Clinical Application And Dosage Exploration Of Hypofractional Radiotherapy In Patients With Stage Ⅲ Non-small Cell Lung Cancer

Currently,stereotactic radiotherapy has become the standard treatment for inoperable or refused surgery patients with non-small cell lung cancer（NSCLC）.The clinical application of molecular targeted therapy has significantly prolonged the survival time of a few patients with advanced-stage NSCLC.After all,the applicability of these drugs are narrow,which cannot meet all the patients requirements.At present,the 5-year survival rate of stage Ⅲa NSCLC patients is about 36%.As the standard therapeutic schemes for stage Ⅲb-c NSCLC,concurrent chemoradiotherapy results in the median overall survival time of only19 months and the 5-year survival rate less than 20%.Moreover,concurrent chemoradiotherapy requires a longer course,a higher cost and the huge economic pressure,so this mode has a strong impact on the patients’normal work and life.With the rapid development of modern radiotherapy technology,it is possible to make the hypofractional radiotherapy real.To a large extent,the clinical application of this mode can short the treatment time,decrease the economic pressure of patient,and optimize the cost-effective of radiotherapy.At the same time,in addition to better local tumor control by increasing the bioeffective dose（BED）,large-scale fractional radiotherapy may also activate the body’s autoimmune system to produce a"distant effect",so as to achieve better systemic tumor control.Helical tomotherapy can achieve any dose distribution requirement in human body by using 360 degree rotation.Current dosimetric study indicate that with the advantage of the unique dual pneumatic multi-blade collimator and 51 beam angles,tomotherapy can increase the target dose while get a quick fall off dose around the target area,in order to protect the normal tissues.At the same time,Tomotherapy can provides better conformation and uniformity dose and make it possible to receive higher fractional radiotherapy for stage Ⅲ NSCLC patients with multiple lymph node metastasis.The purpose of our study is to assess the clinical outcomes and toxicit ies following hypofractionation with helical tomographic intensity-modulated radiotherapy technology（tomotherapy）of patients with stage Ⅲ NSCLC who are not candidates for surgery or concurrent c hemoradiation.Secondly,to identify independent prognostic factors that may affect patient’s survival.Thirdly,to find out the more suitable radiotherapy fractionation mode for treating.Forthly,to find out the affecting factors with radiation pneumonia.Lastly,to deduce a new reference irradiation doses of normal lung tissue in accordance with the hypofractional radiotherapy,and to discusse the relationship between a new reference irradiation doses and radiation pneumonia.Materials and Methods:Forty-three patients with stage Ⅲ NSCLC treated between 2011 and 2017 were enrolled.The median age of patients was 69 years（range from 50 to 86）.31 cases are male and 12 cases are female.27 cases were at the Ⅲa stage,and 16 patients were at the Ⅲb stage.Use thermoplastic body mask to fix the patient.Enhanced CT scan was used for CT-simulation,and all patients were reminded to breathe naturally without control.The prescription doses for GTV and CTV were 70Gy and 60Gy,respectively.All therapeutic process was delivered in 15–25 fractions over 3–5 weeks.K-M survival analysis and Cox proportional hazard model were used to analyze the relationship between multi-factors and patient’prognosis.Logistic regression equation were used to analyze the influencing factors with radiation pneumonia.According to the equation of biological effective dose（BED）,the new reference value of normal lung tissue was converted.Meanwhile,analysis the relationship between the new reference value and the occurrence of radiation pneumonia by unpaired T test.Results:The median overall survival（OS）time was 3 4.23（range 11.33–99.33）months.While the median progression-free survival（PFS）was 25.00（range from11.33 to 99.33）months.The estimated 1-,2-,and 3-year overall survival rates were 97.7%,74.4%,and 55.9%,respectively;the corresponding progression free survival rates were 79.1%,53.5%,and 36.1%,respectively.The local disease recurrence,regional disease recurrence and distant metastasis rates at 3 years were4.7%,11.62%,and 55.81%,respectively.The results of univariate analysis and multivariate analysis（Cox proportional hazards model）recognized the dose regimen（GTV/CTV/70/60Gy/15-18f）was the factor associated with better OS and PFS（p<0.05）.Seven patients developed grade 1-2 acute radiation pneumonia（RP）,5 patients developed grade 1-2 late RP,while 3 patients developed grade 3 late RP.None of the patients developed grade 4 radiation lung injury.No significant difference was found between sex,age,TNM-staging,pathological types,the condition of primary tumor and lymph node metastasis,chemotherapy history,targeted therapy,KPS score and dose regimen with radiation pneumonia.The DVH parameters of（GTV/CTV/70/60Gy/15-18f）group and the（GTV/CTV/70/60Gy/19-25f）group were generally the same in total lung V_5-40.Conclusion:Tomotherapy with hypofractional mode may be an effective treatment option for patients with stage Ⅲ NSCLC.The dose regimen of GTV/CTV/70Gy/60Gy/15-18 times might get better survival benefit.So,it may be a viable alternative to surgery with lower incidence of side effects.