Head And Neck Rhabdomyosarcoma Research Articles

Incidence and patterns of lymph node metastases in head and neck rhabdomyosarcoma: One-institution study.

Head and neck rhabdomyosarcoma (HNRMS) is an aggressive malignant soft tissue tumor that easily develops lymph node metastasis (LNM) and distant metastasis. No literature investigates the pattern of LNM in HNRMS. Ninety-five consecutive patients with HNRMS newly diagnosed at one institution between November 2011 and July 2023 were retrospectively reviewed. All the patients underwent head and neck contrast-enhanced MRI and/or CT, PET-CT if necessary. The associations between LNMs and clinical characteristics and histopathological parameters were discovered. 44.2% of patients had evidence of LNM at diagnosis, and the most common LNM occurred in the ipsilateral retropharyngeal space. The primary tumor metastasizes to the retropharyngeal space, and then next to level II is the most common LN drainage basin. In multivariate analysis, only distant metastasis determines the prognosis, other than LN status. LNM has a high incidence in HNRMS and rarely causes contralateral metastasis for localized lesions or skip metastasis.

Nomogram to predict prognosis of head and neck rhabdomyosarcoma patients in children and adolescents.

This study aims to explore the prognostic factors of head and neck rhabdomyosarcoma (HNRMS) in children and adolescents and construct a simple but reliable nomogram model for estimating overall survival (OS) of patients. Data of all HNRMS patients during 2004-2018 were identified from the Surveillance, Epidemiology, and End Result database. Kaplan-Meier method was performed to calculate OS stratified by subgroups and comparison between subgroups was completed by log-rank test. Univariate and multivariate Cox regressions analysis were employed for identifying independent predictors, which subsequently were used for a predictive model by R software, and the efficacy of the model was evaluated by applying receiver operating curve (ROC), calibration and decision curve analysis (DCA). A total of 446 patients were included in the study. The 1-, 3-, and 5-year OS rate of the whole cohort was 90.6%, 80.0%, and 75.5%, respectively. The results of univariate and multivariate Cox regression analysis indicated that the primary site in parameningeal region, alveolar RMS histology, M1 stage, IRS stage 4, surgery, and chemotherapy were significant prognostic factors (all P<0.05). The performance of nomogram model was validated by discrimination and calibration, with AUC values of 1, 3, and 5 years OS of 0.843, 0.851, and 0.890, respectively. We constructed a prognostic nomogram model for predicting the OS in HNRMS patients in children and adolescents and this model presented practical and applicable clinical value to predict survival when choosing treatment strategies.

Adult head and neck rhabdomyosarcoma: radiotherapy- based treatment, outcomes, and predictors of survival

BackgroundAdult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS.MethodsWe retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan–Meier method. The chi-square and Fisher’s exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan–Meier method. Prognostic variables were assessed through univariate Cox analyses.ResultsThe median patient age was 28 years (range, 16–82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival.ConclusionsThe main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

Comparison of Survival Outcomes between Adults and Pediatrics with Non-Metastatic Head and Neck Rhabdomyosarcoma: A SEER Database Analysis of 550 Patients

Despite the long-term survival rate for children with head and neck rhabdomyosarcoma (HNRMS) has improved to over 70-80% due to advancements in therapeutic approaches, the survival outcomes for adult HNRMS have not been thoroughly investigated. Our study aims to compare and analyze the survival outcomes of adult and pediatric patients with non-metastatic HNRMS, with a focus on the effect of different local treatment methods on disease outcomes. We conducted a retrospective analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database covering the period from 2004 to 2018. Our study population consisted of patients with Head and Neck Rhabdomyosarcoma (HNRMS) who had not developed distant metastases and received at least one local treatment, either radiotherapy or surgery. The comparison of overall survival (OS) and cancer-specific survival (CSS) was performed between the adult and pediatric patient groups, and between patients who received surgery (with or without radiotherapy) and those who received radiotherapy only (non-surgery). In the study of 550 patients diagnosed with Head and Neck Rhabdomyosarcoma (HNRMS), data was collected from 181 (32.9%) adult and 369 (67.1%) pediatric patients. The results showed that the adult patient group had a significantly worse outcome compared to the pediatric group in terms of 5-year overall survival (OS) rate (34.9% vs 81.6%, P<0.001) and 5-year cancer specific survival (CSS) rate (59.96% vs 87.48%, P<0.001). Of these patients, 308(56%) underwent radical surgery, with 228 (41.5%) receiving a combination of radiation and surgery and the remaining 242 (44%) receiving radiation therapy alone. No significant differences were found in 5-year OS and CSS rates between the surgery and non-surgery (radiation only) groups in adult patients (34.9% vs 35.0%, P = 0.900; 60.2% vs 59.6%, P = 0.988). However, there were slight differences observed in the pediatric patient group, with the 5-year OS and CSS rates being higher for the surgery group compared to the non-surgery group (86.9% vs 75.9%, P = 0.001 and 90.6% vs 84.2%, P = 0.054, respectively). The results of this cohort study indicate that age plays a crucial role in predicting survival outcomes in patients diagnosed with Head and Neck Rhabdomyosarcoma (HNRMS). The findings highlight the need for age-specific treatment strategies for HNRMS patients. While the data suggests that radiotherapy may be a viable first-line option for non-metastatic adult HNRMS patients, additional research is required to validate these trends.

Non-inferior efficacy of non-surgical treatment to surgical treatment in patients with nonmetastatic head and neck rhabdomyosarcoma: a SEER-based study.

Head and neck rhabdomyosarcoma (HNRMS) is a rare but aggressive malignant neoplasm. Given the young patient age and critical anatomy of the head and neck, performing surgery on the primary tumor still remains debatable. This study aimed to evaluate the impact of the non-surgery-based treatment versus surgery-based treatment on patients with nonmetastatic HNRMS. Patients diagnosed with nonmetastatic HNRMS between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were enrolled in our study. Inverse probability treatment weighting (IPTW) method was employed to balance confounding factors between surgery and non-surgery groups. Kaplan-Meier methods and COX regression analyses were used to analyze survival outcomes of overall survival (OS) and cancer-specific survival (CSS). Prognostic nomogram was established to predict survival. A total of 260 eligible patients were extracted from the SEER database. Kaplan-Meier survival curves revealed that there was no significant difference in OS and CSS between the surgery and non-surgery groups both before and after IPTW (p > 0.05). Cox regression analyses and IPTW-adjusted Cox regression analyses for both OS and CSS showed similar survival between the two groups. Prognostic factors were explored and a nomogram for patients in the surgery group was constructed. Risk stratification based on the nomogram indicated that patients in surgery-high-risk group did not benefit from primary surgery. While those in surgery-low-risk group had an equal survival outcome to those in non-surgery group. Our study revealed that compared to patients receiving surgery, those not receiving surgery had similar survival outcomes for nonmetastatic HNRMS. Our established nomogram may serve as a practical tool for individual prognostic evaluations.

Efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma

Objective: To evaluate the efficacy and influencing factors of surgery combined with neoadjuvant chemoradiotherapy in the treatment of children with non-orbital head and neck rhabdomyosarcoma (HNRMS). Methods: Information from 45 children diagnosed as non-orbital HNRMS and subjected to surgery combined with neoadjuvant chemoradiotherapy in Beijing Children's Hospital affiliated to Capital Medical University from August 2017 to July 2021 was analyzed. The patients included 25 males and 20 females, aged from 1 to 17 years old. The primary tumor site, pathological subtype, clinical stage, risk group, therapeutic regimen, resection range and outcome of all cases were also collected. The survival curves were made using the Kaplan-Meier method and the potential prognostic factors were investigated by Cox regression analysis. Results: Fifteen (33.3%) of 45 children achieved negative surgical margin under complete tumor resection. The postoperative pathological results showed that there were 20 cases of embryonic subtype, 19 cases of alveolar subtype and 6 cases of spindle sclerosis subtype. The postoperative follow-up time ranged from 4 to 71 months, with a median of 26 months. During the follow-up period, 13 children died, among whom brain metastasis was the most common cause of death, accounting for 7/13. The 3-year overall survival rate was 67.6%. Multivariate analysis showed that non-embryonic subtype (HR=6.26, 95%CI: 1.52-25.87, P=0.011) and failure to reach R0 resection (HR=9.37, 95%CI: 1.18-74.34, P=0.034) were independent risk factors affecting overall survival rate. Conclusion: Surgery combined with neoadjuvant chemoradiotherapy can offer a good efficacy for children with non-orbital HNRMS. Non-embryonic subtype and resection without negative operative microscopic margins are independent risk factors for poor prognosis, and brain metastasis is the main cause of death in these children.

Exploration of dose-toxicity for ophthalmological adverse events in pediatric head and neck rhabdomyosarcoma survivors

<h3>Objectives</h3> Ophthalmological adverse events (OAEs) following local treatment for pediatric head and neck rhabdomyosarcoma (HNRMS) are prevalent. More knowledge on specific radiation dose-toxicity relationships for ophthalmological organs at risk (OARs) in children can help to avoid these OAEs. The aim of the present study is to explore the dose-toxicity probability for multiple OAEs seen in long term HNRMS survivors. <h3>Methods</h3> Clinical data on OAEs were systematically assessed in an international cross-sectional cohort that included survivors of pediatric HNRMS with ≥2 years follow-up. Dosimetric data were collected from the original radiotherapy treatment plans. OARs were delineated on the 3D radiotherapy planning CTs. Dose-toxicity probability curves were constructed using binary logistic regression. <h3>Results</h3> 74 eyes in 38 survivors with a median follow-up time of 9 years (range 2 – 27) were analyzed. With the exception of epiphora, dose-toxicity probability curves with good model-fit (AUC under ROC ≥0.8) were constructed for all OAEs. A >20% probability of globe displacement, dry eyes and/or cataract (any grade) at follow-up was seen for mean doses of >40, 10 and 6 GyEQD2 to the orbital bones, lacrimal gland and lens respectively. Retinopathy and optic neuropathy only occurred in eyes receiving maximum doses > 40 and 53 GyEQD2 to the retina and optic nerve respectively. No multivariable analyses were conducted because of low numbers of events per OAE. <h3>Conclusion</h3> We offer the first detailed description of specific dose-toxicity probability for ophthalmological OARs in children derived from clinically assessed OAEs in long-term survivors. These results are critical to: 1) quantify expected variation in clinical toxicity between different treatment techniques, 2) understand the additional OAEs children will incur if prescription dose for orbital RMS is increased from 45 Gy to 50.4 Gy on future clinical trials, and 3) inform physicians and future patients about expected long-term toxicity and necessary surveillance.

Particle beam radiation therapy for head and neck rhabdomyosarcoma in adults

Rhabdomyosarcoma (RMS) is rare in adults, with a significantly worse prognosis than its pediatric counterpart. Radiotherapy (RT) plays a significant role in treating head and neck RMS (HNRMS), but the outcomes of conventional RT are limited by the complex anatomy and unfavorable pathology subtypes of the adult H&N RMS. Here, we aim to report the effectiveness and safety of carbon-ion beam RT (CIRT), either alone or in combination with proton radiotherapy (PRT) in the management of adult HNRMS. Fifteen adult patients with HNRMS were enrolled on a prospective registry protocol between 06/2015 and 12/2019. Eight patients presented with parameningeal tumors, and eight had unfavorable pathology subtypes [alveolar =7, not otherwise specified (NOS) =1]. Eleven patients had gross tumors before the start of RT (volume range, 46.1-137.6 cm3). Two patients failed the earlier RT. All except for one patient received multi-drug chemotherapy. The median absolute dose of particle beam RT was 70.0 Gy [relative biological effectiveness (RBE)]. With a median follow-up of 21 months, local or distant recurrence occurred in three and four patients, respectively, and two added patients had both local and distant failure. One patient died of distant metastasis (DM), and another died of an unrelated condition. The 1- and 2-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) rates were 87.5% and 70.0%, 92.3% and 67.1%, 72.2% and 54.2%, and 65.0% and 24.4%, respectively, for the entire cohort. Both patients who failed earlier RT and received salvage CIRT developed DM but were alive at last follow-up. No acute toxicity of ≥ grade 3 or late toxicity of ≥ grade 2 was observed. CIRT, either used alone or in combination with PRT, is not only feasible and safe but also useful in local disease control for HNRMS. DM is the most important cause of treatment failure; thus, more effective systemic treatment is needed to improve the prognosis of HNRMS further.

Head and neck rhabdomyosarcoma with TFCP2 fusions and ALK overexpression: a clinicopathological and molecular analysis of 11 cases.

Primary intraosseous rhabdomyosarcoma (RMS) is a rare entity defined by EWSR1/FUS-TFCP2 or, less commonly, MEIS1-NCOA2 fusions. The lesions often show a hybrid spindle and epithelioid phenotype, frequently coexpress myogenic markers, ALK, and cytokeratin, and show a striking propensity for the pelvic and craniofacial bones. The aim of this study was to investigate the clinicopathological and molecular features of 11 head and neck RMSs (HNRMSs) characterised by the genetic alterations described in intraosseous RMS. The molecular abnormalities were analysed with fluorescence in-situ hybridisation and/or targeted RNA/DNA sequencing. Seven cases had FUS-TFCP2 fusions, four had EWSR1-TFCP2 fusions, and none had MEIS1-NCOA2 fusions. All except one case were intraosseous, affecting the mandible (n=4), maxilla (n=3), and skull (n=3). One case occurred in the superficial soft tissue of the neck. The median age was 29years (range, 16-74years), with an equal sex distribution. All tumours showed mixed epithelioid and spindle morphology. Immunohistochemical coexpression of desmin, myogenin, MyoD1, ALK, and cytokeratin was seen in most cases. An intragenic ALK deletion was seen in 43% of cases. Regional and distant spread were seen in three and four patients, respectively. Two patients died of their disease. We herein present the largest series of HNRMSs with TFCP2 fusions to date. The findings show a strong predilection for the skeleton in young adults, although we also report an extraosseous case. The tumours are characterised by a distinctive spindle and epithelioid phenotype and a peculiar immunoprofile, with coexpression of myogenic markers, epithelial markers, and ALK. They are associated with a poor prognosis, including regional or distant spread and disease-related death.

Radiotherapy Significantly Improves Long-Term Survival And Local Control Of Head And Neck Rhabdomyosarcoma (HNRMS) In Adults: Retrospective Analysis Of 64 Patients

Rhabdomyosarcomas in adults were rarely reported in the literature. The aim of this study was to analyze the primary site, stage, treatment and prognosis of HNRMS in Adults. The clinical data of adult patients with pathologic diagnosis of HNRMS admitted from October 1999 to July 2018 in Chinese Academy of Medical Sciences Cancer Hospital were retrospectively analyzed. The clinical staging and risk grouping were performed according to International RMS Study Group (IRSG) criterion. A total of 64 patients were included (30 males, 34 females). The median age was 28 years (16-69ys). The pathological type consisted of 28 (43.8%) embryonic RMS, 25 (39.1%) alveolar RMS and 5 (7.9%) pleomorphic RMS. 21 patients (32.8%) got tumors invasion of parameningeal, 38 patients (59.4%) had orbital invasion, included 19 patients (29.7%) had both orbital and parameningeal invasion. IRSG I-IV stage accounted for 57.8%, 10.9%, 18.8%, 12.5% of all the patients. 35.6% patients were classified as low risk, 50.8% patients as medium risk and 13.6% patients as high risk. 28 patients (43.8%) received radical resection, 13 patients achieved R0 resection. 54 patients (84.4%) received radical /adjuvant radiotherapy. Median dose was 69.96Gy (37.5-71.04Gy) of GTV / GTVtb. 46 patients (85.2%) received cervical lymphatic drainage area radiation. A total of 44 patients (68.8%) median completed 4 cycles (1-12 cycles) of chemotherapy. The main chemotherapy regimen was IFO + EPI (52.3%) and CTX + VCR + EPI (25%). Median follow-up for surviving patients was 48 months. 47 patients (73.4%) failed after the treatment, 14 (21.9%) had local recurrence, 34 (53.1%) had distant metastasis. 43 patients (67.2%) were died. The overall 1-, 3- and 5-year over survival (OS) rates were 81.7%, 35.7% and 23.7%, respectively. The median survival time was 20 months. The addition of radiotherapy in treatment significantly improved the OS, progression free survival (PFS) and local-regional recurrence free survival (LRRFS) (3ys OS 36.5% vs 21.8% P = 0.03, 3ys-PFS 27.2% vs 0% P < 0.01, 3ys-LRRFS 77.1% vs 0% P < 0.01). There was no significant difference in LRRFS between patients who received radical radiotherapy and patients received radical surgery (3ys-LRRFS 76.2% vs 70.9% P = 0.79). Multivariate analysis indicated that addition of radiotherapy was the only independent prognostic factor associated with improved OS (RR:0.40, 95%CI 0.20-0.90, P = 0.03). The Adult HNRMS is a kind of tumor with high malignancy and poor prognosis. Radiotherapy added to treatment significantly improved long-term OS and PFS. However, multimodality treatment (surgery, radiotherapy, and chemotherapy) planning and risk stratification is required for all patients to improve the prognosis of Adult HNRMS.

Role of Surgery in Rhabdomyosarcoma of the Head and Neck in Children

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The goal of this research is to analyze the role of surgery in the management of pediatric parameningeal (PM) and non-PM head and neck RMS (HNRMS). Retrospective review. Retrospective chart review of patients <20 years of age treated for HNRMS between 1970 and 2015. Clinical presentation, tumor characteristics, treatment, recurrence, follow-up, and outcome data were collected. Of 97 patients with HNRMS, 56% were male. Overall median (IQR: interquartile range) age at diagnosis was 5.8 (3.3-9.8) years. Sixty-five patients (67%) had PM tumors. Of 75 patients with histologic subtype identified, 51 (53%) had embryonal and 20 (21%) alveolar RMS. Almost all patients received chemotherapy (99%) and radiotherapy (95%). Forty-four patients (45%) underwent surgery. Surgery was more likely to be conducted in patients with lesions of a non-PM site. Median follow-up time was 3.4 years (IQR: 1.1-10.8). In 5 years of follow-up, 20% (17 of 85) died and 29% (20 of 70) had recurrence. The estimated 5-year survival rate was 72% (95% CI, 57.8, 81.5%). Surgery was associated with a reduced risk of mortality after accounting for TNM stage 4 and tumor site (adjusted HR 0.24; 95% CI, 0.07, 0.79; P = .02). The association between surgery and risk of mortality was similar in PM and non-PM tumors. A multimodal protocol for treatment including chemotherapy, surgery, and radiotherapy is the mainstay for management of children with HNRMS. While surgery is more commonly used to treat non-PM HNRMS, patients who are able to undergo surgery have significantly higher 5-year survival. 4 Laryngoscope, 131:E984-E992, 2021.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Proceedings to the 6th Annual Conference of the Particle Therapy Cooperative Group North America (PTCOG-NA): 14-16 October 2019, Hosted by Miami Cancer Institute, part of Baptist Health South Florida, Miami, FL, USA.

Clinical study on 48 children with head and neck rhabdomyosarcoma treated by multi-disciplinary therapy

Objective To explore the short-term efficacy in children with head and neck rhabdomyosarcoma (HN-RMS) treated by multidisciplinary therapy, and to analyze the prognostic factors, so as to guide the diagnosis and treatment. Methods Patients with HN-RMS admitted at Hematology Oncology Center of Beijing Children′s Hospital (BCH), Capital Medical University between December 2012 and May 2017, were included in this case-observation study.The clinical characteristics were analyzed and the treatment effect and prognostic factors were summarized. Results A total of 48 cases were collected, including 36 boys and 12 girls, with a median age of 4.6 years.Primarysite parameningeal RMS(PM-RMS)(34 cases, 70.8%), orbital(2 cases, 4.2%) and non-orbital, non-parameningeal region(12 cases, 25.0%) were found.Twenty cases belonged to alveolar type(41.7%), and 28 cases were of embryonal type(58.3%). The diameter of the tumor was >5 cm(n=25, 52.1%), and ≤5 cm(n=23, 47.9%). IRS staging: there were 29 cases(60.4%) of stage Ⅱ-Ⅲ, 19 cases(39.6%) of stage Ⅳ; 29 cases(60.4%) of low-medium risk, and 19 cases(39.6%) of high risk.Twenty-three patients(47.9%) received surgery, and 25 cases (52.1%) received biopsy only.All patients (48 cases) received systemic chemotherapy.Twenty patients(41.6%) received external radiation, 15 cases (31.3%)received 125I particle implantation, 6 cases (12.5%)received proton therapy, but 3 cases (6.2%)did not receive radiation.The follow-up time lasted 13-57 months[(24.1±12.3) months]. The 2-year overall survival(OS) rate was (66.4±7.2)%, and 2-year event free survival (EFS) rate was (59.9±7.5)%.Patients with tumor diameter ≤5 cm had higher OS and EFS than patients with tumor diameter >5 cm [2-year OS (87.4±6.8)% vs.(42.9±6.8)%, 2-year EFS (78.8±8.6%) vs.(38.5±10.8)%], and the differences were statistically significant (all P=0.006). Patients with orbital and non-orbital, non-parameningeal RMS had higher OS and EFS than PM-RMS [2-year OS 100% vs.(87.5%±11.7)% vs.(57.0±8.8)%; 2-year EFS 100% vs.(88.9±10.5)% vs.(51.1±8.9)% ], and the differences were statistically significant (P=0.008, P=0.030). Patients who received surgery had higher OS and EFS than those who did not received surgery[2-year OS (80.7±8.8)% vs.(53.3±10.4)%; 2-year EFS (71.1±10.1)% vs.(49.5±10.4)%], and the differences were statistically significant (P=0.008, P=0.026). COX regression analysis showed tumor diameter >5 cm was an adverse prognostic factor (OR=4.124, 95%CI: 1.213-14.025, P=0.023). Conclusions PM-RMS accounted for a high proportion in RMS patients.The primary site and the size of the tumor are the main prognostic factors.Intensive therapy is expected to improve the prognosis of HN-RMS with meningeal invasion. Key words: Head and neck rhabdomyosarcoma; Multi-disciplinary treatment; Parameningeal rhabdomyosarcoma; Child

Radical Surgery for Head and Neck Rhabdomyosarcoma Failed Primary Chemotherapy.

The aim of the study was to explore an optimal surgery way for head and neck rhabdomyosarcoma (HNRMS) children who have failed primary chemotherapy. A total of 51 HNRMS children who have failed primary chemotherapy were retrospectively analyzed from April 2005 to May 2017. Surgery was performed in 2 ways, widely radical resection (22 patients) and conservative resection (29 patients). Multivariate analysis was performed to identify the various variables related to overall survival (OS). The estimated 5-year OS was 53%. Embryonic RMS enjoyed a favorable outcome than those nonembryonic RMS (P = 0.03). Head and neck rhabdomyosarcoma children who received partial remission (PR) after primary chemotherapy enjoyed a better outcome than those only achieved stable disease (SD) (P = 0.006). A total of 22 children accepted widely radical resection, whereas 29 patients got conservative resection. Interestingly, the 2 groups did not have a statistical significance (P = 0.86). However, the latter group children have conserved more important organs, such as eyeball, facial nerves, and enough mandible or maxilla bones, and have enjoyed a better life quality. Primary chemotherapy is most important for HNRMS children, which influences the prognosis of HNRMS widely. Conservative resection is an optimal surgery way for HNRMS, bringing a better life quality for these children.

AMORE treatment as salvage treatment in children and young adults with relapsed head-neck rhabdomyosarcoma

Background and purposeSurvival after relapse of head and neck rhabdomyosarcoma (HNRMS) after prior external beam radiotherapy (EBRT) is poor, since options for adequate local treatment are often lacking. In this study we describe our experience with salvage AMORE in patients with relapsed HNRMS after prior EBRT. Materials and methodsPatients with relapsed HNRMS after prior EBRT in which salvage AMORE treatment was considered feasible were analysed; this includes patients with parameningeal, head and neck non-parameningeal and orbital localization. AMORE treatment consisted of Ablative surgery, MOuld technique brachytherapy and surgical REconstruction. ResultsIn total 18 patients received salvage AMORE treatment; nine patients had relapsed parameningeal (PM) RMS, two patients had relapsed head and neck non-parameningeal RMS (HN-nonPM) and seven patients had relapsed orbital RMS. Local control rate was 67% and 5-year overall survival was 54% (95% confidence interval: 31–78%); 3/9 patients with PM RMS, 0/2 patients with HN-nonPM RMS and 6/7 patients with orbital RMS were alive after a median follow-up of 8.6 years. One patient with PM RMS survived more than 5 years after which he died from a secondary cancer. Six patients developed a local relapse (of which one patient also developed a distant metastasis) and two patients developed distant metastases. ConclusionsSalvage AMORE treatment is a feasible and effective local therapy approach even after prior EBRT. Since salvage AMORE treatment is sometimes the only curative option in patient with relapsed HNRMS, we encourage physicians to consider salvage AMORE treatment for patients with relapsed HNRMS after prior EBRT.

Psychosocial well-being of long-term survivors of pediatric head-neck rhabdomyosarcoma.

Head and neck rhabdomyosarcoma (HNRMS) survivors are at risk to develop adverse events (AEs). The impact of these AEs on psychosocial well-being is unclear. We aimed to assess psychosocial well-being of HNRMS survivors and examine whether psychosocial outcomes were associated with burden of therapy. Sixty-five HNRMS survivors (median follow-up: 11.5 years), treated in the Netherlands and the United Kingdom between 1990 and 2010 and alive ≥2 years after treatment visited the outpatient multidisciplinary follow-up clinic once, in which AEs were scored based on a predefined list according to the Common Terminology Criteria for Adverse Events. Survivors were asked to complete questionnaires on health-related quality of life (HRQoL; PedsQL and YQOL-FD), self-perception (KIDSCREEN), and satisfaction with appearances (SWA). HRQoL and self-perception scores were compared with reference values, and the correlation between physician-assessed AEs and psychosocial well-being was assessed. HNRMS survivors showed significantly lower scores on PedsQL school/work domain (P ≤ 0.01, P=0.02, respectively), YQOL-FD domains negative self-image and positive consequences (P ≤ 0.01, P=0.04, respectively) compared with norm data; scores on negative consequences domain were significantly higher (P=0.03). Over 50% of survivors negatively rated their appearances on three or more items. Burden of AEs was not associated with generic HRQoL and self-perception scores, but was associated with disease-specific QoL (YQOL-FD). In general, HRQoL in HNRMS survivors was comparable to reference groups; however, survivors did report disease-specific consequences. We therefore recommend including specific questionnaires related to difficulties with facial appearance in a systematic monitoring program to determine the necessity for tailored care.

Facial asymmetry in head and neck rhabdomyosarcoma survivors.

Radiotherapy is essential for achieving and maintaining local control in head and neck rhabdomyosarcoma (HNRMS) patients. However, radiotherapy may cause outgrowth disturbances of facial bone and soft tissue, resulting in facial asymmetry. The aim of this study was to develop a method to visualize and measure facial asymmetry in HNRMS survivors using three-dimensional (3D) imaging techniques. Facial deformity was evaluated in a multidisciplinary clinical assessment of 75 HNRMS survivors, treated with external beam radiotherapy (EBRT, n = 26) or Ablative surgery, MOulage brachytherapy, and REconstruction (AMORE, n = 49). Individual facial asymmetry was measured using 3D photogrammetry and expressed in a raw asymmetry index and a normalized sex-age-ethnicity-matched asymmetry signature weight. Facial asymmetry was also compared between British and Dutch controls and between survivors and their matched controls. Facial asymmetry was more pronounced with increasing age (P < 0.01) in British controls compared with Dutch controls (P = 0.04). Survivors developed more facial asymmetry than matched controls (P < 0.001). The clinical assessment of facial deformity correlated with the raw asymmetry index (r = 0.60, P < 0.001). 3D imaging can be used for objective measurement of facial asymmetry in HNRMS survivors. The raw asymmetry index correlated with a clinical assessment of facial deformity. Comparisons between treatment groups seemed inappropriate given the differences in facial asymmetry between British and Dutch controls. In future studies, pretreatment images could act as matched controls for posttreatment evaluation.

A clinicopathologic study of head and neck rhabdomyosarcomas showing FOXO1 fusion-positive alveolar and MYOD1-mutant sclerosing are associated with unfavorable outcome

BackgroundBased on their distinctive histologic and genetic features, the latest WHO classification of soft tissue tumors includes four pathologic variants of rhabdomyosarcoma (RMS): embryonal (ERMS), alveolar (ARMS), spindle cell-sclerosing (SRMS-ScRMS) and pleomorphic RMS. The aim of this study focused on a detailed clinicopathologic and survival analysis of head and neck RMS (HNRMS) using the latest pathologic and molecular criteria reflecting this new subclassification in a large cohort. Patients and methodsPatients managed for HNRMS in our institution (1996–2015) were analyzed. The presence of a FOXO1 fusion was required for the classification of ARMS. MYOD1 mutations in SRMS-ScRMS were tested when material available. Univariate and multivariate analyses were performed to evaluate variables related to overall survival (OS). ResultsNinety-nine HNRMS patients (52 males and 47 females, mean of 16years) were included in the study after pathologic re-review. The most common location was parameningeal (PM) (n=64), followed by non-orbital/non-PM (n=25) and orbital (n=10). There were 53 ERMS, 33 fusion-positive ARMS and 13 SRMS-ScRMS [SRMS (8); ScRMS (5)]. The 5-year OS rate for ERMS patients was significantly higher (82%) compared to ARMS (53%) and SRMS-ScRMS (50%) [SRMS (75%); ScRMS (30%)]. Univariate analysis showed that survival was dependent on histology (P=0.012), tumor size >5cm (P<0.001), regional lymph node involvement (P=0.002), metastasis at initial presentation (P<0.001), stage (P<0.001), and recurrence (P=0.002). Multivariate analysis confirmed histologic subtype to be significant (P=0.043). ConclusionOur findings reinforce that HNRMS is a heterogenous disease with ARMS and SRMS-ScRMS having an equally unfavorable outcome.

Long-term effect of chemotherapy–intensity-modulated radiation therapy (chemo-IMRT) on dentofacial development in head and neck rhabdomyosarcoma patients

ABSTRACTDentofacial developmental abnormalities have been reported in head and neck rhabdomyosarcoma (HNRMS) patients treated with conventional radiotherapy technique and chemotherapy. This current study investigates dentofacial long-term effects among HNRMS survivors managed with intensity-modulated radiotherapy (IMRT) and chemotherapy. In general, IMRT is a more effective 3D-conformal radiotherapy technique, which delivers high doses of radiation to the tumor target while minimizing doses received by the surrounding normal tissues. The medical records and radiographs of thirteen patients were reviewed to identify the following: 1. Facial asymmetry and jaw hypoplasia. 2. Effects on the dental tissue causing tooth agenesis/hypodontia, root agenesis/stunting/malformation, and/or enamel hypoplasia. 3. Trismus, hyposalivation/xerostomia. Seven patients presented with facial asymmetry and jaw hypoplasia, 9 patients presented with effects on the dental tissue [root agenesis/stunting/malformation (9), tooth agenesis/hypodontia (7) and enamel hypoplasia (3)] and 7 patients developed trismus and /or xerostomia. All patients with facial asymmetry and jaw hypoplasia also developed dental abnormalities. Patients with dentofacial developmental abnormalities were ≤7 years of age at treatment. Our study shows that dentofacial developmental abnormalities are still a burden in the era of IMRT and as prognosis of childhood malignancy improves and more patients survive, these late dentofacial sequelae among childhood cancer survivors will become more common. Dental oncologists should be integral members in the management of children with head and neck cancers.

Hearing loss in survivors of childhood head and neck rhabdomyosarcoma: a long-term follow-up study.

To determine the hearing status of survivors treated for head and neck rhabdomyosarcoma (HNRMS) at long-term follow-up. Cross-sectional long-term follow-up study. Tertiary comprehensive cancer centre. Survivors treated for HNRMS during childhood in two concurrent cohorts; survivors in London had been treated with external beam radiotherapy (EBRT-based local therapy); survivors in Amsterdam were treated with AMORE (Ablative surgery, MOuld technique afterloading brachytherapy and surgical REconstruction) if feasible, otherwise EBRT (AMORE-based local therapy). We assessed hearing status of HNRMS survivors at long-term follow-up. Hearing thresholds were obtained by pure-tone audiometry. We assessed the hearing thresholds, the number of patients with clinically relevant hearing loss and hearing impairment graded according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4) and Boston criteria. Furthermore, we compared hearing loss between survivors treated with EBRT-based local therapy (London) and AMORE-based local therapy (Amsterdam). Seventy-three survivors were included (median follow-up 11years). We found clinically relevant hearing loss at speech frequencies in 19% of survivors. Multivariable analysis showed that survivors treated with EBRT-based treatment and those with parameningeal tumours had significantly more hearing impairment, compared to survivors treated with AMORE-based treatment and non-parameningeal tumours. One in five survivors of HNRMS developed clinically relevant hearing loss. AMORE-based treatment resulted in less hearing loss compared to EBRT-based treatment. As hearing loss was highly prevalent and also occurred in survivors with orbital primaries, we recommend systematic audiological follow-up in all HNRMS survivors.