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International Journal of Cancer Dec 2020Malignant renal tumours represent 5% of childhood cancers and include types with likely different aetiology: Wilms tumour (WT), rhabdoid renal tumour, kidney sarcomas...
Malignant renal tumours represent 5% of childhood cancers and include types with likely different aetiology: Wilms tumour (WT), rhabdoid renal tumour, kidney sarcomas and renal carcinomas. WT is the most common renal tumour in children, previously shown to vary internationally and with ethnicity. Using the comprehensive database of the International Incidence of Childhood Cancer study (IICC), we analysed global variations and time trends in incidence of renal tumour types in children (age 0-14 years) and adolescents (age 15-19 years). The results were presented by 14 world regions, and five ethnic groups in the US. We included 15 320 renal tumours in children and 800 in adolescents reported to the 163 contributing registries during 2001-2010. In children, age-standardised incidence rate (ASR) of renal tumours was 8.3 per million (95% confidence interval, CI = 8.1, 8.4); it was the highest in North America and Europe (9-10 per million) and the lowest in most Asian regions (4-5 per million). In the US, Blacks had the highest ASR (10.9 per million, 95% CI = 10.2, 11.6) and Asian and Pacific Islanders the lowest (4.4 per million, 95% CI = 3.6, 5.1). In adolescents, age-specific incidence rate of renal tumours was 1.4 per million (95% CI = 1.3, 1.5). WT accounted for over 90% of all renal tumours in each age from 1 to 7 years and the proportion of renal carcinomas increased gradually with age. From 1996 to 2010, incidence remained mostly stable for WT (average annual percent change, AAPC = 0.1) and increased for renal carcinomas in children (AAPC = 3.7) and adolescents (AAPC = 3.2). Our findings warrant further monitoring.
Topics: Adolescent; Child; Child, Preschool; Female; Global Health; Humans; Incidence; Infant; Infant, Newborn; Kidney Neoplasms; Male; Registries; Rhabdoid Tumor; Sarcoma; Wilms Tumor
PubMed: 32902866
DOI: 10.1002/ijc.33147 -
European Journal of Vascular and... Jan 2016To conduct a comprehensive review of cases, presentation, diagnosis, and management of angiosarcoma in arteriovenous fistulae (AVF) created for haemodialysis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE/BACKGROUND
To conduct a comprehensive review of cases, presentation, diagnosis, and management of angiosarcoma in arteriovenous fistulae (AVF) created for haemodialysis.
METHODS
Two authors independently conducted systematic searches and extraction of articles from the Embase, AMED, Health Management Information Consortium, and MEDLINE databases in keeping with the inclusion/exclusion criteria and Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards.
RESULTS
Twenty-two unique patient cases were identified; 20 of the cases were men and mean ± SD age of presentation was 54.9 ± 13.6 years. Nineteen cases were post-transplant and 18 were on antirejection agents. The most common presenting symptom was pain, with or without a mass. The initial diagnosis was most often thrombosis/infection of the AVF and the diagnostic interval to a correct diagnosis of angiosarcoma was between 2 and 40 weeks. Mean ± SD time to presentation of symptoms from fistula formation was 118.9 ± 57.5 months, while from transplant it was 96.9 ± 70.0 months. Amputation was the most common treatment modality and mean ± SD survival was 8.8 ± 3.7 months.
CONCLUSION
Angiosarcoma should be suspected in previously quiescent AVF that presents with pain. The presence of a rapidly enlarging mass or bleeding/bruising should be taken as alarm indicators and warrant urgent investigation in accordance with local cancer guidelines. Any surgical procedure should involve histological samples as a matter of course.
Topics: Amputation, Surgical; Arteriovenous Shunt, Surgical; Hemangiosarcoma; Humans; Pain; Renal Dialysis; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 26482509
DOI: 10.1016/j.ejvs.2015.08.016 -
HGG Advances Oct 2023encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline...
encodes the TINF2 protein, which is a subunit in the shelterin complex critical for telomere regulation. Three recent studies have associated six truncating germline variants in that have previously been associated with a cancer predisposition syndrome (CPS) caused by elongation of the telomeres. This has added to the genes, together with other telomere maintenance genes such as , , , and . We report a clinical study of 102 Danish patients with multiple primary melanoma (MPM) in which a germline truncating variant in (p.(Arg265Ter)) was identified in four unrelated participants. The telomere lengths of three variant carriers were >90% percentile. In a routine diagnostic setting, the variant was identified in two more families, including an additional MPM patient and monozygotic twins with thyroid cancer and other cancer types. A total of 10 individuals from six independent families were confirmed carriers, all with cancer history, predominantly melanoma. Our findings suggest a major role of in Danish patients with MPM. In addition to melanoma, other cancers in the six families include thyroid, renal, breast, and sarcoma, supporting a CPS in which melanoma, thyroid cancer, and sarcoma predominate. Further studies are needed to establish the full spectrum of associated cancer types and characterize lifetime cancer risk in carriers.
Topics: Humans; Melanoma; Thyroid Neoplasms; Sarcoma; Syndrome; Neoplasms, Multiple Primary; Denmark; Telomere-Binding Proteins
PubMed: 37646013
DOI: 10.1016/j.xhgg.2023.100225 -
Internal Medicine (Tokyo, Japan) 2011Primary renal synovial sarcomas (SS) are rare tumors of the kidney. Faria et al first described primary renal synovial sarcoma in 1999 (Mod Pathol 12:94A). In this paper... (Review)
Review
Primary renal synovial sarcomas (SS) are rare tumors of the kidney. Faria et al first described primary renal synovial sarcoma in 1999 (Mod Pathol 12:94A). In this paper we present a primary renal synovial sarcoma case and review the 41 primary renal synovial sarcoma cases reported to date. Primary renal synovial sarcomas can exist in either a monophasic or a biphasic pattern. The monophasic variant of primary renal synovial sarcoma is more common and tends to have a better prognosis than the biphasic variant. We present in this paper, a 68-year-old woman with primary renal synovial sarcoma. She presented with right flank pain and abdominal distention. Postoperative pathology of the 20 cm mass on magnetic resonance imaging showed histologic and immunochemical features of synovial sarcoma with coexisting spindle and epithelial cells. She underwent adjuvant ifosfamide and doxorubicin chemotherapy and was free of disease at 1 year after diagnosis. As a conclusion, physicians should be aware of the possibility of malignancy in cystic renal masses and that synovial sarcoma is one of the possibilities.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Doxorubicin; Female; Humans; Ifosfamide; Kidney Neoplasms; Sarcoma, Synovial; Treatment Outcome
PubMed: 21804284
DOI: 10.2169/internalmedicine.50.5224 -
Diagnostic Pathology Aug 2021A high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone...
BACKGROUND
A high incidence of malignant tumors, such as post-transplant lymphoproliferative disorders (PTLD), Kaposi sarcoma, and renal cancer is common in solid organ and bone marrow transplant recipients. However, myeloid sarcoma (MS) after renal transplantation has rarely been reported and the diagnosis is challenging due to its low incidence.
CASE PRESENTATION
Here, we report a rare case of a 49-year-old man who developed myeloid sarcoma (MS) in the transplanted kidney two years after renal transplantation. Next-generation sequencing (NGS) showed mutations of KRAS and DNMT3A genes in the MS, and no gene mutations in the bone marrow. He presented a normal karyotype of 46, XY. Following treatment with 6 cycles of systemic chemotherapy, the patient was in satisfactory condition with stable serum creatinine (sCr) levels at the 1-year follow-up. In addition, we performed a detailed review with emphasis on the clinical manifestations, and the diagnostic and therapeutic processes of another 7 patients who developed MS following renal transplantation.
CONCLUSIONS
Our report illustrates the clinical utility of comprehensive genomic profiling in benefiting the diagnosis of MS, the selection of therapeutic strategy and the determination of whether MS is donor-derived.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cytarabine; DNA Methyltransferase 3A; DNA Mutational Analysis; Daunorubicin; High-Throughput Nucleotide Sequencing; Humans; Kidney Transplantation; Male; Middle Aged; Mutation; Proto-Oncogene Proteins p21(ras); Sarcoma, Myeloid; Treatment Outcome
PubMed: 34465355
DOI: 10.1186/s13000-021-01141-z -
Cancer Chemotherapy and Pharmacology Dec 2017Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a...
BACKGROUND
Pazopanib is an angiogenesis inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Post hoc analysis of a clinical trial demonstrated a relationship between pazopanib trough concentrations (C) and treatment efficacy. The aim of this study was to explore the pharmacokinetics and exposure-survival relationships of pazopanib in a real-world patient cohort.
PATIENTS AND METHODS
Renal cell cancer and soft tissue sarcoma patients who had at least one pazopanib plasma concentration available were included. Using calculated C values and a threshold of > 20 mg/L, univariate and multivariate exposure-survival analyses were performed.
RESULTS
Sixty-one patients were included, of which 16.4% were underexposed (mean C < 20 mg/L) using the 800 mg fixed-dosed schedule. In univariate analysis C > 20 mg/L was related to longer progression free survival in renal cell cancer patients (34.1 vs. 12.5 weeks, n = 35, p = 0.027) and the overall population (25.0 vs. 8.8 weeks, n = 61, p = 0.012), but not in the sarcoma subgroup (18.7 vs. 8.8 weeks, n = 26, p = 0.142). In multivariate analysis C > 20 mg/L was associated with hazard ratios of 0.25 (p = 0.021) in renal cancer, 0.12 (p = 0.011) in sarcoma and 0.38 (p = 0.017) in a pooled analysis.
CONCLUSION
This study confirms that pazopanib C > 20 mg/L relates to better progression free survival in renal cancer and points towards a similar trend in sarcoma patients. C monitoring of pazopanib can help identify patients with low C for whom individualized treatment at a higher dose may be appropriate.
Topics: Aged; Carcinoma, Renal Cell; Female; Humans; Indazoles; Male; Middle Aged; Pyrimidines; Sarcoma; Sulfonamides; Survival Analysis; Treatment Outcome
PubMed: 29051995
DOI: 10.1007/s00280-017-3463-x -
Pediatric Blood & Cancer Aug 2017A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT)... (Meta-Analysis)
Meta-Analysis Review
Investigating the heterogeneity of alkylating agents' efficacy and toxicity between sexes: A systematic review and meta-analysis of randomized trials comparing cyclophosphamide and ifosfamide (MAIAGE study).
BACKGROUND
A marginal interaction between sex and the type of alkylating agent was observed for event-free survival in the Euro-EWING99-R1 randomized controlled trial (RCT) comparing cyclophosphamide and ifosfamide in Ewing sarcoma. To further evaluate this interaction, we performed an individual patient data meta-analysis of RCTs assessing cyclophosphamide versus ifosfamide in any type of cancer.
METHODS
A literature search produced two more eligible RCTs (EICESS92 and IRS-IV). The endpoints were progression-free survival (PFS, main endpoint) and overall survival (OS). The hazard ratios (HRs) of the treatment-by-sex interaction and their 95% confidence interval (95% CI) were assessed using stratified multivariable Cox models. Heterogeneity of the interaction across age categories and trials was explored. We also assessed this interaction for severe acute toxicity using logistic models.
RESULTS
The meta-analysis comprised 1,528 pediatric and young adult sarcoma patients from three RCTs: Euro-EWING99-R1 (n = 856), EICESS92 (n = 155), and IRS-IV (n = 517). There were 224 PFS events in Euro-EWING99-R1 and 200 in the validation set (EICESS92 + IRS-IV), and 171 and 154 deaths in each dataset, respectively. The estimated treatment-by-sex interaction for PFS in Euro-EWING99-R1 (HR = 1.73, 95% CI = 1.00-3.00) was not replicated in the validation set (HR = 0.97, 95% CI = 0.55-1.72), without heterogeneity across trials (P = 0.62). In the pooled analysis, the treatment-by-sex interaction was not significant (HR = 1.31, 95% CI = 0.89-1.95, P = 0.17), without heterogeneity across age categories (P = 0.88) and trials (P = 0.36). Similar results were observed for OS. No significant treatment-by-sex interaction was observed for leucopenia/neutropenia (P = 0.45), infection (P = 0.64), or renal toxicity (P = 0.20).
CONCLUSION
Our meta-analysis did not confirm the hypothesis of a treatment-by-sex interaction on efficacy or toxicity outcomes.
Topics: Alkylating Agents; Antineoplastic Agents; Cyclophosphamide; Female; Humans; Ifosfamide; Male; Randomized Controlled Trials as Topic; Sarcoma; Sex Characteristics
PubMed: 28111876
DOI: 10.1002/pbc.26457 -
Pediatrics and Neonatology Jun 2014
Topics: Female; Humans; Kidney Neoplasms; Male; Sarcoma, Clear Cell; Wilms Tumor
PubMed: 24685338
DOI: 10.1016/j.pedneo.2014.01.003 -
Journal of Translational Medicine Jan 2024Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma...
BACKGROUND
Osteosarcoma is the most common malignant primary bone tumor in infants and adolescents. The lack of understanding of the molecular mechanisms underlying osteosarcoma progression and metastasis has contributed to a plateau in the development of current therapies. Endoplasmic reticulum (ER) stress has emerged as a significant contributor to the malignant progression of tumors, but its potential regulatory mechanisms in osteosarcoma progression remain unknown.
METHODS
In this study, we collected RNA sequencing and clinical data of osteosarcoma from The TCGA, GSE21257, and GSE33382 cohorts. Differentially expressed analysis and the least absolute shrinkage and selection operator regression analysis were conducted to identify prognostic genes and construct an ER stress-related prognostic signature (ERSRPS). Survival analysis and time dependent ROC analysis were performed to evaluate the predictive performance of the constructed prognostic signature. The "ESTIMATE" package and ssGSEA algorithm were utilized to evaluate the differences in immune cells infiltration between the groups. Cell-based assays, including CCK-8, colony formation, and transwell assays and co-culture system were performed to assess the effects of the target gene and small molecular drug in osteosarcoma. Animal models were employed to assess the anti-osteosarcoma effects of small molecular drug.
RESULTS
Five genes (BLC2, MAGEA3, MAP3K5, STC2, TXNDC12) were identified to construct an ERSRPS. The ER stress-related gene Stanniocalcin 2 (STC2) was identified as a risk gene in this signature. Additionally, STC2 knockdown significantly inhibited osteosarcoma cell proliferation, migration, and invasion. Furthermore, the ER stress-related gene STC2 was found to downregulate the expression of MHC-I molecules in osteosarcoma cells, and mediate immune responses through influencing the infiltration and modulating the function of CD8+ T cells. Patients categorized by risk scores showed distinct immune status, and immunotherapy response. ISOX was subsequently identified and validated as an effective anti-osteosarcoma drug through a combination of CMap database screening and in vitro and in vivo experiments.
CONCLUSION
The ERSRPS may guide personalized treatment decisions for osteosarcoma, and ISOX holds promise for repurposing in osteosarcoma treatment.
Topics: Adolescent; Animals; Humans; Prognosis; Osteosarcoma; Antineoplastic Agents; Algorithms; Bone Neoplasms; Protein Disulfide Reductase (Glutathione)
PubMed: 38229155
DOI: 10.1186/s12967-023-04794-0 -
The Oncologist Jan 2018Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the... (Review)
Review
UNLABELLED
Soft tissue and bone sarcomas are a rare and heterogeneous form of cancer. With standard of care treatment options including surgery, radiation, and chemotherapy, the long-term survival is still low for high-risk soft tissue sarcoma patients. New treatment strategies are needed. Immunotherapy offers a new potential treatment paradigm with great promise. Immunotherapy of soft tissue sarcomas dates back to Dr. Coley's first use of toxins in the late 1800s. A variety of strategies of immunotherapy have been tried in soft tissue and bone sarcomas, including various vaccines and cytokines, with limited success. Results of these early clinical trials with vaccines and cytokines were disappointing, but there are reasons to be optimistic. Recent advances, particularly with the use of adoptive T-cell therapy and immune checkpoint inhibitors, have led to a resurgence of this field for all cancer patients. Clinical trials utilizing adoptive T-cell therapy and immune checkpoint inhibitors in soft tissue and bone sarcomas are under way. This paper reviews the current state of evidence for the use of immunotherapy, as well as current immunotherapy strategies (vaccines, adopative T-cell therapy, and immune checkpoint blockade), in soft tissue and bone sarcomas. By understanding the tumor microenviroment of sarcomas and how it relates to their immunoresponsiveness, better immunotherapy clinical trials can be designed, hopefully with improved outcomes for soft tissue and bone sarcoma patients.
IMPLICATIONS FOR PRACTICE
Immunotherapy is a promising treatment paradigm that is gaining acceptance for the management of several cancers, including melanoma, renal cell carcinoma, prostate cancer, and lung cancer. There is a long history of immunotherapy in the treatment of soft tissue and bone sarcomas, although with little success. It is important to understand past failures to develop future immunotherapy treatment strategies with an improved possibility of success. This article reviews the history of and current state of immunotherapy research in the treatment of soft tissue and bone sarcomas, with particular regard to vaccine trials, adoptive T-cell therapy, and immune checkpoint blockade.
Topics: Bone Neoplasms; Humans; Immunotherapy; Prognosis; Sarcoma
PubMed: 28935774
DOI: 10.1634/theoncologist.2016-0025