Hypofractionated Radiotherapy Combined With Late Course Accelerated Hyperfractionated Radiotherapy For NSCLC

Objective: To investigate the efficiency and toxicity of hypofractionated radiotherapy(HORT) combined with late course accelerated hyperfractionated radiotherapy(LCAHR) for non-small-cell lung cancer(NSCLC). To evaluate the advantage and disadvantage of this combined therapy. To estimate the patients' improvement of quality of life after therapy.Materials and Methods:1. Clinical materials Fifty-six patients with pathologically confirmed NSCLC admitted to Oncology department of Shandong Provincial Hospital from January of 2008 to October of 2008. There were 42 male patients and 14 female patients, aged from 34 to 78, averaged at 56.9 years old. Sorted by the pathological types, there were 33 squamous cell carcinoma, 16 adenocarcinoma, and 7 large cell carcinoma and others. All these patients whose Karnofsky(KPS) scores were all more than senventy had no signs of metastasis or serious physical diseases, with no previous thoracic operation, radiotherapy or chemotherapy and with normal blood cell counts, hepatic and renal function.2. Instruments Primus 3831 linear accelerator was produced by Siemens company. PLATO System of Treatment Planning System (TPS) was produced by Nucletron company of Holland.3. Treatment All the patients were treated by three dimensional conformal radiation therapy (3DCRT) and randomly divided into two groups: 28 patients in treatment group received hypofractionated radiotherapy combined with late course accelerated hyperfractionated radiotherapy, while the other 28 patients in control group received conventional radiotherapy. The treatment group were treated by HORT during the first 1/2 of the whole course with 30Gy in 10 fractions, then LCAHR (1.5Gy per fraction, twice a day) with an interval of more than 6 hours between fractions to a total dose of 60-66Gy. The control group were treated by conventional radiotrerapy all the course, with 66-70Gy in 33-35 fractions in 6.6-7 weeks, 5 fractions per week. The patients had blood routine examination weekly and chest computed tomography (CT) after 20 fractions.4. Observation indexes (1) Effect: It was evaluated by the Response Evaluation Criteria in Solid Tumors( RECIST) published in 2000. The main index was short-term effective rate which was classified into complete remission(CR), partial remission (PR), stabilization of disease(SD)and progression of disease(PD) by the result of imaging examination after radiotherapy. (2)Side effect: It was evaluated by CTCAEv3 criteria. (3) Evaluation of DVH: evaluate the correlation between V₂₀, V₃₀ parameters and acute radiation lung toxicity.5. Estimation of quality of life Quality of life was assesed on the day before radiotherapy and four weeks after the completion of radiotherapy using KPS and Symptom Check List 90(SCL-90). As for KPS, improvement is defined as increase of 20 scores, invalid as decrease of 20 scores and steady as change between them. Psychological status including physical symptoms, compulsive symptoms, personnel relationship, depreesion, anxietas, hostility, fear, monomania, psychosis and others(sleep, diet et al.) were assessed by SCL-90.6. Follow-up All patients were followed up to March of 2009. Three cases were lost and the follow-up rate was 94.6%.7. Statistical analysis Use the SPSS13.0 statistical software. Constitution rate was tested by Chi-square. Difference among means was tested by t test. Correlation analysis was tested by Pearson analysis.Results:1. The short-term effective rate of treatment group and control group was 78.6%(22/28) and 50.0%(14/28) respectively with statistically significant difference. In treatment group, 32.1%(9/28) were CR and 46.4%(13/28) were PR, while in control group, 10.7%(3/28) were CR and 39.3%(11/28) were PR.2. Evaluation of DVH. There were 26 cases of 0 degree of acute lung injury, 16 of 1 degree, 13 of 2 degree and 1 case of 3 degree. The incidence was 13.9% and 45% respectively in low V₂₀ group and high V₂₀ group , 11.4% and 47.6% in low V₃₀ and high V₃₀ group. The correlation analysis between V₂₀, V₃₀ of lung and acute radiation injury showed that the rate of acute radiation injury above 2 degree increased while the parameters above increased.3. Improvement rates of QOL. Assesed by KPS score, improvement rate of treatment group and controle group was 32.9%(9/28) and 28.6%(8/28) respectively with no statistically significant difference. Score of depression, sleep and diet factor in treatment group was lower than control group with statistically significant difference, but score of psychosis was higher. As for others such as physical symptoms, compulsive symptoms, personnel relationship, anxious, hostile, fear, monomania, there was no statistically significant difference between the two groups.4. Side effect. Although acute radiation side effect occurred earlier and more frequently in treatment group, there was no significant difference of acute or late side effect between the two groups and it didn't affect the completion of treatment.Conclusion:Hypofractionated radiotherapy combined with LCAHR for NSCLC can improve short-term effective rate. This combined therapy could also improve the quality of life including KPS score and psychological status. Its side effects were not statistically different from the conventional radiotherapy and were tolerable. The parameter V₂₀ is related to acute radiation-induced lung injury. The value of this combined treatment in long-term results and late radiation side effect need further study clinically.