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Matthias Guckenberger
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ES03 - Understanding and Treating Oligometastatic Diseases (ID 161)
- Event: WCLC 2020
- Type: Educational Session
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 10:30 - 11:30, Scientific Program Auditorium
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ES03.03 - Characterization and Classification of Oligometastatic Disease (ID 3977)
10:30 - 11:30 | Presenting Author(s): Matthias Guckenberger
- 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: 1
- Moderators:
- Coordinates: 1/30/2021, 14:15 - 15:15, Scientific Program Auditorium
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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): Matthias Guckenberger
- 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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P05 - Early Stage/Localized Disease - Radiotherapy (ID 114)
- Event: WCLC 2020
- Type: Posters
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P05.02 - International Delphi Consensus on Radical Thoracic Re-Irradiation for Non-Small Cell Lung Cancer (NSCLC) (ID 1647)
00:00 - 00:00 | Author(s): Matthias Guckenberger
- Abstract
Introduction
Local recurrence or second lung primaries are common indications for radical thoracic re-irradiation (re-RT), affecting approximately 700 patients in the UK annually. Re-RT is usually the only suitable curative-intent treatment but prospective evidence on toxicity, dose constraints, and optimal treatment technique is lacking. We performed a Delphi process to identify areas of consensus in re-RT for NSCLC.
Methods
An international panel of 15 radiation oncologists specialising in lung cancer participated in an initial survey on 23/09/2019 to capture their definition of re-RT, suitable patients, re-RT technique and dose constraints used. The most common responses to questions from the first survey were used to make statements which participants voted on in subsequent rounds using a 5-point Likert scale. Consensus was achieved once 75% of participants agreed with a statement. For the statements which did not reach consensus, respondents provided additional evidence/comments to refine them. In total, four surveys were performed using a web-based survey programme.
Results
All respondents completed three rounds of the survey, with the final round currently in progress. Consensus was achieved within two rounds regarding re-RT indications, patient eligibility and work-up (Table 1). In addition, agreement was reached to use stereotactic ablative body radiotherapy (SABR) if possible for re-RT. Dose constraints, due to the lack of supportive data, required three rounds to develop agreement. Several volumetric lung constraints were suggested, but due to post-radiotherapy fibrosis, it was concluded that there was insufficient evidence to form recommendations (Table 2).
Areas of controversy were how much overlap was significant when performing re-RT, what were the minimum lung function requirements and the minimum safe interval between treatments.
Table 1 Statement Degree of Consensus Indications Re-RT can be considered for suspected new lung primaries with minimal overlap with previous radiotherapy fields. 93% Re-RT can be considered for lung tumours which develop new nodal disease after an initial course of radiotherapy only to the primary tumour (therefore minimal overlap). 100% Re-RT can be considered where a lung tumour relapses locally (or develops a suspected second primary tumour with >50% overlap with the original primary tumour), but low overlap with serial structures in the thorax. 93% Patient eligibility In general, patients should have an ECOG PS of 0 - 2 to be considered for re-RT, with exceptions being made for selected PS 3 patients (e.g. SABR re-RT, or PS 3 due to non-respiratory issues). 93% Re-irradiation should be avoided in patients with interstitial lung disease. 86% Surgery should be considered in all appropriate patients being assessed for re-irradiation. 93% Work-up Essential investigations prior to commencing re-RT are: Whole body PET-CT, CT chest + contrast, and CT/MRI brain. 93-100% Table 2 Statement Degree of consensus Dose constraints For radical re-irradiation, the desirable cumulative maximum point dose constraint to the oesophagus is an EQD2 of 75Gy, although up to 100Gy is acceptable (using an a/b=3), with the volume of the oesophagus getting 55 Gray should be less than 35% (V55Gy<35%). 86% For radical re-irradiation, the desirable cumulative maximum point dose constraint to the spinal cord is an EQD2 of 60Gy (using a/b=2), provided that the initial irradiation dose to the cord did not exceed 50Gy and the interval between treatments is greater than 6 months. 80% For radical re-irradiation, the desirable cumulative maximum dose (Dmax) constraint to the aorta is an EQD2 of 115Gy (a/b=3). The desirable cumulative Dmax to the pulmonary artery is an EQD2 of 110Gy. 80% There is insufficient evidence to suggest volumetric cumulative dose constraints for the lung due to the changes in anatomy and function of the lung after an initial course of radiotherapy. 80% Technique Radical re-irradiation should be performed using highly conformal radiotherapy techniques (e.g. VMAT, Tomotherapy, Cyberknife). 100% Acceptable doses for conventionally fractionated re-RT include 60Gy in 30 fractions or 55Gy in 20 fractions once daily for NSCLC 93% SABR is the preferred re-RT technique where the tumour is not ultra-central, no nodal disease and the tumour volume is small with minimal overlap with OARs. 87% Any dose and fractionation that can safely deliver a BED >100Gy to the tumour is acceptable for radical re-irradiation with SABR. 87%
Conclusion
This Delphi process with international experts has developed key recommendations on the criteria for suitable re-RT patients, dose constraints and preferred technique. These statements can be used to develop prospective trials to provide better evidence for re-RT.
