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.

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial.

INTRODUCTION: Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4-8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT. METHODS AND ANALYSIS: The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: WHO International Clinical Trials Registry (NL8997; https://trialsearch.who.int).

Focused Ultrasound and RadioTHERapy for non-invasive palliative pain treatment in patients with bone metastasis: a study protocol for the three armed randomized controlled FURTHER trial.

BACKGROUND: Cancer-induced bone pain (CIBP), caused by bone metastases, is a common complication of cancer and strongly impairs quality of life (QoL). External beam radiotherapy (EBRT) is the current standard of care for treatment of CIBP. However, approximately 45% of patients have no adequate pain response after EBRT. Magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) may improve pain palliation in this patient population. The main objective of this trial was to compare MR-HIFU, EBRT, and MR-HIFU + EBRT for the palliative treatment of bone metastases. METHODS/DESIGN: The FURTHER trial is an international multicenter, three-armed randomized controlled trial. A total of 216 patients with painful bone metastases will be randomized in a 1:1:1 ratio to receive EBRT only, MR-HIFU only, or combined treatment with EBRT followed by MR-HIFU. During a follow-up period of 6 months, patients will be contacted at eight time points to retrieve information about their level of pain, QoL, and the occurrence of (serious) adverse events. The primary outcome of the trial is pain response at 14 days after start of treatment. Secondary outcomes include pain response at 14 days after trial enrolment, pain scores (daily until the 21st day and at 4, 6, 12 and 24 weeks), toxicity, adverse events, QoL, and survival. Cost-effectiveness and cost-utility analysis will be conducted. DISCUSSION: The FURTHER trial aims to evaluate the effectiveness and cost-effectiveness of MR-HIFU-alone or in combination with EBRT-compared to EBRT to relieve CIBP. The trial will be performed in six hospitals in four European countries, all of which are partners in the FURTHER consortium. TRIAL REGISTRATION: The FURTHER trial is registered under the Netherlands Trials Register number NL71303.041.19 and ClinicalTrials.gov registration number NCT04307914. Date of trial registration is 13-01-2020.

Radioembolization-Induced Changes in Hepatic [18F]FDG Metabolism in Non-Tumorous Liver Parenchyma.

Background: [18F]FDG-PET/CT is increasingly used for response assessments after oncologic treatment. The known response criteria for [18F]FDG-PET/CT use healthy liver parenchyma as the reference standard. However, the [18F]FDG liver metabolism results may change as a result of the given therapy. The aim of this study was to assess changes in [18F]FDG liver metabolism after hepatic 90Y resin radioembolization. Methods: [18F]FDG-PET/CT scans prior to radioembolization and one and three months after radioembolization (consistent with the PERCIST comparability criteria), as well as 90Y-PET/CT scans, were analyzed using 3 cm VOIs. The FDG activity concentration and absorbed dose were measured. A linear mixed-effects logistic regression model and logistic mixed-effects model were used to assess the correlation between the FDG-activity concentration, absorbed dose, and biochemical changes. Results: The median SULVOI,liver at baseline was 1.8 (range = 1.2−2.8). The mean change in SULVOI,liver per month with an increase in time was 0.05 (95%CI 0.02−0.09) at p < 0.001. The median absorbed dose per VOI was 31.3 Gy (range = 0.1−82.3 Gy). The mean percent change in ΔSULVOI,liver for every Gy increase in the absorbed dose was −0.04 (95%CI −0.22−0.14) at p = 0.67. The SULblood and SULspleen results showed no increase. Conclusions: The [18F]FDG metabolism in the normal liver parenchyma is significantly but mildly increased after radioembolization, which can interfere with its use as a threshold for therapy response.

Toxicity comparison of yttrium-90 resin and glass microspheres radioembolization.

BACKGROUND: To investigate the clinical, hematological and biochemical toxicity differences between glass and resin yttrium-90 (90Y)-microspheres radioembolization treatment of primary and metastatic liver disease. METHODS: Between May 2014 and November 2016 all consecutive glass and resin 90Y microspheres radioembolization treatments were retrospectively analyzed. Biochemical, hematological and clinical data were collected at treatment day, two weeks, one month and three months follow-up. Post-treatment 90Y PET/CTs were assessed for the absorbed doses in non-tumorous liver volume (DNTLV) and tumor volume (DTV). Biochemical, hematological and clinical toxicity were compared between glass and resin using chi square tests and repeated ANOVA measures. Biochemical and clinical toxicity was correlated with DNTLV,total by means of Pearson correlation and independent T-tests. RESULTS: A total of 85 patients were included (n=44 glass, n=41 resin). Clinical toxicity the day after treatment (i.e. abdominal pain (p=0.000), nausea (p=0.000) and vomiting (p=0.003)) was more prevalent for resin. Biochemical and hematological toxicities were similar for both microspheres. The DNTLV,total was significantly higher in patients with REILD grade ≥3 in the resin group (43.5 versus 33.3 Gy (p=0.050)). A similar non-significant trend was seen in the glass group: 95.0 versus 69.0 Gy (p=0.144). CONCLUSIONS: The clinical, hematological and biochemical toxicity of radioembolization treatment with glass and resin is comparable, however, post-embolization syndrome related complaints are more common for resin.

Inflammatory markers and long term hematotoxicity of holmium-166-radioembolization in liver-dominant metastatic neuroendocrine tumors after initial peptide receptor radionuclide therapy.

PURPOSE: In patients with neuroendocrine tumor liver metastases, additional tumor reduction can be achieved by sequential treatment with [166Ho]-radioembolization after peptide receptor radionuclide therapy (PRRT). The aim of this study was to analyze hematotoxicity profiles, (i.e. lymphocyte and neutrophile toxicity) and the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and thrombocyte-to-lymphocyte ratio (TLR). METHODS: All patients included in the prospective HEPAR PLuS study were included in this study. Blood testing was performed at baseline (before radioembolization) and at regular intervals during 1-year follow-up. Radiological response was assessed at 3, 6, 9, and 12 months according to RECIST 1.1. Logistic regression was used to analyze the prognostic value of NLR and TLR on response. RESULTS: Thirty-one patients were included in the toxicity analysis; thirty were included in the response analysis. Three weeks after radioembolization, a significant decrease in lymphocyte count (mean change - 0.26 × 109/L) was observed. Ten patients (32.2%) experienced grade 3-4 lymphocyte toxicity. This normalized at 6 weeks and 3 months after treatment, while after 6 months a significant increase in lymphocyte count was observed. An increase in NLR and TLR at 3 weeks, compared to baseline, significantly predicted response at 3 months (AUC = 0.841 and AUC = 0.839, respectively) and at 6 months (AUC = 0.779 and AUC = 0.765). No significant relation with survival was found. CONCLUSIONS: Toxicity after sequential treatment with PRRT and [166Ho]-radioembolization is limited and temporary, while significant additional benefit can be expected. Change in NLR and TLR at 3-weeks follow-up may be valuable early predictors of response. Trial registration ClinicalTrials.gov, NCT02067988. Registered 20 February 2014, https://clinicaltrials.gov/ct2/show/record/NCT02067988 .

Dose-response relationship after yttrium-90-radioembolization with glass microspheres in patients with neuroendocrine tumor liver metastases.

BACKGROUND: In radioembolization, response is achieved through the irradiation and damaging of tumor DNA. For hepatic metastases of neuroendocrine tumors, a dose-response relationship has not been established yet. This study assesses whether increasing tumor-absorbed doses lead to increased response rates. METHODS: We included all patients who underwent yttrium-90 (90Y) glass microspheres radioembolization in our center if both pre- and post-treatment contrast-enhanced CT and post-injection PET/CT were available. Up to five hepatic tumors and the healthy hepatic tissue were delineated, and absorbed dose was quantified using post-injection PET/CT. Response was measured according to RECIST 1.1 on patient and tumor level. Linear mixed models were used to study the relationship between absorbed dose and response on tumor level. Logistic regression analysis was used on patient level to study dose-response and hepatic dose-toxicity relationships. RESULTS: A total of 128 tumors in 26 patients (31 procedures) were included in the response analysis. While correcting for confounding by tumor volume, a significant effect of response on dose was found (p = 0.0465). Geometric mean of absorbed dose for responding tumors was 170 Gy, for stable disease 101 Gy, and for progressive disease 67 Gy. No significant dose-toxicity relationship could be identified. CONCLUSION: In patients with neuroendocrine tumor liver metastases, treated with 90Y-radioembolization, a clear dose-response relationship was found. We propose to perform 90Y-radioembolization with an absolute minimum planned tumor-absorbed dose of 150 Gy.

Combining radiotherapy and focused ultrasound for pain palliation of cancer induced bone pain; a stage I/IIa study according to the IDEAL framework.

BACKGROUND: Cancer induced bone pain (CIBP) strongly interferes with patient's quality of life. Currently, the standard of care includes external beam radiotherapy (EBRT), resulting in pain relief in approximately 60% of patients. Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU) is a promising treatment modality for CIBP. METHODS: A single arm, R-IDEAL stage I/IIa study was conducted. Patients presenting at the department of radiation oncology with symptomatic bone metastases in the appendicular skeleton, as well as in the sacrum and sternum were eligible for inclusion. All participants underwent EBRT, followed by MR-HIFU within 4 days. Safety and feasibility were assessed, and pain scores were monitored for 4 weeks after completing the combined treatment. RESULTS: Six patients were enrolled. Median age was 67 years, median lesion diameter was 56,5 mm. In all patients it was logistically possible to plan and perform the MR-HIFU treatment within 4 days after EBRT. All patients tolerated the combined procedure well. Pain response was reported by 5 out of 6 patients at 7 days after completion of the combined treatment, and stabilized on 60% at 4 weeks follow up. No treatment related serious adverse events occurred. CONCLUSION: This is the first study to combine EBRT with MR-HIFU. Our results show that combined EBRT and MR-HIFU in first-line treatment of CIBP is safe and feasible, and is well tolerated by patients. Superiority over standard EBRT, in terms of (time to) pain relief and quality of life need to be evaluated in comparative (randomized) study.

Phase I feasibility study of Magnetic Resonance guided High Intensity Focused Ultrasound-induced hyperthermia, Lyso-Thermosensitive Liposomal Doxorubicin and cyclophosphamide in de novo stage IV breast cancer patients: study protocol of the i-GO study.

INTRODUCTION: In breast cancer, local tumour control is thought to be optimised by administering higher local levels of cytotoxic chemotherapy, in particular doxorubicin. However, systemic administration of higher dosages of doxorubicin is hampered by its toxic side effects. In this study, we aim to increase doxorubicin deposition in the primary breast tumour without changing systemic doxorubicin concentration and thus without interfering with systemic efficacy and toxicity. This is to be achieved by combining Lyso-Thermosensitive Liposomal Doxorubicin (LTLD, ThermoDox, Celsion Corporation, Lawrenceville, NJ, USA) with mild local hyperthermia, induced by Magnetic Resonance guided High Intensity Focused Ultrasound (MR-HIFU). When heated above 39.5°C, LTLD releases a high concentration of doxorubicin intravascularly within seconds. In the absence of hyperthermia, LTLD leads to a similar biodistribution and antitumour efficacy compared with conventional doxorubicin. METHODS AND ANALYSIS: This is a single-arm phase I study in 12 chemotherapy-naïve patients with de novo stage IV HER2-negative breast cancer. Previous endocrine treatment is allowed. Study treatment consists of up to six cycles of LTLD at 21-day intervals, administered during MR-HIFU-induced hyperthermia to the primary tumour. We will aim for 60 min of hyperthermia at 40°C-42°C using a dedicated MR-HIFU breast system (Profound Medical, Mississauga, Canada). Afterwards, intravenous cyclophosphamide will be administered. Primary endpoints are safety, tolerability and feasibility. The secondary endpoint is efficacy, assessed by radiological response.This approach could lead to optimal loco-regional control with less extensive or even no surgery, in de novo stage IV patients and in stage II/III patients allocated to receive neoadjuvant chemotherapy. ETHICS AND DISSEMINATION: This study has obtained ethical approval by the Medical Research Ethics Committee Utrecht (Protocol NL67422.041.18, METC number 18-702). Informed consent will be obtained from all patients before study participation. Results will be published in an academic peer-reviewed journal. TRIAL REGISTRATION NUMBERS: NCT03749850, EudraCT 2015-005582-23.

Additional holmium-166 radioembolisation after lutetium-177-dotatate in patients with neuroendocrine tumour liver metastases (HEPAR PLuS): a single-centre, single-arm, open-label, phase 2 study.

BACKGROUND: In patients with metastatic neuroendocrine neoplasms, the liver is the most commonly affected organ and a crucial factor for prognosis and survival. Peptide receptor radionuclide therapy can prolong progression-free survival in these patients. Additional treatment of liver disease might further improve outcomes. We aimed to investigate the safety and efficacy of additional holmium-166 (166Ho) radioembolisation after peptide receptor radionuclide therapy in patients with metastatic liver neuroendocrine neoplasms. METHODS: The Holmium Embolization Particles for Arterial Radiotherapy Plus 177Lu-Dotatate in Salvage Neuroendocrine Tumour Patients (HEPAR PLuS) study was a single-centre, phase 2 study done at the University Medical Center Utrecht (Utrecht, Netherlands). Patients, aged at least 18 years, with histologically proven grade 1 or 2 neuroendocrine neoplasms of all origins, an Eastern Cooperative Oncology Group performance status of 0-2, and three or more measurable liver metastases according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria received 166Ho-radioembolisation within 20 weeks after four cycles of peptide receptor radionuclide therapy (lutetium-177-dotatate [177Lu-dotatate]). The primary endpoint was objective liver tumour response in the treated liver volume, defined as complete response (disappearance of all lesions) or partial response (≥30% decrease in the sum of the longest diameters of the target lesions, compared with baseline measurements), according to RECIST 1.1, analysed per protocol at 3 months. Safety was assessed in all patients who received treatment. This study is registered with ClinicalTrials.gov, NCT02067988. Recruitment is completed and long-term follow-up is ongoing. FINDINGS: From Oct 15, 2014, to Sept 12, 2018, 34 patients were assessed for eligibility. 31 patients received treatment and 30 (97%) patients were available for primary endpoint assessment and completed 6 months of follow-up. Three (9%) patients were excluded at screening and one (3%) patient was treated and died before the primary endpoint and was replaced. According to the per-protocol analysis 13 (43%; 95% CI 26-63) of 30 patients achieved an objective response in the treated volume. The most frequently reported Common Terminology Criteria for Adverse Events (CTCAE) grade 3-4 clinical and laboratory toxicities within 6 months included abdominal pain (three [10%] of 31 patients), increased γ-glutamyl transpeptidase (16 [54%]), and lymphocytopenia (seven [23%]). One (3%) fatal treatment-related serious adverse event occurred (radioembolisation-induced liver disease). Two (6%) patients had serious adverse events deemed to be unrelated to treatment (gastric ulcer and perforated cholecystitis). INTERPRETATION: 166Ho-radioembolisation, as an adjunct to peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm liver metastases, is safe and efficacious. Radioembolisation can be considered in patients with bulky liver disease, including after peptide receptor radionuclide therapy. A future randomised, controlled study should investigate the added benefit of this treatment on progression-free survival. FUNDING: None.

The Focused Ultrasound Myoma Outcome Study (FUMOS); a retrospective cohort study on long-term outcomes of MR-HIFU therapy.

OBJECTIVES: Since 2004, uterine fibroids have been treated with MR-HIFU, but there are persevering doubts on long-term efficacy to date. In the Focused Ultrasound Myoma Outcome Study (FUMOS), we evaluated long-term outcomes after MR-HIFU therapy, primarily to assess the reintervention rate. METHODS: Data was retrospectively collected from 123 patients treated with MR-HIFU at our hospital from 2010 to 2017. Follow-up duration and baseline (MRI) characteristics were retrieved from medical records. Treatment failures, adverse events, and the nonperfused volume percentage (NPV%) were determined. Patients received a questionnaire about reinterventions, recovery time, satisfaction, and pregnancy outcomes. Restrictive treatment protocols were compared with unrestrictive (aiming for complete ablation) treatments. Subgroups were analyzed based on the achieved NPV < 50 or ≥ 50%. RESULTS: Treatment failures occurred in 12.1% and the number of adverse events was 13.7%. Implementation of an unrestrictive treatment protocol significantly (p = 0.006) increased the mean NPV% from 37.4% [24.3-53.0] to 57.4% [33.5-76.5]. At 63.5 ± 29.0 months follow-up, the overall reintervention rate was 33.3% (n = 87). All reinterventions were performed within 34 months follow-up, but within 21 months in the unrestrictive group. The reintervention rate significantly (p = 0.002) decreased from 48.8% in the restrictive group (n = 43; follow-up 87.5 ± 7.3 months) to 18.2% in the unrestrictive group (n = 44; follow-up 40.0 ± 22.1 months). The median recovery time was 2.0 [1.0-7.0] days. Treatment satisfaction rate was 72.4% and 4/11 women completed family planning after MR-HIFU. CONCLUSIONS: The unrestrictive treatment protocol significantly increased the NPV%. Unrestrictive MR-HIFU treatments led to acceptable reintervention rates comparable to other reimbursed uterine-sparing treatments, and no reinterventions were reported beyond 21 months follow-up. KEY POINTS: • All reinterventions were performed within 34 months follow-up, but in the unrestrictive treatment protocol group, no reinterventions were reported beyond 21 months follow-up. • The NPV% was negatively associated with the risk of reintervention; thus, operators should aim for complete ablation during MR-guided HIFU therapy of uterine fibroids. • Unrestrictive treatments have led to acceptable reintervention rates after MR-guided HIFU therapy compared to other reimbursed uterine-sparing treatments.

A Pilot Study on Hepatobiliary Scintigraphy to Monitor Regional Liver Function in 90Y Radioembolization.

Radioembolization is increasingly used as a bridge to resection (i.e., radiation lobectomy). It combines ipsilateral tumor control with the induction of contralateral hypertrophy to facilitate lobar resection. The aim of this pilot study was to investigate the complementary value of hepatobiliary scintigraphy (HBS) before and after radioembolization in the assessment of the future remnant liver. Methods: Consecutive patients with liver tumors who underwent HBS before and after 90Y radioembolization were included. Regional (treated/nontreated) and whole liver function and volume were determined on HBS and CT. Changes in regional liver function and volume were correlated with the functional liver absorbed doses, determined on 90Y PET/CT. In addition, the correlation between liver volume and function change was evaluated. Results: Thirteen patients (10 hepatocellular carcinoma, 3 metastatic colorectal carcinoma) were included. Liver function of the treated part declined after radioembolization (HBS-pre, 4.0%/min/m2; HBS-post, 1.9%/min/m2; P = 0.001), whereas the function of the nontreated part increased (HBS-pre, 1.4%/min/m2; HBS-post, 2.8%/min/m2; P = 0.009). Likewise, treated volume decreased (pretreatment, 1,118.7 cm3; posttreatment, 870.7 cm3; P = 0.003), whereas the nontreated volume increased (pretreatment, 412.7 cm3; posttreatment, 577.6 cm3; P = 0.005). Bland-Altman analysis revealed a large bias (29%) between volume decrease and function decrease in the treated part and wide limits of agreement (-7.7%-65.6%). The bias between volume and function change was smaller (±6.0%) in the nontreated part of the liver, but limits of agreement were still wide (-117.9%-106.7%). Conclusion: Radioembolization induces regional changes in liver function that are accurately detected by HBS. Limits of agreement between function and volume changes were wide, showing large individual differences. This finding indicates that HBS may have a complementary role in the management of patients for radiation lobectomy.

Hepatobiliary Imaging in Liver-directed Treatments.

Hepatobiliary scintigraphy (HBS) is an emerging tool in the assessment of hepatic function. This nuclear imaging technique can be used to calculate both global and regional liver function. It has proven to be the most reliable way of assessing the distribution of liver function, especially in patients with impaired liver function due to, for example, cirrhosis or after chemotherapy. There are two types of tracers: Technetium-99m with a type of iminodiacetic acid and Technetium-99m galactosyl human serum albumin. The main indication for HBS is the assessment of the future liver remnant function in patients scheduled to undergo hemihepatectomy; to predict the risk of posthepatectomy liver failure. Another upcoming indication is the use of HBS in patients undergoing radioembolization.

Magnetic Resonance Imaging-Guided High-Intensity Focused Ultrasound is a Noninvasive Treatment Modality for Patients with Abdominal Wall Endometriosis.

Two women (29 and 35 years of age) presented with an abdominal wall mass in close proximity to a cesarean scar. The main complaints consisted of pain at the site of the mass with catamenial exacerbations. Clinical and imaging findings were consistent with abdominal wall endometriosis in both cases. First, hormonal treatment was started, which proved unsuccessful. Typically, at this point, the proposed treatment would be wide surgical excision. Alternatively, magnetic resonance imaging-guided high-intensity focused ultrasound treatment was offered with the goal to diminish pain complaints noninvasively. Upon treatment, both patients' complaints diminished although some cyclic pain persisted. Overall, these cases show that magnetic resonance imaging-guided high-intensity focused ultrasound can be used as a noninvasive treatment method to reduce complaints in patients with abdominal wall endometriosis.

Efficacy of Radioembolization with 166Ho-Microspheres in Salvage Patients with Liver Metastases: A Phase 2 Study.

Radioembolization of liver malignancies with 166Ho-microspheres has been shown to be safe in a phase 1 dose-escalation study. The purpose of this study was to investigate the efficacy of 166Ho radioembolization. Methods: In this prospective single-arm study, 56 patients were enrolled, all with liver metastases refractory to systemic therapy and ineligible for surgical resection. The primary outcome was a response by 2 target lesions on triphasic liver CT scans 3 mo after therapy, as assessed using RECIST, version 1.1. Secondary outcomes included overall tumor response, time to imaging progression, overall survival, toxicity, quality of life, and quantification of the microspheres on SPECT and MRI. Results: Between May 2012 and March 2015, 38 eligible patients were treated, one of whom was not evaluable. In 27 (73%) of 37 patients, the target lesions showed complete response, partial response, or stable disease (disease control) at 3 mo (95% confidence interval [CI], 57%-85%). The median overall survival was 14.5 mo (95% CI, 8.6-22.8 mo). For colorectal cancer patients (n = 23), the median overall survival was 13.4 mo (95% CI, 8.2-15.7 mo). Grade 3 or 4 toxic events after treatment (according to the Common Terminology Criteria for Adverse Events, version 4.03) included abdominal pain (in 18% of patients), nausea (8%), ascites (3%), fatigue (3%), gastric stenosis (3%), hepatic failure (3%), liver abscesses (3%), paroxysmal atrial tachycardia (3%), thoracic pain (3%), upper gastrointestinal hemorrhage (3%), and vomiting (3%). On SPECT, 166Ho could be quantified with high accuracy and precision, with a mean overestimation of 9.3% ± 7.1% in the liver. Conclusion: Radioembolization with 166Ho-microspheres induced a tumor response with an acceptable toxicity profile in salvage patients with liver metastases.

Anatomic versus Metabolic Tumor Response Assessment after Radioembolization Treatment.

PURPOSE: To assess applicability of metabolic tumor response assessment on 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) after radioembolization (RE) in patients with colorectal liver metastases (CRLM) by comparison with one-dimensional size-based response assessment on MR imaging. MATERIALS AND METHODS: This prospective cohort study comprised 38 patients with CRLM undergoing RE. MR imaging and 18F-FDG PET/CT imaging were performed at baseline, 1 month (n = 38), and 3 months (n = 21). Longest tumor diameter (LTD) reduction on MR imaging at these time points was compared with reduction in total lesion glycolysis (TLG) on 18F-FDG PET/CT. Hepatic response was compared between RECIST and total liver TLG and correlated with overall survival (OS). RESULTS: TLG and LTD were positively correlated in 106 analyzed metastases (38 patients) at 1 month and 58 metastases (22 patients) at 3 months. Agreement was poor, with LTD underestimating TLG response. A significant association with prolonged OS was found in total liver TLG at 1 month (HR 0.64, P < .01) and 3 months (HR 0.43, P < .01). For LTD, a significant association with OS was found at 3 months (HR 0.10, P < .01). Important differences in liver response classification were found, with total liver TLG identifying more patients and situations where there appeared to be treatment benefit compared with RECIST. CONCLUSIONS: TLG response assessment on 18F-FDG PET/CT appears to be more sensitive and accurate, especially at early follow-up, than size-based response assessment on MR imaging in patients with CRLM treated by RE. Semiautomated liver response assessment with total liver TLG is objective, reproducible, rapid, and prognostic.

Recommendations for radioembolisation after liver surgery using yttrium-90 resin microspheres based on a survey of an international expert panel.

INTRODUCTION: Guidelines on how to adjust activity in patients with a history of liver surgery who are undergoing yttrium-90 radioembolisation (90Y-RE) are lacking. The aim was to study the variability in activity prescription in these patients, between centres with extensive experience using resin microspheres 90Y-RE, and to draw recommendations on activity prescription based on an expert consensus. METHODS: The variability in activity prescription between centres was investigated by a survey of international experts in the field of 90Y-RE. Six representative post-surgical patients (i.e. comparable activity prescription, different outcome) were selected. Information on patients' disease characteristics and data needed for activity calculation was presented to the expert panel. Reported was the used method for activity prescription and whether, how and why activity reduction was found indicated. RESULTS: Ten experts took part in the survey. Recommendations on activity reduction were highly variable between the expert panel. The median intra-patient range was 44 Gy (range 18-55 Gy). Reductions in prescribed activity were recommended in 68% of the cases. In consensus, a maximum DTarget of 50 Gy was recommended. CONCLUSION: With a current lack of guidelines, large variability in activity prescription in post-surgical patients undergoing 90Y-RE exists. In consensus, DTarget ≤50 Gy is recommended. KEY POINTS: • BSA method does not account for a decreased remnant liver volume after surgery. • In post-surgical patients, a volume-based activity determination method is recommended. • In post-surgical patients, a mean D Target of ≤ 50Gy should be aimed for.