重组人白细胞介素-11预防化疗所致血小板减少的临床研究

目的　评价国产重组人白细胞介素 11(rhIL 11)预防肿瘤化疗患者血小板减少的疗效及不良反应。方法　采用随机双盲自身交叉对照研究方法 ,将试验药品和安慰剂分为A药和B药 ,入选患者随机分为AB组或BA组。在化疗结束后 2 4h开始用药 ,2 5 μg kg体重 ,皮下注射 ,每日 1次 ,连续用药 7～ 14d或至血小板计数≥ 30 0× 10 9 L。结果　有 118例可评价疗效。rhIL 11可显著升高化疗后血小板最低值和化疗第 2 1天血小板值 ,升高幅度分别达 6 0 .7%和 86 .1% (P <0 .0 0 1) ;治疗周期出现血小板减少 (<10 0× 10 9 L)的持续时间为 1.0± 2 .0d ,而对照周期为 6 .9± 5 .4d。主要不良反应为注射部位疼痛 (2 4 .6 % )、红肿 (16 .1% )、硬结 (11.9% )、结膜充血 (16 .1% )、水肿 (8.5 % )、心悸(6 .8% )、乏力 (5 .1% )等 ,大都程度较轻 ,无其他严重不良反应。结论　rhIL 11具有明显的促血小板生成作用 ,可显著减少肿瘤患者化疗后血小板减少的发生 ,缩短血小板减少的持续时间。不良反应较轻且较易处理。     

基因重组人白细胞介素-11治疗化疗所致血小板减少症临床研究

目的：观察基因重组人白细胞介素-11治疗化疗所至血小板减少症的疗效和不良反应。方法：采用自身对照研究,21例接受GP或GC方案化疗的非小细胞肺癌患者,接受化疗后,当血小板下降至≤50&#215;10^9／L时,治疗周期给予rhIL-11 50μg&#183;kg^-1&#183;d-1,皮下注射,连续用药,当血小板≥100&#215;10^9／L,停药;对照周期单纯用化疗,两个周期化疗结束后评价疗效。结果：治疗周期血小板最低值为（30．58&#177;10．10）&#215;10^9／L,对照周期为（20．36&#177;9．21）109／L（P〈0．005）;血小板恢复至100&#215;10^9／L的时间,治疗周期为3．34天&#177;2．61天,对照周期为5．19天&#177;2．34天（P〈0．005）。治疗周期没有患者出现出血倾向,没有输注血小板,对照周期有6例出现全身皮肤散在出血点,6例输注血小板。不良反应主要是轻度水肿、乏力及感冒样症状等。结论：基因重组人白细胞介素-11治疗化疗所至的血小板减少症疗效确切,不良反应轻,安全。     

白细胞介素-11治疗化疗所致血小板减少的临床观察

化疗是治疗中、晚期癌症患者的主要措施之一，为了提高疗效，临床上有时需要提高治疗强度，增加用药剂量，尤其是对化疗敏感的恶性肿瘤。但是，随着治疗强度的提高，随之而来不同程度的骨髓抑制却无法避免，如急性或迟发性血小板减少症、严重的粒细胞减少症等，这也是造成患者死亡的原因之一。血小板的恢复     

基因重组人白细胞介素-11治疗恶性肿瘤化疗所致血小板减少症的临床探讨

目的观察基因重组人白细胞介素-11(rhIL-11)治疗恶性肿瘤化疗所致血小板减少症的临床疗效及不良反应。方法本组51例患者随机分为治疗组(27例)和对照组(24例)。治疗组病例化疗后外周血血小板计数≤50×109/L时,给予rhIL-11 1.5 mg皮下注射,1/d,连续用药5~14 d,平均9.2 d;当外周血血小板升至≥100×109/L时停用rhIL-11观察血像。对照组病例仅以输注血小板及对症治疗为主。结果治疗组患者应用rhIL-11前后自身比较血小板计数最低值显著升高,差异有显著性(P<0.01);治疗组患者化疗后应用rhIL-11血小板计数最低值较对照组化疗后的最低值显著升高,差异也有显著性(P<0.01);治疗组应用白介素-11后血小板计数低于5.0×109/L的天数比对照组明显缩短,两者比较差异也有显著性(P<0.01)。共治疗27例恶性肿瘤化疗所致的血小板减少症,显效9例(33.3%),有效18例(66.7%)。结论在恶性肿瘤化疗所致的血小板减少症的治疗中,rhIL-11的升血小板作用显著、安全、经济实用。     

重组人白细胞介素-11治疗化疗所致血小板减少的临床观察

目的观察重组人白细胞介素-11(rhIL-11)治疗化疗所致血小板(PLT)减少的疗效和不良反应。方法采用病例自身对照研究,对第1个周期化疗(对照组)后PLT≤70×109／L的32例实体瘤患者,第2个周期(治疗组)采用相同方案化疗,化疗结束后24 h开始,皮下注射rhIL-11 25μg／kg体重,每天1次,连用7～14 d,或至PLT≥100×109／L时停药。结果治疗组化疗后各时点PLT计数均高于对照组。化疗后,治疗组和对照组PLT最低值分别为(110．2±53．5)×109/L和(55．6±46．8)×109／L,两组差异有统计学意义(P<0．01)。PLT恢复正常时间,治疗组为2～18 d,对照组为5-27 d,中位数分别为5 d和12 d,两组差异有统计学意义(P<0．01)。治疗组中PLT输注2例,次数为2次,对照组为7例9次,差异有统计学意义(P<0．01)。乏力、关节肌肉酸痛、注射部位疼痛、头痛、心悸、水肿和发热等不良反应多为Ⅰ度和Ⅱ度,可自行缓解。Ⅲ度不良反应为乏力、关节肌肉酸痛、头痛,对症处理后可缓解。结论rhIL-11是治疗化疗后PLT减少的有效药物,不良反应可以耐受。     

重组人白细胞介素-11治疗化疗后血小板减少的临床研究

目的探讨重组人白细胞介素-11(rhIL-11)治疗化疗后血小板减少症的疗效和用药方法。方法回顾性分析该科2000年2月至2004年9月共38例化疗后出现Ⅲ～Ⅳ度血小板减少患者的治疗效果。对照组18例,用利血生、升血小板胶囊等药物;治疗组20例,用rhIL-11。结果治疗组Plt<50×109/L持续时间(2.5d)明显少于对照组(5.1d),差异有显著性(P<0.01);治疗组血小板恢复正常,既Plt>100×109/L所需时间(5.9d)明显少于对照组(13.5d),差异有显著性(P<0.01);停药后血小板数量并未明显回落,能稳定在正常水平。结论重组人白细胞介素-11(rhIL-11)是一种有效、安全的治疗化疗后血小板减少的药物。     

白细胞介素-11治疗化疗所致血小板减少的临床观察

化疗是治疗中、晚期癌症患者的主要措施之一 ,为了提高疗效 ,临床上有时需要提高治疗强度 ,增加用药剂量 ,尤其是对化疗敏感的恶性肿瘤。但是 ,随着治疗强度的提高 ,随之而来不同程度的骨髓抑制却无法避免 ,如急性或迟发性血小板减少症、严重的粒细胞减少症等 ,这也是造成患者死亡的原因之—。血小板的恢复比中性粒细胞的恢复更缓慢、更困难 ,以往通过不断的输注血小板进行治疗 ,但其最大的危险是日益严重的输血相关性病毒或细菌感染。 1 990年 ,白细胞介素 1 1 (In terleukin 1 1 \IL 1 1 )首次被研究人员克隆 ,并初步证实其对血小板的…     

国产重组人白细胞介素-11治疗恶性肿瘤患者化疗所致血小板减少的临床研究

目的评价rhIL-11(巨和粒)在化疗所致血小板减少治疗中的作用。方法将65例化疗后血小板减少的患者随机分为对照组(33例):予常规止血及对症、支持治疗;试验组(32例):除与对照组同样治疗外,加皮下注射巨和粒1.5mg/次,1次/d,比较两组治疗后外周血血小板计数变化及出血症状改善情况。结果试验组血小板计数回升、出血症状的改善较对照组快,血小板计数回升至100×109/L以上的平均时间比对照组短,分别为(5.5±0.5)d和(9.6±1.2)d,两组差异有显著性(P<0.01)。结论巨和粒对化疗所致血小板减少疗效显著,无明显副作用。     

血小板减少症患者促血小板生成素和血清白细胞介素-11水平的检测

 目的 探讨血小板减少症患者血清促血小板生成素（TPO）和白细胞介素－11（IL-11）水平及其与外周血小板计数之间的关系。方法 应用双抗体夹心酶联免疫吸附法（ELISA）测定110例 血小板减少症患者血清TPO和IL-11水平,同时用自动血细胞仪测定其血小板数,以20例健康人为正常对照。结果 原发性血小板减少性紫癜（ITP）血清TPO水平较正常对照组低（P＜0.05）,而IL-11水平较对照组高（P＜0.05）;继发性血小板减少症血清TPO明显高于正常对照组（P＜0.05）;再生障碍性贫血患者的IL-11水平较对照组低（P＜0.05）。相关性分析表明, ITP患者血清TPO水平与血小板计数无相关性（r = 0.160,P＞0.05）,继发性血小板减少症患者血清TPO水平与血小板计数呈负相关（r = - 0.820,P＜0.05）;ITP 患者血清IL-11水平与血小板计数呈负相关（r = -0.559,P＜0.05）。继发性血小板减少症患者血清IL-11水平与血小板计数相关性不明显（r = 0.432,P＞0.05）。结论 本实验结果为进一步探讨血小板减少症患者TPO及IL-11的调控机制,为临床诊断、治疗血小板减少症提供新的理论依据。     

重组人白细胞介素-11治疗实体瘤化疗所致的血小板减少症的随机对照研究

目的:观察重组人白细胞介素-11(rhIL-11)治疗实体瘤化疗所致的血小板减少症的客观疗效;观察rhIL-11在人体的不良反应及其安全性.方法:本研究采用随机对照试验,55例化疗后血小板低于50×109/L的患者,随机分为A组和B组,A组接受rhIL-11,B组不接受rhIL-11治疗.主要观察IL-11能否治疗化疗引起的血小板减少症.结果:A组血小板值在第2～21d均高于B组,第4～21天差别具有显著的统计学意义;A组Ⅱ°、Ⅲ°及Ⅳ°血小板减少的持续天数分别为3.0d、3.2d及0.4d,B组分别为5.1d、5.8d及2.2d,A组血小板减少持续天数短于B组,但无统计学差异.IL-11的不良反应主要包括:心悸、心律失常、水肿、发热、关节肌肉疼痛、注射局部疼痛、皮疹、头痛头晕、乏力等.大多较轻,可以耐受.结论:rhIL-11能刺激血小板增生,治疗化疗引起的血小板降低,是一种有效、安全的治疗血小板减少的药物,值得进一步研究.     

重组人白细胞介素-11（Ⅰ）治疗肿瘤患者放化疗后血小板减少临床观察

目的 观察重组人白细胞介素-11（Ⅰ） [rhIL-11（Ⅰ）]对恶性实体瘤患者放化疗所致血小板减少的疗效及不良反应.方法 选择成都军区总医院2010年12月至2012年12月收治的放化疗后血小板计数（PLT）＜ 50×10^9/L的恶性实体瘤患者96例,采用随机数字表法将患者随机分为两组,观察组给予rhIL-11（Ⅰ）25 g·kg^-1·d^-1皮下注射,对照组给予常规治疗,当血小板升至正常（PLT≥100×10^9/L）或血小板升高绝对值＞50×10^9/L时停药.观察两组患者用药周期中患者生命体征、肝肾功能、凝血功能、心肺功能变化.结果 观察组患者放化疗后血小板最低值平均为（27.4±7.6）×10^9/L,与对照组平均值（28.1±7.9）×10^9/L相比,差异无统计学意义（t=1.083,P＞0.05）;但治疗后观察组血小板升高最高值平均为（116.3±22.8）×10^9/L,显著高于对照组的（76.2±21.3）×10^9/L,差异有统计学意义（t =21.092,P＜0.05）.观察组患者血小板＜50×10^9/L持续天数平均值为（4.3±1.7）d,血小板从最低值升至绝对值大于5万的平均时间为（6.8±2.4）d,均短于对照组,差异具有统计学意义（t=11.347,P＜0.05; t=15.196,P＜0.05）;且两组患者不良反应可耐受,未出现Ⅲ、Ⅳ度不良反应.结论 rhIL-11（Ⅰ）对于治疗恶性实体瘤患者放化疗后血小板减少疗效确切,不良反应耐受性好.     

儿童全脑全脊髓放疗SIOPE指南全脑靶区勾画临床应用研究

目的 根据SIOPE指南勾画全脑全脊髓放疗患者的全脑靶区,验证原计划中未勾画的亚结构欠量情况,为全脑全脊髓放疗儿童患者全脑复发风险的研究提供证据,同时为SIOPE指南全脑靶区勾画临床应用积累经验。方法 选择12例全脑全脊髓放疗的儿童患者,根据2018年SIOPE指南在原有全脑靶区CTVold (全脑组织加筛板)基础上增加勾画亚结构CTVsub (包括眶上裂、圆孔、卵圆孔、颈静脉孔、舌下神经管、内听道以及视神经),合并且外放形成PTVnew。在CTVold基础上往前下方向(颅底方向)外放15mm、其余方向外放3mm适当修改后形成简易PTV (PTVrough)。按照PTVold设计CRTold、IMRTold计划,按照PTVnew设计CRTnew、IMRTnew计划,按照PTVrough设计CRTrough计划。评估基于CTVold靶区的亚结构的遗漏及其基于各个计划的欠量情况。结果 若基于CTVold勾画,则有78.6%的眶上裂、71.99%的圆孔、96.76%的卵圆孔、88.5%的颈静脉孔、97.71%的舌下神经管、99.48%的内听道以及100%的视神经体积被遗漏。基于CRTold、IMRTold计划亚结构的处方剂量覆盖分别仅为91.70%、89.83%。基于CRTold、CRTnew、IMRTold、IMRTnew、CRTrough计划,分别有16.66%、3.57%、20.83%、1.78%、1.19%的亚结构发生欠量。在所有的亚结构欠量中,38.36%、46.58%的欠z量分别发生在CRTold、IMRTold计划中。其中欠量最少、最多的分别为圆孔(0%)、卵圆孔(36.66%)。结论 按照SIOPE指南,在全脑全脊髓放疗患者全脑靶区勾画时,传统的脑组织勾画(包括筛板)将会遗漏部分靶区并且会欠量,其中卵圆孔欠量最严重而在IMRT计划中遗漏靶区的欠量更明显;基于亚结构勾画的计划将明显改善其欠量情况;选择左右对穿照射技术时,采用简易PTV方法可以获得近似的靶区剂量覆盖和危及器官保护,但还需要临床的进一步验证。     

重组人白介素-１１治疗化疗所致血小板减少的临床观察

目的：观察重组人白介素-１１（ｒｈＩＬ-１１）对恶性肿瘤患者因化疗所致血小板减少的疗效及毒副反应。方法：化疗后血小板低于２５×１０９／Ｌ给予ｒｈＩＬ-１１ ５０μｇ／（ｋｇ·ｄ）皮下注射,血小板低于５０×１０９／Ｌ给予ｒｈＩＬ-１１ ２５μｇ／（ｋｇ·ｄ）皮下注射,观察外周血小板变化,血小板升至≥７５×１０９／Ｌ时停药。结果：血小板升至≥７５×１０９／Ｌ所需时间：Ⅲ度２２例（５.０±１.３）天,Ⅳ度８例（１２.４±１.６）天。主要毒副反应为乏力、水肿、关节肌肉疼痛、注射部位疼痛。结论：重组人白介素-１１（ｒｈＩＬ-１１）有升高化疗后血小板减少的作用,毒副反应可耐受。     

Low-dose craniospinal irradiation as a definitive treatment for intracranial germinoma

Purpose: To determine the optimal radiotherapy (RT) dose and volume for treatment of intracranial germinoma.Materials and methods: Eighty-one intracranial germinoma patients (33 pathologically-verified; 48 presumed by radiosensitivity testing) treated with RT alone between 1971 and 2002 were analyzed. The RT volume varied from focal (13) to whole brain (8), or to the entire neuraxis (60). All the cases after 1982 received craniospinal irradiation (CSI). Radiation dose was reduced gradually during the study period from 59 to 39.3 Gy for primary tumors, and from 34.2 to 19.5 Gy for the neuraxis. The median follow-up time was 120 months (48-260 months).Results: Five- and ten-year relapse-free survival rates were 98.8% and 94.1%, respectively. All the recurrences occurred in the patients who received local (4/13) or whole brain RT (1/8). None of the patients who received CSI suffered from a recurrence. Forty-six patients received 45 Gy or less to the primary site and 22 patients received less than 20 Gy to the spinal axis.Conclusion: Low-dose CSI-based RT should remain the standard treatment for intracranial germinoma. The RT dose can be reduced to 39.3 Gy for primary tumor sites and to 19.5 Gy for the spinal axis.     

Field-in-field technique with intrafractionally modulated junction shifts for craniospinal irradiation

PURPOSE: To plan craniospinal irradiation with "field-in-field" (FIF) homogenization in combination with daily, intrafractional modulation of the field junctions, to minimize the possibility of spinal cord overdose. METHODS AND MATERIALS: Lateral cranial fields and posterior spinal fields were planned using a forward-planned, step-and-shoot FIF technique. Field junctions were automatically modulated and custom-weighted for maximal homogeneity within each treatment fraction. Dose-volume histogram analyses and film dosimetry were used to assess results. RESULTS: Plan inhomogeneity improved with FIF. Planning with daily modulated junction shifts provided consistent dose delivery during each fraction of treatment across the junctions. Modulation minimized the impact of a 5-mm setup error at the junction. Film dosimetry confirmed that no point in the junction exceeded the anticipated dose. CONCLUSIONS: Field-in-field planning and modulated junction shifts improve the homogeneity and consistency of daily dose delivery, simplify treatment, and reduce the impact of setup errors.     

Improving the therapeutic ratio of craniospinal irradiation in medulloblastoma

Radiation therapy delivered to the entire cerebrospinal axis is indicated for a number of pediatric brain tumors, especially medulloblastoma. Improved radiotherapy techniques have changed the near fatal prognosis for children with medulloblastoma to a 50%, 5-year survival. Nevertheless, the treatment results in substantial acute toxicity, and many survivors have serious sequelae. Further improvement in survival with optimal surgery and radiotherapy is not expected unless chemotherapy is added. Refinements in radiotherapy technique, however, can improve the therapeutic ratio of the treatment by lowering its side effects. In the last year children who required craniospinal irradiation at M. D. Anderson Hospital were treated with 6 MV photons to the brain and primary tumor and with 15-17 MeV electrons to the spinal canal. The elective dose to the whole brain was 30 Gy in 17 fractions and 30 Gy in 20 fractions to the spine. The primary tumor received an additional 20-25 Gy. An electron-beam dose distribution was drawn on a computerized tomography (CT) reconstructed sagittal plane. The electron energy was selected so that the 90% isodose line was at least 3 mm anterior to the cord after correction for bone heterogeneity. The treatment was well tolerated in the first five patients. It is projected that the current technique will cause fewer late effects and improve the tolerance to chemotherapy.     

A method to improve target dose homogeneity of craniospinal irradiation using dynamic split field IMRT

Purpose

Craniospinal irradiation (CSI) is technically very challenging and field edge matching is needed because of the mechanical limitations of standard linear accelerators. We assessed the feasibility of intensity-modulated radiotherapy (IMRT) in CSI to overcome the standard feathering and dose inhomogeneities associated with the standard feathering technique in the junction areas.

Materials and methods

The use of IMRT in CSI was studied with five patients CT scanned in the supine position. Isocentric treatment plans of three dimensional conventional radiotherapy (3D-CRT) and split field IMRT (sfIMRT) with dynamic intrafractional feathering were created with the same field setup and the resulted dose distributions were compared. The effect of treatment inaccuracy was simulated with an intentional shift of ±3 mm with both treatment plans. Dosimetric verification of the sfIMRT treatment plan was performed with radiographic films placed in a phantom.

Results

The sfIMRT treatment plans resulted in a better dose coverage and uniformity in the target volume. The ±3 mm shift had only a minor effect on the dose distribution of the sfIMRT treatment plan whereas with the 3D-CRT the shift resulted in an error of ±38% of the calculated dose in the spinal cord. The measured dose distribution of the sfIMRT treatment plan correlated well with the calculations.

Conclusions

Improved dose homogeneity in the target volume was achieved with the sfIMRT compared to the conventional 3D-CRT treatment plan. With the sfIMRT technique only a single treatment plan is required to deliver the total treatment dose and the resulting dose distribution is also less volatile for technical uncertainties of the treatment.     

Intensity-modulated radiotherapy for craniospinal irradiation: target volume considerations, dose constraints, and competing risks

PURPOSE: To report the results of an analysis of dose received to tissues and organs outside the target volume, in the setting of spinal axis irradiation for the treatment of medulloblastoma, using three treatment techniques. METHODS AND MATERIALS: Treatment plans (total dose, 23.4 Gy) for a standard two-dimensional (2D) technique, a three-dimensional (3D) technique using a 3D imaging-based target volume, and an intensity-modulated radiotherapy (IMRT) technique, were compared for 3 patients in terms of dose-volume statistics for target coverage, as well as organ at risk (OAR) and overall tissue sparing. RESULTS: Planning target volume coverage and dose homogeneity was superior for the IMRT plans for V(95%) (IMRT, 100%; 3D, 96%; 2D, 98%) and V(107%) (IMRT, 3%; 3D, 38%; 2D, 37%). In terms of OAR sparing, the IMRT plan was better for all organs and whole-body contour when comparing V(10Gy), V(15Gy), and V(20Gy). The 3D plan was superior for V(5Gy) and below. For the heart and liver in particular, the IMRT plans provided considerable sparing in terms of V(10Gy) and above. In terms of the integral dose, the IMRT plans were superior for liver (IMRT, 21.9 J; 3D, 28.6 J; 2D, 38.6 J) and heart (IMRT, 9 J; 3D, 14.1J; 2D, 19.4 J), the 3D plan for the body contour (IMRT, 349 J; 3D, 337 J; 2D, 555 J). CONCLUSIONS: Intensity-modulated radiotherapy is a valid treatment option for spinal axis irradiation. We have shown that IMRT results in sparing of organs at risk without a significant increase in integral dose.