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E. Haura
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MINI 02 - Immunotherapy (ID 92)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:P. Forde, S.J. Antonia
- Coordinates: 9/07/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
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MINI02.07 - Preclinical Rationale for a Phase I/II Study of Pembrolizumab (P) and Vorinostat (V) in Immune Therapy Naïve and Pretreated Stage IV NSCLC (ID 734)
11:20 - 11:25 | Author(s): E. Haura
- Abstract
- Presentation
Background:
The WHO estimated that 1.6 million people died of lung cancer in 2012. Nivolumab, an anti-PD-1 immune checkpoint inhibitor, was FDA approved on March 4, 2015 for platinum-refractory, metastatic, squamous-cell NSCLC, based upon a RR to single agent nivolumab of ~15% and improved OS. Combinatorial strategies may enhance these outcomes. Increased tumor expression of T cell chemokines, such as CCL5 and CXCL10, is associated with a better response to immunotherapy. Furthermore, expression of T cell chemokines is strongly and positively associated with increased T cell infiltration and improved patient survival. Therefore, enhancement of expression of T cell chemokines may augment response to PD-1 blockade immunotherapy.
Methods:
FDA-approved oncology agents were utilized from the Approved Oncology Drugs Set (97 agents) from the Developmental Therapeutics program of NCI. LKR cells were plated in 96-well plates, and a viability assay was performed 48 hours after drug administration (Cell Counting Kit-8, Dojindo Laboratories). Mice were bred and housed in the animal facility at Moffitt Cancer Center. Cells were harvested in logarithmic growth phase after being cultured for less than 2 weeks. 1x10[6] LKR or 344SQ cells were injected s.c. and tumors were monitored for growth by measurements 2-3 times per week. Romidepsin was injected i.p. (2mg/kg) on days 14,16, and 18 after tumor inoculation. Anti-PD-1 was injected i.p. (300μg/mouse) on days 15, 17, and 19 after tumor inoculation. Relative tumor size between treatment groups was analyzed using the t test with Welch’s correction.
Results:
Histone deacetylase inhibitors (HDACi), including vorinostat, emerged as the only class of agents in a 97-drug screen capable of inducing expression of multiple T cell chemokines, including CCL5, CXCL9, and CXCL10, in mouse and human lung cancer cell lines and primary tumors. HDACi’s ability to induce T cell chemokine expression was dependent on both JAK-STAT and NF-kB pathways. HDACi (romidepsin) treatment of mice bearing LKR tumors did not substantially cause tumor shrinkage but significantly reduced growth (p<0.0001; final tumor volume). This effect of HDACi was completely T cell dependent. LKR tumor cells had low cell surface expression of PD-L1 but which was substantially increased by IFN-g. PD-1 blockade with mAb reduced tumor growth but rarely induced rejection. However, when PD-1 blockade was combined with HDACi, 9 out of 11 mice demonstrated complete tumor rejection. HDACi anti-tumor response correlated with T cell chemokine induction in tumors and greater presence of tumor-infiltrating lymphocytes (TILs). We next used a mouse tumor model (344SQ) that was relatively resistant to anti-PD-1 treatment. PD-1 blockade combined with HDACi significantly reduced growth of these tumors compared to untreated (p=0.0003), anti-PD-1 alone (p=0.01), or HDACi (p=0.004) alone treated mice.
Conclusion:
HDACi not only enhanced anti-tumor response against PD-1 blockade sensitive tumors (LKR), but also induced response against PD-1 blockade resistant tumors (344SQ). HDACi induces JAK-STAT and NF-kB dependent chemokine expression and may induce tumor-infiltrating lymphocytes. Thus, a Phase I/randomized Phase II clinical trial of vorinostat, an orally active, small molecule HDACi, plus pembrolizumab, an anti-PD-1 humanized monoclonal IgG4-kappa antibody, is planned in patients with immune therapy naïve and pre-treated metastatic NSCLC.
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MINI02.12 - Distribution of Immune Markers and Their Association with Overall Survival and Time to Progression in Non-Small-Cell Lung Cancer (NSCLC) (ID 3108)
11:50 - 11:55 | Author(s): E. Haura
- Abstract
- Presentation
Background:
Inducible nitric oxide synthase (iNOS) and reactive nitrosylation are important mediators of tumor immunosuppression by myeloid-derived suppressor cells (MDSCs). However, the role of CD33+ peritumoral PMN-MDSCs in these pathways remains unclear. We conducted a retrospective cohort study of NSCLC subjects treated with surgery, with the primary objective to determine the association of MDSC biomarkers with time to progression (TTP) and overall survival (OS).
Methods:
Inclusion criteria: Surgically treated NSCLC of all stages at a single institution between 1996 and 2010. Somatic mutations tested by PCR. Anti-human antibodies optimized for immunohistochemistry. Samples scored by blinded pathologist based on intensity and percentage of peritumoral cells. Peritumoral nitrotyrosine (NT) and iNOS used Allred scoring. Time to progression (TTP) defined as time from resection to progression event or censored at last evaluation. Overall survival (OS) defined as time from resection to death.
Results:
Of 458 tumor samples, 366 lung primaries, 38 soft tissue metastases, and 39 brain metastases. Demographics: median age 67 yrs, 54% female, 96% Caucasian. Of 151 tested for somatic mutations, 36% KRASm, 8.6% EGFRm, 25% p53m, respectively. Histology: adenocarcinoma 76%, squamous 10%. Higher % CD3+ tumor infiltrating lymphocytes (TILs) and CD33+ myeloid cells were observed in tumors than normal tissue (p < .0001 and p = .002, respectively). More CD3+ TILs observed in soft tissue metastases than primary lung tumors (p < .0001). No difference in iNOS expression between tumor and normal lung tissue. More CD3+ TIL was observed in p53 mutant tumors (p=.03). iNOS was positively correlated with CD3+ TIL (p < .001) and CD73+ epithelial cells (p <.001), but not CD33+ myeloid cells. NT expression correlated with the absence of CD3+ TIL (p = .02), consistent with its putative immunosuppressive activity. Median TTP: 10.4 months; 320 (69.7%) events. Median OS: 35.4 months; 353 (77.1%) events. Expectedly, presence of CD3+ TIL was associated with favorable OS; HR 0.5 [0.4 – 0.7], p < .0001, and TTP; HR 0.7 [.5 – .9], p =.009. CD33+ myeloid cells were associated with favorable OS; HR 0.6 [0.5-0.8], p = .0002. Presence of peritumoral iNOS trended toward favorable OS; HR 0.81 [0.6-1.0], p = .07. Peritumoral iNOS was not associated with TTP. Figure 1
Conclusion:
Increased presence of TILs in p53 mutant tumors has been reported in other cancers, and may be related to somatic mutational load. An inflamed tumor phenotype was associated with improved overall survival. Unexpectedly, iNOS was positively correlated with both CD3+ infiltration and overall survival.
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MINI 09 - Drug Resistance (ID 107)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:L. Villaruz, J. Minna
- Coordinates: 9/07/2015, 16:45 - 18:15, 205+207
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MINI09.06 - Oncogenic Drivers including RET and ROS1 plus PTEN Loss and MET by IHC in Patients with Lung Adenocarcinomas: Lung Cancer Mutation Consortium 2.0 (ID 2114)
17:15 - 17:20 | Author(s): E. Haura
- Abstract
- Presentation
Background:
The Lung Cancer Mutation Consortium (LCMC) 1.0 demonstrated multiplexed genomic platforms can assay 10 oncogenic drivers in tumor specimens from patients with lung adenocarcinomas. 28% of the patients with oncogenic drivers could be effectively targeted. The survival of these 275 patients treated with targeted agents was longer than the patients who were not treated with a targeted agent (Kris and Johnson JAMA 2014). The efficiency of Next-Generation Sequencing enables more comprehensive testing of additional aberrations with less tumor tissue. LCMC 2.0 was initiated to test tumor specimens for 12 oncogenic drivers and to provide the results to clinicians for treatment decisions and research purposes.
Methods:
The 16 site LCMC 2.0 is testing tumors from 1000 patients with lung adenocarcinomas in CLIA laboratories for mutations in KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, and NRAS, MET DNA amplification, and rearrangements in ALK as done in LCMC 1.0. The new genes that were added because of emerging information about potential therapeutic targets include MAP2K1 mutations, RET and ROS1 rearrangements, PTEN (MAb 138G4) loss and MET (MAb SP44) overexpression by immunohistochemistry (IHC). All patients were diagnosed with stage IIIB/IV lung adenocarcinoma after May 2012, had a performance status 0-2, and available tumor tissue.
Results:
Of 1073 patients registered, data is now reported for 759. The median age of the patients is 65 (23-90). The population includes 369 (55%) women; 164 (24%) never smokers, 399 (59%) former smokers, and 73 (11%) current smokers; 26 (4%) Asians, 58 (9%) African American, 548 (81%) Caucasian, and 43 (6%) of other races. As of April 2015 information on genomic and immunohistochemical changes for 675 eligible patients were recorded in our database. Alterations in oncogenic drivers were found in 45% of samples as follows: 159 KRAS (24%), 88 EGFR (13%), 25 ALK (4%), 19 BRAF (3%), 17 PIK3CA (3%), 9 HER2 (1%), 4 NRAS (1%) 0 AKT1, 28 had ≥ 2 findings (4%) and 25 MET DNA amplification (4%). The new genes studied in LCMC 2.0 revealed 1 MAP2K1 mutation (<1%), 19 RET (3%) and 9 ROS (1%) rearrangements, 94 had PTEN loss (14%), and 362 with MET overexpression (54%). As expected, PIK3CA mutations and PTEN loss by IHC were mutually exclusive in 109 of 111 (98%) patients’ tumors. Seventeen of the 23 (74%) with MET DNA amplification studied thus far with IHC had MET overexpression. Next-Generation platforms were used at 13 of 16 LCMC 2.0 sites.
Conclusion:
Next-Generation Sequencing is rapidly becoming routine practice at LCMC 2.0 centers with use going from 0 to 81% of sites since 2012. LCMC 2.0 identified additional targets (RET and ROS1 rearrangements and PTEN loss). PIK3CA and PTEN were largely mutually exclusive and an actionable oncogenic driver has been identified in the 45% of initial lung adenocarcinoma specimens. Supported by Free to Breathe
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MINI09.13 - Neuropilin-2 Promotes Acquired Resistance to EGFR-TKI Associated with the Epithelial–Mesenchymal Transition in Lung Cancer (ID 1271)
17:55 - 18:00 | Author(s): E. Haura
- Abstract
Background:
Lung cancer accounts for one-fifth of cancer deaths worldwide with invasion, metastases and drug resistance representing major causes of mortality and barriers to cure. While lung cancers with activating mutations in the EGF receptor (EGFR) are susceptible to tyrosine kinase inhibitors (TKI), such as erlotinib and gefitinib, the efficacy of these agents is limited by the inevitable development of resistance. The epithelial-mesenchymal transition (EMT), by which epithelial cells acquire a mesenchymal and invasive phenotype, is one mechanism promoting EGFR-TKI resistance, including resistance to 3[rd] generation T790M-specific inhibitors. However, the molecular connections between EMT and resistance are not well understood. Here we report that upregulation of Neuropilin-2 (NRP2) is crucial for development of EGFR-TKI resistance associated with the EMT. NRP2 is a cell surface receptor for SEMA3F, a secreted semaphorin with tumor suppressor activity that is down-regulated during EMT. NRP1 and NRP2 are also co-receptors and signaling enhancers for several growth-promoting ligands such as VEGF, HGF and FGF. We previously reported that NRP2 was induced by TGFβ as part of an EMT response in lung cancers and that NRP2 knockdown suppressed the EMT phenotype, including local tumor invasion in a subcutaneous xenograft model.
Methods:
Immunohistochemistry (IHC) was performed for NRP2 on patient biopsies, before and after development of gefitinib resistance. EGFR mutant NSCLC cell lines, transfected with control or NRP2-specific shRNAs, were selected for gefitinib/erlotinib resistance in vitro, using progressively increasing concentrations or continuous exposure to IC~50~ levels of EGFR TKIs. Western blot analysis confirmed changes in NRP2 expression along with selected markers of EMT. MTS viability assays determined drug sensitivity while migration and invasion were assessed using Boyden chambers. Growth as spheroids was assessed in 1% methylcellulose medium in low-adherence plates.
Results:
Increased NRP2 was observed in lung tumor biopsies following acquisition of EMT-associated gefitinib-resistance, and in HCC4006-ER cells, which acquired a stable erlotinib-resistant EMT phenotype. In vitro, using multiple EGFR mutant cell lines, NRP2 knockdown blocked acquired gefitinib-resistance, arising both spontaneously following growth in IC~50~ concentrations or after exposure to TGFβ. Of interest, spontaneously-resistant cells exhibited increased migration similar to cells stimulated with TGFβ. NRP2 knockdown also blocked tumorsphere formation, which has been associated with stem-cell characteristics and drug resistance.
Conclusion:
Collectively, our results demonstrate that NRP2 is a mediator of acquired EGFR-TKI resistance. The results also suggest that NRP2 blocking antibodies could be useful for enhancing the duration of response to EGFR inhibitors, including those targeting the T790M mutation.
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MINI 22 - New Technology (ID 134)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
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MINI22.13 - Discussant for MINI22.10, MINI22.11, MINI22.12 (ID 3480)
17:55 - 18:05 | Author(s): E. Haura
- Abstract
- Presentation
Abstract not provided
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MS 13 - The Other "-omics" (ID 31)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:I. Laird-Offringa, J. Herman
- Coordinates: 9/08/2015, 14:15 - 15:45, Mile High Ballroom 2a-3b
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MS13.02 - Proteomics and Phosphoproteomics (ID 1905)
14:40 - 15:00 | Author(s): E. Haura
- Abstract
Abstract:
I will discuss opportunities and future directions in profiling lung cancer using mass spectrometry based proteomic technologies. This includes a proposal to perform deep integrated proteo-genomics studies on cancer subtypes to produce more complete views of the tumor architecture, allow contextual understanding of major drug targets, and discover new lung cancer subtypes. Alterations in the genomes of cancers ultimately get integrated and produce a cancer proteome that can be analyzed using modern state of the art mass spectrometry proteomic tools. For example, signaling pathways and networks involved in cancers are built using a ‘parts list’ of the cancer genome, such as through integrating mutated genes, genes altered through differential expression (i.e. copy number gain or loss), and through regulation by micro-RNA molecules. DNA sequencing-based atlases exist for major tumors allowing ‘part lists’ for cancers; however, these atlases lack integration with expressed proteomes and signaling architectures. By taking into account all these alterations in the cancer genome, cancer proteomics can annotate and prioritize proteins and pathways important for cancer growth and survival. Furthermore, microenvironmental influences, known to be important in drug response, are lacking from these DNA based studies. Proteomics can inform about active pathways driving cancers and lead to novel combination therapy approaches for targeting complex oncogenic networks. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly used to study cancer proteomes. This includes examining the ‘expressed proteome’ through shotgun proteomics, global signaling by annotating key post-translational events (phosphorylation, acetylation, ubiquination) events in cancers or assembling protein-protein interaction data that yield network views of cancer. This allows unbiased and global views of signaling events in cancer thus offering complementary views of cancer biology that are not considered by sequencing of genes or gene expression. By integrating DNA-RNA-proteome-network type data, the co-existing driver processes instilled by the genome that either surround or act in parallel to drug targets can be mapped directly onto cancer molecular machines that drive cancer progression and response to therapy. Discovery proteomics has become a widely used tool in our laboratory. This approach provides an unbiased view of the components in a sample, supporting the testing of multiple hypotheses and generating new leads. I will discuss examples integrating complementary mass spectrometry approaches to build molecular snapshots of cancer proteomes, including phosphoproteomics in tumors related to drug resistance (1, 2), drug affinity selection of proteins and identification of drug targets using mass spectrometry (3-6), and protein-protein interaction mapping(7-9). Literature Cited: 1. Yoshida T, Zhang G, Smith MA, Lopez AS, Bai Y, Li J, Fang B, Koomen JM, Rawal B, Fisher KJ, Chen YA, Kitano M, Morita Y, Yamaguchi H, Shibata K, Okabe T, Okamoto I, Nakagawa K, Haura EB. Tyrosine phosphoproteomics identified both co-drivers and co-targeting strategies for T790M-related EGFR-TKI resistance in non-small cell lung cancer. Clin Cancer Res. 2014. doi: 10.1158/1078-0432.CCR-13-1559. PubMed PMID: 24919575. 2. Bai Y, Kim JY, Watters JM, Fang B, Kinose F, Song L, Koomen JM, Teer JK, Fisher K, Chen YA, Rix U, Haura EB. Adaptive Responses to Dasatinib-Treated Lung Squamous Cell Cancer Cells Harboring DDR2 Mutations. Cancer Res. 2014;74(24):7217-28. doi: 10.1158/0008-5472.CAN-14-0505. PubMed PMID: 25348954. 3. Remsing Rix LL, Kuenzi BM, Luo Y, Remily-Wood E, Kinose F, Wright G, Li J, Koomen JM, Haura EB, Lawrence HR, Rix U. GSK3 alpha and beta are new functionally relevant targets of tivantinib in lung cancer cells. ACS Chem Biol. 2014;9(2):353-8. doi: 10.1021/cb400660a. PubMed PMID: 24215125; PubMed Central PMCID: PMC3944088. 4. Gridling M, Ficarro SB, Breitwieser FP, Song L, Parapatics K, Colinge J, Haura EB, Marto JA, Superti-Furga G, Bennett KL, Rix U. Identification of kinase inhibitor targets in the lung cancer microenvironment by chemical and phosphoproteomics. Mol Cancer Ther. 2014;13(11):2751-62. doi: 10.1158/1535-7163.MCT-14-0152. PubMed PMID: 25189542; PubMed Central PMCID: PMC4221415. 5. Li J, Rix U, Fang B, Bai Y, Edwards A, Colinge J, Bennett KL, Gao J, Song L, Eschrich S, Superti-Furga G, Koomen J, Haura EB. A chemical and phosphoproteomic characterization of dasatinib action in lung cancer. Nat Chem Biol. 2010;6(4):291-9. doi: 10.1038/nchembio.332. PubMed PMID: 20190765; PubMed Central PMCID: PMC2842457. 6. Chamrad I, Rix U, Stukalov A, Gridling M, Parapatics K, Muller AC, Altiok S, Colinge J, Superti-Furga G, Haura EB, Bennett KL. A miniaturized chemical proteomic approach for target profiling of clinical kinase inhibitors in tumor biopsies. J Proteome Res. 2013;12(9):4005-17. doi: 10.1021/pr400309p. PubMed PMID: 23901793; PubMed Central PMCID: PMC4127982. 7. Smith MA, Hall R, Fisher K, Haake SM, Khalil F, Schabath MB, Vuaroqueaux V, Fiebig HH, Altiok S, Chen YA, Haura EB. Annotation of human cancers with EGFR signaling-associated protein complexes using proximity ligation assays. Sci Signal. 2015;8(359):ra4. doi: 10.1126/scisignal.2005906. PubMed PMID: 25587191. 8. Li J, Bennett K, Stukalov A, Fang B, Zhang G, Yoshida T, Okamoto I, Kim JY, Song L, Bai Y, Qian X, Rawal B, Schell M, Grebien F, Winter G, Rix U, Eschrich S, Colinge J, Koomen J, Superti-Furga G, Haura EB. Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms. Mol Syst Biol. 2013;9:705. doi: 10.1038/msb.2013.61. PubMed PMID: 24189400; PubMed Central PMCID: PMC4039310. 9. Haura EB, Muller A, Breitwieser FP, Li J, Grebien F, Colinge J, Bennett KL. Using iTRAQ combined with tandem affinity purification to enhance low-abundance proteins associated with somatically mutated EGFR core complexes in lung cancer. Journal of Proteome Research. 2011;10(1):182-90. Epub 2010/10/16. doi: 10.1021/pr100863f. PubMed PMID: 20945942; PubMed Central PMCID: PMC3017669.
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-002 - Protein Signaling Analysis of KRAS Mutant Lung Adenocarcionomas Reveals Variable MAPK and mTOR Pathway Activation (ID 2280)
09:30 - 09:30 | Author(s): E. Haura
- Abstract
Background:
Despite the numerous efforts made to target KRAS directly, this protein is still undruggable. A number of therapeutics that target linked KRAS pathway members have been tested, but their efficacy in KRAS mutant lung adenocarcinoma is still controversial. Understanding the biochemically linked protein signaling network associated with a KRAS mutation may lead to the identification of therapeutic targets to identify patients that may benefit from a therapeutic agent targeting KRAS downstream substrates.
Methods:
Thirty-four archived samples from surgically-treated KRAS mutant adenocarcinomas were included in this study. Samples were collected at the H.Lee Moffitt Cancer Center & Research Institute (Tampa, FL) and at the Santa Maria della Misericordia Hospital (Perugia, Italy). Pure cancer epithelial cell subpopulations were isolated using Laser Capture Microdissection. The expression/activation level of 155 proteins was then measured by Reverse Phase Protein Microarray, a high-throughput semi-quantitative platform.
Results:
The protein activation level of ERK (as measured by phosphorylation of T202/Y204), a direct downstream substrate of KRAS activity, was highly variable across KRAS mutant samples. While a subgroup of patients showed, as expected, high activation of ERK, approximately 2/3 of the patients had a comparable ERK activation level to the wild-type counterpart previously analyzed. The activation level of the remaining protein signaling analytes was then compared between samples with high and low ERK activation. Tumors with high levels of ERK activation showed a significant increase in the signaling network of: 1) the MAPK proliferative pathway including Ras-GRF1 S916, Mek 1/2 S217/221, MSK1 S360, p38MAPKinase T180/Y182 (p=0.03, p<0.01, p=0.04, p<0.01 respectively), 2) the AKT-mTOR pathway including Akt S473, AMPKα1 S485, ATP Citrate Lyase S454, LKB1 S428, mTOR S2448, p70S6K T389, p70S6K T412, 4E-BP1 S65 (p<0.01, p<0.01, p<0.01, p<0.01, p<0.01, p<0.01, p=0.02, p=0.03 respectively).
Conclusion:
This analysis suggests that the signaling network of KRAS mutant lung adenocarcinomas, while manifesting expected ERK activation as a group, is highly variable. In fact a majority of KRAS mutant tumors had the same range of MEK-ERK activation as KRAS WT tumors. Analysis of high and low ERK activation in the KRAS mutant tumors revealed druggable protein signaling activation of a number of important targets. If validated in a larger study set, these data may have important clinical implication for the allocation of patients toward more effective and specific targeted treatments.
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P1.11 - Poster Session/ Palliative and Supportive Care (ID 229)
- Event: WCLC 2015
- Type: Poster
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.11-012 - Process for Developing a Rapid Tissue Donation Program in a Thoracic Program: Ethical and Logistical Considerations (ID 1602)
09:30 - 09:30 | Author(s): E. Haura
- Abstract
Background:
Rapid tissue donation (RTD), also known as “warm autopsy,” is a novel method of tissue procurement for research purposes where tissues from the primary tumor and metastatic sites are collected within 24 hours of patient death. These tissues provide tremendous research possibilities and hope for new cancer treatments. However, recruiting for RTD has ethical challenges such as diminishing patients’ hope and causing distress to Next of Kin (NoK). Presently there is limited RTD education, training, or protocols for biomedical researchers and healthcare professionals (HCPs) to address the psychosocial and ethical aspects of the request for postmortem tissue donation. The purpose of this study was to: i) identify barriers and facilitators to RTD recruitment and tissue collection from key stakeholders; ii) identify the RTD processes used in other organizations and programs; and iii) establish a standardized process for RTD in a Thoracic Oncology Program at a Comprehensive Cancer Center.
Methods:
Mixed methods were used for each of the 3 purposes of the study: i) formative research (surveys and focus groups) was conducted to explore knowledge, perceptions, and barriers and facilitators to patient recruitment to RTD across key stakeholders including HCPs (n= 91), cancer patients/survivors and advocates, caregivers, physicians and clinic staff (n=42); ii) semi-structured interviews with hospice staff, morgue pathologists, funeral home directors, national organ/tissue donation programs (n= 27); and iii) conducted an extensive review of the literature regarding existing models of RTD.
Results:
Results from part 1 of the study identified several barriers including use of the word “autopsy”; discussing RTD during an initial appointment; approaching patients who attended visits alone; having staff discuss RTD with patients; and expecting all physicians would want to assist with recruitment. Facilitators included identifying enthusiastic physicians; establishing that the treating physician should identify who would be a good candidate (interest and willingness); use of the word “donation”; only approaching patients who have expressed interest and are coping well with their diagnosis; engaging family members in the consenting process; developing written educational materials about RTD; and allowing family members the authority to revoke consent after patient death. Results from part 2 identified the need to use a body map to indicate metastatic sites, developing a standardized operation procedure (SOP); restricting the geographic area where patients reside to facilitate quick retrieval; enlisting the help of Hospice, providing training to staff and physicians and developing a mechanism to provide study results to NoK and recognition for donors. Results from part 3 revealed that despite more than 300 publications using tissue collected via RTD, only 1 study actually described the process for obtaining the tissues and consent. Based on these results, a 12-step RTD SOP was developed.
Conclusion:
Ethical guidelines, an SOP, and training for HCPs is needed prior to initiation of an RTD program. A verbatim script is necessary for physicians’ comfort level and to ensure consistent messaging. Our study provides important information about knowledge, attitudes, and logistics related to RTD from all stakeholders and guided the development of a RTD at a Comprehensive Cancer Center.
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-006 - Survival Rates after Surgery for Stage-3A (N2) Non-Small Cell Lung Cancer with Induction versus Adjuvant Chemotherapy+/-Radiation Therapy (ID 3151)
09:30 - 09:30 | Author(s): E. Haura
- Abstract
Background:
We compared survival of stage-3A non-small cell lung cancer (NSCLC) patients (pts) after surgery without or with induction versus adjuvant chemotherapy + radiation therapy (chemo+XRT).
Methods:
We retrospectively analyzed pts with clinical stage-3A (cStage3A) NSCLC and who had surgery without or with induction chemo+XRT or who were pathologic stage-3A (pStage3A) and had adjuvant chemo+XRT. Kaplan-Meier survival curves were compared for these 3 groups, with significant differences at p<0.05 by Chi Square test, with Log Rank (Mantel-Cox), Breslow (Generalized Wilcoxon), and Tarone-Ware pairwise comparisons.
Results:
From 1/1986 to 12/2010, there were 300 NSCLC pts who were cStage3A at surgery. Another 52 pts were not cStage3A at surgery, but were then pStage3A. Of these 352 pts, 192 had curative resection, with 56 pts having surgery alone (SURG), 43 pts having surgery after induction therapy (NEOADJ), and 93 pts having surgery then adjuvant therapy (ADJ). Kaplan-Meier survival for SURG was worse than that for either NEOADJ (p=0.03) or ADJ (p=0.005), while NEOADJ and ADJ had similar survival (p=0.90). Median survival was 18+3 mon (95%CI: 12-24 mon) for SURG, 37+6 mon (95%CI: 25-50 mon) for NEOADJ, and 41+5 mon (95%CI: 31- 51 mon) for ADJ. Survival for NEOADJ chemo-alone pts was better than for SURG pts (p=0.031), while that of NEOADJ chemo+XRT pts was similar to SURG survival (p=0.488). Survival for ADJ chemo-alone pts was better than for SURG pts (p=0.007), while that of ADJ chemo+XRT pts was similar to SURG survival (p=0.163).
Conclusion:
Stage-3A NSCLC pts have improved survival with either induction or adjuvant therapy compared to surgery alone. Patients with induction or adjuvant chemo alone, but not those with induction or adjuvant chemo+XRT, have improved survival compared to surgery alone.
