Hostname: page-component-7c8c6479df-94d59 Total loading time: 0 Render date: 2024-03-28T23:08:16.912Z Has data issue: false hasContentIssue false

Depression, survival, and epidermal growth factor receptor genotypes in patients with metastatic non-small cell lung cancer

Published online by Cambridge University Press:  11 February 2013

William F. Pirl*
Affiliation:
Center for Psychiatric Oncology and Behavioral Sciences, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Lara Traeger
Affiliation:
Center for Psychiatric Oncology and Behavioral Sciences, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Joseph A. Greer
Affiliation:
Center for Psychiatric Oncology and Behavioral Sciences, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Vicki Jackson
Affiliation:
Palliative Care Service, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Inga T. Lennes
Affiliation:
Center for Thoracic Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Emily Gallagher
Affiliation:
Center for Thoracic Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Lecia Sequist
Affiliation:
Center for Thoracic Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
Jennifer S. Temel
Affiliation:
Center for Thoracic Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts
*
Address correspondence and reprint requests to: William Pirl, MGH, Yawkey 10B, 55 Fruit Street, Boston, MA 02114. E-mail: wpirl@partners.org

Abstract

Objective:

Although depression appears to be associated with worse survival from cancer, the underlying mechanisms of this association are unknown. Tumor epidermal growth factor receptor (EGFR) genotype is a known predictor of survival in metastatic non-small cell lung cancer (NSCLC) and appears to be associated with depression. We hypothesized that tumor EGFR genotype may account for a relationship between depression and survival in this population. We investigated this possible relationship in a cohort of patients with metastatic NSCLC, in which we had previously demonstrated an association between depression and worse survival.

Method:

A cohort of 151 patients with newly diagnosed metastatic NSCLC were enrolled and followed in a randomized controlled trial of early palliative care. At enrollment, 150 had depression assessed with the Patient Health Questionnaire-9 (PHQ-9), and categorical scoring for major depressive syndrome (MDS) was used for analyses. Patients with tumor tissue available underwent EGFR genotyping. Associations with survival were tested using Cox proportional hazards models, adjusting for potential confounders.

Results:

Twenty-one patients (14.0%) met criteria for MDS. Forty-four patients (29.3%) had EGFR genotyping, and 17 (38.6%) of these harbored EGFR mutations. Patients with EGFR mutations had significantly lower PHQ-9 scores (p = 0.03), and none met criteria for depression. EGFR mutations were significantly associated with superior survival (p = 0.02). When both depression and EGFR genotype were simultaneously entered into the model, only EGFR mutations remained significantly associated with survival (p = 0.02), and the effect of depression was attenuated.

Significance of results:

Depression is associated with worse survival in metastatic NSCLC, and this relationship may be at least partially explained by tumor EGFR genotype. Further study into whether depression could be associated with specific biologic properties of cancer that vary by genotype is warranted.

Type
Review Articles
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Azzoli, C.G., Baker, S. Jr., Temin, S., et al. (2009). American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. Journal of Clinical Oncology, 27, 62516266.CrossRefGoogle Scholar
Bezjak, A., Tu, D., Seymour, L., et al. (2006). Symptom improvement in lung cancer patients treated with erlotinib: Quality of life analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. Journal of Clinical Oncology, 24, 38313837.CrossRefGoogle ScholarPubMed
Borrell-Pages, M., Rojo, F., Albanell, J., et al. (2003). TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO Journal, 22, 11141124.CrossRefGoogle ScholarPubMed
Dias-Santagata, D., Akhavanfard, S., David, S.S., et al. (2010). Rapid targeted mutational analysis of human tumours: A clinical platform to guide personalized cancer medicine. EMBO Molecular Medicine, 2, 146158.CrossRefGoogle ScholarPubMed
Eberhard, D.A., Johnson, B.E., Amler, L.C., et al. (2005). Mutations in the epidermal growth factor receptor and in KRAS are predictive and prognostic indicators in patients with non-small-cell lung cancer treated with chemotherapy alone and in combination with erlotinib. Journal of Clinical Oncology, 23, 59005909.CrossRefGoogle ScholarPubMed
Ell, K., Xie, B., Quon, B., et al. (2008). Randomized controlled trial of collaborative care management of depression among low-income patients with cancer. Journal of Clinical Oncology, 26, 44884496.Google Scholar
Fann, J.R., Berry, D.L., Wolpin, S., et al. (2009). Depression screening using the Patient Health Questionnaire-9 administered on a touch screen computer. Psycooncology, 18, 1422.CrossRefGoogle ScholarPubMed
Fukuoka, M., Wu, Y.L., Thongprasert, S., et al. (2011). Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). Journal of Clinical Oncology, 29, 28662874Google Scholar
Fukuyama, T., Ichiki, Y., Yamada, S., et al. (2007). Cytokine production of lung cancer cell lines: correlation between their production and the inflammatory/immunological responses both in vivo and in vitro. Cancer Science, 98, 10481054.CrossRefGoogle ScholarPubMed
Gilbert, J. & Davis, F.C. (2009). Behavioral effects of systemic transforming growth factor-alpha in Syrian hamsters. Behavioural Brain Research, 198, 440448.Google Scholar
Gross, A.L., Gallo, J.J. & Eaton, W.W. (2010). Depression and cancer risk: 24 years of follow-up of the Baltimore Epidemiologic Catchment Area sample. Cancer Causes & Control, 21, 191199.CrossRefGoogle ScholarPubMed
Iurisci, I., Rich, T., Levi, F., et al. (2007). Relief of symptoms after gefitinib is associated with improvement of rest/activity rhythm in advanced lung cancer. Journal of Clinical Oncology, 25, e1719.CrossRefGoogle ScholarPubMed
Jehn, C.F., Kuehnhardt, D., Bartholomae, A., et al. (2006). Biomarkers of depression in cancer patients. Cancer, 107, 27232729.CrossRefGoogle ScholarPubMed
Knekt, P., Raitasalo, R., Heliovaara, M., et al. (1996). Elevated lung cancer risk among persons with depressed mood. American Journal of Epidemiology, 144, 10961103.Google Scholar
Kramer, A., Yang, F.C., Snodgrass, P., et al. (2001). Regulation of daily locomotor activity and sleep by hypothalamic EGF receptor signaling. Science, 294, 25112515.Google Scholar
Lutgendorf, S.K., Weinrib, A.Z., Penedo, F., et al. (2008). Interleukin-6, cortisol, and depressive symptoms in ovarian cancer patients. Journal of Clinical Oncology, 26, 48204827.CrossRefGoogle ScholarPubMed
Masago, K., Fujita, S., Hatachi, Y., et al. (2008). Clinical significance of pretreatment serum amphiregulin and transforming growth factor-alpha, and an epidermal growth factor somatic mutation in patients with advanced non-small cell lung cancer. Cancer Science, 99, 22952301.Google Scholar
Miller, A.H., Ancoli-Israel, S., Bower, J.E., et al. (2008). Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. Journal of Clinical Oncology, 26, 971982.Google Scholar
Mok, T.S., Wu, Y.L., Thongprasert, S., et al. (2009). Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. New England Journal of Medicine, 361, 947957.Google Scholar
Musselman, D.L., Miller, A.H., Porter, M.R., et al. (2001). Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. American Journal of Psychiatry, 158, 12521257.CrossRefGoogle ScholarPubMed
National Lung Screening Trial Research Team, Aberle, D.R., Adams, A.M., et al. (2011). Reduced lung-cancer mortality with low-dose computed tomographic scanning. New England Journal of Medicine, 365, 395409.Google Scholar
Normanno, N., DeLuca, A., Bianco, C., et al. (2006). Epidermal growth factor receptor (EGFR) signaling in cancer. Gene, 366, 216.Google Scholar
Onitilo, A.A., Nietert, P.J. & Egede, L.E. (2006). Effect of depression on all-cause mortality in adults with cancer and differential effects by cancer site. General Hospital Psychiatry, 28, 396402.Google Scholar
Paralkar, V.R., Li, T. & Langer, C.J. (2008). Population characteristics and prognostic factors in metastatic non-small-cell lung cancer: A Fox Chase Cancer Center retrospective. Clinical Lung Cancer, 9, 116121.Google Scholar
Pinquart, M. & Duberstein, P.R. (2010). Depression and cancer mortality: a meta-analysis. Psychological Medicine, 40, 17971810.Google Scholar
Pirl, W.F., Temel, J.S., Billings, J.A., et al. (2008). Depression after diagnosis of non-small cell lung cancer and survival: A pilot study. Psychosomatics, 49, 218224.CrossRefGoogle ScholarPubMed
Pirl, W.F., Traeger, L., Greer, J.A., et al. (2011). Tumor epidermal growth factor receptor genotype and depression in stage IV non-small cell lung cancer. Oncologist, 16, 12991306.CrossRefGoogle ScholarPubMed
Pirl, W.F., Traeger, L., Greer, J.A., et al. (2012). Depression and survival in metastatic NSCLC: impact of early palliative care. Journal of Clinical Oncology, 30, 13101315.Google Scholar
Rich, T.A. (2007). Symptom clusters in cancer patients and their relation to EGFR ligand modulation of the circadian axis. Journal of Supportive Oncology, 5, 167174.Google ScholarPubMed
Rich, T.A., Innominato, P.F., Boerner, J., et al. (2005). Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer. Clinical Cancer Research, 11, 17571763.Google Scholar
Satin, J.R., Linden, W. & Phillips, M.J. (2009). Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis. Cancer, 115, 53495361.CrossRefGoogle ScholarPubMed
Sequist, L.V., Bell, D.W., Lynch, T.J., et al. (2007a). Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. Journal of Clinical Oncology, 25, 587595.Google Scholar
Sequist, L.V., Heist, R.S., Shaw, A.T., et al. (2011). Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Annals of Oncology, 22, 26162624.CrossRefGoogle ScholarPubMed
Sequist, L.V., Joshi, V.A., Jänne, P.A., et al. (2007b). Response to treatment and survival of patients with non-small cell lung cancer undergoing somatic EGFR mutation testing. Oncologist, 12, 9098.Google Scholar
Snodgrass-Belt, P., Gilbert, J.L. & Davis, F.C. (2005). Central administration of transforming growth factor-alpha and neuregulain-1 suppress active behaviors and cause weight loss in hamsters. Brain Research, 1038, 171182.Google Scholar
Spitzer, R.L., Kroenke, K. & Williams, J.B.W. (1999). Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study. Journal of the American Medical Association, 282, 17371744.CrossRefGoogle ScholarPubMed
Su, C, Zhou, C., Zhou, S. & Xu, J. (2010). Serum cytokine levels in patients with advanced non-small cell lung cancer: Correlation with treatment response and survival. Medical Oncology, 28, 14531457.Google Scholar
Stinchcombe, T.E. & Socinski, M.A. (2009). Current treatments for advanced non-small cell lung cancer. Proceedings of the American Thoracic Society, 6, 233241.Google Scholar
Temel, J.S., Greer, J.A., Muzikansky, A., et al. (2010) Early palliative care for patients with metastatic non-small cell lung cancer. New England Journal of Medicine, 363, 733742.Google Scholar
Tracy, S., Mukohara, T., Hansen, M., et al. (2004). Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Research, 64, 72417244.Google Scholar
Vadigepalli, R., Hao, H., Miller, G.M., et al. (2006). Epidermal growth factor receptor-induced circadian-time-dependent gene regulation in suprachiasmatic nucleus. Neuroreport, 17, 14371441.Google Scholar
Volante, M., Saviozzi, S., Rapa, I., et al. (2007). Epidermal growth factor ligand/receptor loop and downstream signaling activation pattern in completely resected nonsmall cell lung cancer. Cancer, 110, 13211328.Google Scholar
Wang, X.S., Shi, Q., Williams, L.A., et al. (2010). Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. Brain, Behavior, and Immunity, 24, 968974.CrossRefGoogle ScholarPubMed
Yonesaka, K., Zejnullahu, K., Lindeman, N., et al. (2008). Autocrine production of amphiregulin predicts sensitivity to both gefitinib and cetuximab in EGFR wild-type cancers. Clinical Cancer Research, 14, 69636973.Google Scholar