten sich zwischen Patienten mit nCRT und Patienten mit pCT keine signifikanten Unterschiede bei Patientencharakteristika und Tumorparametern. Die kumulative Inzidenz von Lokalrezidiven war nach pCT (32,8 %; 95%-KI: 18,0–48,4 %) signifikant höher als nach nCRT (7,4 %; 95%-KI: 2,3–16,5 %) (p = 0,007). Für die kumulative Inzidenz der systemischen Rezidive ergab sich kein signifikanter Unterschied zwischen den Behandlungsgruppen (52,9 %; 95%-KI: 35,4–67,7 % bzw. 38,4 %; 95%-KI: 23,7–52,9 %) (p = 0,347). In der Gesamtkohorte waren Patienten mit pCT signifikant jünger (58,3 Jahre vs. 63,0 Jahre, p = 0,016), hatten häufiger eine komplette Tumorresektion (81 % vs. 67 %, p = 0,033), mehr entfernte Lymphnoten (p = 0,036) und weniger Lymphknotenmetastasen in den resezierten Lymphnoten (p = 0,038) als Patienten mit nCRT. Bezüglich der kumulativen Inzidenz der Lokalrezidive zeigte sich auch hier ein starker Trend hinsichtlich einer verbesserten Lokalkontrolle nach nCRT (25,8 %; 95%-KI: 14,7–38,3 % vs. 12,6 %; 95%-KI: 5,5–22,8 %; p = 0,053). Es ergab sich kein signifikanter Unterschied bezüglich der kumulativen Inzidenz der systemischen Rezidive. Nach Ausschluss von Patienten mit UICC-Stadium IV zeigte sich kein signifikanter Unterschied für das OS.

Schlussfolgerung

In der Subgruppe der AEG im UICC-Stadium II/III zeigte sich nach nCRT eine bessere lokale Kontrolle als nach pCT ohne signifikante Unterschiede bezüglich des OS oder der kumulativen Inzidenz der systemischen Rezidive. In der Gesamtkohorte zeigte sich trotz vermehrter Risikofaktoren zumindest ein starker Trend zu einer verbesserten lokalen Kontrolle nach nCRT.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Klinikum rechts der Isar, Technical University Munich, Ismaninger Str. 22, 81675, Munich, Germany

    Stefan Münch, Daniel Habermehl & Stephanie E. Combs

  2. Institute of Innovative Radiotherapy (iRT), Helmholtz Zentrum München, Ingolstädter Landstraße 1, 85764, Oberschleißheim, Germany

    Daniel Habermehl & Stephanie E. Combs

  3. Department of Surgery, Klinikum Bogenhausen, Städtisches Klinikum München, Munich, Germany

    Ayman Agha

  4. Department of Radiation Oncology, Klinikum Großhadern, Ludwig-Maximilians-University (LMU), Munich, Germany

    Claus Belka

  5. Munich Cancer Registry (MCR), Munich Tumour Centre (TZM), Department of Medical Informatics, Biometry and Epidemiology (IBE), Klinikum Großhadern, Ludwig Maximilians University (LMU), Munich, Germany

    Renate Eckel, Gabriele Schubert-Fritschle & Jutta Engel

  6. Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Helmut Friess

  7. Department of Gastroenterology and Endocrinology, Klinikum Großhadern, Ludwig Maximilians University (LMU), Munich, Germany

    Alexander Gerbes

  8. Department of Surgery, Klinikum Neuperlach, Städtisches Klinikum München, Munich, Germany

    Natascha C. Nüssler

  9. Department of Gastroenterology, Klinikum Bogenhausen, Städtisches Klinikum München, Munich, Germany

    Wolfgang Schepp

  10. Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    Roland M. Schmid

  11. Department of Gastroenterology, Klinikum Neuperlach, Städtisches Klinikum München, Munich, Germany

    Wolfgang Schmitt

  12. Department of Internal Medicine, Klinik Bad Trissl, Oberaudorf, Germany

    Bernhard Weber

  13. Department of Surgery, Klinikum Großhadern, Ludwig Maximilians University (LMU), Munich, Germany

    Jens Werner

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  1. Stefan Münch
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  2. Daniel Habermehl
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  3. Ayman Agha
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  4. Claus Belka
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  9. Natascha C. Nüssler
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  14. Bernhard Weber
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  15. Jens Werner
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  16. Jutta Engel
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Corresponding author

Correspondence to Daniel Habermehl.

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Conflict of interest

S. Münch, D. Habermehl, A. Agha, C. Belka, S.E. Combs, R. Eckel, H. Friess, A. Gerbes, N.C. Nüssler, W. Schepp, R.M. Schmid, W. Schmitt, G. Schubert-Fritschle, B. Weber, J. Werner, and J. Engel declare that they have no competing interests.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Stefan Münch and Daniel Habermehl contributed equally to the manuscript.

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Münch, S., Habermehl, D., Agha, A. et al. Perioperative chemotherapy vs. neoadjuvant chemoradiation in gastroesophageal junction adenocarcinoma. Strahlenther Onkol 194, 125–135 (2018). https://doi.org/10.1007/s00066-017-1225-7

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  • DOI: https://doi.org/10.1007/s00066-017-1225-7

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