Publications

Supplementary Figure from Tumor Genomic Testing for >4,000 Men with Metastatic Castration-resistant Prostate Cancer in the Phase III Trial PROfound (Olaparib)

Background: Early detection of infected patients is one of the most important steps to mitigate spreading of 2019 novel coronavirus (2019-nCoV). Here, we report a set of atypical 2019-nCoV pneumonia cases with gastrointestinal symptoms onset but without fever or other respiratory symptoms.Methods: We retrospectively reviewed data of admitted patients of 2019-nCoV pneumonia with only digestive symptoms and no fever on the onset from January 17-24, 2019 in Renmin Hospital of Wuhan University. The patients' history, clinical features, physical findings, complete blood count, biochemical results, chest X-ray imaging, microbiological investigation and viral pathogens results were recorded and analyzed.Findings: From January 17 to 24, 2020, nine admitted patients with only digestive symptoms and no fever on the onset had been identified as 2019-nCoV infection. None of the patients had history of contact with animals or visited to the Huanan seafood wholesale market in Wuhan, while they all had exposure history of confirmed or suspected 2019-nCoV-infected patients. Six patients had anorexia (66.7%). Other symptoms include nausea, vomit and diarrhea. All presented digestive symptoms occurred 1-3 days (median time: 2.1 days) before the patients' visit. None of the cases had fever on onset while 5 patients occurred fever and/or respiratory symptoms 2-5 days after initial non-specific presentations. Other 4 patients never presented respiratory symptoms or fever in the following admissions. Pulmonary infiltrates including multifocal patchy ground-glass opacities were detected on CT scans in all cases at the day of their first clinic visit. All nine patients were admitted to hospital under isolation, supportive care, remained stable and none of them was transferred to ICU as of Feb 2, 2020.Interpretation: Patients with recent gastrointestinal symptoms as well as confirmed or suspected 2019-nCoV pneumonia exposure history are potential 2019-nCoV pneumonia candidates. It is significant to take atypical symptoms into account to avoid missed diagnosis, and important for gastroenterologists to strengthen protection to avoid possible infection.Funding: Project of Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision (Grant No. 2018BCC337); Hubei Province Major Science and Technology Innovation Project (Grant No. 2018-916-000-008 to Honggang Yu); The National Natural Science Foundation of China [Grant Nos. 81672387 to Honggang Yu]; The National Natural Science Foundation of China [Grant Nos. 81302131 to Ping An]. Declaration of Interest: All authors declared no conflict of interest.Ethical Approval: The study protocol was approved by the ethics committee of Renmin Hospital of Wuhan University.

<p>PDF file - 1129K, Baseline duplicate CTC counts correlation</p>

<div>Abstract<p>Monotherapy with PARP inhibitors is effective for the subset of castrate-resistant prostate cancer (CRPC) with defects in homologous recombination (HR) DNA repair. New treatments are required for the remaining tumors, and an emerging strategy is to combine PARP inhibitors with other therapies that induce DNA damage. Here we tested whether PARP inhibitors are effective for HR-proficient CRPC, including androgen receptor (AR)-null tumors, when used in combination with CX-5461, a small molecule that inhibits RNA polymerase I transcription and activates the DNA damage response, and has antitumor activity in early phase I trials. The combination of CX-5461 and talazoparib significantly decreased <i>in vivo</i> growth of patient-derived xenografts of HR-proficient CRPC, including AR-positive, AR-null, and neuroendocrine tumors. CX-5461 and talazoparib synergistically inhibited the growth of organoids and cell lines, and significantly increased the levels of DNA damage. Decreased tumor growth after combination therapy was maintained for 2 weeks without treatment, significantly increasing host survival. Therefore, combination treatment with CX-5461 and talazoparib is effective for HR-proficient tumors that are not suitable for monotherapy with PARP inhibitors, including AR-null CRPC. This expands the spectrum of CRPC that is sensitive to PARP inhibition.</p></div>

Background: The International Reporting Items for Practice Guidelines in Healthcare (RIGHT) instrument was launched in 2016 to improve the reporting of clinical practice guidelines (CPGs). We aimed to systematically evaluate the reporting quality of CPGs on melanoma using RIGHT.Methods: We systematically searched electronic databases, guideline databases and medical society websites until November 2020 to identify guidelines for melanoma published since 2018. The reporting quality of included guidelines was assessed by calculating the percentages of the 35 items of the RIGHT checklist that were appropriately reported. We stratified the results by selected characteristics to describe the correlation of these factors with reporting quality.Results: A total of 20 guidelines were identified and analyzed. The mean reporting rate was greater than 50% in five of the seven domains of the RIGHT checklist; the remaining two domains (Other information, Review and quality assurance) both had a mean reporting rate of 35.0%. The mean overall reporting rate was 63.7%. No CPG considered equity, feasibility or acceptability of the recommendations (item 14c), and only one CPG described the role of funders (item 18b). Guidelines that reported funding or were published in higher-impact journals tended to have a higher reporting quality, whereas the reporting rate in the one included Chinese-language CPG was low.Conclusions: Reporting quality of melanoma CPGs tends to be relatively good. The CPGs developed in China were however an exception. The use of the 2016 RIGHT tool in guideline development should be encouraged to support rigorous and transparent reporting.

Objectives An outbreak of the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has sickened thousands of people in China. The purpose of this study was to explore the early clinical characteristics of COVID-19 patients with cardiovascular disease (CVD). Methods This is a retrospective analysis of patients with COVID-19 from a single centre. All patients underwent real-time reverse transcription PCR for SARS-CoV-2 on admission. Demographic and clinical factors and laboratory data were reviewed and collected to evaluate for significant associations. Results The study included 541 patients with COVID-19. A total of 144 (26.6%) patients had a history of CVD. The mortality of patients with CVD reached 22.2%, which was higher than that of the overall population of this study (9.8%). Patients with CVD were also more likely to develop liver function abnormality, elevated blood creatinine and lactic dehydrogenase (p<0.05). Symptoms of sputum production were more common in patients with CVD (p=0.026). Lymphocytes, haemoglobin and albumin below the normal range were pervasive in the CVD group (p<0.05). The proportion of critically ill patients in the CVD group (27.8%) was significantly higher than that in the non-CVD group (8.8%). Multivariable logistic regression analysis revealed that CVD (OR: 2.735 (95% CI 1.495 to 5.003), p=0.001) was associated with critical COVID-19 condition, while patients with coronary heart disease were less likely to reach recovery standards (OR: 0.331 (95% CI 0.125 to 0.880), p=0.027). Conclusions Considering the high prevalence of CVD, a thorough CVD assessment at diagnosis and early intervention are recommended in COVID-19 patients with CVD. Patients with CVD are more vulnerable to deterioration.

84 Aim: The aim of this study was to investigate the prognostic value of imaging parameters on FDG-PET, PSMA-PET and bone scintigraphy for progression-free survival (PFS) and overall survival (OS) in patients undergoing Lutetium-177-PSMA617 (LuPSMA) therapy. Methods: Between 10/2015 and 12/2016, 30 patients who received up to 4 cycles of LuPSMA in a prospective study were included. All patients underwent FDG PET/CT, PSMA PET/CT, and bone scintigraphy before the first cycle. PFS and OS of patients were recorded from the first cycle to the time of this analysis. The parameters SUVmax, SUVmean and volume from FDG PET and PSMA PET were measured. For FDG PET, all disease with SUV greater than liver + 2 standard deviations was encompassed (MIM Software). For PSMA-PET, a SUV threshold of 3 was used. For bone scintigraphy, BSI and Number of Lesions were measured (EXINI Bone Scan Index). Survival time analyses used Kaplan-Meier procedures, log-rank test and Cox regression models. Results: In the univariate Cox regression, only the tumor volume in FDG-PET was significant for PFS (p = 0.026) and OS (p = 0.016). Other parameters were not significant. Patients with FDG-positive tumor volume above 500 ml had a shorter overall survival (Median 194 vs. 505 days; p = 0.0052). Conclusions: The results of this work suggest that the FDG-positive tumor volume can be used as a prognostic marker for patients receiving LuPSMA therapy. Together with known prognostic parameters such as ALP, imaging parameters could help identify high-risk patients.

Abstract Background Haematological cancer affects more than 1.3 million people around the world annually and accounted for almost 800,000 deaths globally in 2020. The number of patients with these cancers undergoing bone marrow transplant is increasing. Of note, this intensive treatment is associated with complex and multifactorial side effects, often impacting nutritional status, physical functioning and overall health-related quality of life. The primary aim of this study is to investigate the effectiveness of an eight-week multidisciplinary rehabilitation intervention compared with usual care on the physical function domain of the European Organisation for the Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30 version 3) in patients with haematological cancer following bone marrow transplant. Methods This is a multisite, pragmatic two-arm parallel-group, randomised controlled trial (RCT) with stratified randomisation, powered for superiority, recruiting 170 participants at 30 days following either allogeneic or autologous bone marrow transplant (ACTRN12622001071718). Recruitment sites include three Australian university affiliated teaching hospitals. Participants are eligible if aged ≥ 18 years, treated for haematological cancer with allogeneic or autologous bone marrow transplant and can walk independently. The intervention group will receive eight weeks of twice weekly telehealth-based exercise classes, an initial and follow up dietetics consult, post exercise protein supplements, and a home-based physical activity program, all with embedded behaviour change strategies. The primary outcome is patient reported physical function measured using the EORTC QLQ-C30 version 3. Secondary outcomes include other domains of the EORTC QLQ-C30, fatigue, physical function, physical activity levels, frailty, body composition, sarcopenia and nutrition assessment. We will also undertake a health economic analysis alongside the trial and a process evaluation exploring intervention fidelity, causal mechanisms as well as contextual influences through qualitative enquiry. Discussion The REBOOT trial will add RCT-evidence from a rigorously conducted, statistically powered multi-site trial to existing limited knowledge on the effects of multi-disciplinary rehabilitation for people with haematological cancer. If effectiveness is supported, then implementation of rehabilitation into care pathways for people having bone marrow transplant can be considered. Trial registration ACTRN12622001071718 prospectively registered 03/08/2022, last updated 08/03/2024.