A Multi-Institutional Analysis of Prostate Cancer Patients With or Without 68Ga-PSMA PET/CT Prior to Salvage Radiotherapy of the Prostatic Fossa

Introduction: 68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only. Material and Methods: This retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters. Results: Median follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS ≤ 7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. ≥0.5ng/ml; p<0.001) and sRT dose (<70 vs. ≥70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884). Conclusion: This analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best “diagnostic window” for 68Ga-PSMA PET/CT

A clinical evaluation of the performance of five commercial artificial intelligence contouring systems for radiotherapy

Purpose/objective(s)Auto-segmentation with artificial intelligence (AI) offers an opportunity to reduce inter- and intra-observer variability in contouring, to improve the quality of contours, as well as to reduce the time taken to conduct this manual task. In this work we benchmark the AI auto-segmentation contours produced by five commercial vendors against a common dataset.Methods and materialsThe organ at risk (OAR) contours generated by five commercial AI auto-segmentation solutions (Mirada (Mir), MVision (MV), Radformation (Rad), RayStation (Ray) and TheraPanacea (Ther)) were compared to manually-drawn expert contours from 20 breast, 20 head and neck, 20 lung and 20 prostate patients. Comparisons were made using geometric similarity metrics including volumetric and surface Dice similarity coefficient (vDSC and sDSC), Hausdorff distance (HD) and Added Path Length (APL). To assess the time saved, the time taken to manually draw the expert contours, as well as the time to correct the AI contours, were recorded.ResultsThere are differences in the number of CT contours offered by each AI auto-segmentation solution at the time of the study (Mir 99; MV 143; Rad 83; Ray 67; Ther 86), with all offering contours of some lymph node levels as well as OARs. Averaged across all structures, the median vDSCs were good for all systems and compared favorably with existing literature: Mir 0.82; MV 0.88; Rad 0.86; Ray 0.87; Ther 0.88. All systems offer substantial time savings, ranging between: breast 14-20 mins; head and neck 74-93 mins; lung 20-26 mins; prostate 35-42 mins. The time saved, averaged across all structures, was similar for all systems: Mir 39.8 mins; MV 43.6 mins; Rad 36.6 min; Ray 43.2 mins; Ther 45.2 mins.ConclusionsAll five commercial AI auto-segmentation solutions evaluated in this work offer high quality contours in significantly reduced time compared to manual contouring, and could be used to render the radiotherapy workflow more efficient and standardized

Editorial: Exploring the Potential of PSMA-PET Imaging on Personalized Prostate Cancer Treatment

Prostate cancer (PCa) is the second most frequent cancer diagnosis made in men worldwide (1). Accurate and reliable diagnostic medical imaging is a frequent prerequisite for personalized treatment approaches in patients with PCa by enabling, in part, (i) understanding extent of disease, (ii) accurate segmentation of PCa lesions and, (iii) non-invasive tumor characterization, for example, using radiomics or artificial intelligence tools (2)

Dosimetric Impact of the Positional Imaging Frequency for Hypofractionated Prostate Radiotherapy – A Voxel-by-Voxel Analysis

Background: To investigate deviations between planned and applied treatment doses for hypofractionated prostate radiotherapy and to quantify dosimetric accuracy in dependence of the image guidance frequency. Methods: Daily diagnostic in-room CTs were carried out in 10 patients in treatment position as image guidance for hypofractionated prostate radiotherapy. Fraction doses were mapped to the planning CTs and recalculated, and applied doses were accumulated voxel-wise using deformable registration. Non-daily imaging schedules were simulated by deriving position correction vectors from individual scans and used to rigidly register the following scans until the next repositioning before dose recalculation and accumulation. Planned and applied doses were compared regarding dose-volume indices and TCP and NTCP values in dependence of the imaging and repositioning frequency. Results: Daily image-guided repositioning was associated with only negligible deviations of analyzed dose-volume parameters and conformity/homogeneity indices for the prostate, bladder and rectum. Average CTV T did not significantly deviate from the plan values, and rectum NTCPs were highly comparable, while bladder NTCPs were reduced. For non-daily image-guided repositioning, there were significant deviations in the high-dose range from the planned values. Similarly, CTV dose conformity and homogeneity were reduced. While TCPs and rectal NTCPs did not significantly deteriorate for non-daily repositioning, bladder NTCPs appeared falsely diminished in dependence of the imaging frequency. Conclusion: Using voxel-by-voxel dose accumulation, we showed for the first time that daily image-guided repositioning resulted in only negligible dosimetric deviations for hypofractionated prostate radiotherapy. Regarding dosimetric aberrations for non-daily imaging, daily imaging is required to adequately deliver treatment

Evaluation of intensity modulated radiation therapy dose painting for localized prostate cancer using 68 Ga-HBED-CC PSMA-PET/CT: A planning study based on histopathology reference

AbstractPurposeTo demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using 68Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa).Methods and materials10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%. Two IMRT plans were generated for each patient: Plan77 which consisted of whole-prostate IMRT to 77Gy, and Plan95 which consisted of whole-prostate IMRT to 77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35 fractions). The feasibility of these plans was judged by their ability to adhere to the FLAME trial protocol. TCP-histo/-PET were calculated on co-registered histology (GTV-histo) and GTV-PET, respectively. NTCPs for rectum and bladder were calculated.ResultsAll plans reached prescription doses whilst adhering to dose constraints. In Plan77 and Plan95 mean doses in GTV-histo were 75.8±0.3Gy and 96.9±1Gy, respectively. Average TCP-histo values for Plan77 and Plan95 were 70% (range: 15–97%), and 96% (range: 78–100%, p77 and Plan95 were 55% (range: 27–82%), and 100% (range: 99–100%, p95 (p=0.25). There were no significant differences in rectal (p=0.563) and bladder (p=0.3) NTCPs.ConclusionsIMRT dose painting using PSMA PET/CT was technically feasible and resulted in significantly higher TCPs without higher NTCPs

Radiotherapy for hormone-sensitive prostate cancer with synchronous low burden of distant metastases.

PURPOSE The DEGRO Expert Commission on Prostate Cancer has revised the indication for radiation therapy of the primary prostate tumor in patients with synchronous distant metastases with low metastatic burden. METHODS The current literature in the PubMed database was reviewed regarding randomized evidence on radiotherapy of the primary prostate tumor with synchronous low metastatic burden. RESULTS In total, two randomized trials were identified. The larger study, the STAMPEDE trial, demonstrated an absolute survival benefit of 8% after 3 years for patients with low metastatic burden treated with standard of care (SOC) and additional radiotherapy (RT) (EQD2 ≤ 72 Gy) of the primary tumor. Differences in the smaller Horrad trial were not statistically significant, although risk reduction in the subgroup (< 5 bone metastases) was equal to STAMPEDE. The STOPCAP meta-analysis of both trials demonstrated the benefit of local radiotherapy for up to 4 bone lesions and an additional subanalysis of STAMPEDE also substantiated this finding in cases with M1a-only metastases. CONCLUSION Therefore, due to the survival benefit after 3 years, current practice is changing. New palliative SOC is radiotherapy of the primary tumor in synchronously metastasized prostate cancer with low metastatic burden (defined as ≤ 4 bone metastases, with or without distant nodes) or in case of distant nodes only detected by conventional imaging

PSMA-PET based radiotherapy: a review of initial experiences, survey on current practice and future perspectives

Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography (PET) is an increasingly used imaging modality in prostate cancer, especially in cases of tumor recurrence after curative intended therapy. Owed to the novelty of the PSMA-targeting tracers, clinical evidence on the value of PSMA-PET is moderate but rapidly increasing. State of the art imaging is pivotal for radiotherapy treatment planning as it may affect dose prescription, target delineation and use of concomitant therapy. This review summarizes the evidence on PSMA-PET imaging from a radiation oncologist’s point of view. Additionally a short survey containing twelve examples of patients and 6 additional questions was performed in seven mayor academic centers with experience in PSMA ligand imaging and the findings are reported here

PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml.

PURPOSE The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml. METHODS The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed. RESULTS The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field. CONCLUSION This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field