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Nasopharyngeal carcinoma in a low incidence European area

A prospective observational analysis from the Head and Neck Study Group of the Italian Society of Radiation Oncology (AIRO)

Nasopharynxkarzinom in einem europäischen Gebiet mit geringer Inzidenz

Eine prospektive Beobachtungsanalyse der Kopf- und Hals-Studiengruppe der Italienischen Gesellschaft für Radioonkologie (AIRO)

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Abstract

Purpose

To evaluate the outcomes with respect to long-term survival and toxicity in patients with nasopharyngeal carcinoma (NPC) treated in a European country with low incidence.

Materials and methods

A prospective observational study carried out by the AIRO Head and Neck group in 12 Italian institutions included 136 consecutive patients treated with radiotherapy (RT) ± chemotherapy (CHT) for NPC (without distant metastasis) between January 1, 2008 and December 31, 2010.

Results

The disease-specific survival (DSS), overall survival (OS), and disease-free survival (DFS) at 5 years were 92 (±2), 91 (±3), and 69 % (±5 %), respectively. Distant failure was the most frequent modality of relapse. The local, regional, and locoregional control at 5 years were 89 (±3), 93 (±3), and 84 % (±4 %), respectively. The incidence of acute and late toxicity and the correlations with different clinical/technical variables were analyzed. Neoadjuvant CHT prolongs radiotherapy overall treatment time (OTT) and decreases treatment adherence during concomitant chemoradiotherapy. An adequate minimum dose coverage to PTV(T) is a predictive variable well related to outcome.

Conclusion

Our data do not substantially differ in terms of survival and toxicity outcomes from those reported in larger series of patients treated in countries with higher incidences of NPC. The T stage (TNM 2002 UICC classification) is predictive of DSS and OS. The GTV volume (T ± N) and an adequate minimum PTV(T) coverage dose (D95 %) were also identified as potential predictive variables. Sophisticated technologies of dose delivery (IMRT) with image-guided radiotherapy could help to obtain better minimum PTV(T) coverage dose with increased DFS; distant metastasis after treatment still remains an unresolved issue.

Zusammenfassung

Ziel

Bewertung von langfristigem Überleben und Toxizität bei Patienten mit Nasopharynxkarzinom (NPC), die in einem europäischen Land mit geringer Inzidenz behandelt wurden.

Materialien und Methoden

Die prospektive Beobachtungsanalyse, durchgeführt von der AIRO Kopf- und Hals-Gruppe an 12 italienischen Zentren, beinhaltete 136 Folgepatienten, die zwischen 1. Januar 2008 und 31. Dezember 2010 wegen NPC (ohne Fernmetastasen) mit Strahlentherapie (RT) ± Chemotherapie (CHT) behandelt wurden.

Ergebnisse

Die krankheitsspezifische Überlebensrate (DSS), das Gesamtüberleben (OS) und krankheitsfreie Überleben (DFS) nach 5 Jahren waren jeweils 92 % (±2 %), 91 % (±3 %) und 69 % (±5 %). Die häufigsten Rezidive waren Fernmetastasen. Die Kontrollwahrscheinlichkeit liegt lokal, regional und lokoregional nach 5 Jahren bei 89 % (±3 %), 93 % (±3 %) und 84 % (±4 %). Die Inzidenz der akuten und späten Toxizität und Korrelationen mit verschiedenen klinisch/technischen Variablen wurden analysiert. Neoadjuvante CHT verlängert die Zeit der Gesamtbehandlung und reduziert die Therapiecompliance während der zusammen durchgeführten Radiochemotherapie. Eine angemessene Minimaldosis von PTV(T) ist eine prädiktive Variable, die gut mit der Überlebensquote korreliert.

Schlussfolgerung

Unsere Daten zeigen keinen großen Unterschied bezüglich der Überlebensquote und Toxizität im Vergleich zu denen aus Ländern mit höherer NPC-Inzidenz. Das T‑Stadium (TNM 2002 UICC-Klassifikation) ist prädiktiv für DSS und OS. Das GTV-Volumen (T ± N) und eine ausreichende Mindestdosis an PTV(T) (D95 %) sind zusätzliche potenziell prädiktive Variablen. Weiterentwickelte IMRT-Technologien zur Dosisverabreichung mittels bildgestützter Strahlentherapie könnten zu besserer PTV(T)-Minimaldosis mit erhöhter DFS führen; Fernmetastasen nach der Behandlung bleiben ein ungelöstes Problem.

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Acknowledgements

The authors thank the 136 patients who consented to release their data for the analysis. A particular acknowledgement to Dr. Filippo Bertoni for his help with statistical analyses and to Dr. Gundi Steinhilber for the German translation of the abstract.

Author information

Authors and Affiliations

  1. Istituto del Radio, Brescia University, A.O. Spedali Civili di Brescia, Piazzale Spedali Civili, 1, 25123, Brescia, Italy

    S. Tonoli M.D., R. Gatta & S. M. Magrini

  2. Milan-European Institute of Oncology, Milan, Italy

    D. Alterio

  3. Roma-Isola Tiberina Hospital, Rome, Italy

    O. Caspiani

  4. IRCCS A.O.U. San Martino IST Genoa, Genoa, Italy

    A. Bacigalupo

  5. Bologna-S.Orsola Hospital, Bologna, Italy

    F. Bunkheila

  6. Roma-S.Camillo Hospital, Rome, Italy

    M. Cianciulli

  7. Busto Arsizio Hospital, Busto Arsizio, Italy

    A. Merlotti

  8. Milan University – Monza S. Gerardo Hospital, Milan, Italy

    A. Podhradska

  9. Turin University, Turin, Italy

    M. Rampino

  10. Treviglio Hospital, Treviglio, Italy

    L. Bruschieri

  11. Prato Hospital, Prato, Italy

    S. M. Magrini

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  1. S. Tonoli M.D.
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Corresponding author

Correspondence to S. Tonoli M.D..

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Conflict of interest

S. Tonoli , D. Alterio, O. Caspiani, A. Bacigalupo, F. Bunkheila, M. Cianciulli, A. Merlotti, A. Podhradska, M. Rampino, D. Cante, L. Bruschieri, R. Gatta, and S.M. Magrini state that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Patients’ rights

the treatment given to patients was not experimental, representing the standard treatment in the single institution according to the national and international guidelines. Every patient gave informed consent for the treatment and the permission to use their data for this prospective observational analysis.

Ethical standards

The treatments given to the patients have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Contribution author(s)

Study concept: Sandro Tonoli

Study design: Sandro Tonoli

Data acquisition: S. Tonoli, D. Alterio, O. Caspiani, A. Bacigalupo, F. Bunkheila, M. Cianciulli, A. Merlotti, A. Podhradska, M. Rampino, D. Cante, L. Bruschieri, S.M. Magrini

Quality control of data and algorithms: Sandro Tonoli, Roberto Gatta

Data analysis and interpretation: Sandro Tonoli

Statistical analysis: Sandro Tonoli

Manuscript preparation: S. Tonoli

Manuscript editing: S. Tonoli, D. Alterio, O. Caspiani, A. Bacigalupo, F. Bunkheila, M. Cianciulli, A. Merlotti, A. Podhradska, M. Rampino, D. Cante, L. Bruschieri, S.M. Magrini

Manuscript review: S. Tonoli, D. Alterio, O. Caspiani, A. Bacigalupo, F. Bunkheila, M. Cianciulli, A. Merlotti, A. Podhradska, M. Rampino, D. Cante, L. Bruschieri, S.M. Magrini

Names of principal investigators: S. Tonoli, D. Alterio, O. Caspiani, A. Bacigalupo, F. Bunkheila, M. Cianciulli, A. Merlotti, A. Podhradska, M. Rampino, D. Cante, L. Bruschieri, S.M. Magrini

Caption Electronic Supplementary Material

66_2016_1052_MOESM1_ESM.docx

Table 1: Number and percentage of cases treated with neo-adjuvant chemotherapy and/or concomitant chemotherapy according to the initial clinical stage (TNM 6th ed.)

Table 2: dose/fraction, number of fractions and total doses prescribed for high dose PTV

Table 3: Dose constraints for organs at risk

Table 4: dosimetric results description

Table 5: Radiotherapy overall treatment time (OTT: days) considering patients treated with alternated chemo-RT or not

Table 6: Influence of chemotherapy timing on the prolongation of radiotherapy overall treatment time

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Tonoli, S., Alterio, D., Caspiani, O. et al. Nasopharyngeal carcinoma in a low incidence European area. Strahlenther Onkol 192, 931–943 (2016). https://doi.org/10.1007/s00066-016-1052-2

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  • DOI: https://doi.org/10.1007/s00066-016-1052-2

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