What is the recovery rate and risk of long-term consequences following a diagnosis of COVID-19? - A harmonised, global longitudinal observational study

IntroductionVery little is known about possible clinical sequelae that may persist after resolution of the acute Coronavirus Disease 2019 (COVID-19). A recent longitudinal cohort from Italy including 143 patients recovered after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60 day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical ICU patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. Methods and analysisThis is an international open-access prospective, observational multi-site study. It will enrol patients following a diagnosis of COVID-19. Tier 1 is developed for following up patients day 28 post-discharge, additionally at 3 to 6 months intervals. This module can be used to identify sub-sets of patients experiencing specific symptomatology or syndromes for further follow up. A Tier 2 module will be developed for in-clinic, in-depth follow up. The primary aim is to characterise physical consequences in patients post-COVID-19. Secondary aim includes estimating the frequency of and risk factors for post-COVID-19 medical sequalae, psychosocial consequences and post-COVID-19 mortality. A subset of patients will have sampling to characterize longer term antibody, innate and cell-mediated immune responses to SARS-CoV-2. Ethics and disseminationThis collaborative, open-access study aims to characterize the frequency of and risk factors for long-term consequences and characterise the immune response over time in patients following a diagnosis of COVID-19 and facilitate standardized and longitudinal data collection globally. The outcomes of this study will inform strategies to prevent long term consequences; inform clinical management, direct rehabilitation, and inform public health management to reduce overall morbidity and improve outcomes of COVID-19. Article summaryO_ST_ABSStrengths and limitations of this studyC_ST_ABSO_LIAs an international prospective, observational study we provide open-access standardised tools that can be adapted by any site interested in following up patients with COVID-19, for independent or combined analysis, to forward knowledge into short and long term consequences of COVID-19. C_LIO_LIThis study aims to inform strategies to prevent longer term sequalae; inform clinical management, rehabilitation, and public health management strategies to reduce morbidity and improve outcomes. C_LIO_LIThe protocol will be used for a sub-set of patients, already included in the existing cohort of more than 85,973 individuals hospitalized with confirmed COVID-19 infection across 42 countries (as of 20 July 2020), using the ISARIC/WHO standardized Core- or RAPID Case Report Forms (CRFs). C_LIO_LIThe data will be linked with data on pre-existing comorbidities, presentation, clinical care and treatments documented in the existing cohort already documented using the ISARIC/WHO standardized Core- or RAPID CRFs. C_LIO_LIThe data collection tool is developed to facilitate wide dissemination and uptake, by enabling patient self-assessment, however, follow up of patients requires consent and resources, which might limit the uptake and bias the data towards countries /sites with capacity to follow up patients over time. C_LI

Could semiquantitative FDG analysis add information to the prognosis in patients with stage II/III breast cancer undergoing neoadjuvant treatment?

PURPOSE: We investigated whether maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and whole-body (WB) SUVmax, WB MTV and WB TLG measured by (18)F-FDG PET/CT could improve prognostic stratification in patients with stage II/III breast cancer (BC). METHODS: We prospectively enrolled 99 consecutive women (median age 50 years, range 27 - 77 years) with pathologically proven stage II/III BC who underwent pretreatment FDG PET/CT. WB SUVmax, WB MTV and WB TLG were measured in all malignant lesions. Survival was analysed using the Kaplan-Meier method. Cox proportional hazards models were constructed to test for relationships among WB SUVmax, WB MTV, WB TLG, and overall survival (OS) and disease-free survival (DFS), after adjustment for age, and histopathological and immunohistochemical features (oestrogen/progesterone and HER2 expression, proliferation index and grade). RESULTS: The median values of WB SUVmax, WB MTV and WB TLG were 16.2 (range 1.5 - 33.1), 14 cm(3) (range 0.03 - 708.6 cm(3)) and 62.5 (0.06 - 3869.4), respectively. All WB semiquantitative values were higher in patients with higher TNM stage, although not significantly (all p > 0.05). The median follow-up for surviving patients was 30 months, with a range of 13 - 45 months. Both PFS and OS of patients with low WB SUVmax, WB MTV and WB TLG were longer than that of patients with high WB values for progression, although not statistically significant. However, stratifying the patients in accordance with the stage of disease, both PFS and OS were significantly lower in patients with high WB TLG and stage III than in patients with stage II (p < 0.05). In multivariate analyses, WB MTV and WB TLG were independent prognostic factors for PFS (hazard ratio 1.004, 95% confidence interval 1.002 - 1.006, p < 0.001, and hazard ratio 1.001, 95% confidence interval 1.000 - 1.001, p = 0.011, respectively). CONCLUSION: The addition of WB TLG to clinical data may provide a more detailed prediction of outcome in patients with stage III BC. Moreover, WB MTV and WB TLG are independent factors predicting recurrence of BC. On the contrary, WB SUVmax has poor prognostic significance in this cohort of patients.

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

AIM: This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. PATIENTS AND METHODS: Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. RESULTS: Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. CONCLUSION: The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.