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Late and Long-Term Treatment-Related Effects and Survivorship for Head and Neck Cancer Patients

  • Head and Neck Cancer (CP Rodriguez, Section Editor)
  • Published:
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Opinion statement

The demographics of head and neck cancer (HNC) survivors are changing, contributing to a growing number of survivors and a greater length of survivorship. Curative treatment involves intense multimodal therapy, which contributes to both short-term toxicities and long-term treatment-related effects. Delivering high-quality, relevant cancer survivorship care is a growing national priority. Various survivorship models and tools, such as survivorship care plans, have been utilized in an attempt to enhance care and optimize outcomes. However, an essential, yet understudied, component of high-quality survivorship care is the identification and management of late and long-term treatment-related effects. In this article, we will describe the current advancements in survivorship care as well as the research related to late and long-term treatment effects. While there is a growing body of literature that describes the prevalence of treatment-related effects and their impact on quality of life, more work is needed. Research that investigates the interplay of these complex treatment effects, the biological mechanisms that contribute to their variability, and interventions designed to mitigate them are desperately needed. While de-intensification offers the potential to alleviate these effects for future survivors, we need clinically meaningful assessment tools and therapies to provide the survivors we evaluate and treat daily. Targeted patient-reported outcomes and objective measures validated through clinical research are needed to help us systematically identify and treat late and long-term effects. In order to tailor and optimize the care we provide to our HNC survivors, we will need to leverage these tools as well as the expertise of all members of our multidisciplinary survivorship teams.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel R, Miller L, Jemal A. Cancer Facts & Figures 2020. Atlanta: American Cancer Society; 2020.

    Google Scholar 

  2. Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994–1001.

    Google Scholar 

  3. Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Incidence trends for human papillomavirus-related and -unrelated oral squamous cell carcinomas in the United States. J Clin Oncol. 2008;26(4):612–9.

    Google Scholar 

  4. Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Tân PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24–35.

    CAS  Google Scholar 

  5. O’Rorke MA, Ellison MV, Murray LJ, Moran M, James J, Anderson LA. Human papillomavirus related head and neck cancer survival: a systematic review and meta-analysis. Oral Oncol. 2012;48(12):1191–201.

    Google Scholar 

  6. Gillison ML, Koch WM, Capone RB, Spafford M, Westra WH, Wu L, et al. Evidence for a causal association between human papillomavirus and a subset of head and neck cancers. J Natl Cancer Inst. 2000;92(9):709–20.

    CAS  Google Scholar 

  7. Chaturvedi AK, Anderson WF, Lortet-Tieulent J, Curado MP, Ferlay J, Franceschi S, et al. Worldwide trends in incidence rates for oral cavity and oropharyngeal cancers. J Clin Oncol. 2013;31(36):4550–9.

    Google Scholar 

  8. •• Cohen EE, LaMonte SJ, Erb NL, et al. American Cancer Society Head and Neck Cancer Survivorship Care Guideline. CA Cancer J Clin. 2016;66(3):203–39 Guidelines for primary care physicians and other healthcare providers to facilitate comprehensive follow-up and survivorship care for head and neck cancer patients.

    Google Scholar 

  9. • Nekhlyudov L, Lacchetti C, Davis NB, et al. Head and Neck Cancer Survivorship Care Guideline: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Cancer Society Guideline. J Clin Oncol. 2017;35(14):1606–21.Endorsement of ACS guidelines while emphasizing the critical need for a team-based (e.g., oncologists, primary care physicians, dentists, allied health providers) approach to survivorship care.

    Google Scholar 

  10. American Cancer Society. National Cancer Survivorship Resource Center. https://www.cancer.org/health-care-professionals/national-cancer-survivorship-resource-center.html?srctsNCSRCToolkitSlides. Published 2020. Accessed 5/8/20, 2020.

  11. Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, 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(21):3582–9.

    CAS  Google Scholar 

  12. Institute of Medicine National Research Council. From cancer patient to cancer survivor: lost in transition. Washington: The National Academies Press; 2006.

    Google Scholar 

  13. Hill RE, Wakefield CE, Cohn RJ, Fardell JE, Brierley ME, Kothe E, et al. Survivorship care plans in cancer: a meta-analysis and systematic review of care plan outcomes. Oncologist. 2020;25(2):e351–72.

    Google Scholar 

  14. American College of Surgeons Commission on Cancer. Optimal Resources for Cancer Care: 2020 Standards Chicago, IL2020.

  15. Spears JA, Craft M, White S. Outcomes of cancer survivorship care provided by advanced practice RNs compared to other models of care: a systematic review. Oncol Nurs Forum. 2017;44(1):E34–e41.

    Google Scholar 

  16. Nekhlyudov L, Mollica MA, Jacobsen PB, Mayer DK, Shulman LN, Geiger AM. Developing a quality of cancer survivorship care framework: implications for clinical care, research, and policy. J Natl Cancer Inst. 2019;111(11):1120–30.

    Google Scholar 

  17. Cognetti DM, Villaflor VM, Fakhry C, Miller MC, Malloy KM. Survivorship support in head and neck cancer: American Head and Neck Society survey. Head Neck. 2020;42(5):939–44.

    Google Scholar 

  18. Nilsen ML, Mady LJ, Hodges J, Wasserman-Wincko T, Johnson JT. Burden of treatment: reported outcomes in a head and neck cancer survivorship clinic. Laryngoscope. 2019;129(12):E437–e444.

    Google Scholar 

  19. Eytan DF, Blackford AL, Eisele DW, Fakhry C. Prevalence of comorbidities among older head and neck cancer survivors in the United States. Otolaryngol Head Neck Surg. 2019;160(1):85–92.

    Google Scholar 

  20. Eytan DF, Blackford AL, Eisele DW, Fakhry C. Prevalence of comorbidities and effect on survival in survivors of human papillomavirus-related and human papillomavirus-unrelated head and neck cancer in the United States. Cancer. 2019;125(2):249–60.

    CAS  Google Scholar 

  21. Kawakita D, Abdelaziz S, Chen Y, Rowe K, Snyder J, Fraser A, et al. Adverse respiratory outcomes among head and neck cancer survivors in the Utah Cancer Survivors Study. Cancer. 2020;126(4):879–85.

    Google Scholar 

  22. Patel DA, Sharda R, Hovis KL, Nichols EE, Sathe N, Penson DF, et al. Patient-reported outcome measures in dysphagia: a systematic review of instrument development and validation. Dis Esophagus. 2017;30(5):1–23.

    CAS  Google Scholar 

  23. Aylward A, Abdelaziz S, Hunt JP, Buchmann LO, Cannon RB, Lloyd S, et al. Rates of dysphagia-related diagnoses in long-term survivors of head and neck cancers. Otolaryngol Head Neck Surg. 2019;161(4):643–51.

    Google Scholar 

  24. Huh G, Ahn S-H, Suk J-G, Lee MH, Kim WS, Kwon SK, et al. Severe late dysphagia after multimodal treatment of stage III/IV laryngeal and hypopharyngeal cancer. Jpn J Clin Oncol. 2020;50(2):185–92.

    Google Scholar 

  25. Givens DJ, Karnell LH, Gupta AK, Clamon GH, Pagedar NA, Chang KE, et al. Adverse events associated with concurrent chemoradiation therapy in patients with head and neck cancer. Arch Otolaryngol Head Neck Surg. 2009;135(12):1209–17.

    Google Scholar 

  26. • Hutcheson KA, Nurgalieva Z, Zhao H, et al. Two-year prevalence of dysphagia and related outcomes in head and neck cancer survivors: an updated SEER-Medicare analysis. Head Neck. 2019;41(2):479–87.SEER database analysis indicating the significant prevalence of dysphagia, especially among patients who received multimodal therapy, at 2-years post-treatment.

    Google Scholar 

  27. Aylward A, Park J, Abdelaziz S, Hunt JP, Buchmann LO, Cannon RB, et al. Individualized prediction of late-onset dysphagia in head and neck cancer survivors. Head Neck. 2020;42(4):708–18.

    Google Scholar 

  28. Kannan RA, Arul Ponni TR. Dose to swallowing structures and dysphagia in head and neck intensity modulated radiation therapy - a long term prospective analysis. Rep Pract Oncol Radiother. 2019;24(6):654–9.

    Google Scholar 

  29. Ozkaya Akagunduz O, Eyigor S, Kirakli E, et al. Radiation-associated chronic dysphagia assessment by flexible endoscopic evaluation of swallowing (FEES) in head and neck cancer patients: swallowing-related structures and radiation dose-volume effect. Ann Otol Rhinol Laryngol. 2019;128(2):73–84.

    Google Scholar 

  30. Hutcheson KA, Bhayani MK, Beadle BM, Gold KA, Shinn EH, Lai SY, et al. Eat and exercise during radiotherapy or chemoradiotherapy for pharyngeal cancers: use it or lose it. JAMA Otolaryngol Head Neck Surg. 2013;139(11):1127–34.

    Google Scholar 

  31. Mortensen HR, Jensen K, Aksglæde K, Lambertsen K, Eriksen E, Grau C. Prophylactic swallowing exercises in head and neck cancer radiotherapy. Dysphagia. 2015;30(3):304–14.

    CAS  Google Scholar 

  32. Cnossen IC, van Uden-Kraan CF, Witte BI, Aalders YJ, de Goede CJT, de Bree R, et al. Prophylactic exercises among head and neck cancer patients during and after swallowing sparing intensity modulated radiation: adherence and exercise performance levels of a 12-week guided home-based program. Eur Arch Otorhinolaryngol. 2017;274(2):1129–38.

    Google Scholar 

  33. Sharma A, Patel S, Baik FM, Mathison G, Pierce BHG, Khariwala SS, et al. Survival and gastrostomy prevalence in patients with oropharyngeal cancer treated with transoral robotic surgery vs chemoradiotherapy. JAMA Otolaryngol Head Neck Surg. 2016;142(7):691–7.

    Google Scholar 

  34. Hutcheson KA, Warneke CL, Yao C, et al. Dysphagia after primary transoral robotic surgery with neck dissection vs nonsurgical therapy in patients with low- to intermediate-risk oropharyngeal cancer. JAMA Otolaryngol Head Neck Surg. 2019.

  35. Nichols AC, Theurer J, Prisman E, Read N, Berthelet E, Tran E, et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2. Randomised Trial Lancet Oncol. 2019;20(10):1349–59.

    CAS  Google Scholar 

  36. ClinicalTrials.gov. National Library of Medicine (U.S.) (2013). Transoral surgery followed by low-dose or standard-dose radiation therapy with or without chemotherapy in treating patients with HPV positive stage III-IVA oropharyngeal Cancer Identifier NCT01898494. Retrieved from https://clinicaltrials.gov/ct2/show/NCT01898494. Accessed 19 June 2020.

  37. Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–67.

    Google Scholar 

  38. ClinicalTrials.gov. National Library of Medicine (U.S.). (2018). Study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy (IMSTAR-HN). Identifier NCT03700905. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03700905. Accessed 19 June 2020.

  39. ClinicalTrials.gov. National Library of Medicine (U.S.) (2017). S Chemoradiation vs immunotherapy and radiation for head and neck cancer Identifier NCT03383094. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03383094. Accessed 19 June 2020.

  40. ClinicalTrials.gov. National Library of Medicine (U.S.). (2019). De-intensified radiation therapy with chemotherapy (cisplatin) or immunotherapy (nivolumab) in treating patients with early-stage, HPV-positive, non-smoking associated oropharyngeal cancer. Identifier NCT03952585. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03952585. Accessed 19 June 2020.

  41. ClinicalTrials.gov. National Library of Medicine (U.S.). (2018). Adjuvant de-escalated radiation + adjuvant nivolumab for intermediate-high risk P16+ oropharynx cancer. Identifier NCT03715946. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03715946. Accessed 19 June 2020.

  42. Ma Y, Green R, Pan S, McCabe D, Goldberg L, Woo P. Long-term voice outcome following radiation versus laser microsurgery in early glottic cancer. J Voice. 2019;33(2):176–82.

    Google Scholar 

  43. Miyamaru S, Minoda R, Kodama N. Long-term changes in vocal function after supracricoid partial laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer. Head Neck. 2019;41(1):139–45.

    Google Scholar 

  44. Hendriksma M, van Loon Y, Klop WMC, Hakkesteegt MM, Heijnen BJ, el Hasnaoui I, et al. Quality of life and voice outcome of patients treated with transoral CO(2) laser microsurgery for early glottic carcinoma (T1-T2): a 2-year follow-up study. Eur Arch Otorhinolaryngol. 2019;276(3):805–14.

    Google Scholar 

  45. van Gogh CDL, Verdonck-de Leeuw IM, Langendijk JA, Kuik DJ, Mahieu HF. Long-term efficacy of voice therapy in patients with voice problems after treatment of early glottic cancer. J Voice. 2012;26(3):398–401.

    Google Scholar 

  46. Jotic A, Stankovic P, Jesic S, Milovanovic J, Stojanovic M, Djukic V. Voice quality after treatment of early glottic carcinoma. J Voice. 2012;26(3):381–9.

    Google Scholar 

  47. Johansson M, Finizia C, Persson J, Tuomi L. Cost-effectiveness analysis of voice rehabilitation for patients with laryngeal cancer: a randomized controlled study. Support Care Cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2020.

  48. Kondo T, Sugauchi A, Yabuno Y, Kobashi H, Amano K, Aikawa T, et al. Performance status scale for head and neck scores for oral cancer survivors: predictors and factors for improving quality of life. Clin Oral Investig. 2019;23(4):1575–82.

    Google Scholar 

  49. Kainulainen S, Koivusalo AM, Roine RP, Wilkman T, Sintonen H, Törnwall J, et al. Long-term quality of life after surgery of head and neck cancer with microvascular reconstruction: a prospective study with 4.9-years follow-up. Oral Maxillofac Surg. 2020;24(1):11–7.

    Google Scholar 

  50. Kamal M, Barrow MP, Lewin JS, Estrella A, Gunn GB, Shi Q, et al. Modeling symptom drivers of oral intake in long-term head and neck cancer survivors. Support Care Cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2019;27(4):1405–15.

    Google Scholar 

  51. Ma SJ, Rivers CI, Serra LM, Singh AK. Long-term outcomes of interventions for radiation-induced xerostomia: a review. World J Clin Oncol. 2019;10(1):1–13.

    Google Scholar 

  52. Felice DEF, Pranno N, Papi P, Brugnoletti O, Tombolini V, Polimeni A. Xerostomia and clinical outcomes in definitive intensity modulated radiotherapy (IMRT) versus three-dimensional conformal radiotherapy (3D-CRT) for head and neck squamous cell carcinoma: a meta-analysis. In Vivo. 2020;34(2):623–9.

    Google Scholar 

  53. Jensen SB, Vissink A, Limesand KH, Reyland ME. Salivary gland hypofunction and xerostomia in head and neck radiation patients. J Natl Cancer Inst Monogr. 2019;2019(53).

  54. Cramer JD, Johnson JT, Nilsen ML. Pain in head and neck cancer survivors: prevalence, predictors, and quality-of-life impact. Otolaryngol Head Neck Surg. 2018;159(5):853–8.

    Google Scholar 

  55. Cata JP, Patino M, Gorur A, et al. Persistent and chronic postoperative opioid use in a cohort of patients with oral tongue squamous cell carcinoma. Pain Med. 2019.

  56. Craker NC, Gal TJ, Wells L, Schadler A, Pruden S, Aouad RK. Chronic opioid use after laryngeal cancer treatment: a VA study. Otolaryngol Head Neck Surg. 2020;162(4):492–7.

    Google Scholar 

  57. • Nilsen ML, Lyu L, Belsky MA, et al. Impact of neck disability on health-related quality of life among head and neck cancer survivors. Otolaryngol Head Neck Surg. 2020;162(1):64–72.A cross-sectional analysis demonstrating the high prevalence of neck pain and disability in head and neck cancer patients who underwent nonsurgical treatment.

    Google Scholar 

  58. Aggarwal P, Zaveri JS, Goepfert RP, Shi Q, du XL, Swartz M, et al. Swallowing-related outcomes associated with late lower cranial neuropathy in long-term oropharyngeal cancer survivors: cross-sectional survey analysis. Head Neck. 2019;41(11):3880–94.

    Google Scholar 

  59. Dong Y, Ridge JA, Ebersole B, Li T, Lango MN, Churilla TM, et al. Incidence and outcomes of radiation-induced late cranial neuropathy in 10-year survivors of head and neck cancer. Oral Oncol. 2019;95:59–64.

    Google Scholar 

  60. Rodriguez AM, Komar A, Ringash J, Chan C, Davis AM, Jones J, et al. A scoping review of rehabilitation interventions for survivors of head and neck cancer. Disabil Rehabil. 2019;41(17):2093–107.

    Google Scholar 

  61. Bigelow EO, Blackford AL, Eytan DF, Eisele DW, Fakhry C. Burden of comorbidities is higher among elderly survivors of oropharyngeal cancer compared with controls. Cancer. 2020;126(8):1793–803.

    Google Scholar 

  62. Petrovic I, Baser R, Blackwell T, McCarthy C, Ganly I, Patel S, et al. Long-term functional and esthetic outcomes after fibula free flap reconstruction of the mandible. Head Neck. 2019;41(7):2123–32.

    Google Scholar 

  63. Zer A, Pond GR, Razak ARA, Tirona K, Gan HK, Chen EX, et al. Association of neurocognitive deficits with radiotherapy or chemoradiotherapy for patients with head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2018;144(1):71–9.

    Google Scholar 

  64. ClinicalTrials.gov. National Library of Medicine (U.S.). (2018). PRO-ACTIVE: Prophylactic Swallow Intervention for Patients Receiving Radiotherapy for Head and Neck Cancer (PRO-ACTIVE). Identifier NCT03455608. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03455608. Accessed 19 June 2020.

  65. ClinicalTrials.gov. National Library of Medicine (U.S.). (2015). Standard follow-up program (SFP) for head and neck cancer patients treated with curative primary or postoperative radiotherapy or chemoradiation (H&NTOX). Identifier NCT02435576. Retrieved from https://clinicaltrials.gov/ct2/show/NCT02435576?term=late+toxicity&cond=Head+and+Neck+Cancer&draw=2&rank=1. Accessed 19 June 2020.

  66. Forastiere AA, Zhang Q, Weber RS, Maor MH, Goepfert H, Pajak TF, 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(7):845–52.

    CAS  Google Scholar 

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Authors and Affiliations

  1. School of Nursing, Department of Acute and Tertiary Care, University of Pittsburgh, 318A Victoria Building, 3500 Victoria Street, Pittsburgh, PA, 15261, USA

    Marci Lee Nilsen PhD, RN, CHPN

  2. School of Medicine, Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA

    Marci Lee Nilsen PhD, RN, CHPN & Jonas T. Johnson MD

  3. School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Michael A. Belsky MS

  4. School of Medicine, Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA

    Nicole Scheff PhD

  5. Division of Hematology/Oncology, UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Dan P. Zandberg MD

  6. School of Medicine, Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA

    Heath Skinner MD, PhD

  7. UPMC Hillman Cancer Center, Pittsburgh, PA, USA

    Robert Ferris MD, PhD

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  1. Marci Lee Nilsen PhD, RN, CHPN
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Correspondence to Marci Lee Nilsen PhD, RN, CHPN.

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Marci Lee Nilsen declares that she has no conflict of interest. Michael A. Belsky declares that he has no conflict of interest. Nicole Scheff declares that she has no conflict of interest. Jonas T. Johnson declares that he has no conflict of interest. Dan P. Zandberg has received research funding (paid to his institution) from Bristol-Myers Squibb, Merck, Aduro Biotech, Astellas, Lilly, and GlaxoSmithKline. Heath Skinner declares that he has no conflict of interest. Robert Ferris has received research funding/funding for clinical trials from AstraZeneca/MedImmune, Merck, and TTMS; has received compensation for service as a consultant from Aduro Biotech, Iovance Biotherapeutics, Nanobiotix, Ono Pharmaceutical, TTMS, and Torque Therapeutics, Inc.; has served on advisory boards for AstraZeneca/Medimmune, EMD Serono, GlaxoSmithKline, MacroGenics, Merck, Numab Therapeutics AG, Oncorus, Pfizer, PPD, and Regeneron Pharmaceuticals; and owns stock in TTMS.

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Nilsen, M.L., Belsky, M.A., Scheff, N. et al. Late and Long-Term Treatment-Related Effects and Survivorship for Head and Neck Cancer Patients. Curr. Treat. Options in Oncol. 21, 92 (2020). https://doi.org/10.1007/s11864-020-00797-x

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