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.

Association between treatment-related lymphopenia and survival in glioblastoma patients following postoperative chemoradiotherapy.

PURPOSE: Our study investigated the association between treatment-related lymphopenia and overall survival (OS) in a series of glioblastoma (GBM) patients. We also explored clinical and dosimetric predictors of lymphocytes depletion. METHODS: Between 2015 and 2019, 64 patients were treated at the same institution with postoperative chemoradiotherapy. Peripheral lymphocyte count (PLC) data and dose-volume histogram parameters were collected. Radiotherapy (RT) schedule consisted in standard total dose of 60 Gy in 30 daily fractions, with concomitant and adjuvant temozolomide (TMZ). Posttreatment acute absolute lymphopenia (nadir AAL) was calculated as a PLC lower than 1.0â€¯× 103/mm3. Acute relative lymphopenia (ARL) was expressed by the nadir-PLC/baseline-PLC ratio < 0.5. Nadir-PLC was the lowest PLC registered between the end of RT and the first month of follow-up. Survival rates were estimated with Kaplan-Meier curves. Clinical and dosimetric variables related to AAL/ARL and OS were identified by univariate and multivariate analyses. RESULTS: A total of 57 patients were eligible and included in the analyses. The median PLC was significantly decreased following chemoradiotherapy (2180/mm3 vs 900/mm3). Median OS was 16 months (range 5-55 months), with no significant difference between patients who developed nadir AAL and those who did not (16 months vs 16.5 months; p = 0.304). When considering ARL vs non-ARL, median OS was 14 months vs 26 months (p = 0.013), respectively. In multivariate Cox regression only age, sex, extent of surgery, access to adjuvant chemotherapy and brain D98% were independently associated with OS. CONCLUSION: Although iatrogenic immunosuppression could be associated with inferior clinical outcomes, our data show that treatment-related lymphopenia does not adversely affect GBM survival. Prospective studies are required to confirm these findings.

Ablative Radiation Therapy for Unfavorable Prostate Tumors (ABRUPT): Preliminary Analysis of Toxicity and Quality of Life from a Prospective Study.

PURPOSE: To assess late gastrointestinal (GI) and genitourinary (GU) side effects in patients with organ-confined unfavorable prostate cancer (PCa) treated with single-dose ablative radiation therapy (SDRT). METHODS AND MATERIALS: Thirty patients enrolled in a single-arm prospective trial received 24 Gy SDRT to the whole prostate with urethra-sparing and organ motion control delivered on a Linac platform with a 10 MV flattening filter-free single partial arc. Androgen deprivation therapy was prescribed as per standard of care. Treatment-related acute and late GU and GI toxicities (Common Terminology Criteria for Adverse Events_v5 scale) and quality of life (QoL) outcomes (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-PR25/C30, International Prostate Symptom Score [IPSS]) were assessed at different time points. Minimal important difference (MID) was established as a change of >0.5 pooled standard deviations from baseline. Statistical analysis included analysis of variance and logistic regression. RESULTS: Median follow-up was 18 months (range, 6-31 months), with no ≥G3 late side effects observed. G2 late GI and G2 late GU toxicities occurred in 1 and 2 patients, respectively. GI toxicity of any grade correlated with maximum rectal dose (P = .021). Lower baseline QoL score (P = .025), higher baseline IPSS score (P = .049), acute GU toxicity (P = .029), and acute urinary domain MID (P = .045) predicted GU toxicity of any grade. In multivariate analysis (MVA), only baseline QoL score (odds ratio [OR], 0.95, P = .031) and acute GU toxicity (OR, 8.4, P = .041) remained significant. Significant QoL change was observed only in the urinary domain (P = .005), with a median increase from 8 to 17. Late urinary MID correlated with acute urinary MID (P = .003), acute QoL MID (P = .029), acute GU toxicity (P = .030), and lower baseline urinary score (P = .033). In MVA, only acute urinary MID predicted late urinary MID (OR, 9.7, P = .035). CONCLUSIONS: Our findings provide promising data on the feasibility and safety of 24 Gy whole-gland SDRT with urethra-sparing and organ motion control, in association with androgen deprivation therapy and an adequate prophylactic medication, in organ-confined unfavorable PCa. Long-term follow-up is needed to confirm these results.

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.

Dosimetric Impact of Intrafraction Prostate Motion and Interfraction Anatomical Changes in Dose-Escalated Linac-Based SBRT.

The dosimetric impact of intrafraction prostate motion and interfraction anatomical changes and the effect of beam gating and motion correction were investigated in dose-escalated linac-based SBRT. Fifty-six gated fractions were delivered using a novel electromagnetic tracking device with a 2 mm threshold. Real-time prostate motion data were incorporated into the patient's original plan with an isocenter shift method. Delivered dose distributions were obtained by recalculating these motion-encoded plans on deformed CTs reflecting the patient's CBCT daily anatomy. Non-gated treatments were simulated using the prostate motion data assuming that no treatment interruptions have occurred. The mean relative dose differences between delivered and planned treatments were -3.0% [-18.5-2.8] for CTV D99% and -2.6% [-17.8-1.0] for PTV D95%. The median cumulative CTV coverage with 93% of the prescribed dose was satisfactory. Urethra sparing was slightly degraded, with the maximum dose increased by only 1.0% on average, and a mean reduction in the rectum and bladder doses was seen in almost all dose metrics. Intrafraction prostate motion marginally contributed in gated treatments, while in non-gated treatments, further deteriorations in the minimum target coverage and bladder dose metrics would have occurred on average. The implemented motion management strategy and the strict patient preparation regimen, along with other treatment optimization strategies, ensured no significant degradations of dose metrics in delivered treatments.

Outcomes and toxicity following post-operative hypofractionated radiotherapy to the regional nodes and the breast or the chest wall in locally advanced breast cancer.

OBJECTIVES: We aimed to analyze the impact of a 3-week schedule of HypoFractionated (HF) radiotherapy (RT) after axillary dissection and breast surgery, in terms of safety and efficacy in patients with locally advanced breast cancer (BC). METHODS: Eligible patients were females with Stage IIA - IIIC BC who underwent axillary dissection and breast surgery, either quadrantectomy or mastectomy. HF RT was delivered in 15 or 16 fractions for a total dose of 40.05 Gy or 42.56 Gy, respectively, to the clavicular nodal region along with the whole breast (HF WBRT) or the chest wall (HF PMRT), according to the type of surgery. Locoregional recurrence (LRR), distant metastases-free survival (DMFS), overall survival (OS) and acute and late treatment-related toxicities were estimated. RESULTS: 57 patients with a median age of 60 years (32-85) were retrospectively analyzed. 34 (60%) of patients underwent breast conservative surgery in the form of quadrantectomy and 23 (40%) were offered radical mastectomy. All patients underwent hypofractionated regional nodal irradiation (HF RNI). 34 (60%) of them underwent HF WBRT, while 23 (40%) received HF PMRT.At a median follow-up of 80 months (30-113), the 7-year LRR-free survival was 93% (95% CI, 74%-95%). The same features for DMFS and OS were 76% (95% CI, 52%-78%) and 67% (95% CI, 50%-80%), respectively. Only one (2%) patient experienced G3 acute skin toxicity. No grade ≥2 late toxicity was observed. CONCLUSION: Our study shows that HF RNI with HF RT to the whole breast or the chest wall after breast surgery is safe and effective in patients with locally advanced BC. Longer follow-up is needed to strengthen further analyses on late toxicity and clinical outcomes. ADVANCES IN KNOWLEDGE: This paper adds to the evidence that post-operative RNI with WBRT or PMRT can be safely and effectively delivered with 3-week HF regimen. Locally advanced BC patients can be offered HF RT to the regional nodes and the breast or the chest wall regardless the type of surgery.

Intrafraction Prostate Motion Management During Dose-Escalated Linac-Based Stereotactic Body Radiation Therapy.

Background: Extreme hypofractionation requires tight planning margins, high dose gradients, and strict adherence to planning criteria in terms of patient positioning and organ motion mitigation. This study reports the first clinical experience worldwide using a novel electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated linac-based stereotactic body radiation therapy (SBRT). Methods: Thirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The EM tracking device consisted of an integrated Foley catheter with a transmitter. Patients were simulated and treated with a filled bladder and an empty rectum. Setup accuracy was achieved by ConeBeam-CT (CBCT) matching, and motion was tracked during all the procedure. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, the displacements that would have occurred without any intrafraction organ motion management (i.e. no interruptions and repositionings) were simulated. Results: In 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position. In 25 (45%) a correction was mandated, but only in 10 (18%), the beam delivery was interrupted. Total treatment time lasted on average 10.2 minutes, 6.7 minutes for setup, and 3.5 minutes for beam delivery. Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would have been 6.9 minutes and 3.2 minutes, respectively. The prostate would have been found outside the tolerance in 8% of the total session time, in 4% of the time during the setup, and in 14% during the beam-on phase. Predominant motion pattern was posterior and its probability increased with time, with a mean motion ≤ 2 mm occurring within 10 minutes. Conclusions: EM real-time tracking was successfully implemented for intrafraction motion management during dose-escalated prostate SBRT. Results showed that most of the observed displacements were < 2 mm in any direction; however, there were a non-insignificant number of fractions with motion exceeding the predefined threshold, which would have otherwise gone undetected without intrafraction motion management.

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.

Treatment outcome and compliance to dose-intensified linac-based SBRT for unfavorable prostate tumors using a novel real-time organ-motion tracking.

PURPOSE/OBJECTIVES: To report preliminary data on treatment outcome and compliance to dose-intensified organ sparing SBRT for prostate cancer using a novel electromagnetic transmitter-based tracking system (RayPilotÒ System) to account for intra-fractional organ motion. MATERIAL/METHODS: Thirteen patients with intermediate unfavorable (9) and selected high-risk (4) prostate cancer underwent dose-escalated SBRT in 4 or 5 fractions (BED1.5 = 279 Gy and 253 Gy, respectively). The VMAT treatment consisted in two 6FFF or 10FFF full arcs optimized to have the 95% isodose covering at least 95% of the PTV (2 mm isotropic expansion of the CTV). Whenever the real-time tracking registered a displacement that exceeded 2 mm during the setup and/or the beam delivery, the treatment was interrupted and the prostate motion was promptly corrected. The incidence of treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity, patient QoL and PSA outcomes were computed from the start of treatment to the last follow-up date. RESULTS: All patients completed the treatment in the expected time (10.2 +/- 4.2 minutes) and their compliance to the procedure was excellent. No clinically significant acute Grade 2 or higher GI (rectal) and GU side effects were observed within 90 days from the treatment completion. The median IPSS increased from 8 at baseline to 12 one-month after treatment and settled to 6 at 3 months. EPIC-26 scores in the urinary domain decreased from a median baseline of 86 pre-treatment to 79 at one-month and returned to baseline at a later timepoint (median score of 85 at 3 months). EPIC-26 scores in the bowel domains did not show significant changes within 3 months following RT. The prostate was found within 1 mm from its initial position in 78% of the beam-on time, between 1 and 2 mm in 20%, and exceeded 2 mm only in 2%, after correction for motion which was performed in 45% of the fractions, either during setup or beam delivery. CONCLUSIONS: Our preliminary findings show that dose intensified SBRT for unfavorable prostate tumors does not come at the cost of an increased toxicity, provided that a reliable technique for real time prostate monitoring is ensured. Fast FFF beams contributed to reduce intra-fractional motion. These observations need to be confirmed on a larger scale and a longer follow up.

Attitudes, practices and perspectives on imaging strategies in prostate cancer: a national cross-sectional survey involving expert radiation oncologists on behalf of AIRO (Italian association of radiotherapy and clinical oncology) GU group.

Although high sensitive imaging modalities such as MRI and PSMA PET/CT are becoming available for prostate cancer (PCa), the clinical benefit of an earlier detection of subclinical disease remains yet undetermined. Given these uncertainties, univocal recommendations are often lacking. The present survey was therefore developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of expert radiation oncologists and delineate a representation of current clinical practice in our country. A nationwide cross-sectional survey was conducted in Italy by administering an anonymous questionnaire to experienced radiation oncologists, representative of the genitourinary (GU) tumor board at their Institution, using the cloud-based platform SurveyMonkey®. For each question, a consensus was achieved when ≥ 75% of the responders agreed on the same response. Thirty nine AIRO members from different Italian centers who were deemed experts in GU field accessed the proposed survey and completed all sections. Explored topics included staging of organ-confined disease, management of biochemical and local recurrence, imaging in the metastatic setting, imaging following metastasis-directed therapy (MDT), and future considerations. Response rate for single item of the questionnaire ranged between 51.2% and 100%. Expert GU AIRO members agree that advanced molecular and functional imaging are expanding their role in local and distant staging of PCa, as well as in the oncologic management and in the assessment of treatment response. However, many controversial issues still exist on the best timing for a diagnostic evaluation and the most appropriate imaging to aim at this purpose.