Early Quality of Life Outcomes In Head And Neck Cancer Survivors With EORTC QLQ-C30 And EORTC QLQ-HN35 In An Asian Tertiary Center

Background The objective of the study was to evaluate the quality of life (QOL) of head and neck cancer survivors after treatment and to identify patients’ main concerns. The study also aims to establish pre-treatment reference values particularly for the Asian patient. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Head and Neck module (EORTC QLQ-HN35) were used for objective evaluation. Methods Patients planned for elective surgery for head and neck cancers were enrolled in the study. The questionnaires were completed at pre-treatment and at 6 months after surgery. Results were compared with previously published reference values. Results 140 patients completed both questionnaires. Locally advanced tumour and extent of surgery [tracheostomy (p<0.01), surgical ap (p<0.01)] were associated with lower global health scores. Adjuvant treatment was also a contributory factor (p<0.01). Dysphagia and social eating was a primary concern within our population.


Abstract
Background The objective of the study was to evaluate the quality of life (QOL) of head and neck cancer survivors after treatment and to identify patients' main concerns. The study also aims to establish pretreatment reference values particularly for the Asian patient. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Head and Neck module (EORTC QLQ-HN35) were used for objective evaluation.
Methods Patients planned for elective surgery for head and neck cancers were enrolled in the study. The questionnaires were completed at pre-treatment and at 6 months after surgery. Results were compared with previously published reference values.
Results 140 patients completed both questionnaires. Locally advanced tumour and extent of surgery [tracheostomy (p<0.01), surgical ap (p<0.01)] were associated with lower global health scores. Adjuvant treatment was also a contributory factor (p<0.01). Dysphagia and social eating was a primary concern within our population.
Conclusion Treatment of head and neck cancers is safe but there is poor QOL in the early post-treatment period especially with eating. Previously published data suggests improvement after a year.

Background
Head and neck malignancies are cancers that can arise from the lip, oral cavity, pharynx, larynx, salivary glands or the facial sinuses. Due to the complexity in the anatomy and functions of the head and neck region, curative multimodality treatment can result in considerable long-lasting morbidity. Ideal treatment requires a ne balance between adequate disease clearance and the preservation of reasonable form and function. As a result, patients may sometimes be left with chronic dysfunction which can impact their physical, social and emotional functions as well as their overall quality of life (QOL). [1][2][3] The European Organisation for Research and Treatment of Cancer Quality of Life (EORTC) Group introduced a survey tool in 1994 as a means of measuring the QOL in cancer patients. Since then, there has been re nement of the questionnaires with speci c disease site modules. The EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and the EORTC Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) has been in use worldwide as a reliable tool for assessing the QOL in head and neck cancer survivors. 4 -6 This has been useful in identifying which impairments encountered by the patients affect their daily activities of living the most after treatment. In addition, analysis of the QOL study results can help to identify subgroups of patient who are more likely to be affected and therefore require additional targeted support for recovery.

Study design
This was a prospective study performed at a single tertiary institution in Singapore with patients recruited between the study period of 01/09/2015 -06/02/2020. Patients scheduled for major head and neck surgery are seen in a combined outpatient clinic consisting of different members of the healthcare team. The patients were recruited at this point and the initial survey conducted by an advanced practice nurse (APN). The English versions of both questionnaires were used in this study. The APN provided verbal translations for patients who were not English literate. Patients were invited to join the study if they were scheduled for a major elective head and neck surgery. Patients planned for thyroid or salivary gland surgery were only included if the surgery entailed more than resection of the gland with or without lymphatic clearance. Exclusion criterion included patients who subsequently did not undergo surgery, underwent neck dissection alone, benign histology of the resected specimen or patients who were unable to complete the 6-month survey. The study was approved by the local institutional review board.
Two QOL questionnaire tools were employed, namely the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and the Head and Neck Cancer module (EORTC QLQ-H&N35). The survey was carried out by the APN at recruitment as well as at one month and six months after their surgery. The interview was carried out either via face-to-face in the clinic or over the telephone and recorded in a central electronic database. All questions are scored on a 4 point Likert scale. Scores from both questionnaires are then translated to a 0 -100 points scale as per the scoring manual. Higher scores in the functional and global health status scales indicated towards better levels of functioning whereas higher scores in the symptom scales demonstrated higher levels of symptoms. The scores at diagnosis are presented for use as reference values for future studies. Our study population was then divided into subgroups and evaluated to identify patient, disease or treatment factors that would impact the patients' quality of life post treatment. The QOL scores were also compared against two recent large QOL studies on head and neck cancer survivors, Hammerlid

Subgroup analysis
The study population was divided into subgroups of patient and disease characteristics as well as extent of treatment received. The global health status (GHS) scores at 6-months post treatment were analyzed across the different subgroups (Table 5). None of the patient or socioeconomic characteristics were found to have a signi cant impact on the GHS scores. There was no difference in the GHS scores between gender, age groups or social factors. Patients reported a lower GHS score the more extensive the treatment received. For the sake of clarity, the subsequent scores are reported as the mean and standard deviation with the relevant p-value. Patients who underwent a tracheostomy had a lower score than those who did not [71.4 (15.5) vs 65.6 (14.0), p<0.01]. This was also true for patients who required a surgical ap. Patients who did not receive a ap scored higher than those with a free or pedicled ap [71.2 (13.7) vs 65.8 (15.4) vs 57.1 (12.2), p<0.01]. Adjuvant treatment was also associated with a lower GHS score (p<0.01). The stage of the disease was found to have impacted the patients, with locally advanced disease or a higher AJCC stage associated with lower GHS scores for both (p<0.01).

EORTC QLQ-C30
The results of the EORTC QLQ-C30 scores are as published in Table 6. The scores taken at 6 months after treatment were analyzed against the scores at diagnosis. There was no signi cant difference in the GHS despite the interval since treatment (p=0.82). Patients reported a lower physical functional scale after treatment [94.9 (11.0) vs 90.9 (17.2), p=0.05]. However, the patients felt emotionally better than at diagnosis  (Table 6). Our study population also reported less symptoms than both Hammerlid et al and Liao et al.

EORTC QLQ-HN35
The results of the EORTC QLQ-HN35 are shown in Table 7

Discussion
Our study populations reported a lower physical functional score at 6 months after treatment than at diagnosis. However, there was no speci c signi cant changes in the different categories of physical dysfunction. Hammerlid et al demonstrated that patients experience the most deterioration after treatment.
The study also showed that patients showed the most improvement only at one year after treatment. 7 In a systematic review by Klein J et al looking at 18 studies, chemoradiotherapy was shown to be a factor in the deterioration of the patient's QOL. Klein J et al reported the persistence of poorer QOL scores at 6 months when compared to the pre-treatment scores. These studies reported an improvement in most domains back to baseline only at 1 year after treatment. 8 Wang K et al also reported that radiotherapy and neck dissection were associated with worse symptoms at 6 months post-treatment especially with pain and mouth opening.
These patients reported normalization of the dysfunctions over time. 9 Similar ndings were re ected in our patients' scores especially with over 63% of the study patients still recuperating from adjuvant therapy. A proposed continuation of the study may show a return to baseline at 1 year.
QOL scores were signi cantly lower the more extensive the disease. Our study has also identi ed that lower GHS scores are associated with the extent of resection required, tracheostomy creation, surgical ap reconstruction and adjuvant therapy. The main difference post treatment was the increased need for nutritional supplements and is likely due to the persistent dysphagia as noted when compared against Hammerlid et al and Liao et al. Dysphagia, oral pain and xerostomia are a recognized complication from radiotherapy. 10,11 As the majority of our study population received adjuvant radiotherapy, this would account for the persistent dysphagia and the need for nutritional supplements as reported at the 6 months mark.
The different socioeconomic subgroups were not found to have a difference in outcomes. Contrary to our ndings, Liao et al observed that a high socioeconomic status was associated with a better global QOL. 6 This was similarly reported by Tribius S et al that long term QOL was poorer in patients with a lower socioeconomic background. 12 Janda M et al also observe a similar trend in that higher education levels and being married were associated with greater social and functional wellbeing. 13 In a study by Gopal KS et al, patients with a lower education level or lower income were noted to have a poorer outcome with a higher cancer mortality rate. 14 The authors postulate that this could be a result of the local health care system which heavily subsidizes the nancial costs to allow the general population access to affordable universal health care.
There were several limitations to our study design. The questionnaires were completed by a trained member of the study team after conducting a verbal interview with the patients. In addition, our local population, especially the older generation have a limited pro ciency of the English language. In these cases, the interviewer acted as a translator using the English versions of both questionnaire modules. As a result, there exists a potential interviewer bias which could have been avoided with a self-reported approach.
Furthermore, there has been a recent revision to the EORTC Head and Neck Module (EORTC QLQ-HN43). This latest edition will likely replace the EORTC QLQ-HN35 as the standard for future QOL studies. 15

Conclusion
The QOL of head and neck cancer survivors is expected to decline in the interim period following surgery.
Socioeconomic factors were not found to have a role in the outcomes. Patients experience more dysfunction especially with swallowing and social eating the more extensive the disease and the surgery. Adjuvant chemoradiotherapy was shown to be a contributing factor to the lower QOL. Current literature supports the ndings of an initial decline after treatment with most dysfunctions returning to baseline after approximately a year. Our ndings suggest that further rehabilitation targeted towards swallowing will be bene cial for the patients. A continuation of the study with analysis of the QOL scores at 1 year post treatment would be helpful to determine if our head and neck cancer survivors experience the same.

Declarations Funding
The authors did not receive any support from any organization for the study.

Con icts of Interest
The authors declares that they have no con ict of interest.
Availability of data and material Data will be made available via correspondence with the correspondent author.