Circulating Biomarkers, Fraction of Exhaled Nitric Oxide, and Lung Function in Patients With Human Immunodeficiency Virus and Tuberculosis.

BACKGROUND: Identification of proinflammatory factors responding to Mycobacterium tuberculosis is important to reduce long-term sequelae of pulmonary tuberculosis (TB). METHODS: We examined the association between plasma biomarkers, the fraction of exhaled nitric oxide (FeNO), and lung function among a prospective cohort of 105 adults newly diagnosed with TB/human immunodeficiency virus (HIV) in South Africa. Participants were followed for 48 weeks from antiretroviral therapy (ART) initiation with serial assessments of plasma biomarkers, FeNO, lung function, and respiratory symptoms. Linear regression and generalized estimating equations were used to examine the associations at baseline and over the course of TB treatment, respectively. RESULTS: At baseline, higher FeNO levels were associated with preserved lung function, whereas greater respiratory symptoms and higher interleukin (IL)-6 plasma levels were associated with worse lung function. After ART and TB treatment initiation, improvements in lung function were associated with increases in FeNO (rate ratio [RR] = 86 mL, 95% confidence interval [CI] = 34-139) and decreases in IL-6 (RR = -118 mL, 95% CI = -193 to -43) and vascular endothelial growth factor ([VEGF] RR = -178 mL, 95% CI = -314 to -43). CONCLUSIONS: Circulating IL-6, VEGF, and FeNO are associated with lung function in adults being treated for TB/HIV. These biomarkers may help identify individuals at higher risk for post-TB lung disease and elucidate targetable pathways to modify the risk of chronic lung impairment among TB survivors.

Lung function and collagen 1a levels are associated with changes in 6 min walk test distance during treatment of TB among HIV-infected adults: a prospective cohort study.

BACKGROUND: Patients with tuberculosis (TB) and HIV often present with impairments in lung function and exercise capacity after treatment. We evaluated clinical and immunologic variables associated with a minimum clinically important difference (MCID) in the change in the 6 min walk test distance during the first 24 weeks of antiretroviral (ART) and anti-tubercular therapy. METHODS: Adults initiating ART and anti-TB treatment in the setting of newly-diagnosed HIV and pulmonary TB were enrolled in a prospective cohort study in South Africa. Patients underwent 6 min walk tests and spirometry at weeks 0, 4, 12, and 24 and biomarker level measurements early during treatment, at weeks 0, 4, and 12, when inflammation levels are typically elevated. Biomarkers included matrix metalloproteinases-1 (MMP-1), tissue inhibitor of MMP (TIMP)-1, collagen 1a, IL-6, IL-8, vascular cell adhesion molecule 1 (VCAM-1), C-X-C motif chemokine 10 (CXCL-10), CXCL-11, macrophage colony-stimulating factor (M-CSF), plasminogen activator, vascular endothelial growth factor, and chemokine (C-C) motif-2 (CCL-2). An MCID was derived statistically, and achievement of an MCID was modeled as the outcome using logistic regression model. RESULTS: Eighty-nine patients walked an average of 393 (± standard deviation = 69) meters at baseline, which increased by an average of 9% (430 ± 70 m) at week 24. The MCID for change in walk distance was estimated as 41 m. Patients experiencing an MCID on treatment had worse lung function, lower 6 min walk test distance, higher levels of proinflammatory biomarkers including TIMP-1 and M-CSF, and lower levels of collagen 1a at baseline. Experiencing an MCID during treatment was associated with increases in forced expiratory volume in 1-s [odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.05-1.33] and increases in blood collagen 1a levels (OR = 1.31, 95%CI 1.06-1.62). CONCLUSIONS: ART and TB treatment are associated with substantial improvements in 6 min walk test distance over time. Achievement of an MCID in the 6 min walk test in this study was associated with more severe disease at baseline and increases in collagen 1a levels and lung function during therapy.

Normal Variants, Pitfalls, and Artifacts in Ga-68 Prostate Specific Membrane Antigen (PSMA) PET/CT Imaging.

The advent of gallium 68 prostate specific membrane antigen (PSMA) PET imaging has revolutionized the diagnosis and treatment of prostate cancer. PSMA is a transmembrane glycoprotein that is overexpressed in prostate cancer and yields images with high tumor-to-background contrast. Effective "one-stop-shop" imaging of the prostate, lymph nodes, soft tissue, and bone is achieved with PSMA PET. Compared to conventional imaging, PSMA PET provides superior sensitivity and specificity and plays a pivotal role in staging high-risk prostate cancer as well as in biochemical recurrence by identifying oligometastatic disease. PSMA PET furthermore assists in the selection of patients with metastatic castrate resistant prostate cancer for possible treatment (e.g., labeled with a beta emitter lutetium 177) by using a theranostic approach. The term "prostate specific" is a misnomer as PSMA is also present in other malignant and benign conditions since it acts as a folate hydrolase. To avoid pitfalls and false-positives, a sound knowledge of the normal biodistribution of PSMA as well as other potential causes for false-positive uptake is imperative. This review will describe the expected patterns of distribution of Ga 68 PSMA PET imaging and the common pitfalls noted in published literature since the topic is still evolving.

Normal Variants and Pitfalls of 18F-FDG PET/CT Imaging in Pediatric Oncology.

Positron emission tomography (PET) with 2-[fluorine-18] fluoro-2- deoxy-D-glucose (FDG) is a well-established modality that is used in adult oncologic imaging. Its use in pediatric oncology has increased over time. It enables increased diagnostic accuracy due to the combination of functional and morphologic imaging, resulting in optimal patient management. However, the clinician should be aware that the normal distribution of FDG uptake in children differs from adults. Also, even though FDG is used widely in oncology, it is not tumor specific. Uptake of FDG may be seen in numerous benign conditions, including inflammation, infection, and trauma. Proper interpretation of pediatric FDG PET/CT studies requires knowledge of the normal distribution of FDG uptake in children, and an insight into the physiologic variants, benign lesions, and PET/CT related artifacts. Understanding the potential causes of misinterpretation increases the confidence of image interpretation, reduce the number of unnecessary follow-up studies, optimize treatment and more importantly, reduce the radiation exposure to the patient. We review and discuss the physiological distribution of FDG uptake in children, the variation in distribution, lesions that are benign that could be misinterpreted as malignancy, and the various artifacts associated with PET/CT performed in pediatric oncology patients. We add a pictorial illustration to prompt understanding and familiarity of the above-mentioned patterns. Therefore, we believe that this review will assist in reducing possible mistakes by reading physicians and prevent incorrect interpretation.

18F-FDG PET/CT Imaging: Normal Variants, Pitfalls, and Artifacts Musculoskeletal, Infection, and Inflammation.

18F-FDG PET/CT is an integral part of modern-day practice, especially in the management of individuals presenting with malignant processes. The use of this novel imaging modality in oncology has been rapidly evolving. However, due to its detection of cellular metabolism, it is not truly tumor specific. 18F-FDG is also used in the detection of infective and inflammatory disorders. One of the challenges experienced with 18F-FDG PET/CT imaging is the correct differentiation of abnormal uptake that is potentially pathologic, from physiological uptake. Imaging readers, particularly the nuclear physicians, therefore need to be aware of normal physiological variants of uptake, as well as potential pitfalls and artifacts when imaging with 18F-FDG. This is true for musculoskeletal uptake, where more than often, infective and inflammatory processes should not be mistaken for malignancy. This article aims to provide a pictorial review and analysis of cases that depict musculoskeletal, infective, and inflammatory uptake as normal variants, pitfalls, and artifacts on 18F-FDG PET/CT imaging. The impact of this article is to help in the minimizing of poor imaging quality, erroneous interpretations and diminishes misdiagnoses that may impact on the adequate management of patients with undesirable consequences.

Normal Variants, Pitfalls and Artifacts in Ga-68 DOTATATE PET/CT Imaging.

Indium 111 DTPA Octreotide (Octreoscan) has been the pillar of Somatostatin receptor (SSTRs) imaging in nuclear medicine for over three decades. The advent of PET/CT brought new analogs of somatostatin that have higher affinity and improved resolution due to their labeling to Gallium 68 for positron imaging. The most used analogs include DOTATATE, DOTATOC and DOTANOC. However, Gallium 68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE) is probably the most common non-FDG (fluoro-2-deoxy glucose) PET tracer alongside PSMA (prostate specific membrane antigen). In contrast to F18-labeled FDG, it does not require proximity to a cyclotron due to the availability of the Ga68 generator. DOTATATE is a somatostatin analog which allows whole body imaging of somatostatin receptors on cell surfaces. 68Ga-DOTA compounds provide the imaging standard for well-differentiated (Grade 1 and low grade 2) neuro-endocrine tumors (NETs) and is utilized in the staging and characterization and restaging of patients with NETs. 68Ga DOTATATE has a complementary role with 18F-FDG where tumors may exhibit varying degrees of differentiation. It furthermore has application as a prelude to therapy in selecting patients for peptide receptor radionuclide therapy using a theranostic approach. A sound knowledge of the normal biodistribution of the radiotracer is imperative for optimal patient outcome and to avoid potential false positives such as inflammation, normal pancreatic uncinate process uptake and osteoblastic activity. In this review, we will describe the normal appearances of the 68Ga DOTATATE and the potential pitfalls with the support of images to aid in improving interpretation of this crucial innovative tool in the management of individuals with tumors expressing SSTRs.

F-18 Fluoro-2-Deoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) Imaging in Melanoma: Normal Variants, Pitfalls, and Artifacts.

Multimodality imaging has revolutionized diagnostic imaging for several oncologic pathologies including melanoma. Although F-18 fluoro-2-deoxyglucose positron emission tomography/ computed tomography [18F]FDG PET/CT has a high sensitivity in stage III and IV melanoma, several normal variants, and imaging pitfalls may result in falsely increased or reduced tracer uptake that may negatively impact diagnostic accuracy. In addition to normal physiologic tracer uptake, differences in the biological and molecular characteristics of different types of melanoma are also responsible for pitfalls. For instance, [18F]FDG PET/CT has a low sensitivity for detecting brain metastases due to normal physiologic [18F]FDG uptake in brain tissue while hepatic metastases from cutaneous melanoma are more [18F]FDG-avid than hepatic metastases from uveal melanoma. With the introduction of immunotherapies for melanoma, treatment response assessment using [18F]FDG PET/CT has a reduced specificity. This is due to hypermetabolic immune-related adverse effects such as hepatitis, dermatitis, and colitis resulting in false-positive uptake. In addition, immune therapy-induced initial increase in tumor uptake followed by disease response (pseudo-progression) is a cause of false-positive scan interpretation. Specific technical artifacts impact disease detection in [18F]FDG PET/CT melanoma imaging. The identification of small metastatic lymph nodes and lung nodules may be limited by the resolution of the PET/CT camera (partial volume effect). Computed tomography (CT) attenuation correction results in less apparent skin and subcutaneous lesions. Pictorial illustrations will be central to this paper for the description of these normal variants, imaging artifacts, and pitfalls. It is critical for the imaging specialist to have a clear understanding of these potential limitations of 18F-FDG PET/CT imaging in individuals who are referred with melanoma.

Experiences and Perceptions of Nuclear Medicine Technologists in the Assessment of Myocardial Perfusion Image Quality.

Nuclear medicine technologists (NMTs) are experts in the acquisition of myocardial perfusion (MP) images, in addition to the many other types of images acquired in nuclear medicine departments. NMTs are expected to ensure that images are of optimal quality in order to facilitate accurate interpretation by nuclear medicine physicians (NMPs). However, ensuring optimal image quality is a shared responsibility between NMTs and NMPs. The shared responsibilities have resulted in inconsistences in the assessment of MP image quality among NMTs in different departments. Little is known about the perceptions and experiences of NMTs on the assessment of MP image quality. Therefore, the focus of this research study was NMTs. The aim of this qualitative study was to explore and describe the perceptions and experiences of NMTs on the assessment of MP image quality. The research question was, "How do NMTs perform the responsibility of ensuring MP image quality?" Methods: The study followed a qualitative explorative approach using focus groups as a means of collecting data. Nineteen NMTs from 4 academic hospitals were purposefully selected to participate. A semistructured questionnaire was used to conduct the focus groups. The collected data were managed using a computer-aided qualitative data analysis software program to formulate codes, categories, and themes. Results: Two overarching themes emerged from the data: the management of MP images, and the resources required to support NMTs. NMTs differed in their management of MP images because of the prevailing circumstances in their respective departments. In addition, the results suggested that NMTs' level of involvement in the assessment of MP image quality was influenced by the availability of resources required for processing and assessing image quality. Conclusion: Despite the shared responsibility in the assessment of MP image quality with NMPs, NMTs considered themselves as playing a major role. However, resources to facilitate the assessment of image quality are considered necessary and should be available to support NMTs in submitting images of optimal quality for interpretation.

Pulmonary restriction predicts long-term pulmonary impairment in people with HIV and tuberculosis.

BACKGROUND: While tuberculosis is considered a risk factor for chronic obstructive pulmonary disease, a restrictive pattern of pulmonary impairment may actually be more common among tuberculosis survivors. We aimed to determine the nature of pulmonary impairment before and after treatment among people with HIV and tuberculosis and identify risk factors for long-term impairment. METHODS: In this prospective cohort study conducted in South Africa, we enrolled adults newly diagnosed with HIV and tuberculosis who were initiating antiretroviral therapy and tuberculosis treatment. We measured lung function and symptoms at baseline, 6, and 12 months. We compared participants with and without pulmonary impairment and constructed logistic regression models to identify characteristics associated with pulmonary impairment. RESULTS: Among 134 participants with a median CD4 count of 110 cells/µl, 112 (83%) completed baseline spirometry at which time 32 (29%) had restriction, 13 (12%) had obstruction, and 9 (7%) had a mixed pattern. Lung function was dynamic over time and 30 (33%) participants had impaired lung function at 12 months. Baseline restriction was associated with greater symptoms and with long-term pulmonary impairment (adjusted odds ratio 5.44, 95% confidence interval 1.16-25.45), while baseline obstruction was not (adjusted odds ratio 1.95, 95% confidence interval 0.28-13.78). CONCLUSIONS: In this cohort of people with HIV and tuberculosis, restriction was the most common, symptomatic, and persistent pattern of pulmonary impairment. These data can help to raise awareness among clinicians about the heterogeneity of post-tuberculosis pulmonary impairment, and highlight the need for further research into mediators of lung injury in this vulnerable population.

Imaging Lymphoma With F-18 Fluorodeoxyglucose PET-CT: What Should Be Known About Normal Variants, Pitfalls, and Artifacts?

18F fluorodeoxyglucose ([F-18] FDG) PET-CT has gained popularity in the management of many types of malignancies. Today, imaging patients with lymphoma using of [F-18] FDG PET-CT not only is considered as a state-of-the-art tool but also has taken a central place for therapeutic decisions. In fact, accurate staging at diagnosis is imperative to prevent under treatment of individuals with advanced disease. In Hodgkin's lymphoma, in particular, the current role of interim [F-18] FDG PET imaging goes beyond speculations in the adaptation of different therapeutic strategies. Therefore, the use of such a critical imaging modality should go hand in hand with sound interpretation that provides accurate results. As the number patients referred for PET-CT continues to increase, imaging specialists should remain aware of the inherent limitations linked to the integrated imaging system that may introduce potential pitfalls related to the machine or the administered [F-18] FDG. Knowledge of the normal physiologic biodistribution of [F-18] FDG, its physiologic variants, and of all the potential pitfalls and artifacts is paramount to avoid misinterpretation. Recognition of the limitations of [F-18] FDG PET-CT will increase the confidence of practicing clinicians on the modality and impact positively on the management of patients. In this article, we will review the normal physiological variants, technical artifacts, and diagnostic pitfalls in lymphoma. Highlighting the limitations of [F-18] FDG PET-CT imaging should warn interpreting specialists to find measures that mitigate them and improve reporting results.

Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients.

Background: A Phase III randomized controlled trial investigating the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for locally advanced cervical cancer patients is being conducted in South Africa (Human Research Ethics Committee approval: M1704133; ClincialTrials.gov ID: NCT03332069). Two hundred and ten participants were randomized and 202 participants were eligible for six month local disease control evaluation. Screening 18F-FDG PET/CT scans were conducted and repeated at six months post-treatment. Significant improvement in local control was reported in the mEHT group and complete metabolic resolution (CMR) of extra-pelvic disease was noted in some participants. We report on an analysis of the participants with CMR of disease inside and outside the radiation field. Method: Participants were included in this analysis if nodes outside the treatment field (FDG-uptake SUV>2.5) were visualized on pre-treatment scans and if participants were evaluated by 18F-FDG PET/CT scans at six months post-treatment. Results: One hundred and eight participants (mEHT: HIV-positive n = 25, HIV-negative n = 29; Control Group: HIV-positive n = 26, HIV-negative n = 28) were eligible for analysis. There was a higher CMR of all disease inside and outside the radiation field in the mEHT Group: n = 13 [24.1%] than the control group: n = 3 [5.6%] (Chi squared, Fisher's exact: p = 0.013) with no significant difference in the extra-pelvic response to treatment between the HIV-positive and -negative participants of each group. Conclusion: The CMR of disease outside the radiation field at six months post-treatment provides evidence of an abscopal effect which was significantly associated with the addition of mEHT to treatment protocols. This finding is important as the combined synergistic use of radiotherapy with mEHT could broaden the scope of radiotherapy to include systemic disease.

Novel Quantitative PET Imaging Techniques in Tuberculosis.

The role of fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in tuberculosis (TB) continues to expand in disease detection, assessment of the extent of the disease, and treatment response monitoring. This article reviews available data regarding the use of FDG-PET/CT in patients with TB. A new method of quantification for patients with TB is introduced. This method produces robust parameters that represent the total disease burden.

Analysis of the effects of mEHT on the treatment-related toxicity and quality of life of HIV-positive cervical cancer patients.

Introduction: HIV infection is associated with increased treatment-related toxicity and worse outcomes in locally advanced cervical cancer patients (LACC), especially in resource-constrained settings. Local control (LC) in a phase III randomized, controlled trial investigating modulated electro-hyperthermia (mEHT) on LACC patients in South Africa (ethics registration: M120477/M190295), was significantly higher in participants randomized to receive chemoradiotherapy (CRT) with mEHT compared to CRT alone (stratum: HIV status, accounting for age and stage). This analysis investigates whether mEHT adds to the toxicity profile of CRT in HIV-positive LACC participants.Methods: Inclusion criteria: signed informed consent; International Federation of Gynecology and Obstetrics stages IIB to IIIB squamous cell carcinoma of the cervix; HIV-positive patients: CD4 count >200 cell/µL/on antiretroviral treatment for >6 months; eligible for CRT with radical intent. Recruitment: January 2014 to November 2017 (ClinicalTrials.gov: NCT03332069). Acute toxicity (evaluated using CTCAE v4 criteria) and quality of life (according to EORTC forms) in 206 participants randomized for treatment were evaluated alongside the LC results to determine safety and efficacy in HIV-positive participants.Results: Compliance to mEHT treatment was high (97% completed ≥8 treatments) with no significant differences in CRT-related toxicity between treatment groups or between HIV-positive and -negative participants. Adverse events attributed to mEHT were minor, even in obese patients, and did not affect CRT compliance. Participants treated with mEHT reported improved fatigue, pain, emotional and cognitive functioning.Conclusion: mEHT did not cause unexpected CRT-related toxicities and is a safe treatment modality for HIV-positive patients, with minor limitations regarding body weight, even in a low-resource setting.

A Common NLRC4 Gene Variant Associates With Inflammation and Pulmonary Function in Human Immunodeficiency Virus and Tuberculosis.

BACKGROUND: Inflammasomes mediate inflammation in adults living with both human immunodeficiency virus (HIV) and tuberculosis (TB), but the relevance of inflammasome gene polymorphisms in TB-associated pulmonary damage is unknown. We hypothesized that functional single-nucleotide polymorphisms (SNPs) in inflammasome pathway genes modify systemic and pulmonary inflammation, contributing to respiratory impairment in adults living with HIV/pulmonary TB. METHODS: This was a prospective cohort study set in South Africa following individuals living with HIV/TB up to 48 weeks post-antiretroviral therapy (ART) initiation. Ten functional SNPs in 5 inflammasome pathway genes were related to circulating inflammatory biomarkers and lung function assessed by spirometry pre- and post-ART initiation. Analyses used 2-sided t tests, Wilcoxon rank sum tests, Spearman correlation coefficients, linear regression, and generalized estimating equation models. RESULTS: Among 102 patients with baseline samples, the minor allele (T) in NLRC4 rs385076 was independently associated with lower levels of interleukin (IL)-18 and IL-6 before and up to 12 weeks post-ART initiation (Benjamini-Hochberg corrected P values < .02). Patients with the CT/TT genotypes also had improved lung function vs CC patients up to 48 weeks post-ART initiation (forced vital capacity, 206 mL higher; 95% confidence interval [CI], 67-345 mL; P = .004 and forced expiratory volume in 1 second, 143 mL higher; 95% CI, 11-274 mL; P = .034). CONCLUSIONS: A common SNP in the NLRC4 inflammasome may modify TB-associated inflammation in clinically relevant ways. This SNP may identify high-risk groups for lung damage in TB. Inhibition of NLRC4 activity may be an important approach for TB host-directed therapy.

Declines in Lung Function After Antiretroviral Therapy Initiation in Adults With Human Immunodeficiency Virus and Tuberculosis: A Potential Manifestation of Respiratory Immune Reconstitution Inflammatory Syndrome.

End-organ impairment has received relatively little research attention as a possible manifestation of tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS). In this prospective cohort study, one-half of adults with human immunodeficiency virus and pulmonary tuberculosis experienced meaningful declines in lung function on antiretroviral therapy, suggesting a role for lung function in TB-IRIS definitions.

Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis.

BACKGROUND: Immune restoration on antiretroviral therapy (ART) can drive inflammation in people living with human immunodeficiency virus (HIV) who have pulmonary tuberculosis (TB), but its effects on the lungs have not been assessed. We evaluated associations between pulmonary inflammation, recovery of pathogen-specific CD4 T-cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB. METHODS: This was a prospective cohort study in South Africa, following adults with HIV and pulmonary TB prior to and up to 48 weeks after ART initiation. Pulmonary-specific inflammation was defined as total glycolytic activity (TGA) on [18]F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) at baseline and 4 weeks after ART initiation. Spirometry, respiratory symptom tests, and flow cytometry were performed at the same times to assess lung involvement and the frequency of mycobacteria-specific CD4 T-cells. In addition, we evaluated lung function longitudinally up to 48 weeks after ART initiation. RESULTS: Greater lung TGA on FDG PET-CT was associated with worse lung function and respiratory symptoms prior to ART initiation, and nearly half of subjects experienced worsening lung inflammation and lung function at Week 4 of ART. Worsening Week 4 lung inflammation and pulmonary function were both associated with greater increases in pathogen-specific functional CD4 T-cell responses on ART, and early decreases in lung function were independently associated with persistently lower lung function months after TB treatment completion. CONCLUSIONS: Increases in pulmonary inflammation and decreases in lung function are common on ART, relate to greater ART-mediated CD4 T-cell restoration, and are associated with the persistent impairment of lung function in individuals with HIV/TB.

Fluorine-18 fluorodeoxyglucose positron emission tomography in assessing myocardial viability in a tertiary academic centre in Johannesburg, South Africa: a pilot study.

BACKGROUND: Positron emission tomography detects patients with myocardial contractile dysfunction secondary to ischaemic heart disease who may benefit from coronary revascularisation. METHODS: We reviewed technetium-99m sestamibi singlephoton emission computed tomography (SPECT) and fluorine-18 fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) data from 236 patients imaged between January 2009 and June 2015. The patients were grouped into three groups: no evidence of viability, viability 1-10% and viability > 10%. RESULTS: Viability exceeding 10% was evident in 55% of the patients. On multivariate analysis, aspirin intake [OR: 1.92; 95% CI: 1.08-3.41; p = 0.026] and hypertension [OR: 1.89; 95% CI: 1.07-3.33; p = 0.029] were clinical factors associated with the presence of myocardial viability. CONCLUSION: Our study demonstrated that F18-FDG PET was able to identify 55% of patients with ischaemic heart disease with viability in more than 10% of the total myocardium when using a 17-segment model.

The effect of modulated electro-hyperthermia on local disease control in HIV-positive and -negative cervical cancer women in South Africa: Early results from a phase III randomised controlled trial.

BACKGROUND: The global burden of cervical cancer remains high with the highest morbidity and mortality rates reported in developing countries. Hyperthermia as a chemo- and radiosensitiser has shown to improve treatment outcomes. This is an analysis of the local control results at six months post-treatment of patients enrolled in an ongoing study investigating the effects of the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for the treatment of HIV-positive and -negative cervical cancer patients in a low-resource setting. METHODS: This ongoing Phase III randomised controlled trial, conducted at a state hospital in Johannesburg, South Africa, was registered with the appropriate ethics committee. After signing an informed consent, participants with FIGO stages IIB to IIIB squamous cell carcinoma of the cervix were randomised to receive chemoradiotherapy with/without mEHT using a secure online random-sampling tool (stratum: HIV status) accounting for age and stage. Reporting physicians were blind to treatment allocation. HIV-positive participants on antiretroviral treatment, or with a CD4 count >200cell/µL were included. mEHT was administered 2/weekly immediately before external beam radiation. The primary end point is local disease control (LDC) and secondary endpoints are toxicity; quality of life analysis; and two year survival. We report on six month LDC, including nodes visualised in the radiation field on 18F-FDG PET/CT (censored for six month survival), and six month local disease free survival (LDFS) (based on intention to treat). Trial status: Recruitment closed (ClinicalTrials.gov: NCT03332069). RESULTS: 271 participants were recruited between January 2014 and November 2017, of which 210 were randomised for trial and 202 were available for analysis at six months post-treatment (mEHT: n = 101; Control: n = 101). Six month LDFS was higher in the mEHT Group (n = 39[38.6%]), than in the Control Group (n = 20[19.8%]); p = 0.003). LDC was also higher in the mEHT Group (n = 40[45.5%]) than the Control Group (n = 20[24.1%]); (p = 0.003). CONCLUSION: Our results show that mEHT is effective as a chemo-radiosensitiser for cervical cancer, even in high risk a patients and resource-constrained settings.

Defining Characteristics of Nodal Disease on PET/CT Scans in Patients With HIV-Positive and -Negative Locally Advanced Cervical Cancer in South Africa.

Literature reports increased FDG nodal uptake in HIV-positive patients. Our aim is to identify differences in presentation and characteristics of FDG-avid lymph nodes between HIV-positive and HIV-negative locally advanced cervical cancer (LACC) patients in our clinical setting. We evaluated 250 pre-treatment 18F-FDG PET/CT imaging studies from women screened for a phase III randomised controlled trial investigating modulated electro-hyperthermia as a radiosensitiser (Ethics approval: M120477). The number of nodes; size; maximum standardised uptake value (SUVmax); symmetry; and relationship between nodal size and SUVmax uptake, were assessed by region and by HIV status. In total, 1314 nodes with a SUVmax ≥ 2.5 were visualised. Of 128(51%) HIV-positive participants, 82% were on antiretroviral therapy (ART) and 10 had a CD4 count <200 cells/µL. Overall pattern of presentation and nodal characteristics were similar between HIV-positive and -negative groups and the uniformity in presentation of the nodes draining the cervix strongly suggests these nodes may be attributed to malignancy rather than HIV infection. Novel findings: HIV infection is associated with: >four nodes visualised in the neck, symmetrical inguinal lymph nodes, increased rates of supraclavicular node visualisation; FDG-avid axillary nodes were more common, but not exclusive, in HIV-positive participants. 18F-FDG PET/CT is a reliable staging method for LACC in HIV-positive patients who are not in acute stages of HIV infection, have a CD4 count >200 cells/µL, and/or are on ART and there is a potential risk of underestimating metastatic spread by attributing increased nodal metabolic activity to HIV infection in these patients.