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• KB planning was applied to SBRT prostate cancer with CyberKnife. • The KB model generated DVH prediction for the bladder, the rectum and femoral heads. • A KB-based template was efficiently tuned for both sequential and VOLO algorithms. • The KB-model was able to generate high-quality automatic plans for both modalities. To extend the knowledge-based (KB) automatic planning approach to CyberKnife in the case of Stereotactic Body Radiation Therapy (SBRT) for prostate cancer. Seventy-two clinical plans of patients treated according to the RTOG0938 protocol (36.25 Gy/5fr) with CyberKnife were exported from the CyberKnife system to Eclipse to train a KB-model using the Rapid Plan tool. The KB approach provided dose-volume objectives for specific OARs only and not PTV. Bladder, rectum and femoral heads were considered in the model. The KB-model was successfully trained on 51 plans and then validated on 20 new patients. A KB-based template was tuned in the Precision system for both sequential optimization (SO) and VOLO optimization algorithms. Plans of the validation group were re-optimized (KB-TP) using both algorithms without any operator intervention and compared against the original plans (TP) in terms of OARs/PTV dose-volume parameters. Paired Wilcoxon signed-rank tests were performed to assess statistically significant differences (p < 0.05). Regarding SO, automatic KB-TP plans were generally better than or equivalent to TP plans. PTVs V95% was slightly worse while OARs sparing for KB-TP was significantly improved. Regarding VOLO optimization, the PTVs coverage was significantly better for KB-TP while there was a limited worsening in the rectum. A significant improvement was observed in the bladder in the range of low-intermediate doses. An extension of the KB optimization approach to the CyberKnife system has been successfully developed and validated in the case of SBRT prostate cancer. [ABSTRACT FROM AUTHOR]

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

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

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

Background After interstitial prostate iodine-125 brachytherapy (BT), prostate-specific antigen (PSA) evolution in time could predict overall biochemical relapse, but, considering the single patient, it is influenced by the presentation PSA amount and by the prostatic volume. It is also challenging to differentiate a PSA bounce from a biochemical relapse. Purpose To determine the usefulness of PSA percentage (PP) defined as the rate between PSA presented by a patient at time “t” and the PSA that the same patient had presented at the time of diagnosis (t0) assumed as 100% in predicting biochemical relapse and in differentiating them from PSA Bounces. Methods and Materials We included 721 patients from Milan S. Raffaele Turro (399) and Lucca Campo di Marte (then S. Luca) Hospital (322). The mean age of patients was 66.5 years (range, 50–79). Mean followup was 150 months (range, 24–180). For each patient, PSA was recorded before and after iodine-125 BT, and PPs were calculated. Cox regression model, relative operating characteristic curves, and Kaplan–Meier regression model were elaborated, and a cutoff of 20% was defined. Results We observed that PP >20% is an independent variable highly associated with relapse risk ( p < 0.0001) with a sensitivity of 79.7%, a specificity of 82%, and an hazard ratio of 12.1, since the 6 months of followup. A PSA increase above the nadir should be because of bounce (sensitivity and specificity of 81.4%, p < 0.0001) if patient had experienced at 6 months a PP <20%. Conclusions PP might represent an early and useful tool, predictive of clinical outcome in patients after BT for prostate cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: To assess the impact of using MRI and Helical Tomotherapy (HT) compared to 3DCRT and dynamic IMRT on the dose to the penile bulb (PB). Materials and methods: Eight patients diagnosed with prostate cancer entered a treatment protocol including CT and MRI simulation. The prostate apex was defined on both MRI and CT. Treatment plans (HT, Linac-IMRT, 3DCRT and conventional technique), were elaborated on both MRI and CT images. A dose of 71.4Gy (2.55Gy/fraction) was prescribed; it was requested that PTVs be covered by 95% isodose line. The mean dose and V50 of PB were evaluated. Results: PTV-MRI plans reduced PB mean dose and V50 compared to PTV-CT plans. This improvement, deriving also from the treatment modality, was 89% for 3DCRT, 99% for Linac-IMRT and 97% for HT (p <0.01), considering V50. Conventional plans resulted in a significantly higher mean PB dose/V50 compared to 3DCRT-PTV-CT (+27%/+38%), Linac-IMRT-PTV-CT (+42%/+57%) and HT-PTV-CT (+32%/+48%) (p <0.01). The comparison between conventional and PTV-MRI techniques showed a still larger increase: +73%/+93% 3DCRT; +86%/+99% Linac-IMRT; +56%/+99% HT (p <0.01). The PB mean dose reduction with Linac-IMRT compared to 3DCRT was 24% (p =0.034) and 40% (p =0.027) for PTV-CT and PTV-MRI, respectively. This gain remained significant even when comparing Linac-IMRT to HT: 21% (p =0.07) PTV-CT and 68% (p =0.00002) PTV-MRI. HT was superior to 3DCRT with respect to PTV-CT (average gain 4%, p =0.044), whereas it resulted to be detrimental considering PTV-MRI (26Gy vs 16.5Gy), possibly due to the helical delivery of HT; however, in a patient where the distance bulb-PTV <1cm, HT provided better PB sparing than 3DCRT (29.5Gy vs 45.2Gy). Conclusions: MRI allowed efficient sparing of PB irrespective of the treatment modality. Linac-IMRT was shown to further reduce the dose to the bulb compared to 3DCRT and HT. [Copyright &y& Elsevier]

Purpose: To report planning and acute toxicity data of the first 60 patients treated within a Phase I–II study with moderate hypofractionation by image-guided helical tomotherapy. Methods and Materials: Various clinical target volumes (CTVs) were defined: CTV1—pelvic nodes; CTV2—upper portion of seminal vesicles; CTV3—lower portion of SV; CTV4—prostate; overlap between planning target volume (PTV) 4 and rectum. Different doses to each PTV were simultaneously delivered in 28 fractions. For 31 low-risk patients: 56.0, 61.6, and 71.4 Gy for PTV2–4, respectively; for 20 intermediate-risk patients: 51.8, 61.6, 65.5, and 74.2 Gy for PTV1–4, respectively; for 9 high-risk patients: 51.8 and 65.5 Gy for PTV1–2 and 74.2 Gy for PTV3–4. For all patients, the dose to overlap was 65.5 Gy. Results: The mean fraction of rectum receiving more than 65 Gy (V65) and rectal Dmax were 10% and 70.8 Gy respectively. In cases of pelvic node irradiation, the intestinal cavity (outside PTV) receiving > 45 and 50 Gy was 86 and 12 cc, respectively. A homogeneous dose distribution within each PTV was guaranteed. Acute genitourinary toxicity according to RTOG scoring system was as follows: 21/60 (35%) Grade 1, 12/60 (20%) Grade 2, 2/60 (3%) Grade 3. Acute rectal toxicities were: 18/60 (30%) Grade 1. Twelve (20%) patients showed Grade 1 upper intestinal toxicity (uGI). No patients experienced ≥ Grade 2 acute rectal or uGI side effects. Conclusions: This study shows excellent results with regard to acute toxicity. Further research is necessary to assess definitive late toxicity and tumor control outcome. [Copyright &y& Elsevier]

Abstract: The aim of this paper is to supplement the GEC/ESTRO/EAU recommendations for permanent seed implantations in prostate cancer to develop consistency in target and volume definition for permanent seed prostate brachytherapy. Recommendations on target and organ at risk (OAR) definitions and dosimetry parameters to be reported on post implant planning are given. [Copyright &y& Elsevier]