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Advances in Clinical and Experimental... Oct 2023Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and represents a high-grade neoplasm of skeletal myoblast-like cells. About 40% of all... (Review)
Review
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and represents a high-grade neoplasm of skeletal myoblast-like cells. About 40% of all registered soft tissue tumors are RMSs. This paper describes our current understanding of the RMS subtypes (alveolar (ARMS), embryonic (ERMS), pleomorphic (PRMS), and spindle cell/sclerosing (s/scRMS)), diagnostic methods, molecular bases, and characteristics. We also present the currently used treatment methods and the potential use of natural substances in the treatment of this type of cancer. Natural cytotoxic substances are compounds that have been the subject of numerous studies and discussions in recent years. Since anti-cancer therapies are often limited by a low therapeutic index and cancer resistance to pharmacotherapy, it is very important to search for new, effective compounds. Additionally, compounds of a natural origin are usually readily available and have a reduced cytotoxicity. Thus, the undiscovered potential of natural anti-cancer compounds makes this field of research a very important area. The introduction of model species into research examining the use of natural cytostatic therapies for RMS will allow for further assessment of the effects of these compounds on cancerous and healthy tissues.
Topics: Child; Humans; Cytostatic Agents; Rhabdomyosarcoma; Sarcoma; Soft Tissue Neoplasms
PubMed: 36920267
DOI: 10.17219/acem/161165 -
Pediatric Blood & Cancer Mar 2021Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and...
BACKGROUND
Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG).
METHODS
We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine + dactinomycin + cyclophosphamide (VAC) or VAC alternating with vincristine + irinotecan (VI). Local treatment was similar in both protocols.
RESULTS
The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [CI]: 39-59) and 44% (95% CI: 30-58), and overall survival (OS), 51% (95% CI: 41-61) and 53.6% (95% CI: 40-68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those with FOXO1-negative (49.3% vs 73%, P = .034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative.
CONCLUSIONS
The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Lymph Nodes; Male; Prognosis; Retrospective Studies; Rhabdomyosarcoma, Alveolar; Survival Rate
PubMed: 33245207
DOI: 10.1002/pbc.28832 -
The American Journal of Pathology Jun 2022Rhabdomyosarcoma (RMS), the most common malignant soft tissue tumor in children, has several histologic subtypes that influence treatment and predict patient outcomes....
Rhabdomyosarcoma (RMS), the most common malignant soft tissue tumor in children, has several histologic subtypes that influence treatment and predict patient outcomes. Assistance with histologic classification for pathologists as well as discovery of optimized predictive biomarkers is needed. A convolutional neural network for RMS histology subtype classification was developed using digitized pathology images from 80 patients collected at time of diagnosis. A subsequent embryonal rhabdomyosarcoma (eRMS) prognostic model was also developed in a cohort of 60 eRMS patients. The RMS classification model reached a performance of an area under the receiver operating curve of 0.94 for alveolar rhabdomyosarcoma and an area under the receiver operating curve of 0.92 for eRMS at slide level in the test data set (n = 192). The eRMS prognosis model separated the patients into predicted high- and low-risk groups with significantly different event-free survival outcome (likelihood ratio test; P = 0.02) in the test data set (n = 136). The predicted risk group is significantly associated with patient event-free survival outcome after adjusting for patient age and sex (predicted high- versus low-risk group hazard ratio, 4.64; 95% CI, 1.05-20.57; P = 0.04). This is the first comprehensive study to develop computational algorithms for subtype classification and prognosis prediction for RMS histopathology images. Such models can aid pathology evaluation and provide additional parameters for risk stratification.
Topics: Child; Deep Learning; Disease-Free Survival; Humans; Prognosis; Rhabdomyosarcoma; Rhabdomyosarcoma, Embryonal
PubMed: 35390316
DOI: 10.1016/j.ajpath.2022.03.011 -
Clinical and Experimental Medicine Oct 2023Rhabdomyosarcoma (RMS) is an aggressive rare neoplasm that derives from mesenchymal cells, which frequently develops resistance to the current therapies and the...
Rhabdomyosarcoma (RMS) is an aggressive rare neoplasm that derives from mesenchymal cells, which frequently develops resistance to the current therapies and the formation of metastases. Thus, new therapies are needed. The alteration of iron metabolism in cancer cells was effective in reducing the progression of many tumors but not yet investigated in RMS. Here we investigated the effect of iron modulation in RMS both in vitro and in vivo. We first characterized the most used RMS cell lines representing the most common subtypes, embryonal (ERMS, RD cells) and alveolar (ARMS, RH30 cells), for their iron metabolism, in basal condition and in response to its modulation. Then we investigated the effects of both iron overload and chelation strategies in vitro and in vivo. RMS cell lines expressed iron-related proteins, even if at lower levels compared to hepatic cell lines and they are correctly modulated in response to iron increase and deprivation. Interestingly, the treatment with different doses of ferric ammonium citrate (FAC, as iron source) and with deferiprone (DFP, as iron chelator), significantly affected the cell viability of RD and RH30. Moreover, iron supplementation (in the form of iron dextran) or iron chelation (in the form of DFP) were also effective in vivo in inhibiting the tumor mass growth both derived from RD and RH30 with iron chelation treatment the most effective one. All the data suggest that the iron modulation could be a promising approach to overcome the RMS tumor growth. The mechanism of action seems to involve the apoptotic cell death for both iron supplementation and chelation with the concomitant induction of ferroptosis in the case of iron supplementation.
Topics: Humans; Cell Line, Tumor; Rhabdomyosarcoma; Apoptosis; Iron; Iron Chelating Agents
PubMed: 36764998
DOI: 10.1007/s10238-023-01012-5 -
Scientific Reports Nov 2021Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been...
Rhabdomyosarcomas (RMS) represent a family of aggressive soft tissue sarcomas that present in both children and adults. Pathologic risk stratification for RMS has been based on histologic subtype, with poor outcomes observed in alveolar rhabdomyosarcoma (ARMS) and the adult-type pleomorphic rhabdomyosarcoma (PRMS) compared to embryonal rhabdomyosarcoma (ERMS). Genomic sequencing studies have expanded the spectrum of RMS, with several new molecularly defined entities, including fusion-driven spindle cell/sclerosing rhabdomyosarcoma (SC/SRMS) and MYOD1-mutant SC/SRMS. Comprehensive genomic analysis has previously defined the mutational and copy number spectrum for the more common ERMS and ARMS and revealed corresponding methylation signatures. Comparatively, less is known about epigenetic correlates for the rare SC/SRMS or PRMS histologic subtypes. Herein, we present exome and RNA sequencing, copy number analysis, and methylation profiling of the largest cohort of molecularly characterized RMS samples to date. In addition to ARMS and ERMS, we identify two novel methylation subtypes, one having SC/SRMS histology and defined by MYOD1 p. L122R mutations and the other matching adult-type PRMS. Selected tumors from adolescent patients grouped with the PRMS methylation class, expanding the age range of these rare tumors. Limited follow-up data suggest that pediatric tumors with MYOD1-mutations are associated with an aggressive clinical course.
Topics: Adolescent; Adult; Aged; Biomarkers, Tumor; Child; Child, Preschool; Computational Biology; DNA Copy Number Variations; DNA Methylation; Diagnosis, Differential; Disease Susceptibility; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; In Situ Hybridization; Infant; Male; Middle Aged; Mutation; Rhabdomyosarcoma; Whole Genome Sequencing; Young Adult
PubMed: 34782706
DOI: 10.1038/s41598-021-01649-w -
International Journal of Molecular... Feb 2024Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic... (Review)
Review
Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, or . ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.
Topics: Humans; Rhabdomyosarcoma, Alveolar; Transforming Growth Factor beta; Transforming Growth Factor beta1; Paired Box Transcription Factors; Epithelial-Mesenchymal Transition; Rhabdomyosarcoma; Oncogene Proteins, Fusion
PubMed: 38474036
DOI: 10.3390/ijms25052791 -
Dento Maxillo Facial Radiology Dec 2021To retrospectively analyze magnetic resonance imaging (MRI) features of various pathological subtypes of sinonasal rhabdomyosarcoma (RMS) and explore correlations...
OBJECTIVE
To retrospectively analyze magnetic resonance imaging (MRI) features of various pathological subtypes of sinonasal rhabdomyosarcoma (RMS) and explore correlations between imaging features and pathological subtypes.
METHODS
In total, 11 cases with embryonal, alveolar or pleomorphic sinonasal RMSs, confirmed by surgical pathology, were selected. Their characteristics and distinctive imaging features were analysed, and the correlation between pathology and imaging features was explored.
RESULTS
Bone destruction was observed in all 11 cases with RMS. Expansive growth was predominant in three alveolar and three embryonal RMS cases, and creeping growth was predominant in two alveolar, two embryonal and one pleomorphic RMS cases. Signs of residual mucosa were observed in all 11 cases, and 10 cases showed involvement of multiple sinus cavities and orbital cavities. All cases exhibited mild-to-intermediate enhancement.
CONCLUSION
Sinonasal RMSs have the following characteristic MRI features: ethmoid sinuses and middle nasal conchae are the prevalent sites; lesions are mainly of mild enhancement; tumours exhibit signs of residual mucosa, mild-to-intermediate enhancement and frequent orbital involvement; bone invasion and bone destruction are frequently observed; and haematogenous metastasis is not as common as lymphatic metastasis. RMSs of various pathological subtypes were not significantly distinct by imaging.
Topics: Humans; Magnetic Resonance Imaging; Paranasal Sinuses; Retrospective Studies; Rhabdomyosarcoma
PubMed: 33835837
DOI: 10.1259/dmfr.20210030 -
Journal of Oral and Maxillofacial... 2023Rhabdomyosarcoma (RMS) is the most common sarcoma among children and accounts for 20% of soft tissue sarcomas. In children, close to 50% of rhabdomyosarcomas arise in...
Rhabdomyosarcoma (RMS) is the most common sarcoma among children and accounts for 20% of soft tissue sarcomas. In children, close to 50% of rhabdomyosarcomas arise in the head and neck. RMS of the oral cavity is rare and is seen in only 10-12% of all head and neck lesions and the involvement of the jaws is extremely rare. Histopathologically, the various types are pleomorphic type, botryoid type, spindle cell type, embryonal, and alveolar type of RMS. The alveolar variant accounts for almost 30% of all rhabdomyosarcomas and tends to arise in patients of the age group 10-25 years. We present a case of orofacial RMS in a young adult who was referred to our Institution for the management of an odontogenic lesion of the maxilla. The clinicopathological aspects and poor survival rate as a consequence of delayed diagnosis are discussed. We dentists may misdiagnose it as an odontogenic tumour due to its location in the oral and maxillofacial region. Careful clinical history and examination and investigations may help to narrow down the diagnosis. Expert opinion and referrals to oral pathologists and oncologists are essential to arrive at early diagnosis and to initiate the treatment.
PubMed: 37854913
DOI: 10.4103/jomfp.jomfp_534_22 -
BMJ Case Reports Mar 2021Alveolar rhabdomyosarcoma (ARMS) has a predilection for the peripheral extremities, and brain metastases are rare, with only a few cases reported after the initial...
Alveolar rhabdomyosarcoma (ARMS) has a predilection for the peripheral extremities, and brain metastases are rare, with only a few cases reported after the initial diagnosis. We present a 22-year-old male patient with a right orbital-ethmoidal ARMS who presented with a recurrence to the brain 1 year after the initial diagnosis. He was referred to our institution due to acute neurological deterioration. A brain MRI was performed, showing an enhancing bilateral parafalcine lesion centred about the bilateral cingulate gyri with extension into the corpus callosum. The patient was taken to the operating room for a stereotactic biopsy under general anaesthesia, which was compatible with metastatic ARMS. Our case is exceedingly rare, considering the initial diagnosis of an orbital/ethmoidal ARMS, its subsequent metastasis to the brain and its clinical sequelae after a biopsy. Prognosis after cerebral metastatic ARMS is dismal, with most patients expiring due to central nervous system metastatic disease.
Topics: Adult; Brain; Brain Neoplasms; Humans; Male; Neoplasm Recurrence, Local; Rhabdomyosarcoma; Rhabdomyosarcoma, Alveolar; Young Adult
PubMed: 33664037
DOI: 10.1136/bcr-2020-240516 -
Frontiers in Oncology 2022Rhabdomyosarcoma (RMS) is a soft tissue tumor, which is the most common in the head, neck, limbs, and trunk. RMS originating from the epididymis is extremely rare....
Rhabdomyosarcoma (RMS) is a soft tissue tumor, which is the most common in the head, neck, limbs, and trunk. RMS originating from the epididymis is extremely rare. Herein, we reported a 34-year-old patient with RMS on the right epididymis. For this case, right epididymal mass resection was performed and intraoperative freezing suggested a malignant tumor. Right testicular radical resection was subsequently adopted, with right epididymal alveolar RMS being pathologically diagnosed. Alternating VAC/VI chemotherapy was given after surgery, and tumor recurrence has not been found so far.
PubMed: 36408167
DOI: 10.3389/fonc.2022.1027504