International working group for myelofibrosis research and treatment response assessment and long-term follow-up of 50 myelofibrosis patients treated with thalidomide-prednisone based regimens

Introduction: Congenital myasthenic syndromes (CMS) refer to a heterogenic group of neuromuscular transmission disorders. CMS-subtypes are diverse regarding exercise intolerance and muscular weakness, varying from mild symptoms to life-limiting forms with neonatal onset. Long-term follow-up studies on disease progression and treatment-response in pediatric patients are rare.Patients and Methods: We analyzed retrospective clinical and medication data in a cohort of 32 CMS-patients including the application of a standardized, not yet validated test (CMS-ST) to examine muscular strength and endurance in 21 patients at the last follow-up. Findings obtained in our cohort were compared with long-term follow-up studies of (adult) CMS-cohorts from the literature by considering the underlying molecular mechanisms. Outcomes of CMS-ST were compared to results of normal clinical assessment.Results: Thirty-two pediatric patients with defects in eight different CMS-genes were followed by a median time of 12.8 years. Fifty-nine percentage of patients manifested with first symptoms as neonates, 35% as infants. While 53% of patients presented a reduced walking distance, 34% were wheelchair-bound. Even under adequate therapy with pyridostigmine (PS) and 3,4-diaminopyridine, CHAT-mutations led to the progression of muscular weakness partly in combination with persistent respiratory and bulbar symptoms. RAPSN, CHRND, and CHRNB1 patients with neonatal manifestation, early respiratory problems, and bulbar symptoms showed a good and maintained treatment response. CHAT and CHRNE patients required higher PS dosages, whereas RAPSN patients needed a lower mean dosage at the last follow-up. The benefits of short-term medication and long-term progression of symptoms were highly dependent on the specific genetic defect. CMS-ST was carried out in 17/21 patients, determined affected muscle groups including bulbar and ocular symptoms, some of which were not reported by the patients.Conclusions: Our findings and comparison with the literature- suggest a better treatment-response and less severe progression of symptoms present in patients suffering from mutations in CMS-genes directly associated with receptor deficiency, while patients with defects leading to synaptopathy and presynaptic defects tend to have worse outcomes. Assessment of affected muscular groups and clinical symptoms by CMS-ST may be a useful tool for optimal therapeutic management of the patients, especially for future clinical studies.

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Automatic Segmentation of Metastatic Breast Cancer Lesions on 18F-FDG PET/CT Longitudinal Acquisitions for Treatment Response Assessment

Cancers ◽

10.3390/cancers14010101 ◽

2021 ◽

Vol 14 (1) ◽

pp. 101

Author(s):

Noémie Moreau ◽

Caroline Rousseau ◽

Constance Fourcade ◽

Gianmarco Santini ◽

Aislinn Brennan ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Response ◽

Automatic Segmentation ◽

Metastatic Breast ◽

Response Assessment ◽

Imaging Biomarkers ◽

Pet Ct ◽

Treatment Response Assessment

Metastatic breast cancer patients receive lifelong medication and are regularly monitored for disease progression. The aim of this work was to (1) propose networks to segment breast cancer metastatic lesions on longitudinal whole-body PET/CT and (2) extract imaging biomarkers from the segmentations and evaluate their potential to determine treatment response. Baseline and follow-up PET/CT images of 60 patients from the EPICUREseinmeta study were used to train two deep-learning models to segment breast cancer metastatic lesions: One for baseline images and one for follow-up images. From the automatic segmentations, four imaging biomarkers were computed and evaluated: SULpeak, Total Lesion Glycolysis (TLG), PET Bone Index (PBI) and PET Liver Index (PLI). The first network obtained a mean Dice score of 0.66 on baseline acquisitions. The second network obtained a mean Dice score of 0.58 on follow-up acquisitions. SULpeak, with a 32% decrease between baseline and follow-up, was the biomarker best able to assess patients’ response (sensitivity 87%, specificity 87%), followed by TLG (43% decrease, sensitivity 73%, specificity 81%) and PBI (8% decrease, sensitivity 69%, specificity 69%). Our networks constitute promising tools for the automatic segmentation of lesions in patients with metastatic breast cancer allowing treatment response assessment with several biomarkers.

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Delayed contrast and multiparametric MRI for treatment response assessment in brain metastases following stereotactic radiosurgery

Neuro-Oncology ◽

10.1093/neuonc/noab195.056 ◽

2021 ◽

Vol 23 (Supplement_4) ◽

pp. iv22-iv23

Author(s):

Markand Patel ◽

Dilina Rajapakse ◽

Jian Ping Jen ◽

Sara Meade ◽

Helen Benghiat ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Treatment Response ◽

Sensitivity And Specificity ◽

Neuroendocrine Tumour ◽

Response Assessment ◽

Multiparametric Mri ◽

Treatment Response Assessment ◽

Measuring Signal

Abstract Aims Following stereotactic radiosurgery (SRS), brain metastases can increase in size in up to a third of cases. Conventional magnetic resonance imaging (MRI) has a limited role to distinguish between tumour recurrence and SRS-induced changes, which can impact patient management. Delayed contrast MRI treatment response assessment maps (TRAM) use the principle of contrast clearance seen in other tumours, where high vascularity shows a rapid rise in contrast as well as rapid clearance, whereas areas of damaged or low vascularity show accumulation of contrast. We aimed to assess the ability of delayed contrast MRI and multiparametric MRI techniques of diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) to distinguish between radiation-related effects and tumour tissue, as these techniques assess tissue physiological and metabolic information. Method A retrospective review was performed on 23 patients who had delayed contrast and multiparametric MRI between October 2018 to April 2020. Studies were restricted to cases with brain metastases enlarging post-SRS with uncertainty at the MDT meeting regarding progression or treatment-related change, impacting the patient’s management. MRI was performed at 3T including DWI, PWI, MRS with short and intermediate echo times, and 3D T1 MPRAGE at 3-5, 20-30 and 70-90 minutes after administration of intravenous contrast. Contrast clearance analysis was performed by selecting an enhancing region of interest (ROI), measuring signal intensities at the three different timepoints and taking apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) values from the ROI. Choline/Creatine values were calculated from a single-voxel (10 mm isotropic) encompassing the entire contrast-enhancing lesion. Outcome was established from MRI follow-up at 6 months, with a stable or responding lesion considered treatment-related changes and increase considered progression. Results Across 23 patients, 24 metastases were assessed. Two patients were excluded as appropriate follow-up was not available. Sites of primary tumours included breast (n=8), lung (n=6), melanoma (n=4), neuroendocrine tumour from the lung (n=2) and renal cell carcinoma (n=2). Mean age was 56 years and 50% were female. In this cohort, 59% (n=13) were classified as having radiation-related changes on follow-up. Delayed MRI contrast clearance between the 3-5 and 70-90 minute imaging was significantly higher in cases of progression (23.6% vs. 2.5% decrease, p<0.05), as were the rCBV and Cho/Cr ratio (rCBV 3.1 vs. 1.5 and Cho/Cr ratio 2.3 vs. 1.4, p<0.05). Accuracy, sensitivity and specificity of using TRAM alone (contrast clearance decrease of >0%) for progression was 63%/100%/38%, PWI alone (rCBV cut-off 2.0) yielded results of 77%/75%/79% and for both Cho/Cr ratio alone (cut-off 1.8) and combined with TRAM, it was 90%/88%/92%. Neuroradiologist assessment of all techniques was 95%/100%/92%. Conclusion This study shows the effectiveness of delayed contrast and multiparametric MRI for treatment response assessment in patients with brain metastases treated by SRS in clinical practice. Although a delayed contrast MRI study is a very sensitive tool for detecting tumour progression, it lacks specificity. The accuracy of differentiating between tumour and treatment-related effects increases when delayed contrast MRI is used in combination with other advanced techniques such as MRS. By combining all these techniques, neuroradiologists had the highest accuracy, sensitivity and specificity for detecting progression in post-SRS brain metastases.

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