Head and Neck Cancers

  • Daniel M. TrifilettiEmail author
  • Nicholas G. Zaorsky
  • Henry S. Park


This chapter discusses the general management of patients with head and neck cancers, with special focus on principles that guide radiotherapy management. Several key components of trimodality care and radiation field design are discussed.


Larynx Oropharynx Skin IMRT Oral cavity TORS Nasopharynx 


  1. 1.
    Apisarnthanarax S, Elliott DD, El-Naggar AK, et al. Determining optimal clinical target volume margins in head-and-neck cancer based on microscopic extracapsular extension of metastatic neck nodes. Int J Radiat Oncol Biol Phys. 2006;64:678–83.PubMedCrossRefGoogle Scholar
  2. 2.
    Ben-David MA, Diamante M, Radawski JD, et al. Lack of osteoradionecrosis of the mandible after intensity-modulated radiotherapy for head and neck cancer: likely contributions of both dental care and improved dose distributions. Int J Radiat Oncol Biol Phys. 2007;68:396–402.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Caudell JJ, Schaner PE, Desmond RA, et al. Dosimetric factors associated with long-term dysphagia after definitive radiotherapy for squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2010;76:403–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Chen AM, Li BQ, Lau DH, et al. Evaluating the role of prophylactic gastrostomy tube placement prior to definitive chemoradiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys. 2010;78:1026–32.PubMedCrossRefGoogle Scholar
  5. 5.
    Kotz T, Federman AD, Kao J, et al. Prophylactic swallowing exercises in patients with head and neck cancer undergoing chemoradiation: a randomized trial. Arch Otolaryngol Head Neck Surg. 2012;138:376–82.PubMedCrossRefGoogle Scholar
  6. 6.
    McGuirt WF, McCabe BF. Significance of node biopsy before definitive treatment of cervical metastatic carcinoma. Laryngoscope. 1978;88:594–7.PubMedCrossRefGoogle Scholar
  7. 7.
    Mehanna H, Wong WL, McConkey CC, et al. PET-CT surveillance versus neck dissection in advanced head and neck cancer. N Engl J Med. 2016;374:1444–54.PubMedCrossRefGoogle Scholar
  8. 8.
    Ettl T, El-Gindi A, Hautmann M, et al. Positive frozen section margins predict local recurrence in R0-resected squamous cell carcinoma of the head and neck. Oral Oncol. 2016;55:17–23.PubMedCrossRefGoogle Scholar
  9. 9.
    Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375:1856–67.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Gregoire V, Ang K, Budach W, et al. Delineation of the neck node levels for head and neck tumors: a 2013 update. DAHANCA, EORTC, HKNPCSG, NCIC CTG, NCRI, RTOG, TROG consensus guidelines. Radiother Oncol. 2014;110:172–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Gregoire V, Eisbruch A, Hamoir M, et al. Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck. Radiother Oncol. 2006;79:15–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Annane D, Depondt J, Aubert P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. J Clin Oncol. 2004;22:4893–900.PubMedCrossRefGoogle Scholar
  13. 13.
    Bardy J, Molassiotis A, Ryder WD, et al. A double-blind, placebo-controlled, randomised trial of active manuka honey and standard oral care for radiation-induced oral mucositis. Br J Oral Maxillofac Surg. 2012;50:221–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Delanian S, Chatel C, Porcher R, et al. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys. 2011;80:832–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Garcia-Serra A, Amdur RJ, Morris CG, et al. Thyroid function should be monitored following radiotherapy to the low neck. Am J Clin Oncol. 2005;28:255–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Mercado G, Adelstein DJ, Saxton JP, et al. Hypothyroidism: a frequent event after radiotherapy and after radiotherapy with chemotherapy for patients with head and neck carcinoma. Cancer. 2001;92:2892–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Henke M, Alfonsi M, Foa P, et al. Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2011;29:2815–20.PubMedCrossRefGoogle Scholar
  18. 18.
    Chen AM, Hall WH, Li J, et al. Brachial plexus-associated neuropathy after high-dose radiation therapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2012;84:165–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Martinez-Monge R, Gomez-Iturriaga A, Cambeiro M, et al. Phase I-II trial of perioperative high-dose-rate brachytherapy in oral cavity and oropharyngeal cancer. Brachytherapy. 2009;8:26–33.PubMedCrossRefGoogle Scholar
  20. 20.
    Cook B, Dvorak T. Wikibooks Radiation Oncology. Accessed April 2018.
  21. 21.
    Edge S, Byrd D, Compton C, et al. AJCC cancer staging manual. New York: Springer; 2010.Google Scholar
  22. 22.
    Hansen E, Roach M. Handbook of evidence-based radiation oncology. 2nd ed. Cham: Springer; 2010.CrossRefGoogle Scholar
  23. 23.
    Hristov B, Lin SH, Christodouleas JP. Radiation oncology – a question based review. 2nd ed: LWW; 2014.Google Scholar
  24. 24.
    Mortality in patients with small choroidal melanoma. COMS report no. 4. The Collaborative Ocular Melanoma Study Group. Arch Ophthalmol. 1997;115:886–93.Google Scholar
  25. 25.
    The COMS randomized trial of iodine 125 brachytherapy for choroidal melanoma: V. Twelve-year mortality rates and prognostic factors: COMS report No. 28. Arch Ophthalmol. 2006;124:1684–93.Google Scholar
  26. 26.
    Diener-West M, Hawkins BS, Markowitz JA, et al. A review of mortality from choroidal melanoma. II. A meta-analysis of 5-year mortality rates following enucleation, 1966 through 1988. Arch Ophthalmol. 1992;110:245–50.PubMedCrossRefGoogle Scholar
  27. 27.
    Hawkins BS. The Collaborative Ocular Melanoma Study (COMS) randomized trial of pre-enucleation radiation of large choroidal melanoma: IV. Ten-year mortality findings and prognostic factors. COMS report number 24. Am J Ophthalmol. 2004;138:936–51.PubMedCrossRefGoogle Scholar
  28. 28.
    Nag S, Quivey JM, Earle JD, et al. The American Brachytherapy Society recommendations for brachytherapy of uveal melanomas. Int J Radiat Oncol Biol Phys. 2003;56:544–55.PubMedCrossRefGoogle Scholar
  29. 29.
    Straatsma BR, Diener-West M, Caldwell R, et al. Mortality after deferral of treatment or no treatment for choroidal melanoma. Am J Ophthalmol. 2003;136:47–54.PubMedCrossRefGoogle Scholar
  30. 30.
    Al-Sarraf M, LeBlanc M, Giri PG, et al. Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol. 1998;16:1310–7.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Baujat B, Audry H, Bourhis J, et al. Chemotherapy in locally advanced nasopharyngeal carcinoma: an individual patient data meta-analysis of eight randomized trials and 1753 patients. Int J Radiat Oncol Biol Phys. 2006;64:47–56.PubMedCrossRefGoogle Scholar
  32. 32.
    Chen QY, Wen YF, Guo L, et al. Concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial. J Natl Cancer Inst. 2011;103:1761–70.PubMedCrossRefGoogle Scholar
  33. 33.
    Lee AW, Lau WH, Tung SY, et al. Preliminary results of a randomized study on therapeutic gain by concurrent chemotherapy for regionally-advanced nasopharyngeal carcinoma: NPC-9901 Trial by the Hong Kong Nasopharyngeal Cancer Study Group. J Clin Oncol. 2005;23:6966–75.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Lee AW, Tung SY, Chan AT, et al. Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 2006;66:142–51.PubMedCrossRefGoogle Scholar
  35. 35.
    Lee N, Harris J, Garden AS, et al. Intensity-modulated radiation therapy with or without chemotherapy for nasopharyngeal carcinoma: radiation therapy oncology group phase II trial 0225. J Clin Oncol. 2009;27:3684–90.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Lee N, Xia P, Quivey JM, et al. Intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: an update of the UCSF experience. Int J Radiat Oncol Biol Phys. 2002;53:12–22.PubMedCrossRefGoogle Scholar
  37. 37.
    Sultanem K, Shu HK, Xia P, et al. Three-dimensional intensity-modulated radiotherapy in the treatment of nasopharyngeal carcinoma: the University of California-San Francisco experience. Int J Radiat Oncol Biol Phys. 2000;48:711–22.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Lin JC, Wang WY, Liang WM, et al. Long-term prognostic effects of plasma epstein-barr virus DNA by minor groove binder-probe real-time quantitative PCR on nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2007;68:1342–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Wei WI, Sham JS. Nasopharyngeal carcinoma. Lancet. 2005;365:2041–54.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Kam MK, Leung SF, Zee B, et al. Prospective randomized study of intensity-modulated radiotherapy on salivary gland function in early-stage nasopharyngeal carcinoma patients. J Clin Oncol. 2007;25:4873–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Pow EH, Kwong DL, McMillan AS, et al. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: initial report on a randomized controlled clinical trial. Int J Radiat Oncol Biol Phys. 2006;66:981–91.PubMedCrossRefGoogle Scholar
  42. 42.
    Bristol IJ, Ahamad A, Garden AS, et al. Postoperative radiotherapy for maxillary sinus cancer: long-term outcomes and toxicities of treatment. Int J Radiat Oncol Biol Phys. 2007;68:719–30.PubMedCrossRefGoogle Scholar
  43. 43.
    Dulguerov P, Jacobsen MS, Allal AS, et al. Nasal and paranasal sinus carcinoma: are we making progress? A series of 220 patients and a systematic review. Cancer. 2001;92:3012–29.PubMedCrossRefGoogle Scholar
  44. 44.
    Le QT, Fu KK, Kaplan MJ, et al. Lymph node metastasis in maxillary sinus carcinoma. Int J Radiat Oncol Biol Phys. 2000;46:541–9.PubMedCrossRefGoogle Scholar
  45. 45.
    Allen MW, Schwartz DL, Rana V, et al. Long-term radiotherapy outcomes for nasal cavity and septal cancers. Int J Radiat Oncol Biol Phys. 2008;71:401–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Cantu G, Bimbi G, Miceli R, et al. Lymph node metastases in malignant tumors of the paranasal sinuses: prognostic value and treatment. Arch Otolaryngol Head Neck Surg. 2008;134:170–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Kim SJ, Kim K, Kim BS, et al. Phase II trial of concurrent radiation and weekly cisplatin followed by VIPD chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell Lymphoma: consortium for improving survival of lymphoma study. J Clin Oncol. 2009;27:6027–32.PubMedCrossRefGoogle Scholar
  48. 48.
    Isobe K, Uno T, Tamaru J, et al. Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters. Cancer. 2006;106:609–15.PubMedCrossRefGoogle Scholar
  49. 49.
    Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363:24–35.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Ang KK, Trotti A, Brown BW, et al. Randomized trial addressing risk features and time factors of surgery plus radiotherapy in advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001;51:571–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Beitler JJ, Zhang Q, Fu KK, et al. Final results of local-regional control and late toxicity of RTOG 9003: a randomized trial of altered fractionation radiation for locally advanced head and neck cancer. Int J Radiat Oncol Biol Phys. 2014;89:13–20.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Bernier J, Cooper JS, Pajak TF, et al. Defining risk levels in locally advanced head and neck cancers: a comparative analysis of concurrent postoperative radiation plus chemotherapy trials of the EORTC (#22931) and RTOG (# 9501). Head Neck. 2005;27:843–50.PubMedCrossRefGoogle Scholar
  53. 53.
    Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004;350:1945–52.PubMedCrossRefGoogle Scholar
  54. 54.
    Calais G, Alfonsi M, Bardet E, et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst. 1999;91:2081–6.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004;350:1937–44.PubMedCrossRefGoogle Scholar
  56. 56.
    Eisbruch A, Harris J, Garden AS, et al. Multi-institutional trial of accelerated hypofractionated intensity-modulated radiation therapy for early-stage oropharyngeal cancer (RTOG 00-22). Int J Radiat Oncol Biol Phys. 2010;76:1333–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Grabenbauer GG, Rodel C, Brunner T, et al. Interstitial brachytherapy with Ir-192 low-dose-rate in the treatment of primary and recurrent cancer of the oral cavity and oropharynx. Review of 318 patients treated between 1985 and 1997. Strahlenther Onkol. 2001;177:338–44.PubMedCrossRefGoogle Scholar
  58. 58.
    Marcial VA, Pajak TF, Kramer S, et al. Radiation Therapy Oncology Group (RTOG) studies in head and neck cancer. Semin Oncol. 1988;15:39–60.PubMedGoogle Scholar
  59. 59.
    Pignon JP, le Maitre A, Maillard E, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009;92:4–14.PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Posner MR, Hershock DM, Blajman CR, et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007;357:1705–15.CrossRefGoogle Scholar
  61. 61.
    Vermorken JB, Remenar E, van Herpen C, et al. Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer. N Engl J Med. 2007;357:1695–704.CrossRefGoogle Scholar
  62. 62.
    D’Cruz AK, Vaish R, Kapre N, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med. 2015;373:521–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Kuo P, Mehra S, Sosa JA, et al. Proposing prognostic thresholds for lymph node yield in clinically lymph node-negative and lymph node-positive cancers of the oral cavity. Cancer. 2016;122:3624–31.PubMedCrossRefGoogle Scholar
  64. 64.
    Daly ME, Le QT, Kozak MM, et al. Intensity-modulated radiotherapy for oral cavity squamous cell carcinoma: patterns of failure and predictors of local control. Int J Radiat Oncol Biol Phys. 2011;80:1412–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Peters LJ, Goepfert H, Ang KK, et al. Evaluation of the dose for postoperative radiation therapy of head and neck cancer: first report of a prospective randomized trial. Int J Radiat Oncol Biol Phys. 1993;26:3–11.PubMedCrossRefGoogle Scholar
  66. 66.
    Blanchard P, Baujat B, Holostenco V, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): a comprehensive analysis by tumour site. Radiother Oncol. 2011;100:33–40.PubMedCrossRefGoogle Scholar
  67. 67.
    Ang KK, Zhang Q, Rosenthal DI, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32:2940–50.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    O’Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17:440–51.PubMedCrossRefGoogle Scholar
  69. 69.
    Husain ZA, Chen T, Corso CD, et al. A comparison of prognostic ability of staging systems for human papillomavirus-related oropharyngeal squamous cell carcinoma. JAMA Oncol. 2017;3:358–65.PubMedCrossRefGoogle Scholar
  70. 70.
    Huang SH, Perez-Ordonez B, Weinreb I, et al. Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer. Oral Oncol. 2013;49:79–85.PubMedCrossRefGoogle Scholar
  71. 71.
    Chin RI, Spencer CR, DeWees T, et al. Reevaluation of postoperative radiation dose in the management of human papillomavirus-positive oropharyngeal cancer. Head Neck. 2016;38:1643–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Overgaard J, Mohanti BK, Begum N, et al. Five versus six fractions of radiotherapy per week for squamous-cell carcinoma of the head and neck (IAEA-ACC study): a randomised, multicentre trial. Lancet Oncol. 2010;11:553–60.PubMedCrossRefGoogle Scholar
  73. 73.
    Koutcher L, Sherman E, Fury M, et al. Concurrent cisplatin and radiation versus cetuximab and radiation for locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2011;81:915–22.PubMedCrossRefGoogle Scholar
  74. 74.
    Chera BS, Amdur RJ, Tepper J, et al. Phase 2 trial of de-intensified chemoradiation therapy for favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma. Int J Radiat Oncol Biol Phys. 2015;93:976–85.PubMedCrossRefGoogle Scholar
  75. 75.
    Fakhry C, Zhang Q, Nguyen-Tan PF, et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol. 2014;32:3365–73.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    O’Sullivan B, Huang SH, Perez-Ordonez B, et al. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol. 2012;103:49–56.PubMedCrossRefGoogle Scholar
  77. 77.
    Porceddu SV, Pryor DI, Burmeister E, et al. Results of a prospective study of positron emission tomography-directed management of residual nodal abnormalities in node-positive head and neck cancer after definitive radiotherapy with or without systemic therapy. Head Neck. 2011;33:1675–82.PubMedCrossRefGoogle Scholar
  78. 78.
    Barker CA, Morris CG, Mendenhall WM. Larynx-sparing radiotherapy for squamous cell carcinoma from an unknown head and neck primary site. Am J Clin Oncol. 2005;28:445–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Erkal HS, Mendenhall WM, Amdur RJ, et al. Squamous cell carcinomas metastatic to cervical lymph nodes from an unknown head-and-neck mucosal site treated with radiation therapy alone or in combination with neck dissection. Int J Radiat Oncol Biol Phys. 2001;50:55–63.PubMedCrossRefGoogle Scholar
  80. 80.
    McQuone SJ, Eisele DW, Lee DJ, et al. Occult tonsillar carcinoma in the unknown primary. Laryngoscope. 1998;108:1605–10.PubMedCrossRefGoogle Scholar
  81. 81.
    Reddy SP, Marks JE. Metastatic carcinoma in the cervical lymph nodes from an unknown primary site: results of bilateral neck plus mucosal irradiation vs. ipsilateral neck irradiation. Int J Radiat Oncol Biol Phys. 1997;37:797–802.PubMedCrossRefGoogle Scholar
  82. 82.
    Shoushtari A, Saylor D, Kerr KL, et al. Outcomes of patients with head-and-neck cancer of unknown primary origin treated with intensity-modulated radiotherapy. Int J Radiat Oncol Biol Phys. 2011;81:e83–91.PubMedCrossRefGoogle Scholar
  83. 83.
    Galloway TJ, Ridge JA. Management of squamous cancer metastatic to cervical nodes with an unknown primary site. J Clin Oncol. 2015;33:3328–37.PubMedCrossRefGoogle Scholar
  84. 84.
    Jesse RH, Perez CA, Fletcher GH. Cervical lymph node metastasis: unknown primary cancer. Cancer. 1973;31:854–9.PubMedCrossRefGoogle Scholar
  85. 85.
    Mourad WF, Hu KS, Shasha D, et al. Initial experience with oropharynx-targeted radiation therapy for metastatic squamous cell carcinoma of unknown primary of the head and neck. Anticancer Res. 2014;34:243–8.PubMedGoogle Scholar
  86. 86.
    Chen AM, Bucci MK, Quivey JM, et al. Long-term outcome of patients treated by radiation therapy alone for salivary gland carcinomas. Int J Radiat Oncol Biol Phys. 2006;66:1044–50.PubMedCrossRefGoogle Scholar
  87. 87.
    Chen AM, Bucci MK, Weinberg V, et al. Adenoid cystic carcinoma of the head and neck treated by surgery with or without postoperative radiation therapy: prognostic features of recurrence. Int J Radiat Oncol Biol Phys. 2006;66:152–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Chen AM, Garcia J, Lee NY, et al. Patterns of nodal relapse after surgery and postoperative radiation therapy for carcinomas of the major and minor salivary glands: what is the role of elective neck irradiation? Int J Radiat Oncol Biol Phys. 2007;67:988–94.PubMedCrossRefGoogle Scholar
  89. 89.
    Laramore GE, Krall JM, Griffin TW, et al. Neutron versus photon irradiation for unresectable salivary gland tumors: final report of an RTOG-MRC randomized clinical trial. Radiation Therapy Oncology Group. Medical Research Council. Int J Radiat Oncol Biol Phys. 1993;27:235–40.PubMedCrossRefGoogle Scholar
  90. 90.
    Mendenhall WM, Morris CG, Amdur RJ, et al. Radiotherapy alone or combined with surgery for adenoid cystic carcinoma of the head and neck. Head Neck. 2004;26:154–62.PubMedCrossRefGoogle Scholar
  91. 91.
    Mendenhall WM, Morris CG, Amdur RJ, et al. Radiotherapy alone or combined with surgery for salivary gland carcinoma. Cancer. 2005;103:2544–50.PubMedCrossRefGoogle Scholar
  92. 92.
    Terhaard CH, Lubsen H, Rasch CR, et al. The role of radiotherapy in the treatment of malignant salivary gland tumors. Int J Radiat Oncol Biol Phys. 2005;61:103–11.PubMedCrossRefGoogle Scholar
  93. 93.
    Amini A, Waxweiler TV, Brower JV, et al. Association of adjuvant chemoradiotherapy vs radiotherapy alone with survival in patients with resected major salivary gland carcinoma: data from the National Cancer Data Base. JAMA Otolaryngol Head Neck Surg. 2016;142:1100–10.PubMedCrossRefGoogle Scholar
  94. 94.
    Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med. 1991;324:1685–90.Google Scholar
  95. 95.
    Forastiere AA, Goepfert H, Maor M, et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med. 2003;349:2091–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31:845–52.PubMedCrossRefGoogle Scholar
  97. 97.
    Lefebvre JL, Andry G, Chevalier D, et al. Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891. Ann Oncol. 2012;23:2708–14.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Lefebvre JL, Rolland F, Tesselaar M, et al. Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy. J Natl Cancer Inst. 2009;101:142–52.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Olsen KD. Reexamining the treatment of advanced laryngeal cancer. Head Neck. 2010;32:1–7.PubMedGoogle Scholar
  100. 100.
    Richard JM, Sancho-Garnier H, Pessey JJ, et al. Randomized trial of induction chemotherapy in larynx carcinoma. Oral Oncol. 1998;34:224–8.PubMedCrossRefGoogle Scholar
  101. 101.
    Trotti A 3rd, Zhang Q, Bentzen SM, et al. Randomized trial of hyperfractionation versus conventional fractionation in T2 squamous cell carcinoma of the vocal cord (RTOG 9512). Int J Radiat Oncol Biol Phys. 2014;89:958–63.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Weber RS, Berkey BA, Forastiere A, et al. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11. Arch Otolaryngol Head Neck Surg. 2003;129:44–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Yamazaki H, Nishiyama K, Tanaka E, et al. Radiotherapy for early glottic carcinoma (T1N0M0): results of prospective randomized study of radiation fraction size and overall treatment time. Int J Radiat Oncol Biol Phys. 2006;64:77–82.PubMedCrossRefGoogle Scholar
  104. 104.
    Akimoto T, Nonaka T, Kitamoto Y, et al. Radiation therapy for T2N0 laryngeal cancer: a retrospective analysis for the impact of concurrent chemotherapy on local control. Int J Radiat Oncol Biol Phys. 2006;64:995–1001.PubMedCrossRefGoogle Scholar
  105. 105.
    Beitler JJ, Muller S, Grist WJ, et al. Prognostic accuracy of computed tomography findings for patients with laryngeal cancer undergoing laryngectomy. J Clin Oncol. 2010;28:2318–22.PubMedCrossRefGoogle Scholar
  106. 106.
    Bhayani MK, Hutcheson KA, Barringer DA, et al. Gastrostomy tube placement in patients with hypopharyngeal cancer treated with radiotherapy or chemoradiotherapy: factors affecting placement and dependence. Head Neck. 2013;35:1641–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Furusaka T, Matsuda A, Saito T, et al. Concurrent chemoradiation therapy with docetaxel (DOC) for laryngeal preservation in T2N0M0 glottic squamous cell carcinomas. Acta Otolaryngol. 2013;133:99–112.PubMedCrossRefGoogle Scholar
  108. 108.
    Garden AS, Forster K, Wong PF, et al. Results of radiotherapy for T2N0 glottic carcinoma: does the “2” stand for twice-daily treatment? Int J Radiat Oncol Biol Phys. 2003;55:322–8.PubMedCrossRefGoogle Scholar
  109. 109.
    Le QT, Fu KK, Kroll S, et al. Influence of fraction size, total dose, and overall time on local control of T1-T2 glottic carcinoma. Int J Radiat Oncol Biol Phys. 1997;39:115–26.PubMedCrossRefGoogle Scholar
  110. 110.
    Machtay M, Moughan J, Trotti A, et al. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008;26:3582–9.PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Janoray G, Pointreau Y, Garaud P, et al. Long-term results of a multicenter randomized phase III trial of induction chemotherapy with Cisplatin, 5-fluorouracil, +/− Docetaxel for Larynx preservation. J Natl Cancer Inst. 2016;108:1–7.Google Scholar
  112. 112.
    Brierley JD, Panzarella T, Tsang RW, et al. A comparison of different staging systems predictability of patient outcome. Thyroid carcinoma as an example. Cancer. 1997;79:2414–23.PubMedCrossRefGoogle Scholar
  113. 113.
    Chen J, Tward JD, Shrieve DC, et al. Surgery and radiotherapy improves survival in patients with anaplastic thyroid carcinoma: analysis of the surveillance, epidemiology, and end results 1983-2002. Am J Clin Oncol. 2008;31:460–4.PubMedCrossRefGoogle Scholar
  114. 114.
    De Crevoisier R, Baudin E, Bachelot A, et al. Combined treatment of anaplastic thyroid carcinoma with surgery, chemotherapy, and hyperfractionated accelerated external radiotherapy. Int J Radiat Oncol Biol Phys. 2004;60:1137–43.PubMedCrossRefGoogle Scholar
  115. 115.
    Haigh PI, Ituarte PH, Wu HS, et al. Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival. Cancer. 2001;91:2335–42.PubMedCrossRefGoogle Scholar
  116. 116.
    Kebebew E, Greenspan FS, Clark OH, et al. Anaplastic thyroid carcinoma. Treatment outcome and prognostic factors. Cancer. 2005;103:1330–5.PubMedCrossRefGoogle Scholar
  117. 117.
    Robbins RJ, Schlumberger MJ. The evolving role of (131)I for the treatment of differentiated thyroid carcinoma. J Nucl Med. 2005;46(Suppl 1):28S–37S.PubMedGoogle Scholar
  118. 118.
    Rosenbluth BD, Serrano V, Happersett L, et al. Intensity-modulated radiation therapy for the treatment of nonanaplastic thyroid cancer. Int J Radiat Oncol Biol Phys. 2005;63:1419–26.PubMedCrossRefGoogle Scholar
  119. 119.
    Tennvall J, Lundell G, Hallquist A, et al. Combined doxorubicin, hyperfractionated radiotherapy, and surgery in anaplastic thyroid carcinoma. Report on two protocols. The Swedish Anaplastic Thyroid Cancer Group. Cancer. 1994;74:1348–54.PubMedCrossRefGoogle Scholar
  120. 120.
    Tsang RW, Brierley JD, Simpson WJ, et al. The effects of surgery, radioiodine, and external radiation therapy on the clinical outcome of patients with differentiated thyroid carcinoma. Cancer. 1998;82:375–88.PubMedCrossRefGoogle Scholar
  121. 121.
    Ang KK, Peters LJ, Weber RS, et al. Postoperative radiotherapy for cutaneous melanoma of the head and neck region. Int J Radiat Oncol Biol Phys. 1994;30:795–8.PubMedCrossRefGoogle Scholar
  122. 122.
    Ballo MT, Bonnen MD, Garden AS, et al. Adjuvant irradiation for cervical lymph node metastases from melanoma. Cancer. 2003;97:1789–96.PubMedCrossRefGoogle Scholar
  123. 123.
    Ballo MT, Garden AS, Myers JN, et al. Melanoma metastatic to cervical lymph nodes: can radiotherapy replace formal dissection after local excision of nodal disease? Head Neck. 2005;27:718–21.PubMedCrossRefGoogle Scholar
  124. 124.
    Ballo MT, Strom EA, Zagars GK, et al. Adjuvant irradiation for axillary metastases from malignant melanoma. Int J Radiat Oncol Biol Phys. 2002;52:964–72.PubMedCrossRefGoogle Scholar
  125. 125.
    Beadle BM, Guadagnolo BA, Ballo MT, et al. Radiation therapy field extent for adjuvant treatment of axillary metastases from malignant melanoma. Int J Radiat Oncol Biol Phys. 2009;73:1376–82.PubMedCrossRefGoogle Scholar
  126. 126.
    Bonnen MD, Ballo MT, Myers JN, et al. Elective radiotherapy provides regional control for patients with cutaneous melanoma of the head and neck. Cancer. 2004;100:383–9.PubMedCrossRefGoogle Scholar
  127. 127.
    Burmeister BH, Mark Smithers B, Burmeister E, et al. A prospective phase II study of adjuvant postoperative radiation therapy following nodal surgery in malignant melanoma-Trans Tasman Radiation Oncology Group (TROG) Study 96.06. Radiother Oncol. 2006;81:136–42.PubMedCrossRefGoogle Scholar
  128. 128.
    Chang DT, Amdur RJ, Morris CG, et al. Adjuvant radiotherapy for cutaneous melanoma: comparing hypofractionation to conventional fractionation. Int J Radiat Oncol Biol Phys. 2006;66:1051–5.PubMedCrossRefGoogle Scholar
  129. 129.
    Overgaard J. The role of radiotherapy in recurrent and metastatic malignant melanoma: a clinical radiobiological study. Int J Radiat Oncol Biol Phys. 1986;12:867–72.PubMedCrossRefGoogle Scholar
  130. 130.
    Overgaard J, Gonzalez Gonzalez D, Hulshof MC, et al. Randomised trial of hyperthermia as adjuvant to radiotherapy for recurrent or metastatic malignant melanoma. European Society for Hyperthermic Oncology. Lancet. 1995;345:540–3.PubMedCrossRefGoogle Scholar
  131. 131.
    Sause WT, Cooper JS, Rush S, et al. Fraction size in external beam radiation therapy in the treatment of melanoma. Int J Radiat Oncol Biol Phys. 1991;20:429–32.PubMedCrossRefGoogle Scholar
  132. 132.
    Agrawal S, Kane JM 3rd, Guadagnolo BA, et al. The benefits of adjuvant radiation therapy after therapeutic lymphadenectomy for clinically advanced, high-risk, lymph node-metastatic melanoma. Cancer. 2009;115:5836–44.PubMedCrossRefGoogle Scholar
  133. 133.
    Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16:522–30.PubMedCrossRefGoogle Scholar
  134. 134.
    Kirkwood JM, Manola J, Ibrahim J, et al. A pooled analysis of eastern cooperative oncology group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. 2004;10:1670–7.PubMedCrossRefGoogle Scholar
  135. 135.
    Balch CM, Soong SJ, Smith T, et al. Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas. Ann Surg Oncol. 2001;8:101–8.PubMedGoogle Scholar
  136. 136.
    Wu S, Cho E, Li WQ, et al. History of severe sunburn and risk of skin cancer among women and men in 2 prospective cohort studies. Am J Epidemiol. 2016;183:824–33.PubMedPubMedCentralCrossRefGoogle Scholar
  137. 137.
    Thomas JM, Newton-Bishop J, A’Hern R, et al. Excision margins in high-risk malignant melanoma. N Engl J Med. 2004;350:757–66.PubMedCrossRefGoogle Scholar
  138. 138.
    Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Robert C, Thomas L, Bondarenko I, et al. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med. 2011;364:2517–26.PubMedCrossRefGoogle Scholar
  140. 140.
    Avril MF, Auperin A, Margulis A, et al. Basal cell carcinoma of the face: surgery or radiotherapy? Results of a randomized study Br J Cancer. 1997;76:100–6.PubMedGoogle Scholar
  141. 141.
    Balamucki CJ, Mancuso AA, Amdur RJ, et al. Skin carcinoma of the head and neck with perineural invasion. Am J Otolaryngol. 2012;33:447–54.PubMedCrossRefGoogle Scholar
  142. 142.
    Garcia-Serra A, Hinerman RW, Mendenhall WM, et al. Carcinoma of the skin with perineural invasion. Head Neck. 2003;25:1027–33.PubMedCrossRefGoogle Scholar
  143. 143.
    Mendenhall WM, Parsons JT, Mendenhall NP, et al. T2-T4 carcinoma of the skin of the head and neck treated with radical irradiation. Int J Radiat Oncol Biol Phys. 1987;13:975–81.PubMedCrossRefGoogle Scholar
  144. 144.
    Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate of nonmelanoma skin cancer in the United States, 2006. Arch Dermatol. 2010;146:283–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Mendenhall WM, Kirwan JM, Morris CG, et al. Cutaneous Merkel cell carcinoma. Am J Otolaryngol. 2012;33:88–92.PubMedCrossRefGoogle Scholar
  146. 146.
    Mojica P, Smith D, Ellenhorn JD. Adjuvant radiation therapy is associated with improved survival in Merkel cell carcinoma of the skin. J Clin Oncol. 2007;25:1043–7.PubMedCrossRefGoogle Scholar
  147. 147.
    Poulsen M, Rischin D, Walpole E, et al. High-risk Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group Study--TROG 96:07. J Clin Oncol. 2003;21:4371–6.PubMedCrossRefGoogle Scholar
  148. 148.
    Lewis KG, Weinstock MA, Weaver AL, et al. Adjuvant local irradiation for Merkel cell carcinoma. Arch Dermatol. 2006;142:693–700.PubMedGoogle Scholar
  149. 149.
    Ghoshal S, Chakraborty S, Moudgil N, et al. Quad shot: a short but effective schedule for palliative radiation for head and neck carcinoma. Indian J Palliat Care. 2009;15:137–40.PubMedPubMedCentralCrossRefGoogle Scholar
  150. 150.
    Nguyen NT, Doerwald-Munoz L, Zhang H, et al. 0-7-21 hypofractionated palliative radiotherapy: an effective treatment for advanced head and neck cancers. Br J Radiol. 2015;88:20140646.PubMedPubMedCentralCrossRefGoogle Scholar
  151. 151.
    Petersen IA, Kriss JP, McDougall IR, et al. Prognostic factors in the radiotherapy of Graves’ ophthalmopathy. Int J Radiat Oncol Biol Phys. 1990;19:259–64.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Daniel M. Trifiletti
    • 1
    Email author
  • Nicholas G. Zaorsky
    • 2
  • Henry S. Park
    • 3
  1. 1.Mayo ClinicJacksonvilleUSA
  2. 2.Penn State Cancer InstituteHersheyUSA
  3. 3.Yale School of MedicineNew HavenUSA

Personalised recommendations