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G. Defraene
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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): G. Defraene
- 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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P1.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 212)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.03-021 - Lung Damage Quantification on CT Scans Strengthens Radiation-Induced Lung Toxicity Prediction Models (ID 2932)
09:30 - 17:00 | Author(s): G. Defraene
- Abstract
Background:
Predictive models for radiation-induced lung toxicity have shown a lack of validation and low values of area under the curve (AUC) below 0.7, for various reasons. Radiation-induced lung tissue damage scored as density changes on CT scans proved to be a less multifactorial endpoint compared to dyspnea. Its continuous variation in the patient population is an indication that it could be an expression of patient-specific radiosensitivity variation. This study explores the advantage of incorporating patient-specific lung damage measures in the classical predictive models based on mean lung dose (MLD).
Methods:
61 stage I-IV lung cancer patients treated with chemoradiotherapy were retrieved from two hospitals. Prescribed dose was 66 Gy in fractions of 2 Gy (concurrent) or 2.75 Gy (sequential). Baseline and follow-up dyspnea scores were retrospectively assessed according to CTCAE 4.0. Image analysis of the radiation-induced lung damage was performed by comparison of the baseline planning CT~0~ and the non-rigidly registered follow-up CT~fup~. The median Hounsfield Unit increase (∆HU=HU~fup~-HU~0~) was calculated per dose bin of 5 Gy. The local dose-∆HU response curve was described using a sigmoidal model. This resulted in a sigmoidal parameter D~50~ (corresponding to 50% of the saturation level of ∆HU) for each patient, as an expression of the patient-specific lung tissue radiosensitivity. Logistic models predicting dyspnea increase with respect to the baseline score were then built using MLD and D~50~ as covariates. The likelihood-ratio identified significant differences between nested models.
Results:
Dyspnea score increase by 2 grades was observed in 9 patients (14,8%), while an increase by 1 grade was observed in 29 patients (47.5%). The average timepoint of CT~fup~ was 2.3 months after end of radiotherapy. For 51 patients the sigmoidal dose-∆HU fits were acceptable (sum of squared residuals below 10 HU per datapoint on average). 10 of these patients did not show any dose response in the analysed dose range. The 41 reacting patients showed large variation in D~50 ~(median: 34.8 Gy, range: 12.1 Gy-70.0 Gy) and were further analysed. Predictive models based on MLD alone had AUCs of 0.71 and 0.65 for dyspnea increase by 1 and 2 grades respectively. Incorporating the CT damage measure D~50~ as second covariate resulted in models with 0.73 and 0.83 respectively. The advantage of incorporating D~50~ was significant in the second fit (p=0.05).
Conclusion:
A significant improvement of predictive models for radiation-induced lung toxicity was achieved using patient-specific lung damage measured on CT scans. An early detection of the patient-specific D~50~ through dedicated per-treatment imaging optimized for the detection of lung tissue changes is crucial for the clinical implementation of the model. Future work analysing more CT features could also improve the model.
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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): G. Defraene
- 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: 2
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.03-022 - Is the Radiosensitivity of the Tumour Related to That of the Lung? A CT-Based Response Analysis of Both (ID 2829)
09:30 - 17:00 | Author(s): G. Defraene
- Abstract
Background:
Lung tissue damage after radiotherapy scored as density changes on CT scans proved to be a less multifactorial endpoint compared to dyspnea. Its continuous variation in the patient population is an indication that it could be an expression of patient-specific radiosensitivity variation. This study linked patients’ lung damage measures defined on CT with tumour shrinkage.
Methods:
32 stage I-IV lung cancer patients treated with chemoradiotherapy were studied. Prescribed dose was 66 Gy in fractions of 2 Gy (concurrent) or 2.75 Gy (sequential). Image analysis of the radiation-induced lung damage was performed by comparison of the baseline planning CT~0~ and the non-rigidly registered follow-up CT~fup~. The median Hounsfield Unit increase (∆HU=HU~fup~-HU~0~) was calculated per dose bin of 5 Gy. The local dose-∆HU response curve was described using a sigmoidal model. This resulted in a sigmoidal parameter D~50~ (corresponding to 50% of the saturation level of ∆HU) for each patient, as an expression of the patient-specific lung tissue radiosensitivity. On both the CT~0~ and CT~fup~ scans, an experienced radiation oncologist delineated the tumour gross target volume (GTV). Volumetric (volume and equivalent diameter) and intensity-based (median, maximal and minimal HU) features were collected for all GTVs.
Results:
The average timepoint of CT~fup~ was 2.3 months after end of radiotherapy. For 25 patients the sigmoidal dose-∆HU fits were acceptable (sum of squared residuals below 10 HU per datapoint on average). 8 of these patients did not show any dose response in the analysed dose range. The 17 reacting patients showed large variation in D~50 ~(median: 30.9 Gy, range: 15,8 Gy-70,0 Gy) and were further analysed. Their median GTV volumes were 25.9cc (range 1.3cc-275.9cc) and 5.2cc (range 0.4cc-42.4cc) on CT~0~ and CT~fup ~respectively~.~ No correlation of tumour intensity-based features with lung D~50~ was observed. The relative diameter change of tumour however showed moderate correlation (R[2]=0.21) with lung radiosensitivity (see Figure). Patients with D~50~ below the population’s median showed a mean reduction of tumour diameter of 46.8%, while this was 30.0% in the group with high D~50 ~(p=0.03).Figure 1
Conclusion:
The patient-specific D~50~ for lung damage shows correlation with tumour shrinkage. This corroborates the hypothesis that it is a measure of intrinsic radiosensitivity. This study shows that imaging characteristics can provide independent and reproducible measures of radiosensitivity and can play a crucial role in defining patient-specific therapeutic ratio and thus treatment selection. Future radiogenomics studies could also benefit from the input of imaging.
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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): G. Defraene
- 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.
