同步化放疗治疗小细胞肺癌临床观察

 目的 观察同步化放疗治疗小细胞肺癌局限期的近期疗效。方法 采用EP方案化疗：顺铂（DDP）60 mg／m2，第1天静脉滴注；依托泊苷（VP16）100 mg／m2，第1 ~ 5天静脉滴注，每3周重复1次。第2周期开始同步放疗，共化疗4 ~ 6周期，放疗DT 5 600 cGy。结果 24例患者中CR18例（75.0 %），PR5例（20.8 %），PD1例（4.2 %），有效率95.8 %。毒副反应主要是骨髓抑制、胃肠道反应及放射性食管炎，但不严重。结论 EP方案化疗联合同步放疗治疗小细胞肺癌局限期近期效果好，患者也能耐受。     

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。     

局限期小细胞肺癌加速超分割放疗同步EP方案化疗的剂量递增I期研究

背景与目的加速超分割放疗（每日两次方案）联合EP方案同步化疗是美国国立综合癌症网络（Na-tional Comprehensive Cancer Network, NCCN）指南推荐的局限期小细胞肺癌的标准治疗方式,但国人对EP方案标准化疗剂量耐受性尚不明确。本研究旨在探讨局限期小细胞肺癌同步放化疗EP方案的最大耐受剂量。方法研究纳入病理证实的局限期小细胞肺癌患者,进行加速超分割放疗同步EP方案（依托泊苷+顺铂）化疗,放疗处方剂量为45 Gy/30 f,1.5 Gy/f,每日两次,同一日两次放疗间隔时间≥6 h,5天/周,共3周完成。化疗方案采用依托泊苷联合顺铂,每21天为1周期,具体依托泊苷100 mg/m2,d1-d3,顺铂采用剂量递增的方式（第1组为70 mg/m2 d1,第2组为75 mg/m2 d1）。主要观察指标为治疗期间的血液学毒性。次要观察指标为非血液学毒性和1年总生存期（overall sur-vival, OS）、无进展生存期（progression free survival, PFS）。根据不良事件常用术语评定标准（Common Terminology Criteria for Adverse Events, NCI-CTCAE）4.0,最大耐受剂量设定为6例患者中不超过1例患者出现剂量限制毒性（4级血液学毒性）的剂量,同时下一剂量组6例患者至少2例出现剂量限制性毒性。结果研究共纳入20例局限期小细胞肺癌患者,平均年龄49.50（30-68）岁。第1组入组6例患者,1例患者出现4度中性粒细胞减少;后第2组入组14例患者,1例患者出现4度中性粒细胞减少。其中,第1组有4例患者出现≥3度血液学毒性,1例患者出现3度以上放射性食管炎;第2组有10例患者出现≥3度血液学毒性,无患者出现3度以上放射性食管炎。中位随访9.0个月（3.2个月-36.2个月）,1年OS、PFS分别为91%、62%。结论局限期小细胞肺癌患者采用加速超分割放疗联合EP方案化疗将顺铂剂量递增至75 mg/m2是安全的,其有效性还需要进一步扩大样本量和随访更长的时间来证实。     

EP方案联合放疗治疗局限期小细胞肺癌的临床研究

目的研究EP方案联合三维适形及加速超分割放疗治疗48例局限期小细胞肺癌的疗效及不良反应。方法化疗采用EP方案，即VP-16＋DDP；放疗采用加速超分割即每周5天，每日两次，每次1．5Gy，总剂量54Gy／36F。同时采用三维适形技术。放疗在化疔的第1个疗程中第1、2周内开始。结果治疗过程中放射性肺炎发生率48％，其中Ⅲ级为4％；急性放射性食管炎发生率为：75％，Ⅲ～Ⅳ级为13％；骨髓抑制发生率为69％，Ⅲ～Ⅳ级为21％；1、2年生存率分别为88％、57％；1、2年局控率分别为89％、81％。结论EP方案联合三维适形及加速超分割放疗治疗局限期小细胞肺癌，可获得较高的局控率和生存率，而不良反应不大，可耐受，2年以上生存率有待进一步观察。     

化疗联合超分割放疗治疗小细胞肺癌临床疗效分析

目的 观察EP方案化疗与超分割放疗治疗局限期小细胞肺癌的疗效.方法 局限期小细胞肺癌58例随机分为化放组(30例)和单化组(28例).化疗采用EP方案化疗1～2周期后放射治疗1个疗程后再化疗4周期.1.4～1.5 Gy/次,2次/d,放疗总剂量为DT45～54 Gy.单化组为EP方案化疗4～6周期.结果 化放组与单化组的1、2年生存率分别为76.7%(23/30)、43.3%(13/30)和46.4%(13/28)、17.9%(5/28)(X2=5.62,4.39;P＜0.05),局部复发率分别为23.3%(7/30)和50.0%(14/28)(X2=4.46,P＜0.05).结论 化疗联合超分割放疗治疗小细胞肺癌能提高患者的近期生存率,毒副反应可耐受.     

局限期小细胞肺癌放化疗综合治疗

[目的]研究常规放疗及加速超分割放疗联合化疗治疗局限期小细胞肺癌的近期疗效及生存期.[方法]1998年2月至2000年5月间,局限期小细胞肺癌共72例随机分为2组,常规放疗组34例和加速超分割放疗组38例.两组接受EP方案化疗2个疗程后开始放疗.常规放疗组2Gy/次,每天1次,每周5次,总量(56～60)Gv/(5.6～6)w.加速超分割组放疗1.4Gy/次,每日2次,2次间隔≥6小时,每周5日,总量56Gy/4w.放射野包括原发灶,同侧肺门、纵隔淋巴引流区.2组病人在完成放疗后继续EP方案化疗4个疗程.[结果]全组总有效率77.8%,中位生存期18个月,常规放疗组和加速超分割放疗组两组近期疗效分别为70.6%和84.2%(P＞0.05),两组1、2、3年生存率分别为76.5%、23.3%、10.9%和80.0%、32.6%、11.7%(P＞0.05).[结论]加速超分割放疗组的近期疗效及长期生存率等同于常规分割放疗组.     

超分割放疗同步NP方案化疗局部晚期非小细胞肺癌的Ⅱ期临床研究

目的 评价超分割放疗同步NP方案化疗局限期非小细胞肺癌的疗效及毒副反应。方法 35例局部晚期非小细胞肺癌患者KPS评分≥70，中位年龄57岁。男30例，女5例；鳞癌22例，腺癌12例，大细胞癌1例；ⅢA期5例，ⅢB期30例。采用6～8MVX线超分割放疗（1．25cGy／次，2次／d，间隔6h以上，总剂量60Gy）和NP方案同步化疗（去甲长春花碱12．5ms／m^2，第1、8、15天给药，顺铂60～80mg／m^2第2天给药，共2～4个周期）。按WHO近期疗效及毒副标准评价治疗结果，用Kaplan-Meier法计算生存率。结果 全组中位随访32个月（5～40个月）。完全缓解1例，部分缓解19例，无变化13例，进展2例，有效率为57％。1、2、3年生存率分别为54％、29％和17％，中位生存期14．5个月（11～18个月）。放射性食管炎27例，放射性肺炎9例，恶心21例，白细胞减少23例，血小板减少9例，贫血5例。结论 超分割放疗同步NP方案化疗局限期非小细胞肺癌是一种可接受的治疗方案，近期疗效有所改善，但毒副反应也有增加。     

加速超分割放疗加化疗治疗局限期小细胞肺癌临床Ⅱ期试验结果分析

目的　研究加速超分割放疗加化疗治疗局限期小细胞肺癌的耐受性、副反应和疗效。方法　 5 7例中男 5 0例 ,女 7例 ,中位年龄 6 0岁。放疗为 1.4Gy/次 ,2次 /d ,间隔 >6h ,5d/周 ;总剂量为 5 6Gy,4 0分次 ,4周完成。照射剂量未经肺和空气等不均匀组织密度校正。化疗采用EP(依托泊甙5 0～ 70mg/m2 ,第 1～ 3天 ;顺铂 2 5～ 30mg/m2 ,第 1～ 3天 )方案 ,总共 6个周期。结果　 3例未完成既定治疗计划。完成化疗周期数中位值为 6个 ,中位间期为 4 .9周。急性放射性食管炎发生率为 72 % ,其中 3级为 7%。急性放射性肺炎发生率为 6 4 % ,其中 3级为 4 %。中位生存时间为 2 4个月 ,1、2、3年生存率分别为 81%、4 9%、2 1%。 13例发生局部复发 ,9例在照射野内 ,4例在野外。 1、2、3年局部控制率分别为 85 %、74 %、6 8%。 4 4例远地转移 ,其中 6 6 %的部位在脑。 1、2、3年远地转移率分别为31%、5 9%、79%。结论　加速超分割放疗加化疗能为局限期小细胞肺癌患者所耐受 ,局部控制和生存有所改善 ;化疗周期数的增加有可能补偿剂量强度和间期的不足     

胸部放疗分割与局限期小细胞肺癌失败模式的相关性研究

目的：分析比较加速超分割与常规分割胸部放疗后局限期小细胞肺癌失败模式的差异。方法：回顾性调查我院2006年10月至2012年12月期间住院治疗的114例局限期小细胞肺癌患者病历资料,记录患者的治疗前临床特征、放疗分割方案、复发转移部位和放疗毒副反应。结果：局部／区域或远地转移作为首先失败模式和总体失败模式在常规分割组和超分割组的差异均无统计学意义（P ＞0．05）。超分割组中 II －III 级放射性肺炎和放射性食管炎的发生率均较常规分割组明显增高,其差异有显著统计学意义（P ＝0．006和 P ＝0．001）。结论：小细胞肺癌加速超分割胸部放疗未改变局部／区域复发和远地转移模式,但明显增加治疗毒性。加速超分割胸部放疗是否优于常规分割值得进一步研究。     

局限期小细胞肺癌三维适形超分割放疗及同步化疗的临床研究

目的：观察三维适形超分割放疗及同步化疗治疗局限期小细胞肺癌（LSCLC）的疗效及不良反应。方法：50例LSCLC患者随机分为同步化疗及三维适形超分割放疗DT54Gy组（治疗组）和三维适形超分割放疗DT45Gy组（对照组）。化疗采用EP方案化疗：足叶乙甙（VP-16）100mg/m2,第1-5天;顺铂（DDP）40mg/m2,第1-3天化疗一周期,再同步放化疗,然后继续化疗,共4-6周期。放疗采用三维适形超分割放疗,1.5Gy次/,2次/d,间隔≥6h,5d周/。治疗组肿瘤量DT54Gy,对照组DT45Gy。结果：治疗组与对照组的近期有效率（CR＋PR）分别为92.0%和84.0%。1、2、3年生存率分别为80.0%、40.0%、24.0%和76.0%、32.0%、16.0%（P〉0.05）。中位生存期分别为24.6和22.3个月。1＋2级放射性食管炎、肺炎、骨髓抑制发生率相似。结论：3DCRT超分割放疗及同步化疗在总剂量为54Gy组可获得满意的近、远期疗效,不良反应稍高但可以耐受。     

改良同步后程加速超分割放化疗治疗局部晚期食管鳞癌的临床观察

 目的 探讨改良同步后程加速超分割放疗联合含铂类方案的化疗治疗局部晚期食管鳞癌的疗效和不良反应.方法 68例经病理证实的食管鳞癌患者入组。先行常规分割放疗40 Gy/20次后改行加速超分割放疗1.4 Gy/次,2次/d,间隔≥6 h,照射14次,总剂量59.6 Gy。同步给予以顺铂为基础的联合化疗2个周期,同步放化疗结束后再行2周期化疗。观察患者近期疗效,1、3、5年生存率及治疗相关不良反应。结果 所有患者完成放疗计划,总有效率为91.6%（62/68）。1、3、5年生存率分别为75.5%、46.5%、22.7%。≥3级放射性食管炎的发生率为26.4%;无3级及以上的放射性肺炎发生;放射性皮肤损伤多为0~1级;3级白细胞减少和血小板减少的发生率分别为29.4%和7.4%,4级白细胞减少和血小板减少的发生率均为2.9%。无食管狭窄及严重的肺纤维化发生,有2例（2.9%）出现食管纵隔瘘。结论 改良同步后程加速超分割放化疗治疗局部晚期食管鳞癌疗效满意,治疗相关不良反应发生率降低。     

Study of paclitaxel, etoposide, and cisplatin chemotherapy combined with twice-daily thoracic radiotherapy for patients with limited-stage small-cell lung cancer: a Radiation Therapy Oncology Group 9609 phase II study.

PURPOSE: To determine the response rate, progression-free survival and overall survival, and toxicity of paclitaxel, etoposide, and cisplatin combined with accelerated hyperfractionated thoracic radiotherapy in patients with limited-disease (LD) small-cell lung cancer (SCLC). PATIENTS AND METHODS: LD-SCLC patients with measurable disease, Karnofsky performance score of > or = 70, and adequate organ function who were previously untreated were eligible for the study. Treatment was as follows. In cycle 1 of chemotherapy, concurrent thoracic radiation therapy was administered. In cycles 2 to 4, chemotherapy was administered alone. In cycle 1, chemotherapy consisted of paclitaxel 135 mg/m(2) intravenous over 3 hours on day 1, etoposide 60 mg/m(2) intravenous on day 1 and 80 mg/m(2) orally on days 2 and 3, and cisplatin 60 mg/m(2) intravenous on day 1. In cycles 2 to 4, the paclitaxel dose was increased to 175 mg/m(2), with the etoposide and cisplatin doses remaining the same as in cycle 1. The thoracic radiation therapy consisted of 1.5 Gy in 30 fractions (total dose, 45 Gy) administered 5 days a week for 3 weeks. RESULTS: Fifty-five patients were enrolled onto the study, and 53 were assessable. The major toxicities included grade 3 and 4 acute neutropenia (32% and 43%, respectively) and grade 3 and 4 esophagitis (32% and 4%, respectively). Two patients died as a result of therapy (one died of acute respiratory distress syndrome, and one died of sepsis). There was one late fatal pulmonary toxicity. The median survival time was 24.7 months. The 2-year survival rate was 54.7%. The median progression-free survival time was 13 months, with a 2-year progression-free survival rate of 26.4%. CONCLUSION: Although this therapeutic regimen is effective in the treatment of patients with LD-SCLC, it is unlikely that the three-drug combination with thoracic radiation therapy will improve the survival times compared with the etoposide plus cisplatin chemotherapy regimen with thoracic radiation therapy in LD-SCLC patients.     

Phase II trial of irinotecan and cisplatin with early concurrent radiotherapy in limited-disease small-cell lung cancer

BACKGROUND: A Phase II trial of irinotecan and cisplatin (IP) with early concurrent radiotherapy was performed in limited-disease small-cell lung cancer (LD-SCLC) to evaluate the efficacy and toxicity. METHODS: For untreated LD-SCLC patients, irinotecan (60 mg/m2, Days 1, 8, and 15) and cisplatin (40 mg/m2, Days 1 and 8) were repeated every 4 weeks for a maximum of 6 cycles. Thoracic radiotherapy of 1.8 Gy/day was begun on Day 1 of the second chemotherapy cycle, up to a total of 45 to 54 Gy. Prophylactic cranial irradiation (30 Gy in 10 fractions) was performed on patients with a complete response (CR). RESULTS: Thirty-three LD-SCLC patients were enrolled. The median age was 60 years and 31 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Twelve (36.4%) patients had N3 disease. The response rate was 87.9%, with a CR rate of 45.5%. At a median follow-up period of 27 months the median progression-free survival (PFS) and overall survival (OS) were 14.4 and 26.1 months, respectively, with 2-year PFS and OS rates of 26.8% and 54.9%. The dominating toxicity was neutropenia, with grade 3-5 of 81.8%. The most common grade 3-5 nonhematologic toxicities were diarrhea (21.2%), anorexia (21.2%), and fatigue (21.2%). Grade 3-5 radiation esophagitis and pneumonitis occurred in 18.2% and 9.1% of patients, respectively. There were 2 treatment-related deaths from sepsis and radiation pneumonitis. CONCLUSIONS: IP with early concurrent radiotherapy was effective and tolerable in untreated LD-SCLC.     

局限期小细胞肺癌三维适形超分割放疗及同步化疗的临床研究

目的:观察三维适形超分割放疗及同步化疗治疗局限期小细胞肺癌(LSCLC)的疗效及不良反应。方法:50例LSCLC患者随机分为同步化疗及三维适形超分割放疗DT54Gy组(治疗组)和三维适形超分割放疗DT45Gy组(对照组)。化疗采用EP方案化疗:足叶乙甙(VP-16)100mg/m2,第1-5天;顺铂(DDP)40mg/m2,第1-3天化疗一周期,再同步放化疗,然后继续化疗,共4-6周期。放疗采用三维适形超分割放疗,1.5Gy次/,2次/d,间隔≥6h,5d周/。治疗组肿瘤量DT54Gy,对照组DT45Gy。结果:治疗组与对照组的近期有效率(CR+PR)分别为92.0%和84.0%。1、2、3年生存率分别为80.0%、40.0%、24.0%和76.0%、32.0%、16.0%(P>0.05)。中位生存期分别为24.6和22.3个月。1+2级放射性食管炎、肺炎、骨髓抑制发生率相似。结论:3DCRT超分割放疗及同步化疗在总剂量为54Gy组可获得满意的近、远期疗效,不良反应稍高但可以耐受。     

Neoadjuvant chemotherapy followed by late-course accelerated hyperfractionated radiation therapy for locally advanced non-small-cell lung cancer: long-term results of a phase I/II clinical trial

Toxicity, response, and long-term results of a definitive chemotherapy/radiation therapy (RT) protocol in patients with unresectable stage III non-small-cell lung cancer (NSCLC) were evaluated. Two cycles of cisplatin-based chemotherapy were delivered before RT, and another 2 cycles were added for patients who responded to the first 2 cycles of chemotherapy. The first course of radiation covered the primary lesion and elective nodal regions, given in 2 Gy per fraction, 5 days a week for a dose of 40 Gy. Late-course hyperfractionated accelerated RT was delivered to the gross tumor twice a day for an additional 27 Gy within 2 weeks, using 1.5 Gy per fraction. Fifty-three patients with unresectable stage IIIA (N2) and IIIB NSCLC were eligible for analysis. Twelve patients developed grade 3 neutropenia, and 3 patients developed grade 4 neutropenia. Grade 2 or 3 esophagitis was observed in 14 and 2 patients, respectively, and grade 2 or 3 pneumonitis was observed in 9 and 1 patient, respectively. Six patients developed grade 2 and 1 patient developed grade 3 late lung toxicity. The median survival time was 15.5 months. Twenty-six of 53 patients (49%) have died of locoregional progression inside the thorax. The distant metastasis rate was 59.5% (22 of 37 patients) for those who did not respond to chemotherapy and 18.8% (3 of 16 patients) for those who responded to chemotherapy (P = 0.006). Late-course hyperfractionated accelerated RT combined with induction chemotherapy was well tolerated and yielded long-term results that compare favorably with those of studies using 2 cycles of induction chemotherapy and conventional fractionated RT. However, local control was still discouraging.     

每周低剂量长春瑞滨、顺铂同步后程适形放射治疗局部晚期非小细胞肺癌的Ⅱ期临床研究

目的：探讨每周低剂量长春瑞滨（NVB）、顺铂（PDD）同步后程适形放射治疗局部晚期非小细胞肺癌（NSCLC）的可行性及观察其近期疗效和毒副反应。方法：首程经病理确诊的21例局部晚期NSCLC（根据UICC1997分期标准ⅢA期8例，ⅢB期13例）患者，符合KPS≥70分，年龄≤70岁，近3月体重下降≤5％，器官功能正常。全部患者均行每周1次低剂量NP方案（NVB12．5mg／m^2，PDD20mg／m^2）化疗，共7～9次。每周化疗结束后立即行放疗，先期同步常规放疗38Gy／19F，继之适形放疗推量至60～64Gy／6～7周；锁骨上区照射者推量至60Gy。结果：21例全部完成治疗计划，可行疗效评估，肺原发灶完全缓解（CR）14、3％（3／21），部分缓解（PR）61、9％（13／21），无变化和进展（NC＋PD）22．8％（5／21），总有效率（CR＋PR）为76．2％（16／21）。1年和2年生存率分别为76．2％、40、8％。3～4级白细胞减少发生率为33．3％（7／21）；3级血小板减少发生率为4．8％（1／21）；3级放射性食管炎9．6％（2／21）；无3级及以上放射性肺炎的发生。加用糖皮质激素后症状及影像学表现均好转，无治疗相关性死亡。结论：同期化疗加适形放疗治疗局部晚期NSCLC能为绝大多数患者耐受，有较好的近期疗效，值得临床进一步研究。     

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.     

194 hepatocellular cancers treated by radiation and chemotherapy combinations: toxicity and response: a Radiation Therapy Oncology Group Study

Hepatocellular carcinoma is known to have a doubling time of approximately 41 days. This rapid cell division suggested that hyperfractionated radiation and chemotherapy might add an advantage in gaining remission of this malignancy. One hundred and thirty-five patients (70% with metastasis and/or previous treatment) were prospectively treated with single daily fractions to the liver (3.0 Gy external beam radiation, total dose 21.0 Gy), and chemotherapy for hepatocellular carcinoma. The low dose chemotherapy used in conjunction with the radiation was 2 hr before treatment on days 1, 3, 5, and 7 and consisted of Adriamycin, 15 mg IV and 5-FU, 500 mg IV. These patients were compared to a second group of 59 patients (80% with metastases and/or previous treatment) treated using the same chemotherapy regimen but using hyperfractionated whole liver external beam irradiation (1.2 Gy twice daily, 4 hr between treatments, 5 days per week to 24.0 Gy, 10 MV photons). Response was determined by CT scan tumor volumetric analysis. The response rate for the single daily fraction patient group was 22% and for the new hyperfractionated group, 18% (p = 0.68). Toxicity was evaluated by RTOG criteria. The grade 4 hematologic toxicity noted in the daily fraction patient group was 6%. Among 59 patients treated with the hyperfractionated liver irradiation, 2% experienced grade 4 hematologic toxicity. Esophagitis occurred in 1% of patients in the standard fractionation group and 19% in the hyperfractionated group (p = 0.0001). Grade 1-4 thrombocytopenia occurred in 49% of patients in the conventional group and 68% in the hyperfractionated group (p = 0.03). Normal liver volume changes with treatment were measured with CT scan tumor volumetric analysis. The hyperfractionated group experienced a median of 11 cc increase in liver volume and the conventional group a 46 cc decrease, but the difference was not significant. Hyperfractionated radiation did not demonstrate a significant benefit over standard daily radiation, but acute toxicity appeared to be higher.     

Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant chemotherapy in esophageal cancer: phase II study

Purpose

Concomitant use of chemotherapy and a radiation dose schedule that is more efficient compared to conventional radiotherapy may provide better outcomes in patients with esophageal cancer. This study aimed to assess the efficacy and tolerability of neoadjuvant cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy regimen in this group of patients.

Methods and materials

A total of 20 newly diagnosed treatment-naïve esophageal cancer patients were included in the study. Neoadjuvant cisplatin and 5-FU were given with 28-day intervals in a total of three courses. Along with the third course of chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 day.

Results

All patients could receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade III acute toxicity (50%). None of the acute toxicity reactions required treatment discontinuation. Grade III or higher subacute/late toxicity occurred in 10 patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable disease, with only 1 patient (5%) having progressive disease. Seven patients underwent surgery. Overall, 8 patients (40%) had local control. The 5 years overall survival rate was 38.1%.

Conclusions

Neoadjuvant hyperfractionated accelerated radiotherapy plus chemotherapy may help to target local disease control and increase survival in patients with esophageal cancer. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum tumor control rates with minimal toxicity.Key Words: Neoadjuvant radiochemotherapy, esophageal cancer, hyperfractionated-accelerated radiotherapy, toxicity, safety