First Clinical Experience With [68Ga]Ga-FAPI-46-PET/CT Versus [18F]F-FDG PET/CT for Nodal Staging in Cervical Cancer.

INTRODUCTION: In several solid tumors, fibroblast activation protein (FAP) is overexpressed by cancer-associated fibroblasts in the tumor microenvironment. Preliminary evidence suggests that detection and staging are feasible with PET/CT imaging using [68Ga]-radiolabeled inhibitors of FAP also in cervical cancer (CC). Our study aims to explore the accuracy of [68Ga]Ga-fibroblast activation protein inhibitor (FAPI)-46 PET/CT and [18F]F-FDG PET/CT compared with histopathological results of surgical lymph node (LN) staging before primary chemoradiation. METHODS: Seven consecutive women with treatment-naive and biopsy-proven locally advanced CC underwent both whole-body [68Ga]Ga-FAPI-46- and [18F]F-FDG PET/CT, for imaging nodal staging before systematic laparoscopic lymphadenectomy of the pelvic and para-aortic region. Location and number of suspicious LNs in PET imaging were recorded and compared with the results of histopathological analysis, including immunohistochemical staining for FAP. RESULTS: All 7 patients had focal uptake above background in their tumor lesions in [68Ga]Ga-FAPI-46 PET/CT. [68Ga]Ga-FAPI-46 PET/CT showed a higher tumor-to-background ratio (TBR) in primary tumor as well as in LN metastasis. Median TBRmax values using liver were 32.02 and 5.15 for [68Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT, respectively. Median TBRmax using blood pool was 18.45 versus 6.85 for [68Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT, respectively. Higher TBR also applies for nodal metastasis: TBRmax was 14.55 versus 1.39 (liver) and 7.97 versus 1.8 (blood pool) for [68Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT, respectively. Overall, [68Ga]Ga-FAPI-46 PET/CT detected more lesions compared with [18F]F-FDG PET/CT. Following surgical staging, a total of 5 metastatic LNs could be pathologically confirmed, of which 2 and 4 were positive by [18F]F-FDG PET/CT and [68Ga]Ga-FAPI-46 PET/CT, respectively. CONCLUSION: [68Ga]Ga-FAPI-46 PET/CT seems useful to improve detection of nodal metastasis in patients with CCs. Future studies should aim to compare [68Ga]Ga-FAPI-46 PET/CT to surgical staging of pelvic and para-aortic LNs in patients with locally advanced CC.

Early economic modeling of magnetic resonance image-guided high intensity focused ultrasound compared to radiotherapy for pain palliation of bone metastases.

Introduction: Magnetic Resonance Image-guided High Intensity Focused Ultrasound (MR-HIFU) is a non-invasive treatment option for palliative patients with painful bone metastases. Early evidence suggests that MR-HIFU is associated with similar overall treatment response, but more rapid pain palliation compared to external beam radiotherapy (EBRT). This modelling study aimed to assess the cost-effectiveness of MR-HIFU as an alternative treatment option for painful bone metastases from the perspective of the German Statutory Health Insurance (SHI). Materials and methods: A microsimulation model with lifelong time horizon and one-month cycle length was developed. To calculate the incremental cost-effectiveness ratio (ICER), strategy A (MR-HIFU as first-line treatment or as retreatment option in case of persistent pain or only partial pain relief after EBRT) was compared to strategy B (EBRT alone) for patients with bone metastases due to breast, prostate, or lung cancer. Input parameters used for the model were extracted from the literature. Results were expressed as EUR per quality-adjusted life years (QALYs) and EUR per pain response (i.e., months spent with complete or partial pain response). Deterministic and probabilistic sensitivity analyses (PSA) were performed to test the robustness of results, and a value of information analysis was conducted. Results: Compared to strategy B, strategy A resulted in additional costs (EUR 399) and benefits (0.02 QALYs and 0.95 months with pain response). In the base case, the resulting ICERs (strategy A vs. strategy B) are EUR 19,845/QALY and EUR 421 per pain response. Offering all patients MR-HIFU as first-line treatment would increase the ICER by 50% (31,048 EUR/QALY). PSA showed that at a (hypothetical) willingness to pay of EUR 20,000/QALY, the probability of MR-HIFU being cost-effective was 52%. The expected value of perfect information (EVPI) for the benefit population in Germany is approximately EUR 190 Mio. Conclusion: Although there is considerable uncertainty, the results demonstrate that introducing MR-HIFU as a treatment alternative for painful bone metastases might be cost-effective for the German SHI. The high EVPI indicate that further studies to reduce uncertainty would be worthwhile.

Head-to-Head Comparison of [68 Ga]Ga-FAPI-46-PET/CT and [18F]F-FDG-PET/CT for Radiotherapy Planning in Head and Neck Cancer.

INTRODUCTION: In head and neck cancers (HNCs), fibroblast activation protein (FAP) is expressed by cancer-associated fibroblasts (CAFs) in the tumor microenvironment. Preliminary evidence suggests that detection and staging is feasible with positron emission tomography (PET/CT) imaging using [68 Ga]-radiolabeled inhibitors of FAP ([68 Ga]Ga-FAPI-46) in HNCs. This study aims to compare [68 Ga]Ga-FAPI-46 PET/CT and [18F]-fluorodeoxy-D-glucose ([18F]F-FDG) PET/CT with a focus on improved target volume definition and radiotherapy planning in patients with HNC referred for chemoradiation. METHODS: A total of 15 patients with HNCs received both [68 Ga]Ga-FAPI-46 PET/CT and [18F]F-FDG PET/CT with a thermoplastic mask, in addition to initial tumor staging by conventional imaging with contrast-enhanced CT and/or MRI. Mean intervals between FAPI/FDG and FAPI/conventional imaging were 4 ± 20 and 17 ± 18 days, respectively. Location and number of suspicious lesions revealed by the different procedures were recorded. Subsequently, expert-generated gross tumor volumes (GTVs) based on conventional imaging were compared to those based on [18F]F-FDG and [68 Ga]Ga-FAPI-46 PET/CT to measure the impact on subsequent radiation planning. RESULTS: All patients had focal FAPI uptake above background in tumor lesions. Compared to FDG, tumor uptake (median SUVmax 10.2 vs. 7.3, p = 0.008) and tumor-to-background ratios were significantly higher with FAPI than with FDG (SUVmean liver: 9.3 vs. 3.2, p < 0.001; SUVmean bloodpool: 6.9 vs. 4.0, p < 0.001). A total of 49 lesions were recorded. Of these, 40 (82%) were FDG+ and 41 (84%) were FAP+. There were 5 (10%) FAP+/FDG- lesions and 4 (8%) FAP-/FDG+ lesions. Volumetrically, a significant difference was found between the GTVs (median 57.9 ml in the FAPI-GTV, 42.5 ml in the FDG-GTV, compared to 39.2 ml in the conventional-GTV). Disease stage identified by FAPI PET/CT was mostly concordant with FDG PET/CT. Compared to conventional imaging, five patients (33%) were upstaged following imaging with FAPI and FDG PET/CT. CONCLUSION: We demonstrate that [68 Ga]Ga-FAPI-46 -PET/CT is useful for detecting tumor lesions in patients with HNCs. There is now a need for prospective randomized studies to confirm the role of [68 Ga]Ga-FAPI-46 PET/CT in relation to [18F]F-FDG PET/CT in HNCs and to evaluate its impact on clinical outcome.

Managing patient flows in radiation oncology during the COVID-19 pandemic : Reworking existing treatment designs to prevent infections at a German hot spot area University Hospital.

PURPOSE: The described work aimed to avoid cancellations of indispensable treatments by implementing active patient flow management practices and optimizing infrastructure utilization in the radiation oncology department of a large university hospital and regional COVID-19 treatment center close to the first German SARS-CoV­2 hotspot region Heinsberg in order to prevent nosocomial infections in patients and personnel during the pandemic. PATIENTS AND METHODS: The study comprised year-to-date intervention analyses of in- and outpatient key procedures, machine occupancy, and no-show rates in calendar weeks 12 to 19 of 2019 and 2020 to evaluate effects of active patient flow management while monitoring nosocomial COVID-19 infections. RESULTS: Active patient flow management helped to maintain first-visit appointment compliance above 85.5%. A slight appointment reduction of 10.3% daily (p = 0.004) could still significantly increase downstream planning CT scheduling (p = 0.00001) and performance (p = 0.0001), resulting in an absolute 20.1% (p = 0.009) increment of CT performance while avoiding overbooking practices. Daily treatment start was significantly increased by an absolute value of 18.5% (p = 0.026). Hypofractionation and acceleration were significantly increased (p = 0.0043). Integrating strict testing guidelines, a distancing regimen for staff and patients, hygiene regulations, and precise appointment scheduling, no SARS-CoV­2 infection in 164 tested radiation oncology service inpatients was observed. CONCLUSION: In times of reduced medical infrastructure capacities and resources, controlling infrastructural time per patient as well as optimizing facility utilization and personnel workload during treatment evaluation, planning, and irradiation can help to improve appointment compliance and quality management. Avoiding recurrent and preventable exposure to healthcare infrastructure has potential health benefits and might avert cross infections during the pandemic. Active patient flow management in high-risk COVID-19 regions can help Radiation Oncologists to continue and initiate treatments safely, instead of cancelling and deferring indicated therapies.