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。     

直肠癌术前IMRT同期化疗与VMAT同期化疗的急性不良反应比较

目的 比较静态IMRT和VMAT用于直肠癌术前同期放化疗的急性不良反应及耐受性。方法 2006—2013年共 242例患者接受IMRT或VMAT同期化疗,VMAT组 61例,IMRT组 181例(其中简化IMRT 137例,7个野IMRT 44例)。全组均予盆腔放疗5OGy分25次5周完成,同期化疗连用5周(卡培他滨每天1650 mg/m²,奥沙利铂每周50 mg/m²)。组间差异行χ²检验。结果 全组因不良反应中断放疗者7.9%,VMAT和IMRT组相当(4.9%∶8.8%,P=0.325),IMRT组中简化IMRT和7个野IMRT的也相近(8.0%∶11.4%,P=0.498)。全组最常见急性不良反应为白细胞下降(69.4%,≥3级5.8%)、腹泻(65.5%,≥3级20.7%)、放射性皮炎(62.0%,≥3级7.9%),其中VMAT和IMRT组的相当(68.9%∶69.6%,P=0.911;63.9%∶67.4%,P=0.620;65.6%∶60.8,P=0.504),只有VMAT组体重下降低于IMRT组(3.3%∶12.7%,P=0.036)。IMRT组中简化IMRT和7个野IMRT组的急性不良反应也相近(70.0%∶65.9%,P=0.539;68.66%∶63.6%,P=0.540;8.0%∶9.1%,P=0.824),但≥3级不良反应中简化IMRT组的呕吐明显好于7个野IMRT组(0: 6.8%,P=0.002)。 结论 直肠癌术前同期放化疗采用不同调强技术的耐受性良好、急性不良反应基本相当,IMRT技术间的个别不良反应差别有待探索。     

直肠癌术前IMRT技术的临床应用进展

对近10年来20余篇有关直肠癌术前放疗文献进行阅读,以了解IMRT在直肠癌术前应用情况,并探讨IMRT作为直肠癌术前常规放疗技术的临床应用价值。     

局部中晚期直肠癌术前新辅助同期加量IMRT联合术前化疗的Ⅱ期临床研究

目的 观察评估局部中晚期直肠癌术前SIB-IMRT联合1周期卡培他滨诱导化疗联合全直肠系膜切除术治疗方案的可行性、安全性及疗效。方法 2015-2016年入组37例局部中晚期直肠癌患者接受术前放疗,直肠病变及阳性淋巴结给予58.75 Gy分25次,盆腔淋巴引流区给予50.00 Gy分25次,同步卡培他滨化疗。同步放化疗结束后休息1周继续行1周期卡培他滨诱导化疗。同步放化疗结束后6~8周接受直肠癌根治术。研究主要终点为pCR,次要终点为TN降期率、保肛手术率、不良反应等。结果 37例患者顺利完成术前同步放化疗,32例行手术治疗,4例因症状缓解拒绝手术,1例患者因肛周水肿手术延迟。pCR率为34%(11/32),TN降期率为91%(29/32),R₀切除率为100%,保肛手术率为75%(24/32)。放化疗期间大部分为1、2级急性不良反应,3、4级不良反应共3例。术后并发症为输尿管损伤(1例)和肠梗阻(1例),围手术期内未见死亡。结论 局部中晚期直肠癌行术前SIB-IMRT联合1周期卡培他滨术前化疗及全直肠系膜切除术方案的初步结果表明其近期疗效好、安全可行、急性不良反应轻。     

直肠癌IMRT中不同体位对靶区剂量覆盖影响

目的 探讨直肠癌IMRT中仰卧位和俯卧位对靶区剂量覆盖的影响,为直肠癌IMRT体位的选择提供参考。方法 选取24例接受术后辅助放疗的直肠癌患者,仰卧位和俯卧位各12例。所有患者在治疗前和治疗过程中(第1—4周)各扫描一组定位CT,分别定义为Plan、1W、2W、3W、4W。基于不同CT影像图像分别勾画OAR。PlanCT与第1—4周CT分别进行图像融合,将PlanCT的CTV和PTV分别拷贝至第1—4周CT上,将基于PlanCT的治疗计划分别拷贝至第1—4周CT,评估靶区处方剂量覆盖率并计算靶区剂量覆盖不合格率,同时在医科达MOSAIQ网络中读取每例患者每次治疗时加速器治疗床位置数据并计算床位总体偏差值。成对t检验比较2组数据差异,Pearson检验进行相关性分析。结果 在治疗过程中俯卧位患者的CTV、PTV靶区剂量覆盖不合格率高于仰卧位(19%：0%,70%：54%),总体偏差值与靶区剂量覆盖率存在显著相关性(r=-0.683,P=0.000)。俯卧位患者的总体偏差值为(1.23±0.76) cm明显大于仰卧位患者的(0.28±0.18) cm (P=0.001),其中y、z轴向偏差最为明显(P=0.003、0.003)。俯卧位患者小肠V5、V10明显小于仰卧位患者(P=0.003、0.004),其慢性不良反应也明显较少(P=0.041)。结论 直肠癌IMRT患者选择仰卧位能保持较好的靶区剂量覆盖率,而俯卧位因使用腹板装置会导致体位重复性变差,进而影响靶区剂量覆盖。尽管俯卧位联合腹板可以减少小肠耐受剂量,但应采取有效的保证患者体位重复性的措施。     

局部晚期直肠癌同期放化疗的多中心随机临床研究

目的 观察两种不同化疗方案同期联合三维适形放疗对局部晚期(不可手术)直肠癌患者的治疗依从性及疗效,并比较两组间差异.方法 76例经病理证实的局部晚期或局部.区域复发直肠癌患者,随机分为奥沙利铂组和卡培他滨组,两组患者均接受了全盆腔三维适形放疗D_T 46～50 Gy分23～25次,后缩野至肿瘤区继续推量至D_T 64～66 Gy分32～33次.前者同期接受奥沙利铂130 mg/m~2第1天,氟尿嘧啶350 mg/m~2第1～5天,甲酰四氢叶酸200 mg/m~2第1～5天,每4周为1个周期,共2个周期;后者接受卡培他滨1650 mg/(m~2·d),分2次口服,第1～14天,每3周为1个周期,共2个周期.结果 中位随访19个月.奥沙利铂组和卡培他滨组患者的总有效率、中位生存时间、1年生存率、2年总生存率分别为64%、22个月、68%、21%和58%、18个月、63%、19%,两组间差异无统计学意义(χ~2=0.08,P=0.772;u=17.71,P=0.077;χ~2=0.97,P=0.326).两组患者均无3级以上毒副反应发生,其中卡培他滨组在中性粒细胞减少、腹泻、恶心呕吐和周围神经系统一级及以上毒副反应发生率均明显低于奥沙利铂组,分别为39.5%:77.7%(z=-3.97,P=0.000)、47.4%:88.9%(z=-4.78,P=0.000)、68.4%:97.2%(z=-3.17,P=0.000)和5.3%:66.7%(z=-6.56,P=0.000).结论 同期放化疗是局部晚期(不可手术)直肠癌患者较理想的治疗方法,其治疗依从性高,疗效确切,值得临床进一步推广.     

鼻咽癌HT与IMRT急性不良反应比较

目的 比较鼻咽癌螺旋断层放疗(HT)和调强放疗(IMRT)的急性不良反应。方法 对2016年收治的100例鼻咽癌放疗患者进行回顾分析,HT组50例,IMRT组50例。全部患者均予以同步放化疗,放疗选用6MV X线照射,剂量为68.2~73.8Gy分30~34次。采用RTOG评分标准分别对皮肤、口腔黏膜、唾液腺及下咽/食管的急性不良反应进行评价。配对t检验两组差异。结果 两组靶区剂量PTVnx、PTVnd(左)及PTVnd(右)均相近(P>0.05),HT组危及器官剂量低于IMRT组(P<0.05)。HT组不良反应发生率分别为皮肤0级14%、1级68%、2级18%,口腔黏膜0级10%、1级54%、2级36%;唾液腺1级74%、2级26%,下咽/食管0级10%、1级60%、2级28%、3级2%。IMRT组的分别为皮肤1级52%、2级48%;口腔黏膜1级58%、2级42%,唾液腺1级28%、2级72%,下咽/食管1级40%、2级60%。HT组皮肤、唾液腺和下咽/食管急性不良反应优于IMRT组(P<0.05),口腔黏膜反应相近(P>0.05)。HT组仅皮肤反应发生时间比IMRT组晚(P<0.05),其他相近(P>0.05)。结论 HT和IMRT均能满足鼻咽癌放疗靶区剂量分布要求,但在危及器官保护和急性不良反应程度及出现时间上HT更具优势。     

直肠癌术后IMRT±化疗疗效及预后分析

目的 探讨直肠癌术后IMRT±化疗的疗效及预后影响因素。方法 回顾分析2009—2013年间218例直肠癌术后IMRT患者的临床资料。共208例(95.4%)患者进行了化疗, 方案以氟尿嘧啶为主。采用Kaplan-Meier法计算生存率, Logrank检验和单因素预后分析, Cox模型多因素预后分析。结果 随访率97.7%。1、3年OS率分别为90.8%、75.2%, DFS率分别为85.3%、70.5%, LRFS率分别为96.7%、88.1%。全组3—4级急性不良反应发生率为28.4%, 主要表现为3级白细胞减少(13.8%)和腹泻(11.0%)。单因素预后分析表明术前CEA、CA199水平、肿瘤最大径、肿瘤部位、分化程度、肿瘤浸润深度、淋巴结转移数、TNM分期、神经侵犯、手术方式、TME、术前肠梗阻和术前贫血为影响因素(P=0.006、0.000、0.000、0.017、0.000、0.016、0.000、0.011、0.001、0.001、0.006、0.037和0.010);多因素预后分析显示术前CEA水平、肿瘤部位、TNM分期、术前肠梗阻和术前贫血为影响因素(P=0.000、0.000、0.000、0.001和0.001)。结论 直肠癌术后IMRT±化疗疗效肯定, 不良反应轻, 治疗依从性较高。术前CEA水平、肿瘤部位、TNM分期、术前肠梗阻和术前贫血为预后影响因素。     

局部晚期直肠癌术前同期放化疗临床及病理降期效果的探讨

目的:探讨局部晚期直肠癌术前同期放化疗后临床及病理降期情况及其相关影响因素.方法:回顾性分析30例行术前同期放化疗的局部晚期直肠癌患者的临床资料,放疗采取三维适形放疗技术,同期化疗为奥沙利铂与卡培他滨联合方案.评价其术前临床及术后病理降期效果并分析相关影响因素. 结果:术前临床评价T分期降期率达73.3%(22/30),17例N+患者10例淋巴结完全消退;术后病理发现,14例患者T分期下降,降期率为46.7%,其中5例患者达pCR,完全缓解率为16.7%(5/30).单因素分析显示,放疗后继续服用卡培他滨及放疗至手术间歇期长者肿瘤降期率高.除1例放疗期间出现膀胱瘘者,仅1例出现Ⅲ级造血系统毒副反应,未见Ⅳ级毒副反应.结论:局部晚期直肠癌术前同期放化疗耐受性良好,有效率高,更加合理的同期化疗需更进一步的临床试验证实.     

直肠癌IMRT中腹膜腔限量取代肠管限量保护小肠的可行性研究

目的 在直肠癌IMRT过程中,通过比较腹膜腔(PS)和小肠肠管(BL)两种限量条件下的小肠剂量体积和正常组织并发症概率(NTCP),探讨PS限量取代BL限量保护小肠的可行性。方法 选取接受术后辅助放疗的直肠癌患者24例,仰卧和俯卧体位各12例。患者在治疗前和疗程中1~4周各扫描一组CT分别定义为Plan、1周、2周、3周、4周,在每组CT影像上分别勾画PS和BL轮廓。在Plan CT上根据PS、BL两种限量方法分别设计IMRT计划P_PS、P_BL,然后拷贝至1~4周 CT,分别评估每组CT上P_PS、P_BL两种计划的小肠剂量体积和NTCP。结果 24例患者共扫描109套CT影像,设计并拷贝计划218组。PS、BL体积中位数分别为1339.28、250.27 cm³,基于Plan CT两种计划(P_PS、P_BL)的PS和肠管V₁₅中位数分别为918.96、199.57 cm³。基于所有CT影像P_PS计划的小肠剂量体积绝大部分都小于P_BL计划,其中V₁₅为170.07 cm³∶178.58 cm³(P=0.000),两者存在显著相关性(P=0.000)。P_PS计划的慢性、急性不良反应NTCP均明显小于P_BL计划(2.80%∶3.00%,P=0.018;57.32%∶58.64%,P=0.000)。仰卧和俯卧两种体位患者中P_PS计划的绝大部分小肠剂量体积和NTCP都小于P_BL计划,其中V₁₀、V₁₅、V₃₀和急性不良反应NTCP的P值均<0.05。结论 在直肠癌IMRT中将PS限量方法取代BL限量来保护小肠是可行的,可以参考V₁₅<830 cm³作为其剂量限制目标函数。     

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.     

Clinical and dosimetric predictors of acute hematologic toxicity in rectal cancer patients undergoing chemoradiotherapy

Background and purposeTo identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer.Materials and methodsWe analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models.ResultsNadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p = 0.04), and patients ⩾59 years of age had a lower hemoglobin ratio trend during PRT (p = 0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p = 0.03), and women had lower hemoglobin cell count trend compared to men (p = 0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p = 0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p = 0.03) and sacral BM V45 (p = 0.03) were associated with a lower WBC and ANC ratio at nadir, respectively.ConclusionsHT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered.     

调强放疗技术对骨髓的保护作用

调强放疗(IMRT)技术应用于肿瘤放疗日益受到关注.骨髓对射线极其敏感,骨髓功能成像技术提高了放疗的精确性,IMRT技术可有目的地减少骨髓受量,降低骨髓的受照射体积,从而有助于降低放疗后急性骨髓抑制的发生概率,值得在临床推广应用.     

Impact of intensity-modulated radiotherapy on acute hematologic toxicity in women with gynecologic malignancies

: To evaluate the impact of intensity-modulated whole pelvic radiotherapy (IM-WPRT) on acute hematologic toxicity (HT) in gynecology patients.

: Between February 2000 and June 2001, 36 patients (24 cervix, 12 uterus) received IM-WPRT. The target consisted of the upper vagina, parametria, uterus, and presacral and pelvic lymph nodes. Using commercially available software, seven or nine coplanar IM-WPRT plans were generated. The planning goals were to irradiate the target while minimizing the dose to the small bowel, bladder, and rectum. Pelvic bone marrow (BM) was not a constraint in the planning process. The variables analyzed included white blood count (WBC), absolute neutrophil count (ANC), platelets, and hemoglobin (Hgb) obtained before and weekly during RT. As a comparison, the HT in 88 patients (44 cervix, 44 uterus) treated to the same target volume and total dose (45 Gy) with conventional four-field WPRT was analyzed. In addition, the medullary spaces within the pelvic bones in 10 women were contoured and the average dose-volume histograms representing the pelvic BM were compared between the two groups.

: IM-WPRT patients had a lower median age (p = 0.008), higher percentage of squamous histologic features (p = 0.04), and were more likely to receive chemotherapy (CTX) (p = 0.02) than were the WPRT patients. No differences were seen in the baseline WBC, ANC, platelet, or Hgb levels between the two groups. Grade 2 or greater WBC, ANC, and Hgb toxicity was seen in 19.4%, 9.1%, and 8.6% of the IM-WPRT patients, respectively. Comparable rates were seen in the WPRT patients (WBC 21.6%, p = 0.79; ANC 8.3%, p = 0.91; Hgb 9.2%, p = 0.94). No Grade 2 or greater platelet toxicity was seen in either group. Significant HT was infrequent in women treated with RT alone and was comparable in the two groups. In contrast, WPRT + CTX patients experienced more Grade 2 or greater WBC toxicity (60% vs. 31.2%, p = 0.08) and developed lower median WBC (2.8 vs. 3.6 μg/dL, p = 0.05) and ANC (1874 vs. 2669, p = 0.04) nadirs than did IM-WPRT + CTX patients. Moreover, CTX was held more often in the WPRT group secondary to HT (40% vs. 12.5%, p = 0.06). Although Grade 2 or greater ANC (23.5% vs. 15.3%) and Hgb (35.2% vs. 15.2%) toxicity were lower in the IM-WPRT + CTX group, these differences did not reach statistical significance (p = 0.58 and p = 0.22, respectively). The comparison of pelvic BM dose-volume histograms revealed that IM-WPRT planning resulted in significantly less BM volume being irradiated compared with WPRT planning, particularly within the iliac crests.

: IM-WPRT has a favorable impact on the risk of acute HT in gynecology patients, particularly in those receiving CTX. Future work is needed to optimize BM sparing in these patients to reduce the risk of significant HT further.     

直肠癌同步放化疗患者营养状态与放化疗不良反应相关性分析

目的 分析直肠癌同步放化疗患者营养状态与放化疗近期不良反应的相关性。方法 收集2018-2019年间浙江省肿瘤医院收治的115例行同步放化疗的直肠癌患者,同时采用欧洲营养风险筛查工具(NRS 2002)和患者主观整体评估量表(PG-SGA)评估患者放疗期间的营养风险状况,采用美国RTOG及不良反应常见术语标准评估急性放化疗不良反应。Spearman′s分析营养状态与放化疗急性不良反应相关性。结果 从放化疗开始前到放化疗第4周患者的营养风险呈逐步增加趋势,随后营养风险又逐步下降。NRS 2002评分和PG-SGA评分均与直肠癌放化疗患者血液学不良反应(r=0.26,P<0.05;r=0.31,P<0.01)、上消化道反应(r=0.51,P<0.01;r=0.63,P<0.01)、下消化道反应(r=0.23,P<0.05;r=0.45,P<0.01)、疲劳(r=0.47,P<0.01;r=0.64,P<0.01)均呈正相关,并且PG-SGA和不同不良反应之间的相关性系数大于NRS 2002。分层分析显示Ⅱ-ⅢB期、<65岁及术后辅助放化疗患者,营养状况和不良反应程度显著相关(均P<0.05)。结论 直肠癌患者同步放化疗期间存在较高的营养不良风险,营养不良风险越高患者放化疗急性不良反应通常越大,建议加强直肠癌放化疗期间的动态营养评估及支持。