MRI-guided stereotactic ablative body radiotherapy versus CT-guided percutaneous irreversible electroporation for locally advanced pancreatic cancer (CROSSFIRE): a single-centre, open-label, randomised phase 2 trial.

BACKGROUND: Pancreatic ductal adenocarcinoma is an aggressive disease with a dismal prognosis. Stage III locally advanced pancreatic cancer is considered unresectable and current palliative chemotherapy regimens only modestly improve survival. Guidelines suggest chemoradiation or stereotactic ablative body radiotherapy (SABR) could be beneficial in certain circumstances. Other local treatments such as irreversible electroporation could enhance patient outcomes by extending survival while preserving quality of life. We aimed to compare the efficacy and safety of MRI-guided SABR versus CT-guided percutaneous irreversible electroporation following standard FOLFIRINOX chemotherapy. METHODS: CROSSFIRE was an open-label, randomised phase 2 superiority trial conducted at the Amsterdam University Medical Centre (Amsterdam, Netherlands). Eligible patients were aged 18 years or older with confirmed histological and radiological stage III locally advanced pancreatic cancer. The maximum tumour diameter was 5 cm and patients had to be pretreated with three to eight cycles of FOLFIRINOX. Patients were randomly assigned (1:1) to MRI-guided SABR (five fractions of 8 Gy delivered on non-consecutive days) or CT-guided percutaneous irreversible electroporation using a computer-generated variable block randomisation model. The primary endpoint was overall survival from randomisation, assessed in the intention-to-treat population. Safety was assessed in the per-protocol population. A prespecified interim futility analysis was done after inclusion of half the original sample size, with a conditional probability of less than 0·2 resulting in halting of the study. The trial was registered at ClinicalTrials.gov, NCT02791503. FINDINGS: Between May 1, 2016, and March 31, 2022, 68 patients were enrolled and randomly assigned to SABR (n=34) or irreversible electroporation (n=34), of whom 64 were treated according to protocol. Of the 68 participants, 36 (53%) were male and 32 (47%) were female, with a median age of 65 years (IQR 57-70). Median overall survival from randomisation was 16·1 months (95% CI 12·1-19·4) in the SABR group versus 12·5 months (10·9-17·0) in the irreversible electroporation group (hazard ratio [HR] 1·39 [95% CI 0·84-2·30]; p=0·21). The conditional probability to demonstrate superiority of either technique was 0·13; patient accrual was therefore stopped early for futility. 20 (63%) of 32 patients in the SABR group versus 19 (59%) of 32 patients in the irreversible electroporation group had adverse events (p=0·8) and five (16%) patients in the SABR group versus eight (25%) in the irreversible electroporation group had grade 3-5 adverse events (p=0·35). The most common grade 3-4 adverse events were cholangitis (two [6%] in the SABR group vs one [3%] in the irreversible electroporation group), abdominal pain (one [3%] vs two [6%]), and pancreatitis (none vs two [6%]). One (3%) patient in the SABR group and one (3%) in the irreversible electroporation group died from a treatment-related adverse event. INTERPRETATION: CROSSFIRE did not identify a difference in overall survival or incidence of adverse events between MRI-guided SABR and CT-guided percutaneous irreversible electroporation after FOLFIRINOX. Future studies should further assess the added value of local ablative treatment over chemotherapy alone. FUNDING: Adessium Foundation, AngioDynamics.

Local Treatment of Colorectal Liver Metastases in the Presence of Extrahepatic Disease: Survival Outcomes from the Amsterdam Colorectal Liver Met Registry (AmCORE).

BACKGROUND: The simultaneous presence of colorectal liver metastases (CRLMs) and extrahepatic metastases in patients with colorectal cancer (CRC) can be considered a relative contraindication for local treatment with curative intent. This study aims to assess the survival outcomes of patients with CRLMs and extrahepatic metastases after comprehensive local treatment of all metastatic sites. METHODS: Patients with CRLMs who received local treatment of all metastatic sites were extracted from the prospective AmCORE registry database and subdivided into two groups: CRLM only vs. CRLM and extrahepatic metastasis. To address potential confounders, multivariate analysis was performed. The primary endpoint was overall survival (OS). RESULTS: In total, 881 patients with CRLM only and 60 with CRLM and extrahepatic disease were included, and the median OS was 55.7 months vs. 42.7 months, respectively. Though OS was significantly lower in patients with concomitant extrahepatic metastases (HR 1.477; 95% CI 1.029-2.121; p = 0.033), the survival curve plateaued after 6.2 years. Extrahepatic manifestations were pulmonary (43.3%), peritoneal (16.7%) and non-regional lymph node metastases (10.0%). In patients with pulmonary and non-regional lymph node metastases, OS did not significantly differ from patients with CRLM-only disease; concomitant peritoneal metastases showed an inferior OS (HR 1.976; 95% CI 1.017-3.841, p = 0.041). CONCLUSIONS: In this comparative series, OS was inferior for patients with multi-organ metastatic CRC versus patients with CRLMs alone. Nonetheless, the long-term survival curve plateau seemed to justify local treatment in a subset of patients with multi-organ metastatic CRC, especially for patients with CRLMs and pulmonary or lymph node metastases.

The Added Value of Transcatheter CT Hepatic Angiography (CTHA) Image Guidance in Percutaneous Thermal Liver Ablation: An Experts' Opinion Pictorial Essay.

With the rapidly evolving field of image-guided tumor ablation, there is an increasing demand and need for tools to optimize treatment success. Known factors affecting the success of (non-)thermal liver ablation procedures are the ability to optimize tumor and surrounding critical structure visualization, ablation applicator targeting, and ablation zone confirmation. A recent study showed superior local tumor progression-free survival and local control outcomes when using transcatheter computed tomography hepatic angiography (CTHA) guidance in percutaneous liver ablation procedures. This pictorial review provides eight clinical cases from three institutions, MD Anderson (Houston, TX, USA), Gustave Roussy (Paris, France), and Amsterdam UMC (Amsterdam, The Netherlands), with the intent to demonstrate the added value of real-time CTHA guided tumor ablation for primary liver tumors and liver-only metastatic disease. The clinical illustrations highlight the ability to improve the detectability of the initial target liver tumor(s) and identify surrounding critical vascular structures, detect 'vanished' and/or additional tumors intraprocedurally, differentiate local tumor progression from non-enhancing scar tissue, and promptly detect and respond to iatrogenic hemorrhagic events. Although at the cost of adding a minor but safe intervention, CTHA-guided liver tumor ablation minimizes complications of the actual ablation procedure, reduces the number of repeat ablations, and improves the oncological outcome of patients with liver malignancies. Therefore, we recommend adopting CTHA as a potential quality-improving guiding method within the (inter)national standards of practice.

Recurrent Colorectal Liver Metastases: Upfront Local Treatment versus Neoadjuvant Systemic Therapy Followed by Local Treatment (COLLISION RELAPSE): Study Protocol of a Phase III Prospective Randomized Controlled Trial.

PURPOSE: The objective of the COLLISION RELAPSE trial is to prove or disprove superiority of neoadjuvant systemic therapy followed by repeat local treatment (either thermal ablation and/or surgical resection), compared to repeat local treatment alone, in patients with at least one recurrent locally treatable CRLM within one year and no extrahepatic disease. METHODS: A total of 360 patients will be included in this phase III, multicentre randomized controlled trial. The primary endpoint is overall survival. Secondary endpoints are distant progression-free survival, local tumour progression-free survival analysed per patient and per tumour, systemic therapy-related toxicity, procedural morbidity and mortality, length of hospital stay, pain assessment and quality of life, cost-effectiveness ratio and quality-adjusted life years. DISCUSSION: If the addition of neoadjuvant systemic therapy to repeat local treatment of CRLM proves to be superior compared to repeat local treatment alone, this may lead to a prolonged life expectancy and increased disease-free survival at the cost of possible systemic therapy-related side effects. LEVEL OF EVIDENCE: Level 1, phase III randomized controlled trial. TRIAL REGISTRATION: NCT05861505. May 17, 2023.

Efficacy of Thermal Ablation for Small-Size (0-3 cm) versus Intermediate-Size (3-5 cm) Colorectal Liver Metastases: Results from the Amsterdam Colorectal Liver Met Registry (AmCORE).

PURPOSE: Thermal ablation is widely recognized as the standard of care for small-size unresectable colorectal liver metastases (CRLM). For larger CRLM safety, local control and overall efficacy are not well established and insufficiently validated. The purpose of this comparative series was to analyze outcomes for intermediate-size versus small-size CRLM. MATERIAL AND METHODS: Patients treated with thermal ablation between December 2000 and November 2021 for small-size and intermediate-size CRLM were included. The primary endpoints were complication rate and local control (LC). Secondary endpoints included local tumor progression-free survival (LTPFS) and overall survival (OS). RESULTS: In total, 59 patients were included in the intermediate-size (3-5 cm) group and 221 in the small-size (0-3 cm) group. Complications were not significantly different between the two groups (p = 0.546). No significant difference between the groups was found in an overall comparison of OS (HR 1.339; 95% CI 0.824-2.176; p = 0.239). LTPFS (HR 3.388; p < 0.001) and LC (HR 3.744; p = 0.004) were superior in the small-size group. Nevertheless, the 1-, 3-, and 5-year LC for intermediate-size CRLM was still 93.9%, 85.4%, and 81.5%, and technical efficacy improved over time. CONCLUSIONS: Thermal ablation for intermediate-size unresectable CRLM is safe and induces long-term LC in the vast majority. The results of the COLLISION-XL trial (unresectable colorectal liver metastases: stereotactic body radiotherapy versus microwave ablation-a phase II randomized controlled trial for CRLM 3-5 cm) are required to provide further clarification of the role of local ablative methods for intermediate-size unresectable CRLM.

The Added Diagnostic Value of Transcatheter CT Hepatic Arteriography for Intraprocedural Detection of Previously Unknown Colorectal Liver Metastases During Percutaneous Ablation and Impact on the Definitive Treatment Plan.

PURPOSE: This study assessed the diagnostic value of CT hepatic arteriography (CTHA) for the intraprocedural detection of previously unknown colorectal liver metastases (CRLM) and the impact on the definitive treatment plan. MATERIALS AND METHODS: All patients treated with CTHA-guided percutaneous ablation for CRLM between January 2012 and March 2022 were identified from the Amsterdam Colorectal Liver Met Registry (AmCORE). Radiology reports of the ablative procedure and follow-up imaging were reviewed to see if (a) previously unknown CRLM were detected intra-procedurally and if (b) new CRLM, potentially missed on CTHA, appeared within 6 months following the procedure; three abdominal radiologists re-reviewed the baseline CTHA scans of these patients with early recurrence. To ratify immediate ablations of concomitantly detected CRLM, the upper limit of false positives was predefined at 10%. RESULTS: One hundred and fifty-two patients were included. With CTHA, a total of 17 additional tumours in 15 patients were diagnosed and treated immediately, two representing disappeared tumours following systemic chemotherapy. Compared to the conventional contrast-enhanced (ce)CT, ceMRI and 18F-FDG PET-CT, adding CTHA was superior for the detection of CRLM (P < .001). Within 12 months of follow-up 121, new CRLM appeared in 49/152 patients (32.2%); retrospective blinded assessment revealed 56 to already be visible on the baseline CTHA scan (46%); four lesions without substrate on follow-up scans were considered false positives (n = 4/60; 7%). Arterial ring enhancement was the most frequently reported imaging characteristic (n = 45/60; 75%). CONCLUSION: The subsequent use of CTHA has added value for the detection of previously unknown and vanished CRLM. Taking into account the low number of false positives (7%) and the favourable safety profile of percutaneous ablation, we believe that immediate ablation of typical ring-enhancing supplementary tumours is justified and sufficiently validated. LEVEL OF EVIDENCE: Level 3; individual cross-sectional study with consistently applied reference standard and blinding.

Unresectable Intermediate-Size (3-5 cm) Colorectal Liver Metastases: Stereotactic Ablative Body Radiotherapy Versus Microwave Ablation (COLLISION-XL): Protocol of a Phase II/III Multicentre Randomized Controlled Trial.

BACKGROUND: Although microwave ablation (MWA) has a low complication rate and good efficacy for small-size (≤ 3 cm) colorectal liver metastases (CRLM), local control decreases with increasing size. Stereotactic body radiotherapy (SBRT) is gaining interest as a potential means to treat intermediate-size CRLM and might be less susceptible to increasing volume. The objective of this study is to compare the efficacy of MWA to SBRT in patients with unresectable, intermediate-size (3-5 cm) CRLM. METHODS: In this two-arm, multicentre phase II/ III randomized controlled trial, 68 patients with 1-3 unresectable, intermediate-size CRLM suitable for both MWA and SBRT, will be included. Patients will be treated with MWA or SBRT as randomised. The Primary endpoint is local tumour progression-free survival (LTPFS) at 1 year (intention-to-treat analysis). Main secondary endpoints are overall survival, overall and distant progression-free survival (DPFS), local control (LC) and procedural morbidity and mortality and assessment of pain and quality of life. DISCUSSION: Current guidelines lack clear recommendations for the local treatment of liver only intermediate-size, unresectable CRLM and studies comparing curative intent SBRT and thermal ablation are scarce. Although safety and feasibility to eradicate tumours ≤ 5 cm have been established, both techniques suffer from lower LTPFS and LC rates for larger-size tumours. For the treatment of unresectable intermediate-size CRLM clinical equipoise has been reached. We have designed a two-armed phase II/ III randomized controlled trial directly comparing SBRT to MWA for unresectable CRLM 3-5 cm. LEVEL OF EVIDENCE: Level 1, phase II/ III Randomized controlled trial. TRIAL REGISTRATION: NCT04081168, September 9th 2019.

Tissue Resistance Decrease during Irreversible Electroporation of Pancreatic Cancer as a Biomarker for the Adaptive Immune Response and Survival.

PURPOSE: To correlate irreversible electroporation (IRE) procedural resistance changes with survival outcomes and the IRE-induced systemic immune response in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Data on IRE procedural tissue resistance (R) features and survival outcomes were collected from patients with LAPC treated within the context of 2 prospective clinical trials in a single tertiary center. Preprocedural and postprocedural peripheral blood samples were prospectively collected for immune monitoring. The change (ie, decrease) in R during the first 10 test pulses (ΔR10p) and during the total procedure (ΔRtotal) were calculated. Patients were divided in 2 groups on the basis of the median change in R (large ΔR vs small ΔR) and compared for differences in overall survival (OS) and progression-free survival and immune cell subsets. RESULTS: A total of 54 patients were included; of these, 20 underwent immune monitoring. Linear regression modeling showed that the first 10 test pulses reflected the change in tissue resistance during the total procedure appropriately (P < .001; R2 = 0.91). A large change in tissue resistance significantly correlated with a better OS (P = .026) and longer time to disease progression (P = .045). Furthermore, a large change in tissue resistance was associated with CD8+ T cell activation through significant upregulation of Ki-67+ (P = .02) and PD-1+ (P = .047). Additionally, this subgroup demonstrated significantly increased expression of CD80 on conventional dendritic cells (cDC1; P = .027) and PD-L1 on immunosuppressive myeloid-derived suppressor cells (P = .039). CONCLUSIONS: IRE procedural resistance changes may serve as a biomarker for survival and IRE-induced systemic CD8+ T cell and cDC1 activation.

Transcatheter CT arteriography-guided irreversible electroporation of locally advanced pancreatic adenocarcinoma: A pictorial essay.

Visibility of the tumour and its surroundings during the ablative procedure is crucial for optimal treatment planning, needle placement, ablation zone coverage and postprocedural control. The use of transcatheter CT arteriography providing real-time image guidance has proven to be of additional value for thermal liver ablation. The general advantages of the technique could be of value for other indications and ablation techniques as well, especially when requiring multiple needle placements in the vicinity of precarious vascular structures. This pictorial essay presents six clinical cases that illustrate transcatheter CT arteriography guidance during the treatment of locally advanced pancreatic cancer with irreversible electroporation. The illustrations highlight the technique's ability to improve visibility of vascular structures and the advantage of real-time monitoring and treatment of intraprocedural vascular complications. The use of transcatheter CT arteriography can support the interventionalist with respect to periprocedural safety and accuracy of electrode placement for pancreatic irreversible electroporation.

The Diagnostic Value of Multifrequency Tympanometry in Patients with Ménière's Disease: A Prospective Analysis.

INTRODUCTION: Diagnosing Ménière's disease (MD) by its characteristics such as episodes of vertigo, fluctuating hearing loss, and tinnitus with aural fullness remains challenging. Available tests evaluating the presence of endolymphatic hydrops (EH) are often expensive or time assuming. An in-office quick and simple non-invasive diagnostic test is multifrequency tympanometry (MFT). It can measure conductance at 2 kHz probe tones, which was demonstrated to reflect variations in cochlear pressure. Previous studies investigating MFT as a diagnostic test for MD showed conflicting outcomes possibly biased by their retrospective design. METHODS: We prospectively collected MFT results (Y width) in patients with dizziness and compared MFT test results in affected (group 1) and unaffected (group 2) ears of 37 MD subjects and in control ears of 33 non-MD subjects (group 3). RESULTS: The mean value of the Y width in affected ears was 315.6 ± 70.2 daPa compared to 292.3 ± 98.6 daPa in unaffected ears in MD subjects and 259.4. ± 60.6 daPa in the non-MD group. A positive test result (i.e., a Y width of 235 daPa or more) was found in 35 ears in the MD group, 21 times involving the affected ear and 14 times involving the unaffected ear, compared to 16 in the non-MD group. No significant differences between the three groups could be demonstrated (p > 0.05). We found a sensitivity of 58.3% and specificity of 66.3% for detecting EH in an affected ear in MD subjects. CONCLUSION: There is a trend towards increased conductance tympanometry in affected ears. However, we noticed a high false positive rate of MFT and do not support standardized use of MFT as an additional diagnostic tool for detecting EH in MD patients. A negative test result on the contrary is unlikely related to EH.

Volume-outcome relationship in intra-abdominal robotic-assisted surgery: a systematic review.

As robotic-assisted surgery (RAS) expands to smaller centres, platforms are shared between specialities. Healthcare providers must consider case volume and mix required to maintain quality and cost-effectiveness. This can be informed, in-part, by the volume-outcome relationship. We perform a systematic review to describe the volume-outcome relationship in intra-abdominal robotic-assisted surgery to report on suggested minimum volumes standards. A literature search of Medline, NICE Evidence Search, Health Technology Assessment Database and Cochrane Library using the terms: "robot*", "surgery", "volume" and "outcome" was performed. The included procedures were gynecological: hysterectomy, urological: partial and radical nephrectomy, cystectomy, prostatectomy, and general surgical: colectomy, esophagectomy. Hospital and surgeon volume measures and all reported outcomes were analysed. 41 studies, including 983,149 procedures, met the inclusion criteria. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale and the retrieved data was synthesised in a narrative review. Significant volume-outcome relationships were described in relation to key outcome measures, including operative time, complications, positive margins, lymph node yield and cost. Annual surgeon and hospital volume thresholds were described. We concluded that in centres with an annual volume of fewer than 10 cases of a given procedure, having multiple surgeons performing these procedures led to worse outcomes and, therefore, opportunities should be sought to perform other complimentary robotic procedures or undertake joint cases.

IUCrData launches Raw Data Letters.

A new category of articles - Raw Data Letters - is introduced to IUCrData.

Proximal Interphalangeal Joint Arthroplasty Using a Silicone Implant: A Comparison Between Integra and NeuFlex in 72 Cases.

BACKGROUND: Osteoarthritis of the hand can lead to pain, stiffness, and deformation, and thus to functional disability. The purpose of this study was to compare short-term clinical outcomes of 2 silicone proximal interphalangeal (PIP) joint implants, NeuFlex and Integra, in patients with primary osteoarthritis. METHODS: We included 72 PIP joints, of which 40 were replaced by a NeuFlex implant and 32 by an Integra implant. The average follow-up was 12 months for the Integra group and 16 months for the NeuFlex group. RESULTS: There was no change in active flexion preoperatively and postoperatively. Extension lag and Disabilities of the Arm, Shoulder, and Hand score decreased substantially in both groups, whereas grip strength and Patient-Specific Functional Scale (PSFS) score increased. All patients were satisfied. Between groups, there was a significant difference in the PSFS score, in favor of the Integra group. CONCLUSIONS: Both implants have excellent results, but more research is needed with more patients to prevent bias and to determine the long-term outcome of these implants.

The perceived quality of video consultations in geriatric outpatient care by early adopters.

PURPOSE: The COVID-19 pandemic caused rapid implementation and upscaling of video consulting. This study examined the perceived quality of care delivered through video consulting at a geriatric outpatient clinic, and how this related to adoption issues and barriers early adopting professionals found themselves confronted with. METHODS: We performed a qualitative study using semi-structured interviews with healthcare professionals complemented by the views of geriatric patients, family caregivers and medical secretaries. Participants from five academic centers and six teaching hospitals were included. Three researchers conducted the interviews, coded the data, and used thematic analysis. RESULTS: Interviews were conducted with 13 healthcare professionals, 8 patients, 7 family caregivers, and 4 medical secretaries. From these early adopters, we infer five criteria positively contributing to perceived quality of care provided by video consulting: (1) the patient has an intact cognitive function; (2) a family caregiver with digital literacy can be present; (3) doctor and patient already have an established relationship; (4) no immediate need for physical examination or intervention; and (5) the prior availability of a comprehensive and concise medical history. Overall, the uptake of video consulting in geriatric outpatient care appeared to be slow and laborious due to several implementation barriers. CONCLUSION: The implementation of video consulting use among geriatricians and geriatric patients at the geriatric outpatient clinic was slow due to the absence of many facilitating factors, but video consulting might be offered as an alternative to face-to-face follow-up to suitable patients in geriatric outpatient clinics.

Pneumococcal genetic variability in age-dependent bacterial carriage.

The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort - all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort (h2 = 0.10, 95% CI 0.00-0.69) and stronger evidence in the second cohort (h2 = 0.56, 95% CI 0.23-0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort (h2serotype = 0.07, 95% CI 0.04-0.14 and h2GPSC = 0.06, 95% CI 0.03-0.13) and the second cohort (h2serotype = 0.11, 95% CI 0.05-0.21 and h2GPSC = 0.20, 95% CI 0.12-0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10-9) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations.

Ex vivo-expanded human CD19+TIM-1+ regulatory B cells suppress immune responses in vivo and are dependent upon the TIM-1/STAT3 axis.

Regulatory B cells (Breg) are a heterogenous population with immune-modulating functions. The rarity of human IL-10+ Breg makes translational studies difficult. Here we report ex vivo expansion of human B cells with in vivo regulatory function (expBreg). CD154-stimulation of human CD19+ B cells drives >900-fold expansion of IL-10+ B cells that is maintained in culture for 14 days. Whilst expBreg-mediated suppressive function is partially dependent on IL-10 expression, CRISPR-mediated gene deletions demonstrate predominant roles for TIM-1 and CD154. TIM-1 regulates STAT3 signalling and modulates downstream suppressive function. In a clinically relevant humanised mouse model of skin transplantation, expBreg prolongs human allograft survival. Meanwhile, CD19+CD73-CD25+CD71+TIM-1+CD154+ Breg cells are enriched in the peripheral blood of human donors with cutaneous squamous cell carcinoma (SCC). TIM-1+ and pSTAT3+ B cells are also identified in B cell clusters within histological sections of human cutaneous SCC tumours. Our findings thus provide insights on Breg homoeostasis and present possible targets for Breg-related therapies.

Construct Validity of the Steep Ramp Test for Assessing Cardiorespiratory Fitness in Patients With Breast Cancer and the Effect of Chemotherapy-Related Symptom Burden.

OBJECTIVE: To investigate the construct validity of the Steep Ramp Test (SRT) by longitudinally comparing the correlation between maximum short exercise capacity of the SRT and direct measurements of peak oxygen consumption (Vo2peak) during or shortly after treatment in patients with breast cancer and the potential effect of chemotherapy-induced symptom burden. DESIGN: Cross-sectional. SETTING: Multicenter. PARTICIPANTS: We used data from 2 studies that included women with breast cancer treated with chemotherapy, resulting in 274 observations. A total of 161 patients (N=161) performed the cardiopulmonary exercise test and the SRT in 2 test sessions on different time points around chemotherapy treatment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue was assessed with the Multidimensional Fatigue Inventory, and nausea and vomiting and pain by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The longitudinal correlation between the maximum short exercise capacity and Vo2peak was investigated using a linear mixed model. Interaction terms were added to the model to investigate whether the correlation varied by symptom burden. RESULTS: We found a statistically significant moderate correlation between Vo2peak and maximum short exercise capacity (0.61; 95% confidence interval, 0.51-0.70; P<.01) over time. This correlation was slightly attenuated (-0.07; 95% confidence interval, -0.13 to 0.00; P=.04) in patients with chemotherapy-related nausea and vomiting, indicating smaller correlations of Vo2peak with the maximum short exercise capacity with increasing symptom burden. Pain and fatigue did not significantly modify the correlation. CONCLUSIONS: The SRT can only be used as a proxy for changes in aerobic capacity with great caution and with attention for the level of nausea and vomiting.

Competing magnetic states andM-Hloop splitting in core-shell NiO nanoparticles.

Magnetic relaxation in a nanoparticles system depends on the intra-particle interactions, reversal mechanism, the anisotropy field, easy axis distribution, particle volume, lattice defects, surface defects, materials composite, etc. Here we report the competing magnetic states between superparamagnetic blocking and Néel transition states in 14 nm core-shell NiO nanoparticles. A crossover temperature of 50 K was observed for both these states from the zero field cooled/field cooled magnetization curves taken at different fields. At crossover temperature, an interestingM-Hloop splitting is observed which is attributed to the slow spin relaxation. This anomalousM-Hloop splitting behaviour was found to be particle size dependent and suppressed for diameters above and below 14 nm which indicates a critical size for these competing magnetic states. Additional neutron diffraction experiments confirmed this observation. This experimental study provides a new insight for the understanding of intra-particle interactions in fine antiferromagnetic nanoparticles and obtained results are an important step towards deeper understanding of the competing/non-competing modes between superparamagnetic blocked and Néel transition states.

Improved Outcomes of Thermal Ablation for Colorectal Liver Metastases: A 10-Year Analysis from the Prospective Amsterdam CORE Registry (AmCORE).

BACKGROUND: To analyze long-term oncological outcomes of open and percutaneous thermal ablation in the treatment of patients with colorectal liver metastases (CRLM). METHODS: This assessment from a prospective, longitudinal tumor registry included 329 patients who underwent 541 procedures for 1350 CRLM from January 2010 to February 2021. Three cohorts were formed: 2010-2013 (129 procedures [53 percutaneous]), 2014-2017 (206 procedures [121 percutaneous]) and 2018-2021 (206 procedures [135 percutaneous]). Local tumor progression-free survival (LTPFS) and overall survival (OS) data were estimated using the Kaplan-Meier method. Potential confounding factors were analyzed with uni- and multivariable Cox regression analyses. RESULTS: LTPFS improved significantly over time for percutaneous ablations (2-year LTPFS 37.7% vs. 69.0% vs. 86.3%, respectively, P < .0001), while LTPFS for open ablations remained reasonably stable (2-year LTPFS 87.1% [2010-2013], vs. 92.7% [2014-2017] vs. 90.2% [2018-2021], P = .12). In the latter cohort (2018-2021), the open approach was no longer superior regarding LTPFS (P = .125). No differences between the three cohorts were found regarding OS (P = .088), length of hospital stay (open approach, P = .065; percutaneous approach, P = .054), and rate and severity of complications (P = .404). The rate and severity of complications favored the percutaneous approach in all three cohorts (P = .002). CONCLUSION: Over the last 10 years efficacy of percutaneous ablations has improved remarkably for the treatment of CRLM. Oncological outcomes seem to have reached results following open ablation. Given its minimal invasive character and shorter length of hospital stay, whenever feasible, percutaneous procedures may be favored over an open approach.

Microwave Ablation, Radiofrequency Ablation, Irreversible Electroporation, and Stereotactic Ablative Body Radiotherapy for Intermediate Size (3-5 cm) Unresectable Colorectal Liver Metastases: a Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Based on good local control rates and an excellent safety profile, guidelines consider thermal ablation the gold standard to eliminate small unresectable colorectal liver metastases (CRLM). However, efficacy decreases exponentially with increasing tumour size. The preferred treatment for intermediate-size unresectable CRLM remains uncertain. This systematic review and meta-analysis compare safety and efficacy of local ablative treatments for unresectable intermediate-size CRLM (3-5 cm). RECENT FINDINGS: We systematically searched for publications reporting treatment outcomes of unresectable intermediate-size CRLM treated with thermal ablation, irreversible electroporation (IRE) or stereotactic ablative body-radiotherapy (SABR). No comparative studies or randomized trials were found. Literature to assess effectiveness was limited and there was substantial heterogeneity in outcomes and study populations. Per-patient local control ranged 22-90% for all techniques; 22-89% (8 series) for thermal ablation, 44% (1 series) for IRE, and 67-90% (1 series) for SABR depending on radiation dose. Focal ablative therapy is safe and can induce long-term disease control, even for intermediate-size CRLM. Although SABR and tumuor-bracketing techniques such as IRE are suggested to be less susceptible to size, evidence to support any claims of superiority of one technique over the other is unsubstantiated by the available evidence. Future prospective comparative studies should address local-tumour-progression-free-survival, local control rate, overall survival, adverse events, and quality-of-life.