1,721,037 research outputs found
CheckMate 9ER patient-reported outcomes: the patient is not willing to give up
Full text linkClinical decisions, in addition to be supported by research evidence, should accommodate patients’ preferences. Before choosing a treatment, we as clinicians should ask ourselves how much the patient is ready and willing to accept in exchange for an uncertain benefit.
Therefore, we must first offer patients clear and accurate information about the potential benefits and harms of the recommended treatment, and secondly we must use valid tools to assess patients’ perceptions of their general health and cancer symptoms over time
Despite an Abundance of Active Treatment Options for Renal Cell Carcinoma, Shadows Still Obscure the Light
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Concurrent Stereotactic Ablative Radiotherapy and Antiangiogenic Targeted Agents: Redefining the Therapeutic Strategy
No full textIf, on one hand, the prognosis for patients with metastatic renal cell carcinoma (mRCC) has greatly improved with immune-based combinations, on the other hand their effectiveness could theoretically lead to a decrease in the use of locoregional treatments, such as cytoreductive nephrectomy, and radiotherapy (RT).
However, RT as a whole, and stereotactic ablative body RT (SABR) in particular, should be regarded as a key treatment option within the global strategy for this disease. [...
Single nucleotide polymorphisms in angiogenesis-related genes and outcomes from antiangiogenic therapies in renal cell carcinoma: really a step towards personalized oncology, or not at all?
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Cisplatin-based chemotherapy for the treatment of metastatic collecting duct carcinomas: A real-world, retrospective analysis
Full text linkCollecting duct carcinomas (CDCs) are a particularly rare subtype of kidney cancer, endowed by a particularly poor prognosis. Since no active treatments have been established for CDCs, due to similarities with upper tract urothelial carcinomas, the use of the cisplatin-gemcitabine doublet is usually recommended. Here we report a retrospective analysis of 36 metastatic CDCs treated, as everyday clinical practice, with either cisplatin-gemcitabine or cisplatin-gemcitabine-paclitaxel from 2005 to 2021. Thirty-three patients received gemcitabine (1000 mg/m(2), days 1 and 8) and cisplatin (70 mg/m(2), day 1), while 3 were treated with paclitaxel (80 mg/m(2), days 1 and 8), gemcitabine (1000 mg/m(2), days 1 and 8) and cisplatin (70 mg/m(2), day 1), every 21 days for a maximum of 6 cycles. Eight out of 36 patients (22.2%) experienced a partial response, while 9 others (25%) had a disease stabilization. No benefit was observed in the only 3 patients treated with the triplet. Median PFS was just 6 months, while median OS was 8 months. The commonest grade ≥3 treatment-related adverse events were: neutropenia (75%, 11.1% of febrile neutropenia), anemia (50%), thrombocytopenia (38.8%), and vomiting (8.3%). Dose omissions and dose reductions were common, and few frail patients started the treatment with a 25% dose reduction. In conclusion, our real-world experience confirmed the modest activity and relevant toxicity of cisplatin-based chemotherapy for the treatment of CDCs. More translational studies and novel study designs are thus badly needed in these still orphan tumors
Artificial intelligence-based prediction of overall survival in metastatic renal cell carcinoma
Full text linkBackground and objectivesInvestigations of the prognosis are vital for better patient management and decision-making in patients with advanced metastatic renal cell carcinoma (mRCC). The purpose of this study is to evaluate the capacity of emerging Artificial Intelligence (AI) technologies to predict three- and five-year overall survival (OS) for mRCC patients starting their first-line of systemic treatment. Patients and methodsThe retrospective study included 322 Italian patients with mRCC who underwent systemic treatment between 2004 and 2019. Statistical analysis included the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis for the prognostic factors' investigation. The patients were split into a training cohort to establish the predictive models and a hold-out cohort to validate the results. The models were evaluated by the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. We assessed the clinical benefit of the models using decision curve analysis (DCA). Then, the proposed AI models were compared with well-known pre-existing prognostic systems ResultsThe median age of patients in the study was 56.7 years at RCC diagnosis and 78% of participants were male. The median survival time from the start of systemic treatment was 29.2 months; 95% of the patients died during the follow-up that finished by the end of 2019. The proposed predictive model, which was constructed as an ensemble of three individual predictive models, outperformed all well-known prognostic models to which it was compared. It also demonstrated better usability in supporting clinical decisions for 3- and 5-year OS. The model achieved (0.786 and 0.771) AUC and (0.675 and 0.558) specificity at sensitivity 0.90 for 3 and 5 years, respectively. We also applied explainability methods to identify the important clinical features that were found to be partially matched with the prognostic factors identified in the Kaplan-Meier and Cox analyses. ConclusionsOur AI models provide best predictive accuracy and clinical net benefits over well-known prognostic models. As a result, they can potentially be used in clinical practice for providing better management for mRCC patients starting their first-line of systemic treatment. Larger studies would be needed to validate the developed mode
HER2-Positive Urothelial Carcinoma: Current Evidence on Targeted Agents and Immunotherapy-Based Combinations
No full textDespite the introduction of immunotherapy and antibody–drug conjugates (ADCs), 5-year survival rates for advanced urothelial cancer (UC) remain unsatisfactory. Modest results with conventional systemic treatments have prompted the need for tailored therapies that exploit actionable mutations, such as those involving the human epidermal growth factor receptor (HER)-2 proto-oncogene, which plays a key role in regulating cell growth, differentiation, and survival. HER2-positive UC accounts for 13–25% of all locally advanced/metastatic UC. HER2 overexpression in UC varies widely by tumour stage and is usually a late phenomenon associated with poorer prognosis. Given the crucial biological role of HER2 in UC and the proven activity of anti-HER2 drugs in other solid tumours (e.g. breast and gastric cancer), in this comprehensive review, we analyse clinical trials using HER2-targeting strategies in HER2-positive metastatic UC. Clinical trials of anti-HER2 monoclonal antibodies and tyrosine kinase inhibitors in UC have shown limited efficacy. On the other hand, HER2-targeted ADCs such as trastuzumab deruxtecan and disitamab vedotin have shown encouraging results. However, the most interesting data come from the combination of HER2-targeted ADCs with immunotherapy because of the synergistic action of the two drugs: HER2-directed ADCs, with their cytotoxic effect, lead to the release of cancer antigens, enhancing the anti-tumour immune response, which is boosted by the immune checkpoint inhibitor. Moreover, this combination strategy may also offer some advantages in rewiring the tumour microenvironment, favouring an anti-cancer immune response. ADC and immune checkpoint inhibitor combinations are supported by solid preclinical evidence and are emerging as novel and promising tailored therapeutic approaches for advanced UC
Sarcoidosis-like reactions in metastatic renal cell carcinoma patients treated with immune-based combinations
No full textAim: The incidence of drug-induced sarcoidosis-like reactions (DISR) in patients treated with immune checkpoint inhibitors (ICIs) is rising. We determine the incidence and characteristics of DISR in a metastatic renal cell carcinoma (mRCC) population. Methods: We retrospectively reviewed clinico-radiological data of 83 mRCC patients treated at a single institution with immune-based combinations. Results: 15 patients received immune-doublet (ipilimumab-nivolumab), while 68 patients received other immune-based combinations. Two cases of DISR (2.4%) were evidenced, with enlargement of mediastinal lymph nodes that mimicked disease progression, thus requiring a biopsy which showed histological features of DISR. Conclusion: In our series of the incidence of DISR, radiological and clinical features, are in line with literature. DISR diagnosis is often only radiological, and its occurrence is possibly associated with a better outcome.The development of sarcoidosis-like lesions (DISR) is a rare event observed in cancer patients receiving immunotherapy. DISR occurrence represents a huge diagnostic issue, because its clinical and radiological features simulate disease progression. We present a series of 83 patients with kidney cancer receiving immunotherapy. During the therapy, two of these patients showed enlargement of chest lymph nodes that could be interpreted as disease progression. However, the microscopic analysis of these lymph nodes showed evidence of DISR. In conclusion, DISR should be adequately recognized to correctly manage patients who receive immunotherapy.The development of sarcoidosis-like lesions is a rare event in cancer patients receiving immunotherapy. The occurrence of DISR may mimic disease progression, and it represents a diagnostic issue, considering the growing number of resected RCC treated with adjuvant immunotherapy
MiT translocation renal cell carcinoma: A review of the literature from molecular characterization to clinical management
No full textMicrophthalmia Transcription Factor (MiT) family aberration-associated renal cell carcinoma is a rare disease, whose true prevalence is unknown, due to the need of molecular confirmation, commonly by Fluorescent In Situ Hybridization (FISH), for its diagnosis. In fact, this tumor is commonly misdiagnosed, often labeled as clear cell RCC, papillary RCC and chromophobe RCC. It is typically observed in young patients, and it can have indolent or aggressive behavior. In the case of aggressive behavior, the disease is rapidly progressive, showing little-to-no response to the drugs commonly used to treat the usual types of RCC. In this review, we focus on the biological and pathological features of this neoplasm, their impact on its clinical manifestations and we analyze the few experiences of treatment reported in the literature
IL-8 and its role as a potential biomarker of resistance to anti-angiogenic agents and immune checkpoint inhibitors in metastatic renal cell carcinoma
Full text linkThe therapeutic armamentarium of metastatic Renal Cell Carcinoma (mRCC) has consistently expanded in recent years, with the introduction of VEGF/VEGFR (Vascular Endothelial Growth Factor/Vascular Endothelial Growth Factor Receptor) inhibitors, mTOR (mammalian Target Of Rapamycin) inhibitors and Immune Checkpoint (IC) inhibitors. Currently, for the first-tline treatment of mRCC it is possible to choose between a VEGFR-TKI (VEGFR-Tyrosine Kinase Inhibitor) monotherapy, an ICI-ICI (Immune Checkpoint Inhibitor) combination and an ICI-VEGFRTKI combination. However, a consistent part of patients does not derive benefit from first-line therapy with ICIs; moreover, the use of combination regimens exposes patients to significant toxicities. Therefore, there is a critical need to develop prognostic and predictive biomarkers of response to VEGFR-TKIs and ICIs, and measurement of serum IL-8 is emerging as a potential candidate in this field. Recent retrospective analyses of large phase II and phase III trials found that elevated baseline serum IL-8 correlated with higher levels of tumor and circulating immunosuppressive myeloid cells, decreased T cell activation and poor response to treatment. These findings must be confirmed in prospective clinical trials; however, they provide evidence for a potential use of serum IL-8 as biomarker of resistance to VEGFR-TKIs and ICIs. Considering the amount of new agents and treatment regimens which are transforming the management of metastatic renal cell carcinoma, serum IL-8 could become a precious resource in tailoring the best therapy for each individual patient with the disease
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