局限期小细胞肺癌同步推量调强放疗的I期/II期临床研究

背景与目的同步放化疗是局限期小细胞肺癌的标准治疗,但患者局部复发率和远处转移率仍较高,本研究旨在评估同步推量调强放疗治疗局限期小细胞肺癌的安全性和有效性。方法符合局限期小细胞肺癌的患者纳入研究行同步放化疗,放疗采用每日两次方案,应用经典“3+3”模式对肿瘤大体体积（gross target volume, GTV）进行同步推量剂量递增,设定为三个剂量梯度,分别为45 Gy/30 f（单次剂量1.50 Gy）、50 Gy/30 f（单次剂量1.67 Gy）和54 Gy/30 f（单次剂量1.80 Gy）。计划靶体积均为45 Gy/30 f。主要研究终点为放疗期间及结束3个月内毒性反应。次要研究终点包括1年生存率、无进展生存期、局部无进展生存期。结果研究共入组26例患者,中位年龄为52岁（30岁-68岁）。26例患者中,1例出现3级放射性食管炎,未观察到3级及以上放射性肺炎。中位随访时间11.2（3.2-36.2）个月,1年生存率、无进展生存率和局部无进展生存率分别为89.0%、51.0%和85.0%。结论局限期小细胞肺癌采用化疗联合同步推量调强放疗,将GTV由45 Gy提升至54 Gy是安全有效的。     

Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience

PURPOSE: To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma. METHODS AND MATERIALS: Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40-55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed. RESULTS: The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy (p = 0.40), percentage of lung volume receiving 20 Gy (V(20)) of 0.2% vs. 2.3% (p = 0.51), and percentage of lung volume receiving 5 Gy (V(20)) of 92% vs. 66% (p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V(20) (6.9% vs. 1.9%), and V(5) (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up. CONCLUSIONS: With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.     

非小细胞肺癌三维适形放疗剂量递增的临床研究

目的通过临床剂量递增获得非小细胞肺癌（NSCLC）三维适形放射治疗的最大耐受剂量并观察其疗效。方法对84例Ⅰ～Ⅲ期NSCLC采用三维适形放射治疗（3D-CRT）,不进行区域淋巴结预防性照射。在CTV照射患者60Gy（2Gy/次,1次/天,5天/周）后,开始对GTV进行剂量递增。2～4Gy/次,递增次数为3～11次。根据肺V20和将患者分为V20〈25%组和V2025%～36%组,两组患者再根据总剂量分剂量亚组,观察放射性损伤发生率和疗效。以≥15%的患者出现3级以上急性放射性肺损伤（RTOG）为限制剂量递增标准。结果全组84例。V20〈25%组45例,剂量亚组分别为70Gy、74Gy、78Gy、82Gy。3级放射性肺炎发生率为4.4%（2/45）。V2025%～36%组39例,剂量亚组分别为66Gy、70Gy、74Gy、78Gy。3级放射性肺炎发生率为5.1%（2/39）。全组中位生存时间14个月,1、2年总生存率分别为69.5%、52.8%,1、2年局部控制率分别为79.7%、53.6%。随着剂量增加,1、2年生存率和局部控制率有所增高,但统计学检验均无统计学差异（P〉0.05）。结论采用3DCRT治疗NSCLC时,提高局部放射剂量应考虑正常肺组织所受照射的剂量和体积。当V20〈25%时,可以安全地递增到82Gy,其放射性损伤可以接受;当V20为25%～36%时,可以递增到76Gy。但当V20〉30%时,增加到更高的放射剂量应谨慎,而提高局部剂量对生存率和局部控制率的意义仍有待进一步研究。     

适形调强放疗同期整合瘤床推量治疗肺癌脑转移瘤的可行性研究

背景与目的：肺癌脑转移的发生率呈上升趋势,适形调强放射治疗(intensity-modulated radiotherapy,IMRT)+瘤床同期整合推量(simultaneous integrated boost,SIB)技术对于脑转移患者是一种新的治疗选择。本研究旨在探讨全脑IMRT+瘤床SIB治疗合并1~4个肺癌脑转移灶患者的近期临床疗效及治疗相关不良反应,明确该方案的可行性。方法：前瞻性收集2014年6月-2015年6月在江门市中心医院确诊为肺癌脑转移(转移病灶数1~4个)的32例患者,所有患者均行全脑5野IMRT(40 Gy/20 f)+瘤床SIB(50 Gy/20 f),分别评价其靶区剂量分布、放疗总有效率、肿瘤局部控制率、1年生存率、各种急性及晚期不良反应。结果：所有患者均完成放疗。全组2级呕吐、恶心和癫痫发生率分别为9.4%、15.6%和12.5%,2例出现2级认知功能障碍,4例出现2级记忆力损伤,2例出现3级记忆力损伤,无4级急性及晚期不良反应。放疗总有效率为71.9%,肿瘤局部控制率为96.9%,1年生存率为44%。结论：全脑5野IMRT(40 Gy/20 f)+瘤床SIB(共10 Gy,即总量50 Gy/20 f) 治疗1~4个肺癌脑转移灶是可行的。     

Individualized radical radiotherapy of non-small-cell lung cancer based on normal tissue dose constraints: a feasibility study

PURPOSE: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. METHODS AND MATERIALS: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An (18)F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. RESULTS: Mean delivered dose was 63.0 +/- 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. CONCLUSIONS: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.     

Fludarabine allows dose reduction for total body irradiation in pediatric hematopoietic stem cell transplantation

PURPOSE: To examine, in the setting of total body irradiation (TBI) for the preparation of pediatric hematopoietic stem cell transplantation (HSCT), whether TBI dose can be reduced without compromising the efficacy of a regimen consisting of fludarabine and radiotherapy; and whether there is any increased risk of pulmonary toxicity due to the radiosensitizing effect of fludarabine. METHODS AND MATERIALS: A total of 52 pediatric patients with hematologic malignancies received TBI-based conditioning regimens in preparation for allogeneic HSCT. Twenty-three patients received 12 Gy in 4 daily fractions in combination with cyclophosphamide, either alone or with other chemotherapeutic and biologic agents. Twenty-nine patients received 9 Gy in 3 fractions in conjunction with fludarabine and melphalan. Clinical and radiation records were reviewed to determine engraftment, pulmonary toxicity (according to Radiation Therapy Oncology Group criteria), transplant-related mortality, recurrence of primary disease, and overall survival. RESULTS: The two groups of patients had comparable pretransplant clinical characteristics. For the 12-Gy and 9-Gy regimens, the engraftment (89% and 93%; p = 0.82), freedom from life-threatening pulmonary events (65% and 79%; p = 0.33), freedom from relapse (60% and 73%; p = 0.24), and overall survival (26% and 47%; p = 0.09) were not statistically different. CONCLUSIONS: The addition of fludarabine and melphalan seems to allow the dose of TBI to be lowered to 9 Gy without loss of engraftment or antitumor efficacy.     

造血干细胞移植前全身照射的毒副反应及影响因素分析

目的　观察和分析造血干细胞移植前采用全身照射治疗所产生的近期和晚期毒副反应。方法　自１９９９年５月至２００５年１２月,我科对３１２例造血干细胞移植患者进行了全身照射。采用６０Ｃｏγ射线照射,患者取侧卧体位,腹脐处中心平面剂量率控制在４～６ｃＧｙ／ｍｉｎ,平均（５.２±１.１３）ｃＧｙ／ｍｉｎ,总剂量７～１２Ｇｙ,分１～３次照射,每天照射１次,照射期间制作个体化的肺挡铅进行肺屏蔽。结果　在全身照射后,患者近期出现了Ⅰ ～Ⅱ级的发热、胃肠道反应、口腔炎及出血性膀胱炎,均可耐受,无需特殊处理。间质性肺炎发生率为９.９％,造血系统重建和干细胞植活率达７０％以上,患者均未出现严重的肾功能衰竭。结论　采用剂量率５ｃＧｙ／ｍｉｎ照射,总照射剂量控制在７～１２Ｇｙ,肺中位剂量不超过７.５Ｇｙ,１次／天,共照射１～３次的剂量分割模式,是有效和安全的造血干细胞移植预处理方案。     

Lethal pulmonary complications significantly correlate with individually assessed mean lung dose in patients with hematologic malignancies treated with total body irradiation

PURPOSE: To assess the impact of lung dose on lethal pulmonary complications (LPCs) in a single-center group of patients with hematologic malignancies treated with total body irradiation (TBI) in the conditioning regimen for bone marrow transplantation (BMT). METHODS: The mean lung dose of 101 TBI-conditioned patients was assessed by a thorough (1 SD around 2%) in vivo transit dosimetry technique. Fractionated TBI (10 Gy, 3.33 Gy/fraction, 1 fraction/d, 0.055 Gy/min) was delivered using a lateral-opposed beam technique with shielding of the lung by the arms. The median lung dose was 9.4 Gy (1 SD 0.8 Gy, range 7.8--11.4). The LPCs included idiopathic interstitial pneumonia (IIP) and non-idiopathic IP (non-IIP). RESULTS: Nine LPCs were observed. LPCs were observed in 2 (3.8%) of 52 patients in the group with a lung dose < or = 9.4 Gy and in 7 (14.3%) of 49 patients in the >9.4 Gy group. The 6-month LPC risk was 3.8% and 19.2% (p = 0.05), respectively. A multivariate analysis adjusted by the following variables: type of malignancy (acute leukemia, chronic leukemia, lymphoma, myeloma), type of BMT (allogeneic, autologous), cytomegalovirus infection, graft vs. host disease, and previously administered drugs (bleomycin, cytarabine, cyclophosphamide, nitrosoureas), revealed a significant and independent association between lung dose and LPC risk (p = 0.02; relative risk = 6.7). Of the variables analyzed, BMT type (p = 0.04; relative risk = 6.6) had a risk predictive role. CONCLUSION: The mean lung dose is an independent predictor of LPC risk in patients treated with the 3 x 3.33-Gy low-dose-rate TBI technique. Allogeneic BMT is associated with a higher risk of LPCs.     

Toxicity and dosimetry of fractionated total body irradiation prior to allogeneic bone marrow transplantation using a straightforward radiotherapy technique

Since 1989, we have used a relatively straightforward technique for giving total body irradiation (TBI), using anterior and posterior parallel opposed fields with the arms and fists acting as compensators. The dosimetry, toxicity and outcome of 48 patients (26 adults, 22 children) treated with TBI using this technique have been audited. A dose of 14.4 Gy in eight fractions over 4 days was prescribed to all patients with an unrelated donor and 12 Gy in six fractions over 3 days to those with a sibling donor. From May 1994, all children received 14.4 Gy because of a recommendation from the United Kingdom Children's Cancer Study Group. The range of lung dosimetry was −6% to +7% when the dose was specified to the lung maximum. The trunk doses were all within ±10% of the prescribed dose. Doses to other regions of the body were less homogeneous but clinically acceptable in that the minimum doses were never less than −10% of the prescribed dose. Mucositis was the most common side effect; its treatment with opioids was more frequent after 14.4 Gy than after 12 Gy (P = 0.0004) and in adults than in children (P = 0.01). No cataracts have yet been seen in these patients. The radiation was not found to be a proven cause of clinical pneumonitis, although there was one death due to interstitial pneumonitis, which was likely to have been caused by cytomegalovirus infection in which radiation pneumonitis could not be excluded. There were no other suspected TBI-related deaths.In conclusion, this straightforward technique achieved acceptable dosimetry and was well tolerated.     

Promising clinical outcome of stereotactic body radiation therapy for patients with inoperable Stage I/II non-small-cell lung cancer

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy in patients with Stage I/II non-small-cell lung cancer. METHODS AND MATERIALS: Forty-three patients with inoperable Stage I/II non-small-cell lung cancer underwent treatment prospectively using the stereotactic gamma-ray whole-body therapeutic system (body gamma-knife radiosurgery) with 30 rotary conical-surface Co(60) sources focused on the target volume. Low-speed computed tomography simulation was conducted, which was followed by three-dimensional conformal radiotherapy planning. A total dose of 50 Gy was delivered at 5 Gy/fraction to the 50% isodose line covering the planning target volume, whereas a total dose of 70 Gy was delivered at 7 Gy/fraction to the gross target volume. The median follow-up duration was 27 months. RESULTS: Three to 6 months after treatment, the complete response rate for body-gamma knife radiosurgery was 63%, and the overall response rate was 95%. The 1-year, 2-year, and 3-year local control rates were all 95% in all patients. The 1-year, 2-year, and 3-year overall survival rates were 100%, 91%, and 91%, respectively, in patients with Stage I disease and 73%, 64%, and 64%, respectively, in those with Stage II disease. Only 2.3% (1/43) of the patients had Grade 3 pneumonitis. CONCLUSION: Our highly focused stereotactic body radiotherapy method resulted in promising local control and survival with minimal toxicity.     

肝癌移植术后肺内转移的体部伽玛刀应用分析

目的：探讨肝癌移植术后肺内转移的体部伽玛刀治疗方法及其效果。方法：2004年11月-2009年10月,应用体部伽玛刀治疗肝癌移植术后肺内转移患者12例。应用50％-80％等剂量曲线包绕靶区,剂量18—42Gy／3—8次,3次／周。肿瘤中心最大剂量12-14Gy、P1V外的正常组织在2Gy／次以下;应用剂量体积直方图（DVH）减少正常组织受照体积。结果：治疗后3月复查CT,总局部控制率91．7％（11／12）。中位生存时间10个月。无Ⅲ级以上放射性肺炎。结论：三维适形放射治疗对于肝癌移植术后肺内转移患者有较好的疗效,多病灶、多次治疗仍具较好疗效。     

局部晚期非小细胞肺癌VMAT初步疗效和不良反应分析

目的 评估VMAT用于局部晚期非小细胞肺癌(NSCLC)放疗近期疗效和不良反应。 方法 2016年间无法手术的局部晚期NSCLC患者共 58例接受同步放化疗或序贯放化疗,其中男 47例。放疗剂量为 38~66 Gy,53例(92%)患者放疗剂量≥56 Gy。放疗中位次数30次,单次剂量 1.8~3.0 Gy。28例(48%)患者接受同步化疗。 结果 中位随访时间9个月,1年总生存率84%,1年无进展生存48%。11例(19%)患者发生症状性放射性肺炎,其中1例患者因为放射性肺炎死亡。31例(53%)患者在放疗后半年内CT发现无症状性肺局部纤维化。17例(29%)患者出现2级食管炎,10例(17%)患者发生≥3级不良反应,其中9例为白细胞减少。 结论 采用VMAT行局部晚期NSCLC胸部放疗近期疗效理想,不良反应可接受,肺炎风险未见增加。     

体部伽玛刀联合化疗治疗局部晚期非小细胞肺癌疗效观察

目的：观察体部伽玛刀联合化疗治疗不能手术或拒绝手术的局部晚期（WHO分期Ⅲa、Ⅲb）非小细胞肺癌（non-small cell lung cancer,NSCLC）的疗效和不良反应。方法：将2006年8月到2009年2月期间,我院治疗的110例符合入选条件的局部晚期NSCLC患者随机分成治疗组和对照组。治疗组：体部伽玛刀加化疗。体部伽玛刀治疗：单次处方剂量50%等剂量曲线为350cGy-400cGy,每天一次,共12-14次,总剂量49Gy-56Gy。化疗：采用紫杉醇＋顺铂方案,于伽玛刀治疗后1周左右开始,平均4个周期。对照组：常规放射治疗加化疗。采用60Co体外照射,放射剂量为50Gy-54Gy,180cGy-200cGy/次,每周5次,5-6周完成,化疗方案同治疗组。结果：治疗组：有效率为81.94%,1年、2年生存率分别为65.28%、47.22%,放射性肺炎发生率3.57%。对照组：有效率为63.16%,1年、2年生存率分别为39.47%、23.68%,放射性肺炎发生率16.67%,差异有统计学意义。结论：体部伽玛刀联合化疗对不能手术或拒绝手术的局部晚期NSCLC有效,不良反应轻微。     

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant

PurposeTo apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation.Material and methodsThe study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse ≤ 3 months; (3) ECOG-PS ≥ 1; (4) bulk ≥ 5 cm; and (5) inadequate response to salvage chemotherapy.ResultsThe median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1–7 months), and the median involved-field radiotherapy dose was 35 Gy (range, 12–40 Gy). At a median follow-up of 35 months (range, 1–132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score = 0, score = 1, score = 2, and score = 3 to 5, respectively (P = 0,01). Among the 12 patients having at least three risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis.ConclusionThe adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.     

后程加速超分割放射治疗中晚期肺鳞癌的临床研究后程加速超分割放射治疗中晚期肺鳞癌的临床研究

目的 评价后程加速超分割放射治疗肺鳞癌的放射反应、并发症、近期疗效和远期疗效。方法 66例中晚期肺鳞癌随机均分至2个组。常规分割放射治疗（CF）组：2.0Gy/次,1次/d,5d/周。大野照至44Gy（分22次,4.4周完成）后缩野照射临床肿瘤区,总剂量达66～70Gy,总疗程为6.6～7.0周;后程加速超分割放射治疗（LCAF）组：前2/3疗程放射治疗方法同常规放射治疗组,缩野后加速超分割照射,1.5Gy/次,2次/d ,间隔6h;照射8～9个治疗日,总剂量68～71Gy,总疗程6.0～6.2周。照射野设计及放射线类型2个组均相同。结果 （1）疗效：完全缓解（CR）率和总有效（CR PR）率LCAF组分别为21.2%和87.8%,CF组分别为9.1%和63.6% ,2个组总有效率差异有显著性意义（X^2=5.280,P=0.022）。1、2年生存率和局部控制率LCAF组分别为75.7%、61.5%和69.7%、46.2%,CF组分别为57.6%、28.6%、和51.5%、21.4%,2个组差异有显著性意义（ X^2=4.476,P=0.037和X^2=4.087,P=0.043）。（2）放射性食管炎：LCAF组为81.8%,CF组为54.5%(X^2=5.657,P=0.018）。（3）2个组放射性气管炎、肺炎及肺纤维化均无差异。结论 后程加速超分割放射治疗肺鳞癌,患者均能耐受,近期疗效和1、2年生存率及局部控制率明显优于常规放射治疗,有望获得较好的远期疗效。     

Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial.

Thirty-six patients with advanced hematologic malignancy were entered into a Phase I study designed to define the maximum tolerated dose of unshielded total body irradiation delivered from dual 60 Cobalt sources at an exposure rate of 8 cGy/min and given in fractions twice daily for total doses ranging from 12 Gy to 17 Gy. All patients received cyclophosphamide, 120 mg/kg administered over 2 days before total body irradiation. Allogeneic marrow was infused from HLA-identical siblings (n = 29) or one locus HLA incompatible family members (n = 3); three patients received cryopreserved autologous marrow and one patient received syngeneic marrow. The maximum tolerated dose of total body irradiation given as 2 Gy fractions twice a day was 16 Gy. One of eight patients receiving 12 Gy, none of four receiving 14 Gy, three of 20 receiving 16 Gy, and two of four receiving 17 Gy developed severe (Grade 3-4) regimen-related toxicity. The primary dose limiting toxicity was pneumonitis, followed by veno-occlusive disease of the liver, renal impairment, and mucositis. Five patients (14%) are alive, four disease-free 798-1522 days posttransplant. Twenty (56%) relapsed posttransplant. Further investigation of regimens containing 16 Gy of hyperfractionated total body irradiation is warranted to assess anti-tumor efficacy.     

Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma

PURPOSE: To describe the initial experience at Dana-Farber Cancer Institute/Brigham and Women's Hospital with intensity-modulated radiation therapy (IMRT) as adjuvant therapy after extrapleural pneumonectomy (EPP) and adjuvant chemotherapy. METHODS AND MATERIALS: The medical records of patients treated with IMRT after EPP and adjuvant chemotherapy were retrospectively reviewed. IMRT was given to a dose of 54 Gy to the clinical target volume in 1.8 Gy daily fractions. Treatment was delivered with a dynamic multileaf collimator using a sliding window technique. Eleven of 13 patients received heated intraoperative cisplatin chemotherapy (225 mg/m(2)). Two patients received neoadjuvant intravenous cisplatin/pemetrexed, and 10 patients received adjuvant cisplatin/pemetrexed chemotherapy after EPP but before radiation therapy. All patients received at least 2 cycles of intravenous chemotherapy. The contralateral lung was limited to a V20 (volume of lung receiving 20 Gy or more) of 20% and a mean lung dose (MLD) of 15 Gy. All patients underwent fluorodeoxyglucose positron emission tomography (FDG-PET) for staging, and any FDG-avid areas in the hemithorax were given a simultaneous boost of radiotherapy to 60 Gy. Statistical comparisons were done using two-sided t test. RESULTS: Thirteen patients were treated with IMRT from December 2004 to September 2005. Six patients developed fatal pneumonitis after treatment. The median time from completion of IMRT to the onset of radiation pneumonitis was 30 days (range 5-57 days). Thirty percent of patients (4 of 13) developed acute Grade 3 nausea and vomiting. One patient developed acute Grade 3 thrombocytopenia. The median V20, MLD, and V5 (volume of lung receiving 5 Gy or more) for the patients who developed pneumonitis was 17.6% (range, 15.3-22.3%), 15.2 Gy (range, 13.3-17 Gy), and 98.6% (range, 81-100%), respectively, as compared with 10.9% (range, 5.5-24.7%) (p = 0.08), 12.9 Gy (range, 8.7-16.9 Gy) (p = 0.07), and 90% (range, 66-98.3%) (p = 0.20), respectively, for the patients who did not develop pneumonitis. CONCLUSIONS: Intensity-modulated RT treatment for mesothelioma after EPP and adjuvant chemotherapy resulted in a high rate of fatal pneumonitis when standard dose parameters were used. We therefore recommend caution in the utilization of this technique. Our data suggest that with IMRT, metrics such as V5 and MLD should be considered in addition to V20 to determine tolerance levels in future patients.     

Feasibility of sparing lung and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer

PURPOSE: To investigate the possibility of using intensity-modulated radiotherapy (IMRT) to reduce the irradiated volumes of the normal lung and other critical structures in the treatment of non-small-cell lung cancer (NSCLC) and to investigate the effect of IMRT on the potential of spreading low doses to large volumes of normal tissues in such treatment. METHODS AND MATERIALS: A retrospective treatment planning study was performed to compare IMRT and conventional three-dimensional conformal radiation therapy (3D-CRT) for 10 NSCLC patients (Stage I-IIIB). In the IMRT plans, three to nine coplanar beams were designed to treat 95% of the planning target volume with 63 Gy and to minimize the volumes of the normal lung, esophagus, heart, and spinal cord irradiated above their tolerance doses. The two types of plans were compared with respect to the planning target volume coverage, dose-volume histograms, and other dosimetric indexes of the normal structures. RESULTS: Comparing the nine-beam IMRT plan with the 3D-CRT plan, the percentage of lung volume that received >20 Gy and the mean lung dose were reduced for all cases, with a median reduction of 8% and 2 Gy, respectively. An additional reduction of the >5-Gy volume and >10-Gy volume for the lung and thoracic tissue was more difficult with IMRT, although still possible using fewer beams in IMRT. The integral dose to the entire thorax was equivalent and even reduced for 8 of 10 cases using IMRT. CONCLUSION: It is possible to reduce the volumes of low doses (such as the >10-Gy volume and >20-Gy volume) for thoracic normal tissues using IMRT. The increased integral dose and low-dose volumes can be avoided for IMRT if such concerns are addressed carefully in the inverse planning process and with optimization of the IMRT beam configuration.     

Toxicity and outcome results of RTOG 9311: a phase I-II dose-escalation study using three-dimensional conformal radiotherapy in patients with inoperable non-small-cell lung carcinoma

PURPOSE: To evaluate prospectively the acute and late morbidities from a multiinstitutional three-dimensional radiotherapy dose-escalation study for inoperable non-small-cell lung cancer. METHODS AND MATERIALS: A total of 179 patients were enrolled in a Phase I-II three-dimensional radiotherapy dose-escalation trial. Of the 179 patients, 177 were eligible. The use of concurrent chemotherapy was not allowed. Twenty-five patients received neoadjuvant chemotherapy. Patients were stratified at escalating radiation dose levels depending on the percentage of the total lung volume that received >20 Gy with the treatment plan (V(20)). Patients with a V(20) <25% (Group 1) received 70.9 Gy in 33 fractions, 77.4 Gy in 36 fractions, 83.8 Gy in 39 fractions, and 90.3 Gy in 42 fractions, successively. Patients with a V(20) of 25-36% (Group 2) received doses of 70.9 Gy and 77.4 Gy, successively. The treatment arm for patients with a V(20) > or =37% (Group 3) closed early secondary to poor accrual (2 patients) and the perception of excessive risk for the development of pneumonitis. Toxicities occurring or persisting beyond 90 days after the start of radiotherapy were scored as late toxicities. The estimated toxicity rates were calculated on the basis of the cumulative incidence method. RESULTS: The following acute Grade 3 or worse toxicities were observed for Group 1: 70.9 Gy (1 case of weight loss), 77.4 Gy (nausea and hematologic toxicity in 1 case each), 83.8 Gy (1 case of hematologic toxicity), and 90.3 Gy (3 cases of lung toxicity). The following acute Grade 3 or worse toxicities were observed for Group 2: none at 70.9 Gy and 2 cases of lung toxicity at 77.4 Gy. No patients developed acute Grade 3 or worse esophageal toxicity. The estimated rate of Grade 3 or worse late lung toxicity at 18 months was 7%, 16%, 0%, and 13% for Group 1 patients receiving 70.9, 77.4, 83.8, or 90.3 Gy, respectively. Group 2 patients had an estimated late lung toxicity rate of 15% at 18 months for both 70.9 and 77.4 Gy. The prognostic factors for late pneumonitis in multivariate analysis were the mean lung dose and V(20). The estimated rate of late Grade 3 or worse esophageal toxicity at 18 months was 8%, 0%, 4%, and 6%, for Group 1 patients receiving 70.9, 77.4, 83.8, 90.3 Gy, respectively, and 0% and 5%, respectively, for Group 2 patients receiving 70.9 and 77.4 Gy. The dyspnea index scoring at baseline and after therapy for functional impairment, magnitude of task, and magnitude of effort revealed no change in 63%, functional pulmonary loss in 23%, and pulmonary improvement in 14% of patients. The observed locoregional control and overall survival rates were each similar among the study arms within each dose level of Groups 1 and 2. Locoregional control was achieved in 50-78% of patients. Thirty-one patients developed regional nodal failure. The location of nodal failure in relationship to the RT volume was documented in 28 of these 31 patients. Twelve patients had isolated elective nodal failures. Fourteen patients had regional failure in irradiated nodal volumes. Two patients had both elective nodal and irradiated nodal failure. CONCLUSIONS: The radiation dose was safely escalated using three-dimensional conformal techniques to 83.8 Gy for patients with V(20) values of <25% (Group 1) and to 77.4 Gy for patients with V(20) values between 25% and 36% (Group 2), using fraction sizes of 2.15 Gy. The 90.3-Gy dose level was too toxic, resulting in dose-related deaths in 2 patients. Elective nodal failure occurred in <10% of patients.