Skip to main content
SpringerLink
Log in

Hyperfractionated radiotherapy for head and neck cancer: general results of theCatalan Institute of Oncology (ICO)

Radioterapia hiperfraccionada en el cáncer de cabeza y cuello: resultados generales del Institut Català d’ Oncologia

  • Originales
  • Published:
Revista de Oncología Aims and scope Submit manuscript

Abstract

Purpose. In order to provide more information for the clinician and to analyse the role of twice-a-day radiotherapy on the specific overall survival (OS), disease-free survival (DFS), local disease-free survival (LDFS), metastasis free survival (MFS) and toxicity, a retrospective study of head and neck cancer at Institut Català d’Oncologia has been undertaken.

Patients and methods. From 1992 to 1999, 373 patients were selected for this study with a median follow-up period of 20.96 months (range 9–95). Mean age of the patients was 57 years (range 18–85). Stages were distributed as follows: 66 patients in stage II (17.7%), 100 in stage III (26.8%) and 198 (53,1%) in stage IV. Twice-a-day radiotherapy was administered to head and neck cancer with a curative intent in all patients. Three hundred and fifty-seven patients received 1.2 Gy per fraction with a 6-hour interfraction interval, and 15 patients received 1.6 Gy per fraction with the same interval. The primary site in most patients was the oropharynx, hypopharynx, or larynx. All patients received radiotherapy to the primary site, with or without planned neck dissection after radiotherapy. Induction chemotherapy was used in same indications. Surgery at the primary site was reserved for salvage of radiotherapy failures. Mean given dose was 79.14 Gy (range 64.80–84) with twice-a-day external radiation therapy. One hundred and sixty-nine patients (45.30%) received induction chemotherapy as part of the initial treatment plan. Univariate and multivariate analysis has been carried out.

Results. OS for the entire group was 71.57% at 2 years and 58.76% at 5 and 8 years. Probability of DFS was 68.34% at 2 years, 53.95% at 5 years and 48.53% at 8 years. The LDFS was 72.84%, 60.26% and 54.20% at 2, 5 and 8 years respectively. The MFS probability was 88.14%, 82.27% and 78.35% at 3, 5 and 8 years respectively.

Multivariated analysis to OS demonstrate that localization (oropharynx, hypopharynx, supraglottis, rinopharynx, and glottis in growing order of survival), stage (IV, III and II in growing order of survival), and feeding through a nasogastric tube (with and without in a growing order of survival) were prognostic factors. Multivariated analysis for DFS demonstrate that patients with a stage III and IV, oropharynx localization and patients that received feeding through a nasogastric tube were prognostic factors. Multivariated analysis for LDFS demonstrated that localization (oropharynx, hypopharynx, supraglottis, glottis and rinopharynx in growing order of survival), stage (IV, III and II in a growing order of survival) and total dose (in a growing survival order: less or equal to 78.4 Gy, superior to 80.4 Gy, between 79.4 and 80.4 Gy, and between 78.4 and 79.4 Gy) remains as a prognostic factors. Multivariated analysis for MFS demonstrate that localization (glottis versus supraglottis, oropharynx, rinopharynx, hypopharynx) was a prognostic factor. Mucosal toxicity was frequent (87.9% ≥ grade III) but manageable. Thirty percent of patients required feeding tube.

Conclusion. We conclude that patients with head and neck cancer undergoing twice-a-day external radiotherapy can be effectively managed. Overall survival and long-term local control are excellent and toxicity is acceptable.

Resumen

Propósito. Desarrollar un estudio prospectivo del cáncer de cabeza y cuello en el Institut Català d’Oncologia con el objetivo de proveer información para el clínico y analizar el papel de la radioterapia dos veces al día sobre la supervivencia específica global (SG), la supervivencia libre de enfermedad (SLE), la supervivencia libre de enfermedad local (SLEL), la supervivencia libre de metástasis (SLM) y la toxicidad.

Pacientes y métodos. Desde 1992 a 1999 se seleccionaron para este estudio 373 pacientes con cáncer de cabeza y cuello, con un período de seguimiento medio de 20,96 meses (rango 9–95). La edad media de los pacientes fue 57 años (rango 18–85). Los estadios se distribuyeron como sigue: 66 pacientes en estadio II (17,7%), 100 en estadio III (26,8%) y 198 en estadio IV (53,1%). La radioterapia dos veces al día se administró con una intención curativa en todos los pacientes. Trescientos cincuenta y siete pacientes recibieron 1,2 Gy por fracción con un intervalo entre fracciones de 6 horas y 15 pacientes recibieron 1,6 Gy por fracción en el mismo intervalo. Los sitios primarios fueron en la mayoría de los pacientes la orofaringe, la hipofaringe o la laringe. Todos los pacientes recibieron radioterapia en el sitio primario con o sin disección de cuello después de radioterapia. Se utilizó quimioterapia de inducción con las mismas indicaciones. Se utilizó cirugía en el sitio primario sólo en los casos de fallo de la radioterapia. La dosis media dada fue de 79,14 Gy (rango 64,80–84) con terapia de radiación externa dos veces al día. Ciento sesenta y nueve pacientes recibieron quimioterapia de inducción como parte del plan inicial de tratamiento. El análisis estadístico se realizó mediante análisis univariante y multivariante.

Resultados. La SG para el grupo completo fue de 71,57% a los dos años y 58,76% a los 5 y 8 años. La probabilidad de SLE fue de 68,34% a los 2 años, 53,95% a los 5 años y 48,53% a los 8 años. La SLEL fue de 72,84%, 60,26% y 54,20% a los 2, 5 y 8 años, respectivamente. La probabilidad de SLM fue 88,14%, 82,27% y 78,35% a los 3, 5 y 8 años respectivamente.

El análisis multivariante de la SG demostró que la localización (orofaringe, hipofaringe, supraglotis, rinofaringe y glotis en orden creciente de supervivencia), estadio (IV, III y II en orden creciente de supervivencia) y alimentación mediante tubo nasogástrico (con y sin en orden creciente de supervivencia) fueron factores pronóstico. El análisis multivariante de la SLE demostró que los estadios III y IV, la localización orofaríngea, y la alimentación mediante tubo nasogástrico fueron factores pronóstico. El análisis multivariante de la SLEL demostró que la localización (orofaringe, hipofaringe, supraglotis, glotis y rinofaringe en orden creciente de supervivencia), estadio (IV, III y II en orden creciente de supervivencia) y dosis total (en orden creciente de supervivencia: menor o igual a 78,4 Gy, superior a 80,4 Gy, entre 79,4 y 80,4 Gy, y entre 78,4 y 79,4 Gy) fueron factores pronóstico. El análisis multivariante de la SLM demostró que la localización (glotis frente a supraglotis, orofaringe, rinofaringe, hipofaringe) fue factor pronóstico. La toxicidad de la mucosa fue frecuente (87,9% mayor o igual a grado III) pero manejable. El 30% de los pacientes requirieron ser intubados para su alimentación.

Conclusión. Los pacientes con cáncer de cabeza y cuello que reciben una radioterapia externa dos veces al día pueden ser tratados efectivamente. La supervivencia global y el control local a largo plazo son excelentes y la toxicidad es aceptable.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Thames HD, Whithers HR, Peters LJ, Fletcher GH. Changes in early and late radiation responses with altered dose fractionation: Implications for dose-survival relationships. Int J Radiat Oncol Biol Phys 1982;8:219–26.

    Article  Google Scholar 

  2. Withers HR, Peters LJ, Thames HD, Fletcher GH. Hyperfractionation. Int J Radiat Oncol Biol Phys 1982;8:1807–9.

    Article  CAS  Google Scholar 

  3. Hall EJ. Radiobiology for the Radiologist. 4th ed. Philadelphia, PA: Lippincott, 1994.

    Google Scholar 

  4. Steel GG. Basic Clinical Radiobiology. London: Edward Arnold, 1993.

    Google Scholar 

  5. Beck-Bornholdt HP, Dubben HH, Liertz-Petersen C, Willers H. Hyper fractionation: where do we stand? Radio Oncol 1997;43:1–21.

    Article  CAS  Google Scholar 

  6. Stuschke M, Thames HD. Hyperfractionated radiotherapy of human tumours: Overview of the randomised clinical trials. Int J Radia Oncol Biol Phys 1997;37(2):259–67.

    Article  CAS  Google Scholar 

  7. Baumann M, Bentzen SM, Kiang Ang K. Hyper fractionated radiotherapy in head and neck cancer: a second look at the clinical data. Radio Oncol 1998;46:127–30.

    Article  CAS  Google Scholar 

  8. Horiot JC, Le Fur R, Guyen TN, et al. Hyper fractionation versus conventional fractionation in or pharyngeal carcinoma: final analysis of a randomised trial of the EORTC cooperative group of radiotherapy. Radio Oncol 1992;25:231–41.

    Article  CAS  Google Scholar 

  9. Bentzen SM, Dische S. Altered fractionation in radiotherapy for head and neck cancer: too early to close the race and announce the winner? Radio Oncol 1999;51:105–7.

    Article  CAS  Google Scholar 

  10. Kaplan EL, Meier P. Nonparametric estimation for incomplete observations. J Amer Statist Assoc 1958;53:457–81.

    Article  Google Scholar 

  11. Mantel N, Haenszel W. Chi-square tests with one-degree of freedom extensions of Mantel-Haenszel procedure. J Am Stat Assoc 1963;58:690–700.

    Google Scholar 

  12. Cox DR. Regression models and life tables. J R Stat Soc 1972;34(B):187–220.

    Google Scholar 

  13. Wang CC. Local control of or pharyngeal carcinoma after two accelerated hyper fractionation radiation therapy schemes. Int J Radiat Oncol Biol Phys 1988;14:1143–6.

    Article  CAS  Google Scholar 

  14. Wang CC, Blitzer PH, Suit HD. Twice-a-day radiation therapy for cancer of the head and neck. Cancer 1985;55:2100–4.

    Article  CAS  Google Scholar 

  15. Wang CC. Improved local control of advanced or pharyngeal carcinoma following twice-daily radiation therapy [abstract]. Am J Clin Oncol 1985;8:22.

    Article  Google Scholar 

  16. Wang CC, Suit HD, Blitzer DP, Blitzer PH. Twice-a-day radiation therapy for supraglotic carcinoma. Int J Radiat Oncol Biol Phys 1986;12:3–7.

    Article  CAS  Google Scholar 

  17. Wang CC. The enigma of accelerated hyper fractionated radiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys 1988;14:209–10.

    Article  CAS  Google Scholar 

  18. Johnson CR, Schmidt-Ullrich RK, Arthur DW, et al. Standard once-daily versus twice daily concomitant boost accelerated super fractionated irradiation for advanced squamous cell carcinoma of the head and neck: preliminary results of a prospective randomised trial [abstract]. Int J Radiat Oncol Biol Phys 1995;32:162.

    Article  Google Scholar 

  19. Dische S, Saunders M, Barrett A, et al. A randomised multicentre trial of CHART versus conventional radiotherapy in head and neck cancer. Radio Oncol 1997;44:123–36.

    Article  CAS  Google Scholar 

  20. Jackson SM, Weir LM, Hay JH, Tsang V, Durham JS. A randomised trial of accelerated versus conventional radiotherapy in head and neck cancer. Radio Oncol 1997;43:39–46.

    Article  CAS  Google Scholar 

  21. Horiot JC, Bontemps P, Van den Bogaert W, et al. Accelerated fractionation (AF) compared to conventional fractionation (CF) improves loco-regional control in the radiotherapy of advanced head and neck cancers: results of the EORTC 22851 randomised trial. Radio Oncol 1997;44:111–21.

    Article  CAS  Google Scholar 

  22. Overgaard J, Sand Hansen H, Overgaard M, et al. Conventional radiotherapy as primary treatment of squamous cell carcinoma of the head and neck: a randomised multicenter study of 5 versus 6 fractions per week: report from the DAHANCA 7 trial [abstract]. Int J Radiat Oncol Biol Phys 1997;32:188.

    Article  Google Scholar 

  23. Parsons JT, Mendenhall WM, Stringer SP, et al. Twice-a-day radiotherapy for squamous cell carcinoma of the head and neck: the University of Florida experience. Head Neck 1993;15:87–96.

    Article  CAS  Google Scholar 

  24. Parsons JT, Cassisi NJ, Million RR. Results of twice-a-day irradiation of squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol Phys 1984;10:2041–51.

    Article  CAS  Google Scholar 

  25. Parsons JT, Mendenhall WM, Million RR, et al. Twice-a-day irradiation of squamous cell carcinoma of the head and neck. Semin Radiat Oncol 1992;2:29–30.

    Article  Google Scholar 

  26. Mendenhall WM, Amdur RJ, Siemann DW, Parsons JT. Altered fractionation in definitive irradiation of squamous cell carcinoma of the head and neck. Curr Oph Oncol 2000; 12:207–14.

    Article  CAS  Google Scholar 

  27. Pinto L, Canary P, Araujo C, Bacelar SC, Souhami L. Prospective randomised trial comparing hyper fractionated versus conventional radiotherapy in stages III and IV or pharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1991;21:557–62.

    Article  CAS  Google Scholar 

  28. Cummings BJ, Keane TJ, Pintilie M, et al. A prospective randomised trial of hyper fractionated versus conventional once daily radiation for advanced squamous cell carcinomas of the pharynx [abstract]. Int. J Radiat Oncol Biol Phys 1996;35:235.

    Article  Google Scholar 

  29. Ang KK. Altered Fractionation Trials in Head and Neck Cancer. Sem Radiat Oncol 1998;48(4):230–6.

    Article  Google Scholar 

  30. Stuschke M, Thames HD. Fractionation sensitivities and dose-control relations of head and neck carcinomas: analysis of the randomised hyper fractionation trials. Radio Oncol 1999;51:113–21.

    Article  CAS  Google Scholar 

  31. Haffty BG. Concurrent chemo radiation in the treatment of head and neck cancer. Hematol Oncol Clin North Am 1999;13:719–42.

    Article  CAS  Google Scholar 

  32. Bourthis J, Pignon JP, Domenge C, et al. Results of 2 meta-analyses on the role of chemotherapy (CT) in head and neck squamous cell carcinoma (HNSCC) [abstract]. Int J Radiat Oncol Biol Phys 1998;42 Suppl 1:145S.

  33. Calais G, Alfonsi M, Bardet E, et al. Radiation alone (RT) versus RT with concomitant chemotherapy (CT) in stages III and IV or pharynx carcinoma: results of the 94.01 randomised study from the French Group of Radiation Oncology for Head and Neck Cancer (GORTEC) [abstract]. Int J Radiat Oncol Biol Phys 1998; 42 Suppl 1:145S.

  34. Wendt TG, Grabenbauer GG, Rodel CM, et al. Simultaneous radio chemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomised multicenter study. J Clin Oncol 1998;16:1318–24.

    Article  CAS  Google Scholar 

  35. Forastiere AA. Head and Neck Cancer: Overview of Recent Development and Future Directions. Semi Oncol 2000;27(4) Suppl 8:1–4.

    CAS  Google Scholar 

  36. Brizel DM, Albers ME, Fisher SR, et al. Hyper fractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 1998;338:1798–804.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Radiation Oncology. Institut Català d’Oncologia, L’Hospitalet del Llobregat, Barcelona, Spain

    Ramón Galiana Santamaría, Ana Boladeras Inglada, Joaquín Gómez Oliveros, Valentí Navarro Pérez & Ferran Guedea Edo

  2. Department of ENT, Ciutat Sanitària i Universitària de Bellvitge (CSUB), L’Hospitalet del Llobregat, Barcelona, Spain

    Manuel Mañós Pujol & Julio Nogués Orpí

  3. Department of Medical Oncology, Institut Català d’Oncologia. L’Hospitalet del Llobregat, Barcelona, Spain

    Ricard Mesía Nin

Authors
  1. Ramón Galiana Santamaría
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ana Boladeras Inglada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joaquín Gómez Oliveros
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Manuel Mañós Pujol
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Julio Nogués Orpí
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ricard Mesía Nin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Valentí Navarro Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ferran Guedea Edo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ferran Guedea Edo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Santamaría, R.G., Inglada, A.B., Oliveros, J.G. et al. Hyperfractionated radiotherapy for head and neck cancer: general results of theCatalan Institute of Oncology (ICO). Rev Oncol 6, 424–434 (2004). https://doi.org/10.1007/BF02712372

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02712372

Key words

Palabras clave

Search

Navigation