Treatment of classical Hodgkin lymphoma in young adults aged 18-30 years with a modified paediatric Hodgkin lymphoma protocol. Results of a multicentre phase II clinical trial (CRUK/08/012).

This phase II trial was designed to determine the safety and efficacy of a modified paediatric risk-stratified protocol in young adults (18-30 years) with classical Hodgkin Lymphoma. The primary end-point was neurotoxicity rate. The incidence of grade 3 neurotoxicity was 11% (80% CI, 5-19%); a true rate of neuropathy of >15% cannot be excluded. Neuropathy and associated deterioration in quality of life was largely reversible. The overall response rate was 100% with 40% complete remission (CR) rate. Twelve months disease-free survival (DFS) was 91%. We demonstrate that a risk-stratified paediatric combined modality treatment approach can be delivered to young adults without significant irreversible neuropathy.

Eligibility for 177Lu-PSMA Therapy Depends on the Choice of Companion Diagnostic Tracer: A Comparison of 68Ga-PSMA-11 and 99mTc-MIP-1404 in Metastatic Castration-Resistant Prostate Cancer.

177Lu-prostate-specific membrane antigen-617 (177Lu-PSMA-617) is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC), with evidence of improved survival over standard care. The VISION trial inclusion criteria required a metastatic lesion-to-liver ratio of greater than 1 on 68Ga-PSMA-11 PET scans. We aimed to determine whether an equivalent ratio is suitable for a SPECT tracer, 99mTc-MIP-1404, and to compare lesion and lesion-to-normal-organ ratios between the 2 radiotracers. Methods: Two cohorts of patients with mCRPC matched for age, prostate-specific antigen level, and total Gleason score, with either 99mTc-MIP-1404 SPECT/CT (n = 25) or 68Ga-PSMA-11 PET/CT (n = 25) scans, were included for analysis. Up to 3 lesions in each site (prostate/prostate bed, lymph nodes, bone and soft-tissue metastases) as well as normal liver, parotid gland, spleen, and mediastinal blood-pool SUVmax were measured. Results: 99mTc-MIP-1404 SPECT lesion SUVmax was not significantly different from 68Ga-PSMA-11 PET (median, 18.2 vs. 17.3; P = 0.93). However, 99mTc-MIP-1404 liver SUVmax was higher (median, 8.5 vs. 5.8; P = 0.002) and lesion-to-liver ratios were lower (median, 2.7 vs. 3.5; P = 0.009). There was no significant difference in parotid gland or splenic SUVmax or lesion-to-parotid gland ratios between the 2 tracers although there was a small difference in lesion-to-spleen ratios (P = 0.034). Conclusion: There are differences in biodistribution and, in particular, liver activity, between 68Ga-PSMA-11 and 99mTc-MIP-1404. Therefore, if 99mTc-MIP-1404 is used to assess eligibility for 177Lu-PSMA-617 therapy, a lower adjusted lesion-to-liver ratio should be used.

Reproducibility of 2D and 3D fractal analysis techniques for the assessment of spatial heterogeneity of regional blood flow in rectal cancer.

PURPOSE: To characterize the two-dimensional (2D) and three-dimensional (3D) fractal properties of rectal cancer regional blood flow assessed by using volumetric helical perfusion computed tomography (CT) and to determine its reproducibility. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Ten prospective patients (eight men, two women; mean age, 72.3 years) with rectal adenocarcinoma underwent two repeated volumetric helical perfusion CT studies (four-dimensional adaptive spiral mode, 11.4-cm z-axis coverage) without intervening treatment within 24 hours, with regional blood flow derived by using deconvolution analysis. Two-dimensional and 3D fractal analyses of the rectal tumor were performed, after segmentation from surrounding structures by using thresholding, to derive fractal dimension and fractal abundance. Reproducibility was quantitatively assessed by using Bland-Altman statistics. Two-dimensional and 3D lacunarity plots were also generated, allowing qualitative assessment of reproducibility. Statistical significance was at 5%. RESULTS: Mean blood flow was 63.50 mL/min/100 mL ± 8.95 (standard deviation). Good agreement was noted between the repeated studies for fractal dimension; mean difference was -0.024 (95% limits of agreement: -0.212, 0.372) for 2D fractal analysis and -0.024 (95% limits of agreement: -0.307, 0.355) for 3D fractal analysis. Mean difference for fractal abundance was -0.355 (95% limits of agreement: -0.869, 1.579) for 2D fractal analysis and -0.043 (95% limits of agreement: -1.154, 1.239) for 3D fractal analysis. The 95% limits of agreement were narrower for 3D than 2D analysis. Lacunarity plots also visually confirmed close agreement between repeat studies. CONCLUSION: Regional blood flow in rectal cancer exhibits fractal properties. Good reproducibility was achieved between repeated studies with 2D and 3D fractal analysis.

Radionuclide calibrator intercomparison study of clinical PET centres in England to a single traceable 68Ge syringe source.

OBJECTIVES: The aim of this study was to characterize national variation in radionuclide calibrator activity response to a single National Institute of Standards and Technology (NIST) traceable reference Ge source used as a surrogate for F at clinical PET centres in England using National Physical Laboratory approved techniques. METHODS: Readings from 20 instruments at 13 centres using local F and Ge factor settings were recorded with the source located in vial and syringe positions. Ten repeat measurements were conducted to investigate repeatability using % coefficient of variability (COV). Comparison ratios to investigate accuracy were made between calibrator responses and decay-corrected NISTref reference activity for syringe and vial position measurements. RESULTS: The maximum %COV was 0.79%, while 90, 95 and 80% of calibrators conformed to 5% accuracy for F syringe, Ge syringe and Ge vial position readings, respectively. We revealed a trend towards reduced bias in measurements using Veenstra devices for F and using Capintec devices for Ge factor settings. CONCLUSIONS: This study demonstrated good repeatability in local device measurements. In total, 70% of English calibrators tested and 88% of all measurements performed achieved 5% accuracy. While statistically significant bias was exhibited between different vendor equipment dependent upon radioisotope selected, our study recommends regular traceability checks for optimum instrument performance conducted within National Metrology Institutes guidelines.

Positron emission tomography PET/CT harmonisation study of different clinical PET/CT scanners using commercially available software.

OBJECTIVES: Harmonisation is the process whereby standardised uptake values from different scanners can be made comparable. This PET/CT pilot study aimed to evaluate the effectiveness of harmonisation of a modern scanner with image reconstruction incorporating resolution recovery (RR) with another vendor older scanner operated in two-dimensional (2D) mode, and for both against a European standard (EARL). The vendor-proprietary software EQ•PET was used, which achieves harmonisation with a Gaussian smoothing. A substudy investigated effect of RR on harmonisation. METHODS: Phantom studies on each scanner were performed to optimise the smoothing parameters required to achieve successful harmonisation. 80 patients were retrospectively selected; half were imaged on each scanner. As proof of principle, a cohort of 10 patients was selected from the modern scanner subjects to study the effects of RR on harmonisation. RESULTS: Before harmonisation, the modern scanner without RR adhered to EARL specification. Using the phantom data, filters were derived for optimal harmonisation between scanners and with and without RR as applicable, to the EARL standard. The 80-patient cohort did not reveal any statistically significant differences. In the 10-patient cohort SUVmax for RR > no RR irrespective of harmonisation but differences lacked statistical significance (one-way ANOVA F(3.36) = 0.37, p = 0.78). Bland-Altman analysis showed that harmonisation reduced the SUVmax ratio between RR and no RR to 1.07 (95% CI 0.96-1.18) with no outliers. CONCLUSIONS: EQ•PET successfully enabled harmonisation between modern and older scanners and against the EARL standard. Harmonisation reduces SUVmax and dependence on the use of RR in the modern scanner. ADVANCES IN KNOWLEDGE: EQ•PET is feasible to harmonise different PET/CT scanners and reduces the effect of RR on SUVmax.

Prognostic value of 18FDG PET/CT volumetric parameters in the survival prediction of patients with pancreatic cancer.

PURPOSE: To investigate the value of 18 FDG PET/CT volumetric parameters in the prediction of overall survival (OS) in patients with pancreatic cancer and also, assess their independence relative to well-established clinico-pathological variables. METHODS: We conducted a retrospective analysis of patients with a confirmed diagnosis of pancreatic cancer who underwent 18 FDG PET/CT. The tumour maximum standardised uptake value (SUVmax) in addition to SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated. The prognostic value of 18 FDG PET/CT and clinico-pathological parameters for OS were assessed using univariate and multivariable analyses. RESULTS: A sum of 89 patients were analysed in this study. Median survival for patients categorised as having high TLG (≥55) and low TLG (<55) was 18 vs 5 months (p < 0.001). Similarly, the respective high vs low SUVmean, MTV and SUVmax were 18 vs 6 months (p = 0.001), 16 vs 6 months (p = 0.002) and 18 vs 6 months (p = 0.001). Univariate analysis showed SUVmax, SUVmean, MTV, TLG, tumour size, tumour differentiation and presence of distant metastasis as prognostic factors for OS. On multivariable analysis, TLG (HR 2.0, 95% CI 1.26-3.18, p = 0.004) and the presence of distant metastasis (HR 3.37, 95% CI 1.97-5.77, p < 0.001) emerged as independent prognostic factors. Subgroup analysis identified TLG as the only significant PET metric after adjusting for the presence of distant metastasis. CONCLUSIONS: 18 FDG PET/CT is a useful tool in the preoperative evaluation of patients with pancreatic cancer. Tumour TLG offer an independent prognostic value in both potentially operable and metastatic disease settings.

Assessment of the spatial pattern of colorectal tumour perfusion estimated at perfusion CT using two-dimensional fractal analysis.

The aim was to evaluate the feasibility of fractal analysis for assessing the spatial pattern of colorectal tumour perfusion at dynamic contrast-enhanced CT (perfusion CT). Twenty patients with colorectal adenocarcinoma underwent a 65-s perfusion CT study from which a perfusion parametric map was generated using validated commercial software. The tumour was identified by an experienced radiologist, segmented via thresholding and fractal analysis applied using in-house software: fractal dimension, abundance and lacunarity were assessed for the entire outlined tumour and for selected representative areas within the tumour of low and high perfusion. Comparison was made with ten patients with normal colons, processed in a similar manner, using two-way mixed analysis of variance with statistical significance at the 5% level. Fractal values were higher in cancer than normal colon (p < or = 0.001): mean (SD) 1.71 (0.07) versus 1.61 (0.07) for fractal dimension and 7.82 (0.62) and 6.89 (0.47) for fractal abundance. Fractal values were lower in 'high' than 'low' perfusion areas. Lacunarity curves were shifted to the right for cancer compared with normal colon. In conclusion, colorectal cancer mapped by perfusion CT demonstrates fractal properties. Fractal analysis is feasible, potentially providing a quantitative measure of the spatial pattern of tumour perfusion.

Scan-time reduction using noise-matched images in 2- and 3-dimensional bismuth germanate PET/CT: clinical study in head and neck cancer.

UNLABELLED: We quantitatively and qualitatively investigated 2-dimensional (2D) and 3-dimensional (3D) imaging with scan-time reduction in 14 patients with 17 lesions, who had known or suspected head and neck cancer, using a bismuth germanate (BGO) crystal based PET/CT scanner with noise-matched images. METHODS: A 2D and 3D acquisition protocol using scan-time reduction on an axial single field of view resulted in a 2D 4-, 3D 4-, 3D 3-, 2D 3-, 2D 2-, and 3D 2-min scan sequence to minimize redistribution and decay bias. Tumor maximum standardized uptake values (SUVmax) and tumor mean standardized uptake values (SUV(mean)) were recorded, and two observers in consensus investigated lesion conspicuity between 2D and 3D paired 4-, 3-, and 2-min noise-matched images. RESULTS: We found some minor advantages quantitatively in favor of 2D scanning, with higher mean SUVmax, and qualitatively in favor of 3D scanning, with lesion conspicuity preference. In our cohort, no great advantage or disadvantage to using either acquisition mode was observed, and all lesions were seen irrespective of acquisition mode and scan time. CONCLUSION: In head and neck cancer patients, we can recommend a scan-time reduction from 4 to 3 min/bed position in 2D acquisitions with a BGO-based PET/CT scanner, using our imaging protocol and reconstruction defaults.

Effect of PET Image Reconstruction Techniques on Unexpected Aorta Uptake

Objectives: To determine if unexpected aorta uptake seen in some patients is influenced by popular modern reconstruction algorithms using semi-quantitative and qualitative analysis. Methods: Twenty-five consecutive patients without suspected vascular disease were selected for 18F-FDG positron emission tomography/ computed tomography (PET/CT) scanning and images of the aorta were created using iterative reconstruction (IT), IT + time of flight (TOF), IT + TOF + point spread function correction (referred collectively as UHD) with and without metal artefact reduction (MAR) algorithms. An experienced radiologist created aorta and blood pool (BP) regions of interests then copied these to all reconstructions for accurate positioning before recording target aorta standardized-uptake-values (SUVmax) and background BP SUVmean. Furthermore, target-to-background ratio (TBRmax) was defined by aorta SUVmax-to-BP SUVmean ratio for more analysis. Results: For aorta SUVmax with IT, IT + TOF, UHD, UHD + MAR reconstructions the mean ± standard deviation recorded were 2.15±0.43, 2.25±0.51, 2.25±0.45 and 2.09±0.4, respectively. Values for BP SUVmean were 1.61±0.31, 1.58±0.28, 1.58±0.28 and 1.47±0.25, respectively. Likewise, for TBRmax these were 1.35±0.19, 1.43±0.21, 1.43±0.19, 1.43±0.18, respectively. ANOVA analysis revealed no significant differences for aorta SUVmax (F(0.86) p=0.46), BP SUVmean (F(1.22) p=0.31) or TBRmax (F(0.99) p=0.4). However, the qualitative visual analysis revealed significant differences between IT + TOF with UHD (p=0.02) or UHD + MAR (p=0.02). Conclusion: Reconstruction algorithm effect on aorta SUVmax or BP SUVmean or TBRmax was not statistically significant. However, qualitative visual analysis showed significant differences between IT + TOF as compared with UHD or UHD + MAR reconstructions. Harmonization of techniques with a larger patient cohort is recommended in future clinical trials.

The effects of N-butylscopolamine on bowel uptake: an 18F-FDG PET study.

PURPOSE: To determine the effect of N-butylscopolamine (buscopan) on intestinal uptake of 18F-FDG. METHODS: Seventy-two oncology patients were prospectively studied and 36 patients received 20 mg of N-butylscopolamine intravenously. All patients were imaged with a Siemens PET scanner. After a 4-h fast, patients were injected with FDG and then scanned 1 h post-injection. Two experienced observers interpreted all studies independently. Scans were scored visually, grading 18F-FDG bowel uptake (0-3) and the influence of bowel uptake to a lack of confidence in scan reporting (0-3). For semi-quantitative comparison, the ratio of radiotracer uptake in the bowel to mean liver (B/L) was obtained. RESULTS: All results were in favour of N-butylscopolamine. For the qualitative data, a Mann-Whitney test was used. Results for contribution of bowel uptake to lack of confidence in reporting scores, showed P=0.0001 for observer 1, and P=0.002 for observer 2; for degree of uptake in bowel scores, observer 1 results gave a value of P=0.0001 and observer 2 P=0.001. For agreement of uptake scores, Kappa index showed 'moderate' agreement between observers for the control group and 'fair' agreement for the N-butylscopolamine group. For contribution of bowel uptake to lack of confidence scores, there was 'very good' agreement for the control group and 'fair' agreement for the N-butylscopolamine group. The semi-quantitative effect of N-butylscopolamine on bowel-to-liver ratio was determined using an unrelated t-test that produced significance at the level of P<0.001. CONCLUSION: This study showed that administration of N-butylscopolamine can reduce artefacts in the bowel during 18F-FDG PET, and can potentially improve accuracy of 18F-FDG PET reporting.

PET-PANC: multicentre prospective diagnostic accuracy and health economic analysis study of the impact of combined modality 18fluorine-2-fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography scanning in the diagnosis and management of pancreatic cancer.

BACKGROUND: Pancreatic cancer diagnosis and staging can be difficult in 10-20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. OBJECTIVE: To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. DESIGN: A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. PARTICIPANTS: Patients with suspected pancreatic malignancy. INTERVENTIONS: All patients to undergo PET/CT following standard diagnostic work-up. MAIN OUTCOME MEASURES: The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients' diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. RESULTS: Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (p = 0.01) and specificity (p = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (p < 0.0002). PET/CT correctly changed the staging of pancreatic cancer in 56 patients (p = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval -0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. CONCLUSION: PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. STUDY REGISTRATION: Current Controlled Trials ISRCTN73852054 and UKCRN 8166. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Evaluation of normal FDG uptake in palatine tonsil and its potential value for detecting occult head and neck cancers: a PET CT study.

OBJECTIVE: The aims of the study were to (1) evaluate the range of physiological FDG uptake in normal pharyngeal palatine tonsil, and (2) investigate the possibility of establishing a cut-off threshold to distinguish between normal pharyngeal palatine tonsil FDG uptake from occult pharyngeal palatine tonsil primary cancer. METHODS: FDG PET CT of 43 consecutive patients with a low risk of head and neck cancer were reviewed by two observers. Axial PET CT was used to identify foci of FDG uptake related to the pharyngeal palatine tonsil. The highest standardized uptake value, SUVmax, of the left and right pharyngeal palatine tonsil was calculated. Similar analysis was performed on 10 consecutive patents with histologically proven occult pharyngeal palatine tonsil primary cancer. RESULTS: The mean SUVmax of the 43 right pharyngeal palatine tonsils was 4.82 (range, 1.16-12.74) and 4.68 (range, 0.88-13.65) for the 43 left pharyngeal palatine tonsils with no statistical difference observed (P=0.4). Normal pharyngeal palatine tonsil uptake was generally symmetrical and there was a positive correlation between SUVmax from the left and right sides which was statistically significant (r=0.9, P<0.0001). In the same patient the difference in SUVmax between left and right pharyngeal palatine tonsil ranged from 0.01 to 2.66 and patients with occult pharyngeal palatine tonsil primary cancer it ranged from 0.85 to 11.08. ROC analysis showed that an 'SUVmax difference' cut-off of 0.83 would achieve a sensitivity of 100% and specificity of 81% for detecting occult pharyngeal palatine tonsil primary cancers. CONCLUSIONS: There is considerable variation of pharyngeal palatine tonsil FDG uptake in patients with no pharyngeal palatine tonsil primary cancer. However, in the same patient there is generally only a small difference in uptake between left and right sides. The absolute difference in SUVmax between left and right pharyngeal palatine tonsil is a potentially useful parameter for distinguishing between normal FDG uptake in pharyngeal palatine tonsil from occult pharyngeal palatine tonsil primary cancer.

PET-NECK: a multicentre randomised Phase III non-inferiority trial comparing a positron emission tomography-computerised tomography-guided watch-and-wait policy with planned neck dissection in the management of locally advanced (N2/N3) nodal metastases in patients with squamous cell head and neck cancer.

BACKGROUND: Planned neck dissection (ND) after radical chemoradiotherapy (CRT) for locally advanced nodal metastases in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Thirty per cent of ND specimens show histological evidence of tumour. Consequently, a significant proportion of clinicians still practise planned ND. Fludeoxyglucose positron emission tomography (PET)-computerised tomography (CT) scanning demonstrated high negative predictive values for persistent nodal disease, providing a possible alternative paradigm to ND. Evidence is sparse and drawn mainly from retrospective single-institution studies, illustrating the need for a prospective randomised controlled trial. OBJECTIVES: To determine the efficacy and cost-effectiveness of PET-CT-guided surveillance, compared with planned ND, in a multicentre, prospective, randomised setting. DESIGN: A pragmatic randomised non-inferiority trial comparing PET-CT-guided watch-and-wait policy with the current planned ND policy in HNSCC patients with locally advanced nodal metastases and treated with radical CRT. Patients were randomised in a 1 : 1 ratio. Primary outcomes were overall survival (OS) and cost-effectiveness [incremental cost per incremental quality-adjusted life-year (QALY)]. Cost-effectiveness was assessed over the trial period using individual patient data, and over a lifetime horizon using a decision-analytic model. Secondary outcomes were recurrence in the neck, complication rates and quality of life. The recruitment of 560 patients was planned to detect non-inferior OS in the intervention arm with a 90% power and a type I error of 5%, with non-inferiority defined as having a hazard ratio (HR) of no higher than 1.50. An intention-to-treat analysis was performed by Cox's proportional hazards model. SETTINGS: Thirty-seven head and neck cancer-treating centres (43 NHS hospitals) throughout the UK. PARTICIPANTS: Patients with locally advanced nodal metastases of oropharynx, hypopharynx, larynx, oral or occult HNSCC receiving CRT and fit for ND were recruited. INTERVENTION: Patients randomised to planned ND before or after CRT (control), or CRT followed by fludeoxyglucose PET-CT 10-12 weeks post CRT with ND only if PET-CT showed incomplete or equivocal response of nodal disease (intervention). Balanced by centre, planned ND timing, CRT schedule, disease site and the tumour, node, metastasis stage. RESULTS: In total, 564 patients were recruited (ND arm, n = 282; and surveillance arm, n = 282; 17% N2a, 61% N2b, 18% N2c and 3% N3). Eighty-four per cent had oropharyngeal cancer. Seventy-five per cent of tested cases were p16 positive. The median time to follow-up was 36 months. The HR for OS was 0.92 [95% confidence interval (CI) 0.65 to 1.32], indicating non-inferiority. The upper limit of the non-inferiority HR margin of 1.50, which was informed by patient advisors to the project, lies at the 99.6 percentile of this estimate (p = 0.004). There were no differences in this result by p16 status. There were 54 NDs performed in the surveillance arm, with 22 surgical complications, and 221 NDs in the ND arm, with 85 complications. Quality-of-life scores were slightly better in the surveillance arm. Compared with planned ND, PET-CT surveillance produced an incremental net health benefit of 0.16 QALYs (95% CI 0.03 to 0.28 QALYs) over the trial period and 0.21 QALYs (95% CI -0.41 to 0.85 QALYs) over the modelled lifetime horizon. LIMITATIONS: Pragmatic randomised controlled trial with a 36-month median follow-up. CONCLUSIONS: PET-CT-guided active surveillance showed similar survival outcomes to ND but resulted in considerably fewer NDs, fewer complications and lower costs, supporting its use in routine practice. FUTURE WORK: PET-CT surveillance is cost-effective in the short term, and long-term cost-effectiveness could be addressed in future work. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13735240. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 17. See the NIHR Journals Library website for further project information.

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia.

OBJECTIVE: Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner. METHODS: Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time. RESULTS: SUVmax exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms. CONCLUSION: Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are consistent with other published studies however more specimens are required for full validation.

Potential novel application of dual time point SUV measurements as a predictor of survival in head and neck cancer.

OBJECTIVES: To examine the potential of pre-treatment dual time point [18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) as a tool for improving the assessment of head and neck cancer. Two main areas were investigated: (a) optimum time to start FDG scanning post-injection and (b) potential of SUV obtained from dual time point scanning as a prognostic indicator of survival. METHODS: Twelve patients with advanced head and neck cancer were prospectively studied. Each patient was scanned using a Siemen's Ecat Exact-47 PET scanner at 1 h and 2 h post-injection. Maximum tumour uptake (SUVt) and ratio of maximum tumour/normal tissue uptake (SUVt/n) were recorded. The optimal time to initiate scanning was investigated by comparing SUVt and SUVt/n with the decision made by two experienced observers as to which scan they preferred to report from, given the choice of the 1 h and 2 h scan in each patient. RESULTS: A significant difference between 1 h and 2 h SUVt (P<0.004, paired t-test) and between 1 h and 2 h SUVt/n (P<0.0003, paired t-test) was observed. All 2 h SUVt and SUVt/n were greater in magnitude than their respective 1 h SUVt and SUVt/n counterparts. The two observers reported an identical number of lesions from the 1 h and 2 h scans but preferred the 2 h data. CONCLUSIONS: Tumour stage and the percentage difference in 1 h and 2 h SUVt showed potential as prognostic indicators of long-term survival.

FLT PET-CT in evaluation of treatment response.

PURPOSE: Review published studies to investigate the value of clinical 3-deoxy-3-(18)F-fluorothymidine (FLT) positron emission tomography (PET) in predicting response to treatment. MATERIALS AND METHODS: Interrogate databases to identify suitable publications between 2007 and 2013 with a minimum of five patients. Articles within the inclusion criteria were reviewed with major findings reported leading to a descriptive analysis of FLT PET in therapy response. RESULTS: Lesions investigated included glioma, head and neck, esophageal, lung, breast, gastric, renal, rectal, sarcomas, germ cell, lymphomas, leukemia, and melanoma resulting in a total of 34 studies analyzed. A variety of therapies were applied and dissimilar PET protocols were widespread making direct comparison between studies challenging. Though baseline, early and late therapy scans were popular particularly in chemotherapy regimes. Most studies investigated showed significantly reduced FLT uptake during or after therapy compared with pretreatment scans. CONCLUSION: Current evidence suggests FLT PET has a positive role to play in predicting therapy response especially in brain, lung, and breast cancers where good correlation with Ki-67 is observed. However, careful attention must be placed in undertaking larger clinical trials where harmonization of scanning and analysis protocols are strictly adhered to fully assess the true potential of FLT PET in predicting response to treatment.

18F-FDG PET/CT appearances of adult pulmonary blastoma.

(18)F-FDG PET/CT scanning plays an important role in the management of thoracic malignancy. The authors would like to present FDG PET/CT images of a rare thoracic malignancy, pulmonary blastoma in adulthood. The patient had recurrent metastatic disease of previously resected primary pulmonary blastoma. The foci of recurrent metastases in lung, mediastinum, and subcutaneous tissue are intensely FDG-avid.

Unexpected Significantly Reduced FDG Uptake in the Cerebrum Compared Against Normal Liver Uptake in a Dying Patient.

UNLABELLED: F-18 FDG PET-CT scanning plays an important role in the management of fever of unknown origin (FUO). Some elderly patients with FUO can be in their terminal stage of life. An elderly woman was referred for a PET-CT scan to find the etiology of FUO. The scan was inconclusive but showed significantly reduced FDG uptake in the brain and heart, despite normal physiological uptake in the liver and bowel. The patient deceased within the hour post scan. Contrary to common belief, we have shown that cerebral glucose metabolism via cerebral perfusion may be compromised before hepatic and bowel perfusion in a dying patient. CONFLICT OF INTEREST: None declared.

Both native and ectopically transplanted hearts shown on FDG PET/CT in a PTLD patient.

Posttransplant lymphoproliferative disorder (PTLD) is one of the unfortunate complications of immunosuppression after allograft transplantation. 18F-FDG PET/CT plays an important role in the diagnosis and management of PTLD. The authors report a PET/CT scan of a young woman who received a heterotopic cardiac transplant, demonstrating 2 functional hearts in the thorax. The scan also demonstrates a small-volume mediastinal lymphadenopathy caused by the PTLD/B-cell lymphoma, subsequently proven by mediastinoscopic biopsy.

FDG injection site extravasation: potential pitfall of misinterpretation and missing metastases.

18F-FDG PET/CT plays an important role in the management of non-small-cell lung cancers (NSCLC). The treatment options for NSCLC depend upon the initial staging of the disease. The authors report a case with a potential pitfall of overlooking a site of FDG uptake as radiopharmaceutical extravasation at an injection site. The PET/CT demonstrated a T2a N2 bronchial carcinoma, with a solitary focus of FDG uptake at the left antecubital fossa where FDG was administered. Careful interpretation of the images reveals a solitary skeletal metastasis in the left proximal ulna, which makes the disease stage IV rather than IIIA, leading to a significant difference in treatment.