Background and Aims

Congenital rhabdomyosarcoma (RMS) represents a challenging disease due its characteristics and the difficulties in delivering treatment in this immature population.

Methods

We analyzed patients with congenital RMS enrolled in the European paediatric Soft tissue sarcoma Study Group protocols. We defined as congenital, RMS diagnosed in the first two months of life and, as infants, those diagnosed >2 to 12 months of age.

Results

115 children aged <1 year were registered, including 24 congenital RMS. In the latter group, all, except one patient (PAX3-FOXO1-positive metastatic RMS), had favorable histology and localized disease. Three patients had VGLL2-CITED2/NCOA2 fusion. No radiotherapy was given, and complete tumor resection was achieved in 10 patients. Chemotherapy doses were adjusted to age and weight. Only two patients required further dose reduction for toxicity.

The 5-years EFS and OS were 75.0% (95% C.I. 52.6-87.9) and 87.3% (65.6-95.7) in the congenital and 68.4% (57.6-77.1) and 86.3% (77.1-92.0) in the infant group, respectively. Progressive disease was the main cause of treatment failure in the congenital group.

Conclusions

Patients with congenital RMS presented with favorable disease, allowing weight and age-adjusted doses of chemotherapy and avoidance of irradiation, without compromising outcome.

Background and Aims

Initial staging of rhabdomyosarcoma is crucial for prognosis and to tailor the treatment. The standard radiology workup (SRW) includes MRI, chest CT and bone scintigraphy, but ¹⁸F-FDG-PET/CT (PET-CT) use is increasing.

The aim of our study is to evaluate the impact of PET-CT in the initial staging of patients with metastatic rhabdomyosarcoma enrolled in the European protocol MTS2008.

Methods

Two authors retrospectively reviewed the SRW and PET-CT reports comparing the number and sites of metastases detected. For bone marrow involvement, PET-CT and bone marrow aspirates/biopsies were compared.

Results

Among 263 metastatic patients enrolled from October 2008 to December 2016, 121 had PET-CT performed at diagnosis, and for 118/121, both PET-CT and all radiological reports were available for review.

PET-CT showed higher sensitivity than SRW in the ability to detect locoregional (96.2% vs. 78.5%, p-value=0.0013) and distant lymph node involvement (94.8% vs. 79.3%, p-value= 0.0242), but sensitivity was lower for intrathoracic sites (lung 79.6% vs. 100%, p-value=0.0025). For bone metastasis, PET-CT was more sensitive than bone scintigraphy (96.4% vs. 67.9%, p-value=0.0116). The PET-CT sensitivity and specificity to detect marrow involvement were 91.8% and 93.8%, respectively.

The mean number of metastatic sites was 1.94 (range 0-5) with PET-CT and 1.72 (range 0-5) with SRW. In 4 (3.4%) patients, PET-CT changed the stage from localized to metastatic disease.

Conclusions

PET can help to identify all involved sites in metastatic RMS patients and can change the stage from localized to metastatic in a limited number of children. This is due to its higher ability to recognize lymph nodes and bone involvement. SRW remains essential to detect lesions in intrathoracic sites. PET-CT could replace bone scintigraphy to study bone involvement.

Background and Aims

EpSSG standard risk non-alveolar rhabdomyosarcoma patients: IRS stage II/III disease at favourable sites, including orbit, head and neck non- parameningeal (HNnonPM), genitourinary non-bladder- prostate (GUnonBP), were eligible for RMS2005 study Subgroup C.

Methods

Subgroup C patients were recommended to receive reduced dose alkylator chemotherapy with five cycles of Ifosfamide, Vincristine and Actinomycin-D (IVA) chemotherapy (30g/m² Ifosfamide) plus radiotherapy, or nine cycles of IVA (54g/m² Ifosfamide) without radiotherapy. Surgical/ delayed excision of the primary tumour (DPE) outcomes were recorded. Univariate analyses were performed.

Results

359 patients including orbit 164 (45.7%), HNnonPM 77 (21.5%) and GUnonBP 118 (32.8%). Five-year event free (EFS) & overall survival (OS) were 77.4% (CI 72.5- 81.6%) & 93.5% (CI 90.1- 95.8%) respectively; no significant differences based on IRS group or site. 232 patients (65%) received radiotherapy. Reduced dose alkylator chemotherapy and radiotherapy significantly improved 5-year EFS: 86.3% (17/ 132 relapsed) versus 65.7% (38/ 113 relapsed) (p=0.0002) for 9 cycles IVA without RT, but not 5-year OS: 93.7% and 93.9% (p=0.8003) respectively.

80/ 248 (32.3%) IRSIII cases had DPE; only 4 had macroscopic residual. For the 60 patients with complete microscopic (R0) resection, there was no significant difference in EFS or OS with adjuvant radiotherapy.

16 patients with favourable disease based on size and age achieved a complete remission with IVA. Local failure occurred in 8 (50%); 7 receiving 9 IVA alone, and 1 receiving 5 IVA, 4 VA and radiotherapy. For orbital tumours 5-year EFS was 22.3% (19/ 26 relapsed) without radiotherapy.

Conclusions

Excellent outcomes were observed for EpSSG Standard Risk Subgroup C rhabdomyosarcoma. For those receiving radiotherapy, reduced dose alkylator chemotherapy should be the standard. Reduced EFS but not OS is observed with the omission of radiotherapy. Adjuvant radiotherapy may be safely omitted for RMS2005 Standard Risk Subgroup C rhabdomyosarcoma where there has been a delayed R0 resection.

Background and Aims

Local therapy for head-neck rhabdomyosarcoma (HNRMS) patients includes radiation therapy potentially combined with surgery. Adverse effects (AEs) of local treatment are prevalent in survivors. Efforts are being made to limit AEs through more conformal radiation techniques and the development of new combined modality strategies. Theoretical differences between strategies exist but the actual clinical benefit in survivors remains unclear. The primary purpose of this study was to describe the prevalence and severity of AEs in HNRMS survivors. Also, the data allowed a comparison of AEs between four local treatment strategies: definitive external beam radiotherapy with photons, definitive external beam radiation with protons, surgery combined with brachytherapy (AMORE), and surgery combined with external beam radiotherapy.

Methods

A trans-Atlantic, international, multicenter cross-sectional cohort study was performed. Survivors with ≥2 years follow-up after treatment for a primary pediatric HNRMS were systematically assesed by a multidisciplinary team systematically following a predefined list of AEs according to the Common Terminology Criteria for Adverse Events v 4.0 system during outpatient clinic visits.

Results

Ninety-nine survivors with a median follow-up of 9 years were included. Eighty-three percent of survivors experienced at least one grade ≥2 AE, survivors had a median of 8 different AEs. Musculoskeletal deformity, cataract, hearing impairment, speech abnormalities and eyelid disfunction were the most common AEs. Tumor size ≥5cm and younger age (0-5y) at diagnosis were independent risk factors for a grade ≥3 AE. Our results suggest variation in type and severity of AEs between different local treatment strategies, but these differences were not statistically significant.

Conclusions

HNRMS survivors are at high risk for a diverse range of toxicity. The nature of AEs varies between local treatment strategies and data from this study may be used to optimize side-effect surveillance. Both dose-effect analyses as well as long-term clinical outcomes are necessary to properly tailor local therapy for children with HNRMS .