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• Segmentation algorithms do not work well on unhealthy lungs as COVID-19 ones. • An Atlas for segmentation of COVID-19 lungs' patients was developed and validated. • Lung histograms parameters could impact the clinical management of COVID-19 patients. • Lung densitometry characterization method integrated to segmentation was implemented. To develop and validate an automated segmentation tool for COVID-19 lung CTs. To combine it with densitometry information in identifying Aerated, Intermediate and Consolidated Volumes in admission (CT1) and follow up CT (CT3). An Atlas was trained on manually segmented CT1 of 250 patients and validated on 10 CT1 of the training group, 10 new CT1 and 10 CT3, by comparing DICE index between automatic (AUTO), automatic-corrected (AUTOMAN) and manual (MAN) contours. A previously developed automatic method was applied on HU lung density histograms to quantify Aerated, Intermediate and Consolidated Volumes. Volumes of subregions in validation CT1 and CT3 were quantified for each method. In validation CT1/CT3, manual correction of automatic contours was not necessary in 40% of cases. Mean DICE values for both lungs were 0.94 for AUTO Vs MAN and 0.96 for AUTOMAN Vs MAN. Differences between Aerated and Intermediate Volumes quantified with AUTO Vs MAN contours were always < 6%. Consolidated Volumes showed larger differences (mean: −95 ± 72 cc). If considering AUTOMAN Vs MAN volumes, differences got further smaller for Aerated and Intermediate, and were drastically reduced for consolidated Volumes (mean: −36 ± 25 cc). The average time for manual correction of automatic lungs contours on CT1 was 5 ± 2 min. An Atlas for automatic segmentation of lungs in COVID-19 patients was developed and validated. Combined with a previously developed method for lung densitometry characterization, it provides a fast, operator-independent way to extract relevant quantitative parameters with minimal manual intervention. [ABSTRACT FROM AUTHOR]

• Development of Custom minibeam collimator. • Dosimetry characteristics evaluated by EBT3 films and TOPAS Monte Carlo. • In vivo experiment using a glioma preclinical model. The purpose of this study is to investigate the dosimetric characteristics of a collimator for minibeam radiotherapy (MBRT) with film dosimetry and Monte Carlo (MC) simulations. The outcome of MBRT with respect to conventional RT using a glioma preclinical model was also evaluated. A multi-slit collimator was designed to be used with commercial small animal irradiator. The collimator was built by aligning 0.6 mm wide and 5 mm thick parallel lead leaves at 0.4 mm intervals. Dosimetry characteristics were evaluated by Gafchromic (CG) films and TOPAS Monte Carlo (MC) code. An in vivo experiment was performed using a glioma preclinical model by injecting two million GL261cells subcutaneously and treating with 25 Gy, single fraction, with MBRT and conventional RT. Survival curves and acute radiation damage were measured to compare both treatments. A satisfactory agreement between experimental results and MC simulations were obtained, the measured FWHM and distance between the peaks were respectively 0.431 and 1.098 mm. In vivo results show that MBRT can provide local tumor control for three weeks after RT treatment and a similar survival fraction of open beam radiotherapy. No severe acute effects were seen for the MBRT group. We developed a minibeam collimator and presented its dosimetric features. Satisfactory agreement between MC and GC films was found with differences consistent with uncertainties due to fabrication and set-up errors. The survival curves of MBRT and open field RT are similar while atoxicity is dramatically lower with MBRT, preliminarily confirming the expected effect. [ABSTRACT FROM AUTHOR]

• Lung densitometry of 251 COVID-19 patients was analyzed with an original method. • Few-CT-features models (with/wout clinical data) predict mortality (AUC = 0.80–0.89). • Training-model (n = 166) performances were confirmed in a validation group (n = 85). To train and validate a predictive model of mortality for hospitalized COVID-19 patients based on lung densitometry. Two-hundred-fifty-one patients with respiratory symptoms underwent CT few days after hospitalization. "Aerated" (AV), "consolidated" (CV) and "intermediate" (IV) lung sub-volumes were quantified by an operator-independent method based on individual HU maximum gradient recognition. AV, CV, IV, CV/AV, IV/AV, and HU of the first peak position were extracted. Relevant clinical parameters were prospectively collected. The population was composed by training (n = 166) and validation (n = 85) consecutive cohorts, and backward multi-variate logistic regression was applied on the training group to build a CT_model. Similarly, models including only clinical parameters (CLIN_model) and both CT/clinical parameters (COMB_model) were developed. Model's performances were assessed by goodness-of-fit (H&L-test), calibration and discrimination. Model's performances were tested in the validation group. Forty-three patients died (25/18 in training/validation). CT_model included AVmax (i.e. maximum AV between lungs), CV and CV/AE, while CLIN_model included random glycemia, C-reactive protein and biological drugs (protective). Goodness-of-fit and discrimination were similar (H&L:0.70 vs 0.80; AUC:0.80 vs 0.80). COMB_model including AVmax, CV, CV/AE, random glycemia, biological drugs and active cancer, outperformed both models (H&L:0.91; AUC:0.89, 95%CI:0.82–0.93). All models showed good calibration (R2:0.77–0.97). Despite several patient's characteristics were different between training and validation cohorts, performances in the validation cohort confirmed good calibration (R2:0–70-0.81) and discrimination for CT_model/COMB_model (AUC:0.72/0.76), while CLIN_model performed worse (AUC:0.64). Few automatically extracted densitometry parameters with clear functional meaning predicted mortality of COVID-19 patients. Combined with clinical features, the resulting predictive model showed higher discrimination/calibration. [ABSTRACT FROM AUTHOR]

To implement knowledge-based (KB) automatic planning for helical TomoTherapy (HTT). The focus of the first clinical implementation was the case of high-risk prostate cancer, including pelvic node irradiation. One hundred two HTT clinical plans were selected to train a KB model using the RapidPlan tool incorporated in the Eclipse system (v13.6, Varian Inc). The individually optimized KB-based templates were converted into HTT-like templates and sent automatically to the HTT treatment planning system through scripting. The full dose calculation was set after 300 iterations without any additional planner intervention. Internal (20 patients in the training cohort) and external (28 new patients) validation were performed to assess the performance of the model: Automatic HTT plans (KB-TP) were compared against the original plans (TP) in terms of organs at risk and planning target volume (PTV) dose–volume parameters and by blinded clinical evaluation of 3 expert clinicians. KB-TP plans were generally better than or equivalent to TP plans in both validation cohorts. A significant improvement in PTVs and rectum–PTV overlap dosimetry parameters were observed for both sets. Organ-at-risk sparing for KB-TP was slightly improved, which was more evident in the external validation group and for bladder and bowel. Clinical evaluation reported KB-TP to be better in 60% of cases and worse in 10% compared with TP (P <.05). The fully KB-based automatic planning workflow was successfully implemented for HTT planning optimization in the case of high-risk patients with prostate cancer. [ABSTRACT FROM AUTHOR]

We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost. From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.14–70.53) years. Histology: 8% in situ carcinoma (ISC), 92% invasive tumors. Molecular subtypes (invasive tumors): 49.9% Luminal A, 33.1% Luminal B Her2 negative (−), 6.2% Luminal B Her2 positive (+), 3.6% Hormone Receptor (HR)- Her2+, 7.1% Triple negative (TNBC), and 0.2% HR+. Chemotherapy (CT) was prescribed in 28% of patients, hormonal therapy in 80.3%, monoclonal antibodies (MAb) in 86.8% of Luminal B Her2+ and 97.7% of HR- Her2+ patients. Median follow up was 72.43 (IQR: 44.63–104.13) months. The 5-year Kaplan-Meier estimates of local relapse-free survival (LRFS) was 97.8%, regional-(RRFS) 98.6%, loco-regional- (LRRFS) 96.9%, distant- (DRFS) 96.6%, disease-free survival (DFS) 94.8% and overall survival (OS) 95.5%. Considering molecular subtypes, 5-year LRFS was: 99.8% for Luminal A, 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 87.9% for HR- Her2+, 95.1% for TNBC and 99.1% for in situ carcinoma. While the overall estimated probability of LR within 5 years after WBHF-IMRT without boost is good (2.2%), molecular subtypes have a strong impact, despite MAb therapy in Her2+ patients, and CT for TNBC patients, and could be used as a parameter in deciding the boost prescription. • Hypofractionated three-weeks radiotherapy ensures good local control whitout boost. • In 1325 early stage breast cancers 5-year local relapse without boost was 2.2%. • Molecular subtypes have a strong impact on estimated probability of local relapse. • 5-year local control (LC) was 99.8% for Luminal A vs 87.9% for HR- Her2+. • 5-year LC was 96.7% for Luminal B Her2-, 94.1% for Luminal B Her2+, 95.1% for TNBC. [ABSTRACT FROM AUTHOR]

• CT RF show large variations against voxel/pixel size and binning for PanNEN patients. • Despite this, the corresponding AUC changes in characterizing PanNEN are limited. • Using a single scanner or contrast images does not significantly affect the results. • Limiting the parameter's set to "more clinical" ranges further reduces AUC changes. To explore the variation of the discriminative power of CT radiomic features (RF) against image discretization/interpolation in characterizing pancreatic neuro-endocrine (PanNEN) neoplasms. Thirty-nine PanNEN patients with pre-surgical high contrast CT available were considered. Image interpolation and discretization parameters were intentionally changed, including pixel size (0.73–2.19 mm2), slice thickness (2–5 mm) and binning (32–128 grey levels) and their combination generated 27 parameter's set. The ability of 69 RF in discriminating post-surgically assessed tumor grade (>G1), positive nodes, metastases and vascular invasion was tested: AUC changes when changing the parameters were quantified for selected RF, significantly associated to each end-point. The analysis was repeated for the corresponding images with contrast medium and in a sub-group of 29/39 patients scanned on a single scanner. The median tumor volume was 1.57 cm3 (16%-84% percentiles: 0.62–34.58 cm3). RF variability against discretization/interpolation parameters was large: only 21/69 RF showed %COV < 20%. Despite this variability, AUC changes were limited for all end-points: with typical AUC values around 0.75–0.85, AUC ranges for the 27 parameter's set were on average 0.062 (1SD:0.037) for all end-points with maximum %COV equal to 5.5% (mean:2.3%). Performances significantly improved when excluding the 5 mm thickness case and fixing the binning to 64 (mean AUC range: 0.036, 1SD:0.019). Using contrast images or limiting the population to single-scanner patients had limited impact on AUC variability. The discriminative power of CT RF for panNEN is relatively invariant against image interpolation/discretization within a large range of voxel sizes and binning. [ABSTRACT FROM AUTHOR]

• KB-optimization for ART early-regression guided boosting technique for rectal cancer. • Robust strategy to scale the KB-model of the first phase to the ART-phase. • Automatic KB-approach showed better/equal performances compared to clinical plans. • A gEUD reduction (up to 3 Gy) was obtained with the KB-optimization. To implement a knowledge-based (KB) optimization strategy to our adaptive (ART) early-regression guided boosting technique in neo-adjuvant radio-chemotherapy for rectal cancer. The protocol consists of a first phase delivering 27.6 Gy to tumor/lymph-nodes (2.3 Gy/fr-PTV 1), followed by the ART phase concomitantly delivering 18.6 Gy (3.1 Gy/fr) and 13.8 Gy (2.3 Gy/fr) to the residual tumor (PTV ART) and to PTV 1 respectively. PTV ART is obtained by expanding the residual GTV, as visible on MRI at fraction 9. Forty plans were used to generate a KB-model for the first phase using the RapidPlan tool. Instead of building a new model, a robust strategy scaling the KB-model to the ART phase was applied. Both internal and external validation were performed for both phases: all automatic plans (RP) were compared in terms of OARs/PTVs parameters against the original plans (RA). The resulting automatic plans were generally better than or equivalent to clinical plans. Of note, V 30Gy and V 40Gy were significantly improved in RP plans for bladder and bowel; gEUD analysis showed improvement for KB-modality for all OARs, up to 3 Gy for the bowel. The KB-model generated for the first phase was robust and it was also efficiently adapted to the ART phase. The performance of automatically generated plans were slightly better than the corresponding manual plans for both phases. [ABSTRACT FROM AUTHOR]

Highlights • The impact of delineation uncertainty on CT features (RF) was quantified for panNEN. • Data of 31 patients and 3 radiologists referred to 69 RF were analyzed. • Volume agreement was good (DICE: 0.78) despite the small values (median: 1.3 cc). • Intra-Class Correlation (ICC) showed very high agreement (ICC > 0.8) for 65/69 RF. • CT radiomics of panNEN is very robust with respect to delineation uncertainty. Abstract Purpose The aim of this study was to quantify the impact of CT delineation uncertainty of pancreatic neuroendocrine neoplasms (panNEN) on Radiomic features (RF). Methods Thirty-one previously operated patients were considered. Three expert radiologists contoured panNEN lesions on pre-surgical high-resolution contrast-enhanced CT images and contours were transferred onto pre-contrast CT. Volume agreement was quantified by the DICE index. After images resampling and re-binning, 69 RF were extracted and the impact of inter-observer variability was assessed by Intra-Class Correlation (ICC): ICC > 0.80 was considered as a threshold for "very high" inter-observer agreement. Results The median volume was 1.3 cc (range: 0.2–110 cc); a satisfactory inter-observer volume agreement was found (mean DICE = 0.78). Only 4 RF showed ICC < 0.80 (0.48–0.73), including asphericity and three RFs (of five) of the neighborhood intensity difference matrix (NID). Conclusions The impact of inter-observer variability in delineating panNEN on RF was minimum, with the exception of the NID family and asphericity, showing a moderate agreement. These results support the feasibility of studies aiming to assess CT radiomic biomarkers for panNEN. [ABSTRACT FROM AUTHOR]

Highlights • White matter is more sensitive to radiation with respect to Gray matter. • MR-Tractography allows to identify the eloquent white matter tracts. • Integration of MR Tractography in Tomotherapy RT planning for brain tumors is investigated. Abstract Introduction Fractionated radiotherapy in brain tumors is commonly associated with several detrimental effects, largely related to the higher radiosensitivity of the white matter (WM) with respect to gray matter. However, no dose constraints are applied to preserve WM structures at present. Magnetic Resonance (MR) Tractography is the only technique that allows to visualize in vivo the course of WM eloquent tracts in the brain. In this study, the feasibility of integrating MR Tractography in tomotherapy treatment planning has been investigated, with the aim to spare eloquent WM regions from the dose delivered during treatment. Methods Nineteen high grade glioma patients treated with fractionated radiotherapy were enrolled. All the patients underwent pre-treatment MR imaging protocol including Diffusion Tensor Imaging (DTI) acquisitions for MR Tractography analysis. Bilateral tracts involved in several motor, language, cognitive functions were reconstructed and these fiber bundles were integrated into the Tomotherapy Treatment planning system. The original plans without tracts were compared with the optimized plans incorporating the fibers, to evaluate doses to WM structures in the two differently optimized plans. Results No significant differences were found between plans in terms of planning target volume (PTV) coverage between the original plans and the optimized plans incorporating fiber tracts. Comparing the mean as well as the maximal dose (Dmean and Dmax), a significant dose reduction was found for most of the tracts. The dose sparing was more relevant for contralateral tracts (P < 0.0001). Conclusion The integration of MR Tractography into radiotherapy planning is feasible and beneficial to preserve important WM structures without reducing the clinical goal of radiation treatment. [ABSTRACT FROM AUTHOR]

Purpose To investigate the robustness of PET radiomic features (RF) against tumour delineation uncertainty in two clinically relevant situations. Methods Twenty-five head-and-neck (HN) and 25 pancreatic cancer patients previously treated with 18 F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT)-based planning optimization were considered. Seven FDG-based contours were delineated for tumour (T) and positive lymph nodes (N, for HN patients only) following manual (2 observers), semi-automatic (based on SUV maximum gradient: PET_Edge) and automatic (40%, 50%, 60%, 70% SUV_max thresholds) methods. Seventy-three RF (14 of first order and 59 of higher order) were extracted using the CGITA software (v.1.4). The impact of delineation on volume agreement and RF was assessed by DICE and Intra-class Correlation Coefficients (ICC). Results A large disagreement between manual and SUV_max method was found for thresholds  ≥50%. Inter-observer variability showed median DICE values between 0.81 (HN-T) and 0.73 (pancreas). Volumes defined by PET_Edge were better consistent with the manual ones compared to SUV40%. Regarding RF, 19%/19%/47% of the features showed ICC < 0.80 between observers for HN-N/HN-T/pancreas, mostly in the Voxel-alignment matrix and in the intensity-size zone matrix families. RFs with ICC < 0.80 against manual delineation (taking the worst value) increased to 44%/36%/61% for PET_Edge and to 69%/53%/75% for SUV40%. Conclusions About 80%/50% of 72 RF were consistent between observers for HN/pancreas patients. PET_edge was sufficiently robust against manual delineation while SUV40% showed a worse performance. This result suggests the possibility to replace manual with semi-automatic delineation of HN and pancreas tumours in studies including PET radiomic analyses. [ABSTRACT FROM AUTHOR]

• KB planning was applied to SBRT prostate cancer with CyberKnife. • The KB model generated DVH prediction for the bladder, the rectum and femoral heads. • A KB-based template was efficiently tuned for both sequential and VOLO algorithms. • The KB-model was able to generate high-quality automatic plans for both modalities. To extend the knowledge-based (KB) automatic planning approach to CyberKnife in the case of Stereotactic Body Radiation Therapy (SBRT) for prostate cancer. Seventy-two clinical plans of patients treated according to the RTOG0938 protocol (36.25 Gy/5fr) with CyberKnife were exported from the CyberKnife system to Eclipse to train a KB-model using the Rapid Plan tool. The KB approach provided dose-volume objectives for specific OARs only and not PTV. Bladder, rectum and femoral heads were considered in the model. The KB-model was successfully trained on 51 plans and then validated on 20 new patients. A KB-based template was tuned in the Precision system for both sequential optimization (SO) and VOLO optimization algorithms. Plans of the validation group were re-optimized (KB-TP) using both algorithms without any operator intervention and compared against the original plans (TP) in terms of OARs/PTV dose-volume parameters. Paired Wilcoxon signed-rank tests were performed to assess statistically significant differences (p < 0.05). Regarding SO, automatic KB-TP plans were generally better than or equivalent to TP plans. PTVs V95% was slightly worse while OARs sparing for KB-TP was significantly improved. Regarding VOLO optimization, the PTVs coverage was significantly better for KB-TP while there was a limited worsening in the rectum. A significant improvement was observed in the bladder in the range of low-intermediate doses. An extension of the KB optimization approach to the CyberKnife system has been successfully developed and validated in the case of SBRT prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: To fit the individual biochemical recurrence-free survival (bRFS) data from patients treated with postprostatectomy radiation therapy (RT) with a comprehensive tumor control probability (TCP) model.Methods and Materials: Considering pre-RT prostate-specific antigen (PSA) as a surrogate of the number of clonogens, bRFS may be expressed as a function of dose-per-fraction-dependent radiosensitivity (αeff), the number of clonogens for pre-RT PSA = 1 ng/mL (C), and the fraction of patients who relapse because of clonogens outside the treated volume (K), assumed to depend (linearly or exponentially) on pre-RT PSA and Gleason score (GS). Data from 894 node-negative, ≥pT2, pN0 hormone-naive patients treated with adjuvant (n=331) or salvage (n=563) intent were available: 5-year bRFS data were fitted grouping patients according to GS (<7:392, =7:383, >7:119).Results: The median follow-up time, pre-RT PSA, and dose were 72 months, 0.25 ng/mL, and 66.6 Gy (range 59.4-77.4 Gy), respectively. The best-fit values were 0.23 to 0.26 Gy(-1) and 10(7) for αeff and C for the model considering a linear dependence between K and PSA. Calibration plots showed good agreement between expected and observed incidences (slope: 0.90-0.93) and moderately high discriminative power (area under the curve [AUC]: 0.68-0.69). Cross-validation showed satisfactory results (average AUCs in the training/validation groups: 0.66-0.70). The resulting dose-effect curves strongly depend on pre-RT PSA and GS. bRFS rapidly decreases with PSA: the maximum obtainable bRFS (defined as 95% of the maximum) declined by about 2.7% and 4.5% for each increment of 0.1 ng/mL for GS <7 and ≥7, respectively.Conclusions: Individual data were fitted by a TCP model, and the resulting best-fit parameters were radiobiologically consistent. The model suggests that relapses frequently result from clonogens outside the irradiated volume, supporting the choice of lymph-node irradiation, systemic therapy, or both for specific subgroups (GS <7: PSA >0.8-1.0 ng/mL; GS ≥7: PSA >0.3 ng/mL). Early RT should be preferred over delayed RT; the detrimental effect of PSA increase can never be fully compensated by increasing the dose, especially for patients with GS ≥7. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the dosimetric accuracy of Pencil beam (PB), Anisotropic Analytical Algorithm (AAA) and Collapsed Cone Convolution Superposition (CCCS) in thoracic tumours for various IMRT techniques. Methods Step-and-shoot Linac IMRT (IMRT), arc volumetric RapidArc (RA) and Helical Tomotherapy (HT) lung treatments for different clinical situations (mediastinum tumour, single metastasis and multiple metastases) were simulated and calculated with PB/AAA, AAA, CCCS, respectively. Delivery quality assurance plans were first verified in homogeneous media (Cheese phantom and ArcCHECK); then several low-density inhomogeneous phantoms were used: the Multiplug ArcCHECK, the commercial ArcCHECK slightly modified with a low density lung–shape insert and a custom-made slab heterogeneous phantom simulating the thorax region. Absolute doses and planar dose maps were checked to assess the agreement between measured and calculated dose distributions. Results In total, data referred to 195 point dose measurements and 189 planar measurements were considered. Average point absolute deviations <3% were found for all the delivery techniques/dose algorithms. In small targets completely embedded in very low density media, deviations up to 7–10% and 4–5% were found for PB and AAA/CCCS respectively. Excellent results were found for planar measurements in ArcCHECK configurations, where ≥95% of points satisfy the 3%/3 mm acceptance criteria for all the algorithms. Conclusions A satisfactory agreement (<2%) between planned and measured doses was generally found for CCCS and AAA, excepting the very critical situation of a small tumour completely embedded in air. A significant dose overestimation (from few to 5–7%) was confirmed for PB in complex inhomogeneous arrangements. [ABSTRACT FROM AUTHOR]

Purpose An adaptive concomitant boost (ACB) for the neo-adjuvant treatment of rectal cancer was clinically implemented. In this study population margins M(90,90) considering rectal deformation were derived for 10 consecutive patients treated at 18 × 2.3 Gy with Helical Tomotherapy (HT) and prospectively validated on 20 additional patients treated with HT, delivering ACB in the last 6 fractions. Methods Sectorial margins M(90,90) of the whole and second treatment parts were assessed for 90% population through a method combining the 90% coverage probability maps of rectal positions (CPC90%) with 3D local distance measurements between the CPC90% and a reference rectal contour. M(90,90) were compared with the margins M(90,90) 95%/99% , ensuring CPC90% coverage with 95%/99% confidence level. M(90,90) of the treatment second part were chosen as ACB margins which were clinically validated for each patient by means of %volume missing of CPC5/6 excluded by the ACB margins. Results The whole treatment M(90,90) ranged between 1.9 mm and 9 mm in the lower-posterior and upper-anterior sectors, respectively. Regarding ACB, M(90,90) were 7 mm in the anterior direction and <5 mm elsewhere. M(90,90) 95%/99% did not significantly differ from M(90,90). The %volume excluded by the ACB margin was<2% for all male and <5% for 9/10 female patients. The dosimetry impact on R_adapt for the patients with the largest residual error was negligible. Conclusions Local deformation measurements confirm an anisotropic motion of rectum once set-up error is rigidly corrected. Margins of 7 mm anterior and 5 mm elsewhere are adequate for ACB. Female patients show a slightly larger residual error. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To assess anatomical, clinical and dosimetric pre-treatment parameters, possibly predictors of parotid shrinkage during radiotherapy of head and neck cancer (HNC). Materials: Data of 174 parotids from four institutions were analysed; patients were treated with IMRT, with radical and adjuvant intent. Parotid shrinkage was evaluated by the volumetric difference (ΔV) between parotid volumes at the end and those at the start of the therapy, as assessed by CT images (MVCT for 40 patients, KVCT for 47 patients). Correlation between ΔVcc/% and a number of dosimetric, clinical and geometrical parameters was assessed. Univariate as well as stepwise logistic multivariate (MVA) analyses were performed by considering as an end-point a ΔVcc/% larger than the median value. Linear models of ΔV (continuous variable) based on the most predictive variables found at the MVA were developed. Results: Median ΔVcc/% were 6.95cc and 26%, respectively. The most predictive independent variables of ΔVcc at MVA were the initial parotid volume (IPV, OR: 1.100; p =0.0002) and Dmean (OR: 1.059; p =0.038). The main independent predictors of ΔV% at MVA were age (OR: 0.968; p =0.041) and V40 (OR: 1.0338; p =0.013). ΔVcc and ΔV% may be well described by the equations: ΔVcc=−2.44+0.076 Dmean (Gy)+0.279 IPV (cc) and ΔV%=34.23+0.192 V40 (%)−0.2203 age (year). The predictive power of the ΔVcc model is higher than that of the ΔV% model. Conclusions: IPV/age and Dmean/V40 are the major dosimetric and clinical/anatomic predictors of ΔVcc and ΔV%. ΔVcc and ΔV% may be well described by bi-linear models including the above-mentioned variables. [Copyright &y& Elsevier]

Abstract: Purpose: To optimise image-guided radiotherapy (IGRT) approaches in set-up error correction for hypofractionated adjuvant treatment of prostate cancer using helical tomotherapy (HT). Methods and materials: HT unit provides megavoltage – CT (MVCT) imaging capability for daily patient set-up. The intrinsic uncertainty of the available image registration techniques was first investigated on a pelvic phantom. To optimise different set-up correction strategies, MVCT data of 37 patients treated with 58Gy delivered in 20 fractions were analyzed. 620 MVCT images were globally available for the analysis. Daily on-line set-up correction without any action level was applied for 27/37 patients. The residual and the effective set-up error were assessed. For 10/37 patients an off-line correction strategy with an action level was applied. Results: Phantom measurements showed an intrinsic uncertainty in MVCT imaging and registration around 0.6mm (±0.5mm) for each of the three main axes. The minimum value of the residual systematic error was found at 7th–10th session, with values between 0.7 and 1.1mm (1 SD); a systematic residual error <2mm for all directions was in any case found at 3th–4th session. This result was also confirmed by the effective systematic set-up error analysis, with a minimum value within 1.5mm nearly at the 4th or 5th fraction. Conclusions: Although the minimum systematic residual error is reached at 7th–10th treatment session, the effective systematic set-up error analysis confirmed that an off-line correction at the 4th fraction without any action level may be a robust compromise with a large sparing of time and resources compared to on-line correction. [Copyright &y& Elsevier]

Abstract: Background and purpose: Image-guided helical tomotherapy (HT) is a new modality for delivering intensity modulated radiation therapy (IMRT) with helical irradiation: the slip ring continuously rotates while the couch moves into the bore. The radiation source (Linac, 6MV) is collimated into a fan beam and modulated by means of a binary multileaf collimator (MLC). A xenon detector array, opposite the radiation source, allows a megavoltage-CT (MVCT) acquisition of patient images for set-up verification. The aim of this paper is to report the results of a two-year quality control (QC) program for the physical and dosimetric characterization of an HT unit installed at our Institute and clinically activated in November 2004, in order to monitor and verify the stability and the reliability of this promising radiation treatment unit. Materials and methods: Conventional Linac acceptance protocols (ATP) and QC protocols were adapted to HT with the addition of specific items reflecting important differences between the two irradiation modalities. QC tests can be summarized as: (a) mechanical and geometrical characterization of the system’s components: evaluation of alignment among radiation source–gantry rotation plan–jaws–MLC–MVCT; (b) treatment beam configuration in static condition: depth dose curves (PDD) and profiles, output factors, output reproducibility and linearity; (c) dynamic component characterization: accuracy and reproducibility of MLC positioning; rotational output reproducibility and linearity, leaf latency, couch movement constancy; (d) gantry–couch and MLC–gantry synchronization; and (e) MVCT image quality. Peculiar periodicity specific tolerance and action levels were defined. Ionization chambers (Exradin A1SL 0.056cc), films (XOmat-V/EDR2), water and solid water phantoms were used to perform quality assurance measurements. Results: Over a two-year period the final average output variation after possible beam output adjustment was −0.2±1% for the static condition and equal to 0±1% for the rotational condition: around 98% of the collected output data was within the action level compared to 94% if no beam output adjustment was considered. An average energy variation of −0.4±0.4% was found. The daily absolute dose verification of IMRT plans showed a dose reproducibility of −0.5±1.2% and −0.4±2.2%, for low and high dose gradient regions, respectively. Source–jaws–MLC and MVCT alignment results and jaw and leaf positioning accuracy were ⩽±1mm. Couch–gantry–MLC synchrony tests showed good stability level (⩽±2mm). Conclusions: QC results indicated good reproducibility of all HT mechanical–dosimetric performance. [Copyright &y& Elsevier]

Radiochromic films (EBT3) are adopted for dosimetric verification and for QA for radiotherapy; however, their use in hadrontherapy is limited to QA procedures. Indeed, a quenching effect occurs consisting of an under-response of the EBT3 film to ion beams with respect to MV-photon beams, at equal dose levels, due to the ion track structure. To investigate the response of EBT3 films irradiated with protons and carbon ions with respect to photons and electrons. The response of EBT3 films to protons and 12C was investigated and compared in terms of Relative Efficiency (RE) with photons and electrons response (dose range 0.4–20 Gy). For protons (63–230 MeV) the RE is constant at 0.984 ± 0.004. For 12C (115–400 MeV/u) the RE is less than unity. The line fit slope for each energy is consistent with zero and the intercepts are 0.695 ± 0.007 (115 MeV/u), 0.773 ± 0.007 (400 MeV/u) and 0.864 ± 0.007 (250 MeV/u). For protons (63–230 MeV) the response of EBT3 is not different from that of photons within experimental uncertainties (2%). For 12C (115–400 MeV/u) EBT3 films show an under-response with respect to photon beams. For 12C ions the response of EBT3 film is dependent on the energy and the under-response is of about 31% for 115 MeV/u, 14% for 250 MeV/u and 23% for 400 MeV/u. [ABSTRACT FROM AUTHOR]

Abstract: Background and Purpose: To investigate the impact of Helical Tomotherapy (HT) upon the dose distribution when compared to our routinely delivered 3D conformal radiotherapy (CRT) in the case of patients affected by stage III non-small-cell lung cancer (NSCLC). Material and methods: Thirteen stage III inoperable NSCLC patients were scheduled to receive 61.2–70.2Gy, 1.8Gy/fraction. Two treatment techniques (HT and CRT) were considered, and in the case of CRT the dose calculation was performed using both the pencil beam (PB) and Anisotropic Analytical Algorithm (AAA) available on the Varian Eclipse planning system. Dose volume constraints for PTV coverage and OAR sparing were assessed for the HT inverse planning with the highest priority upon PTV coverage and spinal cord sparing. The three plans were compared in terms of dose–volume histograms (DVHs) and normal tissue complication probability (NTCP). A statistical analysis was performed using non-parametric Wilcoxon matched pairs tests. Results: In CRT the use of a less accurate algorithm (PB) decreased the monitor unit number by 2.4%. HT significantly improved dose homogeneity within PTV compared with CRT_AAA. For lung parenchyma V20–V40 were lower with HT, corresponding to a decrease of 7% in the risk of radiation pneumonitis. The volume of the heart and esophagus irradiated to >45–60Gy were reduced using HT plans. For eight PTs with an esophagus–PTV overlap >5%, HT significantly reduced both late and acute esophageal complication probability. Conclusions: Our findings obtained in stage III NSCLC patients underline that HT guarantees an important sparing of lungs and esophagus, thus HT has the potential to improve therapeutic ratio, when compared with CRT, by means of dose escalation and/or combined treatment strategy. In CRT of locally advanced lung cancers, the use of a more advanced algorithm would give significantly better modeling of target dose and coverage. [Copyright &y& Elsevier]

Purpose: To assess setup and organ motion error by means of analysis of daily megavoltage computed tomography (MVCT) of patients treated with hypofractionated helical tomotherapy (71.4–74.2 Gy in 28 fractions). Methods and Materials: Data from 21 patients were analyzed. Patients were instructed to empty the rectum carefully before planning CT and every morning before therapy by means of a self-applied rectal enema. The position of the prostate was assessed by means of automatic bone matching (BM) with the planning kilovoltage CT (BM, setup error) followed by a direct visualization (DV) match on the prostate. Deviations between planning and therapy positions referred to BM and BM + DV were registered for the three main axes. In case of a full rectum at MVCT with evident shift of the prostate, treatment was postponed until after additional rectal emptying procedures; in this case, additional MVCT was performed before delivering the treatment. Data for 522 fractions were available; the impact of post-MVCT procedure was investigated for 17 of 21 patients (410 fractions). Results: Prostate motion relative to bony anatomy was limited. Concerning posterior-anterior shifts, only 4.9% and 2.7% of fractions showed deviation of 3 mm or greater of the prostate relative to BM without and with consideration of post-MVCT procedures, respectively. Interobserver variability for BM + DV match was within 0.8 mm (1 SD). Conclusions: Daily MVCT-based correction is feasible. The BM + DV matching was found to be consistent between operators. Rectal emptying using a daily enema is an efficient tool to minimize prostate motion, even for centers that have not yet implemented image-guided radiotherapy. [Copyright &y& Elsevier]

Abstract: Background and purpose: The aim of this study was to analyse our pre-treatment QA data in order to establish uniquely defined agreement criteria between planned and delivered dose distribution for clinical QA practice in IMRT of head and neck (HN) patients. Materials and methods: Pre-treatment QA dosimetry using films in combination with ionisation chambers is routinely evaluated for each patient. This evaluation is performed by comparing planned and measured dose distributions in terms of absolute point dose measurements, planar dose verification and γ function analysis using 4%/3mm values as acceptance criteria. In the current investigation, γ histograms, calculated on dose levels higher than 10% of the prescription dose (1.8Gy/fraction), were further analysed by considering mean values, γ values corresponding to Δ =mean+1.5 SD (named as γ Δ) and the % of points with γ <1, γ <1.5 and γ >2. When considering the patient population, the average values of all these parameters and their confidence limits (mean value+1.5 SD) were calculated. The results here presented refer to 57 HN patients treated in the period September 04–April 06. Results: Better results were found for treatments performed with our newly installed linac (e.g. average γ Δ: 0.8 vs. 1.1 for the preexisting one, p <0.001), due to a more accurate dosimetric configuration. Also, confidence limits for the percentage of points with γ <1, γ <1.5 and γ >2 were found to be quite different for the two linacs (95.3%, 98.9% and 0.4% for the newly installed unit, 87.6%, 95.2% and 2.0% for the preexisting one). Conclusions: Statistical analyses of γ evaluation of QA pre-treatment dosimetry are useful to properly define confidence limits of the agreement between expected and measured fluences based on our institutional experience. Our results confirm that the dosimetry configuration of the beam may significantly affect the agreement between planned and measured IMRT beam fluences. [Copyright &y& Elsevier]