Skip to main content
Log in

Individualized treatment of head neck squamous cell carcinoma patients aged 70 or older with radiotherapy alone or associated to cisplatin or cetuximab: impact of weekly radiation dose on loco-regional control

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

The purpose of this study is to evaluate if, in elderly HNC patients, loco-regional control (LRC) is influenced by average weekly radiation dose (AWD). From 2009 to 2017, 150 consecutive HNC elderly patients were analyzed. AWD was calculated by dividing total dose in Gray by overall treatment time in weeks. Patients were divided in 2 groups: Group 1 (70–75 years) and Group 2 (> 75 years). Primary endpoint was LRC; secondary endpoints were overall survival (OS) and compliance to treatment. The median age was 76 years (range 70–92), the distribution of patients by age was 72 and 78 patients in Group 1 and in Group 2, respectively; overall median follow-up was 23 months. Optimal cut-off of AWD for LRC was 9.236 (p = 0.018). Median OS was 73 months. In univariate survival analysis low PS (p = 0.005), T3–T4 (p = 0.021), Stage III–IV (p = 0.046) and AWDLow (< 9.236) (p = 0.018) were significantly associated with lower LRC; low PS (p < 0.001) and Group 2 (p = 0.006) were also associated with lower OS. Considering patients treated with radiotherapy alone AWDLow was significantly associated with lower LRC (p = 0.04) whereas among patient treated with chemoradiotherapy AWD did not affected LRC (p = 0.18). The multivariate analysis confirmed the significant value of PS for the prediction of LRC and OS (p = 0.035 and p < 0.001, respectively). In elderly patients an AWD of > 9.236 Gy was found to be beneficial for RT alone regimen. When radiotherapy alone is indicated in elderly patients an effort should be made to maintain an increased AWD in order to improve LRC.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc. 2008;83(4):489–501. https://doi.org/10.4065/83.4.489.

    Article  PubMed  Google Scholar 

  2. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27(17):2758–65. https://doi.org/10.1200/JCO.2008.20.8983.

    Article  PubMed  Google Scholar 

  3. Pignon JP, le Maître A, Bourhis J, MACH-NC Collaborative Group. Meta-analyses of chemotherapy in head and neck cancer (MACH-NC): an update. Int J Radiat Oncol Biol Phys. 2007;69(2 Suppl):S112–4. https://doi.org/10.1016/j.ijrobp.2007.04.088.

    Article  PubMed  Google Scholar 

  4. Belgioia L, Desideri I, Errico A, et al. Safety and efficacy of combined radiotherapy, immunotherapy and targeted agents in elderly patients: a literature review. Crit Rev Oncol Hematol. 2019;133:163–70. https://doi.org/10.1016/j.critrevonc.2018.11.009.

    Article  PubMed  Google Scholar 

  5. Murthy VH, Krumholz HM, Gross CP. Participation in cancer clinical trials: race-, sex-, and age-based disparities. JAMA. 2004;291(22):2720–6. https://doi.org/10.1001/jama.291.22.2720.

    Article  CAS  PubMed  Google Scholar 

  6. Porceddu SV, Haddad RI. Management of elderly patients with locoregionally confined head and neck cancer. Lancet Oncol. 2017;18(5):e274–83. https://doi.org/10.1016/S1470-2045(17)30229-2.

    Article  PubMed  Google Scholar 

  7. Allal AS, Maire D, Becker M, et al. Feasibility and early results of accelerated radiotherapy for head and neck carcinoma in the elderly. Cancer. 2000;88(3):648–52.

    Article  CAS  Google Scholar 

  8. Bourhis J, Overgaard J, Audry H, et al. Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH) Collaborative Group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet. 2006;368(9538):843–54. https://doi.org/10.1016/s0140-6736(06)69121-6.

    Article  PubMed  Google Scholar 

  9. Hoffstetter S, Marchal C, Peiffert D, et al. Treatment duration as a prognostic factor for local control and survival in epidermoid carcinomas of the tonsillar region treated by combined external beam irradiation and brachytherapy. Radiother Oncol. 1997;45(2):141–8.

    Article  CAS  Google Scholar 

  10. Budczies J, Klauschen F, Sinn BV, Gyorffy B, Schmitt WD, Darb-Esfahani S, Denkert C. Cutoff finder: a comprehensive and straightforward web application enabling rapid biomarker cutoff optimization. PLoS One 2012;7(12):e51862. https://doi.org/10.1371/journal.pone.0051862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Dragovic AF, Bonner JA, Spencer SA, et al. Impact of average weekly dose of radiation during radiotherapy alone or chemoradiotherapy in head and neck cancer. Head Neck. 2011;33(11):1551–6. https://doi.org/10.1002/hed.21634.

    Article  PubMed  Google Scholar 

  12. Rim CH, Yoon WS, Lee JA, et al. Factors predicting intolerance to definitive conventional radiotherapy in geriatric patients. Strahlenther Onkol. 2018. https://doi.org/10.1007/s00066-018-1318-y.

    Article  PubMed  Google Scholar 

  13. Maciejewski B, Preuss-Bayer G, Trott KR. The influence of the number of fractions and of overall treatment time on local control and late complication rate in squamous cell carcinoma of the larynx. Int J Radiat Oncol Biol Phys. 1983;9(3):321–8.

    Article  CAS  Google Scholar 

  14. Peters LJ, Ang KK, Thames HD Jr. Accelerated fractionation in the radiation treatment of head and neck cancer. A critical comparison of different strategies. Acta Oncol. 1988;27(2):185–94.

    Article  CAS  Google Scholar 

  15. Overgaard J, Hansen HS, Specht L, et al. Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: dAHANCA 6 and 7 randomised controlled trial. Lancet. 2003;362(9388):933–40.

    Article  Google Scholar 

  16. Lacas B, Bourhis J, Overgaard J, et al. MARCH Collaborative Group. Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis. Lancet Oncol. 2017;18(9):1221–37. https://doi.org/10.1016/s1470-2045(17)30458-8.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Juarez JE, Choi J, St John M, et al. Patterns of care for elderly patients with locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 2017;98(4):767–74. https://doi.org/10.1016/j.ijrobp.2017.01.209.

    Article  PubMed  Google Scholar 

  18. Magrini SM, Buglione M, Corvò R, et al. Cetuximab and radiotherapy versus cisplatin and radiotherapy for locally advanced head and neck cancer: a Randomized Phase II Trial. J Clin Oncol. 2016;34(5):427–35. https://doi.org/10.1200/JCO.2015.63.1671.

    Article  CAS  PubMed  Google Scholar 

  19. Buglione M, Maddalo M, Corvò R, et al. Subgroup analysis according to human papillomavirus status and tumor site of a randomized phase ii trial comparing cetuximab and cisplatin combined with radiation therapy for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 2017;97(3):462–72. https://doi.org/10.1016/j.ijrobp.2016.10.011.

    Article  CAS  PubMed  Google Scholar 

  20. Russi EG, Moretto F, Rampino M, et al. Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: literature review and consensus. Crit Rev Oncol Hematol. 2015;96(1):167–82. https://doi.org/10.1016/j.critrevonc.2015.06.001.

    Article  PubMed  Google Scholar 

  21. Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11(1):21–8. https://doi.org/10.1016/S1470-2045(09)70311-0. (Erratum. In: Lancet Oncol. 2010 Jan; 11(1):14).

    Article  CAS  PubMed  Google Scholar 

  22. Baumann M. Is curative radiation therapy in elderly patients limited by increased normal tissue toxicity? Radiother Oncol. 1998;46(3):225–7.

    Article  CAS  Google Scholar 

  23. Oguchi M, Ikeda H, Watanabe T, et al. Experiences of 23 patients ≥ 90 years of age treated with radiation therapy. Int J Radiat Oncol Biol Phys. 1998;41(2):407–13.

    Article  CAS  Google Scholar 

  24. Italiano A, Ortholan C, Dassonville O, et al. Head and neck squamous cell carcinoma in patients aged ≥ 80 years: patterns of care and survival. Cancer. 2008;113(11):3160–8. https://doi.org/10.1002/cncr.23931.

    Article  PubMed  Google Scholar 

  25. Merlano M, Grimaldi A, Benasso M, et al. Alternating cisplatin-5-fluorouracil and radiotherapy in head and neck cancer. Am J Clin Oncol. 1988;11(5):538–42.

    Article  CAS  Google Scholar 

  26. Neve M, Jameson MB, Govender S, et al. Impact of geriatric assessment on the management of older adults with head and neck cancer: a pilot study. J Geriatr Oncol. 2016;7(6):457–62. https://doi.org/10.1016/j.jgo.2016.05.006.

    Article  PubMed  Google Scholar 

  27. Pottel L, Lycke M, Boterberg T, et al. G-8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy. BMC Cancer. 2015;9(15):875. https://doi.org/10.1186/s12885-015-1800-1.

    Article  Google Scholar 

  28. Pottel L, Lycke M, Boterberg T, et al. Serial comprehensive geriatric assessment in elderly head and neck cancer patients undergoing curative radiotherapy identifies evolution of multidimensional health problems and is indicative of quality of life. Eur J Cancer Care (Engl). 2014;23(3):401–12. https://doi.org/10.1111/ecc.12179.

    Article  CAS  Google Scholar 

  29. Agnese D, Belgioia L, Bacigalupo A, et al. Prolonged complete remission after induction chemotherapy followed by chemoradiation with tomotherapy in metastatic nasopharyngeal cancer. Anticancer Res. 2014;34(9):5075–8.

    PubMed  Google Scholar 

  30. Corvò R, Lamanna G, Vagge S, Belgioia L, et al. Once-weekly stereotactic radiotherapy for patients with oligometastases: compliance and preliminary efficacy. Tumori. 2013;99(2):159–63. https://doi.org/10.1700/1283.14186.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

LB, AB, FM, RC contributed to study concepts and design; IC, SC, EV data collection; LB, FM data analysis and interpretation; FM statistical analysis; LB manuscript preparation and editing; AB, RC, GP, SV manuscript review.

Corresponding author

Correspondence to Liliana Belgioia.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Belgioia, L., Bacigalupo, A., Missale, F. et al. Individualized treatment of head neck squamous cell carcinoma patients aged 70 or older with radiotherapy alone or associated to cisplatin or cetuximab: impact of weekly radiation dose on loco-regional control. Med Oncol 36, 42 (2019). https://doi.org/10.1007/s12032-019-1264-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-019-1264-2

Keywords

Navigation