Impact of hydrogel spacer injections on interfraction prostate motion during prostate cancer radiotherapy.

Background The dosimetric advantage of prostate-rectum spacers to displace the anterior rectal wall outside of the high-dose radiation regions has been clearly established in prostate cancer radiotherapy (RT). The aim of this study was to assess the impact of hydrogel spacer (HS) in the interfraction prostate motion in patients undergoing RT for prostate cancer. Material and methods Twenty prostate cancer patients implanted with three fiducial markers (FM) with (n = 10) or without (n = 10) HS were analyzed. Displacements between the prostate isocenter based on the FM's position and the bony anatomy were quantified in the left-right (LR), anterior-posterior (AP), superior-inferior (SI) axes by offline analyses of 122 cone beam computed tomography scans. Group systematic (M), systematic (Σ) and random (σ) setup errors were determined. Results In patients with or without HS, the overall mean interfraction prostate displacements were 0.4 versus -0.4 mm (p = 0.0001), 0.6 versus 0.6 mm (p = 0.85), and -0.6 mm versus -0.3 mm (p = 0.48) for the LR, AP, and SI axes, respectively. Prostate displacements >5 mm in the AP and SI directions were similar for both groups. No differences in M, Σ and σ setup errors were observed in the three axes between HS + or HS- patients. Conclusions HS implantation does not significantly influence the interfraction prostate motion in patients treated with RT for prostate cancer. The major expected benefit of HS is a reduction of the high-dose levels to the rectal wall without influence in prostate immobilization.

Bilateral metallic hip implants: Are avoidance sectors necessary for pelvic VMAT treatments?

PURPOSE: Metallic hip implants (MHI) are common in elderly patients. For pelvic cancers radiotherapy, conventional approaches consist of MHI avoidance during treatment planning, which leads, especially in case of bilateral MHI, to a decreased quality or increased complexity of the treatment plan. The aim of this study is to investigate the necessity of using avoidance sectors (AvSe) using a 2-arcs coplanar pelvic volumetric modulated arc-therapy (VMAT) planning. METHODS: We evaluated: (1) The dose calculation error of a static 6MV open beam traversing a MHI; (2) The magnitude of an error's decrease within the planning target volume (PTV) for a 360° VMAT treatment without AvSe as compared to the static open beam; (3) The dosimetric influence of MHI misalignment generated by patient's repositioning rolls during image-guided radiotherapy (IGRT). RESULTS: (1) In the static 6MV beam configuration, for distances between 0.5cm and 6cm from the MHI, the median (maximum, number of points) dose calculation error was -1.55% (-2.5%, 11); (2) Compared to the static open beam, in the 360° VMAT treatment without AvSe a simulated error was decreased by a factor of 4.4/2.4 (median/minimum); (3) MHI anterior-posterior misalignment exceeding 0.6cm, resulted in error at PTV surface of >2%. CONCLUSIONS: A standard 2 coplanar arcs 360° VMAT treatment, with dedicated artifact reduction algorithms applied, decreased the error of static beam traversing MHI, in patients presenting a bilateral MHI and might be used to treat the pelvic region without MHI avoidance.

3D printing for dosimetric optimization and quality assurance in small animal irradiations using megavoltage X-rays.

PURPOSE: New therapeutic options in radiotherapy (RT) are often explored in preclinical in-vivo studies using small animals. We report here on the feasibility of modern megavoltage (MV) linear accelerator (LINAC)-based RT for small animals using easy-to-use consumer 3D printing technology for dosimetric optimization and quality assurance (QA). METHODS: In this study we aimed to deliver 5×2Gy to the half-brain of a rat using a 4MV direct hemi-field X-ray beam. To avoid the beam's build-up in the target and optimize dosimetry, a 1cm thick, customized, 3D-printed bolus was used. A 1:1 scale copy of the rat was 3D printed based on the CT dataset as an end-to-end QA tool. The plan robustness to HU changes was verified. Thermoluminescent dosimeters (TLDs), for both MV irradiations and for kV imaging doses, and a gafchromic film were placed within the phantom for dose delivery verifications. The phantom was designed using a standard treatment planning software, and was irradiated at the LINAC with the target aligned using kV on-board imaging. RESULTS: The plan was robust (dose difference<1% for HU modification from 0 to 250). Film dosimetry showed a good concordance between planned and measured dose, with the steep dose gradient at the edge of the hemi-field properly aligned to spare the contralateral half-brain. In the treated region, the mean TLDs percentage dose differences (±2 SD) were 1.3% (±3.8%) and 0.9% (±1.7%) beneath the bolus. The mean (±2 SD) out-of-field dose measurements was 0.05Gy (±0.02Gy) for an expected dose of 0.04Gy. Imaging doses (2mGy) still spared the contralateral-brain. CONCLUSIONS: Use of consumer 3D-printers enables dosimetry optimization and QA assessment for small animals MV RT in preclinical studies using standard LINACS.

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial.

PURPOSE: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. METHODS AND MATERIALS: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. RESULTS: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D98% (31.1 vs 30.8 Gy, P < .0001), PTV D2% (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V50% (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V90% (9.1% vs 10.4%, P = .0003) and V80% (13.2% vs 15.7%, P = .0003). CONCLUSIONS: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Dose optimization and endorectal balloon for internal pudendal arteries sparing in prostate SBRT.

PURPOSE: Vessel-sparing radiotherapy has shown promising results in preserving erectile function (EF). Using an endorectal balloon (ERB) may help to reduce the dose to the internal pudendal arteries (IPA) by pushing the prostate forward. We tested this hypothesis and evaluated the limits of IPA dose optimization in prostate cancer patients simulated with and without ERB. MATERIALS AND METHODS: Twelve patients with localized disease were simulated both with and without ERB. IPA were delineated on every CT after MRI registration. Planning target volumes (PTV) were planned to receive 36.25 Gy in 5 fractions with a VMAT technique. Twenty-four initial plans were generated using a knowledge-based planning software without any specific constraints for IPA. Additional stepwise optimization was performed until stabilization of the IPA dose or trespassing of PTV homogeneity limits. RESULTS: Without optimization, the median mean IPA dose (Dmean) was lower with ERB than without (10.5 vs. 12.8 Gy, p = 0.023). After optimization, the IPA Dmean dropped significantly (from 11.1 to 4.8 Gy) without impairing the PTV dose homogeneity and the organs at risk dose constraints. The comparison of the best-optimized plans with and without ERB showed an optimal sparing of IPA using ERB (28% mean dose reduction, p = 0.006; median Dmean of 4.1 Gy vs. 5.7 Gy with and without ERB, respectively). CONCLUSION: IPA dose sparing is feasible without compromising dose prescription and constraints. ERB significantly reduced the dose on IPA compared to plans generated without ERB. As no specific constraints are available for vessel-sparing SBRT, optimal IPA dose reduction should be recommended to maximize EF preservation.

Clinical experience with lung-specific electromagnetic transponders for real-time tumor tracking in lung stereotactic body radiotherapy.

BACKGROUND AND PURPOSES: Motion management is crucial for optimal stereotactic body radiotherapy (SBRT) of moving targets. We aimed to describe our clinical experience with real-time tracking of lung-specific electromagnetic transponders (EMTs) for SBRT of early stage non-small cell lung cancer in free-breathing (FB) or deep inspiration breath-hold (DIBH). MATERIAL AND METHODS: Seven patients were implanted with EMTs. Simulation for SBRT was performed in FB and in DIBH. We prescribed 60 Gy in 3, 5 or 8 fractions to the tumor and delivered SBRT with volumetric modulated arcs and a 6 MV flattening filter free photon beam. Patients' setup at the linac was performed using EMT positions and cone-beam CT (CBCT) verification. Four patients were treated in DIBH because of a dosimetric benefit. We analysed patient alignment and treatment delivery parameters using DIBH or FB and EMT real-time tracking. RESULTS: There were no complications from the EMT implantation. Visual inspection of CBCT before and/or after SBRT revealed good alignment of structures and EMTs. The median setup time was 9.8 min (range: 4.6-34.1 min) and the median session time was 14.7 min (range: 7.3-36.5 min). EMT positions in lungs remained stable during overall treatment and allowed real-time tracking both in FB and in DIBH SBRT. The treatment beam was gated when EMT centroid position exceeded tolerance thresholds ensuring correct delivery of radiation to the tumor. CONCLUSION: Using EMTs for real-time tracking of tumor motion during lung SBRT proved to be safe, accurate and easy to integrate clinically for treatments in FB or DIBH.

Urethra-sparing stereotactic body radiotherapy for prostate cancer: how much can the rectal wall dose be reduced with or without an endorectal balloon?

BACKGROUND: This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate Rwall dose and the potential benefit of an endorectal balloon (ERB) are investigated. METHODS: Ten prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the Rwall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm1 to Vm5). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for Rwall including the median dose and the dose received by 10 to 60% of the Rwall, bladder wall (Bwall) and femoral heads (FHeads) were compared. The monitor units (MU) per plan were recorded. RESULTS: Vm4 reduced by half D30%, D40%, D50%, and Dmed for Rwall and decreased by a third D60% while HIPTV, HIuPRV and DSC remained stable with and without ERB compared to Vmref. HIPTV worsened at Vm5 both with and without ERB. No statistical differences were observed between paired plans on Rwall, Bwall except a higher D2% for Fheads with and without an ERB. CONCLUSIONS: Further optimization to the Rwall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the Rwall can be significantly reduced using a four-step sequential optimization approach.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

PURPOSE: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. METHODS AND MATERIALS: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. RESULTS: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). CONCLUSIONS: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.

In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance.

OBJECTIVE: To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). METHODS: Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. RESULTS: A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25-2.02 Gy) and 1.82 Gy (range, 0.19-2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, -0.11/+0.19 Gy, p=0.102) (median difference of 1.1%, range -6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., -8.9%). CONCLUSIONS: Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors.