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Jacques Grill

Publications and source records attributed to Jacques Grill.

At least 19 recordsLinked to original sources
PubMed2008

Do medulloblastoma tumors meet the Food and Drug Administration criteria for anti-erbB2 therapy with trastuzumab?

Several publications have recently focused on the erbB2 receptor in pediatric medulloblastomas (MBs) and its prognostic consequence. We determined erbB2 expression in 23 MBs at diagnosis. After DNA extraction, quantitative PCR targeting the erbB2 gene was performed and correlated with FISH analysis and immunohistochemistry. The samples were representative of the spectrum of the disease apart from the absence of large cell MBs. Using the tools validated for breast cancers by the FDA, we did not observe any expression or amplification of erbB2 and hence we speculate that MBs are not a good target for treatment with anti-erbB2 antibodies.

Animals↗
PubMed2007

Pediatric craniopharyngiomas: classification and treatment according to the degree of hypothalamic involvement.

OBJECT: The current treatment of craniopharyngiomas is evolving into one of a multimodal approach in which the aim is disease control and improved preservation of quality of life (QOL). To date, an appropriate classification system with which to individualize treatment is absent. The objectives of this study were to identify preoperative prognostic factors in patients with craniopharyngiomas and to develop a risk-based treatment algorithm. METHODS: The authors reviewed data obtained in a retrospective cohort of 66 children (mean age 7.4 years, mean follow-up period 7 years) who underwent resection between 1984 and 2001. Postoperative recurrence rates, vision status, and endocrine function were consistent with those reported in the literature. The postoperative morbidity was related to hypothalamic dysfunction. The preoperative magnetic resonance imaging grade, clinically assessed hypothalamic function, and the sugeon's operative experience (p = 0.007, p = 0.047, p = 0.035, respectively) significantly predicted poor outcome. Preoperative hypothalamic grading was used in a prospective cohort of 22 children (mean age 8 years, mean follow-up period 1.2 years) treated between 2002 and 2004 to stratify patients according to whether they underwent gross-total resection (GTR) (20%), complete resection avoiding the hypothalamus (40%), or subtotal resection (STR) (40%). In cases in which residual disease was present, the patient underwent radiotherapy. There have been no new cases of postoperative hyperphagia, morbid obesity, or behavioral dysfunction in this prospective cohort. CONCLUSIONS: For many children with craniopharyngiomas, the cost of resection is hypothalamic dysfunction and a poor QOL. By using a preoperative classification system to grade hypothalamic involvement and stratify treatment, the authors were able to minimize devastating morbidity. This was achieved by identifying subgroups in which complete resection or STR, performed by an experienced craniopharyngioma surgeon and with postoperative radiotherapy when necessary, yielded better overall results than the traditional GTR.

Adolescent↗
PubMed2006

p53 Pathway dysfunction in primary childhood ependymomas.

BACKGROUND: Childhood ependymoma remains a major therapeutic challenge despite surgery, chemotherapy, and irradiation. We hypothesized that p53 function might be abrogated in ependymomas and implicated in their resistance to anti-cancer therapy. PROCEDURE: Primary ependymomas at diagnosis or relapse from 24 children were analyzed for p53 pathway, using a functional assay in yeast, RT-PCR, Western blot analysis, and/or immunohistochemistry for TP53 mutation, p14(ARF) deletion and promoter hypermethylation, MDM2 and PAX5 expression, respectively. p53-mediated response to radiation-induced DNA damage was evaluated using Western blot and flow cytometry analysis in two ependymoma xenograft models, IGREP37 and IGREP83, derived from primary anaplastic childhood ependymomas. RESULTS: No TP53, MDM2, p14(ARF), PAX5 gene abnormalities were detected in the primary ependymomas tumors and xenografts tested. Interestingly, despite the lack of these abnormalities, p53 induced p21-mediated G(1) growth arrest in response to irradiation was altered in the IGREP37 xenograft tumors. Although irradiation induced necrosis and apoptotic cell death, IGREP37 tumors were moderately sensitive to radiation therapy in vivo. In contrast, irradiation yielded significant tumor growth delays and tumor regressions in the p53 functional IGREP83 xenografts. CONCLUSION: Alterations in p53-mediated growth arrest in ependymomas might be implicated in the radio-resistance of these tumors and demand further evaluation.

Animals↗
PubMed2006

Methylation of RASSF1A and TRAIL pathway-related genes is frequent in childhood intracranial ependymomas and benign choroid plexus papilloma.

Ependymomas (EP) represent the third most frequent type of central nervous system (CNS) tumor of childhood, after astrocytomas and medulloblastomas. No prognostic biological markers are available, and differentiation from choroid plexus papilloma (CPP) is difficult. The present objective was, for a sample of 27 children with intracranial EP and 7 with CPP, to describe and compare the methylation status of 19 genes (with current HUGO symbol, if any): p15INK4a (CDKN2B), p16INK4a and p14ARF (both CDKN2A), APC, RB1, RASSF1A (RASSF1), BLU (ZMYND10) FHIT, RARB, MGMT, DAPK (DAPK1), ECAD (CDH1), CASP8, TNFRSF10C, TNFRSF10D, FLIP (CFLAR), INI1 (SMARCB1), TIMP3, and NF2. Three adult corteses were used as a control. We detected a similar percentage of methylated tumors in both groups (71% in CPP and 77% in EP). No gene was methylated in that control group. RASSF1A was the most frequently methylated gene in both benign tumors (66%) and EP (56%). The genes associated with apoptosis were methylated in both groups of tumors. The percentages of TRAIL pathway genes (CASP8, TFRSF10C, and TFRSF10D) methylated were 30, 9.5, and 36.4%, respectively, in ependymomas and 50, 50, and 16.7%, respectively, in choroid plexus papillomas. No other gene was methylated in the benign tumors, whereas FHIT was methylated in 22%, RARB in 14.8%, BLU in 13.6%, p16INK4a in 11.1%, TNFRSF10C in 9.5%, and DAPK in 7.4% of ependymomas. Although we did not observe a statistical relationship between methylation and clinical outcome, the methylation pattern does not appear to be randomly distributed in ependymoma and may represent a mechanism of tumor development and evolution.

Adolescent↗
PubMed2006

Multimodal treatment of craniopharyngioma: defining a risk-adapted strategy.

Craniopharyngiomas remain a therapeutic challenge in terms of treatment-related morbidity. The fact that they are rare, that they are histologically benign, and that anatomically they are located in a challenging area, made them worthy surgical prizes. Whilst surgery has allowed us to meet the challenge of visual salvage, and the advances in hormone replacement therapy are addressing the endocrine challenge, we are becoming increasingly aware that for many children radical resection comes with the cost of devastating effects on quality of life. Increasingly we are recognizing that the next challenge is preservation of hypothalamic function. This consciousness of the morbidity of radical resection has led us, like many pediatric units, to re-examine multimodal treatment strategies. This review examines the Necker experience, aiming to analyze the factors influencing our decision making for treatment.

Combined Modality Therapy↗
PubMed2005

Topotecan as a radiosensitizer in the treatment of children with malignant diffuse brainstem gliomas: results of a French Society of Paediatric Oncology Phase II Study.

BACKGROUND: The current Phase II study was conducted to evaluate the survival and toxicity observed in children with newly diagnosed brainstem gliomas who were treated with the daily radiotherapy with topotecan used as a radiosensitizer. METHODS: Eligible patients were those ages 3-18 years with previously untreated tumors arising in the pons diagnosed within the previous 6 months. Histologic confirmation was not mandatory provided that the clinical and magnetic resonance imaging findings were typical for a diffusely infiltrating brainstem lesion. Treatment was comprised of a 6-week course of topotecan administered intravenously at a dose of 0.4 mg/m(2)/day over 30 minutes within 1 hour before irradiation. Radiotherapy was comprised of a once-daily treatment of 1.8 grays (Gy) per fraction to a total dose of 54 Gy. RESULTS: Thirty-two patients were included in the current study between August 2000 and October 2002. All patients completed the combined treatment in accordance with the treatment design. Only partial responses were observed, occurring in 40% of the patients. The 9-month and 12-month survival rates were 34.4% +/- 8% and 25.5% +/- 8%, respectively. The median duration of survival for these 32 patients was 8.3 months. An intratumoral cystic/necrotic change was observed in five patients, with clinical impairment noted in two patients. One intratumoral hemorrhage occurred during radiotherapy, and was associated with transitory neurologic impairment. CONCLUSIONS: The findings of the current study regarding newly diagnosed brainstem glioma patients treated with topotecan given as a radiosensitizing agent did not reproduce the encouraging results obtained in preclinical studies. Therefore, the concomitant combination of topotecan and radiotherapy at this schedule and these doses cannot be recommended for the treatment of patients with brainstem gliomas.

Adolescent↗
PubMed2005

Craniopharyngioma: the pendulum of surgical management.

BACKGROUND: For a long time, craniopharyngiomas have been considered surgically attractive tumours. The fact that they are rare, histologically benign, and located in a challenging (but considered accessible) area made them worthy surgical prizes. METHODS: As we have saved vision and "cured" many of these tumours, the insidious and devastating effects on quality of life for these children has become evident. DISCUSSION: The state-of-the-art in the surgical management of craniopharyngioma is now turning to multi-modality treatment strategies (combination surgery and radiotherapy) aiming to limit morbidity. Questions remain-what factors influence our surgical decision making? Do we understand the long-term effects of the radiotherapy now being employed? We review a series of craniopharyngiomas looking for variables that correlated with outcome as perceived in terms of quality of life and we review briefly the history of craniopharyngioma surgery and the relevant literature.

Craniopharyngioma↗
PubMed2005

Conformal radiotherapy, reduced boost volume, hyperfractionated radiotherapy, and online quality control in standard-risk medulloblastoma without chemotherapy: results of the French M-SFOP 98 protocol.

PURPOSE: Between December 1998 and October 2001, patients <19 years old were treated for standard-risk medulloblastoma according to the Medulloblastome-Société Française d'Oncologie Pédiatrique 1998 (M-SFOP 98) protocol. Patients received hyperfractionated radiotherapy (36 Gy in 36 fractions) to the craniospinal axis, a boost with conformal therapy restricted to the tumor bed (to a total dose of 68 Gy in 68 fractions), and no chemotherapy. Records of craniospinal irradiation were reviewed before treatment start. RESULTS: A total of 48 patients were considered assessable. With a median follow-up of 45.7 months, the overall survival and progression-free survival rate at 3 years was 89% and 81%, respectively. Fourteen major deviations were detected and eight were corrected. No relapses occurred in the frontal region and none occurred in the posterior fossa outside the boost volume. Nine patients were available for volume calculation without reduction of the volume irradiated. We observed a reduction in the subtentorial volume irradiated to >60 Gy, but a slight increase in the volume irradiated to 40 Gy. No decrease in intelligence was observed in the 22 children tested during the first 2 years. CONCLUSION: This hyperfractionated radiotherapy protocol with a reduced boost volume and without chemotherapy was not associated with early relapses in children. Moreover, intellectual function seemed to be preserved. These results are promising.

Adolescent↗
PubMed2005

Expression of p53, or targeting towards EGFR, enhances the oncolytic potency of conditionally replicative adenovirus against neuroblastoma.

BACKGROUND: Advanced stage and relapsing neuroblastoma (NB) has a poor prognosis with frequent treatment failures, warranting new treatment options and enhanced local tumor control. Treatment with conditionally replicative adenoviruses (CRAds) has shown effectiveness in various preclinical cancer models, but has not yet been evaluated for local control of NB. Here, we tested the efficacy of the CRAd AdDelta24 and of two AdDelta24 derivatives against NB. Derivative AdDelta24-425S11 infects cells deficient in coxsackie/adenovirus receptor (CAR) via the epidermal growth factor receptor (EGFR). Derivative AdDelta24-p53 expresses the tumor suppressor protein p53 to promote oncolysis. METHODS: Expression of CAR and EGFR, and p53 pathway and DNA damage responses were analyzed in six NB cell lines and two xenografts derived from primary NB using immunohistochemistry, reporter gene transactivation, Western blot and fluorescence-activated cell sorting (FACS) analysis. Efficacy of AdDelta24, AdDelta24-425S11 and AdDelta24-p53 against NB was evaluated in vitro by cell viability analysis and in vivo by monitoring subcutaneous xenograft tumor growth in mice and by histological analysis of treated tumors. RESULTS: Neuroblastoma cell lines were sensitive to oncolysis by AdDelta24, with a higher susceptibility of those with functional p53 and intact DNA damage responses. Compared to AdDelta24, AdDelta24-p53 exhibited enhanced oncolytic potency on all NB cell lines independent of their p53 status and AdDelta24-425S11 was more effective against CAR-low IGR-NB8 cells. Moreover, five daily intratumoral injections of 10(8) plaque-forming units (pfu) of AdDelta24-p53 or AdDelta24-425S11 into subcutaneous IGR-NB8 and IGR-N91 xenografts at an advanced tumor stage yielded significant tumor growth delays (TGD). In contrast, at this dose, AdDelta24 did not cause significant TGD of neuroblastoma xenografts. Injection of AdDelta24-p53 was associated with extensive cell lysis, apoptotic cell death, and fibrous fascicles in the tumors. CONCLUSION: CRAds expressing p53 and targeted towards EGFR appear promising new agents for local control in the treatment of neuroblastoma.

Adenoviridae↗
PubMed2005

Therapeutic schedules influence the pattern of intellectual decline after irradiation of posterior fossa tumors.

BACKGROUND: To evaluate intellectual decline in children with posterior fossa (PF) tumors treated with different therapeutic protocols. PROCEDURE: Forty children had a complete neuropsychological evaluation prospectively twice, at least 6 months year (y) after the end of their treatment. Patients were classified into four groups according to treatment schedules: Group 1 (n = 7) PF radiotherapy (PFRT) alone at 50 Gy; Group 2 (n = 13) reduced-dose cranio-spinal irradiation (CSI) at 25 Gy with a PF boost; Group 3 (n = 9) standard CSI at 35 Gy and a PF boost; and Group 4 (n = 11) high-dose chemotherapy with stem cell support followed by PFRT at 50 Gy. RESULTS: At the first evaluation (mean interval since diagnosis 3.7 y), the mean Full-Scale Intellectual Quotient (FSIQ) was 80 (SD = 19). Only patients in Group 1 had a normal mean IQ score of 92 (SD = 14). At the second evaluation (mean interval since diagnosis 6.3 y), the mean FSIQ scores were significantly lower with a mean difference of 2.4 points, i.e., a yearly decline of one point. The magnitude of the FSIQ decline was positively correlated with the first IQ score (P = 0.0001) and inversely correlated with age at diagnosis (P = 0.0005). A FSIQ decline was observed in all treatment groups except Group 1 (P = 0.005). The differences in FSIQ observed initially between the four treatment groups persisted at the second evaluation. CONCLUSIONS: This study shows that FSIQ continues to decline more than 4 years after the diagnosis but this yearly decline seems to decrease with time from diagnosis. Therapeutic schedules influence the magnitude of this decline. Long-term follow-up into adulthood is necessary to effectively adapt patient rehabilitation.

Adolescent↗
PubMed2005

The therapy of infantile malignant brain tumors: current status?

Malignant brain tumors are not uncommon in infants as their occurrence before the age of three represents 20-25% of all malignant brain tumors in childhood [1]. Genetic predisposition to infantile malignant brain tumors are known in Gorlin syndrome for example who present with desmoplastic medulloblastoma in about 5% of the affected patients. In addition, sequelae from tumor and its treatment are more severe at this age [2]. Thus, malignant brain tumors represent a true therapeutic challenge in neuro-oncology. Before the era of modern imaging and modern neurosurgery these malignant brain tumors were misdiagnosed or could not benefit of the surgical procedures as well as older children because of increased risks in this age group. Since the end of the 80s, noninvasive imaging procedures produce accurate diagnosis of brain tumors and improvement in neurosurgery, neuroanesthesia and perioperative intensive care permit safe tumor resections or at least biopsies. Consequently, the pediatric oncologists are more often confronted with very young children who need a complementary treatment. Before the development of specific approaches for this age group, these children received the same kind of treatment than the older children did, but their survival and quality of life were significantly worse. The reasons of these poor results were probably due in part to the fear of late effects induced by radiation therapy, leading to decrease the necessary doses of irradiation which increased treatment failures without avoiding treatment related complications [3]. At the end of the 80s, pilot studies were performed using postoperative chemotherapy in young medulloblastoma patients. Van Eys treated 12 selected children with medulloblastoma with MOPP regimen and without irradiation; 8 of them were reported to be long term survivors [4]. Subsequently, the pediatric oncology cooperative groups studies have designed therapeutic trials for very young children with malignant brain tumors. Different approaches have been explored: * Prolonged postoperative chemotherapy and delayed irradiation as designed in the POG (Pediatric Oncology Group). * Postoperative chemotherapy without irradiation in the SFOP (Société Française d'Oncologie Pédiatrique) and in the GPO (German Pediatric Oncology) studies. * The role of high-dose chemotherapy with autologous stem cells transplantation was explored in different ways: High-dose chemotherapy given in all patients as proposed in the Head Start protocol. High-dose chemotherapy given in relapsing patients as salvage treatment in the French strategy. In the earliest trials, the same therapy was applied to all histological types of malignant brain tumors and whatever the initial extension of the disease. This attitude was justified by the complexity of the classification of all brain tumors that has evolved over the past few decades leading to discrepancy between the diagnosis of different pathologists for a same tumor specimen. Furthermore, it has become increasingly obvious that the biology of brain tumors in very young children is different from that seen in older children. However, in the analysis of these trials an effort was made to give the results for each histological groups, according to the WHO classification and after a central review of the tumor specimens. All these collected data have brought to an increased knowledge of infantile malignant brain tumors in terms of diagnosis, prognostic factors and response to chemotherapy. Furthermore a large effort was made to study long term side effects as endocrinopathies, cognitive deficits, cosmetic alterations and finally quality of life in long term survivors. Prospective study of sequelae can bring information on the impact of the different factors as hydrocephalus, location of the tumor, surgical complications, chemotherapy toxicity and irradiation modalities. With these informations it is now possible to design therapeutic trials devoted to each histological types, adapted to pronostic factors and more accurate treatment to decrease long term sequelae.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Treatment of medulloblastoma with postoperative chemotherapy alone: an SFOP prospective trial in young children.

BACKGROUND: Morbidity and mortality are high in young children with medulloblastoma who receive craniospinal radiotherapy. We aimed to assess whether adjuvant treatment with protracted chemotherapy alone could replace radiotherapy. METHODS: We enrolled 79 children aged younger than 5 years who had had surgical resection of medulloblastoma onto a multicentre trial. Patients were treated with combination chemotherapy, which did not include methotrexate, for more than 16 months irrespective of the extent of disease. Early postoperative imaging defined three groups: R0M0 (no residual disease, no metastasis), R1M0 (radiological residual disease alone), and RXM+ (presence of metastases). Patients who did not relapse did not receive radiotherapy. Patients who relapsed or had disease progression received salvage treatment, which consisted of high-dose chemotherapy and stem-cell transplantation followed by local or craniospinal radiotherapy. For children classified as R0M0, the primary endpoint was 5-year overall survival and the secondary endpoint was 5-year progression-free survival. For children classified as R1M0 or RXM+, the primary endpoint was best radiological response and the secondary endpoints were 5-year overall survival and 5-year progression-free survival. Analyses were done by intention to treat. FINDINGS: Two of 15 patients classified as RXM+ and four of 17 patients classified as R1M0 had a complete radiological response. 5-year progression-free survival was 29% (95% CI 18-44) in the R0M0 group, 6% (1-27) in the R1M0 group, and 13% (4-38) in the RXM+ group. 5-year overall survival was 73% (59-84) in the R0M0 group, 41% (22-64) in the R1M0 group, and 13% (4-38) in the RXM+ group. In the R0M0 group, 5-year progression-free survival was 41% (26-58) for the 34 patients who underwent gross total resection compared with 0% for the 13 patients who had subtotal resection (relative risk 2.7 [1.3-5.6], p=0.0065). INTERPRETATION: Conventional chemotherapy alone can be used to cure children with non-metastatic medulloblastoma who have gross total resection confirmed by early radiological assessment, but is not sufficient for treatment of those with metastatic or incompletely resected medulloblastoma. Salvage treatment followed by posterior-fossa radiotherapy can effectively treat local relapses or progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Oncolytic virotherapy of meningiomas in vitro with replication-competent adenovirus.

OBJECTIVE: To evaluate the efficacy of the conditionally replicating adenovirus (Ad) Ad.d24 for oncolysis of benign and malignant meningiomas. METHODS: Primary meningioma cells and organotypic spheroids were cultured from tumor biopsies of 12 consecutive unselected patients. Four different Ads were constructed and tested on meningioma cells and spheroids: a replication-deficient Ad encoding the luciferase marker gene (Ad.Luc), a replication-competent Ad with complete E1 region (Ad.E1+), a replication-competent Ad encoding the luciferase gene in the E3 region (Ad.E1Luc), and a conditionally replicating Ad with an E1ACR2 deletion (Ad.d24). Replication of the latter is restricted to cells with a defective retinoblastoma pathway, whereas Ad.E1+ and Ad.E1Luc can replicate in all human cells like a wild-type Ad. Their oncolytic activity was compared in primary meningioma cells and spheroids by use of viability and outgrowth assays. RESULTS: Adenoviral penetration into organotypic meningioma spheroids was detected with the replication-competent Ad.E1Luc, whereas infection with the replication-deficient Ad.Luc was limited to the outer layer of the spheroid. Replication of the Ads and oncolysis was demonstrated in primary cell cultures of meningioma cells at high dose, i.e., greater than 50 plaque-forming units per cell. At a lower dose of 5 plaque-forming units per cell, Ad.d24 kills meningioma cells more efficiently than Ad.E1+. Infection of organotypic meningioma spheroids with Ad.d24 resulted in decreased viability and suppression of outgrowth as compared with untreated control spheroids. CONCLUSION: Infection of meningioma cells and spheroids with replication-competent Ads results in efficient oncolysis. The Ad modified to replicate selectively in retinoblast-mutant cells, Ad.d24, seemed to be an efficient oncolytic agent in benign, atypical, and malignant meningiomas.

Adenoviridae↗
PubMed2005

Preoperative chemotherapy in children with high-risk medulloblastomas: a feasibility study.

OBJECT: The authors set out to evaluate the feasibility and effectiveness of preoperative chemotherapy in treating high-risk medulloblastomas. METHODS: Between 1997 and 2000, 21 children with high-risk medulloblastomas (M > or = 2 and/or T3b/T4 according to the Chang classification) were treated consecutively in a pilot study. The protocol began with treatment of the hydrocephalus and confirmation of the diagnosis. Tumor surgery was performed either after conventional chemotherapy (eight patients) or after subsequent high-dose chemotherapy (HDCT; 11 patients). Two children with early leptomeningeal progression died before surgery. Craniospinal irradiation was applied to children older than 5 years of age, whereas younger children received local irradiation only. Hydrocephalus was present in 17 children and was treated with ventriculocisternostomy in 13 and shunt insertion in four. A biopsy procedure was performed with a stereotactic frame in 10 children, an open surgery was performed in four, an endoscope was used during the ventriculocisternostomy in three, and the diagnosis was made based on cerebrospinal fluid cytological analysis in two. The response rate to the first two courses of chemotherapy was 71% for the tumor and 59% for the metastases. The pathological analysis of the residue after chemotherapy showed true medulloblastomas in seven cases, complete neuroglial maturation in three cases, and a mixture of both in nine cases. Three-year progression-free survival was 37% and was significantly better in children older than 5 years of age. There was one death related to the HDCT. CONCLUSIONS: Preoperative chemotherapy is feasible and safe in children with high-risk medulloblastomas provided that the hydrocephalus can be treated at diagnosis. A larger study is warranted to ensure that the high response rate to adjuvant chemotherapy can lead to better surgical results and survival advantage.

Cerebellar Neoplasms↗
PubMed2004

Oncolytic activity of p53-expressing conditionally replicative adenovirus AdDelta24-p53 against human malignant glioma.

Prognosis of malignant glioma is poor, and results of treatment remain mediocre. Conditionally replicative adenoviruses hold promise as alternative anticancer agents for the treatment of malignant glioma. Here, we evaluated the conditionally replicative adenovirus AdDelta24 and its recently developed derivative AdDelta24-p53, which expresses functional p53 tumor suppressor protein while replicating in cancer cells, for treatment of malignant glioma. In comparison to its parent AdDelta24, AdDelta24-p53 killed most malignant glioma cell lines and primary glioblastoma multiforme short-term cultures more effectively, irrespective of their p53 status. Moreover, AdDelta24-p53 caused more frequent regression and more delayed growth of IGRG121 xenografts derived from a glioblastoma multiforme in vivo. Five intratumoral injections of 10(7) pfu AdDelta24 gave 24 days median tumor growth delay (P < 0.01), 30% tumor regressions, and 30% animals surviving >120 days tumor-free or with a minimal tumor residual. The same dose of AdDelta24-p53 caused >113 days of median tumor growth delay (P < 0.001), 70% tumor regressions, and 60% animals surviving >120 days tumor-free or with a minimal tumor residual. Antitumor effects in vivo were associated with extensive conditionally replicative adenovirus replication, apoptosis induction, and tumor morphology changes, including dissociation, inflammatory cell infiltration, and necrosis. We conclude that conditionally replicative adenoviruses expressing p53 are promising new agents for treatment of malignant glioma.

Adenoviridae↗
PubMed2004

Measuring the neuro-cognitive side-effects of irradiation in children with brain tumors.

BACKGROUND: Reduction of the treatment-related side effects has become one of the main goals of the recent study protocols for brain tumor therapies. When the treatment burden is decreased in patients with good prognostic features, the potential increased risk of relapse has to be counterbalanced by a significantly improved cognitive outcome. This objective is always clearly stated but comprehensive data on the neuropsychological outcomes are seldom reported. PROCEDURES AND RESULTS: The appropriate means to measure the long-term morbidity need to be clarified. Health Status and Quality of Life (QOL) questionnaires can be easily administered but these questionnaires represent usually a composite evaluation where cognition is analyzed along with other items such as mood or pain. However, none of these questionnaires has ever been used to measure a difference in cognitive outcome when comparing two different therapeutic strategies in children. Complete neuropsychological evaluations are time consuming, need specialized psychologists and most of the tests have not been rigourously validated. In this respect, Wechsler scales are, however, robust and objective methods to evaluate intelligence. Several studies have been able to show meaningful differences in IQ scores between treatments in children with posterior fossa tumors, even with small numbers of patients. CONCLUSIONS: In order to evaluate any refinement in the treatment of these patients, widely accepted evaluation tools are needed. Ideally, these methods will have to be sensitive, reproducible, and widely applicable. None of the available tools fullfil all of these criteria but their development should be a major endeavour in modern neuro-oncology.

Brain Neoplasms↗