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Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers

Secondary results of two European randomized phase III trials (ARO 95-06, SAKK 10/94)

Hämoglobin- und Kreatininwerte als prognostische Outcome-Faktoren nach simultaner Radiochemotherapie lokal fortgeschrittener Kopf-Hals-Tumoren

Sekundäre Ergebnisse von 2 randomisierten europäischen Phase-III-Studien (ARO95-06, SAKK 10/94)

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Abstract

Background

To determine the influence of baseline laboratory values on treatment outcome in patients with locally advanced head and neck cancer (HNSCC).

Methods

Data of the randomized trials ARO 95 -06 (n = 384) and SAKK 10 /94 (n = 224) were pooled for a total sample size of 608 patients. Haemoglobin (Hb) and creatinine (Cr) were available at baseline and their association with locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS) was analyzed using univariable and multivariable Cox regression models.

Results

A total of 580 and 564 patients were available with baseline Hb and Cr values in the pooled analysis. Univariable analyses revealed that lower baseline Hb values were significantly associated with decreased LRRFS, DMFS, CSS and OS. This effect remained significant for OS when the treatment arms (radiotherapy [RT] alone vs. chemoradiation [CRT]) were analyzed separately. Higher baseline Cr was associated with improved OS in the pooled analysis. Interestingly, the prognostic value of baseline Cr appeared to be limited to the subgroup of 284 patients who were treated with CRT. In the multivariable Cox regression model lower baseline Hb remained associated with decreased OS both in the patients who received CRT (HR 0.79, 95 % CI 0.66–0.94, p = 0.009) and in those patients who underwent RT alone (HR 0.67, 95 % CI 0.58–0.78, p < 0.001). Increased baseline Cr remained significantly associated with improved OS in patients who underwent CRT (HR 0.79, 95 % CI 0.69–0.92, p = 0.002) but not in those patients who underwent RT alone.

Conclusions

An association between lower baseline Hb and inferior treatment outcome was confirmed. Baseline Cr was introduced as a prognosticator of outcome after CRT for locally advanced HNSCC.

Zusammenfassung

Hintergrund

Untersucht werden sollte der Einfluss von Baseline-Laborwerten auf das Outcome der Behandlung von Patienten mit fortgeschrittenen Kopf-Hals-Tumoren.

Methoden

Daten der randomisierten Studien ARO 95 -06 (n = 384) und SAKK 10 /94 (n = 224) wurden gepoolt, die Gesamtzahl von 608 Patienten wurde untersucht. Der Einfluss der prätherapeutischen Hämoglobin(Hb)- und Kreatininwerte auf das lokoregionäre rezidivfreien Überleben (LRRFS), das fernmetastasenfreie Überleben (DMFS), das krebsspezifische Überleben (CSS) und das Gesamtüberleben (OS) wurde unter Verwendung uni- und multivariabler Cox-Regressionsmodelle untersucht.

Ergebnisse

Insgesamt waren 580 und 564 Patienten mit Hb- und Kreatininwerten in der gepoolten Analyse verfügbar. Univariate Analysen zeigten eine signifikante Assoziation von niedrigen Baseline-Hb-Werten mit vermindertem LRRFS, DMFS, CSS und OS. Dieser Effekt blieb signifikant für das OS, wenn beide Behandlungsarme einzeln untersucht wurden. Höhere Baseline-Kreatininwerte waren mit einem verbesserten OS in der gepoolten Analyse assoziiert. Interessanterweise schien der prognostische Wert des Baseline-Kreatinin auf die Subgruppe der 284 mit simultaner Radiochemotherapie (RCT) behandelten Patienten limitiert zu sein. Nach multivariabler Analyse blieb ein niedriger Baseline-Hämoglobinwert mit einem verminderten OS assoziiert, sowohl bei Patienten mit simultaner RCT als auch bei alleiniger Bestrahlung (HR 0,79, 95 %-KI 0,66–0,94, p = 0,009 bzw. HR 0,67, 95 %-KI 0,58–0,78, p < 0,001). Ein erhöhter Baseline-Kreatininwert blieb signifikant assoziiert mit einem verbesserten OS bei Patienten mit simultaner RCT (HR 0,79, 95 %-KI 0,69–0,92, p = 0,002), aber nicht im Rahmen der alleinigen Bestrahlung.

Schlussfolgerung

Es bestätigte sich ein Zusammenhang zwischen niedrigen Baseline-Hämoglobinwerten und unterlegenem Outcome. Der Baseline-Kreatininwert wurde als neuer prognostischer Faktor für die Behandlungsergebnisse der kombinierten RCT bei fortgeschrittenen Kopf-Hals-Tumoren eingeführt.

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Acknowledgements

For the ARO 95-06 trial the following contributors enrolled patients into the trial without meeting the criteria for authorship: W. Hinkelbein, S. Koswig, P. Wust, H. Frommhold, J. Dunst, M.-L. Sautter-Bihl, M. Fritsche and S. Blass were responsible for data collection and follow-up.

Funding

The ARO 95-06 trial was supported by Grant 70-1693 of the Deutsche Krebshilfe e. V.

The SAKK 10/94 trial was supported by the Swiss State Secretariat for Education, Research and Innovation (SERI).

Author information

Authors and Affiliations

  1. Departments of Radiation Oncology, Charité Universitaetsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Pirus Ghadjar MD, Daniela Joos MD, Carmen Stromberger MD, David Kaul MD, Peter Wust MD & Volker Budach MD

  2. University Hospital Essen, Essen, Germany

    Christoph Pöttgen MD & Daniela Joos MD

  3. SAKK Coordinating Center, Bern, Switzerland

    Stefanie Hayoz PhD

  4. Medical Faculty and University Hospital, Technische Universität Dresden, Dresden, Germany

    Michael Baumann MD

  5. Kantonsspital Aarau, Aarau, Switzerland

    Stephan Bodis MD

  6. Heinrich Heine Universität Düsseldorf, Düsseldorf, Germany

    Wilfried Budach MD

  7. University Hospital Zürich, Zürich, Switzerland

    Gabriela Studer MD

  8. University Hospital Basel, Basel, Switzerland

    Frank Zimmermann MD

  9. Kantonsspital St. Gallen, St. Gallen, Switzerland

    Ludwig Plasswilm MD

  10. Department for Head and Neck Surgery, Charité Universitaetsmedizin Berlin, Berlin, Germany

    Heidi Olze MD

  11. Clinique de Genolier, Genolier, Switzerland

    Jacques Bernier MD

  12. Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland

    Daniel M. Aebersold MD

Authors
  1. Pirus Ghadjar MD
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  2. Christoph Pöttgen MD
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  14. Jacques Bernier MD
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  15. Peter Wust MD
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  17. Volker Budach MD
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Corresponding author

Correspondence to Pirus Ghadjar MD.

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Conflict of interest

P Ghadjar, C. Pöttgen, D. Joos, S Hayoz, M. Baumann, S. Bodis, W. Budach, G. Studer, C. Stromberger, F. Zimmermann, D. Kaul, L. Plasswilm, H. Olze, J Bernier, P. Wust, D.M. Aebersold and V. Budach declare that they have no competing interests.

The accompanying manuscript does not include studies on humans or animals performed by any of the authors.

Caption Electronic Supplementary Material

66_2016_999_MOESM1_ESM.pdf

Supplementary Figure 1: Scatterplot for the association between age and creatinine at baseline. There was only a weak correlation (Pearson correlation coefficient 0.15)

66_2016_999_MOESM2_ESM.pdf

Supplementary Figure 2: Scatterplot for the association between weight and creatinine at baseline. There was only a weak correlation (Pearson correlation coefficient 0.24)

66_2016_999_MOESM3_ESM.docx

Supplementary Table 1: Univariable Cox regression models for the association of baseline creatinine clearance (Cockcroft–Gault) and treatment outcome

66_2016_999_MOESM4_ESM.docx

Supplementary Table 2: Univariable Cox regression models for the association of baseline creatinine clearance (Cockcroft–Gault) and treatment by treatment arm

66_2016_999_MOESM5_ESM.docx

Supplementary Table 3: Treatment outcome analysis following chemoradiation therapy, pooled analysis of SAKK 10/94 and ARO 95-06 trials

66_2016_999_MOESM6_ESM.docx

Supplementary Table 4: Treatment outcome analysis following radiation therapy, pooled analysis of SAKK 10/94 and ARO 95-06 trials

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Ghadjar, P., Pöttgen, C., Joos, D. et al. Haemoglobin and creatinine values as prognostic factors for outcome of concurrent radiochemotherapy in locally advanced head and neck cancers. Strahlenther Onkol 192, 552–560 (2016). https://doi.org/10.1007/s00066-016-0999-3

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  • DOI: https://doi.org/10.1007/s00066-016-0999-3

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