Ki67 and prostate specific antigen are prognostic in metastatic hormone naïve prostate cancer

For metastatic hormone naïve prostate cancer patients, androgen deprivation therapy (ADT) with escalation therapy including docetaxel and/or androgen targeting drugs is the standard therapy. However, de-escalation is preferable to avoid unnecessary side effects, especially from docetaxel, but markers to identify these patients are lacking. The purpose of the present study was to investigate the potential of PSA and Ki67 immunoreactive scores as prognostic and treatment-predictive markers. Prostate biopsies from 92 patients with metastatic hormone naïve PC (PSA > 80 ng/mL or clinical metastases) were immunohistochemically evaluated for PSA and Ki67. Gene expression analysis was performed with Clariom D microarrays to identify the phenotypic profile associated with the immunohistochemistry scores of biopsies. Cox regression analysis for progression free survival after ADT adjustment for age, ISUP, and serum PSA and Kaplan-Meier analyses were performed to assess prognostic values of Ki67, PSA, and the Ki67/PSA ratio. The immunohistochemical score for PSA was the strongest prognostic factor for progression-free and overall survival after ADT. Consequently, the ratio between Ki67 and PSA displayed a stronger prognostic value than Ki67 itself. Further, mRNA expression data analysis showed an association between high Ki67/PSA ratio, cell-cycle regulation, and DNA damage repair. In an exploratory sub-analysis of 12 patients treated with early docetaxel as addition to ADT and matched controls, a high Ki67/PSA ratio showed potential to identify those who benefit from docetaxel. PSA and Ki67 immunoreactive scores are prognostic in the metastatic hormone-sensitive setting, with PSA being superior. The combination of Ki67 and PSA did not give additional prognostic value. The results suggest immunohistochemical scoring of PSA to have potential to improve identification of patients responding well to ADT alone.</p

Strict self-isolation did not protect Swedish cancer patients on active treatment from the risk of becoming seropositive for SARS-CoV-2

Background: Swedish recommendations to reduce the risk of COVID-19 relied on each citizen’s own sense of responsibility rather than mandatory lockdowns. We studied how COVID-19-related self-isolation and anxiety correlated to SARS-CoV-2 seropositivity and PCR-positivity in patients with active cancer treatment. Methods: In a longitudinal cohort study at Uppsala University Hospital patients and cancer personnel were included between April 1st 2020 to August 1st 2020. Serological testing for SARS-CoV-2 was done every 8–12-weeks until 30 March 2021. Patients completed a survey at inclusion regarding self-reported COVID-19-related anxiety and self-isolation. Results: A total of 622 patients [n = 475 with solid malignancies (SM), n = 147 with haematological malignancies (HM)], and 358 healthcare personnel were included. The seropositivity rate was lower for patients than for personnel; 10.5% for SM patients, 6.8% for HM patients, and 16.2% for personnel (p = 0.005). Strict adherence to self-isolation guidelines was reported by 54% of patients but was not associated with a lower risk of becoming seropositive [OR = 1.4 (0.8–2.5), p = 0.2]. High anxiety was expressed by 32% of patients, more often by SM patients than HM patients (34% vs 25% [OR = 1.6 (1.1–2.5, p = 0.03)]). Female gender [OR = 3.5 (2.4–5.2), p  0.001] and being born outside of Europe [OR = 2.9 (1.4–6.4), p = 0.007] were both associated with high anxiety. Patients reporting high anxiety became seropositive to a similar degree as those with low anxiety [OR = 0.7 (0.3–1.2), p = 0.2]. HM patients with PCR-positive COVID-19 were more likely than SM patients to require oxygen therapy, including non-invasive ventilation/intubation (69% vs. 26%, p = 0.005). Conclusion: For Swedish patients on active cancer treatment, high self-assessed COVID-19-related anxiety or strict adherence to self-isolation guidelines were not associated with a lower risk of COVID-19. Patients with HM were less likely to develop serological antibody response after COVID-19 and were more likely to require advanced hospital care, but expressed less COVID-19-related anxiety than patients with SM.</p

ALS Biomarker candidates.

<p>Boxplots showing the CSF levels for follistatin, IL1-alpha and KLK5 for ALS patients and matched controls. The protein levels are compared using the Mann-Whitney U-test and p-values are displayed in the Figures. The limits of detection are indicated by dashed horizontal lines. The y-axes represent Ct-values.</p

Results from univariate and multivariate analysis of ALS patients compared to controls.

<p>Results from univariate and multivariate analysis of ALS patients compared to controls.</p

Protein variation among the investigated individuals.

<p><b>A) Boxplots showing protein concentrations ranges in CSF from 72 individuals without neurological disorders.</b> The concentration ranges between the upper and lower limits of detection for each marker are shown in grey. The numbers below and above the boxplots show the number of patient samples (out of the total 72) that are outside the detection limits. <b>B) Performance measures for each protein assay.</b> The 1^st, 2^nd (median) and 3^rd quartile values of the robust % CV. The numbers of detectable samples out of a total of 72 samples are found at the bottom line for each marker.</p