An individualized radiation dose escalation trial in non-small cell lung cancer based on FDG-PET imaging.

AIM: The aim of the study was to assess the feasibility of an individualized 18F fluorodeoxyglucose positron emission tomography (FDG-PET)-guided dose escalation boost in non-small cell lung cancer (NSCLC) patients and to assess its impact on local tumor control and toxicity. PATIENTS AND METHODS: A total of 13 patients with stage II-III NSCLC were enrolled to receive a dose of 62.5 Gy in 25 fractions to the CT-based planning target volume (PTV; primary turmor and affected lymph nodes). The fraction dose was increased within the individual PET-based PTV (PTVPET) using intensity modulated radiotherapy (IMRT) with a simultaneous integrated boost (SIB) until the predefined organ-at-risk (OAR) threshold was reached. Tumor response was assessed during follow-up by means of repeat FDG-PET/computed tomography. Acute and late toxicity were recorded and classified according to the CTCAE criteria (Version 4.0). Local progression-free survival was determined using the Kaplan-Meier method. RESULTS: The average dose to PTVPET reached 89.17 Gy for peripheral and 75 Gy for central tumors. After a median follow-up period of 29 months, seven patients were still alive, while six had died (four due to distant progression, two due to grade 5 toxicity). Local progression was seen in two patients in association with further recurrences. One and 2-year local progression free survival rates were 76.9% and 52.8%, respectively. Three cases of acute grade 3 esophagitis were seen. Two patients with central tumors developed late toxicity and died due to severe hemoptysis. CONCLUSION: These results suggest that a non-uniform and individualized dose escalation based on FDG-PET in IMRT delivery is feasible. The doses reached were higher in patients with peripheral compared to central tumors. This strategy enables good local control to be achieved at acceptable toxicity rates. However, dose escalation in centrally located tumors with direct invasion of mediastinal organs must be performed with great caution in order to avoid severe late toxicity.

Impact of motion induced artifacts on automatic registration of lung tumors in Tomotherapy.

PURPOSE: Tomotherapy MV-CT acquisitions of lung tumors lead to artifacts due to breathing-related motion. This could preclude the reliability of tumor based positioning. We investigate the effect of these artifacts on automatic registration and determine conditions under which correct positioning can be achieved. MATERIALS AND METHODS: MV-CT and 4D-CT scans of a dynamic thorax phantom were acquired with various motion amplitudes, directions, and periods. For each acquisition, the average kV-CT image was reconstructed from the 4D-CT data and rigidly registered with the corresponding MV-CT scan in a region of interest. Different kV-MV registration strategies have been assessed. RESULTS: All tested registration methods led to acceptable registration errors (within 1.3 ± 1.2 mm) for motion periods of 3 and 6 s, regardless of the motion amplitude, direction, and phase difference. However, a motion period of 5 s, equal to half the Tomotherapy gantry period, induced asymmetric artifacts within MV-CT and significantly degraded the registration accuracy. CONCLUSIONS: As long as the breathing period differs from 5 s, positioning based on averaged images of the tumor provides information about its daily baseline shift, and might therefore contribute to reducing margins, regardless of the registration method.

Assessment of tumor motion reproducibility with audio-visual coaching through successive 4D CT sessions.

This study aimed to compare combined audio-visual coaching with audio coaching alone and assess their respective impact on the reproducibility of external breathing motion and, one step further, on the internal lung tumor motion itself, through successive sessions. Thirteen patients with NSCLC were enrolled in this study. The tumor motion was assessed by three to four successive 4D CT sessions, while the breathing signal was measured from magnetic sensors positioned on the epigastric region. For all sessions, the breathing was regularized with either audio coaching alone (AC, n = 5) or combined with a real-time visual feedback (A/VC, n = 8) when tolerated by the patients. Peak-to-peak amplitude, period and signal shape of both breathing and tumor motions were first measured. Then, the correlation between the respiratory signal and internal tumor motion over time was evaluated, as well as the residual tumor motion for a gated strategy. Although breathing and tumor motions were comparable between AC and AV/C groups, A/VC approach achieved better reproducibility through sessions than AC alone (mean tumor motion of 7.2 mm ± 1 vs. 8.6 mm ± 1.8 mm, and mean breathing motion of 14.9 mm ± 1.2 mm vs. 13.3mm ± 3.7 mm, respectively). High internal/external correlation reproducibility was achieved in the superior-inferior tumor motion direction for all patients. For the anterior posterior tumor motion direction, better correlation reproducibility has been observed when visual feedback has been used. For a displacement-based gating approach, A/VC might also be recommended, since it led to smaller residual tumor motion within clinically relevant duty cycles. This study suggests that combining real-time visual feedback with audio coaching might improve the reproducibility of key characteristics of the breathing pattern, and might thus be considered in the implementation of lung tumor radiotherapy.

Helical tomotherapy for SIB and hypo-fractionated treatments in lung carcinomas: a 4D Monte Carlo treatment planning study.

PURPOSE: To evaluate the impact of intra-fraction motion induced by regular breathing on treatment quality for helical tomotherapy treatments. MATERIAL AND METHODS: Four patients treated by simultaneous-integrated boost (SIB) and three by hypo-fractionated stereotactic treatments (hypo-fractionated, 18 Gy/fraction) were included. All patients were coached to ensure regular breathing. For the SIB group, the tumor volume was delineated using CT information only (CTV(CT)) and the boost region was based on PET information (GTV(PET), no CTV extension). In the hypo-fractionated group, a GTV based on CT information was contoured. In both groups, ITVs were defined according to 4D data. The PTV included the ITV plus a setup error margin. The treatment was planned using the tomotherapy TPS on 3D CT images. In order to verify the impact of intra-fraction motion and interplay effects, dose calculations were performed using a previously validated Monte Carlo model of tomotherapy (TomoPen): first on the planning 3D CT ("planned dose") and second, on the 10 phases of the 4D scan. For the latter, two dose distributions, termed "interplay simulated" or "no interplay" were computed with and without beamlet-phase correlation over the 10 phases and combined using deformable dose registration. RESULTS: In all cases, DVHs of "interplay simulated" dose distributions complied within 1% of the original clinical objectives used for planning, defined according to ICRU (report 83) and RTOG (trials 0236 and 0618) recommendations, for SIB and hypo-fractionated groups, respectively. For one patient in the hypo-fractionated group, D(mean) to the CTV(CT) was 2.6% and 2.5% higher than "planned" for "interplay simulated" and "no interplay", respectively. CONCLUSION: For the patients included in this study, assuming regular breathing, the results showed that interplay of breathing and tomotherapy delivery motions did not affect significantly plan delivery accuracy. Hence, accounting for intra-fraction motion through the definition of an ITV volume was sufficient to ensure tumor coverage.