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Depression and Survival in Metastatic Non–Small-Cell Lung Cancer: Effects of Early Palliative Care
Open accessAbstract
Purpose: In a randomized trial, early palliative care (EPC) in patients with metastatic non–small-cell lung cancer (NSCLC) was observed to improve survival. In a secondary analysis, we explored the hypothesis that the survival benefit resulted from improving depression. Patients and Methods: In total, 151 patients with newly diagnosed metastatic NSCLC participated in a randomized trial of EPC integrated with standard oncology care versus standard oncology care alone. Depression was assessed at baseline and at 12 weeks with the Patient Health Questionnaire-9 (PHQ-9) and was scored diagnostically by using Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria for major depression syndrome (MDS). Depression response was considered ≥ 50% reduction in PHQ-9 scores at 12 weeks. Survival differences were tested with log-rank and Cox proportional hazards models. Results: At baseline, 21 patients (14%) met MDS criteria. MDS significantly predicted worse survival (hazard ratio, 1.82; P = .02). Patients assigned to EPC had greater improvements in PHQ-9 scores at 12 weeks (P < .001); among patients with MDS, those receiving EPC had greater rates of depression response at 12 weeks (P = .04). However, improvement in PHQ-9 scores was not associated with improved survival, except in a sensitivity analysis in which patients who died before 12 weeks were modeled to have worse depression. The group randomly assigned to EPC remained independently associated with survival after adding improvement in PHQ-9 scores to the survival model. Conclusion: Depression predicted worse survival in patients with newly diagnosed metastatic NSCLC. Although EPC was associated with greater improvement in depression at 12 weeks, the data do not support the hypothesis that treatment of depression mediated the observed survival benefit from EPC.
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“Hospice use of any type and duration is strongly associated with better OS in patients with advanced cancer,119 including those specifically with lung cancer.120”
From Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update (2015) · cites this paper as [120]
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“recently reported that the presence of major depression was associated with worse survival in patients with non-small cell lung carci noma, although treatment of such depression did not yield survival benefit (Pirl et al., 2012).”
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Discussing the Evidence for Upstream Palliative Care in Improving Outcomes in Advanced Cancer
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“Previous research has identified two core ACT mechanisms(22,23): (1) opening up toward internal experience through acceptance and cognitive defusion (observing thoughts in a more objective manner), and (2) moving in meaningful life directions by clarifying personal values and pursuing activities and decisions that ref…”
InfluentialMulticomponent Palliative Care Interventions in Advanced Chronic Diseases: A Systematic Review
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“In them, rates of “severe” depressive symptoms have ranged from 14 % [11] to 41 % [12,13].”
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“Some studies of advanced cancer patients have associated depressive symptoms with shorter survival times [34,35], although there appears to be no relationship with disease progression [36].”
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“There is accumulating evidence of an association between psychological distress and poor outcomes in patients with cancer [4-6]; therefore, treating psychological distress might represent another option for cancer treatment.”
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Depression Negatively Impacts Survival of Patients with Metastatic Prostate Cancer
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“A small scale randomized trial demonstrated that major depression syndrome significantly predicted worse survival in patients with metastatic non-small-cell lung cancer [7].”
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Bandieri, E., Banchelli, F., Artioli, F., Mucciarini, C., Razzini, G., Cruciani, M., Potenza, L., D’Amico, R., Efficace, F., Bruera, E. D., et al. (2019) · BMJ Supportive & Palliative Care · doi:10.1136/bmjspcare-2019-001794 · Cited by 42
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“And psychological disorder of depression and anxiety had been regarded as a predictor of shorter survival in patients with lung cancer [11].”
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“(34, 35) The comparator group had no claims for depression at any time.”
BackgroundTreatment Receipt and Outcomes among Lung Cancer Patients with Depression
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Self-citationCoping Strategy Influences Quality of Life in Patients With Advanced Lung Cancer by Mediating Mood
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“Depression is linked with worse lung cancer survival (e.g. Arrieta et al. 2013; Pirl et al. 2012; Sullivan et al. 2014).”
BackgroundPrognostic Implications of Depression and Inflammation in Patients With Metastatic Lung Cancer
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“Months from first contact to first survey; median [IQR] 8 [1-28] 8 [1-28] 6 [1-25] 8 [1-29] 12 [2-34]”
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“The basis for this improvement in median survival is the subject of much ongoing debate.(16,17) With randomly allocated intervention groups evenly matched for performance status, gender, age, and disease stage, the observation is likely due to improvements in symptom control, quality of life, and mood, as for cancer p…”
BackgroundChemotherapeutic Response and Prognosis among Lung Cancer Patients with and without Depression
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“Previous studies have suggested a certain association of depression with increased mortality among lung cancer patients [15-21].”
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Geerse, O. P., Stegmann, M., Kerstjens, H. A. M., Hiltermann, T. J. N., Bakitas, M. A., Zimmermann, C., Deal, A. M., Brandenbarg, D., Berger, M. Y., & Berendsen, A. J. (2018) · Journal of Pain and Symptom Management · doi:10.1016/j.jpainsymman.2018.08.011 · Cited by 29
Lyons, K. D., Padgett, L. S., Marshall, T. F., Greer, J. A., Silver, J. K., Raj, V. S., Zucker, D. S., Fu, J. B., Pergolotti, M., Sleight, A. G., et al. (2018) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21549 · Cited by 29
Self-citationAng, K., Hepgul, N., Gao, W., & Higginson, I. J. (2017) · Palliative Medicine · doi:10.1177/0269216317717369 · Cited by 29
Recommendations for Follow-up Care for Gynecologic Cancer Survivors
Elit, L. M., & Reade, C. J. (2015) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000001129 · Cited by 29
“Adequate pain and symptom management is vital to maintaining quality of life (QOL).(3) Follow-up assessments are an opportunity for other”
BackgroundIntegrated Palliative Care and Oncologic Care in Non-Small-Cell Lung Cancer
Chandrasekar, D., Tribett, E., & Ramchandran, K. (2016) · Current Treatment Options in Oncology · doi:10.1007/s11864-016-0397-1 · Cited by 14
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“Among individuals with cancer, lung cancer patients are at particularly great risk of developing depression [1], and depression may negatively affect treatment outcomes [3, 4].”
BackgroundPrevalence of Depression and its Correlations: a Cross-sectional Study in Thai Cancer Patients
Maneeton, B., Maneeton, N., & Mahathep, P. (2012) · Asian Pacific Journal of Cancer Prevention · doi:10.7314/apjcp.2012.13.5.2039 · Cited by 28
“(Massie and Holland, 1984; Ciaramella and Poli, 2001; Uchitomi et al., 2003; Katz et al., 2004; Ell et al., 2005; Boyd et al., 2012; Kim et al., 2012; Mitchell et al., 2012; Palmer et al., 2012; Pirl et al., 2012; Tada et al., 2012; Warmenhoven et al., 2012; Yu et al., 2012).”
BackgroundWong, A. N., Reddy, A. S., Williams, J. L., Wu, J., Liu, D., & Bruera, E. D. (2016) · Journal of Oncology Practice · doi:10.1200/jop.2015.006619 · Cited by 28
Kirk, D. L., Kabdebo, I., & Whitehead, L. (2021) · Journal of Clinical Nursing · doi:10.1111/jocn.15794 · Cited by 23
“Many studies have also indicated a potential causal link between distress and poorer quality of life, which may also negatively impact survival (Brown et al., 2003; Massie, 2004; Pirl et al., 2012).”
BackgroundSchwam, Z. G., Burtness, B. A., Yarbrough, W. G., Mehra, S., Husain, Z. A., & Judson, B. L. (2015) · Cancer Medicine · doi:10.1002/cam4.546 · Cited by 26
“Implementation of early palliative care has been shown to not only improve quality of life, but to lead to longer survival in select cancer patients [30, 31].”
BackgroundThe role of depression and neuroimmune axis in the prognosis of cancer patients.
Aldea, M. D., Craciun, L., Tomuleasa, C., & Crivii, C. B. (2014) · PubMed · Cited by 26
Research on psychological and social factors in palliative care: An invited commentary
Rodin, G. (2013) · Palliative Medicine · doi:10.1177/0269216313499961 · Cited by 29
Vanbutsele, G., Belle, S. V., Laat, M. D., Surmont, V. F. M., Geboes, K. P., Eecloo, K., Pardon, K., & Deliëns, L. (2015) · BMC Health Services Research · doi:10.1186/s12913-015-1207-3 · Cited by 25
“8 months compared with those who received the standard care alone [4, 10, 11].”
BackgroundPrescott, A. T., Hull, J. G., Dionne-Odom, J. N., Tosteson, T. D., Lyons, K. D., Li, Z., Li, Z., Dragnev, K. H., Hegel, M. T., Steinhauser, K. E., et al. (2017) · Health Psychology · doi:10.1037/hea0000544 · Cited by 25
“However, two groups that tested for mediation in this way did not find evidence of such an association (Giese-Davis et al., 2011; Pirl et al., 2012).”
BackgroundResultInfluentialQuality of Life following Stereotactic Radiosurgery for Single and Multiple Brain Metastases
Miller, J. A., Kotecha, R. R., Barnett, G. H., Suh, J. H., Angelov, L., Murphy, E. S., Vogelbaum, M. A., Mohammadi, A. M., & Chao, S. T. (2017) · Neurosurgery · doi:10.1093/neuros/nyw166 · Cited by 24
Barbaret, C., Delgado-Guay, M. O., Sanchez, S., Brosse, C., Ruer, M., Rhondali, W., Monsarrat, L., Michaud, P., Schott, A., Bruera, E. D., et al. (2019) · The Oncologist · doi:10.1634/theoncologist.2018-0353 · Cited by 24
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“It has been hypothesized that palliative care may confer benefits via enhanced communication of patient preferences and symptom management, thus helping reduce unintended harms of high-intensity treatment leading to a potential survival benefit.(21,22) Alternatively, another possibility is that the benefits of EPC are…”
BackgroundJankowska‐Polańska, B., Polański, J., Chabowski, M., Rosińćzuk, J., & Mazur, G. J. (2019) · Advances in experimental medicine and biology · doi:10.1007/5584_2019_448 · Cited by 25
Targeting those with decreased meaning and peace: a supportive care opportunity
Brown, A. J., Sun, C. C., Urbauer, D. L., Zhukovsky, D. S., Levenback, C., Frumovitz, M., Thaker, P. H., Bodurka, D. C., & Ramondetta, L. M. (2014) · Supportive Care in Cancer · doi:10.1007/s00520-014-2568-6 · Cited by 24
Troy, J. D., de Castro, C. M., Pupa, M. R., Samsa, G., Abernethy, A. P., & LeBlanc, T. W. (2018) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2017.7048 · Cited by 22
Depressive Symptoms in Newly Diagnosed Lung Carcinoma: Prevalence and Associated Risk Factors
Shahedah, K., How, S., Jamalludin, A., Faiz, M. T. M., Kuan, Y., & Ong, C. (2018) · Tuberculosis and Respiratory Diseases · doi:10.4046/trd.2018.0048 · Cited by 16
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“Previous studies showed that patients with NSCLC and their caregivers are highly vulnerable to psychosocial morbidity and high levels of distress including depression, anxiety, and reduced QOL.(3,13,14) Distress is a frequently reported 842373 ICTXXX10.”
BackgroundIdentifying Palliative Care Needs Among Older Adults in Nonclinical Settings
Kozlov, E., Cai, A., Sirey, J. A., Ghesquiere, A., & Reid, M. C. (2018) · American Journal of Hospice and Palliative Medicine® · doi:10.1177/1049909118777235 · Cited by 21
Zambrano, S. C., Fliedner, M., & Eychmüller, S. (2016) · Current Opinion in Supportive and Palliative Care · doi:10.1097/spc.0000000000000240 · Cited by 20
“Other studies identified improvements in symptoms [3,24], depression [24,25], distress [26], quality of life [3,24,27], and satisfaction with care and communication [3,28,29].”
BackgroundRhondali, W., Yennurajalingam, S., Ferrer, J. G., Chisholm, G. B., Filbet, M., & Bruera, E. D. (2013) · Supportive Care in Cancer · doi:10.1007/s00520-013-2042-x · Cited by 20
“[10] suggested in a small group of patients with lung cancer that the palliative care interventions result in decreasing depression.”
BackgroundSurrogate marker analysis in cancer clinical trials through time-to-event mediation techniques
Vandenberghe, S., Duchateau, L., Slaets, L., Bogaerts, J., & Vansteelandt, S. (2017) · Statistical Methods in Medical Research · doi:10.1177/0962280217702179 · Cited by 19
Nottelmann, L., Grøenvold, M., Vejlgaard, T. B., Petersen, M. A., & Jensen, L. H. (2017) · BMC Cancer · doi:10.1186/s12885-017-3558-0 · Cited by 19
Johnsen, A. T., Damkier, A., Vejlgaard, T. B., Lindschou, J., Sjøgren, P., Gluud, C. N., Neergaard, M. A., Petersen, M. A., Lundorff, L. E., Pedersen, L., et al. (2013) · BMC Palliative Care · doi:10.1186/1472-684x-12-37 · Cited by 18
“A recent randomised trial investigated ‘early SPC’ plus standard treatment versus standard treatment alone [5-7].”
Jones, D., Vichaya, E. G., Cleeland, C. S., Cohen, L. G., Thekdi, S. M., Wang, X. S., & Fisch, M. J. (2014) · Journal of Oncology Practice · doi:10.1200/jop.2013.001112 · Cited by 18
Advanced cancer as a risk for major depressive episodes
Meyer, F. L., Fletcher, K., Prigerson, H. G., Braun, I. M., & Maciejewski, P. K. (2014) · Psycho-Oncology · doi:10.1002/pon.3722 · Cited by 18
Oluyase, A. O., Higginson, I. J., Yi, D., Gao, W., Evans, C., Grande, G., Todd, C. J., Costantini, M., Murtagh, F. E., & Bajwah, S. (2021) · Health Services and Delivery Research · doi:10.3310/hsdr09120 · Cited by 19
Integration between Oncology and Palliative Care: A Plan for the Next Decade?
Kaasa, S., Knudsen, A. K., Lundeby, T., & Loge, J. H. (2017) · Tumori Journal · doi:10.5301/tj.5000602 · Cited by 17
“A recent article examined the rationale for discontinuation of chemotherapy for metastatic non-small-cell lung cancer and identified a large variability in these processes, unrelated to time of death (19).”
BackgroundEffect of Treating Depressive Disorders on Mortality of Cancer Patients
Sherrill, C., Smith, M. H., Mascoe, C., Bigus, E., & Abbitt, D. (2017) · Cureus · doi:10.7759/cureus.1740 · Cited by 17
Race and Ethnicity in the Evidence for Integrating Palliative Care Into Oncology
Pirl, W. F., Saez-Flores, E., Schlumbrecht, M. P., Nipp, R. D., Traeger, L. N., & Kobetz, E. K. (2018) · Journal of Oncology Practice · doi:10.1200/jop.17.00016 · Cited by 18
Self-citation
Metadata
- Authors
- Pirl, W. F., Greer, J. A., Traeger, L., Jackson, V., Lennes, I. T., Gallagher, E. R., Perez-Cruz, P., Heist, R. S., & Temel, J. S.
- Affiliations
- Massachusetts General Hospital (US)
- All authors: Massachusetts General Hospital Cancer Center, Boston, MA.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2012-04-20
- Volume
- 30
- Issue
- 12
- Pages
- 1310-1315
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC3341144
- OpenAlex
- W2136456300
- Cited by
- 228
- References
- 28
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 5 · 2023: 6 · 2022: 18 · 2021: 8 · 2020: 21 · 2019: 14 · 2018: 28 · 2017: 28 · 2016: 23 · 2015: 19 · 2014: 19 · 2013: 18 · 2012: 5
- FWCI
- 18.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (K23CA115908)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative Care and End-of-Life Issues
- Health Sciences › Medicine › Oncology › Cancer survivorship and care
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Palliative and Oncologic Care
- Keywords
- early palliative care, metastatic non-small cell lung cancer, depression, survival, major depressive disorder, PHQ-9, mediation analysis, psychological distress in cancer patients
- MeSH terms
- Age Factors, Aged, Carcinoma, Non-Small-Cell Lung, Depressive Disorder, Female, Humans, Lung Neoplasms, Male, Middle Aged, Palliative Care, Prognosis, Quality of Life, Reference Values, Sex Factors, Time Factors, Comorbidity, Proportional Hazards Models, Survival Analysis, Risk Assessment, Terminally Ill, Secondary Prevention
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