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。     

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。     

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.     

Initial evaluation of treatment-related pneumonitis in advanced-stage non-small-cell lung cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy

PURPOSE: To investigate the rate of high-grade treatment-related pneumonitis (TRP) in patients with advanced non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: From August 2002 to August 2005, 151 NSCLC patients were treated with IMRT. We excluded patients who did not receive concurrent chemotherapy or who had early-stage cancers, a history of major lung surgery, prior chest RT, a dose <50 Gy, or IMRT combined with three-dimensional conformal RT (3D-CRT). Toxicities were graded by Common Terminology Criteria for Adverse Events version 3.0. Grade > or = 3 TRP for 68 eligible IMRT patients was compared with TRP among 222 similar patients treated with 3D-CRT. RESULTS: The median follow-up durations for the IMRT and 3D-CRT patients were 8 months (range, 0-27 months) and 9 months (range, 0-56 months), respectively. The median IMRT and 3D-CRT doses were 63 Gy. The median gross tumor volume was 194 mL (range, 21-911 mL) for IMRT, compared with 142 mL (range, 1.5-1,186 mL) for 3D-CRT (p = 0.002). Despite the IMRT group's larger gross tumor volume, the rate of Grade > or = 3 TRP at 12 months was 8% (95% confidence interval 4%-19%), compared with 32% (95% confidence interval 26%-40%) for 3D-CRT (p = 0.002). CONCLUSIONS: In advanced NSCLC patients treated with chemoradiation, IMRT resulted in significantly lower levels of Grade > or = 3 TRP compared with 3D-CRT. Clinical, dosimetric, and patient selection factors that may have influenced rates of TRP require continuing investigation. A randomized trial comparing IMRT with 3D-CRT has been initiated.     

三维适形放射治疗局部晚期肺癌所致急性食管损伤相关因素分析

 目的 探讨三维适形放射治疗局部晚期中央型非小细胞肺癌所致急性食管损伤相关因素分析。方法 2002年8月-2005年10月，76例NSCLC患者接受三维适形放射治疗，对三维适形计划及患者临床资料进行单因素、多因素分析，评价食管损伤。结果 76例NSCLC中，共发生急性食管炎27例．Ⅰ级15例、Ⅱ级6例、Ⅲ级6例。相关分析显示与急性食管炎相关的因素有食管V50食管所受平均剂量、同期化疗。Logistic多元回归结果显示急性放射性食管炎发生的影响因素为化疗、食管V50（OR值分别为3．193，1．034）。结论 三维适形放射治疗局部晚期中央型非小细胞肺癌时放射所致急性食管损伤与放化疗同期进行和食管V50明显相关。     

Rectal sequelae after conformal radiotherapy of prostate cancer: dose-volume histograms as predictive factors.

PURPOSE: To identify clinically relevant parameters predictive of late rectal bleeding derived from cumulative dose-volume histograms (DVHs) of the rectum after conformal radiotherapy of prostate cancer. MATERIALS AND METHODS: One hundred and nine patients treated with 3D conformal radiotherapy between 1/1994 and 1/1996 for localized prostate cancer (clinical stage T1-T3) were available for analysis. All patients received a total dose of 66 Gy/2 Gy per fraction (specified at the International Commission on Radiation Units and Measurements ICRU reference point). DVHs of the contoured rectum were analyzed by defining the absolute (aV) and relative (rV) rectum volume that received more than 30% (V30), 50% (V50), 70% (V70), 80% (V80), 90% (V90) and 100% (V100) of the prescribed dose. Additionally, a new aspect of DVH analysis was investigated by calculation of the area under the DVH-curve between several dose levels (area under the curve (AUC)-DVH). DVH-variables were correlated with radiation side effects evaluated in 3-6 months intervals and graded according to the EORTC/RTOG score. The median follow-up was 30 months (12-60 months). RESULTS: Univariate and multivariate stepwise Cox-Regression analysis including age, PTV, rectum size, rV100, rV90, rV80, rV70, rV50 rV30 and aV30 to aV100 were calculated. Late rectal bleeding (EORTC/RTOG grade 2) was significantly correlated with the percentage of rectum volume receiving > or = 90% of the prescribed dose (rV90) (P = 0.007) and inversely correlated in a significant way with the size of contoured rectum (P = 0.006) in multivariate analysis. In our series, a proportion of the rectum volume > or = 57% were included in the 90%-isodose (rV90 > or = 57%) in one half of the patients, with an actuarial incidence of 31% of late rectal bleeding at 3 years. In the other half of the patients, when rV90 < 57%, the 3-year actuarial incidence was 11% (P < 0.03). CONCLUSION: Our data demonstrate a dose-volume relationship at the reference dose of 60 Gy ( approximately 90% of the prescribed dose) with respect to late rectal toxicity. The rV90 seems to be the most useful and easily obtained parameter when comparing treatment plans to evaluate the risk of rectal morbidity.     

256例局部晚期NSCLC患者IMRT后急性症状性食管炎预测因素分析

目的 探索局部晚期NSCLC患者IMRT后急性症状性食管炎的发生率及相关预测因素。方法 2007—2011年间在本院治疗的256例未手术的Ⅲ期NSCLC患者。放疗靶区包括原发肺肿瘤及受累淋巴引流区, 中位剂量为60 Gy分30次(50~70 Gy)。109例(42.6%)接受同期化疗。放疗期间及放疗结束后3个月内出现≥2级急性食管炎(症状性食管炎)作为终点事件, 采用CTCAE3.0评估急性食管炎级别。采用Logistic回归模型对预测因素进行分析。结果 174例患者(68%)出现治疗相关的≥2级急性食管炎, 其中154例(60.2%)为2级、20例(7.8%)为3级。≥2级急性食管炎发生时的中位剂量为30 Gy (11~68 Gy)。食管V₅—V₆₀、食管平均剂量及年龄是≥2级急性食管炎的预测因素(P=0.021、0、0.010), 其中高龄是保护性因素;食管V₅₀—V₆₀、同期化疗、体重指数是≥3级急性食管炎的预测因素(P=0.010、0.003、0.019), 其中高体重指数是保护性因素。结论 局部晚期NSCLC患者IMRT后食管V₅₀—V₆₀和同期化疗是≥3级急性食管炎的预测因素, 食管V₅₀对预测≥2级、≥3级急性食管炎都有较高价值。     

Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma.

BACKGROUND: The current study was undertaken to evaluate the incidence and predictors of late toxicity in patients with localized prostate carcinoma treated with high dose three-dimensional conformal radiotherapy (3D-CRT). METHODS: A total of 743 patients with prostate carcinoma classified as T1c-T3 were treated with 3D-CRT that targeted the prostate and seminal vesicles. A minimum tumor dose of 64.8 gray (Gy) was given to 96 patients (13%), 70.2 Gy to 266 patients (365), 75.6 Gy to 320 patients (43%), and 81.0 Gy to 61 patients (8%). The median follow-up time was 42 months (range, 18-109 months). Late toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. RESULTS: Late gastrointestinal (GI) and urinary (GU) toxicities were absent or minimal (Grade 0 or 1) in 90% of patients. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GI toxicities was 11% and 0.75%, respectively. A multivariate analysis identified doses > or =75.6 Gy (P<0.001), history of diabetes mellitus (P = 0.01), and the presence of acute GI symptoms during treatment (P = 0.02) as independent predictors of Grade > or =2 late GI toxicity. The 5-year actuarial likelihood of the development of Grade 2 and 3 late GU toxicities was 10% and 3%, respectively. Doses > or =75.6 Gy (P = 0.008) and acute GU symptoms (P<0.001) were independent predictors of Grade > or =2 late GU toxicity. Among 544 patients who were potent before treatment (73% of all patients), 211 (39%) became impotent after 3D-CRT. The 5-year actuarial risk of potency loss was 60%. Doses > or =75.6 Gy (P<0.001) and the use of neoadjuvant androgen deprivation (P = 0.01) were independent predictors of posttreatment erectile dysfunction. CONCLUSIONS: The incidence of severe late complications after high dose 3D-CRT was minimal. Radiation doses > or =75.6 Gy and the presence of acute treatment-related symptoms during 3D-CRT correlated with a higher incidence of Grade > or =2 late GI and GU toxicities. In addition to higher doses, the use of androgen deprivation therapy increased the likelihood of permanent impotence in these patients. Intensity-modulated radiotherapy, which makes it possible to enhance the conformality of the dose distribution, has recently been implemented in an attempt to reduce the incidence of moderate grade toxicities in patients receiving high dose 3D-CRT.     

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.     

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.     

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.     

Conformal therapy improves the therapeutic index of patients with anal canal cancer treated with combined chemotherapy and external beam radiotherapy

PURPOSE: To evaluate the clinical outcomes of three-dimensional conformal radiotherapy (3D-CRT) in patients with anal canal cancer, in terms of local control (LC), freedom from relapse (FFR), and overall survival (OS) rates, and to estimate long-term toxicity data. METHODS AND MATERIALS: Sixty historical patients, treated with conventional radiation techniques (C-RT), were used as controls, and 62 consecutive patients were treated with 3D-CRT. Patients treated with 3D-CRT received 54 Gy in 30 fractions delivered continuously, compared with 45-58.9 Gy (median dose, 54 Gy) in a split course in patients treated with C-RT. Chemotherapy consisted of 5-fluorouracil with either mitomycin-C or cis-platinum given concurrently with radiation. Survival curves were performed using the Kaplan-Meier model, and the Cox proportional hazards model was used for multivariate analysis of risk factors. RESULTS: No differences in stage and age distribution were observed between the two groups. Patients treated with 3D-CRT and C-RT had an actuarial 5-year LC rate of 85.1% and 61.1%, respectively (p = 0.0056); the FFR rate was 70.2% and 46.1% (p = 0.0166), and the OS rate was 80.7% and 53.9% (p = 0.0171). In multivariate analysis, factors of significance for LC were nodal (N) status (p < 0.001); for OS, 3D-CRT (p = 0.038), N status (p = 0.011), and T status (p = 0.012); and for FFR, 3D-CRT (p = 0.024) and N status (p < 0.001). CONCLUSION: The use of 3D-CRT allows patients with anal canal cancer to complete radiation and chemotherapy without interruption for toxicity, with significant improvements in LC, FFR, and OS.     

Gross tumor volume, critical prognostic factor in patients treated with three-dimensional conformal radiation therapy for non-small-cell lung carcinoma.

PURPOSE: Three-dimensional conformal radiation therapy (3D-CRT) has recently become widely available with applications for patients with non-small-cell lung cancer (NSCLC). These techniques represent a significant advance in the delivery of radiotherapy, including improved ability to delineate target contours, choose beam angles, and determine dose distributions more accurately than were previously available. The purpose of this study is to identify prognostic factors in a population of NSCLC patients treated with definitive 3D-CRT. METHODS AND MATERIALS: Between March 1991 and December 1998, 207 patients with inoperable NSCLC were treated with definitive 3D-CRT. Tumor targets were contoured in multiple sections from a treatment planning computed tomography (CT) scan. Three-dimensional treatment volumes and normal structures were reconstructed. Doses to the International Commission on Radiation Units and Measurements (ICRU) reference point ranged from 60 to 83.85 Gy with a median dose of 70 Gy. The median dose inhomogeneity was +/- 5% across planning target volume. Outcome was analyzed by prognostic factors for NSCLC including pretreatment patient and tumor-related factors (age, gender, race, histology, clinical stage, tumor [T] stage, and node [N] stage), parameters from our 3D-CRT system (gross tumor volume [GTV] in cm3), irradiation dose prescribed to isocenter, volume of normal lung exceeding 20 Gy (V20), and treatment with or without chemotherapy. The median follow-up time was 24 months (range, 7.5 months to 7.5 years). RESULTS: One and two-year overall survival rates for the entire group were 59% and 41%, respectively. Overall survival, cause-specific survival, and local tumor control were most highly correlated with the GTV in cm3. On multivariate analysis the independent variable most predictive of survival was the GTV. Traditional staging such as T, N, and overall clinical staging were not independent prognostic factors. Patients receiving ICRU reference doses > or =70 Gy had better local control and cause-specific survivals than those treated with lower doses (p = 0.05). Increased irradiation dose did not improve overall survival. CONCLUSIONS: GTV as determined by CT and 3D-CRT planning is highly prognostic for overall and cause-specific survival and local tumor control and may be important in stratification of patients in prospective therapy trials. T, N, and overall stage were not independent prognostic factors in this population of patients treated nonsurgically. The value of dose escalation beyond 70 Gy should be tested prospectively by clinical trial.     

Long-term urinary toxicity after 3-dimensional conformal radiotherapy for prostate cancer in patients with prior history of transurethral resection

PURPOSE: To report on the long-term urinary morbidity among prostate cancer patients with a prior history of a transurethral resection of the prostate (TURP) treated with high-dose 3-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS: Between 1988 and 1997, 1100 patients with clinically localized prostate cancer were treated with 3D-CRT. Of these, 120 patients (8%) were identified as having had a prior TURP and are the subjects of this analysis. The median age was 71 years (range: 49-83 years). The clinical stages of the patients were T1c: 33 (28%); T2a: 38 (32%); T2b: 15 (13%); and T3: 34 (27%). Neoadjuvant androgen ablation therapy was given to 39 (33%). The median radiation dose prescribed to the planning target volume was 75.6 Gy (range: 64.8-81 Gy). The median elapsed time from TURP to initiation of 3D-CRT was 69 months (range: 4-360 months). The median follow-up time was 51 months (range: 18-109 months). RESULTS: Five patients of the 120 with a prior history of TURP (4%) developed a urethral stricture after 3D-CRT which was corrected with dilatation. The 5-year actuarial likelihood of >/= Grade 2 late urinary toxicities was 9%. No Grade 4 urinary toxicities were observed in this group of patients. Among 110 patients who were completely continent of urine prior to 3D-CRT, 10 (9%) developed stress incontinence requiring 1 pad daily for protection or experienced occasional leakage (not requiring pad protection). The 5-year incidence of >/= Grade 1 stress incontinence was 18% in patients who developed acute >/= Grade 2 GU symptoms during the course of 3D-CRT compared to 7% for patients who experienced Grade 1 or no acute urinary symptoms (p = 0.05). The radiation dose (>/=75.6 Gy vs. <75.6 Gy), the number of prior TURP procedures, or the volume of resected tissue at the time of TURP had no significant impact on the long-term urinary morbidity outcome. A multivariate analysis demonstrated that the presence of Grade 2 acute urinary symptoms was the only predictor of >/= Grade 1 stress incontinence after 3D-CRT in this group of patients. CONCLUSIONS: Despite prior TURP, the incidence of >/= Grade 3 urinary toxicities is low. Nevertheless, especially among patients with a prior history of TURP who experience Grade 2 acute urinary symptoms during radiation treatment, a higher risk of stress incontinence is observed.     

Induction chemotherapy plus three-dimensional conformal radiation therapy in the definitive treatment of locally advanced non-small-cell lung cancer

PURPOSE: To evaluate our institution's experience using chemotherapy in conjunction with three-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS: From 1991 to 1998, 152 patients with Stage III non-small-cell lung cancer (NSCLC) were treated with 3D-CRT at Memorial Sloan-Kettering Cancer Center. A total of 137 patients (90%) were surgically staged with either thoracotomy or mediastinoscopy. The remainder were staged radiographically. Seventy patients were treated with radiation therapy alone, and 82 patients received induction chemotherapy before radiation. The majority of chemotherapy-treated patients received a platinum-containing regimen. Radiation was delivered with a 3D conformal technique using CT-based treatment planning. The median dose in the radiation alone group was 70.2 Gy, while in the combined modality group, it was 64.8 Gy. RESULTS: The median follow-up time was 30.5 months among survivors. Stage IIIB disease was present in 36 patients (51%) in the radiation-alone group and 57 patients (70%) in the combined-modality group. Thirty-nine patients had poor prognostic factors (KPS < 70 or weight loss > 5%), and they were equally distributed between the two groups. The median survival times for the radiation-alone and the combined-modality groups were 11.7 months and 18.1 months, respectively (p = 0.001). The 2-year rates of local control in the radiation-alone and combined-modality groups were 35.4% and 43.1%, respectively (p = 0.1). Grade 3 or worse nonhematologic toxicity occurred in 20% of the patients receiving radiation alone and in 16% of those receiving chemotherapy and radiation. Overall, there were only 4 cases of Grade 3 or worse esophagitis. CONCLUSION: Despite more Stage IIIB patients in the combined-modality group, the addition of chemotherapy to 3D-CRT produced a survival advantage over 3D-CRT alone in Stage III NSCLC without a concomitant increase in toxicity. Chemotherapy thus appears to be beneficial, even in patients who are receiving higher doses of radiation therapy than are typically given with conventional techniques. Because locoregional failure remains a major challenge in patients with advanced disease, 3D-CRT in conjunction with chemotherapy may allow safe treatment to the dose levels required to further enhance local control.     

Three-dimensional conformal radiation therapy for non-small-cell lung cancer: a phase I/II dose escalation clinical trial

PURPOSE: A prospective Phase I/II dose escalation study was conducted to determine the maximum tolerated dose (MTD) in three-dimensional conformal radiation therapy (3D-CRT) for non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: MTD would be reached via a dose escalation study. After 42 Gy/21 fractions, 4.2 weeks by conventional fractionated irradiation through anteroposterior/posteroanterior fields, the 3D-CRT technique was used as boost. The planned total dose escalation depended on lung volume irradiated. According to the percentage of lung volume receiving >20 Gy, the patients were divided into three subgroups (i.e., <25%, 25%-37%, and >37%). The scheduled dose escalation began with 69 Gy and continued to 78 Gy. The boost doses were delivered at 3 Gy per fraction, once per day, five fractions per week. Each dose level includes 5 patients. Besides radiotherapy, all patients received neoadjuvant and adjuvant chemotherapy with MVP regimen (Mitomycin, Vindesine, cis-platium). The criterion for stopping further dose escalation was > or =20% of patients with > or =RTOG Grade 3 radiation pneumonitis. RESULTS: Between June 1999 and February 2001, 50 patients had been enrolled in this study, including 4 with Stage II disease, 31 with Stage IIIa disease, and 15 with Stage IIIb disease. The dose escalation plan has been completed. All subgroups reached the highest predetermined dose levels (i.e., 78 Gy for the <25% subgroup, 78 Gy for the 25-37% subgroup, and 75 Gy for the >37% subgroup). Although none of the subgroups developed more than 20% of >/=Grade 3 acute pneumonitis, dose escalation was terminated because long-term follow-up was needed to observe late complications. Median follow-up time (MFT) for the entire group was 18 months (6-37 months). The most common acute complication was esophagitis in 56% of patients with RTOG Grade 1-2, and in 4% with Grade 3. Acute radiation pneumonitis developed in 36% of patients with RTOG Grade 1-2. Only 1 patient had Grade 3 pneumonitis, which was in the 25-37% subgroup at 75 Gy. The hematopoietic toxicity appeared in 58% of patients with Grade 1-2, and 8% with Grade 3. As to late complications, only 30% of patients developed pulmonary fibrosis of RTOG Grade 1-2. The median survival time for the entire group was 18 months. Two-year overall survival, locoregional progression-free rate, and distant metastasis rate were 44%, 40%, and 41%, respectively. CONCLUSIONS: Although MFT was 18 months, it had not yet been declared because a longer follow-up was needed to observe the late complications. The 2-year overall survival of 44% was very encouraging and implied that 3D-CRT combined with chemotherapy would improve the outcome for locally advanced NSCLC.     

Improved local control with higher doses of radiation in large-volume stage III non-small-cell lung cancer

PURPOSE: It has been suggested that larger tumor volume is associated with poor survival in patients with non-small-cell lung cancer (NSCLC). We investigated whether high-dose radiation improved local control in patients with large-volume Stage III NSCLC. METHODS AND MATERIALS: Seventy-two patients with Stage III NSCLC and gross tumor volumes (GTV) of greater than 100 cc were treated with three-dimensional conformal radiotherapy (3D-CRT). Patients were divided into two groups: those treated to less than 64 Gy (37 patients) and those treated to 64 Gy or higher (35 patients). RESULTS: The 1-year and 2-year local failure rates were 27% and 47%, respectively, for Stage III patients treated to 64 Gy or higher, and 61% and 76%, respectively, for those treated to less than 64 Gy (p = 0.024). The median survival time for patients treated to 64 Gy or higher was 20 months vs. 15 months for those treated to less than 64 Gy (p = 0.068). Multivariate analysis revealed that dose and GTV are predictors of local failure-free survival. A 10 Gy increase in dose resulted in a 36.4% decreased risk of local failure. CONCLUSIONS: Our data suggest that administration of higher doses using 3D-CRT improves local control in Stage III NSCLC patients with large GTVs.     

Dosimetric correlations of acute esophagitis in lung cancer patients treated with radiotherapy

PURPOSE: To evaluate the factors associated with acute esophagitis in lung cancer patients treated with thoracic radiotherapy. METHODS AND MATERIALS: We examined 35 patients with non-small-cell lung cancer (n = 27, 77%) and small-cell lung cancer (n = 8, 23%) treated with thoracic radiotherapy between February 2003 and November 2004. The median patient age was 70 years (range, 50-83 years). The disease stage was Stage I in 2 patients (6%), Stage II in 1 (3%), Stage IIIa in 10 (28%), Stage IIIb in 9 (26%), and Stage IV in 9 (26%); 4 patients (11%) had recurrent disease after surgery. A median dose of 60 Gy (range, 50-67 Gy) was given to the isocenter and delivered in single daily fractions of 1.8 or 2 Gy. With heterogeneity corrections, the median given dose to the isocenter was 60.3 Gy (range, 49.9-67.2 Gy). Of the 35 patients, 30 (86%) received concurrent chemotherapy consisting of a platinum agent, cisplatin or carboplatin, combined with paclitaxel in 18 patients (52%), irinotecan hydrochloride in 7 (20%), vincristine sulfate and etoposide in 2 (5%), vinorelbine ditartrate in 1 (3%), etoposide in 1 (3%), and docetaxel in 1 patient (3%). Three of these patients underwent induction therapy with cisplatin and irinotecan hydrochloride, administered before thoracic radiotherapy, and concurrent chemotherapy. Esophageal toxicity was graded according to the Radiation Therapy Oncology Group criteria. The following factors were analyzed with respect to their association with Grade 1 or worse esophagitis by univariate and multivariate analyses: age, gender, concurrent chemotherapy, chemotherapeutic agents, maximal esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving >10 to >65 Gy in 5-Gy increments. RESULTS: Of the 35 patients, 25 (71%) developed acute esophagitis, with Grade 1 in 20 (57%) and Grade 2 in 5 (14%). None of the patients had Grade 3 or worse toxicity. The most significant correlation was between esophagitis and percentage of esophageal volume receiving >35 Gy on univariate (p = 0.002) and multivariate (p = 0.018) analyses. CONCLUSION: The percentage of esophageal volume receiving >35 Gy was the most statistically significant factor associated with mild acute esophagitis.