Metastatic Papillary Renal Cell Carcinoma Research Articles

Pure Metastatic Papillary Renal Cell Carcinoma Without Renal Mass: A Case Report and Literature Review

Renal cell carcinoma (RCC) is the most common solid lesion in the kidney and accounts for approximately 90% of all kidney malignancies. Metastasis usually occurs a few years after the diagnosis of RCC, but metastases can be seen at first presentation in some patients. Pure metastasis of RCC without kidney lesions is an extremely rare seen entity. Herein, we aimed to present a pure metastatic RCC (mRCC) in several lymph nodes without a kidney mass. A 41-year-old male was diagnosed with multiple lymphadenopathies based on imaging conducted after a work accident. No other lesion was detected. An excisional biopsy was performed on the supraclavicular lymph node. Histopathological examination of sample revealed a Type 2 papillary RCC metastasis. No primary lesion was observed in both kidneys in CT/MRI imaging. As a result, the patient was diagnosed as a pure metastatic papillary RCC and sunitinib treatment was started. After the treatment, metastatic lesions regressed, however, patient died due to COVID-19. In the literature, mRCC of unknown primary represents an aggressive metastatic malignancy and can be considered a poor prognostic factor in itself. However, in some cases as such in our patient, appropriate treatment could be beneficial in terms of metastatic regression. Pure metastatic RCC has been reported with only case reports and series. The treatment and prognosis in these patients are heterogeneous.

Lenvatinib and pembrolizumab in patients with metastatic papillary renal cell carcinoma: A phase 2 pilot study.

109 Background: Traditionally, metastatic papillary renal cell carcinoma (papillary mRCC) has been treated with tyrosine kinase inhibitors, resulting in a 23% objective response rate and a progression-free survival of 9 months (SWOG 1500 trial). Combinations of immunotargeted therapy have shown improved outcomes in clear-cell mRCC. This prospective pilot study aimed to evaluate the preliminary efficacy of combining lenvatinib with pembrolizumab in patients with papillary mRCC. Methods: At study entry in August 2021, patients with papillary mRCC types 1 or 2, multiple measurable lesions per RECIST 1.1 criteria, and no prior therapy for advanced disease were included. The primary endpoint was the objective response rate. The study employed Simon's two-stage design (Simon, 1989) to test the null hypothesis that the true response rate is 23% against a one-sided alternative. In the first stage, 5 patients were enrolled. If there were 1 or fewer responses among these initial 5 patients, the study would be halted. The null hypothesis would be rejected if 6 or more responses were observed in the entire cohort of 12 patients. This design yields a type I error rate of 0.05 and power of 0.8 when the true response rate is 63%. Results: As planned, 5 patients were enrolled in the stage 1. The median age was 57.4 years. Among them, 4 patients were diagnosed with papillary RCC type 2, and 3 patients had an unresected primary tumor. Additionally, 1 patient presented with brain metastases. The objective response rate was 100%, of which there was 1 complete and 4 partial responses. As of the last follow-up, the status of patients on therapy was as follows: i) three patients remained on therapy for more than 12 months; ii) one patient experienced disease progression after 14.3 months of treatment; iii) one patient who initially had an ongoing response developed grade 3 uncontrolled diarrhea after 5.5 months from the start of therapy. Despite the positive outcomes observed in stage 1 of the study, the enrollment was stopped. This decision was influenced by emerging results from the large phase 2 trial KEYNOTE-B61, as reported by Chung-Han Lee et al. (ASCO 2023). Conclusions: All patients responded to lenvatinib and pembrolizumab therapy. These results suggest promising efficacy of the combination in metastatic papillary RCC. Clinical trial information: KCRB01012021 .

Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma.

To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review. Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review. Amongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR. The PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines. In this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial.

PD-L1 expression and its prognostic value in metastatic papillary renal cell carcinoma: Results from a GETUG multicenter retrospective cohort

IntroductionPapillary renal cell carcinoma (pRCC) is a rare and aggressive cancer with no specifically established therapeutic strategy in the metastatic setting. Combinations of tyrosine kinase and immune checkpoint inhibitors (ICI) are a promising option. We aimed to study the immune landscape of metastatic pRCC, and its interactions with angiogenesis pathways, to search for potential therapeutic targets. MethodsThe expression of immune markers (PD-L1, PD-1, PD-L2, LAG-3) and angiogenic pathways (CAIX, c-MET), was analyzed by immunohistochemistry on 68 metastatic pRCC retrieved from a retrospective multicenter GETUG cohort.Our primary endpoint was to estimate the prevalence of PD-L1 expression and its prognostic impact in metastatic pRCC. Secondary endpoints included the evaluation of other immune markers (PD-1, PD-L2, and LAG-3) and their association with PD-L1. We also assessed angiogenic markers and their association with PD-L1. ResultsOverall, 27.9 % of tumors were PD-L1 positive. PD-L2 was more frequently expressed (45.6 %), PD-1 and LAG-3 were positive in 17.6 % and 19.1 % respectively. None of these markers was correlated with PD-L1 expression. 66 % (45/68) expressed at least one immune marker, and 43 % (29/68) were “double-positive”, as they expressed both immune and angiogenic markers. OS was significantly shorter for patients with PD-L1 positive pRCC. A multivariate analysis confirmed a significant association between PD-L1 expression and shorter overall survival (HR = 4.0, p = 0.01). ConclusionThese results reinforce clinical data on the expected benefit of ICI in metastatic pRCC treatment, as PD-L1 expression is a factor of poor prognosis in this multicenter cohort.

PD-L1 expression and its prognostic value in metastatic papillary renal cell carcinoma: Results from a GETUG multicenter retrospective cohort.

PD-L1 expression and its prognostic value in metastatic papillary renal cell carcinoma: Results from a GETUG multicenter retrospective cohort.

A phase I/II, open label, single arm study on safety, tolerability and anti-tumour effiacy of orellanine treatment in patients with metastatic clear-cell or papillary renal cell carcinoma.

A phase I/II, open label, single arm study on safety, tolerability and anti-tumour effiacy of orellanine treatment in patients with metastatic clear-cell or papillary renal cell carcinoma.

Complete response of metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus to nivolumab plus cabozantinib

IntroductionThe effectiveness of nivolumab plus cabozantinib for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus remains unclear.Case presentationA 77‐year‐old male was diagnosed with right papillary renal cell carcinoma with a metastatic lesion on Gerota's fascia, lymph node metastasis, and inferior vena cava tumor thrombus. He was treated with nivolumab plus cabozantinib. As all lesions regressed enough to permit complete resection, radical nephrectomy, thrombectomy, and retroperitoneal lymph node dissection were performed. No viable malignant cells were identified histopathologically. Despite the discontinuation of nivolumab plus cabozantinib, there has been no recurrence for 9 months.ConclusionNivolumab plus cabozantinib has effectiveness for metastatic papillary renal cell carcinoma with inferior vena cava tumor thrombus.

MP28-14 Real-World Survival Outcomes Associated With Immunotherapy, Targeted Therapy, and Combination Therapy for Metastatic Papillary Renal Cell Carcinoma

You have accessJournal of UrologyErrata1 Jul 2023MP28-14 Real-World Survival Outcomes Associated With Immunotherapy, Targeted Therapy, and Combination Therapy for Metastatic Papillary Renal Cell Carcinomais correction ofMP28-14 REAL-WORLD SURVIVAL OUTCOMES ASSOCIATED WITH IMMUNOTHERAPY, TARGETED THERAPY, AND COMBINATION THERAPY FOR METASTATIC PAPILLARY RENAL CELL CARCINOMA View All Author Informationhttps://doi.org/10.1097/JU.0000000000003517AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Volume 209, Supplement 4, Page e376: The eighth through 14th authors’ names are Monica Morgan, Brian J. Miles, Taliah Muhammad, Maryam Anis, Monty Aghazadeh, Jun Zhang, and Eleni Efstathiou, and the 17th author’s name is Brian Rini. The online and PDF versions of the article have been updated. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology23 Mar 2023MP28-14 REAL-WORLD SURVIVAL OUTCOMES ASSOCIATED WITH IMMUNOTHERAPY, TARGETED THERAPY, AND COMBINATION THERAPY FOR METASTATIC PAPILLARY RENAL CELL CARCINOMA Volume 210Issue 1July 2023Page: 224-224 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement Advertisement PDF downloadLoading ...

#3697 FAMILIAL PAPILLARY RENAL CELL CARCINOMA: A CASE REPORT

Abstract Background and Aims The incidence of Renal Cell Carcinoma (RCC) is the 9th commonest cancer worldwide. It originates from the renal tubular epithelium and to date has been subclassified into five different categories. Of which, papillary carcinoma is one subclassification and it includes two variants: sporadic and hereditary. This case report aims to outline a rare case of hereditary papillary RCC and the implications for the family involved. Method We performed a retrospective assessment of clinical and radiological characteristics of the index patient and affected relatives. Genetic diagnosis and management have been summarised. Results A 62-year-old male (II.1) was diagnosed with RCC after presenting with right-sided flank pain and multiple complex cystic lesions within both kidneys. A kidney biopsy revealed a papillary structure with foamy histocytes and clear cell-type epithelium clusters. Immunostaining of tumour cells demonstrated CK7 and P504S positivity consistent with RCC. Subsequently, he underwent bilateral nephrectomies and being rendered anephric, was commenced on haemodialysis. He underwent deceased donor renal transplantation four years later at the age of 66 (HLA 1:2:1, CMV -/-, cRF 35%) and remains dialysis independent six years on. After the diagnosis of the index patient, his son (III.1) was found to have multifocal papillary RCC, having also presented with flank pain, but this time in his 30s (Fig. 1). Patient III.1 underwent genetic testing which revealed a missense variant in the MET gene (NM_000245.4 c.3308G>A; p.Gly1103Glu). The variant affects a highly conserved residue in the Tyrosine Kinase domain of the MET protein. Pathogenic activating variants are associated with RCC. Identification of the same variant in the affected father with bilateral disease allowed classification of the variant as likely pathogenic according to the ACMG criteria [1]. The father has seven children, all of whom have now been tested. 5/7 of them have been found to carry the likely pathogenic MET missense variant. Of the 4 asymptomatic carriers, all are under surveillance by regular renal imaging and (one has had radiofrequency ablation). Conclusion The case outlines a rare form of hereditary RCC and the implications that detection of the genetic variant has meant in terms of early diagnosis of disease. Incidence of RCC is increasing worldwide. Hereditary papillary RCC is rare, it is typically inherited in an autosomal dominant pattern. Germline mutations in the MET proto-oncogene are located at 7q31, which encodes for the tyrosine kinase signaling pathway. Variants lead to uncontrolled activation of MET protein and aberrant cell growth [2]. Discussion Hereditary papillary RCC has an estimated incidence of < 1:1500000, its rarity highlighted by the fact that only ∼35 families have been reported worldwide in literature. In these cases it exhibits 100% penetrance, with patients developing renal cell carcinoma typically between their fifth and sixth decade [3]. We would like to acknowledge the family involved in this case report. As with many cancers, early diagnosis is helped by detection of a genetic variant, leading to improved long-term disease-free survival. In the case of metastatic papillary RCC 2-year survival is still estimated at 18% (3).

P381 TEAMWORK IS SUCCESSFULL (4): PROGRESSION OF CORONARY ATHEROSCLEROSIS IN A PERIPHERAL T–CELL LYMPHOMA AND PAPILLARY RENAL CELL CARCINOMA SURVIVOR

Abstract Introduction Growing evidence highlight cancer and cardiovascular diseases (CVD) share common risk factors, including genetic ones, and underlying pathogenesis. Such paradigm has significant implications for cancer survivors, an exponential growing cohort of patients (Pts), due to notable improvements in survival achieved with new oncological treatments. However, many new agents of targeted– and immuno–therapy can cause cardiac damage, mainly for vascular involvement, a pathophysiological mechanism different from classic chemotherapeutic agents. We present the case of left ventricular systolic dysfunction (LVSD) in a man with metastatic papillary renal cell carcinoma (PRCC) previously exposed to anthracyclines for former peripheral T–cell lymphoma (PTCL). He came to our attention for cardiological assessment before starting immunotherapy (Nivolumab), due to the failure of Tyrosine kinase inhibitor (TKIs) (Pazopanib) treatment. Clinical case A 74–year–old Pt with hypertension, severe renal dysfunction, dyslipidemia, and exertional dyspnea (NYHA II) presented at transthoracic echocardiogram (TTE) a normal size chambers with mild concentric hypertrophy and a clinically stable moderate LVSD (LVEF 35–40%) at periodic evaluation. Pt was also performing his radiological follow–up for the estimation of metastases with CT, twice a year since 2016. A retrospective review of these non–contrast and non–ECG–gated CT highlighted an extensive increase in coronary artery calcifications during the last four years, started with the beginning of TKIs therapy. In 2018 only mild LAD calcification was detectable (Figure 1), while in 2022 a severe three–vessel coronary atherosclerosis was present (Figure 3). After multi–disciplinary discussion, an aggressive correction of multiple cardiovascular risk factors (starting Rosuvastatin and adjusting Bisoprolol) was performed and immunotherapy started without any adverse event. Conclusions Non–ECG–gated CT routinely performed for monitoring the state of the oncological disease is a useful tool for the evaluation of coronary artery calcific burden and accelerated atherosclerosis. It provides additional information beyond the traditional evaluation of CV risk and must be integrated with clinical and laboratory data.

Comparative real-world survival outcomes of metastatic papillary and clear cell renal cell carcinoma treated with immunotherapy, targeted therapy, and combination therapy.

While there are a plethora of studies supporting novel treatment approaches in metastatic clear cell renal cell carcinoma (ccRCC), much of the data used to inform care of patients with metastatic papillary RCC (pRCC) is extrapolated from ccRCC. Several recent phase III trials have supported the use of immunotherapy (IO) and targeted therapy (TT)+IO in ccRCC, without corresponding data for pRCC. Using ccRCC as a comparison group, we sought to describe real-world trends in the utilization of systemic therapy and its impact on overall survival (OS) among patients with metastatic pRCC. Using the National Cancer Database (NCDB), we identified cases of metastatic pRCC and ccRCC between 2015 and 2018. Patients were stratified into groups based on histology and first-line treatments (TT, IO, TT + IO). Differences in baseline characteristics were assessed using the Kruskal-Wallis test for continuous variables, and the Chi-square or Fisher's exact test for categorical variables. Survival analysis was performed using Kaplan-Meier estimates and multivariable Cox regression analyses. A total of 6,920 patients with a diagnosis of metastatic RCC were identified: 594 (8.6%) with pRCC and 6,326 (91.4%) with ccRCC. Overall, 4,710 patients received TT (455 pRCC and 4,255 ccRCC), 1,585 received IO (77 pRCC and 1,508 ccRCC), and 625 received TT+IO (62 pRCC and 563 ccRCC). Temporal trend between 2015 and 2018 revealed an increased utilization of IO and TT + IO for pRCC and ccRCC. In patients with metastatic pRCC, neither IO (HR 1.03; 95% CI 0.75-1.42) nor TT+IO (HR 0.90, 95% CI 0.63-1.28) were associated with better OS compared to TT alone. In contrast, both IO and combination TT and IO were associated with significantly better OS than TT for patients with metastatic ccRCC (IO group: hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.68-0.82; TT+IO group: HR 0.82, 95% CI 0.72-0.93). Cytoreductive nephrectomy was associated with better OS in both pRCC (HR 0.59, 95% CI 0.46-0.77) and ccRCC (HR 0.54, 95% CI 0.50-0.58). Although IO and TT + IO were associated with better OS among patients with metastatic ccRCC, this same effect was not observed among patients with pRCC.

Coexistence of primary pulmonary meningioma and metastatic papillary renal cell carcinoma of the lung: A rare case report with review of the literature

Primary pulmonary meningioma (PPM) is extremely rare tumor and only a few reports have been reported to date. PPM may be overlooked when it coexists with other types of tumors in the lung. It is essential to have a knowledge of the clinicopathological features of PPM and to recognize this rare coexistence. A 57-year-old male underwent surgery for papillary renal cell carcinoma, when 2 pulmonary nodules were detected using chest computed tomography. The coexistence of benign PPM and metastatic papillary renal cell carcinoma was histologically confirmed. A lobectomy was performed. The patient recovered well after surgery and was discharged on postoperative day 4. Duo to the rarity of PPM, it is easily overlooked, especially when it coexists with other tumors in the lung. The possibility of PPM needs to be taken into account when diagnosing pulmonary nodules in clinical practice.

New-onset nephrotic syndrome and acute kidney injury after cabozantinib

Introduction: Renal adverse events related to receptor tyrosine kinase inhibitors (RTKIs) have been reported, including elevated creatinine levels, electrolyte abnormalities, elevated blood pressure, and proteinuria. Cabozantinib is a RTKI approved for patients with renal cell carcinoma (RCC), who have failed other lines of treatment. Here we report a case of nephrotic syndrome with biopsy-proven podocytopathy shortly after starting cabozantinib. Case description: An 80-year-old white man with stage IV metastatic papillary RCC was started on cabozantinib for progressive RCC. At baseline he had chronic kidney disease with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 (serum creatinine 1.3 mg/dL) and a urine microalbumin to creatinine ratio of 5.4 mg/g creatinine. Approximately 3 weeks after starting cabozantinib the patient presented to the hospital with nausea, vomiting, fevers, and failure to thrive and was found to have acute kidney injury (creatinine peaked at 6.0 mg/dL) and nephrotic-range proteinuria, for which a kidney biopsy was performed. Biopsy demonstrated acute tubular necrosis and podocytopathy with 90% foot process effacement. Discussion: Cabozantinib is a recently approved RTKI, which has previously been demonstrated to cause thrombotic micro-angiopathy (TMA). Podocytopathies have been demonstrated by biopsy in cases of other RTKI induced proteinuria, but to our knowledge this is the first case which demonstrates isolated podocytopathy temporally associated with the initiation of cabozantinib.

1472P Biomarkers of the response in metastatic papillary renal cell carcinoma

Papillary Renal Cell Carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC). In silico, we identified 4 subgroups according to the proportion of immune and stromal cell populations in a preliminary study in 271 localized pRCC tumors using RNA-seq data from The Cancer Genome Atlas (TCGA), validated in independent cohort. Thus, the microenvironment of pRCC is yet to be described in a cohort of metastatic pRCC treated with systemic therapy and its association with response and outcomes to be assessed.

Spectrum of lung pathology in medicolegal autopsies at rural teaching hospital

Background: Lungs are the major organs involved by a number of infectious, inflammatory and occupational hazards. They are also involved secondarily by all forms of terminal events like cardiovascular events. Autopsy is a part of pathology that serves as an important tool to identify the cause and manner of death and to learn about methods to prevent them. Methods: This is a retrospective study conducted on the autopsy specimens received in the department of pathology from 1 January 2020 to 31 December 2021. Gross findings were noted at the time of autopsy and the specimen was subjected to routine histopathological processing and hematoxylin and eosin staining. Histopathological findings were noted. Results: Out of total 78 cases, 30.17% shows Congestion and oedema, 24.65% shows Pneumonia. 10.95% and 8.21% shows interstitial changes in the form of interstitial pneumonia or mononuclear interstitial infiltrate and Diffuse alveolar damage respectively, 6.84% shows emphysematous changes and 5.84% shows chronic passive venous congestion. 4.1% cases shows findings of tuberculosis and only 1 case was of lung abscess, metastatic papillary renal cell carcinoma and fibrin thrombi each. Highest number of cases (32) belonged to 16-30 age group. Least number of cases (2) were from >75 age group.

Everolimus or sunitinib as first-line treatment of metastatic papillary renal cell carcinoma: A retrospective study of the GETUG group (Groupe d’Etude des Tumeurs Uro-Génitales)

BackgroundTwo phase II trials (NCT00688753 and NCT00541008) reported efficacy data of sunitinib and everolimus in first-line treatment of metastatic papillary renal cell carcinoma (mpRCC). Although most patients receive sunitinib or a mammalian target of rapamycin (mTOR) inhibitor in first- and second-line treatment, the optimal strategy remained unknown. Material and methodsIn 23 centres of the Groupe d’Etude des Tumeurs Urogénitales group, after centralised pathological review, we analysed retrospectively progression-free survival (PFS) of patients with mpRCC treated in first-line treatment (PFS-1) with sunitinib or everolimus (primary end-point), PFS in second-line treatment (PFS-2), overall survival (OS), objective response rate, disease control rate (DCR), overall sequence and prognostic factors for OS (secondary end-points). ResultsOne hundred thirty-eight patients (119 men and 19 women), median age 62.5 years, with mpRCC type 1 (n = 24) or non–type 1 (n = 114), received first-line sunitinib (n = 107) or everolimus (n = 31). With a median follow-up of 92 months, we found no significant difference between the treatment groups in terms of PFS-1 (5.5 versus 6.2 months) and DCR (69% versus 83%). Ninety-eight patients received a second-line treatment, 69% with mTOR inhibitors after sunitinib and 100% with tyrosine kinase inhibitors after everolimus, with similar DCR (64% versus 58%), median PFS-2 (3.4 versus 4.8 months) and OS (16.0 versus 20.3 months). No factor was prognostic for PFS-1, whereas leukocytosis, anaemia and the time from diagnosis to first systemic therapy < 1 year were prognostic for OS. We found no prognostic difference between both pRCC subtypes. The International Metastatic Renal Cell Database Consortium risk factors were prognostic for OS. ConclusionSunitinib and everolimus had similar efficacy in first-line treatment of patients with mpRCC.

A construction and comprehensive analysis of ceRNA networks and infiltrating immune cells in papillary renal cell carcinoma

BackgroundAs the second most common malignancy in adults, papillary renal cell carcinoma (PRCC) has shown an increasing trend in both incidence and mortality. Effective treatment for advanced metastatic PRCC is still lacking. In this study, we aimed to establish competitive endogenous RNA (ceRNA) networks related to PRCC tumorigenesis, and analyze the specific role of differentially expressed ceRNA components and infiltrating immune cells in tumorigenesis.MethodsCeRNA networks were established to identify the key ceRNAs related to PRCC tumorigenesis based on the 318 samples from The Cancer Genome Atlas database (TCGA), including 285 PRCC and 33 normal control samples. The R package, “CIBERSORT,” was used to evaluate the infiltration of 22 types of immune cells. Then we identified the significant ceRNAs and immune cells, based on which two nomograms were obtained for predicting the prognosis in PRCC patients. Finally, we investigated the co‐expression of PRCC‐specific immune cells and core ceRNAs via Pearson correlation test.ResultsCOL1A1, H19, ITPKB, LDLR, TCF4, and WNK3 were identified as hub genes in ceRNA networks. Four prognostic‐related tumor‐infiltrating immune cells, including T cells CD4 memory resting, Macrophages M1, and Macrophages M2 were revealed. Pearson correlation test indicated that Macrophage M1 was negatively related with COL1A1 (p < 0.01) and LDLR (p < 0.01), while Macrophage M2 was positively related with COL1A1 (p < 0.01), TCF4 (p < 0.01), and H19 (p = 0.032). Two nomograms were conducted with favorable accuracies (area under curve of 1‐year survival: 0.935 and 0.877; 3‐year survival: 0.849 and 0.841; and 5‐year survival: 0.818 and 0.775, respectively).ConclusionThe study constructed two nomograms suited for PRCC prognosis predicting. Moreover, we concluded that H19‐miR‐29c‐3p‐COL1A1 axis might promote the polarization of M2 macrophages and inhibit M1 macrophage activation through Wnt signaling pathway, collaborating to promote PRCC tumorigenesis and lead to poor overall survival of PRCC patients.

Savolitinib: First Approval.

Savolitinib (Orpathys®; HUTCHMED, AstraZeneca) is a receptor tyrosine kinase mesenchymal epithelial transition factor (MET) inhibitor being developed for the treatment of metastatic non-small cell lung cancer (NSCLC), papillary and clear cell renal cell carcinoma (RCC), gastric cancer and colorectal cancer. Based on the results of a pivotal phase II trial in patients with NSCLC/pulmonary sarcomatoid carcinoma, savolitinib was recently granted approval in China (conditional on the results of a phase III trial) for the treatment of metastatic NSCLC with MET exon 14-skipping alterations in patients who have progressed after or who are unable to tolerate platinum-based chemotherapy. This article summarizes the milestones in the development of savolitinib leading to this first approval.

Improved Control of Tyrosine Kinase Inhibitor-Induced Diarrhea with a Novel Chloride Channel Modulator: A Case Report.

Despite the efficacy of tyrosine kinase inhibitors (TKIs) across multiple cancers, side effects including treatment-related diarrhea can impede a patient’s ability to reach therapeutic doses or stay on therapy. Below, we present the case of a 72-year-old patient with metastatic papillary renal cell carcinoma recurrent despite nephrectomy. Over the course of treatment, the patient received multiple different tyrosine kinase inhibitors with varying efficacy. Treatment with the TKI cabozantinib after failure of two prior TKIs resulted in a clinical response with shrinkage of his nodal metastatic disease. However, the severe treatment-related diarrhea refractory to conventional management required both dose holds and dose reductions of cabozantinib. Off-label administration of crofelemer, a novel FDA-approved antidiarrheal agent, successfully controlled the treatment-related diarrhea and allowed resumption and partial dose increase of cabozantinib. This case suggests that crofelemer could be a viable therapeutic strategy to address TKI-induced diarrhea.

Effect of Everolimus Adjuvant to Radical Nephrectomy on a Case of Metastatic Papillary Renal Cell Carcinoma

Effect of Everolimus Adjuvant to Radical Nephrectomy on a Case of Metastatic Papillary Renal Cell Carcinoma