Retrospective analysis of the impact of respiratory motion in treatment margins for frameless lung SBRT based on respiratory-correlated CBCT data-sets.

PURPOSE: To investigate the impact of respiratory motion in the treatment margins for lung SBRT frameless treatments and to validate our treatment margins using 4D CBCT data analysis. METHODS: Two hundred and twenty nine fractions with early stage NSCLC were retrospectively analyzed. All patients were treated in frameless and free breathing conditions. The treatment margins were calculated according to van Herk equation in Mid-Ventilation. For each fraction, three 4D CBCT scans, pre- and postcorrection, and posttreatment, were acquired to assess target baseline shift, target localization accuracy and intra-fraction motion errors. A bootstrap analysis was performed to assess the minimum number of patients required to define treatment margins. RESULTS: The retrospectively calculated target-baseline shift, target localization accuracy and intra-fraction motion errors agreed with the literature. The best tailored margins to our cohort of patients were retrospectively computed and resulted in agreement with already published data. The bootstrap analysis showed that fifteen patients were enough to assess treatment margins. CONCLUSIONS: The treatment margins applied to our patient's cohort resulted in good agreement with the retrospectively calculated margins based on 4D CBCT data. Moreover, the bootstrap analysis revealed to be a promising method to verify the reliability of the applied treatment margins for safe lung SBRT delivery.

Chest-MRI under pulsatile flow ventilation: A new promising technique.

OBJECTIVES: Magnetic resonance imaging (MRI) of the chest has long suffered from its sensitivity to respiratory and cardiac motion with an intrinsically low signal to noise ratio and a limited spatial resolution. The purpose of this study was to perform chest MRI under an adapted non invasive pulsatile flow ventilation system (high frequency percussive ventilation, HFPV®) allowing breath hold durations 10 to 15 times longer than other existing systems. METHODS: One volunteer and one patient known for a thymic lesion underwent a chest MRI under ventilation percussion technique (VP-MR). Routinely used sequences were performed with and without the device during three sets of apnoea on inspiration. RESULTS: VP-MR was well tolerated in both cases. The mean duration of the thoracic stabilization was 10.5 min (range 8.5-12) and 5.8 min (range 5-6.2) for Volunteer 1 and Patient 1, respectively. An overall increased image quality was seen under VP-MR with a better delineation of the mediastinal lesion for Patient 1. Nodules discovered in Volunteer 1 were confirmed with low dose CT. CONCLUSION: VP-MR was feasible and increased spatial resolution of chest MRI by allowing acquisition at full inspiration during thoracic stabilization approaching prolonged apnoea. This new technique could be of benefit to numerous thoracic disorders.

Linear-Endobronchial Ultrasound-Guided Insertion of a Fiducial Marker: A New Tool for Tracking Central Lesions.

Stereotactic body radiotherapy (SBRT) is an effective method for the treatment of localized primary lung tumors. Cyberknife, a highly accurate SBRT technique, follows the target during respiratory cycles using a metallic fiducial marker (FM) previously inserted into the lesion. Various methods have been described for the placement of an FM in peripheral pulmonary lesions; however, none of these is appropriate for mediastinal or hilar tumors. The placement of FMs in central lesions to achieve accurate SBRT is particularly relevant due to their higher mobility during respiratory and cardiac cycles. Here, we describe the use of linear-endobronchial ultrasound for the insertion of an FM marker in a centrally located metastatic melanoma, thereby allowing subsequent treatment with Cyberknife.

Results of Dose-adapted Salvage Radiotherapy After Radical Prostatectomy Based on an Endorectal MRI Target Definition Model.

OBJECTIVES: To assess the outcome of patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP). METHODS: We report on 171 relapsing patients after RP who had undergone an erMRI before SRT. 64 Gy were prescribed to the prostatic bed with, in addition, a boost of 10 Gy to the suspected local relapse as detected on erMRI in 131 patients (76.6%). RESULTS: The 3-year biochemical relapse-free survival (bRFS), local relapse-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival were 64.2±4.3%, 100%, 85.2±3.2%, 100%, and 99.1±0.9%, respectively. A PSA value >1 ng/mL before salvage (P=0.006) and an absence of biochemical progression during RT (P=0.001) were both independently correlated with bRFS on multivariate analysis. No significant difference in 3-year bRFS was observed between the boost and no-boost groups (68.4±4.6% vs. 49.7±10%, P=0.251). CONCLUSIONS: A PSA value >1 ng/mL before salvage and a biochemical progression during RT were both independently correlated with worse bRFS after SRT. By using erMRI to select patients who are most likely expected to benefit from dose-escalated SRT protocols, this dose-adapted SRT approach was associated with good biochemical control and outcome, serving as a hypothesis-generating basis for further prospective trials aimed at improving the therapeutic ratio in the salvage setting.

Sparing healthy lung by focusing the radiation beam flow onto the emphysematous regions in the treatment of lung cancer.

INTRODUCTION: Currently, routine radiotherapy (RT) planning for locally advanced lung cancer (LC) does not take into consideration the functional state of the lung. The goal of this study was to determine if it is technically feasible to integrate the sites of pulmonary emphysema (PE) into the RT planning process. METHODS: Ten patients with LC and PE treated with helical Tomotherapy© were retrospectively included. After extraction by Myrian© software based on diagnostic CT (DCT), the PE data were transferred to the treatment planning system (TPS). PE-optimized plans were performed for patients with significant PE, where the dose was focused onto the PE. We compared the PE-optimized RT plans to the initial RT plans. RESULTS: The median dose to the planning target volume (PTV) was 52 Gy (range, 36-66) in fractions of 2-3 Gy. The median PE volume was 220 cm3 (range: 12-1394), and six patients were eligible for a PE-optimized RT plan. Considering the lung without PE, the V20 and V30 variations were not significant (P > 0.05), the V5 decreased from 50% to 44% after re-planning (P < 0.05). The mean PTV D98 was 50 Gy versus 48 Gy (P < 0.05). CONCLUSION: Focusing the RT beam flow on the PE structure rather than the healthy lung appears feasible, and may be a promising technique to help preserve pulmonary function and minimize RT-related pulmonary toxicity.

Apnea-like suppression of respiratory motion: First evaluation in radiotherapy.

BACKGROUND AND PURPOSE: Compensation for respiratory motion is needed while administering radiotherapy (RT) to tumors that are moving with respiration to reduce the amount of irradiated normal tissues and potentially decrease radiation-induced collateral damages. The purpose of this study was to test a new ventilation system designed to induce apnea-like suppression of respiratory motion and allow long enough breath hold durations to deliver complex RT. MATERIAL AND METHODS: The High Frequency Percussive Ventilation system was initially tested in a series of 10 volunteers and found to be well tolerated, allowing a median breath hold duration of 11.6 min (range 3.9-16.5 min). An evaluation of this system was subsequently performed in 4 patients eligible for adjuvant breast 3D conformal RT, for lung stereotactic body RT (SBRT), lung volumetric modulated arc therapy (VMAT), and VMAT for palliative pleural metastases. RESULTS: When compared to free breathing (FB) and maximal inspiration (MI) gating, this Percussion Assisted RT (PART) offered favorable dose distribution profiles in 3 out of the 4 patients tested. PART was applied in these 3 patients with good tolerance, without breaks during the "beam on time period" throughout the overall courses of RT. The mean duration of the apnea-like breath hold that was necessary for delivering all the RT fractions was 7.61 min (SD=2.3). CONCLUSIONS: This first clinical implementation of PART was found to be feasible, tolerable and offers new opportunities in the field of RT for suppressing respiratory motion.

Reduction of Respiratory Motion During PET/CT by Pulsatile-Flow Ventilation: A First Clinical Evaluation.

UNLABELLED: Respiratory motion negatively affects PET/CT image quality and quantitation. A novel Pulsatile-Flow Ventilation (PFV) system reducing respiratory motion was applied in spontaneously breathing patients to induce sustained apnea during PET/CT. METHODS: Four patients (aged 65 ± 14 y) underwent PET/CT for pulmonary nodule staging (mean, 11 ± 7 mm; range, 5-18 mm) at 63 ± 3 min after (18)F-FDG injection and then at 47 ± 7 min afterward, during PFV-induced apnea (with imaging lasting ≥8.5 min). Anterior-posterior thoracic amplitude, SUVmax, and SUVpeak (SUVmean in a 1-cm-diameter sphere) were compared. RESULTS: PFV PET/CT reduced thoracic amplitude (80%), increased mean lesion SUVmax (29%) and SUVpeak (11%), decreased lung background SUVpeak (25%), improved lesion detectability, and increased SUVpeak lesion-to-background ratio (54%). On linear regressions, SUVmax and SUVpeak significantly improved (by 35% and 23%, respectively; P ≤ 0.02). CONCLUSION: PFV-induced apnea reduces thoracic organ motion and increases lesion SUV, detectability, and delineation, thus potentially affecting patient management by improving diagnosis, prognostication, monitoring, and external-radiation therapy planning.

Optimization of re-irradiation using deformable registration: a case study.

Re-irradiation is frequently performed in radiotherapy (RT) departments. We present an optimization methodology that takes the previous irradiation into account. A 68-year-old female patient suffering from rectal adenocarcinoma, who had previously undergone RT for metastases to the right iliac bone, presented with a recurrence of metastasis to the L5 and the left sacroiliac joint. Re-irradiation was performed using volumetric modulated arc therapy (VMAT). We proceeded to a registration of the previous RT planning CT and RT doses to the new planning CT. Virtual volumes corresponding to the intersection of the small bowel (SB) and each isodose structure were created. We calculated the maximal dose (Dmax) that each virtual structure could receive and considered them as constraints. We called this technique modified VMAT. We compared this technique with a standard VMAT plan and a three-dimensional RT plan. Using the modified VMAT technique, a total dose of 20 Gy in five fractions of 4 Gy was delivered to the planning target volume without any acute toxicity. A composite dosimetry was realized with each technique to compare the dose given to the already irradiated SB. We calculated the Dmax received by the already irradiated SB in equivalent dose of 2 Gy fractions. The Dmax was 46.8, 60 and 52 Gy for modified VMAT, standard VMAT and three-dimensional RT, respectively. Dose deformation was used to create new constraint structures to optimize the dose delivered to surrounding tissues. This methodology is readily feasible in clinical routine to optimize the re-irradiation process.

Dose-adapted salvage radiotherapy after radical prostatectomy based on an erMRI target definition model: toxicity analysis.

BACKGROUND: To assess treatment tolerance by patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an multiparametric endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP). MATERIAL AND METHODS: A total of 171 prostate cancer patients recurring after RP undergoing erMRI before SRT were analyzed. A median dose of 64 Gy was delivered to the prostatic bed (PB) with, in addition, a boost of 10 Gy to the suspected relapse as visualized on erMRI in 131 patients (76.6%). Genitourinary (GU) and gastrointestinal (GI) toxicities were scored using the RTOG scale. RESULTS: Grade ≥ 3 GU and GI acute toxicity were observed in three and zero patients, respectively. The four-year grade ≥ 2 and ≥ 3 late GU and GI toxicity-free survival rates (109 patients with at least two years of follow-up) were 83.9 ± 4.7% and 87.1 ± 4.2%, and 92.1 ± 3.6% and 97.5 ± 1.7%, respectively. Boost (p = 0.048) and grade ≥ 2 acute GU toxicity (p = 0.008) were independently correlated with grade ≥ 2 late GU toxicity on multivariate analysis. CONCLUSIONS: A dose-adapted, erMRI-based SRT approach treating the PB with a boost to the suspected local recurrence may potentially improve the therapeutic ratio by selecting patients that are most likely expected to benefit from SRT doses above 70 Gy as well as by reducing the size of the highest-dose target volume. Further prospective trials are needed to investigate the use of erMRI in SRT as well as the role of dose-adapted protocols and the best fractionation schedule.

A brief report of 10-year trends in the use of stereotactic lung radiotherapy at a dutch academic medical center.

This report describes clinical trends in the use of stereotactic lung radiotherapy in a large single-institution program over the last 10 years. Changes in patient, tumor, and treatment characteristics are highlighted.

Frameless high dose rate stereotactic lung radiotherapy: intrafraction tumor position and delivery time.

Intrafraction change in tumor position (Δ) was evaluated for stereotactic lung radiotherapy delivered with flattening filter free volumetric modulated arc therapy. In 140 fractions from 32 patients mean Δ (±SD) was -0.7±1.4 mm (vertical), -0.7±1.3 mm (longitudinal) and +0.2±1.2 mm (lateral) with mean vector 2.1±1.2 mm. Mean delivery time was 4.4±3.4 min (mean beam-on 1.9±0.4 min).

Breathing adapted radiotherapy: a 4D gating software for lung cancer.

PURPOSE: Physiological respiratory motion of tumors growing in the lung can be corrected with respiratory gating when treated with radiotherapy (RT). The optimal respiratory phase for beam-on may be assessed with a respiratory phase optimizer (RPO), a 4D image processing software developed with this purpose. METHODS AND MATERIALS: Fourteen patients with lung cancer were included in the study. Every patient underwent a 4D-CT providing ten datasets of ten phases of the respiratory cycle (0-100% of the cycle). We defined two morphological parameters for comparison of 4D-CT images in different respiratory phases: tumor-volume to lung-volume ratio and tumor-to-spinal cord distance. The RPO automatized the calculations (200 per patient) of these parameters for each phase of the respiratory cycle allowing to determine the optimal interval for RT. RESULTS: Lower lobe lung tumors not attached to the diaphragm presented with the largest motion with breathing. Maximum inspiration was considered the optimal phase for treatment in 4 patients (28.6%). In 7 patients (50%), however, the RPO showed a most favorable volumetric and spatial configuration in phases other than maximum inspiration. In 2 cases (14.4%) the RPO showed no benefit from gating. This tool was not conclusive in only one case. CONCLUSIONS: The RPO software presented in this study can help to determine the optimal respiratory phase for gated RT based on a few simple morphological parameters. Easy to apply in daily routine, it may be a useful tool for selecting patients who might benefit from breathing adapted RT.

Predicted risk of radiation-induced cancers after involved field and involved node radiotherapy with or without intensity modulation for early-stage hodgkin lymphoma in female patients.

PURPOSE: To assess the excess relative risk (ERR) of radiation-induced cancers (RIC) in female patients with Hodgkin lymphoma (HL) female patients treated with conformal (3DCRT), intensity modulated (IMRT), or volumetric modulated arc (RA) radiation therapy. METHODS AND MATERIALS: Plans for 10 early-stage HL female patients were computed for 3DCRT, IMRT, and RA with involved field RT (IFRT) and involvednode RT (INRT) radiation fields. Organs at risk dose--volume histograms were computed and inter-compared for IFRT vs. INRT and 3DCRT vs. IMRT/RA, respectively. The ERR for cancer induction in breasts, lungs, and thyroid was estimated using both linear and nonlinear models. RESULTS: The mean estimated ERR for breast, lung, and thyroid were significantly lower (p < 0.01) with INRT than with IFRT planning, regardless of the radiation delivery technique used, assuming a linear dose-risk relationship. We found that using the nonlinear model, the mean ERR values were significantly (p < 0.01) increased with IMRT or RA compared to those with 3DCRT planning for the breast, lung, and thyroid, using an IFRT paradigm. After INRT planning, IMRT or RA increased the risk of RIC for lung and thyroid only. CONCLUSIONS: In this comparative planning study, using a nonlinear dose--risk model, IMRT or RA increased the estimated risk of RIC for breast, lung, and thyroid for HL female patients. This study also suggests that INRT planning, compared to IFRT planning, may reduce the ERR of RIC when risk is predicted using a linear model. Observing the opposite effect, with a nonlinear model, however, questions the validity of these biologically parameterized models.

Involved-node and involved-field volumetric modulated arc vs. fixed beam intensity-modulated radiotherapy for female patients with early-stage supra-diaphragmatic Hodgkin lymphoma: a comparative planning study.

PURPOSE: A comparative treatment planning study was performed to compare volumetric-modulated arc (RA) to conventional intensity modulated (IMRT) for involved-field (IFRT) and involved-node (INRT) radiotherapy for Hodgkin lymphoma (HL). METHODS AND MATERIALS: Plans for 10 early-stage HL female patients were computed for RA and IMRT. First, the planning target volume (PTV) coverage and organs at risk (OAR) dose deposition was assessed between the two modalities. Second, the OAR (lung, breast, heart, thyroid, and submandibular gland) dose-volume histograms were computed and compared for IFRT and INRT, respectively. RESULTS: For IFRT and INRT, PTV coverage was equally homogeneous with both RA and IMRT. By and large, the OAR irradiation with IFRT planning was not significantly different between RA and IMRT. For INRT, doses computed for RA were, however, usually lower than those with IMRT, particularly so for the lung, breast, and thyroid. Regardless of RA and IMRT modalities, a significant 20-50% decrease of the OAR computed mean doses was observed with INRT when compared with IFRT (Breast D(Mean) 1.5 +/- 1.1 vs. 2.6 +/- 1.7 Gy, p < 0.01 and 1.6 +/- 1.1 vs. 2.9 +/- 1.9 Gy, p < 0.01 for RA and IMRT, respectively). CONCLUSIONS: RA and IMRT results in similar level of dose homogeneity. With INRT but not IFRT planning, the computed doses to the PTV and OAR were usually higher and lower with RA when compared to IMRT. Regardless of the treatment modality, INRT when compared with IFRT planning led to a significant decrease in OAR doses, particularly so for the breast and heart.