[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial.

BACKGROUND: The TheraP study reported improved prostate-specific antigen responses with lutetium-177 [177Lu]Lu-PSMA-617 versus cabazitaxel in men with metastatic castration-resistant prostate cancer progressing after docetaxel. In this Article, we report the secondary outcome of overall survival with mature follow-up, and an updated imaging biomarker analysis. We also report the outcomes of participants excluded due to ineligibility on gallium-68 [68Ga]Ga-PSMA-11 and 2-[18F]fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET-CT. METHODS: TheraP was an open-label, randomised phase 2 trial at 11 centres in Australia. Eligible participants had metastatic castration-resistant prostate cancer progressing after docetaxel, and PET imaging with [68Ga]Ga-PSMA-11 and 2-[18F]FDG that showed prostate-specific membrane antigen (PSMA)-positive disease and no sites of metastatic disease with discordant 2-[18F]FDG-positive and PSMA-negative findings. Participants were randomly assigned (1:1) to treatment with [177Lu]Lu-PSMA-617 (every 6 weeks for a maximum of six cycles; starting at 8·5 GBq, decreasing by 0.5 GBq to 6·0 GBq for the sixth cycle) versus cabazitaxel (20 mg/m2 every 3 weeks, maximum of ten cycles). Overall survival was analysed by intention-to-treat and summarised as restricted mean survival time (RMST) to account for non-proportional hazards, with a 36-month restriction time corresponding to median follow-up. This trial is registered with ClinicalTrials.gov, NCT03392428, and is complete. FINDINGS: 291 men were registered from Feb 6, 2018, to Sept 3, 2019; after study imaging, 200 were eligible and randomly assigned to treatment with [177Lu]Lu-PSMA-617 (n=99) or cabazitaxel (n=101). After completing study treatment, 20 (20%) participants assigned to cabazitaxel and 32 (32%) assigned to [177Lu]Lu-PSMA-617 were subsequently treated with the alternative regimen. After a median follow-up of 35·7 months (IQR 31·1 to 39·2), 77 (78%) participants had died in the [177Lu]Lu-PSMA-617 group and 70 (69%) participants had died in the cabazitaxel group. Overall survival was similar among those assigned to [177Lu]Lu-PSMA-617 versus those assigned to cabazitaxel (RMST 19·1 months [95% CI 16·9 to 21·4] vs 19·6 months [17·4 to 21·8]; difference -0·5 months [95% CI -3·7 to 2·7]; p=0·77). No additional safety signals were identified with the longer follow-up in this analysis. 80 (27%) of 291 men who were registered after initial eligibility screening were excluded after [68Ga]Ga-PSMA-11 and 2-[18F]FDG PET. In the 61 of these men with follow-up available, RMST was 11·0 months (95% CI 9·0 to 13·1). INTERPRETATION: These results support the use of [177Lu]Lu-PSMA-617 as an alternative to cabazitaxel for PSMA-positive metastatic castration-resistant prostate cancer progressing after docetaxel. We did not find evidence that overall survival differed between the randomised groups. Median overall survival was shorter for men who were excluded because of low PSMA expression or 2-[18F]FDG-discordant disease. FUNDING: Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, It's a Bloke Thing, CAN4CANCER, and The Distinguished Gentleman's Ride.

Ventilation Heterogeneity Is a Treatable Trait in Severe Asthma.

BACKGROUND: Ventilation heterogeneity (VH) is a feature of asthma and indicates small airway disease. Nuclear imaging methods assess VH, which can facilitate clinical diagnosis and further our understanding of disease aetiology. OBJECTIVE: We sought to assess VH in severe eosinophilic asthma (SEA) using ventilation/perfusion single-photon emission computed tomography (V/P SPECT), and to assess its use as an objective test of the effect of biologic treatment for ventilation defects in SEA. METHODS: Adults (≥18 y) with severe asthma were recruited to participate in a cross-sectional observational study. Participants underwent a clinical assessment and V/P SPECT CT using Technegas as the ventilation agent. Measures were repeated for a nested before-after treatment study in people with SEA commencing biologics. RESULTS: A total of 62 participants with severe asthma were recruited. From this, 38 participants with SEA were included in the before-after study. The VH was associated with clinical variables such as lung function impairment and significantly improved after monoclonal antibody treatment in the severe asthma group. The changes in VH correlated with change in post bronchodilator forced expiratory volume in 1 second (FEV1) %predicted (r = -0.503; P = .001) and post bronchodilator FEV1/FVC (forced vital capacity) (r = -0.415; P = .01). CONCLUSIONS: The VH is clinically significant, measurable, and treatable, which establishes VH as a treatable trait in severe asthma.

Imaging for precision medicine: can V-P SPECT measure mepolizumab response in asthma?

Monoclonal antibody therapies are effective for many but not all people with severe asthma. Precision medicine guides treatment selection using biomarkers to select patients most likely to respond according to their inflammatory endotypes. However, when assessing response to treatment, greater precision is required. We report a case series describing treatment response to mepolizumab in four severe asthma patients, assessed by traditional methods and with objective ventilation/perfusion single photon emission computed tomography (V-P SPECT). In this series, patients with severe asthma received mepolizumab treatment with clinical outcomes recorded at commencement and at approximately 16 weeks post-treatment initiation. V-P SPECT imaging was performed before and after treatment to determine ventilation heterogeneity and perfusion, and its ability to assess treatment responsiveness. V-P SPECT shows promise as an objective measure to assess lung ventilation and perfusion to observe and assess responsiveness to mepolizumab. With quantification, this measure may allow better precision in determining treatment improvements.

[177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial.

BACKGROUND: Lutetium-177 [177Lu]Lu-PSMA-617 is a radiolabelled small molecule that delivers ß radiation to cells expressing prostate-specific membrane antigen (PSMA), with activity and safety in patients with metastatic castration-resistant prostate cancer. We aimed to compare [177Lu]Lu-PSMA-617 with cabazitaxel in patients with metastatic castration-resistant prostate cancer. METHODS: We did this multicentre, unblinded, randomised phase 2 trial at 11 centres in Australia. We recruited men with metastatic castration-resistant prostate cancer for whom cabazitaxel was considered the next appropriate standard treatment. Participants were required to have adequate renal, haematological, and liver function, and an Eastern Cooperative Oncology Group performance status of 0-2. Previous treatment with androgen receptor-directed therapy was allowed. Men underwent gallium-68 [68Ga]Ga-PSMA-11 and 2-flourine-18[18F]fluoro-2-deoxy-D-glucose (FDG) PET-CT scans. PET eligibility criteria for the trial were PSMA-positive disease, and no sites of metastatic disease with discordant FDG-positive and PSMA-negative findings. Men were randomly assigned (1:1) to [177Lu]Lu-PSMA-617 (6·0-8·5 GBq intravenously every 6 weeks for up to six cycles) or cabazitaxel (20 mg/m2 intravenously every 3 weeks for up to ten cycles). The primary endpoint was prostate-specific antigen (PSA) response defined by a reduction of at least 50% from baseline. This trial is registered with ClinicalTrials.gov, NCT03392428. FINDINGS: Between Feb 6, 2018, and Sept 3, 2019, we screened 291 men, of whom 200 were eligible on PET imaging. Study treatment was received by 98 (99%) of 99 men randomly assigned to [177Lu]Lu-PSMA-617 versus 85 (84%) of 101 randomly assigned to cabazitaxel. PSA responses were more frequent among men in the [177Lu]Lu-PSMA-617 group than in the cabazitaxel group (65 vs 37 PSA responses; 66% vs 37% by intention to treat; difference 29% (95% CI 16-42; p<0·0001; and 66% vs 44% by treatment received; difference 23% [9-37]; p=0·0016). Grade 3-4 adverse events occurred in 32 (33%) of 98 men in the [177Lu]Lu-PSMA-617 group versus 45 (53%) of 85 men in the cabazitaxel group. No deaths were attributed to [177Lu]Lu-PSMA-617. INTERPRETATION: [177Lu]Lu-PSMA-617 compared with cabazitaxel in men with metastatic castration-resistant prostate cancer led to a higher PSA response and fewer grade 3 or 4 adverse events. [177Lu]Lu-PSMA-617 is a new effective class of therapy and a potential alternative to cabazitaxel. FUNDING: Prostate Cancer Foundation of Australia, Endocyte (a Novartis company), Australian Nuclear Science and Technology Organization, Movember, The Distinguished Gentleman's Ride, It's a Bloke Thing, and CAN4CANCER.

Regional changes with global brain hypometabolism indicates a physiological triage phenomenon and can explain shared pathophysiological events in Alzheimer's & small vessel diseases and delirium.

While reduced global brain metabolism is known in aging, Alzheimer's disease (AD), small vessel disease (SVD) and delirium, explanation of regional brain metabolic (rBM) changes is a challenge. We hypothesized that this may be explained by "triage phenomenon", to preserve metabolic supply to vital brain areas. We studied changes in rBM in 69 patients with at least 5% decline in global brain metabolism during active lymphoma. There was significant decline in the rBM of the inferior parietal, precuneus, superior parietal, lateral occipital, primary visual cortices (P<0.001) and in the right lateral prefrontal cortex (P=0.01). Some areas showed no change; multiple areas had significantly increased rBM (e.g. medial prefrontal, anterior cingulate, pons, cerebellum and mesial temporal cortices; P<0.001). We conclude the existence of a physiological triage phenomenon and argue a new hypothetical model to explain the shared events in the pathophysiology of aging, AD, SVD and delirium.

Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study.

BACKGROUND: Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management. METHODS: In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358. FINDINGS: From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23-31) greater accuracy than that of conventional imaging (92% [88-95] vs 65% [60-69]; p<0·0001). We found a lower sensitivity (38% [24-52] vs 85% [74-96]) and specificity (91% [85-97] vs 98% [95-100]) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% [32% absolute difference; 28-35] for patients with pelvic nodal metastases, and 95% vs 74% [22% absolute difference; 18-26] for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 [15%] men [10-22] vs 41 [28%] men [21-36]; p=0·008) and had more equivocal findings (23% [17-31] vs 7% [4-13]) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8-12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT. INTERPRETATION: PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning. FUNDING: Movember and Prostate Cancer Foundation of Australia. VIDEO ABSTRACT.

PSMA-PET guided dose-escalated volumetric arc therapy (VMAT) for newly diagnosed lymph node positive prostate cancer: Efficacy and toxicity outcomes at two years.

PURPOSE/OBJECTIVES: There are no published reports of prostate specific membrane antigen (PSMA) positron emission tomography (PET) guided dose-escalated intensity-modulated radiation therapy (DE-IMRT) in newly diagnosed lymph node (LN) positive prostate cancer. We report early toxicity and efficacy outcomes with this approach. MATERIALS/METHODS: Patients with newly diagnosed high-risk prostate cancer were staged using PSMA PET, computed tomography (CT) and bone scans. Patients with LN positive-only metastases were offered curative therapy using 3 months androgen deprivation therapy (ADT) followed by DE-IMRT (using volumetric arc therapy), and 3 years adjuvant ADT. All patients had fiducial marker insertion, with privately insured patients having spacer hydrogel insertion. PET and prostate magnetic resonance imaging were fused with the planning CT. We aimed to deliver 81 Gy in 45 fractions (Fx) to the prostate and PET-positive LNs, and 60 Gy in 45Fx to bilateral elective pelvic LNs. RESULTS: In all, 46 patients were treated, with 83% Gleason 8-10, 67% T3/T4, median number of LNs 2 (range 1-6), and median PET-positive LN volume 1.14 cc (range 0.15-4.14). LNs were outside of standard contouring guidelines in 37% of patients. The mean PET-positive LN clinical target volume dose ranged from 73.3 to 85.9 Gy (median 83.6 Gy). With 24 months median follow-up, two year failure-free survival was 100%, and 2 year overall survival 95.7%. Acute grade 1 and 2 GI toxicity occurred in 48 and 11% of patients, and GU toxicity in 72 and 24%. Late grade 1, 2 and 3 GI toxicity occurred in 13, 2 and 0%, and GU toxicity 28, 13 and 4%. No toxicity was attributable to the high dose LN boost. CONCLUSIONS: PSMA PET-guided DE-IMRT up to 81 Gy to the prostate and involved LNs, and long term ADT, is a promising approach for newly diagnosed LN positive prostate cancer. LN contouring guidelines require re-evaluation in the era of PSMA PET imaging.

FDG-PET parameters predict for recurrence in anal cancer - results from a prospective, multicentre clinical trial.

BACKGROUND: To investigate the prognostic significance of positron emission tomography (PET) parameters from F-18 fluorodeoxyglucose (FDG) PET scans performed pre- and post- chemo-radiotherapy (CRT) for squamous cell carcinoma of the anal canal (AC). METHODS: From January 2013 to January 2017, 19 patients with non-metastatic AC enrolled on a prospective trial underwent FDG-PET/CT imaging before and 12 weeks following CRT. A computer-generated volume of interest (VOI) was snapped around the primary tumour using six different standard uptake value (SUV) thresholds and the following parameters were extracted: SUV max, mean, median, standard deviation and peak as well as metabolic tumour volume (MTV) and total lesion glycolysis. Exact logistic regression and ROC AUC analyses were performed for each metric at each timepoint. RESULTS: With a median follow up of 15.8 months, 3/19 patients had a local recurrence and 5/19 had any recurrence. On post-CRT PET, the median SUV within a VOI bounded by an SUV of 3 correlated with local recurrence (p < 0.01) and demonstrated excellent discrimination (ROC AUC 1.00, perfect separation was achieved at a median SUV of 3.38). The mean SUV at this threshold did not quite reach significance for prediction of local recurrence (p = 0.06) but demonstrated excellent discrimination (ROC AUC 0.91). The MTV bounded by a threshold of 41% SUVmax on the pre-CRT PET predicted for any recurrence (p = 0.03) and showed excellent discrimination (ROC AUC 0.89). CONCLUSIONS: FDG-PET parameters are predictive of recurrence in AC. FDG-PET may represent a valuable tool for prognostication and response assessment in AC. TRIAL REGISTRATION: ANZCTR, ACTRN12614001219673 . Registered 19 November 2014 - Retrospectively registered.

Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography for Prostate Cancer: Distribution of Disease and Implications for Radiation Therapy Planning.

PURPOSE: To explore the prostate-specific membrane antigen (PSMA)-avid distribution of prostate cancer (PC) on positron emission tomography (PET), both at the time of initial diagnosis and at the time of relapse after definitive local treatment. METHODS AND MATERIALS: A total of 179 PSMA PET scans in patients with nil or ≤3 lesions on conventional imaging were retrospectively categorized into 3 subgroups: group A, high-risk PC with no prior definitive therapy (n=34); group B, prior prostatectomy (n=75); and group C, prior radiation therapy (n=70). The numbers and locations of the PSMA-avid lesions were mapped. The PSMA-positive lesions were identified subjectively by a nuclear medicine physician on the basis of clinical experience and taking into account the recent literature and artefacts. RESULTS: A total of 893 PSMA-avid lesions were identified; at least 1 lesion was detected in 80% of all scans. A high detection rate was present even at very low serum PSA levels (eg, at PSA ≤0.20 ng/mL in group B, the detection rate was 46%). Thirty-eight percent of studies revealed extrapelvic disease (41%, 31%, and 46% in groups A, B, and C, respectively). Almost one-third of all studies showed only oligometastases (24%, 36%, and 31% in groups A, B, and C, respectively). A large proportion of these (40%) were a solitary lesion. CONCLUSIONS: Prostate-specific membrane antigen PET demonstrated a large number of otherwise unknown metastatic lesions. Therefore we recommend PSMA PET for more accurate assessment of disease burden in initial staging of high-risk PC, as well as for restaging in patients with prostate-specific antigen relapse after primary therapies. Furthermore, a high proportion of oligometastases on PSMA PET provides a prime opportunity to investigate the role of targeted local therapies for oligometastatic PCs.

Radionuclide bone scan SPECT-CT: lowering the dose of CT significantly reduces radiation dose without impacting CT image quality.

The CT component of SPECT-CT is required for attenuation correction and anatomical localization of the uptake on SPECT but there is no guideline about the optimal CT acquisition parameters. In our department, a standard CT acquisition protocol was changed in 2013 to give lower radiation dose to the patient. In this study, we retrospectively compared the effects on patient dose as well as the CT image quality with current versus older CT protocols. Ninety nine consecutive patients [n=51 Standard dose 'old' protocol (SDP); n=48 lower dose 'new' protocol (LDP)] with lumbar spine SPECT-CT for bone scan were examined. The main differences between the two protocols were that SDP used 130 kVp tube voltage and reference current-time product of 70 mAs whereas the LDP used 110 kVp and 40 mAs respectively. Various quantitative parameters from the CT images were obtained and the images were also rated blindly by two experienced nuclear medicine physicians for bony definition and noise. The mean calculated dose length product of the LDP group (121.5±39.6 mGy.cm) was significantly lower compared to the SDP group patients (266.9±96.9 mGy.cm; P<0.0001). This translated into a significant reduction in the mean effective dose to 1.8 mSv from 4.0 mSv. The physicians reported better CT image quality for the bony structures in LDP group although for soft tissue structures, the SDP group had better image quality. The optimized new CT acquisition protocol significantly reduced the radiation dose to the patient and in-fact improved CT image quality for the assessment of bony structures.

The Role of FDG-PET in the Initial Staging and Response Assessment of Anal Cancer: A Systematic Review and Meta-analysis.

PURPOSE: The aim of this systematic review and meta-analysis was to compare the role of FDG-positron emission tomography (PET) or PET/computed tomography (CT) with conventional imaging in the detection of primary and nodal disease in anal cancer, and to assess the impact of PET or PET/CT on the management of anal cancer. METHODS: A systematic review of the literature was performed. Eligible studies included those comparing PET or PET/CT with conventional imaging in the staging of histologically confirmed anal squamous cell carcinoma (SCC), or studies that performed PET or PET/CT imaging to assess response following treatment. RESULTS: Twelve studies met the inclusion criteria. For the detection of primary disease, CT and PET had a sensitivity of 60 % (95 % confidence interval [CI] 45.5-75.2) and 99 % (95 % CI 96-100), respectively. Compared with conventional imaging, PET upstaged 15 % (95 % CI 10-21) and downstaged 15 % (95 % CI 10-20) of nodal disease. This led to a change in nodal staging in 28 % of patients (95 % CI 18-38). When only studies performing contemporary PET/CT were considered, the rate of nodal upstaging was 21 % (95 % CI 13-30) and the TNM stage was altered in 41 % of patients. Following chemoradiotherapy, 78 % (95 % CI 65-88) of patients had a complete response on PET. CONCLUSION: Compared with conventional imaging, PET or PET/CT alters the nodal status in a sufficient number of cases to justify its routine use in the staging of patients with anal SCC.

Use of imaging for investigation of suspected pulmonary embolism during pregnancy and the postpartum period.

Pulmonary embolism (PE) is recognized as a leading cause of maternal mortality in the developed world; however, it is a very difficult diagnosis to make on clinical grounds, and in most cases imaging is required. Pregnancy is a recognized risk factor for venous thromboembolism, and symptoms of normal pregnancy including shortness of breath, tachycardia and leg swelling are included in clinical tools for risk stratification for PE in the non-pregnant population. This results in a very low threshold for imaging, despite concerns regarding the risk of exposure to ionizing radiation both for the fetus and the maternal breast. We reviewed the results of all ventilation/perfusion scans and computed tomography pulmonary angiograms performed in pregnant women at a single institution to identify how many of these tests were positive for PE, and which clinical features may identify a low-risk group. A total of 386 scans were performed to investigate 375 episodes of suspected PE, representing 1.3-1.5% of pregnant women. Fifteen patients were diagnosed with PE, giving an incidence of one in 2000 maternities. The only statistically significant factors associated with PE were smoking or the presence of multiple risk factors. Clinical features of tachycardia and leg swelling did not provide significant diagnostic value; however, the absence of pleuritic chest pain had a negative predictive value of 97.8%. Arterial blood gas and D-dimer were statistically different between those with and without PE but not to a clinically useful degree. Currently available clinical and laboratory tools are not adequate to exclude a diagnosis of PE in a pregnant patient, thus imaging is justified to exclude PE. Further longitudinal studies to identify a low-risk group who do not require imaging is vital.