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Luigi De Petris
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MA21 - Molecular Subtyping, CBL3, and Non Coding RNA (ID 924)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 205 BD
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MA21.07 - A Nation-Wide Population-Based Mapping of Targetable Alterations in Smoking-Independent Lung Cancer (ID 13145)
15:55 - 16:00 | Author(s): Luigi De Petris
- Abstract
- Presentation
Background
Smoking is by far the most important cause of lung cancer. However, lung cancer among never-smokers is common and increasing [1]. A smoking-independent subgroup of lung adenocarcinoma with certain molecular and clinical features exists [2-3]. Therefore, as 1st project within the Swedish Molecular Initiative against Lung cancer (SMIL) we aim to characterize never-smoking lung cancer for etiological, diagnostic and therapeutic purposes.
a9ded1e5ce5d75814730bb4caaf49419 Method
Through the Swedish National Lung Cancer Registry [1], we identified all individuals who underwent surgery for lung cancer in Sweden 2005-2014 and who were registered as never-smokers (n=540). At each study site (n=6), clinical data were reviewed by a thoracic oncologist/pulmonologist through patients’ medical charts and archived tumor tissues were retrieved and reviewed by a thoracic pathologist. For subsequent studies, we extracted DNA and RNA (using the Qiagen AllPrep kit for FFPE tissue) and constructed tissue microarrays. As a first pre-planned analysis, we performed fusion gene mapping using an RNA-based NanoString nCounter Elements assay, as previously described [4].
4c3880bb027f159e801041b1021e88e8 Result
In the first 212 (out of 540) analyzed samples, we detected 17 fusions involving ALK, 8 involving RET, and 2 involving NRG1. In addition, MET exon 14 skipping was found in 17 samples. In total, these findings involved 21% of analyzed cases. Additional results from further studies on the cohort will be presented.
8eea62084ca7e541d918e823422bd82e Conclusion
SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently collect one of the largest never-smoking lung tumor cohorts worldwide. From the first pre-planned analyses, we conclude that, in a population-based cohort of early stage lung cancer from never-smokers, druggable oncogenic fusions are frequent.
References
1. http://www.cancercentrum.se/vast/cancerdiagnoser/lunga-och-lungsack/kvalitetsregister
2. Staaf J, Jönsson G, Jönsson M, Karlsson A, Isaksson S, Salomonsson A,Pettersson HM, Soller M, Ewers SB, Johansson L, Jönsson P, Planck M. Relation between smoking history and gene expression profiles in lung adenocarcinomas. BMC Med Genomics. 2012 Jun 7;5:22.
3. Karlsson A, Ringnér M, Lauss M, Botling J, Micke P, Planck M, Staaf J. Genomic and transcriptional alterations in lung adenocarcinoma in relation to smoking history. Clin Cancer Res. 2014 Sep 15;20(18):4912-24.
4. Lindquist KE, Karlsson A, Levéen P, Brunnström H, Reuterswärd C, Holm K, Jönsson M, Annersten K, Rosengren F, Jirström K, Kosieradzki J, Ek L, Borg Å, Planck M, Jönsson G, Staaf J. Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer. Oncotarget. 2017 May 23;8(21):34796-34810.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.13-02 - ALK-Translocation and Brain Metastases: A Retrospective Study. Correlation Between Clinical Outcome, Disease Burden and Management. (ID 12949)
16:45 - 18:00 | Author(s): Luigi De Petris
- Abstract
Background
Brain metastases from non‐small cell lung cancer is often regarded as the ominous sign of disease progression .
In the ALK-translocated population, brain metastases are seen in a higher incidence, either at diagnosis or as a common site of progression for patients receiving tyrosine kinase inhibitors (TKI).
The management of brain metastases in this population remains a challenge since several methods of treatment are available. TKI-treatment, especially with second or third generation drugs can be effective but the role of radiation therapy, with either whole brain radiotherapy (wbrt) or stereotactic radiosurgery (srs), has not been fully elucidated.
A retrospective study was conducted at ou Institution in order to evaluate the frequency of brain metastases in this subggroup of patients and in order to explore clinical features associated with survival.
a9ded1e5ce5d75814730bb4caaf49419 Method
88 consecutive patients with advanced ALK+ adenocarcinoma were treated at our institution. during the perod 2011-2018. Data on CNS imaging modality, treatment strategy and outcome was collected by chart review.
4c3880bb027f159e801041b1021e88e8 Result
Cns-imaging with either MRI or CT (in 38% and 62% of the cases respectively) was performed in 73 cases. 44 patients (61%) were found to have CNS metastases (Male/female ratio 48/52%; median age 60y).
23% were found at the time of primary cancer diagnosis, 36% on time of PD on chemotherapy, 34% on PD on crizotinib and 7% at PD on 2nd gen ALKinh .
27% of the patients had 1-3 metastases, 34% 4-10 met and 39 % >10.
Pharmacological treatments in the group as a whole: chemotherapy (n=38); crizotinib (n=35); alectinib (n=10); ceritinib (n=20); brigatinib (n=3), lorlatinib (n=1).
Radiotherapy was administered in 57% as either SRS or WBRT (52/48%) .
Treatment strategies upon discover of CNS-metastes: Radiotherapy solely 27%, combination of radiotherapy and pharmacological treatment in 25%, switch to crizotinib and to 2nd gen ALKi in 18 and13 % respectively.
Median OS from the diagnosis of CNS metastasis was 29months (95% CI 11-59). 1- and 2-year survival was 61% and 51%, respectively.
Neither gender, age, timing for diagnosis of CNS metastases nor the use of radiotherapy were significant prognostic factors for OS (Cox proportional hazard analysis).
Use of 2nd gen ALKin as treatment strategy seemed to be superior to crizotinib and radiotherapy alone even if median OS not yet was reached.
8eea62084ca7e541d918e823422bd82e Conclusion
The high incidence of CNS metastases in this subpopulation of patients (Caucasian with advanced ALK+ NSCLC) was confirmed in this study. The wider implementation of 2nd generation ALKi in clinical practice will probably change the prognosis of these subjects.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.09 - Pathology (Not CME Accredited Session) (ID 975)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.09-05 - Significance of the Expression of PD-L1/PD-1 by Tumoral and Immune Cells in Non-Small Cell Lung Cancer. (ID 14241)
12:00 - 13:30 | Author(s): Luigi De Petris
- Abstract
Background
Non-Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all cases of lung cancer, including adenocarcinoma, squamous cell carcinoma and large cell carcinoma. There is solid evidence that demonstrates the existence of anti-tumor adaptive T-cell mediated immunity activation in lung tumors, indicating that lung cancers are immunogenic. PD-L1and PD-1 expression level in lung cancer may be a predictive biomarker for the use of PD1/PD-L1 inhibitors. However, the reproducibility of PD-L1 staining using different antibodies and platforms is still a matter of debate. We assessed whether PD-L1 expression in non-small cell lung cancer is associated with specific clinical features or survival using four different antibodies and if the expression of PD-1 in TILs correlates with the expression of PD-L1 in same group of cells.
a9ded1e5ce5d75814730bb4caaf49419 Method
PD-L1 and PD-1 status was assessed with IHC (AB clone SP142 and SP263 - Ventana, 22C3, 28-8 – Dako and PD-1) on archival FFPE surgical tumor specimens, arrayed on tissue microarrays (TMAs) with duplicate 1 mm cores, from Karolinska University Hospital. All patients (n = 598) underwent curative surgery between 1987 and 2015. The following cases were excluded from survival analysis (n = 89): R1 resection, early post-operative mortality, adjuvant chemo- or radiotherapy. PD-L1 staining was scored as positive if present in > 1% of tumor cells, independently of staining intensity.
4c3880bb027f159e801041b1021e88e8 Result
Patient and tumor characteristics were as follows. Median age (IQR): 68 years (27-89); gender: male/female 54%/46%; histology: squamous-cell carcinoma (SCC)/Non-squamous (N-Sq)-NSCLC/carcinoid 219 (32%)/394 (58%)/45(7%); p-stage: IA/IB/IIA/IIB/IIIA/IIIB 50%/26%/10%/10%/2%/0.2%. PD-L1 28-8 was positive in 11% of cases, Pearson Chi-square p<0.0001). PD-L1 positivity 22C3/SP263/SP142 was 10%/13%/3%. All carcinoids were negative for PD-L1. In NSCLC, PD-L1 positivity for each antibody was associated with tumor size (T1/T2-4; Fisher’s exact test, p<0.001) and grade of differentiation (G1, G2 and G3; p<0.0002). Statistically significant association between PD-L1 expression and OS was only observed using the clone SP263 (log-rank p=0.013). PD-1 expression in TILs correlates with those of PD-L1 (clone 28-8).
8eea62084ca7e541d918e823422bd82e Conclusion
In this surgical series, the clone SP142 showed less PD-L1 expression in the tumor cells. PD-L1 status was associated with tumor size, grading and only the clone SP263 showed association between its expression and survival ratio. PD-1 expression in TILs correlates with those of PD-L1.
6f8b794f3246b0c1e1780bb4d4d5dc53
