Pediatric Oncology Study Research Articles

Precision medicine in pediatric oncology.

Purpose of reviewThe current review describes recent advances and unique challenges in precision medicine for pediatric cancers and highlights clinical trials assessing the clinical impact of targeted therapy matched to molecular alterations identified by tumor profiling.Recent findingsMultiple prospective clinical sequencing studies in pediatric oncology have been reported in the last 2 years. These studies demonstrated feasibility of sequencing in the clinic and revealed a rate of actionable variants that justifies the development of precision trials for childhood cancer. A number of precision medicine trials are recently completed, underway or in development and these will be reviewed herein, with a focus on highlighting aspects of precision medicine trial design relevant to pediatric oncology.SummaryThe primary results of the first round of pediatric precision oncology clinical trials will provide us with a greater understanding of the clinical impact of linking tumor profiling to selection of targeted therapies. The aggregation of sequencing and clinical data from these trials and the results of biologic investigations linked to these trials will drive further discoveries and broaden opportunities for precision medicine for children with cancer.

Development and inter-rater reliability of a tool assessing hypnotic communication behaviours adopted by nurses caring for children with cancer: The Sainte-Justine Hypnotic Communication Assessment Scale

BackgroundSeveral studies in pediatric oncology have shown the successful effects of using hypnotic communication techniques (HCTech) during painful medical procedures. Since no studies assessed the precise use of these techniques with a validated tool, it is unsure that the observed relationships involve the use of HCTech. ObjectivesTo develop a scale evaluating healthcare professionals’ behaviours when using HCTech and to evaluate its inter-rater reliability. MethodsThis study involved the preliminary steps of the Sainte-Justine Hypnotic Communication Assessment Scale (SJ-HCAS) development process. As part of a larger intervention study, the SJ-HCAS was developed in three steps by five experts and four lay raters using an iterative process applied to subsets of video-recorded nurse-patient interactions. The development aimed to maximize clarity and precision of items as well as minimize redundancy amongst items. Inter-rater reliability was assessed in a randomly selected sample of 1/3 of collected video-recorded interactions (n=42). ResultsThe final version of the scale is composed of 11 items categorized in two domains pertaining to Relationship and Technique. We found excellent inter-rater reliability for both subscores and total score in two independent inter-rater comparisons (median ICC=0.879), with most items showing very good to perfect inter-rater reliability (median Kappa=0.847). ConclusionsThe results support further work with the SJ-HCAS. The scale has the potential to help ensure the integrity of hypnotic communication training in children which could ultimately promote the dissemination of the practice of HCTech.

Pediatric oncology enters an era of precision medicine

With the use of high-throughput molecular profiling technologies, precision medicine trials are ongoing for adults with cancer. Similarly, there is an interest in how these techniques can be applied to tumors in children and adolescents to expand our understanding of the biology of pediatric cancers and evaluate the clinical implications of genomic testing for these patients. This article reviews the early studies in pediatric oncology showing the feasibility of this approach, describe the future plans to evaluate the clinical implications in a multicenter clinical trial and identify the challenges of applying genomics in this patient population.

Acute Leukemia in Down Syndrome Children in Hong Kong: Retrospective Review.

Children with Down syndrome (DS) are at higher risk of developing acute leukemia. Treatment continues to evolve as we accumulate better understanding of the distinctive clinical and biological features of acute leukemia in DS patients. A retrospective review of the clinical features, treatment outcomes, and survival of DS children with acute leukemia in Hong Kong from 1993 to 2013 was conducted. Patients were identified from the registry of the Hong Kong Pediatric Hematology and Oncology study group. This cohort included a total of 29 patients with DS. Ten were diagnosed with acute lymphoblastic leukemia and 19 had acute myeloid leukemia (AML). The mean follow-up duration was 8.3 years (range, 0.6 mo to 18.1 y). The 5-year overall survival and event-free survival for DS-acute lymphoblastic leukemia and DS-AML were 65.6%, 54.9%, 89.5%, and 89.5%, respectively. The clinical characteristics and treatment outcomes of DS patients with acute leukemia in Hong Kong were comparable with results from other international study groups. Patients with DS-AML had a better prognosis.

Prospective study of thromboembolism in 1038 children with acute lymphoblastic leukemia: a Nordic Society of Pediatric Hematology and Oncology (NOPHO) study

ESSENTIALS: Children with acute lymphoblastic leukemia (ALL) are at risk of thromboembolism (TE). This is a prospective evaluation of the incidence, risk factors and outcomes of TE in 1038 children with ALL. TE occurred in 6.1% of children, with the highest incidence (20.5%) among those aged 15-17 years. A TE-associated case fatality of 6.4% indicates that TE is a severe complication of ALL treatment. Thromboembolism (TE) is a major toxicity in children with acute lymphoblastic leukemia (ALL) and may have a negative impact on ALL treatment. To examine the cumulative incidence, outcomes and risk factors associated with TE in children with leukemia. We prospectively evaluated TE in 1038 Nordic children and adolescents (≥ 1 and < 18 years) diagnosed with ALL during 2008-2013 and treated according to the NOPHO (Nordic Society of Pediatric Hematology and Oncology)-ALL 2008 protocol. The cohort was followed until December 2014. Cox proportional regression was used to compute hazard ratios (HRs). TE events (n = 63) occurred most frequently in conjunction with asparaginase (ASP) administration (52/63). The cumulative incidence of TE was 6.1% (95% confidence interval [CI], 4.8-7.7). Being aged 15-17 years was associated with an increased risk of TE (adjusted HR of 4.0; 95% CI, 2.1-7.7). We found a TE-associated 30-day case fatality of 6.4% (95% CI, 1.8-15.5) and TE-related truncation of ASP therapy in 36.2% (21/58). Major hemorrhage occurred in 3.5% (2/58) of anticoagulated patients. Minor hemorrhage was reported in two out of 58 patients. No major bleeds occurred in children who received low-molecular-weight heparin. Methods to identify children and adolescents who will benefit from thromboprophylaxis during ALL treatment are called for. The truncation of ASP should be avoided. The long-term survival outcomes for ALL patients with TE require close monitoring in the future.

Voluntary Informed Consent in Paediatric Oncology Research.

In paediatric oncology, research and treatments are often closely combined, which may compromise voluntary informed consent of parents. We identified two key scenarios in which voluntary informed consent for paediatric oncology studies is potentially compromised due to the intertwinement of research and care. The first scenario is inclusion by the treating paediatric oncologist, the second scenario concerns treatments confined to the research context. In this article we examine whether voluntary informed consent of parents for research is compromised in these two scenarios, and if so whether this is also morally problematic. For this, we employ the account of voluntary consent from Nelson and colleagues, who assert that voluntary consent requires substantial freedom from controlling influences. We argue that, in the absence of persuasion or manipulation, inclusion by the treating physician does not compromise voluntariness. However, it may function as a risk factor for controlling influence as it narrows the scope within which parents make decisions. Furthermore, physician appeal to reciprocity is not controlling as it constitutes persuasion. In addition, framing information is a form of informational manipulation and constitutes a controlling influence. In the second scenario, treatments confined to the research context qualify as controlling if the available options are restricted through manipulation of options. Although none of the influences is morally problematic in itself, a combination of influences may create morally problematic instances of involuntary informed consent. Therefore, safeguards should be implemented to establish an optimal environment for parents to provide voluntary informed consent in an integrated research-care context.

Translating genomic discoveries to the clinic in pediatric oncology.

The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.

The complexity of consenting to clinical research in phase I pediatric cancer studies.

The principal aim of phase I studies is to define the recommended dosing of drugs for phase II studies through assessment of drug pharmacokinetics and observation of the drug's toxicity profile. In the setting of pediatric oncology, the use of an experimental drug in phase I study is offered when prognosis is poor. Thus, phase I oncology studies are not given to patients with a primary purpose of an intent to cure. They may offer little to no treatment benefit and carry a potential toxic effect. They may offer other benefits such as improved quality of life and relief of pain, however. Three parties are involved in the informed consent process: the parents, patients, and physicians. Families report hope as the main cause for enrollment. Physicians focus on providing information so families can decide about participation. Physicians also try to maintain hope despite understanding the nature of the disease. This makes the informed consent complicated for all parties involved in the process. The purpose of this review is to discuss the aims of phase I studies in pediatric oncology and to convey the ethical challenges that patients, parents, and physicians are facing when discussing informed consent with potential study participants.

A 20-year prospective study of Wilms tumor and other kidney tumors: a report from Hong Kong pediatric hematology and oncology study group.

Renal tumors are one of the most common tumors in children. We aim at evaluating the characteristics and the outcome of Wilms tumor and other malignant kidney tumors in Hong Kong. Between January 1990 to December 2010, 68 patients under the age of 18 with malignant renal tumors were diagnosed and received treatment in Hong Kong. Clinical records were updated regularly. Prognostic factors and survival rate were evaluated. Fifty-four patients were diagnosed with Wilms tumor. The annual incidence was estimated to be 2.29 per million. The mean age was 38 months. Median follow-up was 9.2 years. The event-free survival and overall survival rate at 10 years were 85.2% and 92.6%, respectively. A pair of siblings with familial extrarenal Wilms tumor was included. Pulmonary metastasis did exhibit a significant difference in survival rate. Eight cases of clear cell sarcoma of the kidneys were reported and the survival rate was 100%. The clinical characteristics and outcome of the patients diagnosed Wilms tumor were comparable with other developed countries. Relatively high proportion and excellent outcome were found in clear cell sarcoma of the kidneys.

Predictors of stress of parents of a child with cancer: a Jordanian perspective.

Background:Most paediatric oncology studies agree that being parents of a child with cancer is an emotionally stressful event. Although an increasing number of studies have investigated psychological stress of parents of a child with cancer, few of these studies have included both parents or investigated the predictors of high stress levels for the mothers and the fathers. Moreover, studies published over the last few decades were limited to Western countries and have shown inconsistent findings about parental perceived stress whose children have cancer. This study explored differences in predictors of perceived stress between Jordanian mothers and fathers of children with cancer.Methods:This study involved a survey of 300 couples parenting a child with cancer. Participants answered the Arabic version of the Perceived Stress Scale 10-items, demographic and characteristics check list questionnaires. The main aims were to measure perceived stress levels for mothers and fathers, explore the predictors associated with high perceived stress levels and make a comparison between them.Findings:Mothers reported significantly higher stress levels than fathers (p<0.001), with a large effect size (0.30). Some of the factors associated with mothers and fathers high stress levels affected both parents whereas employment status affected only fathers’ stress levels.Conclusions:These findings indicate the need to work with the mothers and the fathers with a child with cancer in Jordan to recognise their psychological needs at the time of diagnosis and followed by on-going psychological support for both parents.

Conservative approach in localised rhabdomyosarcoma of the bladder and prostate: Results from International Society of Paediatric Oncology (SIOP) studies: Malignant mesenchymal tumour (MMT) 84, 89 and 95

The three sequential SIOP MMT studies provide the largest dataset available to date, to define the patient and tumour characteristics, treatment modalities and event-free and overall survival for children with non metastatic rhabdomyosarcoma (RMS) of the bladder and/or prostate (BP). The combined dataset of 172 patients with BP RMS treated on the SIOP MMT 84, 89 and 95 studies was reviewed to determine tumour characteristics, details of treatment and outcome. Median age at diagnosis was 2.5 years (range 2 months-17.8 years) and 138 (79%) were males. Median follow-up was 11.4 years (range 3 months-22 years). The 5-year overall survival of the combined cohort was 77% (CI 70-83%). The 5-year event-free survival was 63% and included 7 patients (4%) who did not achieve complete remission (CR), and 57 (33%) who relapsed. Age ≥ 10 years (RR 3.7) and alveolar pathology (RR 3.3) were identified as independent prognostic factors on multivariate analysis. Fifty-nine (50%) of the 119 survivors were cured without significant local therapy, improving from 31% in MMT84 study to 61% in MMT95 study. The clinical strategy of the MMT studies aims to minimise the burden of therapy whilst maintaining survival rates. Overall survival is comparable to that of other international groups, despite the lower use of radiotherapy and or radical surgery, although number of events experienced is higher. Further assessment of the late effects of therapy is required to confirm whether this approach results in lower morbidity in the long-term.

Clinical exercise interventions in pediatric oncology: a systematic review

Studies in pediatric oncology have shown a positive effect of physical activity on disease- and treatment-related side effects. Although several reviews have approved the benefits of therapeutic exercise for adult cancer patients, no systematic review exists summarizing the evidence of physical activity in pediatric oncology. We identified a total of 17 studies using the PubMed database and Cochrane library. To evaluate the evidence, we used the evaluation system of the Oxford Center for Evidence-Based Medicine 2001. The findings confirm that clinical exercise interventions are feasible and safe, especially with acute lymphoblastic leukemia (ALL) patients and during medical treatment. No adverse effects have been reported. Positive effects were found on fatigue, strength, and quality of life. Single studies present positive effects on the immune system, body composition, sleep, activity levels, and various aspects of physical functioning. Child-specific aspects such as cognitive abilities, growth, adolescence, and reintegration into peer-groups, school, and sports have barely been taken into consideration. The evidence for exercise interventions in pediatric oncology is rated level "3." Although the results are very promising, future research of high methodological quality and focusing on child-specific aspects is needed to establish evidence-based exercise recommendations, particularly for childhood cancer patients.

Improving the prognosis of pediatric hodgkin lymphoma in developing countries: A moroccan society of pediatric hematology and oncology study

The event-free survival (EFS) of children with Hodgkin lymphoma (HL) exceeds 80% in high income countries (HIC), but little is known about this rate in developing countries. A prospective national protocol for children with classical HL was implemented in Morocco to increase EFS by careful risk stratification, providing each cycle of therapy on time, decreasing treatment abandonment, improving communication among healthcare providers, and improving data collection. Patients were stratified into a favorable risk group (Ann Arbor stages I and II, no B symptoms, no bulky disease, and no contiguous (E) lesions) and received four cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) or an unfavorable risk group (all others) who received two cycles of vincristine, procarbazine, prednisone, and doxorubicin (OPPA) and four cycles of cyclophosphamide, vincristine, procarbazine, and prednisone (COPP). All patients received involved-field radiotherapy 25.5 Gy after completion of chemotherapy. EFS was calculated counting death, relapse/resistant disease, and abandonment as events. From February 2004 to December 2007, 160 patients enrolled; 138 (86%) had unfavorable risk features. Twenty patients (12.5%) abandoned treatment, 16 relapsed or had resistant disease, and 6 died (3 unexplained, 2 varicella, and 1 suicide). The estimated 5-year EFS was 70 ± 4% and overall survival 88 ± 3%. Good outcomes for pediatric HL patients can be achieved in LMIC using a multidisciplinary team approach, uniform protocol-based therapy, twinning partnership among oncology units in-country and abroad, and a data collection system to monitor compliance and identify gaps in care.

Prognosis and outcome of relapsed acute lymphoblastic leukemia: A Hong Kong pediatric hematology and Oncology Study Group report

In 2000, the Hong Kong Pediatric Hematology Oncology Study Group started a new relapsed acute lymphoblastic leukemia (ALL) treatment protocol based on modified ALL-REZ BFM 96 protocol aiming at improving the treatment outcome in Chinese children. All patients in Hong Kong with first relapse of childhood ALL were included. Patients were stratified into four risk groups (S1, S2, S3, and S4) and the treatment consisted of intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if indicated. Fifty-six patients were recruited and median age at diagnosis of ALL was 4.6 (range, 0.3-17) years. The median time from initial diagnosis to relapse was 2.5 (range, 0.3-9.1) years and follow-up time was 2.7 (range, 0-9.9) years. Forty-nine patients (87.5%) achieved second complete remission (CR2). CR2 rates for S1, S2, S3, and S4 groups were 100%, 93%, 90%, and 67%, respectively. Five-year overall survival (OS) was 50.5 ± 6.9% and event-free survival (EFS) was 41.5 ± 7.1%. There was no significant difference in survival among S1, S2, and S3 groups but S4 patients performed significantly worse with 5-year OS and EFS of 8% and 0%, respectively. Children with relapsed ALL of S1-S3 risk groups could be successfully treated with intensified treatment protocol. The S4 high risk group needs more innovative approach to improve treatment outcome.

Using Germline Genomics to Individualize Pediatric Cancer Treatments

The amazing successes in cure rates for children with cancer over the last century have come in large part from identifying clinical, genetic, and molecular variables associated with response to therapy in large cooperative clinical trials and stratifying therapies according to the predicted risk of relapse. There is an expanding interest in identifying germline genomic variants, as opposed to genetic variants within the tumor, that are associated with susceptibility to toxicity and for risk of relapse. This review highlights the most important germline pharmacogenetic and pharmacogenomic studies in pediatric oncology. Incorporating germline genomics into risk-adapted therapies will likely lead to safer and more effective treatments for children with cancer.

Abstract 4353: Primary sarcoma of the liver and biliary tract in children: Results for the International Society of Paediatric Oncology (SIOP) studies MMT 84, MMT89 and MMT95

Abstract Purpose: Sarcomas of the liver (SL) are mostly Undifferentiated Embryonal Sarcoma of the Liver (UESL), or RMS. Sarcoma of the biliary tract (SBT) are usually botryoid or embryonal RMS. The prognosis is not well known. The value of common prognostic factors, (histology, tumor size, age, IRS grouping, chemotherapy) have only been described in case reports or very limited series. Patients and Methods: Here, we analyzed outcome and modality of relapse for patients under 18 years of age with nonmetastatic SL and SBT of the prospective SIOP Malignant Mesenchymal Tumors studies (MMT 84, 89 and 95). MMT studies are based on IVA (Ifosfamide, vincristine, actinomycin-D) and local surgery and/or radiotherapy. Results: The MMT studies (1984-2003) included 1554 sarcoma patients, of which 39 SL (11 RMS and 28 UESL) and 8 SBT, total 47 (3%). The median age was 6.3 years, M:F=39:10. The 5 years OS and EFS were 80%, not significantly different in RMS vs. UESL, or liver vs. biliary tract. Pre-surgical T1 vs. T2 tumors were significantly different in prognosis (5-yrs EFS 85 % vs. 62 %, resp.; p=0.03), but this was non-significantly different in the post surgical IRS staging (group I, II vs. III; p=0.08). Age at diagnosis, tumor size or histology, and treatment protocol were none significantly related to outcome. Complete remission (CR) was achieved in 45/47of the patients (96%), 7/47 (15%) after primary surgery, 3/47 after chemotherapy, 31/45 after surgery and chemo, 4/47 after chemo, radiotherapy and surgery, In 22 second, delayed surgery was performed, 21/22 achieved CR. Relapsed patients (11/47; 23%) did not survive. The effect of chemotherapy was no different between studies (MMT 84, 89, 95). Conclusion: In the SIOP MMT studies, an IVA based chemotherapy combined with local treatment resulted in a favorable outcome for sarcomas of the liver and bile duct. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4353. doi:10.1158/1538-7445.AM2011-4353

Long-term Follow-up of Infantile Wilms Tumor Treated According to International Society of Pediatric Oncology Protocol: Seven Years' Follow-up

To report the long-term follow-up of patients with infantile Wilms tumor treated according to the International Society of Pediatric Oncology study 9 protocol. We retrospectively reviewed our medical reports for diagnosed WT in patients aged 6-12 months from January 2001 to January 2009. The clinical presentation, stage, operative details, pathologic findings, and outcomes for these infants were analyzed. We reviewed the charts of these patients throughout the whole disease course through long-term follow-up, paying particular attention to the details of the clinical presentation, stage at presentation versus postoperative stage, intraoperative findings, pathologic findings, and outcomes. The records revealed 16 patients with a median age of 7.5 months. All patients had presented with an abdominal mass, and 25% had presented with abdominal pain and hematuria. Associated congenital anomalies were observed in 16.7% of the patients. A favorable histologic type was found in 91.7% of the patients and 8.3% had an unfavorable histologic type. The median follow-up period was 57 months. Postoperative complete remission was achieved in all patients who underwent surgery. Relapse developed in 1 patient. The 7-year disease-free survival rate was 93.8%, and the 7-year overall survival rate was 75%. The long-term follow-up data using the International Society of Pediatric Oncology study 9 protocol revealed good outcomes. The protocol was a safe and an effective line of therapy, associated with decreased morbidity and improved survival. Also, the reduction in tumor volume resulted in easier surgical procedures, with no intraoperative complications.

Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia

We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.

Multiple Symptoms in Pediatric Oncology Patients: A Systematic Review

Clinical experience suggests that children with cancer experience multiple symptoms as a result of their disease and/ or its treatment. These symptoms may have a negative impact on children's ability to function and on their quality of life. No systematic review has summarized the findings from studies that assessed multiple symptoms in these patients. The purposes of this article are to summarize the findings from the studies of multiple symptoms in pediatric oncology patients and to describe directions for future research. Although there has been a recent increase in the studies of the multiple symptoms in pediatric cancer patients, only 9 studies were found that met the inclusion criteria for this review. Thus, little is known about the relationships between demographic and clinical characteristics and the occurrence of multiple symptoms. Additional research is warranted on the prevalence and impact of multiple symptoms, particularly among homogeneous samples of patients. Future directions for symptom studies in pediatric oncology include symptom cluster research and the search for biological bases for the untoward effects of cancer treatment.

Treatment of Nonmetastatic Cranial Parameningeal Rhabdomyosarcoma in Children Younger Than 3 Years Old: Results From International Society of Pediatric Oncology Studies MMT 89 and 95

To explore a strategy by which radiotherapy (RT) could be avoided in the treatment of young children with parameningeal rhabdomyosarcoma (PM RMS). Fifty-nine children (median age, 2 years 3 months) with nonmetastatic cranial PM RMS were treated in the International Society of Pediatric Oncology MMT 89 and 95 trials between 1989 and 2003. Five-year EFS and OS rates were 46% and 54%, respectively, for the whole group. No standard clinical or pathologic variables had prognostic impact. Fifty (85%) of 59 patients achieved complete local control either with (n = 28) or without (n = 22) RT administered as part of their primary treatment. Nine patients (15%) did not achieve local control (four of whom had had RT), and all died. Patients who received RT had a significantly superior 5-year EFS rate compared with patients who did not receive RT (59% v 28%, respectively). Twenty-three patients (48%) experienced relapse at a median interval of 15 months. Ultimately, only seven patients (12%) were cured without RT, although this represented 32% of those who achieved local control with initial chemotherapy. Despite concerns about the late effects of its use in young children, cure of PM RMS remains unlikely without systematic use of RT. The accurate prediction of the small subset of patients who achieve local control without RT and who do not experience relapse would provide an opportunity for a minority of patients to avoid RT.