Craniospinal irradiation with spinal IMRT to improve target homogeneity

PURPOSE: To report a new technique for the spinal component of craniospinal irradiation (CSI) in the supine position, to describe a verification procedure for this method, and to compare this technique with conventional plans. METHODS AND MATERIALS: Twelve patients were treated between 1998 and 2006 with CSI using a novel technique. Sixteen children were treated with a conventional field arrangement. All patients were followed for outcomes and toxicity. CSI was delivered using a posteroanterior (PA) intensity-modulated radiation therapy (IMRT) spinal field matched to conventional, opposed lateral cranial fields. Treatment plans were generated for each patient using the IMRT technique and a standard PA field technique. The resulting dosimetry was compared to determine target homogeneity, maximum dose to normal tissues, and total monitor units delivered. RESULTS: Evaluation of the spinal IMRT technique compared with a standard PA technique reveals a 7% reduction in the target volume receiving > or =110% of the prescribed dose and an 8% increase in the target volume receiving > or =95% of the prescribed dose. Although target homogeneity was improved, the maximum dose delivered in the paraspinal muscles was increased by approximately 8.5% with spinal IMRT compared to the PA technique. Follow-up evaluations revealed no unexpected toxicity associated with the IMRT technique. CONCLUSIONS: A new technique of spine IMRT is presented in combination with a quality assurance method. This method improves target dose uniformity compared to the conventional CSI technique. Longer follow-up will be required to determine any benefit with regard to toxicity and disease control.     

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.     

Supine craniospinal irradiation using intrafractional junction shifts and field-in-field dose shaping: early experience at Methodist Hospital

PURPOSE: To describe our preliminary experience with supine craniospinal irradiation. The advantages of the supine position for craniospinal irradiation include patient comfort, easier access to maintain an airway for anesthesia, and reduced variability of the head tilt in the face mask. METHODS AND MATERIALS: The cranial fields were treated with near lateral fields and a table angle to match their divergence to the superior edge of the spinal field. The collimator was rotated to match the divergence from the superior spinal field. The spinal fields were treated using a source to surface distance (SSD) technique with the couch top at 100 cm. When a second spinal field was required, the table and collimator were rotated 90 degrees to allow for the use of the multileaf collimator and so the gantry could be rotated to match the divergence of the superior spinal field. The multileaf collimator was used for daily dynamic featherings and field-in-field dose control. RESULTS: With a median follow-up of 20.2 months, five documented failures and no cases of radiation myelitis occurred in 23 consecutive patients. No failures occurred in the junctions of the spine-spine or brain-spine fields. Two failures occurred in the primary site alone, two in the spinal axis alone, and one primary site failure plus distant metastasis. The median time to recurrence was 17 months. CONCLUSION: The results of our study have shown that supine approach for delivering craniospinal irradiation is not associated with increased relapses at the field junctions. To date, no cases of radiation myelitis have developed.     

基于仰卧位全脑全脊髓无缝整体调强技术可行性研究

目的 探讨基于仰卧位情况下开展全脑全脊髓无缝整体调强技术的可行性和安全性。方法 患者在仰卧位下使用头部面膜加体部真空垫固定组合,根据患者身高使用固定间距(20~25 cm)的3个中心坐标。3个中心计划共13个野,在衔接部射野重叠2~3 cm左右,采用固定钨门,逆向优化的方式进行整体计算。对3个等中心和两个射野重叠处靶区分别进行平面剂量通过率及绝对点剂量验证分析。治疗前对3个中心一次性摆位后进行3个中心CBCT扫描,分别得出3个中心在同一坐标系中左右、头脚、前后方向上的误差,并作整体分析。结果 28例患者颈、胸、腹射野等中心点、颈胸射野衔接点、胸腹射野衔接点的平面剂量γ百分通过率和点剂量百分剂量偏差平均分别为99.36%、99.60%、99.75%、94.77%、95.09%和1.56%、-1.56%、0.52%、-0.76%、-1.68%。28例患者共进行162组图像引导放疗,获得486次各中心CBCT图像的摆位偏差,其中颈、胸、腹各中心左右,头脚,前后方向的平均偏差分别为0.17、0.10、0.02 mm,0.06、0.04、0.46 mm,0.19、0.26、0.41 mm。结论 基于仰卧位全脑全脊髓无缝整体调强技术安全可行,值得临床推广。     

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。     

全中枢照射所致血小板减少的临床研究

目的 评价重组人白细胞介素-11(rhIL-11)预防全中枢照射所致血小板减少的疗效和不良反应。 方法 采用随机对照研究方法,将 100例患者随机分为A组(rhIL-11预防治疗组 50例)和B组(对照组 50例)。A组患者放疗过程中血小板计数<100×10⁹/L时或血小板计数较放疗前基线水平下降>50%即开始按50 μg·kg^-1·d^-1剂量给予rhIL-11皮下注射,1 次/d,直至血小板数≥200×10⁹/L时停药。B组患者当血小板计数<50×10⁹/L时则按同样方案进行,直至血小板数≥100×10⁹/L时停药。 结果 92例可评价疗效,rhIL-11可升高全中枢照射中血小板最低值(P<0.01),缩短血小板减少症持续时间(P<0.01),缩短放疗所需时间(P<0.01)。主要不良反应为注射部位疼痛、硬结、红肿、乏力等,但程度较轻。 结论 rhIL-11 具有明显的促血小板生成作用,可显著减少全中枢照射过程中血小板减少的发生,保证放疗的顺利进行,不良反应较轻且较易处理。     

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.     

Radiation dose to the lens during craniospinal irradiation-an improvement in proton radiotherapy technique

PURPOSE: To evaluate the effect of angle modification of cranial field proton beam therapy on the radiation dose delivered to the lens during craniospinal irradiation (CSI). METHODS AND MATERIALS: Thirty-nine patients with central nervous system tumors who received CSI with a posterior fossa boost were analyzed for the radiation dose to the lens. Thirteen patients received cranial field treatment using standard opposed-lateral proton beams, and 26 patients received treatment with angled posterior-oblique proton beams. The lens dose in a test case also was evaluated by comparing conventional X-rays with the two proton beam planning methods by using a CMS/Xio three-dimensional planning system. RESULTS: Substantial lens dose sparing was realized with the angling of the cranial proton beams 15 degrees -20 degrees to the posterior. In the 39 treated patients who were analyzed (median age, 7 years), average dose delivered to the lens was decreased by approximately 50% by angling of the proton beams, with the average maximum dose decreasing from 74% to 40% of the prescribed dose (p < 0.0001). Significant lens sparing was seen in patients 10 years and younger (median age, 6 years; p < 0.0001), whereas an insignificant decrease was seen in older patients (median age, 16 years; p = 0.14). With the opposed-lateral technique (median age, 6 years), the lens dose increased significantly with decreasing age (p = 0.002), whereas there was no effect of age on lens dose in the angled beam-treated group (median age, 8.5 years; p = 0.73). CONCLUSION: The present study clearly shows an advantage in sparing of the lens dose by angling the beams used during proton beam CSI. This effect is most pronounced in patients 10 years and younger because of anatomic effects of sinus development.     

全脑全脊髓放疗骨髓保护的初步研究

目的 分析全脑全脊髓放疗患者骨髓受量与血液学毒性的关系,并初步探索HT及VMAT在全脑全脊髓放疗中骨髓的剂量学差异。方法 收集我院螺旋断层全脑全脊髓放疗20例患者临床资料及HT计划,将计划回传至MIM系统。在CT上依次勾画患者的颅骨、下颌骨、锁骨、胸骨、肩胛骨、肋骨、椎体骨、盆骨,在DVH图上读出上述骨结构及总骨的V2、V5、V10、V15、V20、V25、V30、V35、Dmean、Dmax值,分析上述指标与患者≥2级血液学毒性相关性。再从中选取6例患者为对象,将图像传输至Monaco计划系统并完成VMAT计划,对比两种计划上述骨结构剂量体积差异。采用Spearman相关性分析及Wilcoxon符号秩和检验。结果 患者≥2级白细胞减低与盆骨V25、总骨V5呈正相关(P=0.038、0.025),≥2级血小板减少与盆骨V20呈正相关(P=0.041),≥2级中性粒细胞减低与椎骨V10呈正相关(P=0.036)。患者VMAT与HT计划相比,椎骨、盆骨的各剂量体积指标相近(P>0.05)。结论 全脑全脊髓放疗中患者≥2级白细胞减低与盆骨V25、总骨V5呈正相关,≥2级血小板减少与盆骨V20呈正相关,≥2级中性粒细胞减低与椎骨V10呈正相关。全脑全脊髓放疗患者VMAT与HT计划相比椎骨、盆骨各剂量体积相近。     

Thyroid-stimulating hormone suppression for protection against hypothyroidism due to craniospinal irradiation for childhood medulloblastoma/primitive neuroectodermal tumor

PURPOSE: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. PATIENTS AND METHODS: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of CSI. From 14 days before and up to the end of CSI, patients were administered l-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 mum/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. RESULTS: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the "adequately TSH-suppressed" group and 20% for the "inadequately TSH-suppressed" group (p = 0.02). CONCLUSIONS: Thyroid-stimulating hormone suppression with l-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.     

Physiologic and radiographic evidence of the distal edge of the proton beam in craniospinal irradiation

PURPOSE: Fatty replacement of bone marrow resulting from radiation therapy can be seen on T1-weighted magnetic resonance (MR) images. We evaluated the radiographic appearance of the vertebral bodies in children treated with proton craniospinal irradiation (CSI) to illustrate the distal edge effect of proton radiotherapy. METHODS AND MATERIALS: The study cohort consisted of 13 adolescents aged 12-18 years who received CSI with proton radiotherapy at Massachusetts General Hospital. Ten of these patients had reached maximal or near-maximal growth. Proton beam radiation for these 10 patients was delivered to the thecal sac and exiting nerve roots only, whereas the remaining 3 patients had a target volume that included the thecal sac, exiting nerve roots, and entire vertebral bodies. Median CSI dose was 27 [range, 23.4-36] cobalt gray equivalent (CGE) given in 1.8-CGE fractions. Magnetic resonance images of the spine were obtained after completion of radiotherapy. RESULTS: Magnetic resonance images of patients who received proton radiotherapy to the thecal sac only demonstrate a sharp demarcation of hyperintense T1-weighted signal in the posterior aspects of the vertebral bodies, consistent with radiation-associated fatty marrow replacement. Magnetic resonance images of the patients prescribed proton radiotherapy to the entire vertebral column had corresponding hyperintense T1-weighted signal involving the entire vertebral bodies. CONCLUSION: The sharp delineation of radiation-associated fatty marrow replacement in the vertebral bodies demonstrates the rapid decrease in energy at the edge of the proton beam. This provides evidence for a sharp fall-off in radiation dose and supports the premise that proton radiotherapy spares normal tissues unnecessary irradiation.     

Hypofractionated high-dose irradiation for the treatment of malignant astrocytomas using simultaneous integrated boost technique by IMRT

PURPOSE: We evaluated the clinical significance of hypofractionated high-dose irradiation using simultaneous integrated boost technique with intensity-modulated radiation therapy (IMRT) for the treatment of malignant astrocytomas (MAs). METHODS AND MATERIALS: Twenty-five patients with MAs were treated by IMRT. Three layered planning target volumes (PTVs) were contoured. PTV-1 was the area of enhanced lesion with 5-mm margin; PTV-2 was the area with 15-mm margin surrounding the PTV-1; PTV-3 was the area of perifocal edema. Irradiation was performed in 8 fractions, and only the dose for PTV-1 was escalated from 48 Gy to 68 Gy while maintaining the dose for PTV-2 (40 Gy) and PTV-3 (32 Gy). The clinical outcome of IMRT was compared with 60 MA patients treated by conventional external beam irradiation (EBI). RESULTS: The progression-free survival of patients in the IMRT group was significantly longer than that in the EBI group (p < 0.0001). No distant failure was observed in both groups. In the IMRT group, dissemination was the most frequent cause of death (70%). The overall survival of patients in the IMRT group was better than that in the EBI group (p = 0.043). CONCLUSIONS: Our regimen of IMRT contributed to the control of both the regional and infiltrating tumors, resulting in better survival of patients.     

A comparison of optic nerve dosimetry in craniospinal radiotherapy planned and treated with conventional and intensity modulated techniques

Background and purpose

Some CNS tumours present leptomeningeal dissemination. Craniospinal radiotherapy is complex and recurrences may occur at sites of target volume underdosage. IMRT, being highly conformal to the target, could theoretically underdose the optic nerves if they are not specifically targeted leading to optic nerve recurrences. We analyzed optic nerve dosimetry when they are not specifically targeted.

Materials and methods

We designed 3D-conformal and tomotherapy plans for our last five patients treated to the craniospinal axis, not including the optic nerves in the target volume. We analyzed the dose delivered to the optic nerves, to the anterior and posterior half of the optic nerves, and to a theoretical optic nerve-PTV.

Results

The dose delivered to the optic nerves was similar for both plans in all patients (V95% close to 100%) except one in whom tomotherapy considerably underdosed the anterior optic nerves. The dose to the optic nerve-PTV was lower with tomotherapy in all patients.

Conclusion

Despite not intentionally targeting the optic nerves, the dose to the optic nerves with IMRT was similar to 3D-conformal plans in most cases but left no margin for setup error. In individual cases the anterior half of the optic nerves could be significantly underdosed.     

A low gradient junction technique of craniospinal irradiation using volumetric-modulated arc therapy and its advantages over the conventional therapy

A technique using volumetric-modulated arc therapy (VMAT) fields for craniospinal irradiation with low dose gradients at the field junction was tested for its sensitivity to positional inaccuracy. It was compared against the conventional three-dimensional (3D) conformal radiotherapy in terms of dose uniformity at the junction. Treatment plans generated for ten patients who received craniospinal irradiation (35 Gy in 21 fractions) by VMAT technique at our centre were included in this study. For these patients, 3D conformal radiotherapy plans were also generated in addition to the VMAT treatment plans. Intentional shifting of the cranial field in the superior and then in the inferior directions was done, creating a gap or overlap between the fields. Consequent changes in dose distributions in these two plans to positional inaccuracies were studied. The 3D conformal radiotherapy plans showed large dose variations at the junction due to positional shifts as compared to the VMAT plans. With a 5 mm superior shift of the cranial field isocentre creating a gap between the cranial and spinal fields, the magnitudes of under-dosing were 13.9 ± 3.6 Gy and 4.8 ± 2.0 Gy for 3D conformal radiotherapy and VMAT respectively. When the cranial field was moved by 5 mm inferiorly creating an overlap between the fields, overdose to the effects of 10.3 ± 4.0 Gy and 4.9 ± 1.3 Gy were observed for the 3D conformal radiotherapy plans and VMAT plans respectively. The VMAT technique is insensitive to longitudinal setup errors (1–3 mm) in patients because of the existence of low dose gradients at the junction between fields. This is unlike the 3D conformal radiotherapy plans which have steep dose gradients at the field edges and thus are highly sensitive to setup errors. Such an advantage for VMAT circumvents the need for dose feathering often practiced with the 3D conformal radiotherapy technique and makes the technique simpler to follow.     

A methodology for using SPECT to reduce intensity-modulated radiation therapy (IMRT) dose to functioning lung

PURPOSE: Single photon emission computed tomography (SPECT) provides a map of the spatial distribution of lung perfusion. Thus, SPECT guidance can be used to divert dose away from higher-functioning lung, potentially reducing lung toxicity. We present a methodology for achieving this aim and test it in intensity-modulated radiotherapy (IMRT) treatment-planning. METHODS AND MATERIALS: IMRT treatment plans were generated with and without SPECT guidance and compared for 5 patients. Healthy lung was segmented into four regions on the basis of SPECT intensity in the SPECT plan. Dose was sequentially allowed to the target via regions of increasing SPECT intensity. This process results in reduction of dose to functional lung, reflected in the dose-function histogram (DFH). The plans were compared using DFHs and F(20)/F(30) values (F(x) is the functional lung receiving dose above x Gy). RESULTS: In all cases, the SPECT-guided plan produced a more favorable DFH compared with the non-SPECT-guided plan. Additionally, the F(20) and F(30) values were reduced for all patients by an average of 13.6% +/- 5.2% and 10.5% +/- 5.8%, respectively. In all patients, DFHs of the two highest-functioning SPECT regions were reduced, whereas DFHs of the two lower-functioning regions were increased, illustrating the dose "give-take" between SPECT regions during redistribution. CONCLUSIONS: SPECT-guided IMRT shows potential for reducing the dose delivered to highly functional lung regions. This dose reduction could reduce the number of high-grade pneumonitis cases that develop after radiation treatment and improve patient quality of life.