Recurrent Medulloblastoma Research Articles

High dose chemotherapy with autologous stem cell rescue (ASCR) for recurrent medulloblastoma

11507 Background: Medulloblastoma is a highly lethal disease when it recurs and very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. Methods: Between 8/97 and 8/05 14 patients (M/F 12/2) with recurrent medulloblastoma, aged 2 to 33 years (median, 10.5 years) at ASCR, were treated. Thirteen had relapsed after chemotherapy and craniospinal + posterior fossa irradiation and one after chemotherapy (Baby POG) at a median time of 19 months (7 to 148). One had a local relapse and 13 had dissemination at relapse (M1: 1, M2: 7 and M3: 5) Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/ml × min via Calvert formula) on days −8, −7, −6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days −5, −4, and −3 respectively; followed by ASCR on day 0. Results: Four patients died of treatment-related toxicities at 0, +23, +42 and +51 days post ASCR (bacterial sepsis in 2, CMV infection in 1 and CNS hemorrhage in 1). It should be remarked that all the toxic deaths were observed in patients auto grafted before October 2000. Five of 14 patients (35%) are event-free survivors at a median of 70 months post-ASCR (range: 5 to 86 months). Tumor recurred in the remaining 5 patients at a median time of 2 months post ASCR (2 to 15). All died at +23, +16, +12, +9 and +4 month post ASCR. Conclusions: Our results seem consistent with those published by Dunkel IJ (J. Clin Oncol; 16:222 - 8 1998) and argue about the efficacy of high dose chemotherapy with ASCR to provide long-term survival for some patients with recurrent medulloblastoma. No significant financial relationships to disclose.

C-Myc Overexpression Causes Anaplasia in Medulloblastoma

Both anaplasia and increased c-myc gene expression have been shown to be negative prognostic indicators for survival in medulloblastoma patients. myc gene amplification has been identified in many large cell/anaplastic medulloblastoma, but no causative link between c-myc and anaplastic changes has been established. To address this, we stably overexpressed c-myc in two medulloblastoma cell lines, DAOY and UW228, and examined the changes in growth characteristics. When analyzed in vitro, cell lines with increased levels of c-myc had higher rates of growth and apoptosis as well as significantly improved ability to form colonies in soft agar compared with control. When injected s.c. into nu/nu mice, flank xenograft tumors with high levels of c-myc in DAOY cell line background were 75% larger than those derived from control. Overexpression of c-myc was required for tumor formation by UW228 cells. Most remarkably, the histopathology of the Myc tumors was severely anaplastic, with large areas of necrosis/apoptosis, increased nuclear size, and macronucleoli. Indices of proliferation and apoptosis were also significantly higher in Myc xenografts. Thus, c-myc seems to play a causal role in inducing anaplasia in medulloblastoma. Because anaplastic changes are often observed in recurrent medulloblastoma, we propose that c-myc dysregulation is involved in the progression of these malignant embryonal neoplasms.

Octreotide in the therapy of recurrent medulloblastomas

BACKGROUND: Recurrence of medulloblastoma appears after 30% to 40% of the surgeries. Different from primary medulloblastoma, in which five-year survival rate is 50%, the survival time of relapses much shorter and only 20% of the patients manage to survive a year. There is a logical need for additional methods of treatment of recurrent medulloblastomas. The aim of the study is to determine the effects of intracavitary and long-term subcutaneous application of Sandostatin (octreotide) on the recurrent medulloblastomas. METHODS: Fourteen children aged 4 to 9 years, in which, despite of craniospinal irradiation and chemotherapy came to a recurrence of medulloblastoma during the first 6 months after the surgery, were treated subcutaneously with Sandostatin (octreotide) in a longer period of time. Cerebellar medulloblastomas with a diameter bigger than 20 mm and spinal over 10 mm were removed operatively and octreotide with Beriplast was applied intracavitary. RESULTS: Magnetic resonance of cranioaxis shows that the application of octreotide has caused the disappearance of spinal drop metastases in all 7 patients and the cerebellar metastases smaller than 5 mm in all 4 patients. Subcutaneous application of octreotide combined with intracavitary expresses an antitumoral effect in 2/3 of the relapses. The application of octreotide results with a transformation of Chang's stage M0 into M1 in 71.43% of the patients. CONCLUSION: In the case of in loco or metastatic recurrence of medulloblastomas, intracavitarily and subcutaneously applied octreotide results with a regression of the tumor in a 3 year time within 2/3 of the treated patients.

Survival for children with medulloblastoma following tumor recurrence or progression

1556 Background: Despite improvement in therapies, a substantial number of children with medulloblastoma experience tumor progression. The objectives of this single institution report are to report the 5 year post-progression survival and to identify prognostic factors for survival among children with progressive or recurrent medulloblastoma. Methods: The relationship between post-progression survival and demographic, tumor, and treatment factors were examined among 46 patients (22 females; mean age at diagnosis = 6.5 years; mean age at progression = 8.4 years) with recurrent medulloblastoma. Differences were calculated by Kaplan-Meier log rank analysis. Results: The probability of 5 year post-progression survival among patients in this study with progressive medulloblastoma was 26.3%. Twenty-two (48%) patients had local recurrence only, 5 (11%) had local + distant recurrence, and 19 (41%) had distant recurrence only. Patients with local recurrence only had a significantly prolonged post-progression survival compared to those with local + distant and distant recurrence (p = 0.039). The 17 patients treated with radiation therapy (RT) following progression had prolonged PPS (p = 0.003). Other categorical variables, including patient sex, age < 3 years at diagnosis, age < 6 years at diagnosis, age at progression, interval from diagnosis to progression, initial tumor stage, initial adjuvant therapy, and treatment with chemotherapy or autologous stem cell transplant following progression, were not associated with prolonged post-progression survival. Conclusions: Although the post-progression survival is poor for children with recurrent medulloblastoma, certain patients groups differ appreciably in their likelihood of post-progression survival. Patients with who have a local recurrence only and those who receive RT following progression have prolonged post-progression survival. No significant financial relationships to disclose.

Medulloblastoma in two successive pregnancies

A 24-year old primaparous female at 20 weeks gestation presented acutely with cerebellar symptoms. Magnetic resonance imaging brain showed evidence of a cerebellar vermis lesion. This was diagnosed as medulloblastoma on histopathological analysis. She underwent surgical debulking and radiotherapy. Interestingly, the lesion recurred 4 years later on her second pregnancy. She underwent further surgical debulking and adjuvant chemotherapy. We believe this is the first reported description of recurrent medulloblastoma in successive pregnancies. A brief discussion on this disease and its management in pregnancy setting is also presented.

Three‐year recurrence‐free survival in a patient with recurrent medulloblastoma after resection, high‐dose chemotherapy, and intrathecal Yttrium‐90‐labeled DOTA0‐D‐Phe1‐Tyr3‐octreotide radiopeptide brachytherapy

Most medulloblastomas express high levels of somatostatin type 2 receptors (sst2). DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) specifically binds sst2 in the low nanomolar range. The cytotoxic effect is mediated by the chelated, beta-emitting, metallic radionuclide Yttrium 90 (90Y). The authors applied this innovative treatment option in a boy age 8 years who presented with a recurrent medulloblastoma of the cauda equina: a prognostically poor condition. Targeted radiotherapy was administered to treat minimal sst2-expressing tumor remnants, which persisted despite conventional and high-dose chemotherapy and intercurrent resection of the lesion. A medulloblastoma arising from the floor of the fourth ventricle had been removed surgically; then, the patient was treated with standard adjuvant chemotherapy and craniospinal irradiation according to the prospective HIT '91 protocol. Complete remission was achieved for 20 months, when a drop metastasis of the cauda equina manifested with sensorimotor lumbosacral deficits and urinary incontinence. After four cycles of neoadjuvant chemotherapy (which consisted of combined ifosfamide, carboplatinum and etoposide), two cycles of high-dose chemotherapy and autologous stem cell transplantation were performed; in between, the responding residual tumor within the lumbosacral nerve fibers was microscopically removed. Thereafter, an Indium-111-DOTATOC test injection indicated sst2-expressing tumor remnants within the cauda equina. Consequently, 4 cycles of [90Y]-DOTATOC (4x562.5 megabecquerels) were injected directly into the cerebrospinal fluid in monthly intervals. The consolidating intrathecal brachytherapy using [90Y]-DOTATOC was tolerated well. A complete remission was achieved for a 3-year period. The only remaining deficit was urinary incontinence. Intrathecal administration of targeted radiopeptide brachytherapy in combination with conventional and high-dose chemotherapy and surgical removal represents a promising new option to treat recurrent medulloblastoma and should be explored further.

High-dose chemotherapy with autologous stem cell rescue for children with high risk and recurrent medulloblastoma and supratentorial primitive neuroectodermal tumors

Current treatment for high risk and recurrent medulloblastoma (MB) and supratentorial primitive neuroectodermal tumors (stPNET) has a very poor prognosis in children. High dose chemotherapy (HDCT) and autologous stem cell rescue have improved survival rates. We present 19 patients (thirteen classified in the high risk group and six patients with recurrent disease) that received HDCT and autologous stem cell rescue. In the high risk group [Med Pediatr Oncol 38 (2002) 83], all patients underwent neurosurgical debulking. Standard chemotherapy was prescribed in 10 patients. Radiotherapy was given to 4 patients (all older than 4 years old). In the recurrence disease group [Childs Nerv Syst 15 (1999) 498], five patients underwent surgery. Radiotherapy was given to those who were not previously irradiated. The HDCT in twelve patients consisted of busulfan 4 mg/kg/day, orally over 4 days in 6-hourly divided doses and melphalan at a dose of 140 mg/m2/day by intravenous infusion over 5 min on day -1. Three patients additionally received thiotepa 250 mg/m2/day intravenously over 2 days and four patients additionally received topotecan 2 mg/m2/day over 5 days by intravenous infusion over 30 min. The other seven patients received busulfan and thiotepa at the same doses.Patient's stem cells were mobilized with granulocyte colony-stimulating factor at a dose of 12 microg/kg twice daily subcutaneously for four consecutive days. Cryopreserved peripheral blood progenitor cells were re-infused 48 h after completion of chemotherapy. With a median follow-up of 34 months (range 5-93) eight complete responses and one partial response were observed. Three patients died of treatment-related toxicities (15%). The 2 year event-free survival was 37.67+/-14% in all patients and 57+/-15% for the high risk group. Therefore we conclude that HDCT may improve survival rates in patients with high risk/recurrent MB and stPNET despite treatment toxicity.

Recurrent medulloblastoma – violation of Collin's law by 14 years

We present a case of recurrent medulloblastoma, which violates Collin's law by 14 years. This is one of the longest exceptions to this rule published to date and serves as a reminder of the need for continued vigilance for many years after the original diagnosis.

2-Methoxyestradiol interferes with NF kappa B transcriptional activity in primitive neuroectodermal brain tumors: implications for management.

Medulloblastoma (MB) is a primitive neuroectodermal tumor (PNET) of the central nervous system (CNS) and the most common malignant primary brain tumor in children. Currently, poor risk and recurrent MB patients are treated with cytotoxic chemotherapy alone or in combination with surgery and irradiation. In order to improve on therapeutic outcome and reduce toxicity of current treatment strategies, new and novel therapeutic agents are needed for MB patients. To that purpose, we have examined the effect of 2-methoxyestradiol (2-ME), an endogenous non-toxic estrogenic metabolite on the growth of three medulloblastoma cell lines (DAOY, D341 and D283); and two high-grade anaplastic astrocytoma/glioblastoma cell lines, U-87MG and T-98-G. We present evidence to show that 2-ME preferentially inhibits the growth of medulloblastoma cells significantly by blocking cell cycle progression predominantly in G(2)/M phase. 2-ME treatment results in phosphorylation of cdc25C without any significant alterations in the expression of cyclin B1 or p34cdc2. In addition, we observed a decrease in the levels of 14-3-3 proteins following treatment with 2-ME. Furthermore, 2-ME-mediated growth inhibition is accompanied by induction of apoptosis as evidenced by morphological alterations and DNA fragmentation analysis. Of interest is the finding that 2-ME induced apoptosis is not mediated through alterations in the expression of p53 or Bax and that transcriptional activity of NF kappa B and DNA binding activity is reduced indicating that 2-ME disrupts the NF kappa B signaling pathway. These results suggest that 2-ME may prove to be a useful therapeutic agent in the treatment of PNET brain tumors such as medulloblastoma. In addition, as 2-ME inhibits growth predominantly through G(2)/M block, it may enhance the effectiveness of radiation therapy.

Possible benefits of high-dose chemotherapy and autologous stem cell transplantation for adults with recurrent medulloblastoma.

In an attempt to improve the dismal prognosis of adults with recurrent medulloblastoma, six patients were treated with aggressive salvage therapy including high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). At relapse, all patients underwent surgical debulking followed by HDCT/ASCT and then radiotherapy when possible. The treatment plan included two cycles of HDCT/ASCT; first with cyclophosphamide, etoposide and carboplatin (CECb) and then 2 months later with cyclophosphamide and thiotepa (CT). Three of the six patients received the planned therapy. One patient experienced severe toxicity requiring life-sustaining therapy. This patient developed multi-organ dysfunction including multiple enhancing lesions in both cerebral hemispheres that slowly resolved over several months. Two other patients did not mobilize sufficient stem cells for two ASCT procedures. They received one ASCT conditioned with cyclophosphamide, thiotepa and carboplatin (CTCb). Three of six patients had a complete response (CR); the other three had a partial response (PR). Following the first ASCT, median duration of response was 13.5 months (range 9-29 months) and median survival was 21.5 months (range 12-42 months). There was no treatment-related mortality. We conclude that HDCT/ASCT with CECb-CT or CTCb is active against recurrent medulloblastoma in adults and may be associated with prolonged remissions. Multiple enhancing cerebral lesions on brain MRI early post-HDCT/ASCT may be a consequence of the treatment rather than metastatic disease.

Value of surveillance imaging in the management of medulloblastoma.

To investigate the value of surveillance scanning for the detection of recurrences in medulloblastoma. The charts of 95 patients with medulloblastoma were retrospectively reviewed. Information regarding the patient characteristics, treatment modalities, dates, types and results of CT and MRI studies, the frequency with which recurrences were identified on surveillance images, changes in patient management, outcome of the patients following recurrences, and survival data were analyzed. Thirty-one patients had a recurrence of tumor in the central nervous system; none experienced extraneural relapses. Of all recurrences, 21 were symptomatic and 10 were discovered by surveillance scans asymptomatically. None of the patients with a recurrence survived. For all 95 patients, 5-year overall and event-free survival rates were 47.1 and 49.8%, respectively. In patients with symptomatic and asymptomatic recurrences, the mean time to recurrence since initial diagnosis, the mean duration of survival post-recurrence, and the mean duration of overall follow-up were 19.2 and 26.1 months, 3.6 and 8.0 months, and 22.8 and 34.1 months, respectively. For 95 patients, 468 surveillance and 38 symptomatic images were reviewed as 313 CTs and 193 MRIs. Rate of diagnosis of recurrence per surveillance image was 2.1% (10/468). In our study, surveillance scanning brought no survival advantage since it detected a minority of recurrences. Longer survival achieved by early detection of recurrences might be a reflection of lead-time and length biases. Surveillance procedures will gain more importance as new effective therapeutic options are developed for recurrent medulloblastoma.

Results of three-dimensional stereotactically-guided radiotherapy in recurrent medulloblastoma.

To evaluate survival rates and side effects after stereotactically-guided radiotherapy (SRT) in patients with recurrent medulloblastoma of the brain. Between 1992 and 2000, 20 patients with 29 radiological manifestations were treated with fractionated SRT (n = 21) or radiosurgery (n = 8). Median age was 16 years with 6 patients < or = 14 years. All patients had prior cranio-spinal radiotherapy plus boost to the posterior fossa with a total dose of 54 Gy. Time to recurrence was 33 months mean. Eighteen of the 29 lesions were located within the boost volume. Chemotherapy was given according to current international study protocols (HIT) in all patients. Mean total dose for re-irradiation was 24 Gy for fractionated stereotactically-guided radiotherapy, and 15 Gy for radiosurgery. Mean follow-up was 88.5 months. Overall local control was 89.7%. Thirteen recurrences showed partial or complete response in CT/MR-imaging, 13 showed stable disease. Local tumor progression was seen 5 months mean after radiotherapy in three cases. A multifocal intracranial progression was seen in 9 patients, 5 patients developed additional spinal metastases. Thirteen patients died with disseminated cranio-spinal progression, after 72.6 months median. No late toxicity > CTC II(o) especially no brain radionecrosis was seen after radiotherapy. SRT is effective and safe in the treatment of recurrent medulloblastoma to improve local control without evident side effects. The main problem remains the control of subclinical cranio-spinal dissemination.

Immunohistochemical markers for prognosis of average-risk pediatric medulloblastomas. The effect of apoptotic index, TrkC, and c-myc expression.

Medulloblastomas (MB) are the most common central nervous system malignancies in children. Numerous publications describe certain efforts to identify predictive value of various patterns of MB pathology and immunohistochemistry but received data appear to be controversial. In the present study, the apoptotic index (AI) and immunoexpression of TrkC, and c-myc proteins were investigated in biopsy samples from 68 MB with an average clinical risk to determine their prognostic utility in this tumor category. The number of cases with AI > 1.5% was significantly greater in the group of tumors in patients with recurrent MB and the mean AI was significantly higher in this group -4.7% vs. 1.1%. Furthermore, the number of tumors with AI > 1.5% was greater in the group of tumors in deceased patients and the mean Al was also higher in this group -4.6% vs. 1.2%. Immunoreactivity of the c-myc and TrkC did not show any differences between groups of patients with various clinical outcomes. A close association between Al as a continuous variable and the progression-free and overall survival was found. We found no any differences in survival times for c-myc and TrkC immunoreactivity. Multivariate revealed analysis that AI is a single significant prognostic factor for MB survival. Perhaps, investigations of c-myc and TrkC mRNA levels should be useful for clinical purposes, but in order to introduce these biomolecular markers in clinical protocols its distinct prognostic significance needs to be proved by prospective studies.

MRI features of primary, secondary and metastatic medulloblastoma.

Medulloblastoma is the most frequent paediatric malignant brain tumour. The purpose of this study was to define imaging characteristics and contrast uptake patterns of primary and recurrent medulloblastoma using MRI. The MRI examinations of 17 histologically proven cases of medulloblastoma diagnosed in our institution (13 males and 4 females; mean age 13 years, 7 months) were reviewed in retrospect. Only patients with pre-treatment and follow-up examinations including T2-weighted images (fluid-attenuated inversion recovery or turbo spin echo) and T1-weighted images after contrast injection (0.1 mmol/kg Gd-DTPA) were included in this study. Whereas 6 of 7 tumours ( n=17) were hyperintense on T2-weighted images, contrast enhancement was detected in 13 patients. Fifteen tumours occurred in the cerebellar vermis, two were located in the cerebellar hemispheres. Mean size at the time of presentation was 30.1 mm. All patients presented with some extent of an occlusive hydrocephalus. Local recurrent tumour or metastases were seen in 6 patients (3 months to 7 years, mean age 2.5 years). Whereas the T2 signal intensity of recurrent tumour or subarachnoidal metastases resembled the primary neoplasms, the contrast uptake tended to be less pronounced ( n=3) or was completely absent ( n=2); thus, suggestive signs of primary medulloblastoma are location in the vermis, hyperintensity on T2-weighted images and hydrocephalus. The amount of contrast enhancement is variable and nonspecific. Secondary medulloblastoma manifestation is characterized by T2 hyperintensity but not by contrast uptake.

Analysis of loss of heterozygosity on chromosomes 10q, 11, and 16 in medulloblastomas.

The loss of genetic material from specific chromosome loci is a common feature in the oncogenesis of tumors and is often indicative of the presence of important tumor suppressor genes at these loci. Recent molecular genetic analyses have demonstrated frequent loss of chromosomes 10q, 11, and 16 in medulloblastomas. The aim of this study was to localize the targeted deletion regions on the three aforementioned chromosomes in medulloblastomas. Loss of heterozygosity (LOH) was examined on chromosomes 10q, 11, and 16 in a series of 22 primary and two recurrent medulloblastomas by using polymerase chain reaction-based microsatellite analysis. The DNA extracted from the tumors and corresponding normal blood samples were amplified independently in the presence of radioactively labeled microsatellite primers, resolved by denaturing gel electrophoresis and processed for autoradiography. The DNA obtained from control blood samples that displayed allelic heterozygosity at a given microsatellite locus were considered informative. Loss of heterozygosity was inferred when the allelic signal intensity of the tumor sample was reduced by at least 40%, relative to that of the constitutional control. The LOH analysis demonstrated that deletions of chromosomes 10q, 11p, and 16q are recurrent genetic events in the development of medulloblastomas. Three subchromosomal regions of loss have been identified and are localized to the deleted in malignant brain tumors 1 [DMBT1] gene site on chromosomes 10q25, 11p13-11p15.1, and 16q24.1-24.3. These results indicate that DMBT1 is closely associated with the oncogenesis of medulloblastomas and highlight regions of loss on chromosomes 11p and 16q for further fine mapping and cloning of candidate tumor suppressor genes that are important for the genesis of medulloblastoma.

63. Stereotactic radiotherapy for primary and recurrent brain tumors. A new method for improvement of the treatment results?

To evaluate the effectiveness of the stereotactic radiosurgery (SRS) and stereotactic fractionated radiotherapy in the primary, recurrent and metastatic brain tumors. To present potential usefulness of stereotactic boost in anaplastic astrocytomas (AA) and glioblastoma multiforme (GBM). Between March 2000 and December 2000, SRS was applied in 23 patients (pts) with brain tumors (metastatic tumors – 9 pts, recurrent tumors – 7 pts, primary meningiomas – 4 pts, vascular malformations – 3 pts). Fractionated stereotactic radiotherapy was applied in 6 pts (recurrent anaplastic gliomas – 2 pts, recurrent medulloblastoma – 1 pt, acustic neurinoma – 1 pt, meningioma – 1, pituitary adenoma – 1). Detailed technique of treatment planning is presented and discussed. The planning target volume (PTV) and organs at risk (OAR) were assessed comparing dose statistics, dose volume histograms and RTOG stereotactic radiosurgery criteria. Recommendations regarding the total dose level and fractional dose are proposed. The treatment tolerance and preliminary results are presented. The own protocol of stereotactic boost to residual tumor using SRS after initial conformal radiotherapy in patients with AA and GBM is presented and discussed.

Recurrent medulloblastoma following pediatric double-lung transplant

We report a case of recurrent medulloblastoma following successful pediatric double-lung transplant for chemotherapy-induced pulmonary fibrosis. The patient had an apparent 10-year malignancy-free period prior to the transplant. This case demonstrates a potential complication of lung transplantation in individuals with prior malignancies, and questions whether patients with a history of medulloblastoma are suitable candidates for lung transplantation.

Treatment strategies for medulloblastoma and primitive neuroectodermal tumors

Medulloblastoma and primitive neuroectodermal tumors (PNETs) are the most common malignant brain tumors in children. The concern for late sequelae of neuraxis irradiation and the obligation to improve disease-free survival in children who harbor malignant brain tumors has led to the additional provision of systemic chemotherapy to standard- and reduced-dose radiotherapy, as well as to the evaluation of alternate modes of radiotherapy delivery. Analysis of evidence has suggested that chemotherapy has an impact on length of survival in children with medulloblastoma and PNETs. The question remains as to whether chemotherapy combined with reduced-dose radiotherapy provides greater benefit than standard-dose radiotherapy alone, and which subset of children the treatment most benefits. Also unanswered is the question of whether chemotherapy can serve as the primary treatment in infants with these lesions. In an attempt to help answer these questions, the authors review the major chemotherapy and radiotherapy trials for newly diagnosed patients and those with recurrent medulloblastoma and PNETs.

The Use of the Laitinen Stereoadapter for Three-Dimensional Conformal Stereotactic Radiotherapy

3-D conformal therapy is used to treat a variety of tumors by delivering a high dose to the target volume while minimizing dose to surrounding tissue. Conventional irradiation of intracranial lesions involves treating substantial portions of healthy brain. Stereotactic radiosurgery (SRS) delivers a single fraction to a small lesion targeted by an invasive head frame. The Laitinen stereoadapter is a noninvasive localization/immobilization device that provides the precision of stereotactic techniques (within 2 mm) with the radiobiologic advantage of fractionation. This report describes the Northwestern experience of 3-D conformal Stereotactic radiotherapy (SRT) for intracranial lesions using the Laitinen Stereoadapter for reproducible, noninvasive immobilization. 17 patients with 18 isocenters were treated with SRT via noncoplanar, static, and/or rotational beams. Patient age ranged from 3 to 77. Total doses ranged from 1000 to 5580 cGy at 180 to 400 cGy per fraction. Histologies included primitive neuroectodermal tumor (PNET), recurrent medulloblastoma, mixed germ cell tumor, recurrent juvenile pilocytic astrocytoma, optic glioma, oligodendroglioma, cran-iopharyngioma, meningioma, metastatic carcinoma, and one orbital rhabdomyosarcoma. Patient positioning was checked daily, and verification port films were taken every other day. Port films showed excellent reproducibility of isocenter placement with the Laitinen stereoadapter. Follow-up ranged from 1 to 24 months. Post-treatment radiographic responses were similar to those seen with conventional radiation therapy. The Laitinen stereoadapter is very well tolerated with minimal acute effects. Its use does not require excessive preplanning (i.e., customized oral appliances) and can accommodate any cranial size. Patients can initiate treatment within 24 hours, if necessary. The relocatable frame exploits the accuracy of SRS with the biological advantage of fractionation. We currently use the Laitinen for primary adult and pediatric brain tumors as well as metastatic lesions too large for SRS. Further studies are currently underway to further define its utility.

High-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue for patients with recurrent medulloblastoma. Children's Cancer Group.

Medulloblastoma is a highly lethal disease when it recurs. Very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/mL x min via Calvert formula) on days -8, -7, and -6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days -5, -4, and -3; followed by ASCR on day 0. In addition to the study-prescribed therapy, 21 patients received other treatment: neurosurgical resection in seven, conventional chemotherapy in 17, and external-beam irradiation in 11 cases. Twenty-three patients with recurrent medulloblastoma, aged two to 44 years (median, 13 years) at ASCR, were treated. Three patients died of treatment-related toxicities within 21 days of ASCR; multiorgan system failure in two, and Aspergillus infection with venoocclusive disease in one. Seven of 23 patients (30%) are event-free survivors at a median of 54 months post-ASCR (range, 24 to 78 months). Kaplan-Meier estimates of event-free (EFS) and overall survival are 34% +/- 10% and 46% +/- 11%, respectively, at 36 months post-ASCR. This strategy may provide long-term survival for some patients with recurrent medulloblastoma.