Advertisement

Clinical Significance of Vulnerability Assessment in Patients with Primary Head and Neck Cancer Undergoing Definitive Concurrent Chemoradiation Therapy

Published:January 24, 2020DOI:https://doi.org/10.1016/j.ijrobp.2020.01.004

      Purpose

      This study aimed to identify vulnerable patients with head and neck cancer undergoing concurrent chemoradiation therapy (CCRT) who are susceptible to higher treatment-related adverse effects and have poorer treatment tolerance. This study also aimed to determine whether comprehensive geriatric assessment, developed in the geriatric population, can predict vulnerability to treatment-related adverse events and survival even in nongeriatric patients with head and neck cancer, as well as the prevalence of vulnerability and its effect on toxicities and survival among these patients.

      Methods and Materials

      This prospective cohort study examined 461 patients with primary head and neck cancer who underwent definitive CCRT during 2016 to 2017 at 3 medical centers across Taiwan. Vulnerability is defined as susceptibility to cancer- and treatment-related adverse events that result in poor treatment tolerance and unexpected emergent medical needs, such as hospitalization and emergency room visits. Vulnerability was assessed as impairment with ≥2 dimensions on comprehensive geriatric assessment, 7 days before CCRT. The association of vulnerability with treatment-related adverse events and survival was analyzed.

      Results

      The prevalence of vulnerability was 22.2%, 27.3%, 30.2%, and 27.9% among patients aged 20 to 34, 35 to 49, 50 to 64, and >65 years, respectively. Survival was poorer in vulnerable patients than in nonvulnerable patients (hazard ratio, 1.97; 95% confidence interval, 1.26-3.07; P = .003). Vulnerable patients showed a higher tendency toward CCRT incompletion (19.5% vs 6.1%, P < .001), hospitalization (34.6% vs 23.5%, P = .020), need for tubal feeding (29.3% vs 11.8%, P < .001), and longer length of hospital stay (8.1 days vs 4.0 days, P = .004) than nonvulnerable patients. Hematologic and nonhematologic toxicities were more severe in vulnerable patients than in nonvulnerable patients.

      Conclusions

      Vulnerability, which is an urgent concern when it presents among patients with head and neck cancer, was independently associated with poorer survival and severe treatment-related complications. Vulnerability assessment should be routinely evaluated in all patients with primary head and neck cancer who are undergoing definitive CCRT, not only in such patients who are geriatric.
      To read this article in full you will need to make a payment
      ASTRO Member Login
      ASTRO Members, full access to the journal is a member benefit. Use your society credentials to access all journal content and features.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Seiwert T.Y.
        • Cohen E.E.
        State-of-the-art management of locally advanced head and neck cancer.
        Br J Cancer. 2005; 92: 1341-1348
        • Lorch J.H.
        • Goloubeva O.
        • Haddad R.I.
        • et al.
        Induction chemotherapy with cisplatin and fluorouracil alone or in combination with docetaxel in locally advanced squamous cell cancer of the head and neck: Long-term results of the TAX 324 randomised phase 3 trial.
        Lancet Oncol. 2011; 12: 153-159
        • Adelstein D.J.
        • Li Y.
        • Adams G.L.
        • et al.
        An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer.
        J Clin Oncol. 2003; 21: 92-98
        • Zumsteg Z.S.
        • Kim S.
        • David J.M.
        • et al.
        Impact of concomitant chemoradiation on survival for patients with T1-2N1 head and neck cancer.
        Cancer. 2017; 123: 1555-1565
        • Pignon J.P.
        • le Maître 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
        • Hitt R.
        • Grau J.J.
        • López-Pousa A.
        • et al.
        A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer.
        Ann Oncol. 2014; 25: 216-225
        • Lefebvre J.L.
        • 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: 142-152
        • Haddad R.
        • O’Neill A.
        • Rabinowits G.
        • et al.
        Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): A randomised phase 3 trial.
        Lancet Oncol. 2013; 14: 257-264
        • Orbach D.
        • Sarnacki S.
        • Brisse H.J.
        Neonatal cancer.
        Lancet Oncol. 2013; 14: e609-e620
        • Fried L.P.
        • Tangen C.M.
        • Walston J.
        • et al.
        Frailty in older adults: Evidence for a phenotype.
        J Gerontol A Biol Sci Med Sci. 2001; 56: M146-M156
        • Ethun C.G.
        • Bilen M.A.
        • Jani A.B.
        • et al.
        Frailty and cancer: Implications for oncology surgery, medical oncology, and radiation oncology.
        CA Cancer J Clin. 2017; 67: 362-377
        • Mohile S.G.
        • Dale W.
        • Somerfield M.R.
        • et al.
        Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology.
        J Clin Oncol. 2018; 36: 2326-2347
        • National Comprehensive Cancer Network
        NCCN Clinical Practice Guidelines in Oncology. Older Adult Oncology. Version 2, 2018.
        (Available at:)
        https://www.nccn.org/professionals/physician_gls/PDF/senior.pdf
        Date: 2018
        Date accessed: December 20, 2018
        • Wildiers H.
        • Heeren P.
        • Puts M.
        • et al.
        International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer.
        J Clin Oncol. 2014; 32: 2595-2603
        • Hsu W.L.
        • Yu K.J.
        • Chiang C.J.
        • et al.
        Head and neck cancer incidence trends in Taiwan, 1980 ∼ 2014.
        Int J Head Neck Sci. 2017; 1: 180-189
        • Avisar A.
        • River Y.
        • Schiff E.
        • et al.
        Chemotherapy-related cognitive impairment: Does integrating complementary medicine have something to add? Review of the literature.
        Breast Cancer Res Treat. 2012; 136: 1-7
        • International Society of Geriatric Oncology
        Practice guideline: Comprehensive geriatric assessment (CGA) in oncological patients.
        (Available at:)
        • Mahoney F.I.
        • Barthel D.W.
        Functional evaluation: The Barthel index.
        Md State Med J. 1965; 14: 61-65
        • Lawton M.P.
        • Brody E.M.
        Assessment of older people: Self-maintaining and instrumental activities of daily living.
        Gerontologist. 1969; 9: 179-186
        • Rubenstein L.Z.
        • Harker J.O.
        • Salva A.
        • et al.
        Screening for undernutrition in geriatric practice: developing the short-form mini-nutritional assessment (MNA-SF).
        J Gerontol A Biol Sci Med Sci. 2001; 56: M366-M372
        • Quan H.
        • Sundararajan V.
        • Halfon P.
        • et al.
        Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.
        Med Care. 2005; 43: 1130-1139
        • Overcash J.A.
        • Beckstead J.
        • Moody L.
        • et al.
        The abbreviated comprehensive geriatric assessment (aCGA) for use in the older cancer patient as a prescreen: Scoring and interpretation.
        Crit Rev Oncol Hematol. 2006; 59: 205-210
        • Sheikh J.I.
        • Yesavage J.A.
        Geriatric Depression Scale (GDS). Recent evidence and development of a shorter version.
        in: Brink T.L. Clinical Gerontology: A Guide to Assessment and Intervention. The Haworth Press, Inc, New York1986: 165-173
        • Folstein M.F.
        • Folstein S.E.
        • McHugh P.R.
        “Mini-mental state.” A practical method for grading the cognitive state of patient for the clinician.
        J Psychiatr Res. 1975; 12: 189-198
        • Taylor S.
        • Murthy A.
        • Vannetzel J.
        • et al.
        Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer.
        J Clin Oncol. 1994; 12: 385-395
        • Chang P.H.
        • Yeh K.Y.
        • Wang C.H.
        • et al.
        Impact of the pretreatment Glasgow prognostic score on treatment tolerance, toxicities, and survival in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy.
        Head Neck. 2017; 39: 1990-1996
        • Chang K.P.
        • Lee C.C.
        • Su Y.C.
        • et al.
        Correlation between liver cirrhosis and risk of death from oral cancer: Taiwan cohort study.
        J Laryngol Otol. 2016; 130: 565-570
        • Bøje C.R.
        Impact of comorbidity on treatment outcome in head and neck squamous cell carcinoma - a systematic review.
        Radiother Oncol. 2014; 110: 81-90
        • Rieke K.
        • Schmid K.K.
        • Lydiatt W.
        • et al.
        Depression and survival in head and neck cancer patients.
        Oral Oncol. 2017; 65: 76-82
        • 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: 401-412
        • 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; 15: 875
        • VanderWalde N.A.
        • Deal A.M.
        • Comitz E.
        • et al.
        Geriatric assessment as a predictor of tolerance, quality of life, and outcomes in older patients with head and neck cancers and lung cancers receiving radiation therapy.
        Int J Radiat Oncol Biol Phys. 2017; 98: 850-857
        • Neve M.
        • Jameson M.B.
        • 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: 457-462
        • Forastiere A.A.
        • Zhang Q.
        • Weber R.S.
        • 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: 845-852
        • Huang P.W.
        • Lin C.Y.
        • Hsieh C.H.
        • et al.
        A phase II randomized trial comparing neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in advanced squamous cell carcinoma of the pharynx or larynx.
        Biomed J. 2018; 41: 129-136
        • Garden A.S.
        • Harris J.
        • Vokes E.E.
        • et al.
        Preliminary results of Radiation Therapy Oncology Group 97-03: A randomized phase II trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck.
        J Clin Oncol. 2004; 22: 2856-2864
        • Loong H.H.
        • Ma B.B.
        • Leung S.F.
        • et al.
        Prognostic significance of the total dose of cisplatin administered during concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma.
        Radiother Oncol. 2012; 104: 300-304
        • Ang K.K.
        Concurrent radiation chemotherapy for locally advanced head and neck carcinoma: Are we addressing burning subjects?.
        J Clin Oncol. 2004; 22: 4657-4659
        • Handforth C.
        • Clegg A.
        • Young C.
        • et al.
        The prevalence and outcomes of frailty in older cancer patients: A systematic review.
        Ann Oncol. 2015; 26: 1091-1101
        • Hamaker M.E.
        • Jonker J.M.
        • de Rooij S.E.
        • et al.
        Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: A systematic review.
        Lancet Oncol. 2012; 13: e437-e444
        • Dent E.
        • Lien C.
        • Lim W.S.
        • et al.
        The Asia-Pacific clinical practice guidelines for the management of frailty.
        J Am Med Dir Assoc. 2017; 18: 564-575
        • Huang C.C.
        • Lee J.D.
        • Yang D.C.
        • et al.
        Associations between geriatric syndromes and mortality in community-dwelling elderly: Results of a national longitudinal study in Taiwan.
        J Am Med Dir Assoc. 2017; 18: 246-251
        • Owusu C.
        • Berger N.A.
        Comprehensive geriatric assessment in the older cancer patient: Coming of age in clinical cancer care.
        Clin Pract (Lond). 2014; 11: 749-762
        • Ness K.K.
        • Krull K.R.
        • Jones K.E.
        • et al.
        Physiologic frailty as a sign of accelerated aging among adult survivors of childhood cancer: A report from the St Jude Lifetime cohort study.
        J Clin Oncol. 2013; 31: 4496-4503
        • Rockwood K.
        • Song X.
        • Mitnitski A.
        Changes in relative fitness and frailty across the adult lifespan: Evidence from the Canadian National Population Health Survey.
        CMAJ. 2011; 183: E487-E494
        • Kehler D.S.
        • Ferguson T.
        • Stammers A.N.
        • et al.
        Prevalence of frailty in Canadians 18-79 years old in the Canadian Health Measures Survey.
        BMC Geriatr. 2017; 17: 28
        • Wang C.H.
        • Wang H.M.
        • Pang Y.P.
        • et al.
        Early nutritional support in nonmetastatic stage IV oral cavity cancer patients undergoing adjuvant concurrent chemoradiotherapy: Analysis of treatment tolerance and outcome in an area endemic for betel quid chewing.
        Support Care Cancer. 2012; 20: 1169-1174
        • Chang P.H.
        • Yeh K.Y.
        • Huang J.S.
        • et al.
        Chemoradiotherapy in elderly patients with advanced head and neck cancer under intensive nutritional support.
        Asia Pac J Clin Oncol. 2015; 11: 228-235
        • McCarthy A.L.
        • Peel N.M.
        • Gillespie K.M.
        • et al.
        Validation of a frailty index in older cancer patients with solid tumours.
        BMC Cancer. 2018; 18: 892
        • O’Sullivan B.
        • Huang S.H.
        • 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: 440-451

      Linked Article

      • In Regard to Chou et al
        International Journal of Radiation Oncology, Biology, PhysicsVol. 108Issue 3
        • Preview
          We commend Chou et al for conducting this multicentered prospective study on vulnerability assessment before definitive chemoradiation for head and neck cancers. This study concluded that vulnerability, as measured by comprehensive geriatric assessment (CGA), was independently associated with poorer survival and higher treatment-related toxicities.1
        • Full-Text
        • PDF

      Comments

      Commenting Guidelines

      To submit a comment for a journal article, please use the space above and note the following:

      • We will review submitted comments as soon as possible, striving for within two business days.
      • This forum is intended for constructive dialogue. Comments that are commercial or promotional in nature, pertain to specific medical cases, are not relevant to the article for which they have been submitted, or are otherwise inappropriate will not be posted.
      • We require that commenters identify themselves with names and affiliations.
      • Comments must be in compliance with our Terms & Conditions.
      • Comments are not peer-reviewed.