Differential Response of Pelvic Bone Marrow Fluorodeoxyglucose Uptake in Patients Receiving Concurrent Chemoradiotherapy.

AIMS: Irradiation of pelvic bone marrow (PBM) at the level of the typical low dose bath of intensity-modulated radiotherapy delivery (10-20 Gy) is associated with an increased risk of haematological toxicity, particularly when combined with concurrent chemotherapy. Although sparing of the whole of the PBM at a 10-20 Gy dose level is unachievable, it is known that PBM is divided into haematopoietically active and inactive regions that are identifiable based on the threshold uptake of [18F]-fluorodeoxyglucose (FDG) seen on positron emission tomography-computed tomography (PET-CT). In published studies to date, the definition of active PBM widely used is that of a standardised uptake value (SUV) greater than the mean SUV of the whole PBM prior to the start of chemoradiation. These studies include those looking at developing an atlas-based approach to contouring active PBM. Using baseline and mid-treatment FDG PET scans acquired as part of a prospective clinical trial we sought to determine the suitability of the current definition of active bone marrow as representative of differential underlying cell physiology. MATERIALS AND METHODS: Active and inactive PBM were contoured on baseline PET-CT and using deformable registration mapped onto mid-treatment PET-CT. Volumes were cropped to exclude definitive bone, voxel SUV extracted and the change between scans calculated. Change was compared using Mann-Whitney U testing. RESULTS: Active and inactive PBM were shown to respond differentially to concurrent chemoradiotherapy. The median absolute response of active PBM for all patients was -0.25 g/ml, whereas the median inactive PBM response was -0.02 g/ml. Significantly, the inactive PBM median absolute response was shown to be near zero with a relatively unskewed distribution (0.12). CONCLUSIONS: These results would support the definition of active PBM as FDG uptake greater than the mean of the whole structure as being representative of underlying cell physiology. This work would support the development of atlas-based approaches published in the literature to contour active PBM based on the current definition as being suitable.

Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism.

BACKGROUND: PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers. METHODS: Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging. RESULTS: A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance. CONCLUSIONS: In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

Characterising 18F-fluciclovine uptake in breast cancer through the use of dynamic PET/CT imaging.

BACKGROUND: 18F-fluciclovine is a synthetic amino acid positron emission tomography (PET) radiotracer that is approved for use in prostate cancer. In this clinical study, we characterised the kinetic model best describing the uptake of 18F-fluciclovine in breast cancer and assessed differences in tracer kinetics and static parameters for different breast cancer receptor subtypes and tumour grades. METHODS: Thirty-nine patients with pathologically proven breast cancer underwent 20-min dynamic PET/computed tomography imaging following the administration of 18F-fluciclovine. Uptake into primary breast tumours was evaluated using one- and two-tissue reversible compartmental kinetic models and static parameters. RESULTS: A reversible one-tissue compartment model was shown to best describe tracer uptake in breast cancer. No significant differences were seen in kinetic or static parameters for different tumour receptor subtypes or grades. Kinetic and static parameters showed a good correlation. CONCLUSIONS: 18F-fluciclovine has potential in the imaging of primary breast cancer, but kinetic analysis may not have additional value over static measures of tracer uptake. CLINICAL TRIAL REGISTRATION: NCT03036943.

Time to demand dosimetry for molecular radiotherapy?

Molecular radiotherapy (MRT) has been used clinically for around 75 years. Despite this long history of clinical use, there is no established dosimetry practice for calculating the absorbed dose delivered to tumour targets or to organs at risk. As a result, treatment protocols have often evolved based on experience with relatively small numbers of patients, each receiving a similar administered activity but, potentially, widely varying doses. This is in stark contrast to modern external-beam radiotherapy practice. This commentary describes some of the barriers to MRT dosimetry and gives some opinions on the way forward.

Iodine-131 monitoring in sewage plant outflow.

Three different hospital sites (Oxford, Sutton and Guildford) have performed sampling of their local sewage plant outflow to determine levels of radioactivity resulting from iodine-131 patients undergoing radionuclide therapies. It was found that a maximum of 20% of activity discharged from the hospitals was present in the sewage plant final effluent channel. This is significantly below the level predicted by mathematical models in current use. The results further show that abatement systems to reduce public exposure are unlikely to be warranted at hospital sites.

Management and outcome of appendicitis among octogenarians in an English hospital over a five year period.

INTRODUCTION: There is a different perspective on diagnosis and management of common surgical problems in elderly patients. This study aimed to analyse the management of acute appendicitis in octogenarians. METHODS: A retrospective study investigated all appendicectomies over five years. Patient records were studied for presenting features, pre-operative imaging, pre-operative ASA grade, site of incision, post-operative complications and length of inpatient stay. RESULTS: Presenting symptoms included lower abdominal pain (n = 31, 93.9%), anorexia (n = 19, 57.6%), nausea and vomiting (n = 15, 45.5%) and shifting pain (n = 10, 30.3%). Twenty patients had right iliac fossa pain (60.6%) and seven had pyrexia (21.2%). The commonest co-morbidity was cardiac (n = 19; 58%). The average time from admission to theatre was greater in octogenarian patients (1.24 ± 0.90 days) than other patients (0.64 ± 0.71 days), as was the average length of stay at 11 ± 2.6 days compared with 4.3 ± 3.1 days. The majority of octogenarian patients received a Lanz incision (48.3%), with others receiving laparotomy (24.1%), lower midline (13.8%), gridiron (13.8%), and right paramedian (3.4%). Complications were more common in the octogenarian patients (63.6%) than other patients (22.55%). The most common complications in the octogenarian population were post-operative ileus (n = 7; 21%), wound infection (n = 5; 15.2%) and pneumonia (n = 5; 15.2%). CONCLUSION: Appendicitis in the elderly can result in significant morbidity due to the atypical presentation causing an unnecessary delay in treatment. If indicated, age should not be a contraindication for an appendicectomy. The increased likelihood for these patients to have a post-operative complication should be at the forefront of their care.