Quantitative diffusion-weighted MRI response assessment in rhabdomyosarcoma: an international retrospective study on behalf of the European paediatric Soft tissue sarcoma Study Group Imaging Committee.

OBJECTIVE: To investigate the feasibility of diffusion-weighted magnetic resonance imaging (DW-MRI) as a predictive imaging marker after neoadjuvant chemotherapy in patients with rhabdomyosarcoma. MATERIAL AND METHODS: We performed a multicenter retrospective study including pediatric, adolescent and young adult patients with rhabdomyosarcoma, Intergroup Rhabdomyosarcoma Study group III/IV, treated according to the European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS2005 or MTS2008 studies. DW-MRI was performed according to institutional protocols. We performed two-dimensional single-slice tumor delineation. Areas of necrosis or hemorrhage were delineated to be excluded in the primary analysis. Mean, median and 5th and 95th apparent diffusion coefficient (ADC) were extracted. RESULTS: Of 134 included patients, 82 had measurable tumor at diagnosis and response and DW-MRI scans of adequate quality and were included in the analysis. Technical heterogeneity in scan acquisition protocols and scanners was observed. Mean ADC at diagnosis was 1.1 (95% confidence interval [CI]: 1.1-1.2) (all ADC expressed in * 10-3 mm2/s), versus 1.6 (1.5-1.6) at response assessment. The 5th percentile ADC was 0.8 (0.7-0.9) at diagnosis and 1.1 (1.0-1.2) at response. Absolute change in mean ADC after neoadjuvant chemotherapy was 0.4 (0.3-0.5). Exploratory analyses for association between ADC and clinical parameters showed a significant difference in mean ADC at diagnosis for alveolar versus embryonal histology. Landmark analysis at nine weeks after the date of diagnosis showed no significant association (hazard ratio 1.3 [0.6-3.2]) between the mean ADC change and event-free survival. CONCLUSION: A significant change in the 5th percentile and the mean ADC after chemotherapy was observed. Strong heterogeneity was identified in DW-MRI acquisition protocols between centers and in individual patients.

Useful sonographic findings for diagnosing dermal metastases of rhabdomyosarcoma.

Rhabdomyosarcoma developing in deep locations, such as the genitourinary tract, and perianal and perineal regions, symptoms may be obscure. Dermal rhabdomyosarcoma metastases may be first symptom of that and those arise in the subcutaneous fat tissue, presenting as a high echoic area surrounded by a low echoic area, accompanied by a high echoic peripheral area. These sonographic findings might indicate an aggressive malignant disease, and that would be useful to differentiate from other dermal lesions.

INternational Soft Tissue saRcoma ConsorTium (INSTRuCT) consensus statement: Imaging recommendations for the management of rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue neoplasm in the pediatric population. The survival of children with rhabdomyosarcoma has only marginally improved over the past 25 years and remains poor for those with metastatic disease. A significant challenge to advances in treatment of rhabdomyosarcoma is the relative rarity of this disease, necessitating years to complete clinical trials. Progress can be accelerated by international cooperation and sharing national experiences. This necessitates agreement on a common language to describe patient cohorts and consensus standards to guide diagnosis, treatment, and response assessment. These goals formed the premise for creating the INternational Soft Tissue saRcoma ConsorTium (INSTRuCT) in 2017. Multidisciplinary members of this consortium have since developed international consensus statements on the diagnosis, treatment, and management of pediatric soft-tissue sarcomas. Herein, members of the INSTRuCT Diagnostic Imaging Working Group present international consensus recommendations for imaging of patients with rhabdomyosarcoma at diagnosis, at staging, and during and after completion of therapy. The intent is to promote a standardized imaging approach to pediatric patients with this malignancy to create more-reliable comparisons of results of clinical trials internationally, thereby accelerating progress in managing rhabdomyosarcoma and improving survival.

Cardiac and Pericardial Neoplasms in Children: Radiologic-Pathologic Correlation.

Primary cardiac and pericardial neoplasms are rare in the pediatric population and can include both benign and malignant lesions. Rhabdomyomas, teratomas, fibromas, and hemangiomas are the most common benign tumors. The most common primary cardiac malignancies are soft-tissue sarcomas, including undifferentiated sarcomas, rhabdomyosarcomas, and fibrosarcomas. However, metastatic lesions are more common than primary cardiac neoplasms. Children with primary cardiac and pericardial tumors may present with nonspecific cardiovascular symptoms, and their clinical presentation may mimic that of more common nonneoplastic cardiac disease. The diagnosis of cardiac tumors has recently been facilitated using noninvasive cardiac imaging. Echocardiography is generally the first-line modality for evaluation. Cardiac MRI and CT are used for tissue characterization and evaluation of tumor size, extension, and physiologic effect. The varied imaging appearances of primary cardiac neoplasms can be explained by their underlying abnormality. Treatment of these lesions varies from conservative management, with spontaneous regression of some lesions such as rhabdomyomas, to surgical resection, particularly in patients with associated heart failure. With adequate imaging techniques and knowledge of the pathologic basis of the neoplasm, it is often possible to differentiate benign from malignant tumors, which can greatly affect adequate and timely treatment. ©RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

The magnetic resonance characteristics of sinonasal rhabdomyosarcoma in adults: analysis of 27 cases and comparison with pathological subtypes.

BACKGROUND: Sinonasal rhabdomyosarcoma (RMS) in adults is extremely rare, and early diagnosis and treatment are crucial to improve the patient's prognosis. The purpose of this study was to evaluate the magnetic resonance imaging (MRI) findings of sinonasal RMS in adults and analyze the correlations between the imaging features and pathological subtypes. METHODS: We reviewed 27 patients with pathologically proven RMS of the nasal cavity and paranasal sinuses, including embryonal RMS (ERMS) in 14 patients, alveolar RMS (ARMS) in seven patients, and mixed-type RMS in six patients. Conventional MRI was performed in all 27 patients, and high-resolution diffusion-weighted imaging was conducted in 25 patients. The tumor location, size, morphological features, signal intensity, texture, contrast enhancement characteristics, lymph node metastases, apparent diffusion coefficients (ADCs), and involvement of local soft tissues were independently assessed by two authors. RESULTS: On MR imaging, sinonasal RMS appeared isointense on T1-weighted imaging in 21 cases (77.8%) and heterogeneously hyperintense on T2-weighted imaging in 18 patients (66.7%). After enhancement, the tumors were heterogeneously enhanced in 24 cases (88.9%). Botryoid enhancement with multiple small rings resembling bunches of grapes was found in 15 cases (55.6%). Mucosal invasion of the maxillary sinus was identified in 51.9% patients. Skull and orbit involvement were found in 55.6% and 81.5% patients, respectively. Lymph node metastasis was seen in 18 cases (66.7%). There were significant differences in botryoid enhancement (P = 0.044) and skull involvement (P = 0.044) among different histological subtypes. The mean ADC value of RMS was 0.73 ± 0.082 × 10-3 mm2/s, and there was no significant difference among different histological subtypes. CONCLUSIONS: Some characteristic MRI findings such as botryoid enhancement in the ethmoid sinus, involvement of the orbit and skull, and a lower ADC value can provide important clues for preoperative diagnosis of sinonasal RMS in adults. Further, botryoid enhancement was more common in ERMS, while skull involvement was more common in ARMS.

Correlation between IVIM parameters and microvessel architecture: direct comparison of MRI images and pathological slices in an orthotopic murine model of rhabdomyosarcoma.

OBJECTIVE: This study aimed to explore the correlation between intravoxel incoherent motion (IVIM) parameters and microvessel architecture (microvessel density (MVD), vasculogenic mimicry (VM), and pericyte coverage index (PCI)) in an orthotopic murine model of rhabdomyosarcoma. METHODS: The murine model was established by injecting rhabdomyosarcoma-derived (RD) cells into the muscle. Nude mice underwent routine magnetic resonance imaging (MRI) and IVIM examinations with ten b values (0, 50, 100, 150, 200, 400, 600, 800, 1000, and 2000 s/mm2). D, D*, and f values were calculated with the ADW4.7 workstation. MRI images and pathological slices were directly compared to ensure that radiology parameters accurately reflect pathology. MVD, VM, PCI, and cellularity were obtained by histological analysis. The correlations were assessed between IVIM parameters (D, D*, f, and fD* values) and pathological markers (MVD, VM, PCI, and cellularity). RESULTS: The average of D, D*, f, and fD* values were 0.55 ± 0.07 × 10-3 mm2/s, 5.25 ± 0.73 × 10-3 mm2/s, 13.39 ± 7.68%, and 0.73 ± 0.49 × 10-3 mm2/s, respectively. The average of MVD, VM, PCI, and cellularity were 41.91 ± 10.98, 1.16 ± 0.83, 0.49 ± 0.18, and 39.15 ± 9.00%. D*, f, and fD* values showed a positive correlation with MVD separately, while the D value did not correlate with MVD. D value negatively correlated to VM moderately, and other parameters did not associate with VM. D* and fD* values were positively correlated with PCI, but no correlation was observed between other parameters and PCI. CONCLUSIONS: IVIM may evaluate the tumor microvessel architecture. D*, f, and fD* may reflect the endothelial lining blood vessel; D could indirectly reflect the VM; D* and fD* could reflect PCI(the normal degree of the tumor blood vessel). CLINICAL RELEVANCE STATEMENT: An intravoxel incoherent motion may be useful in assessing rhabdomyosarcoma microvessel structure to predict the target and effectiveness of anti-angiogenic therapy. KEY POINTS: • IVIM may be used to evaluate the tumor microvessel architecture in the mouse rhabdomyosarcoma model. • The MRI-pathology control method achieves correspondence between MRI slices and pathology slices, which ensures the consistency of the ROI of MRI and the pathology observation region.

Primary Gastric Rhabdomyosarcoma.

Primary gastric rhabdomyosarcoma is extremely rare. An 87-year-old man visited our clinic with a chief complaint of abdominal pain. Computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography-CT revealed a massive tumor originating from the muscularis propria of the stomach along with splenic vein tumor thrombosis. We diagnosed the patient with primary gastric rhabdomyosarcoma by an endoscopic ultrasound-guided fine-needle aspiration/biopsy.

Rhabdomyosarcoma presenting as intramuscular haematoma due to brachioradialis tear after trauma.

A man in his 40s with a history of neurofibromatosis type 1 presented to the emergency department with worsening anterior elbow pain and swelling after falling from a chair 2 months prior. An X-ray showed soft tissue swelling without fracture and the patient was diagnosed with a rupture of the biceps muscle. MRI of the right elbow showed a brachioradialis tear with a large haematoma along the humerus. This was initially thought to be a haematoma; therefore, wound evacuation was done twice. When the injury failed to resolve, a tissue biopsy was performed. This revealed a grade 3 pleomorphic rhabdomyosarcoma. It is important to consider malignancy in the differential diagnosis with rapidly growing masses even if the initial presentation is suggestive of a benign condition. Neurofibromatosis type 1 is also associated with a higher risk of malignancy than the general population.

Imaging in rhabdomyosarcoma: a patient journey.

Rhabdomyosarcoma, although rare, is the most frequent soft tissue sarcoma in children and adolescents. It can present as a mass at nearly any site in the body, with most common presentations in the head and neck, genitourinary tract and extremities. The optimal diagnostic approach and management of rhabdomyosarcoma require a multidisciplinary team with multimodal treatment, including chemotherapy and local therapy. Survival has improved over the last decades; however, further improvement in management is essential with current 5-year overall survival ranging from 35% to 100%, depending on disease and patient characteristics. In the full patient journey, from diagnosis, staging, management to follow-up after therapy, the paediatric radiologist and nuclear physician are essential members of the multidisciplinary team. Recently, guidelines of the European paediatric Soft tissue sarcoma Study Group, the Cooperative Weichteilsarkom Studiengruppe and the Oncology Task Force of the European Society of Paediatric Radiology (ESPR), in an ongoing collaboration with the International Soft-Tissue Sarcoma Database Consortium, provided guidance for high-quality imaging. In this educational paper, given as a lecture during the 2022 postgraduate ESPR course, the multi-disciplinary team of our national paediatric oncology centre presents the journey of two patients with rhabdomyosarcoma and discusses the impact on and considerations for the clinical (paediatric) radiologist and nuclear physician. The key learning points of the guidelines and their implementation in clinical practice are highlighted and up-to-date insights provided for all aspects from clinical suspicion of rhabdomyosarcoma and its differential diagnosis, to biopsy, staging, risk stratification, treatment response assessment and follow-up.

Equivocal end-of-therapy imaging findings do not predict a higher risk of local relapse after definitive radiotherapy in pediatric Ewing sarcoma and rhabdomyosarcoma.

BACKGROUND: Posttherapy imaging studies can provide reassurance or induce anxiety regarding risk of recurrence for patients and their families. In some cases, it is difficult to determine if imaging findings represent posttreatment changes or residual disease. Equivocal radiographic findings can occur due to therapy-related inflammation or residual, inactive soft tissue masses, but it is unknown if such findings indicate an increased likelihood of local recurrence. The aim of this study was to assess the value of initial posttherapy scans for predicting local relapse in patients with Ewing sarcoma (EWS) or rhabdomyosarcoma (RMS) who received radiotherapy (RT) for local control. These findings are critical to inform clinicians' surveillance recommendations and ability to accurately counsel patients and their families. PROCEDURE: The primary endpoint was time to local progression (LP). Patients were classified as having posttherapy scans that were "positive" (residual disease within the RT field), "negative" (no evidence of residual disease within the RT field), or "equivocal" (no determination could be made). The value of initial posttreatment scans for predicting LP was assessed using positive predictive value (PPV) and negative predictive value (NPV). RESULTS: Negative imaging findings (n = 51) had an NPV of 88%, and positive imaging findings (n = 1) had a PPV of 100%. When equivocal findings (n = 16) were categorized with negative results (i.e., positive vs. equivocal/negative), the NPV was 90%. When equivocal findings were categorized with positive results (equivocal/positive vs. negative), the PPV was 12%. CONCLUSION: Equivocal findings within the RT field on end-of-therapy imaging studies indicate no higher risk of local recurrence than negative findings. These results may contribute to appropriate surveillance schedules and accurate counseling of patients with RMS and EWS who have received RT for local control.

Magnetic Resonance-Guided High Intensity Focused Ultrasound Generated Hyperthermia: A Feasible Treatment Method in a Murine Rhabdomyosarcoma Model.

Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is an established method for producing localized hyperthermia. Given the real-time imaging and acoustic energy modulation, this modality enables precise temperature control within a defined area. Many thermal applications are being explored with this noninvasive, nonionizing technology, such as hyperthermia generation, to release drugs from thermosensitive liposomal carriers. These drugs can include chemotherapies such as doxorubicin, for which targeted release is desired due to the dose-limiting systemic side effects, namely cardiotoxicity. Doxorubicin is a mainstay for treating a variety of malignant tumors and is commonly used in relapsed or recurrent rhabdomyosarcoma (RMS). RMS is the most common solid soft tissue extracranial tumor in children and young adults. Despite aggressive, multimodal therapy, RMS survival rates have remained the same for the past 30 years. To explore a solution for addressing this unmet need, an experimental protocol was developed to evaluate the release of thermosensitive liposomal doxorubicin (TLD) in an immunocompetent, syngeneic RMS mouse model using MRgHIFU as the source of hyperthermia for drug release.

Relapse after non-metastatic rhabdomyosarcoma: The impact of routine surveillance imaging on early detection and post-relapse survival.

BACKGROUND: Patients with rhabdomyosarcoma (RMS) whose disease relapses have little chance of being cured, so front-line treatments are usually followed up with surveillance imaging in an effort to detect any recurrences as early as possible, and thereby improve post-relapse outcomes. The real benefit of such routine surveillance imaging in RMS remains to be demonstrated, however. This retrospective, single-center study examines how well surveillance imaging identifies recurrent tumors and its impact on post-relapse survival. METHODS: The analysis concerned 79 patients <21 years old treated between 1985 and 2020 whose initially localized RMS relapsed. Clinical findings, treatment modalities, and survival were analyzed, comparing patients whose relapse was first suspected from symptoms they developed (clinical symptoms group) with those whose relapse was identified by radiological surveillance (routine imaging group). RESULTS: Tumor relapses came to light because of clinical symptoms in 42 cases, and on routine imaging in 37. The time to relapse was much the same in the two groups. The median overall survival (OS) and 5-year OS rate were, respectively, 10 months and 12.6% in the clinical symptoms group, and 11 months and 27.5% in the routine imaging group (p-value .327). Among patients with favorable prognostic scores, survival was better for those in the routine imaging group (5-year OS 75.0% vs. 33.0%, p-value .047). CONCLUSION: It remains doubtful whether surveillance imaging has any real impact on RMS relapse detection and patients' post-relapse survival. Further studies are needed to establish the most appropriate follow-up recommendations, taking the potentially negative effects of regular radiological exams into account.

Can 18 F-FDG-Positron Emission Tomography be a Prognostic Tool in Children With Rhabdomyosarcoma Treated With Definitive Radiotherapy?

BACKGROUND: Persisting residual masses at treatment completion are known in rhabdomyosarcoma (RMS) treated with definitive radiotherapy (RT) to the primary site, but their prognostic significance is uncertain. Tumor response as assessed by anatomic imaging is not prognostic and studies based on 18 F-FDG-PET response are limited. We report the prognostic significance of persistent FDG-avidity in residual masses, assessed 3-month postdefinitive RT, in pediatric RMS. MATERIALS AND METHODS: Children 15 years old or below with Group III/IV RMS who received only definitive radiotherapy for local control from June 2013 to December 2018, and had 18 F-FDG-PET CT at 3 months post-RT were retrospectively analyzed for outcomes and other prognostic factors. RESULTS: Sixty-three children were eligible (Group III-55, Group IV-8). 18 F-FDG-PET CT scan done 3 months postradiotherapy showed FDG-avid residual masses in 10 patients (15.9%), anatomic residual in 24 (38.1%), and no anatomic/FDG-avid residual in 29(46.0%). At a median follow-up of 38 months (interquartile range, 24 to 55 mo), 3-year EFS of patients with FDG-avid residual masses was 40.0% (95% CI: 18.7% to 85.5%) versus the rest of the cohort, which was 71.9% (95% CI: 59.8% to 86.5%) ( P =0.008). Three-year OS of patients with FDG-avid residual masses was 50.8% (95% CI: 25.7% to 100.0%) versus the rest of the cohort, which was 77.0% (95% CI: 65.1% to 91.0%) ( P =0.037). Presence of FDG-avid residual disease persisting post-RT affected both EFS [HR-3.34 (95% CI: 1.29 to 8.68) ( P =0.013)] and OS [HR-3.20 (95% CI: 1.01 to 10.12) ( P =0.048)] on univariate analysis and this significance was retained for EFS in multivariate analysis [HR-3.52 (95% CI: 1.33 to 9.30) ( P =0.011)]. CONCLUSIONS: Persistent metabolic activity in residual disease post-chemoradiotherapy in RMS may portend a poorer prognosis with an increased risk of relapse. This subset of high-risk patients needs to be identified, and further trials are warranted to develop strategies to improve their outcomes.