PURPOSE Ablative therapies for primary and secondary liver malignancies are increasingly adopted in current guidelines. Nevertheless, surgical resection remains the gold standard in most curative therapy settings.Extensive studies on mortality and morbidity after ablative treatment of the liver are missing. We investigated complications and mortality after ablative treatment in a large, unselected study cohort. MATERIALS AND METHODS Standardized patient and treatment data in 4374 percutaneous and angiographic ablative procedures of the liver from the DRG-based hospital reimbursement system (diagnosis-related groups) of an academic hospital in Germany were retrospectively evaluated. We analyzed descriptive patient data, length of stay (LOS), pre-existing medical conditions, previous gastrointestinal surgeries, severe complications, and occurrence of death. RESULTS Treatment of secondary liver malignancies constituted over two-thirds of all procedures (71%, n = 3053). The mean LOS was 4.1 ± 3.5 days. Severe complications were documented in 1.4% and in-house death in 0.2% of cases, significantly more often after treatment with chemoembolization of primary liver malignancies (p = 0.003; p = 0.0001).Previous partial liver resection, partial bowel resection, and chronic renal failure were independent risk factors for the occurrence of severe complications. CONCLUSION Severe complications and in-hospital death are rare in the treatment of primary and secondary liver malignancies with percutaneous and angiographic procedures.They are a viable alternative or addition to a surgical approach in treating liver lesions.

Introduction: Interstitial brachytherapy (iBT) is an effective treatment for hepatocellular carcinoma (HCC). Identification of prognostic factors is pivotal for patient selection and treatment efficacy. This study aimed to assess the impact of low skeletal muscle mass (LSMM) on overall survival (OS) and progression-free survival (PFS) of iBT in patients with HCC. Methods: For this single-center study, we retrospectively identified 77 patients with HCC who underwent iBT between 2011 and 2018. Follow-up visits were recorded until 2020. The psoas muscle area, psoas muscle index, psoas muscle density (MD), and the skeletal muscle gauge were assessed on the L3 level on pre-treatment cross-sectional CT scans. Results: Median OS was 37 months. 42 patients (54.5%) had LSMM. An AFP level of >400 ng/ml (hazard ratio [HR] 5.705, 95% confidence interval [CI]: 2.228–14.606, p = 0.001), BCLC stage (HR 3.230, 95% CI: 0.972–10.735, p = 0.026), and LSMM (HR 3.365, 95% CI: 1.490–7.596, p = 0.002) showed a relevant association with OS. Weighted hazard ratios were used to form a predictive risk stratification model with three groups: patients with low risk (median OS 62 months), intermediate risk (median OS 31 months), and high risk (median OS 9 months). The model showed a good prediction of 1-year mortality, with an AUC of 0.71. Higher MD was associated with better PFS (HR 0.920, 95% CI: 0.881–0.962, p < 0.001). Conclusion: In patients undergoing iBT for HCC, LSMM is associated with worse OS. A risk stratification model based on LSMM, AFP >400 ng/mL, and BCLC stage successfully predicted patient mortality. The model may support and enhance patient selection.

To investigate the impact of pentoxifylline (PTX, 3 × 400 mg per day) and ursodeoxycholic acid (UDCA, 3 × 250 mg per day) administered for 12 weeks on radiation-induced liver toxicity. Inclusion criteria were liver metastases of extrahepatic malignancies undergoing HDR-BT. 36 patients were prospectively randomized to the medication (N = 18) or control arm (N = 18) and follow-up by hepatobiliary magnetic resonance imaging (MRI) was scheduled 6 and 12 weeks after local ablation by HDR-BT. We determined the threshold doses of fRILI by image fusion of MRI with the dosimetry data. 32 patients completed the study schedule. Per-protocol treatment was limited to 8 patients in the medication group and 16 patients in the control group. 22 adverse events of any grade likely or certainly related to PTX were recorded in 12 patients leading to the discontinuation of the study medication in 7 patients and to a dose reduction of PTX in 2 patients. In the per-protocol population, statistical analysis failed to prove a reduction of fRILI 6 and 12 weeks after HDR-BT. The incidence of adverse effects attributed to PTX (70.6

As part of a breast-conservation strategy for breast cancer, there are presently no data from randomized controlled studies on the use of intraoperative radiation (IORT) as a tumor bed boost. The effectiveness and safety of IORT as a boost therapy at a tertiary cancer center were retrospectively reviewed in this study. Patients had breast-conserving surgery from 2012 to 2016 that included staging of the axillary lymph nodes, a single dose of 20 Gy IORT with 50-kV photons, whole-breast irradiation (WBI), and (neo-)adjuvant systemic treatment (if applicable). During the follow-up patients were monitored for the assessment of acute and late toxicities (using the Common Terminology Criteria for Adverse Events version 4.03). Results included ipsilateral (IBTR), contralateral (CBE), and distant metastasis-free (DMFS) breast progression-free survival, as well as overall survival (OS). The 68 patients had a median follow-up of 91.5 months (with a range of 9–125). Most patients (n = 51) had T1 disease and were clinically node negative. Only a small number of individuals had triple negative or high-grade illness. The majority of patients had sentinel node biopsy, and three (4.4

PURPOSE:Image-guided interstitial high-dose-rate brachytherapy (iBT) has been demonstrated to offer high local tumor control rates (LTC) of >90% after local ablation of intermediate and advanced hepatocellular carcinoma (HCC; BCLC B and C). The purpose of this study was to show the efficacy of iBT stratified by subgroups and to identify clinical characteristics associated with superior local tumor control (LTC) based on a highly heterogenous patient population METHODS AND MATERIALS: A cumulative number of 286 HCC nodules in 107 patients were retrospectively analyzed. Clinical and imaging follow-ups were conducted every 3 months after treatment. Analyzed clinical factors were: etiology, presence of liver cirrhosis, radiographic features, lesion size, pretreatment, administered dose, presence of portal hypertension, portal vein thrombosis, and level of alpha-fetoprotein (AFP). RESULTS:LTC rate was 88.8% for a median follow-up of 14.3 months (range 3-81 months; 95% CI: 85-92%). Median minimal enclosing tumor dose (D100) was 16.1 Gy (range 7.1-30.3 Gy; reference dose 15 Gy). Subgroup analysis showed significant fewer local recurrences for alcoholic liver disease (ALD)-related HCCs compared to those related to other causes of liver cirrhosis (nonalcoholic fatty liver disease, virus-related liver cirrhosis and other causes) (p = 0.015). LTC was significantly lower after prior surgical resection (p = 0.046). No significant variance was observed for the applied D100 in each group or for all other clinical factors tested. CONCLUSIONS:IBT achieves high LTC rates across treated subgroups. However, further studies should particularly address the possible impact of underlying etiology on local recurrence with emphasis on a possible higher radiosensitivity of ALD-related HCCs.

Purpose In 2012, the CROSS trial implemented a new neoadjuvant radiochemotherapy protocol for patients with locally advanced, resectable cancer of the esophagus prior to scheduled surgery. There are only limited studies comparing the CROSS protocol with a PF-based (cisplatin/5-fluorouracil) nRCT protocol. Methods In this retrospective, monocentric analysis, 134 patients suffering from esophageal cancer were included. Those patients received either PF-based nRCT (PF group) or nRCT according to the CROSS protocol (CROSS group) prior to elective en bloc esophagectomy. Perioperative mortality and morbidity, nRCT-related toxicity, and complete pathological regression were compared between both groups. Logistic regression analysis was performed in order to identify independent factors for pathological complete response (pCR). Results Thirty-day/hospital mortality showed no significant differences between both groups. Postoperative complications ≥ grade 3 according to Clavien-Dindo classification were experienced in 58.8% (PF group) and 47.6% (CROSS group) ( p = 0.2) respectively. nRCT-associated toxicity ≥ grade 3 was 30.8% (PF group) and 37.2% (CROSS group) ( p = 0.6). There was no significant difference regarding the pCR rate between both groups (23.5% vs. 30.5%; p = 0.6). In multivariate analysis, SCC (OR 7.7; p < 0.01) and an initial grading of G1/G2 (OR 2.8; p = 0.03) were shown to be independent risk factors for higher rates of pCR. Conclusion We conclude that both nRCT protocols are effective and safe. There were no significant differences regarding toxicity, pathological tumor response, and postoperative morbidity and mortality between both groups. Squamous cell carcinoma (SCC) and favorable preoperative tumor grading (G1 and G2) are independent predictors for higher pCR rate in multivariate analysis.

Supplementary Figure 2 - PDF file 128K, Cell cycle analyses under cilengitide treatment. Meningioma cell lines treated with cilengitide and analysed for cell cycle changes

Supplementary Figure 1 - PDF file 57K, integrin mRNA expression in meningiomas

Background Interstitial brachytherapy (iBT) has become a viable treatment option in the therapy of early and intermediate stage hepatocellular carcinoma (HCC). Prognostic imaging tools to predict patient outcome are missing. Purpose To assess the predictive value of baseline diffusion-weighted imaging in HCC before iBT with regard to local tumor control and overall survival (OS). Material and Methods We retrospectively identified 107 patients who underwent iBT for HCC from 2011 to 2018 from our database. Apparent diffusion coefficient (ADC) values for each treated lesion were analyzed in region of interest measurements. Additionally, explorative combined ratios adjusting total measured lesion area and mean measured lesion area per patient by ADC values were calculated. Measurements underwent a univariate and multivariate Cox regression analysis. The log rank test was then used to verify prognostic cutoff levels for median survival time. Results A total of 189 lesions in 81 patients were measured. Median survival of patients was 46.0 months. Neither ADC parameter was indicative of local tumor control. Lesion size >5 cm was associated with lower local tumor control (hazard ratio [HR]=4.292, 95% confidence interval [CI]=1.285–14.331; P = 0.018). Average measured lesion area divided by ADCmin (ADCarea mean, min) was identified to independently predict OS (HR=1.994, 95% CI=1.172–3.392; P = 0.011). A cutoff based on the variable's median (0.29 × 10–4 AU) identified patients with poor outcome (OS 36 vs. 61 months) for lower ADCarea mean, min values as verified by the log-rank test ( P = 0.040). Conclusion Pre-treatment ADCarea mean, min may serve as an independent predictor of OS in patients with HCC undergoing iBT.

Supplementary Figure 3 - PDF file 43K, Overall survival of mice treated with cilengitide and control animals

A potential method for focal therapy in locally advanced prostate cancer is focal brachytherapy (F-BT). The purpose of this research was to evaluate midterm F-BT oncologic, functional, and toxicological results in men who had therapy for prostate cancer. Between 2016 and 2020, F-BT was used to treat 37 patients with low- to intermediate-risk prostate cancer. The recommended dosage was 20 Gy. Failure was defined as the existence of any prostate cancer that has persisted in-field after treatment. The F-BT oncologic and functional outcomes served as the main and secondary objectives, respectively. A median 20-month follow-up (range 14–48 months). 37 patients received F-BT and enrolled in the study; no patient experienced a biochemical recurrence in the first 24 months, according to Phoenix criteria. In the control biopsies, only 6 patients showed in-field failure. The median initial IPSS was 6.5, at 6 months was 6.0, and at 24 months was 5.0. When the median ICIQ-SF score was 0 at the baseline, it remained 0 at 6-, 12-, and 24 months. Overall survival and biochemical disease-free survival after 3 years were all at 100

Background and purpose ALBI and IBI are new scores to evaluate the liver function in patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic abilities of those scores in patients treated with interstitial brachytherapy (iBT). Materials and methods 190 patients treated with iBT between 01.01.2006 and 01.01.2018 were included in this study. The clinical target dose was 15 Gy. The patients were all in Child–Pugh stadium A or B and across the Barcelona Clinic Liver Cancer (BCLC) Stages 0–C. Retrospectively ALBI and IBI were calculated pre- and post-therapeutic until 6 months after iBT. Hazards ratios were calculated, and p values corrected using the false discovery rate according to Benjamini and Hochberg. Results The median overall survival was 23.5 months (CI 19–28.5 months), and the median progression-free survival was 7.5 months (CI 6–9 months). Elevated ALBI showed a significantly higher risk to die with a hazard ratio (HR) of 2.010 (ALBI 2 vs. 1) and 4082 (ALBI 3 vs. 1), respectively. The IBI did also show a higher risk with an HR of 1.816 (IBI 1 vs. 0) and 4608 (IBI 2 vs. 0), respectively. Even 3 months after therapy elevated ALBI and IBI showed poor overall survival. Concerning progression-free survival, ALBI and IBI could not provide any relevant additional information. Conclusion ALBI and IBI are useful tools to predict the overall survival in patients treated with iBT and might be helpful to assign the patients to the appropriate therapy.

Purpose: Sarcopenia has been identified as a prognostic marker of clinical outcomes in several diseases. However, the influence of sarcopenia on non-surgical local treatments in breast cancer liver metastases (BCLM) is unknown. Therefore, the purpose of this study was to assess the effect of sarcopenia among patients with BCLM undergoing interstitial brachytherapy (iBT). Aim of the study was to evaluate the influence of baseline computed tomography (CT) psoas body composition parameters, including psoas muscle area (PMA), psoas muscle index (PMI), muscle density, and skeletal muscle gauge (SMG) on clinical variables in patients undergoing image-guided iBT. Material and methods: Computed tomography scans of patients undergoing iBT for BCLM from 2006-2017 were retrospectively analyzed. PMA, PMI, and SMG were measured on pre-treatment CT scans. Parameters were associated with overall survival using logistic regression analysis.Results: Sixty patients were included in the analysis. 27 patients (45%) were considered sarcopenic. Median over-all survival was 27 months (SD = 4.0 months). In univariate analysis, neither PMA (HR = 0.956, 95% CI: 0.855-1.068, p = 0.423), average density (HR = 1.028, 95% CI: 0.985-1.072, p = 0.207), PMI (HR = 0.951, 95% CI: 0.701-1.290, p = 0.746), nor SMG (HR = 1.002, 95% CI: 0.998-1.006, p = 0.440) were associated with overall survival. There was no influence of sarcopenia on OS (HR = 0.975, 95% CI: 0.532-1.787, p = 0.934).Conclusions: Sarcopenia does not predict overall survival in patients undergoing iBT for BCLM. Interstitial BT may therefore be a suggested treatment option in sarcopenic patients with BCLM eligible for local ablation.

Purpose:Image-guided brachytherapy with a single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) is a promising local ablation technique for unresectable liver metastases. The occurrence of needle track seeding after biopsy and microwave ablation (MWA) has been documented primarily in hepatocellular carcinoma (HCC). Comprehensive data on colorectal metastases and treatment with HDR-BT is missing. The aim of this study was to investigate the incidence of extra- and intra-hepatic track seeding after HDR-BT in patients with colorectal metastases of the liver, and the identification of possible risk factors.Material and methods:Patients with at least one treatment of HDR-BT were included. Two readers identified possible track seeding after at least 3 months of follow-up. For verification, we used image fusion of CT/MRI images from 3D irradiation plan and follow-up. Intra- and extra-hepatic seeding were included. As possible risk factors, demographics, tumor grading, and aspects of catheter placement were identified, and generalized linear mixed model for evaluation was applied.Results:On total, 138 patients were included in the study (85 males). We treated 472 liver lesions with 1,107 catheter placements. Sixteen needle track lesions were identified with a catheter-based risk of 1.5% and patient-based risk of 10.9% during a median follow-up of 543 days. Extra-hepatic track seeding (patient-based risk of 1.4%) was found in two patients only. Possible risk factors were tumor grading (p = 0.01) and using MRI-guidance (p = 0.02). There was also a correlation with a high number of interventions per patient (p = 0.009) and number of treated lesions (p = 0.04).Conclusions:Brachytherapy for treatment of colorectal metastases is associated with a similar risk for extra-hepatic track seeding compared to radio-frequency ablation (RFA). Intra-hepatic seeding, which has not been studied extensively before, occurs more often with seeding frequency comparable to biopsy of colorectal metastases. Possible risk factors could be tumor grading and using MRI-guidance.

Purpose: We sought to investigate functional parameters and morphologic changes of the renal parenchyma after treatment with image-guided brachytherapy using single-fraction irradiation (high-dose-rate brachytherapy - HDR-BT) of primary kidney lesions, and primary and secondary lesions of the liver, lymph node, and adrenal gland close to renal structures.Material and methods: Patients ineligible for surgery were included. We prospectively investigated renal function loss within one year via renal scintigraphy and laboratory parameters (KDOQI stage). Radiation exposure to the kidney was measured by volume receiving 5 Gy (V5). We observed morphologic changes on CT or MRI, with follow-up every three months.Results: In total, 35 patients were included (21 males, 14 females). Eight patients were treated for extra-renal ma-lignancies. The mean V5 of the ipsilateral kidney was 70.0 +/- 42.4 ml equaling to 44.9% parenchymal volume. After renal treatment, V5 renal volume was 77.8 +/- 42.2 ml (48.7%) compared with 44.0 +/- 33.0 ml (32.0%) after extra-renal treatment. No significant reduction in KDOQI stage after 12 months of follow-up were found. Three patients developed morpho- logic changes in the renal parenchyma, with only one showing a decrease in renal function after 12 months.Conclusions: CT-guided HDR-BT is a viable treatment modality for local ablative treatment of renal and adjacent masses, with no significant reduction of the KDOQI stage as a predictor for complications of chronic kidney disease. However, larger cohorts need to be analyzed to identify vulnerable patients, as in rare cases, plain dosimetry seems insufficient to predict renal function loss after HDR-BT.