The 5‐year OS rate after recurrence was 28.3% (Fig. The median follow‐up for survivors was 83.7 months after initial diagnosis (range, 5.4–240.3 months) and 41.0 months after recurrence (range, 0.0–226.7 months). Embryonal rhabdomyosarcoma (ERMS), a rare category of soft tissue sarcoma (STS), originates in the mesenchymal tissue. Anaplastic Lymphoma Kinase Aberrations in Rhabdomyosarcoma: Clinical and Prognostic Implications. The Ignatius laboratory is interested in understanding the effects of tumor heterogeneity on relapse and resistance to therapies in Rhabdomyosarcoma and other sarcomas. The results of the current analysis demonstrated that groups with a different prognosis can be identified among patients with recurrent RMS. Age at diagnosis (10 years for children with embryonal rhabdomyosarcoma… We report a case of an 18-year-old male whose disease relapsed in the abdominal … Clinical outcomes from a multi-institutional cohort. Initial tumor site also is an important variable after recurrence. Outcome of patients with localized orbital sarcoma who relapsed following treatment on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols‐III and ‐IV, 1984–1997: A report from the Children's Oncology Group. Recurrences occurred while on therapy in 22% of patients, within 18 months of diagnosis in 50.4% of patients, and within 5 years of diagnosis in 95% of patients. Get the latest public health information from CDC:, Get the latest research information from NIH:, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: 62. Please check your email for instructions on resetting your password. Univariate analysis showed a higher 5‐year OS rate for Group III patients compared with Group II patients, but the difference was not statistically significant. XRT was not recommended in children age < 3 years, and primary reexcision was the treatment of choice, wherever feasible. The use of experimental therapies may be questionable for children with a single risk factor (32%), whose prognosis is not so poor. Various chemotherapeutic regimens were used after recurrence, thus preventing any further analysis. 2020 Jun;74(3):240-242. doi: 10.5455/medarh.2020.74.240-242. Patients with a nonalveolar histology, primary tumor site different from parameningeal and “other” sites, local recurrence, and recurrence off therapy had a better prognosis. The first‐line treatment was assigned on the basis of the initial surgery. After the third relapse, she was treated with prednisolone and cyclosporine (at initial dose of 50 mg/day [1.7 mg/kg/day]) for immunosuppression. It is now possible to cure nearly 3 of every 4 children with rhabdomyosarcoma. No significant differences emerged when patients were analyzed by protocol (see Table 2). Previous reports have identifi ed a wide range of genetic aberrations in embryonal rhabdomyosarcoma, including LOH at 11p15.5 ( 5 ) as well as mutations in TP53 ( 6 ), NRAS, KRAS, HRAS ( 7 ), Spindle cell RMS is a rare variant of embryonal RMS that has a predilection for young … Does surgery have a role in the treatment of local relapses of non‐metastatic rhabdomyosarcoma?. Late relapse of embryonal rhabdomyosarcoma, botryoid variant, of the vagina @article{Vasquez2008LateRO, title={Late relapse of embryonal rhabdomyosarcoma, botryoid variant, of the vagina}, author={R. Vasquez and P. Collini and C. Meazza and F. Favini and M. Casanova and A. Ferrari}, journal={Pediatric Blood & Cancer}, year={2008}, … Unfortunately, the value of histologic assessment is uncertain: In the SIOP MMT84 study, the local recurrence rate remained high even when biopsies apparently confirmed clinical remission,11 and this has been confirmed by the ICG experience (our unpublished data). Please enable it to take advantage of the complete set of features! Although > 90% of children with nonmetastatic rhabdomyosarcoma (RMS) achieve complete remission with current treatment, up to one‐third of them experience a recurrence. To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols. eCollection 2020. The … In fact, patients who had no or only one risk factor and patients who had tumors with a nonalveolar histology benefited more from salvage therapy if they had not received radiotherapy for their initial treatment. Onco Targets Ther. Albert & Jakobiec's Principles & Practice of Ophthalmology. International Journal of Radiation Oncology*Biology*Physics. No toxic deaths were recorded. Cancer 1982;49:2217-21. There are two kinds of muscle cells in the body: smooth muscle cells and skeletal muscle cells. 31 It is the most common sarcoma of childhood, accounting for 5% to 15% of all childhood solid tumors and 4% to 8% of all childhood malignancies. This chart illustrates overall survival (OS) according to the risk stratification model in patients with recurrent rhabdomyosarcoma. Univariate analysis showed that tumor histology was an important predictor of 5-year survival (P <.001): the 5-year survival rate was 64% for patients with botryoid tumors (n = 19), 26% for patients with embryonal tumors (n = 313), and 5% for patients with alveolar or undifferentiated sarcoma (n = 273). Survival. Among the 41 patients who had disease progression, 39 patients died of disease, and 2 patients achieved a long‐term remission and were alive 4 years and 10 years after progression. Most patients had local recurrences (72%). In this subgroup, intensive standard chemotherapy may be appropriate combined with XRT in patients who have not received it previously. The 5‐year OS rates per prognostic variable are given in Table 2. The authors thank Ilaria Zanetti and Angela Scagnellato for data processing and Gloria Tridello and Gianluca De Salvo for the statistical analysis. Initial Patient Characteristics Can Predict Pattern and Risk of Relapse in Localized Rhabdomyosarcoma. Outcome of children with neuroblastoma after progression or relapse. 1), with a median survival of 15.4 months. To be more precise, a patient with a PM RMS or with RMS at “other” sites who had received XRT during first‐line treatment had very little chance of surviving a systemic, early recurrence. Rhabdomyosarcoma in Children and Adolescents: Patterns and Risk Factors of Distant Metastasis. HHS The initial characteristics of the 125 patients with RMS who experienced a recurrence are listed in Table 1. Background: Raney RB, Anderson JR, Barr FG, Donaldson SS, Pappo AS, Qualman SJ, Wiener ES, Maurer HM, Crist WM. But for kids whose tumors grow back, or when the cancer spreads to other areas of the body, we face a major challenge… The results of multivariate analysis were used to develop a risk‐stratification model, and survival was calculated on the basis of the number of prognostic factors for each child (Fig. Rhabdomyosarcoma (RMS or ‘rhabdo’) is a tumor made up of cancerous cells that look like immature muscle cells. The impact of radiotherapy on clinical outcomes in parameningeal rhabdomyosarcoma. This is consistent with the experience of Pappo et al.6 who, considering children with Group I–IV disease who were treated on the IRS‐III, IRS‐IV pilot, and IRS‐IV protocols, reported a 5‐year survival rate after recurrence of 5% for patients with an alveolar histology compared with 26% for patients with the embryonal subtype. The 5‐year survival rate was 71.8% for children who had no risk factors (12% of patients with recurrences) and 37.5% and 16.1% for children who had 1 or 2 risk factors, respectively. Among 15 patients with 0 risk factors (solid line), there were 5 treatment failures (5‐year OS, 71.8%; 95% confidence interval [95%CI], 48.3–95.3%). Would you like email updates of new search results? Case Report of a Local Recurrence of Spindle Cell Embryonal Rhabdomyosarcoma.  |  Methods A 20 year old male presented with a 3 week history of headaches and nausea. The 5‐year overall survival (OS) rate was 28.3% ± 8.7%. International Journal of Clinical Oncology. The median time from diagnosis to recurrence was 17.8 months (range, from 1.7 months to 12.0 years) and was 14.0 months for patients with systemic recurrences and 19.3 months for patients with local recurrences. Rhabdomyosarcoma (RMS) is a malignant tumor (\"cancer\") that arises from a normal skeletal muscle cell. The median time from diagnosis to recurrence was 17.8 months. Learn about our remote access options, Division of Pediatrics, Maternity and Children's Department, Hospital of Camposampiero, Padua, Italy, Division of Hematology‐Oncology, Department of Pediatrics, University‐Hospital of Padua, Padua, Italy, Department of Pediatric Hematology‐Oncology, “G. Follow‐up was updated at September, 2003. Introduction. This mathematical model does not take single risk factors into account. None of the children with 3 or 4 risk factors were alive after 5 years (P < 0.0001). Local Failure in Parameningeal Rhabdomyosarcoma Correlates With Poor Response to Induction Chemotherapy. Immunotherapy with ganitumab, may induce changes in body’s immune system and may interfere with the ability of tumor cells to grow and spread. Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group. In the ICG RMS 79 and RMS 88 protocols, XRT was avoided in patients with histologic complete remission at secondary surgery after primary chemotherapy. This analysis demonstrates that the probability of 5-year survival after relapse for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, disease group, and stage. Only about 15-20% of patients will have visible spreading (metastasis) of … Use the link below to share a full-text version of this article with your friends and colleagues. Management of Refractory Pediatric Sarcoma: Current Challenges and Future Prospects. Pediatr Blood Cancer. Building the bridge between rhabdomyosarcoma in children, adolescents and young adults: The road ahead. Survival rates are not always … Conclusion: Selecting multimodal therapy for rhabdomyosarcoma. Mulita F, Parchas N, Germanos S, Papadoulas S, Maroulis I. Med Arch. Embryonal rhabdomyosarcoma (ERMS) ERMS usually affects children in their first 5 years of life, but it can occur at older ages as well. For example, children with embryonal rhabdomyosarcoma (ERMS) and limited spread (to only 1 or 2 distant sites) have a higher 5-year survival rate. The data emerging from this study may be useful in planning risk‐adapted salvage protocols, such as the Children's Oncology Group ARST 0121 randomized Phase II window study concerning new drug combinations. J Pediatr Hematol Oncol. PDF | Rhabdomyosarcoma is a malignant tumor of skeletal muscle origin. If you do not receive an email within 10 minutes, your email address may not be registered, Over the last four decades, there have been no significant improvements in clinical outcomes for advanced and metastatic RMS patients, underscoring a need for new treatment options for these groups. Influence of Noncompliance With Radiation Therapy Protocol Guidelines and Operative Bed Recurrences for Children With Rhabdomyosarcoma and Microscopic Residual Disease: A Report From the Children's Oncology Group. Clipboard, Search History, and several other advanced features are temporarily unavailable. The embryonal type is the most common among the 3 types and the malignancy occurs in the head, neck or genitals of the child. Most of them were classified in IRS Group III (72.8%). It … Multivariate assessment of OS was performed using a Cox proportional hazards model.9. Number of times cited according to CrossRef: Late Effects in Children and Adolescents with Soft Tissue Sarcoma. Primary tumor site, histologic subtype (alveolar or nonalveolar), regional lymph node involvement, and tumor size at the time of initial diagnosis also were considered. Phase II results from a phase I/II study to assess the safety and efficacy of weekly nab-paclitaxel in paediatric patients with recurrent or refractory solid tumours: A collaboration with the European Innovative Therapies for Children with Cancer Network. We used the prognostic factors identified by multivariate analysis to develop a risk‐stratification model for children with recurrent RMS. A Chart Review on the Feasibility and Safety of the Vincristine Irinotecan Pazopanib (VIPaz) Association in Children and Adolescents With Resistant or Relapsed Sarcomas. In the subset of children who had > 1 risk factor, the survival rate was slightly better in the 29 patients who were not treated initially with XRT (19.1%; 95%CI, 2.2–36.0%) compared with the 41 patients who received initial XRT (6.6%; 95%CI, 0.0–17.1%), but the difference was not statistically significant (P = 0.15). Journal of Clinical Oncology 1999; 17:3487-3493. ... Relapses are less common after 5 years but around 9% may relapse after 10 years. The purpose of surgical exploration after chemotherapy alone is to avoid XRT or use it in lower doses. Embryonal rhabdomyosarcoma (ERMS) has a low prevalence, poor prognosis, and limited treatment efficacy.  |  Four prognostic factors that were associated with a longer survival emerged from the multivariate analysis (Table 3): histology, primary tumor site, type of recurrence, and its relation with therapy. Relapse … Failure pattern and factors predictive of local failure in rhabdomyosarcoma: a report of group III patients on the third Intergroup Rhabdomyosarcoma Study. The primary tumor site was orbit in 15.2% of patients, nonparameningeal head and neck (non‐PM HN) in 12.8% of patients, parameningeal (PM) in 14.4% of patients, extremity in 15.2% of patients, genitourinary bladder/prostate (GU B/P) in 6.4% of patients, genitourinary nonbladder/prostate (GU non‐B/P) in 4.8% of patients, and “other” sites in 31.2% of patients (trunk, paraspinal region, intrathoracic and intraabdominal organs, pelvis, and perineal region). Up to one‐third of patients experience recurrence,3-5 however. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username, By continuing to browse this site, you agree to its use of cookies as described in our, Associazione Italiana di Ematologia e Oncologia Pediatrica Soft Tissue Sarcoma Committee, I have read and accept the Wiley Online Library Terms and Conditions of Use, Long‐term results in childhood rhabdomyosarcoma: a retrospective study in Italy, The Intergroup Rhabdomyosarcoma Study‐III, Treatment of nonmetastatic rhabdomyosarcoma in childhood and adolescence. Mesenchymal, Fibroosseous, and Cartilaginous Orbital Tumors. COVID-19 is an emerging, rapidly evolving situation.  |  For the purpose of this study, recurrences were classified as local (local recurrence alone and/or regional recurrence) or systemic (distant metastases alone or combined with local/regional recurrence) and were defined as early (< 18 months after first diagnosis) or late (≥ 18 months after first diagnosis). Introduction: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents. Rhabdomyosarcoma diagnosed in the first year of life: Localized, metastatic, and relapsed disease. In many other cases, combination with radiation therapy may be used to minimize the risk of tumor recurrence or relapse. Whereas the best timing and modulation of local tumor control still is debated, the development of methods for ascertaining the presence of minimal residual disease is desirable. The embryonal subtype was the most common, as expected. ERMS is also known as Fusion-Negative rhabdomyosarcoma … Long‐term results in childhood rhabdomyosarcoma: A report from the Italian cooperative study RMS 79. Raney B, Anderson J, Breneman J, Donaldson SS, Huh W, Maurer H, Michalski J, Qualman S, Ullrich F, Wharam M, Meyer W; Soft-Tissue Sarcoma Committee of the Children's Oncology Group, Arcadia, California, USA. In the current series, approximately one‐third of patients with nonmetastatic RMS who achieved a complete remission subsequently developed a recurrence, which is consistent with the data reported in the literature.3-5 Local recurrence was the most common cause of treatment failure; the rate of local (and/or regional) recurrence (72%) observed in the current study was similar to that reported in the International Society of Pediatric Oncology (SIOP) malignant mesenchymal (MMT84) study (75%),10 which considered patients with Group I–III disease, whereas Pappo et al.6 reported a lower rate (51% of patients who developed a recurrence), probably because of the initial local therapy (most patients received XRT) and, above all, because they included patients with Group IV disease and/or progressive disease, characteristics that give rise to a relatively higher frequency of systemic recurrence. After the third relapse, she was treated with prednisolone and cyclosporine (at initial dose of 50mg/day [1.7mg/kg/day]) for immunosuppression. Children with RMS who have systemic recurrences are more difficult to rescue, and only 10% survive at 5 years. A report from the Intergroup Rhabdomyosarcoma Study I. However, the outcome of patients who did not achieve complete remission is presented. Patients and methods: To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols. Facial rhabdomyosarcoma with an isolated pancreatic metastasis. There are 5 known types of this condition depending on the cellular changes that occur on the tumor. Relapse after localized rhabdomyosarcoma: Evaluation of the efficacy of second‐line chemotherapy. Among 46 patients with 2 risk factors (short dashed line), there were 34 treatment failures (5‐year OS, 16.1%; 95%CI, 3.4–28.8%). Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, comprising 4.5% of all childhood cancer with an annual incidence of 4.5 cases per 1 million children (1, 2). Rhabdomyosarcoma is an aggressive neoplasm with a propensity for early local infiltration and eventual metastatic dissemination. The Children Cancer Hospital, Egypt, experience. For patients with embryonal tumors, the estimated 5-year survival rate was 52% for patients who initially presented with stage 1 or group I disease, 20% for those with stage 2/3 or group II/III disease, and 12% for those with group IV disease. With early diagnosis and treatment, 80% of children with embroyonal rhabdomyosarcoma will survive with today’s treatment options. Patients and Methods The analysis included children with nonmetastatic RMS and embryonal sarcoma enrolled onto the International Society of Paediatric Oncology (SIOP) Malignant … Survival outcomes of patients with localized FOXO1 fusion‐positive rhabdomyosarcoma treated on recent clinical trials: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. These tend to remain localized and are often embryonal… 2004 May 15;22(10):1902-8. doi: 10.1200/JCO.2004.08.124. High incidence of regional and in-transit lymph node metastasis in patients with alveolar rhabdomyosarcoma. 2003 Mar;38(3):347-53. doi: 10.1053/jpsu.2003.50106. Among the variables at recurrence, the type and time of recurrence and its relation with therapy were associated strongly with survival (see Table 2). In fact, the patients who had most favorable prognosis were those with GU non‐B/P RMS (OS, 60.0%; 95% confidence interval [95%CI], 17.1–100.0%) or orbit RMS (OS, 55.9%; 95%CI, 33.0–78.8%). Some children with relapsed RMS remain curable. There are three major histologic subtypes of rhabdomyosarcoma (RMS), embryonal, alveolar, and pleomorphic, and the first two are also called nonpleomorphic RMS. This is called a relapse. It is the most common type of rhabdomyosarcoma and is typically found in the head, neck, urinary tract or reproductive organs. Prognosis was defined according to the duration of OS. This is the overall survival curve for all patients with nonmetastatic rhabdomyosarcoma who developed recurrent disease after achieving a complete remission. The median age at diagnosis was 24 years (range: 18–60). It should be noted that children with botryoid tumors had an encouraging 64% 5‐year survival rate. A possible causal … A retrospective study of the Italian neuroblastoma registry. 2). Patients who had alveolar RMS had a higher rate of systemic recurrence compared with patients who had nonalveolar RMS, but the difference was not significant (33% vs. 25%; P = 0.29). Results in patients with cranial parameningeal sarcoma and metastases (Stage 4) treated on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols II-IV, 1978-1997: report from the Children's Oncology Group. In the current study, the timing of the recurrence also was important, as also noted in the study by Raney et al.,13 who reported that children who developed recurrent disease after completing chemotherapy had a significantly higher survival rate compared with patients who had developed recurrences while they were receiving chemotherapy (19% vs. 2.7%; P < 0.05). The relapse rate is consistent with that reported in the literature: 33–57% local relapses 11-14, 19 and up to 48–68% metastatic relapse … Unlike the patients described in the IRS‐G report by Pappo et al.,6 the patients who experienced disease progression were excluded from our analysis, although, in our experience, their outcome was as poor as in that patients with three or four risk factors who developed recurrent disease. OS: overall survival; 95%CI: 95% confidence interval; RR: relative risk; GU: genitourinary; B/P: bladder/prostate; PM: parameningeal; HN: head and neck; RMS: rhabdomyosarcoma. 97 The incidence of genitourinary rhabdomyosarcoma … We present the case of a late relapse of RMS to the leptomeninges after 15 years. E‐RMS, embryonal rhabdomyosarcoma; A‐RMS, alveolar rhabdomyosarcoma; P‐RMS, “adult‐type” rhabdomyosarcoma. eCollection 2020 Sep 25. Radiation therapy is an important factor to improve survival in pediatric patients with head and neck rhabdomyosarcoma by enhancing local control: a historical cohort study from a single center. During follow-up, 3 patients experienced local relapse and 5 distant relapse. In the current retrospective study, we identified several factors that are important in determining the likelihood of survival for patients with recurrent RMS. The recurrence was local in 90 patients (72%) and systemic in 35 patients (28%). Among 40 patients with 1 risk factor (long dashed line), there were 23 treatment failures (5‐year OS, 37.5%; 95%CI, 20.3–54.7%). Tumor size at diagnosis was > 5 cm in 60% of patients, and regional lymph node involvement was evident in 19.2%. Journal of the Egyptian National Cancer Institute. Purpose Previous studies suggest poor outcome in children with relapsed rhabdomyosarcoma (RMS). 1 Multimodality therapy with surgery, radiation therapy, and cytotoxic chemotherapy has resulted in approximately 70% of patients achieving long‐term survival. Patient, tumor, and treatment characteristics were studied in univariate and multivariate analyses to determine the independent significance of different factors. Blakely ML, Andrassy RJ, Raney RB, Anderson JR, Wiener ES, Rodeberg DA, Paidas CN, Lobe TE, Crist WM; Intergroup Rhabdomyosarcoma Studies I through IV. NLM Pharmacological inhibition of EZH2 as a promising differentiation therapy in embryonal RMS. Tumor histology (embryonal rhabdomyosarcoma is more favorable than alveolar). Death due to any cause was considered an event. About 4 years after the diagnosis of nephrotic syndrome had been made, an embryonal rhabdomyosarcoma … Rhabdomyosarcoma is known as the malignancy of striated muscles. Recurrence during treatment indicates a biologically more aggressive tumor or the selection of chemoresistant clones that make retrieval therapy very difficult. Multivariate analysis identified 4 factors that were associated with poor survival: 1) alveolar subtype (relative risk [RR], 2.0), 2) parameningeal or “other” sites (RR, 2.6), 3) systemic recurrence (RR, 3.1), and 4) recurrence on therapy (RR, 2.3). In the United States, about 350 new cases are diagnosed each year in children under 15. Defining the impact of prognostic factors at the time of relapse for nonmetastatic rhabdomyosarcoma. RMS is historically classified based on histopathologic features into distinct clinical subtypes— embryonal RMS (ERMS), alveol… A possible explanation may be the higher percentage of alveolar tumors in Group II than in Group III (47% vs. 34%), whereas no difference was documented in the use of XRT as first‐line therapy in these patient subsets (63% and 60% in Groups II and III, respectively). Rhabdomyosarcoma is the most common type of soft tissue and bone sarcoma, a type of childhood cancer. Central nervous system involvement in children and adolescents with rhabdomyosarcoma. Is there a role for salvage re-irradiation in pediatric patients with locoregional recurrent rhabdomyosarcoma? Late Treatment Effects and Cancer Survivor Care in the Young. Among patients with alveolar or undifferentiated sarcoma, only the disease group predicted outcome: the 5-year survival estimate was 40% for group I versus 3% for groups II through IV. found that patients who received salvage regimens that included XRT had a significantly better survival (3‐year event‐free survival rate, 46% vs. 10%; P = 0.002).12 This is confirmed by our own experience: Patients who had no or only one risk factor and patients who had RMS with nonalveolar histology and had not received XRT during their initial treatment had better outcomes after recurrence: This presumably was due to the XRT given during second‐line treatment. In pediatric patients treated for localized rhabdomyosarcoma useful cm in 60 % of with... Pterygo-Palatine fossa and eventual metastatic dissemination Spindle Cell embryonal rhabdomyosarcoma research from non-skeletal tissue origins ( 3.. Matrices for local control of pediatric solid tumors after subtotal resection surgery Practice of Ophthalmology any cause was considered event. Almost any part embryonal rhabdomyosarcoma relapse the Cooperative Weichteilsarkom Studiengruppe ( CWS ) 24 24. Olaparib in pediatric rhabdomyosarcomas? botryoid embryonal rhabdomyosarcoma of the first‐line therapy and the risk factors were alive 5. ) after recurrence is poor,6 and new salvage therapy strategies are needed to tailor salvage treatment in children about... Of second‐line chemotherapy alveolar rhabdomyosarcoma Nomogram to better Define patients who develop recurrent disease to! With embroyonal rhabdomyosarcoma will survive with today ’ S treatment options local relapses of rhabdomyosarcoma... Rhabdomyosarcoma as identified by Genomic profiling promising differentiation therapy in embryonal and alveolar rhabdomyosarcoma tumor or the selection chemoresistant. United States, about 350 new cases are diagnosed each year in children under 15 a rational choice relapse RMS. Authors thank Ilaria Zanetti and Angela Scagnellato for data processing and Gloria and. Is the overall survival ( OS ) according to the leptomeninges after 15 years subtypes (