Impact of extraskeletal metastases on skeletal-related events in metastatic castration-resistant prostate cancer with bone metastases

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has substantially evolved over the last decade. Nonetheless, a better understanding of bone-targeted agents (BTAs) action in mCRPC remains an unmet need. Theuse of BTAs aims to reduce the incidence of skeletal-related events (SREs) in patients with mCRPC. Less frequent BTA schedules are currently being studied to minimize adverse events. In this study, the impact of metastatic compartment (bone and extraskeletal metastases (BESM) vs. bone-only metastases (BOM)) on bone biomarker kinetics, time to first on-study SRE, and symptomatic skeletal events (SSEs) is evaluated. This is a retrospective analysis of the prospective, randomized, multicenter clinical trial of denosumab vs. zoledronic acid in patients with mCRPC and bone metastases. A total of 1901 patients were included, 1559 (82.0%) with BOM and 342 with BESM (18.0%). Bone metastases burden was balanced between groups. Baseline levels and normalization rates of corrected urinary N-terminal telopeptide and bone alkaline phosphatase did not differ between groups. However, BESM patients had a higher risk of SREs (adjusted HR 1.21; 95% CI 1.01-1.46; p = 0.043) and SSEs (adjusted HR 1.30; 95% CI 1.06-1.61; p = 0.014). This difference was more pronounced in the first 12 months of BTA treatment.In mCRPC, strategies of BTA schedule de-escalation may take into account presence of extraskeletal metastases.info:eu-repo/semantics/publishedVersio

Landscape of Current Targeted Therapies for Advanced Colorectal Cancer

Colorectal cancer (CRC) is one of the most frequent and lethal cancer types worldwide. While surgery with chemotherapy and radiotherapy remains the only curative approach for localized CRC, for metastatic disease the therapeutic landscape has significantly evolved over the last years. Development and approval of novel targeted therapies, such as monoclonal antibodies against EGFR and VEGF, have significantly increased the median survival of patients with metastatic disease, with some trials reporting a benefit over 40 months. Increasing accessibility of high throughput sequencing has unraveled several new therapeutic targets. Actionable alterations, such as HER2 overexpression, BRAF mutations, and NTRK fusions, are currently available in metastatic disease, providing significant therapeutic opportunities for these patients, while new emerging agents, as immune checkpoint inhibitors, promise better treatment options in the near future. In this chapter, an overview of established and future CRC targeted therapies in the clinical setting is provided, as well as their mechanism of action, limitations, and future applicability

Prognostic factors for patients treated with abiraterone

© Cecilia Melo Alvim. This work is licensed under the Creative Commons Attribution4.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Aim: To evaluate prostate-specific antigen response (PSAr) defined as a ≥50% decrease in PSA concentration from the pretreatment value, as a prognostic factor in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA). Methods: Retrospective evaluation of patients with mCRPC treated with AA. Results: 124 patients were identified. Median overall survival and progression-free survival for patients achieving PSAr versus patients without PSAr were 29.3 versus 9.7 months and 17.0 versus 5.2 months, respectively. Multivariate analysis confirmed that PSAr correlated with better overall survival (hazard ratio: 0.19; 95% CI: 0.10-0.38; p < 0.001) and progression-free survival (hazard ratio: 0.24; 95% CI: 0.14-0.41; p < 0.001). Conclusion: PSAr can be utilized as prognostic and predictive factors in mCRPC patients treated with AA.info:eu-repo/semantics/publishedVersio

Genetic and microenvironmental intra-tumor heterogeneity impacts colorectal cancer evolution and metastatic development

© The Author(s) 2022 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Colorectal cancer (CRC) is a highly diverse disease, where different genomic instability pathways shape genetic clonal diversity and tumor microenvironment. Although intra-tumor heterogeneity has been characterized in primary tumors, its origin and consequences in CRC outcome is not fully understood. Therefore, we assessed intra- and inter-tumor heterogeneity of a prospective cohort of 136 CRC samples. We demonstrate that CRC diversity is forged by asynchronous forms of molecular alterations, where mutational and chromosomal instability collectively boost CRC genetic and microenvironment intra-tumor heterogeneity. We were able to depict predictor signatures of cancer-related genes that can foresee heterogeneity levels across the different tumor consensus molecular subtypes (CMS) and primary tumor location. Finally, we show that high genetic and microenvironment heterogeneity are associated with lower metastatic potential, whereas late-emerging copy number variations favor metastasis development and polyclonal seeding. This study provides an exhaustive portrait of the interplay between genetic and microenvironment intra-tumor heterogeneity across CMS subtypes, depicting molecular events with predictive value of CRC progression and metastasis development.This work was financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB. This research was also funded by: PTDC/MED-ONC/28660/2017 from Fundação para a Ciência e Tecnologia (FCT) to A.R.G. A.R.G is recipient of Researcher Grant CEECIND/02699/2017 from FCT. The biobanking of CRC samples from Hospital Santa Maria, Lisbon, Portugal was supported by FCT research grant PIC/IC/82821/2007. This work was produced with the support of INCD funded by FCT and FEDER under the project 22153-01/SAICT/2016.info:eu-repo/semantics/publishedVersio

Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma

AimEvaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy.BackgroundAnemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes.Materials and MethodsRetrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5g/dL o

Hepatite A : a propósito de um caso clínico

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014The HAV is a non-enveloped virus and single-stranded RNA, having an essentially fecal-oral transmission. Over 1.5 million people are infected each year, despite the development of a safe and effective vaccine in the 90s. The disease is forgotten in the developed world but numerous outbreaks are described in Europe and USA. It has a high socioeconomic impact at great cost to public health and cause hospitalization in about 30% of symptomatic patients. The mortality rate reaches 2.1% in adults over 40 years and it can cause fulminant hepatitis in 1% of patients. Portugal is currently a country of low endemicy, with the last outbreak in 2004-2005 with 24 reported cases. The symptomatology is age-dependent. In children, it is essentially asymptomatic and more than 70% of adults present with cholestatic hepatitis and jaundice. The diagnosis is made by detection of anti-HAV IgM. We report the case of a Portuguese patient 35 years, male, residing in Angola since 2003, with severe hepatitis and jaundice, changes in liver tests and modification of the prothrombin time.O VHA é um vírus sem envelope e com cadeia única de ARN, tendo uma transmissão essencialmente fecal-oral. Mais de 1,5 milhões de pessoas são infetadas por ano, apesar do desenvolvimento de uma vacina segura e eficaz na década de 90. A doença é esquecida no mundo desenvolvido mas inúmeros surtos são descritos na Europa e EUA. Apresenta elevado impacto socioeconómico com grandes custos de saúde pública e causa hospitalização em cerca de 30% dos doentes sintomáticos. A taxa de mortalidade atinge os 2,1% em adultos com mais de 40 anos e pode causar hepatite fulminante em 1% dos doentes. Portugal é, atualmente, um país de baixa endemicidade, tendo ocorrido o último surto em 2004-2005 com 24 casos reportados. A sintomatologia é dependente da idade do doente. Nas crianças é essencialmente assintomática, enquanto mais de 70% dos adultos apresenta hepatite colestática com icterícia. O diagnóstico é realizado pela deteção de IgM anti-VHA. Apresenta-se o caso de um português de 35 anos, residente em Angola desde 2003, com hepatite A grave com icterícia, alteração das provas hepáticas e alteração do tempo de protrombina

Toxic erythema of chemotherapy induced by liposomal doxorubicin, a clinical case

A 76-year-old woman presented to the medical oncology outpatient clinic with painful, burning, pruritic erythematous plaques involving both palms and axillae that had suddenly appeared five days before. Examination revealed no additional relevant findings and laboratory studies did not show any alteration. The patient had been recently diagnosed with a high-grade angiosarcoma of the breast (probably radiation induced) and after frequent local recurrences, was being treated with liposomal doxorubicin (three cycles were administered, the last of which was seven days before the appearance of the mentioned lesions). Oral corticosteroids were started, treatment with liposomal doxorubicin was stopped, and cutaneous biopsies performed that revealed features compatible with toxic erythema of chemotherapy induced by liposomal doxorubicin. Complete resolution of the cutaneous lesions was verified one month after. No signs of recurrence of angiosarcoma were documented at follow-up three months later