Lucy Pike

FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0

The purpose of these guidelines is to assist physicians in recommending, performing, interpreting and reporting the results of FDG PET/CT for oncological imaging of adult patients. PET is a quantitative imaging technique and therefore requires a common quality control (QC)/quality assurance (QA) procedure to maintain the accuracy and precision of quantitation. Repeatability and reproducibility are two essential requirements for any quantitative measurement and/or imaging biomarker. Repeatability relates to the uncertainty in obtaining the same result in the same patient when he or she is examined more than once on the same system. However, imaging biomarkers should also have adequate reproducibility, i.e. the ability to yield the same result in the same patient when that patient is examined on different systems and at different imaging sites. Adequate repeatability and reproducibility are essential for the clinical management of patients and the use of FDG PET/CT within multicentre trials. A common standardised imaging procedure will help promote the appropriate use of FDG PET/CT imaging and increase the value of publications and, therefore, their contribution to evidence-based medicine. Moreover, consistency in numerical values between platforms and institutes that acquire the data will potentially enhance the role of semiquantitative and quantitative image interpretation. Precision and accuracy are additionally important as FDG PET/CT is used to evaluate tumour response as well as for diagnosis, prognosis and staging. Therefore both the previous and these new guidelines specifically aim to achieve standardised uptake value harmonisation in multicentre settings.

PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study

International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

THE ACOUSTIC PROPERTIES, CENTERED ON 20 MHZ, OF AN IEC AGAR-BASED TISSUE-MIMICKING MATERIAL AND ITS TEMPERATURE, FREQUENCY AND AGE DEPENDENCE

The purpose of this study was to characterize the ultrasonic properties of agar-based tissue-mimicking materials (TMMs) at ultrasound frequencies centered around 20 MHz. The TMM acoustic properties measured are the amplitude attenuation coefficient alpha (dB cm(-1)MHz(-1)), the speed of sound (ms(-1)) and the backscattered power spectral density (distribution of power per unit frequency normalized to the total received power) characteristics of spectral slope (dB MHz(-1)), y-axis intercept (dB) and reflected power (dB). The acoustic properties are measured over a temperature range of 22 to 37 degrees C. An intercomparison of results between two independent ultrasound measurement laboratories is also presented. A longitudinal study of the acoustic properties over a period of two years is also detailed, and the effect of water immersion on the acoustic properties of TMM is measured. In addition, the physical parameters of mass density rho (kg m(-3)) and specific heat capacity C (J kg(-1) K(-1)) are included. The measurement techniques used were based on the substitution technique using both broadband and narrowband pulses centered on 20 MHz. Both the attenuation coefficient and speed of sound (both group and phase) showed good agreement with the expected values of 0.5 dB cm(-1) MHz(-1) and 1540 ms(-1), respectively, with average values over the three-year period of 0.49 dBcm(-1)MHz1 (SD +/- 0.05) and 1540.9 ms(-1) (SD +/- 8.7). These results also showed agreement between the two independent measurement laboratories. Speed of sound and attenuation coefficient were shown to change with temperature with rates of + 2.1 m s(-1) degrees C(-1) and -0.005 dB cm(-1) MHz(-1) degrees C(-1), respectively. Attenuation changed linearly with frequency at the high frequency range of 17 to 23 MHz, and speed of sound was found to be independent of frequency in this range. The spectral slope of relative backscattered power for the material increased with frequency at typically 1.5 dB MHz(-1). This compared favorably with theoretical spectral slope values, calculated for a variety of scatterer sizes, albeit at a lower frequency range. It is also noticed that, on extrapolation back to lower frequencies, the backscatter is comparable with that measured at 7 MHz. Overall, this non-commercial agar-based TMM is shown to perform as expected at the higher frequency range of 17 to 23 MHz and is seen to retain its acoustic properties of attenuation and speed of sound over a three-year period.

Recommendations for the use of PET and PET-CT for radiotherapy planning in research projects.

With the increasing use of positron emission tomography (PET) for disease staging, follow-up and therapy monitoring in a number of oncological indications there is growing interest in the use of PET and PET-CT for radiation treatment planning. In order to create a strong clinical evidence base for this, it is important to ensure that research data are clinically relevant and of a high quality. Therefore the National Cancer Research Institute PET Research Network make these recommendations to assist investigators in the development of radiotherapy clinical trials involving the use of PET and PET-CT. These recommendations provide an overview of the current literature in this rapidly evolving field, including standards for PET in clinical trials, disease staging, volume delineation, intensity modulated radiotherapy and PET-augmented planning techniques, and are targeted at a general audience. We conclude with specific recommendations for the use of PET in radiotherapy planning in research projects.

Positron emission tomography oncology research in the Uk: a comparison with Usa and Europe

PET imaging with 18F-fluorodeoxyglucose (FDG) has become a valuable procedure in oncology patient management and drug development. The availability of non-FDG radiotracers to study different aspects of cancer biology presents new opportunities to improve healthcare outcomes and develop new therapeutics. An investigation has been carried out to determine the extent of the use of non-FDG tracers in the UK, assess overall oncology PET research activity and document current UK PET infrastructure. There has been significant recent investment in PET facilities, increasing the UK’s capacity to undertake PET research. Nevertheless, the UK still has a lower level of PET equipment compared with Europe and the USA. Despite the increase in PET imaging capacity in UK research centres, there has not been an increase in non-FDG research, with most studies utilizing FDG at multiple sites. Most non-FDG trials are single-centre studies at well established centres. High tracer prices, a limited range of non-FDG tracers and restricted geographical availability make multicentre trials with non-FDG radiotracers difficult. Several solutions have been identified: formation of purchasing consortia for 18F-labelled radiotracers, production of radiotracers with longer half-lives and establishment of production at regional supply centres.

Association between hypoxic volume and underlying hypoxia-induced gene expression in oropharyngeal squamous cell carcinoma.

Background:Hypoxia imaging is a promising tool for targeted therapy but the links between imaging features and underlying molecular characteristics of the tumour have not been investigated. The aim of this study was to compare hypoxia biomarkers and gene expression in oropharyngeal squamous cell carcinoma (OPSCC) diagnostic biopsies with hypoxia imaged with 64Cu-ATSM PET/CT.Methods:64Cu-ATSM imaging, molecular and clinical data were obtained for 15 patients. Primary tumour SUVmax, tumour to muscle ratio (TMR) and hypoxic volume were tested for association with reported hypoxia gene signatures in diagnostic biopsies. A putative gene signature for hypoxia in OPSCCs (hypoxic volume-associated gene signature (HVS)) was derived.Results:Hypoxic volume was significantly associated with a reported hypoxia gene signature (rho=0.57, P=0.045), but SUVmax and TMR were not. Immunohistochemical staining with the hypoxia marker carbonic anhydrase 9 (CA9) was associated with a gene expression hypoxia response (rho=0.63, P=0.01). Sixteen genes were positively and five genes negatively associated with hypoxic volume (adjusted P<0.1; eight genes had adjusted P<0.05; HVS). This signature was associated with inferior 3-year progression-free survival (HR=1.5 (1.0–2.2), P=0.047) in an independent patient cohort.Conclusions:64Cu-ATSM-defined hypoxic volume was associated with underlying hypoxia gene expression response. A 21-gene signature derived from hypoxic volume from patients with OPSCCs in our study may be linked to progression-free survival.

Specific recommendations for accurate and direct use of PET‐CT in PET guided radiotherapy for head and neck sites

PURPOSE To provide specific experience-based guidance and recommendations for centers wishing to develop, validate, and implement an accurate and efficient process for directly using positron emission tomography-computed tomography (PET-CT) for the radiotherapy planning of head and neck cancer patients. METHODS A PET-CT system was modified with hard-top couch, external lasers and radiotherapy immobilization and indexing devices and was subject to a commissioning and quality assurance program. PET-CT imaging protocols were developed specifically for radiotherapy planning and the image quality and pathway tested using phantoms and five patients recruited into an in-house study. Security and accuracy of data transfer was tested throughout the whole data pathway. The patient pathway was fully established and tested ready for implementation in a PET-guided dose-escalation trial for head and neck cancer patients. RESULTS Couch deflection was greater than for departmental CT simulator machines. An area of high attenuation in the couch generated image artifacts and adjustments were made accordingly. Using newly developed protocols CT image quality was suitable to maintain delineation and treatment accuracy. Upon transfer of data to the treatment planning system a half pixel offset between PET and CT was observed and corrected. By taking this into account, PET to CT alignment accuracy was maintained below 1 mm in all systems in the data pathway. Transfer of structures delineated in the PET fusion software to the radiotherapy treatment planning system was validated. CONCLUSIONS A method to perform direct PET-guided radiotherapy planning was successfully validated and specific recommendations were developed to assist other centers. Of major concern is ensuring that the quality of PET and CT data is appropriate for radiotherapy treatment planning and on-treatment verification. Couch movements can be compromised, bore-size can be a limitation for certain immobilization techniques, laser positioning may affect setup accuracy and couch deflection may be greater than scanners dedicated to radiotherapy. The full set of departmental commissioning and routine quality assurance tests applied to radiotherapy CT simulators must be carried out on the PET-CT scanner. CT image quality must be optimized for radiotherapy planning whilst understanding that the appearance will differ between scanners and may affect delineation. PET-CT quality assurance schedules will need to be added to and modified to incorporate radiotherapy quality assurance. Methods of working for radiotherapy and PET staff will change to take into account considerations of both parties. PET to CT alignment must be subject to quality control on a loaded and unloaded couch preferably using a suitable emission phantom, and tested throughout the whole data pathway. Data integrity must be tested throughout the whole pathway and a system included to verify that delineated structures are transferred correctly. Excellent multidisciplinary team communication and working is vital, and key staff members on both sides should be specifically dedicated to the project. Patient pathway should be clearly devised to optimize patient care and the resources of all departments. Recruitment of a cohort of patients into a methodology study is valuable to test the quality assurance methods and pathway.

CAN BASELINE PET-CT FEATURES PREDICT OUTCOMES IN ADVANCED HODGKIN LYMPHOMA? A PROSPECTIVE EVALUATION OF UK PATIENTS IN THE RATHL TRIAL (CRUK/07/033)

therapy were eligible. Pts received 2 (cohort 1) or 3 (cohort 2) cycles of weekly BV (1.2 mg/kg days 1, 8, 15 of 28 day cycles); PET‐negative pts proceeded directly to autologous stem cell transplant (ASCT) while PET‐positive pts received augICE before ASCT. Serum cytokines and chemokines (TARC, IL‐6, IL‐10, TNF‐α, IFN‐γ) were measured at baseline and after BV. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured at baseline, after BV and after augICE. Results: 65 pts enrolled (45 cohort 1, 20 cohort 2), including 34 (52%) females, 29 (45%) with advanced stage disease, 34 (52%) with refractory disease (lack of CR after front‐line therapy), 10 (15%) with B symptoms, 24 (37%) with extranodal disease, and 16 (25%) with bulk (any mass > 5 cm). Overall, 18 of 65 (28%) pts achieved complete response (defined as Deauville ≤2) following BV. 19 pts (18 with Deauville 2 response and 1 with Deauville 3 response after BV) proceeded directly to ASCT. Among the other 46 pts, 1 was lost to follow‐up; 45 received augICE chemotherapy of which 31 (69%) achieved CR. Overall, 49 (75%) of 65 pts achieved complete response and 64 pts proceeded to ASCT. 3‐year overall survival and EFS were 95% and 82%. Factors predictive for EFS by univariate analysis included age over 45 years (p = 0.016), refractory disease (p = 0.033), B‐symptoms (p = 0.032), advanced stage at relapse (p = 0.011), as well as baseline MTV, TARC, and TLG (all p < 0.001). Factors that remained prognostic by multivariate analysis were MTV (p < 0.001, HR 54, 95% CI 9‐319) and refractory disease (p = 0.001, HR 82, 95% CI 6.1‐1107). The optimal cut‐off for baseline MTV, determined by a grid search of log‐rank test p values, was 109.5 cm. Using this cutoff, the 3‐year EFS for pts with low (n = 48) and high (n = 12) MTV was 92% and 27% respectively (p < 0.001) (Figure). Conclusion: In this phase II study of PET‐adapted ST with BV and augICE for rel/ref HL, baseline MTV and refractory disease were independent prognostic factors for EFS. Additional studies are needed to confirm the prognostic significance and optimal cutoff for MTV in rel/ref disease. Future studies should optimize efficacy and tolerability of ST by stratifying pts according to risk factors such as baseline MTV.

Accuracy and cost-effectiveness of dynamic contrast-enhanced CT in the characterisation of solitary pulmonary nodules—the SPUtNIk study

Introduction Solitary pulmonary nodules (SPNs) are common on CT. The most cost-effective investigation algorithm is still to be determined. Dynamic contrast-enhanced CT (DCE-CT) is an established diagnostic test not widely available in the UK currently. Methods and analysis The SPUtNIk study will assess the diagnostic accuracy, clinical utility and cost-effectiveness of DCE-CT, alongside the current CT and 18-flurodeoxyglucose-positron emission tomography) (18FDG-PET)-CT nodule characterisation strategies in the National Health Service (NHS). Image acquisition and data analysis for 18FDG-PET-CT and DCE-CT will follow a standardised protocol with central review of 10% to ensure quality assurance. Decision analytic modelling will assess the likely costs and health outcomes resulting from incorporation of DCE-CT into management strategies for patients with SPNs. Ethics and dissemination Approval has been granted by the South West Research Ethics Committee. Ethics reference number 12/SW/0206. The results of the trial will be presented at national and international meetings and published in an Health Technology Assessment (HTA) Monograph and in peer-reviewed journals. Trial registration number ISRCTN30784948; Pre-results.