Diagnosis Of Renal Cell Cancer Research Articles

Predictive value of SIRI and SII for metastases in RCC: a prospective clinical study

ObjectivesIn this prospective cross-sectional clinical study, we aimed to determine the efficiency of preoperative hematological markers namely SIRI (systemic inflammatory response index) and SII (systemic inflammatory index) for renal cell cancer to predict the possibility of postoperative metastases.MethodsIstanbul Education and Research Hospital, Clinic of Urology and Medical Oncology in the clinic between the dates of June 2022 to 2023 February, a diagnosis of renal cell cancer by surgical or medical oncology units imported into the treatment planning of 72 patients were included in the study. All cases with diagnoses of renal cell carcinoma were searched from hospital records. Patients with secondary malignancy, hematological or rheumatological disorders or ones with recent blood product transfusion or diagnoses of infection within the 1-month-time of diagnoses were excluded for data analyses. The data within complete blood counts (CBC) analyzed just before the time of renal biopsy or surgery were studied for SIRI and SII calculations. Twenty-two metastatic and 50 non-metastatic RCC patients were included. SIRI and SII values were compared among groups to seek change of values in case of metastasis and in non-metastatic patients a cut-off value were sought to indicate malignancy before pathological diagnosis.ResultsMean age of non-metastatic RCC patients were 60.12+/-11.55 years and metastatic RCC patients were 60.25+/-11.72. Histological sub-types of the RCC specimens were clear cell (72%), chromophobe cell (17%), papillary cell (7%) and others (4%). Median SIRI values for non-metastatic and metastatic groups were 1.26 and 2.1 (mean+/-S.D. 1.76 +/-1.9 and 3.12+/-4.22 respectively (p < 0.05). Median SII values for non-metastatic and metastatic groups were 566 and 1434 (mean+/-S.D. 870 +/-1019 and 1537+/-917) respectively (p < 0.001). AUC for detection of metastasis were 0.809 for SII and 0.737 for SIRI.ConclusionsSIRI and SII indexes seem to show a moderate efficiency to show metastases in RCC.

TROG 15.03/ANZUP International Multicenter Phase II Trial of Focal Ablative STereotactic RAdiotherapy for Cancers of the Kidney (FASTRACK II)

Stereotactic body radiotherapy (SBRT) is an emerging non-invasive alternative for primary renal cell cancer (RCC) in patients unsuitable for surgery. The objective of the FASTRACK II clinical trial was to investigate the efficacy of SBRT for primary RCC. This non-randomized, intergroup multi-institutional phase II study was activated in 7 Australian centers and 1 Dutch center, through the Trans Tasman Radiation Oncology Group (TROG) and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). Eligible patients had biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, ECOG performance ≤2 and were medically inoperable, high risk or declined surgery. For tumors ≤4 cm a single fraction of 26 Gy was prescribed, for tumors > 4 cm, 42 Gy in three fractions was prescribed. The primary outcome of the study was to estimate the efficacy of SBRT for primary RCC, defined as local control based on RECIST criteria. The study was powered assuming that 1-year local control would be 90%, with the null hypothesis of ≤80% considered undesirable and not worthy of proceeding to a future randomized controlled trial. Between July 2016 and February 2020, 70 patients were enrolled with a median follow-up of 42 months. Median age was 77 years. Forty-nine patients were male (70%), median BMI was 32 and median Charlson comorbidity score was 7. The median [IQR] RENAL complexity score was 8 [7-10]. Biopsy confirmation was 100%. Twenty-three patients (33%) had T1a disease. The median (interquartile range [IQR]) tumor size was 4.6cm [3.7-5.5]; it was 3.3cm [3.0-3.6] in those receiving single fraction (n = 23), and 5.3cm [4.6-6.0] in those receiving 3-fraction SBRT (n = 47). During real-time pre-treatment quality assurance review, 10 cases (14.3%) required resubmission for protocol deviation, 2119 variables were assessed at final review, and final protocol compliance was 99.3%. Seven (10%) patients experienced grade 3 treatment-related adverse events, with no grade 4 or 5 events observed. Eleven (16%) patients reported no adverse events. Local control was 100% throughout the lifetime of the trial (p<0.001). Cancer-specific survival was also 100% throughout the lifetime of the trial. Freedom from distant failure (95% CIs) at 1 and 3 years was 99% (90-100%). Overall survival (95% CIs) at 1 and 3 years was 99% (90-100%) and 82% (70-89%), respectively. Baseline mean eGFR (95% CI) was 61.1 mLs/min (56.6; 65.6) and reduced by -10.8 mLs/min (-13.0; -8.6) by 1-year, by -14.6 mLs/min (-17.0; -12.2) by 2-years and plateaued thereafter. In the first multicenter prospective trial of a non-surgical primary RCC cohort, enrolling mostly T1b+ disease, SBRT was an effective treatment strategy with no observed local failures. We observed an acceptable side effect profile and renal function after SBRT. These outcomes support the design of a future randomized clinical trial of SBRT versus surgery for primary RCC. The trial was registered with ID: NCT02613819.

Diagnostic liquid biopsy biomarkers in renal cell cancer.

The clinical presentation of renal cell cancer (RCC) is shifting towards incidental and early detection, creating new challenges in RCC diagnosis. Overtreatment might be reduced with the development of new diagnostic biomarkers to distinguish benign from malignant small renal masses (SRMs). Differently from tissue biopsies, liquid biopsies are obtained from a patient's blood or urine and, therefore, are minimally invasive and suitable for longitudinal monitoring. The most promising types of liquid biopsy biomarkers for RCC diagnosis are circulating tumour cells, extracellular vesicles (EVs) and cell-free DNA. Circulating tumour cell assays have the highest specificity, with low processing time and costs. However, the biological characteristics and low sensitivity limit the use of these markers in SRM diagnostics. Cell-free DNA might complement the diagnosis of high-volume RCC, but the potential for clinical application in SRMs is limited. EVs have the highest biological abundance and the highest sensitivity in identifying low-volume disease; moreover, the molecular characteristics of these markers make EVs suitable for multiple analytical applications. Thus, currently, EV assays have the greatest potential for diagnostic application in RCC (including identification of SRMs). All these liquid biomarkers have potential in clinical practice, pending validation studies. Biomarker implementation will be needed to alsoimprove characterization of RCC subtypes. Last, diagnostic biomarkers might be extended to prognostic or predictive applications.

Characteristics and outcomes of 795 patients with renal cell cancer following hospitalization for acute myocardial infarction.

e16516 Background: Renal cell cancer (RCC), as with many cancers, is associated with a hypercoagulable state as well as the potential risk of anemia that can lead to various cardio/cerebrovascular complications. Some of the treatments used in RCC like vascular endothelial growth factor (VEGF) inhibitors increase the thrombotic risk. Thus, the management of RCC patients following an episode of Acute Myocardial Infarction (AMI) can be more complex than that of the general population. We, therefore, conducted an in-depth analysis to study the characteristics and outcomes of AMI among RCC patients in the United States. Methods: We used the 2019 National Inpatient Sample (NIS), a yearly set of hospitalization records from the United States. Patients with a primary diagnosis of AMI and a diagnosis of RCC were identified. We excluded all patients below the age of 18 and those with other malignancies. Multiple patient characteristics were compared via Chi-Square tests. We also compared the odds of requiring Coronary artery bypass graft surgery (CABG) and Percutaneous coronary intervention (PCI) among the two groups. The overall mortality rate and adjusted odds ratios were estimated. Results: Our study found 633410 cases of AMI among adults in the United States in 2019. Among them, 795 (0.1%) had a diagnosis of RCC. A higher number of RCC patients were Male (75.5% vs. 62.7%, p &lt; 0.01), racially classified as White (77.1% vs. 73.0%, p &lt; 0.01), aged 60 or more (88.7% vs. 69.8%, p &lt; 0.01), covered by Medicare (72.3% vs. 56.1%, p &lt; 0.01), had hypertension (66.7% vs. 82.7%, p &lt; 0.01), were diabetics (45.9% vs. 41.4%, p &lt; 0.01) or had anemia (42.1% vs. 22.1%, p &lt; 0.01). A lower percentage of RCC patients underwent various procedures following their AMI, as only 6.3% underwent CABG (vs. 7.5% in the non-RCC group), and 27.6% (vs. 45.8% in the non-RCC group) underwent PCI. Patients with RCC were also older (71.62 years vs. 66.64 years, p &lt; 0.01), had a longer hospitalization (5.51 days vs.4.34 days, p &lt; 0.01), which was also associated with a more expensive mean hospital charge ($114572.98 vs. $106241.24). Unfortunately, we also found that the presence of RCC among AMI patients was also linked with a higher odds ratio of mortality (7.5% vs. 4.4%, aOR 1.643, 95% CI 1.249- 2.160, p &lt; 0.01). Conclusions: Our study confirms various differences in patient characteristics among AMI cases with and without RCC. While fewer RCC patients underwent procedures such as CABG or PCI, they experienced a less favorable outcome, including a longer and more costly stay and higher odds of in-hospital death. It is thus vital to screen RCC patients for potential risk factors for AMI, promote primary and secondary prevention measures, and improve hospitalization protocols to identify potential complications.

PSUN266 A Case of Ipilimumab Induced New-Onset type1 Diabetes Mellitus in a Patient With Renal Cell Carcinoma.

Abstract A 50-year-old female with a recent diagnosis of Renal cell cancer (RCC) with hepatic metastasis and hypothyroidism was referred to the clinic for management of Diabetes Mellitus (DM). The patient was diagnosed with RCC in 2017 and was treated with immunotherapy Ipilimumab for two years. No family history of Diabetes Mellitus and denies history of corticosteroid usage. No previous episodes of Diabetic Ketoacidosis. She was diagnosed with GAD65 negative type 1 Diabetes Mellitus one year after starting Ipilimumab and was managed on a basal-bolus insulin regimen. She was on levothyroxine for the last two years for hypothyroidism and remained clinically and biochemically euthyroid. She attained menopause 10years ago. Physical examination is unremarkable with normal monofilament tests. Initial labs showed a Complete blood count within normal. The comprehensive metabolic panel showed Glucose 104mg/dl (74-106 mg/dl), Potassium 4.2 mmol/L (3.5 -5.0 mmol/L), Bicarb 25mmol/L (21-33 mmol/L).Hb A1C 6.5%, C-peptide 0.3ng/ml(0.8-3.85ng/ml), GAD 65, ia2 and insulin antibodies negative,TSH 3.420uIU/L (0.5-4.5 uIU/L), Free T4 1.16ng/dl (0.79-2.35 ng/dL), Total T3 78 (71-180ng/dl),Thyroid Peroxidase Antibodies(TPO) negative.Pituitary hormone analysis ruled out possible central, which showed FSH &amp;gt;200 IU/L, LH 78.6 IU/L, ACTH 31pg/mL(10-60pg/mL), Serum AM cortisol within normal. Her DM1 was well controlled with an insulin pump with DEXCOM for continuous glucose monitoring, requiring a total daily dose of around 15-20 units/day. The patient currently remains asymptomatic and will be followed in the clinic with labs. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Diagnosis of urogenital cancer combining deep learning algorithms and surface-enhanced Raman spectroscopy based on small extracellular vesicles

PurposeTo identify and compare the capacities of serum and serum-derived small extracellular vesicles (EV) in diagnosis of common urogenital cancer combining Surface-enhanced Raman spectroscopy (SERS) and Convolutional Neural Networks (CNN). Materials and methodsWe collected serum samples from 32 patients with prostate cancer (PCa), 33 patients with renal cell cancer (RCC) and 30 patients with bladder cancer (BCa) as well as 35 healthy control (HC), which were thereafter used to enrich extracellular vesicles by ultracentrifuge. Label-free SERS was utilized to collect Raman spectra from serum and matched EV samples. We constructed CNN models to process SERS data for classification of malignant patients and healthy controls (HCs). ResultsWe collected 650 and 1206 spectra from serum and serum-derived EV, respectively. CNN models of EV spectra revealed high testing accuracies of 79.3%, 78.7% and 74.2% in diagnosis of PCa, RCC and BCa, respectively. In comparison, serum SERS-based CNN model had testing accuracies of 73.0%, 71.1%, 69.2% in PCa, RCC and BCa, respectively. Moreover, CNN models based on EV SERS data show significantly higher diagnostic capacities than matched serum CNN models with the area under curve (AUC) of 0.80, 0.88 and 0.74 in diagnosis of PCa, RCC and BCa, respectively. ConclusionDeep learning-based SERS analysis of EV has great potentials in diagnosis of urologic cancer outperforming serum SERS analysis, providing a novel tool in cancer screening.

Window-of-opportunity clinical trial platform for evaluation of novel treatment strategies in renal cell cancer (WIRE).

TPS406 Background: Renal cell cancer (RCC) is the 7th commonest cancer in the UK. The WIRE trial ‘exploits’ a window-of-opportunity between clear cell RCC diagnosis and nephrectomy to use vascular endothelial growth factor tyrosine kinase inhibitors, PARP inhibitors, and immune checkpoint inhibitor therapies in isolation and in combination. WIRE aims to provide biological proof-of-mechanism of these therapies, and build on encouraging pre-clinical evidence of DNA damage response inhibition to be an effective future therapeutic strategy in RCC. Methods: WIRE is a phase II, multi-IMP, multi-arm, non-randomised clinical trial featuring a Bayesian adaptive design with five treatment arms, and three recruitment stages per arm. The treatment groups: cediranib, cediranib and olaparib, olaparib, durvalumab, and durvalumab and olaparib form the initial set of therapy options with the opportunity for additional treatments to be deployed on this platform-trial in future. The primary endpoint for the first three arms is tumour capillary permeability, measured using multiparametric MRI, defined as a 30% reduction in Ktrans compared to pre-treatment. Whereas in the remaining two arms the primary endpoint is changed to intra-tumoural CD8 positive T cells, defined as an increase of 30% cell count compared to pre-treatment. Up to 76 evaluable participants will be recruited. Monotherapy arms will recruit a maximum of 12 participants each, whereas a maximum of 20 participants will be recruited into each dual-therapy arm. Participants are assigned to the current recruiting arm for treatment lasting between 14 and 28 days before proceeding with standard-of-care nephrectomy. Participants will undergo a biopsy and imaging before and after treatment for primary endpoint analysis, alongside blood and urine collections for translational endpoints. A final two follow-up visits are scheduled before concluding the trial pathway. Rapid interim analysis will follow at the end of a recruitment stage to determine whether to cease recruitment to the current treatment arm due to biological response, or due to futility – defined as lacking in promising evidence for proof of mechanism. Alternatively, if more data is required, recruitment will continue within the same treatment arm until the next interim analysis, where endpoints are re-examined. This highly-efficient design accelerates the exploration of multiple therapies with a strong emphasis on determining early proof-of-mechanism. Promising therapies can then be taken forward to later phase trials in RCC with greater confidence. Clinical trial information: NCT03741426.

P-EUS01 Pancreatic metastases from Renal Cell Cancer; endosonographic features and outcomes of a rare clinical entity

Abstract Background The pancreas is a rare site for metastatic deposits in the absence of disseminated metastatic disease. They can be difficult to differentiate from primary pancreatic malignancy based on the clinical history and radiological features alone. Renal cell cancer (RCC) is the most common source. We describe their endosonographic characteristics and clinical outcomes. Methods Patients undergoing EUS- FNB with a positive diagnosis of pancreatic metastatic disease from RCC from 2017 to 2019 were retrospectively identified. Recorded variables included patient demographics, endosonographic features and patient outcomes. Results Five patients were identified. Mean age was 63 (range 53-72 years old). Mean time from diagnosis of the primary RCC to diagnosis of pancreatic metastasis was 12.75 years (range 6-18 years). All had resection of the primary lesion. Mean diameter on EUS was 37.80mm (range 15mm to 100mm). The lesions were homogenous, well-circumscribed, hypoechoic and hypervascular. Tissue acquisition was performed using a 22G FNB needle. Two underwent surgical resection of the metastasis, one of which had recurrence at the surgical bed after 26 months. One had disseminated malignancy at the time of diagnosis. One passed away prior to surgical resection. Conclusions Pancreatic metastasis from renal cell cancer have characteristic endosonographic features and can present many years after initial diagnosis and resection. EUS-FNB has a central role in confirming this diagnosis.

Gastrointestinal Metastases From Primary Renal Cell Cancer: A Single Center Review.

Introduction: Digestive metastases (DMs) from renal cell cancer (RCC) are rare. Over the past decade, the overall survival of metastatic RCC (mRCC) has been improved by tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors. The main objective of this study was to assess the incidence of metastases of the digestive tract in this new field of treatment. The secondary objectives were to evaluate the clinical characteristics, prognosis, treatments used for DMs, and median time between the diagnosis of RCC or mRCC and DMs.Materials and Methods: A retrospective analysis of data collected from all patients with mRCC between 2007 (the time of TKI was a standard of care) and 2019 was carried out at the Paoli-Calmettes Institute (Marseille, France). Computer research software using artificial intelligence (ConSoRe®) was used to identify patients and assess their characteristics.Results: Between January 2007 and December 2019, 11 out of 660 (1.6%) mRCC patients had metastases of the gastrointestinal tract. The median age was 62 years. Of the 11 patients, 81.8% experienced digestive bleeding or anemia. Only 2 patients were asymptomatic. The metastases were mainly duodenal (50%) and gastric (41.6%). The median time from cancer diagnosis and from metastatic disease to gastrointestinal metastasis was 4.3 years (3 months−19.2 years) and 2.25 years (0 days−10.2 years), respectively. Local treatment was performed in 38.5% of cases by endoscopy (60%), surgery (20%) and radiotherapy (40%) with success rates of 33, 100, and 50%, respectively. Etiological treatment was modified following the discovery of DM in 84.6% of the cases. The median survival was 1 year from the diagnosis of DM (13 days−9.4 years). Two patients were still alive 2.9 and 9.4 years after the diagnosis of DM.Conclusion: This is the largest monocentric retrospective analysis of DM in patients with RCC. It seems to be a rare and late event in the course of the disease. Local treatment combined with systemic treatment could improve survival. In the context of prolonged survival with the new based immunotherapy treatments in mRCC, we suggest that unexplained anemia or persistent digestive symptoms could be explored by endoscopy.

Differentiating renal pelvic cancer from renal cell carcinoma with 18-fluorodeoxyglucose positron emission tomography-computed tomography.

The differential diagnosis of pelvis renalis cancer (PRC) from renal cell cancer (RCC) is difficult. Because of that, in this study, we compared the standardized uptake value (SUV) with positron emission tomography-computed tomography (PET-CT) of the RCC and PRC. Twenty-one patients (12 males, 9 females; age range: 33-74 years; mean age ± standard deviation [SD]: 57.14 ± 17.6) with suspected primary renal cell cancer as Group 1 and 8 patients (6 male, 2 female; age range, 61-81; mean age ± SD, 71.5 ± 5.65) with suspected renal pelvis cancer as Group 2 detected by conventional imaging techniques (CT, magnetic resonance [MR] imaging, ultrasound, intravenous urogram, CT urography, MR urography) underwent fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT imaging between August 2010 and October 2012. Mean age is 57.14 (33-74) years in Group 1 and 71.5 (61-81) years in Group 2, respectively. The mean maximum SUV (SUVmax) value was 4.6 ± 2.1 in RCC group and 16.6 ± 6.9 in PRC group. At the 18-FDG PET/CT scanning, SUVmax value higher in patients with PRC than in the patients with RCC. It was statistically different (P < 0.001). We suggested that PET/CT can be used for the differential diagnosis of renal pelvis tumor and RCC. However, further studies with larger patient number are needed to confirm our suggestion. To clarify the mechanisms of underlying these differences, molecular advanced molecular studies are needed.

Venous Thromboembolism Incidence and Impact on Survival in Patients with Brain Metastases

Background: Patients with brain metastases are considered especially high risk for venous thromboembolism (VTE). The incidence of VTE following a diagnosis of brain metastases and the impact of VTE on overall survival among patients with brain metastases have not been well characterized. Methods: Using the linked Surveillance, Epidemiology and End Results (SEER) and Medicare databases between 2008-2015, we identified all patients ≥66 years with a primary diagnosis of lung, renal cell, breast cancer or melanoma and brain metastases (ICD-9-CM 198.3 present anytime in Medicare claims). Patients were required to have continuous Medicare part A and B enrollment from 12 months before and 12 months after diagnosis or until death. The primary outcome was incidence of VTE (deep vein thrombosis or pulmonary embolism or both) in the 12- months following a diagnosis of brain metastases. Patients with a VTE diagnosis prior to brain metastases were excluded. Incidence rates were calculated as VTE events per 100 patient years. Tumor specific multivariable Cox proportional hazards model adjusting for age, sex, race, time from primary cancer diagnosis to brain metastasis, comorbidities and VTE as a time varying covariate was used to assess the association of VTE and 12-month overall survival following a diagnosis of brain metastasis. Results: Among 154,918 individuals with a primary cancer diagnosis of interest, 21,623 (14.0%) had a brain metastasis diagnosis. Majority of patients with brain metastases had a primary diagnosis of lung cancer (N=19,141 (88.5%)), followed by melanoma (N=1,607 (7.4%)), renal cell cancer (N=576 (2.7%)) and breast cancer (299 (1.4%)). The baseline characteristics are highlighted in Table 1. Among these patients, VTE was diagnosed in 3,432 (15.9%). In the year following a diagnosis of brain metastasis, the incidence of VTE per 100 patient-years was highest among those with a diagnosis of renal cell cancer (19.4), followed by breast (16.3), lung (16.0) and melanoma (12.5). The median time to VTE from a diagnosis of brain metastasis is 1 month (IQR 0-3 months) and the cumulative incidence of VTE stratified by tumor type and accounting for the competing risk of death over 12 months is illustrated in Figure 1.The median overall survival following a diagnosis of brain metastasis was 2.7 months (95% CI 2.1-3.1 months). In a multivariable Cox proportional hazards model, a diagnosis of VTE following brain metastasis was associated with increased risk of death in patients with lung cancer (HR 1.23 (95% CI 1.18-1.28)), renal cell cancer (HR 1.36 (95% CI 1.06-1.75)) and melanoma (HR 1.32 (95% CI 1.12-1.55)), but not breast cancer (HR 1.16 (95% CI 0.80-1.69)). Conclusions: This large real-world retrospective cohort analysis demonstrates and quantifies the high tumor specific incidences of VTE among individuals with brain metastases. The VTE incidence rates observed are comparable to metastatic pancreatic cancer and highest in the initial 3 months following a diagnosis of brain metastasis. Furthermore, a diagnosis of VTE is associated with a reduced 12-month overall survival in this patient population. We are mindful to highlight the inherent limitations of claims data in identifying clinical events such as brain metastases and VTE, thus possible misclassification and selection biases should be considered when interpreting these findings. However, considering the complexity of managing VTE in this high-risk patient population and the high thrombotic burden demonstrated, these findings warrant further prospective validation. Disclosures Key: Takeda: Research Funding; Grifols: Research Funding; Uniqure: Consultancy; Novo Nordisk: Other: Chair of Grants Committee. Lund:GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company; AbbVie: Research Funding.

The Impact Of Succinate Dehydrogenase Gene (SDH) Mutations In Renal Cell Carcinoma (RCC): A Systematic Review.

IntroductionRenal cell cancer (RCC) syndrome is linked to Krebs cycle compartments and their coding genes' alterations like succinate dehydrogenase genes (SDHx). Here we present a systematic review of the SDH genes’ mutations and their impact on both RCC diagnosis and prognosis.MethodsThis systematic review includes any study in which tissue samples of RCC are considered in correlation with the SDHx mutations, microsatellite instability (MSI), and protein expression. For this purpose, a systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted and finally 5384 articles were recruited. All studies' content was checked to find the related ones which were 145 articles, which with data extraction were limited to nineteen.ResultsThe final selected nineteen studies investigating the SDHx role in RCC tumor genesis were included, among which fifteen were mutation analysis, three were just SDHx protein expression, and two were MSI and mutation analysis studies. A total of 432 RCC patients were reported by SDH mutations, and 64 patients with MSI and SDH expression change were reported in 514 surgically resected renal epithelial tumors. The most common mutation was the single nucleotide variant rs772551056 (c.137G>A) of SDHB. For SDHC, c.380A>G presented in 48 RCC patients, and for SDHA a novel germline mutation c.2T>C: p.M1T in an occasional case of gastrointestinal stromal tumor intricate with RCC.ConclusionRCC as an aggressive type of kidney cancer needs some biomarkers to be diagnosed exactly. It was shown recently that the succinate dehydrogenase gene variations can provide this diagnostic and prognostic biomarker. For this purpose, SDHB rs772551056 associated with its protein expression alterations can be taken into account. It is possible that a novel mutation of SDHA (c.2T>C: p.M1T) can provide evidence of GIST associated with RCC as well.

Immunotherapy-induced endocrinopathies: A multi-center experience.

e14251 Background: Endocrinopathies account for approximately 10% of immune-related adverse events.1 Methods: We carried out a retrospective review of 100 patients who received immunotherapy at two hospital sites between 2012 and 2019. Our aim was to ascertain the overall rate of immunotherapy-induced endocrinopathy and assess the impact of immunotherapy on pre-existing diabetes and thyroid dysfunction. Results: 28 out of 100 patients had pre-existing thyroid dysfunction, 36% of these experienced further thyroid dysfunction on immunotherapy. 41 patients had a diagnosis of renal cell cancer, and had treatment with a tyrosine kinase inhibitor prior to treatment with Nivolumab. Eighteen of these patients had a pre-existing thyroid dysfunction. Of these 18 patients, 44% experienced further thyroid dysfunction following immunotherapy. Of the 23 patients who received a tyrosine kinase inhibitor, who had no pre-existing thyroid dysfunction, 17% developed thyroid dysfunction on Nivolumab. 15% of patients without a pre-existing thyroid dysfunction developed a new thyroid dysfunction while on immunotherapy. Seven patients had diabetes mellitus prior to commencing immunotherapy, diabetes control did not disimprove during treatment. One case of diabetes was diagnosed on immunotherapy(1%). One case of adrenalitis(1%) and two cases of hypophysitis(2%) were diagnosed on immunotherapy. The adrenalitis occurred on Nivolumab (1.35%). Both cases of hypophysitis occurred on ipililumab(14%). The overall rate of new immunotherapy-induced endocrinopathy was 15%. Conclusions: The rates of endocrinopathy observed de novo are in line with published rates.1,2,3,4 In this small study, an increased rate of thyroid dysfunction was observed in patients with pre-existing thyroid dysfunction. Prior treatment with a tyrosine kinase inhibitor did not cause an increase in the rate of thyroid dysfunction. Ipilimumab was observed to be a risk factor for development of hypophysitis. [Table: see text]

Right atrial mass resembling ball valve thrombus in a patient with renal cell cancer

A middle-aged woman was admitted with progressive shortness of breath for 3 weeks. Clinical exam was unremarkable and further work-up was pursued. CT chest showed a cardiac mass and multiple...

TROG 15.03 phase II clinical trial of Focal Ablative STereotactic Radiosurgery for Cancers of the Kidney - FASTRACK II

BackgroundStereotactic ablative body radiotherapy (SABR) is a non-invasive alternative to surgery to control primary renal cell cancer (RCC) in patients that are medically inoperable or at high-risk of post-surgical dialysis. The objective of the FASTRACK II clinical trial is to investigate the efficacy of SABR for primary RCC.MethodsFASTRACK II is a single arm, multi-institutional phase II study. Seventy patients will be recruited over 3 years and followed for a total of 5 years. Eligible patients must have a biopsy confirmed diagnosis of primary RCC with a single lesion within a kidney, have ECOG performance ≤2 and be medically inoperable, high risk or decline surgery. Radiotherapy treatment planning is undertaken using four dimensional CT scanning to incorporate the impact of respiratory motion. Treatment must be delivered using a conformal or intensity modulated technique including IMRT, VMAT, Cyberknife or Tomotherapy. The trial includes two alternate fractionation schedules based on tumour size: for tumours ≤4 cm in maximum diameter a single fraction of 26Gy is delivered; and for tumours > 4 cm in maximum diameter 42Gy in three fractions is delivered. The primary outcome of the study is to estimate the efficacy of SABR for primary RCC. Secondary objectives include estimating tolerability, characterising overall survival and cancer specific survival, estimating the distant failure rate, describing toxicity and renal function changes after SABR, and assessment of cost-effectiveness of SABR compared with current therapies.DiscussionThe present study design allows for multicentre prospective validation of the efficacy of SABR for primary RCC that has been observed from prior single institutional and retrospective series. The study also allows assessment of treatment related toxicity, overall survival, cancer specific survival, freedom from distant failure and renal function post therapy.Trial registrationClinicaltrials.govNCT02613819, registered Nov 25th 2015.

Перспективы использования раман-флуоресцентной спектроскопии в диагностике почечно-клеточного рака

Перспективы использования раман-флуоресцентной спектроскопии в диагностике почечно-клеточного рака

MicroRNA-1 and MicroRNA-21 Individually Regulate Cellular Growth of Non-malignant and Malignant Renal Cells.

Due to its poor prognosis, it is increasingly necessary to understand the biology of renal cell cancer (RCC). Therefore, we investigated the role of microRNAs miR-1 and miR-21 in the growth of RCC cells compared to that of non-malignant renal cells. Four malignant cell lines (Caki-1, 786-O, RCC4, A498) were examined regarding their cell growth, microRNA and telomerase expression, and were compared to non-malignant RC-124 renal cells. Inconsistencies appeared in the panel of RCC cells regarding antiproliferative and proliferative properties of miR-1 and miR-21, respectively. Notably, and most likely due to immortaliziation, non-malignant RC-124 cells exhibited telomerase expression and activity. miR-1 and miR-21 functionality in cancer progression, particularly in tumor growth, may be more dependent on the individual cellular context and may reflect RCC heterogeneity. Thus, both microRNAs, in combination with other stratifying biomarkers, may be useful in terms of RCC diagnosis, prognosis, or treatment response.

Prevalence and Characteristics of Patients with Suspected Inherited Renal Cell Cancer: Application of the ACMG/NSGC Genetic Referral Guidelines to Patient Cohorts.

Patients with suspected hereditary renal cell cancer (RCC) are under-referred for genetic evaluation. Characterizing the prevalence and characteristics of suspected inherited RCC is a crucial step toward advancing personalized, genetically-based cancer risk management for patients and their families. To evaluate the prevalence and characteristics of suspected inherited RCC syndromes based on consensus criteria, we performed a cross-sectional analysis of patients with a diagnosis of RCC in SEER (2001-2011, n=105,754) and in our institutional cancer registry (2004-2013, n=998). Consensus criteria for referral of patients with RCC for genetic evaluation from the American College of Medical Genetics and Genomics and National Society of Genetic Counselors (ACMG/NSGC) were applied to the two cohorts. The associations between meeting referral criteria with demographic characteristics were assessed with chi-square tests. Overall, 24.0% of the SEER cohort and 33.7% of our institutional cohort met ACMG/NSGC referral criteria for genetic counseling. While white patients more commonly met early onset clear cell RCC criteria, black patients met papillary RCC criteria at twice the rate of whites in both cohorts (p<0.0001). As many as 1 in 5 individuals with RCC meet referral criteria for genetic evaluation based on newly emerging guidelines, with differences in pathology noted by race. Prospective genetic testing studies utilizing emerging referral guidelines should help to refine the genetic spectrum of inherited kidney cancer. This study supports efforts to increase awareness of referral of patients with RCC for genetic counseling particularly among urologic providers.

Kidney cancer demographics and outcome data from 2013 at a tertiary cancer hospital in India.

The stage at diagnosis of renal cell cancer (RCC) in developed countries is lower due to increased utilization of routine health checkups by patients compared to developed countries. This study aims to determine the sociodemographic and clinical distribution of RCC in patients presenting to Tata Memorial Hospital (TMH). We performed a retrospective audit of all patients presenting to TMH with a diagnosis of RCC. Data were retrieved from our electronic medical record system from January 1, 2013 to December 31, 2013. The survival analysis was done by Kaplan-Meir analysis method of estimating survival. Log-rank test of comparison was applied to estimate the difference in the survival among the different stages of renal cancer. Of the 35,197 new registered patients at TMH, 338 were diagnosed with RCC. Most patients were in the 50-60 years age group, with 56.6 years being the median age at presentation. Among patients treated at TMH, 84 underwent surgery and tyrosine kinase inhibitor was given in 55 (16%) patients. The patients' characteristics, clinical characteristics of RCC, treatment modalities offered, and survival of patients treated for RCC are presented in this paper. In the absence of robust Indian data on RCC, this audit provides baseline information on epidemiology, stage at presentation, and outcomes of RCC at our center compared with the West.

Different Cytokine and Chemokine Expression Patterns in Malignant Compared to Those in Nonmalignant Renal Cells

Objective Cytokines and chemokines are widely involved in cancer cell progression and thus represent promising candidate factors for new biomarkers. Methods Four renal cell cancer (RCC) cell lines (Caki-1, 786-O, RCC4, and A498) and a nonmalignant renal cell line (RC-124) were examined with respect to their proliferation. The cytokine and chemokine expression pattern was examined by a DNA array (Human Cytokines & Chemokines RT2 Profiler PCR Array; Qiagen, Hilden, Germany), and expression profiles were compared. Results Caki-1 and 786-O cells exhibited significantly increased proliferation rates, whereas RCC4 and A498 cells demonstrated attenuated proliferation, compared to nonmalignant RC-124 cells. Expression analysis revealed 52 cytokines and chemokines primarily involved in proliferation and inflammation and differentially expressed not only in malignant and nonmalignant renal cells but also in the four RCC cell lines. Conclusion This is the first study examining the expression of 84 cytokines and chemokines in four RCC cell lines compared to that in a nonmalignant renal cell line. VEGFA, NODAL, and BMP6 correlated with RCC cell line proliferation and, thus, may represent putative clinical biomarkers for RCC progression as well as for RCC diagnosis and prognosis.