Prognosis Of Medulloblastoma Research Articles

Expression of c-jun and c-fos oncogene in medulloblastoma and its clinical significance

To study the potential relationship between the expressions of c-jun and c-fos oncogenes and the prognosis of medulloblastoma. The specimens from 70 cases of medulloblastoma of the posterior fossa and 10 cases of normal cerebellar tissues were collected to determine c-jun and c-fos expressions by immunohistochemical staining in formalin fixed paraffin-embedded sections. (1) It showed that c-fos and c-jun protein expression was negative in 10 normal cerebellar tissue, while positive c-fos, c-jun immunoreactivity was found in 70 medulloblastoma specimens. The positive rate of c-jun and c-fos was 80% and 77%, respectively. There was high expression of c-jun and c-fos protein in medulloblastoma tissues. (2) There were positive correlations and strong co-operativity between c-jun and c-fos expression (r = 0.493, P < 0.01). (3) Correlative analysis indicated that expression of c-jun, c-fos were significantly correlated with survival time (c-jun: r = -0.447, P < 0.01; c-fos: r = -0.590, P < 0.01). The higher the expression level of c-jun and c-fos protein was, the worse the prognosis was in medulloblastoma patients. High expression of c-jun and c-fos protein could be noted in medulloblastoma tissues. The two transcription factors show positive correlation and strong co-existence between c-jun and c-fos expressions. The expression levels of c-jun as well as c-fos are negatively correlated with the mortality rate and life expectancy of patients with medulloblastoma. In addition, the co-expression of c-jun and c-fos could serve as an indicator for judging the prognosis of medulloblastoma.

Survival of children under 3 years old with medulloblastoma: a study from the Mexican Cooperative Group for Childhood Malignancies (AMOHP)

The prognosis of medulloblastoma in children under 3 years of age is poor. A retrospective analysis was performed to evaluate children under 3 years of age with medulloblastoma. Overall survival (OS) and progression-free survival (PFS) were assessed in children with and without metastasis. A total of 534 children were diagnosed with medulloblastoma during the study period, 49 (9.1%) of whom were under 3 years of age and were evaluated. Their ages ranged from 5 to 35 months with a mean of 18.5 months. In 39 (79.6%) of these patients the tumors were staged as T3M0 or under, while 10 (20.4%) had metastasis at diagnosis. The OS was 38% and PFS 37% in the whole series, while PFS was 32% in those with metastasis and 40% in those without ( P=0.78). For those who received radiotherapy the PFS was 62%, and in those not treated with radiotherapy PFS was nil ( P=0.0001). When the children were divided into those who received surgical treatment plus chemotherapy and those who received surgery plus radiotherapy plus chemotherapy, the PFS was nil and 66%, respectively ( P=0.00001). Because of the high morbidity of radiotherapy in children under 3 years old, surgery continues to be the basis of improved prognosis, followed by chemotherapy.

Medulloblastoma: experience of a single institution.

The treatment of medulloblastoma has changed considerably during the last decades. Treatment differences between centers may affect a multicenter analysis. We analyzed data from patients of a single institution gathered over a long period of time. Between 1968 and 1995, 60 patients with medulloblastoma were treated at the University of Munster. Thirty-six were male, 24-female. The ages ranged between 11 months and 32 years. Data were retrospectively analyzed from files. Survival was estimated using the Kaplan Meier method and compared using the logranktest and multivariance analysis. The 5-year survival rate was 37%. This included an early mortality of 20% within the first two months, prior to 1980. Significant single, positive, prognostic factors included: no solid metastases (p = 0.001), age > 10 years (p < 0.002); total resection (p < 0.025); posterior fossa radiation with more than 50 Gy (p = 0.04); and intense chemotherapy (p = 0.02). Male patients did slightly worse (not significant). The three-year event-free survival rate of 16 patients treated after 1991 was 70%. The prognosis of medulloblastoma has clearly improved with the reduction of the perioperative mortality, standardized radiotherapy, and the introduction of intense chemotherapy.

Prognosis of medulloblastoma in infants.

The prognosis of medulloblastoma in children less than 3 years old is usually considered to be rather poor. However, recent experiences with this type of tumour seem to indicate that survival in this specific subgroup of patients can be longer than expected. Nineteen infants with posterior fossa tumours treated by the authors in the period 1983-1994, all of them with symptoms presenting during the 1st year of life and all operated on before the end of the 2nd year of life, have been retrospectively analysed. Total tumour removal was achieved in 14 cases, subtotal in 1 and partial in 3. One subject underwent only a biopsy of the tumour. In 14 patients a CSF shunt was inserted. Chemotherapy was administered to 18 out of the 19 patients in the series. At the time of the study, 11 children had died (57.9%) and 8 were alive (42.1%; mean survival 86.5 months). One patient died of complications secondary to the surgical treatment. Three patients died because of local recurrence of the tumour after apparent total excision, death supervening 5, 12 and 18 months after the surgical treatment. A further 2 patients in whom total tumour removal had been performed died 3 and 17 months after surgery of local recurrence of the disease associated with regional metastases. Progression of the residual tumour, accompanied by metastatic dissemination in 3 cases, accounted for death in the other 5 patients who did not survive. Brain stem infiltration appeared to be the most significant adverse prognostic factor. All 8 long-term survivors had their tumour totally excised. Five of them underwent radiotherapy when at least 2 years old. On the basis of the results, the authors conclude that the current prognosis of infants with medullo-blastoma is not necessarily any worse than that of older children with the same disease and that chemotherapy can be particularly useful in this subgroup of patients, as shown by 3 long-term survivals obtained in children treated with this type of therapy only.

Cerebellar medulloblastomas: a comparison between adults and children

A retrospective analysis of 19 medulloblastomas in patients aged 2 to 24 years was conducted employing 14 children (<15 years old) and 5 adults. All patients received gross total excision of the tumour with postoperative craniospinal irradiation. The patients were then followed up for more than 5 years. To determine which factors influenced the prognosis of these two age groups, we analysed the differences of the proliferating cell nuclear antigen (PCNA), the degree of tumour invasion and the outcome between adult and childhood medulloblastomas. In summary, medulloblastomas in adults and children had similar cell proliferative activity and long term survival rates but the tumours with brain stem invasion, which commonly occurred in children, had an early recurrence rate and a poor prognosis. The prognosis of medulloblastoma may depend upon the degree of tumour invasion of the brain stem.

A review of the factors influencing the prognosis of medulloblastoma. The importance of cell differentiation.

The clinical, therapeutic, and histological features of 54 patients with medulloblastoma were analyzed retrospectively by a multivariate approach with regard to prognosis. The overall 5-year survival rate was 60%, with 48% of patients free of recurrence at 5 years. Cell differentiation, when present, was associated with a significantly longer recurrence-free period. Seventy-two percent of patients with the histological finding of cell differentiation were recurrence-free at 5 years. A marginally significant increase in the 5-year survival rate was also seen in association with differentiation. Only 34% of the patients whose tumor exhibited necrosis were alive at 5 years. There was no statistically significant difference in 5-year survival for children under 3 years of age or for the group of children aged 5 years or under. However, a significantly larger fraction (72%) of the group aged 5 years or under had a recurrence-free period of 5 years or more. Other factors including sex, extent of surgical resection. Chang tumor stage, posterior fossa radiation dose, and adjuvant chemotherapy did not influence prognosis.

Treatment and prognosis of medulloblastoma--a study of 13 surgical cases (author's transl)

Thirteen cases of medulloblastoma were experienced. All of the patients were operated on and the diagnosis was confirmed histologically. Nine were then treated with cranial and spinal irradiation. Three patients received incomplete irradiation and one died without it. A one year-old and a 14 year-old boys among the nine patients with completed scheduled irradiation showed no recurrence or metastasis; the former for seven years and four months and the latter for five years. In the other seven cases, five had local recurrences and six had spinal metastasis. Four of these patients also showed second recurrences and/or metastasis. There were three spinal, one frontal, one extracranial metastases and two local recurrences. Recurrences and/or metastases in three of these seven cases were aggressively treated with re-irradiation and combined-chemotherapy (vincristine, procarbazine and predonisolone, including methtrexate occasionally). Patients with recurrence and/or metastasis after one year or with survival times of more than three years were found to be older, had radical operations and received less primary dosis in the posterior fossa and a higher dosis in the spinal canal, compared with patients with early recurrence and/or metastasis or with short survival periods. Three patients who received re-irradiation and combined chemotherapy and one patient who was treated with antibiotics for meningitis are alive at present. It was clear that not only the age of patients and operative procedures, but the spinal irradiation dosis influenced the time of recurrence or metastasis and survival. Primary spinal irradiation doses were below 2, 500 rads in seven of the nine cases who completed initial cranial and scheduled spinal irradiation. It seems that a low dosis in the spinal canal decreased the survival rate compared with those in other institutions using higher spinal doses. Complete irradiation of the entire CNS at certain doses (whole brain: 4, 000-5, 000 rads, posterior fossa: 4, 500-5, 000 rads, and spinal: 3, 000-3, 500 rads) and early postoperative chemotherapy are recommended, and aggressive treatment including re-operation, re-irradiation and long term combined-chemotherapy is indispensable to combat recurrence and metastasis.

Treatment and prognosis of medulloblastoma.

In the 27-year period from 1932 to 1959, 22 patients were treated for cerebellar medulloblastoma, the diagnosis being verified in 19. Seven typical case histories are given. Five patients were living 7 or more years later without evidence that either brain or spinal cord had been damaged by the radiation applied. The results showed that a patient treated with a depth dose of 5,000 roentgens may be cured without damage to the normal brain tissue surrounding the tumor and that a dose of 1,500 to 2,000 roentgens to the cord sometimes prevents recurrence without damage to the cord. Since these experiences do not justify the hopeless attitude of the past towards this admittedly serious disease, it is believed that a word of encouragement should be given to the child's relatives.

The Prognosis of Medulloblastoma in Children

The te rm medul lob las toma was introduced to distinguish this neoplasm as a specific tumor ent i ty by Bailey and Cushing in 19~5. 8 Cushing had opera ted upon tumors of this type as early as 1903. TM Bailey and Cushing believed tha t a fa ta l outcome was inevitable, but t ha t radiat ion t h e r a p y was conclusively beneficial in prolonging the average postoperat ive survival. 9 This me thod of t reat m e n t had been used since 1919.19 Not ing an incidence of 6 cases of spinal meningeal metas tases among their to ta l of 61, they extended the field of irradiat ion to include routinely the spinal axis in 19~72 Thei r goal of operat ion was to unblock the aqueduct , ra ther than to a t t e m p t gross total removal of the t umor? 9 Subsequent repor t s have been in substantial agreement wi th the ear ly views of Bailey and Cushing regarding t r e a t m e n t and prognosis 1 0 -12 ,16 ,18 ,25 ,29-31 ,38 ,43 ,46 ,51 ,54-56 The futi l i ty of a t t e m p t i n g cure by radical operat ion has become well establ ished? 2 On the other hand, i r radiat ion wi thout operat ion has been condemned. I r reparab le damage m a y occur during the delay necessitated by trial irradiation of a radioresis tant , benign tumor incorrectly diagnosed2 7 Fur thermore , irradiation wi thout pr ior decompression risks a fatal edema. 17 The possible advan tage of avoiding operat ive dissemination of t u m o r cells through the subarachnoid space has assumed less importance since it has been shown tha t seeding may occur even wi thout operation?,~3 Survivals longer than 5 years have been repor ted sporadical]y?4,17,20-24,2~-2s,32,34-~6,40, 41,4~-49,6z,sa In some of these cases the diagnosis has been disputed or actual ly changed. 7, 12,17,57 The m a t t e r is fur ther complicated by the failure of m a n y authors to confine their reports to tumors occurring in children, 14,17, 20,21,24,26,27,32,;~4,36,47-49,53 since similar tumors in the adul t have been thought to have a more favorable prognosisN ,5~ Bailey believes t h a t the medul loblas toma occurs only in children under 15 and tha t the leptomeningeal sarcoma has often been confused with it in the adult . 5 While this m a y be a m a t t e r of opinion, we feel t h a t analyses clearly distinguishing between cases in children and in adul ts are more meaningful. The most optimist ic repor t o ther t han our own is tha t of Pa te rson and F a r r ? 5 In 1953 they repor ted 6 children with 5-year survivals among ~1 opera ted upon and irradiated.