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S. Peeters
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MINI 01 - Pathology (ID 93)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:W.A. Franklin, A.G. Nicholson
- Coordinates: 9/07/2015, 10:45 - 12:15, Mile High Ballroom 2c-3c
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MINI01.11 - Transcriptome Sequencing of Tumor vs. Surrounding Non-Malignant Lung Tissue in Non-Small Cell Lung Cancer (ID 1765)
10:45 - 12:15 | Author(s): S. Peeters
- Abstract
Background:
Both the response and the therapeutic ratio of targeted agents in NSCLC may depend on the expression of the target molecules in the tumor and the surrounding non-malignant lung tissue. We therefore performed transcriptome analysis and investigated correlations with histology, gender, age, CRP level and smoking status as well as evaluated the differential pathway expression in primary resected NSCLC and the surrounding non-malignant lung of the same patient.
Methods:
Transcriptome sequencing was performed on the primary tumor and distant lung tissue of the same patient from resection specimens of NSCLC patients. Differential gene expression between different conditions was identified using the statistical algorithms Cufflinks, EdgeR and DeSeq. Differential expression with P-values <0.05 after Benjamini-Hochberg correction was considered significant. Pathway analysis for overall tumor versus distant lung tissue was performed with the PANTHER gene classification platform using the Cufflinks, DeSeq and EdgeR differentially expressed gene sets as input.
Results:
Twenty-five patients were studied, 19 males and 6 females, with a median age of 69 years. Ten were current smokers, 14 former smokers (>4 weeks before surgery) and 1 non-smoker. Eleven patients had squamous cell carcinoma, 14 adenocarcinoma. A heat map with the results for the most commonly targeted genes in NSCLC is represented in figure 1. When compared to distant lung tissue, PD-L1 was downregulated in tumor tissue of adenocarcinoma and active smokers, but not in squamous cell carcinoma or ex-smokers. Internal control of tumor tissue of squamous vs. adenocarcinoma and ex-smokers vs. active smokers shows an important trend towards a higher expression of PD-L1 in squamous cell carcinoma and ex-smokers in both Cufflinks and EdgeR algorithms. Additional pathway analysis revealed 188 differentially regulated pathways. The most notable were downregulation of VEGF signaling, angiogenesis and B and T cell activation in tumor tissue when compared to distant lung tissue. Figure 1
Conclusion:
Our first results show a higher expression of PD-L1 in squamous tumors than in adenocarcinoma and a higher expression in tumors of ex-smokers than in those of active smokers. This may have consequences for the therapeutic ratio with anti-PD-L1 treatment. Downregulation of VEGFR-genes in tumor tissue was observed across almost all conditions. We will make this data more complete by adding methylation data as well as immunohistochemistry for protein localization.
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.11 - Optimization of Gross Tumour Volume Definition in Lung-Sparing Volumetric Modulated Arc Therapy for Pleural Mesothelioma (ID 2860)
16:45 - 18:15 | Author(s): S. Peeters
- Abstract
- Presentation
Background:
High dose lung-sparing pleural radiotherapy for malignant pleural mesothelioma (MPM) is difficult. Given the steep dose gradient with volumetric modulated arc therapy (VMAT), accurate target delineation is critical. The optimal imaging modality to define radiotherapy target volumes has not been studied in depth. This is the aim of the present study.
Methods:
Twelve consecutive patients with a histopathological diagnosis of stage I-IV MPM (6 left-sided and 6 right-sided) were included. CT scans with intravenous (IV) contrast, [18]F-FDG PET/CT scans, MRI scans (post-contrast T1-weighted and T2-weighted) and diffusion-weighted images (DWI) were obtained and downloaded from the institutional database onto a standalone image fusion workstation (MIM Software Inc., Cleveland, OH, USA) for image registration and contouring. CT scans were rigidly co-registered with ~18~FDG-CT-PET, with MRI scans and with DWI scans. Four sets of pleural GTVs were defined: 1) a CT-based GTV (GTV~CT~); 2) a PET/CT-based GTV (GTV~CT+PET/CT~); 3) a T1/T2-weighted MRI-based GTV (GTV~CT+MRI~); 4) a DWI-based GTV (GTV~CT+DWI~). Only the pleural tumor was contoured; mediastinal nodes were excluded. In each of the 4 co-registrations, a “quantitative” and a “qualitative” (visual) evaluation of the volumes were performed. “Quantitative” evaluation was carried out through the coefficient of variation (COV; the ratio between the standard deviation [SD] and the mean: a measure of the dispersion of a distribution) and the Jaccard index (the ratio between the union and the intersection between two volumes: a measure of overlap). “Qualitative” evaluation consisted of a visual identification of any additional tumor site in each of the 4 obtained co-registrations.
Results:
Compared to CT-based GTV definition, PET/CT identified additional tumour sites in 12/16 patients. Compared to either CT or PET/CT, MRI and DWI identified additional tumour sites in 15/16 patients. Additional tumour sites were mainly the parietal pleura, the diaphragm and the chest wall. Mean GTV~CT~, GTV~CT+PET/CT~, GTV~CT+MRI~ and GTV~CT+DWI~ (+SD) were respectively 630.1 mL (+302.81), 640.23 (+302.83), 660.8 (+290.8) and 655.2 mL (+290.7). Mean Jaccard index was lower in MRI-based contours versus all the others.
Conclusion:
To the best of our knowledge, this is the first study showing that the integration of the MRI (T1/T2-weighted) and DWI into the target volume definition in lung-sparing hemi-thoracic VMAT in MPM may allow to improve the accuracy of target delineation and reduce the likelihood of geographical misses.
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P1.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 224)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.08-006 - Lung Toxicity after Post-Operative Radiotherapy after EPP for Mesothelioma and Pneumonectomy for Non-Small Cell Lung Cancer (ID 2863)
09:30 - 17:00 | Author(s): S. Peeters
- Abstract
Background:
Our hypothesis is that MPM patients treated with post-operative RT after EPP are more prone to develop lung toxicity compared to non-small cell lung cancer (NCSLC) patients treated with post-operative RT after pneumonectomy, since their higher baseline inflammation status.
Methods:
We retrospectively reviewed the records of 39 consecutive patients with MPM who received post-operative RT after extrapleural pneumonectomy (EPP), and of 10 consecutive patients with non-small cell lung cancer who received post-operative RT after pneumonectomy between March 2003 and March 2012 at the University Hospitals of Leuven. For MPM patients, the planning target volume was defined as the entire hemi-thorax, chest wall incisions, drain sites, and involved nodal stations. Prescription dose was 54 Gy in 2-Gy fractions delivered to the planning target volume (PTV). For NSCLC patients, the planning target volume was defined as mediastinal nodal stations according to the pathologic nodal involvement. Prescription dose was 54-66 Gy in 2-Gy fractions delivered to the PTV. Both cohorts received induction systemic chemotherapy before surgery. Primary endpoint was lung toxicity. Dyspnea was graded using the Common Toxicity Criteria (CTC) v. 4.03 and was recorded before RT, 45 days after the completion of RT and every 3 months thereafter until the completion of the follow up. Dosimetric dose-volume parameters (lung V5, lung V20, mean lung dose [MLD], mean heart dose, heart V45) were retrieved for both cohorts. The correlation between the dosimetric parameters and the toxicity (dyspnea score) was investigated.
Results:
In MPM patients, the dyspnea score was 0-1 in 24/39 patients (61.5%), 2 in 11/39 patients (28.2%), 3 in 3/39 patients (7.7%) and 4 in 1/39 patients (2.5%). No grade 5 toxicity was recorded. In NSCLC patients, only grade 0-1 dyspnea was registered (grade 0: 4/10 patients; grade 1: 6/10 patients). Mean MLD was 7.56 Gy (range: 1.60-14.80; SD: 3.65) for the MPM group and 5.96 Gy (range: 3.2-14.5; SD: 3.57) for the NSCLC group. Univariate analysis showed a significant correlation between grade > 2 dyspnea and MLD, lung V5 and lung V20.
Conclusion:
Post-operative radiotherapy after EPP is well-tolerated, with 10% of patients experiencing grade > 3 dyspnea. Strict dose-constraints should be applied when radiotherapy is administered in multimodality treatment.
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P2.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 213)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-023 - In-Field Nodal Relapse after Irradiation for Locally Advanced Non-Small-Cell Lung Cancer: Is There a Dose-Effect Relationship? (ID 3201)
09:30 - 17:00 | Author(s): S. Peeters
- Abstract
Background:
We investigated whether prescribed radiation dose is related to in-field nodal relapse. Since in-field nodal relapse is rare according to current literature, the influence of radiation dose on the incidence could be questioned.
Methods:
A retrospective analysis of prospective data was performed. Pathologic lymph nodes were registered based on RECIST 1.1 criteria. An in-field nodal relapse is defined as an increase of at least 20% of the short axis diameter and a minimum absolute increase of 2 mm, taking as reference the short axis diameter measured 3 months (+/-2 months) after radiation therapy. Three subgroups were defined based on EQD2,T (group A: EQD2,T < 50 Gy, group B: EQD2,T 50-55 Gy, group C: EQD2,T > 55 Gy). An actuarial Kaplan-Meier analysis was performed to evaluate the cumulative proportion of in-field nodal relapse per subgroup. A Cox proportional hazards regression analysis was performed to take initial nodal diameter into account.
Results:
A total of 75 patients were reviewed. Sixty-two patients (83%) had stadium IIIA/IIIB disease. Twelve patients (16%) had stadium IV NSCLC who were treated with a radical oligometastatic approach. One patient (1%) had stadium IIB disease. Sixteen patients (21%) were treated with radiotherapy alone (38% group A, 25% group B, 38% group C). Sequential chemoradiotherapy was given in 47 patients (63%) (32% group A, 45% group B and 23% group C). Twelve patients (16%) received concurrent chemoradiotherapy (33% group A, 66% group B). Group A consisted of 25 patients (median age: 65 years (range 45-88), median follow-up: 6 months (range 1-54)). Thirty-three patients were included in group B (median age: 59 years (range 45-80), median follow-up: 8 months (range 1-86)). Group C consisted of seventeen patients (median age: 67 years (range 54-83), median follow-up: 9 months (range 2-45)). In all three groups median number of follow-up CT scans is 2 (range of 1-11 for group A and C, range of 1-13 for group B). Any relapse occurred in fifty-eight patients (77,3%). Nineteen patients (33%) had a locoregional failure only. Twenty-two patients (38%) had distant failure only, either by progression of a known metastasis or occurrence of a new distant lesion. Seventeen patients (29%) had a locoregional and distant failure at once. A total of 142 lymph nodes were taken into account (55 (39%) in group A, 52 (37%) in group B and 35 (25%) in group C). The average baseline short axis diameter per group was 16,3 mm, 15,8 mm and 14,6 mm for group A, B and C respectively. An actuarial Kaplan-Meier analysis performed on all lymph nodes (n=142) showed no significant difference between subgroups (p=0,24). A Cox proportional hazards regression analysis didn’t show a significant effect of baseline nodal diameter on in-field nodal relapse (p=0,82).
Conclusion:
Prescribed radiation dose is not related to the occurrence of in-field nodal relapse. There was no relation between initial lymph node diameter and in-field nodal relapse.
