Dosimetric and Clinical Predictors of Acute Esophagitis in Lung Cancer Patients in Turkey Treated with Radiotherapy

Background: The purpose of this study was to determine the clinical and dosimetric factors associated withacute esophagitis (AE) in lung cancer patients treated with conformal radiotherapy (RT) in Turkey. Materialsand Methods: In this retrospective review 104 lung cancer patients were examined. Esophagitis grades wereverified weekly during treatment, and at 1 week, and 1 and 2 months afterwards. The clinical parametersincluded patient age, gender, tumor pathology, number of chemotherapy treatments before RT, concurrentchemotherapy, radiation dose, tumor response to RT, tumor localization, interruption of RT, weight loss, tumorand nodal stage and tumor volume. The following dosimetric parameters were analyzed for correlation of AE:The maximum (Dmax) and mean (Dmean) doses delivered to the esophagus, the percentage of esophagus volumereceiving ≥10 Gy (V10), ≥20 Gy (V20), ≥30 Gy (V30), ≥35 Gy (V35), ≥40 Gy (V40), ≥45 Gy (V45), ≥50 Gy (V50) and ≥60Gy (V60). Results: Fifty-five patients (52.9%) developed AE. Maximum grades of AE were recorded: Grade 1 in51 patients (49%), and Grade 2 in 4 patients (3.8%). Clinical factors had no statistically significant influence onthe incidence of AE. In terms of dosimetric findings, correlation analyses demonstrated a significant associationbetween AE and Dmax (>5117 cGy), Dmean (>1487 cGy) and V10-60 (percentage of volume receiving >10 to 60 Gy).The most significant relationship between RT and esophagitis were in Dmax (>5117 cGy) (p=0.002) and percentageof esophageal volume receiving >30 Gy (V30>31%) (p=0.008) in the logistic regression analysis. Conclusions: Themaximum dose esophagus greater than 5117 cGy and approximately one third (31%) of the esophageal volumereceiving >30 Gy was the most statistically significant predictive factor associated with esophagitis due to RT.     

Predictors of acute esophagitis in patients with non-small-cell lung carcinoma treated with concurrent chemotherapy and hyperfractionated radiotherapy followed by surgery

PURPOSE: To evaluate possible clinical and dosimetric predictors of acute esophagitis in patients with locally advanced non-small-cell lung carcinoma treated in a prospective Phase I-II trimodality protocol. METHODS AND MATERIALS: The data from 36 patients with Stage III non-small-cell lung carcinoma treated in a Phase I-II high-dose concurrent chemoradiotherapy protocol were analyzed for possible predictors of acute esophagitis. The median age was 58 years (range, 38-77 years). Patients included in this study had either Stage IIIA (n = 24) or IIIB (n = 12) disease. All patients were treated with induction concurrent carboplatin (area under the plasma concentration-time curve 1), vinorelbine (5-15 mg/m(2)), and hyperfractionated radiotherapy (69.6 Gy) followed by consolidation chemotherapy (carboplatin area under the plasma concentration-time curve 6, vinorelbine 25 mg/m(2), docetaxel 75 mg/m(2)) or surgery (n = 19) plus consolidation chemotherapy. Acute toxicities were graded using the Radiation Therapy Oncology Group criteria. The following clinical and dosimetric parameters were analyzed: age, gender, race, T stage, N stage, pretreatment body mass index, percentage of weight lost during therapy, pretherapy serum albumin, tumor location, length of esophagus in treatment field, percentage of esophagus volume treated to >40, >45, >50, >55, >60, and >65 Gy. These parameters were coded and analyzed against Grade 2 and worse esophagitis using univariate and multivariate regression analyses. RESULTS: Of the 36 patients, Grade 1, 2, and 3 acute esophagitis was observed in 16 (44%), 12 (33%), and 2 (5.5%) patients, respectively. Grade 4 or 5 toxicity was not observed in this patient cohort. Only the pretreatment body mass index (rho = -0.431, p = 0.004) and percentage of esophagus volume treated to >50 Gy (rho = 0.297, p = 0.040) demonstrated a statistically significant correlation with the incidence of Grade 2 or worse esophagitis on univariate analysis. These parameters retained their statistical significance on multivariate regression analysis (p = 0.029 and 0.049, respectively). CONCLUSION: In patients undergoing concurrent high-dose chemotherapy and hyperfractionated radiotherapy, a low pretherapy body mass index and percentage of esophagus volume treated to >50 Gy were significantly associated with acute Grade 2 or worse esophagitis.     

Dosimetric comparison between IMRT and VMAT in patients undergoing internal mammary lymph node radiotherapy after modified radical mastectomy

Objective To investigate the dosimetric differences in volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in patients receiving adjuvant radiotherapy and internal lymph node irradiation after left-sided modified radical mastectomy. Methods VMAT and IMRT radiotherapy plans were established for 20 patients undergoing left-sided modified radical mastectomy. The dosimetric parameters of the target area and organs at risk were calculated by the dose volume histogram. The categorical variables were tested by χ² or Fisher′s exact probability test. The continuous variables with normal distribution were analyzed by paired-t test or rank-sum test. Results Among the two radiotherapy techniques, the homogeneity index of IMRT was significantly higher than that of VMAT (P<0.05). The time of VMAT treatment was significantly shorter than that of IMRT (P<0.01). VMAT was superior to IMRT in V20Gy and V30Gy of the affected lung (both P<0.05). VMAT was superior to IMRT in the left anterior descending coronary artery Dmean, Dmax, and heart V30Gy, V40Gy, Dmean and Dmax(all P<0.01). The esophageal Dmean in the VMAT group was superior to that in the IMRT group (P<0.05). The V5Gy and V10Gy of the contralateral lung and the Dmax of the esophagus in the IMRT group were significantly better compared with those in the VMAT group (all P<0.05). Conclusions VMAT can significantly reduce the dose of the heart, contralateral lung, spinal cord, esophagus and other vital organs, and shorten the treatment time. For patients who need adjuvant radiotherapy and internal mammary lymph node irradiation after left-sided modified radical mastectomy, VMAT technology can better protect normal tissues than IMRT.     

乳腺癌改良根治术后内乳淋巴结放疗患者VMAT与IMRT计划剂量学比较

目的 探讨容积调强弧形治疗(VMAT)和固定野动态调强放疗(IMRT)在左侧乳腺癌改良根治术后需辅助放疗并内乳淋巴结照射患者的剂量学差异。方法 对20例左侧乳腺癌患者制定VMAT和IMRT两种放疗计划。通过剂量体积直方图计算靶区和危及器官剂量学参数。对分类变量行χ²或Fisher′s精确概率法检验,连续变量根据正态性采用配对t检验或秩和检验。结果 IMRT靶区均匀性指数比VMAT高(P<0.05)。VMAT治疗时间较IMRT更短(P<0.01)。VMAT患侧肺V20Gy、V30Gy优于IMRT (P<0.05)。VMAT在冠脉左前降支Dmean、Dmax和心脏V30Gy、V40Gy、Dmean、Dmax优于IMRT (P<0.01)。食管DmeanVMAT优于IMRT (P<0.05),但健侧肺V5Gy、V10Gy和食管DmaxIMRT优于VMAT (P<0.05)。结论 VMAT可以显著减少心脏、健侧肺、脊髓、食管照射剂量,缩短治疗时间。对于左侧乳腺癌根治术后需辅助放疗并照射内乳淋巴结的患者,VMAT技术比IMRT技术可以更好保护正常组织。     

Combination of longitudinal and circumferential three-dimensional esophageal dose distribution predicts acute esophagitis in hypofractionated reirradiation of patients with non-small-cell lung cancer treated in stereotactic body frame

PURPOSE: To evaluate dosimetric predictors of acute esophagitis (AE) and clinical outcome of patients with non-small-cell lung cancer (NSCLC) receiving reirradiation. METHODS AND MATERIALS: Seventeen patients with NSCLC received reirradiation to the lung tumors/mediastinum, while immobilized in stereotactic body frame (SBF). CT simulation and hypofractionated three-dimensional radiotherapy were used. Two axial segments of esophagus contours merged together were defined as esophagus disc (ED). For each ED, the percentage (%) of the volume of esophageal circumference treated to % of prescribed dose (PD) was assessed. Number of EDs with 50% or any % of volume (V) of esophageal circumference receiving more than or equal to (>/=) 50%, 80%, and 100% of PD (50% V >/=50% PD; 50% V >/=80% PD; any % V >/=100% PD) were calculated. These dosimetric variables and the length of the esophagus within the radiation therapy (RT) port were correlated with AE using exact Wilcoxon test. RESULTS: A median RT dose was 32 Gy with a median fraction size of 4 Gy. Eleven of 13 patients presenting with pain and/or shortness of breath had complete or partial resolution of symptoms. Median survival time from the start of reirradiation in SBF until death was 5.5 months. AE was observed in 7 patients and resolved within 3 months of RT completion. No Grade 3 or higher events were noticed. The length of the esophagus within RT port did not predict for AE (p = 0.71). However, an increased number of EDs predicted for AE for the following dosimetric variables: 50% V >/=50% PD (p = 0.023), 50% V >/=80% PD (p = 0.047), and any % V >/=100% PD (p = 0.004). Patients with at least 2 EDs receiving >/=100% PD to any % V of circumference had AE compared to those with zero EDs. CONCLUSIONS: Reirradiation using hypofractionated three-dimensional radiotherapy and SBF immobilization is an effective strategy for palliation of symptoms in selected patients with recurrent NSCLC. The length of the esophagus in the RT field does not predict for AE. However, an increasing number of EDs displaying the combination of longitudinal and circumferential three-dimensional dose distribution along the esophagus is a valuable predictor for AE.     

Localized volume effects for late rectal and anal toxicity after radiotherapy for prostate cancer

PURPOSE: To identify dosimetric parameters derived from anorectal, rectal, and anal wall dose distributions that correlate with different late gastrointestinal (GI) complications after three-dimensional conformal radiotherapy for prostate cancer. METHODS AND MATERIALS: In this analysis, 641 patients from a randomized trial (68 Gy vs. 78 Gy) were included. Toxicity was scored with adapted Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer (RTOG/EORTC) criteria and five specific complications. The variables derived from dose-volume histogram of anorectal, rectal, and anal wall were as follows: % receiving > or =5-70 Gy (V5-V70), maximum dose (Dmax), and mean dose (D(mean)). The anus was defined as the most caudal 3 cm of the anorectum. Statistics were done with multivariate Cox regression models. Median follow-up was 44 months. RESULTS: Anal dosimetric variables were associated with RTOG/EORTC Grade > or =2 (V5-V40, D(mean)) and incontinence (V5-V70, D(mean)). Bleeding correlated most strongly with anorectal V55-V65, and stool frequency with anorectal V40 and D(mean). Use of steroids was weakly related to anal variables. No volume effect was seen for RTOG/EORTC Grade > or =3 and pain/cramps/tenesmus. CONCLUSION: Different volume effects were found for various late GI complications. Therefore, to evaluate the risk of late GI toxicity, not only intermediate and high doses to the anorectal wall volume should be taken into account, but also the dose to the anal wall.     

High-dose conformal radiotherapy for treatment of stage IIIA/IIIB non-small-cell lung cancer: technical issues and results of a phase I/II trial

PURPOSE: We completed a Phase I/II clinical trial (Lineberger Comprehensive Cancer Center 9603), in which we treated 62 Stage IIIA/IIIB inoperable non-small-cell lung cancer (NSCLC) patients with two cycles of induction carboplatin/paclitaxel chemotherapy, followed by concurrent weekly carboplatin/paclitaxel with radiation doses escalated from 60 to 74 Gy. The median survival of 24 months, 3-year survival rate of 38%, and the high dose of radiation used justified a critical analysis of the technical and clinical components of this trial. METHODS AND MATERIALS: Between 1996 and 1999, 62 sequential patients with inoperable Stage IIIA/IIIB NSCLC were enrolled and treated with two cycles of induction carboplatin (area under the concentration curve = 6 using the Calvert equation) and paclitaxel (225 mg/m(2)), followed by an escalating radiation dose of 60-74 Gy with concurrent carboplatin weekly (area under the concentration curve = 2) and paclitaxel weekly (45 mg/m(2)). The goals of the trial were to determine whether 74 Gy of radiation could be safely delivered under these circumstances and whether patients could potentially benefit in terms of survival. The radiation treatment plans for all 62 patients were reviewed to determine the prechemotherapy and postchemotherapy tumor volume, as well as the dose-volume histograms of the normal lung and esophagus. RESULTS: Of the 62 patients who entered the trial, 48 completed the entire course of treatment. At last follow-up, 20 patients were alive (crude survival rate 32%). With a median follow-up of 43 months, the median survival was 24 months. The survival rate was 50% at 2 years and 38% at 3 years. Cox regression analysis showed that survival was best predicted by whether the patient had received radiotherapy (finished the trial), performance status, disease stage, and log postchemotherapy tumor volume. The 3-year survival rate for the 48 patients finishing the trial was 45%. Eight patients (13%) suffered locoregional relapse as the only site of failure. Only 1 patient had Grade 2 radiation pneumonitis. Five patients (8%) had Radiation Therapy Oncology Group Grade 3 or 4 esophagitis; 40 (65%) had a Grade 1 or 2 esophagitis. Esophageal toxicity could be predicted by the length of esophagus receiving 40 or 60 Gy. CONCLUSION: Radiation doses of 74 Gy, when given under the guidelines of the Lineberger Comprehensive Cancer Center 9603, appear to be safe and may possibly contribute to increased survival in patients with inoperable Stage IIIA/IIIB NSCLC.     

Dose-volumetric parameters of acute esophageal toxicity in patients with lung cancer treated with three-dimensional conformal radiotherapy

PURPOSE: To retrospectively evaluate which dose-volumetric parameters are associated with the risk of > or = Grade 3 acute esophageal toxicity (AET) in lung cancer patients treated with three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: One hundred twenty-four lung cancer patients treated curatively with 3D-CRT were retrospectively analyzed. All patients received conventionally fractionated radiotherapy (RT) with median dose of 60 Gy (range, 54-66 Gy) delivered in 30 fractions (range, 27-33 fractions). Thirty-one patients underwent curative surgery before RT. Ninety-two patients received chemotherapy (induction, 18; concurrent +/- induction, 74). Acute esophageal toxicity was scored by Radiation Therapy Oncology Group criteria. The parameters analyzed included sex; age; Karnofsky performance score; weight loss; surgery; concurrent chemotherapy; the percentages of organ volume receiving > or =20 Gy (V20), > or =30 Gy (V30), > or =40 Gy (V40), > or =50 Gy (V50), > or =55 Gy (V55), > or = 58 Gy (V58), > or =60 Gy (V60), and > or =63 Gy (V63); the percent and absolute length of the esophagus irradiated; the maximum and mean dose to the esophagus; and normal tissue complication probability. RESULTS: Of the 124 patients, 15 patients (12.1%) had Grade 3 AET, and 1 (0.8%) patient had Grade 4 AET. There was no fatal Grade 5 AET. In univariate and multivariate logistic regression analyses, concurrent chemotherapy and V60 were significantly associated with the development of severe (> or = Grade 3) AET (p < 0.05). Severe AET was observed in 15 of 74 patients (20.3%) who received concurrent chemotherapy, and in 1 of 50 patients (2.0%) who did not (p = 0.002). Severe AET was observed in 5 of 87 patients (5.7%) with V60 < or = 30% and in 11 of 37 patients (29.7%) with V60 > 30% (p < 0.001). Among 50 patients who did not receive concurrent chemotherapy, severe AET was observed in 0 of 43 patients (0%) with V60 < or = 30% and in 1 of 7 patients (14.2%) with V60 > 30% (p = 0.140). Among 74 patients who received concurrent chemotherapy, severe AET was observed in 5 of 44 patients (11.4%) with V60 < or = 30% and in 10 of 30 patients (33.3%) with V60 > 30% (p = 0.037). CONCLUSIONS: Concurrent chemotherapy and V60 were associated with the development of severe AET > or = Grade 3. For patients being treated with concurrent chemotherapy, V60 is considered to be a useful parameter predicting the risk of severe AET after conventionally fractionated 3D-CRT for lung cancer.     

适形放疗晚期肺癌放射性食管炎相关因素分析

目的分析Ⅲ～Ⅳ期非小细胞肺癌三维适形放射治疗中急性放射性食管损伤（AE）的发生率及其相关因素。方法选择2006年3月至2008年11月行三维适形放疗的晚期肺癌患者195例,男165例,女30例。其中有79例患者行同步放化疗,中位等效生物剂量为72.0Gy,观察AE的发生率,采用单因素和多因素变量分析方法,对选择的临床和剂量学因素进行与2级以上AE的相关性分析。结果 2级AE38例（19.5%）,3级AE25例（12.8%）。单变量分析显示,临床因素中疗前体重下降≥5%、同时化放疗、淋巴结分期、临床类型和后程超分割放疗与2级以上AE有相关性,剂量学指标中食管受照最大剂量、平均剂量、V20、V25、V30、V35、V40、V45、V50、V55、V60的差异均有统计学意义（P〈0.001）,同时放化疗和V55在BinaryLogistic多因素分析中的差异有统计学意义。结论期非小细胞肺癌三维适形放射治疗中,同时化放疗和V55是预测AE最有价值的指标。     

食管癌螺旋断层放疗及三维适形调强放疗计划剂量学研究

目的 近年来放射治疗设备不断更新,放疗技术持续发展,肿瘤放疗方式有了更多的选择.本研究通过评估食管癌的螺旋断层放疗(tomotherapy, TOMO)及三维适形调强放疗(intensity modulation radiation therapy, IMRT)的剂量学特性,为临床上食管癌放疗方式的选择提供依据.方法 选取2014-07-13-2015-02-25浙江省肿瘤医院胸部肿瘤放疗科10例食管癌患者,勾画靶区及正常器官后,分别传输至Raystation及TOMO计划系统,给予肿瘤原发灶(PGTV)61.6 Gy/28次,计划靶区(PTV)56.0 Gy/28次,根据RTOG 1106标准限制危及器官(organs at risk, OAR)剂量.分别对靶区的剂量体积直方图(dose volume histogram, DVH)、均匀性指数(homogeneity index, HI)、适形性指数(conformal index CI)和OAR(肺、心脏、脊髓)受照最大剂量及平均剂量进行评估.结果 两种计划都能满足处方剂量要求和危及器官受量限制.TOMO计划中PGTV的中位均匀性指数(HI)为0.057 5,优于IMRT计划的0.073 5, P=0.047.TOMO计划中PTV的中位适形性指数(CI)为0.785,优于IMRT计划的0.682 5, P=0.009.TOMO计划中PGTV的中位最大剂量Dmax为64.9 Gy,明显低于IMRT计划的66.5 Gy, P=0.005;TOMO计划中PTV的中位最大剂量Dmax为64.1 Gy,明显低于IMRT计划的64.9 Gy, P=0.028. TOMO计划的中位总的肺剂量为10.8 Gy,低于IMRT计划的11.9 Gy, P=0.005.TOMO计划的中位总的心脏剂量为22.6 Gy,明显低于IMRT计划的24.3 Gy, P=0.028. TOMO计划的中位脊髓最大剂量为40.2 Gy,明显低于IMRT计划的41.7 Gy, P=0.007.结论 食管癌放疗中TOMO放疗计划对比IMRT放疗计划,具有更好的靶区覆盖适形性及剂量分布均匀性,同时明显减少双肺、心脏及脊髓的受照剂量.     

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: a preliminary report of a phase I dose escalation trial from the Carolina Conformal Therapy Consortium

The maximum tolerated dose of conformal radiation therapy delivered at 1.6 Gy bid is being assessed in patients with unresectable stage IIB-IIIB non-small cell lung cancer who have been treated with induction regimens consisting of carboplatin plus paclitaxel or carboplatin plus vinorelbine. Data from the early stages of this parallel phase I study show that the two induction regimens are similar in toxicity and that both induce partial responses in 45% of patients. Both regimens can be followed by conformal radiotherapy using an accelerated hyperfractionated schedule to a dose of at least 80 Gy without experiencing unacceptable toxicity. Key morbidity observed thus far has involved the esophagus. Further cohorts of patients will receive higher doses of conformal radiotherapy (in 6.4 Gy increments) until the maximum tolerated dose is reached.     

Comparison of cervical esophagus dose-volumes for three radiotherapy techniques for head and neck cancer

PURPOSE: This study compares the radiation dose-volume of the cervical esophagus during head and neck radiotherapy using three different techniques. METHODS: Treatment plans of 58 patients from 3/04 to 1/06 treated with bilateral head and neck radiotherapy were analyzed retrospectively. A comparison of the cervical esophagus dose with three-field 3D conformal RT (3DRT, n=34), whole-field IMRT (WF-IMRT, n=12), and half-beam IMRT (HB-IMRT, n=12) was performed. The volumes of esophagus receiving > or =50Gy (V50), > or =54Gy (V54) and > or = 60Gy (V60) and lengths receiving circumferential dose > or = 50Gy (L50) and > or = 54Gy (L54) were evaluated. RESULTS: Maximum dose, V54 and L54 were greater for the first 2cm and entire cervical esophagus with WF-IMRT than HB-IMRT or 3DRT. In patients requiring a high match, WF-IMRT was associated with a greater maximum dose, V54 and L54 than HB-IMRT and 3DRT (p<0.05). In the low match group, WF-IMRT was associated with a greater V54 and L54 (p<0.05). Low neck disease, low primary site, and definitive radiotherapy were associated with increased irradiation of the esophagus. CONCLUSION: Treatment of the lower neck with IMRT is associated with increased irradiation to the cervical esophagus, and dose constraints should be included to reduce toxicity.     

腹、盆腔肿瘤放疗后急性放射性肠道损伤的剂量学因素分析

目的：探讨腹、盆腔肿瘤患者接受调强放射治疗（IMRT）后出现≥2级急性放射性肠道损伤与患者临床特征参数及小肠（small bowel,SB）剂量体积参数的相关性。方法：回顾分析63例接受 IMRT 的腹、盆腔肿瘤患者资料,应用 CTCAE 3．0评分标准对患者急性放射性肠道损伤进行评价分级,分析患者临床特征参数及小肠受照的剂量体积参数（Dmax、Dmin、Dmean、D2cc、D5cc及小肠接受的 V5～60的绝对体积）与急性放射性肠道损伤发生的相关性。结果：所有患者 IMRT 后在急性观察期内,发生≥2级急性放射性肠道损伤13例,发生率为20．63％（13／63）。单因素分析发现小肠 V20～60、D2cc、D5cc 与≥2级急性放射性肠道损伤的发生相关。多因素分析发现小肠的 V20、V55是≥2级急性放射性肠道损伤发生的独立影响因素（P ＝0．025和0．004）。V20＝183cm3、V55＝2cm3可看作小肠的放射耐受剂量,其对≥2级急性放射性肠道损伤预测的灵敏度均为0．846,特异度分别为0．800、0．960。结论：对于行 IMRT 治疗后的腹、盆腔肿瘤患者,小肠的 V20、V55是预测≥2级急性放射性肠道损伤有独特意义的影响因素。     

鼻咽癌IMRT后甲状腺功能减退的相关剂量体积研究

目的 通过对原发性甲状腺功能减退危险因素分析,探寻IMRT鼻咽癌患者甲状腺功能损伤的剂量体积阈值。方法 对2008—2010年间IMRT初治鼻咽癌113例病例进行回顾分析,所有病例均有完整临床资料以及疗前和疗后2年内甲状腺功能生化检查结果。计算甲状腺和垂体不同体积剂量参数,观察IMRT治疗后甲状腺功能损伤相关剂量体积阈值以及临床影响因素。结果113例患者中位随诊期62个月,其中41例(36.3%)出现临床甲状腺功能减退,28例(24.8%)出现亚临床甲状腺功能减退(仅TSH升高),出现时间(3~60个月,中位数12个月)。单因素分析中患者年龄、甲状腺受照D_mean、V₄₀、V₄₅、V₅₀、V₅₅、V₆₀是放疗后甲状腺功能减退的影响因素(P均<0.05)。多因素分析显示仅V₅₀、年龄与甲状腺功能减退发生有关(P均=0.002)。采用ROC曲线对预测变量分析结果显示年龄>45岁且V₅₀<50%时甲状腺功能减退发生率为31.8%,而V₅₀≥50%且年龄<45岁时甲状腺功能减退发生率为79.3%。结论 IMRT甲状腺V₅₀>50%是甲状腺功能减退发生的影响因素,年龄<45岁患者IMRT时应对甲状腺限量降低。     

适形放疗晚期肺癌放射性食管炎相关因素分析

目的分析Ⅲ~Ⅳ期非小细胞肺癌三维适形放射治疗中急性放射性食管损伤(AE)的发生率及其相关因素。方法选择2006年3月至2008年11月行三维适形放疗的晚期肺癌患者195例,男165例,女30例。其中79例患者行同步放化疗,中位等效生物剂量为72.0 Gy,观察AE的发生率,采用单因素和多因素变量分析方法,对选择的临床和剂量学因素进行与2级以上AE的相关性分析。结果 2级AE 38例(19.5%),3级AE 25例(12.8%)。单变量分析显示,临床因素中疗前体重下降≥5%、同时化放疗、淋巴结分期、临床类型和后程超分割放疗与2级以上AE有相关性,剂量学指标中食管受照最大剂量、平均剂量、V20、V25、V30、V35、V40、V45、V50、V55、V60的差异均有统计学意义(P<0.001),同时放化疗和V55在Binary Logistic多因素分析中的差异有统计学意义。结论Ⅲ~Ⅳ期非小细胞肺癌三维适形放射治疗中,同时化放疗和V55是预测AE最有价值的指标。     

食管癌VMAT与IMRT剂量比较的Meta分析

目的 对食管癌VMAT与IMRT靶区和OAR剂量比较行Meta分析。方法 文献检索纳入相关研究,分析靶区和OAR剂量参数、机器跳数及治疗时间。结果 17项研究的323病例纳入Meta分析。VMAT计划中GTV的D_mean、在总剂量≤50.4 Gy时PTV的D_mean和在总剂量>50.4 Gy时PTV的D_max优于IMRT (P=0.009、0.043、0.039)。心脏D_mean、V₃₀、V₄₀,脊髓D_max,肺V₅、V₁₀、D_mean差异均无统计学意义(P>0.05);VMAT计划中肺的V₁₅、V₂₀、V₃₀优于IMRT计划(P=0.001、0.000、0.023)。VMAT计划中单次照射1.8、2.0 Gy的机器跳数较IMRT计划分别减少275.4、134.2 MU (P=0.000、0.022);VMAT计划中单次照射1.8、2.0 Gy的TT比IMRT计划分别缩短323.5、193.7 s (P=0.000、0.009)。结论 VMAT计划能显著减少TT和机器跳数、提高设备使用率,降低肺受照剂量和RP发生风险。VMAT与IMRT相比在照射总剂量≤50.4 Gy时除PTV的D_mean和GTV的D_mean、D_max外,靶区其他剂量参数均无明显优势。对脊髓和心脏保护VMAT也无明显优势。     

Phase I study of concurrent real-time tumor-tracking thoracic radiation therapy with paclitaxel and carboplatin in locally advanced non-small cell lung cancer

Introduction

Although paclitaxel with carboplatin and thoracic radiotherapy has improved survival for patients with locally advanced unresectable non-small cell lung cancer (NSCLC), the optimal dose of paclitaxel has not been well defined in Japan. This study was conducted to determine the maximum tolerated dose (MTD) and recommended dose (RD) of paclitaxel in combination with carboplatin and concurrent real-time tumor-tracking thoracic radiation therapy (thoracic RTRT).

Patients and methods

Previously untreated patients with histologically confirmed, locally advanced unresectable NSCLC were eligible. Before treatment, gold markers were inserted into the lung and the mediastinum of all patients. RTRT comprised a total of 66 Gy at 2 Gy/fraction, 5 days/week, for 7 weeks. Patients received paclitaxel at a starting dose of 40 mg/m² followed by carboplatin at a fixed area under the curve (AUC) of 2, as a weekly regimen with RTRT. The dose of paclitaxel was escalated by 5 mg/m² per level.

Results

Eight patients with locally advanced unresectable NSCLC were enrolled and treated with two dose levels of paclitaxel (40 mg/m² and 45 mg/m²), carboplatin (AUC = 2) and RTRT. No dose limiting toxicities (DLTs) were observed at Level 1 (paclitaxel, 40 mg/m² and carboplatin, AUC = 2). At Level 2 (paclitaxel, 45 mg/m² and carboplatin, AUC = 2), two of five patients experienced DLTs, in the form of esophagitis and discontinuation of chemotherapy more than twice. The MTD and RD of paclitaxel were thus defined as 45 mg/m² and 40 mg/m², respectively.

Conclusions

This phase I study was well tolerated and the RD of paclitaxel and carboplatin with RTRT is 40 mg/m² at AUC = 2, respectively. Further studies are warranted to evaluate the efficacy of this regimen.     

Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer

PURPOSE: To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. RESULTS: Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. CONCLUSION: IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.     

Phase I/IIa study of cisplatin and gemcitabine as induction chemotherapy followed by concurrent chemoradiotherapy with gemcitabine and paclitaxel for locally advanced non-small-cell lung cancer.

PURPOSE: This is a phase I/IIa study to assess tolerance of gemcitabine and paclitaxel with radiotherapy in locally advanced non-small-cell lung cancer after induction chemotherapy. PATIENTS AND METHODS: Fifty-seven patients with stage III non-small-cell lung cancer were treated with cisplatin 80 mg/m2 on days 1 and 22 and gemcitabine 1,250 mg/m2 on days 1, 8, 22, and 28. Chemoradiotherapy began on day 43 as follows: cohort 1 (n = 9), gemcitabine 300 mg/m2 and paclitaxel 35 mg/m2 weekly (except week 9); cohort 2 (n = 9), gemcitabine 150 mg/m2 and paclitaxel 35 mg/m2 weekly (except week 9); cohort 3 (n = 10) and the 25 phase IIa patients, gemcitabine 300 mg/m2 and paclitaxel 135 mg/m2 every 21 days. Patients were treated with three-dimensional thoracic radiotherapy concurrently to 60 Gy. RESULTS: Weekly chemotherapy resulted in grade 4 esophageal and grade 3 or higher pulmonary toxicities. Reduction in dose density (cohort 3) led to a tolerable toxicity profile and was chosen as the phase IIa regimen. The response rate to induction was 49%, with stable disease in 40% of the patients. The response rate after consolidation therapy was 75% (94% for weekly chemotherapy v 82% for every 3 weeks). Median survival was 23 months, and 3-year survival was 45% for eligible patients. Local relapse occurred in 20% of the patients. Performance status of more than 1 predicted for poor outcome, but baseline pulmonary function did not. Dosimetric parameters including V15, V20, V30 (percent lung volume receiving > or = 15, > or = 20, and > or = 30 Gy, respectively), and mean lung dose correlated with pulmonary toxicity. CONCLUSION: Additional investigation with the 3-week schedule is warranted in patients with a good performance status based on the safety profile and preliminary efficacy data observed in this study.