ABSTRACT
BACKGROUND: Parameningeal rhabdomyosarcoma (PM-RMS) is a rare and aggressive soft tissue malignancy that primarily occurs in the head and neck region. The standard treatment approach for RMS involves a multimodal therapy regimen, which includes surgery, chemotherapy, and radiotherapy. However, the routine use of radiotherapy and chemotherapy in young patients with RMS in the head and neck region can lead to adverse effects on dental development and thereby, pose a challenge in planning dental intervention. CASE PRESENTATION: This case report outlines the dental and facial developmental consequences in a 13-year-old child, who received chemo-radiotherapeutic intervention at the age of 7 years for the management of PM-RMS. Following treatment, the child exhibited significant dental complications, including arrested root growth and restricted mouth opening. CONCLUSIONS: This case highlights the necessity for interdisciplinary collaboration between oncologists, dentists, and other healthcare professionals to mitigate the adverse effects on dental health and overall quality of life in patients undergoing chemo-radiotherapy for rhabdomyosarcoma.
Subject(s)
Rhabdomyosarcoma , Humans , Adolescent , Rhabdomyosarcoma/complications , Rhabdomyosarcoma/therapy , Male , Tooth Root/abnormalities , Tooth Root/diagnostic imaging , Dentition, PermanentABSTRACT
Chimeric antigen receptor (CAR) T-cells targeting Fibroblast Growth Factor Receptor 4 (FGFR4), a highly expressed surface tyrosine receptor in rhabdomyosarcoma (RMS), are already in the clinical phase of development, but tumour heterogeneity and suboptimal activation might hamper their potency. Here we report an optimization strategy of the co-stimulatory and targeting properties of a FGFR4 CAR. We replace the CD8 hinge and transmembrane domain and the 4-1BB co-stimulatory domain with those of CD28. The resulting CARs display enhanced anti-tumor activity in several RMS xenograft models except for an aggressive tumour cell line, RMS559. By searching for a direct target of the RMS core-regulatory transcription factor MYOD1, we identify another surface protein, CD276, as a potential target. Bicistronic CARs (BiCisCAR) targeting both FGFR4 and CD276, containing two distinct co-stimulatory domains, have superior prolonged persistent and invigorated anti-tumor activities compared to the optimized FGFR4-specific CAR and the other BiCisCAR with the same 4-1BB co-stimulatory domain. Our study thus lays down the proof-of-principle for a CAR T-cell therapy targeting both FGFR4 and CD276 in RMS.
Subject(s)
B7 Antigens , Immunotherapy, Adoptive , Receptor, Fibroblast Growth Factor, Type 4 , Receptors, Chimeric Antigen , Rhabdomyosarcoma , Xenograft Model Antitumor Assays , Receptor, Fibroblast Growth Factor, Type 4/metabolism , Receptor, Fibroblast Growth Factor, Type 4/genetics , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/immunology , Rhabdomyosarcoma/genetics , Humans , Animals , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Cell Line, Tumor , Mice , Immunotherapy, Adoptive/methods , B7 Antigens/metabolism , B7 Antigens/immunology , B7 Antigens/genetics , MyoD Protein/metabolism , MyoD Protein/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Child , Female , Mice, SCID , Mice, Inbred NODABSTRACT
BACKGROUND: Recently, the infiltration of a subpopulation of cells represented by mononucleated cells extracted from peripheral blood [Peripheral Blood-Mononuclear Cells (PB-MNCs)] is becoming a useful technique for medical and surgical regenerative procedures. Due to the angiogenetic and regenerative properties of PB-MNCs, the infiltration of these cells is, in our opinion, a new option indicated in the treatment of pathologies characterized by tissue dystrophy, loss of vascularization, and non-healing wounds. CASE PRESENTATION: A 25-year-old active smoker patient was diagnosed with Rhabdomyosarcoma of the anterior tibial muscle of his left leg and treated with neoadjuvant chemo- and radiotherapy (RT). After the tumor excision, the patient developed wound dehiscence with bone exposure and a perilesional radiation-induced chronic dermatitis characterized by skin dyschromia and hair thinning along the treated area. The patient underwent surgical debridement and reconstruction with autologous skin grafts and dermal substitutes, with poor outcomes due to graft failure. The patient was subsequently treated with surgical debridement and coverage with a reverse sural fascia-cutaneous flap. After 13 days, wound dehiscence was observed, and reconstruction of the dehiscent areas was performed with a split-thickness autologous skin graft with no success. After wound debridement, a new split-thickness skin graft was performed, and a concentrate of autologous PB-MNCs was injected in the flap and perilesional skin. After 14 days, graft take was reached, and improvements in perilesional tissue tropism were noted. At 2 months follow-up, the patient appeared completely healed. CONCLUSIONS: In our opinion, the use of PB-MNCs to treat conditions characterized by tissue dystrophy, which require neoangiogenesis and cell regeneration, can be a useful and unconsidered technique that could be utilized to improve tissue tropism. Furthermore, prospective trials are necessary to validate our observations.
Subject(s)
Leukocytes, Mononuclear , Humans , Male , Adult , Leukocytes, Mononuclear/transplantation , Plastic Surgery Procedures/methods , Lower Extremity , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/surgery , Wound HealingABSTRACT
Rhabdomyosarcoma (RMS) is among the most common pediatric solid malignancies. Fusion-negative, embryonal RMS is the predominant histology among prostate and bladder lesions. Management strategies depend on the clinical stage and risk group. Although the optimal strategy continues to evolve, the field has transitioned from radical upfront resection to organ preservation strategies with multi-modal therapy, including chemotherapy, radiation, and surgery. Survivors frequently develop late complications, including impaired fertility and sexual function, bladder dysfunction, and secondary malignancies. Our case describes an 11-year-old male who developed a radiation-induced prostatic sarcoma. We present a novel surgical technique and highlight the importance of multidisciplinary care.
Subject(s)
Neoplasms, Radiation-Induced , Prostatic Neoplasms , Rhabdomyosarcoma , Sarcoma , Humans , Male , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Child , Sarcoma/etiology , Sarcoma/therapy , Sarcoma/radiotherapy , Neoplasms, Radiation-Induced/etiology , Neoplasms, Radiation-Induced/diagnosis , Rhabdomyosarcoma/radiotherapy , Rhabdomyosarcoma/therapy , Prostatectomy/adverse effects , Prostatectomy/methodsSubject(s)
Rhabdomyosarcoma , Humans , China/epidemiology , Retrospective Studies , Rhabdomyosarcoma/therapy , Child , Male , Female , Child, Preschool , Meningeal Neoplasms/therapyABSTRACT
OPINION STATEMENT: Rhabdomyosarcoma, a soft tissue sarcoma commonly observed in childhood, requires multidisciplinary treatment, including surgical tumor resection, chemotherapy, and radiation therapy. Although long-term survival can be expected in patients with localized rhabdomyosarcoma, the clinical outcomes in patients with metastatic or unresectable rhabdomyosarcoma remain unsatisfactory. To improve the outcomes of rhabdomyosarcoma, it is important to explore effective systemic treatments for metastatic rhabdomyosarcoma. Currently, multiagent chemotherapy comprising vincristine, actinomycin D, and ifosfamide/cyclophosphamide remains standard systemic treatment for rhabdomyosarcoma. On the other hand, new treatment, such as immune checkpoint inhibitors and molecular targeted drugs, have demonstrated superior clinical outcomes compared to those of standard treatments in various type of malignancies. Therefore, it is necessary to assess the efficacies of these treatments in patients with rhabdomyosarcoma. Recent clinical studies have shown efficacies and safeties of temozolomide combined with vincristine/irinotecan, olaratumab combined with doxorubicin or vincristine/irinotecan, and long-term maintenance therapy. Furthermore, basic researches demonstrated new therapeutic targets. Future studies using these approaches are required to assess their clinical significances.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Rhabdomyosarcoma , Humans , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/diagnosis , Rhabdomyosarcoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Management , Treatment Outcome , Molecular Targeted Therapy , Combined Modality Therapy/methods , Clinical Decision-Making , Clinical Trials as TopicABSTRACT
BACKGROUND: Novel therapies are needed for relapsed and refractory rhabdomyosarcoma (RRMS). Phase II clinical trials in RRMS have typically utilized radiologic response as the primary activity endpoint, an approach that poses several limitations in RRMS. In this analysis, we aimed to estimate an event-free survival (EFS) endpoint for RRMS that could be used as a benchmark for future studies. PROCEDURE: We performed a retrospective study of patients with RRMS enrolling on 13 single-agent phase II Children's Oncology Group and legacy group trials from 1997 to 2016. All included trials used radiographic response as their primary activity endpoint. Six-month EFS was estimated from time of trial enrollment with 95% confidence intervals. Clinical characteristics, including trial of enrollment, sex, age, race, histology, number of prior chemotherapies, and radiographic response were evaluated for their impact on 6-month EFS. RESULTS: We identified 175 patients across 13 trials. The 6-month EFS was 16.8% (11.6%-22.8%). No differences were seen in 6-month EFS based on age, sex, race, or histology. There were nonsignificant trends toward improved 6-month EFS for patients with less than or equal to two prior lines of therapy versus higher than two, for patients enrolled on trials that achieved their primary radiographic response endpoint versus trials that did not, and for patients who achieved complete or partial response compared to those achieving stable disease. CONCLUSIONS: The prognosis of RRMS enrolled on single-agent phase II trials is poor. This pooled 6-month EFS of RRMS on single-agent trials may be used as a RRMS-specific benchmark for future single-agent phase II trials.
Subject(s)
Clinical Trials, Phase II as Topic , Neoplasm Recurrence, Local , Rhabdomyosarcoma , Humans , Female , Male , Child , Rhabdomyosarcoma/mortality , Rhabdomyosarcoma/drug therapy , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/pathology , Retrospective Studies , Child, Preschool , Adolescent , Infant , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/drug therapy , Survival Rate , Prognosis , Follow-Up StudiesSubject(s)
Antineoplastic Combined Chemotherapy Protocols , Rhabdomyosarcoma , Humans , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/pathology , Walker-Warburg Syndrome/therapy , Walker-Warburg Syndrome/genetics , Male , Combined Modality Therapy , Feasibility StudiesABSTRACT
Importance: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma. Objective: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma. Design, Setting, and Participants: In this cohort study, data were obtained for individuals, aged 0.01-23.23 years, newly diagnosed with rhabdomyosarcoma who were treated across 171 Children's Oncology Group sites from March 15, 1999, to December 8, 2017. Data analysis was performed from June 16, 2021, to May 15, 2023. Exposure: The presence of a CPV in 24 rhabdomyosarcoma-associated cancer-predisposition genes (CPGs) or an expanded set of 63 autosomal-dominant CPGs. Main Outcomes and Measures: Overall survival (OS) and event-free survival (EFS) were the main outcomes, using the Kaplan-Meier estimator to assess survival probabilities and the Cox proportional hazards regression model to adjust for clinical covariates. Analyses were stratified by tumor histology and the fusion status of PAX3 or PAX7 to the FOXO1 gene. Results: In this study of 580 individuals with rhabdomyosarcoma, the median patient age was 5.9 years (range, 0.01-23.23 years), and the male-to-female ratio was 1.5 to 1 (351 [60.5%] male). For patients with CPVs in rhabdomyosarcoma-associated CPGs, EFS was 48.4% compared with 57.8% for patients without a CPV (P = .10), and OS was 53.7% compared with 65.3% for patients without a CPV (P = .06). After adjustment, patients with CPVs had significantly worse OS (adjusted hazard ratio [AHR], 2.49 [95% CI, 1.39-4.45]; P = .002), and the outcomes were not better among patients with embryonal histology (EFS: AHR, 2.25 [95% CI, 1.25-4.06]; P = .007]; OS: AHR, 2.83 [95% CI, 1.47-5.43]; P = .002]). These associations were not due to the development of a second malignant neoplasm, and importantly, patients with fusion-negative rhabdomyosarcoma who harbored a CPV had similarly inferior outcomes as patients with fusion-positive rhabdomyosarcoma without CPVs (EFS: AHR, 1.35 [95% CI, 0.71-2.59]; P = .37; OS: AHR, 1.71 [95% CI, 0.84-3.47]; P = .14). There were no significant differences in outcome by CPV status of the 63 CPG set. Conclusions and Relevance: This cohort study identified a group of patients with embryonal rhabdomyosarcoma who had a particularly poor outcome. Other important clinical findings included that individuals with TP53 had poor outcomes independent of second malignant neoplasms and that patients with fusion-negative rhabdomyosarcoma who harbored a CPV had outcomes comparable to patients with fusion-positive rhabdomyosarcoma. These findings suggest that germline CPV testing may aid in clinical prognosis and should be considered in prospective risk-based clinical trials.
Subject(s)
Neoplasms, Second Primary , Rhabdomyosarcoma , Child , Humans , Female , Male , Cohort Studies , Prospective Studies , Rhabdomyosarcoma/genetics , Rhabdomyosarcoma/therapy , Genetic Testing , Germ CellsABSTRACT
PURPOSE: Primary intrascrotal rhabdomyosarcoma (RMS) is a rare and aggressive tumor. The purpose of this study was to investigate the prognostic factors of intrascrotal RMS in children. METHODS: All pediatric patients with intrascrotal RMS diagnosed between 2000 and 2018 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. To compare survival curves, the log-rank test was employed. A multivariate Cox proportional hazards model was developed to investigate the effect of each factor on overall survival (OS). A nomogram was created using the outcomes of the Cox regression model. RESULTS: A total of 102 pediatric patients with intrascrotal RMS were identified. Overall survival rates for all patients were 90.6% at 3-year and 87.2% at 5-year, respectively. Survival rates differed significantly by SEER stage and surgery; however, chemotherapy and removal of lymph nodes showed no significant difference. The outcome of Cox proportional hazard regression revealed that SEER stage and surgery were important independent predictors in this model. Furthermore, we developed a nomogram for predicting OS in pediatric intrascrotal RMS based on the Cox regression model. The risk of death increased with stage in patients. Additionally, patients who underwent surgery had a lower mortality risk than those who did not. CONCLUSIONS: Our findings show that SEER stage and surgery are the most important indicators of OS in children with intrascrotal RMS, providing critical epidemiological information for clinical therapy.
Subject(s)
Genital Neoplasms, Male , Rhabdomyosarcoma , Scrotum , Humans , Male , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/mortality , Child , Child, Preschool , Prognosis , Genital Neoplasms, Male/therapy , Genital Neoplasms, Male/pathology , Genital Neoplasms, Male/mortality , Infant , Survival Rate , SEER Program , Nomograms , Adolescent , Retrospective StudiesABSTRACT
BACKGROUND: The objective of this study was to investigate the role of clinical factors together with FOXO1 fusion status in patients with nonmetastatic rhabdomyosarcoma (RMS) to develop a predictive model for event-free survival and provide a rationale for risk stratification in future trials. METHODS: The authors used data from patients enrolled in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) RMS 2005 study (EpSSG RMS 2005; EudraCT number 2005-000217-35). The following baseline variables were considered for the multivariable model: age at diagnosis, sex, histology, primary tumor site, Intergroup Rhabdomyosarcoma Studies group, tumor size, nodal status, and FOXO1 fusion status. Main effects and significant second-order interactions of candidate predictors were included in a multiple Cox proportional hazards regression model. A nomogram was generated for predicting 5-year event-free survival (EFS) probabilities. RESULTS: The EFS and overall survival rates at 5 years were 70.9% (95% confidence interval, 68.6%-73.1%) and 81.0% (95% confidence interval, 78.9%-82.8%), respectively. The multivariable model retained five prognostic factors, including age at diagnosis interacting with tumor size, tumor primary site, Intergroup Rhabdomyosarcoma Studies clinical group, and FOXO1 fusion status. Based on each patient's total score in the nomogram, patients were stratified into four groups. The 5-year EFS rates were 94.1%, 78.4%, 65.2%, and 52.1% in the low-risk, intermediate-risk, high-risk, and very-high-risk groups, respectively, and the corresponding 5-year overall survival rates were 97.2%, 91.5%, 74.3%, and 60.8%, respectively. CONCLUSIONS: The results presented here provide the rationale to modify the EpSSG stratification, with the most significant change represented by the replacement of histology with fusion status. This classification was adopted in the new international trial launched by the EpSSG.
Subject(s)
Nomograms , Rhabdomyosarcoma , Humans , Rhabdomyosarcoma/mortality , Rhabdomyosarcoma/pathology , Rhabdomyosarcoma/therapy , Male , Female , Child, Preschool , Child , Prognosis , Infant , Risk Assessment , Adolescent , Europe/epidemiology , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Oncogene Proteins, Fusion/geneticsABSTRACT
OBJECTIVES: To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS). METHODS: Retrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019. RESULTS: Of 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7-FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow-up time was 34.3 months. The 3-year overall survival (OS) and event-free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region. CONCLUSION: Majority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7-FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.
Subject(s)
Nasolabial Fold , Rhabdomyosarcoma , Child , Humans , Nasolabial Fold/pathology , Neoplasm Recurrence, Local , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/pathology , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
BACKGROUND: The aim of this study was to assess the clinical impact of indeterminate pulmonary nodules (no more than four pulmonary nodules of less than 5 mm or one nodule measuring between 5 and less than 10 mm by computed tomography [CT]) in children and adolescents with adult-type non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) at diagnosis. METHODS: Patients with NRSTS treated in 11 centers as part of the European paediatric Soft Tissue Sarcoma Study Group (EpSSG) were retrospectively assessed. Local radiologists, blinded to clinical information except for patients' age and tumor histotype, reviewed the chest CT at diagnosis and filled out a case report form. Because patients with or without indeterminate nodules in the EpSSG NRSTS 2005 study received the same type of treatment, event-free survival (EFS) and overall survival (OS) between groups by log-rank test were compared. RESULTS: Overall, 206 patients were examined: 109 (52.9%) were without any nodules, 78 (38%) had at least one indeterminate nodule, and 19 (9.2%) had nodules meeting the definition of metastases, which were then considered to be misclassified and were excluded from further analyses. Five-year EFS was 78.5% (95% CI, 69.4%-85.1%) for patients without nodules and 69.6% (95% CI, 57.9%-78.7%) for patients with indeterminate nodules (p = .135); 5-year OS was 87.4% (95% CI, 79.3%-92.5%) and 79.0% (95% CI, 67.5%-86.8%), respectively (p = .086). CONCLUSIONS: This study suggests that survival does not differ in otherwise nonmetastatic patients with indeterminate pulmonary nodules compared to nonmetastatic patients without pulmonary nodules. PLAIN LANGUAGE SUMMARY: Radiologists should be aware of the classification of indeterminate pulmonary nodules in non-rhabdomyosarcoma soft tissue sarcomas and use it in their reports. More than a third of patients with non-rhabdomyosarcoma soft tissue sarcoma can be affected by indeterminate pulmonary nodules. Indeterminate pulmonary nodules do not significantly affect the overall survival of pediatric patients with non-rhabdomyosarcoma soft tissue sarcoma.
Subject(s)
Rhabdomyosarcoma , Sarcoma , Soft Tissue Neoplasms , Humans , Child , Adult , Adolescent , Retrospective Studies , Sarcoma/drug therapy , Rhabdomyosarcoma/therapy , Soft Tissue Neoplasms/pathology , Progression-Free SurvivalABSTRACT
Soft tissue sarcomas (STS) represent a heterogeneous group of extraskeletal mesenchymal tumors that affect individuals throughout the entire age continuum. Despite this pervasive influence, key differences exist in the presentation of these sarcomas across varying age groups that have prevented a more uniform approach to management. Notably, rhabdomyosarcoma (RMS) is more common in children, while most nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) subtypes are more prevalent in adults. Older patients with NRSTS appear to have more molecularly complex biology and often present with more advanced disease compared with children. Poorer outcome disparities are observed in older patients with RMS despite receiving similar treatment as younger patients. In this review, we highlight differences in epidemiology, biology, and management paradigms for pediatric and adult patients with STS and explore opportunities for a unified approach to enhance the care and outcomes within the AYA population.
Subject(s)
Rhabdomyosarcoma , Sarcoma , Soft Tissue Neoplasms , Child , Humans , Adolescent , Young Adult , Aged , Sarcoma/therapy , Sarcoma/drug therapy , Rhabdomyosarcoma/epidemiology , Rhabdomyosarcoma/genetics , Rhabdomyosarcoma/therapy , Soft Tissue Neoplasms/epidemiology , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/therapyABSTRACT
KEY POINTS: Surgery in adults with head and neck rhabdomyosarcoma does not improve survival rates. Surgery should be performed deliberately and focused on the timing of combined treatment modality. Adult head and neck rhabdomyosarcoma benefits from salvage surgery following chemoradiotherapy.
Subject(s)
Head and Neck Neoplasms , Rhabdomyosarcoma , Humans , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/therapy , Rhabdomyosarcoma/surgery , Rhabdomyosarcoma/therapy , Adult , Retrospective Studies , Male , Female , Middle Aged , Salvage Therapy , Combined Modality Therapy , Chemoradiotherapy , Treatment Outcome , Aged , Young AdultABSTRACT
Rhabdomyosarcoma (RMS), a tumor that consists of poorly differentiated skeletal muscle cells, is the most common soft-tissue sarcoma in children. Despite considerable progress within the last decades, therapeutic options are still limited, warranting the need for novel approaches. Recent data suggest deregulation of the Smyd1 protein, a sumoylation target as well as H3K4me2/3 methyltransferase and transcriptional regulator in myogenesis, and its binding partner skNAC, in RMS cells. Here, we show that despite the fact that most RMS cells express at least low levels of Smyd1 and skNAC, failure to upregulate expression of these genes in reaction to differentiation-promoting signals can always be observed. While overexpression of the Smyd1 gene enhances many aspects of RMS cell differentiation and inhibits proliferation rate and metastatic potential of these cells, functional integrity of the putative Smyd1 sumoylation motif and its SET domain, the latter being crucial for HMT activity, appear to be prerequisites for most of these effects. Based on these findings, we explored the potential for novel RMS therapeutic strategies, employing small-molecule compounds to enhance Smyd1 activity. In particular, we tested manipulation of (a) Smyd1 sumoylation, (b) stability of H3K4me2/3 marks, and (c) calpain activity, with calpains being important targets of Smyd1 in myogenesis. We found that specifically the last strategy might represent a promising approach, given that suitable small-molecule compounds will be available for clinical use in the future.
Subject(s)
Rhabdomyosarcoma , Transcription Factors , Child , Humans , Transcription Factors/metabolism , DNA-Binding Proteins/metabolism , Rhabdomyosarcoma/genetics , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/pathology , Muscle Fibers, Skeletal/metabolism , Cell Differentiation/genetics , Cell Line, TumorABSTRACT
Perianal/perineal rhabdomyosarcomas (PRMS) is rare, and the outcome is poor. A 29-year-old female presented with perineal rhabdomyosarcomas revealed metastases to inguinal lymph nodes on the bilateral side. Disease progression was discovered when the patient got adjuvant epirubicin, ifosfamide, and bevacizumab for 2 cycles. After 3 cycles of nivolumab, dacarbazine, cisplatin, and vinblastine therapy, a partial response was identified in the patient. The surgical resection was performed. The patient received neoadjuvant chemotherapy before surgery and was weak after surgery, so he did not receive chemoradiotherapy. The patient succumbed after 11 months postoperatively due to widespread intraabdominal metastasis.
Subject(s)
Rhabdomyosarcoma , Male , Female , Humans , Adult , Rhabdomyosarcoma/diagnosis , Rhabdomyosarcoma/therapy , Rhabdomyosarcoma/pathology , Neoadjuvant Therapy , Lymph Nodes/pathology , Ifosfamide , Disease Progression , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Objective:To explore the clinical manifestations,the type of pathology, treatment and prognosis of laryngeal rhabdomyosarcoma, and to enhance the understanding of the clinical characteristics of the disease, while improving the diagnosis rateand reducing the misdiagnosis rate, in order to explore effective diagnosis and treatment methods. Methods:A retrospective analysis was conducted on the clinical data of 5 cases of laryngeal rhabdomyosarcoma treated in the First Affiliated Hospital of Zhengzhou University from May 2015 to May 2021. Results:All 5 cases of laryngeal rhabdomyosarcoma were misdiagnosed in the early stage. with tumors mostly occurring in the vocal cords and appearing as smooth mass. The clinical symptoms were mostly hoarseness. According to pathological classification, three cases were embryonic type, one case was polymorphic type, and one case was spindle type.Three patients died due to tumor recurrence, one patient had multiple systemic metastases, and another patient who underwent surgical resection in the early stage and supplemented with postoperative radiotherapy and chemotherapyhas been followed up to date without recurrence. Conclusion:Laryngeal rhabdomyosarcoma has low incidence rate, high malignancy degree and poor prognosis. It is easy to be misdiagnosed as a benign mass. Extensive surgical resection combined with radiotherapy and chemotherapy should be performed as soon as possible after diagnosis.