Anne Negård

Background: Multiparametric MRI (mpMRI) offers non-invasive characterization of renal microstructure and function, but its clinical translation is hindered by the lack of standardized post-processing. Manual segmentation is widely used but inherently observer-dependent. This study aimed to quantify the intra- and interobserver variability in manual segmentation of a comprehensive renal mpMRI protocol in a diverse cohort of patients with biopsy-confirmed chronic kidney disease (CKD). Methods: Seventy-two patients scheduled for diagnostic kidney biopsy were prospectively enrolled. Participants underwent mpMRI on a 1.5-T system prior to biopsy, including kidney volume assessment, T1 mapping, T2* [blood oxygen level-dependent (BOLD)], diffusion-weighted imaging [apparent diffusion coefficient (ADC)], arterial spin labeling (ASL), phase-contrast renal artery flow, and T1-rho mapping. Manual segmentation of the renal cortex and medulla was performed on three representative coronal slices. Two trained independent observers (one nephrologist, one radiologist) analyzed the cohort to assess interobserver variability. One observer repeated the full analysis after a six-month washout period to assess intraobserver variability. Agreement was evaluated using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. Results: Complete datasets were available for 64 patients (mean estimated glomerular filtration rate 44 mL/min/1.73 m²; range, 3–132 mL/min/1.73 m²). Intra- and interobserver ICCs indicated good-to-excellent agreement for T1, T2*, and ADC in both cortical and medullary compartments (ICC range, 0.84–0.99). ASL showed excellent intraobserver reliability (ICC =0.94), but interobserver agreement was only good (ICC =0.78). Renal artery flow measurements also demonstrated good intra- and interobserver agreement (ICC =0.82 for both). T1-rho showed moderate-to-good intraobserver agreement (ICC range, 0.73–0.81) but was limited by image quality. Conclusions: Manual segmentation of renal cortex and medulla yields highly reproducible measurements for T1, T2*, ADC, renal artery flow and ASL in a mixed CKD population, supporting their validity for clinical research. However, the proportional bias in the Bland-Altmann plots for ASL and renal artery flow highlights the necessity for rigorous standardization of vessel selection and potential automation to ensure reliability across different readers.

Background: The randomized METIMMOX trial evaluated short-course oxaliplatin-based chemotherapy alternating with the immune checkpoint inhibitor nivolumab in patients with previously untreated, unresectable abdominal metastases from microsatellite-stable/mismatch repair-proficient colorectal cancer. A subgroup receiving this experimental treatment showed remarkably improved outcome compared to control arm patients who received chemotherapy alone and had median progression-free survival (PFS) of 9.3 months. We examined whether the kinetics of serum carcinoembryonic antigen (CEA) could provide insights into responsiveness to the METIMMOX regimen. Methods: Patients were randomly assigned to the control arm (oxaliplatin with bolus 5-fluorouracil/folinic acid, Q2W) or the experimental arm (alternating two cycles of chemotherapy Q2W and nivolumab Q2W). In this post hoc biomarker analysis, CEA levels were measured at baseline, at each treatment administration, and every two months during prespecified treatment breaks. Patients were categorized according to CEA kinetics—Flare (transient ≥ 20% increase above baseline), Non-responding (gradual increase), and Stable/Responding (values around baseline or gradually decreasing). Results: Flare comprised 16 out of 71 patients. According to Log rank test, experimental-arm Flare (n = 6) had significantly improved PFS (median 34.9 months) compared to Stable/Responding (n = 21; median PFS 9.9 months; p = 0.005) and Non-responding (n = 9; median PFS 2.1 months; p = 0.007). Flare was not associated with improved PFS for control-arm subjects. Adjusted Cox regression analysis indicated that experimental-arm Flare exhibited a lower progression risk than Non-responding for up to 6.2 months, creating an observation period for a potential decrease following the initial increase. Conclusion: CEA-Flare may indicate immune checkpoint inhibitor responsiveness following short-course oxaliplatin-based chemotherapy in this patient population; however, this is an exploratory finding that requires prospective validation. Plain Language Summary: This study examined whether changes in the blood marker CEA can help identify patients who benefit from a new treatment approach for large bowel cancer. The METIMMOX study tested alternating standard chemotherapy and immunotherapy in patients whose cancer had spread to abdominal organs and could not be surgically removed. All patients had a common type of bowel cancer that usually does not respond well to immunotherapy. Some patients who received the combined treatment performed much better than expected, with their cancer staying under control longer than those who received chemotherapy alone. The researchers studied changes in CEA levels over time during treatment. Based on these changes, patients were grouped into the following three patterns:CEA flare: a temporary increase (at least 20%) followed by a decreaseNon-responding: a steady increase in CEAStable/responding: stable or gradually decreasing CEA levels Among patients who received alternating chemotherapy and immunotherapy, those who showed a CEA flare had much better outcomes. Their cancer remained under control for a median time of almost 3 years, compared with approximately 10 months for patients with stable/responding CEA levels and only 2 months for those which non-responding CEA levels. This benefit was not seen in the patients who received chemotherapy alone, meaning that a CEA flare may signal a positive immune response after chemotherapy. In summary, a short-term increase in CEA (CEA flare) may be a helpful sign that patients with large bowel cancer spread to other organs respond well to a combination of chemotherapy and immunotherapy.

Background and purpose: The apparent diffusion coefficient (ADC), derived from diffusion-weighted MRI (DWI), is commonly calculated using a monoexponential model. However, there is no consensus on optimal b-value selection for ADC quantification in rectal cancer. This prospective observational study evaluated how varying b-value combinations influence ADC values. Patient/material and methods: DWI with seven b-values (b = 0, 25, 50, 100, 500, 1,000, and 1,300 s/mm2) was acquired from 23 rectal cancer patients in the OxyTarget study (NCT01816607) using a 1.5T Philips Achieva scanner. Two radiologists independently delineated whole-tumour volumes of interest. ADC values were calculated using 18 different b-value combinations and compared with a biexponential reference. Results: Tumour ADCs varied significantly across b-value combinations. Excluding low b-values (b ≤ 100 s/mm²) led to reduced ADCs. Although b = 0 s/mm² is commonly included in ADC calculations, this study demonstrates that its inclusion leads to substantial overestimation. The use of two or three b-values from b = 500, 1,000, and 1,300 s/mm² yielded the smallest deviations from the biexponential reference. Interpretation: In rectal cancer, tumour ADC calculated using the monoexponential model is strongly influenced by the choice of b-values. By eliminating the contribution from perfusion (b ≤ 100 s/mm2) the uncertainty in the calculations is significantly reduced. Our findings support the use of b-values exceeding 100 s/mm², ideally in combination with a high b-value of at least 1,000 s/mm², when assessing diffusion using the monoexponential model. Consistent b-value combinations across studies are recommended for reliable quantitative comparisons of ADC values.

Interobserver agreement for CT-based assessment of small renal masses during active surveillance was similar between routine-dose and lower-dose images acquired using iterative reconstruction, and deep learning–based denoising enabled dose reduction to submillisievert levels.

Purpose: Immune checkpoint inhibition (ICI) may result in tumor response patterns that differ from efficacy measures of directly cytotoxic chemotherapies. Hence, the selection of patients for experimental ICI schedules, for instance in MSS-mCRC, calls for applicable and reliable signals of activity or early failure that enable treatment adaptation and maintain patient safety. Experimental procedures: In the ongoing METIMMOX phase 2 study, we hypothesize that patients with previously untreated unresectable MSS-mCRC can obtain durable disease control to ICI when given short-course oxaliplatin-based chemotherapy (2 cycles of FLOX Q2W) before 2 cycles of nivolumab (240 mg Q2W) in a repeat sequential schedule to a total of 8 cycles. Patients have been randomly assigned to either this experimental study arm or a control arm of 8 FLOX cycles Q2W (standard-of-care; SoC), in both cases before treatment break until disease progression and reintroduction of a new treatment sequence. Radiologic response assessment is performed every 8 weeks with progression-free survival (PFS) as the primary end point. Results: At analysis 10 November 2021, median PFS was 9.3 months (95% CI, 8.3-10.3) for SoC (n = 34) and 11.4 months (95% CI, 7.4-15.5) for the experimental therapy (n = 39) (p = 0.335; log-rank test). In the latter group, 37 patients had available response evaluation at minimum 8 weeks of study treatment, as 2 patients (compared to 4 in the control group) had discontinued treatment due to intolerable toxicity before the first post-baseline assessment. The control arm patients had deeper responses with mean 23% (SD, 19%) target lesion reduction compared to mean 8%(SD, 33%) reduction for the experimental schedule (p = 0.028; Student’s t-test). We categorized the experimental arm patients into those with ≥10% (n = 20) or Citation Format: Sebastian Meltzer, Anne Negård, Hanne Mari Hamre, Christian Kersten, Eva Hofsli, Marianne Grønlie Guren, Halfdan Sørbye, Kjersti Flatmark, Anne Hansen Ree. Early radiologic signal of nivolumab responsiveness after short-course oxaliplatin-based chemotherapy in microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1279.

Tumor delineation is time- and labor-intensive and prone to inter- and intraobserver variations. Magnetic resonance imaging (MRI) provides good soft tissue contrast, and functional MRI captures tis...

Sex differences, tumor vascularity, and blood flow seen on multiecho dynamic contrast–based MRI scans enabled prediction of treatment response and overall survival in patients with rectal cancer. Background MRI is the standard tool for rectal cancer staging. However, more precise diagnostic tests that can assess biologic tumor features decisive for treatment outcome are necessary. Tumor per...