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Desmoplastic nodular medulloblastoma in young children: a management dilemma.

ABSTRACT: Background:Children with desmoplastic nodular medulloblastoma (DNMB) have excellent survival, leading multiple groups globally to attempt reduction of treatment-related morbidity. In 2013, the Children's Oncology Group began a clinical trial (ACNS1221) eliminating both radiation therapy (RT) and intraventricular methotrexate for children under 3 years of age with localized DNMB, aiming to build upon the excellent outcomes of the German HIT trials. ACNS1221 has recently closed due to increased incidence of recurrences noted at the 2-year interim analysis, raising important questions regarding optimal therapy for DNMB. Methods:A review of major clinical trials that included children with DNMB was performed through July 2017. Results:One hundred and eighty-eight DNMB patients enrolled on 11 prospective clinical trials were identified. The use of marrow-ablative chemotherapy and autologous hematopoietic cell rescue (AuHCR) or treatment with intraventricular methotrexate has been associated with excellent outcomes. RT was usually required for patients with evidence of disease at the end of therapy. Conclusions:The minimal intensity and duration of chemotherapy required to maximally cure children with DNMB without need of RT remains unknown. Further trials are required to better identify a subset of DNMB patients who can be cured without marrow-ablative chemotherapy or intraventricular methotrexate.

SUBMITTER: AbdelBaki MS

PROVIDER: S-EPMC6280315 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Desmoplastic nodular medulloblastoma in young children: a management dilemma.

AbdelBaki Mohamed S MS Boué Daniel R DR Finlay Jonathan L JL Kieran Mark W MW

Neuro-oncology 20180701 8

<h4>Background</h4>Children with desmoplastic nodular medulloblastoma (DNMB) have excellent survival, leading multiple groups globally to attempt reduction of treatment-related morbidity. In 2013, the Children's Oncology Group began a clinical trial (ACNS1221) eliminating both radiation therapy (RT) and intraventricular methotrexate for children under 3 years of age with localized DNMB, aiming to build upon the excellent outcomes of the German HIT trials. ACNS1221 has recently closed due to incr ...[more]

PMID: 29156007

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Project description:Objective Medulloblastoma is the most common malignant brain tumor in children younger than four years of age. Children diagnosed with desmoplastic nodular medulloblastoma (DNMB) have more favorable survival outcomes when compared to other subtypes of this disease and, to date, the demographics of DNMB have only been characterized by a few small clinical case series. Additionally, the current effort is being made at reducing radiotherapeutic modalities in this patient population to avoid the adverse effects associated with radiotherapy in children. Therefore, the goal of this study was to characterize the demographics, treatments, and survival outcomes of patients with DNMB using a large federal database. Methods The Surveillance, Epidemiology, and End Results database was queried to retrieve demographical, treatment, and survival data for patients diagnosed with DNMB. Statistical testing was performed with the R software stats package (R Foundation for Statistical Computing, Vienna, Austria). Student's t tests and analysis of variance tests were used to measure differences among survival rates. Results Data from 360 patients with DNMB were retrieved from 1975-2016. There was a higher prevalence of DNMB in children younger than four years of age (33% of all cases). Males had a higher prevalence than females (57%). There was a preponderance of diagnoses in white individuals (82% of all cases) and more diagnoses in the Pacific Coast region (49% of all cases). Distant metastases were present at initial diagnosis in 8.7%. Surgery was performed in almost all patients, and gross total resection was achieved in 77%. The overall rate of survival was 77.8% at five years; age, sex, race, and geographical region of diagnosis were not associated with differences in survival outcomes. Patients with no radiotherapy had a lower rate of survival compared to patients with postoperative radiotherapy (mean difference = 19.7%; [95% CI 1.4%-38.0%], p = 0.0314). However, radiotherapy did not improve survival outcomes in patients undergoing chemotherapeutic treatment to a degree with any statistical significance. There was no statistically significant improvement in survival for patients undergoing radiotherapy prior to procedure when compared to patients with no radiotherapy. Conclusions In patients undergoing chemotherapeutic treatment for the DNMB subtype of medulloblastoma specifically, additional radiotherapy may offer only minimal benefit to the survival outcome. It is essential continued clinical trials be performed for the purpose of devising alternate treatments to radiotherapy.

Project description:BackgroundDesmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival.MethodsA retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed.ResultsThe review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days).ConclusionCytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.

Project description:BackgroundDesmoplasia in medulloblastoma is often diagnosed in adult patients and was repeatedly associated with improved results. Today, all medulloblastoma patients receive intensive multimodal treatment including surgery, radiotherapy and chemotherapy. This study was set up to investigate treatment outcome and prognostic factors after radiation therapy in patients with desmoplastic medulloblastomas.MethodsTwenty patients treated for desmoplastic medulloblastoma in the Department of Radiation Oncology at the University of Heidelberg between 1984 and 2007 were included. Data were collected retrospectively. Tumor resection was performed in all patients. All patients underwent postsurgical radiotherapy (RT). Two patients underwent whole brain radiotherapy (WBRT), and 18 patients received craniospinal irradiation (CSI). In all patients, an additional boost was delivered to the posterior fossa. The median dose to the whole brain and the craniospinal axis was 35.2 Gray (Gy), and 54.4 Gy to the posterior fossa. Fourteen patients received chemotherapy, including seven who were treated with combined radiochemotherapy and twelve who received adjuvant chemotherapy. Statistical analysis was performed using the log-rank test and the Kaplan-Meier method.ResultsMedian follow-up was 59 months. Overall (OS), local (LPFS) and distant progression-free survival (DPFS) was 80%, 71.2%, and 83.3% at 60 months. Patients who suffered from local or distant relapses had significantly worse outcome. Five patients died from recurrent medulloblastoma. Treatment-associated toxicity was acceptable.ConclusionsMultimodal approaches with surgical resection followed by chemoirradiation achieved high response rates with long OS in desmoplastic medulloblastoma patients. Staging parameters expected to predict for poor prognosis did not significantly influence outcome. However, success of any first line regimen had strong impact on disease control, and remission was achieved in no patient with relapsing disease. Multimodal concepts must be evaluated in further clinical trials.

Project description:PurposeNodular desmoplastic medulloblastoma (ND) and medulloblastoma with extensive nodularity (MBEN) have been associated with a more favorable outcome in younger children. However, treatment-related neurotoxicity remains a significant concern in this vulnerable group of patients.Patients and methodsACNS1221 was a prospective single-arm trial of conventional chemotherapy for nonmetastatic ND and MBEN based on a modified HIT SKK 2000 regimen excluding intraventricular methotrexate, aiming to achieve similar outcome (2-year progression-free survival [PFS] ? 90%) with reduced treatment-related neurotoxicity. Secondary objectives included feasibility of timely central pathology review and evaluation of tumor molecular profile.ResultsTwenty-five eligible patients (15 males and 10 females; median age, 18.7 months) were enrolled. Eighteen patients had ND and 7 had MBEN histology. Three patients had residual disease at baseline. The study closed early because of a higher than expected relapse rate. Twelve patients experienced relapse-local (n= 6), distant (n = 3), and combined (n = 3)-at a median of 9.8 months from diagnosis (range, 8.9-13.7 months), and 2 patients died of disease. Two-year PFS and overall survival rates were 52% (95% CI, 32.4% to 71.6%) and 92% (95% CI, 80.8% to 100.0%) respectively. Patients older than 12 months of age (P = .036) and ND histology (P = .005) were associated with worse PFS. No patients with MBEN histology experienced relapse. All tumor samples clustered within the sonic hedgehog (SHH) group. Methylation analysis delineated 2 subgroups, SHH-I and SHH-II, which were associated with 2-year PFS rates of 30.0% (95% CI, 1.6% to 58.4%) and 66.7% (95% CI, 44.0% to 89.4%), respectively (P = .099).ConclusionThe proposed modified regimen of conventional systemic chemotherapy without serial intraventricular methotrexate injection failed to achieve the targeted 2-year PFS of 90%. With this cohort, we prospectively confirmed the existence of two SHH subgroups and observed a trend toward worse outcome for SHH-I patients.

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Desmoplastic nodular medulloblastoma in young children: a management dilemma.

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Desmoplastic nodular medulloblastoma in young children: a management dilemma.

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