MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY BÙI THẾ ANH HEALTH-RELATED QUALITY OF LIFE OF LARYNGEAL CANCER PATIENTS PRE- AND POST- SURGICAL TREATMENT Major: Otorhinolaryngology Code: 62.72.01.55 SUMMARY OF THESIS FOR DOCTOR OF MEDICINE HANOI - 2019 THESIS COMPLETED IN: HANOI MEDICAL UNIVERSITY Supervisor: Assoc Prof Pham Tuan Canh, MD, PhD Reviewer 1: Reviewer 2: Reviewer 3: Thesis will be defended at University level Doctoral thesis assessment committee at Hanoi Medical University Thesis can be found in: National library of Vietnam Hanoi Medical University library INTRODUCTION Topic "quality of life" was obviuosly mentioned in philossophy, literature and sociology Recently, this topic has been widely mentioned in other different fields In medicine, this topic appears as "health-related quality of life" (HRQOL) After World Health Organisation, HRQOL is an assessment of how the individual's well-being may be affected over time by a disease, disability or disorder Healthiness is not only evaluated in medical view but also in psychological, social and economic views Nowadays, the "outcome" is used to measure treatment result so QOL is considered as an outcome of treatment, especially in oncology because every modality of cancer treatment can eliminate the tumor but also affect patient's quality of life QOL researches provide complete and thorough information about the disease process as well as post-treatment health status, therefore it help patients (Pt) both in selecting appropriate treatment method and improving their post-treatment adaptation Laryngeal cancer is a malignancy disease originating from epithelial cells in larynx Laryngeal cancer can be cured by multimodal treatment (surgery, radiotherapy or chemo-radiotherapy), with 5-year overall survival rate about 60% The disease itself and its surgical treatment can change the laryngeal structure and therefore affect laryngeal functions Laryngeal cancer surgery may also change patients' appearance and cause cosmetic effect Those anatomical and functional changes can impact patient's quality of life in physical, emotional and social scales (voice disorder, reduction of speech communication, swallowing disorder, eating habitude, reduction of olfactory and gustatory ability, dyspnea, cough, limited social integration, loss of work, increasing risk of stress and depression) Based on these essential quality of life informations, healthcare professionals can provide good recommendation for patients pre-treatment; plan post-treatment psychological consult and adaptive rehabilitation for every single patient Up to now, there are few published researches in Vietnam mentioned health-related quality of life of laryngeal cancer pre- and post- surgical treatment The study "Quality of life of laryngeal cancer pre- and post- surgical treatment" was carried out with aims: 1.Evaluate pre-operative health-related quality of life of laryngeal cancer Evaluate post-operative health-related quality of life of laryngeal cancer 3.Compare pre-operative and post-operative health-related quality of life to improve patient consultation NEW CONTRIBUTIONS OF THESIS  For the fisrt time, health-related quality of life assessment using modern tool (EORTC-C30 and EORTC-H&N35 questionnaires) was successfully applied on Vietnamese laryngeal cancer patients pre-operation and post-operation  Provide a thorough database about health-related quality of life of Vietnamese laryngeal cancer patient treated with different surgical techniques (Transoral Laser Microsurgery, Open Partial Laryngectomy and Total Laryngectomy) in occasions: preoperation, month, months, months and 12 months postoperation Post-operative QOL in three patient groups were worse both in functional scales and symptom scales, the most significant declineation was seen within total laryngectomy group This declineation in QOL existed for longtime post-operatively STRUCTURE OF THESIS This thesis contains 116 pages in which Introduction (2 pages), Chapter (Overview - 31 pages), Chapter (Materials and Methods: 12 pages), Chapter (Results: 36 pages), Chapter (Disscussion: 31 pages), Conclusion (2 pages), Recommendation (1 page), New contributions of thesis (1 page) There are 28 tables, charts, figures and 155 references (11 references in Vietnamese, 143 references in English, reference in French) Chapter OVERVIEW 1.3.Physiology of larynx There are main functions of human larynx:  Protection: larynx works as a sphincter, preventing the ingress of anything other than air into lower respiratory tract (trachea, bronchi and lungs)  Speech: Sound is produced by the larynx when expiratory airflow from lung and bronchi) goes through glottis and induces vibration of free edges of the vocal folds  Regulation of airflow: Larynx helps control the volume of inspiratory and expiratory airflow; it also stops the respiratory process temporarily during swalowing phase  Closure of glottis: Forced expiration against a tightly closed glottis is known as the Valsalva maneuver It is important in defecation and also serves to stabilize the thorax during heavy lifting by the arms 1.5.Treatment of laryngeal cancer Treament of laryngeal cancer includes surgery, radiotherapy or chemotherapy (single- or multi-modal treatment) Surgery is still the most common method of treatment in Vietnam Early stage disease (S1 - S2) is treated by conservative surgery (transoral laser microsurgery; laryngofissure or open partial laryngectomy) When the disease is on locally advanced stage but resectable: indication of total laryngectomy plus neck dissection and adjuvant radiotherapy With advanced stage and unresectable disease: indication of concurrent chemoradiotherapy or palliative treatment 1.5.1.Surgery Common surgical techniques for laryngeal cancer in Vietnam are: transoral laser microsurgery, laryngofissure, partial laryngectomy with crico-epiglotto-hyoidoplasty or total laryngectomy * Transoral laser microsurgery (TLM): tumor mass is resected together with partial or total cordectomy (other structures may also be included in the resection: impaired vocal process, anterior commissure, ventricular fold, subglottic mucosa) Anatomy of glottis and vocal cords is modified after TLM, therefore glottis can not close properly in phonation and voice is disturbed (hoarseness, breathy voice, increased effort required to talk) Sometimes glottic scar (possible sequelae of TLM) can cause glottic stenosis and laryngeal dyspnea *Laryngofissure: thyroid cartilage is cut vertically in the midline to approach endolarynx, the tumor mass and ipsilateral vocal cord are resected completely Anatomy of glottis and vocal cords is modified after laryngofissure, therefore glottis can not close properly in phonation and voice is disturbed (hoarseness, breathy voice, increased effort required to talk) Sometimes glottic scar (possible sequelae of laryngofissure) can cause glottic stenosis and laryngeal dyspnea *Supracricoid partial laryngectomy with crico-epiglottohyoidoplasty: The tumor mass is resected together with a portion of thyroid cartilage, two vocal cords, two ventricular folds, petiole Preservative structures include most of epiglottis, hyoid bone, cricoid cartilage and at least one arytenoid cartilage Many functions of larynx (Protection, speech and swallowing) are affected after the surgery, causing voice disorders, swallowing disorder, cough, aspiration and inhalation pneumonia *Total laryngectomy (TL): tumor mass is resected together with the whole larynx structure, hyoid bone, one or two tracheal rings and infrahyoid muscles Removal of the entire larynx and separation of the upper and lower airways results in a significant alteration in the ability to verbally communicate After total laryngectomy, the vibrating body is removed and there is alteration of the air source and resonant tract Other functions (protection of lower respiratory tract and respiratory regulation) are also severely impacted 1.6.Introduction of "health-related quality of life" “Health-related quality of life” is an assessment of how the individual's well-being may be affected over time by a disease, disability or disorder Characteristics of HRQOL include: selfreported, subjective, multi-dimensional and changes over time HRQOL may be measured globally or componently with different domains: physical activity, psychological state, social interaction and somatic sensation / symptoms HRQOL research plays more and more important role in general medicine In oncology, HRQOL is considered an index in assessing treatment outcomes (similar to other classic indexes such as overall survival, 5-year specific survival…) HRQOL research provides multi-dimensional information about patient's health status as well as adverse effects during or after treatment Based on these data, healthcare professionals can plan to treat those adverse effects and apply better rehabilitation for patients In clinical practice, HRQOL data give patients more concrete information about the disease process and prognosis This information contributes in patient's decisionmaking before treatment HRQOL research also helps to compare different treatment modalities and to assess novel therapeutic treatment 1.7.Tools to measure HRQOL of laryngeal cancer patients It is common to use subjective methods to measure HRQOL: those methods are patient-reported questionnaires Two questionnaires were selected (EORTC-C30 and EORTC-H&N35, developed by European Organization of Research and Treatment of Cancer) to use as measuring tool to assess HRQOL of laryngeal cancer in this study 1.8.Post-operative QOL of laryngeal cancer patients Treatment of head and neck cancer (including laryngeal cancer) can cause many sequelae: voice disorder, swallowing disorder, dyspnea, cough, mouth dryness, olfactory and gustatory deficiency, teeth damage, pain in mouth, lomited moth opening, change in appearance These sequelae can affect patient's QOL in many different way There have been many published studies about QOL of laryngeal cancer patients after surgical treatment (TLM; open partial laryngectomy - OPL; or TL) However, most of those studies were cross-sectional or retrospective studies: all laryngeal patients treated with surgery were recruited into the study sample, then they were classified into different groups (depend on type of surgery) and QOL were measured The different interval between surgery and OQL assessment timepoint could cause bias in QOL measurement because QOL might change over time Some authors reduced this bias by using longitudinal prospective study method: laryngeal cancer patients were recruited into study sample before surgery, then QOL was measured at the same timepoint after surgery According to these longitudinal prospective studies: postoperative QOL of laryngeal cancer patients changed significantly within the first year post-operation and became stable since then Based on this result, we decided to assess post-operative QOL of laryngeal cancer patients at specific timepoints: month, months, months and 12 months post-operatively There was some limit in published longitudinal studies: QOL of laryngeal cancer patients was assessed with only one technique of surgery (TLM, OPL or TL) then QOL of patients underwent different techniques could not be compared Chapter MATERIALS AND METHODS 1.Study subjects Sample patients were selected among laryngeal cancer patients underwent curative surgery in Department of Oncology - Head and Neck Surgery (National ENT Hospital of Vietnam - 78 Giai Phong Road, Dong Da - Hanoi) Sample selection criteria Patient with definitive diagnosis of primary laryngeal cancer (confirmed by histological result of squamous cell carcinoma) without any previous treatment; All medical records were available; curative surgery indicated; Agreed to participate into this study; Had at least 12 months of follow-up; completely all questionnaires at all timepoints: pre-operation; month, months, months and 12 months post-operation Sample patients Patients were categorized into three groups based on surgical treatment of the primary tumor These groups were: Group 1-TLM, Group 2-Open Partial Laryngectomy (OPL), and Group 3-Total Laryngectomy (TL) Exclusion criteria Exclusion criteria included: previous treatment of cancer, distant metastases or second primary tumor (confirmed before treatment or during first-year follow-up period), palliative surgical treatment, cognitive impairment or lack of proficiency in Vietnamese, or loss to follow-up at any time-point 2.2.Methods of study This was a longitudinal prospective study with convinience sampling There was no control group in the study 2.3.Tool of measurement In this study, two questionnaires were used to assess QOL of laryngeal cancer patients: EORTC QLQ-C30 and EORTC QLQH&N35 C30 is the core questionnaire for all cancer patients; and H&N35 is the specific module for head and neck cancer patients (including laryngeal cancer) using in combination with C30 These two questionnaires were well developed by European Organisation of Research and Treatment of Cancer The EORTC QLQ-C30, which assesses physical, psychological and social functions of cancer patients, includes 30 questions, 24 of which form nine scales representing various dimensions for health-related QOL, including a global scale, five functional scales (physical, role, emotional, cognitive, and social), and three symptom scales (fatigue, pain, and nausea) The remaining six items measure cancer-oriented symptoms (dyspnea, insomnia, appetite, constipation, diarrhea, and financial difficulty) The EORTC QLQ-H&N35, which assesses QOL, includes 35 questions, which constitute seven symptom scales (pain, dysphagia, gustatory and olfactory senses, speech, social eating, social contact, and sexuality), and six single items for symptoms specific to head and neck cancers Responses were converted into a linear scoring scale, with values ranging from to 100 per EORTC Scoring Manual 2.5.QOL scales and items used in this study QOL of laryngeal cancer patients was measured and evaluated 12 Table 3.16: QOL scores (symptom scales) in group LASER preand post-operation Post-operation Item / scale Preop month 𝑋̅ month 𝑋̅ month 𝑋̅ 12 month 𝑋̅ Appetite loss 8.8 16.7* 30.7** 20.2* 16.7* Sticky saliva 4.4 17.5** 30.7** 22.8** 18.4** Senses problems 6.1 9.7 22.4** 16.7** 11.8* Opening mouth 0.9 7.0* 8.8** 5.3* 6.1 Social eating 3.9 11.8* 28.3** 11.6** 8.8 Fatigue 11.1 18.7* 28.9** 27.5* 17.2 Dry mouth 14.1 21.1 35.1** 24.4* 19.3 Swallowing 7.0 11.4 23.1** 12.9** 11.5 Speech problem 40.9 52.3* 65.5** 48.8 43.9 Financial difficulty 14.9 32.5** 26.3* 17.5 13.2 Pain 8.8 9.7 16.2* 7.9 6.1 Pain in mouth 5.3 11.4 22.6** 7.9 7.0 Teeth 24.6 17.5 28.9 30.7 33.3* Coughing 22.8 29.8 48.3** 28.1 26.3 Dyspnea 13.2 13.2 29.8** 14.9 13.2 Social contact 13.5 18.3 24.2** 15.3 13.9 Insomnia 31.6 34.2 57.0** 41.2 35.9 Constipation 15.8 14.9 20.2 14.9 23.7* Feeling ill 8.8 16.7 28.9** 14.9 10.5 Nausea-vomiting 3.9 6.1 6.1 2.2 1.3 Diarrhea 2.6 2.4 1.8 1.5 Less sexuality 35.9 33.5 47.4 41.7 39.0 (*): p < 0.05; (**): p < 0.01 (in comparison with pre-operation) Values > 20 were in bold font (can have impact to QOL) 13 Table 3.17: QOL score (general QOL and functional scales) in group LASER pre- and post-operation Post-operation Item / scale Preop Global QOL Physical functioning Role functioning Emotional functioning Cognitive functioning Social functioning 74.8 95.3 92.9 87.1 92.9 95.6 month 𝑋̅ month 𝑋̅ month 𝑋̅ 12 month 𝑋̅ 62.2* 90.2* 86.4* 78.5* 89.5 79.4** 60.1** 79.7** 62.3** 70.4** 75.9** 66.7** 70.0 84.0** 70.2** 88.2 85.5* 78.5** 74.3 85.9** 73.3** 89.9 87.7 79.4** Table 3.18: QOL score (general QOL and functional scales) in group OPL pre- and post-operation Post-operation Item / scale Preop month 𝑋̅ month 𝑋̅ month 𝑋̅ 12 m.nth 𝑋̅ Global QOL 77.8 55.2** 65.8** 70.3** 75.3 Physical functioning 94.7 77.9** 86.5** 91.5* 93.9 Role functioning 98.7 53.0** 65.7** 72.7** 77.0** Emotional functioning 74.5 77.3 90.8** 95.0** 95.8** Cognitive functioning 94.7 86.0** 94.3 94.0 94.7 Social functioning 92.7 58.0** 72.1** 75.3** 79.9** (*): p < 0.05; (**): p < 0.01 (in comparison with pre-operation) Values < 80 were in bold font (can have impact to QOL) 14 Table 3.19: QOL scores (symptom scales) in group OPL preand post-operation Post-operation Item / scale Preop month 𝑋̅ month month 𝑋̅ 𝑋̅ 12 month 𝑋̅ Speech problem 31.8 68.9** 55.1** 48.9** 47.3** Social contact 3.3 33.5** 13.2** 9.1** 8.3* Coughing 7.3 58.1** 36.7** 28.7* 27.3** Swallowing 4.7 29.7** 15.1** 13.7** 10.7** Dry mouth 10.0 31.3** 18.1* 18.0* 23.4* Senses problems 2.0 17.1** 9.1** 9.3** 7.7* Social eating 1.0 35.5** 20.3** 15.3** 13.7** Less sexuality 22.3 61.3** 40.1** 35.1** 31.7* Fatigue 4.9 30.7** 14.9** 10.9* 8.0 Appetite loss 11.3 39.2** 24.7** 18.7* 10.7 Sticky saliva 8.0 32.1** 16.7* 14.1 14.0* Pain 2.1 22.0** 8.7* 3.7 4.1 Pain in mouth 4.0 27.0** 11.2** 6.8 4.5 Dyspnea 14.1 39.3** 28.0* 18.7 15.3 Insomnia 30.1 54.7** 40.0* 35.3 28.0 Feeling ill 4.7 37.3** 15.3** 9.3 4.7 Opening mouth 3.3 15.3** 8.2 5.3 4.7 Nausea - vomiting 3.7 17.3** 5.0 2.1 1.3 Constipation 18.7 10.7* 12.0 19.3 24.1 Financial difficulty 8.7 23.3* 20.7 13.3 12.7 Teeth 18.7 20.7 18.1 24.7 23.3 Diarrhea 2.1 12.7 5.3 4.7 3.3 (*): p < 0.05; (**): p < 0.01 (in comparison with pre-operation) Values > 20 were in bold font (can have impact to QOL) 15 Table 3.20: QOL scores (symptom scales) in group TL pre- and post-operation Post-operation Item / scale Preop month 𝑋̅ month 𝑋̅ month 𝑋̅ 12 month 𝑋̅ Speech problems 36.6 92.5** 87.4** 82.3** 79.9** Social contact 1.9 53.2** 42.2** 34.9** 22.9** Coughing 9.0 72.9** 45.9** 34.2** 44.1** Opening mouth 0.9 9.9** 7.2* 7.3* 7.2* Dry mouth 4.5 35.1** 35.2** 30.6** 31.5** Sticky saliva 1.8 36.9** 37.8** 26.1** 28.8** Senses problems 0.5 41.0** 47.3** 48.7** 45.9** Social eating 2.3 52.5** 29.5** 22.1** 20.5** Appetite loss 9.9 55.9** 34.2** 23.4** 22.5** Fatigue 2.7 43.5** 24.0** 14.7** 11.1** Less sexuality 13.9 82.4** 65.8** 54.9** 42.8** Feeling ill 3.6 61.3** 36.9** 26.1** 15.3** Financial difficulty 9.0 39.6** 38.7** 30.6** 22.5** Dyspnea 13.5 43.2** 30.6** 22.5** 18.9 Insomnia 35.1 68.5** 46.9* 42.3 36.9 Constipation 11.7 3.6* 11.7 5.4 25.2** Diarrhea 0 10.8** 16.2** 0.9 Pain 3.2 31.9** 12.6** 3.2 0.9 Pain in mouth 4.1 40.8** 17.8** 5.2 2.7 Swallowing 8.1 42.8** 19.6** 14.9 11.9 Nausea-vomiting 4.9 30.6** 8.1 2.3 1.8 Teeth 17.1 23.4 20.7 27.0* 24.3 (*): p < 0.05; (**): p < 0.01 (in comparison with pre-operation) Values > 20 were in bold font (can have impact to QOL) 16 Table 3.21: QOL score (general QOL and functional scales) in group TL pre- and post-operation Post-operation Item / scale Pre-op month 𝑋̅ month 𝑋̅ month 𝑋̅ 12 month 𝑋̅ 68.0** Global QOL 77.9 38.7** 50.7** 59.6** Physical functioning 94.6 69.9** 85.2** Role functioning 98.2 44.1** 54.1** 61.3** Emotional functioning 73.9 68.5 Cognitive functioning 98.2 82.9** 90.1* 85.6** 90.8** 94.1* 93.2* 92.4 64.4** 94.6** 96.9 Social functioning 96.4 38.7** 48.2** 62.2** 65.3** (*): p < 0.05; (**): p < 0.01 (in comparison with pre-operation) Values < 80 were in bold font (can have impact to QOL) Chapter DISCUSSION 4.2.Pre-operative QOL of laryngeal cancer patients Pre-operative QOL of laryngeal cancer patients was affected in "Global QOL", "emotional functioning" scale and three symptom scales "speech problems", "insomnia", "less sexuality" Our result was similar to the study of Johansson et al In laryngeal cancer, speech disorder always the major symptom which appears at early onset and lasts for long time, therefore this symptom causes great impact on patient's QOL At pre-operation, patients often worried about their disease and their treatment process (including the 17 operation) That bad mood expresses in "insomnia" symptom as well as negative "emotional functioning" All these impaction was reflected in the deterioration of "global QOL" 4.3 Pre-operative QOL of laryngeal cancer patients 4.3.1.Group TLM There was a moderate, clinically significant worsening in global health QOL status at month post-surgery (p