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Rolf Lewensohn
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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
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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 | Author(s): Rolf Lewensohn
- 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)
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-33 - An Open-Label PET-MRI Study to Determine Brain Exposure of Osimertinib in Patients with EGFR Mutant NSCLC and CNS Metastases (ID 142)
10:15 - 18:15 | Author(s): Rolf Lewensohn
- Abstract
Background
CNS metastases are associated with poor prognosis in patients with advanced NSCLC. Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations, and has demonstrated efficacy in NSCLC CNS metastases. Osimertinib has also shown superior brain exposure (preclinical/clinical), compared to other EGFR-TKIs. We report preliminary data on brain distribution of 11C-labelled osimertinib ([11C]osimertinib) in patients with NSCLC with brain metastases (BM) using positron emission tomography (PET). Early effects on BM measured by magnetic resonance imaging (MRI) is also presented.
Method
This open-label, single-centre Phase I study (NCT03463525) enrolled adult patients with EGFR-mutated advanced NSCLC and BM, as confirmed by MRI. Patients could be EGFR-TKI-naïve or have progressed on a prior EGFR-TKI with confirmed EGFR T790M. Intravenous microdoses of [11C]osimertinib and PET examinations were performed pre-dose on Day1, ~6hrs post-dose on Day2, and following ≥21 days of once-daily dosing with osimertinib 80mg. Following the 3rd PET scan, patients completed another MRI scan to investigate early effects on tumour size according to RECIST 1.1 criteria. The primary objective was determination of brain exposure of [11C]osimertinib at baseline and following treatment, in the whole brain. During PET examinations, arterial blood samples were collected to measure radioactivity/radiometabolites of [11C]osimertinib.
Result
Currently, six patients have been screened. Three enrolled, of whom two completed all imaging visits. PET examinations demonstrated rapid uptake of [11C]osimertinib into the brain and distribution into metastases; MRI scans showed significant decrease in size of brain lesions after 21 treatment days, consistent with partial response according to RECIST 1.1 criteria (Figure).
Conclusion
These early outcomes support the CNS efficacy reported in previous osimertinib studies: high brain-uptake and efficacy after a short dosing period. Further data on distribution, efficacy and PET/MRI imaging will be presented.
