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Background: We evaluated efficacy and toxicity of 68 Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery. Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68 Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03. Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68 Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5-139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2-10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7-230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4-42) all patients were alive. Estimated 1-year PSA- control ( n  = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient. Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68 Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response.

Introduction: A previous pattern-of-failure study has suggested that up to 50% of the loco-regional failures (LRF) in head and neck squamous cell carcinoma (HNSCC) occur outside the initial hypoxic volume determined by [ 18 F]-fluoromisonidazole-PET ([ 18 F]-FMISO-PET). The aim of the present analysis was to correlate spatial patterns of failure with respect to the pretherapeutic dynamic [ 18 F]-FMISO-PET/CT in HNSCC after radiochemotherapy (RCT)., Material and Methods: Within a running phase 2 trial using [ 18 F]-FMISO-PET imaging prior to RCT in HNSCC patients (n = 54), we have observed so far 11 LRF with a minimum follow-up of 12 months. For nine patients, LRF imaging (CT or [ 18 F]-FDG-PET/CT) for pattern-of-failure analysis was available. Analysis included the static 4-h hypoxic subvolume (V H ) as well as a M-parameter volume (V M ), which is derived from modeling of dynamic PET. Deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [ 18 F]-FMISO-PET/CT and the planning CT was done to quantify the hypoxic subvolumes compared to the recurrent tumor volume. Moreover, a point-of-origin analysis was performed., Results: A total of five local, two regional and two loco-regional recurrences were detected. After deformable image registration of the CT scan with the recurrent tumor to the pre-treatment [ 18 F]-FMISO-PET/CT and the planning CT, a significant overlap of the recurrence volume with [ 18 F]-FMISO-positive subvolumes in the initial gross tumor volume (GTV) was observed. Median overlap of 40.2%, range 9.4-100.0%, for V H and 49.0%, range 4.4-96.4%, for V M was calculated. The point-of-origin analysis showed median distances of 0.0 mm, range 0.0-11.3 mm to V H and 8.6 mm, range 0.0-15.5 mm to V M , respectively., Conclusions: Our data suggest that loco-regional recurrences after RCT originate from the initial GTV (primary tumor and/or lymph node metastases) containing hypoxic subvolumes, which supports the concept of hypoxia imaging-based dose escalation.

Background: PET imaging may be used to personalize radiotherapy (RT) by identifying radioresistant tumor subvolumes for RT dose escalation. Using the tracers [ 18 F]-fluorodeoxyglucose (FDG) and [ 18 F]-fluoromisonidazole (FMISO), different aspects of tumor biology can be visualized. FDG depicts various biological aspects, e.g., proliferation, glycolysis and hypoxia, while FMISO is more hypoxia specific. In this study, we analyzed size and overlap of volumes based on the two markers for head-and-neck cancer patients (HNSCC)., Material and Methods: Twenty five HNSCC patients underwent a CT scan, as well as FDG and dynamic FMISO PET/CT prior to definitive radio-chemotherapy in a prospective FMISO dose escalation study. Three PET-based subvolumes of the primary tumor (GTV prim ) were segmented: a highly FDG-avid volume V FDG , a hypoxic volume on the static FMISO image acquired four hours post tracer injection (V H ) and a retention/perfusion volume (V M ) using pharmacokinetic modeling of dynamic FMISO data. Absolute volumes, overlaps and distances to agreement (DTA) were evaluated., Results: Sizes of PET-based volumes and the GTV prim are significantly different (GTV prim >V FDG >V H >V M ; p < .05). V H is covered by V FDG or DTAs are small (mean coverage 74.4%, mean DTA 1.4 mm). Coverage of V M is less pronounced. With respect to V FDG and V H , the mean coverage is 48.7% and 43.1% and the mean DTA is 5.3 mm and 6.3 mm, respectively. For two patients, DTAs were larger than 2 cm., Conclusions: Hypoxic subvolumes from static PET imaging are typically covered by or in close proximity to highly FDG-avid subvolumes. Therefore, dose escalation to FDG positive subvolumes should cover the static hypoxic subvolumes in most patients, with the disadvantage of larger volumes, resulting in a higher risk of dose-limiting toxicity. Coverage of subvolumes from dynamic FMISO PET is less pronounced. Further studies are needed to explore the relevance of mismatches in functional imaging.

Background: Previous studies suggested the maximum tumor to background ratio (TBRmax) in FMISO PET images as a potentially predictive parameter for local control after radio-chemotherapy (CRT) in head and neck squamous cell carcinomas (HNSCC). However, different TBRmax thresholds for stratification were reported, implying that a common threshold cannot readily be used among different institutions without the risk of reducing prediction accuracy. Therefore, this study investigated the robustness of using a common pre-defined TBRmax, simulating a multicenter clinical trial., Material and Methods: FMISO PET/CT was performed four hours post-injection in 22 patients with advanced HNSCC in a phase II FMISO dose escalation study. PET background regions of interest (ROIs) were manually defined in deep neck muscles. TBRmax was calculated as the mean of the highest-valued voxels within the high risk RT planning target volume. Its predictive power with respect to local control was tested, classifying patients using median TBRmax as threshold. The influence of systematically varying quantification between institutions was studied in silico by applying offsets of ± 10% and ± 20% to the TBRmax of all patients, while the threshold remained constant. The effect was analyzed using a receiver operating characteristic (ROC). True positive and false positive rates (TPR/FPR) as well as positive and negative predictive values (PPV/NPV) were evaluated., Results: For the reference condition without an offset the median TBRmax was 2.0 (1.4-3.5). Patients were classified using this threshold and TPR = 0.7, FPR = 0.4, PPV = 0.5 and NPV = 0.8 were observed. Accuracy declined with increasing offsets. Negative offsets of -10% and -20% resulted in TPR = 0.43 and 0.14, FPR = 0.20 and 0.13, PPV = 0.50 and 0.33 and NPV = 0.75 and 0.68, respectively. Positive offsets of + 10% and + 20% resulted in TPR = 1.00 and 1.00, FPR = 0.53 and 0.67, PPV = 0.47 and 0.41 and NPV = 1.00 and 1.00, respectively., Conclusions: Using a common pre-defined TBRmax threshold in multicenter trials requires careful standardization and harmonization of all steps from patient preparation to image analysis. Our results indicate that TBRmax should deviate less than 10% from reference conditions (absolute value in this dataset ± 0.2). This conclusion likely applies to all low contrast nitroimidazole hypoxia PET tracers.

Purpose: The diagnosis of tuberculosis as an etiological factor in patients with uveitis is difficult because of lack of specific diagnostic tests. The authors report 2 cases of occlusive retinal vasculitis, in which (18)F-FDG-PET/CT was helpful for the diagnosis of tuberculosis as a presumptive cause of intraocular inflammation., Methods: In 2 patients with severe occlusive retinal vasculitis and positive QuantiFERON TB-Gold test, (18)F-FDG-PET/CT, transbronchial needle-aspiration biopsy, and microbiological investigation were performed., Results: (18)F-FDG-PET/CT showed increased fluorodeoxyglucose uptake in some mediastinal and hilar lymph nodes. After needle-aspiration biopsy of PET-positive lymph nodes, M. tuberculosis was recovered in culture in both cases. Remission of uveitis was achieved only after a combination therapy with 3 anti-tubercular agents and systemic steroids., Conclusion: The authors favor the use of (18)F-FDG-PET/CT in patients with sight-threatening intraocular inflammation and positive interferon-gamma release assay. Anti-tubercular therapy, together with anti-inflammatory treatment, may lead to a remission in such patients.