化学减容术联合~（125）I巩膜敷贴器近距离放射治疗眼内视网膜母细胞瘤
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摘要
视网膜母细胞瘤(retinoblastoma,RB)是婴幼儿最常见的眼内恶性肿瘤,严重危害患儿的视力和生命。尽早就诊,及时恰当的治疗是挽救患儿生命的关键。若不加以诊治,90%的患儿将失去生命。传统的治疗方案包括:眼球摘除术,眶内容剜除术,外放射治疗等,早期挽救了患儿的生命,同时也带来了致残,致畸等问题,甚至增加了患儿日后放疗区域第二肿瘤发生的几率,对患儿的身心健康发育以及社会、家庭产生深刻影响。近年来,国际上关于视网膜母细胞瘤治疗的概念发生了重大改变,主要表现在:化疗辅助局部治疗逐渐成为了视网膜母细胞瘤的一线治疗方法,保守治疗新纪元的开创,避免了传统治疗方法为患儿带来的创伤与痛苦,同时提高了患儿的生活质量。
我国每年新增视网膜母细胞瘤患儿2000人左右。由于国家医疗条件的局限,家长对该病的认识能力有限,许多患儿就诊时疾病已经发展到较晚期。在给患儿制订治疗方案时,期待在挽救其生命的同时,尽量保留眼球,甚至保存视力,因此使用当前国际上常用的化疗辅助局部治疗的方法势在必行。针对我国视网膜母细胞患儿的病情特点,巩膜敷贴器放射治疗以其治疗效果明确,使用安全方便等成为了局部辅助治疗的首选。
有研究表明:化学减容疗法中,采用卡铂,依托泊甙和长春新碱(CEV)方案效果较为稳定,可在化疗3个疗程后辅助局部治疗加强肿瘤的退缩。在巩膜敷贴器放射治疗当中,125I粒子具有低能量,理想剂量分布,移动方便等物理学特性,对于减少射线对眼球的损伤和降低人体的过量照射起到至关重要的作用。因此,对化学减容辅助局部治疗效果的观察研究有助于进一步探索视网膜母细胞瘤的保守治疗方法并达到提高视网膜母细胞瘤患儿的生存率以及生活质量的目的。
目的:通过临床应用化学减容术联合125I巩膜敷贴器近距离放射治疗眼内期视网膜母细胞瘤患儿,观察眼内视网膜母细胞瘤(RB)患儿接受治疗后的效果,探讨化学减容术联合125I巩膜敷贴器近距离放射治疗的有效性并对治疗的并发症做以初步了解。
方法:
1研究对象:2004年1月至2007年12月间就诊于北京武警总医院眼眶病研究所的视网膜母细胞瘤患儿,21例27只眼。男13例16只眼,女8例11只眼。双眼患儿9例15只眼,患儿初诊时年龄最小6月,最大8岁。
2确诊筛查病例:初步诊断视网膜母细胞瘤的患儿,对其进行R-E分级,确定Ⅳ级b以下患儿初步纳入本组研究。
3化学减容治疗:化学减容术采用卡铂,依托泊甙和长春新碱(CEV)方案,平均应用4.5个疗程。观察其治疗效果,并根据患儿对药物的反应做以判断是否进入下一步治疗或其他针对治疗。
4近距离放射治疗:符合条件的患儿给予个体定制的125I巩膜敷贴器:全麻下手术放置,平均照射7天,然后取出。
5术后对患儿密切随访:平均随访时间为24个月。
6详细记录各项检查数据:就诊至复查时的所有肿瘤相关高度,基底大小数值以及视网膜,视乳头,黄斑,玻璃体情况。
7将相关数据输入SPSS10.0统计软件包进行统计分析,采用计量资料的配对t检验,Fisher精确概率法,P<0.05为具有统计学显著性差异。
结果:最终接受化学减容术联合125I巩膜敷贴器近距离放射治疗的患儿有21例,共计27只眼,其中,患儿接受化学减容2-6个疗程(平均4.5个疗程),接受125I巩膜敷贴器近距离放射治疗5-10天(平均7天),肿瘤顶端接受放射剂量约2700cGy-5500cGy(平均3700cGy),肿瘤基底接受放射剂量约7560cGy-10280cGy(平均约8520cGy),并对其进行了术后的随访以及观察,时间为2-43个月(平均24个月)。观察期内18例患儿存活,占85.7%,3例患儿死亡,占14.3%,均死亡于脑转移。18例患儿的22只眼当中,所有患儿肿瘤皆有退变(缩小),其中,肿瘤退变,目前为止未再复发的15例患儿(19只眼),肿瘤复发者3例(3只眼),行眼球摘除。复发病例均局限在眼内,未出现转移病变,在放射区域未见第二肿瘤发生。1例患儿因为玻璃体腔出血行眼球摘除术,术后病理检查未见到视网膜母细胞瘤细胞。最终眼球的保留率达到66.67%。随访期内患儿病情均得到良好控制,且所有眼球保留患儿视力尚佳。治疗前后肿瘤最大基底直径以及厚度有显著性差异(P<0.05)。
结论:化学减容术联合125I巩膜敷贴器近距离放射治疗是有效治疗视网膜母细胞瘤患儿疾病,保留患儿眼球的保守治疗方案,尽量避免了眼球摘除术,外放射治疗给患儿带来的致残以及致畸可能。在经过化学减容术联合125I巩膜敷贴器近距离放射治疗后,玻璃体腔出血以及眼球萎缩是比较常见的并发症,更多的并发症目前尚未见到。化学减容术联合125I巩膜敷贴器近距离放射治疗眼内视网膜母细胞瘤是有临床应用价值的保守治疗方案,但是远期疗效以及并发症的出现仍需进一步追踪观察。
Retinoblastoma is the most common intraocular malignant tumor of early childhood. RB brings serious jeopardize to vision and life of children. In order to save the life of the patient, the key point is visit as soon as possible, and to be treated in time. Orthodox therapeutic regimen included: enucleation, external beam radiotherapy and so on. Through save the life, the normal physical and mental health of child development must be negatively effective, even the society and family will be disadvantaged a lot. In the last decade, the management of retinoblastoma has gradually changed: The most important recent advance in the management of retinoblastoma is the use of intravenous chemotherapy for tumor reduction, a technique of neoadjuvant chemotherapy termed“chemoreduceion”. This is followed by tumor consolidation with focal measures such as thermotherapy, cryotherapy, and plaque radiotherapy. The advantage of this approach is that enucleation and radiotherapy may be avoided. The challenge remains, however, in remaining the eye and vision.
It is estimated that of the 2000 new cases of retinoblastoma seen in our country. Many of them present with symptom of advanced stage: leukocoria, strabismus. Initial disease detection at the point of leukocoria or strabismus correlated with high patient survival rates and poor ocular survival rates for the presenting eye. So chemoreduction continues to play a major sole in the management of retinoblastoma, in most cases, especially when it is the child’s only remaining eye, the treatment strategy is to avoid enucleation to allow some sight for the child and to avoid external beam radiotherapy to minimize local induction of second cancer. With these considerations, plaque radiotherapy often is the most reasonable treatment choice; it allows globe and sight preservation and has not been associated with an increased risk for radiation-induced second cancers.
The physicians at most institutions prefer to use three agents: carboplatin, etoposide, and vincristine. This strategy provides reduced tumor volume and often permits consolidation with methods other than radiotherapy. 125Iodine is currently the most commonly used isotope in brachytherapy for retinoblastoma. This isotope is advantageous because of its physical characteristics, shielding properties, and low exposure to the patient and personnel. The radioactive seeds can be placed into a custom-built plaque designed to match the size of the lesion. The gold shields of 125I plaques also minimize excess radiation exposure for the patient, the patient’s family, and the medical staff. Over the past years, we have gained an understanding of the indication, limitation and therapeutic efficacy of Chemoreduction plus 125I episcleral plaque brachytherapy for retinoblastoma. In this alysis, we specifically evaluate the results of Chemoreduction plus 125I episcleral plaque brachytherapy as a primary treatment for solid retinoblastoma.
Objective: This research is to observe tumor control, assess the therapeutic effect and complications of Chemoreduction plus 125I episcleral plaque brachytherapy for retinoblastoma.
Methods:
1 Research object: Children with retinoblastoma initially examined on the Institute of Orbital Disease, General Hospital of Chinese people’s Armed Police Forces who is treatment of Chemoreduction plus 125I episcleral plaque brachytherapy.
2 Diagnosis and Screening case: Diagnosed patients with intraocular retinoblastoma were staged according to Reese-Ellsworth (R-E) classification. The inclusion criteria were R-E groups 1-4.
3 Chemoreduction: Consisted of intravenous carboplatin, etoposide and vincristine(CEV), all children were given 2-6 cycles chemotherapy at 3 weekly intervals. (Mean of 4.5 cycles)
4 Brachytherapy: 125I episcleral plaque was adopt in Brachytherapy, plaque placement is performed in the operating room under general anesthesia, which was implanted in episcleral that the tumor’basilar part was corresponding. After average lay up for 7 days, then take out the plaque.
5 Postop follow-up visit: The mean follow-up duration was 24 months.
6 At each follow-up visit, data were gathered on tumor control and treatment complications.
7 Statistical descriptive analyses comprised: Measurement data matched-pairs t-test and Fisher exact test were employed to verify the association between the outcome and the independent variables. For all test P<0.05 were adopted for statistical significance difference.
Results: During the study period, 27 eyes were treated with chemoreduction plus 125I episcleral plaque brachytherapy in 21patients. Patients were given 2-6 cycles chemotherapy at 3 weekly intervals(average 4.5 cycles), 125I episcleral plaque radiotherapeutic was lied up for 5-10days (average 7 days), the dose is 3650 cGy-6300 cGy (average 4300 cGy) to the apex of the tumor ,4800 cGy-32000 cGy (average 14800 cGy) to the base of the tumor. Post-operation, the follow-up time is 2-43 months (average 23 months). 18 patients (85.7%) survived and were followed-up, 3 patients (14.3%) died, all due to intracranial metastasis of the tumor. Among these 18 patients (22 eyes), tumor cataplasia appeared in 15 patients (19 eyes). 3 patients (3 eyes) were enucleated for tumor relapse. All these cases were limited in eye-ball, no signs of tumor metastasis, and deuto-tumor de novo in radiation area. 1 case was enucleated because of hemorrhage in vitreous chamber. Eye-ball reservation rate was 66.67%. During followed-up time, the patient's condition in all of the 18 patients was controlled well, all of who have a useful vision. There was a statistically significant difference with the biggest basement-diameter and thickness of tumor between therapies-before and therapies-after.
Conclusions: Chemoreduction plus 125I episcleral plaque brachytherapy is a relatively utility treatment approach to retinoblastoma, which can eliminate the need for enucleation or EBRT. In major concern with Chemoreduction plus 125I episcleral plaque brachytherapy is the complications: the most common complication is vitreous hemorrhage, and the next is atrophia bulbi. There was no mention of other obviously complication in this study. Chemoreduction plus 125I episcleral plaque brachytherapy for retinoblastoma is a worthy clinical application, yet, the prostecdtive efficacy need keeping on observation.
我国每年新增视网膜母细胞瘤患儿2000人左右。由于国家医疗条件的局限,家长对该病的认识能力有限,许多患儿就诊时疾病已经发展到较晚期。在给患儿制订治疗方案时,期待在挽救其生命的同时,尽量保留眼球,甚至保存视力,因此使用当前国际上常用的化疗辅助局部治疗的方法势在必行。针对我国视网膜母细胞患儿的病情特点,巩膜敷贴器放射治疗以其治疗效果明确,使用安全方便等成为了局部辅助治疗的首选。
有研究表明:化学减容疗法中,采用卡铂,依托泊甙和长春新碱(CEV)方案效果较为稳定,可在化疗3个疗程后辅助局部治疗加强肿瘤的退缩。在巩膜敷贴器放射治疗当中,125I粒子具有低能量,理想剂量分布,移动方便等物理学特性,对于减少射线对眼球的损伤和降低人体的过量照射起到至关重要的作用。因此,对化学减容辅助局部治疗效果的观察研究有助于进一步探索视网膜母细胞瘤的保守治疗方法并达到提高视网膜母细胞瘤患儿的生存率以及生活质量的目的。
目的:通过临床应用化学减容术联合125I巩膜敷贴器近距离放射治疗眼内期视网膜母细胞瘤患儿,观察眼内视网膜母细胞瘤(RB)患儿接受治疗后的效果,探讨化学减容术联合125I巩膜敷贴器近距离放射治疗的有效性并对治疗的并发症做以初步了解。
方法:
1研究对象:2004年1月至2007年12月间就诊于北京武警总医院眼眶病研究所的视网膜母细胞瘤患儿,21例27只眼。男13例16只眼,女8例11只眼。双眼患儿9例15只眼,患儿初诊时年龄最小6月,最大8岁。
2确诊筛查病例:初步诊断视网膜母细胞瘤的患儿,对其进行R-E分级,确定Ⅳ级b以下患儿初步纳入本组研究。
3化学减容治疗:化学减容术采用卡铂,依托泊甙和长春新碱(CEV)方案,平均应用4.5个疗程。观察其治疗效果,并根据患儿对药物的反应做以判断是否进入下一步治疗或其他针对治疗。
4近距离放射治疗:符合条件的患儿给予个体定制的125I巩膜敷贴器:全麻下手术放置,平均照射7天,然后取出。
5术后对患儿密切随访:平均随访时间为24个月。
6详细记录各项检查数据:就诊至复查时的所有肿瘤相关高度,基底大小数值以及视网膜,视乳头,黄斑,玻璃体情况。
7将相关数据输入SPSS10.0统计软件包进行统计分析,采用计量资料的配对t检验,Fisher精确概率法,P<0.05为具有统计学显著性差异。
结果:最终接受化学减容术联合125I巩膜敷贴器近距离放射治疗的患儿有21例,共计27只眼,其中,患儿接受化学减容2-6个疗程(平均4.5个疗程),接受125I巩膜敷贴器近距离放射治疗5-10天(平均7天),肿瘤顶端接受放射剂量约2700cGy-5500cGy(平均3700cGy),肿瘤基底接受放射剂量约7560cGy-10280cGy(平均约8520cGy),并对其进行了术后的随访以及观察,时间为2-43个月(平均24个月)。观察期内18例患儿存活,占85.7%,3例患儿死亡,占14.3%,均死亡于脑转移。18例患儿的22只眼当中,所有患儿肿瘤皆有退变(缩小),其中,肿瘤退变,目前为止未再复发的15例患儿(19只眼),肿瘤复发者3例(3只眼),行眼球摘除。复发病例均局限在眼内,未出现转移病变,在放射区域未见第二肿瘤发生。1例患儿因为玻璃体腔出血行眼球摘除术,术后病理检查未见到视网膜母细胞瘤细胞。最终眼球的保留率达到66.67%。随访期内患儿病情均得到良好控制,且所有眼球保留患儿视力尚佳。治疗前后肿瘤最大基底直径以及厚度有显著性差异(P<0.05)。
结论:化学减容术联合125I巩膜敷贴器近距离放射治疗是有效治疗视网膜母细胞瘤患儿疾病,保留患儿眼球的保守治疗方案,尽量避免了眼球摘除术,外放射治疗给患儿带来的致残以及致畸可能。在经过化学减容术联合125I巩膜敷贴器近距离放射治疗后,玻璃体腔出血以及眼球萎缩是比较常见的并发症,更多的并发症目前尚未见到。化学减容术联合125I巩膜敷贴器近距离放射治疗眼内视网膜母细胞瘤是有临床应用价值的保守治疗方案,但是远期疗效以及并发症的出现仍需进一步追踪观察。
Retinoblastoma is the most common intraocular malignant tumor of early childhood. RB brings serious jeopardize to vision and life of children. In order to save the life of the patient, the key point is visit as soon as possible, and to be treated in time. Orthodox therapeutic regimen included: enucleation, external beam radiotherapy and so on. Through save the life, the normal physical and mental health of child development must be negatively effective, even the society and family will be disadvantaged a lot. In the last decade, the management of retinoblastoma has gradually changed: The most important recent advance in the management of retinoblastoma is the use of intravenous chemotherapy for tumor reduction, a technique of neoadjuvant chemotherapy termed“chemoreduceion”. This is followed by tumor consolidation with focal measures such as thermotherapy, cryotherapy, and plaque radiotherapy. The advantage of this approach is that enucleation and radiotherapy may be avoided. The challenge remains, however, in remaining the eye and vision.
It is estimated that of the 2000 new cases of retinoblastoma seen in our country. Many of them present with symptom of advanced stage: leukocoria, strabismus. Initial disease detection at the point of leukocoria or strabismus correlated with high patient survival rates and poor ocular survival rates for the presenting eye. So chemoreduction continues to play a major sole in the management of retinoblastoma, in most cases, especially when it is the child’s only remaining eye, the treatment strategy is to avoid enucleation to allow some sight for the child and to avoid external beam radiotherapy to minimize local induction of second cancer. With these considerations, plaque radiotherapy often is the most reasonable treatment choice; it allows globe and sight preservation and has not been associated with an increased risk for radiation-induced second cancers.
The physicians at most institutions prefer to use three agents: carboplatin, etoposide, and vincristine. This strategy provides reduced tumor volume and often permits consolidation with methods other than radiotherapy. 125Iodine is currently the most commonly used isotope in brachytherapy for retinoblastoma. This isotope is advantageous because of its physical characteristics, shielding properties, and low exposure to the patient and personnel. The radioactive seeds can be placed into a custom-built plaque designed to match the size of the lesion. The gold shields of 125I plaques also minimize excess radiation exposure for the patient, the patient’s family, and the medical staff. Over the past years, we have gained an understanding of the indication, limitation and therapeutic efficacy of Chemoreduction plus 125I episcleral plaque brachytherapy for retinoblastoma. In this alysis, we specifically evaluate the results of Chemoreduction plus 125I episcleral plaque brachytherapy as a primary treatment for solid retinoblastoma.
Objective: This research is to observe tumor control, assess the therapeutic effect and complications of Chemoreduction plus 125I episcleral plaque brachytherapy for retinoblastoma.
Methods:
1 Research object: Children with retinoblastoma initially examined on the Institute of Orbital Disease, General Hospital of Chinese people’s Armed Police Forces who is treatment of Chemoreduction plus 125I episcleral plaque brachytherapy.
2 Diagnosis and Screening case: Diagnosed patients with intraocular retinoblastoma were staged according to Reese-Ellsworth (R-E) classification. The inclusion criteria were R-E groups 1-4.
3 Chemoreduction: Consisted of intravenous carboplatin, etoposide and vincristine(CEV), all children were given 2-6 cycles chemotherapy at 3 weekly intervals. (Mean of 4.5 cycles)
4 Brachytherapy: 125I episcleral plaque was adopt in Brachytherapy, plaque placement is performed in the operating room under general anesthesia, which was implanted in episcleral that the tumor’basilar part was corresponding. After average lay up for 7 days, then take out the plaque.
5 Postop follow-up visit: The mean follow-up duration was 24 months.
6 At each follow-up visit, data were gathered on tumor control and treatment complications.
7 Statistical descriptive analyses comprised: Measurement data matched-pairs t-test and Fisher exact test were employed to verify the association between the outcome and the independent variables. For all test P<0.05 were adopted for statistical significance difference.
Results: During the study period, 27 eyes were treated with chemoreduction plus 125I episcleral plaque brachytherapy in 21patients. Patients were given 2-6 cycles chemotherapy at 3 weekly intervals(average 4.5 cycles), 125I episcleral plaque radiotherapeutic was lied up for 5-10days (average 7 days), the dose is 3650 cGy-6300 cGy (average 4300 cGy) to the apex of the tumor ,4800 cGy-32000 cGy (average 14800 cGy) to the base of the tumor. Post-operation, the follow-up time is 2-43 months (average 23 months). 18 patients (85.7%) survived and were followed-up, 3 patients (14.3%) died, all due to intracranial metastasis of the tumor. Among these 18 patients (22 eyes), tumor cataplasia appeared in 15 patients (19 eyes). 3 patients (3 eyes) were enucleated for tumor relapse. All these cases were limited in eye-ball, no signs of tumor metastasis, and deuto-tumor de novo in radiation area. 1 case was enucleated because of hemorrhage in vitreous chamber. Eye-ball reservation rate was 66.67%. During followed-up time, the patient's condition in all of the 18 patients was controlled well, all of who have a useful vision. There was a statistically significant difference with the biggest basement-diameter and thickness of tumor between therapies-before and therapies-after.
Conclusions: Chemoreduction plus 125I episcleral plaque brachytherapy is a relatively utility treatment approach to retinoblastoma, which can eliminate the need for enucleation or EBRT. In major concern with Chemoreduction plus 125I episcleral plaque brachytherapy is the complications: the most common complication is vitreous hemorrhage, and the next is atrophia bulbi. There was no mention of other obviously complication in this study. Chemoreduction plus 125I episcleral plaque brachytherapy for retinoblastoma is a worthy clinical application, yet, the prostecdtive efficacy need keeping on observation.
引文
1 李 凤 鸣 . 中 华 眼 科 学 . 北 京 : 人 民 卫 生 出 版社,1996,2225~2233
2 Abramson DH, Schefler AC. Update on retinoblastoma. The Journal of Retinal and Vitreous, 2004, 24: 828~848
3 Azar D, Donaldson C, Kalapesi F, et al. Retinoblastoma in New South Wales 1975-2001. J Pediatr Hematol Oncol, 2006, 28: 642~646
4 Shields CL, Shields JA, De Potter P, et al. Plaque radiotherapy in the management of retinoblastoma: Use as a primary and secondary treatment. Ophthalmology, 1993, 100(2): 216~224
5 Shields CL, De Potter P, Himelstein BP, et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol, 1996, 114(11): 1330~1338
6 Beck MN, Bslmer A, Dressing C. First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma. J Clin oncol, 2000, 18(15): 2881~2887
7 Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma. Analysis of tumor control and rishs for recurrences in 457 tumors. Am J Ophthalmol, 2004,138:329~337
8 Shields CL, Shields JA, Minelli S, et al. Regression ofretinoblastoma after plaque radiotherapy. Am J Ophthalmol, 1993, 115(2): 181~189
9 Aerts I, Pacquement H, Doz F, et al. Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institute Curie. Eur J Cancer, 2004, 40: 1522~1529
10 Shields JA, Shields CL. Atlas of Intraocular tumors. Philadelphia: Lipincott Williams & Wilkins, 1999, 207~232
11 Shields CL, Shields JA. Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabism, 1999, 36: 8~18
12 Ferris FL, Chew EY. A new era for the treatment of retinoblastoma. Arch Ophthalmol, 1996, 114: 1412~1417
13 Gunduz K, Gunalp I, Yalcindag N, et al. Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. Ophthalmology, 2004, 111: 1917~1924
14 Wilson MW, Rodriguez-Galindo C, Haik BG, et al. Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma. Ophthalmology, 2001, 108: 2106~2114
15 Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol, 2002, 133:657~664
16 杨新吉,肖利华等.视网膜母细胞瘤的化学减容治疗[J].眼科新进展. 2007,27(2): 135~137
17 Imhof SM, Mourits MP, Hofman P, et al. Quantification of orbital and mid-facial growth retardation after megavoltage external-beam irradiation in children with retinoblastoma. J Ophthalmology, 1993, 103: 263~268
18 Shields CL, Shields JA. Diagnosis and management of retinoblastoma. Cancer Control, 2004, 11: 317-327
19 Shields CL, Shields JA, Cater J, et al. Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Ophthalmology, 2001, 108: 2116~2121
20 Schiavetti A, Hadjistilianou T, Clerico A, et al. Conservative therapy in intraocular retinoblastoma response/recurrence rate. J Pediatr Hematol Oncol, 2005, 27: 3~6
21 Shields CL, Mashayekhi A, Sun H, et al. Iodine 125 Plaque Radiotherapy as Salvage Treatment for Retinoblastoma Recurrence after Chemoreduction in 84 Tumors. Ophthalmology, 2006, 113: 2087~2092
1 李 凤 鸣 . 中 华 眼 科 学 . 北 京 : 人 民 卫 生 出 版社,1996,2225~2233
2 Shields CL, Shields JA, De Potter P, et al. Plaque radiotherapy in the management of retinoblastoma. Use as a primary and secondary treatment. Ophthalmology, 1993, 100(2): 216~224
3 Shields CL, De Potter P, Himelstein BP, et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol, 1996, 114(11): 1330~1338
4 Shields JA, Shields CL. Intraocular tumors: a text and atlas Philadelphia: WB Saunder, 1992, 377~392
5 Shields JA, Shields CL. Atlas of intraocular tumors. Philadelphia: Lipincott Williams & Wilkins, 1999, 207~232
6 Shields CL. Shields JA. Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabism, 1999, 36:8~18
7 Shields CL, Shield JA. Diagnosis and management of retinoblastoma. Cancer Control, 2004, 11: 317~327
8 Lee WH, Bookstein R, Hong F, et al. Human retinoblastoma susceptibility gene: cloning, identification and sequence. [J], Science, 1987, 235(4794) : 1394~1399
9 Knudson AG Jr. Mutation and cancer. Statistical study of retinoblastoma.[J], Proc Natl Acad Sci USA, 1971, 68:820~823
10 Comings. A general theory of carcinogenesis. Proc Natl Acad Sci USA, 1973, 70(12): 3324~3328
11 Shields JA. Diagnosis and management of intraocular tumors. St. Louis, MO: CV Mosby, 1983: 439
12 Bedford MA, Bedetto C, Macfaul PA. Retinoblastoma, a study of 139 patients. Br J Ophthalmol, 1971, 55: 19~27
13 Balmer A, Gailloud C. Retinoblastoma in: diagnosis and treatment. Including a clinical study, In: Straub W, ed. Turning points in cataract formation, syndromes, and Retinoblastoma. New York, NY: Karger, 1983: 36~100
14 Tarkkanen A, Tuovinen E. Retinoblastoma in Finland 1912-1964.Acta Ophthalmol, 1971, 49: 293~300
15 潘叶,宋国祥.眼眶 CT 显示钙斑的临床意义.中华眼科杂志, 2004, 40:217~219
16 Rechitsky S, Verlinsky O, Chistokhina A, et al. Preimplantation genetic diagnosis for cancer predisposition. Reprod Biomed Online, 2002, 5: 148~155
17 Reese AB, Ellsworth RM. The evaluation and current concept of retinoblastoma therapy. Trans Am Ophthalmol Otolaryngol, 1963, 67: 164~172
18 Howarth C, Meyer D, Hustu HO, et al. Stage at related combined modality treatment of retinoblastoma: Result of a prospective study, Cancer, 1980, 45:851~860
19 Shields CL, Mashayekhi A, Angela K, et al. The International classification of retinoblastoma predictschemoreduction success. Ophthalmology, 2006, 113(12): 2276~2280
20 Shields JA, Shields CL. Enucleation technique for children with retinoblastoma. J peadiatr Ophthalmol Strabismus, 1992, 29(4): 218~222
21 Shields CL, Mashayekhi A, Demirci H,et al. A simplified classification for retinoblastoma. In:11th International retinoblastoma symposium, 2003, Paris, France, 2003
22 Schiedler V, Dubovy SR, Murray TG. Snare technique for enucleation of eyes with advanced retinoblastoma; Arch Ophthalmol, 2007, 125: 680~683
23 孙宪丽.儿童肿瘤.见:郑邦和.眼科临床与实践.北京:北京出版社,1998,613
24 Xu K, Rosenwaks Z, Beaverson K, et al. Preimplantation genetic diagnosis for retinoblastoma: the first reported liveborn. Am J Opthalmol, 2004, 137(1): 18~23
25 Abramson DH, Schefler AC, Dunkel IJ, et al. Neoplasms of the eye. In: Kufe DW, Pollack RE, Weichselbaum RR, et al. Cancer Medicine.6 ed. Hamilton: BC D ECKER, Inc, 2003: 1233~1250
26 Abramson DH, Schefler AC. Update on retinoblastoma. Retina, 2004, 24(6): 828~848
27 Lincoff H,McLean J,Long R .The cryosurgical treatment of intraocular tumors. Am J Ophthalmol, 1967, 63(3): 389~99
28 McDaid C, Hartley S, Bagnall, et al. Systematic review of effectiveness of different treatments for childhoodretinoblastoma. Health Technol Assess, 2005, 11, 9(48): iii, ix~x, 1~145
29 Lagendijk. A microwave heating technique for the hyperthermic treatment of tumours in the eye, especially retinoblastoma. Phys Med Biol, 1982, 27(11): 1313~1324
30 Shields JA, Shields CL, De Potter, et al. Bilateral macular retinoblastoma managed by chemoreduction and chemothermotherapy. Arch Ophthalmol, 1996, 114(11): 1426~1427
31 Shields JA, Shields CL, Cater J, et al. Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors Ophthalmology, 2001, 108: 2116~2121
32 Black L, McCormick B, Abramson DH, et al. External beam radiation therapy and retinoblastoma: long term results in the comparison of two techniques. Int J Radiat Incol Biolphys, 1995, 35:45~57
33 Imhof SM, Mourits MP, Hofman P, et al. Quantification of orbital and mid-facial growth retardation after megavoltage external-beam irradiation in children with retinoblastoma. J Ophthalmology, 1996, 103(2): 263~268
34 Shields CL, Mashayekhi A, Sun H, et al. Iodine 125 Plaque Radiotherapy as Salvage Treatment for Retinoblastoma Recurrence after Chemoreduction in 84 Tumors. Ophthalmology, 2006, 113: 2087~2092
35 Laville I, Pigaglio S. Photodynamic efficiency of diethyleneglycol-linked glycoconjugated porphyrins in human retinoblastoma cells. J Med Chem, 2006, 4, 20, 49(8): 2558~2567
36 Kupfer C. Retinoblastoma treated with intravenous nitrogen mustard. Am J Ophthalmol, 1953, 36: 1721~1724
37 Moll AC, Imhof SM, Schouten-Van Meeteren AY, et al. Chemoreduction for retinoblastoma. Arch Ophthalmol, 2003, 121(10): 1513~1517
38 Shields JA, Shields CL, Meadows AT. Chemoreduction in the management of retinoblastoma. Am J Ophthalmol, 2005, 9, 140(3): 505~506
39 Gunduz K, Gunalp I, Yalcindag N, et al. Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. Ophthalmology, 2004, 111: 1917~1924
40 Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol, 2002, 133: 657~664
41 Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma: Analysis of tumor control and risks for recurrence in 457 tumors. Am J Ophthalmol, 2004, 138: 329~337
42 Lee TC, Hayashi NI, Dunkel IJ, et al. New retinoblastomatumor formation in children treated initially with systemic carboplatin. Ophthalmology, 2003, 110: 1989~1994
43 Borras T. Recent developments in ocular gene therapy. Exp Eye Res, 2003, 76(6): 643~652
44 Herenu CB, Morel GR, Bellini L, et al. Gene therapy in the neuroendocrine system. Front Horm Res , 2006, 35: 135~142
2 Abramson DH, Schefler AC. Update on retinoblastoma. The Journal of Retinal and Vitreous, 2004, 24: 828~848
3 Azar D, Donaldson C, Kalapesi F, et al. Retinoblastoma in New South Wales 1975-2001. J Pediatr Hematol Oncol, 2006, 28: 642~646
4 Shields CL, Shields JA, De Potter P, et al. Plaque radiotherapy in the management of retinoblastoma: Use as a primary and secondary treatment. Ophthalmology, 1993, 100(2): 216~224
5 Shields CL, De Potter P, Himelstein BP, et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol, 1996, 114(11): 1330~1338
6 Beck MN, Bslmer A, Dressing C. First-line chemotherapy with local treatment can prevent external-beam irradiation and enucleation in low-stage intraocular retinoblastoma. J Clin oncol, 2000, 18(15): 2881~2887
7 Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma. Analysis of tumor control and rishs for recurrences in 457 tumors. Am J Ophthalmol, 2004,138:329~337
8 Shields CL, Shields JA, Minelli S, et al. Regression ofretinoblastoma after plaque radiotherapy. Am J Ophthalmol, 1993, 115(2): 181~189
9 Aerts I, Pacquement H, Doz F, et al. Outcome of second malignancies after retinoblastoma: a retrospective analysis of 25 patients treated at the Institute Curie. Eur J Cancer, 2004, 40: 1522~1529
10 Shields JA, Shields CL. Atlas of Intraocular tumors. Philadelphia: Lipincott Williams & Wilkins, 1999, 207~232
11 Shields CL, Shields JA. Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabism, 1999, 36: 8~18
12 Ferris FL, Chew EY. A new era for the treatment of retinoblastoma. Arch Ophthalmol, 1996, 114: 1412~1417
13 Gunduz K, Gunalp I, Yalcindag N, et al. Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. Ophthalmology, 2004, 111: 1917~1924
14 Wilson MW, Rodriguez-Galindo C, Haik BG, et al. Multiagent chemotherapy as neoadjuvant treatment for multifocal intraocular retinoblastoma. Ophthalmology, 2001, 108: 2106~2114
15 Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol, 2002, 133:657~664
16 杨新吉,肖利华等.视网膜母细胞瘤的化学减容治疗[J].眼科新进展. 2007,27(2): 135~137
17 Imhof SM, Mourits MP, Hofman P, et al. Quantification of orbital and mid-facial growth retardation after megavoltage external-beam irradiation in children with retinoblastoma. J Ophthalmology, 1993, 103: 263~268
18 Shields CL, Shields JA. Diagnosis and management of retinoblastoma. Cancer Control, 2004, 11: 317-327
19 Shields CL, Shields JA, Cater J, et al. Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors. Ophthalmology, 2001, 108: 2116~2121
20 Schiavetti A, Hadjistilianou T, Clerico A, et al. Conservative therapy in intraocular retinoblastoma response/recurrence rate. J Pediatr Hematol Oncol, 2005, 27: 3~6
21 Shields CL, Mashayekhi A, Sun H, et al. Iodine 125 Plaque Radiotherapy as Salvage Treatment for Retinoblastoma Recurrence after Chemoreduction in 84 Tumors. Ophthalmology, 2006, 113: 2087~2092
1 李 凤 鸣 . 中 华 眼 科 学 . 北 京 : 人 民 卫 生 出 版社,1996,2225~2233
2 Shields CL, Shields JA, De Potter P, et al. Plaque radiotherapy in the management of retinoblastoma. Use as a primary and secondary treatment. Ophthalmology, 1993, 100(2): 216~224
3 Shields CL, De Potter P, Himelstein BP, et al. Chemoreduction in the initial management of intraocular retinoblastoma. Arch Ophthalmol, 1996, 114(11): 1330~1338
4 Shields JA, Shields CL. Intraocular tumors: a text and atlas Philadelphia: WB Saunder, 1992, 377~392
5 Shields JA, Shields CL. Atlas of intraocular tumors. Philadelphia: Lipincott Williams & Wilkins, 1999, 207~232
6 Shields CL. Shields JA. Recent developments in the management of retinoblastoma. J Pediatr Ophthalmol Strabism, 1999, 36:8~18
7 Shields CL, Shield JA. Diagnosis and management of retinoblastoma. Cancer Control, 2004, 11: 317~327
8 Lee WH, Bookstein R, Hong F, et al. Human retinoblastoma susceptibility gene: cloning, identification and sequence. [J], Science, 1987, 235(4794) : 1394~1399
9 Knudson AG Jr. Mutation and cancer. Statistical study of retinoblastoma.[J], Proc Natl Acad Sci USA, 1971, 68:820~823
10 Comings. A general theory of carcinogenesis. Proc Natl Acad Sci USA, 1973, 70(12): 3324~3328
11 Shields JA. Diagnosis and management of intraocular tumors. St. Louis, MO: CV Mosby, 1983: 439
12 Bedford MA, Bedetto C, Macfaul PA. Retinoblastoma, a study of 139 patients. Br J Ophthalmol, 1971, 55: 19~27
13 Balmer A, Gailloud C. Retinoblastoma in: diagnosis and treatment. Including a clinical study, In: Straub W, ed. Turning points in cataract formation, syndromes, and Retinoblastoma. New York, NY: Karger, 1983: 36~100
14 Tarkkanen A, Tuovinen E. Retinoblastoma in Finland 1912-1964.Acta Ophthalmol, 1971, 49: 293~300
15 潘叶,宋国祥.眼眶 CT 显示钙斑的临床意义.中华眼科杂志, 2004, 40:217~219
16 Rechitsky S, Verlinsky O, Chistokhina A, et al. Preimplantation genetic diagnosis for cancer predisposition. Reprod Biomed Online, 2002, 5: 148~155
17 Reese AB, Ellsworth RM. The evaluation and current concept of retinoblastoma therapy. Trans Am Ophthalmol Otolaryngol, 1963, 67: 164~172
18 Howarth C, Meyer D, Hustu HO, et al. Stage at related combined modality treatment of retinoblastoma: Result of a prospective study, Cancer, 1980, 45:851~860
19 Shields CL, Mashayekhi A, Angela K, et al. The International classification of retinoblastoma predictschemoreduction success. Ophthalmology, 2006, 113(12): 2276~2280
20 Shields JA, Shields CL. Enucleation technique for children with retinoblastoma. J peadiatr Ophthalmol Strabismus, 1992, 29(4): 218~222
21 Shields CL, Mashayekhi A, Demirci H,et al. A simplified classification for retinoblastoma. In:11th International retinoblastoma symposium, 2003, Paris, France, 2003
22 Schiedler V, Dubovy SR, Murray TG. Snare technique for enucleation of eyes with advanced retinoblastoma; Arch Ophthalmol, 2007, 125: 680~683
23 孙宪丽.儿童肿瘤.见:郑邦和.眼科临床与实践.北京:北京出版社,1998,613
24 Xu K, Rosenwaks Z, Beaverson K, et al. Preimplantation genetic diagnosis for retinoblastoma: the first reported liveborn. Am J Opthalmol, 2004, 137(1): 18~23
25 Abramson DH, Schefler AC, Dunkel IJ, et al. Neoplasms of the eye. In: Kufe DW, Pollack RE, Weichselbaum RR, et al. Cancer Medicine.6 ed. Hamilton: BC D ECKER, Inc, 2003: 1233~1250
26 Abramson DH, Schefler AC. Update on retinoblastoma. Retina, 2004, 24(6): 828~848
27 Lincoff H,McLean J,Long R .The cryosurgical treatment of intraocular tumors. Am J Ophthalmol, 1967, 63(3): 389~99
28 McDaid C, Hartley S, Bagnall, et al. Systematic review of effectiveness of different treatments for childhoodretinoblastoma. Health Technol Assess, 2005, 11, 9(48): iii, ix~x, 1~145
29 Lagendijk. A microwave heating technique for the hyperthermic treatment of tumours in the eye, especially retinoblastoma. Phys Med Biol, 1982, 27(11): 1313~1324
30 Shields JA, Shields CL, De Potter, et al. Bilateral macular retinoblastoma managed by chemoreduction and chemothermotherapy. Arch Ophthalmol, 1996, 114(11): 1426~1427
31 Shields JA, Shields CL, Cater J, et al. Plaque radiotherapy for retinoblastoma: long-term tumor control and treatment complications in 208 tumors Ophthalmology, 2001, 108: 2116~2121
32 Black L, McCormick B, Abramson DH, et al. External beam radiation therapy and retinoblastoma: long term results in the comparison of two techniques. Int J Radiat Incol Biolphys, 1995, 35:45~57
33 Imhof SM, Mourits MP, Hofman P, et al. Quantification of orbital and mid-facial growth retardation after megavoltage external-beam irradiation in children with retinoblastoma. J Ophthalmology, 1996, 103(2): 263~268
34 Shields CL, Mashayekhi A, Sun H, et al. Iodine 125 Plaque Radiotherapy as Salvage Treatment for Retinoblastoma Recurrence after Chemoreduction in 84 Tumors. Ophthalmology, 2006, 113: 2087~2092
35 Laville I, Pigaglio S. Photodynamic efficiency of diethyleneglycol-linked glycoconjugated porphyrins in human retinoblastoma cells. J Med Chem, 2006, 4, 20, 49(8): 2558~2567
36 Kupfer C. Retinoblastoma treated with intravenous nitrogen mustard. Am J Ophthalmol, 1953, 36: 1721~1724
37 Moll AC, Imhof SM, Schouten-Van Meeteren AY, et al. Chemoreduction for retinoblastoma. Arch Ophthalmol, 2003, 121(10): 1513~1517
38 Shields JA, Shields CL, Meadows AT. Chemoreduction in the management of retinoblastoma. Am J Ophthalmol, 2005, 9, 140(3): 505~506
39 Gunduz K, Gunalp I, Yalcindag N, et al. Causes of chemoreduction failure in retinoblastoma and analysis of associated factors leading to eventual treatment with external beam radiotherapy and enucleation. Ophthalmology, 2004, 111: 1917~1924
40 Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol, 2002, 133: 657~664
41 Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma: Analysis of tumor control and risks for recurrence in 457 tumors. Am J Ophthalmol, 2004, 138: 329~337
42 Lee TC, Hayashi NI, Dunkel IJ, et al. New retinoblastomatumor formation in children treated initially with systemic carboplatin. Ophthalmology, 2003, 110: 1989~1994
43 Borras T. Recent developments in ocular gene therapy. Exp Eye Res, 2003, 76(6): 643~652
44 Herenu CB, Morel GR, Bellini L, et al. Gene therapy in the neuroendocrine system. Front Horm Res , 2006, 35: 135~142