Highlights High-risk HPV infection is less frequently detected in HIV-positive non-metastatic ASCC compared with HIV-negative cases. Mutational profile identified in the non-metastatic ASCC cohort revealed expected similarities with metastatic ASCC. High PD-L1 expression levels are associated with high CD3 and CD8 TIL density, complete response to treatment, and good survival outcome of ASCC patients. PD-L1 is a reliable predictive and prognostic biomarker that allows the stratification in low- vs. high-risk ASCC patients at their initial therapeutic approach.

Aims: Senna alata (Carrion crow bush), Senna bicapsularis (Money bush) and Pityrogramma calomelanos (Wild maran) are known for their value in traditional medicine. The study was an effort to identify, environment friendly antifungal compounds from these locally available plants against fungal pathogen Curvularia lunata. Study Design: An experiment based study done to identify antifungal property and phytochemical identification of C. lunata. Place and Duration of Study: Plants were collected from the coastal areas of Guyana and identified at the Biodiversity Center, University of Guyana, Guyana between January 2017- May 2017. Methodology: Phytochemical extraction was conducted using soxhlet and rotovap apparatus. Hexane, methanol and aqueous extracts of plants were analyzed for antifungal properties. Antifungal activity was tested using the poisoned food and well diffusion technique. Data analysis of the study was done using R-Studio Program for statistical computing and graphics. A Tukey test was done along with ANOVA and Boxplots. Results: Methanol extract of P. calomelanos showed maximum antifungal activity with an inhibition percentage of 60.3% at 400 µl, with poison food technique. With well diffusion method, P. calomelanos showed an inhibition zone of 54 mm at 500 µl. Saponins, steroids and glycosides were identified with methanol extract of P. calomelanos. Conclusion: The finding of this study indicates, the possible use of P. calomelanos extract as an antifungal agent against C. lunata and its potential to control fungal plant diseases.

4054 Background: NMASCC is a rising incidence disease with up to 30% of treatment failure to achieve complete response (CR) after standard chemoradiotherapy (CRT) leading to severe morbidity and death. Stage III-TNM, p53 mutations, HPV negativity, HIV infection are linked to treatment failure. We investigated the predictive/prognostic role of TNM, CR, HPV, PDL1 positivity and CD3/CD8 densities in NM-ASCC from a single institution. Methods: All 79 eligible consecutive NMASCC pts (available FFPE pre-treatment samples) seen from October-2009 to April-2019 having completed definitive CRT (50.4 Gy Pelvic Radiotherapy with Mitomycin-C 12mg/m2/IV/d1-5 / FU 1000mg/m2/d1-4 d29-32 (28%), Mitomycin-C/Capecitabine 825 mg/m2/bid (38%), Cisplatin 60 mg/m2/IV d1-29 and 5FU (34%) were analyzed. Mean age: 59 (range 26-87), 72% female, Stage III: 59%, HPV positive: 86% (HPV-16: 80%);14% HIV positive. IHC assessed by two pathologist for PD-L1 expression (ClonSP263) and CD3-CD8+ TILS densities (Clone 2GV6, Clone SP57). HPV-DNA assessed by PCR (BSGP5+/6+ multiplexed with beta-globin). Kaplan-Meier survival, CR, DFS, OS and Univariate analyses were performed using Cox proportional hazard model. Results: CR achieved within 6 months of treatment completion was 68%( 53pts). Median follow-up after treatment completion: 35 months (range 6 –149). As of February 2020, 82% (65 pts) are alive, no evidence of disease:(57%) 46 pts, recurrence rate: 26%(22 pts), cancer death: 18% (14 pts). PDL1+ tumors ( > 1% positivity-CPS score): 56%, expression levels: 1-5% (57%,26p), > 10%-100% (43%,19p). PDL1+ had a strong association with CR (p = 0.021); higher PDL1+ levels had 8-fold of CR-likelihood than PDL1 negative.(OR 8.50 vs. 1.12). Significative Spearman correlation between PDL1 tumors with CR and CD3-CD8 TILS density was observed (R = 0.43,p = 0.0017 and R = 0.36,p = 0.00094 respectively), albeit CD3-CD8 failed to reach significance as prognostic factors for either CR, DFS or OS. Only CR and PDL1 positive were strongly significantly associated to DFS (HR 0.10 [IC 95% 0.04-0.28] p < 0.001 and HR 0.28 [IC 95% 0.11-0.73] p = 0.006) and OS (HR 0.12 [IC 95% 0.03-0.45] p < 0.001 and HR 0.15 [IC 95% 0.03-0.68] p < 0.004). Low prevalence of HPV negative, early tumors, HIV positive cases in our series probably impacted in statistical power for prognosis correlation. Conclusions: PDL1 positivity was the strongest predictive/prognostic factor in NM-ASCC. Alternative therapeutics options to standard CRT should be explored on poor-risk patients as HPV-negative, P53-mutated and PDL1 negative patients.

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La terapia endocrina (TE) es el estándar de tratamiento del cáncer de mama metastásico (CMM) RH+/HER2-. Sin embargo, los datos de la práctica clínica demuestran que una alta proporción de pacientes son tratados con quimioterapia (QT). Nuestro objetivo fue obtener información del mundo real sobre el tratamiento en pacientes con cáncer de mama metastásico (CMM) luminal, comparando el uso de TE versus QT en los últimos 25 años. Para el análisis se establecieron cuatro cohortes de tiempo: (A: 1994-1999, B: 2000- 2009, C: 2010-2015 y D: 2016-2020). La TE fue el tratamiento de primera línea en el 67%; 70% y 87% de los pacientes en las cohortes B, C y D respectivamente (ajustado por comparaciones múltiples, p=0.0024). La proporción de pacientes que recibieron QT en primera línea comenzó a disminuir en más del 30% en la cohorte B (2000- 2009) a menos del 15% en la cohorte D (2016- 2020) debido a la inclusión de los inhibidores de quinasas dependientes de ciclinas 4/6 (CDKi). En el análisis multivariado de la cohorte B y C, los factores asociados con un menor uso de QT fueron las metástasis óseas exclusivas, menos de 2 sitios metastásicos y un bajo KI 67%. Los patrones de tratamiento para CMM RH+/HER2- han cambiado sustancialmente en los últimos años a partir del advenimiento de los CDKi en la cohorte D. Nuestros datos informan una disminución del porcentaje de pacientes tratadas con QT en primera línea en la vida real.