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Isabelle Opitz
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ES23 - Beyond the TNM (ID 194)
- Event: WCLC 2020
- Type: Educational Session
- Track: Staging
- Presentations: 1
- Moderators:
- Coordinates: 1/31/2021, 10:30 - 11:30, Scientific Program Auditorium
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ES23.04 - Revision of N Descriptors Should NOT Include Microscopic vs Bulky Mets, # of Mets vs Stations, Nodal Zones, etc (ID 4035)
10:30 - 11:30 | Presenting Author(s): Isabelle Opitz
- Abstract
- Presentation
Abstract not provided
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MA06 - Molecular Developments and Novel Treatments in Mesothelioma and Thymoma (ID 134)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 2
- Moderators:
- Coordinates: 1/30/2021, 14:15 - 15:15, Scientific Program Auditorium
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MA06.03 - Phosphorylated Ribosomal Protein S6, Correlation With Characteristics and Clinical Outcome in Patients With MPM: Results from ETOP Mesoscape (ID 2260)
14:15 - 15:15 | Presenting Author(s): Isabelle Opitz
- Abstract
- Presentation
Introduction
Malignant pleural mesothelioma (MPM) is an aggressive malignancy with increasing prevalence and poor prognosis. The European Thoracic Oncology Platform (ETOP) Mesoscape project was designed to address clinical, pathological, and molecular characteristics of MPM patients and their impact on outcome, along with having formalin-fixed paraffin embedded tumour tissue available for central analysis. In previous studies the phosphorylated ribosomal protein S6 (pS6), which is a downstream target of PI3K /mTORC1 signaling, was associated with clinical outcome, and low pS6 immunoreactivity was significantly correlated with longer progression free survival in other MPM patients. Correlating pS6 with the clinical as well as pathological information in Mesoscape allows researchers to improve the knowledge and facilitate decision-making in patients with MPM.
Methods
A biobank with fully annotated tissue samples was established for ETOP Mesoscape, and Tissue Micro Arrays (TMAs) were constructed. Expression of phospho-S6 (p-S6, Ser240/244, Cell Signaling Technology, 1:50 dilution) was explored in the ETOP Mesoscape cohort. Immunohistochemical evaluation of the TMAs was conducted by two independent observers in a blinded manner. The staining intensity was semi-quantitatively scored 0 (negative), 1 (weak), 2 (moderate), or 3 (strong). Furthermore, the percentage of cells with any positivity was proportionally scored 0 (0%), 0.1 (1%–9%), 0.5 (10%–49%), or 1.0 (50% and more). An aggregate H-score was obtained by multiplication of intensity with percentage staining (final range: 0-3 per core). The final H-score was determined by averaging the H-scores of all the cores from the same patient. Patients’ classification as pS6-high/low, was based on median H-score.
Results
Up to 14 July 2020, the ETOP Mesoscape included pS6 IHC results on 269 of the 499 patients from 10 centers, diagnosed between 1999-2018. The remaining cases are currently undergoing pS6 scoring.
Overall, patients in the Mesoscape database are primarily men (84%), of 0/1 ECOG Performance status (46/46%), with known previous exposure to asbestos (75%) and a median age of 64 years. The primary histology of included tumours is epithelioid (72%), followed by biphasic (22%) and sarcomatoid (6%). Clinical staging is available for 77%. The stage distribution (I/II/III/IV) is 14/29/42/15%.
Calretinin and WT1 are detected in the vast majority of patients tested (Calretinin: 97%; WT1: 89%). Also, 90% (of those tested) are CK5/6 positive, 91% D2-40 positive and 97% Pan-CK positive. Palliative treatment has been administered in 41%.
PS6-high patients (128 patients with H-score>1.375) are significantly associated with higher age, more T-stage of 3/4, and higher percentage of right localization compared to pS6-low patients (141 patients with H-score≤1.375). Overall survival (OS) is non-significantly different between pS6-low and pS6-high patients (medians: 21.4 months; 95%CI:[15.3-23.4] and 17.8 months; 95%CI:[15.1-20.7], respectively; log-rank p=0.61]. In the multivariate Cox model, pS6 is also non-significant (p=0.31), while gender, histology, and treatment strategy are the only significant survival predictors.
Conclusion
Based on preliminary data, high pS6 expression is associated with higher age and T-stage; effect in survival is non-significant. Updated and additional results on the expression and clinical significance of pS6 from the full ETOP Mesoscape cohort will be presented at the conference.
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MA06.06 - Intracavitary Cisplatin-Fibrin followed by Irradiation after Lung Sparing Surgery in a Rat Model of Malignant Mesothelioma (ID 2167)
14:15 - 15:15 | Author(s): Isabelle Opitz
- Abstract
- Presentation
Introduction
Localized treatment after tumor resection in malignant pleural mesothelioma (MPM) is aiming for better local tumor control. Here we tested the safety and efficacy of combination treatment with intracavitary cisplatin-fibrin (cis-fib) plus hemithoracic irradiation (IR), applied after lung sparing surgery, in an orthotopic immunocompetent rat model.
Methods
We randomized male F344 rats into five groups (cis-fib (n=9), 10Gy IR (n=6), 20Gy IR (n=9), cis-fib+10Gy IR (n=6), cis-fib+20Gy IR (n=9)). Sub-pleural (parietal) tumor implantation was performed on day 0 with 1 million syngeneic rat mesothelioma cells (IL45-luciferase). We detected tumor nodule formation in all animals by bioluminescence imaging (BLI) on day 8. Tumors were resected on day 9 followed by treatment with intracavitary cis-fib or NaCl-fib. On day 12, CT guided local irradiation in a single high dose (dose rate: 3Gy/min) of the former tumor region, resembling IMRT in human patients, was applied. We monitored animal’s health status daily and tumor growth every 3 days by BLI.
Results
None of the animals, whether with radiotherapy alone or in combination with cis-fib, showed any signs of pulmonary side effects. None had reduced pulmonary functions, measured by increased breathing or the appearance of blue or white colored ears/extremities/eyes assuming desaturation. No weight loss was observed after 10Gy IR, either alone or in combination with cis-fib. Treatment with a single dose of 20Gy IR or cis-fib+20Gy IR caused weight loss on the day after treatment but all animals regained weight 2 days thereafter. No deterioration of body conditioning or activity score were observed in the immediate post-interventional phase. Regarding efficacy, we detected comparable tumor growth in animals treated with 10Gy IR compared to no IR (cis-fib) group. Thus, we decided to escalate to 20Gy after treating 6 animals/group. Three days after treatment with 20Gy IR (day 15), we detected a significant difference in tumor growth in IR alone compared to cis-fib+IR group (mean tumor growth (%) 539 vs 252; p=0.04). On day 21, there was a significant difference in tumor growth between cis-fib vs cis-fib+IR treated tumors (mean tumor growth (%) 2295 vs 660; p=0.01) (figure1).
Conclusion
Irradiation alone and in combination with local intracavitary cis-fib application in rats is safe up to a dosage of 20Gy. The administration of local 20Gy radiotherapy in combination with cis-fib enhances tumor control while only minimally (and short term) affecting animal’s well-being. These data suggest a promising effect of combined local treatment with cis-fib+IR for MPM.
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P22 - Mesothelioma, Thymoma and Other Thoracic Malignancies - Case Reports (ID 136)
- Event: WCLC 2020
- Type: Posters
- Track: Mesothelioma, Thymoma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P22.03 - Not Every FDG Avid Spot is Tumor (ID 1113)
00:00 - 00:00 | Presenting Author(s): Isabelle Opitz
- Abstract
Introduction
Surgical resection of malignant pleural mesothelioma following induction chemotherapy provides to date the best treatment approach in selected cases. There are patients with exceptionally long freedom from recurrence following multimodality treatment (1). Follow-up imaging is difficult to interpret, even in the era of PET-CT scans. In the present case, local recurrence was suspected eight months after extended pleurectomy/decortication (EPD) following induction chemotherapy.
Methods
A 66- year old patient was diagnosed with epithelioid malignant pleural mesothelioma of the left hemithorax. The patient underwent platin-based induction chemotherapy with the addition of pemetrexed and a left sided EPD and intraoperative application of cisplatin-fibrin within our clinical phase II study. The peri- and postoperative phase was uneventful.
Results
Eight months after the initial operation the patient underwent repeated surgical revisions with VAC dressings due to soft tissue infection within the former thoracotomy and involvement of the 7th rib. The resulting defect was covered with a serratus flap. The microbiological work up revealed an osteomyelitis with Aspergillus niger. Antimycotic therapy was established and planned to administer for at least 6-12 months, depending on the patient`s clinical and inflammatory status. Three months later the a combined positron-emission tomography and computed tomography (PET/CT) scan showed a progressive metabolic activity with a maximum standard uptake value (SUVmax) of 12,2 at the 1st rib and the adjoining sternum, suspicious of local recurrence (picture). This was first seen eight months postoperatively in a PET/CT scan. Another surgical resection of the first rib followed by a coverage with pectoralis muscle flap was performed. The definite histology showed no signs of tumor relapse, but another florid purulent osteomyelitis.
Red arrow marks the FDG activity with a SUVmax of 12, 2
Conclusion
Although, local recurrence remains the determining factor after multimodality therapy approach in MPM patients, not everything that shows progressive metabolic activity is tumor. Histological work up needs to be obtained to give an accurate statement.
