Treatment of metastatic gastric adenocarcinoma with image-guided high-dose rate, interstitial brachytherapy as second-line or salvage therapy

PURPOSEWe aimed to evaluate the safety and effectiveness of image-guided high-dose rate interstitial brachytherapy (iBT) for the treatment of patients with hepatic, lymphatic, and pancreatic metastases originating from gastric cancer, an entity rarely surgically treatable with curative intent.METHODSTwelve patients with a cumulative number of 36 metastases (29 liver, 2 pancreatic, 5 lymph node) from histologically proven gastric adenocarcinoma received iBT between 2010 and 2016 and were retrospectively analyzed. Every patient underwent palliative chemotherapy prior to iBT. The iBT procedure employs a temporarily, intratumorally placed iridium-192 source in a single fraction with the goal of tumor cell eradication. Effectiveness was assessed clinically and by radiologic imaging every three months.RESULTSLocal tumor control was achieved in 32 of all treated metastases (89%). Four lesions showed a local recurrence after 7 months. Lesion sizes varied from 9 to 102 mm with a median of 20 mm. The median progression-free survival was 6.6 months (range, 1.8–46.8 months). The median overall survival was 11.4 months (range, 5–47 months). One patient suffered a major complication following iBT, hepatic hematoma and abscess (Common Terminology Criteria for Adverse Events grade 3), successfully dealt with by transcutaneous drainage.CONCLUSIONiBT is an overall safe procedure, which facilitates high rates of local tumor control in treatment of metastatic gastric adenocarcinoma. Compared with surgical metastasectomy, similar overall survival rates could be achieved in our patient collective after iBT application

Image-guided interstitial high-dose-rate brachytherapy in the treatment of metastatic esophageal squamous cell carcinoma

Purpose: To evaluate the efficacy of computed tomography (CT)- and magnetic resonance imaging (MRI)-guided interstitial high-dose-rate brachytherapy (HDR IBT = IBT) in patients with metastatic esophageal squamous cell carcinoma. Material and methods: Eleven patients with 21 unresectable metastases of histologically proven esophageal squamous cell carcinoma were included in this retrospective study. Fourteen visceral and 7 lung metastases were treated with image-guided (CT or open MRI guidance) IBT using a 192 lridium source (single fraction irradiation). Clinical and imaging follow-up were performed every 3 months after treatment. Primary endpoint was local tumor control (LTC) and safety. Furthermore, we analyzed safety, progression-free survival (PFS), and overall survival (OS). Results: The median diameter of the target lesions was 2.2 cm (range: 0.7-6.8 cm), treated with a median D-100 of 20.1 Gy (range: 10-25 Gy). During a median follow-up of 6.3 months (range: 3-21.8 months), three patients displayed local recurrences, resulting in LTC of 85.7%. Median PFS was 3.4 months and median OS after IBT was 13.7 months. No severe adverse events (grade 3+) requiring hospitalization or invasive intervention were recorded. Conclusions: Image-guided IBT is a safe and effective treatment in patients with metastasized esophageal squamous cell carcinoma

Intra-hepatic Abscopal Effect Following Radioembolization of Hepatic Metastases

Purpose!#!To search for abscopal effects (AE) distant to the site of radiation after sequential Yittrium-90 (Y-90) radioembolization (RE) of liver malignancies.!##!Methods and materials!#!In this retrospective analysis, all patients treated by RE between 2007 and 2018 (n = 907) were screened for the following setting/conditions: sequential RE of left and right liver lobe in two sessions, liver-specific MRI (MRI1) acquired max. 10 days before or after first RE (RE1), liver-specific MRI (MRI2) acquired with a minimum time interval of 20 days after MRI1, but before second RE (RE2). No systemic tumor therapies between MRI1 and MRI2. No patients with liver cirrhosis. Metastases > 5 mm in untreated liver lobes were compared in MRI1 and MRI2 and rated as follows: same size or larger in MRI2 = no abscopal effect (NAE); > 30% shrinkage without Y-90 contamination in SPECT/CT = abscopal effect (AE).!##!Results!#!Ninety six of 907 patients met aforementioned criteria. Median time-frame between RE1 and MRI2 was 34 (20-64) days. These 96 cases had 765 metastases which were evaluable (median 5(1-40) metastases per patient). Four patients could be identified with at least one shrinking metastasis of the untreated site: one patient with breast cancer (3 metastases: 0 NAE; 3 AE), one patient with prostate cancer (6 metastases: 3 NAE; 3 metastases > 30% shrinkage but possible Y-90 contamination) and two patients with shrinkage of one metastasis each but less than 30%.!##!Conclusion!#!Our retrospective study documents AE after RE of liver tumors in 1 out of 96 cases, 3 other cases remain unclear

Multidisciplinary Treatment of Patients with Progressive Biliary Tract Cancer after First-Line Gemcitabine and Cisplatin: A Single-Center Experience

Background: Patients with unresectable biliary tract cancer (uBTC) who progress despite first-line gemcitabine plus cisplatin (GC) treatment have limited systemic options with a modest survival benefit. Data are lacking on the clinical effectiveness and safety of personalized treatment based on multidisciplinary discussion for patients with progressing uBTC. Methods: This retrospective single-center study included patients with progressive uBTC who received either best supportive care or personalized treatment based on multidisciplinary discussion, including minimally invasive, image-guided procedures (MIT); FOLFIRI; or both (MIT and FOLFIRI), between 2011 and 2021. Results: Ninety-seven patients with progressive uBTC were identified. Patients received best supportive care (n = 50, 52%), MIT (n = 14, 14%), FOLFIRI (n = 19, 20%), or both (n = 14, 14%). Survival after disease progression was better in patients who received MIT (8.8 months; 95% CI: 2.60–15.08), FOLFIRI (6 months; 95% CI: 3.30–8.72), or both (15.1 months; 95% CI: 3.66–26.50) than in patients receiving BSC (0.36 months; 95% CI: 0.00–1.24, p 10%) grade 3–5 adverse events were anemia (25%) and thrombocytopenia (11%). Conclusion: Multidisciplinary discussion is critical for identifying patients with progressive uBTC who might benefit the most from MIT, FOLFIRI, or both. The safety profile was consistent with previous reports

Anti-inflammatory Effects of Alcohol Are Associated with JNK-STAT3 Downregulation in an In Vitro Inflammation Model in HepG2 Cells

Background. In several preclinical and in vitro models of acute inflammation, alcohol (ethanol, EtOH) has been described as an immunomodulatory agent. Similarly, in different pathologies, clinical observations have confirmed either pro- or anti-inflammatory effects of EtOH. The liver plays an important role in immunity and alcohol metabolism; therefore, we analysed dose- and time-dependent effects of EtOH on the inflammatory response of human liver cells in an in vitro model of acute inflammation. Methods. HepG2 cells were stimulated with IL-1β and subsequently exposed to EtOH in a low or high dose (85 mM, LoD or 170 mM, HiD) for 1 h (acute exposure) or 72 h (prolonged exposure). IL-6 and TNF-α release was determined by ELISA. Cell viability, adhesion of isolated neutrophils to HepG2 monolayers, their ICAM-1 expression, and the activation of stress-induced protein kinase/c-Jun N-terminal kinase (SAPK/JNK) or signal transducer and activator of transcription 3 (STAT3) were analysed. Results. In this experimental design, EtOH did not markedly change the cell viability. Acute and prolonged exposure to EtOH significantly reduced dose-independent IL-1β-induced IL-6 and TNF-α release, as well as adhesion capacity to pretreated HepG2 cells. Acute exposure to EtOH significantly decreased the percentage of ICAM-1-expressing cells. IL-1β stimulation notably increased the activation of SAPK/JNK. However, low-dose EtOH exposure reduced this activation considerably, in contradiction to high-dose EtOH exposure. Acute exposure to LoD EtOH significantly diminished the IL-1β-induced STAT3 activation, whereas an acute exposure of cells to either HiD EtOH or in a prolonged setting showed no effects on STAT3 activation. Conclusion. EtOH exerts anti-inflammatory potential in this in vitro model of hepatic inflammation. These effects are associated with the reduced activation of JNK/STAT3 by EtOH, particularly in the condition of acute exposure to low-dose EtOH