Project description:Renal cell carcinoma (RCC) remains a public health issue and seems to be increasing. A significant proportion of RCC patients will develop pulmonary metastasis at some point in their evolution. In this review, we aimed to update the surgical management of pulmonary metastases as well as systemic therapy, including targeted therapies, according to recent data in the literature. We retrospectively reviewed studies evaluating the benefit of pulmonary metastasectomy in RCC patients and evaluating the place of different chemotherapies, targeted therapies and immunotherapies through November 1, 2019. Several retrospective studies have shown the benefit of pulmonary metastasectomy in metastatic RCC (mRCC), most in a situation with only pulmonary metastases. According to the prognostic criteria of the IMDC risk model, the patient is classified into a prognostic group to identify the best systemic treatment. With the development of targeted therapies, the modalities are multiple and may involve tyrosine kinase inhibitors/checkpoint inhibitors and soon vaccine therapy or CAR-T cells. At the local level, in patients who cannot benefit from surgery, stereotactic radiotherapy or radiofrequency has a place to be considered. Although there is a lack of a randomized study, pulmonary metastasectomy appears to be feasible and effective. The place and modalities of systemic therapies in the era of targeted therapies remain to be more clearly defined.
Project description:Tivozanib is an oral selective vascular endothelial growth factors receptor (VEGFR) tyrosine kinase inhibitor that is recently approved by the European Medicines Agency for the treatment of previously untreated patients with metastatic renal cell carcinoma (mRCC) as well as for those patients with disease progression during or after cytokine therapy. Nowadays, in first-line and second-line treatment of mRCC, there is an abundance of options, mainly consisting of VEGFR-directed tyrosinekinase inhibitors. This review focusses on the role of tivozanib with respect to patient selection and future perspectives in this fast-changing landscape.
Project description:BackgroundAxitinib is a next-generation, selective tyrosine kinase inhibitor targeting the vascular endothelial growth factor receptors. It is approved for the treatment of metastatic renal cell carcinoma (mRCC) based on a demonstrated progression-free survival advantage over sorafenib in the second-line treatment setting. However, given the variety of available targeted therapies for mRCC, appropriate patient selection for the available therapies remains a significant clinical challenge.PurposeThis review summarizes the available evidence on the clinical, toxicity, and pharmacologic considerations for determining appropriate patient selection for axitinib therapy. In addition, it describes recent data on the use of predictive biomarkers to guide clinical management. This paper consists of material obtained via PubMed and Medline literature searches through October 2015.ConclusionAxitinib has a well-established role in the management of mRCC. Consistent clinical efficacy has been demonstrated across prognostic risk groups and prior therapeutic exposures. Although axitinib is generally well tolerated, appropriate toxicity management is critical to maximizing drug delivery and optimizing treatment outcomes. Although incident hypertension has been associated with improved clinical outcomes on axitinib, there are currently no validated clinical or genetic predictive biomarkers to guide patient selection.
Project description:The core function of a multidisciplinary team (MDT) is to bring together a group of healthcare professionals from different fields in order to determine patients' treatment plan. Most of head and neck cancer (HNC) units are currently led by MDTs that at least include ENT and maxillofacial surgeons, radiation and medical oncologists. HNC often compromise relevant structures of the upper aerodigestive tract involving functions such as speech, swallowing and breathing, among others. The impairment of these functions can significantly impact patients' quality of life and psychosocial status, and highlights the crucial role of specialized nurses, dietitians, psycho-oncologists, social workers, and onco-geriatricians, among others. Hence, these professionals should be integrated in HNC MDTs. In addition, involving translational research teams should also be considered, as it will help reducing the existing gap between basic research and the daily clinical practice. The aim of this comprehensive review is to assess the role of the different supportive disciplines integrated in an MDT and how they help providing a better care to HNC patients during diagnosis, treatment and follow up.
Project description:Stereotactic ablative radiotherapy (SABR) has challenged the conventional wisdom surrounding the radioresistance of renal cell carcinoma (RCC). In the past decade, there has been a significant accumulation of clinical data to support the safety and efficacy of SABR in RCC. Herein, we review the use of SABR across the spectrum of RCC. We performed an online search of the Pubmed database from January 1990 through April 2023. Studies of SABR/stereotactic radiosurgery targeting primary, extracranial, and intracranial metastatic RCC were included. For SABR in non-metastatic RCC, this includes its use in small renal masses, larger renal masses, and inferior vena cava tumor thrombi. In the metastatic setting, SABR can be used at diagnosis, for oligometastatic and oligoprogressive disease, and for symptomatic reasons. Notably, SABR can be used for both the primary renal tumor and metastasis-directed therapy. Management of RCC is evolving rapidly, and the role that SABR will have in this landscape is being assessed in a number of ongoing prospective clinical trials. The objective of this narrative review is to summarize the evidence corroborating the use of SABR in RCC.
Project description:The past decade has seen a rapid proliferation in the number and types of systemic therapies available for renal cell carcinoma. However, surgery remains an integral component of the therapeutic armamentarium for advanced and metastatic kidney cancer. Cytoreductive surgery followed by adjuvant cytokine-based immunotherapy (predominantly high-dose interleukin 2) has largely given way to systemic-targeted therapies. Metastasectomy also has a role in carefully selected patients. Additionally, neoadjuvant systemic therapy may increase the feasibility of resecting the primary tumor, which may be beneficial for patients with locally advanced or metastatic disease. Several prospective trials examining the role of adjuvant therapy are underway. Lastly, the first immune checkpoint inhibitor was approved for metastatic renal cell carcinoma (mRCC) in 2015, providing a new treatment mechanism and new opportunities for combining systemic therapy with surgery. This review discusses current and historical literature regarding the surgical management of patients with advanced and mRCC and explores approaches for optimizing patient selection.
Project description:Opinion statementThe treatment landscape of renal cell carcinoma (RCC) has evolved significantly over the past three decades. Active surveillance and tumor ablation are alternatives to extirpative therapy in appropriately selected patients. Stereotactic body radiation therapy (SBRT) is an emerging noninvasive alternative to treat primary RCC tumors. The advent of immune checkpoint inhibitors (ICIs) has greatly improved the overall survival of advanced RCC, and now the ICI-based doublet (dual ICI-ICI doublet; or ICI in combination with a vascular endothelial growth factor tyrosine kinase inhibitor, ICI-TKI doublet) has become the standard frontline therapy. Based on unprecedented outcomes in the metastatic with ICIs, they are also being explored in the neoadjuvant and adjuvant setting for patients with high-risk disease. Adjuvant pembrolizumab has proven efficacy to reduce the risk of RCC recurrence after nephrectomy. Historically considered a radioresistant tumor, SBRT occupies an expanding role to treat RCC with oligometastasis or oligoprogression in combination with systemic therapy. Furthermore, SBRT is being investigated in combination with ICI-doublet in the advanced disease setting. Lastly, given the treatment paradigm is shifting to adopt ICIs at earlier disease course, the prospective studies guiding treatment sequencing in the post-ICI setting is maturing. The effort is ongoing in search of predictive biomarkers to guide optimal treatment option in RCC.
Project description:Cabozantinib is an oral tyrosine kinase inhibitor (TKI) with activity against several receptors involved in the angiogenesis pathway, including vascular endothelial growth factor receptor (VEGFR), c-MET and AXL. The antiangiogenic properties of cabozantinib led to its use as a monotherapy for the treatment of metastatic renal cell cancer (RCC), and quickly resulted in this treatment becoming part of the standard of care for these tumors. Since the advent of immune checkpoint inhibitors (ICIs), new standards of care have emerged in first-line settings, involving dual ICI or ICI-VEGF-TKI (including ICI-cabozantinib) combination treatments, and leading to a more complex algorithm of care. Cabozantinib remains an option in second-line settings and is still a first-line standard of care treatment in cases where the use of ICIs is contraindicated. This review focuses on the selection of patients who may benefit most from cabozantinib therapy, including those with bone and brain metastases and those with a non-clear cell RCC histology. The need to consider disease-related symptoms, comorbidities, age, drug interactions and biomarker analyses in the choice of therapeutic strategy is also highlighted. Finally, the perspectives for the use of cabozantinib in RCC treatment are discussed.
Project description:First-line treatment for metastatic renal cell carcinoma (mRCC) rapidly shifted in recent years with the advent of combination therapies, including immune checkpoint inhibitor (ICI) doublets and combinations of an ICI with a vascular endothelial growth factor receptor (VEGFR) targeted tyrosine kinase inhibitor (TKI). Despite improvements in overall survival and many durable responses, there exists a significant number of patients who fail to respond to these agents, and many patients eventually progress. Given the rapid changes in the front-line setting, it is essential to understand treatment options in refractory mRCC. Here, we review the evidence behind current options for later-line therapies, often involving additional VEGFR-TKIs alone or in combination with mammalian target of rapamycin (mTOR) targeted agents, as well as situations where consideration of immunotherapy rechallenge may be appropriate. Additionally, we describe ongoing clinical trials examining concurrent ICI and TKI in the refractory setting, as well as those studying novel agents, such as targeted drug-antibody conjugates and hypoxia inducible factor 2α (HIF-2α) inhibitors. Finally, we review considerations for non-clear cell histologies in the refractory setting and mechanisms of resistance in mRCC.