A L Billett

Dana-Farber Cancer Institute, Boston, Massachusetts, United States

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Publications (37)316.24 Total impact

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    ABSTRACT: Pediatric patients who experience a bone marrow relapse of precursor-B acute lymphoblastic leukemia are cured <50% of the time. This study was designed to determine if intensification of therapies with known activity in this disease would improve the cure rates for patients with relapsed acute lymphoblastic leukemia. Patients were treated with intensive asparaginase during induction followed by repeated cycles of ifosfamide/etoposide and cytarabine/idarubicin. Patients with well-matched related donors were encouraged to undergo hematopoietic stem cell transplant as consolidation. The results of this study demonstrate no significant difference in disease-free survival in patients who received chemotherapy alone (45%) or chemotherapy followed by allogeneic stem cell transplant (50%). Furthermore, results from this study show no significant difference in event-free survival (39.9%±6.2%) or overall survival (41.6%±6.1%) at 8 years when compared with previous studies using less intensive regimens. Our results suggest that alternative therapies are needed to improve cure rates for pediatric patients with relapsed leukemia.
    Journal of Pediatric Hematology/Oncology 07/2013; · 0.97 Impact Factor
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    ABSTRACT: BACKGROUND: The outcome of treatment for pediatric Hodgkin lymphoma (HL) is excellent using chemotherapy and radiation. However, a minority of patients will relapse after treatment, but additional therapy achieves durable second remission in many cases. The optimal surveillance strategy after modern therapy for HL has not been well defined. PROCEDURES: We reviewed the outcomes of pediatric patients with HL treated between 1990 and 2006 to determine the primary event that led to the detection of relapse. We determined the probability of relapse detection by routine follow-up procedures, including history, physical examination, laboratory tests, and imaging, and determined the impact of each of these screening methods on the likelihood of survival after relapse. RESULTS: Relapse occurred in 64 of 402 evaluable patients (15.9%) at a median of 1.7 years from the time of diagnosis. The majority of relapses (60%) were diagnosed at a routine visit, and patient complaint was the most common initial finding that led to a diagnosis of relapse (47% of relapses). An abnormal finding on physical examination was the primary event in another 17% of relapses, and imaging abnormalities led to the diagnosis in the remaining 36%. Laboratory abnormalities were never the primary finding. The method of detection of relapse and timing (whether detected at a routine visit or an extra visit) did not impact survival. CONCLUSIONS: In pediatric HL, most relapses are identified through history and physical examination. Frequent imaging of asymptomatic patients does not appear to impact survival and is probably not warranted. Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.
    Pediatric Blood & Cancer 05/2013; · 2.35 Impact Factor
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    ABSTRACT: Across 36 US pediatric oncology centers, 576 central line-associated bloodstream infections (CLABSIs) were reported over a 21-month period. Most infections occurred in those with leukemia and/or profound neutropenia. The contribution of viridans streptococci infections was striking. Study findings depict the contemporary epidemiology of CLABSIs in hospitalized pediatric cancer patients.
    Infection Control and Hospital Epidemiology 03/2013; 34(3):316-20. · 4.02 Impact Factor
  • New England Journal of Medicine 12/2012; 367(26):2461-3. · 51.66 Impact Factor
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    ABSTRACT: More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects. To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone (VAMP) in patients with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy. Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012. The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy. Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low. Two-year event-free survival was 90.8% (95% CI, 84.7%-96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P = .61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) for febrile neutropenia or nonneutropenic infection. Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed. Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival. clinicaltrials.gov Identifier: NCT00145600.
    JAMA The Journal of the American Medical Association 06/2012; 307(24):2609-16. · 29.98 Impact Factor
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    ABSTRACT: Prior studies suggest an increased risk of lymphoma in adults with inflammatory bowel disease (IBD). Cases of lymphoma have also been reported in children with IBD. However, the precise risk of lymphoma in relation to drug exposure has not been ascertained in children. We conducted a single-center, retrospective study of 1560 children and young adults with IBD evaluated at Children's Hospital Boston between 1979 and 2008. Of this group, 186 patients were excluded due to incorrect diagnosis, one-time second-opinion visits, or missing hospital records. The remaining 1374 patients had charts reviewed to determine whether lymphoma developed while they were receiving their clinical care at our institution and the duration of exposure to various IBD medications. The rate of lymphoma was calculated in patient-years of exposure for each class of medications utilized in IBD. Of 1374 patients (741 male; age at diagnosis 12.1 ± 4.0 years; 791 Crohn's disease [CD], 535 ulcerative colitis [UC], 48 IBD unclassified), we identified two patients who developed lymphoma (one Hodgkin, one anaplastic large cell), in 6624 patient-years of follow-up (mean duration follow-up 4.8 years per patient). Both patients were males (ages 12 and 18 years at time of lymphoma onset) and were receiving thiopurines but had not yet received biologics at the time of their cancer diagnosis. They were both treated with chemotherapy and are alive without cancer 32+ and 76+ months since diagnosis. The absolute incidence rate of lymphoma for patients having received thiopurines was 4.5 per 10,000 patient-years compared to the expected rate of 0.58 per 10,000 patient-years, with a standardized incidence ratio (SIR) of 7.51 (95% confidence interval [CI] 0.74-41.98). The overall risk of lymphoma in children with IBD is low, with only two cases seen in our hospital over a 30-year period. The lymphoma risk (as estimated by SIR) in children receiving thiopurines is comparable to that reported in studies of adults. While there may be an increased risk of lymphoma in children treated with thiopurines, the risk did not reach statistical significance in this large cohort.
    Inflammatory Bowel Diseases 09/2011; 18(5):838-43. · 5.12 Impact Factor
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    ABSTRACT: To evaluate outcome and assess complications in children and adolescents with low-risk Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) chemotherapy and low-dose, involved-field radiation therapy (IFRT). One hundred ten children with low-risk Hodgkin's disease were treated with four cycles of VAMP and 15 Gy IFRT for those who achieved a complete response (CR) or 25.5 Gy for those with a partial response after two cycles of VAMP. With median follow-up of 9.6 years (range, 1.7 to 15.0), 5- and 10-year overall survival were 99.1% and 96.1%, respectively, and 5-and 10-year event-free survival (EFS) were 92.7% and 89.4%. Factors contributing to 10-year EFS were: early CR (P = .02), absence of B symptoms (P = .01), lymphocyte predominant histologic subtype (P = .04), and less than three initial sites of disease (P = .02). Organ toxicity has been limited to correctable hypothyroidism in 42% of irradiated patients, and one case of cardiac dysfunction. Seventeen healthy babies have been born to 106 survivors. There have been two malignant tumors: one thyroid cancer within the radiation therapy field and one Ewing's sarcoma outside the radiation therapy field. Risk-adapted, combined-modality therapy using VAMP chemotherapy with radiation is effective and well tolerated. Pediatric patients with low-risk Hodgkin's disease can be cured with therapy without an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiotherapy. Thus, these children are expected to retain normal fertility, organ function, and be at low risk of a second malignant tumor.
    Journal of Clinical Oncology 02/2007; 25(3):332-7. · 18.04 Impact Factor
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    ABSTRACT: Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% +/- 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% +/- 11.3% and 77.7% +/- 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% +/- 10.8% and 80.2% +/- 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported. Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.
    Journal of Clinical Oncology 08/2006; 24(19):3142-9. · 18.04 Impact Factor
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    ABSTRACT: The best treatment approach for children with B-precursor acute lymphoblastic leukemia (ALL) in second clinical remission (CR) after a marrow relapse is controversial. To address this question, we compared outcomes in 188 patients enrolled in chemotherapy trials and 186 HLA-matched sibling transplants, treated between 1991 and 1997. Groups were similar except that chemotherapy recipients were younger (median age, 5 versus 8 years) and less likely to have combined marrow and extramedullary relapse (19% versus 30%). To adjust for time-to-transplant bias, treatment outcomes were compared using left-truncated Cox regression models. The relative efficacy of chemotherapy and transplantation depended on time from diagnosis to first relapse and the transplant conditioning regimen used. For children with early first relapse (< 36 months), risk of a second relapse was significantly lower after total body irradiation (TBI)-containing transplant regimens (relative risk [RR], 0.49; 95% confidence interval [CI] 0.33-0.71, P < .001) than chemotherapy regimens. In contrast, for children with a late first relapse (> or = 36 months), risks of second relapse were similar after TBI-containing regimens and chemotherapy (RR, 0.92; 95% CI, 0.49-1.70, P = .78). These data support HLA-matched sibling donor transplantation using a TBI-containing regimen in second CR for children with ALL and early relapse.
    Blood 07/2006; 107(12):4961-7. · 9.78 Impact Factor
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    ABSTRACT: Relapsed acute lymphoblastic leukemia (ALL) in children is associated with a poor outcome, especially for those patients whose relapse occurs during the first 36 months after diagnosis. The best therapy for these patients is not known. This study was designed to evaluate the feasibility of enrolling children with recurrent ALL in a standardized treatment protocol that included receipt of a hematopoietic stem cell transplant (HSCT). Eligible patients with a bone marrow relapse of non-T, non-B ALL underwent a common induction and consolidation followed by receipt of either an allogeneic HSCT from a human leukocyte antigen (HLA)-identical sibling or an autologous HSCT purged with B-4 blocked ricin. A common conditioning regimen was used for all patients. Twenty-eight patients from eight institutions were enrolled. Fourteen patients did not receive a transplant during the study, because of toxicity (4), relapse (1), inadequate purging (1), and parental or physician preference for an alternative donor transplant (8). Six patients received allogeneic HSCTs. Five of them have remained in remission for a median of 78 months. Eight patients received autologous HSCTs purged with B4-blocked ricin. Four have remained in remission for a median of 94 months. Of the nine patients who received alternative donor transplants, only two remain in remission. We conclude that well designed and controlled prospective studies are necessary to define the role of HSCTs in children with recurrent ALL. In order to be successful, such studies must have the full support of participating centers. Autologous HSC transplantation may have a role in the treatment of relapsed ALL, but further studies are needed.
    Journal of Pediatric Hematology/Oncology 05/2006; 28(4):210-5. · 0.97 Impact Factor
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    ABSTRACT: Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease. We performed a phase II study with patients stratified as follows: stratum 1: > or = 25% bone marrow blasts in first relapse; stratum 2: > or = 25% bone marrow blasts in > or = second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g/m2 daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg/m2/d for strata 1 and two patients and 400 mg/m2/d for strata 3 and four patients. We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of > or = grade 3 neurologic adverse events in 27 patients (18% of patients). Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival.
    Journal of Clinical Oncology 05/2005; 23(15):3376-82. · 18.04 Impact Factor
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    ABSTRACT: To evaluate the efficacy of stereotactic radiotherapy (SRT) for small, localized, pediatric brain tumors and to determine the patterns of failure. A total of 81 patients were enrolled in an institutional review board-approved prospective Dana-Farber Cancer Institute protocol between 1992 and 1998. Of the 81 patients, 50 had low-grade astrocytoma, 23 had residual or recurrent craniopharyngioma, 4 had posterior fossa ependymoma, and 4 had other histologic types. All patients underwent biopsy for diagnosis, with the exception of patients with neurofibromatosis and radiographic evidence of an optic system tumor. The neurocognitive outcome for all patients was also an endpoint of the study and will be reported separately. This report focused on the patients with low-grade gliomas only. Of the 50 patients, 26 were males and 24 females; the median age was 9 years (range, 2-26 years). The indications for treatment of patients with low-grade gliomas were progression during or after chemotherapy or progression after surgery alone. SRT was delivered using a dedicated 6-MV linear accelerator. Immobilization was accomplished with a removable head-frame. CT and MRI fusion was used for treatment planning. The target volume generally included the preoperative tumor plus a 2-mm margin for the planning target volume. The median collimator size was 47.25 mm (range, 30-60 mm). Three to nine arcs were used to deliver a mean total dose of 52.2 Gy in 1.8-Gy daily fractions. With a median follow-up of 6.9 years (range, 0.9-10.2 years), the progression-free survival rate was 82.5% at 5 years and 65% at 8 years. The overall survival was 97.8% at 5 years and 82% at 8 years. Six patients had local progression. Two of the patients with local progression had pathologic progression to anaplastic astrocytoma 3 and 7 years after initial SRT. Five patients, all with optic system/hypothalamic primary tumors, developed central nervous system dissemination 1.0-7.4 years after SRT. One patient developed a presumed radiation-induced primitive neuroectodermal tumor 6 years after initial treatment. Six patients died, three of dissemination, two of progression to higher grade tumors, and one of a secondary radiation-induced tumor. All 6 cases of local progression were within the primary tumor bed at the time of progression and had received the full prescription dose. No marginal failures occurred. Stereotactic radiotherapy provides excellent local control for children with small, localized low-grade glial tumors. Marginal failures have not been observed, supporting the use of limited margins to minimize late sequelae using stereotactic immobilization and planning techniques.
    International Journal of Radiation OncologyBiologyPhysics 03/2005; 61(2):374-9. · 4.52 Impact Factor
  • International Journal of Radiation Oncology Biology Physics - INT J RADIAT ONCOL BIOL PHYS. 01/2005; 63.
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    ABSTRACT: To describe the neuropsychological functioning of children treated with surgery only for localized brain tumors in Dana-Farber Cancer Institute Protocol 92-077. Subsequent reports will describe the neuropsychological functioning of children treated with surgery and stereotactic radiation therapy on Dana-Farber Cancer Institute 92-077. The intellectual functioning of 106 patients was evaluated within 3 months after surgery. An in-depth assessment of the neuropsychological functioning, including an impairment index, was conducted for a subset of 77 school-age children (6-16 yr old) across six functional domains. Descriptive statistics were generated; binomial distribution analyses were performed to assess whether the proportion of individuals with impaired performance on each measure exceeded normative expectations. The impairment index assessed whether poor performance was attributable to a few children or reflected the performance of the cohort as a whole. Although the Full Scale IQ was within normative expectations, the Verbal IQ was higher than the Performance IQ with 45% of individuals showing a significant discrepancy (P < 0.01) between these scales. There was an increased prevalence of poor performance for measures of motor output, verbal memory, and visuospatial organization. The distribution of the impairment index indicated moderate impairment across the school-age cohort rather than severe impairment in a few patients. The results document a moderate level of neuropsychological morbidity among children with brain tumors before stereotactic radiation therapy, presumably referable to the tumor itself and the surgery. The extent to which stereotactic radiation therapy may increase this burden will be assessed in follow-up studies evaluating the longitudinal neuropsychological data.
    Neurosurgery 07/2003; 52(6):1348-56; discussion 1356-7. · 2.53 Impact Factor
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    ABSTRACT: Evaluation of pretreatment factors to identify children at high risk for relapse after combined-modality therapy for Hodgkin's disease. From 1990 to 2000, 328 pediatric patients with clinical stage I to IV Hodgkin's disease were treated with chemotherapy and low-dose involved-field radiotherapy on prospective, collaborative, risk-adapted protocols at three institutions. Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year disease-free survival (DFS) and overall survival (OS). With a median follow-up of 59 months (range, 8 to 125 months), the 5-year DFS and OS for all patients were 83% and 93%, respectively. Several factors were associated with inferior DFS and OS by univariate analysis. By multivariate analysis, male sex; stage IIB, IIIB, or IV disease; bulky mediastinal disease; WBC more than 13.5 x 10(3)/mm3; and hemoglobin less than 11.0 g/dL were significant for inferior DFS. A prognostic index was developed incorporating the five significant factors from the multivariate analysis, assigning each a score of 1. The 5-year DFS and OS for children with a prognostic score of 0 to 1 were 94% and 99%; score 2, 85% and 96%; score 3, 71% and 92%; and score 4 or 5, 49% and 72%, respectively. There was a significant difference in DFS among each of these groups, with significantly worse OS in those with a score of 4 to 5. A prognostic index that was based on five pretreatment factors correlated with inferior DFS by multivariate analysis stratified patients by outcome; this may be useful in assigning children with Hodgkin's disease to risk-adapted therapy.
    Journal of Clinical Oncology 06/2003; 21(10):2026-33. · 18.04 Impact Factor
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    ABSTRACT: To determine the toxicity and maximum tolerated dose of etanidazole administered concurrently with hyperfractionated radiation therapy (HRT) for children with brainstem glioma. Eighteen patients with brainstem glioma were treated with etanidazole and HRT on a dose escalation protocol (Phase I trial) between 1990 and 1996. All patients had MRI confirmation of diffuse pontine glioma and signs/symptoms of cranial nerve deficit, ataxia, or long tract signs of <6 months' duration. Cervicomedullary tumors were excluded. Patients (median age: 8.5 years; 11 males, 7 females) received HRT to the tumor volume plus a 2-cm margin with parallel-opposed 6-15-MV photons. The total dose was 66 Gy in 44 fractions (1.5 Gy b.i.d., with at least 6 h between fractions) for the first 3 patients and 63 Gy in 42 fractions for the subsequent 15 patients. Etanidazole was administered as a rapid i.v. infusion 30 min before the morning fraction of HRT. Planned doses of etanidazole were 1.8 g/m(2) x 17 doses (30.6 g/m(2)) at Step 1 to a maximum of 2.4 g/m(2) x 21 doses (50.4 g/m(2)) at Step 8. Dose escalation was planned with 3 patients at each of the 8 levels. Three patients were treated at each dose level except Level 2, on which only 1 patient was treated. The highest dose level achieved was Level 7, which delivered a total etanidazole dose of 46.2 g/m(2). Two patients were treated at this level, and both patients experienced Grade 3 toxicity in the form of a diffuse cutaneous rash. Three patients received a lower dose of 42 g/m(2) (dose Level 6) without significant toxicity, and this represents the maximum tolerated dose (MTD). There were 23 cases of Grade 1 toxicity (10 vomiting, 5 peripheral neuropathy, 2 rash, 2 constipation, 1 weight loss, 3 others), 11 cases of Grade 2 toxicity (4 vomiting, 2 skin erythema, 2 constipation, 1 arthralgia, 1 urinary retention, 1 hematologic), and 4 Grade 3 toxicities (2 rash, 1 vomiting, 1 skin desquamation). Grade 2 or 3 peripheral neuropathy was not seen at any dose level. The median survival from the start of treatment was 8.5 months (range: 3-58 months). The MTD of etanidazole in children receiving HRT for brainstem glioma is 42 g/m(2), with cutaneous rash as the dose-limiting toxicity. This is in contrast to the adult experience, which demonstrates a 24% lower MTD of 34 g/m(2) limited by peripheral neuropathy.
    International Journal of Radiation OncologyBiologyPhysics 04/2003; 55(5):1182-5. · 4.52 Impact Factor
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    ABSTRACT: To evaluate outcome and assess toxicity of children and adolescents with early-stage, favorable Hodgkin's disease treated with vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and low-dose, involved-field radiation. One hundred ten patients with clinical stages I and II, favorable (nonbulky) Hodgkin's disease were treated with four cycles of VAMP chemotherapy and 15 Gy involved-field radiation for those who achieved a complete response, or 25.5 Gy for those who achieved a partial response to two cycles of VAMP. With a median follow-up of 5.6 years (range, 1.1 to 10.4 years), the 5-year survival and event-free survival were 99% (lower confidence limit [CL], 97.4%) and 93% (lower CL, 88.6%), respectively. Factors associated with event-free survival of 100% were complete response to two cycles of VAMP and histology other than nodular sclerosing Hodgkin's disease (NSHD). No serious early or late toxicity has been observed. Patients presenting with clinical stages I and IIA, nonbulky disease involving fewer than three nodal sites have a projected survival and event-free survival of 100% and 97% (lower CL, 93%), respectively, at 5 years. Risk-adapted, combined-modality therapy using only four cycles of VAMP chemotherapy with 15 to 25.5 Gy of involved-field radiation for patients with early-stage/favorable Hodgkin's disease is highly effective and without demonstrable late effects. These results indicate that pediatric patients with stages I and II favorable Hodgkin's disease can be cured with limited therapy that does not include an alkylating agent, bleomycin, etoposide, or high-dose, extended-field radiation therapy.
    Journal of Clinical Oncology 08/2002; 20(14):3081-7. · 18.04 Impact Factor
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    ABSTRACT: To improve efficacy and reduce toxicity of treatment for children with acute lymphoblastic leukemia. Patients from all risk groups, including infants and those with T-cell disease, were treated between 1987 and 1991. Standard-risk (SR) patients did not receive cranial irradiation, whereas high-risk (HR) and very high-risk (VHR) patients participated in a randomized comparison of 18 Gy of cranial irradiation conventionally fractionated versus two fractions per day (hyperfractionated). At a median follow-up of 9.2 years, the 9-year event-free survival (EFS +/- SE) was 75% +/- 2% for all 369 patients, 77% +/- 4% for the 142 SR patients, and 73% +/- 3% for the 227 HR/VHR patients (P =.37 comparing SR and HR/VHR). The CNS, with or without concomitant bone marrow involvement, was the first site of relapse in 19 (13%) of the 142 SR patients: 16 (20%) of 79 SR boys and three (5%) of 63 SR girls. This high incidence of relapses necessitated a recall of SR boys for additional therapy. CNS relapse occurred in only two (1%) of 227 HR and VHR patients. There were no outcome differences found among randomized treatment groups. Nine-year overall survival was 84% +/- 2% for the entire population, 93% +/- 2% for SR children, and 79% +/- 3% for HR and VHR children (P <.01 comparing SR and HR/VHR). A high overall survival outcome was obtained for SR patients despite the high risk of CNS relapse for SR boys, which was presumed to be associated with eliminating cranial radiation without intensifying systemic or intrathecal chemotherapy. For HR/VHR patients, inability to salvage after relapse (nearly all of which were in the bone marrow) remains a significant clinical problem.
    Journal of Clinical Oncology 01/2002; 20(1):237-46. · 18.04 Impact Factor
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    ABSTRACT: To describe neuropsychological functioning (with a specific focus on cognition and memory) after surgical treatment of craniopharyngiomas. Sixteen patients who were between 6 and 15 years of age at the time of surgery comprised the sample. Each child had been treated for a craniopharyngioma with surgery only, on Dana-Farber Cancer Institute Protocol 92-077. The overall level of cognitive functioning was well within the average range, with both language and visuospatial functioning being generally intact; however, specific memory problems, in both the language and visuospatial domains, were evident. Although general cognitive functioning was intact after the surgical treatment of craniopharyngiomas, difficulties in the retrieval of learned information were observed. Neuropsychological assessments, with a focus on memory recall, should be a component of the medical management plan for each child.
    Neurosurgery 12/2001; 49(5):1053-7; discussion 1057-8. · 2.53 Impact Factor
  • M W Kieran, A Billett
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    ABSTRACT: Approaches to cancer therapy for most tumors in adults and children have changed little in 50 years: surgery, radiation, and chemotherapy are standard for many solid tumors. When the concept of angiogenesis in cancer biology was introduced in the 1970s, there was little recognition of the therapeutic potential of attacking a tumor's blood supply. Advances in understanding the molecular processes that regulate tumor blood supply and novel agents that can interfere with them have generated a great deal of scientific interest and excitement. This article reviews the current understanding of angiogenesis and its role in cancer then discusses new therapeutic options in animals and humans, with a focus on pediatric tumors and the potential for treating them.
    Hematology/Oncology Clinics of North America 11/2001; 15(5):835-51, viii. · 2.08 Impact Factor

Publication Stats

916 Citations
316.24 Total Impact Points

Institutions

  • 1992–2011
    • Dana-Farber Cancer Institute
      • Department of Pediatric Oncology
      Boston, Massachusetts, United States
  • 2006
    • Nemours
      Jacksonville, Florida, United States
  • 1996–2005
    • Boston Children's Hospital
      • Department of Psychiatry
      Boston, Massachusetts, United States
  • 1993–2001
    • Harvard Medical School
      • • Department of Radiation Oncology
      • • Department of Pediatrics
      Boston, MA, United States