Hartsell W F, Gajjar A, Heideman R L, Langston J A, Sanford R A, Walter A, Jones D, Chen G, Kun L E
Department of Radiation Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Int J Radiat Oncol Biol Phys. 1997 Aug 1;39(1):15-24. doi: 10.1016/s0360-3016(97)00136-3.
To evaluate the effects of preirradiation chemotherapy on patterns of failure in children with medulloblastoma.
Fifty-three patients (pts) with medulloblastoma were given preirradiation chemotherapy as initial postoperative treatment at St. Jude Children's Research Hospital from November 1984 to September 1993. Patients < or = 3 years of age (n = 23) received chemotherapy (CH) with delayed craniospinal irradiation (CSI). Children > or = 3 years with more advanced disease (T3b-T4, M+ or measurable residual after resection) were given CH followed by CSI (30 patients). Chemotherapy regimen depended on protocol, but usually included cis- or carboplatin and etoposide, +/- cyclophosphamide and vincristine.
Actuarial overall survival and event-free survival rates are 60% (95% confidence interval [41,79]) and 37% [19,55] at 5 years. Children < or = 3 at diagnosis: six of 23 pts completed CH without progression and received consolidative CSI; all six are alive with no evidence of disease (NED) at 2.4-9.1 years. Seventeen patients progressed during CH and were then given CSI. Sites of progression during CH were posterior fossa (PF) in 11 patients, neuraxis (NEUR) in 4, and PF+NEUR in 2. Following CSI, 7 patients are alive NED at 2.0-8.6 years; 10 patients died of progressive disease. Eleven patients had M0 disease at diagnosis; 8 (73%) progressed during CH, 3 in the neuraxis. Children > or = 3 at diagnosis: 20 of 30 patients completed pre-CSI CH without progression; 15 are alive NED at 1.3-9.2 years, and 5 showed post-CSI progression in the PF (n = 3), in the NEUR (n = 1) and in bone marrow (n = 1). Ten of the 30 (33%) patients progressed on CH (6 in NEUR, 4 in PF); 5 are alive and NED or with stable disease. Seventeen patients had M0 disease at diagnosis; 3 out of 17 (18%) progressed during CH, 2 in NEUR and 1 in an extraneural site. In the total group of 30 patients, 11 have had disease recurrence after completion of XRT. The actuarial rate of failure was 23 +/- 9% for the patients < or = 3 years of age and 21 +/- 8% for the older children when evaluated at 4 months after diagnosis (at the completion of chemotherapy in the older children but during the ongoing chemotherapy in the younger children).
In patients presenting with M0 disease and receiving pre-CSI chemotherapy, the risk of neuraxis progression seems to increase with duration of chemotherapy. The sites of progression during preirradiation chemotherapy are nearly equally divided between posterior fossa and other neuraxis sites. CSI salvage of patients progressing on chemotherapy is possible in approximately 50% of patients. Following CSI, neuraxis progression is more frequent than posterior fossa relapse.
评估放疗前化疗对髓母细胞瘤患儿失败模式的影响。
1984年11月至1993年9月期间，53例髓母细胞瘤患者在圣裘德儿童研究医院接受放疗前化疗作为术后初始治疗。年龄≤3岁的患者（n = 23）接受化疗（CH）并延迟进行全脑脊髓放疗（CSI）。年龄≥3岁且疾病进展更严重（T3b - T4、M +或切除后有可测量残留）的儿童先接受CH，然后进行CSI（30例患者）。化疗方案取决于方案，但通常包括顺铂或卡铂以及依托泊苷，±环磷酰胺和长春新碱。
5年时精算总生存率和无事件生存率分别为60%（95%置信区间[41, 79]）和37%[19, 55]。诊断时年龄≤3岁的儿童：23例患者中有6例在未进展的情况下完成CH并接受巩固性CSI；这6例患者均存活，在2.4 - 9.1年时无疾病证据（NED）。17例患者在CH期间病情进展，随后接受CSI。CH期间进展部位为后颅窝（PF）的有11例患者，神经轴（NEUR）的有4例，PF + NEUR的有2例。CSI后，7例患者在2.0 - 8.6年时存活且无疾病；10例患者死于疾病进展。11例患者诊断时为M0期疾病；8例（73%）在CH期间病情进展，3例在神经轴部位。诊断时年龄≥3岁的儿童：30例患者中有20例在CSI前的CH中未进展；15例在1.3 - 9.2年时存活且无疾病，5例在CSI后在PF（n = 3）、NEUR（n = 1）和骨髓（n = 1）出现进展。30例患者中有10例（33%）在CH期间病情进展（6例在NEUR，4例在PF）；5例存活且无疾病或病情稳定。17例患者诊断时为M0期疾病；17例中有3例（18%）在CH期间病情进展，2例在NEUR，1例在神经外部位。在30例患者的总体组中，11例在放疗完成后出现疾病复发。诊断后4个月评估时（年龄较大儿童化疗完成时，但年龄较小儿童化疗进行期间），年龄≤3岁患者的精算失败率为23 ± 9%，年龄较大儿童为21 ± 8%。
在表现为M0期疾病并接受CSI前化疗的患者中，神经轴进展风险似乎随化疗持续时间增加。放疗前化疗期间的进展部位在后颅窝和其他神经轴部位之间几乎平分。化疗进展的患者中约50%可通过CSI挽救。CSI后，神经轴进展比后颅窝复发更频繁。
