A National Referral Service for Paediatric Brachytherapy: An Evolving Practice and Outcomes Over 13 Years.

AIMS: Most children requiring radiotherapy receive external beam treatment and few have tumours suitable for brachytherapy. No paediatric radiotherapy centre will treat enough patients from its own normal catchment population for expertise in brachytherapy to be developed and sustained. Following discussion and agreement in the national paediatric radiotherapy group, a service for paediatric brachytherapy in the UK has been developed. We report the process that has evolved over more than 10 years, with survival and functional outcome results. MATERIALS AND METHODS: Since 2009, potential patients have been referred to the central paediatric oncology multidisciplinary team meeting, where imaging, pathology and treatment options are discussed. Since 2013, the National Soft Tissue Sarcoma Advisory Panel has also reviewed most patients, with the principal aim of advising on the most suitable primary tumour management for complex patients. Clinical assessment and examination under anaesthetic with biopsies may be undertaken to confirm the appropriateness of brachytherapy, either alone or following conservative surgery. Fractionated high dose rate brachytherapy was delivered to a computed tomography planned volume after implantation of catheters under ultrasound imaging guidance. Since 2019, follow-up has been in a dedicated multidisciplinary clinic. RESULTS: From 2009 to 2021 inclusive, 35 patients (16 female, 19 male, aged 8 months to 17 years 6 months) have been treated. Histology was soft-tissue sarcoma in 33 patients and carcinoma in two. The treated site was pelvic in 31 patients and head and neck in four. With a median follow-up of 5 years, the local control and overall survival rates are 100%. Complications have been few, and functional outcome is good. CONCLUSION: Brachytherapy is effective for selected paediatric patients, resulting in excellent tumour control and good functional results. It is feasible to deliver paediatric brachytherapy at a single centre within a national referral service.

Long-term urological complications after conservative local treatment (surgery and brachytherapy) in children with bladder-prostate rhabdomyosarcoma: A single-team experience.

BACKGROUND: Outcome of children with bladder-prostate rhabdomyosarcoma (RMS) has improved with multimodal therapies, including surgery and/or radiotherapy for local treatment. Our aim was to report long-term urological complications after a conservative approach combining conservative surgery and brachytherapy. PATIENTS AND METHODS: Eighty-six patients, free of disease, were retrospectively reviewed. Symptoms related to urinary tract obstruction, incontinence, infection, and lithiasis were reported and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) classification. Only symptomatic patients underwent urodynamic studies. Risk factors for complications were analyzed. RESULTS: There were 76 males and 10 females. The median follow-up was 6.3 years (18 months to 24 years). Complications occurred after a median follow-up of 5 years (0-21). Twenty-two patients (26%) had long-term urological complications. Urinary tract obstruction was found in 15 patients (17%) and urinary incontinence in 14 patients (16%). Recurrent urinary tract infection occurred in four patients and urinary lithiasis in four (5%). The underlying physiopathology included bladder dysfunction in 15 patients (17%), urethral stenosis in six (7%), and ureterovesical junction stenosis in five (6%). On univariate analysis, posterior bladder wall dissection (p = .001), bladder neck trigone dissection (p = .010), and partial prostatectomy (p = .023) were significantly associated with an increased risk of bladder dysfunction; on multivariate analysis, only age ≤2 years (p = .028) at operation and posterior bladder wall dissection (p = .006) were found to be significant. CONCLUSION: The conservative surgical approach combined with brachytherapy for bladder-prostate RMS leads to long-term urological complications in 26% of survivors. Optimizing brachytherapy doses for young children and establishing a clear and long-term follow-up protocol could help to reduce these complications.

Bladder function after conservative surgery and high-dose rate brachytherapy for bladder-prostate rhabdomyosarcoma.

BACKGROUND: Conservative surgery (CS) brachytherapy (BT) techniques for local therapy in bladder-prostate rhabdomyosarcoma (BP-RMS) seek to retain organ function. We report bladder function after high-dose rate (HDR) BT combined with targeted CS for any vesical component of BP-RMS. PROCEDURE: Prospective cohort of all BP-RMS patients between 2014 and 2019 receiving HDR-BT (iridium-192, 27.5 Gy in five fractions) with/without percutaneous endoscopic polypectomy (PEP) or partial cystectomy (PC). Functional assessment included frequency-volume chart, voided volumes, post-void residual, flow studies, continence status and ultrasound scanning; abnormalities triggered video urodynamics. RESULTS: Thirteen patients (10 male), aged 9 months to 4 years (median 23 months), presented with localised fusion-negative embryonal BP-RMS measuring 23-140 mm (median 43 mm) in cranio-caudal extent. After induction chemotherapy, local treatment consisted of PC+BT in three, PEP+BT in four and BT alone in six. At a median 3.5 years (range 21 months to 7 years) follow-up, all were alive without relapse. At a median age of 6 years (4-9 years), the median bladder capacity was 86% (47%-144%) of that expected for age, including 75% (74%-114%) after PC. Radiation dose to the bladder was associated with urinary urgency, but not bladder capacity or nocturnal enuresis. Complications occurred in two: one urethral stricture and one vesical decompensation in a patient with pre-existing high-grade vesico-ureteric reflux (VUR). The remaining patients were dry by day; five with anticholinergic medication for urinary urgency. Three patients are enuretic. CONCLUSIONS: Day-time dryness at a median 3.5 years after CS-HDR-BT was achieved in 92%, with 85% voiding urethrally, and 62% attaining day-and-night continence aged 4-9 years. We report reduced open surgery with minimally invasive percutaneous surgery, with HDR-BT or BT alone being suitable for many.

Sedation practices during high dose rate brachytherapy for children with urogenital and perianal rhabdomyosarcoma.

BACKGROUND: A novel concept for an organ-preserving treatment of pediatric urogenital and perianal rhabdomyosarcoma includes high dose rate brachytherapy following surgical tumor resection. For the duration of the brachytherapy of 6 days plus 2-day recovery break the patients are not allowed to move and are kept under deep sedation, which can lead to difficult weaning from mechanical ventilation, withdrawal, delirium, and prolonged hospital stay. The aim of this study was to evaluate a protocol which includes a switch from fentanyl to ketamine 3 days prior to extubation to help ensure a rapid extubation and transfer from PICU. METHODS: Patients who underwent surgical tumor resection of rhabdomyosarcoma and subsequent brachytherapy were treated according to a standardized protocol. We evaluated doses of fentanyl, midazolam and clonidine, time of extubation, length of PICU stay and occurrence of withdrawal symptoms and delirium. We compared fentanyl dose at time of extubation, duration of weaning from mechanical ventilation and time to discharge from PICU with patients after isolated severe traumatic brain injury. RESULTS: Twentytwo patients (age 39.9 ± 29.8 months) were treated in our PICU to undergo brachytherapy. Extubation was performed 21.6 ± 13.5 h after the last brachytherapy session with an average fentanyl dose of 1.5 ± 0.5 µg/kg/h and patients were discharged from PICU 58.4 ± 30.3 h after extubation, which all is significantly lower compared to the control group (extubation after 88.0 ± 42.2 h, p < 0.001; fentanyl dose at the time of extubation 2.5 ± 0.6 µg/kg/h, p < 0.001; PICU discharge after 130.1 ± 148.4 h, p < 0.009). Withdrawal symptoms were observed in 9 patients and delirium in 13 patients. CONCLUSION: A standardized analgesia and sedation protocol including an opioid break, scoring systems to detect withdrawal symptoms and delirium, and tapering plans contributes to successful early extubation and discharge from PICU after long-term deep sedation.

Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma: Compliance and early clinical results.

OBJECTIVE: No data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters. MATERIALS AND METHODS: Treatment parameters and outcome of consecutive BP RMS patients treated in our center were examined. Treatment was carried out as part of a multimodal conservative radio-surgical treatment. Four single leader plastic tubes were implanted under perioperative guidance, encompassing the prostate/bladder neck. Tubes were systematically sutured to the bladder wall. Treatment planning was based on a computed tomography and followed Paris system rules. Continuous hourly pulses of 0.42Gy were delivered, to a total dose of 60Gy. RESULTS: 32 patients were treated, median age 2.6years (10months-12years). Median duration of each pulse was 8.5min (3.8-17.4min). The minimal dose in the most irradiated 1cm3 of rectum was 44.7Gyα/ß=3 (range: 4.1-77.3Gyα/ß=3). Brachytherapy was conducted without significant compliance concern in all but two patients, 24 and 25months-old, who pulled out plastic tubes before treatment completion. Another child needed re-planning because of slight tube displacement. With median follow-up of 14.4months (15days-75months), all patients were free from any relapse after local treatment. Four grade 3 acute urinary complications were encountered. All long-term side effects were grade 2 or less. CONCLUSION: PDR brachytherapy is feasible in very young patients, and associated with acceptable acute toxicity rates. Longer follow-up is required to ensure that local control and long-term side effects profile are comparable to the results of low dose rate brachytherapy.

Quality of life and functional outcome of male patients with bladder-prostate rhabdomyosarcoma treated with conservative surgery and brachytherapy during childhood.

PURPOSE: The aim of this study was to report the long-term results of a conservative local treatment of male patients with bladder-prostate rhabdomyosarcoma (BPRMS) focusing on their outcome and quality of life (QoL). METHODS AND MATERIALS: From 1991 to 2007, 27 male patients were treated by a single team, according to the ongoing European protocols. Surgical procedure was partial cystectomy or partial prostatectomy or both, followed by low-dose-rate interstitial brachytherapy. Three patients died of metastases and two were excluded; 22 patients, who were long-term survivors with their bladder, received a QoL questionnaire derived from the International Workshop on BPRMS. Urodynamic studies were performed when patients had abnormal continence. RESULTS: Median age at surgery was 24 months (14 months-11 years). Median followup after surgery was 10 years (5-21 years); 18 male patients (77%) completed the questionnaire at a median age of 13 years (7-25 years); 13 considered themselves as having a normal QoL, with normal urinary continence (9 of 13) or very rare diurnal dribbling (4 of 13). Four male patients had frequent diurnal dribbling requiring protection for three of them and one was submitted to intermittent catheterism for a postoperative neurogenic bladder. Urodynamic studies were performed in 11 patients with urinary disturbance, often revealing detrusor sphincter dyssynergia. All pubertal patients considered themselves as having normal erections. Three sexually active patients reported having satisfying sex and orgasms. Two patients had normal ejaculations. CONCLUSIONS: The majority of long-term male survivors (76%) within this cohort considered themselves as having a normal QoL after the combined conservative local treatment of their BPRMS.