OBJECTIVE: To analyze the clinical features and genotype of a child with Schmid type metaphyseal chondrodysplasia. METHODS: Clinical data of the child and her parents was collected. The child was subjected to high-throughput sequencing, and candidate variant was verified by Sanger sequencing of her family members. RESULTS: Whole exome sequencing revealed that the child has harbored a heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene, which was not found in either of her parents. The variant was not found in the HGMD and ClinVar databases, and was rated as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The heterozygous c.1772G>A (p.C591Y) variant of the COL10A1 gene probably underlay the Schmid type metaphyseal chondrodysplasia in this child. Genetic testing has facilitated the diagnosis and provided a basis for genetic counselling and prenatal diagnosis for this family. Above finding has also enriched the mutational spectrum of the COL10A1 gene.
Humans ; Child ; Female ; Mutation ; Osteochondrodysplasias/diagnosis* ; Heterozygote ; Molecular Biology

Objective:To retrospectively analyze the failure patterns and outcomes of patients with locally advanced hypopharyngeal squamous cell carcinoma (HPSCC) after undergoing induction chemotherapy (IC) followed by definitive radiotherapy.Methods:For patients with locally advanced HPSCC who were treated with IC and definitive radiotherapy from August 2008 to December 2019, their data were collected from the medical records system, and their clinical characteristics, failure patterns, and survival were retrospectively analyzed.Results:A total of 116 eligible patient with squamous cell carcinoma were included in this study. with a median age of 59 (39-79), and 3, 3, 60, and 50 of them had stage Ⅱ, Ⅲ, Ⅳ A, and Ⅳ B HPSCC, respectively. Among these patients, 81 received 1~2 cycles of IC, and 35 received 3-4 cycles of IC. After treatment with IC, 54, 13, and 49 patients received concurrent chemoradiotherapy, radiotherapy combined with targeted therapy, and radiotherapy alone, respectively. The median follow-up was 34.6 months (95% CI: 28.7-40.5 months). The 3-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), metastasis-free survival (MFS), progression-free survival (PFS), and overall survival (OS) of all the patients were 63.5%, 82.8%, 75.2%, 47.3%, and 43.1%, respectively. Median PFS and OS were 26.1 and 28.0 months, respectively. Treatment failure was reported in 59 patients, of whom 22, 5, 12, 10, 3, 6 and 1 experienced local, regional, distant only, local-regional, regional-distant, local-distant, and local-regional-distant failure, respectively. The objective response rate (CR+ PR) of patients after IC was 55.2% (64/116). The LRFS, RRFS, PFS, and OS of IC responders (CR+ PR) were better than those of IC non-responders (SD+ PD) ( χ2 = 12.52, 5.16, 13.19, 11.72, all P< 0.05). Conclusions:IC combined with radical radiotherapy has efficacy to a certain extent in the treatment of locally advanced HPSCC, and locoregional recurrence predominates the failure patterns. The prognosis of IC responders is significantly better than that of IC non-responders.

Objective:To evaluate the survival outcomes of radiotherapy in patients with newly-diagnosed metastatic head and neck squamous cell carcinoma (HNSCC) based on data from the Surveillance, Epidemiology and End Results (SEER) database.Methods:A total of 1226 patients newly-diagnosed with metastatic HNSCC between 2010 and 2015 were selected from the SEER database. There were 762 patients (62.1%) in the radiotherapy group and 464 patients (37.9%) in the non-radiotherapy group. Kaplan-Meier method was used to calculate the cancer-specific survival (CSS) and overall survival (OS). The effect of radiotherapy on survival was assessed by Cox multivariate regression and Propensity score-matched analyses (PSM). According to the results of multivariate analysis, the patients were further divided into low-, intermediate- and high-risk groups, and the effect of radiotherapy on survival was analyzed in different risk groups.Results:The median CSS and OS time of the whole group was 11.0 months and 10.0 months, respectively. For patients in the radiotherapy group and non-radiotherapy group, the median CSS time was 13.0 months and 6.0 months, and the median OS time was 12.0 months and 6.0 months, respectively. Multivariate analysis showed that age (CSS, P=0.045;OS, P=0.002), primary tumor site (CSS, P=0.021;OS, P<0.001), T stage (CSS, P=0.001;OS, P=0.002), N stage (CSS, P=0.002;OS, P<0.001), number of metastatic organs (CSS, P<0.001;OS, P<0.001), surgery (CSS, P<0.001;OS, P<0.001), radiotherapy (CSS, P<0.001;OS, P<0.001), and chemotherapy (CSS, P<0.001;OS, P<0.001)were the independent prognostic factors. After PSM, patients with and without radiotherapy in the low-,intermediate-,and high-risk groups, the 3-year CSS rates were 62.5% vs 23.5%( P=0.008), 22.4% vs 15.7%( P=0.001)and 10.5% vs 9.6%( P=0.203), respectively; the 3-year OS were 58.0% vs 20.8%( P=0.002), 19.8% vs 12.7%( P=0.001)and 7.0% vs 6.1%( P=0.166), respectively. Conclusion:Radiotherapy significantly improves CSS and OS in the low- and intermediate-risk groups, but patients in the high-risk group do not benefit from radiotherapy.

Objective:To assess the efficacy and toxicity of chemoradiotherapy in the treatment of early stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL).Methods:Retrospective review was conducted for 174 patients with pathological proved early stage ENKTCL who were treated in the Department of Radiation Oncology, Peking University Cancer Hospital & Institute. The Kaplan-Meier survival analysis was adopted to calculate the local-regional control (LRC), overall survival (OS), and progression free survival (PFS), and the Log-rank test COX regression model were applied to univariate and multivariate analyses.Results:The patients in this study included 102 and 72 patients diagnosed with Ann Arbor stage-Ⅰ and stage-Ⅱ, respectively. Among them, two patients received radiotherapy alone and 172 patients were treated with combined chemoradiotherapy. The overall response rate of all the patients was 94.2%, with a complete response (CR) rate of 87.9% (153). Furthermore, the rates of 5-year OS, PFS, and LRC were 87.3%, 83.1%, and 91.9%, respectively. The most common toxicities during the chemotherapy and radiotherapy included myelosuppression and oral mucositis, with grade ≥ 3 myelosuppression and grade ≥ 3 oral mucositis accounting for 62.1% and 10.9% of all patients, respectively. As shown by multivariate analysis, the adverse prognostic factors for OS included age > 60, B symptoms, and stage Ⅱ, while the adverse prognostic factors for PFS included age > 60 and stage Ⅱ. Meanwhile, the PFS rate was significantly improved by increasing the radiation dose (≥ 50 Gy vs.<50 Gy), and the 5-year PFS rates of the two groups were 83.5% and 76.5%, respectively [hazard ratio ( HR) 0.374; 95% CI, 0.169-0.826; P=0.015]. Conclusions:A good therapeutic effect can be achieved for early stage NK/T-cell lymphoma and the toxicities after combined chemoradiotherapy can be tolerated.

Objective:To observe the changes of nutrition impact symptoms (NIS) and fat-free mass and analyze the relationship between them in patients with head and neck cancer (HNC) during radiotherapy.Methods:A convenient sampling method was adopted to select HNC patients who received radiotherapy in the outpatient clinic of department of radiotherapy for head and neck cancer in a cancer hospital in Beijing from March 2017 to January 2020. The nutrition impact symptoms (NIS) were assessed by a nutrition impact symptoms checklist and the fat free mass was assessed by bioelectrical impedance analysis at three time points: before radiotherapy (T1), during radiotherapy (T2) and at the end of radiotherapy (T3). The Generalized Estimating Equations (GEE) was used to analyze the relationship between them.Results:A total of 542 HNC patients were included in the analysis. During radiotherapy, the patients' NIS number and score presented an increasing trend, reaching the highest level and peaked at the end of radiotherapy. The change of fat-free mass showed a decreasing trend and reached the minimum at the end of radiotherapy. Patients with higher NIS scores had more percentage loss of fat-free mass.Conclusions:During radiotherapy, patients with HNC showed an increase in NIS score and lost fat-free mass. Patients with higher NIS score lost more percentage of fat-free mass, which suggested that clinical medical staff should pay attention to NIS management and take comprehensive intervention measures in time to reduce the loss of fat-free mass.

Objective:To explore overall survival(OS) and prognostic factors of brainstem gliomas (BSG) after intensity modulated radiotherapy (IMRT) by a retrospective single-center analysis.Methods:A total of twenty-one patients with BSG were collected in the Department of Radiation Oncology, Peking University Cancer Hospital from January 2012 to September 2019. All patients underwent IMRT. OS and potential prognostic factors were analyzed, including gender, age, operation type, imaging classification, tumor location, WHO grade, chemotherapy, radiotherapy pattern, time interval between morbidity and the first treatment, and radiation dose.Results:Eighteen of twenty-one patients were followed up more than 3 months. The median follow-up time was 15.5 (5.3-25.6) months. The median overall survival (mOS) was 20 (14.1-25.8) months. The 1 and 2-year OS rates were 86.2% and 34.5% respectively. Operation type, imaging classification, tumor location, WHO grade and radiotherapy pattern were the prognosis factors ( χ2=4.829-20.261, P<0.05). Conclusions:Patients with maximal safe surgical resection, focal endogenesis / exogenesis, tumor located in mesencephalon, low-grade gliomas and/or received postoperative radiotherapy have a better prognosis. It has certain reference value for guiding the clinical practice.

Objective:To investigate the clinical efficacy of concurrent chemotherapy in intensity-modulated radiotherapy (IMRT) for patients with stage Ⅲ nasopharyngeal carcinoma (NPC).Methods:Clinical data of 251 patients with stage Ⅲ NPC treated with IMRT alone or concurrent chemoradiotherapy (CCRT) at Sun Yat-sen University Cancer Center from February 2001 to December 2008 were retrospectively analyzed. The prognostic factors of NPC were analyzed and the efficacy of CCRT was assessed. The survival rate was calculated by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. The prognostic factors were analyzed by Cox model.Results:The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for NPC patients were 88.6%, 81.1%, 68.8% and 75.1%, respectively. Univariate and multivariate analyses demonstrated that N staging and nasopharyngeal tumor volume were the most important prognostic factors, and concurrent chemotherapy significantly improved PFS and OS (both P<0.05). In T 3N 0-1 patients, there was no significant difference in survival indexes between IMRT alone and CCRT (10y-LRFS: 93.8% vs. 93.2%, P=0.933; 10y-DMFS: 80.9% vs. 86.8%, P=0.385; 10y-PFS: 70.6% vs. 77.7%, P=0.513; 10y-OS: 71.8% vs. 83.6%, P=0.207). For T 1-3N 2 patients, CCRT was significantly better than radiotherapy alone in LRFS, PFS, and OS (10y-LRFS: 87.3% vs. 66.7%, P=0.016; 10y-PFS: 70.2% vs. 41.0%, P=0.003; 10y-OS: 78.5% vs. 51.7%, P=0.008), whereas there was an increasing trend in DMFS (10y-DMFS: 80.3% vs. 66.4%, P=0.103). Conclusions:Concurrent chemotherapy can improve clinical prognosis of stage Ⅲ NPC patients, and the most survival benefits are obtained in the N 2 group. Individualized treatment options should be delivered based on the risk of treatment failure.

Objective To describe the characteristics of radiation induced mucositis in patients withhead and neck cancer ( HNC) during radiotherapy, and analyze the effect of radiation induced mucositis on diet patterns and weight change and the influencing factors for radiation induced mucositis. Methods Patients with HNC treated with radiotherapy in one cancer hospital were recruited. Data were collected before, during and at the end of the radiotherapy, which included radiation induced oral and pharyngeal mucositis, pain during eat-ing, diet patterns and weight. Results Two hundred and two patients were completely investigated and 43.5％and 34. 2％ of the patients suffered from moderate to severe (≥grade 2) oral mucositis and pharyngeal mucosi-tis, respectively during the radiotherapy. At the end of radiotherapy, 53. 5％ and 51. 5％ of the patients suffered from moderate to severe oral mucositis and pharyngeal mucositis (≥grade 2 ) , respectively. Oral and pharyngeal mucositis were significantly correlated with pain during eating, diet patterns and weight ( P<0. 05) . Tumor site was the main reason that affected the severity of mucositis ( Wald χ2 =26. 033, 14. 216;P<0.001). Conclusion Radiation induced mucositis was gradually aggravated with radiotherapy progress, which is closely related to pain during eating, change of diet patterns and weight loss. The severity of mucositis is re-lated to the tumor site. Measures should be taken to strengthen the management of adverse reactions and nutri-tional status of patients.

Objective To review the failure patterns and clinical outcomes for patients with cervical esophageal carcinoma (CEC) undergoing definitive radiotherapy (RT).Methods Medical records,clinical characteristics and outcomes of patients with CEC treated by definitive RT from August 2008 to May 2017 were retrospectively reviewed and analyzed.Results A total of 97 patients with squamous cell CEC were enrolled in this study with a median age of 59 years old (range 18-78 years old).There were 34 patients with limited cervical esophagus,and 63 patients with diseases beyond cervical region,respectively.There were 69,7,and 6 patients with Bronchi invasion,thyroid lobes involvement and aortic involvement,respectively.There were 11,80 and 6 patients with stage Ⅱ,Ⅲ and Ⅳ (non-regional lymph node metastases),respectively.The median dose to the gross tumor volume (GTV) was 66 Gy,in which 46 patients received above 66 Gy and 51 patients received less than 66 Gy,respectively.The median progression free survival (PFS) and overall survival (OS) were 16.03 and 23.30 months,respectively,with a median follow-up of 14.90 months.The 1,2,3-year PFS and OS were 56.86％,30.35％,26.34％,and 72.54％,47.94％,40.81％,respectively.Sixty-one patients had treatment failure at their last follow-up,in which 40,27,and 18 patients developed local failure,regional failure,and distant metastasis,respectively.Univariate analysis revealed that thyroid lobes involvement resulted in lower PFS (x2 =5.773,P＜0.05) and OS (x2 =13.461,P＜0.05),and bronchi involvement (x2 =4.283,P＜0.05) was associated with lower OS.Multivariate analysis indicated that aortic involvement and thyroid lobes involvement were associated with lower PFS (x2 =6.796,4.548,P＜0.05) and OS (x2 =13.421,10.581,P＜0.05),and GTV dose above 66 Gy was associated with higher OS (x2=5.296,P＜0.05).Conclusions Local-regional recurrence was the main failure pattern for patients with CEC after definitive RT.Aortic,thyroid lobes,and/or bronchi involvement were associated with poor prognosis,and GTV dose ≥66 Gy tended to improve OS.Prospective studies with larger population were needed to further confirm this study.

Objective To evaluate the efficacy and safety of recombinant adenovirus-p53(rAdp53) injection combined with radiotherapy and hyperthermia in the treatment of unresectable advanced soft tissue sarcoma.Methods In this retrospective study, we evaluated 76 patients with unresectable advanced primary or recurrent soft tissue sarcoma treated in our hospital from November 2005 to November 2012.These patients received radiotherapy and hyperthermia with rAdp53(p53 group, n=41) or without rAdp53(control group, n=35).rAdp53((1-2)×1012viral particles each time, once a week, 8 times on average) was injected into the tumor or infused into the pelvic cavity.Radiotherapy (2 Gy each time, 5 times a week) was performed for the planning target volume at 56.3±5.3 Gy in the p53 group and 58.1±4.2 Gy in the control group, with no significant difference between the two groups (P>0.05).Superficial or deep thermotherapy was employed 8 times on average (twice a week).Clinical features, response rate, time to progression (TTP), overall survival (OS), and adverse events were compared between the two groups (P>0.05).The Kaplan-Meier method was used to calculate OS;the log-rank test was used for survival difference analysis and univariate prognostic analysis;the chi-square test was used for comparison of categorical data.Results At 2 months after treatment, the p53 group had significantly increased response rate (partial response+ complete response+ stable disease)(85% vs.54%, P=0.003) and local control rate (49% vs.23%, P=0.020) as well as prolonged TTP (12 months vs.5 months, P=0.010) and OS (48 months vs.31 months, P=0.049), as compared with the control group.No adverse events caused by radiotherapy and hyperthermia except transient fever were seen in the two groups.Conclusions Concurrent radiotherapy and hyperthermia combined with rAdp53 injection is effective and safe for patients with advanced soft tissue sarcoma.