1,019 research outputs found
Cardiotoxicity mechanisms of the combination of BRAF-inhibitors and MEK-inhibitors
No full textMany new drugs have appeared in last years in the oncological treatment scenario. Each drug carries an important set of adverse events, not less, cardiovascular adverse events. This aspect is even more important considering the increasing use of combination therapies with two drugs, or three drugs as in some ongoing clinical trials. Besides it represents a growing problem for Cardiologists, that face it in every day clinical practice and that will face it probably more and more in the coming years. This work reviews the mechanism of action of BRAF-inhibitors and MEK-inhibitors used together, the pathophysiological mechanisms that lead to cardiovascular toxicity. Particularly, it focuses on hypertension and ejection fraction reduction development. Then, it follows the examination of published data for each combination therapy. A Literature research was carried out using Pubmed selecting review articles, original studies and clinical trials, but mainly focusing on phase 3 studies. This work aims to summarize the knowledge about BRAF-inhibitor and MEK-inhibitor treatment and its cardiovascular toxicity to make it usable and give the basic tools to Cardiologists and Oncologists for a better management of cancer patient undergoing this treatment. Besides a deeper knowledge of the cardiovascular adverse events linked to this treatment and the magnitude of their expression and frequency can lead to a targeted cardiological treatment
Semi-automated volumetric analysis in the NELSON trial for lung cancer screening: Is there room for diagnostic experience yet
No full textThe reliability of lung cancer screening based on low-dose computed tomography (LDCT) instead of X-ray is supported by a reduction of lung cancer mortality by 20% for high-risk subjects (1). As a consequence, this approach is recommended in heavy smokers.
However, some questions about the modality of screening have not been answered yet. Among these some issues appear more relevant:
What subjects should be considered at high risk?
How long time should elapse between screening rounds?
What patterns of nodules should be considered as suspicious for lung cancer?
What nodule size would induce a greater suspicion of malignancy
Petals and thorns in programmed death-ligand 1 testing: Is all non–small cell lung cancer diagnostic material suitable?
No full textRussell-Goldman et al1 recently published in CancerCytopathology an article on the cytologic-histologiccorrelation of programmed death-ligand 1 (PD-L1)in lung carcinomas
Emily Brontë : the mind of a visionary
No full textBibliography: leaves 216-226.This dissertation is an investigation of the visionary and philosophical aspects of Emily Brontë's works. The first five chapters deal with the visionary process such as visions, spirit guides, dreams, imagination, encounters with the darker side of the self and a union with the divine. There is considerable evidence of these mystical avenues in both her poetry and in Wuthering Heights which have been explored. It is shown how Emily Brontë's mysticism is a direct result of personal experiences which augment her reputation as one of the leading mystics in the world of literature. There are however tensions in her works, such as the cynicism of her own intellect in accepting the visionary experiences as authentic and periods of suffering when her faith is tested. These tensions have been considered within the context of her mystical encounters and philosophy. The remaining four chapters deal with the philosophy of Emily Brontë per se. Her beliefs in respect of heaven and hell, mercy and justice, power and survival, and pantheism are considered in depth. It is argued that she is an unorthodox thinker who does not believe in an eternal hell and that she has drawn inspiration for this idea from Frederick Maurice and Ralph Waldo Emerson. It is also shown how issues of power have been of interest to her from a young age and how this needs to be integrated within her philosophy. To the writer power needs to be tempered by compassion if it is to be of use to society or the individual. Her pantheistic spirit is also investigated and related to the mystical ideas
What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment
No full textThe RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation
Lenograstim in Preventing Chemotherapy-induced Febrile Neutropenia in Patients with Soft Tissue Sarcoma
No full textBackground: Neutropenia and its complications represent one of the principal dose-limiting toxicity issues in chemotherapeutic regimens for soft tissue sarcoma. Prophylactic granulocyte colony-stimulating factor (G-CSF) reduces the risk of febrile neutropenia (FN). The correct timing of G-CSF administration should be considered in order to optimize the prophylactic treatment. Patients and Methods: Patients (>= 18 years old) affected by soft tissue sarcoma and treated with epirubicin and ifosfamide, underwent prophylactic treatment with G-CSF (lenograstim at 263 mu g) from day 5 to day 9. The proportion of patients experiencing FN and G4 neutropenia was considered. Results: A total of 36 patients receiving three cycles of chemotherapy with epirubicin plus ifosfamide were treated. None developed FN; G4 neutropenia was reported in 17% of patients. No treatment delay or dose reduction was required, no antibiotic therapy was administered and no hospitalization occurred. Conclusion: Five-day lenograstim treatment is efficient as prophylaxis of FN for soft tissue sarcoma chemotherapy regimens and allows maintenance of chemotherapy dose intensity
Targeting RET-rearranged non-small-cell lung cancer: future prospects
No full textGiuseppe Bronte, Paola Ulivi, Alberto Verlicchi, Paola Cravero, Angelo Delmonte, Lucio Crinò Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy Abstract: Non-small-cell lung cancer (NSCLC) patients with mutated or rearranged oncogene drivers can be treated with upfront selective inhibitors achieving higher response rates and longer survival than chemotherapy. The RET gene can undergo chromosomal rearrangements in 1%–2% of all NSCLC patients, involving various upstream fusion partners such as KIF5B, CCDC6, NCOA4, and TRIM33. Many multikinase inhibitors are active against rearranged RET. Cabozantinib, vandetanib, sunitinib, lenvatinib, and nintedanib achieved tumor responses in about 30% of these patients in retrospective studies. Prospective phase II trials investigated the activity and toxicity of cabozantinib, vandetanib, sorafenib, and lenvatinib, and did not reach significantly higher response rates. VEGFR and EGFR inhibition represented the main ways of developing off-target toxicity. An intrinsic resistance emerged according to the type of RET fusion partners, as KIF5B-RET fusion is the most resistant. Also acquired mutations in rearranged RET oncogene developed as resistance to these multikinase inhibitors. Interestingly, RET fusions have been found as a resistance mechanism to EGFR-TKIs in EGFR-mutant NSCLC patients. The combination of EGFR and RET inhibition can overcome this resistance. The limitations in terms of activity and tolerability of the various multikinase inhibitors prompted the investigation of new highly selective RET inhibitors, such as RXDX-105, BLU-667, and LOXO-292. Some data emerged about intracranial antitumor activity of BLU-667 and LOXO-292. If these novel drugs will achieve high activity in RET rearranged NSCLC, also these oncogene-addicted tumors can undergo a significant survival improvement. Keywords: RET, non-small-cell lung cancer, multi-kinase inhibitors, gene rearrangemen
What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment
No full textThe RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation
Tmb in nsclc: A broken dream?
No full textAlthough immune checkpoint inhibitors have changed the treatment paradigm of a variety of cancers, including non-small-cell lung cancer, not all patients respond to immunotherapy in the same way. Predictive biomarkers for patient selection are thus needed. Tumor mutation burden (TMB), defined as the total number of somatic/acquired mutations per coding area of a tumor genome (Mut/Mb), has emerged as a potential predictive biomarker of response to immune checkpoint inhibitors. We found that the limited use of TMB in clinical practice is due to the difficulty in its detection and compounded by several different biological, methodological and economic issues. The incorporation of both TMB and PD-L1 expression or other biomarkers into multivariable predictive models could result in greater predictive power
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