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PurposeTreatment options for unresectable paraganglioma (PGL)/pheochromocytoma (PCC), especially with uncontrolled secondary hypertension (HTN), are limited. Preliminary studies with peptide receptor radionuclide therapy (PRRT) suggest efficacy, but data on HTN control and survival are lacking. We assessed PRRT outcomes in such patients from two referral centers.MethodsTwenty consecutive patients (13 men; age range, 21 to 77 years) with high somatostatin receptor (SSTR) expression treated with 177Lu-DOTA-octreotate, nine with radiosensitizing chemotherapy, were retrospectively reviewed. Median cumulative activity was 22 GBq (median 4 cycles). Fourteen patients were treated for uncontrolled HTN and six for progressive or symptomatic metastatic disease or local recurrence.ResultsThree months after PRRT, 8 of 14 patients treated for HTN required reduced medication doses, 5 had no change in anti-HTN doses, and 1 was lost to follow-up. Eighty-six percent had serum chromogranin-A reduction. Of the entire cohort, 36% had disease regression (29% partial and 7% minor response) on computed tomography, with stable findings in 50%. Three other patients had bony disease evaluable only on SSTR imaging (2 partial response and 1 stable). Median progression-free survival was 39 months; median overall survival was not reached (5 deaths; median follow-up, 28 months). Four patients had grade 3 lymphopenia; 2 had grade 3 thrombocytopenia. Renal impairment in 2 patients was attributed to underlying disease processes.ConclusionsPRRT achieves worthwhile clinical and biochemical responses with low toxicity and encouraging survival in PGL/PCC. Because PRRT has logistic and radiation-safety advantages compared to 131I-MIBG therapy, further prospective evaluation is warranted.This study showed favorable disease control, clinical effectiveness, overall survival, and low toxicity with PRRT in patients with functional metastatic PCC/PGL from two referral centers.

The 2020 publicized deaths of George Floyd and Breonna Taylor have increased social attention to incidents of police use of force in the USA. The spotlight of these events has created a divisive outlook on police tactics. Further, the current political climate has accentuated opposing viewpoints that highlight either the need for police reform or a steadfast stance on law and order. It is widely disputed whether heightened media reporting can influence individuals. This study uses historical posts from the official X, formerly known as Twitter, handles of CNN and Fox News beginning March 25, 2020, and ending November 3, 2020. A content analysis of this sample was conducted to develop thematic messages from each news provider. Results indicate that both news sources use political ideologies to characterize the same reported events. CNN focused specifically on victimology while Fox News emphasized the lawlessness of citizen demonstrations. CNN coverage centers on public demonstrations and the need for criminal justice reform. Alternatively, FOX News coverage characterizes riots and the call for steadfast law enforcement efforts to maintain public safety. The described characteristics share perspectives from the “warrior” and “guardian” roles of police officers.

Purpose Point-spread function (PSF) or PSF + time-of-flight (TOF) reconstruction may improve lesion detection in oncologic PET, but can alter quantitation resulting in variable standardized uptake values (SUVs) between different PET systems. This study aims to validate a proprietary software tool (EQ.PET) to harmonize SUVs across different PET systems independent of the reconstruction algorithm used. Methods NEMA NU2 phantom data were used to calculate the appropriate filter for each PSF or PSF+TOF reconstruction from three different PET systems, in order to obtain EANM compliant recovery coefficients. PET data from 517 oncology patients were reconstructed with a PSF or PSF+TOF reconstruction for optimal tumour detection and an ordered subset expectation maximization (OSEM3D) reconstruction known to fulfil EANM guidelines. Post-reconstruction, the proprietary filter was applied to the PSF or PSF+TOF data (PSF EQ or PSF+TOF EQ ). SUVs for PSF or PSF+TOF and PSF EQ or PSF+TOF EQ were compared to SUVs for the OSEM3D reconstruction. The impact of potential confounders on the EQ.PET methodology including lesion and patient characteristics was studied, as was the adherence to imaging guidelines. Results For the 1380 tumour lesions studied, Bland-Altman analysis showed a mean ratio between PSF or PSF+TOF and OSEM3D of 1.46 (95 %CI: 0.86–2.06) and 1.23 (95 %CI: 0.95–1.51) for SUV max and SUV peak , respectively. Application of the proprietary filter improved these ratios to 1.02 (95 %CI: 0.88–1.16) and 1.04 (95 %CI: 0.92–1.17) for SUV max and SUV peak , respectively. The influence of the different confounding factors studied (lesion size, location, radial offset and patient’s BMI) was less than 5 %. Adherence to the European Association of Nuclear Medicine (EANM) guidelines for tumour imaging was good. Conclusion These data indicate that it is not necessary to sacrifice the superior lesion detection and image quality achieved by newer reconstruction techniques in the quest for harmonizing quantitative comparability between PET systems.

In locally advanced lung cancer, established baseline clinical variables show limited prognostic accuracy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) radiomics features may increase accuracy for optimal treatment selection. Their robustness and added value relative to current clinical factors are unknown. Hence, we identify robust and independent PET radiomics features that may have complementary value in predicting survival endpoints. A 4D PET dataset (n = 70) was used for assessing the repeatability (Bland-Altman analysis) and independence of PET radiomics features (Spearman rank: |ρ|<0.5). Two 3D PET datasets combined (n = 252) were used for training and validation of an elastic net regularized generalized logistic regression model (GLM) based on a selection of clinical and robust independent PET radiomics features (GLMall). The fitted model performance was externally validated (n = 40). The performance of GLMall (measured with area under the receiver operating characteristic curve, AUC) was highest in predicting 2-year overall survival (0.66±0.07). No significant improvement was observed for GLMall compared to a model containing only PET radiomics features or only clinical variables for any clinical endpoint. External validation of GLMall led to AUC values no higher than 0.55 for any clinical endpoint. In this study, robust independent FDG PET radiomics features did not have complementary value in predicting survival endpoints in lung cancer patients. Improving risk stratification and clinical decision making based on clinical variables and PET radiomics features has still been proven difficult in locally advanced lung cancer patients.

Background Immune checkpoint blockade such as ipilimumab and anti-PD1 monoclonal antibodies have significantly improved survival in advanced melanoma. Biomarkers are urgently needed as a majority of patients do not respond, despite treatment-related toxicities. We analysed pre-treatment 18 F-fluorodeoxyglucose positron emission tomography/computerised tomography (FDG PET/CT) parameters to assess its correlation with patient outcome. Methods This retrospective study evaluated pre-treatment FDG PET/CT scans in a discovery cohort of patients with advanced melanoma treated with ipilimumab or anti-PD1. Pre-treatment scans were assessed for maximum tumoral standardised uptake value (SUVmax), metabolic tumour volume (MTV) and spleen to liver ratio (SLR). Progression-free survival (PFS) and overall survival (OS) were characterised and modelled using univariable and multivariable analyses. Correlation of SLR and OS was validated in an independent cohort. Blood parameters and stored sera of patients from the discovery cohort was analysed to investigate biological correlates with SLR. Results Of the 90 evaluable patients in the discovery cohort: 50 received ipilimumab monotherapy, 20 received anti-PD1 monotherapy, and 20 patients received ipilimumab followed by anti-PD1 upon disease progression. High SLR > 1.1 was associated with poor PFS (median 1 vs 3 months; HR 3.14, p  = 0.008) for patients treated with ipilimumab. High SLR was associated with poor OS after ipilimumab (median 1 vs 21 months; HR 5.83, p  = 0.0001); as well as poor OS after first line immunotherapy of either ipilimumab or anti-PD1 (median 1 vs 14 months; HR 3.92, p  = 0.003). The association of high SLR and poor OS after ipilimumab was validated in an independent cohort of 110 patients (median 2.3 months versus 11.9 months, HR 3.74). SLR was associated with poor OS in a multi-variable model independent of stage, LDH, absolute lymphocyte count and MTV. Conclusions Pre-treatment Spleen to liver ratio (SLR) > 1.1 was associated with poor outcome after ipilimumab in advanced melanoma. This parameter warrants prospective evaluation.

True total-body and extended axial field-of-view (AFOV) PET/CT with 1m or more of body coverage are now commercially available and dramatically increase system sensitivity over conventional AFOV PET/CT. The Siemens Biograph Vision Quadra (Quadra), with an AFOV of 106cm, potentially allows use of significantly lower administered radiopharmaceuticals as well as reduced scan times. The aim of this study was to optimise acquisition protocols for routine clinical imaging with FDG on the Quadra the prioritisation of reduced activity given physical infrastructure constraints in our facility. Low-dose (1 MBq/kg) and ultra-low dose (0.5 MBq/g) cohorts, each of 20 patients were scanned in a single bed position for 10 and 15 min respectively with list-mode data acquisition. These data were then reconstructed simulating progressively shorter acquisition times down to 30 s and 1 min, respectively and then reviewed by 2 experienced PET readers who selected the shortest optimal and minimal acquisition durations based on personal preferences. Quantitative analysis was also performed of image noise to assess how this correlated with qualitative preferences. At the consensus minimum acquisition durations at both dosing levels, the coefficient of variance in the liver as a measure of image noise was 10% or less and there was minimal reduction in this measure between the optimal and longest acquisition durations. These data support the reduction in both administered activity and scan acquisition times for routine clinical FDG PET/CT on the Quadra providing efficient workflows and low radiation doses to staff and patients, while achieving high quality images.

PurposeInflammatory FDG uptake in the lung (PET-pneumonitis) following curative-intent radiotherapy (RT)/chemo-RT (CRT) in non-small cell lung cancer (NSCLC) can pose a challenge in FDG-PET/CT response assessment. The aim of this study is to describe different patterns of PET-pneumonitis to guide the interpretation of FDG-PET/CT and investigate its association with tumor response and overall survival (OS).MethodsRetrospective analysis was performed on 87 NSCLC patients in three prospective trials who were treated with radical RT (n = 7) or CRT (n = 80), with baseline and post-treatment FDG-PET/CT. Visual criteria were performed for post-treatment FDG-PET/CT response assessment. The grading of PET-pneumonitis was based on relative lung uptake intensity compared to organs of reference and classified as per Deauville score from grade 1–5. Distribution patterns of PET-pneumonitis were defined as follows: A) patchy/sub-pleural; B) diffuse (involving more than a segment); and C) peripheral (diffusely surrounding a photopenic region).ResultsFollow-up FDG-PET/CT scans were performed approximately 3 months (median, 89 days; interquartile range, 79–93) after RT. Overall, PET-pneumonitis was present in 62/87 (71%) of patients, with Deauville 2 or 3 in 12/62 (19%) and 4 or 5 in 50/62 (81%) of patients. The frequency of patterns A, B and C of PET-pneumonitis was 19/62 (31%), 20/62 (32%) and 23/62 (37%), respectively. No association was found between grade or pattern of PET-pneumonitis and overall response at follow-up PET/CT (p = 0.27 and p = 0.56, respectively). There was also no significant association between PET-pneumonitis and OS (hazard ratio [HR], 1.3; 95% confidence interval [CI], 0.6–2.5; p = 0.45). Early FDG-PET/CT response assessment, however, was prognostic for OS (HR, 1.7; 95% CI, 1.2–2.2; p < 0.001).ConclusionPET-pneumonitis is common in early post-CRT/RT, but pattern recognition may assist in response assessment by FDG-PET/CT. While FDG-PET/CT is a powerful tool for response assessment and prognostication, PET-pneumonitis does not appear to confound early response assessment or to independently predict OS.

PurposeThis pilot study assessed the independent and incremental value of 68Ga-V/Q PET/CT as compared with CT pulmonary angiography (CTPA) for the management of cancer patients with suspected acute pulmonary embolism (PE).MethodsAll 24 cancer patients with suspected acute PE prospectively recruited underwent both 68Ga-V/Q PET/CT and CTPA within 24 h. PET/CT was acquired after inhalation of Galligas prepared using a Technegas generator and administration of 68Ga-macroaggregated albumin. Initially, PET/CT and CTPA scans were read independently with the reader blinded to the results of the other imaging study. CTPA and PET/CT were then coregistered and reviewed by consensus between a radiologist and nuclear medicine physician. The therapeutic management was established by the managing physician based on all available data.ResultsThe diagnostic conclusion was concordantly negative in 18 patients (75%). Of the six discordant diagnoses on independent reading, combined interpretation of V/Q PET/CTPA enabled a consensus conclusion in two patients, excluding PE in one and confirming PE in the other, similar to the initial diagnostic conclusion of the V/Q PET/CT. Of the remaining four patients, three had a single subsegmental thrombus on CTPA but a negative V/Q PET/CT scan, and two of these did not receive long-term anticoagulation and did not have a venous thromboembolic event during a 3-year follow-up period. The third patient, along with a patient with a positive V/Q PET/CT scan but a negative CTPA scan, presented with acute complications preventing any conclusions with regard to the appropriateness of the V/Q PET/CT results in the management of PE. Overall, V/Q PET had an impact on management in four patients (17%).ConclusionIn this pilot study, we demonstrated the feasibility and potential utility of V/Q PET/CT for the management of patients with suspected PE. V/Q PET/CT may be of particular relevance in patients with equivocal findings or isolated subsegmental findings on CTPA, adding further discriminatory information to allow important decision-making regarding the use or withholding of anticoagulation. Given the other advantages of V/Q PET/CT (reduced acquisition time, low radiation dose), and with the increasing availability of 68Ga generators, PET/CT is a potential replacement for V/Q SPECT/CT imaging.

Background The role of FDG-PET/CT imaging in assessing response to immunotherapy in advanced cutaneous squamous cell carcinoma (CSCC) is unknown. This study compared complete metabolic response (CMR) rates by FDG-PET and RECIST1.1 via CT or MRI in patients on cemiplimab for >  10 months. Methods This was a single-centre retrospective study of 15 patients treated with cemiplimab for advanced CSCC who had CT/MRI and FDG-PET/CT at >  10 months to assess metabolic treatment response. The median age was 73 years (range 55–84) and 93% were male. RECIST1.1 and PERCIST1.0 tumor responses were evaluated by blinded readers. Results Seventy-three percent (11/15) (95%CI 44.9, 92.2%) achieved a CMR on PET. Of these 11, on RECIST1.1 there was one complete response, 9 partial responses and one stable disease. Conclusions In patients on cemiplimab for >  10 months, there was discordance between CR rates on FDG-PET versus RECIST1.1. FDG-PET/CT may have utility for clarifying depth of response in patients treated with immunotherapy for CSCC.

BackgroundIn the curative-intent treatment of locally advanced lung cancer, significant morbidity and mortality can result from thoracic radiation therapy. Symptomatic radiation pneumonitis occurs in one in three patients and can lead to radiation-induced fibrosis. Local failure occurs in one in three patients due to the lungs being a dose-limiting organ, conventionally restricting tumour doses to around 60 Gy. Functional lung imaging using positron emission tomography (PET)/CT provides a geographic map of regional lung function and preclinical studies suggest this enables personalised lung radiotherapy. This map of lung function can be integrated into Volumetric Modulated Arc Therapy (VMAT) radiotherapy planning systems, enabling conformal avoidance of highly functioning regions of lung, thereby facilitating increased doses to tumour while reducing normal tissue doses.Methods and analysisThis prospective interventional study will investigate the use of ventilation and perfusion PET/CT to identify highly functioning lung volumes and avoidance of these using VMAT planning. This single-arm trial will be conducted across two large public teaching hospitals in Australia. Twenty patients with stage III non-small cell lung cancer will be recruited. All patients enrolled will receive dose-escalated (69 Gy) functional avoidance radiation therapy. The primary endpoint is feasibility with this achieved if ≥15 out of 20 patients meet pre-defined feasibility criteria. Patients will be followed for 12 months post-treatment with serial imaging, biomarkers, toxicity assessment and quality of life assessment.DiscussionUsing advanced techniques such as VMAT functionally adapted radiation therapy may enable safe moderate dose escalation with an aim of improving local control and concurrently decreasing treatment related toxicity. If this technique is proven feasible, it will inform the design of a prospective randomised trial to assess the clinical benefits of functional lung avoidance radiation therapy.Ethics and disseminationThis study was approved by the Peter MacCallum Human Research Ethics Committee. All participants will provide written informed consent. Results will be disseminated via publications.Trials registration numberNCT03569072; Pre-results