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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 79-84

Study of association of age at presentation with outcome in patients with head-and-neck cancer


1 Department of Radiotherapy, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India
2 Department of Radiodiagnosis, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India
3 Department of Community Medicine, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh, India

Date of Submission06-Sep-2020
Date of Decision29-Jan-2021
Date of Acceptance01-Feb-2021
Date of Web Publication17-Jul-2021

Correspondence Address:
Radha Kesarwani
Department of Radiotherapy, Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh 211002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCSR.JCSR_80_20

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  Abstract 


Background: Elderly patients with head-and-neck cancer (HNC) are increasing in number. Outcome of HNC with relation to age is controversial.
Methods: In this hospital-based retrospective study, medical records of 76 patients of HNC who were treated with surgery followed by radiotherapy or radiotherapy with or without chemotherapy were analysed. The patients were divided into two age groups: Group I patients ≥55 years and Group II patients <55 years. Patient characteristics, treatment and toxicities were evaluated. They were followed-up clinically and radiologically up to a median time of 16 months.
Results: Complete response was 94.4% and 80.05% in Group I and II, respectively. Disease-free survival (DFS) was 53.67% and 47.8% in Group I and II, respectively (P = 0.332), whereas overall survival (OS) was 67.34% and 49.42% in two groups, respectively (P = 0.234); hence, DFS and OS are not statistically significant.
Conclusion: Complete response was more frequently among patients older than 55 years in comparison to patients younger than 55 years, even though the dose delivered to them is lower. There was no statistically significant difference in both groups with respect to DFS and OS. Haematological toxicities were found more in older patients in comparison to patients younger than 55 years.

Keywords: Head and neck cancer, outcome, radiotherapy


How to cite this article:
Kesarwani R, Singh A, Singh V, Prakash G. Study of association of age at presentation with outcome in patients with head-and-neck cancer. J Clin Sci Res 2021;10:79-84

How to cite this URL:
Kesarwani R, Singh A, Singh V, Prakash G. Study of association of age at presentation with outcome in patients with head-and-neck cancer. J Clin Sci Res [serial online] 2021 [cited 2021 Aug 3];10:79-84. Available from: https://www.jcsr.co.in/text.asp?2021/10/2/79/321702




  Introduction Top


Cancer is a disease of ageing; approximately 60% of all cancers and 70% of cancer mortality occur in persons aged 65 years and above.[1] The number of cancer patients over the age of 65 years is projected to significantly increase over the next 20 years. In India, 11% of its population will include geriatric population (>60 years age) by the year 2020.[2] The incidence of cancer increases with age, and more than 12%–23% of all cancers occur after the age of 65 years.[3] In India, head and neck cancers (HNCs) are common and account for about 30% of cancers in males and about 13% in females. In males, the oral cavity and pharynx followed by the larynx, and in females, oral cavity are the commonly affected sites.[4]

Cancers of the head and neck are the fifth most common cancer worldwide and responsible for more than 200,000 deaths per year.[5] More than 50% of HNC cases occur in patients aged >60 years and 28% occur in patients aged >70 years. With an ageing population, we will likely face increasing numbers of elderly HNC patients in the coming years. Despite this, few studies have focused specifically on the characteristics and treatment of older patients with head and neck squamous cell carcinoma (HNSCC). Of those studies that exist, several have shown that elderly patients can achieve outcomes similar to those of younger patients if treated with similar therapies.[6],[7],[8],[9],[10],[11],[12] Others have noted worse outcomes in older patients but have concluded that the higher risk of mortality is entirely due to higher comorbidity status and competing causes of mortality rather than chronological age,[13],[14] whereas others have suggested that age is an independent prognostic variable.[14],[15] Several studies[16],[17],[18] have also concluded that geriatric patients with HNC frequently receive nonstandard and less aggressive therapies than their younger counterparts. Receiving nonstandard therapy is an independent risk factor for decreased survival.[19],[20] Moreover, many of the prospective clinical trials have excluded this group of patients from the trials, and thus, no worthwhile clinical studies were forthcoming from this age group, especially in the Indian setup.

This study aimed to assess the characteristics and outcome of HNC patients in older than 55 years in comparison to patients younger than 55 years who underwent surgery followed by radiotherapy or definitive radiotherapy with or without chemotherapy.


  Material and Methods Top


This study included 76 patients who visited our hospital with HNC from September 2018 to December 2018. Written informed consent was obtained from all the participants. The study was cleared by the Ethics Committee of Moti Lal Nehru Medical College, Prayagraj, Uttar Pradesh. Patients were divided into two groups based on ages at their initial visits: The first group aged more than 55 years and the second group aged <55 years. We assessed the male-female ratio, primary tumour sites, disease stage, applied treatments and cure rate.

The primary tumour sites were classified as larynx, oral cavity, oropharynx, larynx or others, while tumour stage was classified as either early tumour (Stage I or II) or advanced tumour (Stage III or IV), according to the 8th edition of the Union for International Cancer Control classification of malignant tumours.[21] All patients who have completed treatment and at least 3 months of follow-up or event occurred before that period were included in the study.

All these patients received radiotherapy with telecobalt 60 machine beam either after surgery (primary or followed by neoadjuvant chemotherapy) or as definitive treatment modality, with or without sequential and/or concurrent chemotherapy. The pre-treatment evaluation was included a complete history and physical examination including a complete head and neck examination; mirror and fibre-optic examination as clinically indicated, chest X-ray, complete blood count, liver and renal biochemistry, biopsy, chest imaging and computed tomography (CT) of the head-and-neck region.

All these patients were immobilised in the treatment position (supine with extended neck) with thermoplastic cast with suitable neck rest. Treatment field marked on telecobalt machine as per clinical staging, and then radio-opaque copper wire was placed on marked field. Contrast-enhanced CT axial images with 2.5 mm slice thickness and with proper field of view were acquired in the treatment position with immobilisation aids after intravenous injection of 40 mL of the contrast media on CT scanner. Then, field was reviewed on CT scan and changed accordingly to include tumour and risk group of cervical lymph nodes with appropriate margins. All patients had bilateral lymph nodes irradiation either definitive or post-operative radiotherapy along with primary tumour region's irradiation using telecobalt machine by two parallel opposed fields.

The dose was calculated for maximum inter-field separation at the level of tumour. The prescribed dose to the non-involved lymph node level was 56–60 Gy/28–30 fractions over 5½ to 6 weeks. Involved lymph node levels was planned to receive 60–66 Gy in 6–6½ weeks in post-operative setting and 66–70 Gy in 6–7 weeks in patients who received definitive radiotherapy in fractions of 2 Gy.

Patients were seen weekly during radiotherapy. Acute radiation toxicities were always graded and recorded. After the completion of the treatment, patients were seen every month during the 1st year, every 2 months in the 2nd year and every 3–6 months thereafter. The first post-treatment CT was obtained 2–6 months after the completion of radiotherapy; thereafter, regular CT or magnetic resonance imaging studies were obtained every 6–12 months or earlier on indication.

Statistical analysis

Data for applied treatment and outcome, disease-free survival (DFS) rate and post-treatment toxicities were studied using Chi-square test. Kaplan–Meier curves were used for calculating DFS and overall survival (OS) for both groups.


  Results Top


The older age group ≥55 years) comprised of 36 patients their mean age was 59.3 (range 55–67) years; there were 28 males. The younger age group (<55 years) comprised of 40 patients. Their mean age was 42.5 (range 31–52) years; there were 36 males.

The patient characteristics are shown in [Table 1]. Squamous cell carcinoma was predominant histologic type in both the groups (91.7% and 95.0%, respectively) [Table 1]. All patients in the older age group, had advanced stage (Stage III or IV). In the younger age group, 8 patients (20.0%) belonged to early stage and 32 patients (80.0%) belonged to an advanced stage.
Table 1: Characteristics of patients

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[Table 2] shows the details of the applied treatments in each category. The combined modality (surgery + radiotherapy) treatment category comprised 20 of 36 patients (55.6%) in the older age group and 24 of 40 patients (60.0%) in the younger age group. The single modality treatment radiotherapy category comprised 16 of 36 patients (44.4%) in the older age group and 16 of 40 patients (40.0%) in the younger age group.
Table 2: Applied treatment, outcome and toxicities of both groups

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[Table 2] shows the number of patients who developed recurrence and metastases in both treatment categories. Recurrence and metastases occurred in 4 of 36 patients (11.1%) and 2 of 36 (5.6%), respectively, in the older age group and 7 of 40 patients (17.5%) and 1 of 40 (2.5%), respectively, in the younger age group. The recurrence rate was higher in the younger age group than the older age group, whereas metastases were higher in older age group than younger age group, but the difference was not significant (P = 0.777914).

Kaplan–Meier estimator curve of DFS in both groups, the 1-year DFS in the old age group (36 patients) was 53.7%, while that in the young group (40 patients) was 47.8%, although the difference is not significant (P = 0.332). As shown in [Figure 2], Kaplan–Meier estimator curve of OS in both groups, the 1-year OS in the old age group (36 patients) was 67.3%, whereas that in the young age group (40 patients) was 49.4%, difference not significant (P = 0.234). Mean survival time was (9.00 months ± 1.29 standard deviation [SD]; 95% confidence interval [CI]) for group I and (9.50 months ± 1.32 SD; 95%CI) for Group II. Details of survival observed in some of the patients is shown in [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5].
Figure 1: Disease-free survival curve

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Figure 2: Overall survival

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Figure 3: Axial contrast-enhanced computed tomography of 48-year-old male patient with left-sided floor of the oral cavity mass and contralateral lymph nodes postoperative showing post-operative oedema and changes (a). The patient was subjected to radiotherapy with telecobalt and disease-free survival rate came out to be 10 months. Photomicrograph of the biopsy specimen showing solid sheet of malignant cells, having high nuclear:cytoplasmic ratio and coarse chromati suggestive of squamous cell carcinoma (Haematoxylin and eosin, X 100) (b)

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Figure 4: Axial contrast-enhanced computed tomography of a 60-year-old male with hypodense mass involving oral cavity, palate and posterior part of the tongue characterised as squamous cell carcinoma on histopathology, underwent radiotherapy. Disease-free survival rate was 9 months and patient developed skin and mucosal reactions

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Figure 5: Axial contrast-enhanced computed tomography of a 51-year-old male showing heterogeneous, mildly enhancing mass involving left lateral aryepiglottic folds, pre-epiglottic space and intrinsic muscle extension with crossing of midline-Grade IV squamous cell carcinoma. The patient underwent radiotherapy with disease-free survival of 7 months and developed laryngeal oedema

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[Table 2] shows toxicities stratified by patients group with skin reactions being most common in old age with low-grade tumours (66.7%; χ2 = 1.0794; P = 0.2988) and laryngeal reactions being most common in patients <55 year of age with high grade tumours (60%; χ2 = 0.4023; P = 0.5259).


  Discussion Top


Older patients (herein, defined as ≥55 years) with HNC often have co-morbid conditions that often impair their functional status that may decrease their ability to receive and tolerate upfront surgery followed by concurrent chemoradiotherapy or for inoperable cases concurrent chemoradiotherapy with or without salvage surgery. Head-and-neck cancer in India causes predominantly by the use of tobacco, paan and betel nut after prolonged exposure in elderly age group which also result in significant co-morbidity in contrast to the Western population where the incidence of HPV-related cases are high in numbers. The definition of the older patient population is somewhat varying so we have selected 56 years as the cut-off point.

Osteoporosis, Alzheimer's disease, frailty, obesity, diabetes mellitus, hypercholesterolaemia, hypertension, cardiac failure and ischemic heart disease usually in our population start at 50 years, so considering old age after 56 years will make this group having similar risk factors. Subjects over 56 years of age may have different response to the treatment of cancer as compare of younger than that age group is because of effect of these associated diseases on compromising blood supply and this also having impact on response of radiotherapy/surgery/chemotherapy on the outcome of disease. Younger patients are more likely to undergo upfront surgery which alters vascularity/lymphatic flow pattern further causing altered radiation response as compare to no upfront surgery in older patients.

Our results of treatment of cancer of the head and neck in older patients versus younger patients were similar to an earlier research study, which reported that particularly, head-and-neck squamous cell carcinoma in elderly patients did not seem to have a significantly different outcome when compared with head and neck squamous cell carcinoma occurring in younger patients. When properly monitored, conventional therapies seem feasible in older patients.[11] Another research study by Hasegawa et al.[22] had a similar outcome as our study. In this study, the ratio of patients with underlying diseases in the old-old group was significantly higher than in the young-old group, but there was no significant difference in the curative rate between the two (old-old, 81.9%; young-old, 82.7%). The 5-year, cause-specific survival in the curative treatment category was significantly lower in the old-old (66.1%) group than the young-old (94.1%) group. Similar to our retrospective survival data, in the majority of studies comparing treatment modalities between older and younger cohorts with HNC, older patients did not appear to have worse survival than their younger peers. Limited data suggest that selected older patients have survival outcomes similar to younger patients when treated primarily with surgery,[23] which was not the primary treatment in our retrospective study. An earlier study performed a comparison of 39 patients ≥70 years receiving accelerated concomitant boost radiation with 80 patients <70 years receiving the same radiation regimen.[24] There was no observed difference in 3-year OS or local control between the two groups.

In our study, older patients did not experience inferior survival in comparison to younger patients. Although distant metastasis was more frequently evident in older individuals and local recurrence was higher in younger individuals, these were not statistically significant. In our study, 1-year disease free and OS was higher in older individuals in comparison to younger individuals although not significant. It may be due to less aggressive behaviour of tumour in older individuals, although further evidence is needed to draw any conclusion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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