Ⅲ期非小细胞肺癌周剂量多西他赛同步适形放疗

发布时间：2018-08-04 22:01

【摘要】：目的本研究的目的主要是分析多西他赛每周给药方案同步联合三维适形放疗治疗Ⅲ期非小细胞肺癌的疗效、生存状况及毒副反应发生情况。方法 99例Ⅲ期非小细胞肺癌（包括Ⅲ A期及ⅢB期）均经细胞学或组织学证实。治疗前接受1～2周期的全身化疗。既往患者应用的化疗方案均为TP方案（多西他赛75mg/m2,顺铂75mg/m2）。 1化疗方法：同步放化疗时化疗方案为给予多西他赛每周方案化疗，剂量为多西他赛35mg/m2，每周应用1次。化疗前一天开始常规应用地塞米松16mg预处理，连用3天；并于用多西他赛前半小时常规应用西咪替丁400mg静脉滴注及异丙嗪25mg肌肉注射。 2放疗方法：放疗采用三维适形放疗，射线能量为6Mv-X线或15Mv-X线，累及野照射，常规分割，照射剂量共60Gy～66Gy。扫描前常规应用碘伏醇100ml静脉注射。扫描层厚为3mm～5mm。扫描范围自环状软骨水平至右肾上腺水平。CT图像上传至Eclipse计划系统或Precise计划系统进行勾画靶区及危及器官。再由物理师在TPS系统下制定放疗计划，采用3～5个照射野进行照射，剂量评估经剂量体积直方图（DVH）评价双肺限制剂量为V20≤28%，脊髓限制剂量为最大剂量≤45Gy，心脏限制剂量为V40≤30%，食管限制剂量为V45≤33%，臂丛神经限制剂量最大剂量≤66Gy。处方剂量的评估要求为PTV接受110%处方剂量的体积＜20%；PTV接受115%处方剂量的体积＜5%；PTV接受93%的处方剂量的体积＜1%；90%～95%等剂量线包绕90%～95%PTV,90%的PTV接受最低吸收剂量。T1～2期患者的放疗剂量为60Gy，T3～4期患者的放疗剂量为64～66Gy。锁骨上区有淋巴结转移的患者锁骨上区采用单独钴60γ射线或12MeV电子线野照射，剂量同胸部放疗的剂量。 3其他治疗方法：化疗后每周监测血常规指标，每两周监测肝肾功能及水电解质变化。白细胞≤2.0×109时使用粒细胞集落刺激因子（G-CSF）支持。G-CSF的用药剂量为5μg/kg/d，用药途径均为皮下注射。诱导化疗期间出现2级以上骨髓抑制的患者预防性应用G-CSF。用药时机为化疗后24～72小时开始使用，直到粒细胞降至最低点后回升正常时或白细胞升至10.0×109时停药。肝功能下降的患者给予甘草酸二铵进行保肝治疗，直至转氨酶恢复至正常水平。当出现有发热症状的放射性肺炎时给予痰细菌培养加药敏试验，根据药敏试验结果选择合理的抗生素治疗，并给予止咳祛痰等对症处理。放射性食管炎伴有进食疼痛加重时,应用表面麻醉剂及糖皮质激素。当患者出现白细胞下降时应用普通升白药物例如地榆生白片、利可君、鲨肝醇等。结果 1完成治疗情况：99例患者均全部完成治疗，没有因毒副反应终止放疗者。仅有其中有10例患者由于短暂性骨髓抑制、放射性肺炎及放射性食管炎等没有完成预期6周的周剂量多西他赛化疗。中位放疗持续时间为43天（±2天），，中位放疗剂量为62Gy（60Gy～66Gy）。 2疗效评价：完全缓解13例（13.1%），部分缓解35例（35.4%），稳定24例（24.2%），进展17例（17.2%），死亡7例（7.1%），失访3例（3.0%）。其中有效率（完全缓解+部分缓解）为48.5%，疾病控制率（完全缓解+部分缓解+稳定）为72.7%。 3生存分析：随访时间为6.5～38.4个月，中位随访时间为22.4个月。中位疾病进展时间为11.3个月（95%CI为8.3～14.7月），中位生存时间为18.6个月（95%CI为14.0～23.2月）。1年生存率77.8%，2年生存率为57.6%，3年生存率为33.3%（P=0.04）。 4毒副反应：主要的毒副反应为放射性食管炎、恶心及放射性肺炎等。但程度均较轻，经过对症支持处理后缓解且均能完成治疗。最常见的毒副反应为放射性食管炎，1～2级发生率为52.5%（52/99）,3级发生率为12.1%(12/99)。其次为恶心，1～2级发生率为32.3%（32/99）,3级发生率为3.0%(3/99)。放射性肺炎的发生几率相对较低，1～2级放射性肺炎发生率为10.1%（10/99），1例（1.0%）患者出现3级放射性肺炎，1例（1.0%）患者出现4级放射性肺炎。其余的急性治疗反应发生率均较低，如黏膜炎、吞咽困难、腹泻、发热、白细胞下降、血小板减少、皮肤损伤等。结论周剂量多西他赛同步三维适形放疗治疗Ⅲ期非小细胞肺癌近期疗效满意，有效率、无进展生存率及总生存率均达到预期目标，不良反应较轻，值得临床进一步推广及开展大规模随机对照研究。
[Abstract]:objective
The purpose of this study was to analyze the efficacy, survival and side effects of the weekly administration of docetaxel combined with three dimensional conformal radiotherapy in the treatment of stage III non-small cell lung cancer.
Method
99 cases of stage III non-small cell lung cancer (including stage III A and stage III B) were confirmed by cytology or histology. 1~2 cycles of systemic chemotherapy were received before treatment. The chemotherapy regimens used by the patients were all TP regimen (docetaxel 75mg/m2, cisplatin 75mg/m2).
1 chemotherapy method: the chemotherapy regimen was given to docetaxel weekly regimen, dosed docetaxel 35mg/m2 and 1 times a week. The routine use of dexamethasone 16mg pretreatment one day before chemotherapy was used for 3 days, and the intravenous drip of cimetidine 400mg and the 25mg muscle of promethazine were used in the first half hour of docetaxel. The meat is injected.
2 the radiotherapy method: the radiotherapy was treated with three-dimensional conformal radiotherapy, radiation energy was 6Mv- X or 15Mv- x, involving field irradiation, routine segmentation, and routine application of 100ml intravenous injection of iodophor before 60Gy ~ 66Gy. scanning. The scanning layer was 3mm to 5mm. scanning range from the level of cricoid cartilage to the right adrenal level.CT image to Eclipse program The system or Precise plan system was used to draw the target area and endanger the organ. Then the physical therapist made the radiotherapy plan under the TPS system and irradiated in 3~5 irradiated fields. The dose volume histogram (DVH) was used to evaluate the restriction dose of the double lung to V20 less than 28%, the maximum dose of the spinal cord was less than 45Gy, and the limited dose of the heart was V40 less than 30%. The restricted dose of the esophagus was V45 < 33%. The evaluation of the maximum dose of the brachial plexus limited dose of the dose < 66Gy. was less than 20%; the volume of the 110% prescription dose for PTV was less than 20%; the volume of the 115% prescription dose for PTV was less than 5%; the volume of the prescription dose of the PTV received 93% was 1%; the 90% to 95% dose lines were around 90% to 95%PTV, and the PTV in the PTV received the lowest sucking. The dose of radiotherapy for.T1 to 2 patients was 60Gy, and the dose of Co 60 gamma ray or 12MeV electron field irradiation in the supraclavicular region of the patients with stage T3 to 4 with the dose of 64 ~ 66Gy. with lymph node metastasis in the supraclavicular region was treated with the dose of the chest radiotherapy.
3 other treatment methods: Monitoring Blood Routine Indexes every week after chemotherapy, monitoring liver and kidney function and water electrolyte every two weeks. The dosage of granulocyte colony-stimulating factor (G-CSF) using granulocyte colony-stimulating factor (G-CSF) for.G-CSF was 5 u g/kg/d, and the drug route was subcutaneous injection. Patients with more than 2 myelosuppression during chemotherapy were induced. The use of prophylactic use of G-CSF. is to start 24~72 hours after chemotherapy, until the granulocyte drops to the lowest point and goes back to normal or when leukocytes rise to 10 x 109. Patients with liver function decline are treated with Diammonium Glycyrrhizinate for liver preservation until the aminotransferase is restored to normal level. The sputum bacteria culture and drug sensitivity test were given, rational antibiotic treatment was selected according to the results of drug sensitivity test, and cough and expectorant treatment was given. The use of surface anesthetic and glucocorticoid when the pain was aggravated. Liking, shark liver alcohol, etc.
Result
1 complete treatment: all of the 99 patients completed the treatment. There were only 10 patients who had not completed the expected weekly dose of docetaxel chemotherapy for 6 weeks due to transient myelosuppression, radionuclitis and radioactive esophagitis. The duration of middle radiotherapy was 43 days (2 days), and the dose of middle radiotherapy. 62Gy (60Gy to 66Gy).
2 evaluation of curative effect: complete remission in 13 cases (13.1%), partial remission in 35 cases (35.4%), stable 24 cases (24.2%), 17 cases (17.2%), 7 cases (7.1%) death and 3 cases (3%). The effective rate (complete remission + partial remission) was 48.5%, and the rate of disease control (complete remission + partial remission + stability) was 72.7%.
3 survival analysis: the follow-up time was 6.5 to 38.4 months and the median follow-up time was 22.4 months. The progression time of the median disease was 11.3 months (95%CI 8.3 to 14.7 months), the median survival time was 18.6 months (95%CI 14 to 23.2 months) and the survival rate was 77.8%, 2 survival rate was 57.6%, and the survival rate was P=0.04 (P=0.04).
4 side effects: the main toxic and side effects were radioactive esophagitis, nausea and radiation pneumonia. But the degree was mild, after symptomatic support treatment. The most common toxic and side effects were radioactive esophagitis, the incidence of grade 1~2 was 52.5% (52/99), the incidence of grade 3 was 12.1% (12/99). Secondly, nausea, 1~2 grade The rate was 32.3% (32/99), the incidence of grade 3 was 3% (3/99). The incidence of radiation pneumonia was relatively low, the incidence of grade 1~2 radiation pneumonia was 10.1% (10/99), 1 cases (1%) had 3 levels of radionuclide pneumonia and 1 cases (1%) had recurrent pneumonia. The incidence of other acute treatment reactions was low, such as mucositis, dysphagia, diarrhea. Fever, leukocyte decline, thrombocytopenia, skin damage and so on.
conclusion
The efficacy of weekly dose of docetaxel in the treatment of stage III non-small cell lung cancer is satisfactory, effective, no progression survival rate and total survival rate have reached the expected goal, and the adverse reaction is light. It is worthy of clinical further promotion and large-scale randomized controlled study.
【学位授予单位】：泰山医学院
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R734.2;R730.55

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