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- Osteosarcoma pathogenesis leads the way to new target treatmentsPublication . Fernandes, Isabel; Alvim, Cecilia; Brás, Raquel; Esperança Martins, Miguel; Costa, LuisOsteosarcoma (OS) is a rare condition with very poor prognosis in a metastatic setting. Basic research has enabled a better understanding of OS pathogenesis and the discovery of new potential therapeutic targets. Phase I and II clinical trials are already ongoing, with some promising results for these patients. This article reviews OS pathogenesis and new potential therapeutic targets.
- A case of success: complete response to Radium-223 in metastatic castration-resistant prostate cancerPublication . Soares De Pinho, Inês; Esperança Martins, Miguel; Machado, Bárbara; Dâmaso, Sara; Brás, Raquel; Cantinho, Guilhermina; Fernandes, Isabel; Costa, LuisRadium-223 dichloride (Ra223) is the first targeted alpha agent approved for treating metastatic castration-resistant prostate cancer (mCRPC) with bone-exclusive disease. A benefit in overall survival and time to the first symptomatic skeletal-related event was shown in the Alpharadin in Symptomatic Prostate Cancer Patients (ALSYMPCA) trial. However, this trial did not describe a bone scan response to Ra223, and there is no universal consensus about how it should be monitored. Furthermore, a scintigraphy flare phenomenon may lead to false-positive tracer uptake in responsive cases, thereby misleading the interpretation of imaging results. We present the case of a 67-year-old male with mCRPC and exclusive bone disease treated with Ra223. The bone scintigraphy after the end of the treatment showed an apparent aggravation of the lesions, corresponding to a flare phenomenon, with an almost complete resolution after three months. The patient maintained a scintigraphic response for seven months.
- Genomic profiling of sarcomas: a promising weapon in the therapeutic arsenalPublication . Brás, Raquel; Lopez-Presa, Dolores; Esperança Martins, Miguel; Alvim, Cecilia; Gallego Páez, Lina Marcela; Costa, Luis; Fernandes, IsabelSarcomas are rare malignant mesenchymal neoplasms, and the knowledge of tumor biology and genomics is scarce. Chemotherapy is the standard of care in advanced disease, with poor outcomes. Identifying actionable genomic alterations may offer effective salvage therapeutic options when previous lines have failed. Here, we report a retrospective cohort study of sarcoma patients followed at our center and submitted to comprehensive genomic profiling between January 2020 and June 2021. Thirty patients were included, most (96.7%) with reportable genomic alterations. The most common alterations were linked to cell cycle regulation (TP53, CDKN2A/B, and RB1 deletions and CDK4, MDM2, and MYC amplifications). Most patients (96.7%) had microsatellite stability and low tumor mutational burden (≤10 muts/megabase (Mb); median 2 Muts/Mb). Two-thirds of patients had actionable mutations for targeted treatments, including five cases with alterations amenable to targeted therapies with clinical benefit within the patient's tumor type, ten cases with targetable alterations with clinical benefit in other tumor types, and five cases with alterations amenable to targeting with drugs under investigation in a clinical trial setting. A significant proportion of cases in this study had actionable genomic alterations with available targeted drugs. Next-generation sequencing is a feasible option for identifying molecular drivers that can provide therapeutic options for individual patients. Molecular Tumor Boards should be implemented in the clinical practice to discuss genomic findings and inform clinically relevant targeted therapies.