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Heliyon Apr 2024Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on...
Clear cell renal cell carcinoma (ccRCC) presents challenges in early diagnosis and effective treatment. In this study, we aimed to establish a prognostic model based on G2M checkpoint-related genes and identify associated clusters in ccRCC through clinical bioinformatic analysis and experimental validation. Utilizing a single-cell RNA dataset (GSE159115) and bulk-sequencing data from The Cancer Genome Atlas (TCGA) database, we analyzed the G2M checkpoint pathway in ccRCC. Differential expression analysis identified 45 genes associated with the G2M checkpoint, leading to the construction of a predictive model with four key genes (E2F2, GTSE1, RAD54L, and UBE2C). The model demonstrated reliable predictive ability for 1-, 3-, and 5-year overall survival, with AUC values of 0.794, 0.790, and 0.794, respectively. Patients in the high-risk group exhibited a worse prognosis, accompanied by significant differences in immune cell infiltration, immune function, TIDE and IPS scores, and drug sensitivities. Two clusters of ccRCC were identified using the "ConsensusClusterPlus" package, cluster 1 exhibited a worse survival rate and was resistant to chemotherapeutic drugs of Axitinib, Erlotinib, Pazopanib, Sunitinib, and Temsirolimus, but not Sorafenib. Targeted experiments on RAD54L, a gene involved in DNA repair processes, revealed its crucial role in inhibiting proliferation, invasion, and migration in 786-O cells. In conclusion, our study offers valuable insights into the molecular mechanisms underlying ccRCC, identifying potential prognostic genes and molecular subtypes associated with the G2M checkpoint. These findings hold promise for guiding personalized treatment strategies in the management of ccRCC.
PubMed: 38617927
DOI: 10.1016/j.heliyon.2024.e29289 -
Radiology Case Reports Nov 2023We present the case of a 75-year-old female in which a pulmonary tumor embolism was detected incidentally on a prostate-specific membrane antigen positron emission...
We present the case of a 75-year-old female in which a pulmonary tumor embolism was detected incidentally on a prostate-specific membrane antigen positron emission tomography-computed tomography restaging scan. This occurred on the background of renal cell carcinoma in remission with pazopanib systemic therapy and a right nephrectomy 4 years prior. An avidity to prostate-specific membrane antigen in the superior lingula of the left upper lobe of the lung coupled with contrast-enhanced computed tomography findings found the lesion to be a tumor thrombus. This case serves to highlight the effectiveness of incorporating contrast-enhanced computed tomography with prostate-specific membrane antigen positron emission tomography and to consider the rare diagnosis of a pulmonary tumor embolism.
PubMed: 37745764
DOI: 10.1016/j.radcr.2023.08.090 -
Journal of Radiation Research Jan 2024Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can...
Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.
Topics: Humans; Hemangiosarcoma; Radiotherapy, Intensity-Modulated; Scalp; Retrospective Studies; Treatment Outcome; Radiotherapy Dosage
PubMed: 37996084
DOI: 10.1093/jrr/rrad089 -
SAGE Open Medical Case Reports 2023This case report highlights the adverse effects of pazopanib, a vascular endothelial growth factor receptor inhibitor, on wound healing after Mohs surgery. A 79-year-old...
This case report highlights the adverse effects of pazopanib, a vascular endothelial growth factor receptor inhibitor, on wound healing after Mohs surgery. A 79-year-old male with metastatic renal cell carcinoma of the lung, on 600 mg daily pazopanib, underwent Mohs surgery for a nodular basal cell carcinoma on his right leg. Despite multiple wound care strategies, his wound deteriorated over 4 months. Discontinuing pazopanib resulted in rapid wound closure within 2 months. However, metastatic lung nodules grew, prompting treatment with immune checkpoint inhibitors, nivolumab, and ipilimumab, which were discontinued due to complications. Near-complete wound healing was observed prior to reintroducing pazopanib (6 months after initial discontinuation), which again led to wound deterioration. Pazopanib negatively impacts wound repair by inhibiting cell proliferation and angiogenesis. Depending on the malignancy or tumor, cessation of pazopanib, or switching to a course of immune checkpoint inhibitors may be warranted perioperatively.
PubMed: 37736143
DOI: 10.1177/2050313X231200967 -
Renal Failure Dec 2023
Topics: Humans; Radiodermatitis; Kidney Neoplasms; Hair; Acute Kidney Injury
PubMed: 37264782
DOI: 10.1080/0886022X.2023.2213778 -
Cureus Jun 2024Background Treatment of metastatic renal cell cancer (mRCC) has revolutionized with the introduction of anti-VEGF tyrosine kinase inhibitors (TKIs) and immune checkpoint...
Background Treatment of metastatic renal cell cancer (mRCC) has revolutionized with the introduction of anti-VEGF tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs). There is limited data in the literature on the outcomes of Indian patients treated with TKI. Here, we report the outcome of mRCC treated with first-line TKI in a resource-poor setting. Material and methods This is a single-center retrospective study of clear cell mRCC treated with first-line TKI from June 2012 to December 2022. Demographic characteristics and treatment details, including outcome data, were captured from electronic medical records. Patients who received at least one week of therapy were eligible for survival analysis. Results A total of 345 patients with metastatic clear cell histology were analyzed, with a median age of 61 years (range: 20-84 years). One hundred and eighty patients (52%) underwent nephrectomy before systemic therapy. The majority received pazopanib (257 patients, 75%), followed by sunitinib (36 patients, 10%) and cabozantinib (21 patients, 6%); 145 (45%) patients required dose interruption, and 143 (43%) required dose modification of TKI for adverse events. After a median follow-up of 44 months, the median progression-free survival (PFS) was 20.3 months (95% CI: 17.8-24.8), and the median overall survival (OS) was 22.7 months (95% CI: 18.8-28.3). In the poor-risk International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) group, no prior nephrectomy emerged as an independent poor-risk factor for both PFS and OS in multivariate analysis. Conclusion This is the largest single-center cohort of clear cell mRCC from Asia. Median PFS was 20.3 months with predominantly TKI monotherapy. In the poor-risk IMDC group, no prior nephrectomy emerged as an independent poor-risk factor for both PFS and OS.
PubMed: 38855498
DOI: 10.7759/cureus.61978 -
Frontiers in Bioscience (Landmark... Jan 2024Emerging evidence suggests the biological implications of N6-methyladenosine (m6A) in carcinogenesis. Herein, we systematically analyzed the role of m6A modification in...
OBJECTIVE
Emerging evidence suggests the biological implications of N6-methyladenosine (m6A) in carcinogenesis. Herein, we systematically analyzed the role of m6A modification in renal cell carcinoma (RCC) progression.
METHODS
Based on 23 m6A regulators, unsupervised clustering analyses were conducted to determine m6A modification subtypes across 893 RCC specimens in the Cancer Genome Atlas (TCGA) cohort. By performing principal component analysis (PCA) analysis, m6A scoring system was developed for evaluating m6A modification patterns of individual RCC patients. The activity of signaling pathways was assessed by gene-set variation analysis (GSVA) algorithm. The single-sample gene set enrichment analysis (ssGSEA) algorithm was applied for quantifying the infiltration levels of immune cells and the activity of cancer immunity cycle. Drug responses were estimated by genomics of drug sensitivity in cancer (GDSC), the Cancer Therapeutics Response Portal (CTRP) and Preservice Research Institute for Science and Mathematics (PRISM) database.
RESULTS
Five m6A modification subtypes were characterized by different survival outcomes, oxidative stress, cancer stemness, infiltrations of immune cells, activity of cancer immunity cycle, programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression and microsatellite instability (MSI) levels. According to m6A score, RCC patients were categorized into high and low m6A score groups. Patients with high m6A score displayed a prominent survival advantage, and the prognostic value of m6A score was confirmed in two anti-PD-1/PD-L1 immunotherapy cohorts. m6A score was significantly linked to oxidative stress-related genes, and high m6A score indicated the higher sensitivity to axitinib, pazopanib and sorafenib and the lower sensitivity to sunitinib.
CONCLUSION
This study analyzed the extensive regulatory mechanisms of m6A modification on oxidative stress, the tumor microenvironment, and immunity. Quantifying m6A scores may enhance immunotherapeutic effects and assist in developing more effective agents.
Topics: Humans; Carcinoma, Renal Cell; B7-H1 Antigen; Tumor Microenvironment; Kidney Neoplasms; Methylation
PubMed: 38287827
DOI: 10.31083/j.fbl2901033 -
Frontiers in Immunology 2023With the rapidly evolving of immune checkpoint inhibitors (ICIs), it has shown remarkable clinical benefits in treating various cancers. However, immune-related adverse...
With the rapidly evolving of immune checkpoint inhibitors (ICIs), it has shown remarkable clinical benefits in treating various cancers. However, immune-related adverse events (irAEs) remain a significant challenge in the management of patients undergoing immunotherapy. There are limited data about immunotherapy re-challenge in patients with renal clear cell cancer who had irAE in the initial ICI therapy. In this study, we reported the case of a patient with advanced renal clear cell cancer who developed serious irAEs but also achieved a partial remission of tumor after ICI combined with pazopanib in the first-line treatment. After intravenous methylprednisolone therapy for two weeks, the patient fully recovered from treatment-related toxicities. After a multidisciplinary treatment (MDT) discussion and a communication with the patient, the decision was made to undergo a new fully humanized programmed death 1 (PD-1) agent, zimberelimab, combined with pazopanib for immune restart therapy. After two cycles of treatment, the patient demonstrated a partial response (PR), and the disease remained in continuous remission without any irAE at our last follow-up after 14 months' treatment. Re-challenging with immunotherapy after irAEs is an emerging strategy that offers the potential for additional clinical benefits to previously responding patients. However, careful patient selection and monitoring are essential to maximize the safety and efficacy of this approach.
Topics: Humans; Immune Checkpoint Inhibitors; Indazoles; Carcinoma, Renal Cell; Kidney Neoplasms
PubMed: 37915573
DOI: 10.3389/fimmu.2023.1270828 -
Advances in Radiation Oncology Jul 2024The purpose of this investigation was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) for pulmonary metastases from pediatric sarcomas.
PURPOSE
The purpose of this investigation was to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) for pulmonary metastases from pediatric sarcomas.
METHODS AND MATERIALS
This study was a single institutional retrospective chart review including patients younger than 21 years of age at diagnosis who had received SBRT for pulmonary metastasis from metastatic sarcoma. Our current electronic record system was queried for all eligible patients. Primary endpoint was tumor response as defined by Respone Evaluation Criteria in Solid Tumors 1.1 criteria. Secondarily, we analyzed factors that affected tumor response as well as toxicity of treatment. Median dose was 50 Gy ranging from 30 to 60 Gy in 5 fractions to the planning tumor volume.
RESULTS
There were 7 patients, ranging in age from 6 to 21 years with a total of 14 pulmonary lesions treated with SBRT. Median and mean follow-up times for the 7 patients were 10.6 months and 15.9 months, respectively. The complete response rate was 50%, partial response 21%, stable disease 21%, and progressive disease 7%. Four of the 7 patients were treated with concurrent systemic therapy, 3 of which were targeted oral therapies. Additionally, we observed that patients who were on targeted therapy such as regorafenib or pazopanib seemed to have better local control compared with patients without targeted therapy.
CONCLUSIONS
With an overall response rate of 92%, SBRT provided a noninvasive effective palliative treatment option with few side effects in this small retrospective study of 7 patients. A larger prospective clinical trial is warranted to evaluate the role of SBRT in the treatment of unresectable metastatic pediatric sarcomas.
PubMed: 38799105
DOI: 10.1016/j.adro.2024.101517 -
Biomolecules & Biomedicine Jun 2024Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or...
Which factors help to determine the long-term response to first-line tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma: A Turkish multi-centre study.
Many developing countries lack access to recommended first-line treatments for metastatic renal cell carcinoma (mRCC), such as immune checkpoint inhibitors (ICIs) or ICI-tyrosine kinase inhibitor (TKI) combinations. As a result, predictive markers are necessary to identify patients who may benefit from single-agent TKIs for long-term response. This study aims to identify such parameters. This was a multi-centre, retrospective study of patients with mRCC who were undergoing first-line treatment with sunitinib or pazopanib. Patients who had been diagnosed with mRCC and had not experienced disease progression for 36 months or more were deemed to have achieved a long-term response. Predictive clinical and pathological characteristics of patients who did not experience long-term disease progression were investigated. A total of 320 patients from four hospitals were included in the study. The median age of the patients was 60 years (range 20-89 years). According to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification, 109 patients were classified as having favourable risk and 211 were in the intermediate-poor risk group. The median progression-free survival (PFS) and overall survival (OS) for all patients were 12.5 months and 76.4 months, respectively. In the long-term responder's group, the median PFS was 78.4 months. Among all patients, prior nephrectomy, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) <1, and the absence of brain metastasis were predictive factors for long-term response. For patients in the favourable risk group, the lack of brain metastasis was a predictor of long-term response. In the intermediate-poor risk group, prior nephrectomy and ECOG PS <1 were predictive factors for long-term response. Some individuals with mRCC may experience a durable response to TKIs. The likelihood of a long-term response can be determined by factors such as nephrectomy, ECOG PS < 1, and the absence of brain metastases.
PubMed: 38920621
DOI: 10.17305/bb.2024.10512