Psychological distress is common in lung cancer patients with a poor prognosis. The present study aims to investigate the efficacy of collaborative care for patients with newly diagnosed inoperable lung cancer in South Korea. The study is a three-arm parallel-groups nonrandomized clinical trial with an active arm that includes distressed patients who receive collaborative care, one comparison arm that includes distressed patients who receive enhanced usual care, and another comparison arm that includes non-distressed patients. In total, 267 consecutive patients newly diagnosed with medically inoperative lung cancer will be recruited. The primary outcomes are the changes in Hospital Anxiety and Depression Scale-depression and the Distress Thermometer at 12 and 32 weeks after enrollment. Sub-analyses of patients in the active arm of the study will include a comparison of the efficacy of a combination of oral antidepressant (escitalopram) treatment and collaborative care versus that of collaborative care alone.
Every year, more than 200,000 patients are newly diagnosed with cancer in South Korea [
Screening for and management of distress in cancer patients are recommended [
Collaborative care models can increase the accessibility of mental health services, and thus may be helpful in overcoming these barriers to successfully managing depression in cancer patients [
Advanced lung cancer patients were reported a very poor prognosis; the 5-year survival rate of this population is less than 40% [
Despite the promising findings of previous studies, they have had several limitations. Most of these studies were conducted in the USA or the UK [
To overcome the limitations of previous trials, the present authors designed a clinical trial of collaborative care in South Korea. The target population is patients with medically inoperable lung cancer who had a poor prognosis and/or advanced stage of disease.
To ensure homogeneity with respect to the phase of cancer treatment, the enrollment period was limited to patients within 3 months of their initial lung cancer diagnosis. To understand the efficacy of the intervention, the collaborative care intervention group will be compared to two control arms: a group of patients with distress who did not want the intervention and a group of patients without distress. Thus, this study is a non-randomized clinical trial with a three-arm parallel-group design that investigates the efficacy of collaborative care for patients with newly diagnosed inoperable lung cancer in South Korea. The primary hypothesis is that the collaborative care group will report less psychological distress than the enhanced usual care (EUC) group but greater distress than the non-distressed group at 12 and 32 weeks after enrollment. The secondary hypotheses are that QoL, level of functioning, and other psychological/physical symptoms will show greater improvement in the collaborative care group than in the EUC group, but will remain worse than the levels of the non-distressed group. Third, it is hypothesized that a sub-analysis of the collaborative care group will show that psychological distress will improve more rapidly in the patients that receive a combination of oral antidepressant treatment and collaborative care compared to those who receive collaborative care alone.
This study is a three-arm parallel-group non-randomized clinical trial that collects primary outcome data at 12 and 32 weeks after enrollment. The CONSORT flow chart of the study is presented in
Participants are consecutively recruited from the Lung and Esophageal Cancer Clinic at Chonnam National University Hwasun Hospital, South Korea. The inclusion and exclusion criteria are summarized in
The following sociodemographic and clinical data are obtained via interview or clinical record at baseline: age, sex, years of formal education, history of alcohol and/or smoking, history of depression and/or anxiety, and information about the cancer. Genetic and serological information regarding the 5-HTT and BDNF genes and vitamin D, respectively, are also collected. Personality and religiosity are assessed using the Korean version of the 10-item Big Five Inventory (BFI-10) [
Patients who met the eligibility criteria and agreed to participate in the study are screened for distress using the Hospital Anxiety and Depression Scale-depression (HADS-D) [
The collaborative care model is based on the published literature, i.e., the Depression Care for People with Cancer (DPCP) model [
It will be also recommended that all patients in the collaborative care group concurrently undergo antidepressant treatment; patients who agreed are prescribed escitalopram (5–20 mg per day) by a psychiatrist. All other interventions in the collaborative care group are the same for patients who agreed and those who do not agree to take medication.
The EUC and non-distressed groups receive an educational leaflet three times during the 12-week treatment period. These patients also receive the typical clinical management for psychological difficulties, i.e., consultations with and/or visits to the psychiatric department based on their condition and agreement.
The schedule of assessment for the study is summarized in
This study included the following assessment scales: Eastern Cooperative Oncology Group Performance Status [
The primary outcome measures are changes in the HADS-D and DT score at 12 and 32 weeks after enrollment.
Secondary outcome measures will include changes in the BPRS-suicidality subscale, RDC/ICSD-2, ALFI-MMSE, MINIMDD, MADRS, HADS-anxiety, BHS, EORTC QLQ c-30, DSII, disease status, and survival.
The necessary sample size was calculated using the G power tool 3.1 [
After all outcome data have been collected at 12 and 32 weeks after enrollment, a main analysis of the non-distressed, EUC, and collaborative care arms will be performed using RMANOVA. Additionally, a sub-analysis within the collaborative care arm comparing those who received collaborative care in combination with escitalopram versus those who did not receive escitalopram will be conducted using RMANOVA.
The trial was approved by the Chonnam National University Hwasun Hospital Institutional Review Board (CNUHH 2014-056) and registered at
The research was funded by a grant of the Korea Health 21 R&D, Ministry of Health and Welfare, Republic of Korea (HI10C2020) and National Research Foundation of Korea Grant (NRF-2015M3C7A1028899) to Professor JM Kim.
The authors have no potential conflicts of interest to disclose.
Conceptualization: Jae-Min Kim, Seon-Young Kim, In-Jae Oh, YoungChul Kim. Formal analysis: Sung-Wan Kim, Seon-Young Kim. Funding acquisition: Jae-Min Kim. Investigation: Seon-Young Kim, Cheol-Kyu Park. Methodology: Jae-Min Kim, Il-Seon Shin. Supervision: Il-Seon Shin, Young-Chul Kim. Visualization: Seon-Young Kim. Writing—original draft: Jae-Min Kim, Seon-Young Kim. Writing—review & editing: Jae-Min Kim, Seon-Young Kim, Sung-Wan Kim, Il-Seon Shin, Cheol-Kyu Park, InJae Oh, Young-Chul Kim
Flow chart of the trial. The box with thick broken line is main trial arms, and with thin broken line is sub-analysis arms. CBT: cognitive behavioral therapy, DT: Distress Thermometer, HADS-D: Hospital Anxiety and Depression Scale-depression, Tx: treatment.
Selection criteria of the study
Inclusion criteria |
Older than 25 years of age |
Newly diagnosed with primary lung cancer within 3 months |
Medically inoperable lung cancer |
Can speak Korean |
Can understand the purpose of study |
Exclusion criteria |
Dementia or other major cognitive impairment |
Acute suicidal risk or psychotic symptoms |
History of psychotic disorders |
Acute massive hemorrhagic event within 1 week |
Platelet count <130,000 per μL |
Corrected QT interval >500 ms |
Severe renal function impairment (creatinine clearance <30 mL/min) |
Taking antidepressant in the enrollment period |
Untreated or remnant another primary cancer than lung cancer |
Session structure of intervention
Session | Time | Content |
---|---|---|
Session 1 | 1st week | Introduction and relationship building |
Relaxation training: breathing exercises | ||
Education: nutrition and smoking cessation | ||
Session 2 | 2nd week | Relaxation training: progressive muscle relaxation |
Mindful breathing | ||
Session 3 | 3rd week | Experiencing and expressing emotions |
Relaxation training: guided imagery relaxation | ||
Session 4 | 4th week | Cognitive work with anxiety and depression (e.g., Searching for alteration, weighing advantages and disadvantages, Information seeking) |
Session 5 | 6th week | Evaluating my support system |
Asking for support | ||
Session 6 | 8th week | Being active-I: activity scheduling |
Session 7 | 10th week | Being active-II: activity scheduling |
Planning ahead | ||
Session 8 | 12th week | Communication techniques |
Final review and wrap-up |
Schedule of assessment for the study
B1 | 2 W |
4 W |
8 W |
12 W | 32 W | 3 year | |
---|---|---|---|---|---|---|---|
Socio-demographic characteristics | V | ||||||
Clinical characteristics | V | ||||||
Records of anti-cancer treatment | V | V | V | V | V | V | |
Genetic/serologic information | V | ||||||
Disease status and survival | V | V | V | V | V | V | V |
Measurements | |||||||
Big Five Inventory-10 | V | ||||||
Duke religion questionnaire | V | ||||||
ECOG-Performance Status | V | V | V | V | V | V | |
MMRC dyspnea scale | V | V | V | V | V | V | |
Confusion Assessment Method | V | V | V | V | V | V | |
BPRS-suicidality subscale | V | V | V | ||||
RDC/ICSD-2 | V | V | V | ||||
ALFI-MMSE | V | V | V | ||||
MINI-MDD | V | V | V | ||||
Montgomery Åsberg Depression Rating Scale | V | V | V | V | |||
Hospital Anxiety and Depression Scale | V | V | V | V | V | V | |
Distress Thermometer | V | V | V | V | V | V | |
Screening questionnaire of restless leg syndrome | V | V | V | ||||
Beck Hopelessness Scale | V | V | V | ||||
EORTC QLQ c-30 | V | V | V | ||||
Demoralization-II | V | ||||||
UKU side effect profile |
V | V | V | V | V |
additional assessments for collaborative care group only.
ALFI-MMSE: adult lifestyles and function interview of the mini-mental state exam, BPRS: brief psychiatric rating scale, ECOG: eastern cooperative oncology group, EORTC QLQ c-30: european organization for research and treatment of cancer core questionnaire, MINI-MDD: the mini international neuropsychiatric interview, MMRC: modified medical research council, RDC/ICSD-2: research diagnostic criteria for insomnia/international classification of sleep disorders-second edition, UKU: udvalg for kliniske undersogelser