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Luigi De Petris
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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
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P1.14-37 - Lung Cancer in Never-Smokers: A Nationwide Population Based Mapping of Targetable Alterations (ID 2735)
09:45 - 18:00 | Author(s): Luigi De Petris
- 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.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-27 - Apparent Diffusion Coefficient (ADC) Change on Repeated Diffusion-Weighted MRI During Chemotherapy for Stage IV Lung NSCLC (ID 1896)
10:15 - 18:15 | Author(s): Luigi De Petris
- Abstract
Background
Diffusion-weighted magnetic resonance imaging (DWI) depicts the random Brownian movement of water molecules in biological tissues. The net displacement of these molecules diffusing across an area of tissue per second is the apparent diffusion coefficient (ADC). ADC has proven useful in detection, characterization and treatment response monitoring of malignant diseases and is used routinely in the investigation of cancer of the prostate. The role of MRI in the follow up of treated lung cancer remains unclear.
Previous publications have suggested that it could function as a biomarker in chemoraditherapy treated NSCLC. Very little has been published about chemotherapy treated tumours.
Method
20 patients with stage IV adenocarcinoma were enrolled between September 2014 and April 2017. They received treatment with carboplatin/placitaxel and bevacizumab (7,5mg/kg) with maintenance bevacizumab if response. Two patients, in whom the lesion proved to be too small to measure (<2 ml), were excluded.
Characteristics of the remaining 18 patients: 8 f/10m, median age 69 (51 -77), median survival 9 month (1-NR, follow up 60months) and median time to treatment failure 6 month (1-37).
DWI was performed at baseline, 2w, 4w and 16w. Four patients did not participate in the full study program. Two examinations were incomplete due to technical problems, and 8 MRI examinations were excluded due to the tumors becoming too small in size (<2 ml). A total of 57 MRI examinations were included.
Result
The ADC value at baseline varied between 950 and 1584mm2/s (median 1228).
ADC values both increased and decreased during treatment (% change at week 2 range -11 to 24%, at w4 -14 to 34%, at 16 w -27 to 10%).
The evolution of the ADC values at the different timepoints did not show any statistical significant increase or decrease (using Mean Comparison with Student t’s test, Prob>Chisq 0,2159). Proportion Hazard analysis did not show any statistical correlation between the baseline ADC value, the change in ADC value and overall survival, nor between ADC values, change in ADC values and time to treatment failure.
Conclusion
Repeated MRI in lung cancer is feasible. The clinical value of ADC measurements in the follow up of chemotherapy treated lung cancer needs further investigations.
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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): Luigi De Petris
- 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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P2.12 - Small Cell Lung Cancer/NET (ID 180)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.12-06 - Factors of Importance for Survival After Platinum Re-Challenge in Platinum-Sensitive Small-Cell Lung Cancer Patients (ID 2609)
10:15 - 18:15 | Presenting Author(s): Luigi De Petris
- Abstract
Background
Small-cell lung cancer (SCLC) patients showing sensitivity to platinum-based chemotherapy (PDCT) are usually offered the same combination at the time of tumor progression, if this occurs >3 months after the completion of the first-line treatment. However, no decision tools are available to predict what patients might benefit most from this approach. The aim of the present study was to investigate if certain clinical factors could be of prognostic relevance for re-challenge of PDCT in previously platinum-sensitive patients
Method
This retrospective study was based on patients diagnosed with SCLC in Sweden between January 2008 and February 2016. The study included patients who had received ≥ 1 cycle of PDCT in the 1st and 2nd line setting, respectively, and had “sensitive relapse”, which was defined as PFS ≥180 days after the start of first-line PDCT. The following baseline characteristics were collected; Age, Gender, Stage of the disease, presence of Brain metastasis, treatment with Consolidating thoracic radiotherapy or Prophylactic brain irradiation (PCI) after completion of 1st line PDCT and “Sensitivity days”, which was defined as the interval between the initiation of 1st and 2nd line PDCT, respectively. In addition, Performance status (PS) and Laboratory values (Hb, Na, C-reactive protein, Albumin, LDH) before starting 2nd line PDCT were compiled. The uni- and multi-variate analyses were performed using the cox proportional hazards regression model to assess the relationship between clinical characteristics and prognosis. Overall survival was defined as the interval between the initiation of 2nd line until death due to any cause.
Result
The patient cohort consisted of 101 subjects. The distribution of baseline characteristics was as follows: male/female 46/55, median age (IQR) 68y (61-72), Stage II/III/IV 3/41/57, Brain metastases present/absent 39/62, Thoracic radiotherapy Y/N 30/71, PCI Y/N 52/49, median Sensitivity days (IQR) 399 days (307-511), PS 0/1/2/3 23/38/36/4. The statistically significant independent prognostic factors for overall survival on the multivariate model were PS, LDH values (HR, 95% CI for unit increase 2.10, 1.13-3.91), PCI (HR, 95% CI for presence vs absence 0.27, 0.13-0.56) and “Sensitivity days” (HR, 95% CI for unit increase 0.15, 0.07-0.32).
Conclusion
The results of this retrospective data analysis suggest that besides PS, other clinical factors that showed robust prognostic relevance for re-challenge with PDCT in platinum-sensitive SCLC are baseline LDH values, the time elapsed between the start of 1st-line PDCT until the start of 2nd-line PDCT, which we have defined as “Sensitivity days”, and the administration of PCI after completion of 1st-line chemotherapy. These elements might potentially be taken into consideration for patient selection in this setting.
