Late Sequelae of Childhood and Adolescent Nasopharyngeal Carcinoma Survivors After Radiotherapy
Condition: Nasopharyngeal Carcinoma
MeSH terms: Carcinoma; Nasopharyngeal Carcinoma
Study type: Observational

Summary: 
      Although children and adolescents are more likely to have advanced disease at onset, they
      generally have a significantly better chance of survival. With combined chemotherapy and
      radiotherapy, overall survival has been reported more than 75% in most pediatric studies.
      However, little research focuses on long-term morbidities of children and adolescent
      nasopharyngeal carcinoma (NPC) survivors, and most studies are small scale and have short
      follow-up time. Therefore, this study analyzed the long-term morbidities of children and
      adolescent NPC survivors after radiotherapy. Factors associated with those morbidities were
      also analyzed.

      We reviewed the medical records of all NPC patients younger than 18 years old treated at Sun
      Yat-sen University Cancer Center (SYSUCC) from February 1991 to October 2010. Detailed
      medical records were taken from our institutional database. Patients were also followed using
      comprehensive questionnaires and phone calls. We extracted data on clinical characteristics,
      histopathology, imaging findings, treatment, outcomes, and late morbidities.

      Patients with early-stage (stage I and II) disease were treated with radiotherapy alone, and
      patients with advanced-stage disease (stage III and IV) were treated with a combination of
      radiotherapy and chemotherapy. Radiotherapy technology included conventional radiotherapy
      (CRT) and intensity-modulated radiotherapy (IMRT).

      We retrospectively reviewed these medical records to collect the required data. All survivors
      returned to the hospital for follow-up examinations at least every 3 months for the first
      year, at least every 6 months in the 2nd year, and at least every one year thereafter until
      the latest follow-up. As part of our routine clinical practice, all patients underwent
      follow-up MRI examinations of the nasopharynx and neck at least every 6 to 12 months.

      Radioactive toxicity on organs was evaluated based on National Cancer Institute Common
      Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.

      Analyses were performed using SPSS software, version 16.0 (SPSS, Chicago, IL). Chi-squared
      tests and binary regression analysis were used to compare the CI of treatment comorbidities
      between different groups of survivors. A P value of 0.05 was chosen as the criteria for
      statistical significance.
    

Detailed description: 
      Introduction Nasopharyngeal carcinoma (NPC) is an uncommon childhood malignancy. As the high
      incidence of local-regional advanced disease, its undifferentiated histology and its close
      association with Epstein-Barr virus (EBV) , it is distinguishable from the adult form of the
      disease. Treatment strategies for childhood NPC follow guidelines established for adults.
      Although children and adolescents are more likely to have advanced disease at onset, they
      generally have a significantly better chance of survival. With combined chemotherapy and
      radiotherapy, overall survival has been reported more than 75% in most pediatric studies.
      However, late sequelae such as endocrinopathies, hearing disorder, dental problems, life-long
      dry mouth, and secondary neoplasms have been reported. Little research focuses on long-term
      morbidities of children and adolescent NPC survivors, and most studies are small scale and
      have short follow-up time. Therefore, this study analyzed the long-term morbidities of
      children and adolescent NPC survivors after radiotherapy. Factors associated with those
      morbidities were also analyzed.

      Methods and Materials Patients We reviewed the medical records of all NPC patients younger
      than 18 years old treated at Sun Yat-sen University Cancer Center (SYSUCC) from February 1991
      to October 2010. Detailed medical records were taken from our institutional database.
      Patients were also followed using comprehensive questionnaires and phone calls. All patients
      were restaged according to the Union for International Cancer Control (UICC) TNM
      classification version 2009 of NPC. We extracted data on clinical characteristics,
      histopathology, imaging findings, treatment, outcomes, and late morbidities. Informed consent
      was obtained from all patients.

      Treatment protocols The main treatment strategy for patients was based on the National
      Comprehensive Cancer Network Guidelines. Patients with early-stage (stage I and II) disease
      were treated with radiotherapy alone, and patients with advanced-stage disease (stage III and
      IV) were treated with a combination of radiotherapy and chemotherapy. NPC patients were
      treated with a high-dose of radiotherapy to the nasopharynx and the involved lymph nodes of
      the neck, and a moderate dose of radiation to uninvolved nodes and surrounding tissues.
      Radiotherapy technology included conventional radiotherapy (CRT) and intensity-modulated
      radiotherapy (IMRT). Patients between 1991 and 2004 received CRT. Post 2004, IMRT became the
      standard strategy treatment. During the study period, chemotherapy guidelines for NPC were
      implemented as follows: no chemotherapy for patients with stage I to II disease, and
      concurrent chemoradiotherapy + neoadjuvant chemotherapy for stage III to IVa-c.

      Follow up We retrospectively reviewed these medical records to collect the required data. All
      survivors returned to the hospital for follow-up examinations at least every 3 months for the
      first year, at least every 6 months in the 2nd year, and at least every one year thereafter
      until the latest follow-up. As part of our routine clinical practice, all patients underwent
      follow-up MRI examinations of the nasopharynx and neck at least every 6 to 12 months.

      Evaluation Criterion Radioactive toxicity on organs was evaluated based on National Cancer
      Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 3.0.

      Statistical analysis Analyses were performed using SPSS software, version 16.0 (SPSS,
      Chicago, IL). Chi-squared tests and binary regression analysis were used to compare the CI of
      treatment comorbidities between different groups of survivors. A P value of 0.05 was chosen
      as the criteria for statistical significance.
    

Intervention name(s): survivors treated with CRT
Intervention type(s): Radiation
Intervention description(s): Radiotherapy technology included conventional radiotherapy (CRT) and intensity-modulated radiotherapy (IMRT).
Other intervention name(s): survivors treated with IMRT
Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        All NPC patients younger than 18 years old treated at SYSUCC from February 1991 to October
        2010.
      
Keywords: Childhood and Adolescent; Survivors; Radiotherapy; Late Sequelae