Script-based automatic radiotherapy planning for cervical cancer.

BACKGROUND: This study aimed to develop fully automated script-based radiotherapy treatment plans for cervical cancer patients, and evaluate them against clinically accepted plans, as validation before clinical implementation. MATERIAL AND METHODS: In this retrospective planning study, treatment plans for 25 locally advanced cervical cancer (LACC) patients with up to three dose levels were included. Fully automated plans were created using an in-house developed Python script in RayStation, and compared to clinically accepted manually made plans. Quantitatively, relevant dose statistics were compared, and average dose volume histograms (DVHs) were analyzed. Qualitatively, a blinded plan comparison was conducted between the clinical and automatic plans. The accuracy of treatment plan delivery was verified with the Delta4 Phantom+. RESULTS: The quantitative evaluation showed that target coverage was acceptable for all the automatic and clinical plans. The automatic plans were significantly more conformal than the clinical plans; median of 1.03 vs. 1.12. Mean doses to almost all organs at risk (OARs) were reduced in the automatic plans, with a median reduction of between 0.6 Gy and 1.9 Gy. In the blinded plan comparison, the automatic plans were the preferred plans or of equal quality as the clinical plans in 99% of the cases. In addition, plan delivery was excellent, with a mean gamma passing rate of 99.8%. Complete script-based plans were generated in 30-45 min; about four to ten times faster than manually made plans. CONCLUSION: The automatic plans had acceptable target coverage, lower doses to almost all OARs, more conformal dose distributions, and were predominantly preferred by the clinicians. Based on these results, our institution has implemented the script for clinical use.

Locoregional breast radiotherapy including IMN: optimizing the dose distribution using an automated non-coplanar VMAT-technique.

BACKGROUND: Volumetric Modulated Arc Therapy (VMAT) offers better conformity, homogeneity and sparing of the heart and ipsilateral lung for locoregional radiotherapy in left-sided breast cancer compared to three-dimensional conformal radiotherapy (3D-CRT). However, conventional coplanar VMAT (cVMAT) can result in higher doses to the normal tissue on the contralateral side. This study investigates a non-coplanar VMAT-technique (ncVMAT) to mitigate this issue. MATERIAL AND METHODS: CT series of 20 left sided breast cancer patients were included for planning of locoregional breast radiotherapy including internal mammary nodes (IMN). Three treatment plans; 3D-CRT, cVMAT and ncVMAT, were generated for each patient with a prescription dose of 40.05 Gy in 15 fractions. Both VMAT-techniques consisted of a single arc in the axial plane, while ncVMAT included an additional arc in the sagittal plane. All plans were optimized to cover the clinical target volume (CTV) by 38.05 Gy for the breast and 36.05 Gy for lymph nodes, with as low as possible dose to organs at risk. RESULTS: Full CTV coverage was achieved for all plans. Both cVMAT and ncVMAT delivered more conformal and homogeneous target doses than 3D-CRT. Doses to the heart and ipsilateral lung were significantly lower with ncVMAT compared to both cVMAT and 3D-CRT. ncVMAT reduced doses to both the contralateral breast and lung compared to cVMAT and achieved levels similar to 3D-CRT for the contralateral breast and moderately higher doses for the contralateral lung. Delivery of high doses (>30 Gy) to the contralateral side was completely avoided with ncVMAT, contrary to the results for cVMAT and 3D-CRT. CONCLUSION: ncVMAT reduced doses to the heart and ipsilateral lung as compared to both cVMAT and 3D-CRT. All contralateral dose metrics were reduced with the novel ncVMAT technique compared to cVMAT, and the mean contralateral breast doses were similar to 3D-CRT.

Training, validation, and clinical implementation of a deep-learning segmentation model for radiotherapy of loco-regional breast cancer.

AIM: To train and validate a comprehensive deep-learning (DL) segmentation model for loco-regional breast cancer with the aim of clinical implementation. METHODS: DL segmentation models for 7 clinical target volumes (CTVs) and 11 organs at risk (OARs) were trained on 170 left-sided breast cancer cases from two radiotherapy centres in Norway. Another 30 patient cases were used for validation, which included the evaluation of Dice similarity coefficient and Hausdorff distance, qualitative scoring according to clinical usability, and relevant dosimetric parameters. The manual inter-observer variation (IOV) was also evaluated and served as a benchmark. Delineation of the target volumes followed the ESTRO guidelines. RESULTS: Based on the geometric similarity metrics, the model performed significantly better than IOV for most structures. Qualitatively, no or only minor corrections were required for 14% and 71% of the CTVs and 72% and 26% of the OARs, respectively. Major corrections were required for 15% of the CTVs and 2% of the OARs. The most frequent corrections occurred in the cranial and caudal parts of the structures. The dose coverage, based on D98 > 95%, was fulfilled for 100% and 89% of the breast and lymph node CTVs, respectively. No differences in OAR dose parameters were considered clinically relevant. The model was implemented in a commercial treatment planning system, which generates the structures in 1.5 min. CONCLUSION: Convincing results from the validation led to the decision of clinical implementation. The clinical use will be monitored regarding applicability, standardization and efficiency.

Robustness of VMAT and 3DCRT plans toward setup errors in radiation therapy of locally advanced left-sided breast cancer with DIBH.

PURPOSE: The aim of our study was to evaluate and compare the robustness of treatment plans produced using the volumetric modulated arc-therapy (VMAT) and the standard three-dimensional conformal radiotherapy (3DCRT) techniques by estimating perturbed doses induced by localization offsets for deep inspiration breath-hold (DIBH) in locally advanced breast cancer radiation therapy. METHODS: Twenty patients with left breast carcinoma requiring radiation therapy were analysed in this planning study. Robust VMAT plans regarding minimum CTV doses and standard 3DCRT plans were produced, and perturbed doses were calculated in accordance with localization values from the weekly offline imaging protocol. Offsets from 5 weeks were summed to a perturbed overall treatment plan. Dose criteria for evaluation were coverage and homogeneity of the target, as well as doses to organs at risk. RESULTS: VMAT plans resulted in significantly better target coverage compared to 3DCRT, as well as lowered doses to heart and left anterior descending artery, while the perturbed doses were less variable for VMAT than 3DCRT plans. Homogeneity was significantly improved in VMAT plans. The statistical analysis taking all organs into account found that VMAT plans were more robust than 3DCRT to localization offsets (p = .001). The overall mean setup-deviation for the DIBH-patients was less than 2 mm in all directions. CONCLUSIONS: VMAT plans were more robust on average than conventional 3DCRT plans for DIBH when localization errors were taken into consideration. The combination of robust VMAT planning and DIBH generally improves the homogeneity and target doses.

Monitoring deep inspiration breath hold for left-sided localized breast cancer radiotherapy with an in-house developed laser distance meter system.

Deep inspiration breath hold (DIBH) in left-sided breast cancer radiotherapy is a technique to reduce cardiac and pulmonary doses while maintaining target coverage. This study aims at evaluating an in-house developed DIBH system. Free-breathing (FB) and DIBH plans were generated for 22 left-sided localized breast cancer patients who had radiation therapy (RT) after breast-conserving surgery. All patients were treated utilizing an in-house laser distance measuring system. 50 Gy was prescribed, and parameters of interest were target coverage, left anterior descending coronary artery, (LAD) and heart doses. Portal images were acquired and the reproducibility and stability of DIBH treatment were compared to FB. The comparing result shows there is a significant reduction in all LAD and heart dose statistics for DIBH compared to FB plans without compromising the target coverage. The maximum LAD dose was reduced from 43.7 Gy to 29.0 Gy and the volume of the heart receiving >25 Gy was reduced from 3.3% to 1.0% using the in-house system, both statistically significant. The in-house system gave a reproducible and stable DIBH treatment where the systematic error ∑, and random error σ, were less than 2.2 mm in all directions, but were not significantly better than at FB. The system was well tolerated and all patients completed their treatment sessions with DIBH.

Intrafractional baseline drift during free breathing breast cancer radiation therapy.

BACKGROUND: Intrafraction motion in breast cancer radiation therapy (BCRT) has not yet been thoroughly described in the literature. It has been observed that baseline drift occurs as part of the intrafraction motion. This study aims to measure baseline drift and its incidence in free-breathing BCRT patients using an in-house developed laser system for tracking the position of the sternum. MATERIALS AND METHODS: Baseline drift was monitored in 20 right-sided breast cancer patients receiving free breathing 3D-conformal RT by using an in-house developed laser system which measures one-dimensional distance in the AP direction. A total of 357 patient respiratory traces from treatment sessions were logged and analysed. Baseline drift was compared to patient positioning error measured from in-field portal imaging. RESULTS: The mean overall baseline drift at end of treatment sessions was -1.3 mm for the patient population. Relatively small baseline drift was observed during the first fraction; however it was clearly detected already at the second fraction. Over 90% of the baseline drift occurs during the first 3 min of each treatment session. The baseline drift rate for the population was -0.5 ± 0.2 mm/min in the posterior direction the first minute after localization. Only 4% of the treatment sessions had a 5 mm or larger baseline drift at 5 min, all towards the posterior direction. Mean baseline drift in the posterior direction in free breathing BCRT was observed in 18 of 20 patients over all treatment sessions. CONCLUSIONS: This study shows that there is a substantial baseline drift in free breathing BCRT patients. No clear baseline drift was observed during the first treatment session; however, baseline drift was markedly present at the rest of the sessions. Intrafraction motion due to baseline drift should be accounted for in margin calculations.

Development of a deep inspiration breath-hold system for radiotherapy utilizing a laser distance measurer.

Deep inspiration breath-hold (DIBH) is a technique for treating left-sided breast cancer (LSBC). In modern radiotherapy, one of the main aims is to exclude the heart from the beam aperture with an individualized beam design for LSBC. A deep inhalation will raise the chest wall while the volume of the lungs increase, this will again push the heart away from the breast to be treated. There are a few commercial DIBH systems, both invasive and noninvasive. We present an alternative noninvasive DIBH system based upon an industrial laser distance measurer. This system can be installed in a treatment room at a low cost; it is very easy to use and requires limited amount of training for the personnel and the patient. The system is capable of measuring the position of the chest wall with high frequency and precision in real time. The patient views its breathing curve through video glasses, and gets instructions during the treatment session. The system is well tolerated by test subjects due to its noninvasiveness.

Monte Carlo linear accelerator simulation of megavoltage photon beams: independent determination of initial beam parameters.

PURPOSE: To individually benchmark the incident electron parameters in a Monte Carlo model of an Elekta linear accelerator operating at 6 and 15 MV. The main objective is to establish a simplified but still precise benchmarking procedure that allows accurate dose calculations of advanced treatment techniques. METHODS: The EGSnrc Monte Carlo user codes BEAMnrc and DOSXYZnrc are used for photon beam simulations and dose calculations, respectively. A 5 × 5 cm(2) field is used to determine both the incident electron energy and the electron radial intensity. First, the electron energy is adjusted to match the calculated depth dose to the measured one. Second, the electron radial intensity is adjusted to make the calculated dose profile in the penumbrae region match the penumbrae measured by GafChromic EBT film. Finally, the mean angular spread of the incident electron beam is determined by matching calculated and measured cross-field profiles of large fields. The beam parameters are verified for various field sizes and shapes. RESULTS: The penumbrae measurements revealed a non-circular electron radial intensity distribution for the 6 MV beam, while a circular electron radial intensity distribution could best describe the 15 MV beam. These electron radial intensity distributions, given as the standard deviation of a Gaussian distribution, were found to be 0.25 mm (in-plane) and 1.0 mm (cross-plane) for the 6 MV beam and 0.5 mm (both in-plane and cross-plane) for the 15 MV beam. Introducing a small mean angular spread of the incident electron beam has a considerable impact on the lateral dose profiles of large fields. The mean angular spread was found to be 0.7° and 0.5° for the 6 and 15 MV beams, respectively. CONCLUSIONS: The incident electron beam parameters in a Monte Carlo model of a linear accelerator could be precisely and independently determined by the benchmarking procedure proposed. As the dose distribution in the penumbra region is insensitive to moderate changes in electron energy and angular spread, accurate penumbra measurements is feasible for benchmarking the electron radial intensity distribution. This parameter is particularly important for accurate dosimetry of mlc-shaped fields and small fields.

Early effects of contemporary breast radiation on health-related quality of life - predictors of radiotherapy-related fatigue.

BACKGROUND AND PURPOSE: The aim of this study was to report on early effects of contemporary radiotherapy (RT) on health-related quality of life (HRQOL) and explore treatment-related contributors to the development of fatigue during RT in breast cancer (BC) patients. MATERIAL AND METHODS: Consecutive BC patients (n = 248) referred for postoperative RT at St. Olavs University Hospital in Trondheim, Norway were enrolled from February 2007 to October 2008. Clinical- and treatment data were recorded, and HRQOL were assessed before starting (baseline) and immediately after ending RT using the "EORTC QLQ-C30" and the breast module "EORTC QLQ-BR23". Change scores from baseline were calculated. Predictors of increased fatigue during RT were explored with multiple regression analysis adjusted for relevant confounders. RESULTS: The global QOL- and all functional scales remained stable, except for "future perspective" which improved significantly during RT. Breast symptoms and fatigue increased significantly during RT. Groups with elevated baseline fatigue remained more stable during RT than those with lower levels at baseline. The body volume receiving 40 Gy or more (V40) was a significant predictor of increased fatigue during RT adjusted for chemotherapy, comorbidity and age (p = 0.035). CONCLUSION: Contemporary RT has limited early effects on HRQOL. V40 is a significant predictor of RT-related fatigue.

Superficial doses in breast cancer radiotherapy using conventional and IMRT techniques: a film-based phantom study.

BACKGROUND AND PURPOSE: Superficial doses in radiotherapy are affected by the treatment technique. The implications for breast cancer treatments were evaluated. MATERIAL AND METHODS: Four treatment techniques relevant for breast cancer irradiation were evaluated; tangential standard, tangential IMRT, 7-field IMRT (arc-like field arrangement) and hybrid IMRT (an IMRT plan mixed with non-modulated fields). Only 6MV photons were used. GafChromic EBT film was used for dose measurements at the surface, in the skin (0-5mm depth) and in the superficial parts of CTV (5-10mm depth) of an anthropomorphic thorax phantom. RESULTS: Only small differences in superficial doses were observed between tangential standard and tangential IMRT. Compared to the tangential standard plan, the surface and skin doses were reduced with the 7-field IMRT plan, on average by 20% and 5%, respectively, while hybrid IMRT reduced the surface and skin doses medially (by 44% and 8%, respectively) and increased the surface and skin dose laterally (by 40% and 15%, respectively). Minimum superficial CTV doses varied between regions, but were mainly between 90% and 95% of the target dose for all plans, only the hybrid IMRT plan resulted in a region with minimum dose below 90%. CONCLUSIONS: Compared to tangential irradiation, skin sparing was achieved by the 7-field IMRT plan. The minimum dose in the superficial parts of the CTV was below 95% of the target dose for all plans investigated.

Relative biological effectiveness of photon energies used in brachytherapy and intraoperative radiotherapy techniques for two breast cancer cell lines.

BACKGROUND: Partial breast irradiation (IORT or brachytherapy) differ from external radiation of whole breast in terms of irradiated volumes, fractionation, radiation energy and dose rate; all factors influencing the treatment outcome in a complex manner. Theoretically obtained RBE values comparing effects of radiation used in IORT and external therapy are published, but experimental studies are required to confirm these data. The aim of this study is to establish such RBE values for two breast cancer cell lines. MATERIALS AND METHODS: Colony formation of breast cancer cell lines (MCF-7 and T-47D) were studied after photon irradiation with qualities and dose rates used in IORT, brachytherapy and external radiation. RBE values from survival data were used to compare effects. RESULTS: Increasing the photon energy (dose rate 0.2 Gy/min) from 50 kV (Intrabeam) to 380 keV (¹9²Ir source) and 6 MV (linear accelerator) yielded an increase in the cell survival, whereas increasing the dose rate to 6 Gy/min had minor effect. Average RBE values for 50 kV with 6 MV as reference radiation varied from about 1.4 (for doses < 5 Gy) to > 1.9 (for doses < 0.02 Gy) for MCF-7 cells and from about 1.4 to > 3.1 for T-47D cells for the same dose levels. Corresponding RBE values for 380 keV radiation were about 1.4 for MCF-7 cells and 1.3-2.3 for T-47D cells. CONCLUSION: RBE data for breast cancer cells exposed to radiation used in IORT, brachytherapy or external radiation differ among the cell lines tested. The values are in agreement with published theoretical and experimental work.

GafChromic EBT film dosimetry with flatbed CCD scanner: a novel background correction method and full dose uncertainty analysis.

Film dosimetry using radiochromic EBT film in combination with a flatbed charge coupled device scanner is a useful method both for two-dimensional verification of intensity-modulated radiation treatment plans and for general quality assurance of treatment planning systems and linear accelerators. Unfortunately, the response over the scanner area is nonuniform, and when not corrected for, this results in a systematic error in the measured dose which is both dose and position dependent. In this study a novel method for background correction is presented. The method is based on the subtraction of a correction matrix, a matrix that is based on scans of films that are irradiated to nine dose levels in the range 0.08-2.93 Gy. Because the response of the film is dependent on the film's orientation with respect to the scanner, correction matrices for both landscape oriented and portrait oriented scans were made. In addition to the background correction method, a full dose uncertainty analysis of the film dosimetry procedure was performed. This analysis takes into account the fit uncertainty of the calibration curve, the variation in response for different film sheets, the nonuniformity after background correction, and the noise in the scanned films. The film analysis was performed for film pieces of size 16 x 16 cm, all with the same lot number, and all irradiations were done perpendicular onto the films. The results show that the 2-sigma dose uncertainty at 2 Gy is about 5% and 3.5% for landscape and portrait scans, respectively. The uncertainty gradually increases as the dose decreases, but at 1 Gy the 2-sigma dose uncertainty is still as good as 6% and 4% for landscape and portrait scans, respectively. The study shows that film dosimetry using GafChromic EBT film, an Epson Expression 1680 Professional scanner and a dedicated background correction technique gives precise and accurate results. For the purpose of dosimetric verification, the calculated dose distribution can be compared with the film-measured dose distribution using a dose constraint of 4% (relative to the measured dose) for doses between 1 and 3 Gy. At lower doses, the dose constraint must be relaxed.

Radiation improves the distribution and uptake of liposomal doxorubicin (caelyx) in human osteosarcoma xenografts.

Liposomal drug delivery appears to improve the antitumor effect and reduce toxicity compared with the free drug. The therapeutic index may be improved further by combining cytotoxic drugs and radiotherapy. Successful therapy requires that the cytotoxic agents reach the tumor cells. Therefore, we studied tumor growth and the microdistribution of liposomal doxorubicin (Caelyx) with and without additional ionizing radiation in human osteosarcoma xenografts in athymic mice. Caelyx was injected i.v. 1 day before single or fractionated radiotherapy. Both chemoirradiation regimens induced significant tumor growth delays and worked synergistically. Confocal laser scanning microscopy showed that intact liposomes were located in close proximity to endothelial cells, and the distribution of released doxorubicin was heterogeneous. Before radiotherapy, hardly any doxorubicin was localized in the central parts of the tumor. Radiotherapy increased the tumor uptake of doxorubicin by a factor of two to four, with drug being redistributed farther from the vessels in the tumor periphery and located around vessels in the central parts of the tumor. Colocalization of doxorubicin and hypoxic cells showed no distribution of drug into hypoxic areas. Dynamic contrast-enhanced magnetic resonance imaging (MRI) 1 day before the injection of Caelyx and 2 days after treatment start showed that the combined treatment reduced the vascular volume and the vascular transfer rate of the MRI tracer. The results show that chemoirradiation with Caelyx induces synergistic treatment effects. Improved intratumoral drug uptake and distribution are responsible to some extent for the enhanced antitumor effect.