Update of human spinal cord reirradiation tolerance based on additional data from 38 patients

PURPOSE: To update a combined analysis of all published clinical data. METHODS AND MATERIALS: We collected data from 38 additional patients treated in our department or published in four different reports and calculated the biologically effective dose (BED) according to the linear-quadratic model using an alpha/beta value of 2 Gy for cervical and thoracic cord and 4 Gy for lumbar cord. In this model, a dose of 50 Gy given in single daily fractions of 2 Gy is equivalent to a BED of 100 Gy(2) or 75 Gy(4). RESULTS: The 2005 risk score based on three variables (cumulative BED, highest BED of all treatment series in a particular individual, and interval), which discriminate three different risk groups, does not require modification. The low-risk group now contains 1 case of radiation myelopathy (RM) after hypofractionated stereotactic reirradiation. Therefore, the rate increased from 0% to 3%. Intermediate-risk patients developed RM in 25%, and high-risk patients in 90%. When the interval between the two treatment courses is not shorter than 6 months and the dose of each course is < or =98 Gy(2), the cumulative BED where no case of RM has yet been reported is 120 Gy(2). CONCLUSIONS: Based on these updated results, the risk of RM appears small after < or =135.5 Gy(2) when the interval is not shorter than 6 months and the dose of each course is < or =98 Gy(2). We would recommend limiting the dose to the lowest feasible level. The influence of very steep dose gradients from stereotactic and intensity-modulated approaches (i.e., a more complex volume-effect) requires further evaluation.     

The radiation dose-response of the human spinal cord

PURPOSE: To characterize the radiation dose-response of the human spinal cord. METHODS AND MATERIALS: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and alpha/beta ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. RESULTS: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The alpha/beta = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. CONCLUSIONS: The estimate of alpha/beta is smaller than usually quoted, but values this small were found in some studies. Using alpha/beta = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation.     

Application of radiotherapy with the extension of spinal cord for esophageal cancer

Objective To analyze the setup and residual errors of spinal cord during online CT-guided radiotherapy for patients with esophageal cancer, and to discuss the necessity of segmental extension of spinal cord. Methods According to the radiotherapy site, 60 cases of esophageal cancer were divided into the neck, chest and abdomen groups, 20 cases in each group. Cervical pleura or vacuum bag was fixed, IMRT technology was adopted, and pre-treatment CT images were obtained by CTVision, and 20 consecutive CT scans were collected for each case. CT images were imported into MIM software. The parameters of the setup errors were processed and extracted. The CT spinal cord was delineated for verification and planning, and the Dice coefficient, Hausdorff maximum distance and centroid coordinate of the delineated spinal cord were processed and extracted. Compatibility anova data were adopted. The calculation formula of the extension margin is MPRV= 1.3 ∑total+0.5 σtotal. Results Residual centroid method was employed. Non-on-line and on-line CT-guided radiotherapy, the extension margins of neck,chest, abdominal spinal cord in the x-, y-and z-axis were 3.86,5.37,6.36 mm;3.45,3.83,4.51 mm;4.05,4.83,7.06 mm,vs,2.85,2.19,2.83 mm;2.32,2.20,2.16 mm;2.86,2.21,2.83 mm, respectively. During residual Hausdorff distance method,non-on-line and on-line CT guided radiotherapy,the extension margins of neck, chest, abdominal spinal cord in the x-, y-and z-axis were 3.10, 5.33,6.15 mm;3.30,3.77,4.61 mm;3.35,4.76,6.87mm,vs,2.12,2.06,2.32 mm;2.12,2.06,2.32 mm;2.12,2.06,2.32 mm,respectively. Conclusion The setup errors and residual errors are different in each segment of spinal cord. Henc, different extension margins should be given.     

食管癌放疗脊髓外扩范围应用研究

目的 分析食管癌在线CT引导放疗不同部位脊髓分次间摆位误差和残差,探讨脊髓分段外放的必要性。方法 依照食管癌患者放疗部位选颈、胸、腹段脊髓各20例。颈胸膜或真空袋固定,IMRT技术,采用CTVision获取治疗前位置验证CT图像,每例收集连续20次。在MIM软件上导入CT图像,处理并提取摆位参数。勾画验证和计划CT脊髓,处理并提取勾画脊髓的Dice系数、Hausdorff距离最大值、质心坐标值。采用配伍方差分析数据,外扩值计算公式为MPRV=1.3∑总群体+0.5σ总群体。结果 残差质心方法,非在线和在线CT引导颈、胸、腹段脊髓x、y、z轴向外扩值分别为3.86、5.37、6.36mm,3.45、3.83、4.51mm,4.05、4.83、7.06mm和2.85、2.19、2.83mm,2.32、2.20、2.16mm,2.86、2.21、2.83mm。残差Hausdorff距离方法,非在线和在线CT引导颈、胸、腹椎脊髓脊髓x、y、z轴向外扩值分别为3.10、5.33、6.15mm,3.30、3.77、4.61mm,3.35、4.76、6.87mm和2.12、2.06、2.32mm,2.12、2.06、2.32mm,2.12、2.06、2.32mm。结论 各段脊髓摆位误差、残差均不同,应给予不同外扩范围。     

Short-course radiotherapy is not optimal for spinal cord compression due to myeloma

PURPOSE: To investigate the suitability of short-course radiotherapy (RT) for spinal cord compression (SCC) in myeloma patients. METHODS AND MATERIALS: Data for 172 myeloma patients irradiated between January 1994 and December 2004 for SCC were retrospectively evaluated. Short-course RT (1 x 8 Gy, 5 x 4 Gy, n = 61) and long-course RT (10 x 3 Gy, 15 x 2.5 Gy, 20 x 2 Gy, n = 111) were compared for functional outcome up to 24 months after RT. In addition, 10 potential prognostic factors were investigated. RESULTS: Improvement of motor function occurred in 90 patients (52%). Forty-seven percent of nonambulatory patients regained the ability to walk. Functional outcome was significantly influenced by the time of developing motor deficits before RT. Improvement of motor function was more frequent after long-course RT than after short-course RT: 59% vs. 39% (p = 0.10) at 1 month, 67% vs. 43% (p = 0.043) at 6 months, 76% vs. 40% (p = 0.003) at 12 months, 78% vs. 43% (p = 0.07) at 18 months, and 83% v 54% (p = 0.33) at 24 months. A subgroup analysis of the long-course RT group demonstrated a similar functional outcome for 10 x 3 Gy when compared with 15 x 2.5 Gy and 20 x 2 Gy. CONCLUSIONS: Long-course RT is preferable for SCC in myeloma patients because it resulted in better functional outcome than short-course RT. Treatment with 10 x 3 Gy can be considered appropriate.     

Conservative surgery and radiotherapy in the treatment of spinal cord astrocytoma

Spinal cord astrocytomas are rare neoplasms, and optimaltreatment guidelines are undefined. 23 patients with spinalcord astrocytomas were treated between 1984 and 1993with conservative surgery and postoperative radiotherapy. The meanage was 31 years. Twelve patients were maleand eleven female. All patients presented with neurologicdeficits. Cervical cord was involved in five patients,cervicothoracic in four, thoracic in eight and thoracolumbarin six. Five patients had intramedullary cysts. Fifteenpatients had low grade tumors and six highgrade. Surgery was near total excision in threepatients, partial excision in ten and biopsy inten patients. All patients received postoperative radiotherapy toa median dose of 45 Gy in 25fractions over 5 weeks. The median followup was51 months (range 7–143 months). At 6 monthspost radiotherapy, twelve patients had improvement of neurologicstatus, nine had stable status, and two deteriorated.The actuarial overall survival was 55% at 5years and 39% at 10 years. The actuarialprogression free survival probability was 75% at 5years and 55% at 10 years. Five patientshad local failure and two failed at distantsites. Twelve patients died, six due to progressivedisease, five due to complications of paraplegia andone patient of unrelated causes. Tumor grade wasa significant prognostic factor for overall survival. 5year overall survival was 79% for low gradetumors. No patient with high grade tumor survivedmore than 2 years and the median survivalwas 10 months. Low grade, female sex andpresence of intramedullary cysts were associated with significantlyimproved progression free survival. Conservative surgery followed byradiotherapy appears to have a role in achievingtumor control and neurologic recovery in patients withlow grade astrocytomas of the spinal cord. Treatmentresults of high grade tumors remain poor andnew therapeutic strategies need to be studied.     

原发性椎管内黑色素瘤4例报告

 本文报告了4例原发性椎管内黑色素瘤，男2例，女2例，位于颈段1例，胸段3例，均为髓外硬膜下。随访2例生存3年死亡，2例8个月内死亡。本病临床诊断非常困难，均于术中或术后确诊。手术应尽量切除肿瘤，术后采取综合治疗以期获得长期生存。     

Ependymomas of the spinal cord

Many patients with spinal cord ependymomas (SCE) undoubtedly benefit from post-operative radiation therapy; however, because of the wide variability in the total doses given, the optimal post-operative dose for SCE remains unclear. Several recent papers recommend total doses of 4000 rad to 5000 rad in $\text{4}\text{1}\text{2}$ to 6 weeks. Unfortunately, only a small number of patients reported in the literature have been consistently treated to these high dose recommendations. Nine consecutive adult patients with SCE have been treated in a consistent way at Yale-New Haven Hospital with total doses of approximately 4500 rad to 5000 rad at 180 rad to 200 rad per day. The acute and chronic morbidity from such treatment has been minimal and no patient has had a local recurrence at 8 months to 8 years following treatment.     

Tanycytic ependymoma of the spinal cord with anaplastic cytological features

In a 43-year-old man, an intramedullary spinal cord tumor spreading from the level of the T2 to T5 vertebrae was subtotally resected. The tumor predominantly consisted of a fascicular proliferation of spindle cells having bland nuclei and bipolar, long cytoplasmic processes, and a few perivascular pseudo-rosettes were found. Although there were no true ependymal rosettes, intracytoplasmic dot-like immunoreactivity for epithelial membrane antigen (EMA) was found in a few cells. In some areas, a dense and diffuse proliferation of anaplastic, short-spindled cells having hyperchromatic nuclei and scant cytoplasm was noted, and the Ki-67 labeling index was remarkably higher (18.2%) in these areas. Neither microvascular proliferation nor necrosis was observed. In the boundary region, these two areas showed gradual transition from one to the other. The patient has remained free from recurrence for 10 months postoperatively. This is the first documentation of tanycytic ependymoma in which tumor cells showed anaplastic cytological features.     

Late effects of 50 McVd→Be neutron and cobalt-60 irradiation of rhesus monkey cervical spinal cord

The cervical spinal cords of 30 rhesus monkeys were irradiated with 50 MeV_d→Be neutrons or ⁶⁰Co gamma rays to evaluate the dose-response relationships for radiation myelopathy. Three groups were treated with 50 MeV_d→Be neutrons using dosage schedules of 1300 rad_mγ (Group I), 1425 rad_mγ (Group II), or 1550 rad_mγ (Group III) in nine fractions over 29 days. Three groups were irradiated with ⁶⁰Co gamma rays using dosage schedules of 4620 rad_mγ (Group IV), 5390 rad_mγ (Group V), or 5940 rad_mγ (Group VI) in 22 fractions over 29 days. A significant dose-response relationship was observed for the groups treated with neutrons. Whereas none of the monkeys in Group I showed clinical evidence of neurologic dysfunction, all five animals in Group III became paralyzed. One animal in Group II developed transient neck stiffness and mild unilateral leg paresis. No definitive signs of neurologic injury were seen in any of the animals irradiated with ⁶⁰Co. The histopathologic changes correlated well with the clinical observations. All of the animals in Group III exhibited moderate to severe malacia and demyelination of the white matter of the cervical spinal cord. The histologic data indicated that the RBE for five times weekly fractionation (～270 rad_mγ⁶⁰Co. fractions) was in the range of 4.2 to 4.6, since the malacia and demyelination in the spinal cords irradiated with 5940 rad_mγ of ⁶⁰Co. γ-rays were greater than that observed in the spinal cords irradiated with 1300 rad_mγ of neutrons but less than the changes in those irradiated with 1425 rad_mγ of neutrons.     

脊柱结核合并脊髓损伤患者的手术治疗

目的探讨在化疗基础上,一期手术病灶清除、植骨、内固定治疗脊柱结核伴脊髓损伤的临床疗效。方法回顾性分析2003年4月至2011年4月,我科收治的脊柱结核并脊髓损伤患者42例。根据脊髓损伤神经学国际标准（americanspinalinjuryassociation,ASIA）神经功能评分进行ASIA残损分级,B级14例,C级19例,D级9例。在标准化疗基础上根据脊髓损伤发展情况,24例化疗后3～4周手术,18例化疗未达2周,但脊髓损伤症状进行性加重或脓肿较多而进行手术。采用一期病灶清除、植骨、内固定手术治疗,术后严格强化四联抗结核治疗,术后3个月改三联化疗9～15个月。神经功能障碍改善情况采用ASIA神经功能评价,对其神经功能恢复、病灶愈合及内固定情况等进行分析研究。结果所有患者随访18～40个月,平均24个月。经X线、CT或MRI检查,病灶无残留,后凸角度矫正满意,随访无明显丢失;所有病例ASIA神经功能评价最终随访均得到明显好转,术前感觉评分（90.93±35.59）,运动评分（51.04±11.86）;末次随访感觉评分（185.58±30.41）,运动评分（85.21±11.48）,和术前比较差异有统计学意义（P＜0.01）;所有病灶治愈,骨性愈合,无1例结核复发;无断钉、断棒及内固定松动、窦道形成等相关并发症。结论脊柱结核伴神经压迫多缓慢产生,症状持续时间越长、瘫痪越重,预后越差,应在标准化疗基础上尽早手术,一期病灶清除、植骨、内固定治疗,效果满意。     

Reirradiation of metastatic spinal cord compression: Definitive results of two randomized trials

Purpose

Incidence, outcome and prognostic factors of metastatic spinal cord compression (MSCC) patients reirradiated for in-field recurrence were analyzed. Radiation therapists’ attitude in reirradiate spinal cord relapses, doses adopted and incidence of myelopathy were also examined.

Materials and methods

Data deriving from 579 evaluable patients entered two randomized trials on radiotherapy (RT) for MSCC were revised.

Results

Twenty-four (4.15%) patients had an in-field recurrence and 12 (50%) were reirradiated. At the time of analysis all reirradiated patients had died. Median time from first and second RT was 5 months (range, 2-31). Six patients received an 8 Gy single-dose, 2 patients 5 × 3 Gy and remaining four patients 2 × 8, 5 × 4, or a single dose of 7 and 4 Gy, respectively. The median cumulative Biologically Effective Dose (BED) calculated was 114.5 Gy₂ (range, 80-120 Gy₂). Six of seven (85.7%) ambulant patients maintained walking ability, whereas none of five not ambulant patients recovered the function. Median duration of response was 4.5 months (range, 1-24). The effect of reirradiation on motor function was significantly associated with walking capacity before reirradiation. Myelopathy was never recorded.

Conclusions

In MSCC reirradiation was safe and effective. Patient walking capacity before reirradiation was the strongest prognostic factor for functional outcome. Reirradiation was given in about one-half of patients with in-field recurrence and different doses and fractionations were used, even though cumulative BED was in all cases ?120 Gy₂.     

调强放疗中摆位误差对脊髓剂量的影响

目的探讨调强放疗中分次间摆位误差对脊髓物理剂量和生物效应剂量的影响。方法在治疗计划系统上模拟实际的摆位过程和无摆位误差的原计划进行比较,确定1个疗程中脊髓累积受照的物理剂量和生物效应剂量与相应计划值的差别。模拟在8例鼻咽癌患者的治疗计划上进行。每个病例有5种摆位情况:S0为原计划之摆位无摆位误差;S1、S2、S3和S4为模拟摆位,S1、S2和S3有同样的系统摆位误差,S1无随机摆位误差,S2的随机摆位误差小于S3;S2、S3的摆位误差呈正态分布;S4无随机摆位误差,系统摆位误差大于S1、S2和S3。结果与S0相比,S1、S2、S3和S4的脊髓参考点疗程累积剂量分别增加6.9%±1.3%、7.0%±1.4%、7.8%±1.5%和11.6%±1.0%;其总生物效应剂量分别增加9.2%±1.8%、9.7%±1.9%、11.2%±2.2%和15.7%%±1.4%;S2、S3分次剂量有波动,分次剂量标准偏差分别为11.4%±2.6%、16.6%±2.8%。结论较小的摆位误差也会造成脊髓剂量较大的改变;系统摆位误差主要影响疗程总量,而随机摆位误差主要产生分次间剂量波动;同样改变见于生物效应剂量且稍大于物理剂量。     

~(60)Co平移扫描照射在全脊髓放射治疗中的应用

目的　研究平移扫描照射在全脊髓放射治疗中的应用、剂量学特点和移动半影。方法　 5例病例行全脊髓平移扫描照射。平移床由本院和浙江大学联合研制 ,最大移动距离 6 0cm。采用电离室法测量剂量。治疗时准直器窗口 5cm× 10cm ,平移床可往返运动。结果　平移扫描照射提高了百分深度量 ;剂量分布非常均匀 ,明显优于固定野常规分野照射 ;全部病例都未观察到急性神经系统反应。结论　 60 Co平移扫描照射在剂量分布学上有明显的优点 ,是一种较传统方法更有效、更安全的治疗方法     

Temozolomide for recurrent low-grade spinal cord gliomas in adults

BACKGROUND: There is no standard therapy for surgery- and radiotherapy-resistant, recurrent, low-grade spinal cord gliomas. Therefore, a retrospective study of temozolomide (TMZ) in adults with recurrent low-grade spinal cord gliomas with a primary objective of determining progression-free survival (PFS) was performed. METHODS: Twenty-two patients (11 men and 11 women) aged 20 years to 55 years (median, 35 years) with recurrent spinal cord gliomas (World Health Organization grade 2 astrocytoma in 19 patients and oligoastrocytoma in 3 patients) were treated. All had previously been treated with surgery and involved-field radiotherapy. Thirteen patients underwent repeat surgery. All patients were chemotherapy-naive. TMZ was administered at a dose of 150-200 mg/m(2)/day for 5 consecutive days every 4 weeks (operationally defined as a single cycle). Neurologic and neuroradiographic evaluations were performed every 8 weeks. RESULTS: All patients were evaluable for toxicity and response. A total of 266 cycles of TMZ (median, 14 cycles; range, 2 cycles-24 cycles) was administered. TMZ-related toxicity included constipation (9 patients, 1 with grade 3), lymphopenia (9 patients, 1 with grade 3), fatigue (7 patients, 1 with grade 3), neutropenia (6 patients, 2 with grade 3), and thrombocytopenia (6 patients, 2 with grade 3). Four (18%) patients demonstrated a partial radiographic response, 12 (55%) demonstrated stable disease, and 6 (27%) had progressive disease after 2 cycles of TMZ. Time to tumor progression ranged from 2 months to 28 months (median, 14.5 months). Survival ranged from 4 months to 39 months (median, 23 months). PFS at 6 months, 12 months, 18 months, and 24 months was 64%, 64%, 41%, and 27%, respectively. CONCLUSIONS: TMZ demonstrated modest efficacy with acceptable toxicity in this cohort of adult patients with recurrent low-grade spinal cord gliomas.     

A basis for blocking the spinal cord in opposed field irradiation

The concept of partial tolerance is applied to the equivalent dose formula for spinal cord tolerance to allow for the change in dose when open and blocked fields are used in a course of radiotherapy. The field arrangement considered is parallel opposed irradiation. Certain assumptions are made regarding the contribution of dose to the spinal cord from open and blocked fields, which allows for the development of an equation to calculate the number of fractions that require spinal cord shielding in the posterior field. The use of a form to facilitate these calculations is described.     

Childhood glioblastoma multiforme of the spinal cord

Astrocytoma accounts for more than 50% of all central nervous system tumours diagnosed, with particular prevalence in the 15‐ to 34‐year‐old age bracket, rarely arising in younger children. In 1995, a 7‐year‐old boy presented in Emergency with a 3‐day history of severe radicular back pain and associated muscle spasms, exacerbated by lying on his back. Both bone scan and plain X‐rays were unremarkable; however, MRI showed a 3‐cm space‐occupying lesion at the level of T5‐T6. The patient proceeded to biopsy and partial excision of the tumour through laminectomy, histology confirming an anaplastic astrocytoma (glioblastoma multiforme), St Anne Mayo grade 4. Treatment consisted of a radical course of radiotherapy alone, delivering a total dose of 44.8 Gy at 1.6 Gy per fraction. The treatment comprised of three phases using two oblique wedged fields on a 6 MV linear accelerator. The patient remains disease free 7 years post treatment, with the only effect noted being a slight kyphoscoliosis at the site of the laminectomy and radiation. This report highlights the efficacy of combined surgery and radiation therapy in the management of spinal cord glioblastoma multiforme in preventing tumour recurrence, with acceptable morbidity. Further evaluation of the treatment efficacy would be difficult because of the scarcity of such cases.     

External beam radiotherapy for primary spinal cord tumors

Summary Of 34 evaluated patients with primary spinal cord tumors, 32 were irradiated at our institutions between 1969 and 1983. The results are reported of 32 patients, 16 with ependymoma and 16 with astrocytoma, who were treated with postoperative external beam radiotherapy following biopsy or subtotal resection. Twenty-nine patients received 45–55 Gy megavoltage beam irradiation in five to six weeks, and the remaining three patients received less than 40 Gy. The minimum follow-up was five years. Five- and ten-year actuarial survival rates for the entire group of patients were 73% (22/30) and 50% (8/16), respectively, including three patients who were salvaged by surgery after radiotherapy failures. Corresponding five- and ten-year relapse-free survival rates were 60% (18/30) and 32% (6/19), respectively. Of the 29 patients who received more than 45 Gy, relapse-free survival at five years was 63% (17/27). Treatment failed in 13 patients, and all of those failures were within the irradiated portals. Patients with ependymomas have significantly better relapse free survival than those with astrocytomas, 80% vs. 40% (p < 0.05). There was a significant difference in survival between patients with tumors involving the cervical spine and those with tumors in the other locations, 45% vs. 89% (p < 0.05). There was no significant difference in survival between patients with cauda equina tumors and those with tumors of the spinal cord, 100% vs. 68% (p > 0.05). No radiotherapy-related neurological deficit was noted with a maximum 20 year follow-up. This study confirms that external beam radiotherapy is a safe and effective treatment modality for primary spinal cord tumors.