| Objectives:To investigate the clinical features and etiology of double primary malignant neoplasm (DPMN) with nasopharyngeal carcinoma (NPC) and factors affecting the interval of radiation-induced neoplasm(RIN) following nasopharyngeal carcinoma.Methods:Clinical materials of 94 cases had DPMN with nasopharyngeal carcinoma who were diagnosed and treated in our institution were collected during January,2006-March,2015.In this period, there were 3533 firstly-diagnosed NPC cases, including 1669 cases received conventional radiotherapy, 1687 cases received intensity modulated radiotherapy (IMRT),171 cases received three-dimensional conformal radiotherapy and 6 cases without receiving radiotherapy after inducing chemotherapy. Ninety-four cases were divided into three groups, as A,B and C. Group A:DPMN cases with NPC as the first primary malignant tumor; Group B:DPMN cases with NPC as the second primary malignant tumor. Both group A and group B were metachronous DPMN; group C:synchronal DPMN cases with NPC and those outside head and neck. For those with radiation-induced neoplasm, Using t-test and COX hazard model was to evaluate the factors affecting the interval between RIN and NPC. The p values less than 0.05 (two-sided) were considered to be significant.Results:Among 94 cases with DPMN, forty-six cases were with NPC as first tumor being diagnosed before 31st, December 2005, while the second primary cancer was diagnosed after 1st January,2006. The first and second tumors in the 48 cases with DPMN were both diagnosed after 1st January,2006, accounted for 1.36% of newly diagnosed NPC in the same period. Eighty cases were metachronous carcinoma, and fourteen cases were synchronic carcinoma, mean age of these was 51.7±10.9 years. Among them,77 cases were men and 17 cases were women, with gender ratio being 4.53:1, mean age was 50.0±6.9 years for female and men patients 52.1±11.6 years for male. Among 66 cases in group A,58 cases were men,8 cases were women with sex ratio being 7.25:1,mean diagnose age of the first tumor being 43.0±11.9 years (14～72 years), and mean diagnose age of the second tumor being 51.7～11.7 (21～75) years. As for the sites of the second tumor’s lesion,40 cases located in head and neck which were considered as radiation-induced neoplasm, among whom there were 32 cases treated by conventional radiotherapy before 31st December 2005; among those treated during January 2006 and March 2015,4 cases underwent conventional radiotherapy, including one was sarcoma,4 cases underwent IMRT. And the incidence of radiation-induced neoplasm after receiving conventional radiotherapy was 0.240%, including incidence of sarcoma was 0.06%, and the incidence of radiation-induced neoplasm after receiving IMRT was 0.237%. However, chi-square test showed difference of incidence between the incidence of the two radiation-induced neoplasm had no statistical significance. Eleven cases in our cohort were with DPMN in lung, and 9 cases in digestive system,2 cases in urogenital system,3 cases in hematologic system, and one with melanoma in foot. Interval between the diagnosis time point of the first and second malignant tumors ranged from 7 months to 372 months, with mean value being 105.9±70.2 months, and Univariate analysis showed gender, age diagnosed NPC and radiation model were related with interval between NPC and RIN. COX hazard model suggested radiation model was a dependent influencing factor of the interval between NPC and RIN. Group B had 14 cases including 7 men and 7 female with sex ratio being 1:1. Their diagnosed age of the first tumor ranged from 36 years to 68 years with mean age being 49.9±9.8 years. Their diagnosed age of the second tumor ranged from 42 years to 74 years with mean age being 55.4±9.4 years. As for the original site of first tumor:3 case located in head and neck,2 cases in breast,2 in stomach,3 cases in urogenital system,3 cases were lymphoma, one sarcoma in the upper arm. The interval of these cases in group B between first and second tumor ranged from 24 months to 180 months with mean value being 68.4±47.4months. Group C had 14 cases including 12 males and 2 cases female with sex ratio of 6:1. Their age when diagnosed ranged from 35 years to 61 years with mean being 48.1±7.7 years. Primary sites of secondary tumor:6 cases were in head and neck, one in lung,6 cases in digestive system, one was lymphoma, Interval between time when NPC diagnosed and that when secondary tumor range from 0 month months to 6 months with mean being 1.5±2.2 months. Pathological types of the 94 cases in the whole cohort included 22 cases with sarcoma,36 cases with adenocarcinoma,22 cases with squamous cell carcinoma,7 cases with hematological malignancy and 7 cases with other type.Conclusions:Firstly, DPMN cases with NPC as the first primary tumor may be common, and DPMN cases used to appear mostly in male, the high peak age of DPMN was 40-60 years. In addition, Pathological types of DPMN located in head and neck were mainly sarcoma and squamous carcinoma, while adenocarcinoma mostly occurred out of head and neck. Secondly, radiation model of NPC cases may be a dependent influencing factors of the interval between NPC and RIN. Age diagnosed NPC may be related with interval between NPC and RIN,patients’gender had a trend to influence interval between NPC and RIN. Thirdly, combining our research and the published data in our institution during 1985-2005, we found incidence of radiation-induced cancer or sarcoma following NPC radiotherapy appeared be declining and had no proof to indicate IMRT could cause increasing incidence of radiation-induced neoplasm, this needs further follow-up study for corresponding cases in future and multiple-central collect more larger sample to research. Finally there are many factors can influence occurrence of DPMN with NPC, their pathogenesises are implicated, these conclusions should be further verified by multiple-central, random, double-blind, prospective studies involving larger sample. |
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