Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

In-vitro investigation of cardiac implantable electronic device malfunction during and after direct photon exposure: A three-centres experience.

PURPOSE: Radiotherapy may cause malfunction of implantable cardioverter-defibrillators (ICDs) and pacemakers (PMs). We carried-out a multicentre randomized in-vitro study on 65 ICDs and 145 PMs to evaluate malfunctions during and after direct irradiation to doses up to 10 Gy. METHODS: Three centres equipped with different linear accelerator and treatment-planning systems participated in the study. Computed Tomography (CT) acquisitions were performed to build the treatment plans. All devices were exposed to dose of 2, 5, or 10 Gy (6 MV). All devices underwent a baseline examination and 64 wireless real-time telemetry-transmissions (47 ICDs and 17 PMs) were monitored during photon exposures. All devices were interrogated after exposure and once monthly for six subsequent months. RESULTS: Fifty-four of the 64 wireless-enabled CIEDs (84.4%) recorded noise-related interferences during exposure. In detail, 40/47 ICDs (85.1%) reported interference, of which 16 ICDs (34%) reported potentially clinically relevant pacing inhibition and inappropriate detections. Following exposure, a soft reset occurred in 1/145 PM (0.7%) while 7/145 PMs (4.8%) reported battery issues. During the six-month follow-up, 1/145 PM (0.7%) reported a soft reset, while 12/145 more PMs (8.3%) and 1/64 ICD (1.5%) showed abnormal battery depletion. All reported issues occurred independently of exposure dose. Finally, irreversible effects on software and battery life occurred in only non-MRI-compatible devices. CONCLUSION: ICDs mostly featured real-time transient sensing issues, while PMs mostly experienced long-term battery or software issues that were observed immediately following radiation exposure and during follow-up. Irreversible effects on battery life and software occurred in only non-MRI-compatible devices.

Neutron and photon out-of-field doses at cardiac implantable electronic device (CIED) depths.

The accuracy of an out-of-field dose from an Elekta Synergy accelerator calculated using the X-ray Voxel Monte Carlo (XVMC) dose algorithm in the Monaco treatment planning system (TPS) for both low-energy (6 MV) and high-energy (15 MV) photons at cardiac implantable electronic device (CIED) depths was investigated through a comparison between MCNPX simulated out-of-field doses and measured out-of-field doses using three high spatial and sensitive active detectors. In addition, total neutron equivalent dose and fluence at CIED depths of a 15-MV dose from an Elekta Synergy accelerator were calculated, and the corresponding CIED relative neutron damage was quantified. The results showed that for 6-MV photons, the XVMC dose algorithm in Monaco underestimated out-of-field doses in all off-axis distances (average errors: -17% at distances X < 10 cm from the field edge and -31% at distances between 10 < X ≤ 16 cm from the field edge), with an increasing magnitude of underestimation for high-energy (15 MV) photons (up to 11%). According to the results, an out-of-field photon dose at a shallower CIED depth of 1 cm was associated with greater statistical uncertainty in the dose estimate compared to a CIED depth of 2 cm and clinical depth of 10 cm. Our results showed that the relative neutron damage at a CIED depth range for 15 MV photon is 36% less than that reported for 18 MV photon in the literature.

The influence of basic plan parameters on calculated small field output factors - A multicenter study.

PURPOSE: The influence of basic plan parameters such as slice thickness, grid resolution, algorithm type and field size on calculated small field output factors (OFs) was evaluated in a multicentric study. METHODS AND MATERIALS: Three computational homogeneous water phantoms with slice thicknesses (ST) 1, 2 and 3 mm were shared among twenty-one centers to calculate OFs for 1x1, 2x2 and 3x3 cm2 field sizes (FSs) (normalized to 10x10 cm2 FS), with their own treatment planning system (TPS) and the energy clinically used for stereotactic body radiation therapy delivery. OFs were calculated for each combination of grid resolution (GR) (1, 2 and 3 mm) and ST and finally compared with the OFs measured for the TPS commissioning. A multivariate analysis was performed to test the effect of basic plan parameters on calculated OFs. RESULTS: A total of 509 data points were collected. Calculated OFs are slightly higher than measured ones. The multivariate analysis showed that Center, GR, algorithm type, and FS are predictive variables of the difference between calculated and measured OFs (p < 0.001). As FS decreases, the spread in the difference between calculated and measured OFs became larger when increasing the GR. Monte Carlo and Analytical Anisotropic Algorithms, presented a dependence on GR (p < 0.01), while Collapsed Cone Convolution and Acuros did not. The effect of the ST was found to be negligible. CONCLUSIONS: Modern TPSs slightly overestimate the calculated small field OFs compared with measured ones. Grid resolution, algorithm, center number and field size influence the calculation of small field OFs.

Dose calculation accuracy in proximity of a pacemaker: A multicenter study with threecommercial treatment planning systems.

This study compares Treatment Planning System (TPS) out of field dose calculation on a pacemaker (PMK) during external beam radiotherapy treatment. We consider four TPSs (Elekta-Monaco, Oncentra- Masterplan and two Philips-Pinnacle3) commissioned for two linacs (Elekta Sinergy and Varian Clinac) delivering two test beams (a highly modulated one and a square field) and two clinical breast plans. To calculate and measure dose to a PMK we built a Real Water3 phantom with a PMK embedded in it. Measures are performed with thermo-luminescent dosimeters and Mosfet dosimeters. We evaluate differences between TPS calculated values for the dose to the PMK (both point dose and dose-volume histogram parameters) when the PMK is positioned in the first 10 cm outside the radiation fields. TPS calculation accuracy is evaluated comparing such values with measures. Differences in TPS calculations are on average 3.5 cGy Gy-1 for the modulated beam, and always lower than 2 cGy Gy-1 for the square beam. TPS dose calculation depends mostly on the TPS algorithm and model rather than the linac commissioned. TPSs considered show different degrees of calculation accuracy. In the first 4 cm to the field edge three out of four TPSs are in good agreement with measurements in the square beam, but only one keeps the agreement in the modulated beam: the others show over and underestimations up to +20% -40%. The same accuracy is found considering a homogeneous phantom. Our results confirm what reported in previous studies and highlight the impact of TPS commissioning.

A multicenter dosimetry study to evaluate the imaging dose from Elekta XVI and Varian OBI kV-CBCT systems to cardiovascular implantable electronic devices (CIEDs).

The increasing use of daily CBCT in radiotherapy has raised concerns about the additional dose delivered to the patient, and it can also become a concern issue for those patients with cardiovascular implantable electronic devices (CIEDs) (Pacemaker [PM] and Implantable Cardioverter Defibrillator [ICD]). Although guidelines highly recommend that the cumulative dose received by CIEDs should be kept as low as possible, and a safe threshold based on patient risk classification needs to be respected, this additional imaging dose is not usually considered. Four centers with different dosimetry systems and different CBCT imaging protocols participated in this multicenter study to investigate the imaging dose to the CIEDs from Elekta XVI and Varian OBI kV-CBCT systems. It was found that although imaging doses received by CIEDs outside the CBCT field are negligible, special attention should be paid to this value when CIEDs are inside the field because the daily use of CBCT can sometimes contribute considerably to the total dose received by a CIED.

Impact of residual setup error on parotid gland dose in intensity-modulated radiation therapy with or without planning organ-at-risk margin.

PURPOSE: To estimate the dosimetric impact of residual setup errors on parotid sparing in head-and-neck (H&N) intensity-modulated treatments and to evaluate the effect of employing an PRV (planning organ-at-risk volume) margin for the parotid gland. PATIENTS AND METHODS: Ten patients treated for H&N cancer were considered. A nine-beam intensity-modulated radiotherapy (IMRT) was planned for each patient. A second optimization was performed prescribing dose constraint to the PRV of the parotid gland. Systematic setup errors of 2 mm, 3 mm, and 5 mm were simulated. The dose-volume histograms of the shifted and reference plans were compared with regard to mean parotid gland dose (MPD), normal-tissue complication probability (NTCP), and coverage of the clinical target volume (V95% and equivalent uniform dose [EUD]); the sensitivity of parotid sparing on setup error was evaluated with a probability-based approach. RESULTS: MPD increased by 3.4%/mm and 3.0%/mm for displacements in the craniocaudal and lateral direction and by 0.7%/ mm for displacements in the anterior-posterior direction. The probability to irradiate the parotid with a mean dose > 30 Gy was > 50%, for setup errors in cranial and lateral direction and < 10% in the anterior-posterior direction. The addition of a PRV margin improved parotid sparing, with a relative reduction in NTCP of 14%. The PRV margin compensates for setup errors of 3 mm and 5 mm (MPD < or = 30 Gy in 87% and 60% of cases), without affecting clinical target volume coverage (V95% and EUD variations < 1% and < 1 Gy). CONCLUSION: The parotid gland is more sensitive to craniocaudal and lateral displacements. A setup error of 2 mm guarantees an MPD < or = 30 Gy in most cases, without adding a PRV margin. If greater displacements are expected/accepted, an adequate PRV margin could be used to meet the clinical parotid gland constraint of 30 Gy, without affecting target volume coverage.

Optimization of the gafchromic EBT protocol for IMRT QA.

Quality assurance of external beam (radio)therapy (EBT) requires tools with specific characteristics. A radiochromic film dubbed "Gafchromic EBT" (G-EBT) that is particularly suited for external beam therapy because of its features was introduced in 2004. Its characteristics, especially the high spatial resolution, make it suitable for measurement of dose distributions in radiotherapy, especially intensity-modulated radiation therapy (IMRT). While several aspects of the film characteristics have been previously reported separately, we present a comprehensive evaluation centered on practical IMRT verification, leading to an optimized protocol. Therefore the constancy within one batch, the relationship between optical density (OD) and dose (dose range between 1.4 Gy and 8.4 Gy) and the dose rate dependence for four dose rates (55, 108, 217, 441 MU/min) were investigated. In addition to these characteristics, energy dependence between two energies (50kV and 6 MV), tissue equivalency, post irradiation coloration over one month, pressure and temperature sensitivity were evaluated. We then optimized the protocol using the G-EBT films, in combination with an EPSON-Expression 1680 pro flatbed scanner, for IMRT QA, while either striving to keep the compound error as small as possible or trying to reduce evaluation time. As a basis for this protocol optimization, the characteristics of the scanner (such as inhomogeneity of the scanning field) and its software (such as consequences of extracting only the red color channel) had to be determined first. The interaction of film and scanner (variation of the OD depending on the scanning direction or the scanning resolution) was assessed as well. Using the optimized protocol for IMRT QA, the compound error could be reduced to approximately 2% for a quality-driven approach and maximum 5.5% for an approach attempting to reduce procedure time. While the quality-driven approach provides appropriate accuracy for individual patient QA, the procedure-time driven approach can only be used for preliminary measurements.