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.

Post-mastectomy radiotherapy: Impact of bolus thickness and irradiation technique on skin dose.

PURPOSE: To determine 10 MV IMRT and VMAT based protocols with a daily bolus targeting a skin dose of 45 Gy in order to replace the 6 MV tangential fields with a 5 mm thick bolus on alternate days method for post-mastectomy radiotherapy. METHOD: We measured the mean surface dose along the chest wall PTV as a function of different bolus thicknesses for sliding window IMRT and VMAT plans. We analyzed surface dose profiles and dose homogeneities and compared them to our standard 6 MV strategy. All measurements were performed on a thorax phantom with Gafchromic films while dosimetric plans were computed using the Acuros XB algorithm (Varian). RESULTS: We obtained the best compromise between measured surface dose (mean dose and homogeneity) and skin toxicity threshold obtained from the literature using a daily 3 mm thick bolus. Mean surface doses were 91.4 ±â€¯2.8% [85.7% - 95.4%] and 92.2 ±â€¯2.3% [85.6% - 95.2%] of the prescribed dose with IMRT and VMAT techniques, respectively. Our standard 6 MV alternate days 5 mm thick bolus leads to 89.0 ±â€¯3.7% [83.6% - 95.5%]. Mean dose differences between measured and TPS results were < 3.2% for depths as low as 2 mm depth. CONCLUSION: 10 MV IMRT-based protocols with a daily 3 mm thick bolus produce a surface dose comparable to the standard 6 MV 5 mm thick bolus on alternate days method but with an improved surface dose homogeneity. This allows for a better control of skin toxicity and target volume coverage.

Oligorecurrent nodal prostate cancer: Radiotherapy quality assurance of the randomized PEACE V-STORM phase II trial.

PURPOSE: Aim of this study is to report the results of the radiotherapy quality assurance program of the PEACE V-STORM randomized phase II trial for pelvic nodal oligorecurrent prostate cancer (PCa). MATERIAL AND METHODS: A benchmark case (BC) consisting of a postoperative case with 2 nodal recurrences was used for both stereotactic body radiotherapy (SBRT, 30 Gy/3 fx) and whole pelvic radiotherapy (WPRT, 45 Gy/25 fx + SIB boost to 65 Gy). RESULTS: BC of 24 centers were analyzed. The overall grading for delineation variation of the 1st BC was rated as 'UV' (Unacceptable Variation) or 'AV' (Acceptable Variation) for 1 and 7 centers for SBRT (33%), and 3 and 8 centers for WPRT (46%), respectively. An inadequate upper limit of the WPRT CTV (n = 2), a missing delineation of the prostate bed (n = 1), and a missing nodal target volume (n = 1 for SBRT and WPRT) constituted the observed 'UV'. With the 2nd BC (n = 11), the overall delineation review showed 2 and 8 'AV' for SBRT and WPRT, respectively, with no 'UV'. For the plan review of the 2nd BC, all treatment plans were per protocol for WPRT. SBRT plans showed variability in dose normalization (Median D90% = 30.1 Gy, range 22.9-33.2 Gy and 30.6 Gy, range 26.8-34.2 Gy for nodes 1 and 2 respectively). CONCLUSIONS: Up to 46% of protocol deviations were observed in delineation of WPRT for nodal oligorecurrent PCa, while dosimetric results of SBRT showed the greatest disparities between centers. Repeated BC resulted in an improved adherence to the protocol, translating in an overall acceptable contouring and planning compliance rate among participating centers.

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.

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.

Dose optimization and endorectal balloon for internal pudendal arteries sparing in prostate SBRT.

PURPOSE: Vessel-sparing radiotherapy has shown promising results in preserving erectile function (EF). Using an endorectal balloon (ERB) may help to reduce the dose to the internal pudendal arteries (IPA) by pushing the prostate forward. We tested this hypothesis and evaluated the limits of IPA dose optimization in prostate cancer patients simulated with and without ERB. MATERIALS AND METHODS: Twelve patients with localized disease were simulated both with and without ERB. IPA were delineated on every CT after MRI registration. Planning target volumes (PTV) were planned to receive 36.25 Gy in 5 fractions with a VMAT technique. Twenty-four initial plans were generated using a knowledge-based planning software without any specific constraints for IPA. Additional stepwise optimization was performed until stabilization of the IPA dose or trespassing of PTV homogeneity limits. RESULTS: Without optimization, the median mean IPA dose (Dmean) was lower with ERB than without (10.5 vs. 12.8 Gy, p = 0.023). After optimization, the IPA Dmean dropped significantly (from 11.1 to 4.8 Gy) without impairing the PTV dose homogeneity and the organs at risk dose constraints. The comparison of the best-optimized plans with and without ERB showed an optimal sparing of IPA using ERB (28% mean dose reduction, p = 0.006; median Dmean of 4.1 Gy vs. 5.7 Gy with and without ERB, respectively). CONCLUSION: IPA dose sparing is feasible without compromising dose prescription and constraints. ERB significantly reduced the dose on IPA compared to plans generated without ERB. As no specific constraints are available for vessel-sparing SBRT, optimal IPA dose reduction should be recommended to maximize EF preservation.

Recurrent prostate cancer after radical prostatectomy: restaging performance of 18F-choline hybrid PET/MRI.

To evaluate the diagnostic performance of a whole-body 18F-choline (FCH) hybrid PET/MRI for prostate cancer patients at biochemical relapse after radical prostatectomy (RP) compared to pelvic multiparametric MRI (mpMRI), one of the standard imaging modality for this patient population. From 2010 to 2016, 58 whole-body FCH PET/MRI studies with mpMRI acquisitions were performed in 53 prostate cancer patients relapsing after curative RP. Median PSA and PSA doubling time (PSA DT) at PET study were 1.5 ng/ml and 6.5 months, respectively. The overall positivity rate of FCH PET/MRI was 58.6% (n = 34), dropping to 44% in patients with a PSA ≤ 2 ng/ml (n = 36). Median PSA values in positive and negative PET/MRI studies were 2.2 ng/ml and 0.8 ng/ml, respectively, with no differences in PSA DT (6.5 vs. 6.6 months). A PSA value ≥ 1.5 ng/ml was a significant predictor of positivity on PET/MRI studies. Compared to PET, mpMRI identified more local relapses (17 vs. 14, p = 0.453) while PET outperformed whole-body Dixon MRI for regional (16 vs. 9, p = 0.016) and distant (12 vs. 6, p = 0.031) metastases. Compared to pelvic mpMRI, the treatment approach turned out to be influenced more frequently using whole-body FCH hybrid PET/MRI studies (58.6% vs. 38%). In prostate cancer patients with biochemical recurrence after RP, whole-body FCH PET/MRI achieved a higher detection rate of nodal/distant metastases compared to pelvic mpMRI alone, increasing the change of treatment strategy by more than 20%.

Oligorecurrent Nodal Prostate Cancer: Long-term Results of an Elective Nodal Irradiation Approach.

OBJECTIVES: The objective of this study was to report long-term results of elective nodal radiotherapy (ENRT) in prostate cancer (PCa) patients with oligorecurrent nodal disease after primary treatment. METHODS: Data of 53 oligorecurrent PCa patients (N1 and/or M1a) with ≤5 nodal metastases (n=108) treated with ENRT combined with androgen deprivation therapy (ADT) between 2004 and 2016 were retrospectively reviewed. Median prostate-specific antigen (PSA) and PSA doubling time (DT) were 3.4 ng/mL and 5 months, respectively. At restaging, 45% of the patients presented single nodal metastases, mainly located in the pelvis (n=38). All patients underwent ENRT between 45 and 50.4 Gy with a boost on positive nodes (median 64.4 Gy; 54 to 69 Gy) using mainly VMAT (n=24) or IMRT (n=21) techniques. Concomitant ADT was administered to all patients for a median time of 6 months. RESULTS: After a median follow-up after ENRT of 44 months (range, 2 to 133), the 5-year biochemical disease-free and distant progression-free survival (DPFS) rates were 43% and 58%, respectively, with worse DPFS observed in patients with a PSA-doubling time <3 months (36.8% vs. 63.6%; P=0.029). Seventeen of 19 clinically relapsing patients presented lesions out of the ENRT field, and 10 were again oligometastatic. Only 2 patients presented with a CTCAE v3.0 grade ≥2 genitourinary toxicity. CONCLUSIONS: ENRT combined with short-course ADT is a safe and effective salvage modality for patients with oligorecurrent nodal PCa. Prospective randomized studies comparing focal SBRT versus ENRT are warranted to define the best treatment strategy.

Long-term Results of a Comparative PET/CT and PET/MRI Study of 11C-Acetate and 18F-Fluorocholine for Restaging of Early Recurrent Prostate Cancer.

PURPOSE: The aims of this study were to assess the intraindividual performance of F-fluorocholine (FCH) and C-acetate (ACE) PET studies for restaging of recurrent prostate cancer (PCa), to correlate PET findings with long-term clinical and imaging follow-up, and to evaluate the impact of PET results on patient management. METHODS: Thirty-three PCa patients relapsing after radical prostatectomy (n = 10, prostate-specific antigen [PSA] ≤3 ng/mL), primary radiotherapy (n = 8, prostate-specific antigen ≤5 ng/mL), or radical prostatectomy + salvage radiotherapy (n = 15) underwent ACE and FCH PET-CT (n = 29) or PET-MRI (n = 4) studies in a randomized sequence 0 to 21 days apart. RESULTS: The detection rate for ACE was 66% and for FCH was 60%. Results were concordant in 79% of the cases (26/33) and discordant in 21% (retroperitoneal, n = 5; pararectal, n = 1; and external iliac nodes, n = 1). After a median FU of 41 months (n = 32, 1 patient lost to FU), the site of relapse was correctly identified by ACE and FCH in 53% (17/32) and 47% (15/32) of the patients, respectively (2 M1a patients ACE+/FCH-), whereas in 6 of 32 patients the relapse was not localized. Treatment approach was changed in 11 (34.4%) of 32 patients and 9 (28%) of 32 patients restaged with ACE and FCH PET, respectively. CONCLUSIONS: In early recurrent PCa, ACE and FCH showed minor discrepancies, limited to nodal staging and mainly in the retroperitoneal area, with true positivity of PET findings confirmed in half of the cases during FU. Treatment approach turned out to be influenced by ACE or FCH PET studies in one third of the patients.

Novel 10-fraction breast irradiation in prone and supine position: technical, dosimetric and clinical evaluation.

BACKGROUND: The aim of this study was to evaluate retrospectively the planned dose distribution and acute toxicity of adjuvant hypofractionated whole breast radiotherapy (RT) delivered in the prone vs. supine position. METHODS: Twenty-four patients were enrolled; 12 underwent adjuvant RT with a supine setup and 12 with a prone setup. We included patients according to breast volume (≥500 mL), disease stage (≤pT2/pN1), and clinical/biological features. Patients received a regimen of 35 Gy in 10 fractions for 2.5 weeks, and a concomitant boost of 3/4 Gy in 1 fraction/week. Target coverage was assessed by volume, V90, V95, V100, V103 and V105. Heart, LADCA and ipsilateral lung doses were evaluated according to volume, maximum dose, mean dose, V14, V10 and V5. We evaluated acute skin toxicity during RT, at the end of treatment, and after 1 month according to RTOG scales. RESULTS: Radiobiological equivalence was warranted with satisfactory BED values: considering α/ß = 4 for breast cancer, the 10-fraction schedule equaled 74 or 77 Gy depending on the boost dose (3 Gy vs. 4 Gy, respectively). Toxicity was low and similar for supine and prone treatments. Dose sparing was significant in the ipsilateral lung in the prone position (median Dmax: 28.7 Gy vs. 38.4 Gy; median Dmean: 0.8 Gy vs. 6.3 Gy; median V14: 0.6% vs. 13.5%; median V5: 0 vs. 19.3%, p<0.001). CONCLUSIONS: This novel 10-fraction schedule is feasible and well tolerated; the prone position allows better saving of OARs, with a statistically significant value for the ipsilateral lung.

Ablative or palliative stereotactic body radiotherapy with helical tomotherapy for primary or metastatic lung tumor.

AIM: To evaluate the feasibility and outcomes of stereotactic body radiotherapy (SBRT) by helical tomotherapy (HT) for patients with primary or secondary lung cancer. PATIENTS AND METHODS: Between March 2009 and January 2012, 56 patients were selected as candidates for the study and were divided into two subgroups. The ablative SBRT group included 27 patients with T1-T2 non-small cell lung cancer who received four to five large-dose fractions in two weeks and the palliative SBRT group included 29 patients with lung metastases treated with eight lower-dose fractions in four weeks. RESULTS: No differences in acute toxicities were found between different fractionation schemes with different overall treatment times. Actuarial local control at 24 months was better for the ablative group (69.6%) than for the palliative one (40.4%) (p=0.0019). CONCLUSION: HT-based SBRT was feasible and well-tolerated. Local control was satisfactory for patients treated with ablative SBRT but unsatisfactory for those treated with palliative SBRT. Outcomes also suggest the use of ablative SBRT fractionation for palliative intent.

Once-weekly stereotactic radiotherapy for patients with oligometastases: compliance and preliminary efficacy.

AIMS AND BACKGROUND: This retrospective analysis reports the outcomes obtained with an original once-weekly stereotactic radiotherapy fractionation given to patients affected by evolving oligometastases from different solid malignancies. METHODS: From 2009 to 2011, patients with symptomatic and/or evolving oligometastases were submitted to a median 5-fraction cycle of stereotactic radiotherapy of one fraction per week in order to exploit a radiobiological rationale designed to increase the therapeutic index. Individual fractionation was mainly planned according to patient performance status, oligometastasis size and site, and record of previous irradiation in the same site. RESULTS: Thirty-six patients in stage IV UICC-TNM affected by oligometastases were treated with image-guided intensity-modulated stereotactic tomotherapy with a single weekly radiation. Median age was 70 years (range, 34-89). The median weekly single dose, number of fractions and overall total radiation dose were 7 Gy, 5 fractions and 35 Gy, respectively. Thirty-five (97%) patients completed the treatment schedule. No patient suffered mild or severe radiation-related side effects. Twenty-one (87%) of 24 patients with local pain had complete symptomatic response within 30 days following the end of radiotherapy. Local control assessed at imaging after stereotactic radiotherapy was evidenced in 30 (83%) patients. Median time to response after the end of radiotherapy was 40 days. CONCLUSIONS: The original radiotherapy regimen delivering only a single stereotactic dose per week seems to be highly feasible with an interesting high efficacy rate in patients with oligometastases from different solid tumors. Overall, the once-weekly treatment was very compliant in an advanced cancer stage especially for elderly and frail patients.