1,535 results on '"Wharam MD"'
Search Results
2. Late dental and bone alterations in patients after orbital rhabdomyosarcoma treatment.
- Author
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de Mattos VDA, Ferman SE, Magalhães DMA, da Costa FV, Antunes HS, and Junior AS
- Subjects
- Humans, Male, Female, Cross-Sectional Studies, Adolescent, Child, Child, Preschool, Young Adult, Antineoplastic Combined Chemotherapy Protocols, Chemoradiotherapy methods, Chemoradiotherapy adverse effects, Infant, Cancer Survivors statistics & numerical data, Cyclophosphamide administration & dosage, Vincristine administration & dosage, Rhabdomyosarcoma therapy, Orbital Neoplasms therapy
- Abstract
Purpose: Orbital rhabdomyosarcoma is a rare soft tissue sarcoma in childhood but with a good prognosis. Treatment usually includes surgery, chemotherapy, and radiotherapy. This study aimed to evaluate long-term alterations in teeth and cranial bones in children, adolescents, and young adults after oncologic treatment for childhood orbital rhabdomyosarcoma., Method: This was a cross-sectional study that evaluated patients treated for orbital rhabdomyosarcoma between 1988 and 2011. Demographic, clinical, and treatment data were collected during the study period; also, panoramic radiographs, cephalometric study, and photographs of the face were taken., Results: Eight long-term survivors were studied. Of those, 50% were male, 75% had less than 5 years of treatment, and 88% had only one of the orbits affected by the tumor. Regarding treatment, 50% received 50.4 Gy of radiotherapy in the orbit; the chemotherapy included vincristine, actinomycin D, and cyclophosphamide in 75% of the cases and also ifosfamide and etoposide in 25%. The children presented craniofacial alterations, mainly when radiotherapy occurred between 0 and 5 years old (p = 0.01). The mandibles also showed dental alterations, probably due to chemotherapy., Conclusion: In conclusion, orbital RMS patients treated with chemoradiotherapy, important dental, and facial bone alterations were found. The most significant were in the maxilla and close to the irradiation field. Dental and mandibular bone alterations were also found, indicating the probable chemotherapy action, as this region was not included in the irradiation field., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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3. Prognostic factors in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study
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SHUSTER, JJ, FALLETTA, JM, PULLEN, DJ, CRIST, WM, Humphrey, G B, DOWELL, BL, WHARAM, MD, and BOROWITZ, M
- Published
- 1990
4. Management of pediatric intracranial low-grade gliomas: long-term follow-up after radiation therapy.
- Author
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Huynh-Le MP, Walker AJ, Burger PC, Jallo GI, Cohen KJ, Wharam MD, and Terezakis SA
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Infant, Longitudinal Studies, Male, Proportional Hazards Models, Young Adult, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Disease Management, Glioma diagnosis, Glioma radiotherapy
- Abstract
Introduction: The treatment of pediatric intracranial low-grade gliomas (LGG) generally begins with maximal safe resection. Radiation therapy (RT) and chemotherapy are typically reserved for patients with incomplete resection and/or disease progression. We report long-term treatment outcomes and toxicities in a cohort of pediatric patients with LGG after RT., Methods: Thirty-four patients <21 years old with intracranial LGG who were treated with RT at the Johns Hopkins Hospital were included in this retrospective analysis. Patients were evaluated for overall survival (OS), progression-free survival (PFS), recurrence patterns, and treatment toxicities using descriptive statistics, Kaplan-Meier curves, and Cox proportional hazard regressions., Results: The mean age at diagnosis was 7.9 years (range 1.2-18.3 years) and mean age at RT was 9.8 years (range 3.0-28.9 years). The median follow-up time was 9.8 years after radiation (range 0.8-33.3 years). The estimated 10-year OS and PFS after RT were 92 and 74 %, respectively. Twelve patients had disease progression after RT, and all recurrences were local. Two patients died due to disease progression 2.3 and 9.1 years after RT. One patient had malignant transformation of LGG to high-grade glioma. No significant predictors of PFS were identified on uni- or multivariate analysis. Late effects of LGG and treatment seen were endocrine deficiencies in 16 patients, visual problems in 10 patients, hearing loss in 4 patients, special education requirements for 5 patients, and a vascular injury/demyelination secondary to RT in 1 patient., Conclusion: Our study suggests that the use of radiation in patients with intracranial LGG results in excellent OS and PFS with acceptable toxicity at long-term follow-up.
- Published
- 2016
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5. Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study
- Author
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Sadowitz, PD, primary, Smith, SD, additional, Shuster, J, additional, Wharam, MD, additional, Buchanan, GR, additional, and Rivera, GK, additional
- Published
- 1993
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6. Vincristine, actinomycin, and cyclophosphamide compared with vincristine, actinomycin, and cyclophosphamide alternating with vincristine, topotecan, and cyclophosphamide for intermediate-risk rhabdomyosarcoma: children's oncology group study D9803.
- Author
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Arndt CA, Stoner JA, Hawkins DS, Rodeberg DA, Hayes-Jordan AA, Paidas CN, Parham DM, Teot LA, Wharam MD, Breneman JC, Donaldson SS, Anderson JR, Meyer WH, Arndt, Carola A S, Stoner, Julie A, Hawkins, Douglas S, Rodeberg, David A, Hayes-Jordan, Andrea A, Paidas, Charles N, and Parham, David M
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- 2009
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7. Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma.
- Author
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Loeb DM, Garrett-Mayer E, Hobbs RF, Prideaux AR, Sgouros G, Shokek O, Wharam MD Jr, Scott T, Schwartz CL, Loeb, David M, Garrett-Mayer, Elizabeth, Hobbs, Robert F, Prideaux, Andrew R, Sgouros, George, Shokek, Ori, Wharam, Moody D Jr, Scott, Tammy, and Schwartz, Cindy L
- Abstract
Background: Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of (153)Sm-EDTMP that permits hematopoietic recovery within 6 weeks.Methods: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of (153)Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm(3) and a platelet count >75,000/mm(3) within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions.Results: The maximally tolerated dose of (153)Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed.Conclusions: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered (153)Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma. [ABSTRACT FROM AUTHOR]- Published
- 2009
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8. Samarium Sm 153 and Stem Cell Transplant Followed By Radiation Therapy Patients With Osteosarcoma
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National Cancer Institute (NCI)
- Published
- 2020
9. Delayed primary excision with subsequent modification of radiotherapy dose for intermediate-risk rhabdomyosarcoma: a report from the Children's Oncology Group Soft Tissue Sarcoma Committee.
- Author
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Rodeberg DA, Wharam MD, Lyden ER, Stoner JA, Brown K, Wolden SL, Paidas CN, Donaldson SS, Hawkins DS, Spunt SL, and Arndt CA
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- Abdomen pathology, Child, Child, Preschool, Clinical Trials as Topic, Combined Modality Therapy, Humans, Infant, Infant, Newborn, Neoplasm, Residual, Pelvis pathology, Radiotherapy Dosage, Rhabdomyosarcoma pathology, Thorax pathology, Treatment Failure, Urinary Bladder pathology, Abdomen radiation effects, Pelvis radiation effects, Rhabdomyosarcoma radiotherapy, Rhabdomyosarcoma surgery, Thorax radiation effects, Urinary Bladder radiation effects
- Abstract
The majority of intermediate-risk rhabdomyosarcoma (RMS) patients have gross residual disease (Group III) after their first operative procedure. It is currently not known if local control rates can be maintained when, following induction chemotherapy, the radiation therapy (RT) dose is decreased after a delayed primary excision (DPE). To answer this question we evaluated patients enrolled on COG D9803 (1999-2005) who had Group III tumors of the bladder dome, extremity or trunk (thorax, abdomen and pelvis) were candidates for DPE at Week 12 if the primary tumor appeared resectable. RT dose was then adjusted by the completeness of DPE: no evidence of disease 36 Gy, microscopic residual 41.4 Gy and gross residual disease (GRD) 50.4 Gy. A total of 161 Group III patients were evaluated (24 bladder dome, 63 extremity and 74 trunk). Seventy-three patients (45%) underwent DPE which achieved removal of all gross disease in 61 (84%) who were then eligible for reduced RT dose (43/73 received 36 Gy, 19/73 received 41.4 Gy). The local 5-year failure rate (0% for bladder dome, 7% for extremity and 20% for trunk) was similar to IRS-IV, which did not encourage DPE and did not allow for DPE adapted RT dose reduction. In conclusion, DPE was performed in 45% of Group III RMS patients with tumors at select anatomic sites (bladder dome, extremity and trunk) and 84% of those who had DPE were eligible for RT dose reduction. Local control outcomes were similar to historic results with RT alone., (© 2014 UICC.)
- Published
- 2015
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10. Patterns of failure after involved field radiation therapy for pediatric and young adult Hodgkin lymphoma.
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Huynh-Le MP, Walker AJ, Kominers SD, Paz-Priel I, Wharam MD, and Terezakis SA
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- Adolescent, Adult, Age Factors, Child, Child, Preschool, Disease-Free Survival, Female, Hodgkin Disease diagnosis, Humans, Male, Recurrence, Retrospective Studies, Survival Rate, Time Factors, Chemoradiotherapy, Hodgkin Disease mortality, Hodgkin Disease therapy
- Abstract
Background: Involved field radiation therapy (IFRT) is integral in curative therapy for Hodgkin lymphoma (HL), although primarily used in patients with intermediate/high-risk HL. We present failure patterns and clinical outcomes in a cohort of pediatric and young adult patients with HL treated with IFRT at the Johns Hopkins Hospital., Procedure: Patients ≤40 years old with intermediate/high-risk HL who received chemotherapy and IFRT from 1997 to 2012 were included in this retrospective analysis. Patients were evaluated for failure patterns, overall survival (OS), and event-free survival (EFS) using Kaplan-Meier curves, descriptive statistics, and Cox proportional hazard regressions., Results: We reviewed 74 patients (45 pediatric and 29 young adult) with a median follow-up of 4.4 years. The mean age at diagnosis was 21.4 years. Patients received a median of 29.75 Gy of IFRT (range 15-39.6 Gy). The majority of pediatric patients received ABVE-PC chemotherapy (n = 25) and <30 Gy of radiation (n = 33) while most young adults received ABVD chemotherapy (n = 24) and ≥30 Gy (n = 25). Estimated 5-year OS and EFS were 96% and 81%, respectively. Thirteen patients had recurrence; eight were pediatric. Distant relapse alone comprised 83% of failures in patients receiving ≥30 Gy. Of the seven patients who received <30 Gy and had recurrence, six had local failure as a component of their recurrence. Caucasian race (P = 0.02) and nodular sclerosing histology (P = 0.01) predicted for increased EFS. Late effects were minimal and all deaths (n = 4) were from HL., Conclusions: In this series, pediatric and young adult patients were treated with differing chemoradiation and had distinct recurrence patterns., (© 2014 Wiley Periodicals, Inc.)
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- 2014
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11. Combination of External Beam Radiotherapy With 153Sm-EDTMP to Treat High Risk Osteosarcoma
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National Cancer Institute (NCI) and Jazz Pharmaceuticals
- Published
- 2019
12. Management of pediatric spinal cord astrocytomas: outcomes with adjuvant radiation.
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Guss ZD, Moningi S, Jallo GI, Cohen KJ, Wharam MD, and Terezakis SA
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- Adolescent, Astrocytoma mortality, Astrocytoma pathology, Astrocytoma surgery, Baltimore, Child, Child, Preschool, Disease-Free Survival, Female, Humans, Male, Radiation Injuries complications, Radiation Injuries pathology, Radiotherapy Dosage, Regression Analysis, Retrospective Studies, Spinal Cord Neoplasms mortality, Spinal Cord Neoplasms pathology, Spinal Cord Neoplasms surgery, Tertiary Care Centers, Treatment Outcome, Young Adult, Astrocytoma radiotherapy, Spinal Cord Neoplasms radiotherapy
- Abstract
Purpose: Pediatric intramedullary spinal cord tumors are exceedingly rare; in the United States, 100 to 200 cases are recognized annually, of these, most are astrocytomas. The purpose of this study is to report the outcomes in pediatric patients with spinal cord astrocytomas treated at a tertiary care center., Methods and Materials: An institutional review board-approved retrospective single-institution study was performed for pediatric patients with spinal cord astrocytomas treated at our hospital from 1990 to 2010. The patients were evaluated on the extent of resection, progression-free survival (PFS), and development of radiation-related toxicities. Kaplan-Meier curves and multivariate regression model methods were used for analysis., Results: Twenty-nine patients were included in the study, 24 with grade 1 or 2 (low-grade) tumors and 5 with grade 3 or 4 (high-grade) tumors. The median follow-up time was 55 months (range, 1-215 months) for patients with low-grade tumors and 17 months (range, 10-52 months) for those with high-grade tumors. Thirteen patients in the cohort received chemotherapy. All patients underwent at least 1 surgical resection. Twelve patients received radiation therapy to a median radiation dose of 47.5 Gy (range, 28.6-54.0 Gy). Fifteen patients with low-grade tumors and 1 patient with a high-grade tumor exhibited stable disease at the last follow-up visit. Acute toxicities of radiation therapy were low grade, whereas long-term sequelae were infrequent and manageable when they arose. All patients with low-grade tumors were alive at the last follow-up visit, compared with 1 patient with a high-grade tumor., Conclusion: Primary pediatric spinal cord astrocytomas vary widely in presentation and clinical course. Histopathologic grade remains a major prognostic factor. Patients with low-grade tumors tend to have excellent disease control and long-term survival compared to those with high-grade tumors. This experience suggests that radiation therapy may enhance tumor control with an acceptably low risk of long-term sequelae in this sensitive patient population., (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Published
- 2013
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13. Radiotherapy for rhabdomyosarcoma: indications and outcome.
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Terezakis SA and Wharam MD
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- Humans, Prognosis, Treatment Outcome, Head and Neck Neoplasms radiotherapy, Radiotherapy, Intensity-Modulated methods, Rhabdomyosarcoma radiotherapy
- Abstract
Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Improvements in the clinical outcomes of rhabdomyosarcoma have been secondary to the intensification and refinement of treatment investigated by the Intergroup Rhabdomyosarcoma Study Group. Advances in diagnostic imaging techniques have led to improvements in staging and contribute to precision in radiation field design. Radiation treatment has been integrated into the primary treatment of most patients with rhabdomyosarcoma. Each treatment site has special considerations with regards to prognosis, outcomes and potential morbidities that affect the choice of local therapy. Advanced radiotherapy techniques using conformal treatment with intensity-modulated radiotherapy and proton therapy are particularly advantageous for the treatment of sites close to critical structures, such as the head and neck and genitourinary system. Active investigation is underway to develop strategies to reduce the radiation dose and volume in an effort to minimise late toxicity and improve the therapeutic ratio., (Copyright © 2012 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)
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- 2013
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14. Chemotherapy-refractory cutaneous Langerhans cell histiocytosis treated with radiotherapy.
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Hristov B, Hristov AC, Lin SH, Arceci RJ, and Wharam MD Jr
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- 2011
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15. Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma.
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Loeb DM, Hobbs RF, Okoli A, Chen AR, Cho S, Srinivasan S, Sgouros G, Shokek O, Wharam MD Jr, Scott T, and Schwartz CL
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- Adolescent, Adult, Female, Humans, Male, Organometallic Compounds adverse effects, Organophosphorus Compounds adverse effects, Radiometry, Radiopharmaceuticals adverse effects, Transplantation, Autologous, Bone Neoplasms radiotherapy, Bone Neoplasms surgery, Hematopoietic Stem Cell Transplantation methods, Organometallic Compounds therapeutic use, Organophosphorus Compounds therapeutic use, Osteosarcoma radiotherapy, Osteosarcoma surgery, Radiopharmaceuticals therapeutic use
- Abstract
Background: Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities., Methods: Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response., Results: Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days., Conclusions: Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent., (Copyright © 2010 American Cancer Society.)
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- 2010
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16. Clinical results of a pilot study on stereovision-guided stereotactic radiotherapy and intensity modulated radiotherapy.
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Li S, Kleinberg LR, Rigamonti D, Wharam MD Jr, Rashid A, Jackson J, Djajaputra D, He S, Creasey T, and DeWeese TL
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- Adult, Aged, Aged, 80 and over, Computer Systems, Female, Head diagnostic imaging, Humans, Male, Meningioma radiotherapy, Meningioma surgery, Middle Aged, Patient Positioning methods, Pilot Projects, Radiography, Radiotherapy Planning, Computer-Assisted methods, Young Adult, Head and Neck Neoplasms radiotherapy, Head and Neck Neoplasms surgery, Neuroma, Acoustic radiotherapy, Neuroma, Acoustic surgery, Radiosurgery methods, Radiotherapy, Intensity-Modulated methods, Surgery, Computer-Assisted methods
- Abstract
Real-time stereovision-guidance has been introduced for efficient and convenient fractionated stereotactic radiotherapy (FSR) and image-guided intensity-modulated radiation therapy (IMRT). This first pilot study is to clinically evaluate its accuracy and precision as well as impact on treatment doses. Sixty-one FSR patients wearing stereotactic masks (SMs) and nine IMRT patients wearing flexible masks (FMs), were accrued. Daily target reposition was initially based-on biplane-radiographs and then adjusted in six degrees of freedom under real-time stereovision guidance. Mean and standard deviation of the head displacements measured the accuracy and precision. Head positions during beam-on times were measured with real-time stereovisions and used for determination of delivered doses. Accuracy ± ± precision in direction with the largest errors shows improvement from 0.4 ± 2.3 mm to 0.0 ± 1.0 mm in the inferior-to-superior direction for patients wearing SM or from 0.8 ± 4.3 mm to 0.4 ± 1.7 mm in the posterior-to-anterior direction for patients wearing FM. The image-guidance increases target volume coverage by >30% for small lesions. Over half of head position errors could be removed from the stereovision-guidance. Importantly, the technique allows us to check head position during beam-on time and makes it possible for having frameless head refixation without tight masks.
- Published
- 2010
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17. Prognostic factors in pediatric high-grade astrocytoma: the importance of accurate pathologic diagnosis.
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Hales RK, Shokek O, Burger PC, Paynter NP, Chaichana KL, Quiñones-Hinojosa A, Jallo GI, Cohen KJ, Song DY, Carson BS, and Wharam MD
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- Adolescent, Age Factors, Brain Neoplasms mortality, Child, Child, Preschool, Cohort Studies, Female, Humans, Infant, Kaplan-Meier Estimate, Male, Multivariate Analysis, Neoplasms, Neuroepithelial mortality, Prognosis, Retrospective Studies, Young Adult, Brain pathology, Brain Neoplasms diagnosis, Neoplasms, Neuroepithelial diagnosis, Pediatrics
- Abstract
To characterize a population of pediatric high-grade astrocytoma (HGA) patients by confirming the proportion with a correct diagnosis, and determine prognostic factors for survival in a subset diagnosed with uniform pathologic criteria. Sixty-three children diagnosed with HGA were treated at the Johns Hopkins Hospital between 1977 and 2004. A single neuropathologist (P.C.B.) reviewed all available histologic samples (n = 48). Log-rank analysis was used to compare survival by patient, tumor, and treatment factors. Median follow-up was 16 months for all patients and 155 months (minimum 54 months) for surviving patients. Median survival for all patients (n = 63) was 14 months with 10 long-term survivors (survival >48 months). At initial diagnosis, 27 patients were grade III (43%) and 36 grade IV (57%). Forty-eight patients had pathology slides available for review, including seven of ten long-term surviving patients. Four patients had non-HGA pathology, all of whom were long term survivors. The remaining 44 patients with confirmed HGG had a median survival of 14 months and prognostic analysis was confined to these patients. On multivariate analysis, five factors were associated with inferior survival: performance status (Lansky) <80% (13 vs. 15 months), bilaterality (13 vs. 19 months), parietal lobe location (13 vs. 16 months), resection less than gross total (13 vs. 22 months), and radiotherapy dose <50 Gy (9 vs. 16 months). Among patients with more than one of the five adverse factors (n = 27), median survival and proportion of long-term survivors were 12.9 months and 0%, compared with 41.4 months and 18% for patients with 0-1 adverse factors (n = 17). In an historical cohort of children with HGA, the potential for long term survival was confined to the subset with less than two of the following adverse prognostic factors: low performance status, bilaterality, parietal lobe site, less than gross total resection, and radiotherapy dose <50 Gy. Pathologic misdiagnosis should be suspected in patients who are long term survivors of a pediatric high grade astrocytoma.
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- 2010
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18. Neuroimaging and neuropsychological follow-up study in a pediatric brain tumor patient treated with surgery and radiation.
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Schmidt AT, Martin RB, Ozturk A, Kates WR, Wharam MD, Mahone EM, and Horska A
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- Adolescent, Aspartic Acid analogs & derivatives, Aspartic Acid metabolism, Follow-Up Studies, Humans, Image Processing, Computer-Assisted methods, Language, Magnetic Resonance Imaging methods, Magnetic Resonance Spectroscopy methods, Male, Memory physiology, Neuropsychological Tests, Pediatrics, Proton Therapy, Psychomotor Performance physiology, Visual Perception physiology, Brain Mapping, Cognition physiology, Ependymoma surgery, Radiosurgery methods, Spinal Neoplasms surgery
- Abstract
Intracranial tumors are the most common neoplasms of childhood, accounting for approximately 20% of all pediatric malignancies. Radiation therapy has led directly to significant increases in survival of children with certain types of intracranial tumors; however, given the aggressive nature of this therapy, children are at risk for exhibiting changes in brain structure, neuronal biochemistry, and neurocognitive functioning. In this case report, we present neuropsychological, magnetic resonance imaging, proton magnetic resonance spectroscopic imaging, and diffusion tensor imaging data for two adolescents (one patient with ependymal spinal cord tumor with intracranial metastases, and one healthy, typically developing control) from three time points as defined by the patient's radiation schedule (baseline before the patient's radiation therapy, 6 months following completion of the patient's radiation, and 27 months following the patient's radiation). In the patient, there were progressive decreases in gray and white matter volumes as well as early decreases in mean N-acetyl aspartate/choline (NAA/Cho) ratios and fractional anisotropy (FA) in regions with normal appearance on conventional MRI. At the last follow-up, NAA/Cho and FA tended to change in the direction to normal values in selected regions. At the same time, the patient had initial reduction in language and motor skills, followed by return to baseline, but later onset delay in visuospatial and visual perceptual skills. Results are discussed in terms of sensitivity of the four techniques to early and late effects of treatment, and avenues for future investigations.
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- 2010
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19. Risk of second tumor in intracranial germinoma patients treated with radiation therapy: the Johns Hopkins experience.
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Jabbour SK, Zhang Z, Arnold D, and Wharam MD
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- Adolescent, Adult, Brain Neoplasms radiotherapy, Child, Combined Modality Therapy, Female, Follow-Up Studies, Germinoma radiotherapy, Humans, Incidence, Male, Retrospective Studies, Risk Assessment, Time Factors, Treatment Outcome, Neoplasms, Radiation-Induced epidemiology, Neoplasms, Radiation-Induced etiology, Neoplasms, Second Primary epidemiology, Neoplasms, Second Primary etiology, Radiotherapy adverse effects, Risk
- Abstract
Background: We reviewed the risk of second tumor (ST), both malignant and benign, in germinoma survivors followed at the Johns Hopkins Hospital (JHH)., Methods: Between 1977 and 2002, 27 patients with intracranial germinoma were treated with radiation therapy (RT). In the presence of competing events, a cumulative incidence function of ST was estimated using the minimal time interval from the date of diagnosis to the date of ST, date of death, or date of last follow-up., Results: Five patients (18%) developed a ST of which 4 (15%) were malignant. One developed a benign falcine meningioma. The cumulative incidence of ST was 9% at 11 years (95% CI, 0-22%)., Conclusions: The relative contributions of RT and patient susceptibility to a ST cannot be determined but suggests the need for long-term surveillance, including testicular self-exams in male germinoma survivors. Current trials of chemotherapy and reduced RT dose and volume offer the prospect of a lower risk of treatment-induced ST.
- Published
- 2009
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20. Outcome analysis of childhood low-grade astrocytomas.
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Fisher PG, Tihan T, Goldthwaite PT, Wharam MD, Carson BS, Weingart JD, Repka MX, Cohen KJ, and Burger PC
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- Adolescent, Astrocytoma diagnosis, Astrocytoma therapy, Brain Neoplasms diagnosis, Brain Neoplasms therapy, Child, Child, Preschool, Female, Humans, Infant, Male, Prognosis, Astrocytoma mortality, Brain Neoplasms mortality
- Abstract
Background: We aimed to determine the long-term natural history of low-grade astrocytomas (LGA) in children, with respect to pathology, and to evaluate influence of treatment on survival., Patients and Methods: A consecutive cohort of patients < or =21 years with surgically confirmed LGA from 1965 to 1996 was assembled. All available pathology specimens were reviewed, masked to original diagnosis, patient data, and neuroimaging., Results: Two hundred seventy-eight children (160 males; mean age 9.1 years; tumor location: 77 cerebrum, 62 cerebellum, 51 hypothalamic, 30 thalamus, 9 ventricle, 40 brainstem, and 9 spine) were assessed. Among 246 specimens reviewed, diagnoses were 135 pilocytic astrocytoma (PA), 27 diffuse astrocytoma (DA), 75 unclassifiable well-differentiated astrocytoma (NOS), and 9 subependymal giant cell astrocytoma. At 5 and 10 years from initial surgery, for all LGA overall survival (OS) was 87% and 83%, while progression-free survival (PFS) was 55% and 42%, respectively. Original pathology diagnoses did not predict PFS (P = 0.47), but reviewed diagnoses were significantly associated with PFS (P = 0.007). Reviewed diagnoses were highly associated with OS (P < 0.0001), with 5-year OS for PA 96%, DA 48%, and NOS 86%; these differences remained significant when stratified by location or extent of resection. Among patients with residual tumor after surgery, 5-year PFS was 48% with observation alone (n = 114), no different (P = 0.32) from that achieved with immediate irradiation (n = 86)., Conclusion: LGA, particularly PA, have excellent long-term OS. While tumor location and resection extent affect outcome, pathologic diagnosis when carefully interpreted significantly influences long-term survival. Immediate postoperative irradiation does not confer an advantage in delaying first progression in children with residual PA.
- Published
- 2008
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21. HDAC3 genetic and pharmacologic inhibition radiosensitizes fusion positive rhabdomyosarcoma by promoting DNA double-strand breaks.
- Author
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Cassandri, Matteo, Porrazzo, Antonella, Pomella, Silvia, Noce, Beatrice, Zwergel, Clemens, Aiello, Francesca Antonella, Vulcano, Francesca, Milazzo, Luisa, Camero, Simona, Pajalunga, Deborah, Spada, Massimo, Manzi, Valeria, Gravina, Giovanni Luca, Codenotti, Silvia, Piccione, Michela, Tomaciello, Miriam, Signore, Michele, Barillari, Giovanni, Marchese, Cinzia, and Fanzani, Alessandro
- Published
- 2024
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22. Isolated Optic Nerve Relapse in a Pediatric Patient With T-Cell Lymphoblastic Leukemia: A Brief Report.
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Shenkar, Rakefet, Kahwash, Samir B., Rodriguez, Diana P., Abu Arja, Rolla, Reed, Suzanne M., and Rangarajan, Hemalatha G.
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- 2024
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23. Ewing sarcoma bone metastases: 'you see one, you've seen them all': (commentary on Furth et al., page 607).
- Author
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Wharam MD Jr
- Subjects
- Adolescent, Bone Neoplasms therapy, Female, Humans, Magnetic Resonance Imaging, Neoplasm Staging, Positron-Emission Tomography, Predictive Value of Tests, Sarcoma, Ewing therapy, Sensitivity and Specificity, Treatment Outcome, Bone Neoplasms diagnosis, Bone Neoplasms secondary, Sarcoma, Ewing diagnosis, Sarcoma, Ewing secondary
- Published
- 2006
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24. POG 8625: a randomized trial comparing chemotherapy with chemoradiotherapy for children and adolescents with Stages I, IIA, IIIA1 Hodgkin Disease: a report from the Children's Oncology Group.
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Kung FH, Schwartz CL, Ferree CR, London WB, Ternberg JL, Behm FG, Wharam MD, Falletta JM, de Alarcon P, and Chauvenet AR
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- Adolescent, Adult, Antineoplastic Agents administration & dosage, Bleomycin administration & dosage, Child, Child, Preschool, Combined Modality Therapy, Disease-Free Survival, Female, Hodgkin Disease mortality, Hodgkin Disease pathology, Humans, Male, Mechlorethamine administration & dosage, Neoplasm Staging, Prednisone administration & dosage, Procarbazine administration & dosage, Remission Induction, Vinblastine administration & dosage, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Hodgkin Disease drug therapy, Hodgkin Disease radiotherapy
- Abstract
To determine if 6 courses of chemotherapy alone could achieve the same or better outcome than 4 courses of chemotherapy followed by radiation therapy (chemoradiotherapy) in pediatric and adolescent patients with Hodgkin disease. Children < or =21 years old with biopsy-proven, pathologically staged I, IIA, or IIIA1 Hodgkin disease were randomly assigned 6 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine (treatment 1) or 4 courses of alternating nitrogen mustard, oncovin, prednisone, and procarbazine/doxorubicin, bleomycin, vinblastine, and dacarbazine +2550 cGy involved-field radiotherapy (treatment 2). The complete response rate was 89%, with a complete response and partial response rate of 99.4%. There was no statistically significant difference in event-free survival (EFS) or overall survival between arms. The EFS for those who achieved an early complete response was significantly higher than for those who did not. For pediatric patients with asymptomatic low-stage and intermediate-stage Hodgkin disease, chemotherapy and chemoradiotherapy both resulted in 3-year EFS of approximately 90% and statistically indistinguishable 8-year EFS and overall survival, without significant long-term toxicity. Early response to therapy was associated with higher EFS, a concept that has led to the Children's Oncology Group paradigm of response-based risk-adapted therapy for pediatric Hodgkin disease.
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- 2006
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25. Proton magnetic resonance spectroscopic imaging to differentiate between nonneoplastic lesions and brain tumors in children.
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Hourani R, Horská A, Albayram S, Brant LJ, Melhem E, Cohen KJ, Burger PC, Weingart JD, Carson B, Wharam MD, and Barker PB
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- Adolescent, Astrocytoma pathology, Biopsy, Needle, Brain Neoplasms pathology, Child, Child, Preschool, Diagnosis, Differential, Female, Germinoma pathology, Glioma pathology, Humans, Immunohistochemistry, Male, Neoplasm Staging, Retrospective Studies, Sensitivity and Specificity, Astrocytoma diagnosis, Brain Neoplasms diagnosis, Germinoma diagnosis, Glioma diagnosis, Magnetic Resonance Spectroscopy methods
- Abstract
Purpose: To investigate whether in vivo proton magnetic resonance spectroscopic imaging (MRSI) can differentiate between 1) tumors and nonneoplastic brain lesions, and 2) high- and low-grade tumors in children., Materials and Methods: Thirty-two children (20 males and 12 females, mean age = 10 +/- 5 years) with primary brain lesions were evaluated retrospectively. Nineteen patients had a neuropathologically confirmed brain tumor, and 13 patients had a benign lesion. Multislice proton MRSI was performed at TE = 280 msec. Ratios of N-acetyl aspartate/choline (NAA/Cho), NAA/creatine (Cr), and Cho/Cr were evaluated in the lesion and the contralateral hemisphere. Normalized lesion peak areas (Cho(norm), Cr(norm), and NAA(norm)) expressed relative to the contralateral hemisphere were also calculated. Discriminant function analysis was used for statistical evaluation., Results: Considering all possible combinations of metabolite ratios, the best discriminant function to differentiate between nonneoplastic lesions and brain tumors was found to include only the ratio of Cho/Cr (Wilks' lambda, P = 0.012; 78.1% of original grouped cases correctly classified). The best discriminant function to differentiate between high- and low-grade tumors included the ratios of NAA/Cr and Cho(norm) (Wilks' lambda, P = 0.001; 89.5% of original grouped cases correctly classified). Cr levels in low-grade tumors were slightly lower than or comparable to control regions and ranged from 53% to 165% of the control values in high-grade tumors., Conclusion: Proton MRSI may have a promising role in differentiating pediatric brain lesions, and an important diagnostic value, particularly for inoperable or inaccessible lesions., (Published 2005 Wiley-Liss, Inc.)
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- 2006
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26. Treatment of recurrent glioblastoma multiforme with GliaSite brachytherapy.
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Chan TA, Weingart JD, Parisi M, Hughes MA, Olivi A, Borzillary S, Alahakone D, Detorie NA, Wharam MD, and Kleinberg L
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- Adult, Aged, Benzenesulfonates therapeutic use, Brachytherapy adverse effects, Brachytherapy mortality, Brain Neoplasms mortality, Brain Neoplasms surgery, Combined Modality Therapy, Female, Glioblastoma mortality, Glioblastoma surgery, Humans, Iodine Radioisotopes therapeutic use, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local surgery, Radiotherapy Dosage, Reoperation, Survival Rate, Brachytherapy methods, Brain Neoplasms radiotherapy, Glioblastoma radiotherapy, Neoplasm Recurrence, Local radiotherapy
- Abstract
Purpose: In this study, we assess the efficacy of GliaSite brachytherapy in the treatment of patients with recurrent glioblastoma multiforme (GBM)., Methods and Materials: Between 1999 and 2004, 24 patients with recurrent glioblastoma multiforme were treated with the GliaSite Radiation Therapy System (RTS). The GliaSite is an inflatable balloon catheter that is placed in the resection cavity at the time of surgical resection. Low-dose-rate radiation is then delivered locally by temporarily inflating the balloon with an aqueous solution of organically bound (125)I (Iotrex [sodium 3-((125)I)-iodo-4-hydroxybenzenesulfonate]). Patients at the Johns Hopkins Hospital with recurrent GBM, who were previously treated with surgery and external beam radiotherapy, underwent surgical resection followed by GliaSite balloon implantation. Subsequently, the patients received radiation therapy using the GliaSite to a mean dose of 53.1 Gy. Ten patients were male, and 14 patients were female. The mean age was 48.1 years. All patients had pathologically confirmed recurrent GBM. The median Karnofsky performance status (KPS) was 80. Median follow-up time was 21.8 months., Results: At the time of analysis, 18 patients (75%) had died; 6 patients (25%) were alive. Median survival from diagnosis for all patients was 23.3 months. Median survival after GliaSite brachytherapy was 9.1 months. Patients with a KPS > or =70 had a median survival of 9.3 months, whereas patients with a KPS <70 had a median survival of 3.1 months (p < 0.003). Survival was not significantly different between patients receiving 45 Gy and patients receiving a dose greater than 45 Gy. Acute side effects were minor, consisting of mild nausea and/or headache. One patient developed a wound infection. No incidents of meningitis were observed. Late sequelae were rare, but 2 incidents of symptomatic radiation necrosis were observed. One patient developed transient expressive aphasia., Conclusions: GliaSite radiotherapy confers a prolongation of survival in patients with recurrent glioblastoma multiforme compared to historical controls with recurrent GBM. GliaSite therapy leads to a favorable survival outcome of 9.3 months in patients with KPS > or =70, but only 3.1 months in patients with KPS <70. Favorable survival is observed for patients within each recursive partitioning analysis class. Treatment with GliaSite is safe and generally well tolerated. Additional data are needed to fully assess the therapeutic benefit of GliaSite brachytherapy for recurrent GBM.
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- 2005
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27. Influence of radiation therapy parameters on outcome in children treated with radiation therapy for localized parameningeal rhabdomyosarcoma in Intergroup Rhabdomyosarcoma Study Group trials II through IV.
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Michalski JM, Meza J, Breneman JC, Wolden SL, Laurie F, Jodoin M, Raney B, Wharam MD, and Donaldson SS
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- Central Nervous System Diseases diagnostic imaging, Central Nervous System Diseases etiology, Child, Child, Preschool, Clinical Protocols, Confidence Intervals, Head and Neck Neoplasms diagnostic imaging, Head and Neck Neoplasms mortality, Humans, Infant, Meninges diagnostic imaging, Multivariate Analysis, Radiography, Rhabdomyosarcoma diagnostic imaging, Rhabdomyosarcoma mortality, Survival Rate, Head and Neck Neoplasms radiotherapy, Rhabdomyosarcoma radiotherapy
- Abstract
Purpose: To evaluate the impact of radiation treatment parameters on cancer control outcomes for children with parameningeal rhabdomyosarcoma (PM-RMS) treated on Intergroup Rhabdomyosarcoma Study Group protocols II through IV (including IRS-IV pilot)., Materials and Methods: Radiation therapy (RT) treatment quality was assessed by contemporary review of portal radiographs, simulation films, treatment plans, and, in most cases, cross-sectional diagnostic imaging data for patients treated on Intergroup Rhabdomyosarcoma Study Group protocols II through IV. Five hundred ninety-five patients with PM-RMS were registered on these 4 studies between 1978 and 1997. Most of these patients (95%) had Group III disease. Radiation doses varied over the span of these trials with protocol doses ranging from 40 Gy to 50.4 Gy on IRS-II and IRS-III and 50.4 Gy to 59.4 Gy (hyperfractionated) on IRS-IV pilot and IRS-IV. Patients with high-risk signs of meningeal impingement, including cranial nerve palsy (CNP) or cranial base bone erosion (CBBE) with or without intracranial extension (ICE), were required to start radiotherapy at the time of study entry (Day 0). Among 595 patients reviewed, 385 (65%) had diagnostic images submitted to the Quality Assurance Review Center for assessment of target volume coverage. Only 123 (21%) patients, 49 (40%) of whom were treated on IRS-II, received whole brain RT., Results: The estimated overall survival and failure-free survival rates were 73% and 69% at 5 years, respectively. The estimated 5-year local failure (LF) rate was 17%. The detection of ICE increased from 24% to 41% as more cross-sectional diagnostic images became available. For patients with any sign of meningeal impingement, starting RT <2 weeks after diagnosis (n = 315) had 18% LF compared to 33% LF if started >2 weeks after diagnosis (n = 43) (p = 0.03). For patients with ICE, starting RT <2 weeks after diagnosis (n = 177) resulted in LF in 16% compared to 37% among those who started >2 weeks after (n = 19) (p = 0.07). For patients with CNP and/or CBBE, starting RT <2 weeks after diagnosis (n = 138) resulted in 21% LF compared to 30% among those that started >2 weeks (n = 23) (p = 0.23). In none of these circumstances was the 5-year failure-free survival significantly impacted by this increase in LF. The estimated 3-year survival after local failure was 17% (95% CI, 10%-25%). For patients without signs of meningeal impingement, there was no difference in local control whether they started radiation therapy earlier or later than 10 weeks. Patients with large (> or =5 cm) Group III tumors had an LF rate of 35% if they received less than 47.5 Gy compared to an LF rate of 18% in patients who received less than 47.5 Gy with smaller tumors or a rate of 15% if they received more than 47.5 Gy, irrespective of tumor size (p = 0.14). There was no evidence that whole brain radiation therapy affected LF or reduced central nervous system (CNS) relapse. Multivariate analysis of RT parameters and clinical factors demonstrated that a radiation dose of >47.5 Gy was associated with lower LF. The presence of ICE, CNP, or CBBE and age >10 years at diagnosis were significantly associated with higher rates of local failure., Conclusions: The availability of cross-sectional diagnostic images (CT or MRI) has improved detection of ICE. Starting radiation therapy within 2 weeks of diagnosis for patients with signs of meningeal impingement was associated with lower rates of local failure. When no signs of meningeal impingement were present, delay of radiation therapy for more than 10 weeks did not impact local failure rates. Whole brain radiation therapy is unnecessary in PM-RMS. A dose of at least 47.5 Gy seems to be associated with lower rates of local failure, especially when tumor diameter is > or =5 cm.
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- 2004
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28. Failure pattern and factors predictive of local failure in rhabdomyosarcoma: a report of group III patients on the third Intergroup Rhabdomyosarcoma Study.
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Wharam MD, Meza J, Anderson J, Breneman JC, Donaldson SS, Fitzgerald TJ, Michalski J, Teot LA, Wiener ES, and Meyer WH
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- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Incidence, Infant, Male, Medical Records, Neoplasm Metastasis, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Predictive Value of Tests, Prognosis, Retrospective Studies, Rhabdomyosarcoma mortality, Rhabdomyosarcoma pathology, Survival Analysis, Treatment Failure, United States, Neoplasm Recurrence, Local radiotherapy, Rhabdomyosarcoma therapy
- Abstract
Purpose: To analyze patterns of failure and factors predictive of local treatment failure in children enrolled on the third Intergroup Rhabdomyosarcoma Study who had either biopsy only or subtotal resection of their primary tumor, had no distant metastases, and received radiation therapy for local control., Patients and Methods: Treatment failure was categorized as local, regional nodal, or distant metastatic. The 5-year cumulative risk of failure was estimated for each category and factors predictive of local failure risk were determined using the Cox model and binary recursive partitioning., Results: The estimated 5-year cumulative incidence rates by failure category were: total local (with or without concurrent regional or distant failure), 19%; total regional nodal, 2%; total distant, 11%; and death from toxicity or unknown recurrence type, 4%. Lymph node involvement at diagnosis was the single factor most predictive of increased total local failure risk (5-year cumulative incidence 32%) compared with children with negative nodes or unknown node status (16%). No significant effect on local failure risk was observed by total radiotherapy dose over the prescribed range of 41.4 Gy to 50.4 Gy. For all patients (N = 405), the estimated 5-year failure-free survival and overall survival were, respectively, 70% and 78%., Conclusion: Local failure after radiotherapy for group III rhabdomyosarcoma patients is the predominant type of relapse. Involved lymph nodes at diagnosis predict a higher risk of local and distant treatment failure compared with patients whose lymph nodes are negative.
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- 2004
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29. Efficacy of topotecan and cyclophosphamide given in a phase II window trial in children with newly diagnosed metastatic rhabdomyosarcoma: a Children's Oncology Group study.
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Walterhouse DO, Lyden ER, Breitfeld PP, Qualman SJ, Wharam MD, and Meyer WH
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- Adolescent, Adult, Child, Child, Preschool, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Dactinomycin therapeutic use, Disease-Free Survival, Female, Humans, Male, Neoplasm Metastasis, Rhabdomyosarcoma pathology, Survival Analysis, Topotecan administration & dosage, Topotecan adverse effects, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Rhabdomyosarcoma drug therapy, Topotecan therapeutic use
- Abstract
Purpose: To determine the antitumor activity and toxicity of topotecan given immediately after cyclophosphamide as window therapy, then in combination with conventional agents in pediatric patients with newly diagnosed metastatic rhabdomyosarcoma (RMS)., Patients and Methods: Sixty-one patients younger than 21 years with newly diagnosed metastatic RMS or undifferentiated sarcoma were assigned window therapy (weeks 0 to 6) with topotecan (0.75 mg/m(2) daily x 5 every 21 days) immediately after cyclophosphamide (250 mg/m(2) daily x 5 every 21 days; TC). We continued to give these agents in combination with vincristine (VTC) to patients who showed objective improvement, partial response (PR), or complete response (CR) to TC and alternated courses of VTC with vincristine, dactinomycin and cyclophosphamide (VAC) during weeks 6 to 41 (VTC/VAC). Those who showed no response or progressive disease after TC received only VAC. All patients received radiotherapy to sites of unresected disease (weeks 15 to 21)., Results: The overall response rate (CR + PR) to TC was 47% (95% CI, 35% to 60%). Tumor size < or = 5 cm was associated with early response. Myelosuppression was the primary toxicity to TC. Overall 3-year disease-free survival and survival were estimated to be 10% (95% CI, 2% to 19%) and 20% (95% CI, 8% to 32%), respectively. Toxicity profiles for patients who received VTC/VAC or VAC alone were comparable., Conclusion: Topotecan after cyclophosphamide is a combination that is active against newly diagnosed RMS, with an acceptable toxicity profile. Disease-free survival and overall survival, however, remain disappointing for children with metastatic RMS at diagnosis.
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- 2004
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30. Clinical course and pathologic findings after Gliadel and radiotherapy for newly diagnosed malignant glioma: implications for patient management.
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Kleinberg LR, Weingart J, Burger P, Carson K, Grossman SA, Li K, Olivi A, Wharam MD, and Brem H
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- Adult, Aged, Antineoplastic Agents, Alkylating adverse effects, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Carmustine adverse effects, Combined Modality Therapy, Female, Glioma pathology, Glioma radiotherapy, Glioma surgery, Humans, Male, Middle Aged, Neoplasm Recurrence, Local, Polymers, Reoperation, Retrospective Studies, Survival Analysis, Treatment Outcome, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Alkylating therapeutic use, Brain Neoplasms drug therapy, Carmustine administration & dosage, Carmustine therapeutic use, Glioma drug therapy
- Abstract
Randomized trials have demonstrated Gliadel improves survival for appropriately selected patients with newly diagnosed malignant glioma. As only limited information is available to guide the management of patients who have Gliadel controlled-release BCNU wafers implanted in the cranial resection cavity prior to radiotherapy (RT), this retrospective review was conducted to describe clinical course, toxicity, and pathologic findings after this therapy for newly diagnosed malignant glioma. Forty-six consecutive patients receiving Gliadel (3.8% BCNU impregnated wafers) followed by radiotherapy for newly diagnosed malignant glioma at Johns Hopkins Hospital from 1990 to August 1999 were identified, although one was lost to follow up and is excluded. Patients were evaluated for postoperative infection, pathology at reoperation, and survival. Twenty-eight patients received radiotherapy at Johns Hopkins and these patients are also evaluable for toxicity experienced during and one month after completion of RT. The median age of all patients is 57 years. Eighty-nine percent had glioblastoma, and median follow-up of surviving glioblastoma patients is 16.8 (12-20) months. Postoperative infection or need for reoperation within 30 days was uncommon after Gliadel placement. Full-dose radiotherapy was tolerable after Gliadel implantation. Five patients (19%) developed neurologic symptoms during radiotherapy responding to increased steroids and/or anticonvulsants, whereas an additional 8 of 27 (30%) developed neurologic symptoms during dexamethasone taper that responded to increases in dexamethasone dose. At one month after RT, 58% of patients were still on dexamethasone despite attempted taper. Fifteen of 45 patients, 33% underwent reoperation or biopsy for a new local contrast-enhancing lesion. In five of 15 (33%) the reoperation revealed necrosis or treatment effect without active tumor. Two of five patients with treatment/effect necrosis has a third surgery 2.9 and 3.2 months after the initial reoperation, and treatment effect/necrosis without tumor was demonstrated in both cases. The Kaplan-Meier median survival for all the glioblastoma patients is 12.8 (95% CI 9.6, 15.9) months. For glioblastoma patients under 55 years old, median survival is 15.9 (95% CI 13.5, too few events) months whereas for older patients it is 9.6 (7.7, 14.4) months. We conclude that Gliadel followed by full-dose standard radiotherapy is acutely well tolerated, although, close supervision should be emphasized during dexamethasone taper. Median survival in excess of one year suggests that there are not complications that result in overall premature death. The finding of necrosis/treatment effect was noted in five of 45 (11%) of all patients and five of 15 (33%) of those undergoing reoperation. Therefore, the possibility of necrosis/treatment effect should be considered for each patient with radiographic findings suspicious for local recurrence.
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- 2004
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31. Treatment of localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma: lessons learned from intergroup rhabdomyosarcoma studies III and IV.
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Pappo AS, Meza JL, Donaldson SS, Wharam MD, Wiener ES, Qualman SJ, Maurer HM, and Crist WM
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- Adolescent, Child, Child, Preschool, Combined Modality Therapy, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms radiotherapy, Humans, Infant, Male, Neoplasm Recurrence, Local, Retrospective Studies, Rhabdomyosarcoma mortality, Rhabdomyosarcoma radiotherapy, Antineoplastic Agents therapeutic use, Disease-Free Survival, Head and Neck Neoplasms drug therapy, Rhabdomyosarcoma drug therapy
- Abstract
Purpose: The characteristics and clinical outcomes of children and adolescents with localized nonorbital, nonparameningeal head and neck rhabdomyosarcoma (RMS) treated on national protocols from the Intergroup Rhabdomyosarcoma Group are reported., Patients and Methods: We conducted a retrospective review of 164 children and adolescents enrolled in the third and fourth Intergroup Rhabdomyosarcoma Studies. Variables analyzed included age, sex, primary tumor site, histologic subtype, clinical group, therapy, site and rate of treatment failure, and time to initial recurrence., Results: Localized nonorbital, nonparameningeal RMS accounted for 9% of all cases of RMS. The median age at diagnosis was 5 years; the median follow-up was 6.6 years. Estimated 5-year failure-free survival (FFS) and survival (S) rates were 76% (95% CI, 69% to 83%) and 83% (95% CI, 77% to 89%), respectively. In multivariate analysis, patients with clinically involved regional nodes (N1) had worse FFS (P =.02). For patients with embryonal tumors, FFS was significantly improved, especially among patients with Group I/II without nodal disease clinical Group I, II N0. For patients with alveolar/undifferentiated histology, FFS was significantly worse in children under the age of 1 year. Actuarial estimates of recurrences at 15 years were local (19%), regional (5%), and distant (9%)., Conclusion: More than 80% of patients with RMS of the head and neck are cured of their disease using surgery and vincristine, dactinomycin +/- cyclophosphamide with or without radiotherapy. Our results indicate that early, limited exposure to cyclophosphamide might reduce recurrence in low-risk embryonal patients and that reduced dosages might achieve comparable results with improved toxicity profiles. These hypotheses will be tested in the next generation of trials from the Soft Tissue Committee of the Children's Oncology Group.
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- 2003
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32. Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the Intergroup Rhabdomyosarcoma Study IV.
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Breneman JC, Lyden E, Pappo AS, Link MP, Anderson JR, Parham DM, Qualman SJ, Wharam MD, Donaldson SS, Maurer HM, Meyer WH, Baker KS, Paidas CN, and Crist WM
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Infant, Infant, Newborn, Male, Prognosis, Rhabdomyosarcoma diagnosis, Rhabdomyosarcoma therapy, Survival Rate, Treatment Outcome, United States epidemiology, Rhabdomyosarcoma mortality, Rhabdomyosarcoma secondary
- Abstract
Purpose: To identify risk factors associated with outcomes in children with metastatic rhabdomyosarcoma (RMS) treated on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV)., Patients and Methods: Patients with metastatic RMS were treated with one of two regimens that incorporated a window of either ifosfamide and etoposide (IE) with vincristine, dactinomycin, and cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points were failure-free survival (FFS) and overall survival (OS). Clinical factors including age, histology, sites of primary and metastatic disease, and number of sites of metastatic disease were correlated with those end points., Results: One hundred twenty-seven patients were eligible for analysis. The estimated 3-year OS and FFS for all patients were 39% and 25%, respectively. By univariate analysis, 3-year OS was significantly influenced by histology (47% for embryonal v 34% for all others, P =.026) and increasing number of metastatic sites (P =.028). By multivariate analysis, the presence of two or fewer metastatic sites was the only significant predictor (P =.007 and.006, respectively). The combination of embryonal histology with two or fewer metastatic sites identified a subgroup with 3-year FFS of 40% and OS of 47%., Conclusion: Children with group IV RMS treated on the IRS-IV study had improved OS and FFS if they had two or fewer metastatic sites and embryonal histology. This favorable subset of patients has outcomes approaching those observed in selected patients with localized, nonmetastatic disease. Thus, these patients might not be appropriate candidates for regimens that include experimental agents with substantial toxicities or unproven antitumor activity.
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- 2003
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33. Children from ethnic minorities have benefited equally as other children from contemporary therapy for rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group.
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Baker KS, Anderson JR, Lobe TE, Wharam MD, Qualman SJ, Raney RB, Ruymann FB, Womer RB, Meyer WH, Link MP, and Crist WM
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- Child, Child, Preschool, Cohort Studies, Disease-Free Survival, Humans, Infant, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Rhabdomyosarcoma pathology, Risk, Treatment Failure, Treatment Outcome, United States, Black or African American statistics & numerical data, Rhabdomyosarcoma ethnology, Rhabdomyosarcoma therapy, White People statistics & numerical data
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Purpose: To define the clinical characteristics of rhabdomyosarcoma (RMS) occurring in children from ethnic minorities and determine whether these children have benefited equally from advances in therapy., Patients and Methods: This was a retrospective cohort analysis of children treated on the Intergroup Rhabdomyosarcoma Study Group protocols between 1984 and 1997. The clinical features and outcomes of 336 African-American children and 286 children from other ethnic minorities were compared with those of white children (n = 1,721)., Results: African-American, other ethnic group, and white children enjoyed similar 5-year failure-free survivals (FFS) of 61%, 61%, and 66%, respectively, P =.15. Compared with white children, nonwhite patients more often had (1) invasive, T2 tumors (P =.03); (2) stage 2 or 3 tumors (P =.003); (3) large tumors (more than 5 cm, P <.006); and/or (4) tumors with positive regional nodes (ie, N1, P =.002). Using Cox proportional hazards analysis, seven patient risk categories were defined with significant differences in outcome. This model was then used to search for other factors associated with FFS after adjusting for these risk categories. Only T stage and age remained associated with FFS (P =.001 and P <.001, respectively). After adjusting for T stage, risk category, and age, we explored the relationship of ethnic group to FFS and found that, compared with whites, the relative risk of failure was 1.14 for African-American patients and 1.2 for other ethnic minority patients, values that are not significantly different., Conclusion: Patients from ethnic minority groups more often have larger, invasive tumors with positive lymph nodes. Nevertheless, they have benefited as equally as white children from the dramatic progress in therapy of RMS.
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- 2002
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34. Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997.
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Raney RB, Meza J, Anderson JR, Fryer CJ, Donaldson SS, Breneman JC, Fitzgerald TJ, Gehan EA, Michalski JM, Ortega JA, Qualman SJ, Sandler E, Wharam MD, Wiener ES, Maurer HM, and Crist WM
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- Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Clinical Protocols, Combined Modality Therapy, Cytarabine administration & dosage, Female, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms mortality, Head and Neck Neoplasms radiotherapy, Humans, Hydrocortisone administration & dosage, Infant, Infant, Newborn, Injections, Spinal, Male, Meningeal Neoplasms drug therapy, Meningeal Neoplasms radiotherapy, Meningeal Neoplasms secondary, Methotrexate administration & dosage, Neoplasm Invasiveness, Prognosis, Radiation Dosage, Randomized Controlled Trials as Topic, Rhabdomyosarcoma drug therapy, Rhabdomyosarcoma mortality, Rhabdomyosarcoma pathology, Rhabdomyosarcoma radiotherapy, Survival Analysis, Treatment Outcome, Head and Neck Neoplasms therapy, Meningeal Neoplasms therapy, Outcome Assessment, Health Care, Rhabdomyosarcoma therapy
- Abstract
Background: We reviewed 611 patients with parameningeal sarcoma entered on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978-1997), to delineate treatment results and evaluate prognostic factors., Procedure: Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or surgery followed by multiagent chemotherapy and radiation therapy (XRT). Beginning in 1977, patients with cranial nerve palsy, cranial base bony erosion, and/or intracranial extension at diagnosis were considered as having meningeal involvement. They received triple intrathecal medications, whole brain XRT, and then spinal XRT. These treatments were successively eliminated from 1980 to 1991., Results: The 611 patients' overall survival rate at 5 years was 73% (95% confidence interval, 70-77%). Favorable prognostic factors were: age 1-9 years at diagnosis; primary tumor in the nasopharynx/nasal cavity, middle ear/mastoid, or parapharyngeal areas; no meningeal involvement; and non-invasive tumors (T1). Thirty-five of 526 patients (6.7%) with information about presence/absence of meningeal involvement at diagnosis developed central nervous system (CNS) extension at 5-164 weeks (median, 46 weeks) after starting therapy. The estimated 5-year cumulative incidence rate of CNS extension during the study period was 5-7% (P = 0.88)., Conclusions: Biopsy, XRT to the target volume, and systemic chemotherapy are successful treatments for the large majority of patients with localized parameningeal sarcoma. Carefully defining and irradiating the initial volume should reduce the risk of CNS failure. Aggressive initial surgical management of these patients is unnecessary., (Copyright 2002 Wiley‐Liss, Inc.)
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- 2002
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35. Improved outcome for patients with middle ear rhabdomyosarcoma: a children's oncology group study.
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Hawkins DS, Anderson JR, Paidas CN, Wharam MD, Qualman SJ, Pappo AS, Scott Baker K, and Crist WM
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- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Combined Modality Therapy, Disease Progression, Disease-Free Survival, Ear Neoplasms mortality, Ear Neoplasms pathology, Female, Humans, Male, Multivariate Analysis, Prognosis, Proportional Hazards Models, Radiotherapy, Retrospective Studies, Rhabdomyosarcoma mortality, Rhabdomyosarcoma pathology, Survival Rate, Treatment Outcome, United States epidemiology, Ear Neoplasms therapy, Ear, Middle, Rhabdomyosarcoma therapy
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Purpose: The goal of this study was to define the clinical features and optimal therapy for children and adolescents with middle ear (ME) rhabdomyosarcoma (RMS)., Patients and Methods: We reviewed demographic data, clinical features, therapy (including chemotherapy, surgery, and radiation), and outcome for the 179 eligible patients with ME RMS who were enrolled onto Intergroup Rhabdomyosarcoma Studies (IRS) I through IV or pilot studies between November 1972 and December 1997., Results: Most patients were younger than 10 years old (90%), and 63% were male. Because of the parameningeal location, most tumors were not resected before chemotherapy (group I, < 1%; group II, 4%; group III, 84%; group IV, 12%). Although most tumors were locally invasive (T2, 89%), the majority were small (< or = 5 cm, 66%), lacked nodal metastases (N0, 86%), and had embryonal histology (85%). The 5-year failure-free survival (FFS) and overall survival (OS) estimates were 67% and 72%, respectively. Both FFS and OS improved significantly over the course of IRS I through IV (3-year FFS and OS: IRS-I, 42% and 42%; IRS-II, 70% and 74%; IRS-III, 65% and 72%; IRS-IV pilot, 81% and 96%; IRS-IV, 88% and 88%, P <.001). Lower clinical group or stage and smaller tumor size were associated with better outcome. Age, sex, tumor invasiveness, and nodal metastases were not predictive of outcome., Conclusion: Patients with ME RMS generally present with small, unresectable, invasive tumors at a site traditionally considered prognostically unfavorable. Nevertheless, such patients have benefited markedly from improvements in multimodal, risk-based therapy during the course of IRS I through IV, and with contemporary therapy, most are cured.
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- 2001
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36. Second surgery for recurrent pilocytic astrocytoma in children.
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Bowers DC, Krause TP, Aronson LJ, Barzi A, Burger PC, Carson BS, Weingart JD, Wharam MD, Melhem ER, and Cohen KJ
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- Adolescent, Astrocytoma pathology, Brain pathology, Brain Neoplasms pathology, Child, Child, Preschool, Humans, Infant, Neoplasm Recurrence, Local pathology, Reoperation adverse effects, Retrospective Studies, Treatment Outcome, Astrocytoma surgery, Brain surgery, Brain Neoplasms surgery, Neoplasm Recurrence, Local surgery
- Abstract
Pilocytic astrocytoma (PA) is the most common childhood brain tumor. In cases where the tumor progresses or recurs following primary surgical resection, the appropriate treatment is unclear. Options include chemotherapy, radiation therapy, surgical resection or a combination thereof. To analyze the utility of further surgery, we performed a retrospective, single-institution review of pediatric patients with recurrent PAs from 1990 to 1999 who were treated with a second surgical resection. Patients were excluded if they received adjuvant chemotherapy or radiation therapy. Twenty cases were identified. Tumor locations included: cerebral hemisphere (3), cerebellum (7), optic pathway/hypothalamus (5), thalamus (1) and brainstem (4). The indication for 4 surgeries included an enlarging tumor-associated cyst. At second surgery, 10 of 20 patients had a gross total resection (GTR), 2 a near total resection (NTR), and the remaining 8 patients had a subtotal resection (STR). No patients have died. Two of 10 tumors after GTR, 0 of 2 tumors after NTR, and 7 of 8 tumors after STR had second recurrence/progression at a mean of 15 months (range 4-33 months) following second surgery. The remaining 11 patients are recurrence/progression-free at a mean of 40.7 months (range 19-119 months). Surgery for tumors or midline structures rarely resulted in a GTR (1 of 10 cases). Surgery for tumors located in the cerebral hemispheres or cerebellum resulted in GTR or NTR in all cases and can result in long periods of progression-free survival without further adjuvant treatment., (Copyright 2001 S. Karger AG, Basel)
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- 2001
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37. Prognostic implications for gadolinium enhancement of the meninges in low-grade astrocytomas of childhood.
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Hurwitz MD, Burger PC, Goldthwaite PT, Tihan T, Wharam MD, and Fisher PG
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- Adolescent, Astrocytoma mortality, Astrocytoma pathology, Astrocytoma surgery, Brain Neoplasms mortality, Brain Neoplasms pathology, Brain Neoplasms surgery, Child, Child, Preschool, Cohort Studies, Disease Progression, Female, Follow-Up Studies, Humans, Infant, Male, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local surgery, Survival Rate, Astrocytoma diagnosis, Brain Neoplasms diagnosis, Image Enhancement, Magnetic Resonance Imaging, Meninges pathology
- Abstract
Background: Persistent gadolinium enhancement on MRI of the meninges in some children with low-grade astrocytomas (LGA) is a widely recognized phenomenon. The relationship of this finding with the clinical course is unclear., Methods: From a consecutive cohort of 282 children with pathologically confirmed LGA we identified all patients with asymptomatic gadolinium enhancement of the meninges found on surveillance MRI. A nested case-control study was performed, comparing patients with meningeal enhancement to controls without enhancement., Results: Twenty-one children were identified with meningeal enhancement. The median follow-up was 5.2 years with enhancement noted for a median of 2.2 years. The 5-year overall survival for this cohort was 91.2% (Greenwood SE 8.0%), and the 5-year progression-free survival was 20.9% (SE 11.9%). Five patients are now free of disease, while 15 continue to have stable disease. The overall and progression-free survival was not significantly different compared to controls., Conclusions: Gadolinium enhancement of the meninges on MRI may occur in a significant number of children with LGA, particularly juvenile pilocytic astrocytoma, but does not appear to affect progression-free or overall survival. Change in management based on this finding alone is unwarranted., (Copyright 2001 S. Karger AG, Basel)
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- 2001
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38. The Intergroup Rhabdomyosarcoma Study Group (IRSG): Major Lessons From the IRS-I Through IRS-IV Studies as Background for the Current IRS-V Treatment Protocols.
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Raney RB, Maurer HM, Anderson JR, Andrassy RJ, Donaldson SS, Qualman SJ, Wharam MD, Wiener ES, and Crist WM
- Abstract
Purpose. To enumerate lessons from studying 4292 patients with rhabdomyosarcoma (RMS) in the Intergroup Rhabdomyosarcoma Study Group (IRSG, 1972-1997).Patients. Untreated patients < 21 years of age at diagnosis received systemic chemotherapy, with or without irradiation (XRT) and/or surgical removal of the tumor.Methods. Pathologic materials and treatment were reviewed to ascertain compliance and to confirm response and relapse status.Results. Survival at 5 years increased from 55 to 71% over the period. Important lessons include the fact that extent of disease at diagnosis affects prognosis. Re-excising an incompletely removed tumor is worthwhile if acceptable form and function can be preserved. The eye, vagina, and bladder can usually be saved. XRT is not necessary for children with localized, completely excised embryonal RMS. Hyperfractionated XRT has thus far not produced superior local control rates compared with conventional, once-daily XRT. Patients with non-metastatic cranial parameningeal sarcoma can usually be cured with localized XRT and systemic chemotherapy, without whole-brain XRT and intrathecal drugs. Adding doxorubicin, cisplatin, etoposide, and ifosfamide has not significantly improved survival of patients with gross residual or metastatic disease beyond that achieved with VAC (vincristine, actinomycin D, cyclophosphamide) and XRT. Most patients with alveolar RMS have a tumor-specific translocation. Mature rhabdomyoblasts after treatment of patients with bladder rhabdomyosarcoma are not necessarily malignant, provided that the tumor has shrunk and malignant cells have disappeared.Discussion. Current IRSG-V protocols, summarized herein, incorporate recommendations for risk-based management. Two new agents, topotecan and irinotecan, are under investigation for patients who have an intermediate or high risk of recurrence.
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- 2001
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39. A clinicopathologic reappraisal of brain stem tumor classification. Identification of pilocystic astrocytoma and fibrillary astrocytoma as distinct entities.
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Fisher PG, Breiter SN, Carson BS, Wharam MD, Williams JA, Weingart JD, Foer DR, Goldthwaite PT, Tihan T, and Burger PC
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- Adolescent, Adult, Astrocytoma classification, Brain Stem Neoplasms classification, Child, Child, Preschool, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Neoplasm Staging, Prognosis, Proportional Hazards Models, Retrospective Studies, Astrocytoma pathology, Brain Stem Neoplasms pathology
- Abstract
Background: Brain stem tumors in children have been classified pathologically as low grade or high grade gliomas and descriptively as diffuse gliomas, intrinsic gliomas, midbrain tumors, tectal gliomas, pencil gliomas, dorsal exophytic brain stem tumors, pontine gliomas, focal medullary tumors, cervicomedullary tumors, focal gliomas, or cystic gliomas., Methods: To search for a simplified and prognostic clinicopathologic scheme for brain stem tumors, the authors reviewed a consecutive cohort of patients younger than age 21 years with tumors diagnosed from 1980 through 1997. Pathology specimens and neuroimaging were classified by masked review. Statistical and survival analysis along with Cox proportional hazards regression was performed., Results: Seventy-six patients were identified, with initial diagnostic magnetic resonance imaging available for 51 and pathology specimens for 48 patients. Twenty cases were classified histologically as pilocytic astrocytoma (PA), 14 as fibrillary astrocytoma (FA), and 14 as other tumors or indeterminate pathology. For all tumors, characteristics significantly associated with a worse survival rate were: symptom duration less than 6 months before diagnosis (P = 0.004); abducens palsy at presentation (P < 0.0001); pontine location (P = 0.0002); and engulfment of the basilar artery (P = 0.006). Pilocytic astrocytoma was associated with location outside the ventral pons (P = 0.001) and dorsal exophytic growth (P = 0.013); Fibrillary astrocytoma was associated with symptoms less than 6 months (P = 0. 006), abducens palsy (P < 0.001), and engulfment of the basilar artery (P = 0.002). Pilocytic astrocytoma showed 5-year overall survival (OS) of 95% (standard error [SE], 5%) compared with FA 1-year OS of 23% (SE, 11%;P < 0.0001)., Conclusions: Brain stem tumors can be succinctly and better biologically classified as diffusely infiltrative brain stem gliomas-generally FA located in the ventral pons that present with abducens palsy, often engulf the basilar artery, and carry a grim prognosis-and focal brain stem gliomas-frequently PA arising outside the ventral pons, often with dorsal exophytic growth, a long clinical prodrome, and outstanding prognosis for survival. Our findings emphasize the individuality of PA as a distinct clinicopathologic entity with an exceptional prognosis.
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- 2000
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40. Pre-irradiation evaluation and management of brain metastases. American College of Radiology. ACR Appropriateness Criteria.
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Gaspar LE, Gutin PH, Rogers L, Schneider JF, Larson D, Bloomer WD, Buckley JA, Gibbs FA, Lewin AA, Loeffler JS, Malcolm AW, Mendenhall WM, Schupak KD, Shaw EG, Simpson JR, Wharam MD Jr, and Leibel S
- Subjects
- Brain Neoplasms diagnosis, Brain Neoplasms pathology, Brain Neoplasms radiotherapy, Diagnostic Imaging, Dose-Response Relationship, Radiation, Female, Humans, Male, Middle Aged, Neoplasm Staging, Neurologic Examination radiation effects, Brain Neoplasms secondary, Cranial Irradiation
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- 2000
41. Multiple brain metastases. American College of Radiology. ACR Appropriateness Criteria.
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Shaw EG, Gaspar LE, Gibbs FA, Lewin AA, Wharam MD Jr, Larson D, Bloomer WD, Buckley JA, Loeffler JS, Malcolm AW, Mendenhall WM, Schneider JF, Schupak KD, Simpson JR, Gutin PH, Rogers L, and Leibel S
- Subjects
- Adult, Brain Neoplasms mortality, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Combined Modality Therapy, Dose Fractionation, Radiation, Female, Humans, Male, Middle Aged, Palliative Care, Radiosurgery, Survival Rate, Brain Neoplasms secondary, Cranial Irradiation
- Published
- 2000
42. Follow-up and retreatment of brain metastasis. American College of Radiology. ACR Appropriateness Criteria.
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Simpson JR, Mendenhall WM, Schupak KD, Larson D, Bloomer WD, Buckley JA, Gaspar LE, Gibbs FA, Lewin AA, Loeffler JS, Malcolm AW, Schneider JF, Shaw EG, Wharam MD Jr, Gutin PH, Rogers L, and Leibel S
- Subjects
- Brain Neoplasms mortality, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Combined Modality Therapy, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local surgery, Palliative Care, Radiosurgery, Retreatment, Survival Rate, Brain Neoplasms secondary, Cranial Irradiation, Neoplasm Recurrence, Local radiotherapy
- Published
- 2000
43. Solitary brain metastasis. American College of Radiology. ACR Appropriateness Criteria.
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Loeffler JS, Bloomer WD, Buckley JA, Gutin PH, Malcolm AW, Schupak KD, Larson D, Gaspar LE, Gibbs FA, Lewin AA, Mendenhall WM, Schneider JF, Shaw EG, Simpson JR, Wharam MD Jr, Rogers L, and Leibel S
- Subjects
- Aged, Aged, 80 and over, Brain Neoplasms radiotherapy, Brain Neoplasms surgery, Combined Modality Therapy, Dose Fractionation, Radiation, Female, Humans, Male, Middle Aged, Radiosurgery, Treatment Outcome, Brain Neoplasms secondary, Cranial Irradiation
- Published
- 2000
44. Aggressive surgery is unwarranted for biliary tract rhabdomyosarcoma.
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Spunt SL, Lobe TE, Pappo AS, Parham DM, Wharam MD Jr, Arndt C, Anderson JR, Crist WM, Paidas C, Wiener E, Andrassy RJ, and Schwartz CL
- Subjects
- Biliary Tract Neoplasms mortality, Biliary Tract Neoplasms therapy, Child, Child, Preschool, Combined Modality Therapy, Female, Humans, Infant, Male, Reoperation, Retrospective Studies, Rhabdomyosarcoma mortality, Rhabdomyosarcoma therapy, Treatment Outcome, Biliary Tract Neoplasms surgery, Biliary Tract Surgical Procedures, Rhabdomyosarcoma surgery
- Abstract
Background/purpose: Rhabdomyosarcoma (RMS) of the biliary tract is rare, and, in addition to multiagent chemotherapy with or without radiotherapy (RT), some investigators recommend aggressive surgery. To assess the role of surgery, records of all 25 eligible patients with biliary RMS enrolled in IRSG studies I through IV from 1972 to 1998 were reviewed., Methods: Treatment included surgery with or without vincristine, dactinomycin, cyclophosphamide, doxorubicin, cisplatin, etoposide, ifosfamide, and with or without RT. Data evaluated included clinical presentation, treatment, complications, and outcome., Results: Diagnostic imaging identified the primary tumor but failed to identify regional metastases. Despite aggressive surgery, gross total resection at diagnosis was possible in only 6 cases, 2 of which had negative surgical margins. Although only 6 (29%) patients without distant metastases underwent gross total resection, estimated 5-year survival rate was 78% (95% CI 58%, 97%). Infectious complications were common and frequently associated with external biliary drains. Five (20%) died within the first 2 months, 3 of sepsis., Conclusions: Surgery is critical for establishing an accurate diagnosis and determining the extent of regional disease. Gross total resection is rarely possible despite aggressive surgery, and outcome is good despite residual disease after surgery. External biliary drains increase the risk of postoperative infectious complications.
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- 2000
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45. Tectal gliomas: natural history of an indolent lesion in pediatric patients.
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Bowers DC, Georgiades C, Aronson LJ, Carson BS, Weingart JD, Wharam MD, Melhem ER, Burger PC, and Cohen KJ
- Subjects
- Adolescent, Age of Onset, Astrocytoma complications, Brain Stem Neoplasms complications, Child, Child, Preschool, Disease Progression, Female, Follow-Up Studies, Humans, Infant, Magnetic Resonance Imaging, Male, Prognosis, Survival Analysis, Tomography, X-Ray Computed, Astrocytoma diagnosis, Astrocytoma physiopathology, Brain Stem Neoplasms diagnosis, Brain Stem Neoplasms physiopathology, Mesencephalon
- Abstract
The mesencephalic tectal glioma is a distinctive form of brain stem glioma with an unusually benign clinical course. Periaqueductal location, lack of contrast enhancement, and long periods of stability are classic features. The clinical management of these lesions, especially at the time of radiographic enlargement varies widely in the published literature. It is unclear whether these progressive lesions need to be treated. Accordingly, clinical and radiologic features of 7 patients were reviewed, with attention to the clinical course of the disease after radiologic enlargement. The age at diagnosis ranged from 3.3 to 16.6 years. Six of 7 had MRI tumor enlargement beginning 0.3-5.7 years after initial diagnosis. One of these 6 patients had radiographic progression coupled with a new clinical symptom which was treated with stereotactic radiation therapy. The remaining 5 patients with MRI progression and normal neurological exams were not treated and remain free of new neurologic deficits 1.8-6.9 years after the first radiographic tumor enlargement. The results suggest that pediatric tectal gliomas are a very low-grade lesion. Conservative management in the absence of new clinical symptoms could be argued, reserving radiotherapy or chemotherapy for clinical progression., (Copyright 2000 S. Karger AG, Basel)
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- 2000
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46. Indications for radiotherapy and chemotherapy after complete resection in rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Studies I to III.
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Wolden SL, Anderson JR, Crist WM, Breneman JC, Wharam MD Jr, Wiener ES, Qualman SJ, and Donaldson SS
- Subjects
- Child, Child, Preschool, Clinical Trials as Topic, Combined Modality Therapy, Humans, Infant, Prognosis, Rhabdomyosarcoma drug therapy, Rhabdomyosarcoma surgery, Survival Analysis, Treatment Failure, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Rhabdomyosarcoma pathology, Rhabdomyosarcoma radiotherapy
- Abstract
Purpose: To evaluate the outcome of patients with rhabdomyosarcoma (RMS) treated with complete surgical resection and multiagent chemotherapy, with or without local radiotherapy (RT)., Patients and Methods: Four hundred thirty-nine patients with completely resected (ie, group I) RMS were further treated with chemotherapy (vincristine and actinomycin D +/- cyclophosphamide, doxorubicin, and cisplatin) on Intergroup Rhabdomyosarcoma Studies (IRS) I to III between 1972 and 1991. Eighty-three patients (19%) also received local RT as a component of initial treatment., Results: Eighty-six patients relapsed (10-year failure-free survival [FFS] 79%, overall survival 89%). Six percent of failure sites were local, 6% were regional, and 7% were distant. Poor prognostic factors were tumor size greater than 5 cm, alveolar or undifferentiated histology, primary tumor sites other than genitourinary, and treatment on IRS-I or II. For patients with embryonal RMS who were treated with RT, there was a trend for improved FFS but no difference in overall survival. On IRS-I and II, patients with alveolar or undifferentiated sarcoma who received RT compared with those who did not receive RT had greater 10-year FFS rates (73% v 44%, respectively; P =.03) and overall survival rates (82% v 52%, respectively; (P =.02). Such patients who received RT on IRS III also benefited more than those who did not receive RT (10-year FFS, 95% v 69%; P =.01; overall survival, 95% v 86%; P =.23)., Conclusion: Patients with group I embryonal RMS have an excellent prognosis when treated with adjuvant multiagent chemotherapy without RT. Patients with alveolar RMS or undifferentiated sarcoma fare worse; however, FFS and overall survival are substantially improved when RT is added to multiagent chemotherapy (IRS-I and II). The best outcome occurred in IRS-III, when RT was used in conjunction with intensified chemotherapy.
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- 1999
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47. Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the Intergroup Rhabdomyosarcoma Study Group.
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Pappo AS, Anderson JR, Crist WM, Wharam MD, Breitfeld PP, Hawkins D, Raney RB, Womer RB, Parham DM, Qualman SJ, and Grier HE
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Child, Child, Preschool, Combined Modality Therapy, Female, Humans, Infant, Male, Multicenter Studies as Topic, Predictive Value of Tests, Prognosis, Recurrence, Retrospective Studies, Rhabdomyosarcoma therapy, Risk Factors, Survival Analysis, Rhabdomyosarcoma mortality, Rhabdomyosarcoma pathology
- Abstract
Background: Despite advances in therapy, nearly 30% of children with rhabdomyosarcoma experience progressive or relapsed disease, which is often fatal., Patients and Methods: To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols., Results: The median survival time from first recurrence was 0.8 years; the estimated percentage of patients who survived 5 years from first recurrence was 17% +/- 2% (mean +/- SD). Univariate analysis showed that tumor histology was an important predictor of 5-year survival (P <.001): the 5-year survival rate was 64% for patients with botryoid tumors (n = 19), 26% for patients with embryonal tumors (n = 313), and 5% for patients with alveolar or undifferentiated sarcoma (n = 273). Further analysis identified prognostic factors within histologic subtypes (P <.001). For patients with embryonal tumors, the estimated 5-year survival rate was 52% for patients who initially presented with stage 1 or group I disease, 20% for those with stage 2/3 or group II/III disease, and 12% for those with group IV disease. For patients with stage 1/group I disease, estimated 5-year survival rates were higher for patients with local (72%) or regional (50%) recurrence than for those with distant (30%) recurrence. Among patients with alveolar or undifferentiated sarcoma, only the disease group predicted outcome: the 5-year survival estimate was 40% for group I versus 3% for groups II through IV. We identified a "favorable risk" group (approximately 20% of patients) whose 5-year estimated survival rate was near 50%; for all other patients, the estimated survival was near 10%., Conclusion: This analysis demonstrates that the probability of 5-year survival after relapse for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, disease group, and stage. These findings will form the basis of a multi-institutional risk-adapted relapse protocol for childhood rhabdomyosarcoma.
- Published
- 1999
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48. Does debulking improve survival rate in advanced-stage retroperitoneal embryonal rhabdomyosarcoma?
- Author
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Blakely ML, Lobe TE, Anderson JR, Donaldson SS, Andrassy RJ, Parham DM, Wharam MD, Qualman SJ, Wiener ES, Grier HE, and Crist WM
- Subjects
- Adolescent, Child, Child, Preschool, Female, Humans, Infant, Male, Retrospective Studies, Rhabdomyosarcoma, Alveolar mortality, Rhabdomyosarcoma, Alveolar surgery, Treatment Outcome, Retroperitoneal Neoplasms mortality, Retroperitoneal Neoplasms surgery, Rhabdomyosarcoma, Embryonal mortality, Rhabdomyosarcoma, Embryonal surgery
- Abstract
Unlabelled: BACKGROUND, METHODS, AND PURPOSE: The authors examined demographic and clinical features, therapy, and outcome of patients with advanced (group III or IV) rhabdomyosarcoma (RMS) of the retroperitoneum and nongenitourinary pelvis treated in the Intergroup Rhabdomyosarcoma Study Group (IRSG) III (1984 to 1991, n = 41) or IV pilot (1987 to 1991, n = 53) studies to assess the role of initial debulking surgery., Results: Ninety-four patients with retroperitoneal primary tumors and gross locoregional residual tumor (group III, n = 53) or metastatic disease (group IV tumors, n = 41) were treated with combination chemotherapy (ie, vincristine, dactinomycin, and cyclophosphamide with or without other agents plus radiation therapy, RT) after biopsy only or subtotal resection. These retroperitoneal tumors usually were invasive (T2, 76%). Most patients were younger than 10 years of age (n = 69, 73%), the male to female ratio was 1.4, and tumors usually were embryonal (n = 64, 68%). Overall 4-year failure-free survival (FFS) was 50%; survival was 60%. Survival rate was better for girls (4-year survival rate, 75% v49% for boys; P = .05) and was not significantly different for patients treated in IRS-III (66%) or IRS-IV pilot (52%). However, it was better for patients with embryonal versus alveolar or undifferentiated tumors (4-year survival rate, 70% v 42%; P = .002). In adolescents, RMS is different from that seen in children less than 10 years old; most cases are alveolar or undifferentiated (16 of 29, 55%). Surgery for most (21 of 24) patients with alveolar tumors comprised biopsy only. By contrast, of 64 patients with embryonal tumors, 39 (61%) underwent biopsy only, whereas 25 (39%) had debulking surgery. Patients whose tumors were debulked fared better than those whose tumors underwent biopsy only (4-year FFS rate, 72% v48%; P = 0.03). Patients with group IV embryonal tumors fared unexpectedly better than those with group IV alveolar or undifferentiated tumors (70% versus 42% 4-year survival rate, P < .05), and patients less than 10 years of age with group IV embryonal tumors had 4-year survival rate of 77%, indicating the importance of the biology of these tumors., Conclusions: Multimodal therapy, including multiagent chemotherapy plus RT, appears to improve survival rate in patients with advanced embryonal RMS arising in the retroperitoneum. These data suggest that debulking tumors of embryonal histology improves outcome further. This approach will be assessed in IRSG V.
- Published
- 1999
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49. Outcomes and failure patterns in childhood craniopharyngiomas.
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Fisher PG, Jenab J, Gopldthwaite PT, Tihan T, Wharam MD, Foer DR, and Burger PC
- Subjects
- Adolescent, Child, Child, Preschool, Combined Modality Therapy, Craniopharyngioma radiotherapy, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Neoplasm Recurrence, Local diagnosis, Pituitary Neoplasms radiotherapy, Population Surveillance methods, Postoperative Complications, Retrospective Studies, Survival Analysis, Treatment Failure, Treatment Outcome, Craniopharyngioma surgery, Pituitary Neoplasms surgery
- Abstract
Past studies of craniopharyngiomas in children have shown overall survival (OS) up to 95% at 5 years and 80% progression-free survival (PFS) at 5 years, although many of these series predate modern neuroimaging and current therapeutic management. Moreover, little mention has been made of failure patterns for craniopharyngioma in children. To obtain a contemporary assessment of outcome among pediatric craniopharyngioma patients, and also to determine the failure patterns for this tumor, we completed a retrospective study of a consecutive cohort of all children with craniopharyngioma diagnosed at the Johns Hopkins Hospital from 1980 to 1996. Resection was performed in 30 children, in 8 of whom gross total resection (GTR) was achieved. Initial treatment took the form of GTR followed by observation for 8, subtotal resection (STR) plus observation in 11, and STR followed immediately by radiotherapy in 8. The timing of radiotherapy following STR was unclear for 3. OS was 95.2% (SE= 4.7%) at 5 years, with only 2 children dying after 4 years from diagnosis. Five-year PFS was 59.4% (SE=10.2%). Before surgery, 19 children had visual loss and 15, endocrine deficits; after surgery, 21 children had visual loss and 29, endocrine deficits. Median time to relapse was 0.98 years (SD=2.5 years). Radiographic (n=4) and clinical (n=7) relapses did not differ in time to progression (P=0.32), but radiographic relapses were significantly associated with age at diagnosis less than 5 years (P=0.02). Degree of resection was not significantly associated with PFS (P=0.32) or with postoperative visual or endocrine deficits. Absence of calcification on diagnostic neuroimaging (n=8) was significantly associated with improved PFS [5-year PFS 100% vs. 42.9% (SE=14.7%), P=0.02], even when adjusted for extent of resection (P=0.03). Preoperative visual loss was predictive of postoperative visual loss (P=0.03). Survival for children diagnosed with craniopharyngioma in the current era is outstanding, even with relapse, although postoperative visual and endocrinological morbidities are high. Failures occurred both radiographically and clinically, typically in the first 3-4 years after surgery, suggesting a need for close surveillance initially with neuroimaging, particularly in younger children, and also clinical examination. The short times to relapse observed here may stem from a tendency to delay radiotherapy until recurrence. Lack of calcification at diagnosis is associated with a tendency to remain free of relapse.
- Published
- 1998
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50. Randomized study of intensive MOPP-ABVD with or without low-dose total-nodal radiation therapy in the treatment of stages IIB, IIIA2, IIIB, and IV Hodgkin's disease in pediatric patients: a Pediatric Oncology Group study.
- Author
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Weiner MA, Leventhal B, Brecher ML, Marcus RB, Cantor A, Gieser PW, Ternberg JL, Behm FG, Wharam MD Jr, and Chauvenet AR
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin administration & dosage, Bleomycin adverse effects, Child, Child, Preschool, Combined Modality Therapy, Dacarbazine administration & dosage, Dacarbazine adverse effects, Doxorubicin administration & dosage, Doxorubicin adverse effects, Female, Hodgkin Disease mortality, Hodgkin Disease pathology, Hodgkin Disease radiotherapy, Humans, Male, Mechlorethamine administration & dosage, Mechlorethamine adverse effects, Prednisone administration & dosage, Prednisone adverse effects, Procarbazine administration & dosage, Procarbazine adverse effects, Survival Rate, Vinblastine administration & dosage, Vinblastine adverse effects, Vincristine administration & dosage, Vincristine adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease therapy, Lymphatic Irradiation
- Abstract
Purpose: To determine whether the addition of low-dose total-nodal irradiation (TNI) in pediatric patients with advanced-stage Hodgkin's disease who have received eight cycles of alternating mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) will improve the event-free survival (EFS) and overall survival (OS) when compared with patients who have received chemotherapy only., Patients and Methods: At diagnosis, 183 children and adolescents with stages IIB, IIIA2, IIIB, and IV Hodgkin's disease were randomized to receive eight cycles of alternating MOPP-ABVD with or without low-dose TNI., Results: Of 183 patients, four were rendered ineligible before treatment was initiated. One hundred sixty-one of 179 patients (90%) were in complete remission (CR) at the completion of eight cycles of alternating MOPP-ABVD; 81 were in the chemotherapy-only group and proceeded to observation off therapy, whereas 80 of 161 were to receive combined modality therapy (CMT). Nine of 80 patients randomized at the time of diagnosis to receive CMT did not receive radiation (RT) because of a protocol violation, but were monitored for EFS and OS and included in all analyses. The estimated EFS and OS rates at 5 years for the 179 eligible patients are 79% and 92%, respectively. The actuarial EFS at 5 years was 80% for patients who received CMT and 79% for patients who received MOPP-ABVD only. The OS for the former group is estimated to be 87% and for the latter patients 96%. Age < or = 13 years of age at diagnosis and the attainment of a clinical CR after three cycles of chemotherapy were associated with a statistically significant improved EFS., Conclusion: Our results indicate that after the delivery of eight cycles of MOPP-ABVD, the addition of low-dose RT does not improve the estimated EFS or OS in pediatric patients with advanced-stage Hodgkin's disease.
- Published
- 1997
- Full Text
- View/download PDF
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