Circulating microRNAs as potential new biomarkers for prostate cancer

Since they were first described in the 1990s, circulating microRNAs (miRNAs) have provided an active and rapidly evolving area of current research that has the potential to transform cancer diagnostics and therapeutics. In particular, miRNAs could provide potential new biomarkers for prostate cancer, the most common cause of cancer in UK men. Current diagnostic tests for prostate cancer have low specificity and poor sensitivity. Further, although many prostate cancers are so slow growing as not to pose a major risk to health, there is currently no test to distinguish between these and cancers that will become aggressive and life threatening. Circulating miRNAs are highly stable and are both detectable and quantifiable in a range of accessible bio fluids, thus have the potential to be useful diagnostic, prognostic and predictive biomarkers. This review aims to summarise the current understanding of circulating miRNAs in prostate cancer patients and their potential role as biomarkers

Amplification-free detection of circulating microRNA biomarkers from body fluids based on fluorogenic oligonucleotide-templated reaction between engineered peptide nucleic acid probes: application to prostate cancer diagnosis

Highly abundant in cells, microRNAs (or miRs) play a key role as regulators of gene expression. A proportion of them are also detectable in biofluids making them ideal noninvasive biomarkers for pathologies in which miR levels are aberrantly expressed, such as cancer. Peptide nucleic acids (PNAs) are engineered uncharged oligonucleotide analogues capable of hybridizing to complementary nucleic acids with high affinity and high specificity. Herein, novel PNA-based fluorogenic biosensors have been designed and synthesized that target miR biomarkers for prostate cancer (PCa). The sensing strategy is based on oligonucleotide-templated reactions where the only miR of interest serves as a matrix to catalyze an otherwise highly unfavorable fluorogenic reaction. Validated in vitro using synthetic RNAs, these newly developed biosensors were then shown to detect endogenous concentrations of miR in human blood samples without the need for any amplification step and with minimal sample processing. This low-cost, quantitative, and versatile sensing technology has been technically validated using gold-standard RT-qPCR. Compared to RT-qPCR however, this enzyme-free, isothermal blood test is amenable to incorporation into low-cost portable devices and could therefore be suitable for widespread public screening

Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000-2009

BACKGROUND: Post-molar pregnancy gestational trophoblastic tumours (GTT) have been curable with chemotherapy treatment for over 50 years. Because of the rarity of the diagnosis, detailed structured information on prognosis, treatment escalations and outcome is limited. METHODS: We have reviewed the demographics, prognostic variables, treatment course and clinical outcomes for the post-mole GTT patients treated at Charing Cross Hospital between 2000 and 2009. RESULTS: Of the 618 women studied, 547 had a diagnosis of complete mole, 13 complete mole with a twin conception and 58 partial moles. At the commencement of treatment, 94% of patients were in the FIGO low-risk group (score 0–6). For patients treated with single-agent methotrexate, the primary cure rate ranged from 75% for a FIGO score of 0–1 through to 31% for those with a FIGO score of 6. CONCLUSION: In the setting of a formal follow-up programme, the expected cure rate for GTT after a molar pregnancy should be 100%. Prompt treatment and diagnosis should limit the exposure of most patients to combination chemotherapy. Because of the post-treatment relapse rate of 3% post-chemotherapy, hCG monitoring should be performed routinely

Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

Natural immunity to SARS-CoV-2 and breakthrough infections in vaccinated and unvaccinated patients with cancer

Background Consolidated evidence suggests spontaneous immunity from SARS-CoV-2 is not durable, leading to the risk of reinfection, especially in the context of newly emerging viral strains. In patients with cancer who survive COVID-19 prevalence and severity of SARS-CoV-2 reinfections are unknown. Methods We aimed to document natural history and outcome from SARS-CoV-2 reinfection in patients recruited to OnCovid (NCT04393974), an active European registry enrolling consecutive patients with a history of solid or haematologic malignancy diagnosed with COVID-19. Results As of December 2021, out of 3108 eligible participants, 1806 COVID-19 survivors were subsequently followed at participating institutions. Among them, 34 reinfections (1.9%) were reported after a median time of 152 days (range: 40–620) from the first COVID-19 diagnosis, and with a median observation period from the second infection of 115 days (95% CI: 27–196). Most of the first infections were diagnosed in 2020 (27, 79.4%), while most of reinfections in 2021 (25, 73.5%). Haematological malignancies were the most frequent primary tumour (12, 35%). Compared to first infections, second infections had lower prevalence of COVID-19 symptoms (52.9% vs 91.2%, P = 0.0008) and required less COVID-19-specific therapy (11.8% vs 50%, P = 0.0013). Overall, 11 patients (32.4%) and 3 (8.8%) were fully and partially vaccinated against SARS-CoV-2 before the second infection, respectively. The 14-day case fatality rate was 11.8%, with four death events, none of which among fully vaccinated patients. Conclusion This study shows that reinfections in COVID-19 survivors with cancer are possible and more common in patients with haematological malignancies. Reinfections carry a 11% risk of mortality, which rises to 15% among unvaccinated patients, highlighting the importance of universal vaccination of patients with cancer

Factors Affecting COVID-19 Outcomes in Cancer Patients: A First Report From Guy's Cancer Center in London

Background: There is insufficient evidence to support clinical decision-making for cancer patients diagnosed with COVID-19 due to the lack of large studies. Methods: We used data from a single large UK Cancer Center to assess the demographic/clinical characteristics of 156 cancer patients with a confirmed COVID-19 diagnosis between 29 February and 12 May 2020. Logistic/Cox proportional hazards models were used to identify which demographic and/or clinical characteristics were associated with COVID-19 severity/death. Results: 128 (82%) presented with mild/moderate COVID-19 and 28 (18%) with a severe case of the disease. An initial cancer diagnosis >24 months before COVID-19 [OR: 1.74 (95% CI: 0.71–4.26)], presenting with fever [6.21 (1.76–21.99)], dyspnea [2.60 (1.00–6.76)], gastro-intestinal symptoms [7.38 (2.71–20.16)], or higher levels of C-reactive protein [9.43 (0.73–121.12)] were linked with greater COVID-19 severity. During a median follow-up of 37 days, 34 patients had died of COVID-19 (22%). Being of Asian ethnicity [3.73 (1.28–10.91)], receiving palliative treatment [5.74 (1.15–28.79)], having an initial cancer diagnosis >24 months before [2.14 (1.04–4.44)], dyspnea [4.94 (1.99–12.25)], and increased CRP levels [10.35 (1.05–52.21)] were positively associated with COVID-19 death. An inverse association was observed with increased levels of albumin [0.04 (0.01–0.04)]. Conclusions: A longer-established diagnosis of cancer was associated with increased severity of infection as well as COVID-19 death, possibly reflecting the effects a more advanced malignant disease has on this infection. Asian ethnicity and palliative treatment were also associated with COVID-19 death in cancer patients

Determinants of enhanced vulnerability to COVID-19 in UK cancer patients: a European Study

Background: Despite high contagiousness and rapid spread, SARS-CoV-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom (UK) is the most severely affected country, with a death toll in excess of 100.000 as of January 2021. We aimed to compare the national impact of COVID-19 on the risk of death in UK cancer patients versus those in continental Europe (EU). / Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with COVID-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, including oncological and COVID-19 specific therapy across UK and EU cohorts and evaluated the association of these factors with the risk adverse outcome in multivariable Cox regression models. / Findings: Compared to EU (n=924), UK patients (n=468) were characterised by higher case fatality rates (40.38% versus 26.5%, p<0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after COVID-19 diagnosis (47.64% versus 33.33%, p<0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p<0.01). Receipt of anticancer therapy was lower in UK versus EU patients (p<0.001). Despite equal proportions of complicated COVID-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-COVID-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p<0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient’s age, gender, tumour stage and status, number of co-morbidities, COVID-19 severity, receipt of anticancer and anti-COVID-19 therapy. Rates of permanent cessation of anticancer therapy post COVID-19 were similar in UK versus EU. / Interpretation: UK cancer patients have been more severely impacted by the unfolding of the COVID-19 pandemic despite societal risk mitigation factors and rapid deferral of anticancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-CoV-2 vaccination. Continued evaluation of long-term outcomes is warranted

Time-Dependent COVID-19 Mortality in Patients with Cancer: An Updated Analysis of the OnCovid Registry

Importance: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. Objective: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. Design, Setting, and Participants: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. Exposures: SARS-CoV-2 infection. Main Outcomes and Measures: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). Results: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all P &lt;.001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P =.03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; P =.001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; P &lt;.001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; P &lt;.001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; P &lt;.001) and anti-COVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; P &lt;.001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P &lt;.001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. Conclusions and Relevance: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.