Sequential hemibody and local irradiation with combination chemotherapy for small cell lung carcinoma: a preliminary analysis

Sequential hemibody irradiation (SHB) was integrated with combination chemotherapy and local irradiation (LRT) in the induction and consolidation phases of a therapeutic protocol for small cell lung carcinoma (SCLC). Forty-one previously untreated patients were entered into this program. Among 38 evaluable patients (20 with limited disease [LD] and 18 with extensive disease [ED], the overall response rate was 63% (90% in LD and 33% in ED patients). The estimated overall survival is 8.1 months. The major toxicity has been myelosuppression--especially thrombocytopenia. The frequency of previously described "acute radiation syndromes" and radiation pneumonitis associated with hemibody irradiation have been substantially decreased at the current dosage with premedication and shielding techniques. The integration of SHB as a systemic therapy with combination chemotherapy and LRT is a feasible program for sequential administration of non-cross-resistant agents in SCLC and may be beneficial in patients with limited disease.     

Twice daily thoracic irradiation for limited small cell lung cancer.

Thoracic failure is a significant obstacle to the cure of limited stage small-cell lung cancer (LSCLC) patients treated with combined modality therapy. In 1985 we initiated a prospective trial to evaluate the impact of twice daily thoracic irradiation without concomitant chemotherapy on control of intrathoracic tumor in LSCLC. Twenty-nine patients treated in this fashion were compared with 36 patients treated from 1979-1982 with once daily thoracic irradiation and concomitant chemotherapy. Both groups received the same induction chemotherapy; cyclophosphamide, Adriamycin, and vincristine (CAV) alternating with cisplatin and etoposide. For consolidation, the twice daily patients received thoracic irradiation, 45 Gy in 1.5 Gy fractions given twice daily, and the once daily patients received thoracic irradiation, 45 Gy in 2.5 Gy fractions given once daily with concomitant cyclophosphamide and vincristine. After completion of radiotherapy both groups received maintenance chemotherapy. The complete response (CR) rate after thoracic irradiation was higher for twice daily patients (86% (25/29) compared to the once daily patients [61% (22/36), p = 0.02]. However, this advantage was offset by the shorter duration of thoracic control among CR patients treated with twice daily thoracic irradiation compared to once daily thoracic irradiation (32% vs 67% at 2 years, p less than 0.05). In view of the enhanced initial response of LSCLC to twice daily thoracic irradiation, this basic radiotherapeutic approach seems appropriate, but new strategies using higher doses of twice daily thoracic irradiation or concomitant chemotherapy appear to be necessary to enhance long-term thoracic control.     

Alternating radiotherapy and chemotherapy schedules in small cell lung cancer, limited disease

Sixty-three evaluable patients with limited small cell lung carcinoma were entered into two pilot studies alternating 6 cycles of combination chemotherapy (Doxorubicin 40 mg/m2 d 1; VP16213 75 mg/m2 d 1, 2, 3; Cyclophosphamide 300 mg/m2 d 3, 4, 5, 6; and Methotrexate 400 mg/m2 d 2--plus folinic acid rescue--or Cis-Platinum 100 mg/m2 d 2) with 3 courses of mediastinal radiotherapy as induction treatment. The first course of radiotherapy started 10 days after the second cycle of chemotherapy; there was a 7 day rest between chemotherapy and radiotherapy courses. This 6 month induction treatment was followed by a maintenance chemotherapy. The total mediastinal radiation dose was increased from 4500 rad in the first study to 5500 rad in the second. Both protocols obtained a complete response (CR) rate of greater than 85% (with fiberoptic bronchoscopy and histological verification). Local control at 2 years was 61% in the first study and 82% in the second. Relapse-free survival at 2 years was 32 and 37%, respectively. Toxicity was acceptable. We conclude that our results justify further clinical research in alternating radiotherapy and chemotherapy schedules.     

局限期小细胞肺癌的放射治疗现状和展望

目的:通过复习局限期小细胞肺癌(SCLC)放射治疗的文献,探讨局限期SCLC最佳放射治疗策略.方法:应用计算机检索PubMed和CHKD数据库有关SCLC放射治疗的70篇研究文章,纳入分析39篇,检索词为小细胞肺癌、局限期、放射治疗和预防性脑照射.结果:试验表明放射治疗优于手术治疗,中位总生存期手术组为6个月,放疗组为10个月,差异有统计学意义;Meta分析显示,联合化疗+放疗较单纯联合化疗方法改善了生存期,单纯联合化疗组患者3年生存率为8.9%,联合化疗+放疗组3年生存率为14.3%,P=0.001.预防性脑照射(PCI)的作用已肯定.但是,胸部照射(thoracic radiation therapy, TRT)的剂量、时机和靶体积等问题未完全解决.结论:局限期SCLC的治疗策略为化疗和同步TRT以及预防性脑照射(PCI).胸部照射应该在化疗早期(化疗第1或2个周期)进行,不赞同根据化疗前肿瘤体积来确定照射靶区. PCI应尽可能在化疗完成后就开始.     

调强放疗联合化疗治疗局限期小细胞肺癌近期疗效分析

目的：分析化疗联合调强适形放疗治疗局限期小细胞肺癌（SCLC）的近期疗效和放射损伤情况。方法：42例局限期SCLC采用放化疗综合治疗,放疗常规分割,单次剂量2Gy,每周5次,中位总剂量58Gy。化疗采用卡铂或顺铂＋VP 16为主的方案,4-6个周期。中位随访32个月。结果：全组患者CR为35.7%（15/42）,PR为57.1%（24/42）,SD为7.1%（3/42）,有效率为92.8%。1年总生存率（OS）为75.8%,2年为37.5%,3年为21.5%,中位生存时间为23个月。2级急性放射性肺损伤为4.8%（2/42）,2级晚期放射性肺损伤为7.1%（3/42）,2级急性放射性食管损伤11.9%（5/42）,2级血液学毒性为11.9%（5/42）。结论：化疗联合IMRT用于局限期SCLC治疗,能获得较好的近期疗效和2年生存率,放射损伤在可接受范围,放疗剂量、照射范围值得进一步研究。     

调强放疗联合化疗治疗局限期小细胞肺癌近期疗效分析

目的:分析化疗联合调强适形放疗治疗局限期小细胞肺癌(SCLC)的近期疗效和放射损伤情况。方法:42例局限期SCLC采用放化疗综合治疗,放疗常规分割,单次剂量2Gy,每周5次,中位总剂量58Gy。化疗采用卡铂或顺铂+VP 16为主的方案,4-6个周期。中位随访32个月。结果:全组患者CR为35.7%(15/42),PR为57.1%(24/42),SD为7.1%(3/42),有效率为92.8%。1年总生存率(OS)为75.8%,2年为37.5%,3年为21.5%,中位生存时间为23个月。2级急性放射性肺损伤为4.8%(2/42),2级晚期放射性肺损伤为7.1%(3/42),2级急性放射性食管损伤11.9%(5/42),2级血液学毒性为11.9%(5/42)。结论:化疗联合IMRT用于局限期SCLC治疗,能获得较好的近期疗效和2年生存率,放射损伤在可接受范围,放疗剂量、照射范围值得进一步研究。     

Thoracic radiotherapy variables: influence on local control in small cell lung cancer limited disease

In limited small cell lung cancer (LSCLC), the high local failure rate of chemotherapy by itself (60-100%) and with the addition of external beam radiotherapy (approximately 30%) has led to investigation of methods to improve local control. To that end, we integrated Platinum 60 mg/m2, d. 1, 22 and Etoposide 120 mg/m2, d. 4, 6, & 8; 25, 27 & 29 with concurrent twice-daily 150 cGy (total dose: 4500 cGy). Of 32 consecutively referred patients, 4 with variant histology, 31 were evaluable for toxicity, response, and survival. Two of 4 variant histology patients responded, and 27 of 27 pure small cell responded, p = 0.005. CT scans were inaccurate at forecasting survival. Of 17/32 patients considered "positive," 59% of these were survivors; of those considered "negative," 47% were survivors, p = N.S. Radiation portals were volumetrically conservative; the supraclavicular fossa was included infrequently and the contralateral hilum not at all. Local failure occurred in only 1/27 patients (4%). All four variant patients failed locally, p = 0.001. With a median follow-up of 43 months, the actuarial disease-free survival remains nearly 50%. Variant histology is more predictive of local control than the physical factors of dose or volume.     

Use of hemibody irradiation as a non-cross-resistant agent in combination with systematic chemotherapy in small cell lung cancer

Previously, investigators at this institute have studied the use of upper hemibody irradiation as a consolidation agent following combination chemotherapy for small cell lung cancer. There was no improvement in survival compared to that in the group treated with chemotherapy alone. In our present pilot study, we are investigating the toxicity and efficacy of using hemibody irradiation (HBI) as a non-cross-resistant agent early in a program of alternating chemotherapy consisting of six treatment cycles. Toxicity due to the combined effects of chemotherapy (cisplatin and etoposide plus cyclophosphamide, doxorubicin, and vincristine) plus HBI is reported. The HBI was given at a dose of 1,000 cGy in four fractions for limited disease or as a single 800-cGy dose for extensive disease. Bone marrow suppression following HBI necessitated a subsequent delay in the chemotherapy cycle or dose reduction in 55% of the 33 patients. Six patients developed diffuse interstitial pneumonitis following chemotherapy and HBI; 3 have died, and in 2 of these, the etiology was opportunistic infection. In our previous studies utilizing HBI either alone or as consolidation therapy after induction chemotherapy, a low incidence of lung toxicity occurred. This increased incidence suggests a possible drug-radiation interaction when HBI is used as an alternating agent with doxorubicin and cisplatin.     

局限期小细胞肺癌PET-CT定位适形放疗联合化疗的疗效分析

目的探讨局限期小细胞肺癌PET-CT定位适形放疗联合化疗的疗效。方法回顾性分析局限期小细胞肺癌58例,其中28例经PET-CT扫描(PET-CT组),30例采用普通CT定位(普通CT组),所有患者均用相同剂量适形放疗联合EP方案化疗,观察两组患者的疗效、不良反应及失败原因。结果 PET-CT组的平均GTV与PTV体积均小于普通CT组,PET-CT组的左肺与右肺V20、心脏、食管与脊髓V40均小于普通CT组(P<0.05)。两组近期总有效率差异无统计学意义(P>0.05)。PET-CT组中,1、2级肺和气管的早期与晚期放射损伤发生率低于普通CT组(P均<0.05)。PET-CT组的1、2、3年局部控制率和生存率均高于普通CT组(P<0.01)。PET-CT组纵膈淋巴结复发率低于普通CT组,放化疗后手术切除残存病灶者预后好。治疗失败的主要原因为远处转移。结论PET-CT定位可以优化局限期小细胞肺癌的放疗设野计划,减少正常组织的照射体积与纵膈复发率,放化疗后手术切除残存病灶预后好,远处转移为主要失败原因。     

Prophylactic cranial irradiation for limited non-small cell lung cancer

Seventy-three patients with biopsy-proven limited non-small cell lung cancer (NSCLC) were entered on a combined modality study at the University of Washington. Seventy-five percent (55 of 73) of the patients had a histologic diagnosis of adenocarcinoma or large cell carcinoma, whereas 25% (18 of 73) had squamous cell carcinoma. After two cycles of chemotherapy, patients without evidence of progressive disease received prophylactic cranial irradiation (PCI) and chest radiotherapy, followed by two additional cycles of chemotherapy. Brain computed tomography (CT) scans were performed at 3-month intervals after completion of therapy in all patients, and were additionally performed whenever signs or symptoms developed suggesting neurologic dysfunction or recurrent brain disease. Sixty-five patients were treated with PCI. No clinical or CT evidence of recurrence in the brain has developed in patients who completed PCI. PCI appears to be effective in greatly reducing the incidence of brain relapse in patients with limited NSCLC.     

局限期小细胞肺癌化疗联合加速超分割放疗疗效初步分析

背景与目的:局限期小细胞肺癌(small cell lung cancer,SCLC)对放疗和化疗均敏感.放疗可提高局限期SCLC患者总生存率,降低局部复发率.本研究总结在化疗基础上应用加速超分割放射治疗(hypedractionated accelerated radiotherapy,HART)对局限期SCLC的疗效,评价相关治疗毒性,归纳治疗失败方式.方法:55例局限期SCLC患者经过EP方案诱导化疗,放疗后再以EP方案巩固化疗,完全缓解(complete remission,CR)者行预防性全脑照射(Prophylactic cranial irradiation,PCI).治疗结束后对患者进行随访,并评价其疗效及毒副作用.结果:55例患者放化疗结束时总有效率(CR PR)为87.3%.1、3、5年总生存率分别为79.1%、40.3%、16.1%,中位生存时间18.7个月.Ⅲ度和Ⅳ度血液学毒性分别为23例(41.8%)和16例(29.1%);Ⅰ度和Ⅱ度急性放射性肺炎分别为21例(38.2%)和2例(3.6%),Ⅰ度和Ⅱ度放射性食管炎分别为29例(52.7%)和12例(21.8%),未发生Ⅲ～Ⅳ度非血液学毒性.11例(20.0%)患者出现Ⅰ度肺纤维化,5例(9.1%)为Ⅱ度.2例(3.6%)发生Ⅰ度后期食管损伤.16例(29.1%)局部/区域复发.21例(38.2%)发生远处转移.结论:EP方案化疗合并HART治疗局限期SCIJC毒性轻至中度,患者可以耐受.局部复发和远处转移为主要治疗失败原因.     

PET方案化疗联合胸部放疗治疗局限期小细胞肺癌的疗效观察

回顾性分析PET(Paclitaxel135mg/m2,d1,Vp-1675mg/m2d1~d3,DDP80mg/m2,d1~d3使用)方案化疗联合胸部放疗治疗局限期小细胞肺癌的临床疗效。24例局限期小细胞肺癌接受PET化疗,每3周重复1次,共4~6个周期,胸部放疗于化疗2个周期后开始进行,2Gy/(5次·周),DT50~60Gy/25~30次,治疗达完全缓解者予以全脑预防性放疗DT30Gy/(15次·3周)。结果显示,24例局限期小细胞肺癌患者完全缓解(CR)19例,部分缓解(PR)4例,总缓解率95·8%(CR79·2%,PR16·7%),中位生存期25个月,2、3年生存率分别为50·0%和41·7%,局部复发率29·2%,远处转移率54·2%。PET方案化疗联合胸部放疗治疗局限期小细胞肺癌有较好的缓解率和近期疗效,毒性反应可耐受。     

小细胞肺癌放射治疗进展

目的 放射治疗是小细胞肺癌治疗的主要方式,其实施过程涉及到小细胞肺癌的诸多环节,总结国内外关于小细胞肺癌放射治疗的研究现状,探讨胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中的价值.方法 应用PubMed、西文生物医学期刊文献数据库、中国知网及万方期刊全文数据库检索系统,以"小细胞肺癌,放疗,全脑预防性照射"为中文关键词,以"small cell lung cancer,radiotherapy,prophylactic cranial irradiation"为英文关键词,联合检索1996-01-2016-12的相关文献.共检索到英文文献377篇,中文文献4篇.纳入标准:(1)小细胞肺癌;(2)放疗;(3)全脑预防性照射.排除标准:(1)非小细胞肺癌;(2)手术;(3)化疗.根据剔除标准剔除中文文献2条,英文文献326条,最后纳入分析37篇文献.结果局限期小细胞肺癌的胸部放疗的分割剂量和模式为45 Gy/30次,超分割放疗或60~70 Gy/30~35次,常规分割放疗.胸部放疗参与的最佳时间为于化疗第1个周期或第2个周期参与.胸部同步放化疗结束以后行全脑预防性照射,放疗期间可给予药物盐酸美金刚以保护神经认知功能或海马保护的调强放射治疗;广泛期小细胞肺癌的胸部放疗的分割剂量和模式为30 Gy/10次或45 Gy/15次.全脑预防性照射存在争议.结论胸部放射治疗和全脑预防性照射在小细胞肺癌治疗中起着非常重要的作用.     

局限期小细胞肺癌调强适形放疗同步化疗的临床研究

目的:观察分析调强适形放疗同步化疗与序贯放化疗治疗局限期小细胞肺癌的疗效、毒副反应及生活质量。方法:45例局限期小细胞肺癌患者被随机分成精确放疗加同步化疗组(同步组,23例)与化疗后再放疗组(序贯组,22例)。同步组在化疗的第1个周期开始放疗,序贯组化疗4～6个周期后再进行放疗。两组患者化疗方案均为EP方案,均接受精确放疗,1次/d,(1.8～2.0)Gy/次,5次/周,共28～31次,总剂量50.4～62.0Gy。照射野包括原发病灶和转移淋巴结。结果:同步组和序贯组原发病灶总有效率为95%和86%;12和18个月生存率分别为84%、69%和76%、34%。两组患者的毒副反应均以急性骨髓抑制、放射性食管炎及放射性肺炎为主。同步组Ⅰ～Ⅱ级放射性食管炎和放射性肺炎发生率分别为78%和86%,与序贯组的73%和81%近似。Ⅲ～Ⅳ级急性骨髓抑制发生率同步组和序贯组分别为8%、9%。生活质量QOL评分同步组和序贯组治疗前后差异无统计学意义。结论:调强适形放疗同步化疗局限期小细胞肺癌有较好的疗效,毒副反应为绝大多数患者耐受且生活质量无明显下降,但值得进一步研究。     

122例局限期小细胞肺癌的综合治疗

目的探讨局限期小细胞肺癌(SCLC)患者综合治疗的疗效。方法对手术联合化放综合治疗的122例局限期SCLC进行回顾性分析。结果122例患者的中位生存期为38个月,1、3、5年生存率分别为83.6%、50.0%和38.0%。Ⅰ期、Ⅱ期、Ⅲ期患者的中位生存期分别为未到达、52个月和22个月(P=0.001),5年生存率分别为57.1%、43.1%和28.3%。Ⅲ期患者术后化放疗和术后化疗的中位生存期分别为40个月和20个月,5年生存率分别为45.3%和26.1%(P=0.071)。结论局限期SCLC采用综合治疗显示较好的生存期,TNM分期为影响预后的因子。