|Year : 2015 | Volume
| Issue : 6 | Page : 226-229
Clinical and prognostic analysis in 32 pediatric nasopharyngeal carcinoma
Jing Chen, Fujun Hu
Department of Radiation Oncology, Zhejiang Provincial Cancer Hospital, Hangzhou 310022, Zhejiang Province, China
|Date of Web Publication||26-Oct-2015|
Department of Radiation Oncology, Zhejiang Provincial Cancer Hospital, 38 Guangji Road, Hangzhou 310022, Zhejiang Province
Source of Support: None, Conflict of Interest: None
Objectives: To analyze the clinical outcome and prognostic factors of pediatric nasopharyngeal carcinomas, provide the basis for the rational treatment, and improve the cure rate.
Materials and Methods: Thirty-two pediatric nasopharyngeal carcinoma patients with pathologically confirmed diagnosis and aged from 11 to 18 years old were retrospectively analyzed. All patients received intensity-modulated radiation therapy, dose of GTVnx 6400–7425 cGy, PGTVnx 6400–7050 cGy, PTV 15,400–6000 cGy, PTV 25,000–5490 cGy, and GTVnd 6000–6996 cGy were given. Among these patients, 29 received various chemotherapies. The Kaplan–Meier test and log-rank test of SPSS 17.0 statistic software package were used to calculate survival rate, compare and analyze the survival rates of each group. Cox model was used to analyzing the prognosis factors.
Results: In this study, the median survival time was 44.5 months, and the median follow-up time is 62.5 months. The 1-, 3-, and 5-year overall survival rates were 100.0%, 93.2%, 85.7%, respectively, in stage III, and 94.8%, 88.3%, and 64.7% in stage IV. All patients 1-, 3-, and 5-year overall survival rates were 97.2%, 90.5%, and 74.2%. Univariate analysis resulted that N stage (P = 0.043), chemotherapy (P = 0.003) and the radiotherapy dose (P = 0.028) were significant factors for survival. On multivariate analysis, only the N stage influence survival.
Conclusions: In pediatric nasopharyngeal carcinoma, the more important prognostic factors are N stage, chemotherapy, radiotherapy dose. Patients with N2-3 should be treated with combined chemotherapy and radiotherapy.
Keywords: Childhood, nasopharyngeal carcinoma, prognosis, radiotherapy
|How to cite this article:|
Chen J, Hu F. Clinical and prognostic analysis in 32 pediatric nasopharyngeal carcinoma. J Can Res Ther 2015;11, Suppl S2:226-9
| > Introduction|| |
Nasopharyngeal carcinoma is a malignant tumor of epithelial tissue, the incidence of nasopharyngeal carcinoma is different from the age, race, and geography. In South of China and the Southeast Asia, the tumor mainly occurs in people over the age of 40, and it is rare in children. The incidence rate of nasopharyngeal carcinoma is about 14.6/100,000, accounts for about 1% of pediatric malignant tumors, and 40–50% of pediatric nasopharyngeal malignant tumors. Radiotherapy combined with chemotherapy based cisplatin is the standard treatment for the tumor. There is a retrospective analysis of 32 cases of nasopharyngeal carcinoma patients aged 18 years old and below. It is used to evaluate the treatment ways, curative effects, and complications, and then to explore the factors that affect the prognosis.
| > Materials and Methods|| |
Thirty-two cases of pediatric nasopharyngeal carcinoma were treated in our hospital from September 2004 to January 2013, including 18 males and 14 females. The proportion of male and female is 1.286:1. The age is 11–18 years old, average 15.53 ± 1.61 years old. First symptom: Neck masses in 19 cases (59.37%), nasal congestion in 2 cases (6.25%), headache in 2 cases (6.25%), decreased vision in 1 case (3.12%), neck pain in 2 cases (6.25%), tinnitus with ear fluid flow in 3 patients (9.38%), and epistaxis in 3 cases (9.38%). All cases were confirmed by pathology including nonkeratinizing carcinoma (undifferentiated) 26 cases (81.24%), nonkeratinizing carcinoma (differentiated) 3 cases (9.38%), and low differentiated squamous cell carcinoma 3 cases (9.38%). The metastasis of lung, liver, and bone was clearly defined from chest computed tomography (CT) or chest X-ray, abdominal CT or B-ultrasound and electroconvulsive therapy before treatment. According to 2009 UICC staging criteria, stage I is 0 case, stage II is 1 case, stage III is 14 cases, and stage IV is 17 cases [Table 1].
|Table 1: Clinical characteristics of the 32 patients with nasopharyngeal carcinoma|
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All patients received intensity-modulated radiation therapy, dose of GTVnx 6400–7425 cGy, PGTVnx 6400–7050 cGy, PTV 15,400–6000 cGy, PTV 25,000–5490 cGy, and GTVnd 6000–6996 cGy were given. The dose of important functional organs and endanger organs was limited. The Dmax (maximum dose) brain stem was ≤54 Gy, spinal cord was ≤40 Gy, optic nerve and the optic chiasm was ≤54 Gy, temporomandibular joint was ≤50 Gy, the temporal lobe was ≤54–60 Gy, crystal was <8 Gy, mandible was ≤60 Gy, and 50% volume parotid was ≤30 Gy. Pinnacle 7.6 planning system was used to design the plans through synchronous integrated technology (SMART boost), the doctor outlined the target areas and normal tissues and set the prescription dose and endanger organs dose. The physical therapist made and optimized the intensity modulated radiation therapy (IMRT) plan. The evaluation of treatment plan included the target region, the endanger organ dose volume histogram, and layer evaluation of each section of the equal. The doctors confirmed treatment plan firstly, and then they made the dosimetric verification. Finally, the radiation therapy was carried out.
Among these patients, 29 cases received intensity-modulated radiation therapy and various chemotherapy. Induced chemotherapy in 29 cases, including 19 cases of false positive (FP), 10 cases of true positive (TP). FP: Nedaplatin (NDP) 30 mg/(m 2 day), d1–d3, 5-fluorouracil (5-Fu) 500 mg/(m 2·day), d1–d3 or 5-Fu 800 mg/(m 2 day) continuous intravenous injection (CIV) 72–120 h, 21 day/cycle. TP: Docetaxe l75 mg/(m 2·day), d1, DDP 30 mg/(m 2·day), d1–d3. Radiotherapy or concurrent chemotherapy after 2–4 cycles induced chemotherapy. Synchronous chemotherapy based NDP or DPP 30 mg/(m 2·day) in d1–d3 every 21 days. Seventeen patients receive two to four cycles synchronous chemotherapy. Consolidation chemotherapy was performed about 1 month after radiotherapy there were 10 cases FP, NDP 30 mg/(m 2·day), d1–d3, 5-Fu 500 mg/(m 2·day), and d1–d3 or 5-Fu 800 mg/(m 2·day) CIV 72–120 h, 21 day/cycle. Other regimens based platinum were four cases. All of chemotherapy regimens were used 2–3 cycles in total [Table 2].
|Table 2: Chemotherapy ways of the 29 patients with nasopharyngeal carcinoma|
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Observation and follow-up during treatment
Biochemical and blood routine were checked every week during treatment. The acute responses of radiotherapy and chemotherapy were record. The tumor regression was checked by nasopharyngofiberoscope or indirect nasopharyngoscopy every 7–10 days. Acute toxicity and late adverse reaction evaluation criteria referred to LENT SOMA and Common Terminology Criteria for Adverse Events version 3.0 (CTCAE3.0) grade evaluation criteria. The magnetic resonance (MR), nasopharyngo fiberoscope, chest X-ray, blood test, and B-ultrasound were used to assess the local control rate and record the side effect of radiotherapy. We can evaluate the control rate and record the side effect of radiotherapy by reexamining MR, rhinitis fiberscope, chest X-ray, B-ultrasound, and blood test 1 month after the treatment. To review the cases 1 time every 3 months within 1 year, and every 6 months in 3 years, every 1 year after 5 years later. The patients should be comprehensively evaluated by recording the thirst, neck fibrosis and the loss in the sight and hearing. According to the evaluation of the National Cancer Center of common toxicity criteria (NCI-CTCAE3.0), the main adverse reactions during chemotherapy were granulocyte reduction, thrombocytopenia and hemoglobin decreased. Decreased serum albumin and elevated aminotransferase were the common liver and kidney function damage. Cardiovascular abnormalities consisted of abnormal heart rhythm, electric conduction abnormalities, and cardiac insufficiency.
The survival time was calculated from the diagnosed time to the end of the follow-up. The Kaplan–Meier test and log-rank test of SPSS 17.0 statistic software (SPSS, China, Shanghai) package were used to calculate survival rate, compare, and analyze the survival rates of each group. Cox model was used to analyzing the prognosis factors. The prognosis was evaluated from gender, age, pathological type, T stage, N stage, and chemotherapy in Log-rank test.
| > Results|| |
In this study, the median survival time was 44.5 months. The 1-, 3-, and 5-year overall survival rates were 100.0%, 93.2%, 85.7%, respectively in stage III, and 94.8%, 88.3%, and 64.7% in stage IV. All patients 1-, 3-, and 5-year overall survival rates were 97.2%, 90.5%, and 74.2%. Univariate analysis resulted that N stage (P = 0.043), chemotherapy (P = 0.003) and the radiotherapy dose (P = 0.028) were significant factors for survival. On multivariate analysis, only the N stage influenced survival rate. The median follow-up time is 62.5 months. During the follow-up, metastasis happened in five patients occurred, one of the metastatic lesions occurred in bilateral axillary lymph nodes, others in bone. Recurrence of nasopharyngeal carcinoma was one case, neck recurrence was three cases, and seven patients had been died [Table 3].
|Table 3: Prognostic factors affecting survival analysis of pediatric nasopharyngeal carcinoma|
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Adverse reaction and evaluation
In the induction chemotherapy, there were three levels of adverse reactions, which were mainly the number reduction of cells, platelets decreased and cardiac insufficiency. The symptoms of adverse reactions were relieved after treatment. One patient with grade 4 granular cells and l patient with heart failure delayed more than 1 week for chemotherapy. The drug dose was decreased 10% in the next cycle of chemotherapy if the patients obtained III degree or above adverse reactions. The nasopharyngo fiberoscope, nasopharynx and neck MR, chest and abdomen CT should be used to assess the disease. Referring to RECIST standard, the changes of tumor size and duration were compared before the next treatment. The effect was divided into complete remission (CR), partial remission (PR), stable disease (SD), and progress disease (PD). There were 10 patients with PR, 18 patients with SD, 1 patient with PD. The local control rate was 96.55% [Table 4].
Patients with adverse reactions during radiotherapy had not been interrupted. Part of the patients did not undergo synchronous chemotherapy because they obtained three levels and above toxic effects or adverse reactions during chemotherapy. Mainly recent toxicity was radioactive oral mucosa inflammation, the patients with dry mouth in different degree. Radioactive skin injury of II nd degree happened in two cases (6.25%), five patients (15.63%) appeared I st degree radioactive damage, and they recovered after treatment with recombinant human epidermal growth factor gel, etc. Mainly late adverse reaction were mouth opening difficult and hearing loss. The limited jaw joints was three cases (9.38%). The auditory nerve injury was 5 (15.63%). Neck fibrosis was 2 cases (6.25%), and radioactive decay was 1 case (3.13%). A comprehensive review was used to evaluate the effect after the treatments. Five patients were CR, 32 patients were PR. Three cases were SD and only one people was PD. The clinical benefit rate was 96.97%. Objective response rate was 81.25%; we evaluated the illness by reexamining MR, rhinitis fiberscope, chest X-ray, B-ultrasound, and blood test after 3 months. To review the cases, lymph node residues was 11 cases. Residual tumor was three cases. The local control was 96.88%.
| > Discussion|| |
Pediatric nasopharyngeal carcinoma is a rare malignant tumor; the 5-year survival rate is between 55% and 88.2% after treatment.,, Because of the different treatment ways and periods, survival rates are greatly various. The 5-year survival rate of pediatric nasopharyngeal carcinoma is 74.2% in our study. The traditional two-dimensional radiotherapy cannot ensure that the adjacent normal tissues are fully protected. It is difficult to balance the target area coverage rate and the protection of normal tissue in the locally advanced patients who have appeared skull base invasion or cranial nerve invasion. Cheuk et al. made a study about prognostic factors of pediatric nasopharyngeal carcinoma with two-dimensional radiotherapy. The local relapse-free survival rate was about 63.5%, the incidence of late complications was 83.7%. The patients often be diagnosed at the late stage, and the overall treatment effect is not very ideal. The patients in stage II are only 3.1% and in stage III or IV is about 96.9%. Lin et al. such as study stages III and IV patients accounted for 92%, Cao et al. such as analysis, the data were up to 95.74%. The time from onset to confirm is similar to adult patients, but the number of children with advanced nasopharyngeal carcinoma is still more than the adult group. The reason is maybe there are differences in biological characteristics between pediatric nasopharyngeal carcinoma and adult. One of the 32 cases of pediatric nasopharyngeal carcinoma occurred bilateral axillary lymph nodes metastases.
Four cases were bone metastases. Distant metastasis rate was 15.6%. The recurrence rate was 12.5%. According to distant metastasis rate and transfer characteristics of pediatric nasopharyngeal carcinoma is similar to the adult's. Zhang et al. a retrospective analysis of patients who occurred recurrence showed that they were a liver full 5 years through the treatment. The radiotherapy and chemotherapy can reduce the risk of recurrence, distant metastasis and local areas to improve the curative effect. Our research shows that the 5-year survival rates of patients in N1 and N2 were 90.3% and 67.9%, N stage was independent prognostic factors (P = 0.031) in the multi-factor analysis. The survival rate of patients is significant decrease with increased N staging; all the group of patients who were N2-3 occurred distant metastasis. The N staging is associated with distant metastasis and affects survival. During intensity-modulated radiation therapy, none of the patients interrupted the treatment. Clinical benefit rate was 96.97%, and the objective response rate was 81.25%. The local control rate was 96.88% in the 3 months follow-up after treatment. None of the patients occurred growth retardation or mental disorders that were caused by radiation and chemotherapy. The comprehensive treatment that IMRT followed induction chemotherapy could improve the survival rate of the patients and was safety especially for patients with N2 and N3. The specific comprehensive treatment plan should be analyzed in the further prospective study.
Financial support and sponsorship
Specific miRNA screening and clinical application of radiation sensitivity of NPC Zhejiang provincial Medicine and Health Science Research Fund project(2011RCB008).
Conflicts of interest
There are no conflicts of interest.
| > References|| |
Surveillance Epidemiology and End Results Program, 1975-2000. Division of Cancer Control and Population Sciences, NCI; 2003.
Zubizarreta PA, D'Antonio G, Raslawski E, Gallo G, Preciado MV, Casak SJ, et al.
Nasopharyngeal carcinoma in childhood and adolescence: A single-institution experience with combined therapy. Cancer 2000;89:690-5.
Saeed H, Zaidi A, Adhi M, Hasan R, Dawson A. Pediatric nasopharyngeal carcinoma: A review of 27 cases over 10 years at Shaukat Khanum Memorial Cancer Hospital and Research Center, Pakistan. Asian Pac J Cancer Prev 2009;10:917-20.
Tao CJ, Liu X, Tang LL, Mao YP, Chen L, Li WF, et al.
Long-term outcome and late toxicities of simultaneous integrated boost-intensity modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma. Chin J Cancer 2013;32:525-32.
Hu S, Xu X, Xu J, Xu Q, Liu S. Prognostic factors and long-term outcomes of nasopharyngeal carcinoma in children and adolescents. Pediatr Blood Cancer 2013;60:1122-7.
Cheuk DK, Billups CA, Martin MG, Roland CR, Ribeiro RC, Krasin MJ, et al.
Prognostic factors and long-term outcomes of childhood nasopharyngeal carcinoma. Cancer 2011;117:197-206.
Lin S, Han L, Liao X. Prognosis analysis in 50 pediatric nasopharyngeal carcinoma. J Clin Pediatr 2008;26:11.
Cao K, Yin L, Huang P. The long curative effect in radiotherapy of pediatric nasopharyngeal carcinoma. Chin J Cancer 2004;23:1322-4.
Zhang M, Yu Z, Zhou J. Radiotherapy and clinical effect analysis in children and adolescents of nasopharyngeal carcinoma. J Clin Pract Hosp 2014;11:172-5.
[Table 1], [Table 2], [Table 3], [Table 4]