Elderly patients affected by head and neck squamous cell carcinoma unfit for standard curative treatment: Is de-intensified, hypofractionated radiotherapy a feasible strategy?
Introduction
Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignant tumor worldwide, with over 600.000 new cases diagnosed per year [1]. In last 15 years, human papilloma virus (HPV) infection has been recognized to account for a distinct epidemiologic trend occurring mainly in western countries, leading to a rising incidence of oropharyngeal cancer (OPC) particularly in male patients in their 5 th decade of life [2], [3]. Next to the pathogenesis of HPV-driven OPC [4], the development of HNSCC is still largely the result of a chronic exposure to tobacco and alcohol – induced field cancerization [5] of the upper aerodigestive mucosal tract. As a consequence, almost half of the patients are older than 65 years at diagnosis [6]. In next 20 years, the incidence of HNSCC is expected to increase by 64% in the elderly population [7]. Level 1 evidence [8], [9], [10], [11] supports the use of multimodality treatment for the loco-regionally advanced disease which can be found in over 60% of cases: however, none of the intensified approaches addressed in clinical trials and metanalyses have demonstrated to provide clinical benefit in patients older than 65 years. Moreover, compared with younger subjects, elderly patients with head and neck cancer are more frequently burdened with treatment-induced severe acute toxicity [12], [13], multiple comorbidities [14] and non-cancer related death [15]. The aim of our work was to evaluate the feasibility and clinical benefit of a de-intensified hypofractionated radiotherapy in elderly patients deemed unfit for standard curative treatment, a group for whom at present no specific evidence-based recommendations [16], [17] are available.
Section snippets
Patients
Following the definition of the National Institutes of Health [18], patients with age ≥65 years were defined as old. In case of locally advanced HNSCC for whom the multidisciplinary team recommended a curatively-intended non surgical treatment, a prospective evaluation of frailty was performed when the treating oncologist considered the elderly patient unfit for standard therapy by clinical judgement. First, the Geriatric 8 (G8) screening tool was administered in order to identify subjects
Results
Between December 2011 and July 2016, 36 patients received the described hypofractionated de-intensified RT schedule. Patients’ characteristics are summarized in Table 1. The median age of the cohort was 77.5 (range: 65–91 years), with a high prevalence of male subjects. Notably, the most involved subsite of primary tumor was the oral cavity with a prevalence of 50% (n = 18). In most cases, patients had advanced tumors with stage IVA and IVB disease (86.1%). Only five patients (13.9%) had stage
Is there evidence to treat the elderly HNSCC patients with standard intensified therapy?
Multimodal treatment is standard of care in the curative setting of HNSCC on the basis of level 1 evidence. However, patients’ age is a factor that needs to be carefully taken into account. The individual patient data MACH-NC meta-analysis [8] showed that the concurrent addition of cisplatin-based chemotherapy to radiotherapy yielded a 6.5% improvement in 5-year OS (hazard ratio of death, 0.81; p < 0.0001). At subgroup analysis, the benefit was shown to be diluted with increasing age (test for
Conclusions
A de-intensified, moderately hypofractionated radiation schedule may provide early and mid-term clinical benefit with low toxicity in frail, elderly patients affected by locally advanced HNSCC. In this setting, a PTV larger than 200 cc is an unfavorable prognosticator of response. The treatment of non-metastatic HNSCC patients unfit for intensive standard therapy remains a significant challenge in head and neck oncology, warranting future investigations.
Conflict of interest statement
None declared.
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A systematic review on the association of the G8 with geriatric assessment, prognosis and course of treatment in older patients with cancer
2019, Journal of Geriatric OncologyCitation Excerpt :Five publications had loss to follow-up rates over 10% [12,27,29,42,54], while another 22 publications did not provide sufficient information to assess adequacy of follow-up [18,19,21,24,25,28,30–33,36,37,46,48,49,52,56–60,62]. Of the 24 studies reporting on the association of the G8 with survival, fourteen studies specifically mentioned the sociodemographic and/or clinical characteristics survival analyses were adjusted for [16,20,26,30,32,34,37,40,45,48,54,57,63,66] and seven performed multivariate analysis but did not report for which covariates they adjusted [12,19,21,24,25,28,31]. For another two studies it was unclear whether they performed univariate or multivariate analysis [59,62] and one study only did an univariate analysis [61].
Endoscopic laryngo-pharyngeal surgery for elderly patients
2019, Auris Nasus LarynxCitation Excerpt :These multidisciplinary therapeutic modalities have improved local regional control and overall survival in HNC. However, the treatment of elderly patients remains controversial, in part because elderly patients often have multiple comorbidities, and suffer more treatment-induced adverse effects and non-cancer related death compared to younger patients [2]. Previously, pharyngeal lesions, such as hypopharyngeal cancer, tended to present at an advanced stage and had a poor prognosis [3].
Hypofractionad radiotherapy for elderly with head and neck cancer
2018, Cancer/Radiotherapie