Lung Cancer Pts Research Articles

Satisfaction among lung cancer (LCa) patients (pts) in multidisciplinary (MDC) vs. serial care (SC) settings.

e18254 Background: Coordinated MDC, in which all key specialists concurrently provide early input, develop and execute a consensus plan of care in collaboration with pts and their caregivers, may improve satisfaction with care. We rigorously evaluated this premise. Methods: Prospective clinical cohort study comparing newly-diagnosed LCa pts receiving MDC (n=156) or SC (n=307) in the same healthcare system. Pts were enrolled before treatment onset. At baseline (study entry) and 3 months later, pts and caregivers completed treatment-related measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey, including perceptions of quality of care, satisfaction with care, and extent of involvement in decision making. Satisfaction indices at 3 months will be compared in multiple linear regression models, adjusting for baseline scores and demographic and treatment-related characteristics. Results: Pt characteristics were similar, except for age and stage (Table). At baseline, MDC pts rated their care more positively than SC pts, but satisfaction with provider communication was similar. Three month data are currently being analyzed. Conclusions: MDC provided greater pt satisfaction in the diagnostic phase of LCa care. Further prospective analyses will test the hypothesis that MDC pts experience greater satisfaction with quality of care and provider communication compared to SC pts. Clinical trial information: NCT02123797. [Table: see text]

Distribution and pathogenicity of nsSNPs in receptor tyrosine kinases (RTKs) in non-small cell lung cancer (NSCLC) patients (pts).

e20618 Background: Non-synonymous SNPs (nsSNPs) in RTKs can alter kinase activity and are not exclusive to the tyrosine kinase domain (TKD). In NSCLC, EGFR lesions were previously identified using TKD-limited tests; however, next-generation sequencing (NGS) enables the entire protein sequence of many RTKs to be interrogated. Methods: We analyzed all nsSNPs in 28 RTKs in lung cancer pts who received tumor profiling with Caris NGS from 2013-2015. Mutations were classified by location including the TKD, extracellular domain (ECD), transmembrane domain (TM), juxtamembrane domain (JM), and carboxy-terminal (CT) regions. nsSNPs underwent in silico analysis using PolyPhen-2 (Harvard) to predict pathogenicity. Results: 167 pts (156 NSCLC, 11 SC) were identified with a median age 65 (range 26-85); 51% male; 65% white, 31% black; 77% ≥20 pack-years (py), 11% non-smokers; 52% samples tested were metastases. NSCLC pts were 63% adenocarcinoma, 22%, squamous, 8% large-cell; 81% stage IV, 14% III; 17 were EGFR+, 6 BRAF+, 3 HER2+, 3 ROS1 rearranged and 1 MET exon 14. A total 300 nsSNPs (286 NSCLC, 14 SC) were found in 28 RTKs, excluding EGFR. 123/156 NSCLC pts (79%) and 9/11 SC (82%) had ≥1 RTK lesion with median 2 (range 0-8); 143/300 (48%) nsSNPs were predicted-damaging (pnsSNP) by in silico and 89 pts (53%) had ≥1 pnsSNP (median 1; range 0-5). 28/28 RTKs had ≥3 mutations, with median 11 (range 3-23), and 26/28 contained ≥1 pnsSNP (median 5; range 0-14). RTKs in NSCLC with the most frequent nsSNPs were EPHA3 (14/23 variants were pnsSNP), EPHA5 (11/17), EPHB1 (10/11), RET (9/11), ERBB4 (8/12), ALK (7/16), NTRK3 (7/15), ROS1 (6/22) and FLT1 (6/15). 6/14 lesions in SC pts were pnsSNPs in ERBB3, ERBB4, FGFR1, FLT1, RET and ROS1. nsSNPs were found along RTKs: 57% were ECD (72/172 pnsSNP), 26% TKD (47/77), 10% CT (14/29), 6% JM (8/18) and 1% TM (2/4). 6/6 SC pnsSNPs were ECD. 67% BRAF+ and ROS1-rearranged, 59% EGFR+, 33% HER2+ and 0/1 MET exon 14 pts had ≥1 pnsSNP. Conclusions: Nearly 80% NSCLC and SC pts had ≥1 nsSNP in 28 RTKs, excluding EGFR, with 48% pnsSNPs by in silico analysis. As > 70% nsSNPs were extra-TKD lesions, further characterization is needed to identify kinase-effecting variants and their potential clinical significance.

Immune-related adverse events (IRAEs) in metastatic lung cancer patients receiving PD-1/PD-L1 inhibitors and thoracic radiotherapy.

9079 Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but are associated with unique IRAEs, including pneumonitis (PNS). Thoracic radiotherapy (TRT) is also associated with PNS but it is unknown whether TRT+ICI increases the risk of PNS or other IRAEs. Furthermore, low serum LDH levels are associated with better response/survival to ICI but its potential role as a biomarker for IRAEs is unexplored. Methods: We retrospectively reviewed 164 pts with metastatic lung cancer (95% NSCLC, 5% SCLC) consecutively treated at our institution from 2013-2016 with PD-1/PD-L1 inhibitors and a minimum of one month follow-up, except in cases of rapid death from an IRAE ( n =4). Pts were grouped according to TRT received (+ vs -). IRAE grades were assigned using NCI CTCAE v4.0. Outcomes were compared using Fisher’s exact test and two-sided Student’s t-test. Results: Baseline characteristics such as age, gender, smoking status, supplemental oxygen requirement, median number of chemotherapy lines prior to ICI (1 vs 1), median ICI cycles (5 vs 3), and median follow-up after ICI initiation (8 vs 7 months) were similar in the +TRT ( n = 73) and -TRT ( n =91) groups. Rates of grade ≥ 2 IRAEs (18.1 vs 14.4%, p = 0.67), all-grade PNS (8.2 vs 5.5%, p= 0.54), and grade ≥ 2 PNS (4.1 vs 3.3%, p = 1) were not significantly different between the +TRT and -TRT cohorts. Mean TRT dose was similar between those pts who developed PNS and those who did not (55.8 vs 55.9 Gy). In the +TRT group, 85% received TRT a median of 8.6 months before ICI. Among 7 pts (10%) who had concurrent TRT+ICI, none developed symptomatic PNS. Patients who developed grade ≥ 2 IRAEs ( n= 26) had significantly higher mean serum LDH before initiation of ICI than patients who did not (283 vs 214, ref 98-192 IU/L, p= 0.03). Conclusions: TRT in lung cancer pts receiving ICI was not associated with increased risk of PNS in this series. LDH may be a negative predictive biomarker as pts who suffered grade ≥ 2 IRAEs had significantly higher baseline LDH than those who did not. Larger cohorts and prospective studies would be helpful to validate these findings.

A comparison of liver cancer and lung cancer patients at two Veteran Affairs Medical Centers.

e21642 Background: Little is known about palliative care for liver cancer. In this study, we examined palliative care for liver cancer and lung cancer patients. Methods: In an IRB approved protocol, we reviewed medical records of patients diagnosed with liver cancer who were seen by the palliative care service between 2006 and 2012 at 2 VA medical centers, and matched them to patients with lung cancer by year, KPS, and stage. Veterans were compared by symptom prevalence with the CMSAS and by palliative care interventions. Statistical analyses were performed with SAS Studio Version 3.5. Results: We analyzed a total of 138 male patients at 2 VA centers; 69 with lung cancer and 69 with liver cancer. The mean age in both groups was 65 years and 60% of patients self-identified as a minority. There was a high prevalence of symptoms in both groups. Symptom prevalence differed significantly between liver and lung cancer pts for weight loss and dyspnea at one site, and for feeling drowsy, constipation, at the other site. These differences disappeared in a pooled analysis. During palliative care evaluation, more lung cancer patients received treatment for constipation (n = 44 in lung, 29 in liver, p = 0.0107) and dyspnea treatment (n = 37 in lung, 22 in liver, p = 0.0167). More patients with lung cancer were evaluated by physical therapy (n = 41 in lung, n = 28 in liver, p = 0.0276) and psychiatry (n = 31 in lung, n = 20 in liver, p = 0.032). Conclusions: Differences between lung and liver cancer patients’ symptom prevalence and treatment by palliative care can vary by site. This reinforces the importance of local surveys of symptom prevalence . Further studies should be replicated in other sites.

Veristrat based stratification of responses to immune checkpoint blockade (ICB).

e20512 Background: Veristrat (Biodesix, Boulder, CO) is a blood based proteomic assay that is dominated by inflammatory proteins and is prognostic and predictive in metastatic NSCLC after treatment with platinum based chemotherapy (Gregorc et al, Lancet 2014). Smoldering inflammation in the tumor microenvironment regulates and escalates cancer invasion, angiogenesis and immune surveillance escape (Balkwill and Mantovani, Lancet 2001). There is preclinical evidence to suggest that the tumor microenvironment can be altered with immunomodulatory interventions (Martino et al, 2016). While immune checkpoint blockade has shown durable benefit in metastatic NSCLC, the response rates still hover around 20%. As a result, identification of predictive biomarkers are of critical importance. The predictive value of the Veristrat assay with respect to ICB is poorly defined. Methods: At our institution, 83 pts with metastatic lung cancer pts were treated with nivolumab between 6/2015 to 12/2016. The following clinicopathologic characteristics were abstracted from medical records: tumor histology, Veristrat status, no. of doses of nivolumab, irAEs and overall survival. Results: Of the 83 pts, 65 pts were found to have NSCLC. Veristrat status was available for 17/65 of these pts. Nine pts were identified to have “Veristrat good” and seven pts were “Veristrat poor”. Median number of nivolumab doses was 4. Median survival for all patients was 30 weeks. Median survival was 20 weeks for “Veristrat poor” and 26 weeks for “Veristrat good”(p = 0.68). Grade 3-4 irAEs were noted in 5/9 patients with “Veristrat good” and 5/7 patients with “Veristrat poor”. Conclusions: “Veristrat poor” pts treated with ICB have a lower median survival as compared to “Veristrat good” pts. Our study did not meet statistically significant end point due to limited sample size. Further studies are needed to identify poorly immunogenic tumors and develop novel treatment approaches to optimize outcomes. [Table: see text]

Neurotoxicity associated with anti-PD1 therapy: A multi-center case series.

e21641 Background: The anti-PD1 antibodies (PD1) pembrolizumab and nivolumab are now FDA-approved in multiple malignancies. With increased use, rarer immune-related adverse events (irAEs) not well characterized in clinical trials are being identified, including neurotoxicities. Methods: Patients (Pts) who developed neurotoxicites while being treated with PD1 (alone or in combination) were retrospectively identified from 10 cancer centers. Data regarding treatment, toxicity and outcome were examined. Results: 40 pts (38 melanoma and 2 non-small cell lung cancer pts) developed neurotoxicity; 14 on anti-PD1 monotherapy, 23 in combination or sequence with ipilimumab, and 3 on blinded trials or in combination with interferon. The overall response rate was 90% and median progression free survival was not reached. The median time from treatment initiation to development of neurotoxicity was 7 weeks (range 1-86.5 weeks). 8 pts had died, 5 from disease progression and, 2 from neurotoxicity. 26 pts (65%) developed other irAEs. 27 (67.5%) pts developed toxicities affecting the peripheral nervous system including motor sensory neuropathies (6), sensory neuropathies (4), and Myasthenia Gravis (3). 13 (32.5%) pts developed central nervous system toxicities including aseptic meningitis (6) and encephalitis (4). 24 (60%) pts were treated with steroids alone. 9 pts required further immunomodulation including IVIG (7), plasmapheresis (3), MMF (1) and rituximab (1). 17 (43%) had complete resolution of symptoms, 5 (13%) had stable or worsening neurological disease, and 22 ( 55%) were improving at the time of datacut . 10 pts were retreated with PD1, of which 2 developed exacerbation of prior neurological symptoms. Conclusions: While rare, a variety of neurotoxicities can occur with PD1 treatment. Management may require immunomodulation beyond corticosteroids. Given the high response rate observed in this cohort, such toxicities and their management do not appear to negatively impact treatment response.

The impact of neurocognitive function on health utility scores (HUS) in Stage 4 (S4) lung cancer patients (pts) with and without brain metastases (BrM).

225 Background: As targeted therapies for S4LC pts have improved survival, the impact of health-related quality of life (HRQoL) in these pts grows in importance. In pts with BrM, loss of NCF may affect HRQoL significantly. We evaluated the relationship between NCF and HUS as a measure of HRQoL in S4LC pts. Methods: Self-reported HUS data from EQ5D-3L were obtained cross-sectionally from S4LC pts with (BrM) or without BrM (non-BrM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B). NCF scores were correlated with HUS (Pearson Coefficient, R). Results: BrM (n = 54) and non-BrM (n = 40) patients had similar demographics- overall median age was 61 (range 33-89) years; 59% were female; 45% had EGFR/ALK alterations; BrM pts were treated with whole brain (n = 20), stereotactic radiation (n = 19), both (n = 6), or sole use of systemic agents (n = 6); 3 were observed; 7 had BrM resection. Overall HUS were similar between BrM and non-BrM groups (mean HUS (mHUS): 0.77 vs. 0.78; p = 0.86). However, pts with stable brain disease had higher HUS than those with progressive brain disease (mHUS: 0.80 (n = 36) vs 0.69 (n = 17); p = 0.045). There was a trend towards lower HUS in symptomatic vs. asymptomatic BrM (mHUS: 0.70 (n = 10) vs. 0.78 (n = 43); p = 0.07). Multiple correlations between NCF scores and HUS were found. HLVT-Total Recall correlated with HUS in BrM but not non-BrM (R=0.35, p = 0.01; vs. non- R=0.04, p = 0.84 respectively) as did the HLVT-Recognition (BrM: R=0.32, p = 0.03 vs. non-BrM: R=0.13, p = 0.51). In contrast, TMT-A/B were associated with HUS in both BrM (p = 0.03, 0.06) and non-BrM pts (p = 0.001, 0.03). COWAT was associated with HUS only when all pts were analyzed together (p = 0.04). Conclusions: In S4LC pts, HUS were correlated with multiple measures of NCF. The impact of uncontrolled brain disease and poor NCF on HUS demonstrates that this measure has clinical utility, with important HRQoL implications as metastatic lung cancer pts live longer.

P2.03b-028 Improved Overall Survival Following Implementation of NGS in Routine Diagnostics of Advanced Lung Cancer in Germany: Results of the NGM: Topic: Biomarkers

Broad implementation of molecular diagnostics and personalized cancer care is hampered by insufficient molecular screening, missing reimbursement for comprehensive molecular testing and lack of access to appropriate drugs. The Network Genomic Medicine (NGM) Lung Cancer is a health care provider network offering comprehensive next generation sequencing (NGS)-based multiplex genotyping on a central diagnostics platform in Cologne for all inoperable lung cancer patients (pts) in Germany. The NGS panel used in NGM consists of 14 genes and 102 amplicons to cover potentially targetable aberrations. Mutation analyses were run on an Illumina (MySeq) platform, while FISH analyses were performed separately. In 2015, we have started the second outcome evaluation for all NGM pts who had received NGS-based molecular diagnostics. In particular, we have focused on molecular subgroups of EGFR, ALK, BRAF-V600E, HER2 and ROS1 positive pts and especially on NGM pts treated in clinical trials. From 2013-2015 6210 lung cancer pts (n=4244 non-squamous NSCLC) were genotyped. Preliminary data show the overall survival (OS) of 934 NSCLC pts including of 110 NSCLC pts treated in clinical trials. For 108 EGFR+ pts, the OS of clinical trials pts treated with so called 3rd generation EGFR-TKIs was 55 months (n=25) vs 22 months in control group (n=83) (p=0,002; mean OS: 29 months; 95% CI: 36-83 months). For 85 ALK+ pts, the OS of pts treated in clinical trials was 35 months (n=19) compared to OS of 23 months for 45 pts treated with one ALK inhibitor and 8 months for 19 pts treated with no ALK inhibitors (P<0,0001; mean OS: 22 months; 95% CI: 22-33 months). While the first NGM evaluation in 2013 already showed a survival benefit of 2 years in EGFR-TKI treated EGFR+ pts compared to chemotherapy, our current evaluation in pts treated with 3rd generation EGFR-TKIs after acquired resistance to 1st gen. EGFR-TKIs shows the significant increasing of the OS. Similarly, we show a significant longer OS for ALK+ pts treated with 2 ALK inhibitors compared to treatment with one or no ALK inhibitor. Further results of this ongoing NGM evaluation will be provided.

P1-082 - Analysis of 148 cases of EGFR mutation-positive lung cancer patients

Background: More than 10 years have passed since EGFR gene mutation was discovered in non-small cell lung cancer (NSCLC). Nowadays almost EGFR mutation-positive NSCLC patients (pts) could get longer than 2 year-survival benefit. Purpose&Pts: The clinical characteristics of 489 lung cancer pts, who underwent EGFR gene test in 2002 to 2015, were retrospectively analyzed. Results: Pts included 367 of adenocarcinomas, 9 of adenosquamous carcinomas, and 29 of NSCLCs. They also included 49 of squamous cell carcinomas, 15 of small cell carcinomas, and other lung carcinomas. The EGFR mutations were detected in 148 cases (30.3%). The mutation rate of adenocarcinomas was 37.6%. As the first treatment, 73 pts (49.3%) were treated with molecular targeted therapy, 37 pts (25%) with operation, 21 pts (14.2%) with cytotoxic chemotherapy, 5 pts (3.4%) with radiotherapy, and 1 pt (0.7%) with chemo-radiotherapy. EGFR mutation-positive 120 pts received each of 3 TKIs for any line of the treatment, but 28 pts (18.9%) did not receive TKIs at all. As the second line after TKI, 22 of 39 pts were treated with TKI, and 17 pts with cytotoxic chemotherapy. EGFR mutation-positive non-survivors were 94 (63.5%), and mutation-negative non-survivors were 218 (63.9%). Conclusion: Most of EGFR mutation-positive pts received TKI, but advanced NSCLC pts relapsed, probably due to the resistance to TKIs. New TKIs have been developed to conquer them. Moreover cancer immunotherapy has been shown to be effective in some of NSCLC pts.

A37 - Lung cancer patients and unplanned presentations to hospital: insights from a single institution experience

Background: New treatments for lung cancer (LC) has been introduced in clinical practice over the last years, however significant toxicities are still observed and may lead to unscheduled access to the oncology clinic as well as hospital admission. Furthermore, LC patients (pts) frequently require emergency medical care due to acute symptoms and life-threatening conditions. We report the magnitude of unplanned presentations and risk factors affecting their number and outcome in a University Hospital. Materials and methods: We retrospectively collected a consecutive cohort of 285 LC pts treated with chemotherapy and target therapy at the Department of Oncology of Udine, from 2012 to 2015 regardless of the stage. Our analysis focused on the subgroup of pts that experienced an unplanned accessed at both the Oncology and the Emergency Department. Demographical data, tumour characteristics, treatments information and blood tests have been recorded. Associations between clinico-pathological characteristics and hospitalization were investigated through logistic regression. The impact of patients' characteristics at first access on the number of presentations was explored through Mann-Whitney test. Results: In our study 46% of pts experienced an unplanned access to the Oncology or the Emergency Department: median access for patient is one (1-10). Hospitalization was the outcome of the first access for 16.1% of pts, while 21% of pts experienced one hospitalization overall and 5% of pts were admitted more than once. At first presentation, 74.6% pts had an ECOG PS 0-1; pain (37.7%) and fever (17.6%) were the main diagnoses performed during visit. Pulmonary embolism (PE) was found in 7.1% pts. Anemia and neutropenia was found in 28,2% and 9,2% of pts respectively; however no febrile neutropenia was diagnosed. Accesses to Emergency Department and ECOG PS 2-3 were closely related to hospitalization (respectively OR 2.62, 95%CI 1.05-6.52; p = 0.0385 and OR 6.27 95%CI 2.59-15.31; p < 0.0001). Notably, only diagnosis of PE significantly increased the number of unplanned accesses (P = 0.0387). Conclusion: To explore the impact of LC patients' characteristics on unplanned access pattern and hospitalization, could be crucial in order to better identify frail patients, minimize quality-of-life impairment and over-hospitalization.

Programmed cell death-1 ligand (PD-L1) expression on circulating CD45(-) cells is an independent prognostic factor for overall survival in patients (Pts) with lung cancer in a prospective, multicenter cohort.

8524Background: Lung cancer pts currently require biopsies to diagnose and profile tumors prior to treatment. There is a need for tumor profiling from circulating biomarkers to avoid invasive proce...

Abstract B136: Plasma EGFR mutation detection using a combined exosomal RNA and circulating tumor DNA approach in patients with acquired resistance to first-generation EGFR-TKIs

Abstract Background: After initial responses to tyrosine kinase inhibitors (TKIs), NSCLC patients (pts) harboring EGFR activating mutations inevitably progress, with the “gatekeeper” EGFR T790M resistance mutation accounting for approximately 60% of cases of acquired resistance (AR) to TKIs. EGFR activating and T790M resistance mutations can be found in plasma on both circulating free tumor DNA (ctDNA) and on RNA contained within exosomes. While ctDNA is thought to be primarily released by dying cells, exosome RNA is actively released by many living cells (Jahr et al. Cancer Res 2001; Thery et al. Nat Rev Immunol 2009). Some pts, particularly those with either early stage or intra-thoracic disease, do not seem to release mutations on ctDNA into circulation that is detectable by any current method. Here we present data demonstrating the detection of activating and AR EGFR mutations using a combined single-step exosomal RNA (exoRNA) and ctDNA approach to maximize sensitivity and demonstrate the ability to detect mutations using exosomal RNA on pts previously described as negative by ctDNA methods alone. Methods: Matched pretreatment tumor tissue and plasma were collected from 81 NSCLC pts enrolled in TIGER-X, a Ph1/2 study of rociletinib in previously treated mutant EGFR pts with advanced NSCLC. Among the 81 pts (all enrolled before Dec 2014), 56 cases were randomly chosen from the clinical patient population (including 35 cases ≥10 mutant copies/mL and 21 cases &amp;lt;10 mutant copies/mL) and an additional 25 cases were previously determined to have low T790M levels in plasma (&amp;lt;10 copies/mL) using ctDNA-based approaches. We applied a column-based method (EXO52) to co-isolate both exoRNA and ctDNA from up to 6 mL of patient plasma, where available, and analyzed the mutations with a custom procedure for next generation sequencing (EXO1000). The targeted EXO1000 sequencing panel covers EGFR mutations on exon 19, 20 and 21. A custom library preparation method and bioinformatics pipeline was used to identify rare mutations in a qualitative and quantitative manner. Results: For the 56 cases randomly chosen from the clinical patient population, 54 had valid tumor tissue results. The positive percent agreement (PPA) between plasma and tumor was 96% (52/54) for activating mutations and 86% (42/49) for T790M with tumor as the reference method. For most cases analyzed, the combined mutation signal from exoRNA and ctDNA was greater than the signal from ctDNA alone. Furthermore, we detect mutations in the circulation of some pts who were previously called negative by analysis of ctDNA alone, suggesting improved sensitivity from addition of exoRNA to the analysis. In the subset of pts with low or undetectable levels of ctDNA and valid tumor results (N = 45), we detect activating mutations in 38 of 45 cases (PPA 84%) compared to 27 of 45 (PPA 60%) by ctDNA alone, as well as T790M in 22 of 35 evaluable cases (PPA 63%) compared to 19 of 35 in ctDNA alone (PPA 54%). Conclusions: Our data demonstrate the ability to detect low copy numbers of activating and AR mutations in plasma of lung cancer pts by combining the mutation signal from exoRNA and ctDNA isolated by EXO52 and using the EXO1000 targeted NGS gene panel. By combining these two analytes, a higher sensitivity of mutation detection may be possible compared to analysis by ctDNA alone. Citation Format: Anne K. Krug, Chris Karlovich, Tina Koestler, Kay Brinkmann, Alexandra Spiel, Jennifer Emenegger, Mikkel Noerholm, Vince O'Neill, Lecia V. Sequist, Jean-Charles Soria, Jonathan W. Goldman, D. Ross Camidge, Heather A. Wakelee, Shirish M. Gadgeel, Elaina Mann, Shannon Matheny, Lindsey Rolfe, Mitch Raponi, Daniel Enderle, Johan Skog. Plasma EGFR mutation detection using a combined exosomal RNA and circulating tumor DNA approach in patients with acquired resistance to first-generation EGFR-TKIs. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B136.

Rate of never smokers in non small cell lung cancer (NSCLC) patients.

e19007 Background: There has been significant debate about whether the percentage of never smokers is increasing in lung cancer patients (pts). Using our institutions’ registry data, our objective was to determine if the rate of never smokers is increasing among lung cancer pts. Methods: We conducted a retrospective study using lung cancer registry data from our university hospital at the University of Texas Southwestern Medical Center and our county hospital, Parkland. These registries were queried year by year between 1990 and 2013 for gender, age at diagnosis, diagnosis of NSCLC or small cell lung cancer (SCLC), and self-reported smoking history. Logistic regression analysis was performed to assess the rate of never smokers in NSCLC (N=5,392) and SCLC (N=792) pts. Results: The percentage of never smokers increased among NSCLC pts between 1990 and 2013 [Table]. Univariate logistic regression demonstrated an increasing proportion of never smokers among NSCLC cases (p<0.0001 for year) and multivariate log...

P13. Epidemiologic, and therapeutic strategy of treated non-small cell lung cancer elderly patients in a single institution.

Background Newly diagnosed non-small cell lung cancer (NSCLC) pts ≥40% are over ≥70 y. Due to special parameters combined with PS (≥2), geriatric syndromes the therapeutic decision is a real challenge. The comorbidities make their accrual in trials very poor & receive single agent.

Syndrome of Inappropriate Anti-Diuretic Hormone Secretion (Siadh) in Cancer Patients (Pts): Results of the First Multicenter Italian Survey

ABSTRACT Aim: SIADH may be related to several causes (pulmonary disorders, CNS disturbances, drugs and chemotherapeutic agents), but in the majority of cases it is caused by malignancies. This observational study aimed to analyze treatments and outcome of SIADH in cancer pts. Methods: This study includes 69 consecutive cancer pts who experienced SIADH between 2010 and 2014 in 22 Italian Cancer Centers. Data on clinico-pathology, anticancer and SIADH treatments were recorded and statistically analized. Results: M/F ratio was 47/22, median age was 67 years (range 37-83). Primary tumor was lung cancer in 50 pts (SCLC in 39), while it was GI cancer in 8 pts. Fifty-eight pts were hospitalized due to SIADH, HN at admission was ≤130 mEq/l in 94.3%. Median duration of hospitalization was 13 days (range 3-90). 31 pts received tolvaptan for SIADH treatment (group A); other treatments included hypertonic saline solutions, diuretics, fluids restriction (group B). Group A included a significant higher N° of lung cancer pts (77.4% vs 68.4%) with metastatic disease (80.6% vs 76.3%). Moreover pts in group A had more severe HN at admission: serum sodium was ≤130 mEq/l in 96.7% pts and Conclusions: To our knowledge this is the largest study analyzing SIADH in cancer pts to demonstrate that HN due to SIADH may result in a prolongation of hospitalization and in a worse overall survival when not adequately corrected and that tolvaptan represents an effective treatment potentially improving both. Disclosure: All authors have declared no conflicts of interest.

Overall Survival in Small Cell Lung Cancer Detected with Epithelial, Mesenchymal and Stem Cell Biomarkers

ABSTRACT Aim: Markers of epithelial to mesenchymal transition (EMT) and markers associated with cancer stem cells (CSC) have been associated with increased chemoresistance in small cell lung cancer (SCLC). We and others previously demonstrated that elevated circulating tumour cells (CTC) are associated with worse survival. In the current exploratory study we hypothesized that markers of EMT and CSC in tumour biopsies obtained at diagnosis were associated with overall survival in patients with SCLC. Methods: Biopsies selected from small cell lung cancer pts study published previously by our group [ Ann Oncol 2012;23:2937-42]. Epithelial markers [Cytokeratin 8,18,19 (CK; ab41825, Abcam), EPCAM (VU1D9, cellsignaling), E-cadherin (24E10, cellsignaling)] and mesenchymal markers [Vimentin (V9, Santa Cruz) and c-MET (EP1454Y, Abcam)] were used as biomarkers for EMT. SOX2 (L1D6A2, cellsignaling) and CD44 (IM7, Biolegend) were used as CSC markers. Scoring by two independent observers having no information about clinical outcome. Immuno-Reactive Score (IRS) was made by multiplying percentage (0-6) and intensity (0-3). IRS score>=5 was high, =2 low Results: From 38 patients (mean age 65 yrs [49-84], 18 female pts, ECOG performance score 1 [0-3], extensive disease stage 26 pts, CTC at baseline 19 [0-14040]) adequate material was available to cut at least 10 tumour containing slides for immunohistochemical staining. Staining intensity high/low: CK 10/27; Vimentin 23/15; CD44 19/19; SOX-2 17/21; cMET 19/19; IRS high/low EPCAM 20/18, E-cadherin 14/24. Combining primary tumour low c-MET intensity with high CK intensity and high E-Cadherin IRS resulted in a significantly worse survival vs the c-METhigh/CKlow/E-cadherinlow group, OS 10 vs 24 month, p=0.040. A trend towards a positive correlation between CTC and primary tumor c-METlow was seen, p=0.062. Conclusions: SCLC with an epithelial phenotype (E-Cadhigh, CKhigh, cMETlow) may give rise to more epithelial CTCs in circulation than those with an mesenchymal phenotype and have a worse prognosis. Disclosure: All authors have declared no conflicts of interest.

Chemotherapy use in lung cancer patients during last three months of life: Current practice in a large Israeli health care organization.

e17675 Background: Lung cancer is the second leading cause of cancer-related death in Israel. Aggressive cancer treatment given at late stages of disease raises questions on quality of care, ethical aspects and cost. Objective: To explore the use of anti-cancer chemotherapeutic drugs (CT) in lung cancer patients (pts) that deceased during 2013, within three months of end of life (EOL). Methods: Clalit Health Services (CHS), Israel's largest health-care organization with over 4 million members, serves 52% of the total population. CHSs administrative database was used to extract available clinical and demographic information regarding all of CHS's Lung cancer pts that died during 2013. Data obtained included: cancer diagnoses, demographics, Charlson's comorbidity index and pharmacotherapy provided within 3 months of EOL. Results: 556 CHS pts died from lung cancer in 2013, 184 female (33%). 338 pts received CT within 3 months of EOL (table). Pts that received CT were significantly younger than pts that didn'...

Management approaches and outcomes of lung cancer patients hospitalized for malignant pleural effusions.

9646 Background: Malignant pleural effusion (MPE) in lung cancer is associated with significant morbidity and poor prognosis. There has been a significant lack of progress regarding the current and recommended management of MPE. We studied MPE management in a large cohort of hospitalized lung cancer patients (pts). Methods: We utilized nationwide inpatient data from 2008-2010 from the Agency for Healthcare Research and Quality- Healthcare Cost and Utilization Project. All lung cancer pts with MPE among top 3 discharge diagnoses were selected. Therapeutic procedures used were identified using ICD 9-CM procedure codes. All analyses were performed using SPSS 20.0. Results: A total of 8570 pts, accounting for 2.5% of all lung cancer-related hospitalizations, had MPE (median age- 71 years, whites-66%, females- 48%, teaching hospitals-46%, urban locations- 88%, elective admissions- 16%, median costs- $29,967). Median length of stay (LOS) was 5 days; mortality rate was 10.5% and 70% had major or extreme loss of ...

Do “pan-negative” never-smoker (NS) lung cancer patients (pts) represent a new distinct subgroup? Data from a single-institution experience.

Article Tools Lung Cancer—Non-Small Cell Metastatic Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/jco.2014.32.15_suppl.e19054 Journal of Clinical Oncology - published online before print May 20, 2014 Do “pan-negative” never-smoker (NS) lung cancer patients (pts) represent a new distinct subgroup? Data from a single-institution experience. Chiara BennatixChiara BennatiSearch for articles by this author , Rita ChiarixRita ChiariSearch for articles by this author , Giulio MetroxGiulio MetroSearch for articles by this author , Daniela IaconoxDaniela IaconoSearch for articles by this author , Vincenzo MinottixVincenzo MinottiSearch for articles by this author , Chiara ScafatixChiara ScafatiSearch for articles by this author , Annamaria SiggillinoxAnnamaria SiggillinoSearch for articles by this author , Lorenza PistolaxLorenza PistolaSearch for articles by this author , Maria Francesca CurràxMaria Francesca CurràSearch for articles by this author , Massimiliano FerraldeschixMassimiliano FerraldeschiSearch for articles by this author , Diana GiannarellixDiana GiannarelliSearch for articles by this author , Lucio CrinoxLucio CrinoSearch for articles by this author Show More Division of Medical Oncology, S. Maria della Misericordia Hospital, Perugia, Italy; Division of Medical Oncology, Santa Maria della Misericordia Hospital, Perugia, Italy; Division of Medical Oncology, S Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia, Italy; Division of Medical Oncology, Azienda Ospedaliera, Perugia, Italy; Medical Oncology, S Maria della Misericordia Hospital, Azienda Ospedaliera Perugia, Perugia, Italy; Regina Elena National Cancer Institute, Rome, Italy; University of Perugia, Perugia, Italy Abstract Disclosures https://doi.org/10.1200/jco.2014.32.15_suppl.e19054 Abstract Abstract e19054 Background: Identification of oncogenic drivers has dramatically changed current therapeutic strategies for lung cancer, initiating the era of personalized therapy. "Pan-negative" NS non-small cell lung cancers (NSCLC) represent an exciting challenge to discover rare gene fusions and to define the best treatment options. Methods: From a 243 never-smoker NSCLC database, we identified 113 oncogene-addicted lung tumors, analyzed for a 5-genes panel: EGFR, K-RAS, ALK, ROS1, HER2. Out of the 130 pan-negative pts, we were able to collect archived histological material of 29, to be analyzed for RETgene rearrangement, through the FISH test. Outcomes to first line chemotherapy and TKI treatment, were evaluated by Cox multivariate analysis. Results: Patients characteristics: good clinical conditions (PS ECOG 0-1), predominance of female sex (21 pts, 64%), median age 55 (23-81), advanced moderately and poorly differentiated adenocarcinomas. In our cohort, 3 RET+ cases (10%) were identified, one compatible with KIF5B:RET and the other two with a non-KIF5Bfusion partner. There was no difference neither in progression free survival (PFS) (9 months, mo) for both groups nor in overall response rate (ORR) (66.7% vs 50%; p=0.24) for pts treated with a pemetrexed-based regimen (15 pts, 52%) as compared with the non-pemetrexed group (14 pts, 48%). Median overall survival (OS) of the pts who received pemetrexed was 17 mo compared to 25 mo of the non-pemetrexed subgroup (p=0.03). In our cohort 13 pts received an oral TKI. Median OS showed no significant differences between TKI and not-TKI treatment (22 vs 23 mo, p=0.94). Conclusions: Our study in a highly selected population confirms the lack of benefit in any of the outcome measures in the absence of a genetic driver. Longer survival in “pan-negative” NS lung cancer pts compared to an unselected NSCLC population is probably a result of their distinct clinical features. © 2014 by American Society of Clinical Oncology

Stereotactic Body Radiation Therapy (SBRT) and Image Guided Accelerated Hypofractionated Radiation Therapy (IGAHRT) for the Treatment of Oligometastatic Cancers

Data in support of aggressive treatment of oligometastatic cancers is still relatively modest in scope. We report our experience treating single or multiple sites, as well as outcomes for patients receiving sequential treatment during the course of their disease. Patients treated between 2009 and 2011 with stereotactic body radiation therapy [SBRT] or image-guided accelerated hypofractionated radiation therapy [IGAHRT] for metastatic cancer were screened and included. Patients were treated using an SBRT technique, with a stereotactic body-fixation device and abdominal compression for immobilization during non-spine treatment. SBRT was defined as 1 to 5 fractions (fxs) with a minimum of 9 Gy/fxs. IGAHRT was defined as 6 to 10 fxs and minimum 5 Gy/fxs. 4D CT was used to define an ITV with a 5 mm PTV expansion. Toxicities were recorded per NCI CTCAE v4.0. Kaplan Meier estimates were performed for local control (LC) and overall survival (OS). A Wilcoxon log-rank test was used for comparison. Fifty-seven patients (pts) were treated for oligometastatic cancer (AJCC 7th ed), 2009-2011. Represented histologies included lung (15 pts), GI (16 pts), sarcoma (6 pts), breast (4 pts), head and neck (H&N) (10 pts), and renal (6 pts). Initial metastatic sites treated included lung (36 pts), liver (8 pts), spine (6 pts), adrenal gland (5 pts), lung/liver (1 pt), and lung/adrenal (1 pt). SBRT/IGAHRT dose by site are as follows: lung 26-54 Gy, 1-10 fxs; liver 45-54 Gy, 3-10 fxs; spine 24-50 Gy, 1-10 fxs; adrenal 50 Gy, 10 fxs. The most common IGAHRT dose was 50 Gy/10 fxs. Median follow-up was 19 months (range, 1-43 months) from treatment. 43 pts received chemotherapy prior to SBRT/IGAHRT. 29/57 pts were treated to multiple lesions during a single course. 12/57 pts were treated with several single courses over 36 m, with a maximum of 3 courses. Two yrs LC was 86% (95% CI 70-95%). Median and 2 year OS from diagnosis of metastatic disease were 55 m and 75% respectively. Median OS from first SBRT/IGAHRT was 35 m for all pts, 35 m for lung cancer pts, 29 m GI, 23 m for breast, 13 m for sarcoma, and was not reached in H&N/renal pts. Median OS for lung site vs all other sites was not reached vs 13.5 months (p = 0.01). Two-yr OS for lung site vs all others: 74% vs 43%. Median OS for single vs multi-target: not reached vs 27 months (p = 0.06); Median OS for single SBRT vs multiple courses: 29 m vs 39 m (p = 0.21). No grade 4 or 5 toxicity noted. In these highly selected patients with oligometastatic cancers, multiple courses of SBRT/IGAHRT were used with durable local control. Prolonged survival from original metastatic diagnosis suggests favorable selection bias. Patients with metastasis to lung had superior outcomes when compared to other sites. Patients with multiple lesions during single course tended to fair worse. Additional prospective study is warranted.