International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationOutcomes Following Proton Therapy for Group III Pelvic Rhabdomyosarcoma
Introduction
Pelvic rhabdomyosarcoma (RMS) typically involves tumors of the bladder or prostate diagnosed in young children. Chemotherapy is necessary for systemic disease management, and local tumor management involves surgery, radiation, or a combination of the 2 approaches. Owing to the proximity of critical adjacent pelvic organs and the desire to minimize toxicity, determining the ideal approach to local control can be challenging. Multidisciplinary teams try to optimize the cure rate while maintaining bladder, bowel, reproductive, and musculoskeletal function whenever possible. The rare nature of this tumor and late onset of many side effects have prevented the development of prospective trials directly comparing various local therapies. Thus, we largely depend on retrospective data and secondary analyses to support our treatment approach.
The largest and most infiltrative pelvic RMS are often considered group III, or unresectable, owing to the morbidity associated with an attempt at complete resection at diagnosis. These patients require radiation. Since 2006, proton therapy has been used at the University of Florida with the goals of minimizing toxicity and improving the success of bladder preservation compared with historical management. This rationale is based on dosimetric studies that demonstrate that proton therapy reduces radiation exposure outside of the target in the management of pelvic sarcomas in children.1,2 To further decrease toxicity, we also limited the high-dose radiation to targets using the postinduction chemotherapy tumor volume. The preliminary feasibility of this approach has been studied for RMS arising from other anatomic sites.3
In analyzing this cohort of pediatric patients with group III pelvic RMS enrolled on a prospective outcome study, we specifically explored the following:
- 1.
Can proton therapy delivered to a postinduction chemotherapy target reduce toxicity without increasing local failures?
- 2.
Is there an association between chemotherapy regimen (or other risk factors) and disease control specific to pelvic tumors?
- 3.
How can this group of patients with initially unresectable tumors inform the ideal balance between radiation and surgical approaches to local control?
- 4.
What is the value of additional diagnostic surgery in children with a persistent mass or thickened bladder wall within the 18 months after radiation for pelvic RMS?
Section snippets
Methods and Materials
Between September 2006 and October 2018, 1657 pediatric patients (aged ≤21 years) were treated with proton therapy at the University of Florida. Under an institutional review board–approved prospective study, 31 of these patients were identified and consecutively treated with proton therapy for a group III pelvic RMS with a minimum of 6 months of potential follow-up. Patients who received prior radiation and those with vaginal, cervical, and paratesticular RMS were excluded.
Patients were
Patient, tumor, and treatment characteristics
All 31 patients had Children’s Oncology Group (COG) group III embryonal RMS of the pelvis. The median age at the time of radiation was 2.6 years (range, 1-20 years). Twenty-four patients were male; 24 were white, 4 were black, and 1 was Asian. No patient had a known germline p53 mutation. In total, 20 and 7 patients had tumors of the bladder and prostate, respectively. In 4 patients, the largeness of the tumor prohibited a specific pelvic organ from being designated the primary site. Seven
Discussion
RMS is the most common sarcoma in children, but pelvic RMS represents only 15% to 20% of cases.5 Of these, a smaller subset is nonmetastatic but unresectable at diagnosis and thus designated as group III. Local therapy for group III pelvic RMS presents several challenges owing to the frequent involvement of the bladder, bowel, prostate, urethra, and lymph nodes. Reliable local control usually requires a component of radiation. However, the low incidence of this tumor among children means
Conclusions
This cohort of young children with group III pelvic RMS treated with proton therapy on a prospective outcome study using postchemotherapy target volumes demonstrates similar local control with less toxicity than in historical reports. Using this treatment approach, functional bladder preservation is possible in most patients. For a rare tumor, our findings contribute valuable insight on patient and treatment characteristics influencing prognosis—including the impact of age, chemotherapy, and
References (34)
- et al.
A dosimetric comparison of proton and intensity modulated radiation therapy in pediatric rhabdomyosarcoma patients enrolled on a prospective phase II proton study
Radiother Oncol
(2014) - et al.
Proton radiotherapy for pediatric bladder/prostate rhabdomyosarcoma: Clinical outcomes and dosimetry compared to intensity modulated radiation therapy
Int J Radiat Oncol Biol Phys
(2011) - et al.
Local failure in parameningeal rhabdomyosarcoma correlates with poor response to induction chemotherapy
Int J Radiat Oncol Biol Phys
(2015) - et al.
Local control for intermediate-risk rhabdomyosarcoma: Results from D9803 according to histology, group, site, and size: A report from the Children's Oncology Group
Int J Radiat Oncol Biol Phys
(2015) - et al.
Brachytherapy combined with surgery for conservative treatment of children with bladder neck and/or prostate rhabdomyosarcoma
Int J Radiat Oncol Biol Phys
(2017) - et al.
Risk factors and predictors of severity score and complications of pediatric hemorrhagic cystitis
J Urol
(2014) - et al.
Parameningeal rhabdomyosarcoma in pediatric age: Results of a pooled analysis from North American and European cooperative groups
Ann Oncol
(2014) - et al.
Treatment approach and outcomes in infants with localized rhabdomyosarcoma: A report from the soft tissue sarcoma committee of the Children's Oncology Group
Int J Radiat Oncol Biol Phys
(2019) - et al.
Does bladder preservation (as a surgical principle) lead to retaining bladder function in bladder/prostate rhabdomyosarcoma? Results from Intergroup Rhabdomyosarcoma Study IV
J Urol
(2004) - et al.
Radiation therapy target volume reduction in pediatric rhabdomyosarcoma: Implications for patterns of disease recurrence and overall survival
Cancer
(2013)
The Third Intergroup Rhabdomyosarcoma Study
J Clin Oncol
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
Pediatr Blood Cancer
Treatment efficiency, outcome and surgical treatment problems in patients suffering from localized embryonal bladder/prostate rhabdomyosarcoma: A report from the Cooperative Soft Tissue Sarcoma trial CWS-96
Pediatr Blood Cancer
Results of treatment of fifty-six patients with localized retroperitoneal and pelvic rhabdomyosarcoma: A report from The Intergroup Rhabdomyosarcoma Study-IV, 1991-1997
Pediatr Blood Cancer
Advances in ventriculography and myelography with the non-ionic constrast medium metrizamide
Acta Radiol Suppl
Improvements in the treatment of patients suffering from bladder-prostate rhabdomyosarcoma: A report from the CWS-2002P trial
Ann Surg Oncol
Sequelae of treatment in 109 patients followed for 5 to 15 years after diagnosis of sarcoma of the bladder and prostate. A report from the Intergroup Rhabdomyosarcoma Study Committee
Cancer
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This research was made possible with the support of the William and Joan Mendenhall Endowed Professorship.
Disclosures: In the last 36 months, D.J.I., R.B.M.V., and J.A.B. have received grants from IBA outside of this research.
The data that support the findings of this study are available from the corresponding author upon reasonable request.