Dosimetric comparison of normal breathing and deep inspiration breath hold technique for synchronous bilateral breast cancer using 6MV flattened beam and flattening filter free beam

BackgroundThe present study was to investigate the usefulness of deep inspiration breath hold (DIBH) in bilateral breast patients using 6MV flattened beam (FB) and flattening filter free beam (FFFB).Materials and methodsTwenty bilateral breast cancer patients were simulated, using left breast patients treated with DIBH technique. CT scans were performed in the normal breathing (NB) and DIBH method. Three-dimensional conformal radiotherapy (3DCRT) and volumetric arc therapy (VMAT) plans were generated.ResultsIn our study the best organ at risk (OAR) sparing is achieved in the 3DCRT DIBH plan with adequate PTV coverage (V₉₅ ≥ 47.5 Gy) as compared to 6MV FB and FFFB VMAT DIBH plans. The DIBH scan plan reduces the heart mean dose significantly at the rate of 49% in 3DCRT (p = 0.00) and 22% in VMAT (p = 0.010). Similarly, the DIBH scan plan produces lesser common lung mean dose of 18% in 3DCRT (p = 0.011) and 8% in VMAT (0.007) as compared to the NB scan. The conformity index is much better in VMAT FB (1.04 ± 0.04 vs. 1.04 ± 0.05), p =1.00 and VMAT FFFB (1.04 ± 0.05 vs. 1 ± 0.24, p = 0.345) plans as compared to 3DCRT (1.63 ± 0.2 vs. 1.47 ± 0.28, p = 0.002). The homogeneity index of all the plans is less than 0.15. The global dmax is more in VMAT FFFB DIBH plan (113.7%). The maximum MU noted in the NB scan plan (478 vs. 477MU, 1366 vs. 1299 MU and 1853 vs. 1788 MU for 3DCRT, VMAT FB and VMAT FFFB technique as compared to DIBH scan.ConclusionWe recommend that the use of DIBH techniques for bilateral breast cancer patients significantly reduces the radiation doses to OARs in both 3DCRT and VMAT plans.     

Normal tissue sparing potential of scanned proton beams with and without respiratory gating for the treatment of internal mammary nodes in breast cancer radiotherapy

Proton therapy has shown potential for reducing doses to normal tissues in breast cancer radiotherapy. However data on the impact of protons when including internal mammary nodes (IMN) in the target for breast radiotherapy is comparatively scarce. This study aimed to evaluate normal tissue doses when including the IMN in regional RT with scanned proton beams, with and without respiratory gating. The study cohort was composed of ten left-sided breast patients CT-scanned during enhanced inspiration gating (EIG) and free-breathing (FB). Proton plans were designed for the target including or excluding the IMN. Targets and organs-at-risk were delineated according to RTOG guidelines. Comparison was performed between dosimetric parameters characterizing target coverage and OAR radiation burden. Statistical significance of differences was tested using a paired, two-tailed Student’s t-test. Inclusion of the IMN in the target volume led to a small increase of the cardiopulmonary burden. The largest differences were seen for the ipsilateral lung where the mean dose increased from 6.1 to 6.6 Gy (RBE) (P < 0.0001) in FB plans and from 6.9 to 7.4 Gy (RBE) (P = 0.003) in EIG plans. Target coverage parameters were very little affected by the inclusion of IMN into the treatment target. Radiotherapy with scanned proton beams has the potential of maintaining low cardiovascular burden when including the IMN into the target, irrespective of whether respiratory gating is used or not.     

Impact of acuros XB algorithm in deep-inspiration breath-hold (DIBH) respiratory techniques used for the treatment of left breast cancer

AimTo investigate the impact of Acuros XB (AXB) algorithm in the deep-inspiration breath-hold (DIBH) technique used for treatment of left sided breast cancer.BackgroundAXB may estimate better lung toxicities and treatment outcome in DIBH.Materials and MethodsTreatment plans were computed using the field-in-field technique for a 6 MV beam in two respiratory phases - free breathing (FB) and DIBH. The AXB-calculations were performed under identical beam setup and the same numbers of monitor units as used for AAA-calculation.ResultsMean Hounsfield units (HU), mass density (g/cc) and relative electron density were -782.1 ± 24.8 and -883.5 ± 24.9; 0.196 ± 0.025 and 0.083 ± 0.032; 0.218 ± 0.025 and 0.117 ± 0.025 for the lung in the FB and DIBH respiratory phase, respectively. For a similar target coverage (p > 0.05) in the DIBH respiratory phase between the AXB and AAA algorithm, there was a slight increase in organ at risk (OAR) dose for AXB in comparison to AAA, except for mean dose to the ipsilateral lung. AAA predicts higher mean dose to the ipsilateral lung and lesser V_20Gy for the ipsilateral and common lung in comparison to AXB. The differences in mean dose to the ipsilateral lung were 0.87 ± 2.66 % (p > 0.05) in FB, and 1.01 ± 1.07% (p < 0.05) in DIBH, in V_20Gy the differences were 1.76 ± 0.83% and 1.71 ± 0.82% in FB (p < 0.05), 3.34 ± 1.15 % and 3.24 ± 1.17 % in DIBH (p < 0.05), for the ipsilateral and common lung, respectively.ConclusionFor a similar target volume coverage, there were important differences between the AXB and AAA algorithm for low-density inhomogeneity medium present in the DIBH respiratory phase for left sided breast cancer patients. DIBH treatment in conjunction with AXB may result in better estimation of lung toxicities and treatment outcome.     

Tracking,gating, free-breathing,which technique to use for lung stereotactic treatments? A dosimetric comparison

BackgroundThe management of breath-induced tumor motion is a major challenge for lung stereotactic body radiation therapy (SBRT). Three techniques are currently available for these treatments: tracking (T), gating (G) and free-breathing (FB).AimTo evaluate the dosimetric differences between these three treatment techniques for lung SBRT.Materials and methodsPretreatment 4DCT data were acquired for 10 patients and sorted into 10 phases of a breathing cycle, such as 0% and 50% phases defined respectively as the inhalation and exhalation maximum. GTV_ph, PTV_ph (=GTV_ph + 3 mm) and the ipsilateral lung were contoured on each phase.For the tracking technique, 9 fixed fields were adjusted to each PTV_ph for the 10 phases. The gating technique was studied with 3 exhalation phases (40%, 50% and 60%). For the free-breathing technique, ITV_FB was created from a sum of all GTV_ph and a 3 mm margin was added to define a PTV_FB. Fields were adjusted to PTV_FB and dose distributions were calculated on the average intensity projection (AIP) CT. Then, the beam arrangement with the same monitor units was planned on each CT phase.The 3 modalities were evaluated using DVHs of each GTV_ph, the homogeneity index and the volume of the ipsilateral lung receiving 20 Gy (V_20Gy).ResultsThe FB system improved the target coverage by increasing D_mean (75.87_(T)–76.08_(G)–77.49_(FB)Gy). Target coverage was slightly more homogeneous, too (HI: 0.17_{(T and G)}–0.15_(FB)). But the lung was better protected with the tracking system (V_20Gy: 3.82_(T)–4.96_(G)–6.34_(FB)%).ConclusionsEvery technique provides plans with a good target coverage and lung protection. While irradiation with free-breathing increases doses to GTV, irradiation with the tracking technique spares better the lung but can dramatically increase the treatment complexity.     

Improving Intra-Fractional Target Position Accuracy Using a 3D Surface Surrogate for Left Breast Irradiation Using the Respiratory-Gated Deep-Inspiration Breath-Hold Technique

Purpose

To evaluate the use of 3D optical surface imaging as a surrogate for respiratory gated deep-inspiration breath-hold (DIBH) for left breast irradiation.

Material and Methods

Patients with left-sided breast cancer treated with lumpectomy or mastectomy were selected as candidates for DIBH treatment for their external beam radiation therapy. Treatment plans were created on both free breathing (FB) and DIBH computed tomography (CT) simulation scans to determine dosimetric benefits from DIBH. The Real-time Position Management (RPM) system was used to acquire patient''s breathing trace during DIBH CT acquisition and treatment delivery. The reference 3D surface models from FB and DIBH CT scans were generated and transferred to the “AlignRT” system for patient positioning and real-time treatment monitoring. MV Cine images were acquired during treatment for each beam as quality assurance for intra-fractional position verification. The chest wall excursions measured on these images were used to define the actual target position during treatment, and to investigate the accuracy and reproducibility of RPM and AlignRT.

Results

Reduction in heart dose can be achieved using DIBH for left breast/chest wall radiation. RPM was shown to have inferior correlation with the actual target position, as determined by the MV Cine imaging. Therefore, RPM alone may not be an adequate surrogate in defining the breath-hold level. Alternatively, the AlignRT surface imaging demonstrated a superior correlation with the actual target positioning during DIBH. Both the vertical and magnitude real-time deltas (RTDs) reported by AlignRT can be used as the gating parameter, with a recommended threshold of ±3 mm and 5 mm, respectively.

Conclusion

The RPM system alone may not be sufficient for the required level of accuracy in left-sided breast/CW DIBH treatments. The 3D surface imaging can be used to ensure patient setup and monitor inter- and intra- fractional motions. Furthermore, the target position accuracy during DIBH treatment can be improved by AlignRT as a superior surrogate, in addition to the RPM system.     

Advanced dose calculation algorithms in lung cancer radiotherapy: Implications for SBRT and locally advanced disease in deep inspiration breath hold

PurposeEvaluating performance of modern dose calculation algorithms in SBRT and locally advanced lung cancer radiotherapy in free breathing (FB) and deep inspiration breath hold (DIBH).MethodsFor 17 patients with early stage and 17 with locally advanced lung cancer, a plan in FB and in DIBH were generated with Anisotropic Analytical Algorithm (AAA). Plans for early stage were 3D-conformal SBRT, 45 Gy in 3 fractions, prescribed to 95% isodose covering 95% of PTV and aiming for 140% dose centrally in the tumour. Locally advanced plans were volumetric modulated arc therapy, 66 Gy in 33 fractions, prescribed to mean PTV dose. Calculation grid size was 1 mm for SBRT and 2.5 mm for locally advanced plans. All plans were recalculated with AcurosXB with same MU as in AAA, for comparison on target coverage and dose to risk organs.ResultsLung volume increased in DIBH, resulting in decreased lung density (6% for early and 13% for locally-advanced group).In SBRT, AAA overestimated mean and near-minimum PTV dose (p-values < 0.01) compared to AcurosXB, with largest impact in DIBH (differences of up to 11 Gy). These clinically relevant differences may be a combination of small targets and large dose gradients within the PTV.In locally advanced group, AAA overestimated mean GTV, CTV and PTV doses by median less than 0.8 Gy and near-minimum doses by median 0.4–2.7 Gy.No clinically meaningful difference was observed for lung and heart dose metrics between the algorithms, for both FB and DIBH.ConclusionsAAA overestimated target coverage compared to AcurosXB, especially in DIBH for SBRT.     

Dose-escalated volumetric modulated arc therapy for total marrow irradiation: A feasibility dosimetric study with 4DCT planning and simultaneous integrated boost

PurposeTo evaluate the planning feasibility of dose-escalated total marrow irradiation (TMI) with simultaneous integrated boost (SIB) to the active bone marrow (ABM) using volumetric modulated arc therapy (VMAT), and to assess the impact of using planning organs at risk (OAR) volumes (PRV) accounting for breathing motion in the optimization.MethodsFive patients underwent whole-body CT and thoraco-abdominal 4DCT. A planning target volume (PTV) including all bones and ABM was contoured on each whole-body CT. PRV of selected OAR (liver, heart, kidneys, lungs, spleen, stomach) were determined with 4DCT. Planning consisted of 9–10 full 6 MV photon VMAT arcs. Four plans were created for each patient with 12 Gy prescribed to the PTV, with or without an additional 4 Gy SIB to the ABM. Planning dose constraints were set on the OAR or on the PRV. Planning objective was a PTV D_mean < 110% of the prescribed dose, a PTV V_110% < 50%, and OAR D_mean ≤ 50–60%.ResultsPTV D_mean < 110% was accomplished for most plans (n = 18/20), while all achieved V_110%<50%. SIB plans succeeded to optimally cover the boost volume (median ABM D_mean = 16.3 Gy) and resulted in similar OAR sparing compared to plans without SIB (median OAR D_mean = 40–54% of the ABM prescribed dose). No statistically significant differences between plans optimized with constraints on OAR or PRV were found.ConclusionsAdding a 4 Gy SIB to the ABM for TMI is feasible with VMAT technique, and results in OAR sparing similar to plans without SIB. Setting dose constraints on PRV does not impair PTV dosimetric parameters.     

Characterization of knowledge-based volumetric modulated arc therapy plans created by three different institutions’ models for prostate cancer

BackgroundThe aim of this study was to clarify factors predicting the performance of knowledge-based planning (KBP) models in volume modulated arc therapy for prostate cancer in terms of sparing the organ at risk (OAR).Materials and methodsIn three institutions, each KBP model was trained by more than 20 library plans (LP) per model. To validate the characterization of each KBP model, 45 validation plans (VP) were calculated by the KBP system. The ratios of overlap between the OAR volume and the planning target volume (PTV) to the whole organ volume (V_overlap/V_whole) were analyzed for each LP and VP. Regression lines between dose–volume parameters (V₉₀, V₇₅, and V₅₀) and V_overlap/V_whole were evaluated. The mean OAR dose, V₉₀, V₇₅, and V₅₀ of LP did not necessarily match those of VP.ResultsIn both the rectum and bladder, the dose–volume parameters for VP were strongly correlated with V_overlap/V_whole at institutes A, B, and C (R > 0.74, 0.85, and 0.56, respectively). Except in the rectum at institute B, the slopes of the regression lines for LP corresponded to those for VP. For dose–volume parameters for the rectum, the ratios of slopes of the regression lines in VP to those in LP ranged 0.51–1.26. In the bladder, most ratios were less than 1.0 (mean: 0.77).ConclusionFor each OAR, each model made distinct dosimetric characterizations in terms of V_overlap/V_whole. The relationship between dose–volume parameters and V_overlap/V_whole of OARs in LP predicts the KBP models’ performance sparing OARs.     

Dosimetric effect of intrafraction motion and different localization strategies in prostate SBRT

The aim of this study was to evaluate the dosimetric effect of continuous motion monitoring based localization (Calypso, Varian Medical Systems), gating and intrafraction motion correction in prostate SBRT. Delivered doses were modelled by reconstructing motion inclusive dose distributions for different localization strategies. Actually delivered dose (strategy A) utilized initial Calypso localization, CBCT and additional pre-treatment motion correction by kV-imaging and Calypso, and gating during the irradiation. The effect of gating was investigated by simulating non-gated treatments (strategy B). Additionally, non-gated and single image-guided (CBCT) localization was simulated (strategy C). A total of 308 fractions from 22 patients were reconstructed. The dosimetric effect was evaluated by comparing motion inclusive target and risk organ dose-volume parameters to planned values. Motion induced dose deficits were seen mainly in PTV and CTV to PTV margin regions, whereas CTV dose deficits were small in all strategies: mean ± SD difference in CTVD99% was –0.3 ± 0.4%, −0.4 ± 0.6% and –0.7 ± 1.2% in strategies A, B and C, respectively. Largest dose deficits were seen in individual fractions for strategy C (maximum dose reductions were −29.0% and –7.1% for PTVD95% and CTVD99%, respectively). The benefit of gating was minor, if additional motion correction was applied immediately prior to irradiation. Continuous motion monitoring based localization and motion correction ensured the target coverage and minimized the OAR exposure for every fraction and is recommended to use in prostate SBRT. The study is part of clinical trial NCT02319239.     

In-vivo dosimetry comparison of supraclavicular junction dose for breast and chest-wall patients with and without deep inspiration breath hold (DIBH)

PurposeThe use of deep inspiration breath-hold (DIBH) for patients with left-sided breast cancer reduces cardiac dose, with the aim of reducing the risk of major coronary events. However, this technique has not been universally adopted for patients requiring regional nodal irradiation (RNI) with one concern related to the junction dose. This study evaluates the dose received at the junction for both DIBH and free-breathing patients having tangential breast/chest wall radiation and regional nodal radiation treated with 3D-conformal or hybrid IMRT radiotherapy.MethodsIn-vivo dosimetry measurements utilizing EBT3 GafChromic™ film were performed for 19 patients during three fractions over their course of treatment. The mean junction dose and variability in junction dose were compared between the DIBH and free breathing patients.ResultsOur results show that for voluntary DIBH (v-DIBH) patients the junction dose is more variable between fractions. However, when comparing the average junction dose for DIBH and free breathing patients over the three measurements, the difference was small and not statistically significant. A larger difference was seen when patient measurements were analysed based on treatment linac.ConclusionsThese results show that the mean junction dose is not significantly compromised by the use of v-DIBH. The small possibility of a change in junction dose due to breathing technique should be weighed against the proven increased risks associated with excess cardiac dose received by free-breathing patients. If junction dose is of concern, an in-vivo study, such as this one, could allow cautious introduction of DIBH for patients requiring supraclavicular irradiation.     

Effects of lung tissue characterization in radiotherapy of breast cancer under deep inspiration breath hold when using Monte Carlo dosimetry

PurposeTo investigate the sensitivity of Monte Carlo (MC) calculated lung dose distributions to lung tissue characterization in external beam radiotherapy of breast cancer under Deep Inspiration Breath Hold (DIBH).MethodsEGSnrc based MC software was employed. Mean lung densities for one hundred patients were analysed. CT number frequency and clinical dose distributions were calculated for 15 patients with mean lung density below 0.14 g/cm³. Lung volume with a pre-defined CT numbers was also considered. Lung tissue was characterized by applying different CT calibrations in the low-density region and air-lung tissue thresholds. Dose impact was estimated by Dose Volume Histogram (DVH) parameters.ResultsMean lung densities below 0.14 g/cm³ were found in 10% of the patients. CT numbers below −960 HU dominated the CT frequency distributions with a high rate of CT numbers at −990 HU. Mass density conversion approach influenced the DVH shape. V_4Gy and V_8Gy varied by 7% and 5% for the selected patients and by 9% and 3.5% for the pre-defined lung volume. V_16Gy and V_20Gy, were within 2.5%. Regions above 20 Gy were affected. Variations in air- lung tissue differentiation resulted in DVH parameters within 1%. Threshold at −990 HU was confirmed by the CT number frequency distributions.ConclusionsLung dose distributions were more sensitive to variations in the CT calibration curve below lung (inhale) density than to air-lung tissue differentiation. Low dose regions were mostly affected. The dosimetry effects were found to be potentially important to 10% of the patients treated under DIBH.     

Can the Day 0 CT-scan predict the post-implant scanning? Results from 136 prostate cancer patients

PurposePost-implant CT-scanning is an essential part of permanent prostate brachytherapy. However, the evaluation of post-implant CT dosimetry is not straightforward due to the edema that can modify the dose to the prostate and to the organs at risk. The aim of this study is to evaluate the impact of the timing of the post-implant CT-scan on the dosimetric results and to verify if the Day 0 scan findings can predict Day 50 scanning.Methods136 consecutive patients who received monotherapy with I-125 implants were selected for this study. Two sets of 8 dosimetric quality parameters corresponding to 2 different CT-scans (Day 0 and Day 50) were calculated and compared. The dosimetric parameters included are the percentage volume of the post-implant prostate receiving 80%, 100% and 150% of the prescribed dose, the doses covering 80% and 90% of the prostate volume and the Dose Homogeneity Index. The values of the dose covering 1 cm³ of the rectum and urethra were assessed.ResultsAll the dosimetric parameters of the Day 50 were higher than those of the Day 0 scan. Linear functions were obtained that calculate D₉₀ and V₁₀₀ values at Day 50 based on the Day 0 findings. Rectal and urethral parameters tended to be underestimated on Day 0 CT-scan relative to Day 50 based dosimetry.ConclusionsPredicting the Day 50 dosimetry from the Day 0 scan could be a possible alternative to a Day 50 scan only in specific situations, but with a degree of uncertainty in the predicted values.     

Is the lack of respiratory gating prejudicial for left breast TomoDirect treatments?

Background and purposeTomoDirect (TD) can only operate in free-breathing. The purpose of this study is to compare TD with breath-hold 3D conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) techniques for left breast treatments, and to determine if the lack of respiratory gating is a handicap for cardiac sparing.Materials and methods15 patients treated for left breast had two computed tomography simulation, in free breathing (FB) and in deep-inspiration breath-hold (DIBH). Four treatments were planned: TD-FB, 3DCRT-FB, 3DCRT-DIBH and IMRT-DIBH. Dose to PTV, heart, lungs, right breast and patient were compared.ResultsA slightly lower cardiac mean dose is found for 3DCRT-DIBH than for TD-FB group (1.99 Gy Vs 2.89 Gy, p = 0.0462), while no statistical difference is found for heart V₂₀. TD-FB plans show the best PTV dose homogeneity (0.053, p < 0.001) and the lowest left lung mean dose (5.16 Gy, p < 0.001). No major differences are found for the other organs.ConclusionsTomoDirect and breath-hold 3DCRT are complementary techniques for left breast treatments: for a minority of patients, respiratory gating is mandatory to lower cardiac dose; for the remaining majority of patients, TomoDirect achieves better PTV homogeneity and reduced left lung dose, with cardiac dose equivalent to 3DCRT-DIBH.     

Efficacy of tangential irradiation with volumetric modulated arc therapy on scalp angiosarcoma using medical linac

PurposeTo increase the superficial dose and reduce the brain dose for radiotherapy of scalp angiosarcoma, we propose a novel irradiation technique of tangential irradiation volumetric modulated arc therapy (TI-VMAT).MethodsTI-VMAT and the conventional VMAT treatment plans for thirteen scalp angiosarcoma patients were created with a prescribed dose of 70 Gy. Each treatment was normalized to cover 95% of the planning target volume (PTV) with its prescribed dose. To realize TI-VMAT, an avoidance structure (AS) function was applied. AS was defined as a contour subtracted PTV by a certain space from the brain contour. TI-VMAT treatment plans for six different spaces between PTV and AS were developed and compared with the conventional VMAT treatment plan with respect to the following dosimetric parameters: homogeneity index (HI) and conformity index (CI) of the PTV, mean brain dose, and brain volume irradiated with 20% (V_20% [cc]), 40% (V_40% [cc]), 60% (V_60% [cc]), 80% (V_80% [cc]), and 100% (V_100% [cc]) of the prescribed dose.ResultsHI and CI were comparable between TI-VMAT and the conventional VMAT, the mean brain dose for TI-VMAT with AS defined by a space of 2.0 cm and jaw tracking was 14.27 Gy, which was significantly lower than that for the conventional VMAT (21.20 Gy). In addition, dosimetric parameters such as V_20% [cc] were significantly suppressed compared to those for high doses.ConclusionOur proposed irradiation technique TI-VMAT shows the potential to reduce radiation doses in the brain with maintaining higher dose coverage on the PTV.     

Dosimetric impact of contrast-enhanced 4d computed tomography for stereotactic body radiation therapy of hepatocelluar carcinoma

BackgroundA purpose of the study was to investigate the dosimetric impact of contrast media on dose calculation using average 4D contrast-enhanced computed tomography (4D-CECT) and delayed 4D-CT (d4D-CT) images caused by CT simulation contrast agents for stereotactic body radiation therapy (SBRT) of liver cases.Materials and methodsFifteen patients of liver SBRT treated using the volumetric modulated arc therapy (VMAT) technique were selected retrospectively. 4D-CECT, and d4D-CT were acquired with the Anzai gating system and GE CT. For all patients, gross target volume (GTV) was contoured on the ten phases after rigid registration of both the contrast and delayed scans and merged to generate internal target volume (ITV) on average CT images. Region of interest (ROI) was drawn on contrast images and then copied to the delayed images after rigid registration of two average CT datasets. The treatment plans were generated for contrast enhanced average CT, delayed average CT and contrast enhanced average CT with electron density of the heart overridden.ResultsNo significant dosimetric difference was observed in plans parameters (mean HU value of the liver, total monitor units, total control points, degree of modulation and average segment area) except mean HU value of the aorta amongst the three arms. All the OARs were evaluated and resulted in statistically insignificant variation (p > 0.05) using one way ANOVA analysis.ConclusionsContrast enhanced 4D-CT is advantageous in accurate delineation of tumors and assessing accurate ITV. The treatment plans generated on average 4D-CECT and average d4D-CT have a clinically insignificant effect on dosimetric parameters.     

CyberKnife MLC-based treatment planning for abdominal and pelvic SBRT: Analysis of multiple dosimetric parameters,overall scoring index and clinical scoring

PurposeThis study evaluated the plan quality of CyberKnife MLC-based treatment planning in comparison to the Iris collimator for abdominal and pelvic SBRT. Multiple dosimetric parameters were considered together with a global scoring index validated by clinical scoring.Methods and materialsIris and MLC plans were created for 28 liver, 15 pancreas and 13 prostate cases including a wide range of PTV sizes (24–643 cm³). Plans were compared in terms of coverage, conformity (nCI), dose gradient (R50%), homogeneity (HI), OAR doses, PTV gEUD, MU, treatment time both estimated by TPS (t_TPS) and measured. A global plan quality score index was calculated for IRIS and MLC solutions and validated by a clinical score given independently by two observers.ResultsCompared to Iris, MLC achieved equivalent coverage and conformity without compromising OAR sparing and improving R50% (p < 0.001). MLC gEUD was slightly lower than Iris (p < 0.05) for abdominal cases. MLC reduced significantly MU (−15%) and t_TPS (−22%). Time reduction was partially lost when measured. The global score index was significantly higher for MLC solutions which were selected in 73% and 64% of cases respectively by the first and second observer.ConclusionIris and MLC comparison was not straightforward when based on multiple dosimetric parameters. The use of a mathematical overall score index integrated with a clinical scoring was essential to confirm MLC plans advantages over Iris solutions.     

A prospective comparative dosimetric study between diffusion weighted MRI (DWI) & T2-weighted MRI (T2W) for target delineation and planning in cervical cancer brachytherapy

AimTo evaluate the difference between GTVBT (Gross Tumor Volume at Brachytherapy) and HR CTV (High Risk Clinical Tumor Volume) delineated with DWI and T2W MRI. To evaluate doses to organs at risk and targets from plans generated using T2W and DWI.BackgroundFunctional imaging with DWI can improve cervical tumor distinction as it is more sensitive than T2W MRI even in detecting parametrial invasion. This study does a dosimetric comparison between a T2W and DWI based plan.MethodsFifty carcinoma cervix patients were subjected to MRI based brachytherapy. T2W and a diffusion weighted sequence were acquired. Target delineation and brachytherapy planning was done on both T2W and DWI. Standard DVH parameters were recorded and the treatment was given using the plan generated from T2W images.ResultsGTVBT and HRCTV contours on DWI were different when compared with T2W. Mean GTVBT volume on T2W and DWI was 5.25 and 5.23, respectively (p value 0.8). Mean HRCTV on T2W and DWI was 28.3 and 27 cc, respectively (p value 0.003). Planning on the above volumes resulted in a superior coverage in terms of HRCTV D90 and D100 for DWI based plan, HRCTV D90 — 735.1 and 741 cGy for T2W and DWI, respectively (p value 0.006), HRCTV D100 — 441.05 and 444.5 for T2W and DWI plans, respectively (p value = 0.006). Doses to the OAR were not significantly increased.ConclusionGEC ESTRO based contouring guidelines cover all the functionally abnormal areas on DWI. DWI should only be used as a supplement to T2W for contouring target volumes.     

Application of discrete cosine transform to assess the effect of tumor motion variations on the definition of ITV in lung and liver SBRT

PurposeTo use Discrete Cosine Transform to include tumor motion variations on ITV definition of SBRT patients.MethodsData from 66 patients was collected. 2D planar fluoroscopy images (FI) were available for 54 patients. Daily CBCT projections (CBCTp) from 29 patients were employed to measure interfraction amplitude variability. Systematic amplitude variations were obtained from 17 patients with data from both FI and CBCTp.Tumor motion curves obtained from FI were characterized with a Cosine model (CM), based on cosine functions to the power of 2, 4 or 6, and DCT. Performance of both models was evaluated by means of R² coefficient and by comparing their results on Internal Target Volume (ITV) margins against those calculated from original tumor motion curves.Amplitude variations from CBCTp, as well as estimations of baseline shift variations were added to the DCT model to account for their effect on ITV margins.ResultsDCT replicated tumor motion curves with a mean R² values for all patients of 0.86, 0.91 and 0.96 for the lateral (LAT), anterior-posterior (AP) and cranio-caudal (CC) directions respectively. CM yielded worst results, with R² values of 0.64, 0.61 and 0.74 in the three directions.Interfraction amplitude variation increased ITV margins by a 9%, while baseline shift variability implied a 40% and 80–100% increase for normalized values of baseline shift of 0.2 and 0.4 respectively.ConclusionsProbability distribution functions of tumor positions can be successfully characterized with DCT. This permits to include tumor motion variablilities obtained from patient population into patient specific ITVs.     

Image-guided volumetric arc radiotherapy of pancreatic cancer with simultaneous integrated boost: Optimization strategies and dosimetric results

PurposeTo introduce volumetric modulated arc therapy treatments (VMAT) with simultaneous integrated boost (SIB) for pancreatic cancer and describe dosimetric results on a large patient series.Methods and materials45 patients with pancreatic malignancies were treated with 18 MV single-arc VMAT. Image guidance was performed with daily online kilo-volt cone-beam computed tomography (CBCT). The conformity index (CI) and homogeneity index (HI) to the target volumes, PTV_45Gy and PTV_54Gy, and dose–volume indices to OARs from the QUANTEC task group were reported. The risk of clinical nephritis was evaluated using normal tissue complication probability (NTCP). Treatments were verified in-phantom with the Delta4 system.ResultsAverage CI was 1.06 with 95% confidence intervals (95% CI) of 0.97–1.22 for PTV_45Gy and 1.17 (0.66–1.61) for PTV_54Gy. HI of PTV_54Gy was 1.06 (1.04–1.10). OAR constraints were achieved in all patients, except for kidneys V_12Gy of 48 (35.4–72.3)%. NTCP of the kidneys was 0.98 (0.6–1.7)%. Kidneys V_12Gy and V_20Gy were inversely related to PTV_54Gy CI and maximum dose. All in-phantom tests had gamma pass rates exceeding 95% with global 3% dose difference and 3 mm distance to agreement. Patient shifts measured with CBCT had 95% CI of −0.8, +0.8 in the RL, −0.7, +0.8 in the SI, and −0.8, +0.7 cm in the AP directions.ConclusionsDosimetric results of VMAT were excellent on PTVs and organs at risk. The kidneys represent the dose-limiting organ at risk for this technique. NTCP indicates that this technique is safe from radiation-induced side effects to the kidneys.     

Structure of a Prokaryotic Sodium Channel Pore Reveals Essential Gating Elements and an Outer Ion Binding Site Common to Eukaryotic Channels

Voltage-gated sodium channels (Na_Vs) are central elements of cellular excitation. Notwithstanding advances from recent bacterial Na_V (BacNa_V) structures, key questions about gating and ion selectivity remain. Here, we present a closed conformation of Na_VAe1p, a pore-only BacNa_V derived from Na_VAe1, a BacNa_V from the arsenite oxidizer Alkalilimnicola ehrlichei found in Mono Lake, California, that provides insight into both fundamental properties. The structure reveals a pore domain in which the pore-lining S6 helix connects to a helical cytoplasmic tail. Electrophysiological studies of full-length BacNa_Vs show that two elements defined by the Na_VAe1p structure, an S6 activation gate position and the cytoplasmic tail “neck”, are central to BacNa_V gating. The structure also reveals the selectivity filter ion entry site, termed the “outer ion” site. Comparison with mammalian voltage-gated calcium channel (Ca_V) selectivity filters, together with functional studies, shows that this site forms a previously unknown determinant of Ca_V high-affinity calcium binding. Our findings underscore commonalities between BacNa_Vs and eukaryotic voltage-gated channels and provide a framework for understanding gating and ion permeation in this superfamily.