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Eyelid Rhabdomyosarcoma Survival In Children’s Oncology

Eyelid Rhabdomyosarcoma Survival In Children’s Oncology


Survival outcomes in Orbital Rhabdomyosarcoma (ORMS) typically show excellent results, especially in low-risk cases (stage 1, group I-III, embryonal RMS). However, long-term follow-up data on low-risk ORMS and less common subgroups treated in recent Children’s Oncology Group (COG) trials were previously unreported. To fill this gap, a study identified 218 patients with ORMS enrolled in COG trials from 1997 to 2013.

Among the patients, most had embryonal/botryoid tumors without lymph node involvement. In the low-risk ORMS group (192 patients), 10-year Event-Free Survival (EFS) and Overall Survival (OS) rates reached an impressive 85.5%. Specifically, patients with resected (group I/II) low-risk ORMS had even higher 10-year EFS and OS rates at 88.0% and 97.6%, respectively. The non-low-risk ORMS subgroup (26 patients) showed 5-year EFS and OS rates of 88.5% and 95.8%, respectively.

Notably, even patients with recurrent ORMS exhibited hopeful outcomes, with a 10-year OS rate from the time of recurrence reaching 69.4%. These findings highlight the favorable long-term survival achieved by ORMS patients participating in COG studies between 1997 and 2013, consisting of people with both low and non-low-risk disease. Moreover, a significant proportion of patients with recurrent ORMS demonstrated the potential for achieving long-term survival.

The study sheds light on the positive impact of COG trials in improving the survival rates of patients with ORMS, offering hope for enhanced treatment strategies and better prospects for those diagnosed with this condition.


Orbital rhabdomyosarcoma (ORMS) accounts for 10% of all rhabdomyosarcoma cases. The IRSG designates the orbit as a good primary site using the TNM staging system. Standard therapy for ORMS in subsequent Children’s Oncology Group (COG) and IRSG studies involves biopsy, followed by chemotherapy and radiotherapy, resulting in most patients being diagnosed with group III disease at presentation.

The highest reported failure-free survival (FFS) rate for group III ORMS patients was achieved with intensive therapy on the Intergroup Rhabdomyosarcoma Study IV (IRS-IV). However, this approach increased the risk of long-term morbidity due to high doses of cyclophosphamide or ifosfamide and radiation. Starting in 1997, COG trials categorized patients by risk group, and low-risk studies D9602 and ARST0331 included the majority of ORMS cases (non alveolar; groups I-III). These treatment-reduction trials reported favorable 5-year FFS and OS rates on D9602 (86% and 96%, respectively) and 3-year FFS and OS rates on ARST0331 (86% and 97%, respectively), despite reduced alkylator exposure and radiation dosing for group IIA and III orbit disease.

It is crucial to assess whether these promising survival rates on D9602 and ARST0331, despite therapy reductions, are sustained over time. The study aims to determine the long-term survival outcomes for ORMS on these trials, including less common subgroups such as group I/II low-risk disease and ORMS treated on intermediate and high-risk COG trials between 1997 and 2013.

Furthermore, the study seeks to evaluate the outcomes of patients with alveolar and/or metastatic ORMS (non-low-risk ORMS) on risk-group-stratified COG trials conducted since 1997. Additionally, the study will investigate the outcome of patients with recurrent ORMS, which has been reported retrospectively from IRS-III/IRS-IV but not from more recent COG trials.

In conclusion, this study aims to provide essential insights into the long-term survival outcomes of different subgroups of ORMS treated on COG trials. Understanding these results will aid in refining treatment approaches and potentially improving the quality of life for patients battling this disease.


This study focused on patients diagnosed with Orbital Rhabdomyosarcoma (ORMS) whose primary tumor subsite was located in the orbit or eyelid. The researchers identified these patients from various risk-group–stratified Children’s Oncology Group (COG) Rhabdomyosarcoma (RMS) trials, including D9602, D9802, D9803, ARST0331, ARST0431, ARST0531, and ARST08P1, with published primary articles at the time of the analysis. Prior to enrollment, informed consent or assent was obtained from the patients and/or their parent/guardian, and all trials were approved by relevant institutional review boards.

The study collected demographic information and disease characteristics, such as histology, clinical group, tumor size, invasiveness, nodal status, FOXO1 fusion status (when available), disease response, and recurrence site (when applicable). To ensure consistency, all histologies were classified based on central re-review using current definitions due to evolving RMS histology definitions over time.

The outcomes were evaluated for four specific groups: 

  1. Low-risk ORMS treated on D9602 and ARST0331.
  2. Resected (group I/II), low-risk ORMS treated on D9602 and ARST0331.
  3. Non–low-risk ORMS, defined as ORMS patients enrolled in intermediate-risk and high-risk trials D9802, D9803, ARST0431, ARST0531, and ARST08P1.
  4. Recurrent disease, defined as disease progression or relapse, observed in all trials.

By analyzing these distinct groups, the study aimed to provide valuable insights into the outcomes of patients with ORMS treated under various risk-stratified COG RMS trials. This research approach ensures the accuracy and relevance of the data for refining treatment strategies and improving patient care.


Statistical analysis 

The study’s data on demographics and disease characteristics were presented in a descriptive manner. The research focused on Event-Free Survival (EFS) and Overall Survival (OS) measures. EFS represented the time from the start of treatment until the first occurrence of disease progression, recurrence, second malignancy, or death. OS, on the other hand, denoted the time from the start of treatment to death from any cause, except for recurrent ORMS, where it was defined as the time from the first documented recurrence to death.

The median follow-up was calculated based only on censored times, which accounted for cases where the endpoint event did not occur during the study period. To estimate survival distributions, the study employed the Kaplan-Meier method, with the standard error of the Kaplan-Meier estimate determined using the Peto-Peto method.

The study assessed EFS and OS at the 10-year mark for low-risk ORMS, group I/II low-risk ORMS, and recurrent ORMS. For non-low-risk ORMS, due to the shorter follow-up duration for patients enrolled on ARST0531, EFS and OS were estimated at the 5-year interval.

The analysis was based on the data frozen on June 30, 2018, ensuring that the conclusions drawn from the study were consistent and relevant to the specified timeframe.

In summary, the study meticulously utilized survival metrics and statistical methodologies to analyze the data, providing valuable insights into the outcomes of different ORMS subgroups over specified time periods. The utilization of standardized methods enhances the reliability and credibility of the research findings, making it valuable for guiding future treatment strategies and patient care decisions.


The study identified 218 patients with Orbital Rhabdomyosarcoma (ORMS) who participated in Children’s Oncology Group (COG) trials between 1997 and 2013. Among them, 192 were enrolled in low-risk studies, D9602 and ARST0331. 59.2% of patients were male and aged 1 to 9 years (72.9%). Embryonal/botryoid histology was the most common (77.5%), and most tumors were classified as group III (78.0%), noninvasive (T1), and without clinical regional lymph node involvement (N0).

Low-risk trials exhibited a 10-year Event-Free Survival (EFS) rate of 85.5% and an Overall Survival (OS) rate of 95.6%. There were five patients with group I and 39 patients with group IIA ORMS on low-risk trials, showing a 10-year EFS of 88.0% and 10-year OS of 97.6% for this subgroup.

For non-low-risk ORMS, which included alveolar histology, 5-year EFS and OS rates were 88.5% and 95.8%, respectively. The recurrences primarily occurred in patients younger than 1.5 years with localized, PAX3-FOXO1 fusion-positive alveolar RMS.

Among the 28 patients who experienced a recurrence, the majority were treated on low-risk trials (89.3%) and had embryonal/botryoid histology. The 10-year OS rate from the time of recurrence was 69.4%.

The study’s median follow-up duration for patients was 8.7 years for low-risk ORMS, 9.2 years for group I and IIA ORMS, and 6.9 years for non-low-risk ORMS.

In conclusion, the study provided valuable survival data for different subgroups of ORMS patients treated in COG trials, demonstrating favorable long-term outcomes for low-risk patients and offering insights into the prognosis and treatment approaches for recurrent and non-low-risk ORMS cases. The research contributes to enhancing treatment strategies and care for patients with ORMS.


The study’s findings indicate a positive long-term prognosis for patients with low-risk Orbital Rhabdomyosarcoma (ORMS) on Children’s Oncology Group (COG) trials D9602 and ARST0331. The majority of patients had embryonal tumors without local invasion (T1) or nodal involvement (N0), aligning with previous reports demonstrating low metastatic potential for such tumors. These features allowed for a more limited staging evaluation, omitting bone marrow aspirates/biopsies.

Although the long-term Event-Free Survival (EFS) rate for ORMS on D9602 and ARST0331 was below 90%, the Overall Survival (OS) rate remained above 95%. The reduced cyclophosphamide and radiation doses in comparison to IRS-IV therapy balanced survival with potential long-term toxicities. Importantly, these treatment de-escalations did not lead to late recurrences in ORMS patients. The study also supports the use of reduced radiation doses (36 Gy) for patients with group IIA disease, as it yielded favorable outcomes.

Patients with non-low-risk ORMS also achieved excellent 5-year outcomes with intensified therapy on COG intermediate-risk and high-risk studies. Furthermore, a significant proportion of patients with recurrent ORMS achieved long-term survival, including those treated on ARST0331 and non-low-risk trials with initial cyclophosphamide treatment.

Regarding patients with resected (group I/IIA) ORMS, a notable number were identified, and the majority had favorable outcomes, supporting the efficacy of an initial resection approach. However, achieving up-front negative surgical margins for group I ORMS in the orbit appeared challenging due to limited space, leading to a small representation of this group.

Different international cooperative groups have demonstrated that patients who attain full remission using initial chemotherapy may be successfully treated without radiation. Nonetheless, the omission of radiation requires careful consideration due to the burden of treatment for recurrent disease.

Although the study lacks precise data on radiation therapy reductions and their impact on toxicity, the results support the overall favorable outcomes and emphasize the importance of balancing therapy intensity with potential late effects.

Regarding second malignant neoplasms, they occurred after 5 years and were likely influenced by therapy and cancer-predisposition syndromes. However, germline DNA sequencing data were not available for the cohort.

In conclusion, the study highlights positive long-term survival outcomes for different subgroups of ORMS patients on COG trials. The research findings have implications for treatment decisions and underscore the importance of personalized care for patients with this rare and complex malignancy.

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