Factors Affecting Response and Survival in Radiotherapy

  • Michael AwadallahEmail author
  • Kurt Nisi
  • Ketan J. Patel


We are investigating the different variables that can potentially affect tumor response to radiation therapy. These factors can be tumor-specific, patient-specific, therapy-specific, or a combination of these variables. Noteworthy factors include extranodal extension, tumor microenvironment, time to adjunctive radiation therapy, tumor volume, margin status, adjunctive concurrent chemotherapy, and fractionation schedule/dose. This chapter sheds light on how the previously mentioned factors can potentially impact the efficacy of radiation treatment on locoregional recurrence, overall survival, and disease-free specific survival as a treatment modality for oral cancer.


Radiation therapy Efficacy Extranodal extension Margin status Fractionation dose Tumor volume Locoregional control Chemotherapy 


  1. 1.
    Lavaf A, et al. Adjuvant radiotherapy improves overall survival for patients with lymph node-positive head and neck squamous cell carcinoma. Cancer. 2008;112(3):535–43.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Kao J, et al. Adjuvant radiotherapy and survival for patients with node-positive head and neck cancer: an analysis by primary site and nodal stage. Int J Radiat Oncol Biol Phys. 2008;71(2):362–70.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Sanguineti G, Forastiere AA. Determining the survival benefit of adjuvant radiotherapy in patients with node-positive head and neck cancer. Nat Clin Pract Oncol. 2008;5:694.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Perri F, et al. Radioresistance in head and neck squamous cell carcinoma: biological bases and therapeutic implications. Head Neck. 2015;37(5):763–70.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Silva P, et al. Clinical and biological factors affecting response to radiotherapy in patients with head and neck cancer: a review. Clin Otolaryngol. 2007;32(5):337–45.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Nordsmark M, Overgaard J. A confirmatory prognostic study on oxygenation status and loco-regional control in advanced head and neck squamous cell carcinoma treated by radiation therapy. Radiother Oncol. 2000;57(1):39–43.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Allal AS, et al. Standardized uptake value of 2-[18F] fluoro-2-deoxy-d-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy. J Clin Oncol. 2002;20(5):1398–404.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    La TH, et al. Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2009;74(5):1335–41.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Jeong J, et al. Estimate of the impact of FDG-avidity on the dose required for head and neck radiotherapy local control. Radiother Oncol. 2014;111(3):340–7.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Buffa FM, et al. Molecular marker profiles predict locoregional control of head and neck squamous cell carcinoma in a randomized trial of continuous hyperfractionated accelerated radiotherapy. Clin Cancer Res. 2004;10(11):3745–54.CrossRefGoogle Scholar
  11. 11.
    Begg AC. Predicting recurrence after radiotherapy in head and neck cancer. Semin Radiat Oncol. 2012;22(2):108–18.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Alsner J, Sorensen SB, Overgaard J. TP53 mutation is related to poor prognosis after radiotherapy, but not surgery, in squamous cell carcinoma of the head and neck. Radiother Oncol. 2001;59(2):179–85.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Somers KD, et al. Frequent p53 mutations in head and neck cancer. Cancer Res. 1992;52(21):5997–6000.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Csuka O, et al. Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer. Pathol Oncol Res. 1997;3(3):204–10.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Haffty BG, Glazer PM. Molecular markers in clinical radiation oncology. Oncogene. 2003;22(37):5915–25.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Sittel C, et al. Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity. Oral Oncol. 1999;35(6):583–9.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Jacob R, et al. Heterogeneity of squamous cell carcinomas of the head and neck-analysis of tumor biologic factors and proliferation rates. Laryngoscope. 1996;106(9):1170–5.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Raybaud H, et al. Nuclear DNA content, an adjunct to p53 and Ki-67 as a marker of resistance to radiation therapy in oral cavity and pharyngeal squamous cell carcinoma. Int J Oral Maxillofac Surg. 2000;29(1):36–41.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Ang KK, et al. Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res. 2002;62(24):7350–6.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Fu KK, et al. A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: first report of RTOG 9003. Int J Radiat Oncol Biol Phys. 2000;48(1):7–16.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Ho AS, et al. Quantitative survival impact of composite treatment delays in head and neck cancer. Cancer. 2018;124(15):3154–62.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Overgaard J, 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.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    González Ferreira JA, et al. Effect of radiotherapy delay in overall treatment time on local control and survival in head and neck cancer: review of the literature. Rep Pract Oncol Radiother. 2015;20(5):328–39.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Harris JP, et al. Association of survival with shorter time to radiation therapy after surgery for US patients with head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2018;144(4):349–59.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Graboyes EM, et al. Effect of time to initiation of postoperative radiation therapy on survival in surgically managed head and neck cancer. Cancer. 2017;123(24):4841–50.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Sanguineti G, et al. Accelerated versus conventional fractionated postoperative radiotherapy for advanced head and neck cancer: results of a multicenter phase III study. Int J Radiat Oncol Biol Phys. 2005;61(3):762–71.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Lacas B, et al. Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis. Lancet Oncol. 2017;18(9):1221–37.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Baujat B, et al. Hyperfractionated or accelerated radiotherapy for head and neck cancer. Cochrane Database Syst Rev. 2010;12:Cd002026.Google Scholar
  29. 29.
    Radoi L, Luce D. A review of risk factors for oral cavity cancer: the importance of a standardized case definition. Community Dent Oral Epidemiol. 2013;41(2):97–109, e78–91.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Browman GP, et al. Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med. 1993;328(3):159–63.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Chen AM, et al. Tobacco smoking during radiation therapy for head-and-neck cancer is associated with unfavorable outcome. Int J Radiat Oncol Biol Phys. 2011;79(2):414–9.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Rabinovitch R, et al. Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiotherapy: a secondary analysis of RTOG trial 90-03. Head Neck. 2006;28(4):287–96.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Pai PC, et al. Impact of pretreatment body mass index on patients with head-and-neck cancer treated with radiation. Int J Radiat Oncol Biol Phys. 2012;83(1):e93–e100.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Amit M, et al. Improvement in survival of patients with oral cavity squamous cell carcinoma: an international collaborative study. Cancer. 2013;119(24):4242–8.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Zhang H, et al. Survival outcomes of patients with advanced oral cavity squamous cell carcinoma treated with multimodal therapy: a multi-institutional analysis. J Otolaryngol Head Neck Surg. 2013;42:30.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Iyer NG, et al. Randomized trial comparing surgery and adjuvant radiotherapy versus concurrent chemoradiotherapy in patients with advanced, nonmetastatic squamous cell carcinoma of the head and neck: 10-year update and subset analysis. Cancer. 2015;121(10):1599–607.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Daly ME, et al. Intensity-modulated radiotherapy for oral cavity squamous cell carcinoma: patterns of failure and predictors of local control. Int J Rad Oncol Biol Phys. 2011;80(5):1412–22.CrossRefGoogle Scholar
  38. 38.
    Parsons JT, et al. An analysis of factors influencing the outcome of postoperative irradiation for squamous cell carcinoma of the oral cavity. Int J Radiat Oncol Biol Phys. 1997;39(1):137–48.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Hinerman RW, et al. Postoperative irradiation for squamous cell carcinoma of the oral cavity: 35-year experience. Head Neck. 2004;26(11):984–94.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Bernier J, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350(19):1945–52.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Ooishi M, et al. Patterns of failure after postoperative intensity-modulated radiotherapy for locally advanced and recurrent head and neck cancer. Jpn J Clin Oncol. 2016;46(10):919–27.PubMedCrossRefPubMedCentralGoogle Scholar

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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Department of Oral and Maxillofacial SurgeryNorth Memorial Medical CenterMinneapolisUSA
  2. 2.Minneapolis Radiation OncologyMinneapolisUSA

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