scholarly journals Evolving Patterns of Metastasis in Renal Cell Carcinoma

2021 ◽  
Vol 8 (4) ◽  
pp. 13-19
Author(s):  
Justin Lin ◽  
Yue Zhang ◽  
Wei Hou ◽  
Qian Qin ◽  
Matthew Galsky ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Bone Metastasis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Lung Metastases ◽  
High Rate ◽  
Treatment Modalities ◽  
Metastatic Patterns

Advance diagnostic and treatment modalities have improved outcomes for renal cell carcinoma (RCC) patients, but the prognosis for those with metastatic disease (mRCC) remains poor. As given metastatic distribution is critical in guiding treatment decisions for mRCC patients, we evaluated evolving metastatic patterns to assess if our current practice standards effectively address patient needs. A systematic literature review was performed to identify all publicly available prospective clinical trials in metastatic renal cell carcinoma (mRCC) from 1990 to 2018. A total of 16,899 mRCC patients from 127 qualified phase I–III clinical trials with metastatic site documentations were included for analysis for incidence of metastases to lung, liver, bone, and lymph nodes (LNs) over time. Studies were categorized into three treatment eras based on the timing of regulatory approval: Cytokine Era (1990-2004), vascular endothelial growth factor/tyrosine kinase inhibitor (TKI) Era (2005-2016), and immune checkpoint inhibitor/TKI Era (ICI-TKI, 2017-2018) and also classified as first-line only (FLO) or second-line and beyond (SLB). Overall, an increase in the incidence of bone and LNs metastases in FLO and SLB, and lung metastases in FLO, was seen over the three treatment eras. Generally, the burden of disease is higher in SLB when compared with FLO. Importantly, in the ICI-TKI era, the incidences of bone metastasis are 28% in FLO and 29% in SLB settings. The disease burden in patients with mRCC has increased steadily over the past three decades. Given the unexpectedly high rate of bone metastasis, routine dedicated bone imaging should be considered in all patients with mRCC.

Evolving patterns of metastatic renal cell carcinoma: A meta-analysis.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 563-563
Author(s):  
Justin Lin ◽  
William K. Oh ◽  
Bobby Chi-Hung Liaw ◽  
Matt D. Galsky ◽  
Che-Kai Tsao
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Bone Metastasis ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Temporal Trends ◽  
Treatment Modalities ◽  
Linear Regression Models ◽  
First Line

563 Background: Advances in diagnostic and treatment modalities have resulted in better outcomes in metastatic renal cell carcinoma (mRCC) patients. With new therapies extending survival, we hypothesize that pattern of metastatic disease has evolved over time. We assessed the pattern of metastases as reported in baseline characteristics of prospective clinical trial patients between 1990 and 2018. Methods: This study identified all phase I-III mRCC therapeutic clinical trials published between January 1990 and July 2018 in PubMed and ClinicalTrials.gov. Studies that included patients with other cancers or did not report metastases were excluded. Data was stratified to examine differences in three listed treatment eras for first-line therapy. Linear regression models were used to evaluate temporal trends and subcategorized as either First Line Only treatments (FLO) or Second-Line and Beyond (SLB). Results: 127 clinical trials encompassing 16534 subjects were identified. Between 1990 and 2018, rates of lymph node metastases in the FLO population increased significantly at 1.03% per year ( P < 0.05). The rate of lung and liver metastases in FLO showed a trend of increase at 0.48% and 0.04% per year, respectively, but decreased -0.73% and -0.15% per year in the SLB population. Moreover, rate of bone metastasis showed a trend of increase in both populations, particularly between the VEGF/TKI and Immunotherapy/TKI eras in the SLB population (18.89% to 29.19%). Conclusions: Notable changes were found in the pattern of metastasis in patients with mRCC. Increasing rate of bone metastasis may warrant dedicated bone imaging for routine staging in patients with mRCC. These evolving patterns may have important implications in treatment selection and prognosis in this patient population. [Table: see text]

Pazopanib-associated interstitial lung disease in a patient with renal cell carcinoma

2020 ◽  
Vol 13 (7) ◽  
pp. e235177 ◽  
Author(s):  
Yukinori Harada ◽  
Shintaro Kakimoto ◽  
Taro Shimizu
Keyword(s):  
Renal Cell Carcinoma ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Lung Metastases ◽  
Soft Tissue Sarcomas ◽  
Positive Pressure ◽  
Non Invasive

Pazopanib is a multi-targeted tyrosine kinase inhibitor, which is indicated for use in patients with advanced renal cell carcinoma or advanced soft-tissue sarcomas. Although rare, interstitial lung disease has been reported as among the adverse sequelae of pazopanib therapy. We report the case of a 75-year-old man who developed interstitial lung disease during treatment with pazopanib for renal cell carcinoma with multiple lung metastases. The patient presented with dry cough and new-onset fatigue 3 months after initiation of pazopanib. He had mild hypoxia with bilateral ground-glass opacities on chest CT. He was treated with antibiotics for presumptive pneumonia, but his respiratory status rapidly deteriorated, and he required non-invasive positive pressure ventilation. He recovered on discontinuation of pazopanib and systemic steroids. Clinicians should recognise that interstitial lung disease can occur in patients who are undergoing treatment with pazopanib.

A phase II and biomarker study (MET111644) of the dual Met/VEGFR-2 inhibitor foretinib in patients with sporadic and hereditary papillary renal cell carcinoma: Final efficacy, safety, and PD results.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Toni K. Choueiri ◽  
Ulka N. Vaishampayan ◽  
Jonathan E. Rosenberg ◽  
Theodore Logan ◽  
Andrea Lynne Harzstark ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Plasma Proteins ◽  
Kinase Inhibitor ◽  
Single Agent ◽  
Progression Free Survival ◽  
Papillary Renal Cell Carcinoma ◽  
High Rate ◽  
Dosing Regimens

355 Background: Foretinib is an oral multi-kinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors. Activating mutations and/or amplifications in MET have been described in patients (pts) with papillary renal cell carcinoma (PRC). The aim of this study was to evaluate the efficacy and safety of 2 dosing regimens of single agent foretinib bisphosphate (foretinib) in pts with PRC and to explore modulation of plasma proteins indicative of target inhibition. Methods: Pts were enrolled in 2 cohorts with different dosing schedules of foretinib: 240 mg/day on days 1–5 of every 14 days (intermittent arm) or 80 mg/day (daily dosing arm). The primary endpoint was overall response rate (ORR) targeting an ORR of at least 25%. Pts were stratified based on status of MET pathway activation (germline or somatic MET mutation, MET [7q31] amplification, chromosome 7 gain or none of these). Plasma markers reflecting potential target effects of MET and VEGFR inhibition were also analyzed. Results: Overall, 74 pts were enrolled with 37 in each dosing cohort. ORR was 13.5%, progression-free survival 9.3 months, 1 year overall survival (OS) was 70% and median OS was not reached. The median duration of response was 18.5 months. Of 68 pts with adequate tumor assessment data available, 50 experienced some reduction in the sum of the longest tumor diameters (SLD) ranging from −2% to −75%. The most frequent grade 3/4 adverse events related to foretinib were fatigue (6.8%), hypertension (50%), and diarrhea (6.8%). A high rate of non-fatal pulmonary embolism was observed (11%). There were no significant differences in efficacy or safety between the two cohorts. In both arms, plasma sMET and VEGF increased and sVEGFR2 decreased after 2 cycles indicating target inhibition, but these changes were not associated with response or PFS. Outcomes based on molecular characterization are presented separately at this meeting. Conclusions: In the largest clinical trial devoted to papillary RCC, foretinib demonstrated anti-tumor activity in patients with PRC, modulation of several target indicator plasma proteins, and a manageable toxicity profile.

Rare case of clear cell renal cell carcinoma presenting as a unilateral tonsil lesion

2020 ◽  
Vol 13 (12) ◽  
pp. e237941
Author(s):  
Shawn David Ellis ◽  
Alison Meikle ◽  
Wassim Al-Salti ◽  
Georges Sinclair
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Lung Metastases ◽  
Cell Cancer ◽  
Rare Presentation ◽  
Cell Renal Cell Carcinoma ◽  
History Of ◽  
Diagnosis Of Cancer

A 70-year-old man presented with gradually worsening throat discomfort. He had no prior diagnosis of cancer and no travel history of note. Examination revealed a right-sided painless neck lump. He underwent an MRI of the neck, revealing a gadolinium-enhancing tonsillar mass and two brain lesions. Biopsy of the tonsil lesion was in keeping with an epithelial neoplasm, suggesting metastatic renal cell carcinoma. This was confirmed following a staging CT, which revealed a left renal mass and lung metastases. Due to his brain metastases, the patient has been started on the tyrosine kinase inhibitor cabozantinib. A brief discussion on the diagnostic evaluation of a tonsil mass as a rare presentation of renal cell cancer follows this report.

How Targeted Therapy Influence Renal Surgery for Renal Cell Carcinoma

2020 ◽  
Vol 21 (15) ◽  
pp. 1550-1557
Author(s):  
Francesco Greco ◽  
Michele Marchioni ◽  
Francesco Esperto ◽  
Rocco Papalia ◽  
Luigi Schips ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Systemic Treatment ◽  
Target Therapy ◽  
Tumor Resection ◽  
Tumor Diameter

Between the end of 2005 and the beginning of 2006, several new target therapies have been introduced for the treatment of renal cell carcinoma. In this review, we aimed to explore and summarize the main findings of the use of systemic treatment and its effect on surgery in patients with renal cell carcinoma. We identified three different settings: neoadjuvant and adjuvant settings as well as the association of systemic therapy with surgery in the metastatic renal cell carcinoma patients. Neoadjuvant target therapy with tyrosine kinase inhibitor may facilitate the tumor resection and reduce the overall tumor diameter and its complexity. However, most of the evidence is from small phase I or II clinical trials and results are often conflicting without determining a relevant change in the main parameters investigated, such as tumor complexity. In the adjuvant setting, results from pivotal trials investigating the use of tyrosine kinase inhibitors for patients with non-metastatic RCC treated with surgery discourage this practice. Indeed, most of the evidence from single clinical trials and pooled results from meta-analysis failed to find a survival advantage with the use of adjuvant systemic treatment. To date, an improvement of clinical outcomes after systemic targeted therapies could be only found in the setting of cytoreductive nephrectomy. However, the CARMENA and SURTIME trials recently confirmed the evidence against a surgical treatment in patients with mRCC and poor prognosis. In the near future, significant changes may be introduced by the use of immunotherapies.

scholarly journals Synchronous Primary Renal Cell Carcinoma and Pancreatic Ductal Adenocarcinoma: Case Report and Literature Review

2017 ◽  
Vol 10 (3) ◽  
pp. 1050-1056 ◽  
Author(s):  
Tarik Mahfoud ◽  
Rachid Tanz ◽  
Mohamed Réda Khmamouche ◽  
Mohamed Allaoui ◽  
Rhizlane Belbaraka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastasis ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Cell Carcinoma ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
The Body ◽  
Ductal Adenocarcinoma

Synchronous primary cancers involving the pancreas and kidney are extremely rare and poorly documented. We report the first case of this association treated with chemotherapy and tyrosine kinase inhibitor. A 70-year-old woman presented with a 2-month history of epigastric pain with weight loss of 12 kg. Two weeks previously, she had presented with jaundice and pelvic pain. A computed tomography (CT) scan of the body revealed the presence of an irregular mass in the body of the pancreas, encasing the celiac trunk, with dilatation of the biliary tract. CT also revealed a heterogeneously right renal mass with bone metastasis in the left acetabular cup and the left iliac wing. A biliary metallic prosthesis was performed with a pancreatic mass biopsy. Histology revealed a moderately differentiated pancreatic ductal adenocarcinoma. Another biopsy was performed in the right iliac wing. Pathological examination with immunohistochemistry confirmed the diagnosis of bone metastasis from clear cell renal cell carcinoma. The patient was treated with a combination of gemcitabine, sunitinib, and denosumab. She had a stabilization disease and a prolonged progression-free survival of 9 months. Side effects were manageable and included grade 2 fatigue and grade 2 hypertension. The patient died at 13 months from diagnosis after disease progression. This report suggests that the appropriate treatment for this association in metastatic or unresectable disease is chemotherapy for pancreatic cancer and tyrosine kinase inhibitor for kidney cancer. We also review the appropriate literature concerning that association.

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