Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma.

Background: The clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised. Methods: We applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL. Results: FOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells. Discussion: These findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL.

Deep-learning based classification of a tumor marker for prognosis on Hodgkin's disease.

PURPOSE: Hodgkin's disease is a common malignant disorder in adolescent patients. Although most patients are cured, approximately 10%-15% of patients experience a relapse or have resistant disease. Furthermore, there are no definitive molecular predictors for early identification of patients at high risk of treatment failure to first line therapy. The aim of this study was to evaluate the deep learning-based classifier model of medical image classification to predict clinical outcome that may help in appropriate therapeutic decisions. METHODS: Eighty-three FFPE biopsy specimens from patients with Hodgkin's disease were stratified according to the patient's qPET scores, stained with picrosirius red dye and digitalized by whole slide image scanning. The resulting whole slide images were cut into tiles and annotated by two classes based on the collagen fibers' degree of coloring with picrosirius red. The neural network (YOLOv4) was then trained with the annotated data. Training was performed with 30 cases. Prognostic power of the weakly stained picrosirius red fibers was evaluated with 53 cases. The same neural network was trained with MMP9 stained tissue slides from the same cases and the quantification results were compared with the variant from the picrosirius red cases. RESULTS: There was a weak monotonically increasing relationship by parametric ANOVA between the qPET groups and the percentages of weakly stained fibers (p = .0185). The qPET-positive cases showed an average of 18% of weakly stained fibers, and the qPET-negative cases 10%-14%. Detection performance showed an AUC of 0.79. CONCLUSIONS: Picrosirius red shows distinct associations as a prognostic metric candidate of disease progression in Hodgkin's disease cases using whole slide images but not sufficiently as a prognostic device.

An illuminating piece in the jigsaw of Hodgkin lymphoma risk stratification.

The management strategy of classical Hodgkin lymphoma in children is focussed on maximising therapeutic efficacy while minimising treatment-related toxicity via a risk-adapted and response-based approach. By using volumetric PET parameters, the report of Milgrom and her colleagues shows that combining pretreatment volumetric quantitative PET data with the early response assessment PET2 scan improved risk stratification in children with high-risk classical Hodgkin lymphoma treated on the COG AHOD0831 trial. Commentary on: Milgrom et al. Baseline metabolic tumor burden improves risk stratification in Hodgkin lymphoma: A Children's Oncology Group Study. Br J Haematol 2023;201:1192-1199.

Mapping glioma heterogeneity using multiparametric 18 F-choline PET/MRI in childhood and teenage-young adults.

OBJECTIVE: The heterogeneity of post-treatment imaging remains a significant challenge in children and teenagers/young adults (TYA) diagnosed with glioma. The aim of this study was to evaluate the utility of 18 F-choline PET/MRI in determining intratumoural heterogeneity in paediatric and TYA gliomas. METHODS: Twenty-six patients (mean age 16 years, range 8-22 years) with suspected glioma disease progression were evaluated with 18 F-choline PET/MRI. Relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and maximum standardised uptake values (SUV max ) in enhancing (enh) and non-enhancing (ne) tumour volumes and normal-appearing white matter (wm) were calculated (rCBV enh , rCBV ne , rCBV wm , ADC enh , ADC ne , ADC wm , SUV enh , SUV ne and SUV wm ). RESULTS: Significantly higher SUV enh and SUV ne compared with SUV wm were observed [SUV enh 0.89 (0.23-1.90), SUV ne 0.36 (0.16-0.78) versus SUV wm 0.15 (0.04-1.19); P < 0.001 and P = 0.004, respectively]. Equivalent results were observed for ADV and rCBV (ADC enh , ADC ne : P < 0.001 versus ADC wm ; rCBV enh , rCBV ne : P < 0.001 versus rCBV wm ). The highest values for mean SUV max [0.89 (0.23-1.90)] and mean rCBV [2.1 (0.74-5.08)] were in the enhancing component, while the highest values for ADC [1780 mm 2 /s (863-2811)] were in the necrotic component. CONCLUSION: 18 F-choline PET/MRI is able map imaging heterogeneity in paediatric and TYA gliomas, detecting post-treatment enhancing, non-enhancing, and necrotic tumour components equivalent to ADC and DSC-derived rCBV. This offers potential in the response assessment of diffuse non-enhancing gliomas and in selected cases such as posterior fossa tumours where quantitative MRI is technically difficult.

Management of children and adults with all stages of nodular lymphocyte predominant Hodgkin lymphoma - All StAGEs: A consensus-based position paper from the Hodgkin lymphoma subgroup of the UK National Cancer Research Institute.

A consensus statement for the management for patients of all ages with all stages of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) - All StAGEs - is proposed by representatives of the UK National Cancer Research Institute (NCRI) Hodgkin lymphoma study group and the Children's Cancer & Leukaemia Group. Based on current practices and published evidence, a consensus has been reached regarding diagnosis, staging and risk-ik7 stratified management which includes active surveillance, low- and standard-dose immunochemotherapy and radiotherapy.

Preferred place of death in paediatric, teenage and young adult haemato-oncology patients: a retrospective review.

OBJECTIVES: Identifying the preferred place of death for children/young people with cancer and determining whether this is achieved is pertinent to inform palliative care service provision. The aims of this retrospective case series review were to determine where children/young people with cancer want to die and whether their preferred place of death was achieved. METHODS: Clinical/demographic details, including preferred and actual places of death, were recorded for 121 patients who died between 2012 and 2016 at a tertiary haematology-oncology centre. A logistic regression model was used to determine the odds of achieving the preferred place of death in patient subgroups. RESULTS: 74 (61%) patients had a documented discussion regarding place of death preference. Where a preferred location was identified, 72% achieved it. All patients who wanted to die in the hospital (n=17) or a hospice (n=9) did, but only 58% of patients who wanted to die at home (n=40) achieved this. Of the 42% (n=17) who wanted to die at home but did not, 59% of these were due to rapid deterioration in clinical status shortly after the discussion. Having supportive treatment in the last month of life was associated with increased odds of achieving the preferred place of death versus those who were undergoing chemotherapy/radiotherapy (OR 3.19, 95% CI 1.04 to 9.80, p value=0.04). CONCLUSION: Where hospice/hospital was chosen as the preferred place of death, this was always achieved. Achieving home as the preferred place of death was more challenging and frequently prevented by rapid clinical deterioration. Clinicians should be encouraged to address end-of-life preferences at an early stage, with information provided adequately. Further research should explore implications of these findings on both end-of-life experience and overall service provision.

Renal protection during 177lutetium DOTATATE molecular radiotherapy in children: a proposal for safe amino acid infusional volume during peptide receptor radionuclide therapy.

Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues such as 177-lutetium DOTATATE is an effective treatment modality for neuroendocrine tumours, paragangliomas, and neuroblastomas. However, renal and haematopoietic toxicities are the major limitations of this therapeutic approach. The renal toxicity of PRRT is mediated by renal proximal tubular reabsorption and interstitial retention of the radiolabelled peptides resulting in excessive renal irradiation that can be dose-limiting. To protect the kidneys from PRRT-induced radiation nephropathy, basic amino acids are infused during PRRT as they competitively bind to the proximal tubular cells and prevent uptake of the radionuclide. In adults, 1 L of a basic amino acid solution consisting of arginine and lysine is infused over 4 h commencing 30 min prior to PRRT. However, this volume of amino acids infused over 4 h is excessive in small children and can result in hemodynamic overload. This is all the more relevant in paediatric oncology, as many of the children may have been heavily pretreated and so may have treatment-related renal and or cardiac impairment. We have therefore developed the following guidelines for safe paediatric dosing of renal protective amino acid infusions during PRRT. Our recommendations have been made taking into consideration the renal physiology in small children and the principles of safe fluid management in children.

Neuroblastoma-associated Renal Cell Carcinoma: A Case Report and Review of the Literature.

Neuroblastoma-associated renal cell carcinoma (RCC) is a very rare subtype of renal neoplasia and only a handful of cases have been reported. Here we present a 15-year-old boy with metastatic RCC with a previous history of advanced stage neuroblastoma and germline mutation in the TP53 tumor suppressor gene. The probability of the RCC and indeed, the neuroblastoma itself being related to a cancer predisposition syndrome rather than a therapy induced second malignancy, is discussed.

Treatment outcome with a selective RET tyrosine kinase inhibitor selpercatinib in children with multiple endocrine neoplasia type 2 and advanced medullary thyroid carcinoma.

BACKGROUND: Medullary thyroid carcinoma (MTC) in the context of multiple endocrine neoplasia type 2 (MEN2) is caused by mutations in the RET proto-oncogene. Therefore, in children with MEN2 and advanced MTC, the RET tyrosine kinase (TK) pathway is a target for treatment with selpercatinib, a selective RET TK inhibitor. PATIENTS AND METHODS: A retrospective review of the clinical, genetic, biochemical (calcitonin and carcinoembryonic antigen [CEA]) and imaging data of six medically untreated children with MEN2 and recurrent and or progressive MTC. The main parameters were safety and objective treatment response to selpercatinib. RESULTS: Six children (three males and three females, aged 3-12 years), four with MEN2B and two MEN2A, are reported. All had initial total thyroidectomy and extensive neck dissections but subsequently developed recurrent and progressive disease. All experienced an improvement in clinical symptoms with a concomitant biochemical response evidenced by significant fall in serum calcitonin and CEA concentrations. The fall in serum calcitonin was evident within 2 weeks of the start of selpercatinib, and responses were ongoing at a median follow-up of 13 months (range, 11-22 months). Four children with measurable radiological disease had good volume reduction. The most common adverse effects were transient but reversible grade 1 or 2 increase in alanine aminotransferase, serum bilirubin and constipation. No child required a dose modification or had to discontinue selpercatinib because of a drug-related adverse event. CONCLUSION: Selpercatinib has shown excellent therapeutic efficacy with minimal toxicity in children with MEN2 and progressive metastatic RET-mutated MTC.

18F-FDG PET/MRI for Staging and Interim Response Assessment in Pediatric and Adolescent Hodgkin Lymphoma: A Prospective Study with 18F-FDG PET/CT as the Reference Standard.

Treatment regimens for pediatric Hodgkin lymphoma (HL) depend on accurate staging and treatment response assessment, based on accurate disease distribution and metabolic activity depiction. With the aim of radiation dose reduction, we compared the diagnostic performance of 18F-FDG PET/MRI with a 18F-FDG PET/CT reference standard for staging and response assessment. Methods: Twenty-four patients (mean age, 15.4 y; range, 8-19.5 y) with histologically proven HL were prospectively and consecutively recruited in 2015 and 2016, undergoing both 18F-FDG PET/CT and 18F-FDG PET/MRI at initial staging (n = 24) and at response assessment (n = 21). The diagnostic accuracy of 18F-FDG PET/MRI for both nodal and extranodal disease was compared with that of 18F-FDG PET/CT, which was considered the reference standard. Discrepancies were retrospectively classified as perceptual or technical errors, and 18F-FDG PET/MRI and 18F-FDG PET/CT were corrected by removing perceptual error. Agreement with Ann Arbor staging and Deauville grading was also assessed. Results: For nodal and extranodal sites combined, corrected staging 18F-FDG PET/MRI sensitivity was 100% (95% CI, 96.7%-100%) and specificity was 99.5% (95% CI, 98.3%-99.9%). Corrected response-assessment 18F-FDG PET/MRI sensitivity was 83.3% (95% CI, 36.5%-99.1%) and specificity was 100% (95% CI, 99.2%-100%). Modified Ann Arbor staging agreement between 18F-FDG PET/CT and 18F-FDG PET/MRI was perfect (κ = 1.0, P = 0.000). Deauville grading agreement between 18F-FDG PET/MRI and 18F-FDG PET/CT was excellent (κ = 0.835, P = 0.000). Conclusion:18F-FDG PET/MRI is a promising alternative to 18F-FDG PET/CT for staging and response assessment in children with HL.

Clinical experience of convection-enhanced delivery (CED) of carboplatin and sodium valproate into the pons for the treatment of diffuse intrinsic pontine glioma (DIPG) in children and young adults after radiotherapy.

PURPOSE: Effective treatment of diffuse intrinsic pontine glioma (DIPG) remains a formidable challenge due to inadequate penetration of the blood-brain barrier (BBB) by systemically administered chemotherapies. The BBB can be overcome by directly infusing drugs into pons using method of convection-enhanced delivery (CED). We describe our clinical experience and what we have learned about the safety and feasibility of treating DIPG with intermittent CED of carboplatin and sodium valproate to the pons through the Renishaw Drug Delivery System (RDDS). METHODS: Retrospective review (2017-2020) of children with DIPG, who following radiotherapy, received compassionate treatment commencing 3.3-10 months post-diagnosis (median 4.9 months). They received up to 7 cycles of 3-6 weekly pontine infusions of carboplatin (0.12-0.18 mg/ml) and sodium valproate (14.4-28.8 mg/ml). RESULTS: 13 children 3-19 years (mean 6.9 years) were treated. There were no surgical complications. With the exception of infusion channels blocking in one device, there were no adverse device effects. Two patients developed persistent 6th nerve palsies, which led to drug concentration reduction in the combination therapy. Subsequently infusion/ drug-related toxicities were transient. Tumour was controlled in pons in 10/13 patients. Median progression-free survival (PFS) was 13.0 months, while median overall survival (OS) was 15.3 months. CONCLUSIONS: Use of the RDDS was safe and well tolerated in all 13 patients. Treatment improved control of pontine disease resulting in longer PFS and OS and merits further evaluation in a clinical trial.

Imaging characteristics of H3 K27M histone-mutant diffuse midline glioma in teenagers and adults.

BACKGROUND: To assess anatomical and quantitative diffusion-weighted MR imaging features in a recently classified lethal neoplasm, H3 K27M histone-mutant diffuse midline glioma [World Health Organization (WHO) IV]. METHODS: Fifteen untreated gliomas in teenagers and adults (median age 19, range, 14-64) with confirmed H3 K27M histone-mutant genotype were analysed at a national referral centre. Morphological characteristics including tumour epicentre(s), T2/FLAIR and Gadolinium enhancement patterns, calcification, haemorrhage and cyst formation were recorded. Multiple apparent diffusion coefficient (ADCmin, ADCmean) regions of interest were sited in solid tumour and normal appearing white matter (ADCNAWM) using post-processing software (Olea Sphere v2.3, Olea Medical). ADC histogram data (2nd, 5th, 10th percentile, median, mean, kurtosis, skewness) were calculated from volumetric tumour segmentations and tested against the regions of interest (ROI) data (Wilcoxon signed rank test). RESULTS: The median interval from imaging to tissue diagnosis was 9 (range, 0-74) days. The structural MR imaging findings varied between individuals and within tumours, often featuring signal heterogeneity on all MR sequences. All gliomas demonstrated contact with the brain midline, and 67% exhibited rim-enhancing necrosis. The mean ROI ADCmin value was 0.84 (±0.15 standard deviation, SD) ×10-3 mm2/s. In the largest tumour cross-section (excluding necrosis), an average ADCmean value of 1.12 (±0.25)×10-3 mm2/s was observed. The mean ADCmin/NAWM ratio was 1.097 (±0.149), and the mean ADCmean/NAWM ratio measured 1.466 (±0.299). With the exception of the 2nd centile, no statistical difference was observed between the regional and histogram derived ADC results. CONCLUSIONS: H3 K27M-mutant gliomas demonstrate variable morphology and diffusivity, commonly featuring moderately low ADC values in solid tumour. Regional ADC measurements appeared representative of volumetric histogram data in this study.

Predicting outcome in childhood diffuse midline gliomas using magnetic resonance imaging based texture analysis.

BACKGROUND: Diffuse midline gliomas (DMG) are aggressive brain tumours, previously known as diffuse intrinsic pontine gliomas (DIPG), with 10% overall survival (OS) at 18 months. Predicting OS will help refine treatment strategy in this patient group. MRI based texture analysis (MRTA) is novel image analysis technique that provides objective information about spatial arrangement of MRI signal intensity (heterogeneity) and has potential to be imaging biomarker. OBJECTIVES: To investigate MRTA in predicting OS in childhood DMG. METHODS: Retrospective study of patients diagnosed with DMG, based on radiological features, treated at our institution 2007-2017. MRIs were acquired at diagnosis and 6 weeks after radiotherapy (54Gy in 30 fractions). MRTA was performed using commercial available TexRAD research software on T2W sequence and Apparent Diffusion Coefficient (ADC) maps encapsulating tumour in the largest single axial plane. MRTA comprised filtration-histogram technique using statistical and histogram metrics for quantification of texture. Kaplan-Meier survival analysis determined association of MRI texture parameters with OS. RESULTS: In all, 32 children 2-14 years (median 7 years) were included. MRTA was undertaken on T2W (n=32) and ADC (n=22). T2W-MRTA parameters were better at prognosticating than ADC-MRTA. Children with homogenous tumour texture, at medium scale on diagnostic T2W MRI, had worse prognosis (Mean of Positive Pixels (MPP): P=0.005, mean: P=0.009, SD: P=0.011, kurtosis: P=0.037, entropy: P=0.042). Best predictor MPP was able to stratify patients into poor and good prognostic groups with median survival of 7.5 months versus 17.5 months, respectively. CONCLUSIONS: DMG with more homogeneous texture on diagnostic MRI is associated with worse prognosis. Texture parameter MPP is the most predictive marker of OS in childhood DMG.

Treating papillary and follicular thyroid cancer in children and young people: Single UK-center experience between 2003 and 2018.

AIM: Differentiated thyroid cancer (DTC) in children and adolescents is rare and data about its presentation and management are not well known. The aim of this study was to provide evidence of the current practice in the United Kingdom before the launch of the Rare National Paediatric Endocrine Tumours Guidelines (to be published in 2020). METHODS: Seventy-two children and adolescents with DTC (<18 years) who were treated at our institution between 2003 and 2018 were identified and their presentation, treatment and outcomes were reviewed. RESULTS: Median age at presentation was 12.7 years [range: 1-18] and fifty-two (72%) were girls. Fifty (69.4%) children and adolescents presented with a thyroid nodule. Thirteen (18%) had cervical adenopathy and seven of them (54%) underwent an excision biopsy under GA. Eight patients (11%) had evidence of lung metastases at presentation. Twenty-four patients (33%) underwent a hemithyroidectomy and 22 of those had a completion thyroidectomy subsequently, ten (14%) a total thyroidectomy alone and 37 (51%) a total thyroidectomy with lymph nodes dissection. Seventy patients (97%) underwent adjuvant RAI at our institution. The median number of children and adolescents managed per year was five [range: 0-10]. After an overall median follow-up of 40 months, eight patients (11%) had developed recurrent disease. The 1- and 5-year recurrence-free-survival-rates were 93% and 87%, respectively. Overall survival was 100%, with eight children and adolescents (11%) being alive with disease. CONCLUSION: This study confirms that DTC in children and adolescents is uncommon, is frequently advanced at presentation and has considerable recurrence rates. Despite this, overall survival is excellent. Although the work-up was generally appropriate (image-guided cytology), open biopsy for the diagnosis of lymph node involvement was still employed. The introduction of a specific UK guideline for this age-group will likely result in more tailored-made treatment-pathways and thereby hopefully improve quality and outcomes even further. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: Level IV.

Hybrid PET-MRI Imaging in Paediatric and TYA Brain Tumours: Clinical Applications and Challenges.

(1) Background: Standard magnetic resonance imaging (MRI) remains the gold standard for brain tumour imaging in paediatric and teenage and young adult (TYA) patients. Combining positron emission tomography (PET) with MRI offers an opportunity to improve diagnostic accuracy. (2) Method: Our single-centre experience of 18F-fluorocholine (FCho) and 18fluoro-L-phenylalanine (FDOPA) PET-MRI in paediatric/TYA neuro-oncology patients is presented. (3) Results: Hybrid PET-MRI shows promise in the evaluation of gliomas and germ cell tumours in (i) assessing early treatment response and (ii) discriminating tumour from treatment-related changes. (4) Conclusions: Combined PET-MRI shows promise for improved diagnostic and therapeutic assessment in paediatric and TYA brain tumours.

68Ga-DOTATATE and 123I-mIBG as imaging biomarkers of disease localisation in metastatic neuroblastoma: implications for molecular radiotherapy.

PURPOSE: Iodine-131-labelled meta-iodobenzylguanidine (I-mIBG) and lutetium-177-labelled DOTATATE (Lu-DOTATATE) are used for molecular radiotherapy of metastatic neuroblastoma. These are taken up by the noradrenaline transporter (NAT) and the somatostatin receptor subtype 2 (SSTR-2), respectively. Scintigraphy of iodine-123-labelled meta-iodobenzylguanidine (I-mIBG) and gallium-68 DOTATATE (Ga-DOTATATE) PET are used to select patients for therapy. These demonstrate the extent and location of tumour, and avidity of uptake by cells expressing NAT and SSTR-2, respectively. This study compared the similarities and differences in the anatomical distribution of these two imaging biomarkers in an unselected series of patients with metastatic neuroblastoma undergoing assessment for molecular radiotherapy. METHODS: Paired whole-body planar I-mIBG views and Ga-DOTATATE maximum intensity projection PET scans of metastatic neuroblastoma patients were visually compared. The disease extent was assessed by a semiquantitative scoring method. RESULTS: Paired scans from 42 patients were reviewed. Ga-DOTATATE scans were positive in all patients, I-mIBG scans were negative in two. In two patients, there was a mismatch, with some lesions identified only on the I-mIBG scan, and others visible only on the Ga-DOTATATE scan. CONCLUSION: Ga-DOTATATE and I-mIBG scans yield complementary information. For a more comprehensive assessment, consideration could be given to the use of both I-mIBG and Ga-DOTATATE imaging scans. Because of the heterogeneity of distribution of molecular targets revealed by these techniques, a combination of both I-mIBG and Lu-DOTATATE molecular radiotherapy may possibly be more effective than either alone.

The use of multiparametric 18F-fluoro-L-3,4-dihydroxy-phenylalanine PET/MRI in post-therapy assessment of patients with gliomas.

PURPOSE: To determine the utility of F-fluoro-L-3,4-dihydroxy-phenylalanine (F-DOPA) PET/MRI versus cross-sectional MRI alone in glioma response assessment and identify whether the two techniques demonstrate different tumour features. METHODS: F-DOPA PET/MRI studies from 40 patients were analysed. Quantitative PET parameters and conventional MRI features were recorded. Tumour volume was assessed on both PET and MRI. Using dynamic susceptibility contrast perfusion-weighted imaging, maps of cerebral blood flow (CBF) and cerebral blood volume (CBV) were obtained. Within volume of tumours of tumour features and normal-appearing white matter (NAWM) drawn on MRI, standardised uptake value (SUV)max, CBF and CBV were recorded. Presence of residual active tumour was assessed by qualitative visual assessment. Receiver operating characteristic analysis was performed univariately and on parameter combination to analyse ability to determine presence/absence of disease. Reference standard for presence of viable tissue was biopsy or clinical follow-up. RESULTS: Median SUVmax was 3.4 for low-grade glioma (LGG) and 3.3 for high-grade glioma (HGG). There was a significant correlation between PWI parameters and WHO grade (P < 0.001), but no correlation with SUVmax. Median F-DOPA volume was 8216.88 mm for HGG and 6284.94 mm for LGG; MRI volume was 6316.57 mm and 5931.55 mm, respectively. SUVmax analysis distinguished enhancing and nonenhancing components from necrosis and NAWM and demonstrated active disease in nonenhancing regions. Visually, the modalities were concordant in 37 patients. Combining the multiparametric PET/MRI approach with all available data-enhanced detection of the presence of tumour (area under the curve 0.99, P < 0.01). CONCLUSION: MRI and F-DOPA are complementary modalities for assessment of tumour burden. Matching F-DOPA and MRI in assessing residual tumour volume may better delineate the radiotherapy target volume.

Whole-body magnetic resonance imaging in paediatric Hodgkin lymphoma - evaluation of quantitative magnetic resonance metrics for nodal staging.

BACKGROUND: Whole-body MRI is used for staging paediatric Hodgkin lymphoma, commonly using size thresholds, which fail to detect disease in normal-size lymph nodes. OBJECTIVE: To investigate quantitative whole-body MRI metrics for nodal characterisation. MATERIALS AND METHODS: Thirty-seven children with Hodgkin lymphoma underwent 1.5-tesla (T) whole-body MRI using short tau inversion recovery (STIR) half-Fourier-acquisition single-shot turbo-spin-echo and diffusion-weighted imaging (DWI). 18Flourine-2-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT was acquired as the reference standard. Two independent readers assessed 11 nodal sites. The readers measured short-axis-diameter, apparent diffusion coefficient, (ADC) and normalised T2-signal intensity of the largest lymph node at each site. We used receiver operating characteristics (ROC)/area-under-the-curve (AUC) analysis for each MRI metric and derived sensitivity and specificity for nodes with short-axis diameter ≥10 mm. Sub-analysis of sensitivity and specificity was performed with application of ADC cut-off values (<0.77, <1.15 and <1.79×10-3 mm2 s-1) to 5- to 9-mm nodes. RESULTS: ROC/AUC values for reader 1/reader 2 were 0.80/0.80 and 0.81/0.81 for short-axis-diameter measured using DWI and STIR half-Fourier-acquisition single-shot turbo spin echo, respectively; 0.67/0.72 for normalised T2 signal intensity and 0.74/0.67 for ADC. Sensitivity and specificity for a short-axis diameter ≥10 mm were 84.2% and 66.7% for Reader 1 and 82.9% and 68.9% for Reader 2. Applying a short-axis-diameter ≥10-mm threshold followed by ADC cut-offs to normal-size 5- to 9-mm nodes resulted in sensitivity and specificity for Reader 1 of 88.8% and 60%, 92.1% and 56.7%, and 100% and 16.7%; and for Reader 2, 86.1% and 67.2%, 95.3% and 65.6%, and 100% and 19.7%; and ADC thresholds of <0.77, <1.15, and <1.79×10-3 mm2 s-1, respectively. CONCLUSION: Nodal size measurement provides the best single classifier for nodal disease status in paediatric Hodgkin lymphoma. Combined short-axis diameter and ADC thresholds marginally improve sensitivity and drop specificity compared with size classification alone.