2.1 Patients

We retrospectively reviewed 98 pathologically diagnosed RMS patients whose primary site was in the head and neck region in our hospital from February 2005 to September 2017. The inclusion criteria were as follows: (a) patients diagnosed with head and neck RMS for the first time in our hospital; (b) patients with age <14 years; and (c) patients undergoing surgery, chemotherapy, radiotherapy, and follow-up according to comprehensive treatment of our hospital. Patients who died within 3 months of diagnosis and did not undergo surgical treatment were excluded from this study. This study was approved by the ethics committee of Beijing Tong Ren Hospital. Written informed consent was obtained from all participants and their guardians.

2.2 Diagnostic criteria

Pathological diagnosis was based on surgical resection or tumor biopsy. Histology was mainly classified as embryonal (tumor cells tend to be more elongated and less densely cellular) and alveolar subtypes (tumor cells tend to be smaller and rounder, often with a denser cellularity) (Wexler, Meyer, & Helman, 2011). Risk stratification (Malempati & Hawkins, 2012) (low risk, intermediate risk, and high risk) for RMS was based on both a pretreatment (TNM) staging system (stage 1–4) and a surgical/pathologic clinical grouping system (group I–IV) established by the IRSG (Lawrence, Anderson, Gehan, & Maurer, 1997; Maurer et al., 1988).

2.3 Therapy

Patients received comprehensive treatment. For patients whose tumor could be removed completely, one-stage surgery was performed firstly, and then, 8-cycle chemotherapy was carried out after the complete surgical resection. For patients whose tumor invaded more sites and could not be removed completely, tumor biopsy was performed, and then, 2- to 4-cycle chemotherapy was carried out after obtaining pathological diagnosis. In the case of tumor reduction, the second surgery was performed to remove tumor to the maximum extent, and then, 6-cycle chemotherapy was carried out. Radiotherapy was performed for children over 3 years old (including 3 years old) with group III–IV, and the dose of radiotherapy was 36–45 Gy. Patients with recurrence and metastasis were treated with individualized therapy (CEM [cyclophosphamide/etoposide/melphalan] conditioning regimen combined with autologous peripheral blood stem cell transplantation [APBSCT]) (Huang et al., 2004; Tang et al., 2001) for 2-year total cycles. The successful hematopoietic reconstitution criteria were as follows: nucleated cells ≥0.5 × 10⁹/L, platelet ≥20 × 10⁹/L, and hemoglobin ≥80 g/L.

Patients were treated with the following four chemotherapy regimens alternately: vincristine, actinomycin, and cyclophosphamide (VAC); vincristine, doxorubicin, and cyclophosphamide (VDC); isocyclophosphamide and etoposide (IE); and vincristine, topotecan, and cyclophosphamide (VTC).

2.4 Analysis of therapeutic effect and follow-up

The prognosis of patients was indicated by the overall survival (OS). OS was calculated from the day of first admission to hospital to the time of the last follow-up or death. The evaluation criteria of chemotherapy efficacy were complete remission (CR), partial remission (PR), and progressive disease (PD). CR was defined as disappearance of all known tumor lesions. PR was defined as a reduction of the product of the largest perpendicular diameters of all measurable lesions by more than 50%. PD was defined as the appearance of any new lesion not previously identified or an estimated increase of 25% or more in existing lesions. The patients were followed up to July 2018, with a median follow-up of 41.5 months (range from 2 to 149 months).

2.5 Statistical analysis

All statistical analyses were performed by using SPSS version 20.0 (SPSS Institute). Quantitative data were expressed as means ± standard deviations (SD). Qualitative data were expressed as number and percentage. Prognostic factor was evaluated by univariate and multivariate analysis using Cox's proportional hazards model. Survival curves were calculated by Kaplan–Meier method. Statistical significance was set at p < .05.

3.1 Baseline characteristics

A total of 98 patients (53 males, 45 females; median age: 5.8 years; range from 2 months to 13.4 years) with head and neck RMS were enrolled in this retrospective study from February 2005 to September 2017. The baseline characteristics of included patients were showed in Table 1. Among the 98 patients, 26 (26.5%) were diagnosed within 3 years old (12 patients were diagnosed within 1 years old), 72 (73.5%) were diagnosed after 3 years old (14 patients were diagnosed after 10 years old), 62 (62.3%) patients were embryonal subtype, and 36 (36.7%) patients were alveolar subtype. Among the 36 patients with alveolar subtype RMS, 12 were diagnosed within 3 years old, 23 were diagnosed after 3 years old, and one was diagnosed with positive for fusion of PAX-FOXO1 genes (age: 10 years old). Otherwise, tumor sites of 43 (43.9%) patients were in the orbit region, 46 (46.9%) patients in the para-meningeal region, and 9 (9.2%) patients in nonorbital and nonmeningeal region. In addition, 71 (72.5%) patients were in the clinical group III and 27 (27.5%) patients in group IV. Among the 27 patients with clinical group IV, one was diagnosed within 1 year old, four were diagnosed at 1–3 years old, 21 were diagnosed at 4–9 years old, and 1 was diagnosed after 10 years old. The majority of cases were in intermediate risk (42.9%) and high risk (29.6%).

Among the 98 patients, 83 (84.7%) were administered with radical surgery, 15 (15.3%) with only biopsy, 57 (58.2%) with radiotherapy, and 97 (99.0%) with chemotherapy, 3 (3.1%) with CEM conditioning regimen combined with APBSCT.

3.2 Treatment outcome

In our analysis of 98 patients with head and neck RMS, the median follow-up for survivors was 41.5 months (range, 2–149 months). At the study closing date, there were 60 patients alive, 37 patients had died due to intracranial metastases and tumor progression, one patient was lost to follow-up, and 47 patients relapsed. In addition, 56 (57.1%) cases obtained the CR, 25 (25.5%) cases obtained the PR, and 17 (17.3%) cases obtained the PD. The median disease-specific survival was 60.00 ± 25.36 months, and the overall survival rate was 61.9% (Figure 1). In three cases with APBSCT, two cases obtained the CR, one case recurred 6 months after the operation and died 8 months after the recurrence, and the total survival time was 29 months.

3.3 Analysis of prognostic factors for disease-specific survival

The distribution of clinical and pathologic factors that were predictive for disease-specific survival by both univariate and multivariate analyses was described in Table 2. Univariate analysis revealed that age, pathology type, chemotherapy efficacy, and diagnosis time were significantly associated with survival. The OS rate for patients with age ≤3 and >3 years was 42.3% and 69.0%, respectively (HR = 2.33, p < .05) (Figure 2a). CR was associated with a longer disease-specific survival (OS rate, 86.6%) compared with PR (OS rate, 6.7%) (HR = 16.494, p < .05) (Figure 2b). No statistically significant differences in disease-specific survival were identified when the study group was divided by pathology type (embryonal and alveolar, 61.3% vs. 61.1%) or by diagnosis time (≤2010 year and >2010 year, 62.2% vs. 50.0%). Multivariate analysis showed that age (HR = 0.075; 95% CI: 0.167–4.196; p < .05) and chemotherapy efficacy (HR = 0.004; 95% CI: 0.00–0.030; p < .05) were predictors of improved disease-specific survival.