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Ira J Dunkel

Publications and source records attributed to Ira J Dunkel.

At least 19 recordsLinked to original sources
PubMed2025

Detection and Characterization of RB1 Mosaicism in Patients With Retinoblastoma Receiving cfDNA Test.

IMPORTANCE: Plasma cell-free DNA (cfDNA) testing is increasingly used for disease diagnosis and monitoring in retinoblastoma, with RB1 allele fraction in cfDNA actively corresponding to disease status and treatment response. However, while RB1 mosaicism has been reported in retinoblastoma, its clinical implications and potential impact on cfDNA testing remain unclear. OBJECTIVES: To identify RB1 mosaicism using paired plasma and buffy coat (containing lymphocytes, monocytes, granulocytes, and platelets) DNA testing, and to characterize the implications of RB1 mosaicism on cfDNA testing outcomes. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants with retinoblastoma underwent testing with MSK-ACCESS (Memorial Sloan Kettering-Analysis of Circulating cfDNA to Examine Somatic Status), a clinical assay that combines plasma cfDNA and buffy coat genomic DNA sequencing, enabling the detection and differentiation of somatic, heterozygous, and mosaic variants, between July 2020 and April 2024 at the Memorial Sloan Kettering Cancer Center. Mosaic findings from MSK-ACCESS were correlated with those from a subgroup of patients who concurrently underwent testing using the MSK-IMPACT germline assay. Data analysis was performed from April to September 2024. EXPOSURE: RB1 mosaicism in retinoblastoma. MAIN OUTCOMES AND MEASURES: The RB1 variant allele fractions in cfDNA and buffy coat genomic DNA were used to detect RB1 mosaicism. RESULTS: A total of 136 consecutive patients with retinoblastoma (median age at diagnosis, 1.0 year [IQR, 0.4-1.7 years]; 74 [54.4%] female; 67 with bilateral disease and 69 with unilateral disease) who underwent testing with the MSK-ACCESS assay were included. RB1 mosaicism was identified in buffy coat DNA from 20 patients (14.7%), with consistent results detected in all 11 participants tested concurrently by the MSK-IMPACT (Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets) germline assay. Four participants with RB1 mosaicism previously tested negative for germline RB1 variants by external laboratories. Compared with heterozygous participants, participants with RB1 mosaicism had a lower risk of developing bilateral disease (91.7% vs 55.0%, respectively; difference, 36.7% [95% CI, 13.8%-59.6%]; P = .002). In cfDNA, the mosaicism variant was detected both before and after treatment, with variant allele fraction initially decreasing after treatment but then stabilizing at levels consistent with mosaicism, despite the absence of clinical disease. CONCLUSIONS AND RELEVANCE: The accurate detection and quantification of RB1 mosaicism are crucial. RB1 mosaicism should be considered when RB1 variants persist in cfDNA after treatment without evidence of disease; failure to do so may lead to false-positive results and overtreatment in patients with RB1 mosaicism. Identifying RB1 mosaicism may improve patient counseling, inform treatment decisions, and enhance surveillance efforts.

Humans↗
PubMed2008

Brainstem primitive neuroectodermal tumors (bstPNET): results of treatment with intensive induction chemotherapy followed by consolidative chemotherapy with autologous hematopoietic cell rescue.

We have evaluated the response rate and survival utilizing intensified chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and adjuvant radiation therapy in six young children with newly diagnosed brainstem primitive neuroectodermal tumors (bstPNET). Following maximum surgical resection of the tumor, patients received high dose induction chemotherapy including vincristine, cisplatin, cyclophosphamide, and etoposide. Eligible patients received a single cycle of myeloablative chemotherapy followed by AuHCR. Two patients survive at least 32 months with stable disease. This approach provides an alternative for young patients with bstPNET who in prior reports have had a uniformly fatal prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2007

Recurrent ependymoma treated with high-dose tamoxifen in a peripubertal female: Impact on tumor and the pituitary-ovarian axis.

Due to high rates of recurrence, the prognosis of childhood ependymoma remains guarded. Anecdotal evidence suggests that tamoxifen may have a role in the treatment of these tumors. We present a case of a child with recurrent ependymoma treated with tamoxifen who showed tumor regression on two separate occasions. However, treatment with tamoxifen resulted in the development of large ovarian cysts associated with supraphysiological plasma concentrations of estradiol.

Child↗
PubMed2007

A phase II trial of thalidomide and cyclophosphamide in patients with recurrent or refractory pediatric malignancies.

BACKGROUND: Previous clinical and pre-clinical research has demonstrated synergy between anti-angiogenic agents and cytotoxic chemotherapy. This trial was undertaken to investigate whether the combination of cyclophosphamide and thalidomide would be active against pediatric tumors. PROCEDURE: Patients with pediatric malignancies who had no remaining conventional therapeutic options were recruited from January 1999 to May 2001. They received thalidomide (6-12 mg/kg po every day; maximum daily dose 800 mg) and cyclophosphamide (1,200 mg/m2 IV every 28 days). RESULTS: Twenty-seven patients were enrolled on the study. Seventeen were male and 10 were female. Median age at the time of registration was 15 years (range 1-54 years). The median number of prior treatment regimens was four. Twenty-one patients were evaluable for response; 1 had a partial response (Hodgkin disease), 1 demonstrated stable disease (neuroendocrine tumor), and 19 had progressive disease. The most common toxicities were hematological (leukocytopenia and neutropenia) and gastrointestinal. One patient experienced a grade 3 rash. Fatigue and daytime somnolence were variable. No peripheral neuropathy was observed. CONCLUSION: The combination of thalidomide and cyclophosphamide as described herein has a modest and tolerable toxicity profile but little evidence of efficacy.

Adolescent↗
PubMed2007

Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma.

OBJECTIVE: To assess the outcome and determine risk factors for extraocular relapse in patients with retinoblastoma who had been enucleated after failure of chemoreduction. METHODS: Retrospective study (1995-2002) at three institutions. Pathological risk factors (PRF) were defined as invasion of the anterior segment, choroid, post-laminar optic nerve, subarachnoid space, or sclera according to the local pathology report. Extraocular relapse was defined as an event. RESULTS: One hundred twenty-two patients were included (17 had bilateral enucleation). Chemoreduction included vincristine, carboplatin, and etoposide (n=80, 65.6%), vincristine, and carboplatin (n=17, 13.9%), or carboplatin (n=25, 20.5%). Thirty-five also received external beam radiotherapy (28.7%). PRF included: 39 with choroidal involvement, 9 with anterior segment, 9 with scleral, and 2 with post-laminar optic nerve with subarachnoid invasion. Adjuvant chemotherapy was given to eight patients (6.5%) because of scleral invasion. Four patients had an extraocular relapse after enucleation, two of whom survive after intensive treatment including stem cell rescue. Five-year probability of event-free survival is 0.96. Only scleral invasion and bilateral enucleation were significantly associated with extraocular relapse. CONCLUSIONS: The risk of extraocular relapse is low after enucleation following failure of chemoreduction. Patients who underwent bilateral enucleation and those with scleral invasion are at higher risk of extraocular relapse.

Antineoplastic Agents↗
PubMed2006

Correlation of endoscopic biopsy with tumor marker status in primary intracranial germ cell tumors.

We retrospectively analyzed the results of eight patients who underwent endoscopic biopsy of a newly diagnosed primary intracranial germ cell tumor (GCT), and correlated tumor pathology with serum and cerebrospinal fluid (CSF) tumor markers and treatment outcome in order to determine the reliability of GCT sampling by this method. A biopsy diagnosis was made in each patient, and the tumor histology correlated with tumor marker measurements for all six patients diagnosed with germinoma and for one with a yolk sac tumor. One biopsy revealed only mature teratoma, an inconclusive result since the patient's serum and CSF tumor markers were elevated. No morbidity was experienced as a result of the operative procedure. Five of six patients diagnosed with germinoma responded completely to radiation therapy and are without evidence of disease, while one suffered a likely germinoma recurrence and was subsequently successfully retreated. We conclude that endoscopic biopsy of marker-negative germ cell tumors is a safe, reliable method of establishing a diagnosis of germinoma. However, endoscopic biopsy may fail to yield an accurate diagnosis in cases of malignant non-germinomatous tumor. We would thus conclude that when primary germ cell tumor is considered, endoscopic tumor biopsy is recommended in patients with a negative biochemical analysis, but not suggested for patients presenting with elevated tumor markers.

Adolescent↗
PubMed2006

More aggressive bone marrow screening in retinoblastoma patients is not indicated: the memorial Sloan-Kettering cancer center experience.

BACKGROUND: Bone marrow involvement in retinoblastoma patients is rare in the more industrialized nations. The purpose of the current study was to determine the frequency of bone marrow involvement in our series of retinoblastoma patients and to investigate whether the use of four bone marrow aspirates (BMA) and two bone marrow biopsies (BMB) has greater sensitivity for the detection of metastatic disease compared to what has been previously reported. METHODS: Retrospective analysis of the charts of 54 patients with retinoblastoma was performed. We performed 265 BMA, 134 BMB (4 aspirates and 2 biopsies per evaluation), and 67 lumbar punctures (LPs) in 54 patients with retinoblastoma. RESULTS: There were no patients found with bone marrow or cerebrospinal fluid (CSF) involvement at the time of the initial diagnosis. Although no patient died of distant metastases, two patients developed metastatic disease at recurrence, involving the bone marrow and other sites. For these two patients all four aspirates and two biopsies were positive for disease at the time of recurrence. CONCLUSIONS: Despite the use of four BMA and two BMB (as opposed to one bone marrow aspirate that is routinely performed in other centers), the detection of patients with metastatic disease was similar to what has been previously reported. Based on these data more aggressive evaluation of the bone marrow in retinoblastoma patients with clinically limited disease using four aspirates and two biopsies cannot be supported.

Biopsy, Needle↗
PubMed2006

A proposal for an international retinoblastoma staging system.

BACKGROUND: Although intra-retinal tumor has long been staged presurgically according to the Reese-Ellsworth (R-E) system, retinoblastoma differs from other pediatric neoplasms in never having had a widely accepted classification system that encompasses the entire spectrum of the disease. Comparisons among studies that consider disease extension, risk factors for extra-ocular relapse, and response to therapy require a universally accepted staging system for extra-ocular disease. PROCEDURE: A committee of retinoblastoma experts from large centers worldwide has developed a consensus classification that can encompass all retinoblastoma cases and is presented herein. Patients are classified according to extent of disease and the presence of overt extra-ocular extension. In addition, a proposal for substaging considering histopathological features of enucleated specimens is presented to further discriminate between Stage I and II patients. RESULTS: The following is a summary of the classification system developed-Stage 0: Patients treated conservatively (subject to presurgical ophthalmologic classifications); Stage I: Eye enucleated, completely resected histologically; Stage II: Eye enucleated, microscopic residual tumor; Stage III: Regional extension [(a) overt orbital disease, (b) preauricular or cervical lymph node extension]; Stage IV: Metastatic disease [(a) hematogenous metastasis: (1) single lesion, (2) multiple lesions; (b) CNS extension: (1) prechiasmatic lesion, (2) CNS mass, (3) leptomeningeal disease]. A proposal is also presented for substaging of enucleated Stages I and II eyes. CONCLUSIONS: The proposed staging system is the product of an international effort to adopt a uniform staging system for patients with retinoblastoma to cover the whole spectrum of the disease.

Humans↗
PubMed2005

Brain Stem Tumors.

Brain stem tumors are heterogeneous. They range from the diffuse pontine tumors, which are almost invariably fatal despite all known therapies, to lower-grade focal or exophytic tumors that often have a very good prognosis with surgery or observation only. In this article, we review the epidemiology of brain stem tumors and note that diffuse pontine tumors, although rare, are a significant contributor to mortality among pediatric oncology patients. Diagnosis in typical cases is made using a magnetic resonance imaging scan without biopsy. No highly effective standard treatment exists; therefore, inclusion of eligible patients in well-designed clinical research studies is extremely important. If an appropriate trial is not available, conventionally fractionated external beam radiation therapy can provide good short-term palliation to a significant proportion of patients. An important area of preclinical research that may soon be investigated in clinical trials for patients with diffuse pontine tumors is interstitial infusion of therapeutic agents, and the rationale for that approach is described in detail. Lastly, autopsy should be considered for patients who die of diffuse pontine tumors with the goal of obtaining tumor tissue for biological studies that may in the future lead to novel therapies.

Journal Article↗
PubMed2004

Thiotepa-based high-dose chemotherapy with autologous stem-cell rescue in patients with recurrent or progressive CNS germ cell tumors.

PURPOSE: To evaluate the efficacy and toxicity of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in patients with relapsed or progressive CNS germ cell tumors (GCTs). PATIENTS AND METHODS: Twenty-one patients with CNS GCTs who experienced relapse or progression despite having received initial chemotherapy and/or radiotherapy were treated with thiotepa-based HDC regimens followed by ASCR. RESULTS: Estimated overall survival (OS) and event-free survival (EFS) rates for the entire group 4 years after HDC were 57% +/- 12% and 52% +/- 14%, respectively. Seven of nine (78%) patients with germinoma survived disease-free after HDC with a median survival of 48 months. One patient died as a result of progressive disease (PD) 39 months after HDC, and another died as a result of pulmonary fibrosis unrelated to HDC 78 months after ASCR without assessable disease. However, only four of 12 patients (33%) with nongerminomatous germ cell tumors (NGGCTs) survived without evidence of disease, with a median survival of 35 months. Eight patients with NGGCTs died as a result of PD, with a median survival of 4 months after HDC (range, 2 to 17 months). Patients with germinoma fared better than those with NGGCTs (P =.016 and.014 for OS and EFS, respectively). Patients with complete response to HDC also had significantly better outcome (P <.001 for OS and EFS) compared with patients with only a partial response or stable disease. There were no toxic deaths because of HDC. CONCLUSION: Dose escalation of chemotherapy followed by ASCR is effective therapy for patients with recurrent CNS germinomas and might be effective in patients with recurrent NGGCTs with a low tumor burden.

Adolescent↗
PubMed2004

Primary chemotherapy for intracranial nongerminomatous germ cell tumors: results of the second international CNS germ cell study group protocol.

PURPOSE: The optimum therapy for intracranial nongerminomatous germ cell tumors (NGGCT) remains controversial. The primary objective of this study was to determine whether intensive cisplatin and cyclophosphamide-based combination chemotherapy was effective in patients with intracranial NGGCT. PATIENTS AND METHODS: Twenty patients were enrolled, aged 5 to 41 years (median, 13 years). Initial therapy included two courses of Regimen A (cisplatin, etoposide, cyclophosphamide, and bleomycin). Patients achieving a complete remission (CR) then received two courses of Regimen B (carboplatin, etoposide, and bleomycin). Those in CR after four courses of treatment received one additional course of Regimen A and Regimen B, while those not in CR after four treatment courses underwent second-look surgery and/or irradiation. RESULTS: Sixteen of 17 patients assessable for response after two courses of treatment achieved a CR or partial response (CR + partial response, 0.94; 95% CI, 0.73 to 1.0). With a median follow-up of 6.3 years, 14 of 20 patients are alive without disease; eight patients were without relapse or progression, of whom three received local irradiation in first complete remission in violation of protocol, and six patients were in durable second or third complete remission after further chemotherapy and/or irradiation. The 5-year overall survival and event-free survival were 0.75 (95% CI, 0.56 to 0.94) and 0.36 (95% CI, 0.13 to 0.59), respectively. CONCLUSION: Intensive chemotherapy was effective in one-third of patients in this study. Salvage therapy, including irradiation, was feasible in patients with recurrent disease.

Adolescent↗
PubMed2004

Outcome following initial external beam radiotherapy in patients with Reese-Ellsworth group Vb retinoblastoma.

OBJECTIVE: To describe patient and ocular outcomes following initial treatment with external beam radiotherapy (EBT) in eyes with Reese-Ellsworth group Vb retinoblastoma. METHODS: Retrospective case series (from January 1, 1979, to February 28, 2002). The Kaplan-Meier method was used to analyze survival (ocular and patient) and incidence (second cancer) data. RESULTS: Two hundred forty-three patients with 1 or more Reese-Ellsworth group Vb eyes were identified. Of 284 group Vb eyes, 63 (22.2%) initially received EBT, vs 172 (60.6%) that were initially enucleated. Of the 63 radiated group Vb eyes, 31 (49.2%) had no further tumor growth, 26 (41.3%) developed a recurrence, and 8 (12.7%) developed a new tumor. Of the 63 radiated group Vb eyes, 33 (52.4%) developed ocular complications. The ocular survival rate of radiated group Vb eyes was 81.4% at 1 year and 53.4% at 10 years. Twenty-eight radiated group Vb eyes survived to the last follow-up with visual acuity information. Thirteen patients developed second cancers, 11 in the field of radiation. The probability of developing a second cancer following initial EBT for group Vb disease in patients with bilateral disease was 29.7% by 10 years after diagnosis. Survival from second cancers in patients with bilateral disease initially receiving EBT for group Vb disease was 93.6% at 5 years and 52.6% at 18(1/4) years. No patient with unilateral disease developed a second cancer. Deaths due to metastatic retinoblastoma were uncommon. CONCLUSIONS: To our knowledge, this is the first study focusing exclusively on group Vb eyes treated initially with EBT, most of which were salvaged with vision. Outcome data provided herein are clinically relevant when choosing treatment options for advanced intraocular retinoblastoma.

Eye Enucleation↗
PubMed2004

High-dose chemotherapy with autologous stem-cell rescue in the treatment of patients with recurrent non-cerebellar primitive neuroectodermal tumors.

BACKGROUND: Recurrent non-cerebellar primitive neuroectodermal tumors (PNETs) carry a dismal prognosis when treated with conventional chemotherapy alone. XSWe tested the efficacy of high-dose chemotherapy (HDC) followed by autologous stem-cell rescue (ASCR) in this setting. PROCEDURE: Eligibility mandated either minimal residual disease or evidence of chemosensitivity before HDC. Conditioning consisted of carboplatin (CBDCA) (500 mg/m(2) or AUC = 7 mg/ml min using the Calvert formula) on days -8 to -6, thiotepa (300 mg/m(2)), and etoposide (250 mg/m(2)) on days -5 to -3. Irradiation was given post HDC selectively. RESULTS: Among 17 patients treated in this study, there were eight pineoblastoma(s) (pineo), seven cortical PNETs, and two arising elsewhere. Relapse was either local (nine) or metastatic to the brain (four) or spine (four). Two patients received HDC as the sole therapy for recurrence; additionally, eight underwent surgical debulking before HDC, and nine received irradiation, including six after HDC. Median age at ASCR was 3.9 years. Two patients died of toxicity (11%) and ten experienced tumor relapse (range: 23-361 days post ASCR). Five patients with cortical PNETs remain alive disease-free (median follow-up: 8.3 years); four of them received irradiation post HDC. The difference in 5-year event-free survival (EFS) between patients with pineo and other supratentorial PNETs was significant (0 vs. 62.5 +/- 17%, P = 0.0065). Both surgery at relapse and irradiation post HDC were favorable prognostic factors (P = 0.006 and 0.01, respectively). CONCLUSIONS: Patients with recurrent cortical PNETs can be cured with this strategy. Surgical debulking before, and irradiation after HDC play an important role in treatment success.

Adolescent↗
PubMed2004

Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach.

PURPOSE: High rates of overall and event-free survival have been reported in patients with intracranial germinomas treated with craniospinal radiotherapy. More recently, similar results have been reported with chemotherapy combined with radiotherapy to more localized treatment volumes. Our interest in exploring chemotherapy without radiotherapy in patients with CNS germinomas was based on concerns about the late sequelae of radiotherapy to the brain or neuraxis and also the well documented success of chemotherapy alone in patients with disseminated extracranial germinomas. The primary objective of this study was to determine whether intensive cisplatin and cyclophosphamide-based combination chemotherapy, without radiotherapy, was effective in patients with CNS germinomas. PATIENTS AND METHODS: Nineteen patients were enrolled, ranging in age from 1 to 24 years (median, 14 years). Thirteen were male. Nine had diabetes insipidus. Therapy comprised two courses of Regimen 'A' (cisplatin, etoposide, cyclophosphamide, and bleomycin) followed by MRI evaluation. Patients achieving a complete remission (CR) completed all planned therapy with two courses of regimen 'B' (carboplatin, etoposide, and bleomycin). Patients achieving less than a CR received two courses of Regimen 'B' followed by another evaluation. Those in CR after four courses of treatment received one additional course of Regimen 'A' and Regimen 'B', while those not in CR after four treatment courses underwent second look surgery and/or radiation therapy. RESULTS: Eleven of 11 patients with residual postoperative disease assessable for response achieved a CR. With a median follow-up of 6.5 years, eight out of 19 (0.42) patients remain in CR 1 without radiotherapy and another three patients are in stable second or subsequent remissions. Three patients died from treatment-related toxicity and another died in CR 1 from an uncharacterized leukoencephalopathy. The 5-year event-free survival (EFS) was 0.47 +/- 0.23 and 5-year overall survival (OS) was 0.68 +/- 0.22. CONCLUSIONS: Intensive cisplatin and cyclophosphamide-based chemotherapy was effective in achieving remissions, however, the long-term outcome using this treatment program was unsatisfactory and associated with unacceptable morbidity and mortality, particularly in patients with diabetes insipidus.

Adolescent↗
PubMed2004

Interstitial infusion of carmustine in the rat brain stem with systemic administration of O6-benzylguanine.

Interstitial infusion of carmustine (BCNU) into the rat brain stem in conjunction with systemic administration of O6-benzylguanine (O6-BG) was performed in an effort to assess clinical tolerance. A total of 12 rats underwent stereotactic cannula placement into the pontine segment of the brain stem. Six of the rats underwent a 24-h infusion of BCNU (Volume of infusion [Vi] 200 microl) at its maximal concentrated dose (3.3 mg/ml) in 5% dextrose water. Six additional rats underwent 24-h infusion of BCNU preceded by an intraperitoneal injection of O6-BG at a dose of 50 mg/kg. Serial neurological examinations were performed on all animals. Histologic analyses were performed immediately or 2 weeks following sacrifice. Postoperatively, there were no neurological changes in any of the animals. Postmortem histological examination of the brains showed small pontine cavitary lesions (ranging from 20 to 250 microm) containing variable numbers of macrophages or neutrophils consistent with an inflammatory response. No changes beyond these findings indicated any histological evidence of injury. These finding were limited only to the cannula site and no changes beyond region of the cannula tract were found. These findings indicate that interstitial infusion of BCNU into the brain stem in conjunction with systemic administration of O6-BG is safe in a small animal and may serve as a potential investigative strategy for children with diffuse pontine gliomas.

Animals↗
PubMed2004

Lack of activity of oral etoposide for relapsed intraocular retinoblastoma.

BACKGROUND: Intravenous etoposide is widely used in multiagent chemotherapy regimens for intraocular retinoblastoma despite the lack of phase II data documenting its efficacy. Because oral etoposide has been found to be highly effective in patients with relapsed medulloblastoma and neuroblastoma who had previously received intravenous etoposide, we investigated its use for intraocular retinoblastoma. PROCEDURE: A pilot trial of oral etoposide (50 mg/m2/ day for 21 days) in five children (6 eyes) with relapsed refractory intraocular retinoblastoma was performed. All had previously received chemotherapy, including intravenous etoposide in four patients, and all had received radiation therapy. Three patients (3 eyes) had vitreous seeds. Response was evaluated after one cycle. RESULTS: No serious acute toxicity was encountered, and no responses were noted. Four patients (5 eyes) had progressive disease. Stable disease was noted in one eye without vitreous disease. One patient developed secondary acute myeloid leukemia 30 months after exposure to oral etoposide. CONCLUSIONS: Oral etoposide was not an effective agent in this population. The role of etoposide in the treatment of higher risk intraocular retinoblastoma deserves further study.

Administration, Oral↗
PubMed2003

Patterns of failure using a conformal radiation therapy tumor bed boost for medulloblastoma.

PURPOSE: To assess the patterns of failure for patients with medulloblastoma receiving a conformal tumor bed boost rather than a boost to the entire posterior fossa. PATIENTS AND METHODS: From 1994 to 2002, 32 consecutive patients with newly diagnosed medulloblastoma treated at Memorial Sloan-Kettering Cancer Center (New York, NY) received a conformal boost to the tumor bed in conjunction with craniospinal radiation therapy. Twenty-eight patients also received chemotherapy. The median age was 9 years (range, 3 to 34 years), and the male to female ratio was 3:1. Twenty-seven patients had standard-risk disease, and five patients had high-risk disease. Craniospinal doses ranged from 23.4 to 39.6 Gy, and total tumor bed doses ranged from 54 to 59.4 Gy. RESULTS: With a median follow-up of 56 months, six patients have relapsed; five relapsed outside of the posterior fossa, and one failed within the posterior fossa, outside of the high-dose boost volume. Five-year actuarial disease-free and overall survival rates were 84% and 85%, respectively. Freedom from posterior fossa failure was 100% and 86% at 5 and 10 years, respectively. Freedom from distant failure was 84% at 5 years, with a trend for improvement when full-dose craniospinal radiation (36 to 39.6 Gy) was used compared with a reduced dose (23.4 Gy) of radiation (100% v 63%, respectively; P =.06). No other predictive variables were identified. CONCLUSION: Conformal treatment to the tumor bed allows for significant sparing of critical structures. The posterior fossa failure rate in this series is similar to that reported when the entire posterior fossa is treated. This approach should be investigated further in a phase III trial.

Adolescent↗