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K. Monkhorst
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OA13 - Immunotherapy in Malignant Pleural Mesothelioma: Current Status of Trials and New Approaches (ID 392)
- Event: WCLC 2016
- Type: Oral Session
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
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OA13.01 - A Phase II Study of Nivolumab in Malignant Pleural Mesothelioma (NivoMes): With Translational Research (TR) Biopies (Abstract under Embargo until December 6, 7:00 CET) (ID 3881)
14:20 - 14:30 | Author(s): K. Monkhorst
- Abstract
- Presentation
Background:
No studies have reported any survival benefit in recurrent MPM. We examined the effect of nivolumab, in patients who presented with progressive disease and agreed to have biopsies taken before and during treatment.
Methods:
In this single center, phase II study, patients received nivolumab (3mg/kg q2w) until progression or toxicity. The primary endpoint was an improvement of disease control rate at 12 weeks of 20 to >40% compared to historic control according to a Simon two-stage design. A total of 33 patients were planned with paired biopsies at week -1 and 6 according to treatment start. PD-L1 status and other biomarkers were analyzed.
Results:
From 09-2015 until 06-2016, 38 patients were included with 33 having paired biopsies; 4 were not evaluable. There were no treatment related death and DCR at 12 weeks was 50%. Five patients had a confirmed PR; 12 had SD and 17 PD. Three patients showed pseudo-progression. Grade 3 toxicity occurred in 8 patients leading to discontinuation of the treatment in 4. The table shows the patients/tumor details. PD-L1 ≥1% was expressed in 9/32 evaluable patients with 2/9 having a confirmed PR at 12 weeks.
Conclusion:
Nivolumab in 2[nd] or later lines in recurrent MPM met the primary endpoint. The toxicity was mild and long lasting results were observed. A clear correlation between PD-L1 expression and response was obeserved.Outcome Age mean 66 yrs (51-81) M/F 28 / 6 Epithelial/mixed/non epithelial 28 / 4 / 2 PR/SD/PD 5 / 12 / 17 PD-L1 + (1-10; 10-25; 25-50; >50%) 2 / 1 / 3 / 3 Correlation PR/SD/PD according to PD-L1 expression <1% : 3/8/12 1 - 10% : 0/1/1 10-25% : 0/0/1 25-50% : 1/1/1 > 50% : 1/1/1 Correlation PR/SD/PD with histology Epithelioid : 4/9/15 Mixed : 1/2/1 Non-epithelial : 0/1/1
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-025 - Evaluation of NGS and RT-PCR Methods for ALK Assessment in European NSCLC Patients: Results from the ETOP Lungscape Project (ID 5001)
14:30 - 14:30 | Author(s): K. Monkhorst
- Abstract
Background:
The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%, depending on population and detection method. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase-polymerase chain reaction (RT-PCR) has been advocated and most recently the advent of targeted Next-Generation Sequencing (NGS) for ALK and other fusions has become possible. This is one of the first studies comparing all 4 techniques in resected NSCLC from the large ETOP Lungscape cohort.
Methods:
96 cases from the ETOP Lungscape iBiobank (N=2709) selected based on any degree of IHC staining (clone 5A4 antibody, Novocastra, UK) were examined by FISH (Abbott Molecular, Inc.; Blackhall, JCO 2014), central RT-PCR and NGS. H-score 120 is used as cutoff for IHC+. For both RT-PCR and NGS, RNA was extracted from the same formalin-fixed, paraffin-embedded tissues. For RT-PCR, primers were used covering the most frequent ALK translocations. For NGS, the Oncomine™ Solid Tumour Fusion Transcript Kit was used, allowing simultaneous sequencing of 70 ALK, RET and ROS1 specific fusion transcripts associated with NSCLC, as well as novel ALK translocations using 5’-3’ ALK gene expression ‘Imbalance Assay’.
Results:
NGS provided results for 90 cases, while RT-PCR for 77. Overall, 70 cases have results for all 4 methods, with fully concordant 60 (85.7%) cases (49 ALK-, 11 ALK+). Before employing the ‘Imbalance Assay', in 5 of the remaining 10 cases, NGS differs from the other methods (3 NGS-, 2 NGS+), while in the other 5, NGS agrees with RT-PCR in all, IHC in 2, and FISH in 1. Using the concordant result of at least two of the three methods as true negative/positive, the specificity and sensitivity of the fourth is 96/94/100/96% and 94/94/89/72% for IHC/FISH/RT-PCR/NGS, respectively (incorporating imbalance: NGS sensitivity=83%). Imbalance scores are presented here for 18 NGS- cases: 9 ‘NGS-/FISH+/IHC+’, 9 ‘NGS-/FISH-/IHC-‘. Among the ‘NGS-/FISH+/IHC+’, there is strong evidence of imbalance in 4 cases (score’s range: 0.0144-0.0555), uncertain in 5 (range: 0.0030-0.0087), and no evidence (scores≤0.0004) in the 9 negative cases.
Conclusion:
NGS is a useful screening tool for ALK rearrangement status, superior to RT-PCR when RNA yield is limited. When using NGS, it is critically important to integrate the 5’-3’ imbalance assay and to confirm with one or more additional methods in the ‘imbalance’ cases. Data further highlight the possibility of missing actionable rearrangements when only one screening methodology is available.
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P3.01 - Poster Session with Presenters Present (ID 469)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.01-009 - A Prospective Study of 'Spread through a Knife Surface' (STAKS) in Non-Small Cell Lung Cancer Resection Specimens (ID 4694)
14:30 - 14:30 | Author(s): K. Monkhorst
- Abstract
Background:
An extraneous tissue contaminant on a slide is called a floater. Spread Through Air Spaces (STAS) is in the WHO classification considered as a form of invasion in lung adenocarcinoma. The artifactual spread of tissue fragments during lung specimen sectioning was recently described and termed Spreading Through A Knife Surface (STAKS).1 The purpose of this study was to prospectively examine lung resection specimens for the presence and frequency of STAKS.
Methods:
A prospective, multi-institutional study of NSCLC lobectomy and pneumonectomy resection specimen was performed from January 1 –July 1, 2016. Prosection, sampling and scoring of displaced fragments was undertaken in a systematic manner. The first cut was made with a clean long knife, the second cut was made in a parallel plane to the first cut, without cleaning the knife. Four tissue blocks were sampled: Block 1: first cut, upper part; Block 2: first cut, lower part; Block 3: second cut, upper part; Block 4: second cut, lower part. From these formalin fixed and paraffin embedded tissue blocks a superficial complete H&E stained slide was examined for the presence of displaced tissue fragments at 10x or 20x. A displaced fragment was scored as STAKS if the tissue fragment was at least 0.5 mm from the tumor or if it was on the pleural surface in the plane of the second cut. Benign and malignant STAKS were separately noted.
Results:
A total of 41 resection specimen were included in this study. The mean number of malignant STAKS for blocks 1-4 was 0.36, 1.44, 1.86 and 1.95, respectively and for benign STAKS the mean number was 0.11, 0.11, 0.13 and 0.25, respectively. Almost all STAKS were intra-alveolar. Comparison of malignant STAKS in block 1 (before the tumor was reached) with blocks 2-4 (containing tumor) was significant with p-values (p=0.003 Friedman’s test and post-hoc comparisons p=0.031, p=0.002 and p=0.005, respectively). For benign STAKS no difference was identified (p=0.23). The chance of malignant STAKS seemed to be higher when tumor was cut fresh than when cut after formalin fixation.
Conclusion:
The morphologic definition of STAKS is not different from STAS. This prospective study confirms the presence of benign and malignant STAKS. The presence of malignant STAKS is an artifact and increases with each and every knife cut during tissue sectioning. 1) Thunnissen et al. ArchPatholLabMed2016,140(212-220)
