1,077 research outputs found

    Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer

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    Purpose: Few patients with metastatic triple-negative breast cancer (mTNBC) benefit from immune checkpoint inhibitors (ICI). On the basis of immunotherapy response correlates in other cancers, we evaluated whether high tumor mutational burden (TMB) ≄10 nonsynonymous mutations/megabase and PTEN alterations, defined as nonsynonymous mutations or 1 or 2 copy deletions, were associated with clinical benefit to anti-PD-1/L1 therapy in mTNBC. Experimental design: We identified patients with mTNBC, who consented to targeted DNA sequencing and were treated with ICIs on clinical trials between April 2014 and January 2019 at Dana-Farber Cancer Institute (Boston, MA). Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were correlated with tumor genomic features. Results: Sixty-two women received anti-PD-1/L1 inhibitors alone (23%) or combined with targeted therapy (19%) or chemotherapy (58%). High TMB (18%) was associated with significantly longer PFS (12.5 vs. 3.7 months; P = 0.04), while PTEN alterations (29%) were associated with significantly lower ORR (6% vs. 48%; P = 0.01), shorter PFS (2.3 vs. 6.1 months; P = 0.01), and shorter OS (9.7 vs. 20.5 months; P = 0.02). Multivariate analyses confirmed that these associations were independent of performance status, prior lines of therapy, therapy regimen, and visceral metastases. The survival associations were additionally independent of PD-L1 in patients with known PD-L1 and were not found in mTNBC cohorts treated with chemotherapy (n = 90) and non-ICI regimens (n = 169). Conclusions: Among patients with mTNBC treated with anti-PD-1/L1 therapies, high TMB and PTEN alterations were associated with longer and shorter survival, respectively. These observations warrant validation in larger datasets

    Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network

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    Objetivos: Describir la presentaciĂłn clĂ­nica, el manejo y los resultados de la enfermedad de Kawasaki (EK) en LatinoamĂ©rica y evaluar los indicadores pronĂłsticos tempranos de aneurisma de la arteria coronaria (AAC). Diseño del estudio: Se realizĂł un estudio observacional basado en el registro de la EK en 64 centros pediĂĄtricos participantes de 19 paĂ­ses latinoamericanos de forma retrospectiva entre el 1 de enero de 2009 y el 31 de diciembre de 2013, y de forma prospectiva desde el 1 de junio de 2014 hasta el 31 de mayo de 2017. Se recopilaron datos demogrĂĄficos, clĂ­nicos y de laboratorio iniciales. Se utilizĂł una regresiĂłn logĂ­stica que incorporaba factores clĂ­nicos y la puntuaciĂłn z mĂĄxima de la arteria coronaria en la presentaciĂłn inicial (entre 10 dĂ­as antes y 5 dĂ­as despuĂ©s de la inmunoglobulina intravenosa [IGIV]) para desarrollar un modelo pronĂłstico de AAC durante el seguimiento (>5 dĂ­as despuĂ©s de la IGIV). Resultados: De 1853 pacientes con EK, el ingreso tardĂ­o (>10 dĂ­as tras el inicio de la fiebre) se produjo en el 16%, el 25% tuvo EK incompleta y el 11% fue resistente a la IGIV. Entre los 671 sujetos con puntuaciĂłn z de la arteria coronaria notificada durante el seguimiento (mediana: 79 dĂ­as; IQR: 36, 186), el 21% presentaba AAC, incluido un 4% con aneurismas gigantes. Un modelo pronĂłstico simple que utilizaba sĂłlo una puntuaciĂłn z de la arteria coronaria mĂĄxima ≄2,5 en la presentaciĂłn inicial fue Ăłptimo para predecir la AAC durante el seguimiento (ĂĄrea bajo la curva: 0,84; IC del 95%: 0,80, 0,88). Conclusiones: De nuestra poblaciĂłn latinoamericana, la puntuaciĂłn z de la arteria coronaria ≄2,5 en la presentaciĂłn inicial fue el factor pronĂłstico mĂĄs importante que precediĂł a la AAC durante el seguimiento. Estos resultados resaltan la importancia de la ecocardiografĂ­a temprana durante la presentaciĂłn inicial de la EK. © 2023 Los autoresObjectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). Study design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≄2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). Conclusion: From our Latin American population, coronary artery z-score ≄2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD. © 2023 The Author(s

    Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

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    This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

    The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

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    AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

    TRY plant trait database – enhanced coverage and open access