IMvigor011: a study of adjuvant atezolizumab in patients with high-risk MIBC who are ctDNA+ post-surgery.

The standard-of-care for muscle-invasive bladder cancer is radical surgery with neoadjuvant cisplatin-based chemotherapy. Despite curative intent from these interventions, relapse rates post-surgery remain high, with approximately 50% of patients developing local or distant recurrence within 2 years of surgery and a 5-year survival of only 50-60%. Identifying patients who are high risk for relapse post-surgery is a priority. Monitoring patients for circulating tumor DNA (ctDNA) is a minimally invasive approach that appears attractive for selecting patients potentially suitable for adjuvant treatment with checkpoint inhibitors. IMvigor011 (NCT04660344) is a global, double-blind, randomized phase III study assessing the efficacy of atezolizumab (anti-PD-L1) versus placebo in patients with high-risk muscle-invasive bladder cancer who are ctDNA positive post-cystectomy. The primary end point is disease-free survival in participants who are ctDNA positive within 20 weeks of cystectomy.

Imvigor011 is a clinical trial looking at whether selecting patients who have signs of residual cancer molecules in their blood after having an operation for bladder cancer is better than the standard-of-care surveillance CT scans. This may be useful in picking up cancer that has come back after surgery, before it would be visible on CT scans. Patients who have had surgery for bladder cancer will have regular blood tests for 1 year after their surgery. If this cancer molecule is detected in their blood, it may indicate that the cancer has come back. These patients are then allocated by chance into one of two groups: receiving either an anticancer treatment or a placebo. Previous studies have suggested that giving anticancer treatment to patients who have this residual cancer molecule in their blood will improve how well they do after surgery. Clinical Trial Registration: NCT04660344 (ClinicalTrials.gov).

Is fibromyalgia associated with a unique cytokine profile? A systematic review and meta-analysis.

OBJECTIVES: The aetiology of primary chronic pain syndromes (CPS) is highly disputed. We performed a systematic review and meta-analysis aiming to assess differences in circulating cytokine levels in patients with diffuse CPS (fibromyalgia) vs healthy controls (HC). METHODS: Human studies published in English from the PubMed, MEDLINE/Scopus and Cochrane databases were systematically searched from inception up to January 2020. We included full text cross-sectional or longitudinal studies with baseline cytokine measurements, reporting differences in circulating cytokine levels between fibromyalgia patients and HC. Random-effects meta-analysis models were used to report pooled effects and 95% CIs. This study is registered with PROSPERO (CRD42020193774). RESULTS: Our initial search yielded 324 papers and identified 29 studies (2458 participants) eligible for systematic review and 22 studies (1772 participants) suitable for meta-analysis. The systematic analysis revealed reproducible findings supporting different trends of cytokine levels when fibromyalgia patients were compared with HC, while the chemokine eotaxin, was consistently raised in fibromyalgia. Meta-analysis showed significantly increased TNF-α [standardized mean difference (SMD) = 0.36, 95% CI: 0.12, 0.60, P = 0.0034; I2 = 71%, Q2P = 0.0002], IL-6 (SMD = 0.15, 95% CI: 0.003, 0.29, P = 0.045; I2 = 39%, Q2P = 0.059), IL-8 (SMD = 0.26, 95% CI: 0.05, 0.47, P = 0.01; I2 = 61%, Q2P = 0.005) and IL-10 (SMD = 0.61, 95% CI: 0.34, 0.89, P < 0.001; I2 = 10%, Q2P = 0.34) in fibromyalgia patients compared with HC. CONCLUSION: We found evidence of significant differences in the peripheral blood cytokine profiles of fibromyalgia patients compared with HC. However, the distinctive profile associated with fibromyalgia includes both pro-inflammatory (TNF-α, IL-6, IL-8) and anti-inflammatory (IL-10) cytokines in pooled analysis, as well as chemokine (eotaxin) signatures. Further research is required to elucidate the role of cytokines in fibromyalgia.

Cardiac Metastases in Patients with Neuroendocrine Tumours: Clinical Features, Therapy Outcomes, and Prognostic Implications.

BACKGROUND: Cardiac metastases (CM) from neuroendocrine tumours (NET) are rare; however, with the introduction of new molecular imaging modalities, such as 68Ga-DOTATATE PET-CT for NET diagnosis and re-staging, they are now identified more frequently. This study presents a single-institution experience on the NET CM characteristics, management, and prognostic implications. METHODS: Between January 1998 and January 2020, 25 NET patients with CM were treated in our unit. A retrospective review of electronic records was performed. Overall survival (OS) was assessed by the Kaplan-Meier method. Cox regression models were used to evaluate the association of various clinical variables with OS. RESULTS: The median age in the NET CM cohort was 64 years, with small intestine being the most common primary (84%). Nearly half of the patients suffered either from shortness of breath (48%) or had palpitations (12%). Peptide receptor radionuclide therapy (PRRT) was applied in more than half of the patients (64%), who had an improved trend for a longer median OS compared to those patients who did not receive PRRT (76.0 vs. 14.0 months, p = 0.196). The multivariate analysis demonstrated that concomitant skeletal or pancreatic metastases, as well as N-terminal pro-B-type natriuretic peptide (NT pro-BNP) >2 × upper limit of normal (ULN), were independent poor prognosticators. CONCLUSIONS: Clinical features of NET CM ranged from asymptomatic patients to heart failure. Concomitant bone or pancreatic metastases and NT pro-BNP levels >2 ULN predicted shorter survival time. PRRT serves as a feasible therapy with promising survival benefits; however, more data are needed.

Diagnostic features and management options for duodenal neuroendocrine neoplasms: a retrospective, multi-centre study.

Duodenal neuroendocrine neoplasms (dNENs) are rare neoplasms but their incidence is on the rise. They are classified into 5 sub-types but there remains much heterogeneity in behaviour in particular of non-functioning dNENs. To retrospectively analyse outcomes for all types of dNENs, and highlight prognostic factors associated with worse outcome. 102 (57 m/45f.) patients were identified with mean age at diagnosis 62 (range 32-87) years. The majority were non-functioning tumours 87/102 and median size was 10 mm (range 0.9-130 mm). 83 patients had Stage I or II disease, of which 17 underwent endoscopic resection with R1 rate of 45% and complication rate 12%. 36 patients were kept under endoscopic surveillance. There were 11 deaths of which 4 were disease related. Age and Ki67 > 20% were associated with worse OS in all dNENs. In non-functioning dNENs Ki67 > 3% was a predictor of lymph nodes metastases with OR 18.2 (2.54-13) (p < 0.005) in univariate analyses and liver metastases with OR 6.79 (1.56-29.5) (p < 0.05) in the multivariate analysis. Lesions 11-20 mm in size had OR 11.1 (1.16-106) compared to lesions < 11 mm for the prediction of lymph node metastases in the multivariate analysis (p < 0.05). ROC analysis of size of non-functioning dNENs to predict LN metastases found < 15 mm had an AUROC of 0.9 (0.81-0.99) with a sensitivity of 85% and specificity of 88%. dNENs are increasing in incidence, however low grade and smaller lesions have an indolent course and the role of endoscopic resection and active surveillance needs to be reviewed.

Orbital metastases from neuroendocrine neoplasms: clinical implications and outcomes.

PURPOSE: Neuroendocrine neoplasms (NENs) may rarely metastasise to the orbit. Published data on epidemiology, incidence and preferred treatment is limited. We present the largest cohort of symptomatic and asymptomatic NEN patients with orbital metastases and data on epidemiological parameters, symptoms as well as diagnostic/treatment modalities used. METHODS: We identified patients from our internal NEN database of patients who had also undergone Gallium68-DOTATATE PET (Ga68-DOTA). The diagnosis of orbital metastatic NEN was made on somatostatin receptor imaging and confirmed on a dedicated MRI of orbits. RESULTS: We identified 27 patients of 994 patients evaluated with Ga68-DOTATATE PET imaging during their surveillance monitoring in our department; 15 female, average age at NEN diagnosis 53 years and orbital metastatic NEN diagnosis 59 years. The majority of NEN primaries originated from small bowel (18/27, 66.4%) or pancreas 4/27 (4/27, 14.8%). Hepatic with or without concomitant skeletal metastases were present in 23/27 (85%) of patients. Ocular symptoms and/or signs were evident in 11/27 (41%) of patients. 5/11 symptomatic patients underwent external beam radiotherapy (EBRT) resulting in complete symptoms resolution. The 5-year survival was estimated at 84.1%. CONCLUSIONS: Orbital metastases of NEN have a relatively low prevalence, more commonly associated with small bowel primary. Extraocular muscles are primarily affected, irrespectively of liver disease burden. Survival does not seem to be affected. EBRT is an efficacious treatment modality for both symptom relief and tumour growth control. Administration of peptide receptor radionuclide therapy may occasionally induce temporary ocular symptoms, which resolve following treatment with a short course of steroids.