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V. Westeel
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MINI 04 - Clinical Care of Lung Cancer (ID 102)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 15
- Moderators:L. Gaspar, V. Westeel
- Coordinates: 9/07/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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MINI04.01 - Years of Life Lost and Lifetime Earnings Lost in Metastatic Lung Cancer: Potential Societal Benefits of Improved Survival by Age and Histology (ID 774)
16:45 - 16:50 | Author(s): B. Korytowsky, K. Kulig, M. Halperin, M.D. Danese
- Abstract
- Presentation
Background:
“Years of life lost” (YLL) and “lifetime earnings lost” (LEL) are used to describe the population burden of cancer. Lung cancer (LC) is one of the most common cancers in the US. While it affects older patients, the younger subgroups of LC are large. Approximately 57% of LC cases are metastatic at diagnosis, with a 5-year survival rate of approximately 5%. Nivolumab, a recently-approved fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, demonstrated a mortality risk reduction of 41% compared to docetaxel in patients previously treated with platinum-based therapy for metastatic squamous, non-small cell LC (NSCLC) (hazard ratio [HR]: 0.59; 95% CI: 0.44, 0.79). This analysis quantifies YLL and LEL prior to the introduction of LC immunotherapy in order to benchmark potential population-level effects of improved long-term survival.
Methods:
A simulation model was developed using real-world US patients with LC diagnosed 1/1/2000–12/31/2011 in the Surveillance, Epidemiology, and End Results Program, with follow-up through 12/31/2012. Age-, sex-, and race-specific life expectancy were estimated using flexible parametric survival models. Comparable life expectancy was projected for the general US population using US vital statistics data. Life expectancy was combined with US Bureau of Labor Statistics income data to derive lifetime earnings in 2014 US dollars. Earnings reflect 18 possible income sources, including salary, investments, social security, and other retirement income. Mean YLL and LEL were estimated as the differences between patients with LC and the general US population. Results were stratified by age (<65; ≥65) and histology subtype (small cell, non-squamous NSCLC; squamous NSCLC).
Results:
An estimated 1,223,031 patients in the US were diagnosed with metastatic LC from 2000–2011. Estimated patient counts, expected survival, and expected lifetime earnings within each age and histology subtype are provided (Table). For patients aged <65, YLL per patient due to LC varied from 22.8–23.7 years by histology subtype, while for patients aged ≥65, YLL varied from 9.9–11.3 years. LEL per patient ranged from $862,000–$887,000 for patients aged <65, and from $274,000–$313,000 for patients aged ≥65. Figure 1
Conclusion:
YLL and LEL values across LC histologies are substantial in both older and, perhaps even more noticeably, younger populations. Improvements in survival reported with promising new LC therapies have the potential to substantially decrease the societal burden caused by YLL and LEL.
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MINI04.02 - Value of Innovation in Systemic Therapy for US Patients with Advanced/Metastatic NSCLC (ID 783)
16:50 - 16:55 | Author(s): J. Nilsson, N. Justo, B. Korytowsky, N. Chehab, A. Stanford, A. McGuire
- Abstract
- Presentation
Background:
Lung cancer remains the leading cause of cancer death in the US. Over the past 40 years, treatment approaches have evolved and new systemic anti-cancer therapies have been introduced to the standard of care. With few exceptions, the impact of these agents for patients with advanced/metastatic non-small cell lung cancer (NSCLC) has been arguably minimal, with overall survival (OS) still less than 1 year for most patients. This study analyzed the association of available new systemic therapies with median OS, 1-year OS, and 1-year conditional survival (CS: adjusted probability of survival, specifically probability of living to year 2, given survival at 1-year) in patients with advanced/metastatic NSCLC.
Methods:
This study enrolled adult patients with advanced/metastatic NSCLC diagnosed between 1973 and 2011 in the US Surveillance, Epidemiology, and End Results (SEER-Research) Program of the American National Cancer Institute. We report the data from 1973 to 2008 for this analysis. Thirty-eight cohorts of patients were defined by year of diagnosis. Survivor functions were estimated using Kaplan-Meier analysis, with death as the failure event. Median OS, 1-year OS, and 1-year CS were derived for each year and analyzed graphically. The innovation index was defined as the sum of all systemic anti-cancer treatments available in the US market within a given year between 1973 and 2011 (Lichtenberg; Econ Hum Biol 2003;1:259–266).
Results:
Of 347,709 patients, a clear correlation was observed between the innovation index and survival measures (median OS, 1-year OS, and 1-year CS), with correlation coefficients of 77%, 92%, and 97%, respectively. Median OS, 1-year OS, 1-year CS, and the innovation index are plotted against time (Figure), enabling a comparison of survival measures between 1973 and 2008. Any change in the innovation index is reflected as a change in the survival curves, most notably in the 1-year CS, displaying a 1- or 2-year delay. From 1973 to 2008, median life expectancy of patients increased from 4 to 6 months; 1-year OS and 1-year CS improved by 71% and 31%, respectively. Figure 1
Conclusion:
The availability of systemic anti-cancer treatments for advanced/metastatic NSCLC has resulted in an incremental survival benefit, albeit modest, for US patients diagnosed between 1973 and 2008. Despite progress in treatment, outcomes for this patient population are very poor. Further research is needed to explore these treatment-survival relationships, including the resulting benefit for all patients with advanced/metastatic NSCLC and select patient subgroups.
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MINI04.03 - Real-World Patterns of Access to Cancer Specialist Care Among Patients With Lung Cancer in the United States: A Claims Database Analysis (ID 1592)
16:55 - 17:00 | Author(s): A.K. Ganti, H. Borghaei, F.R. Hirsch, M. Wynes, A. Ravelo, R. Ionescu-Ittu, I. Pivneva, P. Lin, S.S. Ramalingam
- Abstract
- Presentation
Background:
Timely access to specialist care is an important first step in the care of patients with lung cancer (LC). This study describes real-world patterns of access to cancer specialist (CS) care in all LC patients and those with metastatic LC (mLC).
Methods:
Adult patients diagnosed with primary LC or mLC were identified in a US commercial claims database (01/01/2008 - 03/31/2014). Patients’ specialist visits were assessed before and after their first biopsy (index date). All patients had ≥3 months follow-up after index date. CS was defined as oncologists or hematologists. Patients were divided in four mutually exclusive groups based on the specialists seen in the 6 weeks pre-index period: patients seen by CS (± other specialists), pulmonologists (no CS, ± other specialists), internists or family physicians (no CS/pulmonologist, ± other specialists), and other. CS visits in the 8-weeks post-index were assessed for each group. Reversed Kaplan-Meier plots were used to describe time from index date to first CS visit.
Results:
The analysis included 75,163 LC and 25,191 mLC patients, with a median age of 67 [interquartile range (IQR): 59-76)] and 63 (IQR: 57-73) years and a median follow-up of 11 and 9 months, respectively. In the 8-week post-index period, over half of LC patients (54%) and nearly two-thirds of mLC patients (66%) had their first CS visit (Figure 1), while 38% of LC patients and 28% of mLC patients never saw a CS within 1-year of biopsy (Figure 1). In both samples, patients in the CS and pulmonologist pre-index groups were more likely to see a CS in follow-up (Figure 2; p<0.001 for all groups). Figure 1 Figure 1 Figure 2 Figure 2
Conclusion:
A substantial proportion of patients diagnosed with LC and mLC did not see any CS after biopsy, which may negatively affect access to optimal and timely treatment.
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MINI04.04 - Economic Burden of Lung Cancer Patients Treated in Clinical Trials: Experience from a Comprehensive Cancer Center in Germany (ID 2841)
17:00 - 17:05 | Author(s): F. Kron, A. Kostenko, J.P. Glossmann, M. Hallek, I. Dohle, A. Hoss, M. Scheffler, T. Zander, J. Wolf
- Abstract
Background:
Lung cancer leads to the highest costs among cancers in developed countries. Hospital inpatient care is the main cost driver. Comprehensive cancer centers (CCC) are designed to adopt innovative treatment methods within clinical trials. This analysis focuses on the economic burden of clinical trials for advanced lung cancer patients in a CCC in Germany.
Methods:
111 consecutive patients with advanced lung cancer treated in clinical trials (phase I - phase II) were analyzed. We integrated medical and economic data from a business perspective during patients’ in- and outpatient treatment. Different reimbursement systems and cost calculation models are linked with an internal budget system for lung cancer patients.
Results:
79 patients (71.2%) had at least one in-house stay with a total of 204 inpatient cases. 67 different diagnosis-related groups (DRGs) were coded for these cases. Grouping of the DRGs into 4 categories (i. Neoplasm, ii. Infection, iii. Radiotherapy and iv. Rest) reveals a statistically significant difference in the case mix index (p<0.001) and length of hospitalization (p<0.001). Cost type calculation demonstrated labor (46%) and infrastructure (31%) being the predominant cost factors. The average revenues of 1301 outpatient contacts (219 cases per quarter) of all patients are €144. Subgroup analysis of 44 cases with €117 revenues in average identified imaging procedures accounting for 74% of the costs.
Conclusion:
The medical development involves economic risks for the hospital that recommend a fully integrative cost- and sales controlling between the in- and outpatient treatment setting including standards care and clinical trials, which should be discussed with all stakeholder in the healthcare system.
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MINI04.05 - Discussant for MINI04.01, MINI04.02, MINI04.03, MINI04.04 (ID 3308)
17:05 - 17:15 | Author(s): N. Leighl
- Abstract
- Presentation
Abstract not provided
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MINI04.06 - During-Treatment PET Metabolic Tumor Volume (MTV) Instead of FDG Activity Is Predictive of Survival in Patients with Non-Small Cell Lung Cancer (ID 3174)
17:15 - 17:20 | Author(s): F.(. Kong, J.L. Waller, L. Li, K. Frey, M. Piert, D. Owen, M. Stenmark, C. Huang, M. Matuszak, R.K. Ten Haken, T.S. Lawrence
- Abstract
- Presentation
Background:
We have previously reported that tumor reduces in activity and volume during the course of radiotherapy (RT), and such changes were correlated with post-treatment “tumor response”, known as a significant factor for overall survival in patients with non-small cell lung cancer (NSCLC). This study aimed to determine whether the metabolic activity or metabolic tumor volume (MTV) obtained from the during-treatment FDG-PET is predictive of overall survival in NSCLC.
Methods:
Patients with stage I-III NSCLC enrolled in prospective studies with during-treatment FDG-PET were eligible for this study. All patients were treated with a definitive course of RT + chemotherapy. FDG-PET/CT scans were acquired within 2 weeks before RT (pre-RT) and at about two thirds of the total dose delivered (during-RT). PET-MTVs were delineated by a tumor/aorta ratio of 1.5 autosegmentation combined with manual editing based on CT anatomy, as previously described (Mahasittiwat et al, 2013). FDG-activity was measured as maximum standard update value (SUVmax) and the average activity (SUVmean) of the defined MTV. Total lesion glycolysis (TLG) was computed as the product of MTV and SUVmean. CT gross tumor volume (CT-GTV) were also delineated in a consistent manner. Data are presented as mean (95% confident interval). P<0.05 is considered to be statistically significant.
Results:
A total of 129 patients with a minimum follow-up of 24 months (for surviving patients) were included in this study. The majority of subjects were male (73%), white (96%), current or former smokers (87%) with an average age of 67 years (range 45-92). Seventy-nine percent were treated with chemotherapy in combination with RT (dose range 45-90 Gy). Of the pre-RT PET parameters, neither SUVmax nor SUVmean was significant, while CT-GTV (P=0.03), PET-MTV (p=0.008), and PET-TLG (p=0.005) were all significant for overall survival. After 2/3 treatments were delivered, the mean SUVmax, SUVmean, CT-GTV, PET-MTV, and PET-TLG all decreased significantly (P<0.001) and remarkably (more than 30% reduction), with the PET-MTV showing the greatest extent of reduction. During-RT SUVmax or SUVmean were not significantly associated with overall survival, either as continuous variables or as binominal variables (split from median). While during-RT CT-GTV was a significant factor for survival (P=0.04), yet during-RT PET-MTV and PET-TLG as continuous variables were not. However, patients with during-RT PET-MTV values greater than the median had significantly shorter median survival (21 months, 95%CI: 12.1-32.0) than those of below the median (38 months, 95%CI: 29.0-89.9, p=0.01). The absolute reductions in SUVmax or SUVmean or CT-GTV were not, but changes of PET-MTV and PET-TLG during-RT were significantly associated with overall survival. Smaller reductions from Pre-RT to during-RT were associated with an increased risk of death for PET-MTV (HR=1.003, 95%CI: 1.001–1.006, P=0.01) and PET-TLG (HR=1.001, 95%CI: 1.000–1.001, P=0.02), respectively.
Conclusion:
MTV instead of SUV during the course of RT are significantly associated with overall survival in patients with NSCLC. Larger MTV during-RT may lead to worse survival. RTOG1106/ACRIN6697 is ongoing to adapt radiation therapy plan to give higher dose to residual PET-MTV during-RT to improve tumor control and overall survival.
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MINI04.07 - Changes in Skeletal Muscle Index and Body Mass Are Prognostic Factors in First Line Stage IV Non-Small Cell Lung Cancer (NCSCL) Patients (ID 3091)
17:20 - 17:25 | Author(s): M.J. Fidler, S. Kerns, F.M. Esmail, M.D. Martin, S.M. Shors, N. Patel, R.R. Patel, S. Sayidine, S. Basu, R. Pithadia, M. Batus, J.A. Borgia, P. Bonomi, P.N. Shah
- Abstract
- Presentation
Background:
Cancer cachexia is a complex metabolic syndrome affecting 60-80% of patients with non-small cell lung cancer (NSCLC). The characteristic involuntary weight loss observed in cachexia is associated with poor outcomes in advanced NSCLC; however, reduced muscle mass may be a more reliable prognostic indicator. In this study, we examine the impact of changes in weight and skeletal muscle index (SMI) in the first 12-weeks of therapy on clinical outcome parameters for front line stage IV NSCLC patients.
Methods:
Cancer cachexia is a complex metabolic syndrome affecting 60-80% of patients with non-small cell lung cancer (NSCLC). The characteristic involuntary weight loss observed in cachexia is associated with poor outcomes in advanced NSCLC; however, reduced muscle mass may be a more reliable prognostic indicator. In this study, we examine the impact of changes in weight and skeletal muscle index (SMI) in the first 12-weeks of therapy on clinical outcome parameters for front line stage IV NSCLC patients.
Results:
119 patients had serial weights available and were included for analysis: 49% were male, median age of males was 71, and females were 63 years; 82% had smoking history. Histology was predominantly adenocarcinoma and squamous (62% and 22%). Median PFS was 159 days, and medial OS was 314 days. Median weights for males at baseline, 6 weeks, and 12 weeks were 77.3, 76.9, and 77.3 kilograms respectively. Median weights for females at baseline, 6 weeks, and 12 weeks were 67.1, 66.7, 65.8 kilograms respectively. Baseline weights were less for women than men (p<0.0007) but the change in weight with time was not significantly different at measured time points. Weight loss of greater than 10.39 pounds in the first six weeks of treatment was strongly associated with inferior outcomes (PFS 2.35 vs. 6.44 months, p=2.02 x 10[-7]; OS 3.96 vs. 15.48 months, p=8.71 x 10[-9]). Persistent weight loss at 12 weeks was also associated with worse outcomes (PFS p=1.72x10[-7 ], OS p= 0.00286). Within this cohort, 41 patients had baseline SMI measured from their CT scans, 27 patients had additional CT-derived SMI available at 6- and 12- weeks. Patients with SMI decrease at 12 weeks of at least 2.6 units (n=9, 33%) had an inferior median PFS compared with those not meeting this threshold (2.79 months vs. 9.75 months p<0.05). In a multivariate analysis, this loss, when adjusted by gender, remained significantly associated with PFS (HR=2.37, p < 0.05).
Conclusion:
This study shows the prognostic value of weight loss for progression on first line chemotherapy as early as six weeks following therapy initiation. This analysis confirms the significant association between weight loss on serial measurements and inferior survival in stage IV NSCLC pts. Additionally, this is the first report of decreasing CT-derived SMI correlating with inferior progression free survival on front line platinum doublet therapy for NSCLC.
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MINI04.08 - Malignant Pleural Effusions Are Predictive of Peritoneal Carcinomatosis in Patients with Advanced EGFR Positive Non-Small Cell Lung Cancer (ID 3191)
17:25 - 17:30 | Author(s): T. Patil, D.L. Aisner, S.A. Noonan, P.A. Bunn, Jr, E.M. Berge, W.T. Purcell, R. Camidge, L.L. Carr, R.C. Doebele
- Abstract
- Presentation
Background:
Lung cancer is the most frequent cause of cancer death and metastatic disease at the time of initial diagnosis is common. Peritoneal carcinomatosis (PC) from lung cancer is a rare clinical event with a reported incidence of 1.2% (Satoh et al. 2001). However, there are limited data on what factors predict peritoneal progression in lung cancer. Over the last decade, molecular analysis of NSCLC has provided more detailed classification of patterns of metastatic spread. It has also been shown that oncogene-addicted subsets of NSCLC have different patterns of metastatic spread (Doebele et al. 2012). We investigated whether certain baseline patterns of metastatic spread in patients with advanced EGFR mutation positive (EGFR+) NSCLC can predict subsequent PC.
Methods:
We identified 156 patients with EGFR+ (Exon 19 or L858R) mutations from 2009 - 2014, of which 139 had metastatic NSCLC. 11 patients developed PC. This was defined as the presence of biopsy-proven adenocarcinoma from peritoneal fluid or radiographic patterns consistent with omental metastases. We identified areas of metastatic disease in predefined sites (brain, liver, lung, adrenal, soft tissue and pleura) at the time of diagnosis or metastatic recurrence. We noted if patients developed T790M, a resistance mutation to targeted therapy, in EGFR+ patients. A Fisher-Exact test was used to determine statistical significance between metastatic site and subsequent PC.
Results:Table 1 - Sites of metastasis and presence of T790M mutation in patients with PC and without PC
The presence of a pleural effusion was universal in all 11 EGFR+ patients who subsequently developed PC and this finding was statistically significant (P = 0.0001). 9 out of 11 patients with PC were identified to have a T790M mutation, a finding that was statistically significant (P = 0.0001). Except one patient, all EGFR+ patients developed PC following targeted tyrosine kinase therapy.Metastatic site / mutation PC No PC P value Lung 9.1% 38.6% P = 0.06 Liver 18.2% 15.8% P = 0.689 Bone 36.4% 46.8% P = 0.549 Brain 0% 23.7% P = 0.3570 Adrenal 0% 6.4% P = 0.123 Soft tissue 9.1% 2.2% P = 0.265 Pleural effusion 100% 26.6% P = 0.0001 T790M mutation 81.1% 34.5% P = 0.0001
Conclusion:
The presence of a malignant effusion is highly predictive of developing PC in patients with EGFR+ NSCLC. Although the underlying mechanism of PC is not entirely clear, it may be related to serosal communication with subsequent micrometastatic seeding of the peritoneal cavity. The T790M mutation, the most common acquired resistance mechanism to EGFR kinase inhibitors, was significantly more prevalent in the group that developed PC, although it remains unclear whether this mutation has any causative effect on spread to the peritoneum.
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MINI04.09 - The Impact of Next-Generation Sequencing on Clinical Decisions in Lung Cancer (ID 2978)
17:30 - 17:35 | Author(s): A. Belilovski Rozenblum, M. Ilouze, E. Dudnik, D. Flex, L. Soussan-Gutman, A. Dvir, N. Peled
- Abstract
- Presentation
Background:
In the last decade, important advances have been made in understanding genetic and molecular mechanisms of Non-Small Cell Lung Cancer (NSCLC) tumor development. This has led to the creation of innovative, targeted drugs that significantly prolong survival in advanced patients. Recent data shows that 63% of NSCLC tumors harbor at least one activating driver mutation, including treatable mutations such as RET, HER2 and ROS1 gene mutations, besides the regularly screened ALK and EGFR genes that account for 23% of the patients. Clinical cancer genomic profiling tests based on Next Generation Sequencing (NGS) technologies are capable to reveal clinically actionable genetic alterations in up to three times the number of actionable alterations detected by current diagnostic tests. However, there is no data regarding the true impact of these tests on clinical decisions in lung cancer. In this study, our objective is to evaluate the impact of NGS-based genetic profiling tests on treatment strategy in NSCLC patients in the real life setting, considering the additional diagnostic tests performed. Based on clinical experience from Israel, NGS-based tests actively change treatment plans, but the effect size is unknown and merits further investigation.
Methods:
In this retrospective study, data is collected from patient files at the Thoracic Cancer Unit of Davidoff Cancer Center, Rabin Medical Center, Israel. The current study population is 78 NSCLC patients who performed NGS-based genetic profiling tests.
Results:
Out of 78 patients, 58 patient files have already been reviewed and 6 were excluded. Treatment decision change rate after NGS testing was 33% (17 out of 52 patients were treated with a targeted therapy - 24% of the current study population). Interestingly, 9 patients became EGFR and ALK positive by NGS after the previous standard local molecular testing was negative. Based on the RECIST criteria of response evaluation, 41% of the patients had a partial response after switching to targeted therapy, 23% had a complete response, 18% experienced progressive disease and 18% were not evaluated yet. Survival rates will be calculated further in the study based on data availability.
Conclusion:
The use of NGS for tumor classification and treatment planning holds a great potential for improving patient life quality and survival. In this study, we aimed to determine its clinical impact in the real life setting in the treatment of lung cancer. Our partial results show that in addition to performing standard molecular testing for NSCLC, almost a quarter of the patients can be identified having an actionable driver mutation and switched to targeted therapy. Most of these patients showed a positive response to treatment. Although this topic needs to be further assessed in large randomized controlled trials, these positive results emphasize the importance of upfront multiplex testing or suggest such technology as a reflex test in places where the primary kits are done first in sake of cost-benefit.
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MINI04.10 - Discussant for MINI04.06, MINI04.07, MINI04.08, MINI04.09 (ID 3309)
17:35 - 17:45 | Author(s): K. Reckamp
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
The highest percentage of metastasis to the brain exists among non-small cell lung cancer (NSCLC) patients. The exact incidence of brain metastasis (BM) in NSCLC is unknown, but current literature suggests that incidence for this cohort is increasing as cancer patients live longer. To date, only a single Canadian study reporting BM occurrence in lung cancer patients is available. A key limitation to this study is the method of incidence reporting, as number of cases, rather than number of cases as a percentage among lung cancer population. Reliable estimates of BM in NSCLC patients are necessary to further improve patient care and resource allocation.
Methods:
The Alberta Cancer Registry dataset was used to identify all NSCLC patients living in southern Alberta who are consulted at the Tom Baker Cancer Centre, Calgary, Alberta, Canada between 1999 and 2010. These patients were registered and their charts were reviewed for an institutional lung cancer database (Glans-Look Database). NSCLC patients were categorized into two groups: (i) having BM at diagnosis or (ii) developing BM between diagnosis and death. Patient characteristics were compared to the database NSCLC cohort and all metastatic cases. The number of BM cases was reported for each group per year. Incidence was calculated as a percentage of the NSCLC and metastatic disease cases, where applicable. Linear trend testing was performed.
Results:
A total of 5297 NSCLC patients were consulted. The percentage of BM at diagnosis in the cohort was 11% in 1999 and 8% in 2010 (linear trend test p-value=0.010). These numbers were 26% in 1999 and 15% in 2010 (p=0.010) in the metastatic cohort. The percentage of BM developed by death in the NSCLC cohort was 20% in 1999 and 13% in 2010 (p=0.010). These numbers were 44% in 1999 and 26% in 2010 (p=0.009) in the metastatic cohort (Figure 1). Out of 2501 non-metastatic NSCLC patients, 46% developed BM by death in 1999 compared to 62% in 2010 (p=0.14).
Conclusion:
Although the absolute number of NSCLC patients with BM at diagnosis has increased between 1999 and 2010, the incidence, reported as a percentage of the all NSCLC cases, is decreasing. Similar trends were not observed for non-metastatic patients. As a future step, a pre-specified multivariable analyses will be conducted to examine effects of age, gender, histology, smoking, and treatment on rates of BM in NSCLC.Figure 1
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MINI04.12 - Systematic Review of Brain Metastases in Non-Small Cell Lung Cancer (NSCLC) in the United States, European Union, and Japan (ID 1591)
17:50 - 17:55 | Author(s): D.C. Fenske, G.L. Price, A.W. Nyhuis, L.M. Hess
- Abstract
- Presentation
Background:
Prevalence of brain metastases (BRM) is increasing due to better detection methods and patients living longer with their disease, presenting an unmet need. Importantly, BRM are more common in NSCLC than most other cancers. Published literature offers incomplete data on prevalence, treatment, costs, and outcomes associated with BRM in NSCLC. This study was designed to better understand the epidemiology, treatment patterns, costs, and overall survival (OS) of NSCLC patients with BRM in the US, EU, and Japan.
Methods:
A systematic review was conducted by searching PubMed, Ovid, and Embase from January 2003 to December 2013 according to PRISMA guidelines. Keywords, MeSH, and Emtree terminology were used to define the search strategy. Eligible studies were observational, published in English, and peer-reviewed research of patients with NSCLC and BRM. Demographic, clinical, and outcomes data were extracted into Excel. Descriptive statistics were generated with SAS version 9.2. Demographics were summarized and treatment patterns and median OS were assessed by country.
Results:
The literature search identified 8,257 articles and 243 studies were eligible. There were 46,422 NSCLC cases included. Patient characteristics are summarized in Table 1. Treatment patterns for BRM from NSCLC were reported across the US, EU, and Japan. Median OS of NSCLC patients from the time of BRM diagnosis ranged from 5.0 to 13.1 months by country (Figure 1). The rate, by country, of radiation therapy among NSCLC patients with BRM ranged from 32.9% to 90.1%, systemic therapy ranged from 5.8% to 39.7%, and surgery was used in 2.2% to 31.6% of studies. Figure 1 Figure 2
Conclusion:
Reported median OS and treatment patterns were highly variable. Exposure to risk factors associated with BRM may help explain some of the geographic variability in survival. The lack of published cost data underscores the need to quantify the economic burden of BRM on patients and society.
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MINI04.13 - Survival Analysis of 51 Leptomeningeal Metastatic Non Small Cell Lung Cancer Patients Treated with Whole Brain Radiotherapy (ID 2625)
17:55 - 18:00 | Author(s): E. Topkan, B. Akkus Yildirim, O.C. Guler, Y. Ozdemir
- Abstract
Background:
Although leptomeningeal carcinomatosis (LC)in Non small cell lung cancer is less frequently seen in radiotherapy (RT) clinics, it is an important cause of mortality and morbidity. As the median survival is limited to 2-4 months, the role of RT in treatment is controversial. In this Study, we try to analyze the survival rates and associated factors of 51 leptomeningeal brain metastatic NSCLC patients treated with whole brain radiotherapy (WBRT).
Methods:
Between January 2007 to August 2014, during follow up with the diagnosis of NSCLC, 51 patientswho develop LC and treated with WBRT in our clinic had included this study. Patients were treated with 20-30 Gy (3-4 Gy/fr) WBRT. Kaplan-Meier method was used for survival analysis. Bonnefoni correction was performed for survival analysis of groups more than two before statistical analysis.
Results:
Median age of patients were 64 (37-83) and 34(67.7%) of them are male. Patient number with ECOG performance status of 0-1, 2 and 3 were23 (%45.1), 15 (%29.4) and 13 (%25.5) respectively.%58.8 of patients had squamous cell cancer and %41.2 of them were adenocancer. The dose of WBRT in 31 patients was 20 Gy (4 Gy/fr; BED~10~=28 Gy) and 30 Gy (3Gy/fr; BED~10~=39 Gy) in the other 20 patients. At the time of performing these analyses all the patients had died.Median survival was 3.9 ay (%95 CI: 3.3- 4.5). On univaryan analyses, age (≤50 vs. >50; p=0.46), gender (p=0.37),histological subtype (squamous cell vs. adenocancer; p= 0.74) and BED~10~value (39 vs. 28 Gy; p=0.26) did not show any statistically difference but ECOG performance status (0-1 vs. 2-3; p<0.001) was associated with overall survival. Median survival duration times for ECOG 0-1 and 2-3 groups were 5.7 and 3.7 respectively.
Conclusion:
Median survival of 3.9 months of our study is similar with literature but it is also querying the necessity of RT in this group of patients especially with poor performance status. However, the survival benefit of 5.8 months in ECOG performance 0-1 group may lead us to think that WBRT is useful. Although there has been no survival benefit between two RT dose schemes, 20 Gy (4 Gy/fr) may be the treatment of choice because of the shorter duration.
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MINI04.14 - Comparative Survival in Patients with Brain Metastases from Non-Small Cell Lung Cancer Treated before and after Implementation of Radiosurgery (ID 2862)
18:00 - 18:05 | Author(s): A. Swaminath, J. Broomfield, G.R. Pond, S. Caetano, P.M. Ellis, J. Greenspoon
- Abstract
- Presentation
Background:
Survival after a diagnosis of brain metastases (BM) in non-small cell lung cancer (NSCLC) is generally considered poor. We previously reported median survival of approximately 4 months in a cohort of patients treated with whole brain radiotherapy (WBRT), the standard of care in many centres. Since that time, we implemented a program of stereotactic radiosurgery (SRS), based on randomized trials and large prospective series, supporting WBRT + SRS or SRS alone in selected patients. The current study examined survival and prognostic factors in a consecutive cohort of NSCLC BM patients after the introduction of an SRS program.
Methods:
A retrospective review of 167 NSCLC patients referred with BM to a tertiary cancer centre from 2010-2012 (NEW cohort) was undertaken. These data were compared to a prior cohort of 91 patients treated between 2005 and 2007 (OLD cohort). Summary statistics were used to describe the patient characteristics as well as outcomes. The Kaplan-Meier method was used to calculate time-to-event outcomes for overall survival (OS), from the time of BM diagnosis. Cox proportional hazards regression was used to investigate factors prognostic for outcomes. An optimal model was constructed using forward stepwise selection, and tests were two-sided with a p-value <0.05 deemed statistically significant.
Results:
Overall survival from diagnosis of BM (median 4.3 months NEW vs 3.9 months OLD p=0.74) was not significantly different between cohorts. A univariate analysis of the NEW cohort demonstrated significant differences in OS between treatment groups (SRS, WBRT + SRS, WBRT or no treatment), in terms of female gender (p=0.034), lack of neurological symptoms (p=0.001), number of BM (p<0.001), GPA (p=0.001), and ECOG status at BM (p=0.009). Treatment regimen with SRS or WBRT + SRS was significant as a prognostic factor for OS as well (p<0.001). Results were similar if one excluded the no treatment group. As some factors were not collected in the OLD cohort, a separate model was constructed including only data available from both cohorts. After adjusting for factors included in the optimal model, cohort was not statistically significant for OS (hazard ratio=1.03, 95% CI 0.90-1.59; p =0.88). There was a trend towards improved OS in the NEW vs OLD cohorts in patients <50 years of age (median 11.8 vs 7.5 months, p=0.39) and 50-59 years of age (median 7.8 vs 3.7 months, p=0.052); this trend reversed to favour the OLD vs NEW cohort in patients >70 (4.3 vs 2.8 months, p=0.01). This was coincident with increased uptake of chemotherapy (p<0.001) and better ECOG status (p=0.007) in younger age groups in the NEW versus OLD cohort.
Conclusion:
There has been no improvement in survival of NSCLC patients with BM, following the implementation of SRS. Selected patients (younger age, female gender, good fitness, fewer brain metastases) appear to demonstrate improved OS with SRS. However, this may also reflect a better natural history of the disease, or a greater tendency to offer them systemic therapy, in addition to receipt of SRS.
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MINI04.15 - Discussant for MINI04.11, MINI04.12, MINI04.13, MINI04.14 (ID 3310)
18:05 - 18:15 | Author(s): S.S. Yom
- Abstract
- Presentation
Abstract not provided
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Author of
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.08 - Systemic Treatment in Advanced Thymic Epithelial Tumors. Insights From a Prospective Cohort of 888 Patients Enrolled in RYTHMIC (ID 1166)
17:25 - 17:30 | Author(s): V. Westeel
- Abstract
Background:
RYTHMIC (Réseau tumeurs THYMiques et Cancer) is the French nationwide network for thymic malignancies. Starting 2012, all patients diagnosed with thymic tumor had to be enrolled, as recommended by the French National Cancer Institute, part of good clinical practice.
Methods:
RYTHMIC prospective database is hosted by the French Thoracic Cancer Intergroup (IFCT), and collects clinical, imaging, treatment, and follow-up data of patients discussed at the reference national multidisciplinary tumor board (MTB). Data cutoff was April 1[st], 2015 for this analysis.
Results:
1089 questions were raised at the MTB about the management of 888 patients with thymic epithelial tumor. Among assessable cases, Masaoka-Koga stage III-IV tumors accounted for 42% of cases; histology was thymoma in 82% of cases, and thymic carcinoma in 18% of cases. First-line treatment of locally advanced disease, and management (diagnosis and treatment) of recurrent disease led to raise 227 (21%), and 234 (21%) questions at the MTB, respectively, 312 (68%) of which were about the modalities of systemic treatment. Figure 2 shows the proposed regimens for primary (A) and exclusive (B) chemotherapy in treatment-naïve patients, and chemotherapy (C) and targeted agents (D) for recurrent tumors. Combination of cisplatin, adriamycin, and cyclophosphamide and carboplatine, paclitaxel were the most frequently proposed regimens as first- and second-line treatment, respectively. Figure 1 Figure 2
Conclusion:
RYTHMIC is an exhaustive registry of thymic malignancies, which provides unique insights in the management of advanced and recurrent tumors with systemic agents. Meanwhile, limited data have been made available in the literature so far, as clinical trials were conducted in small numbers of patients, and existing databases enrolled a majority of surgically resected, early-stage tumors. Through the use of targeted agents, RYTHMIC allows the rapid implementation of new results in clinical practice, while ensuring patients an equal access to therapeutic innovation. Supported by Institut National du Cancer
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ORAL 27 - Care (ID 123)
- Event: WCLC 2015
- Type: Oral Session
- Track: Advocacy
- Presentations: 1
- Moderators:M.N. Mountain, J. Freeman-Daily
- Coordinates: 9/08/2015, 10:45 - 12:15, 708+710+712
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ORAL27.06 - Disparities in Lung Cancer Incidence and Management Care in France: A Nationwide Cohort Study (the TERRITOIRE Study) (ID 1177)
11:39 - 11:50 | Author(s): V. Westeel
- Abstract
- Presentation
Background:
Reducing health inequalities in oncology is a major public health priority in France, particularly in terms of social and geographic exclusion and equity of access to health care services. However, no specific registry currently exists for patients with lung cancer allowing description and comparison of local situations. Our aim was to use available National medico-administrative databases to constitute a nationwide population-based cohort study to analyze disparities among French areas (the TERRITOIRE study).
Methods:
We included all patients who had a first diagnosis of lung cancer between January 1rst and December 31th 2011 in the National hospitals databases (PMSI, Programme de Médicalisation des Systèmes d'Information). Patients’ data were linked to create a retrospective cohort study with a two-year follow-up period. The 22 administrative regions were considered in this analysis. In addition of demographic characteristics, metastatic status, comorbidities and treatment procedures, we assigned each patient to socioeconomic deprivation and urbanization scores based on their postcode of residence.
Results:
We identified 41,715 patients newly diagnosed for lung cancer. Mean age at diagnosis was 66.4(±11.9) years and most of patients were men (71.8%). Patients from socioeconomic deprived areas represented 27.5% of the whole lung cancer population, ranging from 9.6% to 55.2% according to the region. Incidences of lung cancer were 35.1 per 100,000 in women and 95.3 per 100,000 in men. Age-standardized incidences showed important disparities between French regions ranging from 27.5 to 55.0 and from 82.4 to 118.2 per 100,000 in women and men, respectively. Higher incidences were found in the northern and eastern regions for men and in the southern and eastern regions for women. Although patients living in rural areas were the larger group (34.5%), Age-standardized incidence significantly increased with urbanization: from 61.8 per 100.000 in rural areas to 73.9 per 100.000 in urban areas. A majority of patients was diagnosed at a metastatic stage (52.7%) and regional disparities were important ranging from 45.0% to 58.1%. This rate also appeared higher in patients diagnosed in public hospitals compared to private ones (56.1% vs 42.9%, p<0.0001) and in local hospitals compared to university ones (60.2% vs 49.6%, p<0.0001). Adjusted comparisons showed significantly higher incidences of stage IV patients at the time of diagnosis in five regions for men and two regions for women. A majority of patients (N=23,842; 57.2%) died in the hospital during the 2-year follow-up, including 15,642 patients (71.2%) having metastasis at the time diagnosis.
Conclusion:
We have demonstrated that a comprehensive population-based cohort using medico-administrative data is a suitable approach to illustrate disparities in lung cancer incidence, management care and outcomes in France. Data from this study should help local clinical teams and health stakeholders to better understand inequality issues in their areas.
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ORAL 34 - Quality/Survival/Prognosis in Localized Lung Cancer (ID 153)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:B.C. Cho, R.L. Keith
- Coordinates: 9/09/2015, 16:45 - 18:15, 201+203
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ORAL34.01 - Compliance with Follow-Up Programs After Surgery for Non-Small Cell Lung Cancer in the Phase III IFCT-0302 Trial (ID 2148)
16:45 - 16:56 | Author(s): V. Westeel
- Abstract
- Presentation
Background:
In patients operated on for non-small cell lung cancer, several guidelines recommend a follow-up based on regular clinic visits and chest CT-scans. However, evidence to support these recommendations is poor, in the absence of randomized data. The IFCT-0302 trial is a randomized multicenter trial which compared 2 follow-up programs after complete resection for a clinical stage I, II, IIIA and T4 (pulmonary nodules in the same lobe) N0-2 NSCLC (TNM 6[th] edition). We present the results of compliance with the follow-up programs for the first 2 years after randomization.
Methods:
In the CXR arm, follow-up consisted of clinic visit and chest X-rays. In the CCT arm, patients underwent clinic visit, chest X-rays, thoraco-abdominal CT scan plus fiberoptic bronchoscopy (only mandatory for squamous cell and large cell carcinomas). In both arms, procedures were repeated every 6 months after randomization during the first 2 years, and yearly until 5 years, in the absence of recurrence or second primary cancer. Supplementary procedures were allowed in case of symptoms. Primary endpoint was overall survival.
Results:
Between January 2005 and November 2012, 1775 patients were randomized (CXR: 888; CCT: 887). Patient characteristics were well balanced between the two arms : males 76.3%, median age 62 years (range: 33-87), adenocarcinomas 56.7%, stage I-II 82.1%, lobectomy or bilobectomy 86,8%, pre- and/or post-operative radiotherapy 8.7%, and pre- and/or post-operative chemotherapy 45%. Surveillance was performed in 97% of patients at 6 months, in 94% at 12 months, in 90% at 18 months and in 84% at 24 months, and did not differ between the 2 arms. Intervals between randomization and visits were respected with no difference between arms (mean +/-SD in months from randomization: 5.93 +/- 0.84; 11.95 +/- 0.98; 18.05 +/- 0.99; 24.18 +/-1.30, respectively). In the 757 patients of the CXR arm, who had a follow-up visit at 6 months and no recurrence, 754 (99.6%) had a clinic visit and 730 (96.4%) a chest X-ray. In the 706 patients of the CCT arm who had a follow-up visit at 6 months and no recurrence, 702 (99.4%) had a clinic visit, 478 (67.7%) a chest X-ray, 678 (96%) a chest CT-scan, and 342 (48.4%) a bronchoscopy. Comparable compliance results were observed at 12, 18 and 24 months. In the CXR arm, supplementary thoracic CT-scans were done in 119 patients (15.7 %) at 6 months, in 96 (14.4 %) at 12 months, in 78 (13.2%) at 18 months and in 58 (11.4%) at 24 months. Other supplementary procedures were more frequent in the CCT arm than in the CXR arm, consisting mostly of brain imaging (at 6 months, in 93 (13.2%) and 39 (5.2%) patients, respectively, p<.001).
Conclusion:
Compliance with the follow-up programs was excellent in terms of timing. Chest X-ray was often omitted in the CCT arm. In the CXR arm, supplementary CT-scans that did not lead to a diagnosis of recurrence or second primary cancer were performed in 10 to 15% of patients. In the CCT arm, the most frequently performed supplementary procedure was brain imaging.
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