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A system for internal and voluntary reporting of abnormal events in a Nuclear Medicine Therapy Unit is described. This system is based on the Internet of Things and is composed of an application for mobile devices and a wireless network of detectors. The application is addressed to healthcare professionals and is intended to be a user-friendly tool to make the reporting procedure little laborious. The network of detectors allows for a real-time measurement of the dose distribution in the patient’s room. The staff was involved in all stages, from the design of the dosimetry system and mobile application up to their final testing. Face-to-face interviews were carried out with 24 operators in different roles in the Unit (radiation protection experts, physicians, physicists, nuclear medicine technicians and nurses). The preliminary results of the interviews and the current state of development of the application and the detection network will be described.

PURPOSE To evaluate the accuracy of rigid coregistration between multiparametric magnetic resonance (mpMR) and computed tomography (CT) images for radiotherapy of prostate bed cancer recurrence. MATERIALS AND METHOD Fifty-three patients (59 nodules) accrued in a prospective study on salvage radiotherapy for prostatic bed recurrence were suitable for the analysis. Patients underwent a pre radiotherapy mpMR exam and a planning CT in the same treatment position and with control of organ filling. The site of recurrence was delineated on mpMR images and contours transferred on planning CT images using both rigid and deformable registrations. Coregistrations were evaluated by mathematical operators that quantify deformation (Jacobian determinant and vector curl) and similarity indices (Dice and Jaccard coefficients). Dose coverage was evaluated. RESULTS Deformable registration did not change volumes, (p = 0.92 MW test). The Jacobian coefficient and the vector curl revealed no important image deformations. Dice and Jaccard coefficients indicated dislocation of the nodule volumes. Dislocation magnitude was d = (5.6 ± 3.1) mm. Organ filling was not correlated with deformation or dislocation. Volumes were covered by the 95% isodose in 96% of cases when rigid registration was performed versus 75% of cases when deformed. CONCLUSIONS Rigid image coregistration is sufficiently accurate in this setting. The results indicate that the deformable registration tends to shrink the voxels and to dislocate the ROI, the adopted expansion for the recurrence volume adequately accounts for the observed deformation and dislocation, provided that organ filling is controlled.

Aim: Because the clinical feasibility of stereotactic body radiotherapy (SBRT) for early glottic cancer (T1) is controversial, we report dosimetric results in 27 consecutive patients from a prospective phase I and II study that started in 2017. Methods: In our approach, only the parts of the true vocal cord containing cancer and those immediately adjacent are planned to be treated to 36 Gy and 30 Gy, respectively, in 3 fractions. Several dosimetric metrics for both target volumes and organs at risk were extracted from individual plans and results were compared to those achieved by other authors in a similar setting. Results: Proper coverage was reached at planning in 2/3 of planning treatment volume 30 Gy, but only 4 planning treatment volume 36 Gy; conversely, the maximum dose objective was met for most of the patients on either arytenoid cartilage, but this was not the case for 51.9% and 96.3% of cricoid and thyroid cartilages, respectively. Our dosimetric results are similar to if not better than those achieved by others. Conclusion: SBRT in 3 fractions for T1 glottic lesions is dosimetrically challenging. Clinical validation is awaited.

Objective: To assess the predictive role of response on dynamic contrast enhancement on magnetic resonance imaging (DCE-MRI) of visible local lesions in the setting of salvage radiotherapy (sRT) after radical prostatectomy. Methods: All patients referred for sRT for biochemical failure after radical prostatectomy from February 2014 to September 2016 were considered eligible if they had been restaged with DCE-MRI and had been found to have a visible lesion in the prostatic bed, but no distant/nodal disease on choline positron emission tomography (PET)–computed tomography (CT). Eligible patients were contacted during follow-up and offered reimaging with serial DCE-MRI until lesion resolution. Complete response (CR) was defined as the disappearance of the target lesion on DCE-MRI; prostate-specific antigen (PSA) recurrence was defined as a 0.2 ng/mL PSA rise above the nadir. Median follow-up after sRT was 41.5 months (range, 12.1–61.2 months). Results: Fifty-nine patients agreed to undergo repeated DCE-MRI for a total of 64 studied lesions. Overall, 57 lesions (89.1%) showed a CR after 1 (51 patients) or 2 (6 patients) scans, while 7 lesions did not show any change (no response [NR]). At 42 months, no evidence of biochemical disease (bNED) survival was 74.7±6.4% and 64.3±21.0% for patients with CR and NR lesions, respectively (hazard ratio [HR], 3.181; 95% confidence interval [CI], 0.157–64.364; p = 0.451). When only patients treated with sRT without androgen deprivation were selected ( n = 41), bNED survival rates at 42 months were 72.1±8.0% and 0, respectively (HR, 52.830; 95% CI, 1.893–1474.110; p = 0.020). Conclusions: Patients whose lesions disappear during follow-up have a better outcome than those with unchanged lesions after sRT alone.

Highlights • LRB was correlated to irradiation technique and several % rectal wall cut points. • The predictive role of dosimetric variables relates to the irradiation technique. • Dose volume objectives for patients treated with IMRT/VMAT are reported., Background and purpose Dose-volume objectives for the rectum have been proposed to limit long term toxicity after moderately hypofractionated radiotherapy (MHRT) for localized prostate cancer. The purpose of the present study is to validate and possibly refine dose volume objective for the rectal wall after 20-fraction MHRT. Materials and methods All patients treated by 20-fraction MHRT at a single Institution were identified and relative rectal wall (%RW) DVH retrieved. The endpoint of the study is the development of grade 2+ late rectal bleeding (LRB) according to a modified RTOG scale. Clinical and dosimetric predictors of LRB were investigated at both uni- and multi-variable analysis. Results 293 patients were identified and analyzed. Of them, 35 (12%) developed the endpoint. At univariable analysis, antithrombotic drug usage (yes vs no), technique (3DCRT vs IMRT/VMAT) and several %RW DVH cut-points were significantly correlated with LRB. However, within patients treated by 3DCRT (N = 106), a bi-variable model including anti-thrombotic drug usage and selected %RW dose/volume metrics failed to identify independent dosimetric predictors of LRB. Conversely, within patients treated with intensity modulation (N = 187), the same model showed a progressively higher impact of the percent of RW receiving doses above 40 Gy. Based on this model, we were able to confirm (V32), refine (V60) and identify a novel (V50) cut-point for the %RW. Conclusion We recommend the following dose volume objectives for the %RW in order to minimize the risk of LRB after 20-fraction MHRT: V32 ≤ 50%; V50 ≤ 25.8% and V60 ≤ 10%.

To quantify inter-institute variability of Knowledge-Based (KB) models for right breast cancer patients treated with tangential fields whole breast irradiation (WBI).Ten institutions set KB models by using RapidPlan (Varian Inc.), following previously shared methodologies. Models were tested on 20 new patients from the same institutes, exporting DVH predictions of heart, ipsilateral lung, contralateral lung, and contralateral breast. Inter-institute variability was quantified by the inter-institute SDThe overall inter-institute variability of DVH/Dmean ipsilateral lung dose prediction, was less than 2% (20%-80% dose range) and 0.55 Gy respectively (1SD) for a 40 Gy in 15 fraction schedule; it was0.2 Gy for other OARs. Institute 6 showed the lowest mean dose prediction value and no overlap between PTV and ipsilateral lung. Once excluded, the predicted ipsilateral lung Dmean was correlated with median PTV D99% (RResults show limited inter-institute variability of plan prediction models translating in high inter-institute interchangeability, except for one of ten institutes. These results encourage future investigations in generating benchmarks for plan prediction incorporating inter-institute variability.

The aim of the DeepLook project, funded by INFN (Italy), is to implement a deep learning architecture for Computed Aided Detection (CAD), based on neural networks developed with deep learning methods, for the automatic detection and classification of breast lesions in DBT images. A preliminary step (started 2 years ago and still ongoing) was the creation of a dataset of annotated images. This dataset includes images acquired with different clinical DBT units and different acquisition geometries, on several hundred patients, containing a variety of possible breast lesions and normal cases of absence of lesions. This will make the diagnostic capacity of the CAD system particularly extensive in various clinical situations and on a significant sample of patients, so allowing the network to diagnose various types of lesions (at the level of the single tomosynthesis slices) and capable of operate on commercial DBT systems, also available from different vendors, as found in breast diagnosis departments. The developed CAD and first result of the indication of the slice containing the suspected mass will be presented.

Background: To investigate the predictive role of dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) findings before salvage radiotherapy after radical prostatectomy (RP). Methods: This retrospective study selected patients with biochemical failure (BF) after RP restaged with DCE-MRI. Patients underwent sRT in 30 fractions delivering 66–69 Gy and 73.5 Gy to the prostatic fossa and to the local failure as per DCE-MRI, respectively. Pelvic nodes were treated to 54 Gy in selected patients. The endpoint was BF after sRT. Results: In total, 236 patients were analyzed and 146 (61.9%) had presumed local failure at DCE-MRI: 54.8%, 23.8% and 21.4% were found at the vesico-urethral anastomosis (VUA), the bladder neck and the retro-vesical space, respectively. The presence of a local failure at DCE-MRI halved the risk of BF; VUA-only location and lesion volume were independently correlated with survival without evidence of biochemical failure (bNED) at multivariable analysis. For patients with VUA-only disease up to 0.4 cc, the 4-year-bNED was 94.6% (95%CI: 80.2–98.6%) as opposed to 80.9% (95%CI: 71.6–87.4%) and 73.7% (95%CI: 63.1–81.8%) for other lesions and no macrodisease, respectively. Conclusions: DCE-MRI at restaging for BF after RP provides predictive and therapeutic information. Patients with small lesions at the VUA have an excellent prognosis after sRT.

Background: We aimed assess the detection rate (DR) of positron emission tomography/computed tomography with two novel tracers in patients referred for salvage radiotherapy (sRT) with a presumed local recurrence at multiparametric magnetic resonance (mpMR) after radical prostatectomy (RP). Methods: The present prospective study was conducted at a single institution between August 2017 and June 2020. Eligibility criteria were undetectable PSA after RP, subsequent biochemical recurrence (two consecutive PSA rises to 0.2 ng/mL or greater), a presumed local failure at mpMR, no distant metastases at 18F-fluorocholine PET/CT (CH/PET), no previous history of androgen deprivation therapy. Patients were offered both 64CuCl2 PET/CT (CU/PET) and 64Cu-PSMA PET/CT (PSMA/PET) before sRT. After image co-registration, PET findings were compared to mpMR ones in terms of DR and independent predictors of DR investigated at logistic regression. Results: A total of 62 patients with 72 nodules at mpMR were accrued. Compared to mpMR (DR = 100%, 95%CI: 94.9–100%), DRs were 47.2% (95%CI: 36.1–58.6%) and 54.4% (95%CI: 42.7–65.7%) for CU/PET and PSMA/PET, respectively (p &lt, 0.001 for both). Both experimental PET/CT performed particularly poorly at PSA levels consistent with early sRT. Conclusions: The two novel radiotracers are inferior to mpMR in restaging the prostatic fossa for sRT planning purposes, particularly in the context of early salvage radiotherapy.

Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

Background and purpose: To assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. Materials and methods: Complete data of 415 patients enrolled in a multi institute, prospective trial (#NCT02803086) treated with radical (31%), adjuvant (33%) and salvage (36%) intent at a median dose to pelvic nodes/lymph-nodal area of 53 Gy were available. The most severe changes between baseline and radiotherapy mid-point/end toxicity assessed by Inflammatory Bowel Disease Questionnaire (only Bowel Domain) were considered (ΔIBDQ). The 25th percentile values of these score variations were set as endpoints. DVHs of bowel loops for patients with/without toxicity were compared for each endpoint, having excluded patients with baseline scores

Purpose To assess the toxicity profile of prostate cancer stereotactic body radiation therapy (SBRT) in 3 fractions. Methods and Materials This was a prospective, multicenter phase 2 toxicity study enrolling patients with low to favorable intermediate-risk prostate cancer. Before simulation, 3 to 4 fiducial markers along with a rectal spacer were placed. The target (prostate only) was prescribed 40 Gy, whereas the maximum dose to the urethra was limited to 33 Gy with the highest priority at planning; less stringent objectives were placed on the bladder, the filling of which was controlled via a Foley catheter. Treatment was delivered every other day. Toxicity was prospectively scored with Common Terminology Criteria for Adverse Events, and several patient-reported outcomes were collected. The maximum allowed prevalence rate of grade 2+ genitourinary (GU) toxicity at 1 year was set at 15%, and the study was sized accordingly. Results Between November 2015 and May 2019, 59 patients were enrolled by 3 participating institutions. Acute gastrointestinal toxicity was occasional and mild, whereas 11.9% of patients developed acute grade 2 GU toxicity and 1.7% developed acute grade 3 GU toxicity. No patient had persistent treatment-related grade 2+ GU toxicity at 12 months after SBRT; thus, the null hypothesis was rejected. We observed a clinically relevant worsening of both International Prostate Symptom Score (IPSS) and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores at 12 months compared with baseline. Moreover, we found a strong association between all selected bladder dose/volume metrics at planning and ICIQ-SF worsening at 12 months, whereas for the IPSS, the correlation with bladder dose metrics was marginal. Conclusions The results suggest that at 12 months after treatment, the toxicity profile of SBRT in 3 fractions is acceptable.

Purpose/Objective(s) Post-operative loco-regional (LR) hypofractionated radiotherapy (Hypo-RT) is an attractive approach in locally advanced breast cancer (LABC). The aim of this study is to report the preliminary results of a 10 fraction hypofractionated schedule in patients (pts) with resected LABC. Materials/Methods The present is a single arm phase II study assessing toxicity outcomes after 34 Gy/10 fxs/2 wks to the whole breast/chest wall and to the draining lymph nodes; an optional single fraction 8 Gy boost was administered with electrons to the tumor bed in patients who had undergone conservative surgery. Both acute (CTCAE v4.0) and late (LENT/SOMA) toxicities were collected. All pts but those who underwent mastectomy without reconstruction or with temporary expander were also asked to rate their cosmetic outcome according to the Harvard scale. Toxicity was assessed weekly during RT and then at each follow-up examination (1, 3, 6 months and then yearly). Results From February 2015 to March 2019, 59 women (median age 60 yrs, IQR: 48.3-68.8 yrs) with stage II to IIIA breast cancer who underwent axillary dissection and conservative surgery (83%) or mastectomy (17%) entered the study. One patient refused follow up immediately after the end of RT. Of the 58 evaluable pts, 56 underwent neo-adjuvant (41%) or adjuvant (59%) chemotherapy. Trastuzumab was administered concomitant with RT in all HER2 positive pts (25%). RT was delivered initially with a conformal 3D-CRT (32.8%) and then with an optimized IMRT (67.2%) technique to improve the dose distribution. A deep inspiration breath hold technique was used in compliant left-sided LABC pts (48.4%). All ptscompleted treatment as planned. At a median follow up of 42.3 months (IQR 31.4-57.2 mths), no locoregional failures have been observed. Peak acute toxicity was as follows: grade 0, 30 pts (51.7%); grade 1, 25 pts (43.1%); grade 2, 3 pts (5.2%); no grade > 2 toxicity was recorded. Regarding late toxicity, peak 2 events were found for fibrosis (1 pt, 1.7%), telangiectasia (1 pts, 1.7%); lymphedema (1 pt, 1.7%). One patient (1.7%) experienced grade 3 breast retraction. No other grade 2+ events were reported. Of eligible patients (N = 51) patient-reported cosmetic outcome was excellent, good, fair and poor in 59%, 23.5%, 11.7% and 5.8%, respectively. Conclusion These preliminary data support the feasibility and tolerability of our 10-fraction fractionation schedule targeting the primary site as well as the draining lymph node stations after surgery for LABC.

Background There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double-blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo. Methods Patients undergoing concomitant chemo-intensity-modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w). Results One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%-49% were assigned to the placebo group and 53%-51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors. Conclusion The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed.

Background The role of radiotherapy and brachytherapy in the management of locally advanced cervical and endometrial cancer is well established. However, in some cases, intracavitary brachytherapy (ICBRT) is not recommended or cannot be carried out. We aimed to investigate whether external-beam irradiation delivered by means of intensity-modulated radiation therapy (IMRT) might replace ICBRT in gynaecological cancer when the standard ICBRT boost delivering cannot be administered for technical or clinical reasons. Materials and methods Fifteen already delivered treatments for gynaecological cancer patients were analysed. The treatments were performed through 3-dimensional conformal radiotherapy (3D-CRT) to the whole-pelvis up to the dose of 45-50.4 Gy followed by a boost dose administered with ICBRT in high-dose-rate or pulsed-dose-rate modality. For each patient, IMRT plans were elaborated to mimic the ICBRT. We analysed the ICBRT boost versus IMRT boost in terms of dosimetric and radiobiological aspects. Results Mean conformity index value calculated on boost volume was 0.73 for ICBRT and 0.97 for IMRT. Mean conformation number was 0.24 for ICBRT boost and 0.78 for IMRT boost. Mean normal tissue complication probability (NTCP) values for 3D-CRT plus ICBRT and for IMRT (pelvis plus boost) were, respectively, 28% and 5% for rectum; 1.5% and 0.1% for urinary bladder and 8.9% and 6.1% for bowel. Conclusions Our findings suggest that IMRT may represent a viable alternative in delivering the boost in patients diagnosed with gynaecological cancer not amenable to ICBRT.

To compare long-term late local toxicity after either concomitant or sequential chemoradiation therapy after breast-conserving surgery.From 1997 to 2002, women aged 18 to 75 years who underwent breast-conserving surgery and axillary dissection for early breast cancer and in whom CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy was planned were randomized between concomitant and sequential radiation therapy. Radiation therapy was delivered to the whole breast through tangential fields to 50 Gy in 20 fractions over a period of 4 weeks, followed by an electron boost. Surviving patients were tentatively contacted and examined between March and September 2014. Patients in whom progressive disease had developed or who had undergone further breast surgery were excluded. Local toxicity (fibrosis, telangiectasia, and breast atrophy or retraction) was scored blindly to the treatment received. A logistic regression was run to investigate the effect of treatment sequence after correction for several patient-, treatment-, and tumor-related covariates on selected endpoints. The median time to cross-sectional analysis was 15.7 years (range, 12.0-17.8 years).Of 206 patients randomized, 154 (74.8%) were potentially eligible. Of these, 43 (27.9%) refused participation and 4 (2.6%) had been lost to follow-up, and for 5 (3.2%), we could not restore planning data; thus, the final number of analyzed patients was 102. No grade 4 toxicity had been observed, whereas the number of grade 3 toxicity events was low (8%) for each item, allowing pooling of grade 2 and 3 events for further analysis. Treatment sequence (concomitant vs sequential) was an independent predictor of grade 2 or 3 fibrosis according to both the National Cancer Institute Common Terminology Criteria for Adverse Events (odds ratio [OR], 4.05; 95% confidence interval [CI], 1.34-12.2; P=.013) and the SOMA (Subjective, Objective, Management and Analytic) scale (OR, 3.75; 95% CI, 1.19-11.79; P=.018), as well as grade 2 or 3 breast atrophy or retraction (OR, 3.87; 95% CI, 1.42-10.56; P=.008). No effect on telangiectasia was detected.At long-term follow-up, concomitant chemoradiation therapy has a detrimental effect on both fibrosis and retraction with an approximately 4-fold increase in the odds of grade 2 or 3 toxicity.

Purpose A large-scale multi-institutional planning comparison on lung cancer SABR is presented with the aim of investigating possible criticism in carrying out retrospective multicentre data analysis from a dosimetric perspective. Methods Five CT series were sent to the participants. The dose prescription to PTV was 54 Gy in 3 fractions of 18 Gy. The plans were compared in terms of PTV-gEUD 2 (generalized Equivalent Uniform Dose equivalent to 2 Gy), mean dose to PTV, Homogeneity Index (PTV-HI), Conformity Index (PTV-CI) and Gradient Index (PTV-GI). We calculated the maximum dose for each OAR (organ at risk) considered as well as the MLD 2 (mean lung dose equivalent to 2 Gy). The data were stratified according to expertise and technology. Results Twenty-six centers equipped with Linacs, 3DCRT (4% – 1 center), static IMRT (8% – 2 centers), VMAT (76% – 20 centers), CyberKnife (4% – 1 center), and Tomotherapy (8% – 2 centers) collaborated. Significant PTV-gEUD 2 differences were observed (range: 105–161 Gy); mean-PTV dose, PTV-HI, PTV-CI, and PTV-GI were, respectively, 56.8 ± 3.4 Gy, 14.2 ± 10.1%, 0.70 ± 0.15, and 4.9 ± 1.9. Significant correlations for PTV-gEUD 2 versus PTV-HI, and MLD 2 versus PTV-GI, were observed. Conclusions The differences in terms of PTV-gEUD 2 may suggest the inclusion of PTV-gEUD 2 calculation for retrospective data inter-comparison.

This comprehensive review addresses most organs at risk involved in planning optimization for prostate cancer. It can be considered an update of a previous educational review that was published in 2009 (Fiorino et al., 2009). The literature was reviewed based on PubMed and MEDLINE database searches (from January 2009 up to September 2015), including papers in press; for each section/subsection, key title words were used and possibly combined with other more general key-words (such as radiotherapy, dose-volume effects, NTCP, DVH, and predictive model). Publications generally dealing with toxicity without any association with dose-volume effects or correlations with clinical risk factors were disregarded, being outside the aim of the review. A focus was on external beam radiotherapy, including post-prostatectomy, with conventional fractionation or moderate hypofractionation (

Emerging data are showing the safety and the efficacy of Stereotactic Body Radiation Therapy (SBRT) in prostate cancer management. In this context, the medical physicists are regularly involved to review the appropriateness of the adopted technology and to proactively study new solutions. From the physics point of view there are two major challenges in prostate SBRT: (1) mitigation of geometrical uncertainty and (2) generation of highly conformal dose distributions that maximally spare the OARs. Geometrical uncertainties have to be limited as much as possible in order to avoid the use of large PTV margins. Furthermore, advanced planning and delivery techniques are needed to generate maximally conformal dose distributions. In this non-systematic review the technology and the physics aspects of SBRT for prostate cancer were analyzed. In details, the aims were: (i) to describe the rationale of reducing the number of fractions (i.e. increasing the dose per fraction), (ii) to analyze the features to be accounted for performing an extreme hypo-fractionation scheme (>6-7Gy), and (iii) to describe technological solutions for treating in a safe way. The analysis of outcomes, toxicities, and other clinical aspects are not object of the present evaluation.

Purpose To compare five liver metastasis stereotactic ablative radiotherapy (SABR) plans optimised in fourteen centres with 3D-Conformal-RT, IMRT, VMAT, CyberKnife and Tomotherapy and identify possible dosimetric differences. Methods Dose prescription was 75 Gy in 3 fractions, normalised at 67%–95% isodose. Results Excluding few cases, all institutions achieved the planning objectives. Differences up to 40% and 25% in mean dose to liver and PTV were found. No significant correlations between technological factors and DVH for target and OARs were observed; the optimisation strategies selected by the planners played a key role in the planning procedure. Conclusions The human factor and the constraints imposed to the target volume have a greater dosimetric impact than treatment planning and radiation delivery technology in stereotactic treatment of liver metastases. Significant differences found both in terms of dosimetric target coverage and OAR sparing should be taken into consideration before starting a multi-institutional SARB clinical trial.

The purpose of this study is to evaluate the differences between dose distributions calculated with the pencil beam (PB) and X-ray voxel Monte Carlo (MC) algorithms for patients with lung cancer using intensity-modulated radiotherapy (IMRT) or HybridArc techniques. The 2 algorithms were compared in terms of dose–volume histograms, under normal and deep inspiration breath hold, and in terms of the tumor control probability (TCP). The dependence of the differences in tumor volume and location was investigated. Dosimetric validation was performed using Gafchromic EBT3 (International Specialty Products, ISP, Wayne, NJ). Forty-five Computed Tomography (CT) data sets were used for this study; 40 Gy at 8 Gy/fraction was prescribed with 5 noncoplanar 6-MV IMRT beams or 3 to 4 dynamic conformal arcs with 3 to 5 IMRT beams distributed per arc. The plans were first calculated with PB and then recalculated with MC. The difference between the mean tumor doses was approximately 10% ± 4%; these differences were even larger under deep inspiration breath hold. Differences between the mean tumor dose correlated with tumor volume and path length of the beams. The TCP values changed from 99.87% ± 0.24% to 96.78% ± 4.81% for both PB- and MC-calculated plans ( P = .009). When a fraction of hypoxic cells was considered, the mean TCP values changed from 76.01% ± 5.83% to 34.78% ± 18.06% for the differently calculated plans ( P < .0001). When the plans were renormalized to the same mean dose at the tumor, the mean TCP for oxic cells was 99.05% ± 1.59% and for hypoxic cells was 60.20% ± 9.53%. This study confirms that the MC algorithm adequately accounts for inhomogeneities. The inclusion of the MC in the process of IMRT optimization could represent a further step in the complex problem of determining the optimal treatment plan.

Purpose To investigate the potential of intravoxel incoherent motion (IVIM) MRI for early evaluation of irradiated major salivary glands. Materials and Methods Thirty-four patients with head-neck cancer were included in a prospective study. All patients underwent three serial IVIM-MRI: before, half-way through, and at the end of radiotherapy (RT). Apparent diffusion coefficient (ADC), ADClow derived in the low b-value range, perfusion fraction f, and pure diffusion coefficient D were estimated. Pretreatment values and early changes of diffusion parameters were correlated with parotid mean dose (Dmean) and volume reduction after RT. Results Changes in diffusion parameters over time were all significant (P < 0.001 for ADC, ADClow, and D, P = 0.003 for f). Variations of ADC, ADClow, and f were not correlated with Dmean (P = 0.089, P = 0.252 and P = 0.884, respectively), whereas a significant relationship was found between changes in D and Dmean (r = 0.197 with CI95% = 0.004–0.375, P = 0.046). Pretreatment f and Dmean were the best independent predictors for the percentage shrinkage (P = 0.0003 and 0.0597 respectively; R2 = 0.391). Conclusion Early changes of irradiated major salivary glands can be noninvasively evaluated by IVIM-MRI. Perfusion-related coefficients in conjunction with dosimetric information increase our capability to predict the change in parotid volume and hence, if further validated, guide treatment strategy in RT. J. Magn. Reson. Imaging 2015;41:974–982. © 2014 Wiley Periodicals, Inc.

There is no widely accepted intervention in the prevention of acute mucositis during chemoradiotherapy for head and neck carcinoma. In the present double-blind study, we tested 4 natural agents, propolis, aloe vera, calendula, and chamomile versus placebo.Patients undergoing concomitant chemo-intensity-modulated radiotherapy (IMRT) were given natural agent or matched placebo; grade 3 mucositis on physical examination according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was the primary endpoint. Various covariates were tested at logistic regression, including the individual amount of mucosa receiving at least 9.5 Gy per week (V9.5w).One hundred seven patients were randomized from January 2011 to July 2014, and 104 were assessable (51%-49% were assigned to the placebo group and 53%-51% were assigned to the natural agent). Overall, 61 patients developed peak grade 3 mucositis with no difference between arms (P = .65). Conversely, V9.5w (P = .007) and primary site (P = .037) were independent predictors.The selected natural agents do not prevent mucositis, whereas the role of V9.5w is confirmed.

Background and purpose Intestinal toxicity is commonly experienced during whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer. The aim of the current study was to assess bowel dose–volume relationships for acute patient-reported intestinal symptoms of patients treated with WPRT for prostate cancer. Materials and methods Complete data of 206 patients were available; the median dose to pelvic nodes was 51.8 Gy (range 50.4–54.4, 1.7–2 Gy/fr). Intestinal symptoms were assessed as changes in the Inflammatory Bowel Disease Questionnaire scores relative to the Bowel Domain (IBDQ-B) between baseline and radiotherapy mid-point/end. The 25th percentiles of the most severe worsening from baseline (ΔIBDQ-B) were set as end-points. The impact of bowel loops and sigmoid colon dose–volume/surface parameters as well as selected clinical parameters were investigated using multivariate logistic regression. Results Analyses were focused on the four questions showing a median ΔIBDQ-B > 0. No dose volume/surface parameters were predictive, other than ΔIBDQ5 ≥ 3 (loose stools): when grouping patients according to bowel DVHs (high risk: V20 > 470 cc, V30 > 245 cc, V42 > 110 cc; low risk: all the remaining patients), a two-variable model including high-risk DVH-shape (OR: 9.3) and age (protective, OR: 0.94) was assessed. The model showed good calibration (slope: 1.003, R 2 = 0.92) and was found to be robust after bootstrap-based internal validation. Conclusions Constraining the bowel loops may reduce the risk of loose stools. The risk is higher for younger patients.

PURPOSE: To compare the toxicity and efficacy of hypofractionated (62 Gy/20 fractions/5 weeks, 4 fractions per week) vs. conventional fractionation radiotherapy (80 Gy/40 fractions/8 weeks) in patients with high-risk prostate cancer. METHODS AND MATERIALS: From January 2003 to December 2007, 168 patients were randomized to receive either hypofractionated or conventional fractionated schedules of three-dimensional conformal radiotherapy to the prostate and seminal vesicles. All patients received a 9-month course of total androgen deprivation (TAD), and radiotherapy started 2 months thereafter. RESULTS: The median (range) follow-up was 32 (8-66) and 35 (7-64) months in the hypofractionation and conventional fractionation arms, respectively. No difference was found for late toxicity between the two treatment groups, with 3-year Grade 2 rates of 17% and 16% for gastrointestinal and 14% and 11% for genitourinary in the hypofractionation and conventional fractionation groups, respectively. The 3-year freedom from biochemical failure (FFBF) rates were 87% and 79% in the hypofractionation and conventional fractionation groups, respectively (p = 0.035). The 3-year FFBF rates in patients at a very high risk (i.e., pretreatment prostate-specific antigen (iPSA) >20 ng/mL, Gleason score >or=8, or T >or=2c), were 88% and 76% (p = 0.014) in the former and latter arm, respectively. The multivariate Cox analysis confirmed fractionation, iPSA, and Gleason score as significant prognostic factors. CONCLUSIONS: Our findings suggest that late toxicity is equivalent between the two treatment groups and that the hypofractionated schedule used in this trial is superior to the conventional fractionation in terms of FFBF.

Purpose The aim of this work is to report a retrospective study of radiobiological indicators based on Dose–Volume Histograms analysis obtained by stereotactic radiotherapy treatments. Methods and materials Fifty-five patients for a total of sixty-seven brain metastases with a mean target volume of 8.49cc were treated by Dynamic Conformal Arc Therapy (DCAT) and Intensity-Modulated Stereotactic Radiotherapy (IMRST). The Delivered prescription dose was chosen on the basis of tumor size and location so as to ensure a 100% isodose coverage to the target volume. Results The treatment plans reported a mean value of 10% and 2.19% for the inhomogeneity and conformal index, respectively. The F factor showed we overdosed sixty-three patients delivering an additional 7% dose more than calculated values. The radiobiological parameters: TCP and NTCP showed a complete tumor control limiting the organs at risk damage. Conclusion One goal of stereotactic radiotherapy is to design a treatment plan in which the steep dose gradient achievable minimizes the amount of radiation delivered outside the tumor region. This technique allows to deliver a much larger dose to the target without exceeding the radiation-related tolerance of normal tissues and improving patients' quality of life.

Purpose To assess the macroscopic hematuria rates within a single-institution randomized phase 3 trial comparing dose-escalated, conventionally fractionated radiation therapy (CFRT) and moderately hypofractionated radiation therapy (MHRT) for localized prostate cancer. Methods and Materials Patients with intermediate- to high-risk localized prostate cancer were treated with conformal RT and short-course androgen deprivation. Both the prostate and the entire seminal vesicles were treated to 80 Gy in 40 fractions over 8 weeks (CFRT) or 62 Gy in 20 fractions over 5 weeks (MHRT). The endpoint of the present study was the development of any episode or grade of macroscopic hematuria. The median follow-up period was 93 months (range 6-143). Results Macroscopic hematuria was reported by 25 of 168 patients (14.9%). The actuarial estimate of hematuria at 8 years was 17.0% (95% confidence interval [CI] 10.7%-23.3%). The number of patients with hematuria was 6 and 19 in the CFRT and MHRT arms, respectively, for an actuarial 8-year estimate of 9.7% and 24.3%, respectively (hazard ratio 3.468, 95% CI 1.385-8.684; P =.008). Overall, 8 of 25 patients were found to have biopsy-proven urothelial carcinoma (3 in the CFRT arm and 5 in the MHRT arm; P =.27). Thus, the 8-year actuarial incidence of macroscopic hematuria (after censoring urothelial cancer–related episodes) was 4.1% and 18.2% after CFRT and MHRT, respectively (hazard ratio 4.961, 95% CI 1.426-17.263; P =.012). The results were confirmed by multivariate analysis after accounting for several patient-, treatment-, and tumor-related covariates. Conclusions MHRT was associated with a statistically significant increased risk of macroscopic hematuria compared with CFRT.

Background and purpose To report the treatment-related morbidity in patients with prostate cancer treated with an optimized pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated dose escalation to prostate/prostate bed. Materials and methods Between November 2003 and May 2006, 55 patients with localized prostate cancer and >15% risk of lymph node involvement were treated with pelvic IMRT and simultaneous dose escalation to prostate area. Twenty-four patients received a radical radiation therapy program, and the remaining thirty-one patients received a postoperative irradiation as adjuvant treatment or after biochemical or macroscopic local/regional relapse. After a customized immobilization all patients underwent contrast-enhanced CT. On the CT slices CTV1 and CTV2 were delineated. CTV 1 included the prostate and seminal vesicles or prostate bed. CTV 2 consisted of CTV 1 plus pelvic nodes. CTV 1 and CTV 2 were then expanded by 0.5 and 1cm, respectively, to generate the planning target volumes. IMRT treatment plans were generated using commercial inverse planning software. Total doses of 66–80Gy and 50–59Gy in 33–40 fractions were prescribed to the prostate area and pelvis, respectively. The worst acute and late rectal, intestinal and GU toxicities during and after treatment were scored according to the EORTC/RTOG scales. Results The IMRT dose distribution provided excellent PTV coverage and satisfying sparing of all the organs at risk, with no patient experiencing >grade 2 acute or late toxicities. Patients without acute grade 2 intestinal, rectal, and GU toxicity were 91%, 71%, and 63%, respectively. After a median follow-up of 19 months (interquartile range of 9 to 28 months), late grade 2 toxicity was detected only for rectum, with an actuarial 2-year rate of freedom from G2 rectal bleeding of 92%. (CI 95% 0.83–0.99.) Conclusions Pelvic IMRT and simultaneous dose escalation to prostate area is a well-tolerated technique in patients with prostate cancer requiring treatment of pelvic lymph nodes, and seems to be associated with a lower frequency and severity of side effects when compared with conventional techniques reported in other series.

The purpose of this study was to check the setup and dose delivered to the patients during intraoperative electron beam radiation therapy (IORT) for prostate cancer. Twenty eight patients underwent IORT after radical prostatectomy for prostate cancer by means of a dedicated mobile accelerator, Novac7 (by Hitesys, SpA, Italy). A 9 MeV electron beam at high dose per pulse was used. Eighteen patients received IORT at escalating doses of 16, 18, and 20 Gy at 85% isodose, six patients for each dose level. Further, ten patients received 20 Gy at 85% isodose. The electron applicator position was checked in all cases by means of two orthogonal images obtained with brilliance intensifier. Target and organ at risk doses were measured in vivo by a MOSFETs dosimetry system. MOSFETs and microMOSFET dosimeters were inserted into sterile catheters and directly positioned into the rectal lumen, for ten patients, and into the bladder to urethra anastomosis, in the last 14 cases. Verification at 0 degree led to very few adjustments of setup while verifications at 90 degrees often suggested to bring the applicator closer to the target. In vivo dosimetry showed an absorbed dose into the rectum wall < or =1% of the total dose. The average dose value inside the anastomosis, for the 12 patients analyzed, was 23.7 Gy with a standard deviation of +/-7.6%, when the prescription was 20 Gy at 85% isodose. Using a C-arm mobile image intensifier, it is possible to assess if the positioning is correct and safe. Radio-opaque clips and liquid were necessary to obtain good visible images. In vivo MOSFETs dosimetry is feasible and reliable. A satisfactory agreement between measured and expected doses was found.