Digital Staging of Hepatic Hemangiomas Reveals Spatial Heterogeneity in Endothelial Cell Composition and Vascular Senescence.

Hepatic hemangioma (HH) is the most common benign primary liver tumor; however, despite its high prevalence, a stage-specific classification of this tumor is currently missing. For a spatial stage-specific classification, a tissue microarray (TMA) consisting of 98 HHs and 80 hemangioma margins and 78 distant liver tissues was digitally analyzed for the expression of 16 functional and vascular niche-specific markers. For cross-correlation of histopathology and functional characteristics, computed tomography/MRI imaging data of 28 patients were analyzed. Functional and morphological analyses revealed a high level of intra- and interpatient heterogeneity, and morphological heterogeneity was observed with regard to cellularity, vascular diameter, and endothelial cell subtype composition. While regressed hemangiomas were characterized by low blood vessel density, low beta-catenin levels, and a microvascular phenotype, non-regressed HHs showed a pronounced cellular and architectural heterogeneity. Functionally, cellular senescence-associated p16 expression identified an HH subgroup with high vascular density and increased lymphatic endothelial cell content. Histological HH regions may be grouped into spatially defined morphological compartments that may reflect the current region-specific disease stage. The stage-specific classification of HHs with signs of regression and vascular senescence may allow a better disease course-based and cell state-based subtyping of these benign vascular lesions.

Magnetic resonance guided adaptive stereotactic body radiotherapy for lung tumors in ultracentral location: the MAGELLAN trial (ARO 2021-3).

BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is a standard treatment for inoperable primary and secondary lung tumors. In case of ultracentral tumor location, defined as tumor contact with vulnerable mediastinal structures such as the proximal bronchial tree (PBT) or esophagus, SBRT is associated with an increased risk for severe complications. Magnetic resonance (MR)-guided SBRT can mitigate this risk based on gated dose delivery and daily plan adaptation. The MAGELLAN trial aims to find the maximum tolerated dose (MTD) of MR-guided SBRT of ultracentral lung tumors (ULT). PATIENTS AND METHODS: MAGELLAN is a prospective phase I dose escalation trial. A maximum of 38 patients with primary and secondary ULT with a tumor size ≤ 5 cm will be enrolled. Ultracentral location is defined as an overlap of the planning target volume (PTV) with the PBT or esophagus. Patients are treated at a 0.35 Tesla MR-linac (MRIdian® Linac, ViewRay Inc. ) employing a gating strategy and daily plan adaptation. Dose escalation starts at 10 × 5.5 Gy (biologically effective dose BED3/10: 155.83 Gy/85.25 Gy), may proceed up to 10 × 6.5 Gy (BED3/10: 205.83 Gy/107.25 Gy) and is guided by a customized time-to-event continual reassessment method (TITE CRM) with backup element, which alternately assigns patients to dose escalation and backup cohorts. DISCUSSION: The results of the MAGELLAN trial will guide further research and clinical implementation of MR-guided SBRT as ablative treatment of ULT. Moreover, the combination of MR-guided radiotherapy with TITE-CRM including a backup element may serve as blueprint for future radiation dose escalation studies in critical locations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT04925583 on 14th June 2021.

Outcome after Radiotherapy for Vestibular Schwannomas (VS)-Differences in Tumor Control, Symptoms and Quality of Life after Radiotherapy with Photon versus Proton Therapy.

BACKGROUND: To evaluate differences in local tumor control (LC), symptoms and quality of life (QOL) of 261 patients with VS after stereotactic radiosurgery/hypofractionated stereotactic radiotherapy (SRS/HFSRT) vs. fractionated radiotherapy (FRT) vs. fractionated proton therapy (FPT) were studied. METHODS: For SRS/HFSRT (n = 149), the median fraction dose applied was 12 Gy. For FRT (n = 87) and FPT (n = 25), the median cumulative doses applied were 57.6 Gy and 54 Gy (RBE), respectively. FRT and FPT used single median doses of 1.8 Gy/Gy (RBE). Median follow-up was 38 months. We investigated dosimetry for organs at risk and analyzed toxicity and QOL by sending out a questionnaire. RESULTS: LC was 99.5% at 12 months after RT with no statistical difference between treatment groups (p = 0.19). LC was significantly lower in NF2 patients (p = 0.004) and in patients with higher tumor extension grade (p = 0.039). The hearing preservation rate was 97% at 12 months after RT with no statistical difference between treatment groups (p = 0.31). Facial and trigeminal nerve affection after RT occurred as mild symptoms with highest toxicity rate in FPT patients. CONCLUSION: SRS/HFSRT, FRT and FPT for VS show similar overall clinical and functional outcomes. Cranial nerve impairment rates vary, potentially due to selection bias with larger VS in the FRT and FPT group.

Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma.

PURPOSE: We assessed and compared clinical effects and safety endpoints of three methods of transarterial chemoembolization (TACE), conventional (cTACE), with drug-eluting beads (DEB-TACE), and with degradable starch microspheres (DSM-TACE), used in patients with hepatocellular carcinoma (HCC) in the bridging to liver transplant (LT) and the palliative setting. METHODS: In our center, 148 patients with HCC underwent 492 completed TACE procedures between 2008 and 2017 (158 for bridging to LT; 334 for palliative treatment) which we analyzed retrospectively. Of these procedures, 348 were DEB-TACE, 60 cTACE, and 84 DSM-TACE. RESULTS: The cTACE procedure revealed a significantly longer period of hospitalization (p = 0.02), increased occurrence of nausea (p = 0.025), and rise in alanine transaminase (ALT) levels (p = 0.001), especially in the palliative setting. In the bridging to LT cohort, these clinical endpoints did not reach statistical significance. CONCLUSIONS: The clinical safety of different TACE methods for HCC in both the palliative and the bridging to LT setting was equivalent. In the palliative setting, the cTACE procedure revealed an increased risk for adverse clinical effects such as nausea, elevation of ALT, and a prolonged period of hospitalization what might either be related to the systemic effects of the chemotherapeutic agent or to the differences in both collectives. Thus, further studies must be conducted on a larger number of TACE procedures to effectively explore the clinical side effects of the various TACE variants.

Impact of FAPI-PET/CT on Target Volume Definition in Radiation Therapy of Locally Recurrent Pancreatic Cancer.

(1) Background: A new radioactive positron emission tomography (PET) tracer uses inhibitors of fibroblast activation protein (FAPI) to visualize FAP-expressing cancer associated fibroblasts. Significant FAPI-uptake has recently been demonstrated in pancreatic cancer patients. Target volume delineation for radiation therapy still relies on often less precise conventional computed tomography (CT) imaging, especially in locally recurrent pancreatic cancer patients. The need for improvement in precise tumor detection and delineation led us to innovatively use the novel FAPI-PET/CT for radiation treatment planning. (2) Methods: Gross tumor volumes (GTVs) of seven locally recurrent pancreatic cancer cases were contoured by six radiation oncologists. In addition, FAPI-PET/CT was used to automatically delineate tumors. The interobserver variability in target definition was analyzed and FAPI-based automatic GTVs were compared to the manually defined GTVs. (3) Results: Target definition differed significantly between different radiation oncologists with mean dice similarity coefficients (DSCs) between 0.55 and 0.65. There was no significant difference between the volumes of automatic FAPI-GTVs based on the threshold of 2.0 and most of the manually contoured GTVs by radiation oncologists. (4) Conclusion: Due to its high tumor to background contrast, FAPI-PET/CT seems to be a superior imaging modality compared to the current gold standard contrast-enhanced CT in pancreatic cancer. For the first time, we demonstrate how FAPI-PET/CT could facilitate target definition and increases consistency in radiation oncology in pancreatic cancer.

Applicability of scoring systems predicting outcome of transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: Several scoring systems have been proposed to predict the outcome of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC). However, the application of these scores to a bridging to transplant setting is poorly validated. Evaluation of the applicability of prognostic scores for patients undergoing TACE in palliative intention vs. bridging therapy to liver transplantation (LT) is necessary. METHODS: Between 2008 and 2017, 148 patients with HCC received 492 completed TACE procedures (158 for bridging to transplant; 334 TACE procedures in palliative treatment intention at our center and were analyzed retrospectively. Scores (ART, CLIP, ALBI, APRI, SNACOR, HAP, STATE score, Child-Pugh, MELD, Okuda and BCLC) were calculated and evaluated for prediction of overall survival. ROC analysis was performed to assess prediction of 3-year survival and treatment discontinuation. RESULTS: In patients receiving TACE in palliative intention most scores predicted OS in univariate analysis but only mSNACOR score (p = 0.006), State score (p < 0.001) and Child-Pugh score (p < 0.001) revealed statistical significance in the multivariate analysis. In the bridging to LT cohort only the BCLC score revealed statistical significance (p = 0.002). CONCLUSIONS: Clinical usability of suggested scoring systems for TACE might be limited depending on the individual patient cohorts and the indication. Especially in patients receiving TACE as bridging to LT none of the scores showed sufficiently applicability. In our study Child-Pugh score, STATE score and mSNACOR score showed the best performance assessing OS in patients with TACE as palliative therapy.

Clinical long-term outcome, technical success, and cost analysis of radiofrequency ablation for the treatment of osteoblastomas and spinal osteoid osteomas in comparison to open surgical resection.

OBJECTIVE: To assess the clinical success and costs of computed tomography (CT)-guided radiofrequency ablation (RFA) of osteoblastoma (OB) and spinal osteoid osteoma (OO). MATERIALS AND METHODS: Nineteen patients with OB and eight patients with spinal OO were treated with CT-guided RFA. The OBs were localized in the extremities (n = 10), the vertebral column (n = 2), and (juxta-)articular (n = 7). Dedicated procedural techniques included three-dimensional CT-guided access planning in all cases, overlapping RFA needle positions (median, two positions; range, 1-6 RF-electrode positions) within the OB nidus (multiple ablation technique, n = 15), and thermal protection in case of adjacent neural structure in four spinal OO. The data of eight operated OB and ten operated spinal OO patients were used for comparison. Long-term success was assessed by clinical examination and using a questionnaire sent to all operated and RFA-treated patients including visual analogue scales (VAS) regarding the effect of RFA on severity of pain and limitations of daily activities (0-10, with 0 = no pain/limitation up to 10 = maximum or most imaginable pain/limitation). RESULTS: All patients had a clear and persistent pain reduction until the end of follow-up. The mean VAS score for all spinal OO patients and all OB patients treated either with RFA or with surgical excision significantly decreased for severity of pain at night, severity of pain during the day, and both for limitations of daily and of sports activities. CONCLUSIONS: RFA is an efficient method for treating OB and spinal OO and should be regarded as the first-line therapy after interdisciplinary individual case discussion.

CT-guided radiofrequency ablation of osteoid osteoma: correlation of clinical outcome and imaging features.

PURPOSE: We aimed to retrospectively evaluate the computed tomography (CT) and magnetic resonance imaging (MRI) findings of patients with osteoid osteoma treated with CT-guided radiofrequency ablation (RFA) along with the clinical outcome and long-term success. MATERIALS AND METHODS: Seventy-three CT-guided RFA procedures were performed in 72 patients. The long-term success was assessed using a questionnaire including several visual analog scale scores. The CT evaluation included pre- and immediate postprocedural imaging of all 72 patients, and MRI was performed in 18 patients with follow-up imaging (mean, 3.4±2.2 months). The evaluation criteria included nidus morphology and a correlation with markers of clinical success. RESULTS: The primary technique effectiveness rate was 71/72 (99%). One relapse was successfully retreated, leading to a secondary technique effectiveness rate of 72/72 (100%). The long-term follow-up (mean, 51.2±31.2 months; range, 3-109 months) revealed a highly significant reduction of all assessed limitation scores (P < 0.001). The CT morphology was typical in all cases and did not change during the short-term follow-up. The follow-up MRI patterns varied considerably, including persistent nidus contrast enhancement in one-third (6/18) and persistent marrow edema in half (9/18) of the patients. None of the investigated MRI and CT patterns correlated with the clinical outcome. CONCLUSION: The long-term outcome of CT-guided RFA of osteoid osteoma is excellent. There is no correlation of the CT and MRI patterns with the clinical outcome. Thus, the treatment decisions should not be solely based on the imaging findings. Investigators should also be aware of the variety of imaging patterns after RFA.

CT-guided radiofrequency ablation of osteoid osteoma and osteoblastoma: clinical success and long-term follow up in 77 patients.

The purpose of this study was to retrospectively evaluate long-term success of CT-guided radiofrequency ablation (RFA) in patients with osteoid osteoma (OO) and osteoblastoma (OB) including tumors in critical locations. Eighty-one CT-guided RFA procedures were performed in 77 patients with OO (65 patients) and OB (12) including 6 spinal and 15 intra/periarticular tumors. Procedural techniques included multiple needle positions, three-dimensional access planning, as well as, thermal protection techniques. Long-term success was assessed using a questionnaire including, among others, several VAS (visual analogue scale) scores. All patients completed 3-6 months follow-up, overall response to the questionnaire was 64/77 (83.1%). Primary success rate was 74/77 (96.1%) of all patients. Retreatment with RFA in 3 patients resulted in a secondary success rate of 77/77 (100%). Long-term follow-up (mean, 38.5 months; range, 3-92) revealed a highly significant (p<0.001) reduction of all assessed limitation scores reaching normal or almost normal values. One major complication, a cannula break leading to a secondary short hospital stay, occurred. In conclusion, RFA is a safe and effective long-lasting treatment of OO and OB. Advanced procedural techniques aid treating tumors in critical locations and in the coverage of larger tumors. Besides night pain, RFA also greatly improves other factors negatively affecting the quality of life.