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Aim: The primary aim of this study is to provide preliminary indications for safe constraints of rectum and bladder in patients re-irradiated with stereotactic body RT (SBRT). Methods: Data from patients treated for prostate cancer (PCa) and intraprostatic relapse, from 1998 to 2016, were retrospectively collected. First RT course was delivered with 3D conformal RT techniques, SBRT or volumetric modulated arc therapy (VMAT). All patients underwent re-irradiation with SBRT with heavy hypofractionated schedules. Cumulative dose-volume values to organs at risk (OARs) were computed and possible correlation with developed toxicities was investigated. Results: Twenty-six patients were included. Median age at re-irradiation was 75 years, mean interval between the two RT courses was 5.6 years and the median follow-up was 47.7 months (13.4–114.3 months). After re-irradiation, acute and late G ≥ 2 GU toxicity events were reported in 3 (12%) and 10 (38%) patients, respectively, while late G ≥ 2 GI events were reported in 4 (15%) patients. No acute G ≥ 2 GI side effects were registered. Patients receiving an equivalent uniform dose of the two RT treatments < 131 Gy appeared to be at higher risk of progression (4-yr b-PFS: 19% vs 33%, p = 0.145). Cumulative re-irradiation constraints that appear to be safe are D30% < 57.9 Gy for bladder and D30% < 66.0 Gy, D60% < 38.0 Gy and V122.1 Gy < 5% for rectum. Conclusion: Preliminary re-irradiation constraints for bladder and rectum have been reported. Our preliminary investigation may serve to clear some grey areas of PCa re-irradiation.

Objective: To compare different stereotactic body techniques—intensity-modulated radiotherapy with photons and protons, applied to radiotherapy of prostatic cancer—with simultaneous integrated boost (SIB) on the dominant intraprostatic lesion (DIL). Methods: Ten patients were selected for this planning study. Dosimetric results were compared between volumetric modulated arc therapy, intensity-modulated radiation therapy (IMRT), and intensity-modulated proton therapy both with two (IMPT 2F) and five fields (IMPT 5F) planning while applying the prescription schemes of 7.25 Gy/fraction to the prostate gland and 7.5 Gy/fraction to the DIL in 5 fractions. Results: Comparison of the coverages of the planning target volumes showed that small differences exist. The IMPT-2F-5F techniques allowed higher doses in the targets; conformal indexes resulted similar; homogeneity was better in the photon techniques (2%–5%). Regarding the organs at risk, all the techniques were able to maintain the dose well below the prescribed constraints: in the rectum, the IMPT-2F-5F and IMRT were more efficient in lowering the intermediate doses; in the bladder, the median dose was significantly better in the case of IMPT (2F–5F). In the urethra, the best sparing was achieved only by IMPT-5F. Conclusions: Stereotactic radiotherapy with SIB for localized prostate cancer is feasible with all the investigated techniques. Concerning IMPT, the two-beam technique does not seem to have a greater advantage compared to the standard techniques; the 5-beam technique seems more promising also accounting for the range uncertainty.

Perineal seeding of tumor cells from prostate cancer (PCa) is very rare, and no standard treatment exists for this atypical presentation with no evidence of distant metastases. Local excision or external beam radiotherapy are used as local salvage treatments for such perineal masses, including those occurring after biopsy, surgery, or interstitial brachytherapy. We report on a patient who presented no evidence of disease and no late urinary or gastrointestinal toxicities at 58 months after receiving high-dose-rate brachytherapy (HDR-BT) for perineal recurrence of PCa after radical prostatectomy and salvage external beam radiotherapy. To the best of our knowledge, this is the first case treated with HDR-BT in this scenario.

Objective: To review the therapeutic strategy in Merkel cell carcinoma (MCC) treated with radiotherapy (RT) discussed in a multidisciplinary tumour board. Methods: Clinical records of patients with a diagnosis of MCC and with an indication to undergo RT at the European Institute of Oncology between 2003 and 2018 were reviewed retrospectively. Results: Twenty-six patients were included in the analysis (median age 65 years, range 42–87). Nineteen received adjuvant RT, 4 exclusive RT, and the remainder palliative RT. Intensity-modulated RT was used in 13 cases, a 3D conformal technique in 11 cases, and stereotactic RT in 2 cases. No major toxicities were recorded. The median relapse-free survival (RFS) after adjuvant RT was 20.5 months, while for unknown primary MCC, it was 23 months. In the adjuvant setting, median polyomavirus-positive RFS was 21.5 months (range 1–49) and median polyomavirus-negative RFS was only 14 months (range 4–45). Overall, RFS of polyomavirus-positive and polyomavirus-negative patients was 10.5 and 8 months, respectively. After adjuvant RT, only 1 out of 10 patients had a recurrence in the RT field. At the time of data collection, 16 patients were alive with no evidence of disease, 1 patient was alive with advanced status of disease, 8 patients died of disease progression, and 1 patient died of other causes. Conclusions: The management of unknown primary and polyomavirus-positive cases, which had a better prognosis in our series, may benefit from a multidisciplinary approach, given the limited data available regarding optimal treatment.

To compare clinical outcomes and toxicities of 2 radiation therapy (RT) schemes for localized prostate cancer (PCa): extreme hypofractionation (EH; fractions of 6.5-7 Gy to a total dose of 32.5-35 Gy) and the moderate hypofractionation (MH; 26 fractions of 2.7 Gy to a total dose of 70.2 Gy). A propensity score method was used to compare the EH-RT and MH-RT groups.Our analysis included a total of 421 patients divided in 2 groups: 227 treated with MH-RT and 194 treated with EH-RT (43 and 30 months median follow-up, respectively). Propensity matching created comparable cohorts. Statistical evaluations were performed on the whole cohort, stratifying the analyses by risk strata factors identified with the propensity scores, and on a subgroup of patients matched by propensity score. Multivariate proportional hazard Cox models were used to compare the 2 groups, mainly for gastrointestinal and genitourinary toxicity and secondarily for clinical progression-free survival, biochemical progression-free survival, and overall survival.Considering the whole population, acute genitourinary and gastrointestinal greater than grade 1 was significantly more frequent in the whole MH-RT group (P.001 and P.002, respectively). A borderline significantly greater late genitourinary was confirmed with the multivariate analysis (P = .07). Concerning tumor outcome, no statistically significant differences were observed. After propensity score matching, 226 patients were included in the analysis. The 2 obtained propensity score matched groups did not differ for any of the clinical and pathologic variables considered for the analysis, resulting in well-balanced cohorts. The results obtained on the whole population were confirmed in the matched groups.EH-RT yields a decreased risk of acute or late toxicities compared with MH-RT, and oncologic outcomes were comparable. Our data indicate that EH-RT might be considered as a treatment modality of choice for select patients with PCa.

Purpose To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. Material and methods Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. Results Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. Conclusions Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

The aim is to present the technical feasibility and efficacy of multiple re-irradiation (re-EBRT) for local recurrence of prostate cancer (PCa) using retrospective analysis of an updated series of patients who received ablative re-EBRT with stereotactic image-guided technique for isolated local recurrence of PCa. Eight patients received three RT courses (2 re-RTs); of those 2 received 4 RT courses (3 re-RTs). Local relapse in the prostate was assessed by multiparametric magnetic resonance and/ or choline positron emission tomography. Before treatment planning, all patients had been evaluated for late toxicity from previous RT according to RTOG/EORTC. Biochemical control was assessed according to Phoenix definition. Mean age at the third RT course was 68 (standard deviation, SD: 7.2); all patients had a good performance status. At diagnosis, four cases were classified as high risk PCa, three as intermediate and one as low per NCCN 2017. Biochemical progression free interval after first and second RT-course were 74 (IQR: 59.3-133.6) months and 33 (IQR: 20.8-53.1) months, respectively. Biochemical and radiological response was registered in all patients. At present, seven out of eight patients are disease free. Overall toxicity profile was good; no severe acute or late genitourinary or gastrointestinal events were recorded. Multiple RT courses with high precision technology and image guidance can be proposed as a possible salvage therapy for locally recurrent, low-burden PCa recurrence in adequately selected patients. Deeper understanding of radiobiological effects of hypofractionation and larger series of patients are warranted to fully evaluate the applicability of multiple RT courses in the setting of locally recurrent PCa.

Background The aim of this study is to evaluate the dose delivered and the image quality of pre-treatment MVCT images with Hi-Art TomoTherapy system, varying acquisition and reconstruction parameters. Materials and methods Catphan 500 MVCT images were acquired with all acquisition pitch and reconstruction intervals; image quality was evaluated in terms of noise, uniformity, contrast linearity, contrast-to-noise ratio (CNR) and spatial resolution with the Modulation Transfer Function (MTF). Dose was evaluated as Multi Slice Average Dose (MSADw) and measurements were performed with the Standard TomoTherapy® Quality Assurance Kit composed by the TomoTherapy Phantom, the Exradin A1SL ion chamber and TomoElectrometer. For each pitch-reconstruction interval, acquisitions were repeated 5 times. Results Differences in noise and uniformity, though statistically significant in some cases, were very small: noise ranged from 2.3% for Coarse – 3 mm to 2.4% for Coarse – 6 mm, while uniformity passed from 99.5% for Coarse – 6 mm to 99.8% for Normal – 4 mm. No differences at all were found for CNR for high and low density inserts, while MTF was higher for pitch Coarse, even if no differences in spatial resolution were observed visually (spatial resolution was up to 4 lp/cm for all combinations of pitch and reconstruction interval). Dose was dependent on pitch, being 1.0 cGy for Coarse, 1.5 cGy for Normal and 2.85 cGy for Fine. Conclusions We observed negligible differences in image quality among different pitch and reconstruction interval, thus, considerations regarding pre-treatment imaging modalities should be based only on dose delivered and on the desired resolution along the cranio-caudal axis for image-guided radiotherapy and adaptive radiotherapy purposes.

Purpose To evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer. Material and methods Between January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered. Results At the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively. Conclusions Our preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients' cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence.

As part of the AIRC IG-13218 (NCT01913717), we analyzed data from patients with low- and intermediate-risk prostate cancer treated with extreme hypofractionated radiotherapy (RT) and simultaneous boost to the intraprostatic lesion. The aim of the study is to identify clinically meaningful information through the analysis of validated questionnaires testing gastrointestinal (GI) and genitourinary (GU) RT-related toxicity and their impact on quality of life (QoL). At the end of RT treatment, clinical assessment and prostate-specific antigen (PSA) measurements were performed every 3 months for at least 2 years and GI and GU toxicities were evaluated contextually. QoL of enrolled patients was assessed by International Prostate Symptoms score (IPSS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire—Core 30 (EORTC QLQ-C30), EORTC QLQ prostate specific (QLQ-PR25), and sexual activity by International Index of Erectile Function (IIEF-5). Patients’ score changes were calculated at the end of RT, at one month after RT and at 12 and 24 months. Sixty-five prospectively enrolled patients were analyzed. Extensive analysis of different QoL assessments showed that patients’ tolerance was satisfactory across all the considered time points, with no statistically significant change of QoL from baseline compared to that before RT. Overall survival and biochemical progression-free survival at 2-years were of 98% and 97%, respectively. Despite the toxicity of extreme hypofractionation was low and tumor control was encouraging, a longer follow-up is necessary to confirm our findings. The increasing dose to the dominant intraprostatic lesion does not worsen the RT toxicity and consequently does not affect patients’ QoL, thus questioning the possibility of an even more escalated treatment.

To evaluate the incidence and predictors for late toxicity and tumor outcome after hypofractionated radiotherapy using three different image-guided radiotherapy (IGRT) systems (hypo-IGRT) compared with conventional fractionation without image guidance (non-IGRT). We compared the late rectal and urinary toxicity and outcome in 179 prostate cancer patients treated with hypo-IGRT (70.2 Gy/26 fractions) and 174 non-IGRT patients (80 Gy/40 fractions). Multivariate analysis was performed to define predictors for late toxicity. 5- and 8-year recurrence-free survival (RFS) and overall survival (OS) were analyzed. Mean follow-up was 81 months for hypo-IGRT and 90 months for non-IGRT group. Mainly mild late toxicity was observed: Hypo-IGRT group experienced 65 rectal (30.9% G1/G2; 6.3% G3/G4) and 105 urinary events (56% G1/G2; 4% G3/G4). 5- and 8-year RFS rates were 87.5% and 86.8% (hypo-IGRT) versus 80.4% and 66.8% (non-IGRT). 5- and 8-year OS rates were 91.3% and 82.7% in hypo-IGRT and 92.2% and 84% in non-IGRT group. Multivariate analysis showed that hypo-IGRT is a predictor for late genitourinary toxicity, whereas hypo-IGRT, acute urinary toxicity and androgen deprivation therapy are predictors for late rectal toxicity. Advanced T stage and higher Gleason score (GS) were correlated with worse RFS. A small increase in mild late toxicity, but not statistically significant increase in severe late toxicity in the hypo-IGRT group when compared with conventional non-IGRT group was observed. Our study confirmed that IGRT allows for safe moderate hypofractionation, offering a shorter overall treatment time, a good impact in terms of RFS and providing potentially more economic health care.

Purpose To evaluate toxicity and clinical outcomes in patients with eyelid tumour treated with contact high-dose-rate brachytherapy (HDR-BT). Material and methods Between April 2010 and August 2017, 10 consecutive patients with tumour of the eyelid underwent contact HDR-BT and custom-made surface mould. Every applicator was manually built using conventional thermoplastic material and standard plastic catheters. The median dose prescribed was 42 Gy (range, 30-48) with a median dose per fraction of 3.5 Gy (range, 2-4.5). The dose was delivered in a median of 12 fractions (range, 10-17) over a median of 16 days. In all cases, an ocular shield was placed to reduce the dose to the eye. Acute and late toxicity was evaluated according to RTOG toxicity criteria. Results We analyzed data of 9 of 10 patients (one patient was excluded because he did not give consent for investigation). The median age was 68 years (range, 31-88). According to the TNM-UICC staging system, 4, 1 and 4 patients were stage IA, IB and IC, respectively. Basal cell and sebaceous gland carcinomas were reported in 5 and 2 patients, respectively; other histological types were non-Hodgkin lymphoma and plasmacytoma. After a median follow-up of 51 months (range, 16-90), there was no evidence of local or distant recurrence. The treatment was very well tolerated. Most commonly acute reactions consisted of low grade (G1-G2) conjunctivitis and skin erythema. Only one patient required a temporary interruption of the treatment due to acute G2 conjunctivitis and G3 lid erythema. Only one G2 late toxicity was reported (corneal ulceration), without resulting in functional impairment or blindness. Conclusions Our results suggest that contact HDR-BT with a customized applicator is safe, effective and offers very good local control and can be considered for the treatment of eyelid tumours.

Introduction Of the different treatments for early prostate cancer, hypofractionated external-beam radiotherapy is one of the most interesting and studied options. Methods The main objective of this phase II clinical study is to evaluate the feasibility, in terms of the incidence of acute side effects, of a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer patients treated with the latest imaging and radiotherapy technology, allowing dose escalation to the dominant intraprostatic lesion identified by multiparametric magnetic resonance imaging. Secondary endpoints of the study are the evaluation of the long-term tolerability of the treatment in terms of late side effects, quality of life, and efficacy (oncological outcome). Results The study is ongoing, and we expect to complete recruitment by the end of 2016. Conclusions Like in previous studies, we expect ultra-hypofractionated radiation treatment for prostate cancer to be well tolerated and effective. Trial registration ClinicalTrials.gov identifier: NCT01913717.

To report toxicity and efficacy outcome of moderately hypofractionated image-guided external-beam radiotherapy in a large series of patients treated for prostate cancer (PCa). Between 10/2006 and 12/2015, 572 T1-T3N0M0 PCa patients received 70.2 Gy in 26 fractions at 2.7 Gy/fraction: 344 patients (60%) with three-dimensional conformal radiotherapy (3D-CRT) and 228 (40%) with intensity-modulated radiotherapy (IMRT). Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median age was 74 years (interquartile range 69-77). Compared with 3D-CRT, in IMRT group more high-risk patients (29% vs 18%; P = 0.002) and more high-volume target (75% vs 60%; P 0.001) were included. Acute gastro-intestinal (GI) toxicity G 1 were registered in 8% and in 11% IMRT and 3D-CRT patients, respectively, whereas late GI G 1 were observed in 2% and 16% IMRT and 3D-CRT patients, respectively. Acute genito-urinary (GU) toxicity G 1 were registered in 26% and 40% IMRT and 3D-CRT patients, respectively, whereas late GU G 1 occurred in 5% IMRT and 15% 3D-CRT patients. Multivariate proportional hazard Cox models confirmed significantly greater risk of late toxicity with 3D-CRT compared to IMRT for GU 1 (P = 0.004) and for GI 1 (P 0.001). With a median 4-year follow-up, overall survival (OS), clinical progression-free survival (cPFS) and biochemical PFS (bPFS) for the whole series were 91%, 92% and 91%, respectively. cPFS and bPFS were significantly different by risk groups. Multivariate Cox models for bPFS and cPFS showed no difference between irradiation techniques and a significant impact of risk group and initial PSA. Moderately hypofractionated radiotherapy is a viable treatment option for localized PCa with excellent tumour control and satisfactory toxicity profile. IMRT seems associated with a reduction in toxicity, whereas tumour control was equal between IMRT and 3D-CRT patients and depended mainly on the risk category.

OBJECTIVE: To report preliminary results of a cutting edge extreme hypofractionated treatment with concomitant boost to the dominant lesion for patients with early stage prostate cancer (PCa). METHODS: AIRC-IG-13218 is a prospective Phase II trial started in June 2015. Patients with low and intermediate risk PCa who met the inclusion criteria underwent extreme hypofractionated radiotherapy to the prostate (36.25 Gy in 5 fractions) and a simultaneous integrated boost to the dominant intraprostatic lesion (DIL) to 37.5 Gy. The DIL was identified by a multiparamentric MRI (mpMRI) co-registered with planning CT. Toxicity was assessed according to CTCAE v4.0 and RTOG/EORTC criteria. The preliminary evaluation of the first 13 patients was required to confirm the feasibility of the treatment before completing the enrollment of 65 patients. RESULTS: The first 13 patients completed the treatment between June 2015 and February 2016. With a median clinical follow-up of 17 months (range 11–26), no Grade 3 or 4 early toxicity was reported. CONCLUSIONS: Our preliminary data about early toxicity of an extreme hypofractionated schedule with concomitant boost on the DIL are encouraging. The higher number of patients expected for the trial and a longer follow-up are needed to confirm these results. ADVANCES IN KNOWLEDGE: The use of mpMRI to identify and boost the DIL is an innovative and interesting approach to PCa. Our preliminary findings suggest that dose escalation using DIL boost and extremely hypofractionated radiotherapy regimens might be a safe approach, allowing for short and effective treatment of organ-confined PCa.

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35 Gy in 5 fractions, while 25 patients (13%) received 32.5 Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9–12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2 ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan–Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7 ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients’ quality of life and potential overall health system and social benefits.

Purpose Formulation of a global Unified Dosimetry Index (gUDI) for the evaluation of prostate simultaneous integrated boost Volumetric Modulated Arc Therapy (VMAT by RapidArc) radiotherapy plans. Methods and materials Dose coverage, conformity, homogeneity and dose gradient index could be included in the Unified Dosimetry Index (UDI). We developed a global UDI to evaluate treatment plans containing volumes irradiated with different dose prescriptions: Intensity Modulated Radiation Therapy with simultaneous integrated boost (IMRT-SIB) with 2 dose levels (36.25 Gy/5 fz for the whole prostate gland and 37.5 Gy/5 fz for Dominant Intraprostatic Lesion (DIL)). To validate gUDI scoring system, 65 prostate cancer patients were evaluated. Mean (µ) and standard deviations (σ) were calculated for all dosimetry indices and gUDI. Furthermore, gUDI µ and σ were analyzed to compare and classify treatment plans: plans can be ranked as “excellent”, “good”, “average” or “poor”. Results Prostate Dose Gradient, Prostate Conformity and DIL Conformity indices had highlighted a major deviation from ideal scores. gUDI index classification showed most of the plans scored as “average” and “good”. Conclusion gUDI score can be a useful tool to quantify treatment plans quality also when volumes with different dose-prescription are treated.

Aim: We report on acute toxicity, which is the secondary endpoint of a phase II clinical trial specifically addressed to assess the chronic toxicity of a hypofractionated scheme including a simultaneous integrated boost, with intensity modulated radiotherapy. Materials and methods: From 2/2012 to 12/2013 194 patients with early breast cancer entered a phase II study on hypofractionated radiotherapy including a boost dose to the tumor bed. All patients were operated on conservatively. The whole breast and the tumor bed are planned to receive a dose of 45 Gy and 50 Gy, respectively, in 20 fractions, over 4 weeks. Treatment plans are generated using the TomoDirect modality,which is available on Tomotherapy Hi-Art System (Madison,WI). Acute toxicity was evaluated according to the RTOG acute toxicity scale, up to 6 months after the treatment. Afterwards, chronic toxicity is evaluated using LENT/SOMA scale. Results: 95% of the volume of the breast and boost PTVs received 99% and 100% of the planned dose, as median values, respectively and 0.1% (median value) of the entire breast volume received 100% of the boost dose. The median maximum dose to the breast and to the boost PTVs was 113% and 103.3 %, respectively. At the end of treatment, the acute toxicity, was distributed as follows. As far as erythema was concerned, at the end of treatment, 58% of the patients experienced grade 1 erythema, which dropped to 23% one month later. Grade 2 erythema affected 37% of the cases, and after one month, it decreased to 2%.Only 1 patient (0.5%) complained of Grade 3 erythema at the end of the treatment, which rapidly disappeared afterwards. With regard to breast oedema, at the end of treatment grade 1 was observed in 16% of the cases, for whom it tended to remain stable after one month, while grade 2 oedema was noted in 4% of the cases, decreasing to 1.5% on the first month- follow-up visit. Regarding desquamation, dry desquamation ( grade 1) was observed in less than 10% of cases at the end of treatment, but it tended to increase to 17% one month later. Patchy moist desquamation (grade 2) was present in 1.9% of the patients at the end of radiotherapy, and in 1% of them, one month afterwards. Confluent desquamation (grade 3) was noted only in 1 patient (0.5%), who was receiving concomitant chemotherapy with cyclophospamide, methotrexate and fluoruracil: it was still present 1 month after the radiotherapy completion, as the patient continued to be on chemotherapy. No significantly different side effects were observed between the whole breast and the boost area. No patients experienced any lung and cardiac symptoms. Conclusion: The clinical results of this SIB hypofractionated scheme showed low acute toxicity. In spite of the high dose per fraction, with the tumor bed receiving an even higher dose /per fraction, acute toxicity was within the limit acknowledged by literature for conventional fractionation. This non-rotational treatment option allows us to deliver treatment with a traditional tangent-like dose, without spreading low doses to the adjacent structures. Chronic toxicity will be assessed after 2 years. Therefore, a longer follow-up is needed to assess the effective tolerance to the SIB schedule. Citation Format: Maria Cristina Leonardi, Anna Morra, Federica Cattani, Luigi Santoro, Samantha Dicuonzo, Raffaella Cambria, Rosa Luraschi, Alessia Bazani, Roberta Lazzari, Veronica Dell'Acqua, Roberto Orecchia. Simultaneous integrated boost incorporated into a hypofractionated regimen using tomoDirect: Acute toxicity assessment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-07.

The integration of CT and multiparametric MRI (mpMRI) is a challenging task in high-precision radiotherapy for prostate cancer. A simple methodology for multimodal deformable image registration (DIR) of prostate cancer patients is presented.CT and mpMRI of 10 patients were considered. Organs at risk and prostate were contoured on both scans. The dominant intraprostatic lesion was additionally delineated on MRI. After a preliminary rigid image registration, the voxel intensity of all the segmented structures in both scans except the prostate was increased by a specific amount (a constant additional value, A), in order to enhance the contrast of the main organs influencing its position and shape. 70 couples of scans were obtained by varying A from 0 to 800 and they were subsequently non-rigidly registered. Quantities derived from image analysis and contour statistics were considered for the tuning of the best performing A.A = 200 resulted the minimum enhancement value required to obtain statistically significant superior registration results. Mean centre of mass distance between corresponding structures decreases from 7.4 mm in rigid registration to 5.3 mm in DIR without enhancement (DIR-0) and to 2.7 mm in DIR with A = 200 (DIR-200). Mean contour distance was 2.5, 1.9 and 0.67 mm in rigid registration, DIR-0 and DIR-200, respectively. In DIR-200 mean contours overlap increases of +13 and +24% with respect to DIR-0 and rigid registration, respectively.Contour propagation according to the vector field resulting from DIR-200 allows the delineation of dominant intraprostatic lesion on CT scan and its use for high-precision radiotherapy treatment planning. Advances in knowledge: We investigated the application of a B-spline, mutual information-based multimodal DIR coupled with a simple, patient-unspecific but efficient contrast enhancement procedure in the pelvic body area, thus obtaining a robust and accurate methodology to transfer the functional information deriving from mpMRI onto a planning CT reference volume.

Objective To report the image-guided hypofractionated radiotherapy (hypo-IGRT) outcome for patients with localised prostate cancer according to the new outcome models Trifecta (cancer control, urinary continence, and sexual potency) and SCP (failure-free survival, continence and potency). Patients and Methods Between August 2006 and January 2011, 337 patients with cT1–T2N0M0 prostate cancer (median age 73 years) were eligible for a prospective longitudinal study on hypo-IGRT (70.2 Gy/26 fractions) in our Department. Patients completed four questionnaires before treatment, and during follow-up: the International Index of Erectile Function-5 (IIEF-5), the International Prostate Symptom Score (IPSS), and the European Organization for Research and Treatment of Cancer prostate-cancer-specific Quality of Life Questionnaires (QLQ) QLQ-PR25 and QLQ-C30. Baseline and follow-up patient data were analysed according to the Trifecta and SCP outcome models. Cancer control, continence and potency were defined respectively as no evidence of disease, score 1 or 2 for item 36 of the QLQ-PR25 questionnaire, and total score of >16 on the IIEF-5 questionnaire. Patients receiving androgen-deprivation therapy (ADT) at any time were excluded. Results Trifecta criteria at baseline were met in 72 patients (42% of all ADT-free patients with completed questionnaires). Both at 12 and 24 months after hypo-IGRT, 57% of the Trifecta patients at baseline were still meeting the Trifecta criteria (both oncological and functional success according to the SCP model). The main reason for failing the Trifecta criteria during follow-up was erectile dysfunction: in 18 patients after 6 months follow-up, in 12 patients after 12 months follow-up, and in eight patients after 24 months. Actuarial 2-year Trifecta failure-free survival rate was 44% (95% confidence interval 27–60%). In multivariate analysis no predictors of Trifecta failure were identified. Missing questionnaires was the main limitation of the study. Conclusion The Trifecta and SCP classifications can be used as tools to report RT outcome.

Purpose To assess dose and image quality in phantom with HiArt TomoTherapy and to evaluate the feasibility to acquire pre-treatment images with a pitch Coarse with a 3 mm slice thickness (ST) instead of the currently used 6 mm ST. Methods Multiple Scan Average Dose ( MSAD w ) was calculated according to the literature using a Exradin ion-chamber in a TomoPhant placed at the isocenter. Measurements were repeated 5 times for each combination pitch -ST reconstruction (Fine 1 and 2 mm, Normal 2 and 4 mm and Coarse 3 and 6 mm) for 2 different scan lengths (5 and 10 cm). Image quality was assessed scanning a Catphan500 for 5 times with each combination of pitch and ST and the collected data were evaluated in terms of contrast linearity, signal uniformity, noise, Signal-to-noise (SNR) ratio. In addition, spatial resolution was evaluated both qualitatively and quantitatively. Results MSADw for the 10-cm scan length was of 1.03 ± 0.01 cGy for pitch Coarse, 1.48 ± 0.01 cGy for pitch Normal and 2.83 ± 0.01 cGy for pitch Fine. We found slight lower values for the 5-cm scan length (0.94 ± 0.01 cGy, 1.36 ± 0.01 cGy and 2.67 ± 0.01 cGy for pitch Coarse, Normal and Fine, respectively) due to the lower scattered radiation. Considering image quality, signal uniformity was comparable among the different pitch-ST combinations; noise ranged from 2.4% to 2.5% with no significant differences changing pitch or ST. Signal-to-noise ratio ranged from 40.0 ± 2.0 from pitch Coarse-6 mm to 42.1 ± 1.2 for Normal-4 mm but we found no statistical significance in these differences. MTF 50 % was of 3.3 lp/cm for Coarse, 2.7 lp/cm for Normal and 2.5 lp/cm for Fine. Anyway these differences were not empirically detectable on the images, in which we observed up to 4 lp/cm for all the pitch-ST combinations. Conclusions The acquisitions of pre-treatment images with pitch Coarse and 3 mm ST reconstruction is feasible and justified according to our results.

Purpose Formulation of a global Unified Dosimetry Index (gUDI) for the evaluation of ultra-hypofractionated prostate Volumetric Modulated Arc Therapy (VMAT by RapidArc) treatment plans. Methods Radiotherapy treatment plan quality can be assessed in terms of dose coverage, conformity, homogeneity and dose gradient index. All these parameters could be included in the Unified Dosimetry Index (UDI). We developed a global UDI (gUDI) to evaluate treatment plans containing volumes irradiated with different dose prescriptions: Intensity Modulated Radiation Therapy with simultaneous integrated boost IMRT-SIB with 2 dose levels (36.25 Gy/5 fz for the whole prostate gland and 37.5 Gy/5 fz for Dominant Intraprostatic Lesion (DIL)). gUDI score equals to one for an ideal plan. To validate gUDI scoring system, 65 prostate cancer patients treated with ultra-hypofractionated IMRT-SIB using VMAT technique were evaluated. The computation of gUDI index was performed separately for plans with single or double DIL. Mean ( μ ) and standard deviations ( σ ) were calculated for all dosimetry indices and gUDI. Furthermore, gUDI μ and σ were analyzed to compare and classify treatment plans: under this ranking system, plans can be ranked as “excellent”, “good”, “average” or “poor”. Results Dose Coverage and Homogeneity index scores did not get away from the ideal values, both for the prostate and DIL. No statistical differences were founded for plans with single or double DIL. The gUDI index classification showed only 6 cases in the “poor” region and most of the plans scored as “average” and “good”. Conclusions gUDI score can be a useful tool to quantify treatment plans quality also when different dose prescriptions volumes are treated. Furthermore, gUDI allows to establish a standard on which dosimetry plans can be ranked.

Unfortunately, the denomination of the IEO was incorrectly published in the affiliation of this original.

Electronic portal imaging (EPI) is commonly used to identify and correct for inter-fraction variability in tangential breast irradiation. Based on the institutional policy, EPI registration is performed by either radiation oncologist or therapist. Little data is available on the inter-observer agreement in EPI registration among different health practitioners. The aim of our study was to analyze inter-observer agreement among radiation oncologists and therapists in the evaluation of EPI for breast cancer radiotherapy verification. EPI data of 40 patients treated with tangential fields were independently reviewed by a radiation oncologist (on-line, just before treatment) and off-line by junior and senior therapists. Displacement of each EPI image with respect to the digital reconstructed radiographs (DRRs) was quantified using manual EPI registration based on bony marks with the corresponding DRRs. Agreement between observers was evaluated using weighted Cohen's Kappa statistics. In 95% out of 720 EPI-DRR comparisons, the EPI-DRR misalignment was < 5 mm. The difference between observers was < 2 mm in 666 (92.5%) out of all 720 delta values. High inter-observer agreement was found, with weighted Cohen's Kappa values attesting evaluation overlaps ranging from moderate (among therapists) to almost perfect (among radiation oncologist and therapists). The high agreement among the observers demonstrated the precision of breast localization using EPI. These findings suggest that routine EPI-based patient set-up verification in breast cancer radiotherapy can be safely entrusted to trained therapists (supervision should be assured based on the local tasks definition). Our study might be useful in quality assurance and in the optimization of workload in the radiotherapy departments. They might allow for wider implementation of complex and evolving radiotherapy technologies.

To compare the toxicity of image-guided intensity-modulated radiotherapy (IG-IMRT) to the pelvis or prostate bed (PB) only. To test the hypothesis that the potentially injurious effect of pelvic irradiation can be counterbalanced by reduced irradiated normal tissue volume using IG-IMRT.Between February 2010 and February 2012, 208 patients with prostate cancer were treated with adjuvant or salvage IG-IMRT to the PB (102 patients, Group PB) or the pelvis and prostate bed (P) (106 patients, Group P). The Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria were used to evaluate toxicity.Median follow-up was 27 months. Toxicity G ≥ 2 in Group PB: in the bowel acute and late toxicities were 11.8% and 10%, respectively; urinary acute and late toxicities were 10.8% and 15%, respectively. Toxicity G ≥ 2 in Group P: in the bowel acute and late toxicities were both 13.2%; urinary acute and late toxicities were 13.2% and 15.1%, respectively. No statistical difference in acute or late toxicity between the groups was found (bowel: p = 0.23 and p = 0.89 for acute and late toxicity, respectively; urinary: p = 0.39 and p = 0.66 for acute and late toxicity, respectively). Of the clinical variables, only previous abdominal surgery was correlated with acute bowel toxicity. Dosimetric parameters that correlated with bowel toxicity were identified.The toxicity rates were low and similar in both groups, suggesting that IG-IMRT allows for a safe post-operative irradiation of larger volumes. Further investigation is warranted to exclude bias owing to non-randomized character of the study.Our report shows that modern radiotherapy technology and careful planning allow maintaining the toxicity of pelvic lymph node treatment at the acceptable level, as it is in the case of PB radiotherapy.

Background and purpose To investigate the intra-fraction breast motion during long-lasting treatments of breast cancer with Helical Tomotherapy by means of an optical tracking system. Materials and methods A set of seven radio-transparent passive markers was placed on the thoraco-abdominal surface of twenty breast cancer patients and tracked by an infrared tracking system. A continuous non-invasive monitoring of intra-fraction motion from patient setup verification and correction to the end of radiation delivery was thus obtained. The measured displacements were analysed in terms of cyclic respiratory motion and slow baseline drift. Results The average monitoring time per patient was 15.57 min. The breathing amplitude of the chest was less than 2 mm, on average, along all anatomical directions. The baseline drift of the body led to more significant setup uncertainties than the respiratory motion. The main intra-fraction baseline drifts were in posterior and inferior directions and occurred within the first eight minutes of monitoring. Considering the intra-fraction motion only, the resultant clinical-to-planning target volume safety margins are highly patient-specific and largely anisotropic. Conclusion The non-respiratory motion occurring during prolonged treatments induces notable uncertainties. Non-invasive continuous monitoring of patient setup variations including baseline drifts is recommended in order to minimize dosimetric deviations, which might jeopardize the therapeutic ratio between target coverage and the sparing of organs at risk.

Purpose To compare infrared (IR) optical vs. stereoscopic X-ray technologies for patient setup in image-guided stereotactic radiotherapy. Methods and Materials Retrospective data analysis of 233 fractions in 127 patients treated with hypofractionated stereotactic radiotherapy was performed. Patient setup at the linear accelerator was carried out by means of combined IR optical localization and stereoscopic X-ray image fusion in 6 degrees of freedom (6D). Data were analyzed to evaluate the geometric and dosimetric discrepancy between the two patient setup strategies. Results Differences between IR optical localization and 6D X-ray image fusion parameters were on average within the expected localization accuracy, as limited by CT image resolution (3 mm). A disagreement between the two systems below 1 mm in all directions was measured in patients treated for cranial tumors. In extracranial sites, larger discrepancies and higher variability were observed as a function of the initial patient alignment. The compensation of IR-detected rotational errors resulted in a significantly improved agreement with 6D X-ray image fusion. On the basis of the bony anatomy registrations, the measured differences were found not to be sensitive to patient breathing. The related dosimetric analysis showed that IR-based patient setup caused limited variations in three cases, with 7% maximum dose reduction in the clinical target volume and no dose increase in organs at risk. Conclusions In conclusion, patient setup driven by IR external surrogates localization in 6D featured comparable accuracy with respect to procedures based on stereoscopic X-ray imaging.

To assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA).A total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose-volume histograms (DVH).CTV shifts were negligible in the laterolateral and superior-inferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior-posterior direction (95% CI, 0.83-4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95-99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose-volume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge.Having a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.

Purpose : The goal of this study is to investigate the advantages of large scale optimization methods vs conventional classification techniques in predicting acute toxicity for urinary bladder and rectum due to prostate irradiation. Methods : Clinical and dosimetric data of 321 patients undergoing prostate conformal radiotherapy were recorded. Gastro-intestinal and genito-urinary acute toxicities were scored according to the Radiation TherapyOncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale. Patients were classified in two categories to separate mild (Grade 2). Machine learning methods at different complexity were implemented to predict toxicity as a function of multiple variables. The first approach consisted of a large scale optimization method, based on genetic algorithms (GAs) and artificial neural networks (ANN). The second approach was a binary classifier based on support vector machines (SVM). Results : The ANN and SVM-based solutions showed comparable prediction accuracy, exhibiting an area under the receiver operating characteristic (ROC) curve of 0.7. Different sensitivity and specificity features were measured for the two approaches. The ANN algorithm showed enhanced sensitivity if combined with appropriate classification criteria. Conclusions : The results demonstrate that high sensitivity in toxicity prediction can be achieved with optimized ANNs, that are put forward to represent a valuable support in medical decisions. Future studies will be focused on enlarging the available patient database to increase the reliability of toxicity prediction algorithms and to define optimal classification criteria.

We report on 14 patients treated with linac- or robotic image-guided stereotactic radiotherapy for isolated lymph node recurrence from prostate cancer, up to the mean dose of 30 Gy/3 fractions. At the mean follow-up of 18.6 months, five patients experienced clinical out-field progression. Toxicity was minimal. Further investigation is warranted in order to identify the patients that benefit most from this treatment modality and to define the optimal association of such local approach with androgen deprivation. Hopefully, effective local therapy might reduce the burden of systemic therapies given to the recurrent/metastatic prostate cancer patients.

To analyze the reliability of different methods used in evaluating the risk of late rectal toxicity.The treatment plans of 57 patients treated at the authors' institute between September 1999 and September 2000 for localized prostate cancer using three-dimensional conformal radiotherapy (3D-CRT) were analyzed retrospectively. The expected rate of late rectal toxicity was analyzed (a) by means of the dose-volume histogram (DVH) constraints; (b) by calculating the normal-tissue complication probability (NTCP) using the Lyman-Kutcher-Burman (LKB) model with the radiobiological parameters of either Emami (1991; for toxicity of gradeor= 2) or Rancati (2004; for toxicity of gradeor= 2 andor= 3). Patients were divided into high-/low-risk (HR/LR) groups and the results were compared to the clinical outcome.(a) The HR percentages were 24% and 5% for radical and postsurgical 3D-CRT, respectively. When applying high-dose constraints only, HR percentages were 18% and 5%, respectively. (b) In the case of the NTCP (gradeor= 2), Emami (1991) HR rates were 16% and 11%, and Rancati (2004) HR rates 29% and 11%, for radical and postsurgical treatment, respectively. Only one case with higher-grade toxicity was found. The reported clinical toxicity was 17.8% and 6.7% for gradeor= 2 toxicity, and 3.7% and 0.7% for gradeor= 3 toxicity, for radical and postsurgical treatment, respectively.This study demonstrated that there is an agreement between the toxicity rate evaluated by DVH constraints and by the LKB model and the clinical outcome. In this case, the use of the LKB model can be as reliable as the use of DVH constraints.

The aim of this study was to perform a detailed analysis of the air kerma values around a Liac mobile linear accelerator working in a conventional operating room (OR) for IORT. The Liac delivers electron beams at 4, 6, 8 and 10 MeV. A radiation survey to determine photon leakage and scatter consisted of air kerma measurements on a spherical surface of 1.5 m radius, centered on the titanium exit window of the accelerating structure. Measurements were taken using a 30 cm3 calibrated cylindrical ion chamber in three orthogonal planes, at the maximum electron energy. For each point, 10 Gy was delivered. At selected points, the quality of x‐ray radiation was determined by using lead sheets, and measurements were performed for all energies to investigate the energy dependence of stray radiation. The photon scatter contribution from the metallic internal patient‐shielding in IORT, used to protect normal tissues underlying the target, was also evaluated. At seven locations outside the OR, the air kerma values derived from in‐room measurements were compared to measurements directly performed using a survey meter. The results, for a delivered dose of 10 Gy, showed that the air kerma values ranged from approximately 6 μGy (upper and rear sides of the Liac) to 320 μGy (lateral to beam stopper) in the two orthogonal vertical planes, while values lower than 18 μGy were found in the horizontal plane. At 10 MeV, transmission behind 1 cm lead shield was found to be 42%. The use of internal shielding appeared to increase the photon scatter only slightly. Air kerma values outside the OR were generally lower than 1 mGy for an annual workload of 200 patients. Thus, the Liac can safely work in a conventional OR, while the need for additional shielding mainly depends on patient workload. Our data can be useful for centers planning to implement an IORT program using a mobile linear accelerator, permitting radiation safety personnel to estimate in advance the shielding required for a particular workload. PACS number: 87.55.ne, 87.56.bd

Purpose To present the results of dose escalation using three-dimensional conformal dynamic arc radiotherapy (3D-ART) for prostate cancer. Methods and Materials Five hundred and forty two T1-T3N0M0 prostate cancer patients were treated with 3D-ART. Dose escalation (from 76 Gy/38 fractions to 80 Gy/40 fractions) was introduced in September 2003; 32% of patients received 80 Gy. In 366 patients, androgen deprivation was added to 3D-ART. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria and Houston definition (nadir + 2) were used for toxicity and biochemical failure evaluation, respectively. Median follow-up was 25 months. Results Acute toxicity included rectal (G1-2 28.9%; G3 0.5%) and urinary events (G1-2 57.9%; G3-4 2.4%). Late toxicity included rectal (G1-2 15.8%; G3-4 3.1%) and urinary events (G1-2 26.9%; G3-4 1.6%). Two-year failure-free survival and overall survival rates were 94.1% and 97.9%, respectively. Poor prognostic group (GS, iPSA, T), transurethral prostate resection, and dose >76 Gy showed significant association to high risk of progression in multivariate analysis ( p = 0.014, p = 0.045, and p = 0.04, respectively). The negative effect of dose >76 Gy was not observed ( p = 0.10), when the analysis was limited to 353 patients treated after September 2003 (when dose escalation was introduced). Higher dose was not associated with higher late toxicity. Conclusions Three-dimensional-ART is a feasible modality allowing for dose escalation (no increase in toxicity has been observed with higher doses). However, the dose increase from 76 to 80 Gy was not associated with better tumor outcome. Further investigation is warranted for better understanding of the dose effect for prostate cancer.

To retrospectively evaluate external beam reirradiation (re-EBRT) delivered to the prostate/prostatic bed for local recurrence, after radical or adjuvant/salvage radiotherapy (RT).32 patients received re-EBRT between February 2008 and October 2013. All patients had clinical/radiological local relapse in the prostate or prostatic bed and no distant metastasis. re-EBRT was delivered with selective RT technologies [stereotactic RT including CyberKnife(TM) (Accuray, Sunnyvale, CA); image-guidance and intensity-modulated RT etc.]. Toxicity was evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Biochemical control was assessed according to the Phoenix definition (NADIR + 2 ng ml(-1)).Acute urinary toxicity: G0, 24 patients; G1, 6 patients; G2, 2 patients. Acute rectal toxicity: G0, 28 patients; G1, 2 patients; and G2, 1 patient. Late urinary toxicity (evaluated in 30 cases): G0, 23 patients; G1, 6 patients; G2, 1 patient. Late renal toxicity: G0, 25 patients; G1, 5 patients. A mean follow-up of 21.3 months after re-EBRT showed that 13 patients were free of cancer, 3 were alive with biochemical relapse and 12 patients were alive with clinically evident disease. Four patients had died: two of disease progression and two of other causes.re-EBRT using modern technology is a feasible approach for local prostate cancer recurrence offering 2-year tumour control in about half of the patients. Toxicity of re-EBRT is low. Future studies are needed to identify the patients who would benefit most from this treatment.Our series, based on experience in one hospital alone, shows that re-EBRT for local relapse of prostate cancer is feasible and offers a 2-year cure in about half of the patients.

Aims and Background This study evaluates 3 different imaging modalities—ultrasound (US), stereoscopic X-ray imaging of implanted markers (Visicoils) (X-ray), and kV cone-beam computed tomography (CBCT)—to assess interfraction and intrafraction localization error during conformal radiation therapy of prostate cancer. Methods and Study Design The study population consisted of 186 consecutive prostate cancer patients treated with an image-guided radiotherapy (IGRT) hypofractionated protocol using 3 techniques: 32 with X-ray, 30 with CBCT, and 124 with US. Treatment dose of 70.2 Gy was delivered in 26 fractions with a conformal dynamic arcs technique. Interfraction prostate localization errors were determined for the 3 techniques. Moreover, interfraction and intrafraction prostate motion in terms of translations and rotations, as well as residual errors, were determined with X-ray. Results The systematic and random components of the prostate localization errors were as follows: ( 1 ) with X-ray 3.0 ± 3.4, 2.3 ± 2.7, 1.8 ± 2.3 mm in anterior-posterior (AP), superior-inferior (SI), and left-right (LR) directions and 1.8° ± 1.2°, 2.3° ± 1.5°, 2.7° ± 3.1°, for the yaw, roll, and pitch rotations; ( 2 ) with CBCT3.5 ± 4.2, 3.3 ± 3.3, 2.5 ± 3.1 mm in AP, SI, and LR directions; ( 3 ) with US 3.7 ± 4.7, 3.4 ± 4.3, 2.3 ± 3.5 mm in AP, SI, and LR directions. Residual errors with X-ray were less than 1 mm in all directions. Intrafraction prostate motion of less than 0.5 mm in LR and of the order of 1 mm in AP and SI directions was found. This led to a significant reduction of the margins, potentially important for dose escalation studies. Conclusions Daily on-line IGRT with stereoscopic X-ray imaging allowed a consistent PTV margin reduction considering residual interfraction prostate localization error and intrafraction motion. X-ray offers the best compromise among accuracy, reliability, dose to the patient, and time investment for daily IGRT treatment of prostate.

Background and purpose Limited information is available on the true radiation exposure and associated risks for the relatives of the patients submitted to prostate brachytherapy with permanent implant of radioactive sources and for any other people coming into contact with them. In order to provide appropriate information, we analyzed the radiation exposure data from 216 prostate cancer patients who underwent 125 I or 103 Pd implants at the European Institute of Oncology of Milan, Italy. Patients and methods Between October 1999 and October 2004, 216 patients with low risk prostate carcinoma were treated with 125 I (200 patients) or 103 Pd (16 patients) permanent seed implantation. One day after the procedure, radiation exposure measurements around the patients were performed using an ionization chamber survey meter (Victoreen RPO-50) calibrated in dose rate at an accredited calibration center (calibration Centre SIT 104). Results The mean dose rate at the posterior skin surface (gluteal region) following 125 I implants was 41.3μSv/h (range: 6.2–99.4μSv/h) and following 103 Pd implants was 18.9μSv/h (range 5.0–37.3μSv/h). The dose rate at 50cm from the skin decreased to the mean value of 6.4μSv/h for the 125 I implants and to the mean value of 1.7μSv/h for the 103 Pd implants. Total times required to reach the annual dose limit (1mSv/year) recommended for the general population by the European Directive 96/29/Euratom and by the Italian law (Decreto Legislativo 241/2000) at a distance of 50cm from the posterior skin surface of the implanted patient would be 7.7 and 21.6 days for 125 I and for 103 Pd. Good correlation between the measured dose rates and both the total implanted activity and the distance between the most posteriorly implanted seed and the skin surface of the patients was found. Conclusions Our data show that the dose rates at 50cm away from the prostate brachytherapy patients are very low and that the doses possibly absorbed by the relatives and other members of the general population coming into contact with the treated patients are well below the dose limit set by the European Directive and by the Italian regulation. However, in order to meet the recommendation of the ALARA principle (As Low As Reasonably/Readily Achievable), some advice to the patients should be given, such as to maintain a minimum distance from the patient of 1m, at least for a period equal to one half life of used radionuclide (60 days for 125 I and 15 days for 103 Pd).