| BackgroundNasopharyngeal carcinoma(NPC)is one of the common malignant tumors of the head and neck in southern China and Southeast Asia,with the highest incidence and mortality rate in Guangdong Province.Radiotherapy and radiotherapy-based combination therapy have become the main treatment for NPC,but it is difficult to avoid irradiating adjacent normal tissues and organs when patients undergo head and neck radiotherapy,resulting in different degrees of radioactive skin injury.So far,it has been demonstrated that radiotherapy combined with chemotherapy can significantly improve the local tumor control rate,reduce the distant metastasis rate and thus increase the overall survival rate in locally advanced NPC compared with radiotherapy alone.The long-term prognosis of combined radiotherapy regimens in patients with NPC has been a hot topic in recent years,and compared to Concurrent Chemoradiotherapy(CCRT)or Radiotherapy-Adjuvant Chemotherapy(CCRT-AC),Induction Chemotherapy-Concurrent Chemoradiotherapy(IC-CCRT)has shown considerable compliance and completion rates in patients,but chemotherapy toxicity may be compounded by radiotherapy toxicity and aggravate skin damage.Therefore,early identification of risk factors affecting the development of radiation skin injury in NPC patients with IC-CCRT is the basis for effective screening of high-risk groups to facilitate the development of comprehensive oncologic management and effective prognostic measures,as well as the key to improving patient compliance with consistent treatment,thereby benefiting more NPC patients.Nowadays,the risk factors for radiation skin injury in NPC radiotherapy patients are not clear,and there is a lack of epidemiological studies on the occurrence of radiation skin injury and its influencing factors in NPC patients combined with radiotherapy based on hospital cohort data in China.ObjectiveIn this study,we followed up NPC patients who received Intensity-modulated Radiation Therapy(IMRT)and Three-dimensional Conformal Radiation Therapy(3D-CRT)for the first time,analyzed the clinical characteristics of various types of radiation injuries,compared the risk and severity of radiation skin injuries in different treatment regimens in order to explore the risk factors for the occurrence and development of skin injuries in IC-CCRT and provide a scientific basis for exploring the pattern of radiotherapy-induced injuries and carrying out comprehensive prevention and follow-up management of NPC population in China.MethodsA prospective cohort study was conducted on 937 NPC patients who underwent radiotherapy for the first time from July 1,2013 to June 31,2019 at the Department of Oncology,General Hospital of Southern Theater Command of PLA,Guangzhou,China.The subjects were selected according to inclusion and exclusion criteria,and divided into IMRT and 3D-CRT groups according to radiotherapy modality.The information of follow-up was mainly collected including patients’ treatment history,time and extent of radiation damage during the radiotherapy process to evaluate their recent efficacy and long-term prognosis.The factors influencing the occurrence and aggravation of skin injury were analyzed by Log-rank test and Cox proportional risk model,subgroup analysis was conducted for patients with different therapeutic effects.ResultsDemographic characteristics: During the study period,a total of 937 NPC patients were received IC-CCRT regimen and eligible to participate in this study.535 patients were enrolled,and divided into two cohorts of IMRT(44.67%,239/535)and 3D-CRT(55.33%,286/535).All patients were followed up for a time interval of 4-26 months from the start of radiotherapy to the end of the follow-up process,with a median of 11 months.There were no significant differences in characteristics such as gender,type of inpatient medical insurance,place of birth,history of smoking and alcohol,marital status,current medical history,clinical stage of tumor,and KPS score between the IMRT and 3D-CRT groups,and their basic conditions were balanced and comparable before radiotherapy(P<0.05).Characteristics of radiological skin injury: A total of 522(97.57%)patients developed acute radiological injury during radiotherapy,516(96.45%)and 458(85.61%)patients suffered from oral mucositis and skin injury,respectively.Among them,15(2.80%)and 11(2.06%)patients had severe radiological skin injury and oral mucositis that led to interruption or suspension of radiotherapy.Only 32(5.98%)of the patients who developed skin lesions were correctly diagnosed as radiological skin lesions in their medical records.The incidence of skin lesions in the IMRT and 3D-CRT groups was 89.12% and 82.77%,respectively.The incidence of severe skin lesions in grade III or higher was 30.65%,with 35.98% in the IMRT group and 26.36% in the 3D-CRT group.Log-rank test results showed that the cumulative incidence of skin damage at 3,5,and 7 weeks was 11.35%,49.56%,and 83.19%,respectively,with 14.23%,54.81%,80.07% in the IMRT group and 6.14%,32.89%,65.49% in the 3D-CRT group,respectively.The time of median incidence was26(23-28)days in the IMRT group and 35(32-36)days in the 3D-CRT group.The cumulative incidence of stage III or higher skin lesions at 5,7,and 9weeks was 2.35%,50.59%,and 94.12%,respectively,with 9.66%,14.11%,35.39% in the IMRT group and 0%,27.44%,79.58% in the 3D-CRT group,respectively.IMRT increased the risk of skin injury,while hyper-segmented dose radiotherapy increased the risk of grade III or higher skin injury.Factors influencing the occurrence and degree of radiological skin injury: The results of the Cox proportional risk regression model analysis showed that the risk of developing skin damage decreased in 2017-2019 compared to earlier,but the risk of grade III or higher increased by 86.30%.After adjusting for year of treatment,age,BMI,and duration of radiotherapy at baseline,the risk of skin damage occurred in IMRT increased by 76.10%compared to the 3D-CRT group,and the risk of skin damage occurred in alcohol consumption,tumor stage IVa,IVb,and application of cisplatin-inducing chemotherapeutic agents increased by 43.80%,80.60%,76.10%,and 45.90%,respectively.IMRT did not increase the risk of grade III or higher skin injury compared with the 3D-CRT group;however,hyperfractionated radiotherapy,smokers,tumor stage IVa,IVb,and cisplatin-inducing chemotherapeutic agents were independent risk factors for aggravating skin injury in patients treated with NPC radiotherapy.Compared with conventional fractionated radiotherapy,hyperfractionated radiotherapy had a 3.903-fold increased risk of grade III or higher skin injury.In clinically effective patients,the risk of occurrence was 1.578 times higher in the IMRT group than the 3D-CRT group,while there was no significant difference in the risk of occurrence of grade III or higher skin injury(P<0.05).ConclusionsThe incidence of radiological skin injury during the treatment of IC-CCRT is still at a high level,and the proportion of grade III-IV radiological skin injury has increased compared with previous years.Serious skin injury is one of the main reasons that affects the continuance of radiotherapy,and there is an increased risk of distant metastasis of tumors.Radiotherapy techniques,tumor stages,history of alcohol consumption and the use of inducible chemotherapeutic agents were independent factors affecting skin lesions during NPC radiotherapy.Tumor stage,radiotherapy fractionation dose,smoking history and inducing chemotherapeutic agents were independent factors affecting severe skin injury in NPC radiotherapy.Physicians pay far less attention to the acute adverse effects of radiotherapy,and severe skin injury may weaken the control of distant metastasis rate,so that there is an urgent need to propose corresponding standardized diagnostic and prevention measures.IMRT and hyperfractionated radiotherapy can reduce the treatment compliance of NPC patients.The combination of chemotherapy drugs should avoid the superposition of chemotherapy toxicity and radiotherapy side effects,and improve the effective remission rate and survival rate of tumor. |
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