Patterns of failure and toxicity profile following proton beam therapy for pediatric bladder and prostate rhabdomyosarcoma

Pediatr Blood Cancer. 2019 Nov;66(11):e27952. doi: 10.1002/pbc.27952. Epub 2019 Aug 9.

Abstract

Purpose/objective(s): Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy.

Materials/methods: Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT.

Results: The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both).

Conclusions: PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.

Keywords: bladder; pediatric; prostate; proton beam radiotherapy; rhabdomyosarcoma.

Publication types

  • Observational Study

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child, Preschool
  • Combined Modality Therapy
  • Cystectomy
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Staging
  • Proctitis / etiology
  • Progression-Free Survival
  • Proportional Hazards Models
  • Prospective Studies
  • Prostatectomy
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / surgery
  • Proton Therapy* / adverse effects
  • Proton Therapy* / methods
  • Radiation Injuries / etiology
  • Registries
  • Rhabdomyosarcoma, Alveolar / drug therapy
  • Rhabdomyosarcoma, Alveolar / pathology
  • Rhabdomyosarcoma, Alveolar / radiotherapy
  • Rhabdomyosarcoma, Alveolar / surgery
  • Rhabdomyosarcoma, Embryonal / drug therapy
  • Rhabdomyosarcoma, Embryonal / pathology
  • Rhabdomyosarcoma, Embryonal / radiotherapy*
  • Rhabdomyosarcoma, Embryonal / surgery
  • Risk
  • Tumor Burden
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / radiotherapy*
  • Urinary Bladder Neoplasms / surgery
  • Urinary Incontinence / etiology