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R. Jotte
Moderator of
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ORAL 30 - Community Practice (ID 141)
- Event: WCLC 2015
- Type: Oral Session
- Track: Community Practice
- Presentations: 8
- Moderators:P.S.S. Kho, R. Jotte
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL30.01 - Evolution in the Surgical Care of Non-Small Cell Lung Cancer (NSCLC) Patients in the Mid-South Quality of Surgical Resection (MS-QSR) Cohort (ID 2980)
16:45 - 16:56 | Author(s): X. Yu, E.T. Robbins, N. Faris, R.S. Signore, L. McHugh, R. Eke, M.P. Smeltzer, G. Relyea, C. Fehnel, N. Chakraborty, C. Houston-Harris, F. Lu, B. Wolf, C. Mutrie, L. Deese, E. Crocker, L. Wiggins, P. Levy, R.U. Osarogiagbon
- Abstract
- Presentation
Background:
Surgical resection is the most important curative modality for NSCLC. However, gaps in the quality of surgery adversely affect patients’ survival. In the Mid-South region, at the center of the US lung cancer mortality belt, we began a project in 2009 to improve the quality of surgery and pathology examination across all hospitals. We report the evolution of surgical quality in this region from 2004-2013.
Methods:
The MS-QSR database includes patient-level details from all NSCLC resections in 11 institutions in 5 Dartmouth Hospital Referral Regions in Eastern Arkansas, North Mississippi, and Western Tennessee. Data span the care delivery process from initial radiographic detection, through diagnostic and staging tests, to surgical treatment and post-operative outcomes. We performed trend analysis and comparisons among institutions.
Results:
There were 2,410 curative-intent NSCLC resections. Patient demographics, rates of non-invasive staging tests and pre-operative adjuvant therapy did not change. 92% of patients had a pre-operative CT, 80% had a PET-CT scan. The use of invasive staging tests (endobronchial ultrasound, mediastinoscopy, etc.) increased from 11.3% in 2009 to 22.3% in 2013 (p<0.001). The pneumonectomy rate decreased from 12% in 2004 to 6.2% in 2013 (p=0.05). The margin positivity rate remained stable at 5.8%. Stage distributions remained unchanged, with 63% stage I, 18% stage II, and 19% stage III or above. The total number of lymph nodes retrieved during resection remained unchanged until 2010 (median 4-5 from 2004 to 2010), after which, it increased significantly (median 7 in 2011, 9.5 in 2012, and 10 in 2013) (p<0.001) (figure 1). The mediastinal lymph node (MLN) examination rate increased from 53% in 2004 to 82% in 2013 (p<0.001). However, the rate of non-examination of lymph nodes (pNX) remained stable at 10%. Although the proportion of patients with N1 disease remained stable (17.6%), the proportion with N2 disease increased during a pilot testing phase with a MLN specimen collection kit implementation (10.8% in 2010 and 2011, and 7-8% in all other years). Finally, the re-hospitalization rate was 13.3%; the 60-day mortality rate was 6.4%. Figure 1
Conclusion:
In this population-based cohort, pre-operative and intraoperative nodal staging practice improved significantly. However, other quality measures (margin positivity and pNX rates) need further improvement. This early analysis suggests that a regional quality improvement project can improve overall patient survival in this high lung cancer mortality zone of the US.
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ORAL30.02 - Treatment of Non-Small Cell Lung Cancer in Patients with a High Comorbidity Index (ID 496)
16:56 - 17:07 | Author(s): J. Rios, B. Huang, T. Tucker, J. Nee, M. Oechsli, C. Pinkston, G.H. Kloecker
- Abstract
- Presentation
Background:
Lung cancer has the highest cancer mortality. The life expectancy of untreated NSCLC is dismal, while treatment for NSCLC improves survival. However, the perceived outcome of NSCLC therapy in general is less favorable compared to other types of solid tumors. The presence of comorbidities is thought to play a significant role on the decision to treat or not-to-treat a given patient. We aimed to evaluate the impact of comorbidities on the survival of patients treated for NSCLC.
Methods:
As part of Kentucky's LEADS Collaborative, we identified NSCLC patients older than 65 years between 2007 and 2011 on the SEER Kentucky Cancer Registry (KCR). We linked the SEER KCR data with Medicare claims data for therapies provided (surgery, radiation, chemotherapy) for patients who had Medicare PART A and B coverage, had no HMO coverage 12 months prior to their cancer diagnosis, and had the lung cancer as the first primary cancer. Charlson comorbidity index (CCI) was assigned to each patient based on the linked Medicare data. Kaplan-Meier estimates were plotted. Log-Rank test was used to compare survival estimates. Data on age, sex, CCI, stage, and type of therapy received were included in univariate and multivariate Cox proportional hazard analyses.
Results:
Between 2007 and 2011, we identified 3905 patients for analysis. The population was Caucasian in 95% and African American in 4.6%. 54.4% were male. There were 2336 patients (59.8%) between ages 66 and 75. 770 patients (19.7%) did not receive any surgery, radiation, chemotherapy or any combination of these modalities. The proportion of untreated patient per stage was 9.45% for Stage I, 4.35% for Stage II, 20.76% for Stage III and 26.7% for Stage IV. The median overall survival was 41 months for stage I, 22 months for stage II, 10.5 months for stage III and 4.1 months for stage IV (Log-rank test, P < 0.001) In the survival analysis, treatment for NSCLC resulted in significantly better survival (LR, P < 0.05), for patients that have no comorbidity burden (CCI score of 0), for those who have a low burden of comorbidities (CCI score of 1-2) as well as for those patients that had a significant comorbidity burden (CCI score of 3 or more). The better survival of patients with high burden of comorbidities who received treatment for their disease was consistently observed on Stage I (HR 0.31, 95% CI 0.20-0.48); Stage III (HR 0.27, 95% CI 0.18-0.40) and Stage IV (HR 0.46, 95% CI 0.34-0.62). The multivariate analysis confirms the established factors that negatively impact survival (older age, being male, higher stage, higher grade, and no treatment).
Conclusion:
Undertreatment of lung cancer has many causes, but misconceptions about patients being eligible for treatment play a significant role. The presented SEER-Medicare data demonstrates a significant survival benefit from NSCLC therapy even in those patients with a high burden of comorbidities. The data supports the consideration for therapy even when the comorbidity burden is perceived as high. Further studies are needed to determine the effect of optimal comorbidities management on lung cancer outcomes.
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ORAL30.03 - Access to Cancer Directed Therapies and Cancer Specialists in Patients with Metastatic Lung Cancer (ID 2899)
17:07 - 17:18 | Author(s): A.K. Ganti, F.R. Hirsch, M. Wynes, A. Ravelo, S.S. Ramalingam, R. Ionescu-Ittu, I. Pivneva, P. Lin, H. Borghaei
- Abstract
- Presentation
Background:
Access to cancer specialists and directed therapies is critical in the management of patients with metastatic lung cancer (mLC). This study aims to assess treatment patterns overall and stratified based on whether patients were seen or not by a cancer specialist in patients with de novo mLC.
Methods:
Adult patients diagnosed with de novo mLC between January 1, 2008 and March 31, 2014 were selected from a US commercial health claims database. All patients were followed for a minimum 3 months after the index date, defined as their first biopsy date. Patients who saw an oncologist/hematologist from 6 weeks before index date until the end of follow-up (end of data availability or health plan eligibility) were included in the cohort of patients who saw a cancer specialist. The remaining patients were included in the cohort of patients who did not see a cancer specialist. In both cohorts, the use of systemic antineoplastic therapy (Table 1) and radiation therapy was assessed following the index date.
Results:
The study sample consisted of 25,191 mLC patients, followed for a median of 9 months. Median age was 63 years (interquartile range: 57-73). 28.4% of the patients did not see a cancer specialist. Overall, 89.9% of the mLC patients received a cancer directed therapy during the follow-up (Table 1). The proportion of patients who received a cancer directed therapy during the follow-up was larger among patients seen by a cancer specialist (91.2% vs. 86.7%, p < .0001) (Table 1). Among patients who did not see a cancer specialist, 86.7% received antineoplastic therapy and/or radiotherapy during the follow-up, 2.6% were untreated and admitted to hospice, and 10.6% were untreated and were not admitted to hospice. The majority of patients who were not seen by a cancer specialist and received treatment were seen prior to the initiation of therapy by pulmonologists, internists, family physicians, and/or radiologists. Figure 1
Conclusion:
Approximately one in ten patients with de novo mLC did not receive any cancer directed therapy and a little more than one in four patients were not seen directly by a cancer specialist. Among patients not seen by a cancer specialist many received some form of cancer directed therapy. However, the access to cancer directed therapy of these patients remained significantly lower than that of mLC patients seen by a cancer specialist. Further research should be directed towards understanding and addressing disparities in access to appropriate cancer care.
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ORAL30.04 - Discussant for ORAL30.01, ORAL30.02, ORAL30.03 (ID 3365)
17:18 - 17:28 | Author(s): S. Swisher
- Abstract
- Presentation
Abstract not provided
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- Abstract
- Presentation
Background:
Molecular testing-directed targeted therapies are transforming treatment paradigms for non-small cell lung cancer (NSCLC). The clinical application of next-generation sequencing (NGS) technologies has offered a more comprehensive understanding of the mutational landscape. Efforts have been made in the past three years in the Department of pathology at the Peking Union Medical College Hospital, to adopt NGS in the clinical setting allowing rapid and reliable detection of actionable mutations that facilitate therapeutic decision making and disease prediction for at-risk patients
Methods:
The NextDaySeq Lung panel on Ion Torrent[TM] System and DanPA bioinformatics pipeline have been implemented in our clinical laboratory. The workflow employs novel chemistry in library preparation and innovation in informatics, which allows a 48-hour turnaround from FFPE samples to identification of variants with demonstrated clinical importance. The test sequences 16 exons in EGFR, KRAS, BRAF, PIK3CA, ALK, DDR2 and PDGFRA, covering 82 well recognized hotspots. The end-to-end test performance has been established with analytical sensitivity and specificity as well as the assay’s repeatability and reproducibility. Up to date, more than 200 samples have been examined including both lung adenocarcinoma and lung squamous carcinoma. To characterize the analytical performance, the NGS results have been compared with Sanger sequencing that covers the same exons, as well as QPCR assays (CFDA approved IVD kits) that cover a majority of hotspots within these exons.
Results:
Analysis of 200 cases indicated 100% concordance for reportable variants mutually covered in both NGS and QPCR assays. Eight cases reported at least one additional potentially clinically relevant variant, for example, in EGFR and PIK3CA, that would not have been identified in previously implemented QPCR assays. The mutation rates reported in 200 cases ranged from 2.4% to 84.3% according to DanPA analysis, while Sanger sequencing failed to detect variants in 32 cases with mutation rates lower than 20%. The Indel analysis had been a challenge for previous NGS tests in the lab, and the current test resolved the issue with the DanPA pipeline, demonstrating 100% PPV and NPV values compared with QPCR, and Sanger when mutation rates higher than 20%. Additionally, we documented multiple cases that carry double and triple mutations, which were rare in lung cancer, and also identified several novel mutations.
Conclusion:
Therefore, we reported the validation of NextDaySeq Lung panel for high throughput detection of mutations in NSCLC, and the development of a wet-bench and informatics workflow enabling timely and informative molecular diagnosis. The implementation of the test offers significantly improved information benefit over previous tests, and holds the promise to impact patient management.
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ORAL30.06 - Genomic Analysis of Lung Cancer Tumors from Hispanic Patients Living in the US (ID 420)
17:39 - 17:50 | Author(s): L.E. Raez, J. Mourafetis, A. Kim, B. Hunis, C. Sareli, E. Velis, N. Abrahams, M. Block, F. Tarrazzi, D. Dumercy
- Abstract
- Presentation
Background:
The frequency of epidermal growth factor receptor mutations (EGFR-mut) in tumors from Hispanic (HIS) patients (pts) in Latin-America (LA) might be higher than the rate registered in the world literature from data coming mainly from Non-Hispanic White (NHW) pts with NSCLC (CLICaP: J Clin Oncol. 2012;30:(suppl; abstr e18114)). We wanted to verify this and investigate the gene expression profile (GEP) in tumors from HIS pts with NSCLC living in the US.
Methods:
To identify EGFR-mut and other molecular markers (MM) (ALK and ROS-1 translocations (trans), KRAS, c-Met and BRAF) genomic analysis by next generation sequencing (NGS) and FISH was done in tumors of pts with NSCLC at Memorial Cancer Institute in Florida. All MM were not available for all pts. Pts were divided into groups based on ethnic background. Chi-square and Fisher’s Exact tests were used to assess associations between genetic profile and ethnicity. All summary statistics on time-to-event variables were calculated according to the Kaplan-Meier method and were compared by means of the log-rank test. Adjusted hazard ratios (AHR) and 95% confidence intervals (95% CI) were reported based on the results of a multivariate Cox regression model for overall survival (OS) with adjustment for gender, age, and race. A p value 0.05 was significant. SPSS® software 21 was used for analyses.
Results:
MM were ordered in 282 pts and tumor samples were sufficient in 254 (90%). Of these pts: 35% were HIS, 59% were women, 92% had adenocarcinoma and 38% were non-smokers. EGFR-mut were seen in 21% of the tumors [93 % in exons 19 and 21]. EGFR resistant mutations [exon 20] in 1%. ALK and ROS-1 trans were 3% and 10%. c-MET in 25%, KRAS 24%, and BRAF 4%.
There was no significant association between HIS vs. NHW with any MM: EGFR-mut [χ[2 ]=0.22, p=0.64] or ALK and ROS-1 trans [Fisher’s Exact Tests, p=0.49 and 0.55] or other MM: KRAS, χ[2 ]=0.25, p=0.62, c-MET, χ[2 ]=0.00, p=1.00, or BRAF, Fisher’s Exact Tests, p=0.17. No differences in survival between HIS and NHW regardless of MM. Log Rank (Mantel-Cox) 0.73, p=0.39.MM % in HIS % in NHW # samples EGFR mut 23% 20% 231 ALK trans 4% 3% 209 ROS-1 trans 8% 11% 63 KRAS mut 26% 22% 149 c-MET mut 25% 25% 51 BRAF mut 10% 0% 49
Conclusion:
GEP of NSCLC tumors in HIS pts in the US are similar to NHW contrary to what is found in LA. There might be selection bias in the data from LA due to the fact that very few of the eligible pts in LA are being tested yet, all of our NSCLC pts get GEP in our practice.
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ORAL30.07 - Different Mutation Profiles and Clinical Characteristics Among Hispanic Patients with NSCLC Could Explain The 'Hispanic Paradox' (ID 748)
17:50 - 18:01 | Author(s): M.A. Castillo, L. Ramírez-Tirado, R. Báez-Saldaña, O. Peña-Curiel, E.O. Macedo, G. Saco-Chafre, O. Arrieta Rodriguez
- Abstract
- Presentation
Background:
Sixteen percent of the U.S. population is Hispanic, predominantly of Mexican ancestry. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) in patients with non-small-cell lung cancer (NSCLC) diagnosis. The latter even when most of the Hispanics are diagnosed at advanced stages of disease and are low-income patients. The aim of our study was to analyze the clinical, pathological, and molecular characteristics as well as the outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox".
Methods:
A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007-2014 was analyzed. Their clinical- pathological characteristics, the mutation-status of EGFR and KRAS and the prognosis were evaluated.
Results:
Patients presented with stages of disease: II (0.6%), IIIa (4.8%), IIIb (18.4%) and IV (76.3%). NSCLC was associated with smoking in 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 28.1% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.2% (10.3% men vs. 10.1% in women p= 0.939). The median OS for all patients was 23.0 months [CI95% 19.4-26.2], whereas for patients at stage IV, it was 20.1 months [CI 95% 16.5-23.7]. The independent factors associated with the OS were as follows, the ECOG Performance Status, stage of disease, EGFR and KRAS mutation status.
Conclusion:
The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs.
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ORAL30.08 - Discussant for ORAL30.05, ORAL30.06, ORAL30.07 (ID 3366)
18:01 - 18:11 | Author(s): E.S. Kim
- Abstract
- Presentation
Abstract not provided
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