Long term update on toxicity and survival of a phase II trial of linac-based stereotactic body radiation therapy for low-intermediate risk prostate cancer.

BACKGROUND: In 2016 we published a phase II study exploring safety and efficacy of Stereotactic Body Radiation Therapy (SBRT) delivered with Volumetric Modulated Arc Therapy (VMAT) and Flattening Filter Free (FFF) beams techniques in prostate cancer (PC) patients. We present herein the updated results on late toxicity and long-term survival. METHODS: Patients enrolled in the study had a biopsy-confirmed localized PC and the features of a low- or intermediate-risk disease (National Comprehensive Network Criteria). The radiotherapy (RT) schedule consisted of 35 Gy delivered in five fractions every other day. Toxicities were registered according to the common toxicity adverse events v4.0. Biochemical recurrence was defined as an increase of prostate specific antigen after nadir, confirmed at least once. Local recurrence (LR) and distant metastases were detected either with Choline- or PSMA-PET/CT scans. Kaplan-Meier curves for Biochemical Recurrence-Free Survival (BFS), Local Control (LC), Distant Metastasis Free Survival (DMFS) and Cancer Specific Survival, were calculated by using MedCalc. RESULTS: Ninety patients were submitted to SBRT between February 2012 and March 2015. Fifty-eight patients (64.5%) had a Gleason Score of 6, while 32 (35.5%) had a Gleason Score of 7. A late grade 1 Genito-Urinary toxicity was observed in 54.5% of patients while a grade 2 in 3.3%. A late Gastro-intestinal grade 1 toxicity was reported in 18.9% of patients, while a grade 2 in 2.2%. Erectile dysfunction was reported by 13% of patients No heavier toxicities were observed. At a median follow-up of 102 months, 5- and 8-year BFS were 93.0% and 84.4% respectively, 5- and 8-year LC were 95.2% and 87.0% respectively, 5- and 8-year DMFS were 95.3% and 88.4%, respectively. CONCLUSIONS: This long-term update confirms that SBRT is a valid therapeutic strategy for low-intermediate risk PC. RT with VMAT and FFF warrants optimal results in terms of toxicity and disease control.

Prostate cancer: nuclear medicine imaging in the biochemical recurrence and in oligometastatic disease.

INTRODUCTION: The aim of this article was to offer a comprehensive non-systematic review of the literature about the use of Nuclear Medicine imaging exams for the evaluation of prostate cancer (PCa) in the recurrent setting, with a particular regard to positron emission tomography/computed tomography (PET/CT) imaging. EVIDENCE ACQUISITION: A comprehensive nonsystematic literature review was performed in March 2024. Literature search was updated until March 2024. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations. EVIDENCE SYNTHESIS: Restaging BCR with advanced Nuclear Medicine Imaging, such as prostate-specific membrane antigen-PET/CT could lead to stage migration and pave the way for additional management strategies, such as stereotactic ablative radiotherapy in patients with low-burden or oligometastatic disease, potentially delaying the need of systemic therapies. While OS benefits of targeting PET/CT positive disease are still lacking, data on progression- and metastasis-free-survival are emerging. Improvements in quality-of-life assessments are already evident. CONCLUSIONS: PCa is one of the most common malignancy in men. In the last 10 years PCa imaging has become significantly more accurate and is now essential for the definition of the extent of the disease in different phases of its natural history. This opened the road to novel management strategies, especially in the recurrent setting, in which the oligometastatic state is now being explored in several trials regarding the prognostic significance of metastasis directed therapies aimed at personalizing the treatment for every single patient.

PSMA guided approach for bIoCHEmical relapse after prostatectomy- (PSICHE) trial (NCT05022914). Detection rate and treatment decision after 68Ga-PSMA PET/CT within a prospective study.

BACKGROUND: Ultrasensitive imaging has been demonstrated to influence biochemical relapse treatment. PSICHE is a multicentric prospective study, aimed at exploring detection rate with 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and outcomes with a predefined treatment algorithm tailored to the imaging. METHODS: Patients affected by biochemical recurrence after surgery (prostate specific antigen [PSA] > 0.2 < 1 ng/mL) underwent staging with 68Ga-PSMA PET/CT. Management followed this treatment algorithm accordingly with PSMA results: prostate bed salvage radiotherapy (SRT) if negative or positive within prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease, androgen deprivation therapy (ADT) if nonoligometastatic disease. Chi-square test was used to evaluate the relationship between baseline features and rate of positive PSMA PET/CT. RESULTS: One hundred patients were enrolled. PSMA results were negative/positive in the prostate bed in 72 patients, pelvic nodal or extrapelvic metastatic disease were detected in 23 and 5 patients. Twenty-one patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Fifty patients were treated with prostate bed SRT, 23 patients underwent SBRT to pelvic nodal disease, five patients were treated with SBRT to oligometastatic disease. One patient underwent ADT. NCCN high-risk features, stage > pT3 and ISUP score >3 reported a significantly higher rate of positive PSMA PET/CT after restaging (p = 0.01, p = 0.02, and p = 0.002). By quartiles of PSA, rate of positive PSMA PET/CT was 26.9% (>0.2; <0.29 ng/mL), 24% (>0.3; <0.37 ng/mL), 26.9% (>0.38; <0.51 ng/mL), and 34.7% (>0. 52; <0.98 ng/mL). CONCLUSIONS: PSICHE trial constitute a useful platform to collect data within a clinical framework where modern imaging and metastasis-directed therapy are integrated.

Radiomics-based prognosis classification for high-risk prostate cancer treated with radiotherapy.

OBJECTIVE: The present study aimed to investigate if CT-based radiomics features could correlate to the risk of metastatic progression in high-risk prostate cancer patients treated with radical RT and long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 157 patients were investigated and radiomics features extracted from the contrast-free treatment planning CT series. Three volumes were segmented: the prostate gland only (CTV_p), the prostate gland with seminal vesicles (CTV_psv), and the seminal vesicles only (CTV_sv). The patients were split into two subgroups of 100 and 57 patients for training and validation. Five clinical and 62 radiomics features were included in the analysis. Considering metastases-free survival (MFS) as an endpoint, the predictive model was used to identify the subgroups with favorable or unfavorable prognoses (separated by a threshold selected according to the Youden method). Pure clinical, pure radiomic, and combined predictive models were investigated. RESULTS: With a median follow-up of 30.7 months, the MFS at 1 and 3 years was 97.2% ± 1.5 and 92.1% ± 2.0, respectively. Univariate analysis identified seven potential predictors for MFS in the CTV_p group, 11 in the CTV_psv group, and 9 in the CTV_sv group. After elastic net reduction, these were 4 predictors for MFS in the CTV_p group (positive lymph nodes, Gleason score, H_Skewness, and NGLDM_Contrast), 5 in the CTV_psv group (positive lymph nodes, Gleason score, H_Skewnesss, Shape_Surface, and NGLDM_Contrast), and 6 in the CTV_sv group (positive lymph nodes, Gleason score, H_Kurtosis, GLCM_Correlation, GLRLM_LRHGE, and GLZLM_SZLGE). The patients' group of the training and validation cohorts were stratified into favorable and unfavorable prognosis subgroups. For the combined model, for CTV_p, the mean MFS was 134 ± 14.5 vs. 96.9 ± 22.2 months for the favorable and unfavorable subgroups, respectively, and 136.5 ± 14.6 vs. 70.5 ± 4.3 months for CTV_psv and 150.0 ± 4.2 vs. 91.1 ± 8.6 months for CTV_sv, respectively. CONCLUSION: Radiomic features were able to predict the risk of metastatic progression in high-risk prostate cancer. Combining the radiomic features and clinical characteristics can classify high-risk patients into favorable and unfavorable prognostic groups.

Moderate hypofractionated radiotherapy for post-operative treatment of prostate cancer: long-term outcome and pattern of toxicity.

OBJECTIVE: Postoperative radiotherapy (RT) is an established treatment for prostate cancer (PC). Though hypofractionation is commonly used for radical treatments, open issues still remain in the postoperative setting due to the lack of long-term data. Aim of this study was to evaluate long-term results of postoperative moderately hypofractionated RT (MHRT). METHODS: We conducted a retrospective analysis including PC patients treated with prostatectomy and postoperative MHRT delivered with volumetric modulated arc therapy (VMAT). Endpoints of the analysis included biochemical relapse-free survival (BRFS), distant metastases free-survival (DMFS), overall survival (OS), and pattern of acute and late toxicity. RESULTS: 181 patients were included. Pathological stage was classified as pT3a in 33.6% and pT3b in 30%. Median PSA value before RT was 0.23 ng/ml and median RT total dose was 70 Gy (65-74.2 Gy) in 25/28 fractions. With a median follow-up of 54.5 months, rates of BRFS at 3 and 5 years were 80.7 and 72.3%. ISUP grade group (HR 1.44, p = 0.015), pathological T stage (HR 2.03; p = 0.009), and pre-RT PSA >0.2 ng/ml (HR 2.64; p = 0.015) were correlated with BRFS. Three and 5­year DMFS were 87.4 and 80.8%. ISUP grade group (HR 1.50; p = 0.011) and pre-RT PSA (HR 5.34; p = 0.001) were correlated with DMFS. Five (2.7%) and 3 (1.6%) patients reported late grade 3 GU and GI toxicity, respectively. CONCLUSION: Our results confirm the long-term safety and efficacy of postoperative MHRT for PC. ADVANCES IN KNOWLEDGE: The present paper demonstrates the long-term safety and efficacy of MHRT for postoperative prostate cancer. Reduction of treatment time in long-course radiotherapy has advantages in terms of both patients' quality of life and departmental organization.

[18F]Fluorocholine PET/CT-guided stereotactic body radiotherapy in patients with recurrent oligometastatic prostate cancer.

BACKGROUND: In the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [18F]Fluoro-Methyl Choline ([18F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT). METHODS: Patients with biochemical recurrence limited up to three lesions revealed by [18F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [18F]FMCH PET/CT was considered as the primary endpoint. RESULTS: Forty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5-68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival (p < 0.001). CONCLUSIONS: Based on our findings, [18F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.

Vismodegibfor the treatment of radiation-induced basal cell carcinoma - a case report and brief literature study.

Vismodegib is playing an increasing role in the treatment of locally advanced or metastatic basal cell carcinoma (BCC) that is not a candidate for surgery or radiotherapy, and also in radiation-induced BCC. A 22-year-old man with a history of Hodgkin lymphoma, nodular sclerosis stage IIA, from October 1994 to February 1995 treated with 25 mg/m2 doxorubicin, 10 IU/m2 bleomycin, 6 mg/m2 vinblastine, and 375 mg/m2 dacarbazine for four cycles, followed byconformal beam radiotherapy (EBRT) on laterocervical, supraclavear, and mediastinal nodes up to a total dose of 30 Gy and following EBRT boost on mediastinal nodes up to a dose of 10 Gy. Subsequently, the patient underwent conformal EBRT on lomboaortic nodes up to total dose of 30 Gy at the University Hospital of Pisa until May 1995. There was no evidence of disease, until March 2012 when the patient developed severalBCCs, occurring in the field of prior radiation, treated with local excisions. No mutations of Hedgehog (Hh) pathway or other genes were found and nevoid basal cell carcinoma syndrome was not diagnosed. In February 2018, the patient began therapy with vismodegib at standard dose of 150 mgorally daily and was treated for 10 months, with low adverse events and with pathological complete response of disease until July 2019. This experience shows that there are, however very few, BCCs not associated with genetic disorders. Vismodegib seems to be an effective and safe therapeutic approach also for radiation-related BCCs, associated with relatively low toxicity.

Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study.

Background: While SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. Methods: Patients with PSA levels between 0.1-2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. Results: From April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3-27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 - 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. Conclusions: Our findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

The impact of stereotactic ablative radiotherapy on oligoprogressive metastases from renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) represents 80-90% of all kidney tumors and about 15-25% of patients will develop distant metastases. Systemic therapy represents the standard of care for metastatic patients, but stereotactic ablative radiotherapy (SABR) may play a relevant role in the oligoprogressive setting, defined as the progression of few metastases during an ongoing systemic therapy on a background of otherwise stable disease. Aim of the present study was to analyze the outcome of RCC patients treated with SABR on oligoprogressive metastases. MATERIALS AND METHODS: In this monocenter study, we analyzed patients affected by RCC treated with SABR on a maximum of 5 cranial or extracranial oligoprogressive sites of disease. Endpoints were overall survival (OS), progression-free survival (PFS), and toxicity. RESULTS: We included 74 oligoprogressions (26 intracranial and 48 extracranial) and 57 SABR treatments in 44 patients. Most common concomitant treatments were sunitinib (28, 49.1%), pazopanib (12, 21.0%) and nivolumab (11, 19.3%). Median follow-up was 19.0 months, and 1- and 2-year OS rates were 79.2% and 57.3%, respectively. Repeated SABR was a positive predictive factor for OS (p = 0.034). Median PFS was 9.8 months, with 1- and 2-year rates of 43.2% and 25.8%. At multivariable analysis, disease-free interval (p = 0.022) and number of treated metastases (p = 0.007) were significant for PFS. About 80% of patients continued the ongoing systemic therapy 1- and 2-years after SABR with no grade 3 or 4 toxicities. CONCLUSIONS: we confirmed the efficacy and safety of SABR for oligoprogression from RCC, with the potential to ablate resistant metastases and to prolong the ongoing systemic therapy.

Early biochemical outcomes following PSMA guided approach for bIoCHEmical relapse after prostatectomy-PSICHE trial (NCT05022914): preliminary results.

PSICHE (NCT05022914) is a prospective trial to test a [68Ga]Ga- PSMA-11 PET/CT imaging tailored strategy. All evaluable patients had biochemical relapse after surgery and underwent centralized [68Ga]Ga-PSMA-11 PET/CT imaging. The treatment was performed according pre-defined criteria. Observation and re-staging at further PSA progression were proposed to patients with negative PSMA and previous postoperative RT. Prostate bed SRT was proposed to all patients with a negative staging or positive imaging within prostate bed. Stereotactic body radiotherapy (SBRT) to all sites of disease was used for all patients with pelvic nodal recurrence (nodal disease < 2 cm under aortic bifurcation) or oligometastatic disease. At 3 months after treatment, 54.7% of patients had a complete biochemical response Only 2 patients experienced G2 Genitourinary toxicity. No G2 Gastrointestinal toxicity was recorded. A PSMA targeted treatment strategy led to encouraging results and was well tolerated.

Early Versus Late Postoperative Radiotherapy in Patients With Prostate Cancer: Results of a Single-centre Retrospective Study.

BACKGROUND/AIM: A much-debated topic relating to patients at risk of local prostate cancer recurrence, but with post-operative leveIs of prostate-specific antigen (PSA) lower than 0.2 ng/ml, concerns the best timing of postoperative radiotherapy (RT), adjuvant or salvage? The present monocentric, retrospective study aimed to investigate the best PSA value at which to plan salvage RT for patients with recurrent prostate cancer. PATIENTS AND METHODS: From January 2011 to December 2019, 158 patients were treated with adjuvant RT at Pisa University Hospital, whilst 91 patients underwent salvage RT. We grouped the patients treated with salvage RT using their PSA values at the time of salvage RT: PSA >0.5 ng/ml, PSA between 0 and 0.5 ng/ml, and PSA ≤0.2 ng/ml. The median follow-up was 63 months. Biochemical recurrence-free survival (BFS) measured from surgery was the primary endpoint. RESULTS: Salvage RT led to shorter BFS compared to adjuvant RT considering the whole cohort of patients, with a hazard ratio of 3.195 (95% confidence interval=1.534-6.655, p=0.002). However, analysing only the group of patients with PSA ≤0.2 ng/ml at the time of salvage RT, salvage RT led to BFS similar to that achieved with adjuvant RT (p=0.35). CONCLUSION: Our results suggest that when scheduled for patients with a PSA ≤0.2 ng/ml, salvage RT results in equivalent biochemical control to that with adjuvant RT.

Locally Advanced Non-Small Cell Lung Cancer: Clinical Outcome, Toxicity and Predictive Factors in Patients Treated with Hypofractionated Sequential or Exclusive Radiotherapy.

BACKGROUND: This study evaluated the outcome, toxicity and predictive factors in patients unfit for concurrent chemo-radiotherapy (CT-RT) treated with hypofractionated sequential CT-RT or exclusive radiotherapy (RT) for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: We included patients affected by LA-NSCLC (stage IIA-IVA) treated with a total dose of 50-60 Gy in 20 fractions. The primary outcomes were local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS). Univariate analysis was used to correlate outcomes with prognostic factors. RESULTS: Between 2011 and 2019, 210 patients were treated, 113 (53.8%) with sequential CT-RT and 97 (46.2%) with exclusive RT. After a median follow-up of 15.3 months, 74 patients (35.2%) had a local progression and 133 (63.3%) had a distant progression. The one-, two- and five-year LC were 73.6%, 55.3% and 47.9%, respectively. At the time of analysis, 167 patients (79.5%) died. The one-, two- and five-year OS were 64.7%, 36% and 20%, respectively. PTV volume correlated with PFS (p = 0.001) and LC (p = 0.005). Acute and late toxicity occurred in 82% and 26% of patients. CONCLUSIONS: Albeit with the known limitations of a retrospective and heterogeneous study, our work shows that hypofractionated sequential CT-RT or exclusive RT offer a good local control and toxicity profile and a promising survival rate in LA-NSCLC patients unfit for the concurrent CT-RT scheme.

Oligoprogressive castration-resistant prostate cancer treated with metastases-directed stereotactic body radiation therapy: predictive factors for patients' selection.

Oligoprogression is defined as limited metastatic clone resistant to on-going systemic treatment that grows in a background of stable or responding systemic disease. Aim of the present study was to analyze oligoprogressive prostate cancer (PC) patients treated with stereotactic body radiation therapy (SBRT) during systemic treatment to identify predictive factors and improve patients' selection. We included PC patients treated with SBRT on a maximum of 3 sites of oligoprogression during systemic therapy. Endpoints were freedom from polymetastatic progression (FPP), local control (LC), distant progression free survival (DPFS), overall survival (OS), and next systemic therapy free survival (NEST-FS). Fifty-three patients were treated on 85 oligoprogressive metastases. Lymph nodes were the most common sites (56.47%), followed by bone (39.29%). Median follow-up was 24.9 months. Rates of FPP at 1- and 2-year were 80.1% and 68.9%, respectively. Median time to polymetastatic progression was 33.7 months. Disease free interval (p = 0.004), site of metastases (p = 0.011), and type of systemic therapy (p = 0.003) were significant for FPP. Switch or intensification of systemic therapy after SBRT was observed in 29 (54.72%) patients with a median NEST-FS of 15.2 months. LC at 1- and 2-year was 94.0% and 92.0%, with PSA doubling time resulted to be significantly associated (p = 0.047). Median DPFS was 8.93 months and median OS was 50.6 months. In conclusion, we confirmed the efficacy of SBRT for oligoprogression from PC, with the potential to prolong the on-going systemic therapy and interrupt the metastatic cascade.

Stereotactic Body Radiation Therapy for Lung Metastases From Sarcoma in Oligometastatic Patients: A Phase 2 Study.

PURPOSE: The lung is the most frequent site of metastasis in patients with sarcoma. Pulmonary metastasectomy is the most common treatment performed. Stereotactic body radiation therapy (SBRT) has proven to be a potential alternative to resection. This prospective phase 2 study aimed to assess the role of SBRT for patients with lung metastases. METHODS AND MATERIALS: Adult patients with up to 4 lung metastases (LMs) ≤5 cm in diameter and unsuitable for surgery were included. Dose prescription was based on site and size: 30 Gy/1 fraction for peripheral lesions ≤10 mm, 60 Gy/3 fractions for peripheral lesions 11 to 20 mm, 48 Gy/4 fractions for peripheral lesions >20 mm, and 60 Gy/8 fractions for central lesions. The primary endpoint was the proportion of treated lesions free from progression at 12 months. Secondary endpoints were disease-free survival (DFS), overall survival (OS), and toxicity. RESULTS: Between March 2015 and December 2020, 44 patients with a total of 71 LMs were enrolled. Twelve-month local control was 98.5% ± 1.4%, reaching the primary aim; the median DFS time was 12 months (95% CI, 8-16 months), and the 1-, 2-, 3-, 4-, and 5-year PFS rates were 50% ± 7.5%, 19.5% ± 6.6%, 11.7% ± 5.8%, 11.7% ± 5.8%, and 11.7% ± 5.8%, respectively. The median OS time was 49 months (95% CI, 24-49 months), and the 1-, 2-, 3-, 4-, and 5-year OS rates were 88.6% ± 4.7%, 66.7 ± 7.6%, 56.8% ± 8.4%, 53.0% ± 8.6%, and 48.2% ± 9.1%, respectively. Prognostic factors recorded as significantly affecting survival were age, grade of primary sarcoma, interval time from diagnosis to occurrence of LMs, and number of LMs. No severe pulmonary toxicity (grade 3-4) occurred. CONCLUSIONS: The study found a local control of LMs in almost all patients treated, with negligible toxicity. Survival was also highly satisfactory. Well-designed randomized trials comparing surgery with SBRT for patients with metastatic lung sarcoma are needed to confirm these preliminary data.

Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial.

BACKGROUND: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). METHODS: Patients with post-radical prostatectomy PSA levels of ≥0.1-2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. RESULTS: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55-82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18-1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0-0.48 ng/mL). CONCLUSIONS: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

Charlson comorbidity index and G8 in older old adult(≥80 years) hepatocellular carcinoma patients treated with stereotactic body radiotherapy.

INTRODUCTION: Hepatocellular Carcinoma (HCC) is characterized, in Western countries, by higher incidence and mortality rates in the older adult population. In frail patients, limited therapeutic resources are available due to limited expected benefit concerning the risk of treatment-related toxicity. The aim of our study is to evaluate the role of Stereotactic Body Radiotherapy (SBRT) in the clinical management of older old adults (age ≥ 80 years) HCC patients and to identify predictors of efficacy and toxicity. MATERIAL AND METHODS: Clinical and treatment-related data of older old adults HCC patients treated with SBRT at our institution were retrospectively reviewed. Statistical analysis was carried out to identify variables correlated with impaired outcome and toxicity. RESULTS: Forty-two patients were included, accounting for 63 treated tumors. Median age was 85 (range 80-91) years. Median Charlson Comorbidity Index (CCI) and G8 scores were 10 (range 7-16) and 11 (range 8-14), respectively. SBRT was administered to a median BED10 of 103 Gy10. Median follow-up interval was 11 (range 3-40) months. Two years Local Control (LC), Progression-Free Survival (PFS), and Overall Survival (OS) were 93%, 31%, and 43%, respectively. Acute toxicity occurred in 28% (n = 13) of treatments. A G8 score > 10 was associated with improved survival (p = 0.045), while a CCI ≥10 was correlated with increased acute toxicity (p = 0.021). CONCLUSIONS: SBRT is a safe and effective option in older old adults HCC patients. A comprehensive geriatric assessment (CGA) is advised before treatment decisions to select optimal candidates for SBRT.

Squamous cell carcinoma (SCC) of the Pyriform sinus with multiple metachronous brain metastases, a case report.

BACKGROUND: Distant Metastases from Head and Neck Squamous cell carcinomas are uncommon (9-11%) and they are usually found in the lung and less frequently in the liver, kidney and adrenals. Central nervous system (CNS) metastases are extremely rare (2-8%), and they are described mainly in patients who already have extracranial metastases. So there's scarcity of data about their optimal management . METHODS AND RESULTS: A patient presented CNS metastases after having been successfully treated with induction chemotherapy and definitive radiotherapy for a pyriform sinus carcinoma. The patient's work up, treatment and outcome are described. CONCLUSIONS: CNS metastases from Head and Neck carcinomas are exceptionally rare. Nevertheless, clinicians should be alert of neurological symptoms in these patients, in order to set up a timely assessment and treatment. Secondarily, given the rarity of this condition, additional research on this topic is warranted in order to improve therapeutic strategies and outcomes of such patients.

Assessing the role of Stereotactic Body Radiation Therapy in a large cohort of patients with lymph node oligometastases: Does it affect systemic treatment's intensification?

BACKGROUND AND PURPOSE: Lymph nodes (LN) are common site of oligometastases and stereotactic body radiation therapy (SBRT) represents an effective ablative treatment. Aim of this study was to analyze a large cohort of nodal oligometastases treated with SBRT to identify impact on systemic therapy intensification, pattern of recurrence, and predictive factors. MATERIALS AND METHODS: We included patients with a maximum of 5 oligometastases. Concomitant treatments were allowed. Patients were treated with Volumetric Modulated Arc Therapy (VMAT) and end points were local control of treated metastases (LC), locoregional nodal control (LRNC), distant nodal control (DNC), distant metastases free survival (DMFS), overall survival (OS) and freedom from treatment intensification (FFTI). RESULTS: 418 LN were treated in 278 patients with 327 SBRT treatments. Patients were more commonly affected by colorectal (20.9%) and prostate cancer (17.99%). Most represented schedule was 45 Gy in 6 fractions, with a median BED10 of 78.75 Gy. After median follow-up of 15.1 months, LC at 1 and 2 years were 87.2% and 76.8%, respectively. Prostate primary tumor, small volume, oligorecurrence, and BED10 ≥75 Gy were associated with higher LC. One and 2 years FFTI were 82.8% and 74.5%; in patients reporting intensification of systemic therapy, median time was 8.43 months, while for patients who repeated SBRT, median FFTI was 14.6 months. Rates of LRNC at 1 and 2 years were 70.9% and 57.6%, and DNC were 82.0% and 77.9%. CONCLUSION: With the present analysis, we confirmed on a large cohort the benefit from SBRT on lymph node oligometastases in multidisciplinary management. Combination of SBRT with new systemic therapies, including immunotherapy and targeted therapy, should be investigated to reduce the risk of progression out of the field of irradiation.

Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early Versus Delayed Administration.

BACKGROUND/AIM: In patients with recurrent glioblastoma, the best timing to administer bevacizumab is not well addressed yet. In this study, we reported the results of a monocentric experience comparing the early use of bevacizumab (following the first GBM recurrence) with the delayed administration (following the second or even further GBM recurrences). MATERIALS AND METHODS: This analysis included 129 glioblastoma patients with a median follow-up of 22.4 months (range=5.26-192 months). RESULTS: The median time lapse from diagnosis of glioblastoma to disease recurrence was 11.6 months; 13.1 for patients treated with deferred administration of bevacizumab and 9.9 for patients with early administration (p=0.047). Bevacizumab progression-free survival with early and delayed use was 3.45 and 2.92 months, respectively (p=0.504). Survival time from the start of bevacizumab was 6.18 months in patients with early administration, and 6.47 in the delayed administration one (p=0.318). CONCLUSION: Delayed administration of bevacizumab can be considered in selected patients with less aggressive recurrent glioblastoma.

Image-guided Stereotactic Body Radiotherapy in Metastatic Prostate Cancer.

BACKGROUND/AIM: In the last years, the use of Image Guided Stereotactic Radiotherapy (IG-SBRT) in patients with metastatic prostate cancer has increased. In this study, we aimed to assess the role of IG-SBRT in terms of local control and safety in patients with metastatic prostate cancer. MATERIALS AND METHODS: Primary and secondary endpoints of this prospective observational study were local control and safety related to IG-SBRT. All lesions were treated with 24 Gy as a single fraction or 27 Gy in 3 fractions. After SBRT, Systemic therapies were administered only after the occurrence of more than three synchronous active lesions in oligometastatic patients (patients with less than 4 active synchronous lesions) or new lesions occurrence in patients with more than 3 synchronous lesions. RESULTS: From April 2011 to June 2017, 78 metastatic lesions (32 bone and 46 node) from 51 patients with prostate cancer were treated. After a median follow-up of 18.5 months (range=3-103 months), only 2 lesions (4%) relapsed inside the radiation field. All local recurrences were located on the bone. Estimated 12 and 24 months local control ratios were 98.7 and 97.4%, respectively. Except for one case, toxicity greater than G2 was not recorded. CONCLUSION: IG-SBRT is safe and can be considered as a valid therapy in patients with metastatic prostate cancer requiring a long-lasting metastases control.