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Simple Summary: Studies comparing performances of machine learning (ML) methods in building predictive models of toxicity in RT are rare. Thanks to the availability of a large cohort (n = 1314) of breast cancer patients homogeneously treated with tangential fields, different ML approaches could be compared. This work shows how more complex models typically achieve higher performances. At the same time, for this test case, the importance is given mainly by a few variables, and toxicity can be predicted by simpler models with similar performances. The availability of more individually characterizing features (here partially missing) is expected to have a likely much higher impact than the choice of the best-performing ML/DL approach. Purpose. Different ML models were compared to predict toxicity in RT on a large cohort (n = 1314). Methods. The endpoint was RTOG G2/G3 acute toxicity, resulting in 204/1314 patients with the event. The dataset, including 25 clinical, anatomical, and dosimetric features, was split into 984 for training and 330 for internal tests. The dataset was standardized; features with a high p-value at univariate LR and with Spearman ρ > 0.8 were excluded; synthesized data of the minority were generated to compensate for class imbalance. Twelve ML methods were considered. Model optimization and sequential backward selection were run to choose the best models with a parsimonious feature number. Finally, feature importance was derived for every model. Results. The model's performance was compared on a training–test dataset over different metrics: the best performance model was LightGBM. Logistic regression with three variables (LR3) selected via bootstrapping showed performances similar to the best-performing models. The AUC of test data is slightly above 0.65 for the best models (highest value: 0.662 with LightGBM). Conclusions. No model performed the best for all metrics: more complex ML models had better performances; however, models with just three features showed performances comparable to the best models using many (n = 13–19) features. [ABSTRACT FROM AUTHOR]

Objectives: To assess the potential of radiomic features (RFs) extracted from simulation computed tomography (CT) images in discriminating local progression (LP) after stereotactic body radiotherapy (SBRT) in the management of lung oligometastases (LOM) from colorectal cancer (CRC). Materials and methods: Thirty-eight patients with 70 LOM treated with SBRT were analyzed. The largest LOM was considered as most representative for each patient and was manually delineated by two blinded radiation oncologists. In all, 141 RFs were extracted from both contours according to IBSI (International Biomarker Standardization Initiative) recommendations. Based on the agreement between the two observers, 134/141 RFs were found to be robust against delineation (intraclass correlation coefficient [ICC] > 0.80); independent RFs were then assessed by Spearman correlation coefficients. The association between RFs and LP was assessed with Mann–Whitney test and univariate logistic regression (ULR): the discriminative power of the most informative RF was quantified by receiver-operating characteristics (ROC) analysis through area under curve (AUC). Results: In all, 15/38 patients presented LP. Median time to progression was 14.6 months (range 2.4–66 months); 5/141 RFs were significantly associated to LP at ULR analysis (p < 0.05); among them, 4 RFs were selected as robust and independent: Statistical_Variance (AUC = 0.75, p = 0.002), Statistical_Range (AUC = 0.72, p = 0.013), Grey Level Size Zone Matrix (GLSZM) _zoneSizeNonUniformity (AUC = 0.70, p = 0.022), Grey Level Dependence Zone Matrix (GLDZM) _zoneDistanceEntropy (AUC = 0.70, p = 0.026). Importantly, the RF with the best performance (Statisical_Variance) is simply representative of density heterogeneity within LOM. Conclusion: Four RFs extracted from planning CT were significantly associated with LP of LOM from CRC treated with SBRT. Results encourage further research on a larger population aiming to define a usable radiomic score combining the most predictive RFs and, possibly, additional clinical features. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the dose enhancement and internalization of gold nanoparticles (AuNPs) used as a radiosensitizer agent for rotational radiotherapy of breast cancer using a kilovoltage (kV) X‐ray beam. Methods: Human breast cancer cells MDA‐MB‐231 were incubated with or without 100 μg/mL (4.87 nM) or 200 μg/mL (9.74 nM) 15 nm AuNPs and irradiated with 100 kV, 190 kV, or 6 MV X‐rays. To assess the toxicity of the AuNPs, we performed a Sulforhodamine B assay. Using atomic absorption spectroscopy, scanning electron microscopy, transmission electron microscopy, and time‐lapse optical microscopy (rate of 2 frames per minute), we carried out a quantitative assessment of the amount of gold internalized by MDA‐MB‐231 cells and a characterization of the static and dynamical aspects of this internalization process. Results: No effect of AuNPs alone was shown on cell viability. Time‐lapse optical microscopy showed for the first time AuNPs cellular uptake and the dynamics of AuNPs internalization. Electron microscopy demonstrated AuNPs localization in endosomal vesicles, preferentially in the perinuclear region. After irradiation at doses up to 2 Gy, cell survival fraction curves showed increased mortality with AuNPs, with respect to irradiation without AuNPs. The highest effect of radioenhancement by AuNPs (at 9.74 nM AuNPs concentration) was observed at 190 kV showing a dose enhancement factor of 1.33 ± 0.06 (1.34 ± 0.02 at 100 kV), while at 6 MV it was 1.14 ± 0.06. Conclusions: The observed radio‐sensitization effect is promising for future radio‐enhanced kV radiotherapy of breast cancer and quantitatively in the order of previous observations for 15 nm AuNPs. These results of a significant dose enhancement were obtained at 15 nm AuNPs concentration as low as several nanomolar units, at dose levels typical of a single dose fraction in a radiotherapy session. Dynamical behavior of the 3D spatial distribution of 15 nm AuNPs outside the nucleus of single breast cancer cell was observed, with possible implications for future models of AuNPs sensitization. [ABSTRACT FROM AUTHOR]

Purpose: To implement Knowledge Based (KB) automatic planning for right and left-sided whole breast treatment through a new volumetric technique (ViTAT, Virtual Tangential-fields Arc Therapy) mimicking conventional tangential fields (TF) irradiation. Materials and Method: A total of 193 clinical plans delivering TF with wedged or field-in-field beams were selected to train two KB-models for right(R) and left(L) sided breast cancer patients using the RapidPlan (RP) tool implemented in the Varian Eclipse system. Then, a template for ViTAT optimization, incorporating individual KB-optimized constraints, was interactively fine-tuned. ViTAT plans consisted of four arcs (6 MV) with start/stop angles consistent with the TF geometry variability within our population; the delivery was completely blocked along the arcs, apart from the first and last 20° of rotation for each arc. Optimized fine-tuned KB templates for automatic plan optimization were generated. Validation tests were performed on 60 new patients equally divided in R and L breast treatment: KB automatic ViTAT-plans (KB-ViTAT) were compared against the original TF plans in terms of OARs/PTVs dose-volume parameters. Wilcoxon-tests were used to assess the statistically significant differences. Results: KB models were successfully generated for both L and R sides. Overall, 1(3%) and 7(23%) out of 30 automatic KB-ViTAT plans were unacceptable compared to TF for R and L side, respectively. After the manual refinement of the start/stop angles, KB-ViTAT plans well fitted TF-performances for these patients as well. PTV coverage was comparable, while PTV D1% was improved with KB-ViTAT by R:0.4/L:0.2 Gy (p < 0.05); ipsilateral OARs Dmean were similar with a slight (i.e., few % volume) improvement/worsening in the 15–35 Gy/2–15 Gy range, respectively. KB-ViTAT better spared contralateral OARs: Dmean of contralateral OARs was 0.1 Gy lower (p < 0.05); integral dose was R:5%/L:8% lower (p < 0.05) than TF. The overall time for the automatic plan optimization and final dose calculation was 12 ± 2 minutes. Conclusions: Fully automatic KB-optimization of ViTAT can efficiently replace manually optimized TF planning for whole breast irradiation. This approach was clinically implemented in our institute and may be suggested as a large-scale strategy for efficiently replacing manual planning with large sparing of time, elimination of inter-planner variability and of, seldomly occurring, sub-optimal manual plans. [ABSTRACT FROM AUTHOR]

Objective To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography ( PET)/computed tomography ( CT)-guided radiotherapy ( RT), delivered via helical tomotherapy ( HTT; Tomotherapy® Hi-Art II® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node ( LN) relapses in patients with prostate cancer. Patients and Methods From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline- PET/ CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/ mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline- PET/ CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). Results With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/ mL (hazard ratio [ HR] 3.6, 95% confidence interval [ CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline- PET/ CT-positive LN location ( HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT ( HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs ( HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. Conclusions 11C-choline- PET/ CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate toxicity and outcomes after salvage robotic stereotactic body radiotherapy-SBRT- (CyberKnife®,Accuray, Sunnyvale, Ca) re-irradiation of patients with intraprostatic/prostatic bed recurrences of pelvic malignancies. Methods: From 11/2018 to 10/2021, 20 patients with intraprostatic/prostatic bed recurrence after radiotherapy, diagnosed on MRI/ PET choline/PSMA and/or biopsyproven, underwent a salvage re-irradiation with SBRT: 9 patients with prostate cancer failure after previous radical radiotherapy, and 11 patients after adjuvant/salvage radiotherapy. Median prior RT dose was 70.7 (38.25- 78) Gy and the median interval to SBRT salvage therapy was 79.3 (11-208) months. Median PSA before robotic SBRT was 2.64 (1.14-26.8) ng/ml. Fiducial markers were implanted into the target in 19 of 20 patients. Median SBRT total dose was 35 (30-35) Gy in 5 fractions (EQD2=85 Gy, for α/β 1.5). Median prescription isodose was 70% (59- 81%). In 12 patients, a “urethral sparing” was used. In 10 cases a precautionary therapy with steroids and alphalytics was prescribed during the salvage treatment. Twelve patients received neoadjuvant or concomitant/adjuvant androgen suppressive therapy during their SBRT course. Toxicity was scored in accordance with CTCAE v 5.0. Results: Median follow-up was 17.4 months (2.35- 38.15) months. Acute genitourinary (GU) toxicity was observed in 40% of patients and was limited to grade (G)1 in 35% of patients and G2 (minimal strangury, urgency and occasional urinary incontinence) in 5%. Ten% of patients reported late GU G3 toxicity (urinary retention requiring catheterization and transurethral resection), and 5% G2 urinary toxicity. No acute and late gastrointestinal toxicity was observed. At the last follow-up 2 patients died due to a non cancer-releated cause. Twenty-four-months Kaplan Meier estimates of biochemical relapse-free survival (bRFS) was 78.2% (see Figure 1), local-relapse-free survival (LRFS) 92.3% and distant-metastases-free survival 85.1%. Conclusions: Prostate SBRT re-irradiation with CK is a feasible treatment option, with good short-term outcomes. Longer follow-up is necessary to assess the long-term benefits and to determine late toxicity. [ABSTRACT FROM AUTHOR]

Aims: This study reports the preliminary results of a monoinstitutional experience with stereotactic body radiotherapy (SBRT) performed on oligometastatic gynecological cancer patients. Methods: From 04/2009 to 07/2021, 85 lesions (46 patients) were treated: 5 lesions (4 patients) with Image Guided-helical Intensity Modulated Radiotherapy (IGIMRT) at a median dose of 54 (35-63) Gy in 6 (5-10) median fractions prescribed at 95% of the Planning Target Volume (PTV), and 80 lesions (42 patients) with robotic SBRT at a median dose of 40 (18-60) Gy in 5 (1- 8) fractions, prescribed at a median isodose of 80% (68- 84%). Ten.6% of lesions were in the field of a previous adjuvant/salvage IG-IMRT performed at a median dose of 50.4 Gy. Primary origin was: uterine in 39.1%, ovarian/ fallopian tubes in 34.8%, and cervical/vulvar/vaginal in 26.1% of patients. Metastatic site was: brain in 6.5%, liver in 4.3%, lymph-nodes in 60.9%, lung in 23.9%, and bone in 4.3% of patients. Number of concomitant lesions was 1 in 67.4%, 2 in 19.6%, 3 in 2.12%, 4 in 4.3%, and 5 in 6.5% of patients. De nuovo oligometastatic were 32.6%, induced 23.9%, and relapsed 43.5% of patients. Results: Median age at the treatment was 67.4 years (Interquartile Range, IQR: 58.6-75.7). Median follow-up from initial diagnosis was 75.6 months (IQR:46.4–164.8). Median Biologically Effective Dose(BED) prescribed: 79.2 Gy (IQR:59.5-102.6). Twelve and 24 month local relapsefree survival(LRFS) was 88.3 and 84.3%, respectively, while 12 and 24 month distant relapse-free survival(DRFS) was 44.6 and 27.6%. Twenty-four and 36 months overall survival (OS) was 100% and 85% respectively. Acute toxicity registered was grade (G) 1 13% and G2 6.5%. Late toxicity was 2.2% G1, 2.2% G2 and 2.2% (1 patient) G3 (vertebral fracture). There were no differences in DRFS (see Fig.1) and OS between the three groups. At the multivariate analysis factors predicting distant relapse were: age at diagnosis HR=1.07 (95%CI:1.03-1.13, p=0.0021), number of lesions≥3 vs 1, HR= 4.16 (95%CI:1.34-12.9, p=0.0135), and induced vs de nuovo oligometastatic lesions HR=8.55 (95%CI:1.96-37.3, p=0.0043), but not relapsed vs de nuovo(p=0.067). Conclusion: SBRT is effective for the local control of oligometastatic disease from gynecological tumors, with low toxicity. Distant relapse remains the primary cause of failure after SBRT in oligometastatic gynecological patients, and a number of lesions≥3, age at diagnosis and induced oligometastatic lesions are predictive for distant relapse. [ABSTRACT FROM AUTHOR]

Objective: We analyzed initial outcomes and toxicities of the 2 schedules of stereotactic body radiotherapy (SBRT) in use in our department for prostate cancer (PCa) patients. Materials and methods: Between 10/2017-05/2021, 102 PCa patients were treated using robotic SBRT with two different schedules. Group I included 73 patients treated at 36.25 Gy/ 5 fractions at the 79% median isodose, group II 29 patients treated at 38 Gy/ 4 fractions at the 63% median isodose (urethral sparing HDR-like technique). Median age was 74.5 vs 75.8 years, median initial PSA 7.20 vs 7.65 ng/ml. Gleason score was 3+3 in 11% vs 17.2%, 3+4 in 58.9% vs 51.7%, 4+3 in 17.8% vs 20.7% and not accorded (due to previous androgen deprivation) in 1.4% vs 3.5% of patients. Androgen deprivation therapy (ADT) was prescribed in 45% vs 31% of patients, with a median duration of 7 vs 6 months. Fiducial markers were implanted into the prostate in all patients. In 52% of patients steroid therapy and/or alpha-lytics were prescribed to prevent side effects. Toxicity was scored in accordance with CTCAE v 5.0. Biochemical failure was assessed using the nadir + 2 definition. Results: Median follow-up was 23.4 (0-47.2) months in group I vs 12 (2.78-36.07) months in group II. For acute and late toxicities see Table 1. No acute grade(G) 3 toxicities were registered. One (1.4%) late G3 genitourinary toxicity (transurethral incision) occurred in a patient treated with 36.25 Gy. Median post-SBRT PSA level was 0.342 (0.001-231.00) ng/ml in group I and 0.603 (0.05-10.210) ng/ml in group II. At the last follow up 3 pts had died due to a non-cancer related cause, 4 pts had a biochemical failure with PSMA/CholinePET positive progression: 3 treated at 36.25 Gy and 1 treated at 38 Gy. Two-year biochemical relapse-free survival(bRFS) was 94.8% for the patients of group I and 88.9% for the patients of group II, respectively (p= 0.6). Overall survival (OS) was 85.7%vs 98.4% at 2 years(p=0.35). Disease-free survival(DFS) was 94.8% and 88.9%, respectively (p=0.6). No correlation was found between target volume and toxicity. Conclusion: The urethral sparing technique allowed dose escalation (from 2 Gy equivalent dose-EQD2-91 Gy to EQD2 ≥ 120 Gy with α/β 1.5) without increasing G3 toxicity and with non-inferior bRFS despite less ADT prescription. Longer follow-up is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Objective: Low-dose-rate brachytherapy (LDR-BT) in localized prostate cancer is available since 15 years in Italy. We realized the first national multicentre and multidisciplinary data collection to evaluate LDR-BT practice, given as monotherapy, and outcome in terms of biochemical failure. Methods: Between May 1998 and December 2011, 2237 patients with early-stage prostate cancer from 11 Italian community and academic hospitals were treated with iodine-125 (125I) or palladium-103 LDR-BT as monotherapy and followed up for at least 2 years. 125I seeds were implanted in 97.7% of the patients: the mean dose received by 90% of target volume was 145 Gy; the mean target volume receiving 100% of prescribed dose (V100) was 91.1%. Biochemical failure-free survival (BFFS), disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan–Meier method. Log-rank test and multivariable Cox regression were used to evaluate the relationship of covariates with outcomes. Results: Median follow-up time was 65 months. 5- and 7-year DSS, OS and BFFS were 99 and 98%, 94 and 89%, and 92 and 88%, respectively. At multivariate analysis, the National Comprehensive Cancer Network score (p < 0.0001) and V100 (p = 0.09) were correlated with BFFS, with V100 effect significantly different between patients at low risk and those at intermediate/high risk (p = 0.04). Short follow-up and lack of toxicity data represent the main limitations for a global evaluation of LDR-BT. Conclusion: This first multicentre Italian report confirms LDR-BT as an excellent curative modality for low-/intermediate-risk prostate cancer. Advances in knowledge: Multidisciplinary teams may help to select adequately patients to be treated with brachytherapy, with a direct impact on the implant quality and, possibly, on outcome. [ABSTRACT FROM AUTHOR]

Background: To analyse limits and capabilities in dose calculation of collapsed-cone-convolution (CCC) algorithm implemented in helical tomotherapy (HT) treatment planning system for thorax lesions. Methods: The agreement between measured and calculated dose was verified both in homogeneous (Cheese Phantom) and in a custom-made inhomogeneous phantom. The inhomogeneous phantom was employed to mimic a patient's thorax region with lung density encountered in extreme cases and acrylic inserts of various dimensions and positions inside the lung cavity. For both phantoms, different lung treatment plans (single or multiple metastases and targets in the mediastinum) using HT technique were simulated and verified. Point and planar dose measurements, both with radiographic extended-dose-range (EDR2) and radiochromic external-beamtherapy (EBT2) films, were performed. Absolute point dose measurements, dose profile comparisons and quantitative analysis of gamma function distributions were analyzed. Results: An excellent agreement between measured and calculated dose distributions was found in homogeneous media, both for point and planar dose measurements. Absolute dose deviations <3% were found for all considered measurement points, both inside the PTV and in critical structures. Very good results were also found for planar dose distribution comparisons, where at least 96% of all points satisfied the gamma acceptance criteria (3%-3 mm), both for EDR2 and for EBT2 films. Acceptable results were also reported for the inhomogeneous phantom. Similar point dose deviations were found with slightly worse agreement for the planar dose distribution comparison: 96% of all points passed the gamma analysis test with acceptable levels of 4%-4 mm and 5%-4 mm, for EDR2 and EBT2 films respectively. Lower accuracy was observed in high dose/low density regions, where CCC seems to overestimate the measured dose around 4-5%. Conclusions: Very acceptable accuracy was found for complex lung treatment plans calculated with CCC algorithm implemented in the tomotherapy TPS even in the heterogeneous phantom with very low lung-density. [ABSTRACT FROM AUTHOR]

Purpose. To verify the possibility of using Helical Tomotherapy to safely escalate dose to single or multiple highly radioresistant dominant intra-prostatic lesions (DILs) as assessed by functional magnetic resonance imaging (MRI). Material. In seven intermediate/high risk patients, T2WI, T1WI and DWI MRI imaging showed evidence of one DIL in four patients and two DILs in three patients in the peripheral zone of the prostate. The planning strategy was to deliver median doses of 80, 90, 100 and 120 Gy to PTVDIL while delivering 71.4 Gy/28 fractions (EQD2=75 Gy) to the remaining portion of PTV. A higher priority was assigned to rectal constraints relative to DIL coverage. Rectal NTCP calculations were performed using the most recently available model data. Results. The median dose to DIL could safely be escalated to at least 100 Gy (EQD2,α/β=10=113 Gy) without violating safe constraints for the organs at risk. Typical rectal NTCP values were around or below 1-3% for G3 toxicity and 5-7% for G2-G3 toxicity. For the 100 Gy DIL dose boost strategy, mean D95% of DIL and PTVDIL were 98.8 Gy and 86.7 Gy, respectively. The constraints for bladder, urethra and femoral heads were always respected. Conclusions. IGRT by Helical Tomotherapy may permit the safe escalation of EQD2,α/β=10 to at least 113 Gy to DILs without significantly increasing rectal NTCP compared to plans without dose escalation. A Phase I-II clinical study is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: Several phase III randomized trials of moderate hypofractionation, including a higher proportion of high-risk prostate cancer patients treated only to the prostate, failed to demonstrate the superiority of hypofractionated regimens. There is only one randomized phase III trial, of moderately hypofractionated high-dose radiotherapy to the prostate-only versus pelvic irradiation and prostate boost, with a sufficiently long follow-up. It demonstrated better biochemical and disease-free survival when lymph nodal radiotherapy was added. Here we present the 10-year results of our experience based on an Institutional protocol adopted after a phase I–II study, on patients with unfavorable intermediate- (UIR), high- (HR), and very high-risk (VHR) prostate cancer (PCa) treated with pelvic lymph nodal irradiation (WPRT) and moderately hypofractionated high-dose (HD) simultaneous integrated boost (SIB) to the prostate. Prognostic factors for relapse, as well as acute and late gastro-intestinal (GI) and genito-urinary (GU) toxicity were also analyzed. Aims: To report 10-year outcomes of WPRT and HD moderately hypofractionated SIB to the prostate in UIR, HR, and VHR PCa. Methods: From 11/2005 to 12/2015, 224 UIR, HR, and VHR PCa patients underwent WPRT at 51.8 Gy/28 fractions and SIB at 74.2 Gy (EQD2 88 Gy) to the prostate. Androgen deprivation therapy (ADT) was prescribed in up to 86.2% of patients. Results: Median follow-up was 96.3 months (IQR: 71–124.7). Median age was 75 years (IQR: 71.3–78.1). At last follow up, G3 GI–GU toxicity was 3.1% and 8%, respectively. Ten-year biochemical relapse-free survival (bRFS) was 79.8% (95% CI: 72.3–88.1%), disease-free survival (DFS) 87.8% (95% CI: 81.7–94.3%), overall survival (OS) 65.7% (95% CI: 58.2–74.1%), and prostate cancer-specific survival (PCSS) 94.9% (95% CI: 91.0–99.0%). Only two patients presented local relapse. At univariate analysis, VHR vs. UIR was found to be a significant risk factor for biochemical relapse (HR: 2.8, 95% CI: 1.17–6.67, p = 0.021). After model selection, only Gleason Score ≥ 8 emerged as a significant factor for biochemical relapse (HR = 2.3, 95% CI: 1.12–4.9, p = 0.023). Previous TURP (HR = 3.5, 95% CI: 1.62–7.54, p = 0.001) and acute toxicity ≥ G2 (HR = 3.1, 95% CI = 1.45–6.52, p = 0.003) were significant risk factors for GU toxicity ≥ G3. Hypertension was a significant factor for GI toxicity ≥ G3 (HR = 3.63, 95% CI: 1.06–12.46, p = 0.041). ADT (HR = 0.31, 95% CI: 0.12–0.8, p = 0.015) and iPsa (HR = 0.37, 95% CI: 0.16–0.83, p = 0.0164) played a protective role. Conclusions: WPRT and HD SIB to the prostate combined with long-term ADT, in HR PCa, determine good outcomes with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Purpose. To review planning and image-guidance aspects of more than 3 years experience in the treatment of prostate cancer with Helical Tomotherapy (HT). Methods and materials. Planning issues concerning two Phase I-II clinical studies were addressed: in the first one, 58 Gy in 20 fractions were delivered to the prostatic bed for post-prostatectomy patients: in the second one, a simultaneous integrated boost (SIB) approach was applied for radical treatment, delivering 71.4-74.2 Gy to the prostate in 28 fractions. On-line daily MVCT image guidance was applied: bone match was used for post-operative patients while prostate match was applied for radically treated patients. MVCT data of a large sample of both categories of patients were reviewed. Results. At now, more than 250 patients were treated. Planning data show the ability of HT in creating highly homogeneous dose distributions within PTVs. Organs at risk (OAR) sparing also showed to be excellent. HT was also found to favorably compare to inversely-optimized IMAT in terms of PTVs coverage and dose distribution homogeneity. In the case of pelvic nodes irradiation, a large sparing of bowel was evident compared to 3DCRT and conventional 5-fields IMRT. The analysis of MVCT data showed a limited motion of the prostate (about 5% of the fractions show a deviation ≥3 mm in posterior-anterior direction), due to the careful application of rectal emptying procedures. Based on phantom measurements and on the comparison with intra-prostatic calcification-based match, direct visualization prostate match seems to be sufficiently reliable in assessing shifts ≥3 mm. Conclusions. HT offers excellent planning solutions for prostate cancer, showing to be highly efficient in a SIB scenario. Daily MVCT information showed evidence of a limited motion of the prostate in the context of rectal filling control obtained by instructing patients in self-administrating a rectal enema. [ABSTRACT FROM AUTHOR]