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J. Spicer
Moderator of
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OA10 - EGFR Mutations (ID 382)
- Event: WCLC 2016
- Type: Oral Session
- Track: Biology/Pathology
- Presentations: 8
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OA10.01 - Comprehensive Genomic Profiling and PDX Modeling of EGFR Exon 20 Insertions: Evidence for Osimertinib Based Dual EGFR Blockade (ID 4375)
11:00 - 12:30 | Author(s): J.W. Riess, D.R. Gandara, G.M. Frampton, M. Cheng, P. Lara, K. Kelly, C. Ye, R. Madison, N. Peled, J.A. Bufill, G. Dy, S. Ou, D. Cross, C.J. Bult, S.D. Airhart, P.J. Stephens, J. Ross, V. Miller, S. Ali, J. Keck, P. Mack, A.B. Schrock
- Abstract
Background:
EGFR exon 20 insertion mutations (EGFRex20ins) comprise a subset of EGFR activating alterations relatively insensitive to 1[st] and 2[nd] generation EGFR-TKIs. Comprehensive genomic profiling (CGP) integrated with PDX modeling may identify new EGFR-inhibition strategies for EGFRex20ins.
Methods:
EGFRex20ins and co-occurring genomic alterations were identified by hybrid-capture based CGP performed on 14,483 consecutive FFPE lung cancer specimens to a mean coverage depth of >650X for 236 or 315 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. An EGFRex20ins(N771_P772>SVDNP)/EGFR-amplified tumor (24 copies) from this cohort was implanted subcutaneously into the flank of NOD.Cg-Prkdc[scid]Il2rg[tm1Wjl]/SzJ (NSG) mice for tumor growth inhibition studies (TGI) with vehicle, erlotinib (50 mg/kg PO daily), osimertinib (25 mg/kg PO daily), and osimertinib (25 mg/kg PO daily) plus cetuximab (10 mg/kg IV, 2x/week) administered for 21 days.
Results:
CGP identified 263/14,483 cases (1.8%) with EGFRex20ins, which represent 12% (263/2,251) of EGFR activating mutations in this series. 90% (237/263) were NSCLC-adenocarcinoma, 9% (23/263) were NSCLC-NOS, and 1% (2/263) were sarcomatoid carcinoma. Over 60 unique EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and N771_P772>SVDNP (20%); 6% (15/263) harbored EGFR A763_Y764insFQEA, an EGFRex20ins typically sensitive to erlotinib. Among EGFRex20ins cases, EGFR-amplification occurred in 22% (57/263). Putative co-occurring driver alterations including EGFR (ex19del and L858R), Her2, MET and KRAS tended to be mutually exclusive, occurring only in 5% (12/263) of cases. The most common co-occurring alterations affected TP53 (56%), CDKN2A (22%), CDKN2B (16%), NKX2-1 (14%) and RB1 (11%). Average tumor mutation burden was low (mean 4.3 mutations/Mb, range 0-40.3 mutations/Mb). Clinical outcomes to 1st and 2nd generation EGFR-TKIs were obtained for a subset of cases with various EGFRex20ins, and 0/6 patients had responses. However, robust TGI was observed with combination osimertinib and cetuximab in a highly EGFR-amplified PDX model with a conserved EGFRex20ins (N771_P772>SVDNP) not associated with response to earlier generation EGFR-TKI, and was superior to vehicle, erlotinib or osimertinib alone (D21 mean tumor size 70 mm[3] vs. 1000, 800, 225 mm[3] respectively; p-values all <0.001).
Conclusion:
Diverse EGFRex20ins were detected in 12% of EGFR-mut NSCLC. Available clinical outcomes data demonstrated lack of response to 1[st] and 2[nd] generation EGFR-TKIs. Identification of co-occurring EGFR-amplification in 22% of cases led to testing of a dual EGFR blockade strategy with an EGFR monoclonal antibody and osimertinib, which demonstrated exceptional tumor growth inhibition in an EGFRex20ins PDX minimally responsive to erlotinib. These findings can rapidly be translated into an ongoing clinical trial of osimertinib and necitumumab.
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OA10.02 - Association of Variations in HLA-Class II and Other Loci with Susceptibility to EGFR-Mutated Lung Adenocarcinoma (ID 4192)
11:00 - 12:30 | Author(s): K. Shiraishi, Y. Okada, A. Takahashi, Y. Kamatani, K. Ashikawa, Y. Momozawa, H. Kunitoh, S. Matsumoto, A. Takano, K. Shimizu, A. Goto, K. Tsuta, S. Watanabe, Y. Ohe, Y. Watanabe, Y. Goto, H. Nokihara, K. Furuta, A. Yoshida, K. Goto, T. Hishida, M. Tsuboi, K. Tsuchihara, Y. Miyagi, H. Nakamura, T. Yokose, K. Tanaka, T. Nagashima, Y. Ohtaki, D. Maeda, K. Imai, Y. Minamiya, Y. Shimada, K. Sunami, M. Saito, J. Yokota, F. Matsuda, K. Matsuo, Y. Daigo, M. Kubo, T. Kohno
- Abstract
- Presentation
Background:
Lung adenocarcinoma (LADC) driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Understanding the genetic factors underlying such LADC is required to elucidate disease etiology and to identify effective methods of prevention.
Methods:
We investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls.
Results:
Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2, HLA-class II), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA-class II at 6p21.32 and 6p21.1 (FOXP4) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma (Shiraishi et al., Nature Communications, 2016, in press).
Conclusion:
This study indicates that multiple genetic factors, including an immunologic one, underlie the risk of lung adenocarcinomas with EGFR mutations.
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OA10.03 - YAP-NOTCH and STAT3 Signaling Rebound as a Compensatory Response to Gefitinib or Osimertinib Treatment in EGFR Mutant Lung Cancer (ID 4144)
11:00 - 12:30 | Author(s): R. Rosell, I. Chaib, N. Karachaliou, P. Cao, M.A. Molina Vila, X. Cai, A. Drozdowskyj, J. Yang, C. Hu, A.F. Cardona, A. Frías, C. Lazzari, A. Verlicchi, J. Codony Servat, C. Codony Servat, J.L. Ramírez Serrano, A. Vergnenegre, P.C. Ma, T. Bivona
- Abstract
- Presentation
Background:
Preclinical studies provide insights to therapy mechanisms of resistance that are not feasible with clinical studies. We investigated the signaling pathways that could be involved in adaptive resistance to gefitinib and/or osimertinib in EGFR mutant cells.
Methods:
We performed several laboratory methods to examine the signaling pathways involved in EGFR mutations. Signal transduction pathway analysis was designed using the Ingenuity Pathway Analysis (IPA) software (https://www.ingenuity.com/) Figure 1
Results:
Pathways mediating EGFR mutations are: i) ERK1/2 via Ras and MEK1/2 ii) AKT via PI3K and iii) STAT3 via JAK (Figure). By Western blot analysis, phosphorylation of Tyr705 on STAT3 was noted after 2 hours of gefitinib or osimertinib treatment in PC9 and H1975 EGFR mutant cells. Unexpectedly, YAP1 phosphorylation on Tyr357 and Notch activation was detected. Co-targeting STAT3 and Src with gefitinib or osimertinib ablates activation of STAT3 and YAP1-NOTCH3 signaling pathways (Figure). In vitro and in vivo, the combinatory therapy of gefitinib or osimertinib plus TPCA-1 (a dual inhibitor of IKKs and STAT3) plus saracatinib (a SFK inhibitor) leads to significant tumor shrinkage in PC9 and H1975 cells. In tumor samples of 64 EGFR mutant NSCLC patients treated with gefitinib, the median progression free survival (PFS) was significantly shorter in those with high levels of HES1, ALDH1A1, ALDH1A3, Bmi1, AXL, CDCP1, SHP2 and ILK (Figure). However, the mRNA levels of STAT3 and YAP1 stand out in the prediction of shorter PFS with a hazard ratio of 3.02 and 2.57, respectively (P<0.001)
Conclusion:
For the first time ever, we reported gefitinib induced activation of theYAP1-NOTCH signaling pathway, in addition to activation of STAT3, in EGFR mutant cells. Secondly, co-targeting STAT3 and Src, together with EGFR, causes significant tumor growth inhibition, in comparison with gefitinib or osimertinib single therapy.
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OA10.04 - Discussant for OA10.01, OA10.02, OA10.03 (ID 7008)
11:00 - 12:30 | Author(s): H. Borghaei
- Abstract
- Presentation
Abstract not provided
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OA10.05 - EGFR Gene Mutations Affect Tumor-Infiltrating Stromal Cell Components in Early-Stage Lung Adenocarcinoma (ID 6305)
11:00 - 12:30 | Author(s): T. Shima, T. Shigenobu, M. Shimoda, T. Ohtsuka, H. Asamura, Y. Kanai
- Abstract
- Presentation
Background:
Tumors are complex structures consisting of cancer cells surrounded by a tumor stroma that is now recognized to be critical for cancer progression. Although epidermal growth factor receptor (EGFR) mutations are frequently observed in non-small cell lung carcinoma, it remains poorly understood whether EGFR mutations in cancer cells affect the tumor stroma. In this study, we studied the status of EGFR mutations in early-stage lung adenocarcinoma and analyzed the relations of EGFR mutations to tumor-infiltrating stromal cell components.
Methods:
A total of 152 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete tumor resection in Keio University Hospital between 2010 and 2014 were studied. Genomic DNA was isolated from formalin-fixed, paraffin-embedded tumor sections and mutational analyses of EGFR gene exons 19, 20 and 21 were performed by a polymerase chain reaction-based method. Paraffin sections were also subjected to immunohistochemistry for CD3, FOXP3, CD163 or CD204. Numbers of CD3-, FOXP3-, CD163- or CD204-immunostained cells were counted by observing 5 different fields at x200 magnification.
Results:
EGFR mutations were detected in 71 (47%) of the 152 patients with clinical stage IA lung adenocarcinoma and were found more frequently in women and non-smokers. These contained 38 patients with missense mutations in exon 21 (L858R) and 30 patients with deletions in exon 19. By immunohistochemistry, the number of stromal macrophages positive for CD163 or CD204, markers for tumor-associated macrophages (TAMs), was significantly decreased within tumors with EGFR mutations compared to within those with wild-type EGFR, whereas the number of CD3[+] T cells or FOXP3[+] regulatory T cells was comparable between these groups. Both tumors with missense mutations in exon 21 and deletions in exon 19 had a similar trend toward decreased TAMs in the tumor stroma.
Conclusion:
Our data suggest that EGFR mutations in early-stage lung adenocarcinoma are associated with decreased TAMs in the tumor stroma. EGFR mutation status might act on not only cancer cell behavior but tumor microenvironment.
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OA10.06 - Characteristics and Outcomes of Patients with Lung Cancer Harboring Multiple Molecular Alterations (Biomarker IFCT Study) (ID 5425)
11:00 - 12:30 | Author(s): N. Guibert, F. Barlesi, R. Descourt, H. Léna, B. Besse, M. Beau-Faller, J. Mosser, E. Pichon, J. Merlio, L. Ouafik, F. Guichard, B. Mastroianni, L. Moreau, A. Wdowik, J. Sabourin, A. Lemoine, P. Missy, A. Langlais, D. Moro-Sibilot, J. Mazieres
- Abstract
- Presentation
Background:
Carcinogenesis of non-small cell lung cancer (NSCLC) can be driven by oncogenic addiction that can be targeted by specific inhibitors. It is commonly accepted that these molecular alterations are mutually exclusive. Nevertheless, limited series suggest that concomitant molecular alteration can occur in lung cancer and little is known about their sensitivity to treatment. Based on a nationwide screening program conducted during one year, we aimed to analyze the largest molecular database to date for concomitant mutations in order to determine the prevalence of multiple genomic alterations in NSCLC and their impact on both prognosis and response to treatment.
Methods:
The database of Biomarker France IFCT study collecting the molecular profile of 17 664 NSCLC has been used. The prevalence of multiple alterations and of each association was calculated. Impact on prognosis (overall survival, OS), response to targeted or conventional treatments (progression free survival, PFS and objective response rate, ORR) were established and compared with the population of patients harboring single mutations and full wild-type.
Results:
We identified 162 (0.9%) patients with double genetic alterations and 3 with triple alterations. Multiple mutations involved preferentially KRAS (67.3%), PI3K (53.3%) and EGFR (42.4%). Patients with multiple alterations were male (56.4%) with a median age of 66.7 and essentially adenocarcinoma (83.6%). More never-smokers were observed in comparison with patient with singles alterations (34.7 vs. 25.8 %, p<0.001). OS was not significantly different between single and multiple alterations whatever the type of mutations. Patients with EGFR/KRAS and EGFR/PI3K mutated tumors had worse PFS after biomarker analysis than patients with EGFR single mutation (7.1 and 7.1 months vs. 14.9 months, p=0.02 and 0.002, respectively). Concomitant mutations in patients harboring ALK rearrangement had little impact on OS (17.7 months vs. 20.3 months, p=0.57) or PFS (10.3 months vs. 12.1 months, p=0.93). Patients harboring KRAS mutations with another alteration had similar OS (13.4 vs. 11.2 months, p=0.28), PFS (6.4 months vs. 7.2 months, p=0.78) and ORR to first-line chemotherapy (41.7% vs. 37.2%) to those only harboring KRAS mutations.
Conclusion:
With almost 1% of patients harboring multiple genomic alterations, the dogma of mutually exclusive mutations should be reconsidered. Double mutations do not significantly decrease OS but alter PFS under first line treatment for EGFR mutated patients. Therapies targeting the dominant oncogene remain generally active in this setting.
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OA10.07 - Report on Liquid Biopsies from Advanced Lung Adenocarcinoma Patients and Correlation with Their Tumor Biopsy Profiles (ID 4826)
11:00 - 12:30 | Author(s): E.S. Santos, L.E. Raez, L.D.C. Castillero, C. Marana, B. Hunis
- Abstract
- Presentation
Background:
Liquid biopsy (LBx) has emerged as an alternative tool for the management of advanced lung cancer patients (pts) identifying driver mutations, and hence, improving personalized medicine. There are still controversial issues such as standardization, validation of different technologies, concordance with tissue molecular profile results (TMPR), and others. LBx offers many advantages including non-invasive, bypass tumor heterogeneity, an opportunity for serial measurements to evaluate response or early recurrence, and others.
Methods:
Guardant 360 was analyzed in 100 consecutive stage IV or recurrent lung adenocarcinoma (adeno) pts. Guardant 360 is a panel of 70 genes including single nucleotide variations, amplifications, translocations, and short insertions/duplications/deletions in exons 19 and 20 of the EGFR, and others. Cell-free DNA (cfDNA) is extracted from plasma and genomic alterations are analyzed by massively parallel sequencing of amplified target genes. TMPRs from each subject was obtained or recovered for comparison with their LBx counterparts. TMPRs from this cohort was developed in different CLIA laboratories
Results:
69 pts were females; median age 72 (range, 27-99). 84/100 pts had at least 1 genomic alteration by LBx (range, 1-10). Most common abnormalities found in LBx were: TP53 (37 pts), EGFR (35 pts), NF1 (20 pts), KRAS (12 pts), MET (14 pts). From this 84 pts with + LBx results, 67 pts (80%) had TMPRs for comparison. Main reason for lack of TMPRs: insufficient tumor (19/100; 19%). For comparison between the 2 modalities, we considered all pts with available results in both tests; hence, 81 pts were used to compare tumor biopsy (TBx) vs. LBx. 37 pts out of 81 (46%) had at least 1 similar genomic abnormality found in both TBx and LBx, respectively. Most of the concordance was in EGFR alterations (19/28; 68%). LBx caught 16 additional EGFR genomic aberrations not being identified by TBx. A total of 35 EGFR genomics aberrations were identified in LBx; 16/35 EGFR mutations found in LBx were actionable and 5 of these 16 actionable EGFR mutant cases were only found in LBx not in TBx.
Conclusion:
LBx offers an alternative to identify genomic alterations. Still, insufficient tumor is the major reason for lacking of TMPRs. EGFR mutations are the most common actionable mutations found in LBx; also, it has a high correlation with TBx (68%). LBx identified more gene abnormalities than TBx, and in some cases, the actionable EGFR mutations were found only in LBx sample.
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OA10.08 - Discussant for OA10.05, OA10.06, OA10.07 (ID 7080)
11:00 - 12:30 | Author(s): F. Cappuzzo
- Abstract
- Presentation
Abstract not provided
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Author of
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-046 - Afatinib Benefits Patients with Confirmed/Suspected EGFR Mutant NSCLC, Unsuitable for Chemotherapy (TIMELY Phase II Trial) (ID 4195)
14:30 - 15:45 | Author(s): J. Spicer
- Abstract
Background:
Afatinib is licensed for EGFR-mutant NSCLC without prior TKI therapy, but its efficacy and toxicity in patients unsuitable for platinum-doublet chemotherapy is unknown. One previous study suggested that TKIs could benefit medically unfit EGFR-mutant East Asian patients. We conducted the first such study in a Western population.
Methods:
Single arm phase-II trial. Eligible patients with histologically confirmed NSCLC, comorbidities precluding chemotherapy, with either: (i) confirmed EGFR-mutation and PS 0-3, or (ii) suspected EGFR-mutation (no suitable tissue for genotyping or failed genotyping), but never/former-light smoker, adenocarcinoma and PS 0-2. Patients received oral afatinib (20-40mg daily) until disease progression/toxicity. CT scans performed 4 weeks after starting treatment then every 8 weeks in first year until progression, thereafter every 12 weeks. Primary endpoint was 6-month RECIST-defined progression-free-survival (target 30%).
Results:
39 patients were recruited across 14 UK centres (March 2013-August 2015). Median age 72 years (range 36-90); 30 females, 9 males; 20 confirmed and 19 suspected EGFR-mutant; 8 former and 11 never smokers (among suspected EGFR-positives); 1,1,7,30 in each stage IA,IIIA,IIIB,IV; and 27 PS 0-1, 12 PS 2-3. As of July 2016, 7 patients were still taking afatinib (median time on drug 11 months, range 10-16), and 11 stopped for toxicity. 23/39 patients had at least one grade ≥3 afatinib-related toxicity (all gd3, except two with gd4 [sepsis and hypokalemia], one fatal pneumonitis), mainly: n=13 diarrhoea; n=4 vomiting; n=3 dehydration; n=3 mouth ulcer, all expected for afatinib, and unsurprising in this unfit group. The table shows efficacy. 6-month PFS rate (58%) far exceeded the 30% target; similarly for patients with confirmed (74%) or suspected (41%) EGFR-mutation.Efficacy (26 PFS events, 21 deaths)
Rate (95%CI) at month Alive & progression-free Overall-survival All patients (n=39) 6 58% (43-74) 74% (60-88) 12 34% (18-50) 64% (48-80) Median, months (95%CI) 7.9 (4.6-10.2) 15.5 (10.9-25.1) Confirmed EGFR mutant (n=20) 6 74% (55-94) 85% (69-100) 12 47% (24-70) 85% (69-100) Median, months 10.2 (5.9-not estimable) Not reached Suspected EGFR mutant (n=19) 6 41% (19-64) 63% (41-85) 12 21% (0.1-41) 42% (18-66) Median, months 4.4 (2.6-8.0) 10.9 (3.9-21.0) Lower 95%CI for all 6-month PFS-rates exceed the pre-specified 15% minimum rate. 13% patients survived ≥18 months. 23% patients did not progress <12 months
Conclusion:
The toxicity rate was higher compared to that in fitter patients, but afatinib seems to improve PFS and OS in unfit EGFR-mutant NSCLC, and in suspected-positive patients who would otherwise only receive best supportive care.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-003 - TAX-TORC: The Novel Combination of Weekly Paclitaxel and the Dual mTORC1/2 Inhibitor AZD2014 for the Treatment of Squamous NSCLC (ID 4803)
14:30 - 15:45 | Author(s): J. Spicer
- Abstract
Background:
The dual mTORC1/2 inhibitor AZD2014 has multiple effects on cell growth, apoptosis, angiogenesis and metabolism in cancer cells. AZD2014 increases the efficacy of paclitaxel in preclinical models, including patient derived xenografts. These data and clinical responses in the dose escalation arm of the TAX-TORC study led to an expansion cohort of 40 patients with squamous non-small cell lung cancer (sqNSCLC).
Methods:
Patients, of ECOG performance status 0-1, with sqNSCLC who had received at least one line of platinum-based chemotherapy were eligible for the study. Paclitaxel was dosed once weekly at 80mg/m[2], 6 weeks out of 7. AZD2014 was dosed BD, 3 days per week starting with the paclitaxel dosing. The cohort was started at 50mg AZD2014 BD.
Results:
Thirty-two patients have been treated, 24 male/8 female with median age 68 years. The median number of previous treatments was 1 with 6/32 (19%) having received a prior taxane (docetaxel or paclitaxel). Analysis of data from the first 17 patients, by the safety review committee, showed that fatigue, skin rash and diarrhoea were the most common toxicities in 59%, 47% and 41% patients respectively. The majority of toxicities were CTCAE grades 1 or 2 (112/123, 91%) and reversible with AZD2014 interruption or reduction. However, there were 9 grade 3 and 4 toxicities and 2 incidences of grade 5 respiratory infection. There were 2/17 (12%) responses though patients often stopped early due to toxicity. Following the safety review, the dose of AZD2014 was reduced to 25mg BD which is a pharmacodynamically active dose associated with fewer toxicities. Fifteen additional patients have subsequently been treated at this lower dose. Their most common toxicities were anaemia, alopecia and fatigue in 47%, 47% and 40% patients respectively. There have been no grade 5 events and only 8/78 (10%) grade 3 or 4 toxicities. The response rate in this cohort is 5/15 (33%) and recruitment is ongoing. Archival samples and circulating free DNA at baseline are being assessed with targeted next generation sequencing to explore putative predictive biomarkers for response and resistance.
Conclusion:
We have established a tolerable dose and schedule for the combination of weekly paclitaxel and AZD2014. The promising response rate of 33% in previously treated sqNCSLC patients warrants further investigation. The study is supported by AstraZeneca, Cancer Research UK, Experimental Cancer Medicine Centre and NIHR Biomedical Research Centre Initiatives.
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-037 - Impact of Sarcomatoid Component in Patients with Biphasic Mesothelioma: Review of 118 Patients (ID 5104)
14:30 - 15:45 | Author(s): J. Spicer
- Abstract
Background:
Biphasic mesothelioma has a poor prognosis. There is no clear evidence on the role of multimodality treatment in patients with biphasic mesothelioma. The aim of this study was to analyse the impact of pathological features on survival, to determine which patients may benefit from multimodality treatment.
Methods:
Between January 2005 and December 2015, 214 patients with biopsy-proven biphasic mesothelioma were retrospectively identified to fulfil our inclusion criteria. The primary outcome was survival measured from time of diagnosis. Two slides were reviewed for each patient by a specialist thoracic pathologist. Slides were stained with Hematoxylin and Eosin (H+E) and the immunohistochemically-stained slides were digitally scanned and analysed using a Hamamatsu Nanozoomer scanner (Hamamatsu ‘NDP.View2’). The proportion of epithelioid and sarcomatoid components on each slide was mapped and its area in mm[2] recorded as a percentage of the total tumour area studied. Necrosis and lymphovascular invasion were analyzed. Patients with no slides available were excluded from the analysis (n=96). All eligible patients (n=118) were followed up until May 2016.
Results:
One hundred and eighteen patients were included in the analysis, 106 (89.9%) were male with a median age of 73 (range 53 - 91). Twenty-eight patients (23.7%) underwent Pleurectomy Decortication (PD) and 90 patients received medical treatment alone, either with chemotherapy or best supportive care. The median overall survival (OS) was 11.2 months (range 0.3 – 36.2). At 1 year and 2 years, 49.1% and 6.4% of patients were alive respectively. Univariable analysis revealed both age and PD to be associated with improved survival (p=0.004 and p=0.004). Patients treated with PD had OS of 12.8 months (range 5.6 - 36), compared to 9.2 months (range 0.3 – 31.8) in patients receiving medical treatment alone. No lymphovascular invasion was identified in any specimen. Necrosis was not correlated with survival (p=0.76). The proportion of epithelioid (p=0.45) or sarcomatoid (p=0.60) component within the specimen did not correlate significantly with overall survival. This remained true when patients undergoing surgical PD (epitheloid p=0.42 and sarcomatoid p=0.60) and medical treatment (epitheloid p=0.43 and sarcomatoid p=0.11) were analysed as separate subgroups.
Conclusion:
The prognosis for patients with biphasic mesothelioma remains poor, even after multimodality treatment including pleurectomy decortication (PD). However, necrosis and the proportion of sarcomatoid histology is not helpful in selecting patients with more favourable prognosis, who may benefit from a multimodality approach.
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SH05 - WCLC 2016 Scientific Highlights - Chemotherapy, Targeted Therapy and Immunotherapy of Advanced NSCLC (ID 487)
- Event: WCLC 2016
- Type: Scientific Highlights
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:J. Skřičková, M. Samarzija
- Coordinates: 12/07/2016, 07:30 - 08:30, Hall C1
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SH05.02 - Targeted Therapy of Advanced NSCLC (ID 7130)
07:30 - 08:30 | Author(s): J. Spicer
- Abstract
- Presentation
Abstract not provided
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