This was a pilot controlled study design of stress management program for patients with advanced HNC (SMAP-HNC study) from January 2016 through March 2018. Participants were not reached enough to calculated sample size, though the study was originally designed as a parallel, randomized, open-label study. Patients were recruited from hospitalized patients of the department of head and neck surgery, Medical Hospital, Tokyo Medical and Dental University in Tokyo (TMDU), Japan. TMDU is located at metropolitan area and have good access to public transportation. We included patients who (1) had a larynx, pharynx, or oral cancer, (2) had a pathological diagnosis of squamous cell carcinoma (SCC), (3) suspected to have advanced cancer (stage III to IV), (4) were after initial curative treatment, (5) were older than 20 years and younger than 79 years, and (6) had clinical depressive symptoms (Hospital Anxiety and Depression Scale score ≥ 11). The following patients were excluded from the study: those who were judged by their attending physicians not to participate in this trial because of severe physical, mental or cognitive problems (e.g., serious adverse event, delirium, or dementia) or those who has insufficient Japanese literacy skills.

The sample size calculation was based on previous meta-analysis, which was no significant change in levels of depression following psychotherapy for patients with head and neck cancer (Standardized mean differences = −.00) (Semple et al., 2013). Using the above information as our reference effect size and estimating intervention effect of SMAP-HNC at .20, and that of UC at .00, we needed 126 participants for 80% power and 5% significant level using a two-tailed test. Seventy patients per group were deemed sufficient, even if 10% of patients did not agree to participate or did not complete the questionnaire. However, actual percentage of patients declined to participate for this study was 56.50%.

Patients with meeting inclusion criteria and providing consent were screened for depression with Hospital Anxiety and Depression Scale (HADs). Patients with HADs ≥ 11 received direct contact from researchers, and provided another consent on the randomized controlled trial. They had completed the baseline assessment, and were randomly assigned to the following two groups. All outcomes were evaluated at three points, baseline, post-intervention, and three months after the intervention. This RCT was conducted with technical support from University Research Administration Center in TMDU, and reported according to the principles outlined in the CONSORT statement and checklist (Pandis, Chung, Scherer, Elbourne, & Altman, 2017). Informed consent was obtained from all participants in writing after verbal explanation. Participants answered anonymous questionnaires, and were managed by code number. The trial was approved by the independent Institutional Review Board (IRB) at Tokyo Medical and Dental University (R2015-026-01). The protocol of this trial was registered on UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), #UMIN000018900.

Stress Management Program. The program, which was based on a problem-solving training for head and neck cancer patients and stress coping training for HIV patients, was developed by three clinical psychologists and a psychiatrist. The developed program got clinical advice from three head and neck surgeons and two certified nurses in palliative care. We named this program as “Stress Management Program for Patients with Advanced Head and Neck Cancer (SMAP-HNC)”. SMAP-HNC is conducted by five clinical psychologists with more than three year experiences in hospital setting. The post-treatment session takes around 60 minutes at the time of hospital discharge, and the follow-up session takes around 30 minutes at the first visit. The main purpose of the SMAP-HNC is to (1) enhance the knowledge of stress coping skill, and (2) expand repertoire of stress coping skill. The themes of the post-treatment session are (a) psychoeducation about stress coping for head and neck cancer patients, (b) discussion about present stressors, stress responses, and stress coping, and (c) goal setting related alternative stress coping. Participants got homework between two sessions to do (d) self-monitoring, and (e) recording achievement rate of the goal. Finally, the themes of the follow-up session are (f) confirming the efficacy of alternative coping behavior, and (g) overview.

Usual Care (UC). All patients were treated with usual care by physicians, nurses, and other medical providers. Patients assigned to UC group were banned from receiving psychotherapy or counseling from clinical psychologists during the study period.

Participants who gave informed consent were randomly assigned in a 1:1 ratio to SMAP-HNC or UC by a computer-generated allocation sequence designed by HOPE eACReSS, a web-based randomized program, Fujitsu, Tokyo, Japan. Randomization was carried out with a fixed block size of 6 stratified for age (20-44 years, 45-64 years, or 65-79 years) and sex (men or women) using minimization method. After randomization, allocation result was informed patients face to face before intervention. This study was an open-labeled trial because of the difficulty of using blind experiment in psychotherapy.

Demographic and Clinical Characteristics. We collected demographic and clinical information from the case report form by attending physicians. We included the following data: age, sex, family, employment, primary cancer site, diagnosis cancer stage, ECOG performance status (ECOG-PS), history of cancer treatment, and other clinical problems (e.g. history of smoking).

Depression. Depression was evaluated using the Japanese version of the Hospital Anxiety & Depression Scale (HADS; Kugaya, Akechi, Okuyama, Okamura, & Uchitomi, 1998; Zigmond & Snaith, 1983), which is a 14-item self-related scale. It is a 4-point Likert-type scale ranging from 0 to 3 (overall score range: 0–42). The scale has two factors: anxiety and depression. We used an optimal cut-off point of 10/11 to screen for adjustment disorder or major depressive disorder in first screening for depression in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). This cut-off point gave high enough sensitivity (91.50%) and specificity (65.40%) among Japanese version of HADs.

Quality of Life (QOL). Quality of Life (QOL) were evaluated using the Functional Assessment of Cancer Therapy-Head and Neck Scale (FACT-H&N; List et al., 1996). It is a 38-item self-related scale used to measure function or well-being in cancer patients. The scale has five factors: Physical well-being (7 items), Social/family well-being (7 items), Emotional well-being (6 items), Functional well-being (7 items), and Head and neck cancer subscale (11 items). The reliability and validity of this measure were sufficiently supported in an earlier study (List et al., 1996).

Stress coping strategies were evaluated using the brief COPE, which is a Japanese abbreviated version of the COPE inventory (Carver, 1997; Otsuka, 2008). It consists of 28-items, 14 lower factors, and is a 4-point Likert-type scale ranging from 1 to 4. The reliability and validity of this measure were confirmed in an earlier study (Otsuka, 2008), and the Cronbach's alpha for each factor were .46 (Self-distraction), .47 (Active coping), .69 (Denial), .91 (Substance use), .72 (Use of emotional support), .80 (Use of instrumental support), .73 (Behavioral disengagement), .63 (Venting), .70 (Positive reframing), .67 (Planning), .70 (Humor), .63 (Acceptance), 64 (Religion), and .74 (Self-blame). It has been widely used in studies about cancer patients, especially HNC patients (Richardson, Morton, & Broadbent, 2016).

Insomnia. Insomnia were evaluated using the Japanese version of Athens Insomnia Scale (Okajima, Nakajima, Kobayashi, & Inoue, 2013; Soldatos, Dikeos, & Paparrigopoulos, 2000). It is an 8-item and 4-point Likert-type scale ranging from 0 to 3. It has been developed to assess the subjective sleep difficulty according to diagnostic criteria given in the International Classification of Diseases, 10th Revision. The reliability, validity, and also diagnostic accuracy of this measure were sufficiently supported in an earlier study (Soldatos, Dikeos, & Paparrigopoulos, 2003).

Primary outcome was amount of change in HADs depression score from baseline to post-intervention. Amount of change in HADs depression score were compared between groups using the independent t test and estimated the Hedges’s g and 95% confidence intervals (CIs). In addition, we show only descriptive statistics, and we did not perform any statistical tests to compare the difference between two groups in FACT, Brief COPE, and AIS score as secondary outcome.

Fig. 1 is a flow diagram showing the number of participants at each stage of the study. Of the 83 patients with HNC, data from 46 participants with depression were considered potentially eligible. Twenty patients who agree to participation were enrolled, of whom 10 were randomly assigned to receive SMAP-HNC and 10 were assigned to receive UC. In addition, it has a higher percentage of patients with immediate pain following the treatments and refusal to participate than initially envisioned. Table1 shows the characteristics of patients declined to participate the study. Non-consent rate was 58.70%. The frequency of elderly (≥ 70 years old) patients and men was higher in the patients with declined (Table 1).

Fig. 1.

Flow diagram of participants.

(0.17MB).

The baseline demographic and clinical characteristics of each group participants are shown in Table 2. Of the all 20 randomized patients, 18 patients who completed all the questionnaires items were included in this study.

The primary outcome change among study participants are shown in Table 3. The independent t test revealed that there was no significant difference of HADs depression (Hedges’d g -0.83; 95% CI -1.80 to 0.13) and anxiety (Hedges’d g 0.36; 95% CI -0.57 to 1.30) between two groups. However, this clinical trial is underpowered to perform some statistical test and compare the differences between two intervention groups. According to the descriptive data, post-baseline mean difference of depression score of SMAP-HNC is higher than that score of UC. Descriptive data of secondary outcome are shown in Table 4. We did not carry out the relevant statistical analysis for secondary outcome.