Ga-FAPI-2/4/46 have already been proposed as promising PET-tracers. However, the short half-life of 68 Ga (T1/2 68 min) creates problems with manufacture and delivery. 18 F (T1/2 110 min) labeling would result in a more practical large scale production and a cold-kit formulation would improve the spontaneous availability. The NOTA-chelator ligand FAPI-74 can be labeled with both 18 F-AlF (Aluminum-Fluoride) and 68 Ga. Here we describe the in-vivo evaluation of 18 F-FAPI-74 and a proof-of-mechanism of 68 Ga-FAPI-74 labeled at ambient temperature. Methods: In ten patients with lung cancer PET-scans were acquired at 10 min, 1h and 3h after administration of 259±26 MBq 18 F-FAPI-74. Physiological biodistribution and tumor uptake were semi-quantitatively evaluated based on SUV at each time-point. Absorbed doses were evaluated using OLINDA/EXM 1.1 and QDOSE dosimetry software with the dose calculator IDAC-Dose 2.1. Identical methods were used to evaluate one exam after injection of 263 MBq 68 Ga-FAPI-74. Results: The highest contrast was achieved 1 h p.i. in primary tumors, lymph node and distant metastases with SUVmax >10, respectively. The effective dose per 100 MBq administered activity of 18 F-FAPI-74 was 1.4±0.2 mSv and for 68 Ga-FAPI-74 it was 1.6 mSv. Thus, the radiation burden of a diagnostic 18 F-FAPI-74 PET-scan is even lower than that of PET-scans with 18 F-FDG and other 18 F-tracers; 68 Ga-FAPI-74 is comparable to other 68 Ga-ligands. FAPI-PET/CT supported target volume definition for guiding radiotherapy. Conclusion: High contrast and low radiation burden of FAPI-74 PET/CT favors multiple clinical applications. Centralized large-scale production of 18 F-FAPI-74 or decentralized cold-kit labeling of 68 Ga-FAPI-74 allows flexible routine use.

This randomized trial demonstrates the utility of palliative SBRT for spinal metastases, which was associated with a quicker and improved pain response. Larger ongoing randomized studies will assist in further addressing these endpoints.

Introduction: Local ablative treatment strategies are frequently offered to patients diagnosed with oligometastatic disease. Stereotactic body radiotherapy (SBRT), as ablative treatment option, is well established for lung and liver metastases, whereas for isolated adrenal gland metastases the level of evidence is scarce. Material and methods: This single-institution analysis of oligometastatic or oligoprogressive disease was limited to patients who received SBRT to adrenal metastasis between 2012 and 2019. Patient, tumor, treatment characteristics, and dosimetric parameters were analyzed for evaluation of their effect on survival outcomes. Results: During the period of review 28 patients received ablative SBRT to their adrenal gland metastases. Most common primary tumors were non-small cell lung cancers (46%) with most patients diagnosed with a single adrenal gland metastasis (61%), which occurred after a median time of 14 months. SBRT was delivered to a median biological effective dose at α/β of 10 (BED 10) of 75 Gy (range: 58-151 Gy). Median gross tumor volume (GTV) and median planning target volume (PTV) were 42 and 111 mL, respectively. The homogeneity and conformity indices were 1.17 (range: 1.04-1.64) and 0.5 (range: 0.4.0.99), respectively, with the conformity index being affected by dose restrictions to organs at risk (OARs) in 50% of the patients. Overall response rate based on RECIST criteria was 86% (CR = 29%, PR = 57%) with 2-year local control (LC) of 84.8%, 2-year progression-free survival (PFS) of 26.3%, and 1and 2-year overall survival (OS) of 46.6 and 32.0%, respectively. During follow up, only two local recurrences occurred. A trend for superior LC was seen if BED 10 was ≥75Gy (p = 0.101) or if the PTV was < 100 ml (p = 0.072). SBRT was tolerated well with only mild toxicity. Conclusion: SBRT for adrenal metastases resulted in promising LC with low toxicity. Treatment response appeared to be superior, if SBRT was applied with higher BED. As the close proximity of OARs often limits the application of sufficiently high doses, further dose escalations strategies and techniques should be investigated in future.

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Background: Reductions in tumor movement allow for more precise and accurate radiotherapy with decreased dose delivery to adjacent normal tissue that is crucial in stereotactic body radiotherapy (SBRT). Deep inspiration breath-hold (DIBH) is an established approach to mitigate respiratory motion during radiotherapy. We assessed the feasibility of combining modern optical surface-guided radiotherapy (SGRT) and image-guided radiotherapy (IGRT) to ensure and monitor reproducibility of DIBH and to ensure accurate tumor localization for SBRT as an imaging-guided precision medicine. Methods: We defined a new workflow for delivering SBRT in DIBH for lung and liver tumors incorporating SGRT and IGRT with cone beam computed tomography (CBCT) twice per treatment fraction. Daily position corrections were analyzed and for every patient two points retrospectively characterized: an anatomically stable landmark (predominately Schmorl's nodes or spinal enostosis) and a respiratory-dependent landmark (predominately surgical clips or branching vessel). The spatial distance of these points was compared for each CBCT and used as surrogate for intra-and interfractional variability. Differences between the lung and liver targets were assessed using the Welch t-test. Finally, the planning target volumes were compared to those of free-breathing plans, prepared as a precautionary measure in case of technical or patient-related problems with DIBH. Results: Ten patients were treated with SBRT according this workflow (7 liver, 3 lung). Planning target volumes could be reduced significantly from an average of 148 ml in free breathing to 110 ml utilizing DIBH (p < 0.001, paired t-test). After SGRT-based patient setup , subsequent IGRT in DIBH yielded significantly higher mean corrections for liver targets compared to lung targets (9 mm vs. 5 mm, p = 0.017). Analysis of spatial

Background: The purpose of this study was to compare dosimetric differences related to target volume and organs-at-risk (OAR) using 3D-conformal radiotherapy (3DCRT), volumetric modulated arc therapy (VMAT), TomoTherapy (Tomo), proton radiotherapy (PRT), and carbon ion radiotherapy (CIRT) as part of postoperative thymoma irradiation. Material and methods: This single-institutional analysis included 10 consecutive patients treated with adjuvant radiotherapy between December 2013 and September 2016. CT-datasets and respective RT-structures were anonymized and plans for all investigated RT modalities (3DCRT, VMAT, Tomo, PRT, CIRT) were optimized for a total dose of 50 Gy in 25 fractions. Comparisons between target volume and OAR dosimetric parameters were performed using the Wilcoxon rank-sum test. Results: The best target volume coverage (mean PTV V 95% for all patients) was observed for Tomo (97.9%), PRT (97.6%), and CIRT (96.6%) followed by VMAT (85.4%) and 3DCRT (74.7%). PRT and CIRT both significantly reduced mean doses to the lungs, breasts, heart, and esophagus, as well as the spinal cord maximum dose compared with photon modalities. Among photon-based techniques, VMAT showed improved OAR sparing over 3DCRT. Tomo was associated with considerable low-dose exposure to the lungs, breasts, and heart. Conclusions: Particle radiotherapy (PRT, CIRT) showed superior OAR sparing and optimal target volume coverage. The observed dosimetric advantages are expected to reduce toxicity rates. However, their clinical impact must be investigated prospectively.

This is the first randomized trial to evaluate radiation-induced toxicities after IMRT versus 3DCRT in patients with vertebral metastases. This trial demonstrated an additional improvement for IMRT in terms of acute side effects, although longer follow-up is required to further ascertain other endpoints.

SRS in FFF mode is time efficient and provides similar plan quality with the opportunity of slightly reduced dose exposure to healthy brain tissue when compared to SRS in FF mode. Clinical outcomes appear promising and show only modest treatment-related toxicity.