Muscle-invasive bladder cancer in elderly and frail people: Is hypofractionated radiotherapy a feasible approach when no other local options are available?

AIM: The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments. METHODS: Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria. RESULTS: A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively. CONCLUSION: Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients.

Photon vs proton hypofractionation in prostate cancer: A systematic review and meta-analysis.

BACKGROUND: High-level evidence on hypofractionated proton therapy (PT) for localized and locally advanced prostate cancer (PCa) patients is currently missing. The aim of this study is to provide a systematic literature review to compare the toxicity and effectiveness of curative radiotherapy with photon therapy (XRT) or PT in PCa. METHODS: PubMed, Embase, and the Cochrane Library databases were systematically searched up to April 2022. Men with a diagnosis of PCa who underwent curative hypofractionated RT treatment (PT or XRT) were included. Risk of grade (G) ≥ 2 acute and late genitourinary (GU) OR gastrointestinal (GI) toxicity were the primary outcomes of interest. Secondary outcomes were five-year biochemical relapse-free survival (b-RFS), clinical relapse-free, distant metastasis-free, and prostate cancer-specific survival. Heterogeneity between study-specific estimates was assessed using Chi-square statistics and measured with the I2 index (heterogeneity measure across studies). RESULTS: A total of 230 studies matched inclusion criteria and, due to overlapped populations, 160 were included in the present analysis. Significant lower rates of G ≥ 2 acute GI incidence (2 % vs 7 %) and improved 5-year biochemical relapse-free survival (95 % vs 91 %) were observed in the PT arm compared to XRT. PT benefits in 5-year biochemical relapse-free survival were maintained for the moderate hypofractionated arm (p-value 0.0122) and among patients in intermediate and low-risk classes (p-values < 0.0001 and 0.0368, respectively). No statistically relevant differences were found for the other considered outcomes. CONCLUSION: The present study supports that PT is safe and effective for localized PCa treatment, however, more data from RCTs are needed to draw solid evidence in this setting and further effort must be made to identify the patient subgroups that could benefit the most from PT.

Extreme-hypofractionated RT with concomitant boost to the DIL in PCa: a 5-year update on oncological and patient-reported outcomes for the phase II trial "GIVE ME FIVE".

AIM: The present work reports updated oncological results and patients-reported outcomes at 5 years of phase II trial "Short-term high precision RT for early prostate cancer with SIB to the dominant intraprostatic lesion (DIL) for patients with early-stage PCa". METHODS: Data from patients enrolled within AIRC IG-13218 (NCT01913717) trial were analyzed. Clinical and GU/GI toxicity assessment and PSA measurements were performed every 3 months for at least 2 years after RT end. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and IIEF-5. Patients' score changes were calculated at the end of RT and at 1, 12, and 60 months after RT. RESULTS: A total of 65 patients were included. At a median follow-up of 5 years, OS resulted 86%. Biochemical and clinical progression-free survival at 5 years were 95%. The median PSA at baseline was 6.07 ng/ml, while at last follow-up resulted 0.25 ng/ml. IPSS showed a statistically significant variation in urinary function from baseline (p = 0.002), with the most relevant deterioration 1 month after RT, with a recovery toward baseline at 12 months (p ≤ 0.0001). A numerical improvement in QoL according to the EORTC QLQ-C30 has been reported although not statistically significant. No change in sexual activity was recorded after RT. CONCLUSIONS: The study confirms that extreme hypofractionation with a DIL boost is safe and effective, with no severe effects on the QoL. The increasing dose to the DIL does not worsen the RT toxicity, thus opening the possibility of an even more escalated treatment.

Cyberknife Radiosurgery for Prostate Cancer after Abdominoperineal Resection (CYRANO): The Combined Computer Tomography and Electromagnetic Navigation Guided Transperineal Fiducial Markers Implantation Technique.

In this technical development report, we present the strategic placement of fiducial markers within the prostate under the guidance of computed tomography (CT) and electromagnetic navigation (EMN) for the delivery of ultra-hypofractionated cyberknife (CK) therapy in a patient with localized prostate cancer (PCa) who had previously undergone chemo-radiotherapy for rectal cancer and subsequent abdominoperineal resection due to local recurrence. The patient was positioned in a prone position with a pillow under the pelvis to facilitate access, and an electromagnetic fiducial marker was placed on the patient's skin to establish a stable position. CT scans were performed to plan the procedure, mark virtual points, and simulate the needle trajectory using the navigation system. Local anesthesia was administered, and a 21G needle was used to place the fiducial markers according to the navigation system information. A confirmatory CT scan was obtained to ensure proper positioning. The implantation procedure was safe, without any acute side effects such as pain, hematuria, dysuria, or hematospermia. Our report highlights the ability to use EMN systems to virtually navigate within a pre-acquired imaging dataset in the interventional room, allowing for non-conventional approaches and potentially revolutionizing fiducial marker positioning, offering new perspectives for PCa treatment in selected cases.

Can Ki-67 predict radiotherapy response in neuroendocrine tumors? Retrospective analysis of a monocentric series of patients.

BACKGROUND: The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity. MATERIAL AND METHODS: Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment. RESULTS: Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses. CONCLUSION: No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.

Nodal Merkel Cell Carcinoma with Unknown Primary Site and No Distant Metastasis: A Single-Center Series.

Merkel cell carcinoma (MCC) is a very rare and aggressive neuroendocrine carcinoma originating from Merkel cells, typically with a skin nodule; however, it exceptionally presents with only a basin lymph node localization, with neither a cutaneous primary site nor distant metastases. From 1996 to 2020, among patients with histologically confirmed MCC managed at a neuroendocrine neoplasm-referral center, we selected those with an exclusive nodal basin, no distant metastasis, and an unknown primary site defined by cross-sectional and physical examination. A total of 55 out of 310 patients fulfilled the selection criteria. The median age was 64 years and the majority were males. Inguinal lymph-nodes were the most common anatomic site. With a median follow-up of 4.3 years, the 5-year relapse-free survival (RFS) rate was 56.6 (95% CI 42.0-68.8%) and the 5-year cancer specific survival (CSS) rate was 68.5 (95% CI 52.8-79.9%) for the whole population. The 36 patients (65.5%) undergoing lymphadenectomy (LND) + radiotherapy (RT) ± chemotherapy had a 5-year RFS rate of 87.2% (95% CI 65.5-95.7%) and a 5-year CSS rate of 90.5% (95% CI 67.0-97.5), which were better than those receiving LND alone. In a multivariable analysis, the survival benefit for LND + RT remained significant. Results from one of the largest single-center series of nMCC-UP suggest that a curative approach including RT can be effective, similar to what is observed for stage IIIB MCC. Multicentric studies with homogenous populations should be carried out in this controversial clinical entity, to minimize the risk of biases and provide robust data.

Correlation between radiological and biological features and clinical outcomes in early prostate cancer: an exploratory subgroup analysis.

PTEN deletion and Ki-67 expression are two of the most promising biomarkers in prostate cancer (PCa). In the same manner, multiparametric magnetic resonance imaging (mp-MRI) guided core biopsy is a powerful tool for PCa detection and staging. The aim of the study is to assess whether a correlation can be identified between the pathological stage defined by an mp-MRI-guided core biopsy and Ki-67 expression and PTEN deletion. Such correlation might be useful for staging and treatment personalization in PCa. This investigation was conducted in the context of phase II clinical study "Short-term radiotherapy for early prostate cancer with a concomitant boost to the dominant lesion" (AIRC IG-13218), ClinicalTrials.gov identifier: NCT01913717. Nineteen patients underwent a further in-bore MRI-targeted core biopsy (MRI-TBx) on the dominant intraprostatic lesion (DIL); on this basis, an additional Gleason Score (GS) was determined. PTEN loss and Ki-67 expression on these samples were analyzed and correlated with both risk categories modifications and oncological outcomes (overall survival, biochemical and clinical relapse). GS was upgraded in 5 cases, with 4 patients re-classified as intermediate-risk and 1 patient as high-risk. The latter experienced a clinical local relapse. No correlations between up/down-staging, PTEN deletion, and Ki-67 expression were observed in this cohort. Further investigations are needed towards the identification of a pattern in the tumor aggressiveness-response in PCa treated with ultra-hypofractionated radiotherapy. Moreover, a possible relationship between biomarker analysis and imaging textural features could be explored.

Ultrahypofractionated radiotherapy for localized prostate cancer with simultaneous boost to the dominant intraprostatic lesion: a plan comparison.

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.

Mixed-Beam Approach for High-Risk Prostate Cancer Carbon-Ion Boost Followed by Photon Intensity-Modulated Radiotherapy: Preliminary Results of Phase II Trial AIRC-IG-14300.

PURPOSE: This study represents a descriptive analysis of preliminary results of a Phase II trial on a novel mixed beam radiotherapy (RT) approach, consisting of carbon ions RT (CIRT) followed by intensity-modulated photon RT, in combination with hormonal therapy, for high-risk prostate cancer (HR PCa) with a special focus on acute toxicity. METHODS: Primary endpoint was the evaluation of safety in terms of acute toxicity. Secondary endpoints were early and long-term tolerability of treatment, quality of life (QoL), and efficacy. Data on acute and late toxicities were collected according to RTOG/EORTC. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and sexual activity by IIEF-5. RESULTS: Twenty-six patients were enrolled in the study, but only 15 completed so far the RT course and were included. Immediately after CIRT, no patients experienced GI/GU toxicity. At 1 and 3 months from the whole course RT completion, no GI/GU toxicities greater than grade 2 were observed. QoL scores were overall satisfactory. CONCLUSIONS: The feasibility of the proposed mixed treatment schedule was assessed, and an excellent acute toxicity profile was recorded. Such findings instil confidence in the continuation of this mixed approach, with evaluation of long-term tolerability and efficacy.

Finding safe dose-volume constraints for re-irradiation with SBRT of patients with prostate cancer relapse: The IEO experience.

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.

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.

MRI-based radiomics signature for localized prostate cancer: a new clinical tool for cancer aggressiveness prediction? Sub-study of prospective phase II trial on ultra-hypofractionated radiotherapy (AIRC IG-13218).

OBJECTIVES: Radiomic involves testing the associations of a large number of quantitative imaging features with clinical characteristics. Our aim was to extract a radiomic signature from axial T2-weighted (T2-W) magnetic resonance imaging (MRI) of the whole prostate able to predict oncological and radiological scores in prostate cancer (PCa). METHODS: This study included 65 patients with localized PCa treated with radiotherapy (RT) between 2014 and 2018. For each patient, the T2-W MRI images were normalized with the histogram intensity scale standardization method. Features were extracted with the IBEX software. The association of each radiomic feature with risk class, T-stage, Gleason score (GS), extracapsular extension (ECE) score, and Prostate Imaging Reporting and Data System (PI-RADS v2) score was assessed by univariate and multivariate analysis. RESULTS: Forty-nine out of 65 patients were eligible. Among the 1702 features extracted, 3 to 6 features with the highest predictive power were selected for each outcome. This analysis showed that texture features were the most predictive for GS, PI-RADS v2 score, and risk class; intensity features were highly associated with T-stage, ECE score, and risk class, with areas under the receiver operating characteristic curve (ROC AUC) ranging from 0.74 to 0.94. CONCLUSIONS: MRI-based radiomics is a promising tool for prediction of PCa characteristics. Although a significant association was found between the selected features and all the mentioned clinical/radiological scores, further validations on larger cohorts are needed before these findings can be applied in the clinical practice. KEY POINTS: • A radiomic model was used to classify PCa aggressiveness. • Radiomic analysis was performed on T2-W magnetic resonance images of the whole prostate gland. • The most predictive features belong to the texture (57%) and intensity (43%) domains.

Adjuvant radiotherapy in node positive prostate cancer patients: a debate still on. when, for whom?

OBJECTIVE: To evaluate the impact of adjuvant radiotherapy (aRT) in patients with prostate cancer (PCa) found to have pathological positive lymph nodes (pN1s) after radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND) with regard to distant recurrence-free survival (RFS), according to both main tumour pathological characteristics and number of positive lymph nodes. Biochemical RFS, local RFS, overall survival (OS) and acute and late toxicity were assessed as secondary endpoints. PATIENTS AND METHODS: A retrospective cohort of 187 consecutive patients with pN1 PCa were treated with aRT at the IEO, European Institute of Oncology IRCCS, Milan, Italy. aRT on the tumour bed and pelvis was administered within 6 months of RP. Androgen deprivation therapy was administered according to the guidelines. Univariate and multivariate Cox regression analyses predicting biochemical RFS, local RFS, distant RFS and OS rates were performed to assess whether the number of pN1s represented an independent prognostic factor. The Youden index was computed to find the optimal threshold for the number of pN1s able to discriminate between patients with or without biochemical and clinical relapse. RESULTS: At 5 years, local RFS, distant RFS, biochemical RFS and OS were 68%, 71%, 56% and 94%, respectively. The median follow-up was 49 months. The number of pN1s was significantly associated with biochemical RFS, local RFS and distant RFS. The best threshold for discriminating between patients with or without biochemical and clinical relapse was five pN1s. In multivariate analyses, the number of pN1s was confirmed to be an independent predictor of biochemical RFS, local RFS and distant RFS, but not of OS. Multivariate analyses also showed an increased risk of biochemical relapse for increasing values of initial prostate-specific antigen and for patients with tumour vascular invasion. Local and distant RFS were also inversely correlated with significantly reduced risk for International Society of Urological Pathology grade group <3 (group 1 or 2 compared to group 3). CONCLUSIONS: Our data confirmed the encouraging outcomes of patients with pN1 PCa treated with adjuvant treatments and the key role represented by the number of pN1s in predicting biochemical RFS, clinical RFS and distant RFS. Large prospective cohort studies and randomized clinical trials are needed to confirm these results and to identify the subgroup of patients with pN1 PCa who would most benefit from aRT.

Multidisciplinary team approach for Merkel cell carcinoma: the European Institute of Oncology experience with focus on radiotherapy.

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.

Mixed-beam approach for high-risk prostate cancer: Carbon-ion boost followed by photon intensity-modulated radiotherapy. Dosimetric and geometric evaluations (AIRC IG-14300).

BACKGROUND AND PURPOSE: The aim was to evaluate dosimetric uncertainties of a mixed beam approach for patients with high-risk prostate cancer (PCa). The treatment consists of a carbon ion radiotherapy (CIRT) boost followed by whole-pelvis intensity-modulated RT (IMRT). MATERIALS AND METHODS: Patients were treated with a CIRT boost of 16.6 Gy/4 fractions followed by whole-pelvis IMRT of 50 Gy/25 fractions, with consequent long term androgen deprivation therapy. Deformable computed tomography image registration (DIR) was performed and corresponding doses were used for plan sum. A comparative IMRT photon plan was obtained as whole-pelvis IMRT of 50 Gy/25 fractions followed by a boost of 28 Gy/14 fractions. DIR performances were evaluated through structure-related and image characteristics parameters. RESULTS: Until now, five patients out of ten total enrolled ended the treatment. Dosimetric parameters were lower in CIRT + IMRT than IMRT-only plans for all organs at risk (OARs) except femoral heads. Regarding DIR evaluation, femoral heads were the less deformed OAR. Penile bulb, bladder and anal canal showed intermediate deformation. Rectum was the most deformed. DIR algorithms were patient (P)-dependent, as performances were the highest for P3 and P4, intermediate for P2 and P5, and the lowest for P1. CONCLUSIONS: CIRT allows better OARs sparing while increasing the efficacy due to the higher radio-biological effect of carbon ions. However, a mixed beam approach could introduce DIR problems in multi-centric treatments with different operative protocols. The development of this prospective trial will lead to more mature data concerning the clinical impact of implementing DIR procedures in dose accumulation applications for high-risk PCa treatments.

Phase II prospective trial "Give Me Five" short-term high precision radiotherapy for early prostate cancer with simultaneous boost to the dominant intraprostatic lesion: the impact of toxicity on quality of life (AIRC IG-13218).

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.

PROLAPSE: survey about local prostate cancer relapse salvage treatment with external beam re-irradiation: results of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: We herein present the results of the first Italian Association of Radiotherapy and Clinical Oncology (AIRO) survey regarding salvage external beam re-irradiation of local prostate cancer relapse named PROLAPSE. METHODS: A questionnaire with 12 items was administered to the 775 Italian radiation oncologist members of the AIRO. RESULTS: One hundred of the members completed the survey. The survey highlighted that 59% of the participants are currently performing prostate re-EBRT, while nearly two-thirds (65%) affirmed that they are taking into consideration the procedure in case of intraprostatic relapse. Regarding the clinical target volume (CTV), only a minority (16%) declared to always prefer the partial prostate re-irradiation, while a consistent portion (nearly two-thirds) relied on clinical considerations of the choice towards partial or whole gland irradiation. The main techniques used for re-irradiation resulted to be intensity-modulated RT (IMRT)/volumetric modulated arc therapy (VMAT) and SBRT, having received approximately 40% of responses each. Regarding the criteria for patients' selection, more than 75% of responders agreed on the use of positron emission tomography (PET)/computed tomography (CT)-choline to exclude distant metastases and of multiparametric magnetic resonance imaging (mp-MRI) to detect intraprostatic recurrence. A sufficient timeframe (> 3 years) between primary RT and reirradiation was indicated by more than half of participants as an important driver in decision-making, while histological confirmation of the relapse was considered not essential by more than two-thirds. For the use of concomitant androgen deprivation therapy (ADT), most AIRO members (79%) agreed that the prescription should be based on a case-by-case analysis. Extreme hypofractionation (> 5 Gy/fraction) was preferred by the majority (52%) of the AIRO members. In most centers (more than 74%), the planning dose-volume constraints were generally extrapolated from the published data. In half of the cases, the interviewed responders affirmed that no major gastrointestinal (GI) and genitourinary (GU) toxicities were registered in the follow-up of their re-EBRT patients. Bladder complications represented the most commonly observed form of toxicity, with an incidence of 67%. CONCLUSION: This first AIRO survey about salvage prostate re-EBRT provides an interesting snapshot and suggests increasing interest in re-EBRT patients in Italy. Consensus about some aspects of patients' selection, the necessity of biopsy, fractionation, and highly selective techniques seems feasible, but other key points such as irradiated volume, dosimetry parameters, and hormonal treatment association need to be clarified.

Automatic genetic planning for volumetric modulated arc therapy: A large multi-centre validation for prostate cancer.

PURPOSE: The first clinical genetic autoplanning algorithm (Genetic Planning Solution, GPS) was validated in ten radiotherapy centres for prostate cancer VMAT by comparison with manual planning (Manual). METHODS: Although there were large differences among centres in planning protocol, GPS was tuned with the data of a single centre and then applied everywhere without any centre-specific fine-tuning. For each centre, ten Manual plans were compared with autoGPS plans, considering dosimetric plan parameters and the Clinical Blind Score (CBS) resulting from blind clinician plan comparisons. AutoGPS plans were used as is, i.e. there was no patient-specific fine-tuning. RESULTS: For nine centres, all ten plans were clinically acceptable. In the remaining centre, only one plan was acceptable. For the 91% acceptable plans, differences between Manual and AutoGPS in target coverage were negligible. OAR doses were significantly lower in AutoGPS plans (p < 0.05); rectum D15% and Dmean were reduced by 8.1% and 17.9%, bladder D25% and Dmean by 5.9% and 10.3%. According to clinicians, 69% of the acceptable AutoGPS plans were superior to the corresponding Manual plan. In case of preferred Manual plans (31%), perceived advantages compared to autoGPS were minor. QA measurements demonstrated that autoGPS plans were deliverable. A quick configuration adjustment in the centre with unacceptable plans rendered 100% of plans acceptable. CONCLUSION: A novel, clinically applied genetic autoplanning algorithm was validated in 10 centres for in total 100 prostate cancer patients. High quality plans could be generated at different centres without centre-specific algorithm tuning.

Correction to: Late toxicity of image-guided hypofractionated radiotherapy for prostate: non-randomized comparison with conventional fractionation.

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

Radioablation +/- hormonotherapy for prostate cancer oligorecurrences (Radiosa trial): potential of imaging and biology (AIRC IG-22159).

BACKGROUND: Prostate cancer (PCa) is the second most common cancer among men. New imaging-modalities have increased the diagnosed patients with limited number of metastasis after primary curative therapy, introducing so-called oligometastatic state. Stereotactic body radiotherapy (SBRT) is emerging as a low-toxicity treatment to erase PCa localizations and postpone androgen deprivation therapy (ADT). A deeper understanding of the predictive role of biomarkers is desirable for a targeted treatment selection and surveillance programs. The aims of the RADIOSA trial are: 1. Compare SBRT +/- ADT for oligorecurrent-castration-sensitive PCa (OCS-PCa) in terms of efficacy, toxicity and Quality of Life (QoL). 2. Develop biology/imaging based prognostic tool that allows identifying OCS-PCa subclasses. METHODS: This is a randomized phase II clinical trial, recruiting 160 OCS-PCa in 3 years, with progression-free survival (PFS) as primary endpoint. Three tasks will be developed: 1. Randomized clinical study (3 years for accrual and 2 years for follow-up and data analysis); 2. Imaging study, including imaging registration and METastasis Reporting and Data System (MET-RADS) criteria; 3. Pre-clinical study, development of a biobank of blood samples for the analysis of neutrophil-to-lymphocyte ratio and preparatory for a subsequent miRNA profiling. We aim to determine which arm is justified for testing in a subsequent Phase III trial. A decision-tree algorithm, based on prognosis, biological phenotype and imaging profile, will be developed. DISCUSSION: Recruiting will start in July 2019. SBRT will allow obtaining excellent PFS, local control, QoL and low toxicity. In SBRT arm, ADT deferral will allow for a drug-holiday, delaying the detrimental impact on QoL. A sufficient number of blood samples will be collected to perform biological patient profiling. A stratification tool will be established with an analysis of morphological and functional imaging, based on the use of MET-RADS criteria. So, in conclusion, RADIOSA aims to define the optimal management of bone/nodal PCa relapses in a SBRT regimen. This study will increase our knowledge on low-burden metastatic PCa in the era of high precision and high technology personalized medicine, offering highly effective therapy in terms of clinical outcome and cost-effectiveness. TRIAL REGISTRATION: The RADIOSA study was prospectively registered at clinicaltrials.gov ( NCT03940235 , May 2019).