Survivors Of Rhabdomyosarcoma Research Articles

Systemic sequelae and craniofacial development in survivors of pediatric rhabdomyosarcoma

IntroductionThe aim of this study was to evaluate the systemic sequelae, as well as the dental and craniofacial development, of patients with rhabdomyosarcoma in relation to the treatment received and clinical-pathological variables. Materials and MethodsA retrospective cross-sectional study was performed. All individuals diagnosed with RMS between 1990 and 2022 were considered eligible. Cases who survived the primary tumor were included. Data were collected from medical records, and patients were called for clinical and radiographic examinations. ResultsThirty-eight patients were assessed, with a mean disease-free survival of 216.68 months (±84.99). The primary location of the tumor was mainly the head and neck region (57.9 %). All patients received chemotherapy, and 30 (78.9 %) also underwent radiotherapy. The most frequently observed sequela was sensory impairment, which was significantly associated with tumors in the head and neck (p < 0.05), as well as with the use of radiotherapy (p = 0.034). Root formation failure was observed in 60 % of cases, microdontia in 50 %, and delayed tooth eruption in 40 %. A convex profile was predominant (80 %), along with maxillary (50 %) and mandibular (80 %) retrusion and a skeletal class II diagnosis (60 %). ConclusionsLate systemic, dental, and craniofacial developmental sequelae are observed in pediatric rhabdomyosarcoma survivors, especially in patients who underwent radiotherapy in the head and neck region. Younger individuals at the time of treatment are at greater risk of late sequelae.

Ophthalmologic adverse events in childhood head and neck rhabdomyosarcoma survivors treated according to four different local treatment strategies

IntroductionOphthalmological adverse events (OAEs) are known to frequently occur following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS). The exact nature of these OAEs and the burden they put on survivors is less well described. Moreover, it is suspected there might be differences in the prevalence and nature of OAEs depending on local treatment strategy applied: external beam radiation therapy with photons, external beam radiation therapy with protons, macroscopically radical surgery combined with brachytherapy, or microscopically radical surgery combined with external beam radiation therapy. MethodsWe cross-sectionally assessed 98 HNRMS survivors with long (median 9 years) follow-up time, according to a predefined list of OAEs based on the Common Terminology Criteria for Adverse Events system. We added information from chart reviews on the nature and management of all OAEs scored grade ≥1. We describe the prevalence of OAEs for the different tumor sites and treatment strategies separately. ResultsOAEs occurred following treatment of all HNRMS sites. The most frequently observed OAEs are eyelid abnormalities, dry eyes, and cataracts. Sixty-two percent of survivors had several different OAEs simultaneously. In 27 % of survivors additional (surgical) treatment of OAEs was required during follow-up. The patterns observed suggest a possible relationship between OAE type and treatment strategy. ConclusionOAEs in HNRMS survivors confer a high burden of chronic toxicity. The simultaneous occurrence of multiple OAEs in individual survivors present a particularly challenging clinical scenario and demand specific expertise. We propose a standardized screening scheme to detect possible OAEs in asymptomatic survivors based on primary tumor localization.

Risk factors for neurocognitive impairment, emotional distress, and poor quality of life in survivors of pediatric rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study.

Prevalence and risk of poor psychological outcomes following rhabdomyosarcoma (RMS) are not well-established. Participants in this cross-sectional, case-control study (n=713 survivors, 42.5% female; mean [SD] age, 30.5 [6.6] years; n=706 siblings, 57.2% female; mean age, 32.8,[7.9] years) completed measures of neurocognition, emotional distress, and health-related quality of life (HRQOL). Multivariable logistic regression models identified treatments, health behaviors, and chronic conditions associated with impairment. Relative to siblings, more survivors reported neurocognitive impairment (task efficiency: 21.1% vs. 13.7%, emotional regulation: 16.7% vs. 11.0%, memory: 19.3% vs. 15.1%), elevated emotional distress (somatic distress: 12.9% vs. 4.7%, anxiety: 11.7% vs. 5.9%, depression: 22.8% vs. 16.9%) and poorer HRQOL (physical functioning: 11.1% vs. 2.8%, role functioning due to physical problems: 16.8% vs. 8.2%, pain: 17.5% vs. 10.0%, vitality: 22.3% vs. 13.8%, social functioning: 14.4% vs. 6.8%, emotional functioning: 17.1% vs. 10.6%). Cranial radiation increased risk for impaired task efficiency (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.14-4.63), whereas chest and pelvic radiation predicted increased risk of physical functioning (OR, 2.68; 95% CI, 1.16-6.21 and OR, 3.44; 95% CI, 1.70-6.95, respectively). Smoking was associated with impaired task efficiency (OR, 2.06; 95% CI, 1.14-3.70), memory (OR, 2.23; 95% CI, 1.26-3.95), anxiety (OR, 2.71; 95% CI, 1.36-5.41) and depression (OR, 1.77; 95% CI, 1.01-3.11). Neurologic conditions increased risk of anxiety (OR, 2.30; 95% CI, 1.04-5.10), and hearing conditions increased risk of depression (OR, 1.79; 95% CI, 1.05-3.03). Neurologic and hearing conditions, respectively, were associated with impaired memory (OR, 2.44; 95% CI, 1.20-4.95 and OR, 1.87; 95% CI, 1.05-3.35) and poor health perception (OR, 2.62; 95% CI, 1.62-1.28 and OR, 2.33; 95% CI, 1.34-4.06). RMS survivors are at significant risk for poor psychological outcomes. Advancing therapies for local control, smoking cessation, and managing chronic medical conditions may mitigate poor outcomes following RMS.

Exploration of dose-toxicity for ophthalmological adverse events in pediatric head and neck rhabdomyosarcoma survivors

<h3>Objectives</h3> Ophthalmological adverse events (OAEs) following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS) are prevalent. More knowledge on specific radiation dose-toxicity relationships for ophthalmological organs at risk (OARs) in children can help to avoid these OAEs. The aim of the present study is to explore the dose-toxicity probability for multiple OAEs seen in long term HNRMS survivors. <h3>Methods</h3> Clinical data on OAEs were systematically assessed in an international cross-sectional cohort that included survivors of pediatric HNRMS with ≥2 years follow-up. Dosimetric data were collected from the original radiotherapy treatment plans. OARs were delineated on the 3D radiotherapy planning CTs. Dose-toxicity probability curves were constructed using binary logistic regression. <h3>Results</h3> 74 eyes in 38 survivors with a median follow-up time of 9 years (range 2 – 27) were analyzed. With the exception of epiphora, dose-toxicity probability curves with good model-fit (AUC under ROC ≥0.8) were constructed for all OAEs. A >20% probability of globe displacement, dry eyes and/or cataract (any grade) at follow-up was seen for mean doses of >40, 10 and 6 GyEQD2 to the orbital bones, lacrimal gland and lens respectively. Retinopathy and optic neuropathy only occurred in eyes receiving maximum doses > 40 and 53 GyEQD2 to the retina and optic nerve respectively. No multivariable analyses were conducted because of low numbers of events per OAE. <h3>Conclusion</h3> We offer the first detailed description of specific dose-toxicity probability for ophthalmological OARs in children derived from clinically assessed OAEs in long-term survivors. These results are critical to: 1) quantify expected variation in clinical toxicity between different treatment techniques, 2) understand the additional OAEs children will incur if prescription dose for orbital RMS is increased from 45 Gy to 50.4 Gy on future clinical trials, and 3) inform physicians and future patients about expected long-term toxicity and necessary surveillance.

Delayed diagnosis of pediatric bladder and prostate rhabdomyosarcoma – causes and consequences

Introduction: Pediatric rhabdomyosarcoma (RMS) is a rare disease, affecting 4.5-6.0 per 1 000 000 children a year. Bladder and/or prostate (B&amp;P) is the primary tumor site in approximately 10% of patients. Initial symptoms of B&amp;P RMS in children may mimic more common, benign conditions such as urinary tract infections (UTIs), functional disorders, and congenital anomalies of the urinary tract. Aim: The study aims to emphasize the role of careful clinical examination and strict following the diagnostic guidelines in early detection of pediatric B&amp;P RMS in primary care and emergency department settings. Case study: We present two male patients aged 2.5 and 3 years with embryonal B&amp;P RMS initially manifesting as atypical and/or recurrent UTI. In both children, proper diagnoses were delayed due to careless physical examination and failure to adhere to the current guidelines for UTI management. Despite symptoms of an atypical and severe course of UTI, no imaging examinations had been performed for several weeks until dramatic deteriorations of patients’ general conditions occurred. Results and discussion: The prolonged diagnostic processes caused unnecessary suffering of both children and significant delay of oncological treatment in one. In the latter patient, bladder preservation was not possible, resulting in decreased quality of life. Conclusions: Due to its rarity, B&amp;P RMS is infrequently included in the differential diagnosis in children with recurrent or atypical UTI. However, thorough physical examination and adherence to the guidelines of UTI management enable timely diagnosis of underlying malignancy. Early diagnosis of B&amp;P RMS leads to a better prognosis, less intensive treatment, and improved quality of life of B&amp;P RMS survivors.

Radiological Manifestations of Acquired Dental Developmental Disturbances in Pediatric Head and Neck Rhabdomyosarcoma Survivors

Radiological Manifestations of Acquired Dental Developmental Disturbances in Pediatric Head and Neck Rhabdomyosarcoma Survivors

Outcomes of Bladder Preservation Following Treatment for Rhabdomyosarcoma

Genitourinary rhabdomyosarcoma (RMS) is a relatively uncommon pediatric urologic oncologic condition with significant implications for both short- and long-term bladder functions. It is important for both pediatric and adult urologists to be aware of the pathophysiology, treatment, and long-term prognosis of this tumor and its potential impact on bladder function in both pediatric and adult survivors. Abnormalities in bladder function may arise secondary to surgical or medical management. Typical presenting complaints include lower urinary tract symptoms, which may be more common in pediatric RMS survivors than in survivors of other childhood cancers. Post-treatment evaluation of urinary function should include a baseline urodynamics study and an assessment of symptom severity and bother using validated, age-appropriate questionnaires. Upper tract monitoring should include renal/bladder ultrasound and serum creatinine. Hemorrhagic cystitis, which often develops acutely in patients receiving alkylating agents, may also present as a late effect. Lastly, urinary diversion may be required in patients with bladder/prostate (BP)-RMS either due to initial or delayed cystectomy or due to radiation-related loss of bladder function. Recent data suggest that diversion can maintain excellent quality of life in these patients. Both BP-RMS and its treatments have the potential for profound impacts on long-term bladder function. Most BP-RMS patients will survive beyond their initial diagnosis and treatment, and it is therefore important for both pediatric and adult urologists to be aware of the pathophysiology, treatment, and long-term prognosis of this tumor and its potential impact on bladder function in both pediatric and adult survivors.

Temporal trends among survivors of rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

11570 Background: Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols included treatment modifications, which may have ameliorated late health outcomes for rhabdomyosarcoma (RMS) survivors treated in more recent era. Methods: We evaluated chronic health conditions (CHCs) and late mortality ( &gt; 5 years from diagnosis) among survivors treated 1970-1990 (IRSG I-III) and 1991-1999 (IRSG IV), and associations with specific treatments to identify treatment-related factors for adverse outcomes. Associations between treatments and CHCs and mortality were evaluated using Fine and Gray’s proportional hazards method accounting for competing risks. Results: 856 survivors treated 1970-90 (median diagnosis age 5.4 years [0- 20]) and 306 treated 1991-99 (median diagnosis age 5.5 years [0-20]) were included. Significant exposure differences between eras included higher percentage (53% vs. 17%, p &lt; 0.01) receiving ≥ 20gm/m2 cumulative alkylators in 1991-99, but more receiving platinums (13% vs 5%, p &lt; 0.01) and abdomen/ pelvis radiation (29% vs. 23%, p = 0.04) in 1970-90. 20-year cumulative incidence for any (40% vs. 28%, p &lt; 0.01), ≥2 (16% vs. 7%, p &lt; 0.01), and endocrine (8% vs. 2.5%, p &lt; 0.01) grade 3-5 CHCs was higher in 1970-90 compared to 1991-99. The hazard ratio (HR) for any (HR 0.7, 95% Confidence Interval [CI] 0.55-0.9), ≥2 (HR 0.38, 95% CI 0.22-0.66) and endocrine (HR 0.25, 95% CI 0.09-0.67) grade 3-5 CHC was lower for 1991-99 survivors than 1970-90. The effect of era (1991-99 vs 1970-90, HR 0.73; 95% CI 0.59-0.91) on CHC was not attenuated when treatment variables were added to multivariable model. Exposures with increased risk of grade 3-5 CHC included platinums (hearing, HR 2, 95% CI 1.07-3.8), anthracycline ≥250mg/m2 (cardiovascular, HR 2.7, 95% CI 1.2-6) and abdomen/ pelvis radiation (second malignant neoplasms, HR 2.1, 95% CI 1.1-4, gastrointestinal, HR 7.4, 95% CI 3.5-16 and endocrine, HR 2.5, 95% CI 1.4-4.4). Gonadal dysfunction was the most common endocrine CHC. There was no difference in all cause or cause-specific mortality between the two cohorts. Conclusions: RMS survivors from the IRSG IV era are at reduced risk for late onset chronic health conditions compared to previous era.

Second malignant neoplasms after childhood non-central nervous system embryonal tumours in North America: A population-based study

BackgroundFew studies in North America have quantified the risks of second malignant neoplasms (SMNs) among survivors of childhood non-central nervous system (non-CNS) embryonal tumours due to their rarity. We aimed to investigate these risks by combining population-based data from the United States of America and Canada. MethodsWe evaluated patients with childhood non-CNS embryonal tumours reported to the Surveillance Epidemiology and End Results program and eight Canadian cancer registries from 1969 to 2010. Standardised incidence ratio (SIR) and cumulative incidence of SMNs were calculated. Subgroup analyses were conducted by the type of first primary cancer, age at first primary diagnosis and follow-up duration. FindingsOf the 13,107 survivors, 190 SMNs were reported over 134,548 person-years of follow-up. The SIR for all SMNs combined was 6.4 (95% confidence interval [CI]: 5.5–7.4). Most site-specific SIRs were significantly increased, ranging from 36 (95% CI: 26–49) for bone and joint cancer to 3.1 (95% CI: 1.5–5.2) for brain tumour. The risk for second malignancies declined as the time elapsed from the first primary diagnosis and was less prominent for patients first diagnosed at age 1–4 years. Notably, rhabdomyosarcoma survivors had a higher risk for SMNs than those with other first primaries. The overall cumulative incidence of SMNs was 1.0% at 10 years, increasing to 2.2% at 20 years and 4.1% at 30 years. InterpretationSurvivors with childhood non-CNS embryonal tumours faced an increased risk for SMNs compared to the general population. The risk variations observed in different patient categories may help target prevention strategies in high-risk subgroups.

Facial asymmetry in head and neck rhabdomyosarcoma survivors.

Radiotherapy is essential for achieving and maintaining local control in head and neck rhabdomyosarcoma (HNRMS) patients. However, radiotherapy may cause outgrowth disturbances of facial bone and soft tissue, resulting in facial asymmetry. The aim of this study was to develop a method to visualize and measure facial asymmetry in HNRMS survivors using three-dimensional (3D) imaging techniques. Facial deformity was evaluated in a multidisciplinary clinical assessment of 75 HNRMS survivors, treated with external beam radiotherapy (EBRT, n = 26) or Ablative surgery, MOulage brachytherapy, and REconstruction (AMORE, n = 49). Individual facial asymmetry was measured using 3D photogrammetry and expressed in a raw asymmetry index and a normalized sex-age-ethnicity-matched asymmetry signature weight. Facial asymmetry was also compared between British and Dutch controls and between survivors and their matched controls. Facial asymmetry was more pronounced with increasing age (P < 0.01) in British controls compared with Dutch controls (P = 0.04). Survivors developed more facial asymmetry than matched controls (P < 0.001). The clinical assessment of facial deformity correlated with the raw asymmetry index (r = 0.60, P < 0.001). 3D imaging can be used for objective measurement of facial asymmetry in HNRMS survivors. The raw asymmetry index correlated with a clinical assessment of facial deformity. Comparisons between treatment groups seemed inappropriate given the differences in facial asymmetry between British and Dutch controls. In future studies, pretreatment images could act as matched controls for posttreatment evaluation.

Adverse Events of Local Treatment in Head and Neck Rhabdomyosarcoma Survivors after External Beam Radiotherapy or AMORE Treatment

Adverse Events of Local Treatment in Head and Neck Rhabdomyosarcoma Survivors after External Beam Radiotherapy or AMORE Treatment

An Increased Risk of Second Malignant Neoplasms After Rhabdomyosarcoma: Population-Based Evidence for a Cancer Predisposition Syndrome?

Rhabdomyosarcoma survivors have an increased risk of developing second malignant neoplasms (SMN); this risk is traditionally attributed to the effects of multidisciplinary management required for cure. However, the impact of constitutional predisposition has not been properly analyzed. We analyzed the risk of SMN among 1,151 children diagnosed with rhabdomyosarcoma and reported to the Surveillance, Epidemiology, and End Results registries (SEER-9) from 1973 to 2010. Standardized incidence ratios (SIR) and corresponding 95% confidence intervals (CI) were calculated using SEERStat 8.1.2. Children with pleomorphic and embryonal rhabdomyosarcoma had an increased risk of developing a SMN (SIR = 15.77, 95%CI 1.91-56.96 and SIR = 5.6, 95%CI 3.32-8.85, respectively). The risk was age-dependent; the highest was among children <2 years (SIR = 13.38, 95%CI 4.34-31.22) and the lowest was in children >10 years (SIR = 3.35, 95%CI 1.53-6.35). The risk for the youngest patients was higher for those with embryonal rhabdomyosarcoma (SIR = 14.72, 95%CI 4.01-37.70) compared to other histiotypes. Additionally, the risk of SMN was independent of the use of radiation to the primary (SIR = 6.50, 95%CI 3.97-10.03 and SIR = 4.57, 95%CI 2.09-8.68, for children receiving and not receiving radiation, respectively). The pattern of SMN observed was consistent with the Li-Fraumeni spectrum. Children with rhabdomyosarcoma are at high risk of developing SMN. This risk is higher for a subgroup of young children with pleomorphic and embryonal histologies, and is independent of the use of radiation. This suggests that a subgroup of children with pleomorphic and embryonal rhabdomyosarcoma may have a constitutional cancer predisposition.

Neurocognitive, emotional, and quality of life outcomes in long-term survivors of rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study (CCSS).

10072 Background: Previous studies of rhabdomyosarcoma (RMS) survivors have focused on outcomes related to chronic health conditions. We evaluated neurocognitive, emotional, and quality of life (QOL) outcomes of > 5-year survivors. Methods: 482 survivors diagnosed 1970-1986 (mean age [SD] 7.2 [5.4] years at diagnosis; 24.3 [4.8] years of follow-up) and 393 siblings from the CCSS rated their neurocognition, emotions, and QOL using the Neurocognitive Questionnaire (NCQ), Brief Symptom Inventory-18 (BSI-18), and Medical Outcomes Short Form-36 (SF-36). Based on normative data, impairment was defined as the bottom 10th percentile of performance on the NCQ, the top 10th percentile of symptom prevalence on the BSI-18, and the bottom 15th percentile on each SF-36 subscale. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression. Results: Survivors reported more impairment than siblings on NCQ task efficiency (p < 0.001), higher symptom prevalence on BSI-18 depres...

Adverse events of local treatment in long-term head and neck rhabdomyosarcoma survivors after external beam radiotherapy or AMORE treatment

BackgroundRadiotherapy is a well-known cause of adverse events (AEs). To reduce AEs, an innovative local treatment was developed in Amsterdam: Ablative surgery, MOuld brachytherapy and surgical REconstruction (AMORE).Aims: (1) to determine the prevalence of AEs in HNRMS survivors and (2) to compare AEs between survivors treated with the international standard: external beam radiotherapy (EBRT-based: London) and survivors treated with AMORE if feasible, otherwise EBRT (AMORE-based: Amsterdam). MethodsAll HNRMS survivors, treated in London or Amsterdam between January 1990 and December 2010 (n=153), and alive ⩾2years post-treatment were eligible (n=113). A predefined list of AEs was assessed in a multidisciplinary clinic and graded according to the Common Terminology Criteria for Adverse Events. ResultsEighty HNRMS survivors attended the clinic (median follow-up 10.5years); 63% experienced ⩾1 severe or disabling event, and 76% had ⩾5 AEs (any grade). Survivors with EBRT-based treatment were, after adjustment for site, age at diagnosis, and follow-up duration, at increased risk to develop any grade 3/4 event or ⩾5 AEs (any grade) compared with survivors with AMORE-based treatments (p=0.032 and 0.01, respectively). Five year overall survival (source population) after EBRT-based treatment was 75.0%, after AMORE-based treatment 76.9%, p=0.56. ConclusionThis study may serve as a baseline inventory and can be used in future studies for prospective assessments of AEs following the introduction of novel local treatment modalities. AMORE-based local treatment resulted in similar overall survival and a reduction of AEs secondary to local treatment.

Recognition of Li Fraumeni syndrome at diagnosis of a locally advanced extremity rhabdomyosarcoma

A contemporaneous presentation of a second breast cancer in a mother and an extremity rhabdomyosarcoma (RMS) in her daughter led to the diagnosis of the Li Fraumeni syndrome (LFS). Although the association between LFS and RMS in young patients is well recognised 1 there are no guidelines as to how this knowledge should influence the optimal management of these patients. After reviewing the literature about the natural history of the LFS 2, the incidence of second malignancy (SMN) in RMS survivors 3-6 and the management of extremity RMS 7-9, we are concerned that contemporary RMS treatment, combining non-mutilating surgery with chemoradiotherapy, may be associated with an excessive SMN risk in LFS patients with advanced RMS. We question whether treatment should be individualised and, where possible and acceptable to the family, measures such as amputation should be the considered to attain local control for LFS patients with RMS as this will avoid the need for local radiotherapy without compromising long-term function and quality of life 10.

Physical impairment and social adaptation in adult survivors of childhood and adolescent rhabdomyosarcoma: a report from the Childhood Cancer Survivors Study

Despite interest in the well-being of adult survivors of childhood rhabdomyosarcoma (RMS), few studies have examined their health-related quality of life (HRQOL). This study evaluated physical and social aspects of HRQOL among long-term childhood RMS survivors relative to a sibling comparison group, and assessed whether physical impairment among RMS survivors adversely affected their ability to achieve adult life goals. Using baseline data from the Childhood Cancer Survivor Study, we evaluated self-reported physical impairment and social adaptation among 417 survivors of childhood RMS and 2685 siblings > or =18 years of age at survey completion. Survivors were more likely than siblings to report physical impairment, characterized by: at least one medically diagnosed condition, limitations in the performance of routine activities, a health-related inability to work or attend school, cancer-related pain. Survivors were less likely than siblings to have completed high school, ever worked a job, or ever been married. The odds of completing high school were lower among survivors with performance limitations, a health-related inability to work or attend school, or moderate to high levels of cancer-related pain. Survivors who reported cancer-related pain had an increased likelihood of ever being married. The majority of adult survivors of pediatric RMS are successful in attaining adult life goals despite higher reported occurrence of physical impairment than their sibling counterparts. Additional studies are needed to advance our understanding of other aspects of HRQOL in this population of pediatric cancer survivors.

Long‐term medical effects of childhood and adolescent rhabdomyosarcoma: A report from the childhood cancer survivor study

This study was conducted to evaluate the incidence of adverse medical conditions and to assess the risk of developing these conditions in a cohort of long-term survivors of rhabdomyosarcoma (RMS) diagnosed before age 21. Using data from the Childhood Cancer Survivor Study (CCSS), we evaluated the incidence of self-reported adverse medical conditions for 606 RMS survivors and 3,701 siblings of cancer survivors. Cancer and treatment data abstracted from medical records were used to evaluate the effects of primary tumor site and combined modality therapy on the risk of developing sequelae in survivors. The relative risk (RR) for developing sequelae among survivors compared with siblings was greatest within 5 years after diagnosis. RR was elevated more than 5 years after diagnosis for several conditions (RR, 95% CI) as follows: eye impairment (cataract: 7.4, 2.9-18.9; visual disturbances: 3.2, 2.0-5.1; very dry eyes: 2.0, 1.2-3.3), endocrine impairment (growth hormone deficiency: 83.9, 33.0-213.6; hypothyroidism: 6.9, 4.1-11.3; need for medications to induce puberty: 90.4, 30.2-270.5), cardiopulmonary impairment (congestive heart failure: 43.0, 12.7-145.5; angina-like symptoms: 2.0, 1.3-2.9), neurosensory impairment (legal blindness: 9.8, 4.8-20.0; abnormal sensations: 1.5, 1.0-2.2), and neuromotor impairment (repeated seizures: 2.3, 1.2-4.4; motor problems: 3.7, 2.2-6.4; problems chewing or swallowing: 3.8, 1.9-7.5). Survivors are at risk for developing sequelae many years after their initial diagnosis and treatment. Continued medical surveillance is necessary to ensure the long-term health and well-being of RMS survivors.