【摘要】：目的 本研究的目的主要是分析多西他賽每周給藥方案同步聯(lián)合三維適形放療治療Ⅲ期非小細(xì)胞肺癌的療效、生存狀況及毒副反應(yīng)發(fā)生情況。 方法 99例Ⅲ期非小細(xì)胞肺癌（包括Ⅲ A期及ⅢB期）均經(jīng)細(xì)胞學(xué)或組織學(xué)證實(shí)。治療前接受1～2周期的全身化療。既往患者應(yīng)用的化療方案均為TP方案（多西他賽75mg/m2,順鉑75mg/m2）。 1化療方法：同步放化療時化療方案為給予多西他賽每周方案化療，劑量為多西他賽35mg/m2，每周應(yīng)用1次�；熐耙惶扉_始常規(guī)應(yīng)用地塞米松16mg預(yù)處理，連用3天；并于用多西他賽前半小時常規(guī)應(yīng)用西咪替丁400mg靜脈滴注及異丙嗪25mg肌肉注射。 2放療方法：放療采用三維適形放療，射線能量為6Mv-X線或15Mv-X線，累及野照射，常規(guī)分割，照射劑量共60Gy～66Gy。掃描前常規(guī)應(yīng)用碘伏醇100ml靜脈注射。掃描層厚為3mm～5mm。掃描范圍自環(huán)狀軟骨水平至右腎上腺水平。CT圖像上傳至Eclipse計劃系統(tǒng)或Precise計劃系統(tǒng)進(jìn)行勾畫靶區(qū)及危及器官。再由物理師在TPS系統(tǒng)下制定放療計劃，采用3～5個照射野進(jìn)行照射，劑量評估經(jīng)劑量體積直方圖（DVH）評價雙肺限制劑量為V20≤28%，脊髓限制劑量為最大劑量≤45Gy，心臟限制劑量為V40≤30%，食管限制劑量為V45≤33%，臂叢神經(jīng)限制劑量最大劑量≤66Gy。處方劑量的評估要求為PTV接受110%處方劑量的體積＜20%；PTV接受115%處方劑量的體積＜5%；PTV接受93%的處方劑量的體積＜1%；90%～95%等劑量線包繞90%～95%PTV,90%的PTV接受最低吸收劑量。T1～2期患者的放療劑量為60Gy，T3～4期患者的放療劑量為64～66Gy。鎖骨上區(qū)有淋巴結(jié)轉(zhuǎn)移的患者鎖骨上區(qū)采用單獨(dú)鈷60γ射線或12MeV電子線野照射，劑量同胸部放療的劑量。 3其他治療方法：化療后每周監(jiān)測血常規(guī)指標(biāo)，每兩周監(jiān)測肝腎功能及水電解質(zhì)變化。白細(xì)胞≤2.0×109時使用粒細(xì)胞集落刺激因子（G-CSF）支持。G-CSF的用藥劑量為5μg/kg/d，用藥途徑均為皮下注射。誘導(dǎo)化療期間出現(xiàn)2級以上骨髓抑制的患者預(yù)防性應(yīng)用G-CSF。用藥時機(jī)為化療后24～72小時開始使用，直到粒細(xì)胞降至最低點(diǎn)后回升正常時或白細(xì)胞升至10.0×109時停藥。肝功能下降的患者給予甘草酸二銨進(jìn)行保肝治療，直至轉(zhuǎn)氨酶恢復(fù)至正常水平。當(dāng)出現(xiàn)有發(fā)熱癥狀的放射性肺炎時給予痰細(xì)菌培養(yǎng)加藥敏試驗(yàn)，根據(jù)藥敏試驗(yàn)結(jié)果選擇合理的抗生素治療，并給予止咳祛痰等對癥處理。放射性食管炎伴有進(jìn)食疼痛加重時,應(yīng)用表面麻醉劑及糖皮質(zhì)激素。當(dāng)患者出現(xiàn)白細(xì)胞下降時應(yīng)用普通升白藥物例如地榆生白片、利可君、鯊肝醇等。 結(jié)果 1完成治療情況：99例患者均全部完成治療，沒有因毒副反應(yīng)終止放療者。僅有其中有10例患者由于短暫性骨髓抑制、放射性肺炎及放射性食管炎等沒有完成預(yù)期6周的周劑量多西他賽化療。中位放療持續(xù)時間為43天（±2天），，中位放療劑量為62Gy（60Gy～66Gy）。 2療效評價：完全緩解13例（13.1%），部分緩解35例（35.4%），穩(wěn)定24例（24.2%），進(jìn)展17例（17.2%），死亡7例（7.1%），失訪3例（3.0%）。其中有效率（完全緩解+部分緩解）為48.5%，疾病控制率（完全緩解+部分緩解+穩(wěn)定）為72.7%。 3生存分析：隨訪時間為6.5～38.4個月，中位隨訪時間為22.4個月。中位疾病進(jìn)展時間為11.3個月（95%CI為8.3～14.7月），中位生存時間為18.6個月（95%CI為14.0～23.2月）。1年生存率77.8%，2年生存率為57.6%，3年生存率為33.3%（P=0.04）。 4毒副反應(yīng)：主要的毒副反應(yīng)為放射性食管炎、惡心及放射性肺炎等。但程度均較輕，經(jīng)過對癥支持處理后緩解且均能完成治療。最常見的毒副反應(yīng)為放射性食管炎，1～2級發(fā)生率為52.5%（52/99）,3級發(fā)生率為12.1%(12/99)。其次為惡心，1～2級發(fā)生率為32.3%（32/99）,3級發(fā)生率為3.0%(3/99)。放射性肺炎的發(fā)生幾率相對較低，1～2級放射性肺炎發(fā)生率為10.1%（10/99），1例（1.0%）患者出現(xiàn)3級放射性肺炎，1例（1.0%）患者出現(xiàn)4級放射性肺炎。其余的急性治療反應(yīng)發(fā)生率均較低，如黏膜炎、吞咽困難、腹瀉、發(fā)熱、白細(xì)胞下降、血小板減少、皮膚損傷等。 結(jié)論 周劑量多西他賽同步三維適形放療治療Ⅲ期非小細(xì)胞肺癌近期療效滿意，有效率、無進(jìn)展生存率及總生存率均達(dá)到預(yù)期目標(biāo)，不良反應(yīng)較輕，值得臨床進(jìn)一步推廣及開展大規(guī)模隨機(jī)對照研究。
[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.
【學(xué)位授予單位】：泰山醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R734.2;R730.55

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