Assessment of tumour size in PET/CT lung cancer studies: PET- and CT-based methods compared to pathology

BACKGROUND: Positron emission tomography (PET) may be useful for defining the gross tumour volume for radiation treatment planning and for response monitoring of non-small cell lung cancer (NSCLC) patients. The purpose of this study was to compare tumour sizes obtained from CT- and various more commonly available PET-based tumour delineation methods to pathology findings. METHODS: Retrospective non-respiratory gated whole body [(18)F]-fluoro-2-deoxy-D-glucose PET/CT studies from 19 NSCLC patients were used. Several (semi-)automatic PET-based tumour delineation methods and manual CT-based delineation were used to assess the maximum tumour diameter. RESULTS: 50%, adaptive 41% threshold-based and contrast-oriented delineation methods showed good agreement with pathology after removing two outliers (R(2)=0.82). An absolute SUV threshold of 2.5 also showed a good agreement with pathology after the removal of 5 outliers (R(2): 0.79), but showed a significant overestimation in the maximum diameter (19.8 mm, p<0.05). Adaptive 50%, relative threshold level and gradient-based methods did not show any outliers, provided only small, non-significant differences in maximum tumour diameter (<4.7 mm, p>0.10), and showed fair correlation (R(2)>0.62) with pathology. Although adaptive 70% threshold-based methods showed underestimation compared to pathology (36%), it provided the best precision (SD: 14%) together with good correlation (R(2)=0.81). Good correlation between CT delineation and pathology was observed (R(2)=0.77). However, CT delineation showed a significant overestimation compared with pathology (3.8 mm, p<0.05). CONCLUSIONS: PET-based tumour delineation methods provided tumour sizes in agreement with pathology and may therefore be useful to define the (metabolically most) active part of the tumour for radiotherapy and response monitoring purposes

Mast Cells in Kidney Transplant Biopsies With Borderline T Cell-mediated Rejection and Their Relation to Chronicity

Background. Mast cells are potential contributors to chronic changes in kidney transplants (KTx). Here, the role of mast cells (MCs) in KTx is investigated in patients with minimal inflammatory lesions. Methods. Fourty-seven KTx biopsies (2009-2018) with borderline pathological evidence for T cell-mediated rejection according to the Banff'17 Update were retrospectively included and corresponding clinical data was collected. Immunohistochemistry for tryptase was performed on formalin-fixed paraffin-embedded sections. Cortical MCs were counted and corrected for area (MC/mm²). Interstitial fibrosis was assessed by Sirius Red staining and quantified using digital image analysis (QuPath). Results. Increased MC number was correlated to donor age (spearman's r = 0.35, P = 0.022), deceased donor kidneys (mean difference = 0.74, t [32.5] = 2.21, P = 0.035), and delayed graft function (MD = 0.78, t [33.9] = 2.43, P = 0.020). Increased MC number was also correlated to the amount of interstitial fibrosis (r = 0.42, P = 0.003) but did not correlate with transplant function over time (r = -0.14, P = 0.36). Additionally, transplant survival 2 y post-biopsy was not correlated to MC number (mean difference = -0.02, t [15.36] = -0.06, P = 0.96). Conclusions. MC number in suspicious (borderline) for acute T cell-mediated rejection is correlated to interstitial fibrosis and time post-transplantation, suggesting MCs to be a marker for cumulative burden of tissue injury. There was no association between MCs and transplant function over time or transplant survival 2 y post-biopsy. It remains unclear whether MCs are just a bystander or have pro-inflammatory or anti-inflammatory effects in the KTx with minimal lesions.</p

18F-FDG PET during stereotactic body radiotherapy for stage I lung tumours cannot predict outcome: a pilot study

(18)F-Fluorodeoxyglucose positron emission tomography (FDG PET) has been used to assess metabolic response several months after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. However, whether a metabolic response can be observed already during treatment and thus can be used to predict treatment outcome is undetermined. Ten medically inoperable patients with FDG PET-positive lung tumours were included. SBRT consisted of three fractions of 20 Gy delivered at the 80% isodose at days 1, 6 and 11. FDG PET was performed before, on day 6 immediately prior to administration of the second fraction of SBRT and 12 weeks after completion of SBRT. Tumour metabolism was assessed semi-quantitatively using the maximum standardized uptake value (SUV(max)) and SUV(70%). After the first fraction, median SUV(max) increased from 6.7 to 8.1 (p = 0.07) and median SUV(70%) increased from 5.7 to 7.1 (p = 0.05). At 12 weeks, both median SUV(max) and median SUV(70%) decreased by 63% to 3.1 (p = 0.008) and to 2.5 (p = 0.008), respectively. SUV increased during treatment, possibly due to radiation-induced inflammation. Therefore, it is unlikely that (18)F-FDG PET during SBRT will predict treatment success

Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass

Kidney transplant (KTx) biopsies showing transplant glomerulopathy (TG) (glomerular basement membrane double contours (cg) &gt; 0) and microvascular inflammation (MVI) in the absence of C4d staining and donor-specific antibodies (DSAs) do not fulfill the criteria for chronic active antibody–mediated rejection (CA-AMR) diagnosis and do not fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing the immunomic and transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA-/C4d- with 22 classified as CA-AMR DSA+/C4d+ through novel transcriptomic analysis using the NanoString Banff-Human Organ Transplant (B-HOT) panel and subsequent orthogonal subset analysis using two innovative 5-marker multiplex immunofluorescent panels. Nineteen genes were differentially expressed between the two study groups. Samples diagnosed with CA-AMR DSA+/C4d+ showed a higher glomerular abundance of natural killer cells and higher transcriptomic cell type scores for macrophages in an environment characterized by increased expression of complement-related genes (i.e., C5AR1) and higher activity of angiogenesis, interstitial fibrosis tubular atrophy, CA-AMR, and DSA-related pathways when compared to samples diagnosed with cg+MVI DSA-/C4d-. Samples diagnosed with cg+MVI DSA-/C4d- displayed a higher glomerular abundance and activity of T cells (CD3+, CD3+CD8+, and CD3+CD8-). Thus, we show that using novel multiomic techniques, KTx biopsies with cg+MVI DSA-/C4d- have a prominent T-cell presence and activity, putting forward the possibility that these represent a more T-cell dominant phenotype.</p

Магнитный контроль параметров ферромагнитных объектов методом высших гармоник

В данной работе объектом исследования являются контрольные образцы тороидальной формы из ферромагнитных сталей различных марок, изготовленные согласно ГОСТ 8.377-80, магнитные параметры которых исследуются с помощью разработанной многопараметровой установки для измерения магнитных характеристик MS-1.In this work, the object of the study is the control samples of toroidal shape of ferromagnetic steels of different brands, made according to GOST 8.377-80, the magnetic parameters of which are investigated using the developed multiparameter installation for measuring the magnetic characteristics of MS-1

Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass

Kidney transplant (KTx) biopsies showing transplant glomerulopathy (TG) (glomerular basement membrane double contours (cg) &gt; 0) and microvascular inflammation (MVI) in the absence of C4d staining and donor-specific antibodies (DSAs) do not fulfill the criteria for chronic active antibody–mediated rejection (CA-AMR) diagnosis and do not fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing the immunomic and transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA-/C4d- with 22 classified as CA-AMR DSA+/C4d+ through novel transcriptomic analysis using the NanoString Banff-Human Organ Transplant (B-HOT) panel and subsequent orthogonal subset analysis using two innovative 5-marker multiplex immunofluorescent panels. Nineteen genes were differentially expressed between the two study groups. Samples diagnosed with CA-AMR DSA+/C4d+ showed a higher glomerular abundance of natural killer cells and higher transcriptomic cell type scores for macrophages in an environment characterized by increased expression of complement-related genes (i.e., C5AR1) and higher activity of angiogenesis, interstitial fibrosis tubular atrophy, CA-AMR, and DSA-related pathways when compared to samples diagnosed with cg+MVI DSA-/C4d-. Samples diagnosed with cg+MVI DSA-/C4d- displayed a higher glomerular abundance and activity of T cells (CD3+, CD3+CD8+, and CD3+CD8-). Thus, we show that using novel multiomic techniques, KTx biopsies with cg+MVI DSA-/C4d- have a prominent T-cell presence and activity, putting forward the possibility that these represent a more T-cell dominant phenotype.</p

Continuous hyperfractionated accelerated radiotherapy - Escalated dose (CHART-ED): A phase i study

Patients who present with locally advanced inoperable non-small cell lung cancer (NSCLC) may be suitable for radical radiotherapy. A randomised trial of 563 patients compared CHART and conventional radical radiotherapy (60 Gy/30f) given over 6 weeks and suggested that CHART resulted in a 9% improvement in 2-year survival (Saunders et al., 1999). RT dose escalation for both conventional and CHARTWEL (CHART-WeekEndLess) - fractionation schedules is feasible with modern 3-dimensional CT-based planning techniques and we initiated a phase I CHART dose escalation study in 2009. Methods Patients with WHO performance status 0-2 histologically confirmed, inoperable, stage I-III non-small cell lung cancer were recruited into an open phase I dose escalation trial. Three cohorts of six patients were recruited sequentially. Total dose was escalated from standard CHART radiotherapy of 54 Gy/36f/12 days to 57.6 Gy (2 × 1.8 Gy fractions on day 15, Group 1), 61.2 Gy (4 × 1.8 Gy fractions on days 15-16, Group 2) and 64.8 Gy (6 × 1.8 Gy fractions on days 15-17, Group 3). Results Between April 2010 and May 2012, 18 patients were enrolled from 5 UK centres and received escalated dose radiotherapy. 14 were male, 16 squamous cell histology and 12 were stage IIIA or IIIB. The median age was 70 years and baseline characteristics were similar across the three dose cohorts. One patient did not start escalated radiotherapy but all remaining patients completed their planned radiotherapy schedules. Of these 9 patients have died to date with a median survival of 2 years across the three cohorts. Grade 3 or 4 adverse events (fatigue, dysphagia, nausea and anorexia - classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) were reported in 6 patients but the pre-specified dose limiting toxicities (grade 4 early oesophagitis; grade 3 cardiac, spinal cord and pneumonitis) were not observed. Conclusions CHART remains a radiotherapy schedule in routine use across the UK and in this dose escalation study no dose limiting toxicities were observed. We feel the dose of 64.8 Gy/42f/17 days should be taken forward into further clinical trials. The sample size used in this study was small so we plan a randomised phase II study that includes other radiotherapy schedules to confirm safety and select an accelerated sequential chemo-radiotherapy schedule to take into phase III studies

Comparison of CT and PET-CT based planning of radiation therapy in locally advanced pancreatic carcinoma

Abstract Background To compare computed tomography (CT) with co-registered positron emission tomography-computed tomography (PET-CT) as the basis for delineating gross tumor volume (GTV) in unresectable, locally advanced pancreatic carcinoma (LAPC). Methods Fourteen patients with unresectable LAPC had both CT and PET images acquired. For each patient, two three-dimensional conformal plans were made using the CT and PET-CT fusion data sets. We analyzed differences in treatment plans and doses of radiation to primary tumors and critical organs. Results Changes in GTV delineation were necessary in 5 patients based on PET-CT information. In these patients, the average increase in GTV was 29.7%, due to the incorporation of additional lymph node metastases and extension of the primary tumor beyond that defined by CT. For all patients, the GTVCT versus GTVPET-CT was 92.5 ± 32.3 cm3 versus 104.5 ± 32.6 cm3 (p = 0.009). Toxicity analysis revealed no clinically significant differences between two plans with regard to doses to critical organs. Conclusion Co-registration of PET and CT information in unresectable LAPC may improve the delineation of GTV and theoretically reduce the likelihood of geographic misses.</p

Comparative methods for PET image segmentation in pharyngolaryngeal squamous cell carcinoma

Several methods have been proposed for the segmentation of ¹⁸F-FDG uptake in PET. In this study, we assessed the performance of four categories of ¹⁸F-FDG PET image segmentation techniques in pharyngolaryngeal squamous cell carcinoma using clinical studies where the surgical specimen served as the benchmark