Preirradiation chemotherapy including “eight drugs in 1 day” regimen and high-dose methotrexate in childhood medulloblastoma: results of the M7 French Cooperative Study

1995 ◽  
Vol 82 (4) ◽  
pp. 608-614 ◽  
Author(s):  
J. C. Gentet ◽  
E. Bouffet ◽  
F. Doz ◽  
P. Tron ◽  
H. Roche ◽  
...  

✓ The aim of this study was to evaluate the feasibility and efficacy of a protocol that includes “sandwich” chemotherapy, that is, chemotherapy alternated with radiotherapy, and reduced doses of supratentorial irradiation in children with medulloblastoma. Between March 1985 and September 1988, 70 successive children with newly diagnosed medulloblastoma from eight centers were treated in this prospective nonrandomized study. Patients were assigned to two risk groups. Group A included patients with macroscopically complete or subtotal excision, no brainstem involvement, no atypical cells in the cerebrospinal fluid, normal myelography, and who were more than 2 years of age. Group B patients encompassed those who did not fit the criteria for Group A. Two children were excluded from analysis after histological review confirmed ependymoma. Thus, a population of 68 children was selected, with 31 in Group A and 37 in Group B. Treatment consisted of two courses of the “eight drugs in 1 day” (“8/1”) regimen followed by two courses of high-dose methotrexate (12 g/m2). Radiotherapy was begun during the 7th week after surgery in Group A and during the 5th week in Group B. In patients older than 2 years, the median radiation dose to the posterior fossa, the spinal axis, and the brain was 54 Gy, 36 Gy, and 27 Gy, respectively. Group B patients received postirradiation chemotherapy with four 8/1 courses monthly. The median time from surgery to radiation therapy was 50 days (range 21 to 141 days). One fatality due to chicken pox on Day 102 and one World Health Organization Grade IV infection occurred. The estimated 5- and 7-year disease-free survival (DFS) rates were 62% and 59%, respectively. These were 74% and 62% in Group A and 57% and 57% in Group B. Patient age, extent of resection, and radiation dose to the whole brain had no prognostic value. Patients with metastasis had a nonsignificant trend for a worse prognosis than patients with nonmetastatic disease (7-year DFS 45% vs. 68%, p = 0.11). In Group B, the 7-year DFS rates for children who received more or less than 30 Gy to the brain were 69% and 52% respectively (p = 0.15). There were recurrences in the posterior fossa (37%), spine (20%), and brain (20%). After a review of radiotherapeutic treatments, only one supratentorial failure could be blamed on reduction of the supratentorial radiation dose. This “sandwich” chemotherapy appeared to be feasible and did not show adverse survival data when compared to other series.

1999 ◽  
Vol 91 (2) ◽  
pp. 221-230 ◽  
Author(s):  
Shoju Hiraga ◽  
Norio Arita ◽  
Takanori Ohnishi ◽  
Eiji Kohmura ◽  
Kazumi Yamamoto ◽  
...  

Object. Twenty-nine nonimmunocompromised patients with primary central nervous system (CNS) lymphoma were treated with high-dose methotrexate (MTX) therapy followed by irradiation. The authors investigated the correlation of infusion schedules with MTX penetration into cerebrospinal fluid (CSF), tumor response, and survival to develop a regimen that would lead to better clinical results.Methods. In this study, 100 mg/kg MTX was administered on either a rapid (3-hour) or regular (6-hour) infusion schedule for two or three cycles. Of 28 assessable patients, a complete or partial response was achieved in 15 (93.8%) of 16 who received rapid and in seven (58.3%) of 12 who received regular infusion therapy (p = 0.034). Rapid infusion significantly increased levels of MTX in the CSF (p < 0.001) and resulted in significant tumor volume reduction (p < 0.001). The mean tumor volume after the first, second, and third cycle of rapid infusion therapy was reduced to 34%, 14%, and 9%, respectively, of the initial volume, whereas the corresponding values were 54%, 42%, and 37% for regular infusion. The reduction between the second and third cycle was small and not significant for either schedule. Despite the longer median survival time in patients who underwent rapid MTX infusion and irradiation (> 60 compared with 20 months), the difference in survival was not significant (p = 0.147) because of the small number of patients enrolled. The median survival time was 39.3 months for all assessable patients who received high-dose MTX and radiation therapy, and the median relapse-free survival time was 35.2 months.Conclusions. Rapid infusion enhanced both MTX penetration into the CSF and tumor response and may improve patient survival. Administration of three or more cycles of therapy should be carefully weighed in terms of cytoreductive benefits.


2001 ◽  
Vol 95 (5) ◽  
pp. 791-797 ◽  
Author(s):  
Christian Sainte-Rose ◽  
Giuseppe Cinalli ◽  
Franck E. Roux ◽  
Wirginia Maixner ◽  
Paul D. Chumas ◽  
...  

Object. The authors undertook a study to evaluate the effectiveness of endoscopic third ventriculostomy in the management of hydrocephalus before and after surgical intervention for posterior fossa tumors in children. Methods. Between October 1, 1993, and December 31, 1997, a total of 206 consecutive children with posterior fossa tumors underwent surgery at Hôpital Necker—Enfants Malades in Paris. Excluded were 10 patients in whom shunts had been placed at the referring hospital. The medical records and neuroimaging studies of the remaining 196 patients were reviewed and categorized into three groups: Group A, 67 patients with hydrocephalus present on admission in whom endoscopic third ventriculostomy was performed prior to tumor removal; Group B, 82 patients with hydrocephalus who did not undergo preliminary third ventriculostomy but instead received conventional treatment; and Group C, 47 patients in whom no ventricular dilation was present on admission. There were no significant differences between patients in Group A or B with respect to the following variables: age at presentation, evidence of metastatic disease, extent of tumor resection, or follow-up duration. In patients in Group A, however, more severe hydrocephalus was demonstrated (p < 0.01); the patients in Group C were in this respect different from those in the other two groups. Ultimately, there were only four patients (6%) in Group A compared with 22 patients (26.8%) in Group B (p = 0.001) in whom progressive hydrocephalus required treatment following removal of the posterior fossa tumor. Sixteen patients (20%) in Group B underwent insertion of a ventriculoperitoneal shunt, which is similar to the incidence reported in the literature and significantly different from that demonstrated in Group A (p < 0.016). The other six patients (7.3%) were treated by endoscopic third ventriculostomy after tumor resection. In Group C, two patients (4.3%) with postoperative hydrocephalus underwent endoscopic third ventriculostomy. In three patients who required placement of CSF shunts several episodes of shunt malfunction occurred that were ultimately managed by endoscopic third ventriculostomy and definitive removal of the shunt. There were no deaths; however, there were four cases of transient morbidity associated with third ventriculostomy. Conclusions. Third ventriculostomy is feasible even in the presence of posterior fossa tumors (including brainstem tumors). When performed prior to posterior fossa surgery, it significantly reduces the incidence of postoperative hydrocephalus. The procedure provides a valid alternative to placement of a permanent shunt in cases in which hydrocephalus develops following posterior fossa surgery, and it may negate the need for the shunt in cases in which the shunt malfunctions. Furthermore, in patients in whom CSF has caused spread of the tumor at presentation, third ventriculostomy allows chemotherapy to be undertaken prior to tumor excision by controlling hydrocephalus. Although the authors acknowledge that the routine application of third ventriculostomy in selected patients results in a proportion of patients undergoing an “unnecessary” procedure, they believe that because patients' postoperative courses are less complicated and because the incidence of morbidity is low and the success rate is high in those patients with severe hydrocephalus that further investigation of this protocol is warranted.


1977 ◽  
Vol 47 (1) ◽  
pp. 50-56 ◽  
Author(s):  
Hiroshi Matsumura ◽  
Yasumasa Makita ◽  
Kuniyuki Someda ◽  
Akinori Kondo

✓ We have operated on 12 of 14 cases of arteriovenous malformation (AVM) in the posterior fossa since 1968, with one death. The lesions were in the cerebellum in 10 cases (three anteromedial, one central, three lateral, and three posteromedial), and in the cerebellopontine angle in two; in two cases the lesions were directly related to the brain stem. The AVM's in the anterior part of the cerebellum were operated on through a transtentorial occipital approach.


2002 ◽  
Vol 97 (3) ◽  
pp. 350-354 ◽  
Author(s):  
Takashiro Ohyama ◽  
Yoshichika Kubo ◽  
Hiroo Iwata ◽  
Waro Taki

Object. An interbody fusion cage has been introduced for cervical anterior interbody fusion. Autogenetic bone is packed into the cage to increase the rate of union between adjacent vertebral bodies. Thus, donor site—related complications can still occur. In this study a synthetic ceramic, β—tricalcium phosphate (TCP), was examined as a substitute for autograft bone in a canine lumbar spine model. Methods. In 12 dogs L-1 to L-4 vertebrae were exposed via a posterolateral approach, and discectomy and placement of interbody fusion cages were performed at two intervertebral disc spaces. One cage was filled with autograft (Group A) and the other with TCP (Group B). The lumbar spine was excised at 16 weeks postsurgery, and biomechanical, microradiographic, and histological examinations were performed. Both the microradiographic and histological examinations revealed that fusion occurred in five (41.7%) of 12 operations performed in Group A and in six (50%) of 12 operations performed in Group B. The mean percentage of trabecular bone area in the cages was 54.6% in Group A and 53.8% in Group B. There were no significant intergroup differences in functional unit stiffness. Conclusions. Good histological and biomechanical results were obtained for TCP-filled interbody fusion cages. The results were comparable with those obtained using autograft-filled cages, suggesting that there is no need to harvest iliac bone or to use allo- or xenografts to increase the interlocking strength between the cage and vertebral bone to achieve anterior cervical interbody fusion.


2003 ◽  
Vol 99 (2) ◽  
pp. 181-187 ◽  
Author(s):  
Takeo Goto ◽  
Kenji Ohata ◽  
Toshihiro Takami ◽  
Misao Nishikawa ◽  
Akimasa Nishio ◽  
...  

Object. The authors evaluated an alternative method to avoid postoperative posterior tethering of the spinal cord following resection of spinal ependymomas. Methods. Twenty-five patients with spinal ependymoma underwent surgery between 1978 and 2002. There were 16 male and nine female patients whose ages at the time of surgery ranged from 14 to 64 years (mean 41.8 years). The follow-up period ranged from 6 to 279 months (mean 112.4 months). In the initial 17 patients (Group A), the procedure to prevent arachnoidal adhesion consisted of the layer-to-layer closure of three meninges and laminoplasty. In the subsequently treated eight patients (Group B), the authors performed an alternative technique that included pial suturing, dural closure with Gore-Tex membrane—assisted patch grafting, and expansive laminoplasty. In Group A, postoperative adhesion was radiologically detected in eight cases (47%), and delayed neurological deterioration secondary to posterior tethering of the cord was found in five cases. In Group B, there was no evidence of adhesive posterior tethering or delayed neurological deterioration. A significant intergroup statistical difference was demonstrated for radiologically documented posterior tethering (p < 0.05, Fisher exact test). Moreover, patients with radiologically demonstrated posterior tethering suffered a significant delayed neurological functional deterioration (p < 0.01, Fisher exact test). Conclusions. This new technique for closure of the surgical wound is effective in preventing of postoperative posterior spinal cord tethering after excision of spinal ependymoma.


1999 ◽  
Vol 91 (4) ◽  
pp. 605-609 ◽  
Author(s):  
Petra M. Klinge ◽  
Georg Berding ◽  
Thomas Brinker ◽  
Wolfram H. Knapp ◽  
Madjid Samii

Object. In this study the authors use positron emission tomography (PET) to investigate cerebral blood flow (CBF) and cerebrovascular reserve (CVR) in chronic hydrocephalus.Methods. Ten patients whose mean age was 67 ± 10 years (mean ± standard deviation [SD]) were compared with 10 healthy volunteers who were 25 ± 3 years of age. Global CBF and CVR were determined using 15O—H2O and PET prior to shunt placement and 7 days and 7 months thereafter. The CVR was measured using 1 g acetazolamide. Neurological status was assessed based on a score assigned according to the methods of Stein and Langfitt.Seven months after shunt placement, five patients showed clinical improvement (Group A) and five did not (Group B). The average global CBF before shunt deployment was significantly reduced in comparison with the control group (40 ± 8 compared with 61 ± 7 ml/100 ml/minute; mean ± SD, p < 0.01). In Group A the CBF values were significantly lower than in Group B (36 ± 7 compared with 44 ± 8 ml/100 ml/minute; p < 0.05). The CVR before surgery, however, was not significantly different between groups (Group A = 43 ± 21%, Group B = 37 ± 29%). After shunt placement, there was an increase in the CVR in Group A to 52 ± 37% after 7 days and to 68 ± 47% after 7 months (p < 0.05), whereas in Group B the CVR decreased to 14 ± 18% (p < 0.05) after 7 days and returned to the preoperative level (39 ± 6%) 7 months after shunt placement.Conclusions. The preliminary results indicate that a reduced baseline CBF before surgery does not indicate a poor prognosis. Baseline CBF before shunt placement and preoperative CVR are not predictive of clinical outcome. A decrease in the CVR early after shunt placement, however, is related to poor late clinical outcome, whereas early improvement in the CVR after shunt placement indicates a good prognosis.


1995 ◽  
Vol 83 (4) ◽  
pp. 724-728 ◽  
Author(s):  
Robert Chen ◽  
David R. Macdonald ◽  
David A. Ramsay

✓ The authors describe a case of a diffuse primary leptomeningeal oligodendroglioma in a 17-year-old girl who presented with raised intracranial pressure and hydrocephalus. She underwent imaging studies and a left frontotemporal craniotomy that revealed a cystic oligodendroglioma in the suprasellar cistern and spread of neoplastic cells to the spinal leptomeninges. The tumor showed little response to maximum radiotherapy and chemotherapy, and the patient died from complications of high-dose chemotherapy 2 years after diagnosis. Postmortem examination of the brain and spinal cord revealed diffuse meningeal infiltration by neoplastic cells and no evidence of an intraparenchymal origin. Glial heterotopias were noted at several sites along the brain base, adding circumstantial support to the theory that leptomeningeal gliomas are derived from ectopic glial tissue in the subarachnoid space.


2002 ◽  
Vol 97 (5) ◽  
pp. 1070-1077 ◽  
Author(s):  
Alexandre Carpentier ◽  
Marc Polivka ◽  
Alexandre Blanquet ◽  
Guillaume Lot ◽  
Bernard George

Object. Chordoma is a locally invasive tumor with a high tendency for recurrence for which radical resection is generally recommended. To assess the benefits of aggressive treatment of chordomas, the authors compared results in patients treated aggressively at the first presentation of this disease with results in patients who were similarly treated, but after recurrence. Methods. Among 36 patients with cervical chordomas who were treated at the authors' institution, 22 underwent primary aggressive treatment (Group A) and 14 were treated secondarily after tumor recurrence (Group B). Two cases were excluded from Group A because of unrelated early deaths and three from Group B because of insufficient pre- or postoperative data. Most tumors were located at the suboccipital level and only eight cases at a level below C-2. Radiotherapy and proton therapy were similarly conducted in both groups of patients. The actuarial survival rates were 80 and 65% at 5 and 10 years, respectively, in Group A patients and 50 and 0% at 5 and 10 years, respectively, in Group B patients (p = 0.049, log-rank test). The actuarial recurrence-free rates were 70 and 35% at 5 and 10 years, respectively, in Group A and 0% at 3 years in Group B (p < 0.0001, log-rank test). The numbers of recurrences per year were 0.15 in Group A and 0.62 in Group B (p > 0.05). All other parameters that were analyzed (patient age, delay before diagnosis, clinical symptoms, chondroid type of lesion, and histological features) did not prove to influence prognosis in a statistically significant manner. Conclusions. Aggressive therapy, combining as radical a resection as possible with radiotherapy, seems to improve the prognoses of suboccipital and cervical chordomas when applied at the patient's first presentation with the disease.


Cancer ◽  
1981 ◽  
Vol 47 (7) ◽  
pp. 1762-1765 ◽  
Author(s):  
Debbie Bowles ◽  
Charles Pratt ◽  
William Evans ◽  
Robert A. Price ◽  
Thomas Coburn

1988 ◽  
Vol 69 (3) ◽  
pp. 393-398 ◽  
Author(s):  
Norihiko Tamaki ◽  
Kunio Shirataki ◽  
Noriaki Kojima ◽  
Yoshiteru Shouse ◽  
Satoshi Matsumoto

✓ Nine (15%) of 60 patients with repaired myelomeningocele exhibited late deterioration of neurological function with a tethered cord syndrome. Dense adhesions at the lowest laminae and at the site of previous repair were the most common findings at surgery. Postoperatively, 71% of the patients improved. Magnetic resonance (MR) imaging was performed in 29 of the 60 patients. Eight of these 29 patients exhibited a tethered cord syndrome. The MR images in all patients showed a low-lying conus fixed at the site of previous repair, irrespective of the presence or absence of a tethered cord syndrome. The MR images were classified into two groups depending upon the site of adhesions: Group A had potential sites of tethering at the ventral aspect of the last laminae and at the site of previous repair, and Group B showed the adhesion point only at the site of previous repair. Most patients with a tethered cord syndrome were found to be in Group A; conversely, most patients without the syndrome were in Group B. An enlarged low conus was seen in symptomatic patients more commonly than in those without this syndrome. It is concluded that the presence of adhesions specifically at the last laminae as well as a widened low-lying conus may be the cause of tethered cord syndrome in patients with repaired myelomeningoceles. A clear understanding of the tethering process and preoperative evaluation of potential sites of tethering, based on the MR findings, are very important for planning surgery. The release of adhesions at the lowest laminae by laminectomy appeared essential for improvement.


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