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Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy

Tumorvolumen als prognostischer Marker bei p16-positiven und p16-negativen Patienten mit Oropharyngealkarzinom unter Therapie mit definitiver intensitätsmodulierter Strahlentherapie

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Abstract

Purpose

To investigate the impact of primary gross tumor volume (pGTV) and nodal gross tumor volume (nGTV) in oropharyngeal squamous cell carcinoma (OPSCC) and the difference in their role between human papillomavirus (HPV)-positive and HPV-negative patients.

Methods

The patient cohort consists of 91 OPSCC patients treated with definitive radiochemotherapy or radiotherapy using intensity-modulated radiotherapy (IMRT). All patients had a minimum follow-up of 31 months. Volume measurements were made from computer tomography (CT) scans and HPV status was assessed by p16 immunohistochemistry. The end points were as follows: overall survival (OS), disease-free survival (DFS) and locoregional control (LRC).

Results

pGTV was a significant independent prognostic factor for overall survival (OS; p = 0.020) in p16-negative patients. nGTV of p16-negative tumors had significant prognostic value in all end points in multivariate analyses. High-stage (III–IVc) p16-negative tumors were only associated with significantly poorer OS (p = 0.046) but not with poorer LRC or DFS when compared with the low-stage (I–II) tumors. nGTV of p16-positive tumors was an independent prognostic factor for DFS (p = 0.005) and LRC (p = 0.007) in multivariate analyses.

Conclusion

pGTV may serve as an independent prognostic factor in p16-negative patients and nGTV may serve as an independent prognostic factor both in p16-positive and p16-negative patients treated with radiochemotherapy or radiotherapy using IMRT. Tumor volume may have an impact on selecting patients for de-escalation protocols in the future, both in p16-positive and p16-negative patients.

Zusammenfassung

Zielstellung

Ziel war es, die Bedeutung des makroskopischen Tumorvolumens des Primärtumors („primary gross tumor volume“, pGTV) und des makroskopischen Tumorvolumens der Lymphknoten („nodal gross tumor volume“, nGTV) bei Plattenepithelkarzinomen des Oropharynx („oropharyngeal squamous cell carcinoma“, OPSCC) und deren Unterschiede zwischen für humanes Papillomavirus (HPV) positiven und HPV-negativen Patienten zu untersuchten.

Methoden

In die Studie eingeschlossen wurden 91 OPSCC-Patienten, die mit definitiver intensitätsmodulierter Strahlentherapie („intensity-modulated radiotherapy“, IMRT) mit oder ohne gleichzeitige Chemotherapie behandelt wurden. Bei allen Patienten betrug der Nachbeobachtungszeitraum mindestens 31 Monate. Die Volumenmessungen erfolgten anhand von Computertomographie(CT)-Aufnahmen. Der HPV-Status wurde durch die p16-Immunhistochemie ermittelt. Die Endpunkte waren Gesamtüberleben („overall survival“, OS), krankheitsfreies Überleben („disease-free survival“, DFS) und lokoregionale Kontrolle („locoregional control“, LRC).

Ergebnisse

Das pGTV war ein signifikanter unabhängiger prognostischer Faktor für das OS (p = 0,20) bei p16-negativen Patienten. Das nGTV von p16-negativen Tumoren wies einen signifikanten prognostischen Wert für alle Endpunkte in multivariaten Analysen auf. p16-negative Tumoren in hohen Stadien (III-IVc) waren im Vergleich zu den Tumoren in niedrigeren Stadien (I‑II) nur mit einem signifikant schlechteren OS (p = 0,046), nicht aber mit schlechteren Werten für LRC oder DFS assoziiert. Das nGTV von p16-negativen Tumoren erwies sich in multivariaten Analysen als unabhängiger prognostischer Faktor für DFS (p = 0,005) und LRC (p = 0,007).

Schlussfolgerung

Das pGTV kann als unabhängiger prognostischer Faktor bei p16-negativen Patienten und das nGTV als unabhängiger prognostischer Faktor sowohl bei p16-positiven als auch bei p16-negativen Patienten dienen, bei denen eine Radiochemotherapie oder Strahlentherapie unter Verwendung der IMRT erfolgt. Das Tumorvolumen kann bei der Auswahl der Patienten für ein Deeskalationsprotokoll sowohl bei p16-positiven als auch bei p16-negativen Patienten eine Rolle spielen.

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Acknowledgements

This study was supported by grants from the Helsinki University Hospital Research Fund and the Finska Läkaresällskapet.

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Authors and Affiliations

  1. Department of Otorhinolaryngology—Head and Neck Surgery, University of Helsinki and Helsinki University Hospital, Kasarmikatu 11–13, 00029 HUS, Helsinki, Finland

    Timo Carpén MD, Petri Mattila & Antti Mäkitie

  2. Department of Oncology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Kauko Saarilahti

  3. Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Caj Haglund

  4. Research Program Unit, Translational Cancer Biology, University of Helsinki, Helsinki, Finland

    Caj Haglund & Jaana Hagström

  5. Department of Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Antti Markkola

  6. Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    Jussi Tarkkanen & Jaana Hagström

  7. Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet and Karolinska Hospital, Stockholm, Sweden

    Antti Mäkitie

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  1. Timo Carpén MD
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Correspondence to Timo Carpén MD.

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Conflict of interest

T. Carpén, K. Saarilahti, C. Haglund, A. Markkola, J. Tarkkanen, J. Hagström, P. Mattila, and A. Mäkitie declare that they have no competing interests.

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This article does not contain any studies with human participants or animals performed by any of the authors. Consent was obtained from all patients identifiable from images or other information within the manuscript. In the case of underage patients, consent was obtained from a parent or legal guardian.

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Carpén, T., Saarilahti, K., Haglund, C. et al. Tumor volume as a prognostic marker in p16-positive and p16-negative oropharyngeal cancer patients treated with definitive intensity-modulated radiotherapy. Strahlenther Onkol 194, 759–770 (2018). https://doi.org/10.1007/s00066-018-1309-z

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