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Herausforderungen in der Primärtherapie älterer Patienten mit Kopf-Hals-Tumoren

Challenges in primary treatment of older patients with head and neck cancer

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Die Onkologie Aims and scope

Zusammenfassung

Hintergrund

Die Anzahl älterer Patienten mit Kopf-Hals-Karzinomen nimmt stetig zu. Die Evidenz zur Behandlung ist jedoch limitiert aufgrund der Unterrepräsentation dieser Patienten in den großen therapiedefinierenden Studien.

Fragestellung

Es werden die aktuellen Kontroversen in der Behandlung älterer Patienten mit nichtmetastasierten Kopf-Hals-Karzinomen erörtert.

Material und Methoden

Eine selektive Literatursuche zu dem Thema wurde auf PubMed und Embase durchgeführt; aktuelle Studien wurden auf ClinicalTrials.gov identifiziert.

Ergebnisse

Vor allem die radioonkologischen Behandlungsansätze älterer Patienten mit Kopf-Hals-Karzinomen sind relativ heterogen, auch weil sich die Behandlungsziele von älteren Patienten mit zunehmender Gebrechlichkeit ändern. Es gibt Hinweise für leicht erhöhte therapiebedingte Toxizität bei älteren Kopf-Hals-Karzinompatienten, allerdings unterscheiden sich nach Standardtherapie die Heilungsraten von lokal begrenzten Kopf-Hals-Karzinomen nicht maßgeblich von denen jüngerer Patienten. Geriatrische Screenings älterer Patienten mit Kopf-Hals-Karzinomen werden basierend auf internationalen Leitlinien grundsätzlich empfohlen. Insbesondere bei Vorhandensein von Gebrechlichkeit („frailty“) ist die Anpassung des jeweiligen Therapiekonzepts und die frühzeitige Durchführung geriatrischer Interventionen ratsam. Deeskalationsansätze wie der Ersatz von Cisplatin in der definitiven oder adjuvanten Strahlentherapie bei Patienten mit Kontraindikationen sowie der Einsatz von Immuntherapie parallel zu einer hypofraktionierten Radiotherapie werden aktuell in Studien untersucht.

Schlussfolgerungen

Standardtherapien zeigen trotz tendenziell erhöhter therapieassoziierter Toxizität bei vielen älteren Patienten mit Kopf-Hals-Karzinomen ähnliche onkologische Ergebnisse wie in jüngeren Kohorten. Die Behandlung älterer Kopf-Hals-Tumor-Patienten bedarf daher einer multidisziplinären Beratung unter Einbeziehung der Patienten und der Angehörigen hinsichtlich der Behandlungsziele. Das chronologische Alter allein sollte nicht ausschlaggebend für eine Therapieentscheidung sein.

Abstract

Background

The number of older patients with head and neck cancer is steadily increasing. Evidence for optimal treatment is limited due to the significant underrepresentation of these patients in landmark trials.

Objective

Current controversies in surgical and radiotherapy treatment of older patients with nonmetastatic head and neck cancers are discussed.

Materials and methods

A selective literature search was conducted in PubMed and Embase, and clinical trials on the topic were identified using ClinicalTrials.gov.

Results

Treatment patterns especially for radiotherapy of elderly patients with head and neck cancer demonstrate considerable heterogeneity, due in part to a shift in treatment goals of elderly patients with increasing age. There are data regarding increased treatment-associated toxicities in elderly patients with head and neck cancer, but oncological outcomes for locoregionally confined cancers do not differ after standard treatment between older and younger patients. International guidelines recommend geriatric screening of elderly patients with head and neck cancer, and in case of detected frailty, early inclusion of geriatric specialists and geriatric interventions is recommended. Current clinical trials are investigating concepts for treatment de-escalation such as the replacement of cisplatin as part of definitive or adjuvant chemoradiation or the incorporation of immunotherapy with hypofractionated focal radiotherapy.

Conclusions

Standard treatment demonstrates similar oncological outcomes in many older head and neck cancer patient cohorts compared to younger patients despite a higher rate of treatment-associated toxicities. Therefore, treatment of older head and neck cancer patients requires a multidisciplinary approach involving the patient and their caregivers regarding common treatment goals. Chronological age alone should not be the decisive factor for any treatment decision.

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Literatur

  1. Johnson DE, Burtness B, Leemans CR, Lui VWY, Bauman JE, Grandis JR (2020) Head and neck squamous cell carcinoma. Nat Rev Dis Primers 6(1):92

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lechner M, Liu J, Masterson L, Fenton TR (2022) HPV-associated oropharyngeal cancer: epidemiology, molecular biology and clinical management. Nat Rev Clin Oncol 19(5):306–327

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  4. Szturz P, Vermorken JB (2016) Treatment of elderly patients with squamous cell carcinoma of the head and neck. Front Oncol. https://doi.org/10.3389/fonc.2016.00199

    Article  PubMed  PubMed Central  Google Scholar 

  5. Wiegand S, Dietz A, Wichmann G, Kunz V (2022) Frailty und ihre Bedeutung in der Kopf-Hals-Onkologie. Laryngorhinootologie 101(03):249–258

    Article  PubMed  Google Scholar 

  6. Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA (2009) Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol 27(17):2758–2765

    Article  PubMed  Google Scholar 

  7. Lacas B, Carmel A, Landais C, Wong SJ, Licitra L, Tobias JS et al (2021) Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC group. Radiother Oncol 156:281–293

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK et al (2010) 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 11(1):21–28

    Article  CAS  PubMed  Google Scholar 

  9. Gugić J, Strojan P (2012) Squamous cell carcinoma of the head and neck in the elderly. Rep Pract Oncol Radiother 18(1):16–25

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lu DJ, Luu M, Mita A, Scher K, Shiao SL, Yoshida EP et al (2018) Human papillomavirus-associated oropharyngeal cancer among patients aged 70 and older: dramatically increased prevalence and clinical implications. Eur J Cancer 103:195–204

    Article  PubMed  Google Scholar 

  11. Caparrotti F, O’Sullivan B, Bratman SV, Ringash J, Lu L, Bayley A et al (2017) Exploring the impact of human papillomavirus status, comorbidity, polypharmacy, and treatment intensity on outcome of elderly oropharyngeal cancer patients treated with radiation therapy with or without chemotherapy. Int J Radiat Oncol Biol Phys 98(4):858–867

    Article  PubMed  Google Scholar 

  12. Ruud Kjær EK, Jensen JS, Jakobsen KK, Lelkaitis G, Wessel I, von Buchwald C et al (2020) The impact of comorbidity on survival in patients with head and neck squamous cell carcinoma: a nationwide case-control study spanning 35 years. Front Oncol 10:617184

    Article  PubMed  Google Scholar 

  13. Stordeur S, Schillemans V, Savoye I, Vanschoenbeek K, Leroy R, Macq G et al (2020) Comorbidity in head and neck cancer: Is it associated with therapeutic delay, post-treatment mortality and survival in a population-based study? Oral Oncol 102:104561

    Article  PubMed  Google Scholar 

  14. Rühle A, Stromberger C, Haehl E, Senger C, David H, Stoian R et al (2021) Development and validation of a novel prognostic score for elderly head-and-neck cancer patients undergoing radiotherapy or chemoradiation. Radiother Oncol 154:276–282

    Article  PubMed  Google Scholar 

  15. Kotzerke D, Moritz F, Mantovani L, Hambsch P, Hering K, Kuhnt T et al (2019) The performance of three oncogeriatric screening tools—G8, optimised G8 and CARG—in predicting chemotherapy-related toxicity in older patients with cancer. A prospective clinical study. J Geriatr Oncol 10(6):937–943

    Article  PubMed  Google Scholar 

  16. Neve M, Jameson MB, Govender S, Hartopeanu C (2016) Impact of geriatric assessment on the management of older adults with head and neck cancer: a pilot study. J Geriatr Oncol 7(6):457–462

    Article  PubMed  Google Scholar 

  17. Pottel L, Lycke M, Boterberg T, Pottel H, Goethals L, Duprez F et al (2015) G‑8 indicates overall and quality-adjusted survival in older head and neck cancer patients treated with curative radiochemotherapy. BMC Cancer 15:875

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kunz V, Wichmann G, Wald T, Pirlich M, Zebralla V, Dietz A et al (2022) Frailty assessed with FRAIL scale and G8 questionnaire predicts severe postoperative complications in patients receiving major head and neck surgery. J Clin Med. https://doi.org/10.3390/jcm11164714

    Article  Google Scholar 

  19. Dale W, Klepin HD, Williams GR, Alibhai SMH, Bergerot C, Brintzenhofeszoc K et al (2023) Practical assessment and management of vulnerabilities in older patients receiving systemic cancer therapy: ASCO guideline update. J Clin Oncol. https://doi.org/10.1200/jco.23.00933

    Article  PubMed  Google Scholar 

  20. Extermann M, Aapro M, Bernabei R, Cohen HJ, Droz J‑P, Lichtman S et al (2005) Use of comprehensive geriatric assessment in older cancer patients:: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG). Crit Rev Oncol Hematol 55(3):241–252

    Article  PubMed  Google Scholar 

  21. Paillaud E, Brugel L, Bertolus C, Baron M, Bequignon E, Caillet P et al (2022) Effectiveness of geriatric assessment-driven interventions on survival and functional and nutritional status in older patients with head and neck cancer: a randomized controlled trial (EGeSOR). Cancers 14(13):3290

    Article  PubMed  PubMed Central  Google Scholar 

  22. Haehl E, Rühle A, Spohn S, Sprave T, Gkika E, Zamboglou C et al (2021) Patterns-of-care analysis for radiotherapy of elderly head-and-neck cancer patients: a trinational survey in Germany, Austria and Switzerland. Front Oncol 11:723716

    Article  PubMed  Google Scholar 

  23. Belgioia L, De Felice F, Bacigalupo A, Alterio D, Argenone A, D’Angelo E et al (2020) Results of a survey on elderly head and neck cancer patients on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO). Acta Otorhinolaryngol Ital 40(6):405–409

    Article  PubMed  Google Scholar 

  24. Dronkers EAC, Mes SW, Wieringa MH, van der Schroeff MP, Baatenburg de Jong RJ (2015) Noncompliance to guidelines in head and neck cancer treatment; associated factors for both patient and physician. BMC Cancer 15(1):515

    Article  PubMed  PubMed Central  Google Scholar 

  25. Windon MJ, Fakhry C, Faraji F, Troy T, Gourin CG, Kiess AP et al (2019) Priorities of human papillomavirus-associated oropharyngeal cancer patients at diagnosis and after treatment. Oral Oncol 95:11–15

    Article  PubMed  PubMed Central  Google Scholar 

  26. Brotherston DC, Poon I, Le T, Leung M, Kiss A, Ringash J et al (2013) Patient preferences for oropharyngeal cancer treatment de-escalation. Head Neck 35(2):151–159

    Article  PubMed  Google Scholar 

  27. Dietz A (Hrsg) (2021) The surgical approach to elderly patients with HNSCC. Springer, Cham

    Google Scholar 

  28. Beausang ES, Ang EE, Lipa JE, Irish JC, Brown DH, Gullane PJ et al (2003) Microvascular free tissue transfer in elderly patients: the Toronto experience. Head Neck 25(7):549–553

    Article  PubMed  Google Scholar 

  29. Wester JL, Lindau RH, Wax MK (2013) Efficacy of free flap reconstruction of the head and neck in patients 90 years and older. JAMA Otolaryngol Head Neck Surg 139(1):49–53

    Article  PubMed  Google Scholar 

  30. Grammatica A, Piazza C, Pellini R, Montalto N, Lancini D, Vural A et al (2019) Free flaps for advanced oral cancer in the “older old” and “oldest old”: a retrospective multi-institutional study. Front Oncol 9:604. https://doi.org/10.3389/fonc.2019.00604

    Article  PubMed  PubMed Central  Google Scholar 

  31. Rühle A, Huber PE (2018) Normalgewebe: Strahlenempfindlichkeit, Toxizität, Konsequenzen für die Planung. Radiologe 58(8):746–753

    Article  PubMed  Google Scholar 

  32. Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS et al (2008) Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol 26(21):3582–3589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mayer A, Wenzel W, Wollschläger D, Bostel T, Krüger M, Matthias C et al (2022) Adjuvant chemoradiotherapy in elderly patients with head and neck cancer: a monoinstitutional, two-to-one pair-matching analysis. Strahlenther Onkol 198(2):159–170

    Article  PubMed  PubMed Central  Google Scholar 

  34. Haehl E, Rühle A, David H, Kalckreuth T, Sprave T, Stoian R et al (2020) Radiotherapy for geriatric head-and-neck cancer patients: what is the value of standard treatment in the elderly? Radiat Oncol 15(1):31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V (2020) Squamous cell carcinoma of the oral cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 31(11):1462–1475

    Article  PubMed  Google Scholar 

  36. Mehanna H, Robinson M, Hartley A, Kong A, Foran B, Fulton-Lieuw T et al (2019) Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet 393(10166):51–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Patil VM, Noronha V, Menon N, Singh A, Ghosh-Laskar S, Budrukkar A et al (2023) Results of phase III randomized trial for use of docetaxel as a radiosensitizer in patients with head and neck cancer, unsuitable for cisplatin-based chemoradiation. J Clin Oncol 41(13):2350–2361

    Article  CAS  PubMed  Google Scholar 

  38. Rühle A, Marschner S, Haderlein M, Fabian A, Weymann M, Behrens M et al (2023) Evaluation of concomitant systemic treatment in older adults with head and neck squamous cell carcinoma undergoing definitive radiotherapy. JAMA Netw Open 6(2):e230090

    Article  PubMed  PubMed Central  Google Scholar 

  39. Tao Y, Biau J, Sun XS, Sire C, Martin L, Alfonsi M et al (2023) Pembrolizumab versus cetuximab concurrent with radiotherapy in patients with locally advanced squamous cell carcinoma of head and neck unfit for cisplatin (GORTEC 2015-01 PembroRad): a multicenter, randomized, phase II trial. Ann Oncol 34(1):101–110

    Article  CAS  PubMed  Google Scholar 

  40. Mell LK, Torres-Saavedra P, Wong S, Chang S, Kish JA, Minn AJ et al (2022) Radiotherapy with durvalumab vs. cetuximab in patients with locoregionally advanced head and neck cancer and a contraindication to cisplatin: phase II results of NRG-HN004. Int J Radiat Oncol 114(5):1058

    Article  Google Scholar 

  41. Tao Y, Sun XS, Pointreau Y, Le Tourneau C, Sire C, Kaminsky MC et al (2023) Extended follow-up of a phase 2 trial of xevinapant plus chemoradiotherapy in high-risk locally advanced squamous cell carcinoma of the head and neck: a randomised clinical trial. Eur J Cancer 183:24–37

    Article  CAS  PubMed  Google Scholar 

  42. Moon DH, Avkshtol V, Vo D, Ahn C, Sumer B, Day AT et al (2023) HYPORT: phase 1 study of 3‑week hypofractionated postoperative radiation therapy for head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys. https://doi.org/10.1016/j.ijrobp.2023.06.010

    Article  PubMed  Google Scholar 

  43. Harrington KJ, Burtness B, Greil R, Soulières D, Tahara M, de Castro G Jr. et al (2023) Pembrolizumab with or without chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma: updated results of the phase III KEYNOTE-048 study. J Clin Oncol 41(4):790–802

    Article  CAS  PubMed  Google Scholar 

  44. Saleh K, Auperin A, Martin N, Borcoman E, Torossian N, Iacob M et al (2021) Efficacy and safety of immune checkpoint inhibitors in elderly patients (≥ 70 years) with squamous cell carcinoma of the head and neck. Eur J Cancer 157:190–197

    Article  CAS  PubMed  Google Scholar 

  45. Kim CM, Lee JB, Shin SJ, Ahn JB, Lee M, Kim HS (2022) The efficacy of immune checkpoint inhibitors in elderly patients: a meta-analysis and meta-regression. ESMO Open 7(5):100577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Guigay J, Aupérin A, Fayette J, Saada-Bouzid E, Lafond C, Taberna M et al (2021) Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol 22(4):463–475

    Article  CAS  PubMed  Google Scholar 

  47. Guigay J, Auperin A, Mertens C, Even C, Geoffrois L, Cupissol D et al (2019) Personalized treatment according to geriatric assessment in first-line recurrent and/or metastatic (R/M) head and neck squamous cell cancer (HNSCC) patients aged 70 or over: ELAN (ELderly heAd and Neck cancer) FIT and UNFIT trials. Ann Oncol 30:v450

    Article  Google Scholar 

  48. Bahig H, Huang SH, O’Sullivan B (2022) Oligometastatic head and neck cancer: challenges and perspectives. Cancers 14(16):3894. https://doi.org/10.3390/cancers14163894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Leipzig, Stephanstr. 9a, 04103, Leipzig, Deutschland

    Alexander Rühle &  Nils H. Nicolay

  2. Mitteldeutsches Krebszentrum (CCCG), Universitätsklinikum Leipzig, Leipzig, Deutschland

    Alexander Rühle, Andreas Dietz, Florian Lordick &  Nils H. Nicolay

  3. Klinik für Hals‑, Nasen- und Ohrenheilkunde, Universitätsklinikum Leipzig, Leipzig, Deutschland

    Andreas Dietz

  4. Universitäres Krebszentrum Leipzig (UCCL), Leipzig, Deutschland

    Florian Lordick

  5. Medizinische Klinik und Poliklinik 2 – Onkologie, Gastroenterologie, Hepatologie, Pneumologie, Universitätsklinikum Leipzig, Leipzig, Deutschland

    Florian Lordick

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  1. Alexander Rühle
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  2. Andreas Dietz
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  4. Nils H. Nicolay
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Correspondence to Nils H. Nicolay.

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Interessenkonflikt

A. Rühle erhielt Referenten- und Beraterhonorare, Reisekostenunterstützung sowie Forschungsgelder von Novocure, sowie ein Referentenhonorar von Merck Healthcare Germany. A. Dietz erhielt Beraterhonorare von Merck Serono, Roche, Astra Zeneca, MSC, BMS, Novartis, Sanofi, GSK und Nanobiotix sowie Forschungsförderung durch Roche, Merck Serono und MSD. F. Lordick erhielt Referentenhonorare von art tempi, Astra Zeneca, Bayer, BioNTech, BMS, Daiichi Sankyo, Eli Lilly, Falk Foundation, Incyte, MedUpdate, Merck, MSD, Novartis, Roche, Servier, StreamedUp!, Beraterhonorare von Amgen, Astellas, Astra Zeneca, BMS, Daiichi Sankyo, Gilead, MSD, Novartis, PAGE und erhielt Forschungsunterstützung durch Astellas, Astra Zeneca, BMS, Gilead und MSD. N.H. Nicolay erhielt Referentenhonorare von Merck Healthcare Germany, Falk Foundation und Sun Pharmaceuticals sowie Forschungsförderung durch Novocure.

Für diesen Beitrag wurden von den Autor/-innen keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Rühle, A., Dietz, A., Lordick, F. et al. Herausforderungen in der Primärtherapie älterer Patienten mit Kopf-Hals-Tumoren. Onkologie 30, 103–112 (2024). https://doi.org/10.1007/s00761-023-01418-6

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