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J. Crawford

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    ED02 - Palliative Care in Lung Cancer: A Global Challenge (ID 264)

    • Event: WCLC 2016
    • Type: Education Session
    • Track: Palliative Care/Ethics
    • Presentations: 5
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      ED02.01 - Palliative Care and its Importance for Patients with Lung Cancer (ID 6426)

      11:00 - 12:30  |  Author(s): H. Watzke

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      ED02.02 - Palliative Care in South America (ID 6428)

      11:00 - 12:30  |  Author(s): L.A. Mas Lopez

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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      ED02.03 - Palliative Care in India (ID 6429)

      11:00 - 12:30  |  Author(s): G.S. Bhattacharyya, K. Govindbabu, H. Malhotra, P.M. Parikh

      • Abstract
      • Presentation
      • Slides

      Abstract:
      A cancer diagnosis is one of the most feared events rarely diagnosed before the late 20th century now competes with the Cardio-vascular disease, stroke, respiratory failure. The last half century has produced substantial advances in the treatment and early detection of few types of cancer and atleast modest gain in many other. Yet the reality is that half of the patients diagnosed with cancer will die within the first couple of years. With people living longer, the continued use of tobacco products, infectious disease that transmit cancer causing virus, and epidemic of obesity and arm-chair lifestyle, the cancer burden is projected to increase substantially over the decade. The delivery of high quality cancer care across the care continuum from diagnosis and treatment to maintaining the health of survivors and providing end-of-life care consistent with patients’ needs, values, and preferences. The provision of patient-centered care planning, palliative care, and psychosocial care; the prevention and management of long-term and late effects of cancer treatment; and family caregiver support should span the cancer care continuum from diagnosis through end-of-life care. The full cancer care continuum also includes the domains of prevention and risk reduction and screening. Cancer care for older adults, as noted throughout this report, is especially complex. Age is one of the strongest risk factors for cancer. The majority of cancer diagnoses and cancer deaths occur in individuals 65 years and older, and the majority of cancer survivors are in this age range. There are many important considerations to understanding the prognoses of older adults with cancer and formulating their care plans, such as altered physiology, functional and cognitive impairment, multiple coexisting morbidities, increased side effects of treatment, distinct goals of care, and the increased need for of social support. Their ability to participate in clinical trials has been limited, and thus the evidence base for informing treatment decisions in this population is lacking. The current health care delivery system is poorly prepared to address these concerns comprehensively. Thus, meeting the needs of the aging population will be an integral part of improving the quality of cancer care. Lung cancer is one of the commonest cancer causing death and it presents late. It is an extremely symptomatic disease and majority of the patients succumb to this disease. It is innately human to comfort and provide care to those suffering from cancer particularly who are close to death. Yet what seems evident as an individual’s personal level has by and large no guided policy all over the world. There is no argument that palliative care should be integrated into cancer care from diagnosis to death. Palliative care provides a specialized holistic approach to providing medical care with serious illness and the focus of Palliative Care is on providing relief from symptom and improving the quality of life of patients. Palliative Care is not End-of-Life or hospice but encompasses both. There is a dichotomy in the principle of medical care in cancer which single mindedly focuses on attempts to cure every patient at every stage. Recognition of the importance of symptom control and other aspects of Palliative care from diagnosis through dying process has been growing. Patients should not have to choose between treatment with curative intent or comfort care. There is need for both in varying degrees throughout the course of cancer whether the eventual outcome is survival or death. The goal is to maintain the best possible quality of life allowing the patients to choose whatever treatment they so wish while also meeting the needs of advanced disease through adequate symptom control. This goal is most often not met. For atleast half of those patients dying from cancer - most of whom are elderly and many vulnerable - death entails a spectrum of symptoms including pain, labored breathing, distress, nausea, confusion, and other physical and psychological conditions that go untreated and vastly diminishes the quality of remaining days. The patient is not the only one who suffers; family, care givers undergo unreleaved emotion and financial burden. This cannot be ignored within the context of the patients' who are terminally ill. A major problem in Palliative care is the under recognization, under diagnosis and thus undertreatment of the patients with significant stress ranging from existentional anguish, axiety and depression. Living with and eventually dying from a chronic illness runs substantial cost for patients, family, society and cost of those dying from cancer are 20% higher than average costs. Inadequacy of Palliative and End-of-Life care springs not from a single cause of a sector of society the separation of palliative and hospice care from potentially life prolonging treatment within the health care system, which is both influenced by and affects reimbursement policy; inadequate training of health care personnel in symptom management and other palliative care skills; inadequate standards of care and lack of accountability in caring for dying patients; disparities in care, even when available, for ethnic and socioeconomic segments of the population; lack of information resources for the public dealing with palliative and end-of-life care; lack of reliable data on the quality of life and the quality of care of patients dying from cancer (as well as other chronic diseases); and low level of public sector investment in palliative and end-of-life care research and training. This is not to suggest that there is no relevant ongoing research or relevant question or training program - there are - but the efforts are not coordinated and there is no focus for these activities in the Government agencies. What has resulted is under funding, lack of training and lack of research, leadership, with no sustained program for developing and disseminating Palliative treatment. Care for those approaching death is an integral and important part of health care. Everyone dies, and those at this stage of life deserve attention that is as thorough, active, and conscientious as that granted to those for whom cure or longer life is a realistic goal. Care for those approaching death should involve and respect both patients and those close to them. Particularly for patients with a grim prognosis, clinicians need to consider patients in the context of their families and close relationships and to be sensitive to their culture, values, resources, and other characteristics. Good care at the end of life depends on strong interpersonal skills, clinical knowledge, and technical proficiency , and it is informed by scientific evidence, values, and personal and professional experience. Clinical excellence is important because the frail condition of dying patients leaves little margin to rectify errors. Changing individual behavior is difficult, but changing an organization or a culture is potentially a greater challenge—and often is a precondition for individual change. Deficiencies in care often reflect flaws in how the health care system functions, which means that correcting problems will require change at the system level. The health care community has special responsibility for educating itself and others about the identification, management, and discussion of the last phase of fatal medical problems. Although health care professionals may not have a central presence in the lives of some people who are dying, many others draw heavily on physicians, nurses, social workers, and others for care—and caring. Thus, health care professionals are inescapably responsible for educating themselves and helping to educate the broader community about good care for dying patients and their families. More and better research is needed to increase our understanding of the clinical, cultural, organizational, and other practices or perspectives that can improve care for those approaching death. The knowledge base for good end-of-life care has enormous gaps and is neglected in the design and funding of biomedical, clinical, psychosocial, and health services research. Time is now to integrate Palliative care with mainstream care in cancer.

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      ED02.04 - Palliative Care in South-East Asia (ID 6430)

      11:00 - 12:30  |  Author(s): R.B.L. Lim

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Southeast Asia comprises of 10 main countries including Malaysia, Indonesia, Thailand, Philippines, Singapore, Brunei, Cambodia, Laos, Myanmar and Vietnam. The concept of palliative care first developed around the mid-1980s in Singapore and the Philippines and later in the 1990s in Malaysia, Thailand and Indonesia. In other countries such as Brunei, Cambodia, Myanmar, Vietnam and Laos palliative care has only been developing more rapidly over the past 10 years. Levels of development of palliative care in Southeast Asia are highly variable depending very much upon factors such as availability of medical resources, funding, geography, demographics and the priorities of the country’s leadership. In 2011, the Worldwide Palliative Care Alliance(WPCA) mapped out the global development of palliative care dividing countries into 4 categories. Category 1 where there is no known development of palliative care, category 2 where development is at the level of capacity building, category 3 where there is isolated provision of palliative care services and category 4 where services are approximating integration into mainstream medicine. Among these countries, only Singapore and Malaysia have achieved category 4 status while majority are in category 3 (Indonesia, Thailand, Philippines, Myanmar, Cambodia, Brunei and Vietnam). Regardless of the level of development, challenges faced in developing palliative care in Southeast Asia are common throughout and include first and foremost barriers of drug availability and fear of using opioids amongst public as well medical practitioners. Apart from this is the challenge of public perceptions towards death and dying which have made development of this discipline difficult. Even till today there are many misconceptions regarding the role and concept of palliative care amongst healthcare professionals. For countries that are more advanced in their development, the key challenge now is how to continue development in a sustainable manner and how to improve and maintain standards of care. In Malaysia, palliative care began in the early 1990s with the development of voluntary organisations providing homecare services for patients with terminal cancer. In 1995 the concept was introduced into government hospitals and soon received nationwide support by the Ministry of Health in Malaysia. In 2005, the subspecialty of palliative medicine was established and a formalised training programme for medical specialists was developed. At present there are a total of 18 trained palliative medicine specialists in Malaysia with 2 more in training. In 2014, an advanced diploma programme for nurses, physiotherapists and occupational therapists was developed in the Ministry of Health which has now trained 38 nurses and paramedics who have now become permanent stakeholders in palliative care service provision and development. Apart from this, non-governmental organisations also serve as a backbone to community palliative care services in Malaysia and there are currently 25 services throughout the country providing homecare. It is with such initiatives that Malaysia hopes to create a sustainable and credible workforce to continue the development and growth of palliative care throughout the nation and possibly the region.

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      ED02.05 - Palliative Care in Iran (ID 6431)

      11:00 - 12:30  |  Author(s): R. Malayeri

      • Abstract
      • Presentation
      • Slides

      Abstract:
      It is well known that palliative care is a necessity in cancer patients, as early on as the time of diagnosis. In adult oncology, there is evidence to suggest early specialist palliative care improves HRQOL, mood, treatment decision-making, health-care utilization, advanced care planning, patient satisfaction, and end-of-life care (1). Early admission to community-based palliative care also reduces the use of Emergency departments by cancer patients in the 90 days before death (2). Palliative care for cancer patients is rather new in Iran and has a history of less than 7 years. Here we give an overview on the status of palliative care in Iran. We also present the demographics of our patients in the first and largest palliative care ward in Iran over the last two years. Iran has a population of around 80 million people. In Iran, cancer is known as the third cause of death. Adult morbidity rate of cancer in different regions of Iran is estimated 48-112 cases per million people among the females and 51-144 cases per million people among the males (3). Also, mortality rate related to cancer was about 53500 people in 2014 (4). The majority of cancer patients expire in the intensive care units (ICU), whereas bed occupancy of ICUs is in crises, being about 100% in Iran. For each ICU bed, 4 people are applicants (5). We currently have around 8 active palliative care units for cancer patients and one palliative care ward in Iran, all run by charities. In these palliative care units, we have oncologists, palliative care specialists, pain specialists, psychologists, spiritual care specialists, social workers and dieticians. A total number of 3677 patients, ages between 16 and 94 (Median 61), of whom 3277 (89%) with a similar age distribution had a cancer diagnosis were referred to our palliative care unit in Firoozgar Hospital, which is run by the Ala Charity, in Tehran in the last three years. 1770 female (54%) and 1457 male (46%) advanced cancer patients were referred. A number of 388 (12%) patients had breast cancer, 339 (10%) had hematologic malignancies, 312 (10%) had esophageal or gastric cancer, 311 (10%) had colorectal cancer, 105 (3%) had a cancer of the CNS, 101 (3%) had lymphoma, 93 (3%) had renal cancer, 87 patients (3%) had ovarian cancer, 81 (2%) had lung cancer, 54 patients (2%) had prostate cancer and 50 (2%) had pancreatic cancer. The other 40% of the cancer patients had either less frequent cancers or their exact cancer site was not recorded. In most countries, the gap between death and specific therapies is considered as an indicator of the quality of physician services and more length of time will be a better indicator for physician services, while cancer patients in health system of Iran receive specific treatment and chemotherapy even to moment of death. To consider countless benefits of home care and the patients’ desire to receive services at home, if we can provide the conditions that at least 20% of end stage cancer patients receive home based palliative care, 1000 deaths will occur at home yearly, and 1000 ICU beds will be released for use for other patients with better prognosis for survival (5). For this reason, the Ala charity has also started free of charge home care services in Isfahan and Tehran. Iran, like many other countries, needs many more palliative care units as well as an expansion of home based palliative care services to advanced and very advanced cancer patients. As palliative medicine is not financially lucrative, charities play a major role in setting up, maintaining and expanding these units. References: Salins N, Ramanjulu R, Patra L, Deodhar J, Muckaden MA. Integration of Early Specialist Palliative Care in Cancer Care and Patient Related Outcomes: A Critical Review of Evidence. Indian J Palliat Care. (2016) 22:252-7 McNamara BA, Rosenwax LK, Murray K, Currow DC. Early admission to community-based palliative care reduces use of emergency departments in the ninety days before death. J Palliat Med. (2013) ;16:774-9 Mousavi SM, Gouya MM, Ramazani R, et al. Cancer incidence and mortality in Iran. Annals of Oncology. (2009) ;20:556–63. World Health Organization. Cancer country profiles in Iran 2014. Geneva: WHO; 2014. [cited 29 August 2015]. Avilable from: http://www.who.int/cancer/country-profiles/en/ Heydari H. Home-based Palliative Care: A Strategy for Keeping Intensive Care Unit Beds Vacant. Int J Community Based Nurs Midwifery. (2016);4:186-7.

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    ED06 - Symptom Management in Lung Cancer (ID 269)

    • Event: WCLC 2016
    • Type: Education Session
    • Track: Palliative Care/Ethics
    • Presentations: 1
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      ED06.04 - Biology and Management of Tumor Cachexia (ID 6450)

      16:00 - 17:30  |  Author(s): J. Crawford

      • Abstract
      • Presentation
      • Slides

      Abstract:
      The International Consensus Conference definition of cancer cachexia is a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass with or without fat mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.[1] As clinicians, we define cachexia clinically based on weight loss of 5% or greater or body mass index <20 kg/m[2], with 2% weight loss. On physical exam, we recognize cachexia based on gross loss of muscle mass and weakness, often associated with physical findings such as temporal wasting. However, these patients with physical stigmata of cachexia are a small subgroup of the total population. If one assesses objective measures of muscle mass, approximately half of patients with advanced lung cancer will have muscle wasting at diagnosis and 2/3 of patients will develop it during their treatment course. This muscle wasting or sarcopenia, occurs across all weight groups, including those with normal weight, overweight and obesity.[2] These patients would not be recognized clinically to be cachetic. Yet, they have significant clinical consequences from muscle wasting. The use of standardized CT for the quantitative assessment of skeletal muscle and other body tissues has helped us better understand the importance of muscle and its impact on cancer outcomes.[3] Muscle wasting is associated with an increased risk of dose limiting chemotherapy toxicity, shorter time to disease progression and reduced overall survival. Clinically, the cancer patient with cachexia undergoes a progressive decline in muscle mass with associated anorexia, fatigue and reduced quality of life. Patient reported outcomes include weakness, declining muscle strength, reduced mobility and impact on physical performance. At a molecular level, this loss of muscle mass is associated with a number of biochemical changes in enzymes, regulatory proteins, altered metabolism, increased markers of inflammation and impaired immunity. The driving force for muscle wasting in cancer patients is the competition for nutrients between the cancer and the host often complicated by decreased protein/caloric intake. However, the mechanisms that both incite and promote the ongoing process of muscle loss are complex and include factors associated with direct muscle atrophy, including the release of cytokines such as tumor necrosis alpha and interleukin 6, as well as myostatin and activin. One strategy that might ameliorate the cachexia process include therapeutic approaches that block these cytokine mediated pathways and several agents are in development.[4] Another approach has been to try to increase muscle growth signaling through anabolic pathways such as selective androgen receptor modulators (SARM) and ghrelin minetics. A first in class SARM, enobosarm has shown promising results with improvement of muscle mass and physical function in patients with cachexia.[5] Subsequent phase III trials in patients with advanced lung cancer receiving chemotherapy have shown increase in muscle mass in the enobosarm treatment group versus placebo, but physical function testing using stair climb measurement were inconsistent.[6] Meanwhile, trials of anamorelin, a ghrelin receptor agonist have also demonstrated improvement in skeletal muscle mass. In phase III trials in patients with advanced lung cancer and cachexia, improvement in skeletal muscle mass has been seen along with positive effects on improved appetite and weight gain. Again, functional improvement as measured by hand grip strength was not observed.[7] It is not clear why there is a lack of association of these promising agents that increase muscle mass, with functional improvement. This may reflect issues regarding the patient population, the objective test being used, the duration of treatment or other factors. However, these phase III trials in advanced lung cancer represent an important step forward in our understanding of cachexia and possible therapeutic interventions. Currently, as we are moving forward with the development of new agents for cachexia, it is important for us to recognize the magnitude of the problem in our patients. Until CT imaging becomes a standard clinical technique for assessment of muscle mass, we need to rely on our standard clinical approaches of history and physical exam. Perhaps most importantly, is our documentation of the degree of weight loss in our patients as a routine measure at baseline and during treatment just as we assess other patient reported outcomes such as pain, fatigue and functional status. Incorporating weight loss along with body mass index can be a very powerful tool for predicting outcome and survival for our patients.[8] Moreover, it can help us address potential interventions that may be of benefit for them. While current pharmacologic interventions are of limited benefit, exercise and nutritional support are both important interventions for our patients, along with continuing monitoring of appetite, weight and functional performance during treatment.[9] Cancer treatment itself can be associated with an increase in muscle mass, particularly in patients whose tumors respond well to therapy. However, for those patients who progress through therapy, the toxicity of our treatment only compounds the ongoing cachexia process. Better cancer therapeutics combined with optimum supportive care remain the goal of management. 1. Fearon K, Strasser F, Anker SD, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011 May;12(5):489-95. 2. Prado CM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncology. 2008; 9(7):629-35. 3. Prado CM, Antoun S, Sawyer MB, Baracos VE. Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity. Curr Opin Clin Nutr Metab Care. 2011;14:250–254. 4 Cohen S, Nathan JA, Goldberg AL. Muscle wasting in disease: molecular mechanisms and promising therapies. Nat Rev Drug Discov. 2015 Jan;14(1):58-74. 5. Dobs AS, Boccia RV, Croot CC, et al. Effects of enobosarm on muscle wasting and physical function in patients with cancer: a double-blind, randomised controlled phase 2 trial. Lancet Oncol. 2013 Apr;14(4):335-45. 6. Crawford J, Prado C, Johnston M, Gralla R, Taylor R, Hancock M, Dalton J. Study design and rationale for the phase 3 clinical development program of enobosarm, a selective androgen receptor modulator, for the prevention and treatment of muscle wasting in cancer patients (POWER Trials). Cur Oncol Rep (2016) 18:37. 7. Temel JS, Currow DC, Fearon K, et al. Phase III trials of anamorelin in patients with advanced non-small cell lung cancer (NSCLC) and cachexia (ROMANA 1 and 2). J Clin Oncol 33, 2015 (suppl; abstr 9500) 8. Martin L, Senesse P, Gioulbasanis I, Antoun S, et al. Diagnostic criteria for the classification of cancer-associated weight loss. J Clin Oncol. 2015 Jan 1;33(1):90-9. 9. Crawford J. Clinical results in cachexia therapeutics. Current Opinion in Clinical Nutrition & Metabolic Care. 19(3):199-204, May 2016.

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    P2.03a - Poster Session with Presenters Present (ID 464)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 2
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      P2.03a-008 - Relative Dose Intensity of First-Line Chemotherapy and Overall Survival in Patients With Advanced Non–Small-Cell Lung Cancer (NSCLC) (ID 4736)

      14:30 - 15:45  |  Author(s): J. Crawford

      • Abstract

      Background:
      For patients with advanced NSCLC, chemotherapy dose reductions/delays are commonly used to manage toxicities. However, there is limited information on the relationship between relative dose intensity (RDI) and survival in metastatic NSCLC. Objective: Describe the relationship between RDI and survival in patients with NSCLC in a US community oncology practice setting.

      Methods:
      This was a retrospective study using the McKesson Specialty Health/US Oncology iKnowMed[SM] electronic health record database. Inclusion criteria: Patients with advanced (stage III/IV) NSCLC who initiated first-line, intravenous, myelosuppressive chemotherapy between January 2007 and December 2010. Endpoints: Mean RDI (a composite measure including both dose delays and dose reductions), RDI <85%, and incidences of dose delays ≥7 days and dose reductions ≥15% in any chemotherapy cycle. Dosing analysis covered a period up to 6 months after chemotherapy initiation. Univariable and multivariable analyses for survival were conducted using Cox proportional hazard regression.

      Results:
      Overall, 3866 patients with NSCLC were included; the most common chemotherapy regimens included carboplatin/taxol (n=1733), pemetrexed/carboplatin (n=789), and bevacizumab/carboplatin/taxol (n=734). 709 (18.3%) received colony-stimulating factor primary prophylaxis. The mean (SD) RDI was 83.9% (28.5%), the incidence of RDI <85% was 40.4%, and the incidence of dose delays ≥7 days and dose reductions ≥15% were 32.4% and 50.1%, respectively. Univariable analysis suggested that dose delay ≥7 days was associated with a 22.4% reduction in the risk of death (P<0.0001). Multivariable analysis suggested that RDI and dose delay were significant predictors of survival after controlling for covariates. RDI <85% and dose delay ≥7 days were associated with a 17.6% increase and a 29.0% reduction in risk of death, respectively (Table).

      Conclusion:
      Reduced RDI and chemotherapy dose delays were common in advanced NSCLC and significantly associated with survival in a multivariable analysis. Understanding the complex effect of dose intensity on outcomes will be important for managing toxicities and improving survival.

      Table. Multivariable Cox Regression Analysis for Overall Survival for Patients with Lung Cancer
      Variable HR (95%CI) P Value
      RDI <85% (reference: ≥85%) 1.176 (1.047–1.320) 0.0062
      Dose delay ≥7 days (reference: <7 days) 0.710 (0.630–0.800) <0.0001
      ECOG performance status (reference: status of 0)
      1 1.316 (1.192–1.453) <0.0001
      2 1.654 (1.350–2.027) <0.0001
      Hemoglobin <12 g/dL (reference: ≥12 g/dL) 1.098 (0.993–1.213) 0.0686
      Tumor subgroups (reference: squamous)
      Adenocarcinoma 0.783 (0.698–0.877) <0.0001
      Other 0.932 (0.725–1.199) 0.5855
      ECOG=Eastern Cooperative Oncology Group; HR=hazard ratio; RDI=relative dose intensity.


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      P2.03a-055 - Predicting Risk of Chemotherapy-Induced Severe Neutropenia in Lung Patients: A Pooled Analysis of US Cooperative Group Trials (ID 3975)

      14:30 - 15:45  |  Author(s): J. Crawford

      • Abstract

      Background:
      Neutropenia is the most serious hematologic toxicity associated with the use of chemotherapy. Severe neutropenia (SN) may result in dose delays and/or reductions, and the use of growth colony stimulating factors (CSFs) increases the cost of therapy. Lyman et al. (2011) published a risk model to predict individual risk of neutropenia in patients receiving chemotherapy for multiple types of cancer. The Lyman model (LM) has not been validated by external datasets. We investigated the LM with a large external lung cancer dataset based on clinical criteria of SN and investigated new risk prediction models for SN.

      Methods:
      Stage IIIA/IIIB/IV non-small cell lung cancer (NSCLC) and extensive small cell lung cancer (SCLC) chemotherapy phase II/III trials completed in 1990-2012 were assembled from U.S. cancer cooperative groups. SN was defined as any neutropenic complications grade ≥ 3 according to CTCAE. A risk score was calculated as a weighted sum of regression coefficients of the LM for all patients in the database. The performance of risk models was evaluated by the area under the ROC curve (AUC) with a good model defined as AUC ≥ 0.7. To develop new risk models, a random split was used to divide the database into training cohort (2/3) and testing cohort (1/3). Multivariable logistic regression models with stepwise selection and lasso selection (Tibshirani, 1996) were built in training cohort and validated in testing cohort. Candidate predictors included patient-level and treatment-level variables. The patients with complete data were used for validation and all patients, including those with imputed predictors, were used to develop new risk models.

      Results:
      Eighty seven trials with 14,829 patients were included. The LM had a good performance in SCLC patients (AUC=0.86), but it had poor performance in NSCLC patients (AUC=0.47), and an overall unsatisfactory performance in all patients (AUC=0.56). The stepwise model had superior performance than the lasso model (AUC: 0.84 vs. 0.76) in training, while the lasso model had smaller shrinkage in testing. A parsimonious model, based on histology, prior chemo, platinum-based, taxanes, gemcitabine, CSFs, age as continuous variable, relative dose intensity, and white blood cell (WBC), performed slightly worse (AUC=0.71) in testing than the stepwise model and the lasso model.

      Conclusion:
      The U.S. cooperative group data failed to validate the LM in predicting the risk for severe neutropenia in lung cancer patients receiving chemotherapy. The parsimonious model involving nine predictors showed good performance in predicting severe neutropenia. Prospective validation is warranted.

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    P3.03 - Poster Session with Presenters Present (ID 473)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
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      P3.03-036 - Prognostic Model for Mesothelioma Based on Cancer and Leukemia Group B (CALGB) Trials (Alliance) (ID 3976)

      14:30 - 15:45  |  Author(s): J. Crawford

      • Abstract

      Background:
      Prognostic models play an important role in the design and analysis of mesothelioma treatment trials. The European Organisation for Research and Treatment of Cancer (EORTC) developed a well-known tool in 1998 to predict overall survival (OS) in patients with malignant mesothelioma. In this study, we built and assessed the performance of a new mesothelioma prognostic model OS using data from multiple CALGB clinical trials data.

      Methods:
      This study included 595 mesothelioma patients from fifteen completed CALGB treatment trials accrued between June 1984 and August 2009. We split the cohort of patients into two parts - 67% of patients as training and 33% as testing. We developed a Cox model using the training set with PS, age, WBC count, and platelet count as prognostic variables. To compare the EORTC and our new models, the concordance of predicted survival times and risk scores were estimated by concordance C (c-index) (Harrell et al. 1996) and AUC score at 6-months (Patrick et al. 2000). 95% confidence intervals were calculated for the c-index. Based on the prediction model fit from training set, we partitioned testing set patients into high-risk and low-risk groups using the median for their risk score values for the new model. For the EORTC model, the cut off of 1.27 from the original paper was used to assign the high-risk and low-risk groups. A Log-rank test was used to compare the survival curves of these two groups. We also compared our results with a model using PS alone.

      Results:
      For OS, the EORTC model c-index was 0.55 (0.52, 0.58) and P = 0.0007 comparing high- and low- risk patients for testing set. The new model c-index was 0.60 (0.56, 0.64), with P < 0.000001 for testing set. Using the new model, the median OS in the high-risk and low-risk groups in the testing set were 5.16 (4.70, 6.37) and 10.41 (7.95, 14.32) months, respectively. PS alone produced c-index of 0.55 (0.53, 0.57) and P = 0.0002 for testing set. The AUC scores at 6-months for testing set generated by EORTC and PS alone models are 0.62 and 0.66. The new model generated AUC scores at 6-months of 0.70.

      Conclusion:
      Our new model performs better than the EORTC model or PS alone for survival prognostication in patients with mesothelioma.