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Qing Zhou
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MS 14 - QOL Evaluation in Practice from the Viewpoint of Physicians and Nurses (ID 536)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Nursing/Palliative Care/Ethics
- Presentations: 5
- Moderators:Qing Zhou, Beth Eaby-Sandy
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 315
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MS 14.01 - Elements to Reach the Treatment Goal of Palliation (ID 7706)
11:00 - 11:15 | Presenting Author(s): Christian Klaus Manegold
- Abstract
- Presentation
Abstract:
Despite fast growing information of tumor molecular biology, the increase in the therapeutic portfolio, and a significant improvement in diagnostic radiology, treatment of advanced NSCLC in 2017 remains palliative with still no curative perspective for the vast majority of patients. Therefore, the main treatment goals include the change from an acute into a chronic disease, extending survival times as well as improving or just maintaining quality of life. In order to assure an optimal palliation the majority of patients with advanced NSCLC – considering the high age and concomitant comorbidities - frequently may require modifications of the treatment standard. Furthermore, it can also not be ignored that recently approved novel agents and innovative diagnostic technology represent a growing burden of financial toxicity leading to regional differences in the availability of modern therapy and in the access to molecular testing and modern imaging. Nonetheless, treatment algorithms for advanced NSCLC have over the last decade gradually gained in complexity by incorporating a number of diagnostic and therapeutic achievements allowing personalization, individualization, and precision of therapy. Not only patient factors such as performance status (PS), comorbidity, and patients’ treatment expectation must lead to treatment differentiation and modification but also disease characteristics such as tumor stage, tumor load, histological type (squamous vs non–squamous) and the molecular profile of the tumor (mutant vs wild type) influence the process in reaching the goal of optimal sustainable palliation. Other critical elements in realizing personalized therapy and precision medicine within the process of optimal palliation consist in a rational selection of anti-cancer agents (predictive factors, mode of action, toxicity profile) and their appropriate application (single agent, concomitant combinations, drug sequencing) as well as other novel therapeutic actions such as interventional radiology, modern radio therapy, and minimal surgery. Optimal therapeutic management for sustainable palliation should definitely be based on clinically reliable evidence presented by frequently updated treatment recommendations: Today’s treatment algorithm for advanced NSCLC is challenged by a number of newer agents, such as tyrosine kinase inhibitors, monoclonal antibodies, checkpoint inhibitors (Table 1),
Table 1 and the incorporation of new treatment strategies such as continuation or switch maintenance therapy (Figure 1).Figure 1 Figure 1 For advanced NSCLC (Figure 2) it is generally accepted that platinum based doubled chemotherapy remains the backbone for the majority of our patients with good PS and this combination therapy should be modified according to feasibility and tolerability, comorbidity, patients’ age over 70 years, PS. Figure 2 Figure 2 For wild type non-squamous NSCLC there is pemetrexed which has been shown to be favorable over older cytotoxic agents if combined with platinum based components. In addition, pemetrexed has also sufficiently demonstrated that if it is continued in case non-progression under four cycles of standard platinum based doublet chemotherapy not containing pemetrexed (switch maintenance) or containing pemetrexed (continuation maintenance) prolongs survival. Another agent, the small molecule and EGFR-tyrosine kinase inhibitor erlotinib also prolongs survival if used in the switch maintenance setting but its benefit depends on the quality of response to the chemotherapy and is restricted to patients which have experienced disease stabilization only. The VEGFR-targeting antibody, bevacizumab, if added to platinum based doublet therapy, specifically to carboplatin/paclitaxel significantly improves response rate, duration of response, progression free survival, as well as overall survival in eligible patients. Human immune checkpoint inhibitor-antibodies inhibiting the PD-1 receptor or PD-1 ligand have recently been integrated into the treatment algorithms of wild type NSCLC. Pembrolizumab is currently the only checkpoint inhibitor approved and recommended for first line therapy in patients with a PD-L1 expression level ≥ 50 % and with negative or unknown EGFR/ALC/ROS1 testing. In wild type squamous NSCLC the given treatment options are still limited and platinum based therapy (no pemetrexed, no bevacizumab) remains the recommended treatment standard. Nonetheless, just recently the EGFR-targeting monoclonal antibody necitumumab has shown to significantly improve survival if combined with the standard doublet regimen cisplatin/gemcitabine in comparison to cisplatin/gemcitabine only and therefore, has just recently approved. Maintenance therapy in squamous tumors with docetaxel or erlotinib (switch) or gemcitabine (continuation) may be justified in some patients even here the statistical evidence is weak. For about 10-30% of NSCLC (in Europe < 15%) non-squamous tumors expressing specific molecular features first-line treatment by genotype has been established. Tumors with sensitizing EGFR mutations have been exposed by gefitinib, erlotinib, and afatinib and have shown to prolong progression free survival over standard platinum based doublet standard therapy. In tumors bearing ALK-/ROS1-gene-rearrangements crizotinib and ceritinib have also shown to prolong progression free survival if compared to platinum based / pemetrexed doublet chemotherapy. Therefore, EGFR-TKI therapy (erlotinib, gefitinib, afatinib) should be prescribed for patient with tumors bearing sensitizing EGFR-mutations and for patients with tumors bearing ALK-/ROS1-gene-rearrangements ALK-/ROS1-targeted therapy (crizotinib, ceritinib) should be prescribed. However, for these patients molecular testing is critical and should be used to select patients for EGFR/ALK/ROS1 targeted therapy. Patients with lung adenocarcinoma should not be excluded from testing on the basis of clinical characteristics (ethnicity, gender, smoking status). Last but not least, second-/subsequent-line therapy is another strong element contributing to sustainable palliation in patients with advanced NSCLC. For tumor without driver mutations agents available before 2014 include docetaxel, pemetrexed (for non-squamous cell tumors only) and erlotinib. In recent years the two antiangiogenic agents nintetanib and ramucirumab (both in combination with docetaxel) and three immune checkpoint inhibitors (nivolumab, pembrolizumab, azetolizumab) have been added to the armentarium to treat patients with advanced non-mutated NSCLC who have progressed on or after first-line therapy (Figure 2). In mutated NSCLC several therapeutic options for second-/subsequent line-therapies are recommended depending on the type of progression and the molecular profile of the tumor. Osimertinib has been just recently approved for EGFRm/790M expressing tumors. For ALK-positive tumors ceritinib, alectinib, and crizotinib can be prescribed. In general, selection of agents for second-/subsequent-line therapies is based on whether the drugs have been used earlier, or toxicity or patients view. References are available by the author.2nd-line Docetaxel, Pemetrexed, EGFR-TKI 1st-line Bevacizumab - non-squamous NSCLC | Ramucirumab / Doc - NSCLC | Bevacizumab/Erl. – EGFRm NSCLC | Nintedanib / Doc - non-squamous | Pemetrexed - non-squamous NSCLC | Nivolumab - NSCLC | Pemetrexed, Erlotinib - maintenance | Osimertinib - EGFRmT790M | Gefitinib, Erlotinib, Afatinib - EGFRm | Crizotinib, Ceritinib – ALK | Necitumumab - squamous NSCLC | Alectinib - ALK | Crizotinib - ALK/ROS | Pembrolizumab – PD-L1-low | Ceritinib – ALK | Atezolizumab - NSCLC | Alectinib -ALK | Pembrolizumab - PD-L1-high
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MS 14.02 - Dimensions of Quality of Life in Lung Cancer (ID 7707)
11:15 - 11:30 | Presenting Author(s): Marianne Davies
- Abstract
- Presentation
Abstract:
Lung cancer is the leading cause of death in the world. Approximately 85% of patients are diagnosed with advanced disease, associated with high morbidity and mortality. Lung cancer is associated with a higher burden of symptoms compared to other cancers. Patients may experience symptoms from disease such as cough, dyspnea, anorexia, malaise, pain and anxiety. Lung cancer patients often report symptom clusters (2 or more symptoms occurring simultaneously). Patients may also experience symptoms secondary to immediate and chronic side effects of treatment. Treatments for lung cancer include surgery, radiation therapy, chemotherapy, targeted therapy and immunotherapy. Patients may receive a combination of these therapies either concurrently or sequentially. Each therapy is associated with a unique adverse symptom profile. Collectively these symptoms negatively impact clinical outcomes. High symptom burden is associated with poorer clinical outcomes such as survival and health related quality of life (HRQOL). HRQOL is the evaluation of the patients own life situation from their perspective. HRQOL may also be referred to as patient reported outcomes (PROS) and the measurement referred to as patient reported outcome measures (PROMs). HRQOL is subjective and multidimensional. HRQOL measures include physical, psychological, cognitive, social and life roles. Quality of life may be negatively influenced by risk factors such as co-morbid medical conditions, poor nutritional status, emotional distress, sleep disturbances, poor pulmonary function, poor financial resources, poor social support and past family history. Poor nutritional status, including malnutrition, sarcopenia and cachexia, is associated with poor quality of life, poor response to treatment and decreased survival. Emotional distress, anxiety and depression, is linked to lower HRQOL, increased symptom burden and poorer prognosis. Previous experience with family cancer and perceived risk of cancer, specifically among women, is associated with poorer reported HRQOL. Caregivers of patients with poorer HRQOL have a greater caregiver burden. This in turn negatively impacts the patients HRQOL further. Maximizing quality of life is an essential component of lung cancer management. Pre-diagnosis HRQOL and HRQOL at diagnosis are a strong prognostic factor for survival in lung cancer. HRQOL measurements are useful to evaluate treatment efficacy. HRQOL is an important clinical outcome measure to consider as newer treatments and improved therapeutics are providing the opportunity for long term survival for some patients. It is especially important in cases when therapy is unlikely to be curative, as patients often report that HRQOL is more important than short term survival benefits. Several instruments have been developed to assess HRQOL (Table 1). Some of the tools are generic, some specific to cancer and others that specifically focus on lung cancer. Most of the instruments are questionnaires. Several tools developed demonstrate correlation with performance status, symptoms and survival. Studies suggest that disease specific instruments may enhance outcome measures and be more useful in predicting outcomes. The tools specific to lung cancer include: The Lung Cancer Symptom Scale (LCSS), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTIC-QLQ), Functional Assessment of Cancer Therapy-Lung (FACT-L) and the Short Form Health Survey (SF). The City of Hope Quality of Life Family Care Giver Tool (COH-QOL-FCG) focusses specifically on the quality of life impacted by the family care giver. Table 1
There are some inherent limitations of the instruments. The scales have been developed by health care providers who may have different biases on what defines HRQOL. Therefore, there are likely metrics that are missing from the measures obtained. Accurate and consistent data collection may be influenced by fluctuations in the patients’ health status and symptom burden, making it difficult for them to complete questionnaires. If instruments are completed by a caregiver or healthcare provider, performance status may be used as a proxy for overall HRQOL. While performance status is correlated with HRQOL, it does not include all parameters. Operational barriers may be time demands on the health care provider, space limitations or technology breakdown when using online access. Other barriers may be the influences of language, culture, religion, age and educational level. Health care providers should continue to explore other strategies for capturing HRQOL data. The overall goal of health care providers is to improve the lives of patients. Better HRQOL is associated with better performance status, less frequent symptoms, lower anxiety, and improved response to treatment. Therefore, health care providers should continue to develop strategies that enhance HRQOL. HRQOL assessment provides an opportunity to assess for symptoms and potentially modifiable risk factors that negatively impact HRQOL and long term outcomes. This provides the bases for designing interventions that enhance HRQOL. Ongoing efforts include: refining surgical procedures, radiation techniques, selection of systemic therapeutics (chemotherapy, targeted therapy and immunotherapy) and combinations, with on maintaining efficacy with improved HRQOL outcomes. Focused interventions on modifiable factors may include: aggressive symptom management, structured supportive and palliative care, structured distress screening, resilience building, nutritional support, physical therapy and activity, family caregiver support. Consideration of HRQOL is an integral responsibility of all members of the healthcare team. References Borges, E.L., Franceschini, J., Costa, L.H.D., Gernandes, A.L.G., Jamnik, S. & Santoro, I.L. (2017). Family caregiver burden: the burden of caring for lung cancer patients according to stage and patient quality of life. J. Bras Pneumol. 43 (1): 18-23. Bye, A., Sjøblom, B., Wentzel-Larsen, T., Grønberg, B.H., Baracos, V.E……Jordhøy, M. (2017). Muscle mass and association to quality fo life in non-small cell lung cancer patients. Journal of Cachexia, Sarcopenia and Muscle. May 10. doi: 10.1002/jcsm.12206. [Epub ahead of print] Chabowksi, M, Polanski, J, Mazur, G, Janczak, D. & Rosinczuk, J. (2017). Sociodemographic and clinical determinants of quality of life of patients with non-small cell lung cancer. Advs Exp Medicine, Biology-Neuroscience & Respiration. Jun 2. doi: 10.1007/5584_2017_36. [Epub ahead of print] Delibegovic, A., Sinanovic, O., Galic, G., Sabic, A. & Sabic, D. (2016). The influence of palliative care on quality of life in patients with lung cancer. Mater Sociomed. 28 (6): 420-423. Eser, S., Göksel, T., Erbaycu, A.E., Baydur, H., Başank, B….Eser, E. (2016). Comparison of generic and lung cancer-specific quality of life instruments for predictive ability of survival in patients with advanced lung cancer. Springer Plus.5: 1833. Lou, V.W.Q., Chen, E.J., Jian, H., Zhou, Z., Zhu, J, Li, G. & He, Y. (2017). Respiratory symptoms, sleep, and quality of life in lung cancer. Journal of Pain and Symptom Management. 53 (2): 250-256. Morrison, E.J., Novotny, P.J., Sloan, J.A, Yang, P., Patten, C.A., Ruddy, K.J. & Clark, M.M. (2017). Emotional problems, quality of life, and symptom burden in patients with lung cancer. Clinical Lung Cancer. Mar 2. pii: S1525-7304(17)30051-7. doi: 10.1016/j.cllc.2017.02.008. [Epub ahead of print] Pinheiro, L.C., Zagar, T.M. 7 Reeve, B.B. (2017). The prognostic value of pre-diagnosis health related quality of life on survival: a prospective cohort study of older Americans with lung cancer. Qual Life Res. 26: 1703-1712. Polanski, J, Jankowska-Polanska, B., Rosinczuk, J., Chabowski, M & Szymanska-Chabowska A. (2016). Quality of life of patients with lung cancer. Onco Targets Ther. 9:1023-8.Tool Questions Context Areas The Lung Cancer Symptoms Scale (LCSS) 15 Patient and observer (healthcare professional) forms. Measures physical and functional dimensions EORTC-QLQ C30 30 Cancer symptoms, physical symptoms, 5 functional areas (physical, role, cognitive, emotional, social), overall financial impact. EORTC-QLQ-LC 13 13 Developed as supplement to the QLQ-C30 above. 13 items assess lung cancer symptoms, treatment related side effects (chemotherapy specific) and pain Functional Assessment of Cancer Therapy-Lung (FACT-L) 37 Combination of the FACT-generic 27 questions on general QOL (physical, social and family, emotional, functional well-being and relationship with physician), and 10 items on lung cancer specific symptoms. Short Form Health Survey (SF-36) 36 General health (physical function, role physical function, bodily pain, general health perception, vitality, social functioning, role emotional, mental health) with 2 summary scales measuring physical and mental component scales. City of Hope Quality of Life Family Care Giver Tool (COH-QOL-FCG) 37 Measures physical, psychological, social and spiritual
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MS 14.03 - Estimating Prognosis - How Accurate Can We Be? (ID 7708)
11:30 - 11:45 | Presenting Author(s): Kunihiko Kobayashi
- Abstract
- Presentation
Abstract:
In the lung cancer field, several studies have described the relationship between prognosis and quality of life (QoL), with most reports (Table 1), concluding a QoL evaluation of patients with advanced lung cancer before the start of chemotherapy could predict a patient’s prognosis. Such reports described common features: a poor prognosis for investigated patients whose disease was at an advanced stage and/or who were elderly, and the use of cytotoxic agents or irradiation, with poor efficacy. Molecular targeted drugs for epidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) fusion gene have recently been used in clinical practice. Such agents have led to dramatic improvements in patients with driver mutations. Indeed, we witnessed a “Lazarus response” during the NEJ001 study [1], which investigated the efficacy of an EGFR–tyrosine kinase inhibitor (TKI), gefitinib, for advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations with a poor performance status (PS): The PS improvement rate was 79% (p<0.00005); in particular, 68% of 22 patients improved from ≥PS 3 at baseline to ≥PS 1. And median survival time of the EGFR-mutated patients was 17.8 months, while that of the patients without EGFR mutations was 3.5 months. Unfortunately, following the introduction of “precision medicine” for lung cancer, few reports have described the relationship between prognosis and QoL. Herein, we describe NSCLC patients with an EGFR mutation treated with gefitinib or chemotherapy as first-line treatment in a randomized phase III study, termed NEJ002 [2]. The patients’ QoL was assessed prior to treatment and, thereafter, weekly by the Care Notebook [3]. The relationship between prognosis and QoL data, employed before and 4 weeks after the initiation of treatment, was analyzed by univariate and multivariate Cox regression. QoL data from 148 patients (72 in the gefitinib arm and 76 in the chemotherapy arm) were analyzed. Multivariate Cox regression showed that only a fatigue score on the Care Notebook assessed 4 weeks after the start of gefitinib could predict a patient’s prognosis. Other QoL scores, including those before starting not only gefitinib but also chemotherapy, did not affect survival. Estimating Prognosis - How Accurate Can We Be as the QoL Researcher? We hypothesize answers fall into two patterns: In the case of employing agents with a poor efficacy, such as cytotoxic agents, the QoL score before treatment should be evaluated as done previously. However, when treating with a very effective agent, the QoL score under treatment should be employed because any improvement in prognosis and QoL is strongly dependent on the efficacy of the agent. The next theme is “Estimating Prognosis of the Patient - How Accurate Can We Be as the Attending Physician? Unfortunately, we do not have rigid evidence for employing QoL assessments. Measuring QoL can have clinical benefits as well as research benefits. These include fostering patient–provider communication, helping clinicians and patients to identify problems and set priorities, and to assess therapy, palliative care, and rehabilitation. However, in my experience of validating the Japanese version of the EORTC QLQ-C30 [4], the answering rate for PS 0–2 patients was over 99% (225/228), but the corresponding rates for PS 3 and PS 4 patients were 81% (38/47) and 13% (9/69), respectively. Furthermore, multiple regression analyses showed that Symptom scale (coefficient: 0.188, p=0.001) and Emotional functioning (coefficient: 0.156, p=0.004) significantly related to Global QoL functioning in patients with PS 0-2; however, Symptom scale alone (coefficient: 0.220, p=0.042) significantly correlated to it in those with PS 3-4. Thus, when the patient concentrates on his/her symptoms and/or fails to respond a QoL questionnaire due to poor PS, a known adverse prognostic factor in advanced cancers, the attending doctor could recognize the patient’s short survival. Two studies have succeeded in showing the prolongation of patients’ survival under palliative care. Jennifer et al. [5] randomly assigned patients with newly diagnosed metastatic NSCLC to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. The FACT-L scale, including the lung cancer subscale (LCS) and Trial Outcome Index (TOI), measured at 12 weeks revealed that patients assigned to early palliative care had a better QoL than did patients assigned to standard care (p = 0.03). In addition, median survival was longer among patients receiving early palliative care (11.6 months vs. 8.9 months, p = 0.02). Basch et al. highlightened the importance of monitoring symptoms at ASCO 2017 [6]. Patients receiving routine outpatient chemotherapy for metastatic solid tumors, including lung cancer, were randomly assigned to self-report 12 common symptoms via tablet computers (“PRO intervention”), or to usual care. Median overall survival in the PRO intervention arm was 5 months longer than the control arm (31.2 vs. 26.0 months, HR, 0.832, p = 0.03). These two studies indicate that symptomatic QoL monitoring is critical for clinical practice and for predicting prognosis. Table 1 Studies on relationship between baseline QoL score and survival in advanced NSCLC patients
[1] Inoue A, et al. First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy. J Clin Oncol. 2009;27(9):1394-400. [2] Maemondo M, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010;362(25):2380-8. [3] Kobayashi K, et al. Validation of the care notebook for measuring physical, mental and life well-being of patients with cancer. Qual Life Res. 2005;14(4):1035-43. [4] Kobayashi, K, et al. A cross-validation of the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC QLQ-C30) for Japanese with lung cancer Eur J Cancer 1998;34:810-815. [5] Temel JS, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med. 2010;363(8):733-42. [6] Basch EM, et al. Overall survival results of a randomized trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. (Abstract LBA2) presented in ASCO2017.Reference Therapy type Number of patients Questionnaire Prognostic, baseline scale/item Herndon et al. Cancer 1999, 85:333-340. Cisplatin/vinblastine 206 EORTC QLQ-C30 Pain Langendijk et al. Radiother Oncol 2000,55:19-25. External irradiation (>/=60 Gy) 198 EORTC QLQ-C30 Global QOL Moinpour et al. Qual Life Res 2002,11:115-26. Cisplatin+vinorelbine or Carboplatin+paclitaxel. 222 FACT-L Total FACT-L score Eton et al. J Clin Oncol 2003, 21:1536-1543. Cisplatin+etoposide or Cisplatin+paclitaxel 573 FACT-L + TOI Physical well-being and TOI Maione et al. J Clin Oncol 2005, 23:6865-6872. Vinorelbine+gemcitabine, Vinorelbine alone, or Gemcitabine alone 566 EORTC QOL-C30 Global QOL Sundstrøm S, et al, J Thorac Oncol. 2006;1(8):816-24. Palliative radiotherapy 301 EORTC QOL-C30 Appetite loss Efficace et al. Ann Oncol 2006, 17:1698-1704. Paclitaxel+cisplatin Gemcitabine+cisplatin Paclitaxel+gemcitabine 391 EORTC QLQ-C30 + QLQ-LC13 Pain, and dysphagia
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MS 14.04 - Whole Person Care (ID 7709)
11:45 - 12:00 | Presenting Author(s): Caitlin Broderick
- Abstract
- Presentation
Abstract not provided
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MS 14.05 - Quality of Life in Women with Lung Cancer and Effect of Inner Strength in Mood and QOL (ID 7710)
12:00 - 12:15 | Presenting Author(s): Eunjung Ryu
- Abstract
- Presentation
Abstract:
The incidence rate of lung cancer has declined in males and increased in females in Korea (Jung et al., 2017). In the United States, lung cancer incidence rates began declining in the mid-1980s in men and in the mid-2000s in women because of reductions in smoking prevalence that began decades earlier. Contemporary differences in lung cancer incidence patterns between men and women reflect historical differences in tobacco use (Siegel, Miller, & Jemal, 2016). Women took up smoking in large numbers decades later than men, first initiated smoking at older ages, and were slower to quit, including recent upturns in smoking prevalence in some birth cohorts (Giovino, 2002; Jemal, Ma, Rosenberg, Siegel, & Anderson, 2012). In the United States, the 3 most commonly diagnosed cancers are breast, lung and bronchus, and colorectum, representing one-half of all cases for women (Siegel et al., 2016). The purpose of this study is to analyze the correlation among mood state, distress, symptom experience, inner strength, and quality of life(QoL) in female patients with lung cancer. Also, this study includes descriptive research regarding the influence factors on QoL in them. A total of 206 research subjects who diagnosed with primary lung cancer at a cancer hospital in Gyeonggi, Korea were examined from 1 July 2016 to 31 October 2016. Several instruments were used for research methods: K-POMS-B for mood state, NCCN Distress Thermometer for distress, NCC for understanding aspect of distress, MDASI-LC for symptom experience, ISQ for inner strength, and FACT-G for QoL. Data of this study was analyzed by using SPSS Ver. 23.0 for Windows. The general and diseased characteristics of patients were analyzed through descriptive statistics, frequency, percentage, average, and standard deviation. Independent t-test and One-way ANOVA were used to examine differences according to their characteristics. Bonferroni correction, Pearson correlation coefficient, and hierarchical multiple regression for impact factors of QoL were also used. For reliability, Cronbach’s α was calculated. The results of this study are as fellows; 1. The mean score of the mood disorder was 20.74, symptom experience was 2.88, symptom degree was 2.76, disturbance of daily life was 3.01. The mean score of the inner strength was 97.98. Among sub-categories, the mean score of the searching for meaning on disease was 18.53, fellowship was 27.0, self-determination was 25.2, activity and rest was 27.1. The total mean score of QoL was 66.69, physical stability was 19.13, social stability was 18.04, emotional stability was 16.19, function status was 13.32. The highest result was in physical stability, whereas function status gained the lowest result. The mean score of distress was 4.19, sleep disorder was 3.2, insomnia affecting daily life was 2.45, anxiety symptom was 2.79, anxiety symptom affecting daily life was 2.25, depression was 1.92, depression affecting daily life was 1.68. In categories asking the needs of medical care, it was measured that insomnia was 38.5%, anxiety was 41,7%, depression was 19.9%. 2. The factors affecting in QoL were occupation, expectation of treatment outcome, activity ability, inner strength, symptom experience (the severity of symptom, the severity of disturbance of daily life), and mood state. 3. Higher scores in symptom experience, distress, and mood disorder categories have lower quality of life than those with higher scores of inner strength. 4. As a result of hierarchical analysis, these suggested that occupation status, expectation of treatment outcome (life extension), activity ability, inner strength, and symptom experience (the severity of symptom, the severity of disturbance of daily life) can be beneficial variables of QoL. The model was explained 70.7% of the total variance of quality of life. Cancer as a chronic illness places new demands on patients and families to manage their own care, and it challenges old paradigms that oncology's work is done after treatment. Therefore, to improve the quality of life in women survivors with lung cancer, we need to apply nursing interventions strengthening inner strength, activity ability, performance status, and symptom control.
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JCSE 01 - Joint IASLC/CSCO/CAALC Session: Immunotherapy for Management of Lung Cancer: Ongoing Research from East and West (ID 630)
- Event: WCLC 2017
- Type: Joint Session IASLC/CSCO/CAALC
- Track: Immunology and Immunotherapy
- Presentations: 2
- Moderators:C. Bai, Fred R. Hirsch, Tony SK Mok, Yi-Long Wu
- Coordinates: 10/15/2017, 07:30 - 11:30, F203 (Annex Hall)
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JCSE 01.07 - Ongoing Trials in China on Checkpoint Inhibitors and Other Immunotherapies (ID 8226)
09:00 - 09:20 | Presenting Author(s): Qing Zhou
- Abstract
- Presentation
Abstract:
Immunotherapy gets the breakthrough after almost 100 years of silence. PD1/PD-L1 inhibitors as the representative has been extensively studied in various human malignant tumors and get promising long term response with relatively fewer adverse event. The first PD1 inhibitor indication was approved for melanoma in Japan on July 2014. By the end of December 2016, the US Food and Drug Administration had approved several PD-1 pathway blockade treatments including nivolumab, pembrolizumab and atezolizumab using in first line and second line of NSCLC. But In China, no PD-1 or PD-L1 inhibitors have received marketing approval from the Chinese Food and Drug Administration (CFDA) until July 2017. One sides, IO arena faces intense in-class competition from both MNC (Multi-National Corporation) and domestic pharmaceutical company in China. Now there are 20 IO antibodies from 7 MNCs and 10 pharmaceutical companies in China. But all the antibodies only confined to PD1/PD-L1 and CTLA4, no other hot IO drugs such as IDO or Lag3 et al. In the field of innovation, China is several years behind research in other areas of the world. The other sides various clinical trials are actively investigating MNC and domestic drugs in China. Between January 1, 2013 and April 6, 2017, Clinical Trials.-gov registered 270 international clinical trials using PD-1/PD-L1 therapies for NSCLC (e.g.nivolumab,pembrolizumab,atezolizumab,and durvalumab). These 270 trials included 61 studies that involved East Asian sites and 14studies that involved Chinese sites (12 multinational trials and 2 trials that only evaluated Chinese patients). These trials cover from second line and first line to adjuvant therapy in NSCLC. Most of the ongoing MNC NSCLC clinical trials joined in global study design that may accelerate the patient access to PD1/PD-L1. But Chinese population has relatively high rates of hepatitis B virus infection and much higher proportion of EGFR mutation. The delightful changing recently is some studies emerging to consider the characteristics of the Chinese or Asian populations. Domestic company clinical trials focus on GI (Gastrointestinal) and only 1 NSCLC study in China. Chinese clinical trials using IO remain in their early stages, and further efforts are needed to improve the design of future clinical trials. Meanwhile, the other hot IO drug phase I study need speed up in China.
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JCSE 01.26 - Circulating Cell-Free DNA of Cerebrospinal Fluid May Function as Liquid Biopsy for Leptomeningeal Metastases of ALK Rearrangement NSCLC (ID 10922)
11:30 - 11:30 | Author(s): Qing Zhou
- Abstract
Background:
Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) patients with oncogenic drivers. Resistance mechanisms of LM with ALK rearrangement remained unclear due to limited access to leptomeningeal lesions.
Method:
Primary tumor, cerebrospinal fluid (CSF) and plasma in patients with suspected LM of NSCLC were tested by Next-Generation Sequencing.
Result:
In patents with ALK rearrangement, driver genes were detected in 66.7%, 50.0% and 28.6% patients of CSF cfDNA, CSF precipitates and plasma, respectively; and all of them had much higher allele fractions in CSF cfDNA than the other two media. The diagnosis criteria of LM were positive in brain MRI or CSF cytology, and driver genes were identified in CSF cfDNA of all patients with positive CSF cytology while in those CSF cytology negative all genes were negative. Resistance mutations including gatekeeper genes ALK G1202R and ALK G1269A were identified in CSF cfDNA but they were absent in their plasma. Moreover, tailor therapy based on CSF cfDNA obtained surprising outcomes, and genetic profiles of CSF cfDNA showed dynamic changes, suggesting the potential role of CSF for follow-up studies. Figure 1
Conclusion:
CSF cfDNA could reveal the driver and resistant genes of LM, and it may function as the media of liquid biopsy for LM in NSCLC with ALK rearrangement.
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MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:M.I. Abdul Wahid, Martin Reck
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 313 + 314
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MA 11.03 - Gefitinib as First-Line Treatment of Plasma CtDNA EGFR Mutation-Positive NSCLC Detected by DdPCR: BENEFIT Study (CTONG1405) (ID 9278)
11:10 - 11:15 | Author(s): Qing Zhou
- Abstract
- Presentation
Background:
EGFR mutations in plasma circulating free tumor-derived DNA (ctDNA) as a predictor of EGFR TKI efficacy in patients with NSCLC requires validation in prospective studies. The large, prospective Phase II, single-arm, multicenter BENEFIT study (CTONG1405; NCT02282267) validated the efficacy of first-line gefitinib in EGFR mutation-positive NSCLC detected in plasma ctDNA using droplet digital PCR (ddPCR).
Method:
Patients with stage IV lung adenocarcinoma and plasma ctDNA EGFR-sensitizing mutations (exon 19 del or exon 21 L858R; by ddPCR) received first-line gefitinib (250 mg once-daily) until progressive disease (PD). Blood samples were collected every 8 weeks for dynamic EGFR analysis until PD. Primary endpoint was ORR. Secondary endpoints included PFS, DCR (Week 8), and analysis of baseline ctDNA samples by next-generation sequencing (NGS).
Result:
From December 2014-January 2016, 426 patients from 15 Chinese centers were screened: 391 had matched tissue and blood samples; 188 had ctDNA EGFR mutation-positive NSCLC and received gefitinib; and 183 had ≥1 post-baseline tumor assessment and plasma samples every 8 weeks until PD. At data cutoff (January 31, 2017), 152 patients had progressed. ORR was 72.1% (95% CI 65.0%,78.5%); DCR (Week 8) was 92.3% (95% CI 87.5%,95.8%); and median PFS was 9.5 months (95% CI 9.07,11.04). PFS was significantly shorter in the subgroup with baseline ctDNA de novo T790M mutations (5.0%, n=9) versus the EGFR-sensitizing mutations subgroup (5.6 vs 9.6 months, HR=2.60; 95% CI 1.32,5.12, p=0.004). In patients with Week 8 on-treatment plasma samples (n=167), the subgroup who showed EGFR mutation clearance in ctDNA by ddPCR (88%, 147/167) had longer PFS compared with those who did not (11.0 vs 2.1 months, HR=7.28; 95% CI 4.35,12.18, p<0.0001). The median time to emergence of acquired T790M mutation in plasma was 7.6 months. The T790M-positive rate increased from Week 24 (15.7%) to Week 48 (32.6%), with a corresponding increase in PD rate (24.7% at Week 24, 56.9% at Week 48). Among 180 patients with baseline NGS data, 21 (11.7%) harbored aberrations in additional oncogenic drivers (MET, ERBB2, KRAS, BRAF, RET, or ROS1) and tumor suppressors (TP53, RB1, and PTEN). This subgroup had worse PFS versus those with EGFR-sensitizing mutations alone (3.9 vs 13.0 months, HR=2.83; 95% CI 1.65,4.87, p=0.00016).
Conclusion:
The BENEFIT study prospectively demonstrated that ctDNA-based EGFR mutation detection can be used to select patients for treatment with first-line gefitinib. Dynamic alterations in EGFR mutations could be used to predict efficacy and disease progression, ahead of radiological results.
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OA 10 - Liquid Biopsy for Genomic Alterations (ID 678)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Adrian G. Sacher, Pasi A Jänne
- Coordinates: 10/18/2017, 11:00 - 12:30, F201 + F202 (Annex Hall)
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OA 10.02 - Unique Genetic Profiles from Circulating Cell-Free DNA of Cerebrospinal Fluid in Leptomeningeal Metastases of EGFR Mutant NSCLC (ID 8258)
11:10 - 11:20 | Author(s): Qing Zhou
- Abstract
- Presentation
Background:
Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) with EGFR mutations. Resistance mechanisms of LM remained unclear due to limited access to leptomeningeal lesions.
Method:
Primary tumor, cerebrospinal fluid (CSF) and plasma in patients with suspected LM of NSCLC were tested by Next-Generation Sequencing with 168 genes panel. Thirty patients diagnosed as LM and harboring EGFR mutation were enrolled in this cohort, and CSF cfDNA and plasma of two patients and CSF precipitates of another two patients were not available
Result:
Driver genes were detected in 100% (28/28) , 85.7% (24/28) and 75% (21/28) patients of CSF cfDNA, CSF precipitates and plasma, respectively; and 92.9% (26/28) patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA when compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were privately detected in CSF cfDNA, and CNVs in patients after TKI failure were more complicated when compared to those TKI naïve before LM. MET copy number gain identified in 44.0% (11/25) patients was the most frequent one, other CNVs included ERBB2, KRAS, ALK, MYC and FGFR1. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 67.9% (19/28) CSF cfDNA, which was much higher than that in plasma (2/28, 7.1%; p<0.001), and there was a trend towards higher rate of concomitant resistance mutations in patients with TP53 LOH than those without one (70.6% vs. 25%; p=0.036 ). EGFR T790M was identified in 28% (7/25) patients with progression to TKIs in CSF cfDNA.
Conclusion:
CSF cfDNA could reveal the unique genetic profiles of LM, and it should be the most representative medium of liquid biopsy for LM in NSCLC harboring EGFR mutations.
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P1.01 - Advanced NSCLC (ID 757)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.01-009 - Clinically Primary and Secondary Resistance to ALK Inhibitors in ALK-Positive Advanced Non-Small-Cell Lung Cancer (ID 8739)
09:30 - 09:30 | Author(s): Qing Zhou
- Abstract
Background:
Crizotinib is a standard of care in anaplastic lymphoma kinase(ALK)-positive advanced non-small-cell lung cancers (NSCLC).Undoubtedly,the resistance to crizotinib is a current bottleneck.Hence,it is necessary to explore the resistance mechanisms to ALK inhibitors.
Method:
From October 2010 to May 2017,225 ALK-positive NSCLC patients treated with crizotinib were reviewed at the Guangdong General Hospital in China.The status of ALK rearrangement was assessed by Lysis ALK Break Apart fluorescence in situ hybridization,reverse transcription polymerase chain reaction,or Ventana ALK immunohistochemistry.Next generation sequencing(NGS) was used to test the tissue or plasma from patients with resistance to crizotinib.Primary resistance to crizotinib occurred when Progression-free survival was less than 3 months for the patients treated with crizotinib.
Result:
Among enrolled patients,72.4%(163/225) gained secondary resistance,and 8.9%(20/225) had primary resistance.Molecular mechanisms of clinically primary resistance were shown in Figure a.The variants of ALK fusion were different between primary and secondary resistance patients.There were more variants of ALK fusion appeared in the group with primary resistance except E6-A20 and E13-A20.Among secondary resistant patients，non-EML4 partners fusion,such as DMD-ALK fusion,YWHAQ&TAF1B-ALK fusion,GALNT14-ALK fusion and SLC19A3-CCL20-ALK fusion were found,which responsed to crizotinib treatment.Acquired ALK L1196M/G1269A mutations were found in both primary and secondary resistant patients,and while ALK I1171T mutation was only found in secondary resistantpatients.Wnt signaling pathway was activated significantly after the treatment of crizotinib according to Kyoto Encyclopedia of Genes and Genomes(KEGG) and GeneOntology(GO) analyses.Moreover, AMER1 aberrance was inclined to appear in the primary resistance patients, which was significant different between the two groups in KEGG and GO analyses.Figure 1
Conclusion:
ALK mutations could exist in both primary and secondary resistance to crizotinib in ALK-rearranged NSCLC. Response to crizotinib was also observed in ALK-rearranged NSCLC patients with non-EML4 partners. NGS may facilitate precision treatment for both primary and secondary resistant patients though they have a few differences in molecular mechanisms of resistance.
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P1.01-010 - Circulating Cell-Free DNA of Cerebrospinal Fluid May Function as Liquid Biopsy for Leptomeningeal Metastases of ALK Rearrangement NSCLC (ID 8754)
09:30 - 09:30 | Author(s): Qing Zhou
- Abstract
Background:
Leptomeningeal metastases (LM) are more frequent in non-small cell lung cancer (NSCLC) patients with oncogenic drivers. Resistance mechanisms of LM with ALK rearrangement remained unclear due to limited access to leptomeningeal lesions.
Method:
Primary tumor, cerebrospinal fluid (CSF) and plasma in patients with suspected LM of NSCLC were tested by Next-Generation Sequencing.
Result:
In patents with ALK rearrangement, driver genes were detected in 66.7%, 50.0% and 28.6% patients of CSF cfDNA, CSF precipitates and plasma, respectively; and all of them had much higher allele fractions in CSF cfDNA than the other two media. The diagnosis criteria of LM were positive in brain MRI or CSF cytology, and driver genes were identified in CSF cfDNA of all patients with positive CSF cytology while in those CSF cytology negative all genes were negative. Resistance mutations including gatekeeper genes ALK G1202R and ALK G1269A were identified in CSF cfDNA but they were absent in their plasma. Moreover, tailor therapy based on CSF cfDNA obtained surprising outcomes, and genetic profiles of CSF cfDNA showed dynamic changes, suggesting the potential role of CSF for follow-up studies. Figure 1
Conclusion:
CSF cfDNA could reveal the driver and resistant genes of LM, and it may function as the media of liquid biopsy for LM in NSCLC with ALK rearrangement.
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P1.01-018 - Acquired Resistance to Crizotinib in Advanced NSCLC with De Novo MET Overexpression (ID 10014)
09:30 - 09:30 | Author(s): Qing Zhou
- Abstract
Background:
MET exon14 skipping mutation has been regarded the driver mutation for MET activation, but with relatively low frequency of occurrence. MET overexpression can be a promising biomarker to predict the response to crizotinib. However, little is known about acquired resistance to treatments in tumors with de novo MET overexpression.
Method:
This prospective observational study included 33 NSCLC patients with MET IHC overexpression received crizotinib treatment From January 2013 to June 2017, 23 eligible patients evaluable for response . MET expression level were detected by immunohistochemistry (IHC) with antibody SP44, and ≥50% tumor cells with moderate to high intensity staining were defined as positive. Gene copy numbers were detected by FISH (Met probes from KREATECHTM.), and referring to Cappuzzo scoring system or MET/CEP7 ratio, ≥5 copies were positive or MET/CEP7 ratio ≥1.8 (low ≥1.8-≤2.2, Intermediate >2.2-<5 and High ≥5) was defined as MET amplification;. The status of EGFR, ALK, KRAS and ROS1 were also tested at baseline. Biopsy specimens obtained both at baseline and at the time of progression using targeted next-generation sequencing to assess for mechanisms of resistance.
Result:
Response were evaluable for 23 NSCLC patients with MET overexpression (4 female, 19 male). Fifteen of them achieved partial response (PR, 65.2%), 2 were stable disease (SD) and 6 were progressive disease (PD). All responders had high MET expression , and 12(52.2%) with FISH positive. The PFS and OS in the ITT population were 3.2 and 13.2 month respectively. Median PFS was 7.4m(95% CI,4.5-10.4) for MET IHC (100%+++) patients vs. MET IHC (50%++~100%+++) 1.9m (95% CI 0.9-2.9,P=0.053), For FISH positive patients, mPFS was 8.2 m(95% CI,5.2-11.1) m v.s. FISH negative 1.3m(95% CI,0.2-1.7,p=0.002). Two acquired resistance mechanisms were found after resistance, a 64 male patient with MET IHC 100%×3,FISH (+),crizotinib first line and the best response PR, rebiopsy after resistance showed the MET D1228N mutation by NGS, and the second patient was 50 years old male with MET IHC 100%×3,FISH (+),crizotinib first line and the best response was PR, EGFR amplification were found upon progression when rebiopsy after resistance. The patient acheived PR with subsequent treatment of cetuximab plus Taxel.
Conclusion:
Multiple mechanisms of acquired resistance to crizotinib were found in de novo MET overexpressed patients. A secondary mutation in the MET gene and EGFR amplification may be the two main mechanisms. MET overexpression could be as a biomarker for de novo MET positive NSCLC. FISH seems better in predicting efficacy for MET inhibitor.
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-032 - Observation of Durative Infusion Endostar Combined with Chemotherapy Within Vascular Normalization Period in Advanced NSCLC (ID 9242)
09:30 - 09:30 | Author(s): Qing Zhou
- Abstract
Background:
To investigate the safety and efficacy of recombinant human endostatin (endostar) administrated by durative infusion combined with chemotherapy within the vascular normalization period in treating advanced non‐small cell lung cancer (NSCLC).
Method:
From February 2012 to December 2013, 34 cases of IIIB‐IV NSCLC patients were treated with endostar (15mg/m2) durative infusion combined with chemotherapy within vascular normalization time. Endostar was durative infusion every 24 hour for 7 days, and in the fourth day of the normalization time patients were received combined chemotherapy based on platinum, 21 days per cycle. All patients received 2‐6 cycles; efficacy was evaluated every two cycles, and side effects were recorded every cycle.
Result:
Every patient was received at least 2 cycles, one patient achieved CR, 14 patients were PR and 8 patients were SD. Eleven patients were PD. The overall response rate (ORR) of 34 patients was 44.1%, and non‐squamous NSCLC was 38.9%, squamous NSCLC was 50.0%. First‐line treatment of patient showed higher ORR, 53.9%. Major toxicities related to endostar were sinus tachycardia in one case, and one case hypertension. No serious side effects such as bleeding were observed.
Conclusion:
Endostar (15mg/m2) durative infusion combined with normalization period chemotherapy for NSCLC was an efficacy and safe regimen. A larger prospective randomized controlled clinical study is worth to carry out in future.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-063 - Concomitant EGFR Mutation and ALK Rearrangement in Non-Small-Cell Lung Cancer (ID 10058)
09:30 - 09:30 | Author(s): Qing Zhou
- Abstract
Background:
The concomitance of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement defines a new molecular subtype of non-small-cell lung cancer (NSCLC). We investigated the factors associated with the efficacy of targeted therapy and resistance mechanisms in EGFR/ALK co-altered NSCLCs.
Method:
EGFR mutation was identified with direct sequencing or Scorpion amplification refractory mutation system (ARMS). Relatively low EGFR-mutant abundance is considered as sequencing (-)/ARMS (+), while high abundance as sequencing (+). ALK-positive is assessed with any of the 3 methods: fluorescence in situ hybridization (FISH), rapid amplification of cDNA ends -coupled polymerase chain reaction and sequencing or Ventana immunohistochemistry (IHC). Next-generation sequencing was employed to analyze genetic profiles in patients with specimens before and after targeted therapy.
Result:
From December 2011 to December 2016, sixteen patients were identified with concomitant EGFR/ALK co-alterations, accounting for 0.6% (16/2632) in NSCLC patients, 1.8% (16/867) in EGFR-mutant and 8.6% (16/185) in ALK-positive patients. Five ALK-IHC (-)/FISH (+)/EGFR (+) patients with EGFR-TKIs experienced 3 PR, 1 SD and 1 waitiing for response evaluation, with median PFS of 11 months. Three with relatively low EGFR-mutant abundance achieved PR with crizotinib, while three with relatively high EGFR-mutant abundance obtained 2 PR and 1 SD with EGFR-TKIs. Spatial and inter-tumoral heterogeneity was observed in one EGFR/ALK co-altered patient. (Figure 1B) Two patients with T790M, one with Met pathway activation and two with loss of EGFR mutation were found after resistance to EGFR-TKIs. One with KRAS mutation was found pre- and post-EGFR-TKIs. ALK_F1174C mutation was observed in one patient after progression to crizotinib and ALK_G1202R mutation after resistance to ceritinib.Figure 1
Conclusion:
ALK protein expression, EGFR mutation abundance and tumor heterogeneity were associated with efficacy of targeted treatment for EGFR/ALK co-altered patients. Most mechanisms resistance to EGFR-TKIs and crizotinib were similar to those in typical EGFR mutation and ALK rearrangement respectively.
