Intermediate-term outcome after PSMA-PET guided high-dose radiotherapy of recurrent high-risk prostate cancer patients

Background By the use of PSMA positron emission tomography (PET) detection of prostate cancer lesions with a high sensitivity and specificity combined with a favorable lesion to background contrast is feasible. Therefore, PSMA-PET is increasingly used for planning of radiotherapy treatment; however, any data on intermediate-term outcome is missing so far. Methods Patients with high-risk or very high risk prostate cancer, referred for salvage radiotherapy (SRT, n = 22) between 2013 and 2015, underwent PSMA-PET prior to therapy. Irradiation was planned on PET data with boost to macroscopic tumors/metastases. Treatment related toxicity was measured using Common Terminology Criteria for Adverse Events (CTCAE, v4.0). Result Findings in PSMA-PET led to treatment modifications in 77% of SRT patients compared to available CT information. One patient did not receive irradiation due to disseminated disease, the other patients received increased boost doses to macroscopic disease and/or inclusion of additional target volumes. Toxicity was low as only 2 patients reported toxicities > grade 1. With a Median follow-up time of 29 in patients that were not lost to follow-up, prolonged PSA responses below baseline were observed in the majority of patients (14 of 20). In hormone-naïve SRT patients (n = 11), radiotherapy led to prolonged PSA decrease in 8/11 patients, however with 3 of these 8 patients receiving repeated PSMA based irradiation of novel lesions during follow-up. Conclusion PSMA-PET guided planning of radiotherapy led to change of treatment in the majority of patients. Treatment related toxicity was well tolerated and promising results regarding intermediate-term PSA decrease were observed. Trial registration No trial registration was performed due to retrospective evaluation

Protocol of a phase II trial

Background Current studies on salvage radiotherapy (sRT) investigate timing, dose-escalation and anti-hormonal treatment (ADT) for recurrent prostate cancer. These approaches could either be limited by radiation-related susceptibility of the anastomosis or by suspected side-effects of long-term ADT. A phase II protocol was developed to investigate the benefit and tolerability of regional hyperthermia with moderately dose-escalated radiotherapy. Methods The study hypothesis is that radio-thermotherapy is a safe and feasible salvage treatment modality. The primary endpoint is safety measured by frequency of grade 3+ genitourinary (GU) and gastrointestinal (GI) adverse events (AE) according to Common Toxicity Criteria (CTC) version 4. Feasibility is defined by number of hyperthermia treatments (n ≥ 7) and feasibility of radiotherapy according to protocol. Target volume delineation is performed according to the EORTC guidelines. Radiation treatment is administered with single doses of 2 Gy 5×/week to a total dose of 70 Gy. Regional hyperthermia is given 2×/week to a total of 10 treatments. Results European centres participate in the phase II trial using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The initiating centres were participants of the SAKK 09/10 study, where the same patient criteria and target volume definition (mandatory successful performed dummy run) were applied insuring a high standardisation of the study procedures. Conclusions The introduced phase II study implements highly precise image-guided radiotherapy and regional hyperthermia. If the phase II study is found to be safe and feasible, a multicenter phase III study is planned to test whether the addition of regional hyperthermia to dose-intensified sRT improves biochemical control

68Ga-PSMA-PET/CT-based radiosurgery and stereotactic body radiotherapy for oligometastatic prostate cancer

Background: Androgen deprivation therapy (ADT) remains the standard therapy for patients with oligometastatic prostate cancer (OMPC). Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT)-based stereotactic body radiotherapy (SBRT) is emerging as an alternative option to postpone starting ADT and its associated side effects including the development of drug resistance. The aim of this study was to determine progression free-survival (PFS) and treatment failure free-survival (TFFS) after PSMA-PET/CT-based SBRT in OMPC patients. The efficacy and safety of single fraction radiosurgery (SFRS) and ADT delay were investigated. Methods: Patients with ≤ 5 metastases from OMPC, with/without ADT treated with PSMA-PET/CT-based SBRT were retrospectively analyzed. PFS and TFFS were primary endpoints. Secondary endpoints were local control (LC), overall survival (OS) and ADT-free survival (ADTFS). Results: Fifty patients with a total of 75 metastases detected by PSMA-PET/CT were analyzed. At the time of SBRT, 70% of patients were castration-sensitive. Overall, 80% of metastases were treated with SFRS (median dose 20 Gy, range: 16-25). After median follow-up of 34 months (range: 5-70) median PFS and TFFS were 12 months (range: 2-63) and 14 months (range: 2-70), respectively. Thirty-two (64%) patients had repeat oligometastatic disease. Twenty-four (48%) patients with progression underwent second SBRT course. Two-year LC after SFRS was 96%. Grade 1 and 2 toxicity occurred in 3 (6%) and 1 (2%) patients, respectively. ADTFS and OS rates at 2-years were 60.5% and 100%, respectively. In multivariate analysis, TFFS significantly improved in patients with time to first metastasis (TTM) >36 months (p = 0.01) and PSA before SBRT ≤ 1 ng/ml (p = 0.03). Conclusion: For patients with OMPC, SBRT might be used as an alternative to ADT. This way, the start/escalation of palliative ADT and its side effects can be deferred. Metastases treated with PSMA-PET/CT-based SFRS reached excellent LC with minimal toxicity. Low PSA levels and longer TTM predict elongated TFFS

PET measured hypoxia and MRI parameters in re-irradiated head and neck squamous cell carcinomas: findings of a prospective pilot study [version 2; peer review: 2 approved]

Background: Tumor hypoxia measured by dedicated tracers like [ 18F]fluoromisonidazole (FMISO) is a well-established prognostic factor in head and neck squamous cell carcinomas (HNSCC) treated with definitive chemoradiation (CRT). However, prevalence and characteristics of positron emission tomography (PET) measured hypoxia in patients with relapse after previous irradiation is missing. Here we report imaging findings of a prospective pilot study in HNSCC patients treated with re-irradiation. Methods: In 8 patients with recurrent HNSCC, diagnosed at a median of 18 months after initial radiotherapy/CRT, [ 18F]fluorodeoxyglucose (FDG)-PET/CT (n=8) and FMISO-PET/MRI (n=7) or FMISO-PET/CT (n=1) were performed. Static FMISO-PET was performed after 180 min. MRI sequences in PET/MRI included diffusion-weighted imaging with apparent diffusion coefficient (ADC) values and contrast enhanced T1w imaging (StarVIBE). Lesions (primary tumor recurrence, 4; cervical lymph node, 1; both, 3) were delineated on FDG-PET and FMISO-PET data using a background-adapted threshold-based method. SUV max and SUV mean in FDG- and FMISO-PET were derived, as well as maximum tumor-to-muscle ratio (TMR max) and hypoxic volume with 1.6-fold muscle SUV mean (HV 1.6) in FMISO-PET. Intensity of lesional contrast enhancement was rated relative to contralateral normal tissue. Average ADC values were derived from a 2D region of interest in the tumor. Results: In FMISO-PET, median TMR max was 1.7 (range: 1.1-1.8). Median HV 1.6 was 0.05 ml (range: 0-7.3 ml). Only in 2/8 patients, HV 1.6 was ≥1.0 ml. In FDG-PET, median SUV max was 9.3 (range: 5.0-20.1). On contrast enhanced imaging four lesions showed decreased and four lesions increased contrast enhancement compared to non-pathologic reference tissue. Median average ADC was 1,060 ×10 6 mm 2/s (range: 840-1,400 ×10 6 mm 2/s). Conclusions: This pilot study implies that hypoxia detectable by FMISO-PET may not be as prevalent as expected among loco-regional recurrent, HPV negative HNSCC. ADC values were only mildly reduced, and contrast enhancement was variable. The results require confirmation in larger sample sizes

Shortened Tracer Uptake Time in GA-68-DOTATOC-PET of Meningiomas Does Not Impair Diagnostic Accuracy and PET Volume Definition

Ga-68-DOTATOC-PET/MRI can affect the planning target volume (PTV) definition of meningiomas before radiosurgery. A shorter tracer uptake time before image acquisition could allow the examination of more patients. The aim of this study was to investigate if shortening uptake time is possible without compromising diagnostic accuracy and PET volume. Fifteen patients (f = 12; mean age 52 years (34-80 years)) with meningiomas were prospectively examined with dynamic [68Ga]Ga-68-labeled [DOTA0-Phe1-Tyr3] octreotide (Ga-68-DOTATOC)-PET/MRI over 70 min before radiosurgery planning. Meningiomas were delineated manually in the PET dataset. PET volumes at each time point were compared to the reference standard 60 min post tracer injection (p.i.) using the Friedman test followed by a Wilcoxon signed-rank test and Bonferroni correction. In all patients, the earliest time point with 100% lesion detection compared to 60 min p.i. was identified. PET volumes did not change significantly from 15 min p.i. (p = 1.0) compared to 60 min p.i. The earliest time point with 100% lesion detection in all patients was 10 min p.i. In patients with meningiomas undergoing Ga-68-DOTATOC-PET, the tracer uptake time can safely be reduced to 15 min p.i. with comparable PET volume and 100% lesion detection compared to 60 min p.i

Definitive radiotherapy and Single-Agent radiosensitizing Ifosfamide in Patients with localized, irresectable Soft Tissue Sarcoma: A retrospective analysis

<p>Abstract</p> <p>Background and Purpose</p> <p>Standard therapy for soft-tissue sarcomas remains complete resection. For primary radiotherapy local control rates of 30-45% have been reported. We analyzed retrospectively 11 cases of radiochemotherapy with single-agent ifosfamide in patients with macroscopic soft-tissue sarcomas.</p> <p>Patients and Methods</p> <p>The patients were treated in irresectable high risk situations. Radiation therapy was performed with median 60 Gy. During the first and fifth week the concomitant chemotherapy with ifosfamide was added. Two patients received trimodal therapy with additional regional hyperthermia.</p> <p>Results</p> <p>The therapy was completed in 73% of the patients. Average local control time was 91 months, median disease-free-survival/overall-survival was 8/26 months. Five-year rates for local control/disease free survival/overall survival were 70%/34%/34%. The limited prognosis is mainly caused by systemic treatment failure.</p> <p>Conclusions</p> <p>The data strongly suggest a better outcome of radiochemotherapy with ifosfamide compared to radiotherapy alone and radiotherapy in combination with other radiosensitizers.</p

A dense network of cosmic-ray neutron sensors for soil moisture observation in a highly instrumented pre-Alpine headwater catchment in Germany

Monitoring soil moisture is still a challenge: it varies strongly in space and time and at various scales while conventional sensors typically suffer from small spatial support. With a sensor footprint up to several hectares, cosmic-ray neutron sensing (CRNS) is a modern technology to address that challenge. So far, the CRNS method has typically been applied with single sensors or in sparse national-scale networks. This study presents, for the first time, a dense network of 24 CRNS stations that covered, from May to July 2019, an area of just 1 km2: the pre-Alpine Rott headwater catchment in Southern Germany, which is characterized by strong soil moisture gradients in a heterogeneous landscape with forests and grasslands. With substantially overlapping sensor footprints, this network was designed to study root-zone soil moisture dynamics at the catchment scale. The observations of the dense CRNS network were complemented by extensive measurements that allow users to study soil moisture variability at various spatial scales: roving (mobile) CRNS units, remotely sensed thermal images from unmanned areal systems (UASs), permanent and temporary wireless sensor networks, profile probes, and comprehensive manual soil sampling. Since neutron counts are also affected by hydrogen pools other than soil moisture, vegetation biomass was monitored in forest and grassland patches, as well as meteorological variables; discharge and groundwater tables were recorded to support hydrological modeling experiments. As a result, we provide a unique and comprehensive data set to several research communities: to those who investigate the retrieval of soil moisture from cosmic-ray neutron sensing, to those who study the variability of soil moisture at different spatiotemporal scales, and to those who intend to better understand the role of root-zone soil moisture dynamics in the context of catchment and groundwater hydrology, as well as land–atmosphere exchange processes. The data set is available through the EUDAT Collaborative Data Infrastructure and is split into two subsets: https://doi.org/10.23728/b2share.282675586fb94f44ab2fd09da0856883 (Fersch et al., 2020a) and https://doi.org/10.23728/b2share.bd89f066c26a4507ad654e994153358b (Fersch et al., 2020b)