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G.F. Persson
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MINI 07 - ChemoRT and Translational Science (ID 110)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:D. Raben, B. Kavanagh
- Coordinates: 9/07/2015, 16:45 - 18:15, 201+203
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MINI07.03 - The NARLAL2 Phase III Trial: Heterogeneous FDG-Guided Dose Escalation of Advanced NSCLC. A Clinical Trial by the Danish Lung Cancer Group (ID 2248)
16:55 - 17:00 | Author(s): G.F. Persson
- Abstract
- Presentation
Background:
Locally advanced lung cancer lacks effective treatment options and requires aggressive radiotherapy (RT) with higher doses. In the light of RTOG 0617, multi-center dose escalation trials should avoid increasing organ at risk (OAR) toxicity and require strict quality assurance (QA). Exploiting the predictive value of FDG-PET, sub-volumes can be dose escalated, and by implementing image-guided adaptive RT, the total treatment volume (PTV) can be reduced. Incorporating these elements, the randomized multicenter trial NARLAL2 aims at increasing loco-regional control at 30 months without increasing major toxicity.
Methods:
Figure 1 In the standard arm, the PTV is treated with a homogenous dose of 66 Gy/33 fractions. In the experimental arm, the dose is heterogeneously escalated to the FDG-PET avid volumes, with mean doses up to 95 Gy/33 fractions and 74 Gy/33 fractions to the escalated volumes in the tumor and malignant lymph nodes, respectively. The escalation dose will be limited in favor of OAR constraints. A standard and an experimental treatment plan with similar mean lung doses of maximum 20 Gy are made for each patient prior to randomization. Quality Assurance: FDG-PET scans of a standard phantom (NEMA) and PET signal processing software from all centers were compared and acceptable agreement achieved. Multicenter delineation of OARs was performed and consensus achieved. Treatment planning and adaptive strategy consensus were based on a study including five patients with repeated CT-scans, requiring several steps before the achievable level of dose escalation and the number of patients needed in the trial could be defined. Daily online tumor set-up and adaptive strategies were mandatory. A QA committee for evaluation of RT plans and treatments and a central committee for evaluation of all non-biopsy-verified recurrences were established.
Results:
A mean dose of 91,9 Gy to the FDG-PET avid part of the tumor and 80 Gy to the clinical target volume was achieved in the planning study, corresponding to 16% estimated increase in locoregional control at 30 months. Assuming a loco-regional control of 56% at 30 months in the standard arm, a total of 330 patients were needed in order to resolve this effect with a power of 80% (95% significance level). Recalculation of escalated plans on CT-scans acquired at fraction 20 revealed an increase in OAR doses of 4-7Gy for two of five patients, endorsing the need for adaptive strategies.
Conclusion:
A dose escalation trial with strict QA has been set up. Patient enrollment started January 2015.
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P3.03 - Poster Session/ Treatment of Locoregional Disease – NSCLC (ID 214)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.03-027 - Lung Cancer: Doses to Mediastinal Structures Can Be Reduced with Volumetric Modulated Arc Therapy and Deep Inspiration Breath-Hold Radiotherapy (ID 2888)
09:30 - 09:30 | Author(s): G.F. Persson
- Abstract
Background:
When thoracic radiotherapy (RT) doses are escalated, toxicity from mediastinal structures are a limiting factor (Cannon et al. JCO 2013). In this study we examined, if deep inspiration breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) can decrease the dose to lungs, heart, central bronchi and esophagus compared to free breathing (FB) RT.
Methods:
17 patients with stage III NSCLC were CT scanned in both FB (4DCT) and visually guided voluntary DIBH before radical RT. Lungs, heart, central bronchi, trachea, esophagus and heart subvolumes (coronary arteries and valves) were contoured. Three dimensional conformal (3DC) and VMAT plans were computed on FB and DIBH images. VMAT plans were optimized using constraints for target and lungs. DIBH plans were compared to FB plans. Friedman signed rank test with post-hoc Nemenyi test was applied.
Results:
GTV sizes were slightly smaller in DIBH (mean 119 vs. 132 ml, p=0.01). Lung volume increased in DIBH by median 60% (range 35-108%, p<0.0001) compared to FB. Median and range of dose parameters are listed in the table together with Friedman signed rank test p-values. Mean lung dose was in DIBH reduced with a median 3.2 Gy (p=0.002) with 3DC and 3.5 Gy (p<0.001) with VMAT. DIBH alone did not significantly alter heart, esophagus and trachea-bronchial dose parameters, but VMAT did. The largest differences were found between FB 3DC and DIBH VMAT. Mean doses to coronary arteries, tricuspid and pulmonary valves were significantly reduced with DIBH VMAT compared to FB 3DC (P=0.002-0.04). No differences were found for aortic and mitral valves. Figure 1
Conclusion:
DIBH VMAT decreased the estimated mean doses to heart, lungs, esophagus and bronchii compared to FB 3DC. Possibly, the dose to these structures could be further reduced, had the mediastinal structures been included in the VMAT optimization process. Combining DIBH and VMAT may facilitate dose escalation to target volumes or subvolumes, without decreasing mediastinal toxicity compared to current standard, FB RT.
