GHQ SCORES PREDICT UNIQUELY SUBSEQUENT SURVIVAL IN SUCCESSFULLY TREATED HEAD AND NECK CANCER PATIENTS: A PROSPECTIVE COHORT STUDY

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1 GHQ SCORES PREDICT UNIQUELY SUBSEQUENT SURVIVAL IN SUCCESSFULLY TREATED HEAD AND NECK CANCER PATIENTS: A PROSPECTIVE COHORT STUDY Anne K.H. Aarstad 2,3, Arild A Osthus 1, Jan Olofsson 1,2, Hans J. Aarstad 1,2 1 Department of Surgical Sciences, Faculty of Medicine, University of Bergen, N-5021 Bergen, Norway. 2 Department of Otolaryngology/Head and Neck Surgery, Haukeland University Hospital, Bergen, Norway. 3 Faculty of Health and Social Sciences, Bergen University College, Bergen.

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4 This varied incidence throughout the world implies external causes of the disease

5 Tobacco smoking is an important risk factor of head and neck carcinoma

6 Alcohol consumption is an important risk factor of head and neck carcinoma

7 A combination of smoking and alcohol consumption is what matters. There is a social gradient as to smoking. Head and neck cancer is to some extent a poor man s disease.

8 Survival following diagnosis of oral cavity/pharynx carcinoma Data from the Norwegian cancer registry

9 Sequels following radiation therapy Vissinck, 2003

10 Distress Distress is defined as an unpleasant emotional experience of a psychological, social, or spiritual nature. Distress extends along a continuum, ranging from common normal feelings of vulnerability, sadness, and fear to problems that can become disabling, such as depression, anxiety, panic, social isolation, and spiritual crisis (US National Comprehensive Cancer Network) [White, Macleod, 2002]. Distress may be measured by the General Health Questionnaire. Level of distress may be used as an indicator of mental disease [Vodermaier, 2009]. Bjordal and Kaasa [1995] have e.g. studied distress by the GHQ-20 in long term survivors of HNC. About 30% of patients fulfilled the criteria of being cases. We have shown similar levels of GHQ scores in HNSCC patients [Aarstad et al., 2011].

11 Personality Neuroticism Coping Disease-related factors GHQ 25% Gen QoL Beisland E., Aarstad A.H.K, Østhus A.A., Aarstad H.J. (2012) Stability of distress and health-related quality of life as well as relation to neuroticism, coping and TNM stage in head and neck cancer patients during follow up. Acta Otolaryngol. In press.

12 HRQoL scores predict survival among former HNSCC patients [Østhus et al., 2011].

13 AIM Does the GHQ scores predict survival as well?

14 Patients included By October 1st 2002 all patients (n=162) diagnosed with head and and neck squamous cell carcinoma ( HNSCC) in Western Norway in the period from July 1st 1992 to October 1st 2001, below 80 years of age and who had been disease free for at least one year following therapy by October 1st 2002 were identified. All patients, except for 18 patients who were found not to be eligible for the study, due to cognitive impairment or other serious disease, were approached to participate in this study. Three patients refused to participate and two patients have been lost to follow-up. 139 patients, yielding a 97% total response rate, were enrolled for structured interviews. These were completed in the period between October 21 st 2002 and March 29 th The observation was ended as of June 30 th 2009, yielding a mean observation period of 75±4 (range 63-80) months among the survivors. Twenty-four deaths were observed.

15 Questionnaires employed General Health Questionnaire The general health questionnaire (GHQ)-30 was employed [Goldberg & Williams,1998]. The patients scored according to a standard 4 point response matrix. The GHQ was analyzed with the responses calculated as Likert scores. Quality of life inventory Employed the EORTC QLQ (C30 & H&N35) inventory [Aaronson et al., Bjordal et al., Bjordal et al., 2000]. Answers in a 4-point Likert format, and the scales were transformed so that 0% indicated least and 100% most symptoms. In addition, HRQoL sum scores based on the EORTC QLQ indices were calculated.

16 Patient characteristics N % N % Tumour stage is 6 4, , , , ,4 Nodal stage , , , ,4 Treatment Tumour surgery 86 61,9 Neck dissection 52 37,4 Free flap reconstruction 16 11,5 Gender Male ,8 Female 35 25,2 Co-morbidities Angina pectoris 9 6,5 Myocardial infarction 10 7,2 Heart medication 28 20,1 Asthma and/or chronic bronchitis 13 9,4 Lung medication 6 4,3 Tumour site Larynx 52 37,4 Oral cavity 44 31,7 Oropharynx 31 22,3 Others 12 8,6 Tumour RT 95 68,3 Neck RT 67 48,2 Chemotherapy 6 4,3

17 Post treatment GHQ scores and multiple Cox proportional hazards regression analyses of survival Predictors HR 95% CI P GHQ sum score adjusted by gender and age GHQ sum score ,004 Dichotomized GHQ sum score ,6 0,001 GHQ sum score adjusted for neuroticism and avoidance focused coping* GHQ sum score ,056 Dichotomized GHQ sum score ,015 GHQ sum score adjusted for T-stage and site (oropharynx vs others)* GHQ sum score ,007 Dichotomized GHQ sum score ,019 GHQ sum score adjusted for alcohol consumption and cigarettes smoked per week* H&N HRQoL sum score ,003 Dichotomized GHQ sum score ,001 GHQ sum score adjusted for a sum score of heart disease* GHQ sum score ,009 Dichotomized GHQ sum score ,001 GHQ sum score adjusted for gender, age, neuroticism, avoidance focused coping, T-stage, site (oropharynx versus others), alcohol consumption, cigarettes smoked per week, and a heart disease GHQ sum score ,080 Dichotomized GHQ sum score ,010 *The analyses were in addition to the presented variables adjusted for gender and age

18 Survival dependent on GHQ score p<0.01 p<0.01

19 Survival dependent on H&N HRQoL score p<0.01 p=0.06 Østhus A.A., Aarstad A.K.H., Olofsson J., Aarstad H.J. (2011). Head and neck specific Health Related Quality of Life scores predict subsequent survival in successfully treated head and neck cancer patients; a prospective cohort study. Oral Oncol. 47:

20 Discussion General Health Questionnaire (GHQ) scores predict survival in former HNSCC patients. What are the mechanisms of the GHQ prediction? Is a distressed person more «stressed» (by e.g. from low income or due to death of spouse), with consequently less defense against disease? The close association between Health Related Quality of Life scores indicate that present co-morbidity; perhaps in addition to smoking and alcohol use, is responsible for the GHQ prediction

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22 Tobacco/alcohol metakron = secondary primary

23 Survival dependent on reported hearth disease p<0.05 p<0.05

24 Annual Reviews

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26 Trends in head and neck cancer incidence in Denmark, : Focus on human papillomavirus associated sites International Journal of Cancer Volume 129, Issue 3, pages , 26 OCT 2010 DOI: /ijc

27 Conclusions Our findings indicate a unique survival prediction from distress scores in successfully treated HNSCC patients. The mechanisms are not known In any case, dichotomized GHQ-scores (highest quartile) may be a screening tool for identifying successfully treated HNSCC patients with high mortality risk. The HPV epidemic may change the picture of head and neck cancer from being the poor man s disease to also being the sexual active man s disease.

28 Social gradient in life expectancy and expected lifetime in self rated good health in different smoking categories. Brønnum-Hansen H, Juel K J Epidemiol Community Health 2004;58: by BMJ Publishing Group Ltd