臺灣博碩士論文加值系統

目的
肺癌位居台灣癌症死亡率首位。近年來標靶藥物治療開始普及，作為表皮生長因子接受器酪胺酸基因陽性突變（EGFR mutation）之晚期非小細胞肺癌病人的第一線治療，但多數服用標靶藥物之病人曾反映長期服用標靶藥物所引發之不良副作用及其對生活品質之影響，因此本研究擬針對晚期非小細胞肺癌病人服用標靶藥物期間之生活品質（EORTC QLQ-C30、QLQ-LC13）及其情緒（HADS）相關因素進行縱貫性探討。

方法
採用問卷調查法蒐集資料。以南部某區域教學醫院之晚期非小細胞肺癌且首次療程為標靶藥物治療之患者為對象。收案時間為2016年3月10日至2017年3月31日，收案數為30位，首次治療接受Giotrif、Erlotinib、Gefitinib的晚期非小細胞肺癌有EGFR陽性突變的病人，蒐集資料包括治療前期、第1週、第1個月、第2個月及第3個月等不同時程所出現之藥物副作用程度、影響生活品質層面、憂鬱及焦慮之情緒變化。問卷資料經編碼、清理後，以SPSS 20統計套裝軟體進行分析。除了描述性統計外，將使用GEE進行對整體生活品質及五大功能構面進行變項分析。

結果
隨著治療週期的變化，在第一週和第3月的整體生活品質及功能構面之身體功能在第3月（p<0.05）和情緒功能在第一週至第三月內皆具有統計意義（p <0.05）有顯著改善。其他症狀尺度，治療後3個月，身體症狀如疼痛、呼吸困難、失眠、疲倦和食慾不振等（p<0.05）症狀獲得改善，但標靶藥物治療期間所出現腹瀉、口腔炎之副作用，導致腹瀉、口腔疼痛及吞嚥困難等症狀及頻率增加（p<0.05）。隨著治療週期的變化，憂鬱情緒在治療第一月後對整體生活品質呈負向影響（p<0.019）。

結論
縱貫性研究得知肺癌病人在標靶藥物治療期間影響生活品質之相關因素，建議選擇整體健康生活品質做為治療前後之評估項目，提供相關協助。並且於標靶藥物治療前，及早提供常見副作用預防衛教，如皮膚黏膜照護、口腔照護、腹瀉處置等資訊，密切觀察副作用嚴重等級；因此，治療期間除了改善治療後生活品質主要功能構面及症狀構面，也須注意標靶藥物所產生副作用造成身體症狀之影響。

Objective
Lung cancer is the leading cause of cancer death in Taiwan. Target therapy as first-line in patients with EGFR (epidermal growth factor receptor) mutated advanced NSCLC (non-small cell lung cancer) supports effective treatment option in this setting. The majority of patients taking the long-term use of target therapy suffered from adverse events and the impact of quality of life. The objective of this study aimed to evaluate the relationship of EORTC (European Organization for Research and Treatment of Cancer) QLQ-C30, QLQ-LC13 and HADS (Hospital Anxiety and Depression Scale), and quality of life in patients with NSCLC undergoing different time treatments.

Methods
In this study, a questionnaire was used to collect data. From March 2016 to March 2017, a total of 30 patients with advanced or metastatic EGFR mutations were enrolled in a teaching hospital in southern Taiwan. The patients with advanced or metastatic EGFR mutation-positive NSCLC who received gefitinib, erlotinib, or giotrif as first-line treatment, were invited to complete the EORTC QLQ-C30、QLQ-C13 and HADS on between QOL before target therapy and 1 week,1 month, 2 months, and 3 months after commencing therapy, with a total of 5 visits. The data were analyzed by SPSS 20.0 software using the Generalize estimating equation（GEE）model.

Results
With treatment progression after target therapy, the overall quality of life had significant differences (p <0.05) in the week 1 and month 3. There were significant differences (p <0.05) in the month 3 for body function, and week 1 through month 3 for emotional function. For the other scales, at month 3, improvement of insomnia, pain, dyspnea, fatigue and appetite loss, along with worsening syndromes of diarrhea, sore mouth and dysphagia were observed (p <0.05). Melancholy had a significant effect on overall quality of life after the first month of treatment (p <0.019).

Conclusion
Based on the research results, it is suggested that the overall quality of life be used as the assessment instrument before and after treatment to enable early recognition of arising symptom aggravation. Further, before therapy, support for health education, for example, skin care, oral care, anti-diarrhea, follow up and observation of serious adverse effect is suggested. In summary, during the treatment period, not only is it necessary trying to improve the quality of life for the functional scales and symptomatic scales, but also should pay close attention to the adverse effect of the target therapy on physical functioning.

致 謝 i
中文摘要 ii
英文摘要 iv
目錄 vi
圖目錄 vii
表目錄 viii
第壹章 緒論 1
第貳章 文獻探討 7
第一節 肺癌疾病 7
第二節 標靶藥物治療 14
第三節 晚期肺癌病人之生活品質及相關因素 22
第參章 研究方法 32
第一節 研究設計 32
第二節 研究架構 32
第三節 研究假設 33
第四節 研究場所及對象 37
第五節 研究工具 39
第六節 研究變項 46
第七節 資料分析方法 48
第肆章 研究結果 50
第一節 人口學特性、疾病醫療特性及情緒因素分佈情形 50
第二節 三種標靶藥物治療之常見副作用症狀及嚴重程度 60
第三節 標靶藥物期間之生活品質變化 81
一、GEE雙變量檢定之整體生活品質影響因素 100
二、GEE多變量檢定之整體生活品質影響因素 115
第伍章 討論與建議 125
第一節 討論 125
第二節 研究限制 131
第三節 建議 131
英文文獻 133
中文文獻 141
附錄一 中文版歐洲癌症生活品質（EORTC QLQ-C30）核心問卷 144
附錄二 中文版肺癌生活品質（EORTC QLQ-LC13）問卷 146
附錄三 EORTC QLQ-C30及QLQ-LC13問卷授權 147
附錄四 中文版醫院焦慮與憂鬱量表（HADS）問卷 148
附錄五 醫院焦慮與憂鬱量表（HADS）問卷授權150

英文
Aaronson, N. K., Ahmedzai, S., Bergman, B., Bullinger, M., Cull, A., Duez, N. J., . . . de Haes, J. C.(1993). The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. Journal of the national cancer institute, 85(5), 365-376.
American Joint Commitee on Cancer.(2016). Implementation of AJCC 7th Edition Cancer Staging System. https://cancerstaging.org/Pages/default.aspx
Retrieved on 2016-12-23.
Akin, S., Can, G., Aydiner, A., Ozdilli, K., & Durna, Z. (2010). Quality of life, symptom experience and distress of lung cancer patients undergoing chemotherapy. European journal of oncology nursing, 14(5), 400-409.
Akita, R. W., & Sliwkowski, M. X.(2003). Preclinical studies with Erlotinib (Tarceva). Semin Oncol, 30(3 Suppl 7), 15-24.
Arraras, J. I., Hernandez, B., Martinez, M., Cambra, K., Rico, M., Illarramendi, J. J., . . . Vera, R. （2016）. Quality of Life in Spanish advanced non-small-cell lung cancer patients: determinants of global QL and survival analyses. Springerplus, 5（1）, 836.
Arrieta, Ó., Angulo, L. P., Núñez-Valencia, C., Dorantes-Gallareta, Y., Macedo, E. O., Martínez-López, D., . . . Oñate-Ocaña, L. F.(2013). Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Annals of surgical oncology, 20(6), 1941-1948.
Arrieta, O., Angulo, L. P., Nunez-Valencia, C., Dorantes-Gallareta, Y., Macedo, E. O., Martinez-Lopez, D., . . . Onate-Ocana, L. F.(2013). Association of depression and anxiety on quality of life, treatment adherence, and prognosis in patients with advanced non-small cell lung cancer. Ann Surg Oncol, 20(6), 1941-1948.
Ashbury, F. D., Madlensky, L., Raich, P., Thompson, M., Whitney, G., Hotz, K., . . . Edell, W. S.(2003). Antidepressant prescribing in community cancer care. Supportive care in cancer, 11(5), 278-285.
Bazley, L., & Gullick, W. J. (2005). The epidermal growth factor receptor family. Endocrine-related cancer, 12(Supplement 1), S17-S27.
Beck, A. T., Ward, C., Mendelson, M., Mock, J., & Erbaugh, J.(1962). Reliability of psychiatric diagnoses: 2. A study of consistency of clinical judgments and ratings. American Journal of Psychiatry, 119(4), 351-357.
Beth Eaby, M., & Lacouture, M. E.(2008). An interdisciplinary consensus on managing skin reactions associated with human epidermal growth factor receptor inhibitors. Clinical journal of oncology nursing, 12(2), 283.
Blume-Jensen, P., & Hunter, T.(2001). Oncogenic kinase signalling. Nature, 411(6835), 355-365.
Bonomi, P.(2003). Erlotinib: a new therapeutic approach for non-small cell lung cancer. Expert Opin Investig Drugs, 12(8), 1395-1401.
Buccheri, G., Ferrigno, D., & Tamburini, M.(1996). Karnofsky and ECOG performance status scoring in lung cancer: a prospective, longitudinal study of 536 patients from a single institution. European Journal of Cancer, 32(7), 1135-1141.
Bulgaru, A. M., Mani, S., Goel, S., & Perez-Soler, R.(2003). Erlotinib (Tarceva®): a promising drug targeting epidermal growth factor receptor tyrosine kinase. Expert Review of Anticancer Therapy, 3(3), 269-279.
Chen, Y.-M., Perng, R.-P., Shih, J.-F., Tsai, C.-M., & Whang-Peng, J.(2005 ). Chemotherapy for non-small cell lung cancer in elderly patients. CHEST Journal, 128(1), 132-139.
Cunningham, D., Humblet, Y., Siena, S., Khayat, D., Bleiberg, H., Santoro, A., . . . Verslype, C.(2004). Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. New England journal of medicine, 351(4), 337-345.
Danson, S., Middleton, M. R., O'Byrne, K. J., Clemons, M., Ranson, M., Hassan, J., . . . Thatcher, N.(2003). Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer, 98(3), 542-553.
Dest, V. M.(2000). Lung cancer. RN, 63(5), 32-34.
DeWitt, C. A., Siroy, A. E., & Stone, S. P.(2007). Acneiform eruptions associated with epidermal growth factor receptor–targeted chemotherapy. Journal of the American Academy of Dermatology, 56(3), 500-505.
Engle, J. A., & Kolesar, J. M.(2014). Giotrif: A first-line treatment for selected patients with metastatic non-small-cell lung cancer. Am J Health Syst Pharm, 71(22), 1933-1938.
Ferrans, C. E.(1996). Development of a conceptual model of quality of life. Scholarly inquiry for nursing practice, 10(3), 293-304.
Galimont-Collen, A. F., Vos, L. E., Lavrijsen, A. P., Ouwerkerk, J., & Gelderblom, H.(2007). Classification and management of skin, hair, nail and mucosal side-effects of epidermal growth factor receptor (EGFR) inhibitors. Eur J Cancer, 43(5), 845-851.
Gelibter, A., Ceribelli, A., Pollera, C. F., Milella, M., Moscetti, L., Sperduti, I., & Cognetti, F.(2005). Impact of gefitinib(‘Iressa’)treatment on the quality of life of patients with advanced non-small-cell lung cancer. Journal of cancer research and clinical oncology, 131(12), 783-788.
Giesinger, J. M., et al. (2016). Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust. J Clin Epidemiol 69: 79-88.
Gridelli, C., De Marinis, F., Di Maio, M., Cortinovis, D., Cappuzzo, F., & Mok, T.(2011). Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating Epidermal Growth Factor Receptor mutation: implications for clinical practice and open issues. Lung Cancer, 72(1), 3-8.
Gridelli, C., De Marinis, F., Di Maio, M., Cortinovis, D., Cappuzzo, F., & Mok, T.(2011). Gefitinib as first-line treatment for patients with advanced non-small-cell lung cancer with activating epidermal growth factor receptor mutation: Review of the evidence. Lung Cancer, 71(3), 249-257.
Group, T. W.(1998). The World Health Organization quality of life assessment (WHOQOL): development and general psychometric properties. Social science & medicine, 46(12), 1569-1585.
Gu, G., Zhou, Y., Zhang, Y., & Cui, W. (2016). Increased prevalence of anxiety and depression symptoms in patients with coronary artery disease before and after percutaneous coronary intervention treatment. BMC Psychiatry, 16, 259.
Herbst, R. S., & Kies, M. S.(2002). ZD1839 (Iressa)in non-small cell lung cancer. Oncologist, 7 Suppl 4, 9-15.
Hermann, C. P., & Looney, S. W.(2011). Determinants of quality of life in patients
near the end of life: a longitudinal perspective. Oncol Nurs Forum 38: 23-31,
2011.
Henoch, I., Bergman, B., Gustafsson, M., Gaston-Johansson, F., & Danielson, E.(2007). The impact of symptoms, coping capacity, and social support on quality of life experience over time in patients with lung cancer. Journal of pain and symptom management, 34(4), 370-379.
Hirsh, V.(2011). Giotrif (BIBW 2992)development in non-small-cell lung cancer. Future Oncol, 7(7), 817-825.
Huang, C., Tu, S., Lien, H., Huang, C., Wang, P., & Chie, W. (2015). Conceptual structure of the taiwan chinese version of the EORTC QLQ-C30. Quality of Life Research, 24(8), 1999-2013.
Hynes, N. E., & Lane, H. A. (2005). ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer, 5(5), 341-354.
Ibbotson, T., Maguire, P., Selby, P., Priestman, T., & Wallace, L. (1994). Screening for anxiety and depression in cancer patients: the effects of disease and treatment. Eur J Cancer, 3參考組(1), 37-40.
Iconomou, G., Mega, V., Koutras, A., Iconomou, A. V., & Kalofonos, H. P. (2004). Prospective assessment of emotional distress, cognitive function, and quality of life in patients with cancer treated with chemotherapy. Cancer, 101(2), 404-411.
Ioannou, N., Dalgleish, A. G., Seddon, A. M., Mackintosh, D., Guertler, U., Solca, F., & Modjtahedi, H.(2011). Anti-tumour activity of Giotrif, an irreversible ErbB family blocker, in human pancreatic tumour cells. Br J Cancer, 105(10), 1554-1562.
Iyer, S., Taylor-Stokes, G., & Roughley, A.(2013).Symptom burden and quality of life in advanced non-small cell lung cancer patients in France and Germany. Lung Cancer, 81(2), 288-293.
Karnofsky D, Burchenal J, The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C, ed. Evaluation of Chemotherapeutic Agents. New York, NY: Columbia University Press; 1949:191–205.
Kato, S., Saito, A., Matsuda, N., Suzuki, H., Ujiie, M., Sato, S., . . . Satoh, H. (2017). Management of Giotrif-induced stomatitis. Mol Clin Oncol, 6(4), 603-605.
Kim, B.-J., Park, H.-R., Roh, H. J., Jeong, D.-S., Kim, B. S., Park, K.-W., . . . Kim, S. J.(2010). Chemotherapy-related polyneuropathy may deteriorate quality of life in patients with B-cell lymphoma. Quality of Life Research, 19(8), 1097-1103.
Kris, M. G., Natale, R. B., Herbst, R. S., Lynch Jr, T. J., Prager, D., Belani, C. P., . . . Sandler, A.(2003). Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non–small cell lung cancer: a randomized trial. Jama, 290(16), 2149-2158.
Kulpa, M., Ziętalewicz, U., Kosowicz, M., Stypuła-Ciuba, B., & Ziółkowska, P.(2016). Anxiety and depression and cognitive coping strategies and health locus of control in patients with ovary and uterus cancer during anticancer therapy. Contemp Oncol (Pozn), 20(2), 171-175.
Lacouture, M. E.(2006). Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer, 6(10), 803-812.
Lai, K. L., Tzeng, R. J., Wang, B. L., Lee, H. S., Amidon, R. L., & Kao, S.(2005). Health-related quality of life and health utility for the institutional elderly in Taiwan. Qual Life Res, 14(4), 1169-1180.
Li, T. C., Li, C. I., Tseng, C. H., Lin, K. S., Yang, S. Y., Chen, C. Y., . . . Lin, C. C.
(2012). Quality of life predicts survival in patients with non-small cell lung
cancer. BMC Public Health, 12, 790.
Lynch, T. J., Bell, D. W., Sordella, R., Gurubhagavatula, S., Okimoto, R. A., Brannigan, B. W., . . . Haluska, F. G.(2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non–small-cell lung cancer to gefitinib. New England Journal of Medicine, 350(21), 2129-
2139.
Mehnert, A.(2011). Employment and work-related issues in cancer survivors. Critical reviews in oncology/hematology, 77(2), 109-130.
Metro, G., & Crino, L.(2011). The LUX-Lung clinical trial program of Giotrif for non-small-cell lung cancer. Expert Rev Anticancer Ther, 11(5), 673-682.
Montazeri, A., Gillis, C. R., & McEwen, J.(1998). Quality of life in patients with lung cancer: a review of literature from 1970 to 1995. CHEST Journal, 113(2), 467-481.
Montazeri, A., Milroy, R., Hole, D., McEwen, J., & Gillis, C. R.(1998). Anxiety and depression in patients with lung cancer before and after diagnosis: findings from a population in Glasgow, Scotland. J Epidemiol Community Health, 52(3), 203-204.
Montazeri, A., Milroy, R., Hole, D., McEwen, J., & Gillis, C. R.(2001). Quality of life in lung cancer patients: as an important prognostic factor. Lung Cancer, 31(2-3), 233-240.
Mor, V., Laliberte, L., Morris, J. N., & Wiemann, M.(1984). The Karnofsky performance status scale: an examination of its reliability and validity in a research setting. Cancer, 53(9), 2002-2007.
Morita, S., Okamoto, I., Kobayashi, K., Yamazaki, K., Asahina, H., Inoue, A., . . . Hida, T.(2009). Combined survival analysis of prospective clinical trials of gefitinib for non–small cell lung cancer with EGFR mutations. Clinical Cancer Research, 15(13), 4493-4498.
Murakami, H., Tamura, T., Takahashi, T., Nokihara, H., Naito, T., Nakamura, Y., . . . Yamamoto, N.(2012). Phase I study of continuous Giotrif (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol, 69(4), 891-899.
National Comprehensive Cancer Network . (2016). Non-Small Cell Lung Cancer
. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#nscl .
Retrieved on 2016-12-23.
National Cancer Institute. (2016). Common Terminology Criteria for Adverse Events v4.03(CTCAE). https://ctep.cancer.gov/protocoldevelopment/electronic_
applications/ctc.htm. Retrieved on 2016-12-23.
Ng, S. S., Tsao, M. S., Nicklee, T., & Hedley, D. W.(2002). Effects of the epidermal growth factor receptor inhibitor OSI-774, Tarceva, on downstream signaling pathways and apoptosis in human pancreatic adenocarcinoma. Mol Cancer Ther, 1(10), 777-783.
Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., Mcfadden, E. T., & Carbone, P. P.(1982). Toxicity and response criteria of the Eastern Cooperative Oncology Group. American journal of clinical oncology, 5(6), 649-656.
Olayioye, M. A., Neve, R. M., Lane, H. A., & Hynes, N. E.(2000). The ErbB signaling network: receptor heterodimerization in development and cancer. Embo j, 19(13), 3159-3167.
Owonikoko, T. K., Ragin, C. C., Belani, C. P., Oton, A. B., Gooding, W. E., Taioli, E., & Ramalingam, S. S.(2007). Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. Journal of clinical oncology, 25(35), 5570-5577.
Park, K., Tan, E. H., O'Byrne, K., Zhang, L., Boyer, M., Mok, T., . . . Paz-Ares, L.(2016). Giotrif versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol, 17(5), 577-589.
Pasquini, M., & Biondi, M.(2007). Depression in cancer patients: a critical review. Clinical Practice and Epidemiology in Mental Health, 3(1), 1.
Passaro, A., Di Maio, M., Del Signore, E., Gori, B., & de Marinis, F.(2014). Management of nonhematologic toxicities associated with different EGFR-TKIs in advanced NSCLC: A comparison analysis. Clinical lung cancer, 15(4), 307-312.
Perez-Soler, R., Chachoua, A., Hammond, L. A., Rowinsky, E. K., Huberman, M., Karp, D., . . . Bonomi, P.(2004). Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. J Clin Oncol, 22(16), 3238-3247.
Pfister, D. G., Johnson, D. H., Azzoli, C. G., Sause, W., Smith, T. J., Baker, S., Jr., . . . Somerfield, M. R.(2004). American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol, 22(2), 330-353.
Pinkas-Kramarski, R., Soussan, L., Waterman, H., Levkowitz, G., Alroy, I., Klapper, L., . . . Yarden, Y.(1996). Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. Embo j, 15(10), 2452-2467.
P.M. Fayers, N.K. Aaronson, K. Bjordal, M. Groenvold, D. Curran, A. Bottomley, on
behalf of the EORTC Quality of Life Group. EORTC QLQ-C30 Scoring
Manual. (3rd edn.)EORTC, Brussels (2001).
Radloff, L. S.(1977). The CES-D scale a self-report depression scale for research in the general population. Applied psychological measurement, 1(3), 385-401.
Robert, F., Blumenschein, G., Herbst, R. S., Fossella, F. V., Tseng, J., Saleh, M. N., & Needle, M.(2005). Phase I/IIa study of cetuximab with gemcitabine plus carboplatin in patients with chemotherapy-naïve advanced non–small-cell lung cancer. Journal of clinical oncology, 23(36), 9089-9096.
Saltz, L. B., Meropol, N. J., Loehrer, P. J., Needle, M. N., Kopit, J., & Mayer, R. J.(2004). Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. Journal of Clinical Oncology, 22(7), 1201-1208.
Sandler, A.(2003). Clinical experience with the HER1/EGFR tyrosine kinase inhibitor erlotinib. Oncology (Williston Park), 17(11 Suppl 12), 17-22.
Scope, A., Agero, A. L. C., Dusza, S. W., Myskowski, P. L., Lieb, J. A., Saltz, L., . . . Halpern, A. C.(2007). Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. Journal of Clinical Oncology, 25(34), 5390-5396.
Shepherd , F. A., Rodrigues Pereira , J., Ciuleanu , T., Tan , E. H., Hirsh , V., Thongprasert , S., . . . Seymour , L.(2005). Erlotinib in Previously Treated Non–Small-Cell Lung Cancer. New England Journal of Medicine, 353(2), 123-132.
Sipples, R.(2006). Common side effects of anti-EGFR therapy: acneform rash. Semin Oncol Nurs, 22(1 Suppl 1), 28-34.
Smith, J.(2005). Erlotinib: small-molecule targeted therapy in the treatment of non-small-cell lung cancer. Clin Ther, 27(10), 1513-1534.
Spigel, D. R., Lin, M., O'Neill, V., & Hainsworth, J. D.(2008). Final survival and safety results from a multicenter, open-label, phase 3b trial of erlotinib in patients with advanced nonsmall cell lung cancer. Cancer, 112(12), 2749-
2755.
Sprangers, M. A., Cull, A., Bjordal, K., Groenvold, M., & Aaronson, N. K.(1993). The European Organization for Research and Treatment of Cancer. Approach to quality of life assessment: guidelines for developing questionnaire modules. EORTC Study Group on Quality of Life. Qual Life Res, 2(4), 287-295.
Stinchcombe, T. E., & Socinski, M. A.(2009). Current treatments for advanced stage non-small cell lung cancer. Proc Am Thorac Soc, 6(2), 233-241.
Suzuki, R., Hasegawa, Y., Baba, K., Saka, H., Saito, H., Taniguchi, H., . . . Shimokata, K.(2006). A phase II study of single-agent gefitinib as first-line therapy in patients with stage IV non-small-cell lung cancer. Br J Cancer, 94(11), 1599-1603.
Tanaka, T., Matsuoka, M., Sutani, A., Gemma, A., Maemondo, M., Inoue, A.,. . . Uematsu, K.(2010). Frequency of and variables associated with the EGFR mutation and its subtypes. International Journal of Cancer, 126(3), 651-655.
Teunissen, S., De Graeff, A., Voest, E., & de Haes, J.(2007). Are anxiety and depressed mood related to physical symptom burden? A study in hospitalized advanced cancer patients. Palliative Medicine, 21(4), 341-346.
Tung, H. H., Wei, J., & Chang, C. Y.(2007). Gender differences in quality of life for post coronary artery bypass grafting patients in Taiwan. J Nurs Res, 15(4), 275-284.
Von Plessen, C., Bergman, B., Andresen, O., Bremnes, R. M., Sundstrom, S., Gilleryd, M., . . . Sorenson, S. （2006）. Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer. Br J Cancer, 95（8）, 966-973.
Walker, J., Postma, K., McHugh, G. S., Rush, R., Coyle, B., Strong, V., & Sharpe, M.(2007). Performance of the Hospital Anxiety and Depression Scale as a screening tool for major depressive disorder in cancer patients. Journal of psychosomatic research, 63(1), 83-91.
Ware, J. E., Jr., Kosinski, M., Bayliss, M. S., McHorney, C. A., Rogers, W. H., & Raczek, A.(1995). Comparison of methods for the scoring and statistical analysis of SF-36 health profile and summary measures: summary of results from the Medical Outcomes Study. Med Care, 33(4 Suppl), As264-279.
World Health Organization. (2016). Monitoring health for the SDGs Data visualizations dashboard. http://www.who.int/healthinfo/en/ . Retrieved on 2016-12-22.
Wintner, L., Giesinger, J., Zabernigg, A., Sztankay, M., Meraner, V., Pall, G., . . . Holzner, B.(2013). Quality of life during chemotherapy in lung cancer patients: results across different treatment lines. British journal of cancer, 109(9), 2301-2308.
Xu, Y., Chen, L., Tian, Q., Yang, Z., Zhao, W., Wang, P., . . . Li, C.(2010). Application of epidermal growth factor receptor tyrosine kinase inhibitor as the first-line therapy in patients with advanced non-small cell lung cancer Zhongguo Fei Ai Za Zhi, 13(1), 48-53.
Yang, K.-P.(1995). Predictors of nursing-sensitive patient outcomes in long-term care facilities in Taiwan, ROC.
Zigmond, A. S., & Snaith, R. P.(1983). The hospital anxiety and depression scale. Acta psychiatrica scandinavica, 67(6), 361-370.
Zubrod, C. G., Schneiderman, M., Frei, E., Brindley, C., Gold, G. L., Shnider, B., . . . Jonsson, U. (1960). Appraisal of methods for the study of chemotherapy of cancer in man: comparative therapeutic trial of nitrogen mustard and triethylene thiophosphoramide. Journal of Chronic Diseases, 11(1), 7-33.

中文
台灣版世界衛生組織生活品質問卷發展小組.（2000）. 台灣版世界衛生組織生活品質問卷之發展簡介.中華公共衛生雜誌, 19（4）, 315-324.
吳易霖.（2013）. 肺癌病人生活品質及其相關因素.（碩士）, 國立成功大學, 台南市.
吳金燕.（2005）. 肺癌患者生活品質及其相關因素探討.（碩士）, 中國醫藥大學, 台中市.
吳金燕.（2015）. 肺癌存活者之症狀困擾、疲倦、憂鬱情緒、社會支持、靈性安適與生活品質之相關性探討. 國立臺北護理健康大學, 台北市.
李建山, & 乾光宇.（1975）. 肺癌之早期診斷與治療.當代醫學（18）, 69-75.
李淑芳, 王燕, 辛士珍, & 曹建存.（2012）. 化療對肺癌患者生活質量及焦慮的影響及分析.中國肺癌雜誌, 15（8）, 465-470.
季瑋珠, 楊志新, 許駿, & 賴佳君.（2002）. 癌症病人特定疾病EORTC生活品質量表簡介.台灣醫學, 6（2）, 220-227.
林冠馨.（2006）. 肺癌病人生活品質之縱貫面研究—歐洲癌症治療與研究組織生活品質核心問卷, 肺癌生活品質問卷之反應性與預測死亡的能力.中國醫藥大學醫務管理學系碩士班學位論文, 1-198.
林春香, 劉雪娥, & 王正儀.（1996）. 大腸直腸癌症病人生活品質及其相關因素之探討.護理研究, 4（1）, 13-26.
姚開屏.（2002）. 健康相關生活品質概念與測量原理之簡介.臺灣醫學, 6（2）, 183-192.
胡文鬱, 戴玉慈, 陳慶餘, & 陳月枝.（2003）. 生活品質之概念分析－於探討癌末病人健康相關生活品質之應用.安寧療護雜誌, 8（1）, 45-60.
張黎露, 朱家瑜, 姜紹青, 許麗珠, 黃國埕, 周文珊, . . . 侯秀香.（2015）. 標靶治療藥品之皮膚毒性預防及照護指引.腫瘤護理雜誌, 15, 47-80.
莊永毓, 林青蓉, 楊翠雲, 靳燕芬, & 王碧華.（2013）. 癌症病人的憂鬱症.臺灣醫學, 17（2）, 155-162.
曾俊華. (2005）. 歐洲癌症治療與研究組織生活品質核心問卷、肺癌生活品質問卷之信效度研究. (碩士）, 中國醫藥大學, 台中市.
陳美碧, 謝麗鳳, 林惠蘭, 李淑貞, 林純如, & 蔡欣玲. (2004）. 癌症病人之生活品質及其預測因子.榮總護理, 21(4）, 352-362.
陳育民, 羅永鴻, 吳杰鴻, 李毓芹, 彭瑞鵬, & 彭汪嘉康.（2015）. 使用Erlotinib或化學治療作為野生型上皮細胞生長因素接收器之肺腺癌患者的第二線或後線之治療.台灣癌症醫學雜誌, 2（1）, 3-11.
陳佩英, 史麗珠, 王正旭, 賴裕和, 張獻崑, & 陳美伶.（1999）. 疼痛對癌症病人焦慮與憂鬱之影響.台灣醫學, 3（4）, 373-382.
陳佩英, 郭素青, 張惠甄, 徐一瑱, 林麗玉, & 楊桂美.（2004）. 口腔癌術後病人之身心症狀與調適.安寧療護雜誌, 9（2）, 153-164.
陳秋慧.（2009）. 上皮生長因子接受體抑制劑相關皮膚毒性之照護.腫瘤護理雜誌, 9（2）, 13-22.
陳偉武, 洪敏瑛, & 陳幼貴.（2010）. 肺癌治療回顧及發展.腫瘤護理雜誌, 10（2）, 39-54.
陳雅萍.（2006）. 子宮頸癌住院患者症狀困擾, 憂鬱及生活品質之相關性研究.美和技術學院健康照護研究所學位論文, 1-105.
陳雅萍, 葉淑惠, 龔福財, & 何美瑤. (2007). 子宮頸癌住院病人症狀困擾、憂鬱及生活品質之相關性研究. 實證護理, 3(2), 89-98.
曾俊華.（2005）. 歐洲癌症治療與研究組織生活品質核心問卷、肺癌生活品質問卷之信效度研究.（碩士）, 中國醫藥大學, 台中市.
黃怡靜.（2011）. 早期肺癌術後患者的症狀嚴重度,心理困擾與照護需求之探討. （碩士）, 國立台北護理學院, 台北市.
黃淑儀, & 宋惠娟.（2016）. 憂鬱之概念分析.榮總護理, 33（2）, 204-211.
黃詩尹.（2009）. 肺癌病人治療前生活品質與存活狀況之相關探討. （碩士）, 長庚大學, 桃園縣.
楊志彥&楚新霞.（2016）.化療前後肺癌患者生活質量，焦慮抑鬱情緒變化和生活質量影響因素. 中國醫藥導報, 13（5）, 122-125。
楊佩靜.（2009）.初診斷肺癌患者症狀模組對身體功能狀況與生活品質之影響. (碩士）,國立台北護理學院, 台北市.
楊惠卿, 王麗斐, 張東杰, & 方富民.（2013）. 頭頸癌患者身心社會調適與生活品質之縱貫性研究.護理雜誌, 60（5）, 41-52.
萬崇華, 陳明清, 張燦珍, 湯學良, 孟瓊, & 張曉磬.（2005）. 癌症患者生命質量測定量表EORTC QLQ-C30中文版評介.實用腫瘤雜誌, 20（4）, 353-355.
葉秀珍.（2014）. 生活品質研究的測量、理論與分析.國家與社會（16）, 1-40.
詹瑞君, 廖幼婕, 李芸湘, & 賴裕和.（2014）. 接受標靶治療的肺癌病人身體心像改變之臨床照護.護理雜誌, 61（4）, 90-96.
雷玉華, & 丘周萍.（2000）. 生活品質概念分析.國防醫學, 31（2）,163-169.
廖國盟, & 陳建仁.（1997）. 肺癌之流行病學特徵、危險因子及防治策略.中華公共衛生雜誌, 16（5）, 375-395.
廖斌志, 陳冠字, 林家齊, & 楊志新.（2014）. 表皮生長因子接受器酪胺酸酶抑制劑於晚期肺癌治療. 臺灣醫學, 18（6）, 654-660.
趙慧玲, 黃惠如, 謝碧晴, & 蘇慧芳.（2013）. 癌症病人情緒困擾及其相關因素探討.輔仁醫學期刊, 11（3）, 205-214.
蔡琇文.（1998）. 癌症疼痛特質不確定感與心理困擾之相關性探討.（碩士）,臺北醫學大學, 台北市.
蔡岱蓉. （2013）. 宗教信仰對癌症病人健康影響之初探.（碩士）,臺北醫學大學, 台北市.
衛生福利部國民健康署（2016，11月）. 103年癌症登記年報. 2016年11月9日取自http://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=269&pid=7330.
盧瑞芬, 曾旭民, & 蔡益堅.（2003）. 國人生活品質評量（Ⅰ）：SF-36台灣版的發展及心理計量特質分析.台灣公共衛生雜誌, 22（6）, 501-511.
戴鈺娌. （2014）. 晚期非小細胞肺癌病人化學治療期間之生活品質變化及其影響因素.（碩士）, 長庚大學, 桃園縣.
戴鈺娌, 陳貞秀, 楊政達, 陳綱華, 江明珠, & 唐秀治.（2015）. 統合分析晚期非小細胞肺癌病人化學治療期間生活品質變化及其影響因素.台灣癌症醫學雜誌, 2（3）, 224-233.
簡采汝, & 林哲斌.（2010）. 非小細胞肺癌的維持性治療.台灣癌症醫學雜誌, 26（2）, 45-54.
簡采汝.（2008）.人間淨土的開展:宗教信仰於癌症患者生活品質相關性研究. （碩士）, 法鼓佛教學院, 新北市.