The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.

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Introduction: In the setting of pre-operative neoadjuvant chemotherapy (NAC) for the treatment of breast cancer, it is important to ensure coordination between medical and surgical oncology. A study by Sanford et al. show that patients receiving surgery >8 weeks after NAC have worse overall survival. As NAC continues to expand its role in breast cancer treatment, a closer look at the maximal acceptable time between NAC and surgery becomes more important. We wished to assess the impact of time between last dose of chemotherapy and surgery on pathological complete response (pCR), disease free survival (DFS), overall survival (OS), and surgical complications. Methods: A cohort study was conducted utilizing the BC Cancer Agency's prospective neoadjuvant database, located in Vancouver, BC. Patients were selected if they had undergone NAC with curative intent for treatment of breast cancer, followed by surgical resection. Patients who received neoadjuvant radiation and/or hormone therapy were excluded. Patients were divided into three groups: those who had surgery <4 weeks from last dose of chemo, 4-8 weeks from last dose, and >8 weeks from last dose. Charts were audited for demographic data, tumour characteristics, and complications from surgery. Data was analyzed using a Chi Squared test to determine any differences in pCR, OS, DFS, and surgical complications, between the three different time intervals. Results: 347 patients were identified and included in this study. The median time to surgery after last dose of chemotherapy was 4.86 weeks (range 0.86-22.86 weeks). The percentage of patients that achieved pCR was 31.3%, 30.5%, and 28.6% in the <4 weeks, 4-8 weeks, and >8 weeks groups respectively (p= NS for all comparisons). There was no difference in pCR observed between the three groups based on receptor status. At the median follow up of 3 years, DFS was 85%, 85.8%, and 85.7% in all three groups. Likewise OS was 95%, 90%, and 89% respectively. The rate of surgical complications are 16%, 23.4%, and 21.4% for the three groups respectively (p=NS). Conclusions: This study demonstrated no difference between receiving surgery <4 weeks, 4-8 weeks, or >8 weeks after last dose of NAC on pCR, survival, or surgical complications. This finding was preserved in all receptor subtypes. This has important implications for resource allocation. This data may also help in counselling and easing patient anxiety in terms of the urgency (or lack thereof) and wait times for surgery. Subsequent studies with larger sample sizes will help to ensure that clinical differences in outcomes are not affected by wait times. Comparison of outcome measures based on needle to knife time < 4 weeks (n=80)4-8 weeks (n=239)>8weeks (n=28)p (<4 weeks vs. < 8 weeks)pCR31.3% (25)30.5% (73)28.6% (8)0.791HR+Her2-4.5% (1/22)6.5% (6/92)0% (0/5)--TNBC31.5% (6/19)42.1% (24/57)0% (0/6)--Her2+46.1% (18/39)48.8% (44/90)47.1% (8/17)--3 year DFS85%85.5%85.7%0.9273 year OS95%90%89%0.290Surgical Complication16.3%23.4%21.4%0.536 Citation Format: Lai V, Hajjaj O, Chia S, Simmons C. Needle-to-knife wait time and impact on pCR in patients undergoing neoadjuvant chemotherapy for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-04.

Background Studies in the adjuvant setting suggest that the timing of breast cancer diagnosis, surgery, and chemotherapy might affect outcomes. In the neoadjuvant setting, data exploring whether expeditious neoadjuvant chemotherapy (nac) after diagnosis improves the rate of pathologic complete response (pcr) in breast cancer are limited. Methods Patients who received nac and completed treatment between May 2012 and December 2018 were identified from a prospectively collected database at BC Cancer. Time from diagnosis to start of nac was calculated. Patients were grouped into those who did and did not experience a pcr, and those who started nac within 28 days or after 28 days [time to nac (ttn)]. The association between pcr and ttn was tested using logistic regression. Results In the time period studied, 482 patients who received nac were identified. After exclusions, 421 patients met the eligibility criteria. Median time from biopsy to chemotherapy was 33 days (range: 7–140 days). In 149 patients (35.4%), nac was received within 28 days of diagnosis (range: 7–28 days); in 272 patients (64.6%), it was received after more than 28 days (range: 29–140 days). The overall pcr rate was 31.8%. A trend toward a higher pcr rate, although not statistically significant, was observed in the group that initiated chemotherapy within 28 days (34.2% vs. 30.5%, p = 0.43). In the logistic regression model, rates of pcr were associated with receptor status, but not age, stage, or ttn. Conclusions In the neoadjuvant setting, we observed no difference in the rate of pcr in patients who started nac within 28 days or after 28 days.