宫颈癌放疗血液学毒性与临床因素及骨盆骨髓剂量的相关性研究

目的:探讨临床因素和放疗剂量学因素对宫颈癌放射治疗急性血液学毒性(hematological toxicity,HT)的影响,以寻求方法减少HT的发生。方法:分析2018年11月至2021年2月在我院放疗中心接受根治性放疗的67例宫颈癌患者发生急性血液学毒性的因素,临床因素包括年龄、分期、病理类型、有无同步化疗等,剂量学因素包括骨盆骨髓V5、V10、V15、V20、V25、V30、V35、V40、V45、V50、Dmax、Dmin、Dmedian、Dmean、PTV的V100(%)、Dmedian、Dmean,以及外照射剂量、SIB、外照射野数、CI、HI。结果:单因素及相关分析显示,HT 0-2级与HT 3-4级的分期、同步化疗、骨盆骨髓的V30、V35、V40、V45、V50、Dmax、Dmedian有显著差异（P＜0.05）;Logistic多因素分析显示同步化疗（P=0.002,OR=33.942）、骨盆骨髓V40＞34.116%（P=0.002,OR=11.543）是发生3-4级HT的独立危险因素;亚组分析发现同步化疗患者中,骨盆骨髓V40＞34.116%时发生3-4级HT的患者显著增多（P=0.008）。结论:同步化疗和骨盆骨髓V40＞34.116%是宫颈癌根治性放疗患者发生3-4级急性HT的原因,骨盆骨髓剂量限定有助于减少血液学毒性的发生,使患者顺利完成治疗。     

调强放疗同步化疗治疗宫颈癌血液学毒性相关因素分析

目的 探讨调强放疗同步化疗治疗宫颈癌的过程中出现严重血液学毒性的相关因素。方法 回顾性分析126例调强放疗同步化疗的宫颈癌患者资料,对同步放化疗期间可能与严重血液学毒性相关的因素进行单因素和多因素分析。结果 单因素分析显示严重血液学毒性的发生与治疗前肌酐水平、放疗前是否接受化疗及是否有骨髓抑制、骨盆骨髓平均剂量、V20、V40及V50有关（P<0.05）。多因素分析显示骨盆骨髓平均剂量（OR: 1.004, 95%CI: 1.002~1.007）、V40（<41% vs. ≥41%, OR: 0.040, 95%CI: 0.007~0.235）、V50 （<9% vs. ≥ 9%, OR: 0.040, 95%CI: 0.011~0.152）和治疗前肌酐水平（<65 μmol/L vs.≥65 μmol/L, OR: 0.116, 95%CI: 0.030~0.441）与3~4级血液学毒性相关。结论 治疗前肌酐<65 μmol/L、V40<41%和V50<9%是宫颈癌患者同步放化疗期间3~4级血液学毒性发生率降低的相关因素。骨盆骨髓平均剂量越高,血液学毒性发生率增高。治疗前评估肾功能水平,严格控制骨盆骨髓的放疗照射体积及剂量,能减少宫颈癌患者血液学毒性发生,是顺利完成调强放疗同步化疗的保障。     

直肠癌同步放化疗所致急性骨髓抑制的临床和物理因素分析*

目的:分析直肠癌患者同步放化疗所致急性骨髓抑制的临床和物理因素,为临床治疗提供参考依据。方法:回顾性分析2012年1 月至2015年8 月重庆医科大学附属第一医院肿瘤科接受同步放化疗的直肠癌患者62例,在放疗计划系统中勾画患者的骨盆,将其分成腰骶骨、髂骨及骨盆下部3 部分。应用单因素和多因素分析方法研究直肠癌患者临床和物理因素与急性骨髓抑制的关系。临床因素有患者的性别、年龄、临床分期、原始血色素水平、化疗方案、是否手术及放疗方式;物理因素包括腰骶骨、髂骨、骨盆下部及骨盆V 5、V 10、V 15、V 20、V 25、V 30、V 35、V 40、V 45、V 50、最大剂量（Dmax）及平均剂量（Dmean）。 结果:全组≥ 2 级急性骨髓抑制发生率为61.3%（38/ 62）。 单因素分析显示性别、化疗方案、腰骶骨V 45、髂骨V 20和髂骨V 30与急性骨髓抑制的发生有关。Logistic多元回归分析发现化疗方案和髂骨V 30是影响急性骨髓抑制发生的高危因素,使用受试者工作特征曲线（receiver operating characteristic,ROC ）确定髂骨V 30的界值为44% 。结论:急性骨髓抑制是受多因素综合影响的结果,在直肠癌患者治疗中应综合考虑肿瘤局部控制率和急性骨髓抑制的关系,优选化疗方案,且髂骨V 30控制在44% 以下。      

宫颈癌同步放化疗期间骨髓抑制的特点及影响因素分析

目的:分析宫颈癌同步放化疗期间骨髓抑制的特点及影响因素,为临床提供参考数据。方法:回顾性分析2015年1月至2018年6月期间行同步放化疗的FIGO Ib1-IVa期宫颈癌患者,均接受外照射+腔内放疗+顺铂同期化疗。根据CTCAE 4.03评价骨髓抑制。结果:60例患者,III-IV度白细胞、中性粒细胞、血红蛋白及II-IV度血小板减少比例分别为53.3%、35.0%、20.0%及33.3%。严重骨髓抑制最早出现在放疗开始的第3周,最低值平均出现在放疗开始的第6周。骨盆椎体剂量体积参数与骨髓抑制无关。治疗前的血红蛋白及血小板水平与治疗期间的骨髓抑制相关。ROC曲线确定治疗前血红蛋白低于119.5 g/L或血小板低于351×109/L更可能发生严重骨髓抑制。治疗期间的骨髓抑制不影响放疗但减少同期化疗剂量（P=0.009）。结论:宫颈癌同期放化疗期间的骨髓抑制与基线血红蛋白及血小板水平相关,与骨盆椎体剂量体积参数无关。骨髓抑制不影响放疗但减少同期化疗剂量。基于患者临床特征及骨髓抑制特点制定的个体化监测方案将有助于患者顺利完成治疗。     

宫颈癌术后保护骨髓的调强放疗剂量学研究

背景与目的:同步放化疗已成为有高危因素的宫颈癌术后患者的标准治疗,与单纯放疗相比,同步放化疗确实提高了疗效,但同时也增加了血液学不良反应。本研究通过比较对骨髓进行限量的调强放疗(bone marrow-sparing intensity-modulated radiotherapy,BMS-IMRT)与未对骨髓进行限量的调强放疗(conventional intensity-modulated radiotherapy,IMRT)、三维适形放疗(three-dimension conformalradiation therapy,3D-CRT)在宫颈癌根治术后患者靶体积覆盖及危及器官(organ at risk,OAR)保护方面的差异,确定BMS-IMRT的剂量学优势。方法:对10例宫颈癌根治术后患者分别设计出3D-CRT(四野盒式)、IMRT和BMS-IMRT的3种治疗计划并比较靶区及危及器官剂量分布。靶区处方剂量均为45 Gy,危及器官包括骨髓、小肠、膀胱、直肠和股骨头。所有计划在Pinnacle3(Version 9.2 f)治疗计划系统上完成,最终的剂量计算采用串筒卷积迭加算法进行。结果:3组的靶区覆盖率相似(P>0.05)。BMS-IMRT组的骨髓V5、V10、V20、V30及V40均低于3D-CRT组(P<0.05),且V20、V30、V40低于IMRT组(P<0.05),而BMS-IMRT组与IMRT组小肠、膀胱、直肠的受量差异无统计学意义(P>0.05)。结论:对于宫颈癌术后患者,BMS-IMRT计划在降低骨髓剂量方面优于IMRT和3D-CRT。宫颈癌术后放疗计划设计中增加骨髓的限量有助于降低急性骨髓抑制的发生率。     

限定骨髓剂量的调强放疗对减轻同期放化疗急性血液毒性的研究进展

同期放化疗是目前部分腹盆腔肿瘤的标准治疗,比如大肿块宫颈癌^[1]、Ⅱ期和Ⅲ期直肠癌^[2]、肛管癌^[3-4]、局部晚期胃癌^[5-6]。但是,在增加疗效的同时急性血液毒性(hematologic toxicity,HT)也显著增加^[7-9],并进而增加了感染、输血、使用集落刺激因子机会和延长住院时间。更主要的是,严重的骨髓(bone marrow,BM)抑制还会延迟或中断化疗和放疗的实施^[7-9],有可能降低疗效。此外,局部晚期患者的疗效仍不乐观,可能需要加强治疗强度。因此,如果能降低血液毒性,可能会使患者接受更强的同期放化疗,以期进一步改善疗效。调强放疗(intensity-modulated radiation therapy,IMRT)在提高靶区剂量和降低正常组织剂量方面相对于常规放疗具有绝对优势^[10,11]。既往研究显示盆腔肿瘤接受IMRT时,骨盆BM和腰骶椎BM接受10、20 Gy照射体积(V₁₀、V₂₀)与发生急性HT明显相关^[3,12-14]。因此,减少BM受量体积可减少HT发生和严重程度。因此,运用IMRT剂量学优势,定量研究BM保护IMRT(BM-sparing IMRT,BMS-IMRT)以减轻同期放化疗不良反应是目前研究的热点。     

骨髓保护调强放疗与宫颈癌患者血液学不良反应的相关性

目的 探讨宫颈癌患者在接受同步放化疗时骨盆骨髓保护与急性血液不良反应的关系及与其相关的剂量指标.方法 选取进行治疗的宫颈癌患者300例,其中接受同步放化疗的患者174例,接受单纯放疗的患者126例.在对患者进行放疗前,勾画每位患者的骨盆骨髓,计算患者骨盆骨髓受到10、20、30、40、50 Gy照射的体积百分数和骨髓受照的平均剂量.研究宫颈癌患者骨髓照射体积及平均剂量与急性血液不良反应发生率的关系,并采用多因素Logistic回归分析比较患者的年龄、性别、肿瘤部位、手术方式、病理类型与急性血液不良反应的关系.结果 患者骨盆骨髓受到10、20、30、40、50 Gy照射的体积中位数分别为91.24％、82.05％、60.54％、37.75％、13.35％,骨盆骨髓平均受照剂量为34.10 Gy.接受单纯放疗的126例宫颈癌患者中,发生1～4级急性血液不良反应的患者分别为45例、58例、15例、8例;接受同步放化疗的174例患者中,发生1～4级急性血液不良反应的患者分别为35例、76例、54例、9例.V10≥90％、V20≥75％、V30≥59.2％、V40≥37％及骨盆骨髓平均受照剂量≥34.10 Gy的宫颈癌患者急性血液不良反应发生率均高于V10﹤90％、V20﹤75％、V30﹤59.2％、V40﹤37％及骨盆骨髓平均受照剂量﹤34.10 Gy的宫颈癌患者,差异均有统计学意义(P﹤0.05).患者的年龄、性别、肿瘤部位、病理类型及V10、V20、V30、V40是接受放疗患者急性血液不良反应的影响因素.结论 V10≥90％、V20≥75％、V30≥59.2％、V40≥37％的宫颈癌患者急性血液不良反应的发生率较高,V10、V20、V30、V40可以对接受放化疗的患者发生急性血液不良反应进行预测.     

骨盆骨髓剂量限定调强放疗同步化疗治疗淋巴结阳性宫颈癌患者的剂量学研究

目的 比较骨盆骨髓剂量限定调强放疗(PBMS-IMRT)和调强放疗(IMRT)治疗淋巴结阳性宫颈癌患者的剂量学参数及血液不良反应.方法 将40例ⅡA～ⅣB期盆腹淋巴结阳性宫颈癌初治患者按照随机数字表法分为PBMS-IMRT组和IMRT组,每组20例,对PBMS-IMRT组患者进行骨盆剂量限制,IMRT组不进行骨盆剂量限制,两组放疗后均进行同步化疗.观察两组患者的靶区剂量学参数、危及器官剂量学参数、骨盆剂量学参数及血液不良反应.结果 PBMS-IMRT组患者计划肿瘤体积(PTV)靶区剂量中不均匀指数(HI)与适形指数(CI)均高于IMRT组,差异均有统计学意义(P﹤0.05).PBMS-IMRT组患者膀胱平均剂量(Dmean)低于IMRT组,差异有统计学意义(P﹤0.05).PBMS-IMRT组患者骨盆最大剂量(Dmax)、Dmean、最小剂量(Dmin)及V5、V10、V20、V30、V40、V50均低于IMRT组,差异均有统计学意义(P﹤0.05).PBMS-IMRT组患者血液不良反应发生情况明显优于IMRT组,差异有统计学意义(P﹤0.01).结论 PBMS-IMRT同步化疗治疗淋巴结阳性宫颈癌患者能有效提高靶区的适形度,且对其他危及器官的受量无明显影响,通过进行骨盆剂量限制,明显降低血液不良反应发生率.     

乳腺癌改良根治术后放疗胸骨剂量参数与急性血液学毒性的关系

摘 要：［目的］ 研究乳腺癌改良根治术后放疗胸骨剂量学参数与急性血液学毒性的关系。 ［方法］回顾性分析 2015年12月至 2019年5月于河北省人民医院行乳腺癌改良根治术后放疗的56例患者的临床资料，在剂量体积直方图（dose-volume histogram，DVH）上记录胸骨的V5、V10、V20、V30、V40、Dmean、Dmax、D20、D40、D60、D80，记录患者血液学指标，并进行血液学毒性分级，评价患者胸骨剂量参数与急性血液学毒性的关系。［结果］ 胸骨的V20、V30与≥2级的急性血液学毒性发生相关；胸骨V10、V20、V30、V40、D60、D80与≥2级白细胞毒性发生相关。胸骨V30是≥2级急性血液学毒性发生的独立危险因素（P=0.037）；胸骨V40、D80是≥2级白细胞毒性发生的独立危险因素（P=0.039，P=0.033）。当胸骨V30≥24.38cm3时，≥2级急性血液学毒性发生率明显升高（52% vs 8%，P=0.001），当胸骨V40≥6.48cm3时，≥2级白细胞毒性发生率明显升高（61% vs 32%，P=0.035）。此外，ki-67阳性率越高、化疗—放疗时间间隔越小越容易发生≥2级中性粒细胞毒性（P=0.016，P=0.038）。进一步研究影响胸骨剂量的因素得出体重指数（body mass index，BMI）、胸廓比与胸骨V40剂量呈负性相关。［结论］ 对于乳腺癌改良根治术后行辅助放疗的患者，降低胸骨受照剂量可减少 2 级及以上急性血液学毒性的发生。某些临床因素也会影响急性血液学毒性，要引起足够的重视。     

螺旋断层放疗与常规放疗在全脑全脊髓放疗中的急性血液学毒性比较北大核心CSCD

目的比较螺旋断层放疗和常规放疗在全脑全脊髓放疗中引起的急性血液学毒性。方法回顾性分析70例全脑全脊髓放疗患者放疗期间的急性血液学资料,按治疗技术分为螺旋断层放疗组(HT组14例)和常规放疗组(CRT组56例),参照CTCAE v3.0不良反应评价标准观察患者放疗期间急性血液学毒性情况并比较两组骨髓抑制情况,组间差异性比较采用χ2检验。结果放疗期间HT组和CRT组白细胞、血小板及血红蛋白下降发生率分别为100%、100%、78.6%及91.1%、67.9%、32.1%(P<0.05);两组Ⅲ~Ⅳ度白细胞、血小板、血红蛋白减低的发生率分别为85.7%、50%、14.2%及35.8%、10.7%、0(P<0.05);HT组和CRT组各有92.8%(10/14)和10.7%(6/56)的患者因骨髓抑制延误放疗(P<0.05);HT组平均出现骨髓抑制时间为11.50天,CRT组为17.37天(P<0.05)。放疗前化疗患者较未化疗患者骨髓抑制严重。结论全脑全脊髓螺旋断层放疗骨髓抑制较常规放疗发生率高、程度重,临床需引起重视,可能与骨髓、全身低剂量照射范围及剂量、化疗等因素相关,需进一步研究。     

Association between bone marrow dosimetric parameters and acute hematologic toxicity in anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiotherapy

PURPOSE: To test the hypothesis that the volume of pelvic bone marrow (PBM) receiving 10 and 20 Gy or more (PBM-V(10) and PBM-V(20)) is associated with acute hematologic toxicity (HT) in anal cancer patients treated with concurrent chemoradiotherapy. METHODS AND MATERIALS: We analyzed 48 consecutive anal cancer patients treated with concurrent chemotherapy and intensity-modulated radiation therapy. The median radiation dose to gross tumor and regional lymph nodes was 50.4 and 45 Gy, respectively. Pelvic bone marrow was defined as the region extending from the iliac crests to the ischial tuberosities, including the os coxae, lumbosacral spine, and proximal femora. Endpoints included the white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, and platelet count nadirs. Regression models with multiple independent predictors were used to test associations between dosimetric parameters and HT. RESULTS: Twenty patients (42%) had Stage T3-4 disease; 15 patients (31%) were node positive. Overall, 27 (56%), 24 (50%), 4 (8%), and 13 (27%) experienced acute Grade 3-4 leukopenia, neutropenia, anemia, and thrombocytopenia, respectively. On multiple regression analysis, increased PBM-V(5), V(10), V(15), and V(20) were significantly associated with decreased WBC and ANC nadirs, as were female gender, decreased body mass index, and increased lumbosacral bone marrow V(10), V(15), and V(20) (p < 0.05 for each association). Lymph node positivity was significantly associated with a decreased WBC nadir on multiple regression analysis (p < 0.05). CONCLUSION: This analysis supports the hypothesis that increased low-dose radiation to PBM is associated with acute HT during chemoradiotherapy for anal cancer. Techniques to limit bone marrow irradiation may reduce HT in anal cancer patients.     

Dosimetric predictors of acute hematologic toxicity in cervical cancer patients treated with concurrent cisplatin and intensity-modulated pelvic radiotherapy

PURPOSE: To identify dosimetric parameters associated with acute hematologic toxicity (HT) and chemotherapy delivery in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated pelvic radiotherapy. METHODS AND MATERIALS: We analyzed 37 cervical cancer patients receiving concurrent cisplatin (40 mg/m(2)/wk) and intensity-modulated pelvic radiotherapy. Pelvic bone marrow (BM) was contoured for each patient and divided into three subsites: lumbosacral spine, ilium, and lower pelvis. The volume of each region receiving 10, 20, 30, and > or =40 Gy (V(10), V(20), V(30), and V(40), respectively) was calculated. HT was graded according to the Radiation Therapy Oncology Group system. Multivariate regression models were used to test associations between dosimetric parameters and HT and chemotherapy delivery. RESULTS: Increased pelvic BM V(10) (BM-V(10)) was associated with an increased Grade 2 or worse leukopenia and neutropenia (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.24-3.53; p = 0.006; and OR, 1.41; 95% CI, 1.02-1.94; p = 0.037, respectively). Patients with BM-V(10) > or =90% had higher rates of Grade 2 or worse leukopenia and neutropenia than did patients with BM-V(10) <90% (11.1% vs. 73.7%, p < 0.01; and 5.6% vs. 31.6%, p = 0.09) and were more likely to have chemotherapy held on univariate (16.7% vs. 47.4%, p = 0.08) and multivariate (OR, 32.2; 95% CI, 1.67-622; p = 0.02) analysis. No associations between HT and V(30) and V(40) were observed. Dosimetric parameters involving the lumbosacral spine and lower pelvis had stronger associations with HT than did those involving the ilium. CONCLUSION: The volume of pelvic BM receiving low-dose radiation is associated with HT and chemotherapy delivery in cervical cancer patients undergoing concurrent chemoradiotherapy.     

MRI指导骨髓保护IMRT对直肠癌同期放化疗血液不良反应影响

目的 通过IMRT降低直肠癌患者放疗区域造血活性骨髓的受照射剂量,以其减轻在同期放化疗期间的急性血液不良反应。方法 前瞻性入组直肠癌初治患者,根据盆腔核磁图像确定造血活性骨髓分布并勾画,并对其进行剂量限定(V₅<95%,V₁₀<90%,V₂₀<80%,V₃₀<65%),新辅助治疗方案为IMRT同期化疗(95%PTV₅₀ Gy分25次,2 Gy/次),同期每周奥沙利铂50 mg/m²,卡培他滨每天1650 mg/m²(放疗期间每天2次)。结果 共 35例Ⅱ、Ⅲ期患者完成入组和治疗方案。2-4级血液学不良反应发生率为31%,其中白细胞减少发生率为26%(9例)、中性粒细胞减少发生率为17%(6例)、红细胞减少发生率为3%(1例)、血小板减少发生率为3%(1例)。多元Logistic线性回归分析表明造血活性骨髓 V₅与白细胞、中性粒细胞和血小板最低值均显著相关(P=0.005、0.002、0.017)。结论 根据MR确定的骨盆造血活性骨髓受量与直肠癌患者新辅助同期放化疗急性血液不良反应发生率和严重程度明显相关。临床试验注册 ClinicalTrials.gov,注册号:NCT01863420。     

Lumbosacral spine and marrow cavity modeling of acute hematologic toxicity in patients treated with intensity modulated radiation therapy for squamous cell carcinoma of the anal canal

PurposeTo identify various dosimetric parameters of bone marrow cavity that correlate with acute hematologic toxicity (HT) in patients with anal squamous cell carcinoma treated with definitive chemoradiation therapy (CRT).Methods and materialsWe analyzed 32 patients receiving CRT. The whole pelvic bone marrow (PBM) and the lumbosacral spine (LSS) subregion were contoured for each patient. Marrow cavities were contoured using the Hounsfield units (HUs) of 100, 150, 200, and 250 as maximum density threshold levels. The volume of each region receiving at least 5, 10, 15, 20, 30, and 40 Gy was calculated. The endpoint was grade ≥ 3 HT (HT3 +). Normal-tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. Maximal likelihood estimate was used to compare the parameter set. Logistic regression was used to test associations between HT and both dosimetric and clinical parameters.ResultsTen patients (31%) experienced HT3 +. While dose to both LSS and PBM significantly predicted for HT3 +, LSS was superior to PBM by logistic regression and LKB modeling. Constrained optimization of the LKB model for HT3 + yielded the parameters m = 0.21, n = 1, and TD₅₀ = 32 Gy for LSS. The NTCP fits were better with the whole bone than with marrow cavity using any HU threshold. Mean LSS doses of 21 Gy and 23.5 Gy result in a 5% and 10% risk of HT3 +, respectively. Mean dose and low-dose radiation parameters (V5, V10, V15, V20) of whole bone or bone cavities of LSS were correlated most significantly with HT3 +.ConclusionsFor predicting the risk of HT3 +, whole-bone contours were superior to marrow cavity and LSS was superior to PBM by LKB modeling. The results confirm PBM and LSS as parallel organs when predicting hematologic toxicity. Recommended dose constraints to the LSS are V10 ≤80%. An LSS mean dose of 23.5 Gy is associated with a 10% risk of HT.     

PBMS-IMRT对降低同步放化疗盆腔肿瘤患者血液不良反应研究的新进展

对晚期盆腔肿瘤患者采用同步放化疗可以提高其生存率,但血液等不良反应明显增多,常导致患者不能耐受而中断治疗。限定盆骨骨髓调强放疗(PBMS-IMRT)在降低盆骨骨髓照射剂量和体积方面具有明显优势,本文就PBMS-IMRT与其他照射方式的比较、放疗剂量学参数与血液不良反应的相关性以及勾画精确活性骨髓的影像学方法进行综述。     

Acute esophageal toxicity in non-small cell lung cancer patients after high dose conformal radiotherapy.

BACKGROUND AND PURPOSE: To correlate acute esophageal toxicity with dosimetric and clinical parameters for non-small cell lung cancer (NSCLC) patients treated with radiotherapy (RT) alone or with chemo-radiotherapy (CRT). PATIENTS AND METHODS: We analyzed the data of 156 patients with medically inoperable or locally advanced NSCLC. Seventy-four patients were irradiated with high dose RT only, 45 patients with sequential CRT (Gemicitabine/Cisplatin) and 37 patients with concurrent CRT (Cisplatin daily 6 mg/m(2)). The radiation dose delivered ranged from 49.5 to 94.5 Gy (2.25-2.75 Gy per fraction) with an overall treatment time of 5-6 weeks. For all patients the maximal acute esophageal toxicity (RTOG/EORTC criteria) was scored and related to dose-volume parameters, as well as to clinical and treatment-related parameters. All parameters were tested univariable and multivariable in a binary logistic regression model. The toxicity data of a homogeneous subgroup was fitted to the Lyman-Kutcher-Burman model. RESULTS: Grade 2 acute esophageal toxicity or higher occurred in 27% (n=42) of the patient population of which nine patients developed grade 3 toxicity and one patient grade 4. All 10 patients with grade>or=3 esophageal toxicity received concurrent CRT. At multivariable analysis, the most significant clinical parameter to predict acute esophageal toxicity was the concurrent use of CRT. The most significant dosimetric parameter was the esophagus volume that received at least 35 Gy. The data of the patients who did not receive concurrent CRT were well described by the Lyman-Kutcher-Burman normal tissue complication probability model. The optimal fit of the data of non-concurrent treated patients to this model was obtained using the following values for the parameters: TD(50)=47 Gy (41-60 Gy), n=0.69 (0.18-6.3) and m=0.36 (0.25-0.55) where the numbers between brackets denote the 95% confidence interval. Acute esophageal toxicity was not significantly increased for patients treated with sequential CRT. CONCLUSION: Both concurrent CRT and the volume that receives at least 35 Gy were predictors of acute esophageal toxicity.     

盆腔肿瘤IMRT下骨髓剂量-体积参数与急性血液学毒性相关性研究进展

盆腔恶性肿瘤同期放化疗期间发生骨髓抑制的风险较高,盆腔受照射骨髓(骼)的剂量-体积关系与放化疗期间的急性血液学毒性存在相关,但缺乏此方面公认的参数。盆腔不同部位骨髓(骼)造血能力具有异质性,靠近体中轴的盆腔骨髓造血能力最强,即功能性骨髓。找准盆腔功能性骨髓的剂量-体积参数与盆腔恶性肿瘤放化疗期间急性血液学毒性的关系也许是今后发展方向。     

Dosimetric predictors of acute hematologic toxicity during concurrent intensity-modulated radiotherapy and chemotherapy for anal cancer

Purpose

This study aimed at investigating whether the irradiated volume of pelvic bone marrow (PBM) and specific subsites may predict the occurrence of acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation.

Methods

50 patients, submitted to IMRT and concurrent chemotherapy, were analyzed. Several bony structures were defined on planning-CT: PBM and lumbar-sacral (LSBM), lower pelvis (LPBM) and iliac (IBM) bone marrow. On dose-volume histograms, dosimetric parameters were taken. Endpoints included white blood-cell-count (WBC), absolute-neutrophil-count (ANC), hemoglobin (Hb) and platelet nadirs and acute hematologic toxicity (HT) according to RTOG scoring scale. Generalized linear modeling was used to find correlations between dosimetric variables and blood cell nadirs, while logistic regression analysis was used to test correlation with ≥G3 HT. Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the optimal cut-off points for predictive dosimetric variables with the Youden method.

Results

Maximum detected acute HT comprised 38 % of ≥G3 leukopenia and 32 % of ≥G3 neutropenia. Grade 2 anemia was observed in 4 % of patients and ≥G3 thrombocytopenia in 10 %. On multivariate analysis a higher PBM-V ₂₀ was associated with lower WBC nadir. Increased LSBM-V ₄₀ was correlated with a higher likelihood to develop ≥G3 HT. A cut-off point at 41 % for LSBM-V ₄₀ was found. Patients with LSBM-V ₄₀ ≥41 % were more likely to develop ≥G3 HT (55.3 vs. 32.4 %; p < 0.01).

Conclusions

Increased low-dose to pelvic bony structures significantly predicted for WBC decrease. Medium–high dose to specific osseous subsites was associated with a higher probability of HT. LSBM-V ₄₀ was a strong predictor of ≥G3 HT. A threshold at 41 % for LSBM-V ₄₀ could be used to limit HT.

     

Predicting severe hematologic toxicity from extended-field chemoradiation of para-aortic nodal metastases from cervical cancer

Purpose

The purpose of this study was to determine factors predictive for severe hematologic toxicity (HT) in cervical cancer patients with para-aortic lymph node metastasis treated with concurrent cisplatin chemoradiation to an extended field (EFCRT).