ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial.

PURPOSE: To assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. MATERIAL AND METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. RESULTS: Among the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. CONCLUSIONS: In this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

Five-Fraction Proton Therapy for the Treatment of Skull Base Chordomas and Chondrosarcomas: Early Results of a Prospective Series and Description of a Clinical Trial.

(1) Background: Our purpose is to describe the design of a phase II clinical trial on 5-fraction proton therapy for chordomas and chondrosarcomas of the skull base and to present early results in terms of local control and clinical tolerance of the first prospective series. (2) Methods: A dose of 37.5 GyRBE in five fractions was proposed for chordomas and 35 GyRBE in five fractions for chondrosarcomas. The established inclusion criteria are age ≥ 18 years, Karnofsky Performance Status ≥ 70%, clinical target volume up to 50 cc, and compliance with dose restrictions to the critical organs. Pencil beam scanning was used for treatment planning, employing four to six beams. (3) Results: A total of 11 patients (6 chordomas and 5 chondrosarcomas) were included. The median follow-up was 12 months (9-15 months) with 100% local control. Acute grade I-II headache (64%), grade I asthenia and alopecia (45%), grade I nausea (27%), and grade I dysphagia (18%) were described. Late toxicity was present in two patients with grade 3 temporal lobe necrosis. (4) Conclusions: Hypofractionated proton therapy is showing encouraging preliminary results. However, to fully assess the efficacy of this therapeutic approach, future trials with adequate sample sizes and extended follow-ups are necessary.

Urethra-Sparing Prostate Cancer Stereotactic Body Radiation Therapy: Sexual Function and Radiation Dose to the Penile Bulb, the Crura, and the Internal Pudendal Arteries From a Randomized Phase 2 Trial.

PURPOSE: Erectile dysfunction (ED) is a common side effect after prostate cancer stereotactic body radiation therapy (SBRT). We aimed to assess the correlation between the dose to the penile bulb (PB), internal pudendal arteries (IPA), and crura with the development of ED after ultrahypofractionation as part of a phase 2 clinical trial of urethra-sparing prostate SBRT. METHODS AND MATERIALS: Among the 170 patients with localized prostate cancer from 9 centers included in the trial, 90 men with Common Terminology Criteria for Adverse Events version 4.03 grade 0 to 1 ED (ED-) at baseline treated with 36.25 Gy in 5 fractions were selected for the present analysis. Doses delivered to the PB, crura, and IPA were analyzed and correlated with grade 2 to 3 ED (ED+) development. The effect on quality of life, assessed by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-PR25) questionnaire, was reported. RESULTS: After a median follow-up of 6.5 years, 43% (n = 39) of the patients developed ED+, and 57% (n = 51) remained ED-. The dose delivered to the crura was significantly higher in ED+ patients than in ED- patients (7.7 vs 3.6 Gy [P = .014] for the Dmean and 18.5 vs 7.2 Gy [P = .015] for the D2%, respectively). No statistically significant difference between ED+ and ED- patients was observed for the dose delivered to the PB and IPA. The median ED+-free survival was worse in patients receiving a crura Dmean ≥ 4.7 versus < 4.7 Gy (51.5% vs 71.7%, P = .005) and a crura D2% > 12 versus ≤ 12 Gy (54.9% vs 68.9%, P = .015). No ED+-free survival differences were observed for doses delivered to the PB and IPA. Decline in EORTC QLQ-PR25 sexual functioning was significantly more pronounced in patients with higher doses to the crura. CONCLUSIONS: By keeping a Dmean and D2% to crura below 4.7 and 12 Gy, respectively, the risk of developing ED+ after prostate SBRT may be significantly reduced.

Every-Other-Day Versus Once-a-Week Urethra-Sparing Prostate Stereotactic Body Radiation Therapy: 5-Year Results of a Randomized Phase 2 Trial.

PURPOSE: The objective of this study was to present the 5-year results from a prospective, multicenter, phase 2 randomized trial of every-other-day (EOD) versus once-a-week (QW) urethra-sparing stereotactic body radiation therapy for localized prostate cancer. METHODS AND MATERIALS: Between 2012 and 2015, 170 patients with cT1c-3aN0M0 prostate cancer from 9 European institutions were randomized to 36.25 Gy in 5 fractions (6.5 Gy/fraction to the urethra) delivered either EOD (arm A, n = 84) or QW (arm B, n = 86). The median follow-up was 78 months (interquartile range, 66-89 months) and 77 months (interquartile range, 66-82 months) for arms A and B, respectively. RESULTS: Among the 165 patients treated and retained for the final analysis (arm A, n = 82; arm B, n = 83), acute toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 scale) was mild or absent, with no differences between arms. The 5-year grade 2 or greater genitourinary toxicity-free survival was 75.9% and 76.1% for arms A and B, respectively (P = .945), whereas the 5-year grade 2 or greater gastrointestinal toxicity-free survival was 89% and 92% for arms A and B, respectively (P = .596). No changes in European Organisation for Research and Treatment of Cancer QLQ-PR25 scores were observed in both arms for genitourinary, gastrointestinal, and sexual domains at 5-year follow-up compared with baseline. At the last follow-up, biochemical failure was observed in 14 patients in the EOD arm and in 7 patients in the QW arm, with a 5-year biochemical relapse-free survival rate of 92.2% and 93% for arms A and B, respectively (P = .13). CONCLUSIONS: Stereotactic body radiation therapy for prostate cancer with a 10% dose reduction to urethra was associated with a minimal effect on urinary function and quality of life regardless of an EOD or QW fractionation schedule. Biochemical control so far has been encouraging and much alike in both study arms, although longer follow-up is probably needed to assess the true value of overall treatment time on disease outcome.

Urinary toxicity after salvage re-irradiation for prostate cancer local failure after definitive radiotherapy: a clinical and dosimetric prognostic factors analysis.

Purpose: Predictors of long-term toxicity after prostate cancer re-irradiation are scarce. In this study, we retrospectively assessed the impact of clinical/dosimetric data on late genitourinary (GU) toxicity on fourteen radio-recurrent prostate cancer patients treated with salvage radiotherapy (RT). Material and methods: To identify dose parameters and clinical factors potentially associated to severe long-term GU toxicity, study population was stratified in two groups according to toxicity, including one low-grade group (grade ≤ 2, n = 6) and one high-grade group (grade ≥ 3, n = 8). Dose prescription at primary and salvage-RT in 2 Gy equivalent dose (EQD2Gy) per fraction, treatment techniques, and clinical factors potentially associated to severe GU toxicity were analyzed. Results: At salvage-RT, the median EQD2Gy α/ß = 3 Gy was significantly higher in the high-toxicity group (85 Gy, range, 71-85 Gy) compared to the low-toxicity group (77 Gy, range, 61-85 Gy) (p = 0.01). All patients treated using salvage-RT with a brachytherapy (BT) boost and with a baseline Framingham risk-score of > 20% (n = 8) developed severe GU toxicity, while none of the remaining patients developed a grade 3 or more GU toxicity (p = 0.0003). V70 > 0 and V75 > 0 of the primary treatment were associated with an increased rate of toxicity. Conclusions: Our analysis shows that the delivery of doses up to 75-80 Gy (EQD2Gy, α/ß = 3 Gy) in salvage-RT can be safe in terms of severe GU toxicity avoidance. Furthermore, concomitant cardiovascular comorbidities seem to increase the risk to develop severe GU toxicity.

Prone versus supine free-breathing for right-sided whole breast radiotherapy.

Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right breast cancer patients treated in 2010-2013 who had a dual supine and prone planning were retrospectively identified. A penalty score was computed from the mean absolute dose deviation to heart, lungs, breasts, and tumor bed for each patient's supine and prone plan. Dosimetric advantage of prone was assessed by the reduction of penalty score from supine to prone. The effect of patients' characteristics on the reduction of penalty was analyzed using robust linear regression. A total of 146 patients with right breast dual plans were identified. Prone compared to supine reduced the penalty score in 119 patients (81.5%). Lung doses were reduced by 70.8%, from 4.8 Gy supine to 1.4 Gy prone. Among patient's characteristics, the only significant predictors were the breast volumes, but no cutoff could identify when prone would be less advantageous than supine. Prone was associated with a dosimetric advantage in most patients. It sets a benchmark of achievable lung dose reduction.Trial registration: ClinicalTrials.gov NCT02237469, HUGProne, September 11, 2014, retrospectively registered.

Bilateral metallic hip implants: Are avoidance sectors necessary for pelvic VMAT treatments?

PURPOSE: Metallic hip implants (MHI) are common in elderly patients. For pelvic cancers radiotherapy, conventional approaches consist of MHI avoidance during treatment planning, which leads, especially in case of bilateral MHI, to a decreased quality or increased complexity of the treatment plan. The aim of this study is to investigate the necessity of using avoidance sectors (AvSe) using a 2-arcs coplanar pelvic volumetric modulated arc-therapy (VMAT) planning. METHODS: We evaluated: (1) The dose calculation error of a static 6MV open beam traversing a MHI; (2) The magnitude of an error's decrease within the planning target volume (PTV) for a 360° VMAT treatment without AvSe as compared to the static open beam; (3) The dosimetric influence of MHI misalignment generated by patient's repositioning rolls during image-guided radiotherapy (IGRT). RESULTS: (1) In the static 6MV beam configuration, for distances between 0.5cm and 6cm from the MHI, the median (maximum, number of points) dose calculation error was -1.55% (-2.5%, 11); (2) Compared to the static open beam, in the 360° VMAT treatment without AvSe a simulated error was decreased by a factor of 4.4/2.4 (median/minimum); (3) MHI anterior-posterior misalignment exceeding 0.6cm, resulted in error at PTV surface of >2%. CONCLUSIONS: A standard 2 coplanar arcs 360° VMAT treatment, with dedicated artifact reduction algorithms applied, decreased the error of static beam traversing MHI, in patients presenting a bilateral MHI and might be used to treat the pelvic region without MHI avoidance.

Salvage stereotactic body radiotherapy (SBRT) for intraprostatic relapse after prostate cancer radiotherapy: An ESTRO ACROP Delphi consensus.

BACKGROUND AND PURPOSE: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT. MATERIALS AND METHODS: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation. RESULTS: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure). CONCLUSION: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach.

Is prone free breathing better than supine deep inspiration breath-hold for left whole-breast radiotherapy? A dosimetric analysis.

PURPOSE: The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. METHODS: Left-sided breast cancer patients who had dual computed tomography (CT) planning in prone free breathing (FB) and supine deep inspiration breath-hold (DiBH) were retrospectively identified. Radiation doses to heart, lungs, breasts, and tumor bed were evaluated using the recently developed mean absolute dose deviation (MADD). MADD measures how widely the dose delivered to a structure deviates from a reference dose specified for the structure. A penalty score was computed for every treatment plan as a weighted sum of the MADDs normalized to the breast prescribed dose. Changes in penalty scores when switching from supine to prone were assessed by paired t-tests and by the number of patients with a reduction of the penalty score (i.e., gain). Robust linear regression and fractional polynomials were used to correlate patients' characteristics and their respective penalty scores. RESULTS: Among 116 patients identified with dual CT planning, the prone setup, compared with supine, was associated with a dosimetric gain in 72 (62.1%, 95% CI: 52.6-70.9%). The most significant predictors of a gain with the prone setup were the breast depth prone/supine ratio (>1.6), breast depth difference (>31 mm), prone breast depth (>77 mm), and breast volume (>282 mL). CONCLUSION: Prone compared with supine DiBH was associated with a dosimetric gain in 62.1% of our left-sided breast cancer patients. High pendulousness and moderately large breast predicted for the gain.

Single-fraction prostate stereotactic body radiotherapy: Dose reconstruction with electromagnetic intrafraction motion tracking.

PURPOSE: To reconstruct the dose delivered during single-fraction urethra-sparing prostate stereotactic body radiotherapy (SBRT) accounting for intrafraction motion monitored by intraprostatic electromagnetic transponders (EMT). METHODS: We analyzed data of 15 patients included in the phase I/II "ONE SHOT" trial and treated with a single fraction of 19 Gy to the planning target volume (PTV) and 17 Gy to the urethra planning risk volume. During delivery, prostate motion was tracked with implanted EMT. SBRT was interrupted when a 3-mm threshold was trespassed and corrected unless the offset was transient. Motion-encoded reconstructed (MER) plans were obtained by splitting the original plans into multiple sub-beams with isocenter shifts based on recorded EMT positions, mimicking prostate motion during treatment. We analyzed intrafraction motion and compared MER to planned doses. RESULTS: The median EMT motion range (±SD) during delivery was 0.26 ± 0.09, 0.22 ± 0.14 and 0.18 ± 0.10 cm in the antero-posterior, supero-inferior, and left-right axes, respectively. Treatment interruptions were needed for 8 patients because of target motion beyond limits in the antero-posterior (n = 6) and/or supero-inferior directions (n = 4). Comparing MER vs. original plan there was a median relative dose difference of -1.9% (range, -7.9 to -1.0%) and of +0.5% (-0.3-1.7%) for PTV D98% and D2%, respectively. The clinical target volume remained sufficiently covered with a median D98% difference of -0.3% (-1.6-0.5%). Bladder and rectum dosimetric parameters showed significant differences between original and MER plans, but mostly remained within acceptable limits. CONCLUSIONS: The dosimetric impact of intrafraction prostate motion was minimal for target coverage for single-fraction prostate SBRT with real-time electromagnetic tracking combined with beam gating.

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

PURPOSE: To evaluate the planning feasibility of dose-escalated total marrow irradiation (TMI) with simultaneous integrated boost (SIB) to the active bone marrow (ABM) using volumetric modulated arc therapy (VMAT), and to assess the impact of using planning organs at risk (OAR) volumes (PRV) accounting for breathing motion in the optimization. METHODS: Five patients underwent whole-body CT and thoraco-abdominal 4DCT. A planning target volume (PTV) including all bones and ABM was contoured on each whole-body CT. PRV of selected OAR (liver, heart, kidneys, lungs, spleen, stomach) were determined with 4DCT. Planning consisted of 9-10 full 6 MV photon VMAT arcs. Four plans were created for each patient with 12 Gy prescribed to the PTV, with or without an additional 4 Gy SIB to the ABM. Planning dose constraints were set on the OAR or on the PRV. Planning objective was a PTV Dmean < 110% of the prescribed dose, a PTV V110% < 50%, and OAR Dmean ≤ 50-60%. RESULTS: PTV Dmean < 110% was accomplished for most plans (n = 18/20), while all achieved V110%<50%. SIB plans succeeded to optimally cover the boost volume (median ABM Dmean = 16.3 Gy) and resulted in similar OAR sparing compared to plans without SIB (median OAR Dmean = 40-54% of the ABM prescribed dose). No statistically significant differences between plans optimized with constraints on OAR or PRV were found. CONCLUSIONS: Adding a 4 Gy SIB to the ABM for TMI is feasible with VMAT technique, and results in OAR sparing similar to plans without SIB. Setting dose constraints on PRV does not impair PTV dosimetric parameters.

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial.

PURPOSE: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. METHODS AND MATERIALS: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. RESULTS: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D98% (31.1 vs 30.8 Gy, P < .0001), PTV D2% (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V50% (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V90% (9.1% vs 10.4%, P = .0003) and V80% (13.2% vs 15.7%, P = .0003). CONCLUSIONS: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Atlas Sampling for Prone Breast Automatic Segmentation of Organs at Risk: The Importance of Patients' Body Mass Index and Breast Cup Size for an Optimized Contouring of the Heart and the Coronary Vessels.

OBJECTIVE: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size. METHODS: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliability of the automatic segmentation was assessed in the context of 3-D planning. RESULTS: Accounting for body mass index and breast cup size improved automatic segmentation results compared to breast volume-based sampling, especially for the heart (mean similarity indexes >0.9 for automatic segmentation organs at risk and clinical target volume after RO_A editing). Mean similarity indexes for the left anterior descending artery and the right coronary artery edited by RO_A expanded by 1 cm were ≥0.8. Using automatic segmentation reduced contouring time by 40%. For each parameter analyzed (eg, D2%), the difference in dose, averaged over all patients, between automatic segmentation structures edited by RO_A and the same structure manually drawn by RO_A was <1.5% of the prescribed dose. The mean heart dose was reliable for the unedited heart segmentation, and for right-sided treatments, automatic segmentation was adequate for treatment planning with 3-D conformal tangential fields. CONCLUSIONS: Automatic segmentation for prone breast radiotherapy stratified by body mass index and breast cup size improved segmentation accuracy for the heart and coronary vessels compared to breast volume sampling. A significant reduction in contouring time can be achieved by using automatic segmentation.

Electromagnetic Transponder Localization and Real-Time Tracking for Prostate Cancer Radiation Therapy: Clinical Impact of Metallic Hip Prostheses.

PURPOSE: Our purpose was to assess the ability of electromagnetic transponders (EMTs) to localize and track movements in patients with prostate cancer (PCa) with metallic hip prostheses (MHPs) treated with curative radiation therapy (RT). METHODS AND MATERIALS: Data sets of 8 PCa patients with MHPs (3 bilateral and 5 unilateral) treated between 2016 and 2018 with RT and EMT tracking were retrospectively assessed. The distances between the 3 EMTs (apex to left, left to right, right to apex) and the isocenter were calculated both on planning computed tomography (CT) and cone beam CT (CBCT) at the first treatment fraction and compared with data reported by Calypso. EMT position and treatment interruptions triggered by Calypso were analyzed for all evaluable treatment fractions (n = 120). Localization accuracy was quantified by recording the geometric residual value (expected limit ≤0.2 cm) at the RT setup. RESULTS: The Calypso system was able to localize and track prostate position without any detectable interference from MHP. For every treatment fraction, the agreement between the CBCT images and Calypso guidance was optimal, with EMTs always within the defined tolerance (ie, CT-Calypso or CBCT-Calypso measured differences in inter-EMT distances within 0.3 cm). EMT to isocenter distances measured by Calypso reproduced CT data and were confirmed on CBCT scans. During RT, the EMT centroid exceeded the threshold 24 times (20% of all fractions): 5 times in the left-right, 15 times in the anteroposterior, and 4 times in the superoinferior directions. The largest motions recorded were in the anteroposterior axis: 0.6 cm anteriorly and 0.5 cm posteriorly in patients with unilateral and bilateral MHP, respectively. CONCLUSIONS: Our study represents the first clinical experience assessing the localization and tracking accuracy of Calypso EMTs during curative RT of patients with PCa with unilateral or bilateral MHP.

Resources-Stratified Guidelines for Classical Hodgkin Lymphoma.

Hodgkin lymphoma is a haematological malignancy predominantly affecting young adults. Hodgkin lymphoma is a highly curable disease by current treatment standards. Latest treatment guidelines for Hodgkin lymphoma however imply access to diagnostic and treatment modalities that may not be available in settings with restricted healthcare resources. Considerable discrepancies in Hodgkin lymphoma patient survival exist, with poorer outcomes reported in resources-constrained settings. Resources-stratified guidelines for diagnosis, staging and treatment of Hodgkin lymphoma were derived in an effort to optimize patient outcome provided a given setting of available resources. These guidelines were derived based on the framework of the Breast Health Global Initiative stratifying resource levels in basic, core, advanced and maximal categories.

Once-a-week or every-other-day urethra-sparing prostate cancer stereotactic body radiotherapy, a randomized phase II trial: 18 months follow-up results.

BACKGROUND: To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra-sparing stereotactic body radiotherapy (SBRT) for localized prostate cancer (PCa). METHODS: Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months. RESULTS: Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ-PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate. CONCLUSIONS: At 18 months, urethra-sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW).

FLASH and minibeams in radiation therapy: the effect of microstructures on time and space and their potential application to protontherapy.

After years of lethargy, studies on two non-conventional microstructures in time and space of the beams used in radiation therapy are enjoying a huge revival. The first effect called "FLASH" is based on very high dose-rate irradiation (pulse amplitude ≥106 Gy/s), short beam-on times (≤100 ms) and large single doses (≥10 Gy) as experimental parameters established so far to give biological and potential clinical effects. The second effect relies on the use of arrays of minibeams (e.g., 0.5-1 mm, spaced 1-3.5 mm). Both approaches have been shown to protect healthy tissues as an endpoint that must be clearly specified and could be combined with each other (e.g., minibeams under FLASH conditions). FLASH depends on the presence of oxygen and could proceed from the chemistry of peroxyradicals and a reduced incidence on DNA and membrane damage. Minibeams action could be based on abscopal effects, cell signalling and/or migration of cells between "valleys and hills" present in the non-uniform irradiation field as well as faster repair of vascular damage. Both effects are expected to maintain intact the tumour control probability and might even preserve antitumoural immunological reactions. FLASH in vivo experiments involving Zebrafish, mice, pig and cats have been done with electron beams, while minibeams are an intermediate approach between X-GRID and synchrotron X-ray microbeams radiation. Both have an excellent rationale to converge and be applied with proton beams, combining focusing properties and high dose rates in the beam path of pencil beams, and the inherent advantage of a controlled limited range. A first treatment with electron FLASH (cutaneous lymphoma) has recently been achieved, but clinical trials have neither been presented for FLASH with protons, nor under the minibeam conditions. Better understanding of physical, chemical and biological mechanisms of both effects is essential to optimize the technical developments and devise clinical trials.

Biological and Mechanical Synergies to Deal With Proton Therapy Pitfalls: Minibeams, FLASH, Arcs, and Gantryless Rooms.

Proton therapy has advantages and pitfalls comparing with photon therapy in radiation therapy. Among the limitations of protons in clinical practice we can selectively mention: uncertainties in range, lateral penumbra, deposition of higher LET outside the target, entrance dose, dose in the beam path, dose constraints in critical organs close to the target volume, organ movements and cost. In this review, we combine proposals under study to mitigate those pitfalls by using individually or in combination: (a) biological approaches of beam management in time (very high dose rate "FLASH" irradiations in the order of 100 Gy/s) and (b) modulation in space (a combination of mini-beams of millimetric extent), together with mechanical approaches such as (c) rotational techniques (optimized in partial arcs) and, in an effort to reduce cost, (d) gantry-less delivery systems. In some cases, these proposals are synergic (e.g., FLASH and minibeams), in others they are hardly compatible (mini-beam and rotation). Fixed lines have been used in pioneer centers, or for specific indications (ophthalmic, radiosurgery,…), they logically evolved to isocentric gantries. The present proposals to produce fixed lines are somewhat controversial. Rotational techniques, minibeams and FLASH in proton therapy are making their way, with an increasing degree of complexity in these three approaches, but with a high interest in the basic science and clinical communities. All of them must be proven in clinical applications.

Prostate Cancer Nonascitic Peritoneal Carcinomatosis After Robot-assisted Laparoscopic Radical Prostatectomy: 3 Case Reports and Review of the Literature.

Robot-assisted laparoscopic radical prostatectomy is one of the treatment options for localized prostate cancer, with an excellent disease control rate. However, these patients can experience late disease recurrence with metastatic dissemination. Peritoneal metastases are an uncommon recurrence site. Here, we discuss 3 cases of peritoneal metastases following robot-assisted laparoscopic radical prostatectomy and the mechanisms of peritoneal invasion. Through a literature review and our case reports, we postulate the existence of 2 distinct mechanisms of peritoneal invasion: one being iatrogenic, following a laparoscopic surgery with a well differentiated prostate cancer at a nonadvanced stage of the disease, the other involving the natural course of poor-prognosis tumors, even without surgery.

Image-guided total-body irradiation with a movable electronic portal imaging device for bone marrow transplant conditioning.

INTRODUCTION: To prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage imaging and computed radiographic (CR) films. In order to improve this time-consuming procedure, we developed in our department a dedicated, movable, real-time imaging system for image-guided TBI. MATERIAL & METHODS: The system consists of an electronic portal imaging device (EPID) mounted on a dedicated support whose motion along a rail can be controlled from the linac console outside the bunker room. Images are acquired online using a stand-alone console. To test the system efficacy we retrospectively analyzed data of lung blocks positioning from two groups of 10 patients imaged with EPID or CR-films, respectively. RESULTS: The median number of portal images per fraction was 2 (range 1-5) and 1 (range 1-2) for the EPID and the CR-film system, respectively. The minimum time required for an EPID image acquisition, without interpretation and no need of patient position correction in the bunker, was 20seconds against 214seconds for the CR-film. Lung shielding positioning in the right-left and superior-inferior directions was improved using the EPID system (p<0.01). CONCLUSIONS: Compared to CR-films, our movable real-time imaging EPID system is a simple technical solution able to reduce the minimum imaging time for lung shielding by a factor of 10. With the increased possibility to acquire more images as compared to CR-film system the EPID system has the potential to improve patient alignment, as well as patient's comfort and overall setup time.