Clinical Investigation
Outcomes Following Proton Therapy for Group III Pelvic Rhabdomyosarcoma

https://doi.org/10.1016/j.ijrobp.2019.12.036Get rights and content

Purpose

This study aimed to report on the institutional outcomes after proton therapy for pelvic rhabdomyosarcoma (RMS).

Methods and Materials

Thirty-one children (≤21 years old) with group III pelvic RMS were enrolled on a prospective outcome study and treated between 2007 and 2018. Patients with vaginal/cervical RMS were excluded. The median age was 2.6 years. Twenty-four patients had embryonal RMS. At diagnosis, the median tumor volume was 185 cm3 and the median maximum diameter was 9.4 cm. Seven patients had N1 disease. Nineteen and 12 patients received European Pediatric Soft Tissue Sarcoma Study Group– and Children’s Oncology Group–based chemotherapy, respectively. Fourteen patients underwent resection of the primary tumor after induction chemotherapy, including 6 patients who had a total cystectomy. The median radiation dose was 50.4 Gy relative biological effectiveness.

Results

With a median follow-up of 4.2 years, the 5-year local control, progression-free survival, and overall survival rates were 83%, 80%, and 84%, respectively. Patients <3 years old had better local control (100% vs 68%; P = .02), and patients with embryonal histology had better survival (96% vs 54%; P = .02). No other factors were significantly associated with disease control or survival. Specifically, no statistically significant difference was observed in local control, progression-free survival, or overall survival when comparing patients who underwent biopsy versus gross total resection (75% vs 93%, 68% vs 93%, 75% vs 93%, respectively). Excluding patients who underwent cystectomy, urinary toxicity was limited to 2 patients with nocturnal enuresis. Exploratory surgery to address a persistent mass or thickened bladder wall after radiation was the most common source of serious toxicity.

Conclusions

This cohort of young children with large pelvic tumors treated with proton therapy demonstrates similar local control with less toxicity than historic reports. Functional bladder preservation is possible in most patients. Exploratory biopsy in the 18 months after radiation should be approached with caution.

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

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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.

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