PURPOSE
To compare eye preservation and survival outcomes between biopsy-only and debulking surgical approaches in pediatric orbital rhabdomyosarcoma treated with contemporary multimodal therapy.
METHODS
Retrospective chart review of 27 patients with primary orbital rhabdomyosarcoma treated at Children’s Hospital of Philadelphia between 2006 and 2025. Patients were categorized by initial surgical approach: biopsy-only ( n = 18, 67%) or debulking ( n = 9, 33%). All patients received multimodal therapy including chemotherapy and radiation. Primary outcome was eye preservation. Secondary outcomes included local recurrence, overall survival, and treatment complications.
RESULTS
Median follow-up was 2.32 years (range: 0.4-16.5 years). Baseline characteristics including age, tumor size, tumor location, and histology were well-balanced between groups. Eye preservation was achieved in 89% (16/18) of biopsy-only patients versus 78% (7/9) of debulking patients (OR 2.29, 95% CI 0.28-18.8, P =.58). Local recurrence occurred in 11% (2/18) of biopsy-only patients versus 33% (3/9) of debulking patients ( P =.30). Overall survival was 94% (17/18) in the biopsy-only group versus 78% (7/9) in the debulking group (OR 4.86, 95% CI 0.36-65.6, P =.25). Post-treatment complications including ptosis (70%) and cataracts (44%) did not differ significantly between groups.
CONCLUSIONS
Biopsy-only surgical approaches were noninferior and potentially superior to debulking, achieving comparable or better eye preservation, lower recurrence rates, and improved survival in pediatric orbital rhabdomyosarcoma, despite well-balanced baseline tumor characteristics. The consistent advantage of biopsy-only across multiple independent outcomes supports conservative surgical management that minimizes tissue disruption while maintaining excellent oncologic control. These findings validate current protocols advocating diagnostic biopsy as the primary surgical procedure, with chemotherapy and radiation providing definitive treatment.
Introduction
Rhabdomyosarcoma is the most common primary orbital malignancy in children, with orbital involvement occurring in 10% of rhabdomyosarcoma cases. ,,,, Despite its aggressive histology, orbital rhabdomyosarcoma carries favorable prognosis when treated with contemporary multimodal therapy, with 5-year survival rates exceeding 90%. ,, The evolution from radical surgical excision to tissue-sparing approaches represents a major success in pediatric oncology, with current protocols emphasizing diagnostic biopsy followed by chemotherapy and radiation. ,,
The appropriate extent of initial surgery remains debated. Based on the Intergroup Rhabdomyosarcoma Study Group (IRSG) derived cooperative-group experience and reflected in current NCI and European guidelines, there is scant evidence that debulking surgery, leaving macroscopic residual rhabdomyosarcoma, improves survival compared to biopsy alone. ,,, These findings prompted recommendations for diagnostic biopsy when complete excision with clear margins is not achievable. However, practice patterns vary, with some institutions advocating maximal safe debulking while others strictly adhere to biopsy-only protocols.
Some radiation oncologists favor delivering radiation when the tumor is intact (eg, preoperative or without prior extensive resection), because target-volume delineation is more straightforward, which may allow for more precise RT fields and potentially fewer long-term toxicities. A recent study of orbital rhabdomyosarcoma outcomes by a group in Amsterdam demonstrated excellent outcomes (77% eye preservation, 95% survival) with 95% of patients receiving biopsy-only, supporting conservative approaches. However, direct comparative data examining biopsy vs debulking within uniform treatment protocols remain limited. This study compared eye preservation and survival outcomes between biopsy-only and debulking approaches in orbital rhabdomyosarcoma patients treated with contemporary multimodal therapy.
METHODS
Retrospective chart review was performed on patients with primary orbital rhabdomyosarcoma at Children’s Hospital of Philadelphia between January 1, 2006, and December 1, 2025. This study was approved by the Institutional Review Board of Children’s Hospital of Philadelphia with a waiver of informed consent given the retrospective nature of the investigation. The study adhered to the tenets of the Declaration of Helsinki and complied with the Health Insurance Portability and Accountability Act. Patients were eligible for inclusion if they met all the following criteria: age 21 years or younger at diagnosis, histopathologic confirmation of rhabdomyosarcoma by institutional pathology review, primary tumor location within the orbit, treatment with curative intent including chemotherapy and radiation therapy, and minimum follow-up of 3 months unless death occurred earlier. Patients were excluded if they had nonrhabdomyosarcoma diagnoses, primary nonorbital rhabdomyosarcoma with secondary orbital extension, metastatic disease at presentation, incomplete treatment records, or palliative treatment intent.
Data abstraction was performed through systematic review of electronic medical records, including clinical notes, operative reports, pathology reports, radiology reports, chemotherapy administration records, and radiation oncology treatment summaries. The primary exposure variable was initial surgical approach, classified as biopsy-only or debulking. Patients in the biopsy-only group had incisional biopsy for diagnostic purposes only, with no attempt at tumor debulking or excision. Operative reports were reviewed to confirm that gross tumor mass remained in situ following the procedure. Patients in the debulking group underwent partial tumor resection or excision beyond what was required for diagnostic sampling, with intentional removal of gross tumor bulk.
All patients received multimodal therapy following contemporary protocols active during their treatment era. Chemotherapy treatment followed risk-adapted protocols based on tumor histology, stage, and group assignment. Low-risk patients with Group I or II embryonal rhabdomyosarcoma received vincristine, actinomycin D, and cyclophosphamide for 26 to 46 weeks. Intermediate-risk patients with Group III embryonal or Group I to III alveolar rhabdomyosarcoma received intensified regimens with interval compressed dosing. High-risk patients received investigational regimens through Children’s Oncology Group trials, typically adding additional agents such as topotecan, irinotecan, or anthracyclines. All patients in this cohort received external beam radiation therapy delivered through intensity-modulated radiation therapy or proton beam therapy. Radiation was typically initiated after 12 to 16 weeks of induction chemotherapy. Standard dose was 45 to 50.4 Gy delivered in 1.8 Gy fractions over 5 to 6 weeks. Patients with gross residual disease, positive margins, or unfavorable locations received 50.4 Gy.
The primary outcome was eye preservation, defined as retention of the globe throughout the follow-up period. Patients were considered to have lost eye preservation if they underwent exenteration, which is complete removal of orbital contents, for any indication. Secondary outcomes included local recurrence, defined as radiographic evidence of new or growing tumor within the orbit following achievement of complete clinical response. Overall survival was defined as vital status at last follow-up. Post-treatment complications were assessed including ptosis, cataract, and uveitis. Descriptive statistics were calculated for all variables. Continuous variables were described using medians with ranges. Categorical variables were described using frequencies and percentages. The primary comparison examined eye preservation rates between biopsy-only and debulking groups using Fisher’s exact test. Odds ratios with 95% CIs were calculated. Continuous variables were compared between groups using the Mann–Whitney U test. All statistical tests were two-sided with significance threshold of p <.05. Statistical analyses were performed using Python version 3.12.
RESULTS
Of 27 patients with primary orbital rhabdomyosarcoma who completed curative-intent treatment at our institution, 18 patients (67%) underwent biopsy-only and 9 patients (33%) underwent debulking procedures. Median follow-up for the entire cohort was 2.32 years (range: 0.4-16.5 years; IQR: 1.26-6.5 years). Median follow-up duration was 1.7 years for the biopsy group and 3.8 years for the debulking group ( P =.33).
The median age at diagnosis was 5.4 years (range: 0.2-19.2 years; IQR [IQR]: 3.6-7.4 years). The cohort included 14 males (52%) and 13 females (48%). Racial composition was White in 20 patients (74%), Black in 2 patients (7%), Other in 4 patients (15%), and Multiple Races in 1 patient (4%). Ethnicity was Hispanic or Latino in 3 patients (11%) and Not Hispanic or Latino in 24 patients (89%). Laterality was evenly distributed with right eye in 14 patients (52%) and left eye in 13 patients (48%). The most common presenting feature was proptosis, present in 25 patients (93%). Other findings included periorbital swelling in 18 patients (67%), ptosis in 12 patients (44%), and pain in 3 patients (11%).
Median tumor size was 2.7 cm for the biopsy group vs 2.5 cm for the debulking group ( P =.46). Tumor location by orbital quadrant was superior medial in 9 patients (33%), inferior in 7 patients (26%), superior in 4 patients (15%), superior lateral in 2 patients (7%), inferior medial in 1 patient (4%), lateral in 1 patient (4%), and extensive multiquadrant involvement in 3 patients (11%). Histologic subtypes were embryonal rhabdomyosarcoma in 23 patients (85%) and alveolar rhabdomyosarcoma in 4 patients (15%). All patients had localized disease at presentation with no distant metastases. Comparisons demonstrated no significant baseline differences between groups across patient and tumor characteristics ( Table 1 ).
TABLE 1
Baseline Patient and Tumor Characteristics by Surgical Approach
| Characteristic | Biopsy-Only ( n = 18) | Debulking ( n = 9) | P -Value |
|---|---|---|---|
| Age at diagnosis, years | |||
| Median (range) | 5.3 (0.5-15.7) | 5.4 (0.2-19.2) | .78 |
| IQR | 3.8-6.9 | 2.9-7.8 | |
| Sex, n (%) | 1.00 | ||
| Male | 9 (50%) | 5 (56%) | |
| Female | 9 (50%) | 4 (44%) | |
| Tumor size, cm | |||
| Median (range) | 2.7 (1.3-4.8) | 2.5 (2.2-9.5) | .46 |
| IQR | 2.3-3.1 | 2.3-3.4 | |
| Histology, n (%) | 1.00 | ||
| Embryonal | 15 (83%) | 8 (89%) | |
| Alveolar | 3 (17%) | 1 (11%) | |
| Presenting symptoms, n (%) | |||
| Proptosis | 17 (94%) | 8 (89%) | 1.00 |
| Pain | 2 (11%) | 1 (11%) | 1.00 |
| Treatment received, n (%) | |||
| Chemotherapy | 18 (100%) | 9 (100%) | 1.00 |
| Radiation therapy | 18 (100%) | 9 (100%) | 1.00 |
IQR = interquartile range.
P -values calculated using Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables.
All 27 patients received multimodal therapy. Chemotherapy regimens included vincristine, actinomycin D, and cyclophosphamide in 22 patients (81%), with 5 patients (19%) receiving intensified regimens with additional agents. Median chemotherapy duration was 42 weeks (range 26-60). All patients received external beam radiation therapy: 18 (67%) with IMRT and 9 (33%) with proton beam therapy. Median radiation dose was 50.4 Gy (range 36.0-101.4). Five patients received cumulative doses exceeding 54 Gy due to salvage re-irradiation after recurrence. Median time from surgery to chemotherapy initiation was 10 days (range 3-21, P =.42). Median time to radiation start was 14 weeks (range 10-18, P =.51). Treatment characteristics were similar between biopsy-only and debulking groups, with no significant differences observed ( Table 2 ).
TABLE 2
Treatment Characteristics by Surgical Approach
| Characteristic | Biopsy-Only ( n = 18) | Debulking ( n = 9) | P -Value |
|---|---|---|---|
| Time to chemotherapy, days | |||
| Median (range) | 10 (3-21) | 10 (4-20) | .42 |
| Time to radiation, weeks | |||
| Median (range) | 13 (10-17) | 15 (12-18) | .51 |
| Chemotherapy regimen, n (%) | |||
| VAC-based | 15 (83%) | 7 (78%) | 1.00 |
| Intensified | 3 (17%) | 2 (22%) | |
| Duration, median weeks | 42 (26-60) | 41 (28-58) | .68 |
| Radiation therapy | |||
| Received, n (%) | 18 (100%) | 9 (100%) | 1.00 |
| Median dose (range), Gy | 50.4 (45.0-95.4) | 50.4 (36.0-101.4) | .78 |
| IMRT, n (%) | 11 (61%) | 7 (78%) | .67 |
| Proton beam, n (%) | 7 (39%) | 2 (22%) | |
| Salvage treatment for recurrence | |||
| Re-irradiation, n (%) | 2 (11%) | 3 (33%) | .30 |
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