Effectiveness and complication rates of high intensity focused ultrasound treatment for abdominal wall endometriosis: A systematic review.

In this review, a systematic literature search on the effectiveness and complication rates of ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USg-/MRgHIFU) for abdominal wall endometriosis (AWE) was conducted in six databases in May/June 2023. Original articles of (non)randomized trials, cohort studies, case-control studies and case series published in peer-reviewed journals were included. Of the included studies the level of evidence (LoE) and methodological quality using the ROBINS-I and IHE-QAT was assessed. Primary outcomes were non-perfused volume ratio (NPV%), lesion size, pain scores, side effects and complication rates according to Society of Interventional Radiology (SIR) guidelines. Secondary outcomes were recurrence and re-intervention rates. Seven cohort studies (one of good methodological quality) (LoE 3) on USgHIFU were included (n = 212, AWE lesions = 240-245). Six months after USgHIFU treatment, pain scores were reduced with 3.3-5.2 points (baseline: 5.1-6.8, n = 135). Self-limiting side effects were pain (85.7 % (114/133)) and swelling (34.6 % (46/133)) in the treatment area. Complications occurred in 17.7 % (32/181), all of which were minor. Recurrence occurred in 12.8 % (11/86). Three of these seven cohort studies compared USgHIFU (n = 61) with surgical excision (n = 74). Pooled results showed no significant differences in pain scores, complications (resp. 26.3 % (10/38) vs. 32.6 % (15/46) (p = 0.53)) and recurrences (resp. 4.9 % (3/61) vs. 5.4 % (4/74) (p = 0.90)). This systematic review suggests that HIFU is an effective and safe treatment option for AWE. USgHIFU treatment led to reduced pain scores and lesion size, was free of major complications and had a pooled recurrence rate of 12.8 %. Compared to surgical excision pooled results showed no significant differences in pain scores, complications and recurrences after USgHIFU. However, many of the included studies had limitations in their methodological quality and therefore the results should be interpreted with caution. Well-structured high-quality randomized controlled trials comparing HIFU to standard care should be conducted to provide more conclusive evidence.

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response.

BACKGROUND: The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies. METHODS: We optimized drug screen methods on 5-11 PDOs per condition of the complete set of 23 PDOs from patients treated for metastatic colorectal cancer (mCRC). PDOs were exposed to 5-fluorouracil (5-FU), irinotecan- and oxaliplatin-based chemotherapy. We compared medium with and without N-acetylcysteine (NAC), different readouts and different combination treatment set-ups to capture the strongest association with patient response. We expanded the screens using the optimized methods for all PDOs. Organoid sensitivity was correlated to the patient's response, determined by % change in the size of target lesions. We assessed organoid sensitivity in relation to prior exposure to chemotherapy, mutational status and sidedness. RESULTS: Drug screen optimization involved excluding N-acetylcysteine from the medium and biphasic curve fitting for 5-FU & oxaliplatin combination screens. CellTiter-Glo measurements were comparable with CyQUANT and did not affect the correlation with patient response. Furthermore, the correlation improved with application of growth rate metrics, when 5-FU & oxaliplatin was screened in a ratio, and 5-FU & SN-38 using a fixed dose of SN-38. Area under the curve was the most robust drug response curve metric. After optimization, organoid and patient response showed a correlation coefficient of 0.58 for 5-FU (n = 6, 95% CI -0.44,0.95), 0.61 for irinotecan- (n = 10, 95% CI -0.03,0.90) and 0.60 for oxaliplatin-based chemotherapy (n = 11, 95% CI -0.01,0.88). Median progression-free survival of patients with resistant PDOs to oxaliplatin-based chemotherapy was significantly shorter than sensitive PDOs (3.3 vs 10.9 months, p = 0.007). Increased resistance to 5-FU in patients with prior exposure to 5-FU/capecitabine was adequately reflected in PDOs (p = 0.003). CONCLUSIONS: Our study emphasizes the critical impact of the screening methods for determining correlation between PDO drug screens and mCRC patient outcomes. Our 5-step optimization strategy provides a basis for future research on the clinical utility of PDO screens.

Prophylactic Medication during Radioembolization in Metastatic Liver Disease: Is It Really Necessary? A Retrospective Cohort Study and Systematic Review of the Literature.

PURPOSE: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. METHODS: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (Dh). Logistic regression models were used to investigate if variables (among which are P/UDCA and Dh) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. RESULTS: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. Dh was associated with biochemical toxicity (p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. CONCLUSION: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization.