Virtual Library
Start Your Search
Maria Planck
Author of
-
+
EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.14-16 - Use of Digital Droplet PCR for Detecting EGFR T790M Resistance Mutation in Plasma at Progression on TKI Therapy (Now Available) (ID 2152)
08:00 - 18:00 | Author(s): Maria Planck
- Abstract
Background
Therapy surveillance is a corner stone in advanced lung cancer clinical management. Due to the ease of sampling, analysis of tumor derived circulating DNA in plasma for treatment monitoring and decision making is desirable. Patients with tumors harboring a sensitizing EGFR mutation benefit from targeted therapy using tyrosine kinase inhibitors (TKIs). Unfortunately, the majority of patients develop resistance towards the initially administered TKI either through intrinsic mechanisms of EGFR or mutations of additional genes such as amplification of MET. Osimertinib can be administered at disease progression due to the resistance mutation T790M in EGFR. In this study we used liquid biopsy at progression after TKI treatment to assess mutational status of sensitizing and T790M mutations. In some cases, a tumor biopsy was analyzed in parallel as part of clinical management.
Method
Six 10 ml Streck Cell free BCT® tubes were collected and plasma was isolated. Cell free circulating DNA was purified and used in an ultra-sensitive ddPCR assay IBSAFE (George et al, manuscript in preparation). Both the sensitizing EGFR mutation and T790M was analyzed. In some cases, a solid biopsy was analyzed in the clinic in parallel to our plasma analysis. Patient outcome data will be collected from patient files.
Result
Eighteen of 25 patients tested positive in plasma for the previously known sensitizing EGFR mutation (72%). Twelve of 25 tested positive in plasma for T790M mutation (48%). Among plasma samples positive for the sensitizing mutation, 67% were also positive for T790M. The minor allele frequency (MAF) fraction of T790M in comparison to the sensitizing mutation varied extensively from 0.01% to 90% and also the MAF compared to total DNA varied (0.005% to 23%). Updated clinical follow up data will be presented.
Conclusion
For a subset of patients were a tumor biopsy is not feasible, a liquid biopsy could provide information about the mutational status. As the MAF vary considerably and can be very low, a highly sensitive assay such as the IBSAFE ddPCR assay, capable of confirming a mutation at a MAF as low as 0.005% is advantageous. Further, a large plasma input volume may aid in identifying patients positive for mutations at a low MAF. Updated clinical follow up data will be discussed.
-
+
MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Yuko Minami, Mary Beth Beasley
- Coordinates: 9/10/2019, 11:30 - 13:00, Tokyo (1982)
-
+
MA18.05 - Diagnostic Difference Between Neuroendocrine Markers in Pulmonary Cancers: A Comprehensive Study and Review of the Literature (Now Available) (ID 171)
11:30 - 13:00 | Author(s): Maria Planck
- Abstract
- Presentation
Background
The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non-small cell carcinomas (NSCC) is of high clinical relevance for prognosis and treatment. Diagnosis is based on morphology and immunohistochemical staining. The current WHO classification of lung tumors emphasizes synaptophysin and chromogranin A but also recommends CD56 as NE markers. The aim of the present study was to determine the diagnostic value of the insulinoma-associated protein 1 (INSM1) gene, in comparison with the established neuroendocrine markers, in pulmonary tumors.
Method
Tissue microarrays with tumor tissue from 54 resected pulmonary NE tumors and 632 NSCC were stained for INSM1, CD56, chromogranin A and synaptophysin. In a subset, gene expression data was available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 37 additional studies with data on NE markers in lung cancers from the last 15 years, whereof six with data on INSM1.
Result
Depending on cut-off level (1%+ or 10%+ positive tumor cells), the sensitivity and specificity for INSM1 to separate NE tumors from NSCC were 72-91% and 98-99%, respectively. In comparison, the sensitivity and specificity for CD56 were 85-89% and 96-98%, for chromogranin A 56-67% and 98-99%, and for synaptophysin 85-93% and 86-92%, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity (see table). INSM1 gene expression was clearly associated with NE histology.
Conclusion
The solid data of our investigation and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 or synaptophysin should be the first-hand choice to confirm high-grade NE pulmonary tumors.
Only 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.
-
+
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.14-37 - Lung Cancer in Never-Smokers: A Nationwide Population Based Mapping of Targetable Alterations (ID 2735)
09:45 - 18:00 | Presenting Author(s): Maria Planck
- Abstract
Background
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]. In an ongoing project within the Swedish Molecular Initiative against Lung cancer (SMIL) we currently characterize lung cancer in never-smokers for etiological, diagnostic and therapeutic purposes.
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, clinical data were reviewed by a thoracic oncologist or 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 first preplanned analyses, we performed fusion gene mapping using an RNA based NanoString nCounter Elements assay and mutational profiling by Next Generation Sequencing (NGS) using a 26-gene exon-focused panel, as previously described [4].
Result
Of the 540 never-smokers with surgically resected lung cancer, 69% were females and the majority of cases were adenocarcinomas. The median age at diagnosis was 69 years.
In the first 310 analyzed tumor samples, we so far detected 24 fusions involving ALK (8%), 10 involving RET (3%) and 2 involving NRG1 (<1%). In addition, MET exon 14 skipping was found in 33 samples (11%).
Furthermore, among the so far 147 cases where we have completed both the DNA and the RNA analyses, 59 tumors (40%) harbored EGFR mutations. In total, targetable alterations were revealed either by NanoString or NGS in 63% of tumors from never-smokers in our study.
Conclusion
SMIL is an ongoing nation-wide molecular research collaboration on lung cancer where we currently characterize 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, targetable oncogenic fusions and mutations 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.
-
+
P2.03 - Biology (ID 162)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.03-02 - A Single Sample Predictor of Transcriptional Lung Adenocarcinoma Subtypes: Predicting Biology and Prognosis (ID 2201)
10:15 - 18:15 | Author(s): Maria Planck
- Abstract
Background
Lung adenocarcinoma accounts for nearly 40% of all lung cancers, thereby representing the major histological subtype. Comprehensive molecular studies have proposed three molecular lung adenocarcinoma subtypes termed the terminal respiratory unit (TRU), proximal-inflammatory (PI), and the proximal-proliferative (PP) subtype based mainly on transcriptional patterns. These subtypes have been linked to molecular characteristics but also to differences in prognosis, favoring the TRU subtype compared to the PI and PP (combined PI and PP = non-TRU) subtypes. However, the method used (nearest centroid classification=NCC) to classify samples into transcriptional subtypes depends on the cohort composition, consequently struggle with e.g. reproducibility and classification of single samples. In this study, we aimed to derive a single sample predictor (SSP) of these subtypes, capable of predicting single samples irrespective of technical platforms and cohort composition.
Method
In this study, the gene expression based SSP called “Absolute assignment of breast cancer Intrinsic Molecular Subtype” (AIMS) were trained on a large combined dataset collection (n=1655, 17 datasets) with AC assignment obtained by the NCC method and tested in 5 publicly available gene expression datasets (n=977) with treatment data available. Survival analysis was performed to compare the two classification methods (AIMS vs. NCC) with overall survival (OS) as clinical endpoint. Survival curves were compared using Kaplan-Meier estimates and the log-rank test.
Result
Using AIMS, a SSP of lung adenocarcinoma transcriptional biology and prognosis was successfully trained and tested in publicly available gene expression datasets. The majority of the samples were assigned equally by the two methods. However, a minor subset (n=97) of samples were given discordant labels. The derived SSP had an accuracy of 85.5% in 977 independent validation samples for TRU vs non-TRU cases, independent of gene expression platform. Interestingly, the patient group consisting of samples classified as TRU by the NCC method and nonTRU by AIMS (TRU.nonTRU, Fig.1, orange line), showed a survival outcome more similar to the nonTRU patient group. The reverse was observed for the nonTRU.TRU patient group (Fig.1, grey line) with a survival pattern resembling that of the TRU group. Thus, on a survival basis, the discordant samples seems to be more accurately classified by the AIMS method.
Conclusion
We present a SSP for proposed transcriptional adenocarcinoma subtypes capable of predicting single samples irrespective of technical platform and cohort composition, thereby overcoming critical limitations in the applicability of gene signatures. The classifier provides refined categorization of patients with respect to prognosis, representing a prognostic predictor in lung adenocarcinoma.
-
+
P2.10 - Prevention and Tobacco Control (ID 176)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Prevention and Tobacco Control
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.10-01 - Analysis of Human Papilloma Viruses (HPV) and Human Polyoma Viruses (HPyV) in Lung Cancer from Swedish Never-Smokers (ID 2845)
10:15 - 18:15 | Presenting Author(s): Maria Planck
- Abstract
Background
A possible role for oncogenic infections in the etiology of lung cancer has been investigated in a large number of studies, with contradictory results. High-risk mucosal human papillomaviruses (HPV), recognized as being associated with cervical cancer and oropharyngeal cancer, has been suggested as a causative factor also in lung cancer [1,2], whereas other studies found no, or at most very limited, involvement of HPV in lung cancer [3,4].
To investigate human papillomaviruses (HPV) and human polyomaviruses (HPyV) as possible causative factors behind lung cancer in never-smokers, we analyzed the presence of these viruses in a subset of tumors within a larger Swedish cohort of never-smoking lung cancer patients [Swedish Molecular Initiative against Lung cancer, SMIL; Salomonsson et al. Abstract WCLC 2019].
Method
Eighty-seven surgically resected lung cancer samples from never-smokers, diagnosed 2005-2014 in Stockholm, Sweden, were analyzed by Luminex assays for the presence of 27 HPV types (including all HPV types currently regarded as high-risk types) and for 10 HPyV species (BKPyV, JCPyV, KIPyV, WUPyV, TSPyV, MWPyV, HPyV6, 7, 9, and 10).
Result
All samples were positive for the β-globin gene, confirming the presence, amplification and detection of cellular DNA. All samples were negative for the HPV types included in the assay. The only viral DNA detected in the tumors were low amounts of Merkel cell polyomavirus (MCPyV) DNA, of unknown significance, in 15 samples.
Conclusion
Our study shows no evidence for neither HPV nor HPyV in the etiology of lung cancer in Swedish never-smokers.
References
1. Syrjanen, K. Detection of human papillomavirus in lung cancer: Systematic review and meta-analysis. Anticancer Res 2012, 32, 3235-3250.
2. Ragin, C.; Obikoya-Malomo, M.; Kim, S.; Chen, Z.; Flores-Obando, R.; Gibbs, D.; Koriyama, C.; Aguayo, F.; Koshiol, J.; Caporaso, N.E., et al. Hpv-associated lung cancers: An international pooled analysis. Carcinogenesis 2014, 35, 1267-1275.
3. Koshiol, J.; Rotunno, M.; Gillison, M.L.; Van Doorn, L.J.; Chaturvedi, A.K.; Tarantini, L.; Song, H.; Quint, W.G.; Struijk, L.; Goldstein, A.M., et al. Assessment of human papillomavirus in lung tumor tissue. J Natl Cancer Inst 2011, 103, 501-507.
4. Tang K.W.; Alaei-Mahabadi B.; Samuelsson T.; Lindh M.; Larsson E. The landscape of viral expression and host gene fusion and adaptation in human cancer. Nat Commun 2013, 4, 2513.
5. Swedish Molecular Initiative against Lung cancer, SMIL; Salomonsson A. et al. Lung cancer in never-smokers: A nationwide population based mapping of targetable alterations. 20th World Conference on Lung Cancer (Barcelona, 7-10 Sept, 2019)
