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J.P. Van Meerbeeck
Moderator of
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MS 11 - New Approaches to Combined Modality Therapy for Stage III Disease (ID 29)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 4
- Moderators:D. Jablons, J.P. Van Meerbeeck
- Coordinates: 9/08/2015, 14:15 - 15:45, 605+607
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MS11.01 - The Future of Radiation Therapy in Combined Modality Therapy (ID 1896)
14:15 - 15:45 | Author(s): R. Dziadziuszko
- Abstract
- Presentation
Abstract not provided
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MS11.02 - Future Role of Surgery (Timing, Patient Selection, and New Techniques) (ID 1897)
14:15 - 15:45 | Author(s): W. Weder
- Abstract
- Presentation
Abstract:
The optimal management of locally advanced NSCLC is discussed controversially and depends from various aspects including the extend of N2 disease and/or T-stage as well as the patients risk profile and preference and the institutional experience. Therefore existing guidelines need a balanced modification during the tumorboard taking into account the different aspects relevant for the patient’s outcome and hence to define the best individualized treatment. Due to the lack of fully convincing randomized trials and the diversity of phase II studies and especially the heterogeneity of the study population, it is not surprising that the available evidence is interpreted differently and discussed controversially. Survival data may differ widely between studies and an explanation is often elusive. Patient selection is among other factors the key for differences in outcome. Unfortunately N2 disease is often imprecisely described. Several authors have proposed that N2 disease should be divided into subgroups. The question, whether N2 disease is resectable, cannot be answered easily in borderline situations since several co-founding factors play a role. The question includes at least four different aspects. The first aspect is resectability. The surgeon has to answer if the affected lymph nodes are completely removable. This question is a prerequisite and is typically answered by analysing images especially the CT or PET/CT by an experienced surgeon. The second and even more critical aspect relates to the question if local resection is useful for the patient since N2 disease may be the tip of an iceberg and indicate more than just locally advanced disease and rather a disease with systemic spread of tumor cells to other organs. The third aspect is the response rate of the tumor and mediastinal lymph nodes to neoadjuvant chemo- or chemo-radiotherapy. Finally the fourth consideration has to take into account the risk benefit ratio for the patient regarding the treatment. It is relevant for the decision making to evaluate to what risk the patient is exposed when a lobectomy or pneumonectomy is performed after neoadjuvant therapy. There are subgroups in stage IIIA (N2) which can be defined in which treatment recommendations are agreed among most oncologists, surgeons and radiotherapists. Microscopic N2 found unexpectedly during surgery and a radical resection of the tumor as well of the lymph nodes is possible and tolerated by the patient, surgery should be completed and adjuvant therapy is recommended. On the other hand in cases of bulky multilevel N2 at initial diagnosis and especially persistent after neoadjuvant therapy, surgery is not generally indicated since the patient will not experience a profit. The main controversy occurs in cases with initially diagnosed N2 disease at either a single or in some adjacent stations but surgically resectable. These patients are recommended to undergo neoadjuvant chemo- or chemo-radiotherapy followed by surgery most cases but direct surgery followed by adjuvant treatment is justified in single station N2 without extranodal disease. Definitive chemo-radiotherapy is reserved for those who are not completely resectable or with a high perioperative mortality. In general, these patients require a lobectomy with a complete mediastinal lymphadenectomy. In locally advanced stages, many surgeons still prefer to do these operations though a thoracotomy and in only a smaller percentage of patients can be operated minimal invasively by VATS. The invasiveness of the approach (VATS or open) is in any case of less importance than the completeness of the resection. Pneumonectomy should be avoided whenever possible and reconstructive techniques with bronchial-and or vascular reconstructions (sleeve resections) should be considered. These techniques can be done safely, even after induction chemo-or chemoradiotherapy. However, there are clear situation, when a pneumonectomy is necessary to achieve a complete resection and this should be considered, when the patient tolerates it functionally. Treatment of patients with locally advanced lung cancer is a challenge and requires the expertise of specialists from each discipline who respect the benefit and limitations of each individual technique in order to define the best individual treatment.
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MS11.03 - New Systemic Approaches (Targeted Therapies and Immune Therapies) (ID 1898)
14:15 - 15:45 | Author(s): H. Borghaei
- Abstract
- Presentation
Abstract:
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MS11.04 - Overview of Current International Randomized Trials (ID 1899)
14:15 - 15:45 | Author(s): S. Ekman
- Abstract
Abstract:
Overview Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with regard to tumor extent, prognosis and treatment options. Surgery is indicated in some patients, but the majority of patients receive radiotherapy and chemotherapy alone. The standard of care for unresectable stage III NSCLC patients with a good performance status consists of concurrent chemoradiation. The chemotherapy regimen usually consists of a platinum doublet and radiation doses of at least 60 Gy is standard. The prognosis for these patients remains dismal with a median survival time of 15-22 months and the need for improved treatment approaches is urgent. The optimal choice of chemotherapy and radiation dose and the schedules for these have been under investigation but is still not clearly defined. Radiation dose escalation studies have not resulted in better outcomes and with potentially harmful effects. Clinical studies of targeted agents in unselected patient groups, including therapies against epidermal growth factor receptor (EGFR) and angiogenic factors, have not been successful. The recent advances in molecularly targeted therapies together with technological advances in radiotherapy opens up for novel treatment strategies with potentially improved outcomes and less toxicity. This presentation will give an overview of randomized studies incorporating new approaches to combined modality therapy in stage III disease, including immune therapy with PD-1/PD-L1 inhibitors, inhibitors of EGFR and ALK as well as proton radiotherapy.
Author of
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MINI 24 - Epidemiology, Early Detection, Biology (ID 140)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 2
- Moderators:J. Creaney, M. Carbone
- Coordinates: 9/08/2015, 16:45 - 18:15, 102+104+106
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MINI24.08 - Breath Analysis by Ion Mobility Spectrometry Allows Discrimination of Pleural Mesothelioma Patients From Controls (ID 1508)
16:45 - 18:15 | Author(s): J.P. Van Meerbeeck
- Abstract
Background:
Despite the use of asbestos has been banned in many countries, 125 million people worldwide are still exposed to asbestos and at risk for developing malignant pleural mesothelioma (MPM). Since MPM is a lethal tumor, with diagnosis mainly at advanced stage due to non-specific symptoms and investigations, it is thought that only an early diagnosis will improve patient’s outcome (van Meerbeeck et al., 2011). Breathomics has emerged as a new research field, allowing to detect volatile organic compounds (VOCs) in breath which can be used as non-invasive markers for disease (Lamote et al., 2014). We investigated if asbestos induces VOCs and how breath VOCs could help discriminating MPM patients from occupational asbestos-exposed and non-exposed controls.
Methods:
Twenty-three MPM patients, ten healthy asbestos-exposed (AEx) individuals and twelve healthy non-exposed (HC) persons were included. After a fasting period of 2 hours before the breath sampling, participants breathed tidally for 3 minutes through a mouthpiece connected to a bacteria filter. Subsequently, ten ml alveolar air was sampled via a CO~2~-controlled ultrasonic sensor and analyzed using the BioScout Multicapillary Column/Ion Mobility Spectrometer (MCC/IMS, B&S Analytik, Dortmund, Germany). Per subject a background sample was taken. VOCs were visually selected and their intensity (V) was calculated via on-board VisualNow 3.7 software. After calculating the alveolar gradient, we performed a lasso regression in R to search for peaks that have the most discriminative power to distinguish MPM patients from controls. Predictions were made by leave-one-out cross-validation. The use of breath VOCs on the diagnostic performance was investigated by ROC-analysis.
Results:
Eighty-nine VOCs were selected in breath and background samples. The VOCs P25, P8 and P7 were able to discriminate HC from AEx controls with 91% accuracy (AUC~ROC~=0.95), yielding a sensitivity, specificity and positive (PPV) and negative predictive value (NPV) of respectively 90%, 92%, 90% and 92%. MPM patients were discriminated from AEx by the VOCs P5, P3, P30, P1 and P54 with 82% accuracy (AUC~ROC~=0.73), yielding a sensitivity, specificity and PPV and NPV of respectively 91%, 60%, 84% and 75%. When discriminating MPM patients from pooled HC and AEx controls, the VOCs P5, P3 and P1 were found to be important, yielding 73% accuracy (AUC~ROC~=0.71) and a sensitivity, specificity and PPV and NPV of respectively 70%, 77%, 76% and 71%.
Conclusion:
Breath analysis can discriminate MPM patients from healthy asbestos-exposed persons with 82% accuracy and from combined asbestos-exposed and non-exposed controls with 73% accuracy while healthy asbestos-exposed persons can be discriminated from non-exposed persons with 91% accuracy. The VOCs P25, P8 and P7 seem markers for asbestos-exposure while VOCs P5, P1 and P3 seem linked to MPM pathogenesis after exposure. For screening and to rule out diagnosis, a high sensitivity and NPV are mandatory and to rule in diagnosis, a high specificity and PPV are mandatory, which can enrich a population at risk for follow-up with (annual) CT scans or chest radiography. Hence, our results hold promise to use the breath test for screening of asbestos-exposed healthy seniors.
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MINI24.11 - Expression of PD-1 and Its Ligands in Human Malignant Pleural Mesothelioma (ID 1676)
16:45 - 18:15 | Author(s): J.P. Van Meerbeeck
- Abstract
- Presentation
Background:
The discovery of immune checkpoint receptors as cytotoxic T lymphocyte antigen-4 (CTLA-4) and more recently programmed death-1 (PD-1) introduced a new era in cancer immunotherapy. Immune checkpoints are responsible for controlling and inactivating the immune system in order to avoid autoimmunity and prevent tissue damage. PD-1 is expressed primarily on activated effector T lymphocytes. Its natural ligands are programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2). Expression of PD-L1/PD-L2 on tumor cells or in stroma impairs effector T lymphocyte activity within the tumor microenvironment. Trials with antibodies that block the ligand-immune checkpoint interaction have shown promising results in several cancer types.Data on few mesothelioma patients suggest that blocking immune checkpoints could offer new opportunities for treatment of this very aggressive tumor.. We investigated PD-1, PD-L1 and PD-L2 expression in MPM. Furthermore the effect of interferon-gamma (IFNg), an important cytokine for immune-mediated tumor control, on their expression pattern was analyzed.
Methods:
Flow cytometry and immunohistochemistry (IHC) were used for the expression of PD-1, PD-L1 and PD-L2 on human primary MPM and T cells and on MPM cell lines that cover the three major histological subtypes of of MPM, i.e. epitheloid (M28, H2795, H2818), sarcomatoid (VAMT-1, H2731, H-Meso-1) and mixed (NKI04, MSTO-211H) mesothelioma cells. The effect of stimulation with IFNg on expression of PD-1 and its ligands was measured.
Results:
PD-1 surface expression was found on T cells and not on MPM tumor cells, corresponding to literature showing that PD-1 is only expressed on T cells, B cells and macrophages. Different expression patterns were observed regarding PD-L1 and PD-L2. Flow cytometry showed significant PD-L1 expression on all the epitheloid and sarcomatoid mesothelioma cell lines. Two out of three cell lines tested positive for PD-L2, both for the epitheloid and the sarcomatoid subtype. The mixed cell lines were negative for PD-1 and its ligands. Following IFNg stimulation, PD-L1 and PD-L2 expression was induced or upregulated on all cell lines. Primary MPM cells showed variable expression of PD-L1. IHC data for PD-1 and PD-L1 expression correspond to the flow cytometry results.
Conclusion:
Taken together, these data on PD-1, PD-L1 and PD-L2 expression on human MPM cells and T cells support further investigation of the expression profile of the immune checkpoint PD-1 and its ligands in MPM patients samples. We are currently performing this using multicolor flow cytometry and IHC.
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MINI 38 - Biology and Prognosis (ID 167)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:R. Tsuchiya, M. Wynes
- Coordinates: 9/09/2015, 18:30 - 20:00, 702+704+706
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MINI38.05 - Discussant for MINI38.01, MINI38.02, MINI38.03, MINI38.04 (ID 3449)
18:30 - 20:00 | Author(s): J.P. Van Meerbeeck
- Abstract
- Presentation
Abstract not provided
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.02 - Safety Results of the Consolidation Phase of a Phase III (PROCLAIM): Pemetrexed, Cisplatin or Etoposide, Cisplatin plus Thoracic Radiation Therapy followed by Consolidation Cytotoxic Chemotherapy in Locally Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 645)
10:45 - 12:15 | Author(s): J.P. Van Meerbeeck
- Abstract
- Presentation
Background:
Standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many patients die from recurrent disease, indicating that new treatment strategies are needed.
Methods:
PROCLAIM is a phase III trial comparing overall survival in patients with unresectable stage III nonsquamous NSCLC receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation (Arm A) versus etoposide+cisplatin (EtoCis) and concurrent radiotherapy for 2 cycles followed by consolidation with a platinum-based doublet of choice for up to 2 cycles (Arm B). Possible consolidation therapies in Arm B were EtoCis, vinorelbine+cisplatin (VinCis), and paclitaxel+carboplatin (PacCarb). Overall efficacy and safety results for the intent-to-treat population will be presented in a separate disclosure. Safety was a secondary objective. Interim safety results for the concurrent phase were previously presented. Here we present safety results for the consolidation phase. Treatment-emergent adverse events (TEAEs) were assessed according to the Common Terminology Criteria for Adverse Events (v3.0, CTCAE). TEAE incidences were compared using Fisher’s exact test (two-sided α=0.05).
Results:
Of 598 randomized patients, 555 were treated in the concurrent phase (Arm A: N=283; Arm B: N=272), most of whom (Arm A: n=229 [80.9%]; Arm B: n=202 [74.3%]) continued on to the consolidation phase (Arm B patients: EtoCis [33.5%], PacCarb [26.8%], VinCis [14.0%]). Baseline characteristics, including age, gender, performance status, smoking status, stage, and origin, were well-balanced across arms. Percentages of patients in Arm A completing ≥2, ≥3, and 4 consolidation cycles were 95.2%, 84.3%, and 73.4%, respectively. Percentages of patients in Arm B completing 2 consolidation cycles (maximum) were EtoCis (89.0%), PacCarb (93.2%), and VinCis (86.8%). Mean dose intensities for pemetrexed, etoposide, vinorelbine, cisplatin, paclitaxel, and carboplatin were 95.4%, 94.0%, 84.2%, 91.2%, 88.7%, and 92.7%, respectively. More patients in Arm B, compared to Arm A, experienced dose reductions, dose omissions, and cycle delays. Patients in Arm B reported more grade 3/4/5 drug-related TEAEs than Arm A (51.0% versus 31.0%, p<0.001; Table). Rates of drug-related serious AEs were similar between groups (Arm A: 14.4%; Arm B: 13.4%).Drug-related Grade 3/4/5 TEAEs Occurring in ≥2% of Patients (or of Clinical Relevance) in the Consolidation Phase
CTCAE Arm A (N=229) n (%) Arm B (N=202) n (%) Neutrophils 27 (11.8) 76 (37.6)* Leukocytes 19 (8.3) 29 (14.4) Hemoglobin 6 (2.6) 9 (4.5) Platelets 5 (2.2) 10 (5.0) Febrile neutropenia 7 (3.1) 7 (3.5) Lymphopenia 8 (3.5) 5 (2.5) Pneumonitis/pulmonary infiltrates 5 (2.2) 2 (1.0) Fatigue 2 (0.9) 4 (2.0) Pneumonia 5 (2.2) 0 Esophagitis 0 3 (1.5) *p<0.001, Fisher’s exact test. Note: Of the TEAEs listed here, only one case (0.4%, Arm A, pneumonia) was grade 5.
Conclusion:
During the PROCLAIM consolidation phase, most patients were able to complete the planned number of cycles in either arm, with the highest dose intensity corresponding to pemetrexed. Pemetrexed consolidation had a significantly lower incidence of drug-related grade 3/4/5 TEAEs than the platinum doublets in Arm B. A more detailed analysis of Arm B (by treatment regimen) is underway.
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P1.10 - Poster Session/ Advocacy (ID 228)
- Event: WCLC 2015
- Type: Poster
- Track: Advocacy
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.10-006 - Defining a Standard Set of Patient-Centered Outcomes for Patients with Lung Cancer (ID 78)
09:30 - 17:00 | Author(s): J.P. Van Meerbeeck
- Abstract
Background:
Value-based healthcare improves outcomes while controlling costs. Registries and clinical trials frequently capture survival outcomes for lung cancer, but a unifying set of outcomes that matter to patients is lacking. Our objective was to define a Standard Set of multi-dimensional patient-centered health outcomes for measuring, comparing, and improving lung cancer treatment quality. This Set applies to all patients with newly diagnosed lung cancer, including non-small cell and small-cell lung cancer, treated with either curative or palliative intent.
Methods:
The International Consortium for Health Outcomes Measurement (ICHOM) convened an international, multi-disciplinary working group of medical oncologists, surgeons, radiation oncologists, pulmonologists, palliative care specialists, registry experts, patient representatives, and specialist nurses to review existing data and practices. Using a modified Delphi method, the group developed a consensus Set of important outcomes and case-mix variables for risk adjustment to enable meaningful benchmarking.
Results:
The outcome variables included in the Standard Set are overall survival, disease-specific mortality, cause of death, and treatment-related mortality. We recommend that complications during or within six months of treatment be collected. Patient reported outcomes should be tracked regularly using the EORTC QLQ-C30 core quality of life questionnaire and lung-cancer specific module (EORTC QLQ-LC13). Baseline demographic, clinical, and tumor information is also included in the Standard Set to improve interpretability of comparisons.
Conclusion:
We defined a Standard Set of outcomes that we believe should be measured in all patients with lung cancer. The Set provides a universal rubric for outcome comparisons, with the ultimate goal of improving the value of care. The Lung Cancer Standard Set is made possible through the generous support of the Alliance of Dedicated Cancer Centers
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.04-092 - Sequencing of Actionable EGFR Mutations from PtDNA in NSCLC: A Feasibility Study of Non-Invasive Analysis of Sensitivity to TKI (ID 984)
09:30 - 17:00 | Author(s): J.P. Van Meerbeeck
- Abstract
Background:
In ~10 % of Caucasian patients with non-small cell lung cancer (NSCLC), the presence of an activating epidermal growth factor receptor (EGFR)-mutation has resulted in a more favourable prognosis by its exquisite sensitivity to a targeted treatment with tyrosine kinase inhibitors (TKI’s). However, in up to 20% of those patients, the presence of "driver" alterations cannot reliably be established due to an inadequate diagnostic sample and/or impossibility to re-biopsy a patient. Activating EGFR-mutations can be accurately detected in plasma with a high concordance to matched tumour tissue with allele-specific PCR assays of plasma tumor DNA (ptDNA). This ‘liquid biopsy’ can replace response to treatment, allow detection of early relapse in the follow-up and estimate prognosis. The aim of this study is to assess the feasibility of detecting ptDNA in patients with EGFR mutations, to assess the concordance of ptDNA levels to mutations in matched tissue samples and to correlate ptDNA levels with clinical response or relapse after start of TKI-treatment.
Methods:
Tumour tissue samples of 20 patients (10 with/10 without activating EGFR-mutations), was assessed for the presence of the respective mutation in matched ptDNA, obtained either at presentation or during follow up. DNA was extracted from aliquots (1ml) of plasma with the use of QIamp circulating nucleic acid kit (Qiagen). The target DNA is amplified and detected on the cobas z 480 analyzer using the amplification and detection reagents provided in the cobas EGFR Mutation Test kit. The concordance was estimated with Bayesian variables.
Results:
26 tissue and 34 plasma samples were collected from 20 Caucasian patients with median age of 67 years (54 to 84), 60% female, 30% non-smokers, 100% adenocarcinomas and 95% histologically or cytologically confirmed stage IV NSCLC. The median number of samples per patient was 3 (2 - 5). In the tissue samples 6 patients had an exon 19 deletion, 1 had exon 18 mutation, 2 had exon 20 mutation and in 1 patient a simultaneous exon 19 deletion and T790M mutation. The Bayesian characteristics of ptDNA determination are as follows:A: at sample level ( n = 34) B: at study population level (n = 20) 1. Prevalence of mutation 8.8% 10% 2. Sensitivity 12.5% 20% 3. Specificity 100% 100% 4. PPV 100% 100% 5. NPV 32.2% 55% 6. Accuracy 38% 60% 7. Concordance 11.5% 7.7%
Conclusion:
Detection of ptDNA in EGFR-positive patients is feasible. However, ptDNA mutation testing by cobas[R] 4800_Blood Test was not reliable due to the low analytical sensitivity and the heterogeneity of the patient population. Further studies with other methods as next-generation sequencing or digital droplet PCR are warranted.
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P2.04-094 - Exosomal MiRNA Analysis of Non-Small Cell Lung Cancer (NSCLC) Liquid Biopsies. Mirror of the Disease Status?: Proof of Concept Study (ID 1395)
09:30 - 17:00 | Author(s): J.P. Van Meerbeeck
- Abstract
Background:
The discovery of the alterations in EGFR, c-Met or ALK in NSCLC has driven the development of targeted-drug therapy using tyrosine kinase inhibitors (TKIs). To optimize the use of these TKIs, the discovery of new biomarkers for early detection and disease progression is needed. The exosomes extracted from blood samples could be non-invasive and regularly updated biomarkers. Here we analyze selected exosomal miRNAs to evaluate its biomarker potential in NSCLC.
Methods:
1 ml of serum/plasma sample from 11 NSCLC patients, with different mutations and treatments (and 6 healthy donors as controls), were used as exosome sources. Exosome were isolated through commercial-kit or D~2~O/sucrose density-gradient ultracentrifugation. After exosome characterization (Western-Blot, Transmission Electron Microscopy) a panel of miRNAs (30b-5p, 30c-5p, 103,195,221-3p,222-3p), correlated with NSCLC disease (Garofalo et al, 2013), was analyzed. The miRNAs profile analysis was performed through TaqMan Real-Time PCR and mir-1228-3p was used as endogenous control. The data was processed according to the formula 2[-ΔΔct]. Control values are used as baseline and results are shown in logarithmic scale (figure).
Results:
Patients without molecular alterations (WMA): The levels of miR-30b-5p/30c-5p/103/221-3p/222-3p were down-regulated relative to the healthy controls. The patient with docetaxel treatment (P2) has an increased down-regulation of these miRNAs compared to the non-treated patient (P1). Patient with BRAF G464V: We observed an increased up-regulation of miR-30b-5p/30c-5p/103/221-3p/222-3p just after stopping Erlotinib treatment (P4a) compared with one month after the treatment (P4b). Patients with C-Met 3+ over-expression: We detected an increase of expression of miR-30b-5p/30c-5p and a decrease of expression of mir221-3p/222-3p in a patient treated with Crizotinib (P6) compared to a non-treated patient (P5). Patients with EGFR (exon 19 del): We observed a decrease of expression of mir221-3p/222-3p in a patient treated with Afatinib beyond progression (P8) compared to a non-treated patient (P7). Patients with ALK t(2p23): We detected a decrease of expression of miR-30b-5p/30c-5p/103 compared to healthy controls. No differences between treated (P9-P11) and non-treated (P3) patients were observed. Nevertheless, mir221-3p/222-3p differs significantly between patients treated with Ceritinib one week (P10) and one month (P11) after the treatment was started.
Conclusion:
This panel of exosomal miRNAs derived from patients with varying mutations is responsive to different treatments. The down-regulation of miR-30b-5p/30c-5p in exosomes of patients with WMA and ALK t(2p23) mutations, mirrored the reported low levels of these miRNAs in NSCLC tissue (Zhong et al.,2014). Follow-up analysis to correlate clinical progression and exosome miRNAs profile is currently ongoing. Figure 1
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P3.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 211)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.02-040 - PEARL: Pathologic Effect of NeoAdjuvant Stereotactic Ablative Body Radiotherapy (SABR) in Operable Early Stage Lung Cancer (ID 918)
09:30 - 17:00 | Author(s): J.P. Van Meerbeeck
- Abstract
Background:
SABR is considered a valid alternative to surgical resection in stage IA NSCLC (Senan, TLO 2013). However, doubts persists regarding the risk of local recurrence as lymph node staging is suboptimal and the completeness of pathological response is not verified (Van Schil, TLO 2013).
Methods:
We conducted a prospective phase 2 trial in functionally operable patients with NSCLC, staged cIA after PET/CT and endosonographic staging, who provided informed consent for neoadjuvant SABR, followed by VATS resection of primary tumour and draining lymph nodes.
Results:
We report on 1 patient, after which the trial was prematurely closed. This 57 year old smoker was incidentally diagnosed with a cT1bN0M0 adenocarcinoma in the middle lobe (2.9 x 2.1 cm) and EBUS-confirmed tumour-free ipsilateral hilar and mediastinal lymphnodes. 3 weeks after receiving 20 Gray on the tumour bed on days 1/4/7 each, he underwent a VATS middle lobectomy with systematic lymph node sampling. The resection specimen showed a completely resected 2.5 cm vital adenocarcinoma with invasion of 1/3 hilar lymph nodes (ypT1bpN1M0R0Pl0). 4 cycles of adjuvant cisplatin-based chemotherapy were uneventfully administered and patient remains in complete remission 4 years after resection.
Conclusion:
This prospective case report challenges the completeness of pathological response and of lymph node staging with SABR. Comprehensive bio-imaging will be presented at the meeting.
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P3.07 - Poster Session/ Small Cell Lung Cancer (ID 223)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.07-001 - Anaplastic Lymphoma Kinase (ALK) Gene Rearrangement in Small-Cell Lung Cancer (SCLC): A Single Center Experience (ID 924)
09:30 - 17:00 | Author(s): J.P. Van Meerbeeck
- Abstract
Background:
In small-cell lung cancer little is known about harboring an ALK translocation [1, 2]. The aim of this study was to investigate the prevalence of ALK expression and rearrangement in patients with SCLC.
Methods:
In this retrospective series, archival tissue from 17 treatment naïve patients with SCLC and neuroendocrine tumors was analyzed to detect ALK expression by immunohistochemistry (IHC) in all samples. Cut-off value for positivity was similar as in non-small-cell lung cancer (NSCLC): focally strong staining of the tumor cells Fluorescent in-situ hybridization (FISH) with Vysis LSI ALK probe was performed in the IHC positive cases [3]. The ALK FISH positive cases were submitted for exome sequencing (NGS) (Illumina MiseQ).
Results:
Of the 17 patients 9 were male and 8 female. Of these 17 patients 12 had a SCLC, 3 a neuroendocrine tumor, and 2 a neuroendocrine carcinoma. Three specimens could not be analyzed. Six of 17 specimens were ALK IHC positive, of which one neuroendocrine tumor, one neuroendocrine carcinoma and 4 of the SCLC.
Conclusion:
The IHC expression of ALK suggests a possible role of ALK-TKI in the treatment of SCLC. Mature FISH and NGS data will be presented at the meeting.
