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Sarah S Donaldson

Publications and source records attributed to Sarah S Donaldson.

At least 19 recordsLinked to original sources
PubMed2007

Reinduction of relapsed acute promyelocytic leukemia with ATRA and low dose antimetabolite-based chemotherapy.

While the disease-free survival of acute promyelocytic leukemia (APML) now approaches 75%, some children continue to experience relapses, and questions remain as to the optimal management of these patients. We describe two young children who experienced combined relapses in the bone marrow and extramedullary locations following hematopoietic stem cell transplantation (HSCT). An induction regimen, consisting of all-trans retinoic acid (ATRA), methotrexate, and 6-mercaptopurine (6MP), successfully and safely achieved hematologic remission in one patient and molecular remission in the other. These cases demonstrate that there is a role for ATRA plus differentiating chemotherapy other than arsenic trioxide in the treatment of relapsed APML.

Antimetabolites, Antineoplastic↗
PubMed2006

New primary neoplasms of the central nervous system in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Subsequent primary neoplasms of the central nervous system (CNS) have frequently been described as late events following childhood leukemia and brain tumors. However, the details of the dose-response relationships, the expression of excess risk over time, and the modifying effects of other host and treatment factors have not been well defined. METHODS: Subsequent primary neoplasms of the CNS occurring within a cohort of 14,361 5-year survivors of childhood cancers were ascertained. Each patient was matched with four control subjects by age, sex, and time since original cancer diagnosis. Tumor site-specific radiation dosimetry was performed, and chemotherapy information was abstracted from medical records. Conditional logistic regression was used to estimate odds ratios (ORs), to calculate 95% confidence intervals (CIs), and to model the excess relative risk (ERR) as a function of radiation dose and host factors. For subsequent gliomas, standardized incidence ratios (SIRs) and excess absolute risks (EARs) were calculated based on Surveillance, Epidemiology, and End Results data. RESULTS: Subsequent CNS primary neoplasms were identified in 116 individuals. Gliomas (n = 40) occurred a median of 9 years from original diagnosis; for meningiomas (n = 66), it was 17 years. Radiation exposure was associated with increased risk of subsequent glioma (OR = 6.78, 95% CI = 1.54 to 29.7) and meningioma (OR = 9.94, 95% CI = 2.17 to 45.6). The dose response for the excess relative risk was linear (for glioma, slope = 0.33 [95% CI = 0.07 to 1.71] per Gy, and for meningioma, slope = 1.06 [95% CI = 0.21 to 8.15] per Gy). For glioma, the ERR/Gy was highest among children exposed at less than 5 years of age. After adjustment for radiation dose, neither original cancer diagnosis nor chemotherapy was associated with risk. The overall SIR for glioma was 8.7, and the EAR was 19.3 per 10,000 person-years. CONCLUSIONS: Exposure to radiation therapy is the most important risk factor for the development of a new CNS tumor in survivors of childhood cancers. The higher risk of subsequent glioma in children irradiated at a very young age may reflect greater susceptibility of the developing brain to radiation.

Adolescent↗
PubMed2006

Female survivors of childhood cancer: preterm birth and low birth weight among their children.

BACKGROUND: Improved survival after childhood cancer raises concerns over the possible long-term reproductive health effects of cancer therapies. We investigated whether children of female childhood cancer survivors are at elevated risk of being born preterm or exhibiting restricted fetal growth and evaluated the associations of different cancer treatments on these outcomes. METHODS: Using data from the Childhood Cancer Survivor Study, a large multicenter cohort of childhood cancer survivors, we studied the singleton live births of female cohort members from 1968 to 2002. Included were 2201 children of 1264 survivors and 1175 children of a comparison group of 601 female siblings. Data from medical records were used to determine cumulative prepregnancy exposures to chemotherapy and radiotherapy. Logistic regression was used to estimate odds ratios (ORs) for the association between quantitative therapy exposures and preterm (<37 weeks) birth, low birth weight (<2.5 kg), and small-for-gestational-age (SGA) (lowest 10th percentile) births. All statistical tests were two-sided. RESULTS: Survivors' children were more likely to be born preterm than the siblings' children (21.1% versus 12.6%; OR = 1.9, 95% confidence interval [CI] = 1.4 to 2.4; P<.001). Compared with the children of survivors who did not receive any radiotherapy, the children of survivors treated with high-dose radiotherapy to the uterus (>500 cGy) had increased risks of being born preterm (50.0% versus 19.6%; OR = 3.5, 95% CI = 1.5 to 8.0; P = .003), low birth weight (36.2% versus 7.6%; OR = 6.8, 95% CI = 2.1 to 22.2; P = .001), and SGA (18.2% versus 7.8%; OR = 4.0, 95% CI = 1.6 to 9.8; P = .003). Increased risks were also apparent at lower uterine radiotherapy doses (starting at 50 cGy for preterm birth and at 250 cGy for low birth weight). CONCLUSIONS: Late effects of treatment for female childhood cancer patients may include restricted fetal growth and early births among their offspring, with risks concentrated among women who receive pelvic irradiation.

Adolescent↗
PubMed2006

Local control in pelvic Ewing sarcoma: analysis from INT-0091--a report from the Children's Oncology Group.

PURPOSE: The impact of the modality used for local control of Ewing sarcoma is uncertain. We investigated the relationship between the type of local control modality, surgery, radiation (RT) or both (S + RT), and subsequent risk for local failure (LF) in patients with nonmetastatic pelvic Ewing sarcoma treated on INT-0091. PATIENTS AND METHODS: Patients < or = 30 years with Ewing sarcoma, primitive neuroectodermal tumor or primitive sarcoma of bone were randomly assigned to receive chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin, (VACA) or with these four drugs alternating with ifosfamide and etoposide (VACA-IE). The local control modality, surgery, RT or both was chosen by the treating physicians. The effect of local control modality was assessed after adjusting for the size of tumor (< 8 cm, > or = 8 cm) and chemotherapy type. RESULTS: Seventy-five patients with pelvic tumors and a median follow-up of 4.4 years (0.6 to 11.4 years) comprised the study population. Twelve underwent surgery, 44 received RT, and 19 received both. The 5-year event-free survival (EFS) and cumulative incidence of LF was 49% and 21% (16%, LF only; 5%, LF and distant failure). There was no significant difference in EFS or LF by tumor size (< 8 cm, > or = 8 cm), local control (LC) modality, or chemotherapy. However, VACA-IE seems to confer an LC benefit (11% v 30%; P = .06). CONCLUSION: There was no significant effect of local control modality (surgery, RT or S + RT) selected by the treating physicians on rates of local failure or EFS. However, VACA-IE improves LC (11%) compared with previously published results for pelvic Ewing sarcoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Advances toward an understanding of brainstem gliomas.

The diagnosis of brainstem glioma was long considered a single entity. However, since the advent of magnetic resonance imaging in the late 1980s, neoplasms within this anatomic region are now recognized to include several tumors of varying behavior and natural history. More recent reports of brainstem tumors include diverse sites such as the cervicomedullary junction, pons, midbrain, or the tectum. Today, these tumors are broadly categorized as either diffuse intrinsic gliomas, most often in the pons, or the nondiffuse brainstem tumors originating at the tectum, focally in the midbrain, dorsal and exophytic to the brainstem, or within the cervicomedullary junction. Although we briefly discuss the nondiffuse tumors, we focus specifically on those diffuse brainstem tumors that regrettably still carry a bleak prognosis.

Brain Stem Neoplasms↗
PubMed2006

Thyroid cancer in childhood cancer survivors: a detailed evaluation of radiation dose response and its modifiers.

Radiation exposure at a young age is a strong risk factor for thyroid cancer. We conducted a nested case-control study of 69 thyroid cancer cases and 265 controls from a cohort of 14,054 childhood cancer survivors to evaluate the shape of the radiation dose-response relationship, in particular at high doses, and to assess modification of the radiation effects by patient and treatment characteristics. We considered several types of statistical models to estimate the excess relative risk (ERR), mainly guided by radiobiological models. A two-parameter model with a term linear in dose and a negative exponential in dose squared provided the best parsimonious description with an ERR of 1.3 per gray (95% confidence interval 0.4-4.1) at doses below 6 Gy and a relative decrease in ERR of 0.2% per unit dose squared with increasing dose, that is, decreases in the ERR/Gy of 53% at 20 Gy and 95% at 40 Gy. Further analyses using spline models suggested that the significant nonlinearity at high doses was characterized most appropriately as a true downturn rather than a flattening of the dose-response curve. We found no statistically significant modification of the dose-response relationship by patient characteristics; however, the linear parameter (i.e., the ERR/ Gy at doses less than 6 Gy) did decrease consistently and linearly with increasing age at childhood cancer diagnosis, from 4.45 for 0-1-year-olds to 0.48 for 15-20-year-olds. In summary, we applied models derived from radiobiology to describe the radiation dose-response curve for thyroid cancer in an epidemiological study and found convincing evidence for a downturn in risk at high doses.

Child↗
PubMed2005

Stroke as a late treatment effect of Hodgkin's Disease: a report from the Childhood Cancer Survivor Study.

PURPOSE: The objectives of this report are to examine the incidence of and risk factors for stroke among childhood Hodgkin's disease (HD) survivors. PATIENTS AND METHODS: The Childhood Cancer Survivor Study is a multi-institutional cohort study of more than 5-year cancer survivors diagnosed between 1970 and 1986 and a sibling comparison group. Incidence rates of stroke among HD survivors (n = 1,926) and siblings (n = 3,846) were calculated and compared. Cox proportional hazards models were used to estimate the hazard ratios, reported as relative risks (RR), of developing stroke between HD survivors and siblings. RESULTS: Nine siblings reported a stroke, for an incidence of 8.00 per 100,000 person-years (95% CI, 3.85 to 14.43 per 100,000 person-years). Twenty-four HD survivors reported a stroke. The incidence of late-occurring stroke among HD survivors was 83.6 per 100,000 person-years (95% CI, 54.5 to 121.7 per 100,000 person-years). The RR of stroke among HD survivors was 4.32 (95% CI, 2.01 to 9.29; P = .0002). All 24 survivors received mantle radiation exposure (median dose, 40 Gy). The incidence of late-occurring stroke among HD survivors treated with mantle radiation was 109.8 per 100,000 person-years (95% CI, 70.8 to 161.1 per 100,000 person-years). The RR of late-occurring stroke among HD survivors treated with mantle radiation was 5.62 (95% CI, 2.59 to 12.25; P < .0001). CONCLUSION: Survivors of childhood HD are at increased risk of stroke. Mantle radiation exposure is strongly associated with subsequent stroke. Potential mechanisms may include carotid artery disease or cardiac valvular disease.

Adolescent↗
PubMed2005

Profile of daily life in children with brain tumors: an assessment of health-related quality of life.

PURPOSE: The survival of children with CNS tumors approaches 70%, yet health-related quality of life (HRQOL) has not been investigated rigorously in this population. We aimed to show that universal assessment of HRQOL could be obtained easily by using the PedsQL 4.0 and to provide a composite profile of their daily lives. PATIENTS AND METHODS: The PedsQL was administered to all patients seen in the neuro-oncology clinic at Lucile Packard Children's Hospital (Palo Alto, CA) from December 2001, to September 2002. Patients were compared with healthy controls by using two-sided t tests to evaluate statistically significant differences. RESULTS: One hundred thirty-four patients (73 male; mean age +/- standard deviation, 11.8 +/- 5.4 years; 55 had low-grade glioma, 32 had medulloblastoma/primitive neuroectodermal tumor/embryonal tumor, 17 had malignant astrocytoma, nine had germ-cell tumor, and 21 had other types of tumors) were assessed, each in less than 20 minutes. Scores on both child and parent-proxy reports for the total HRQOL, psychosocial, physical, emotional, social, and school-functioning scales were all significantly lower than controls (P < .01). Patients with low-grade glioma were reported to have the highest total HRQOL. Children receiving radiation therapy (XRT) but no chemotherapy had significantly lower total, psychosocial, emotional, and social functioning than those receiving other treatments, including XRT plus chemotherapy. CONCLUSION: The PedsQL can be used to assess HRQOL rapidly and easily in children with CNS tumors, who have significantly worse HRQOL than healthy children. Children receiving XRT fare worse overall; chemotherapy added to XRT does not seem to worsen HRQOL. Assessment of HRQOL should be included as an outcome in future clinical trials.

Adolescent↗
PubMed2005

Long-term medical effects of childhood and adolescent rhabdomyosarcoma: a report from the childhood cancer survivor study.

BACKGROUND: This study was conducted to evaluate the incidence of adverse medical conditions and to assess the risk of developing these conditions in a cohort of long-term survivors of rhabdomyosarcoma (RMS) diagnosed before age 21. PROCEDURE: Using data from the Childhood Cancer Survivor Study (CCSS), we evaluated the incidence of self-reported adverse medical conditions for 606 RMS survivors and 3,701 siblings of cancer survivors. Cancer and treatment data abstracted from medical records were used to evaluate the effects of primary tumor site and combined modality therapy on the risk of developing sequelae in survivors. RESULTS: The relative risk (RR) for developing sequelae among survivors compared with siblings was greatest within 5 years after diagnosis. RR was elevated more than 5 years after diagnosis for several conditions (RR, 95% CI) as follows: eye impairment (cataract: 7.4, 2.9-18.9; visual disturbances: 3.2, 2.0-5.1; very dry eyes: 2.0, 1.2-3.3), endocrine impairment (growth hormone deficiency: 83.9, 33.0-213.6; hypothyroidism: 6.9, 4.1-11.3; need for medications to induce puberty: 90.4, 30.2-270.5), cardiopulmonary impairment (congestive heart failure: 43.0, 12.7-145.5; angina-like symptoms: 2.0, 1.3-2.9), neurosensory impairment (legal blindness: 9.8, 4.8-20.0; abnormal sensations: 1.5, 1.0-2.2), and neuromotor impairment (repeated seizures: 2.3, 1.2-4.4; motor problems: 3.7, 2.2-6.4; problems chewing or swallowing: 3.8, 1.9-7.5). CONCLUSIONS: Survivors are at risk for developing sequelae many years after their initial diagnosis and treatment. Continued medical surveillance is necessary to ensure the long-term health and well-being of RMS survivors.

Adolescent↗
PubMed2004

High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin's disease: results and prognostic indices.

PURPOSE: To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT). PATIENTS AND METHODS: From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS). RESULTS: At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation). CONCLUSION: More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.

Adolescent↗
PubMed2004

Risk-adapted, combined-modality therapy with VAMP/COP and response-based, involved-field radiation for unfavorable pediatric Hodgkin's disease.

PURPOSE: To evaluate the efficacy of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) and cyclophosphamide, vincristine, and procarbazine (COP) chemotherapy and response-based, involved-field radiation, a combined-modality regimen that limits doses of alkylating agents, anthracyclines, and radiation, in children with advanced and unfavorable Hodgkin's disease. PATIENTS AND METHODS: From 1993 to 2000, 159 children and adolescents with unfavorable Hodgkin's disease received three alternating cycles (total of six cycles) of VAMP/COP chemotherapy followed by response-based, involved-field radiation therapy: 15 Gy was administered to patients achieving a complete response, and 25.5 Gy was administered to those achieving a partial response after the first two cycles of chemotherapy and to all sites of bulky lymphadenopathy. Unfavorable disease was defined as clinical stage I and II with bulky peripheral nodal disease greater than 6 cm, initial bulky mediastinal mass 33% or more of the intrathoracic diameter, and/or "B" symptoms and all stage III and IV. RESULTS: Study enrollment was closed after an interim analysis estimated a 5-year event-free survival (EFS) rate below a predefined level. Disease presentation was localized (stage I/II) in 77 patients (48.4%) and advanced (stage III/IV) in 82 patients (51.6%). At a median follow-up of 5.8 years (range, 1.3 to 10.0 years), 38 patients had events, including relapse/progression (n = 35), second malignancy (n = 2), and accidental death (n = 1); nine relapses (25.7%) occurred greater than 4 years from diagnosis. Five-year survival and EFS estimates are 92.7% +/- 2.5% and 75.6% +/- 4.1%, respectively. CONCLUSION: Risk-adapted combined-modality therapy with VAMP/COP and response-based, involved-field radiation therapy results in an unsatisfactory outcome for pediatric patients with unfavorable presentations of Hodgkin's disease.

Adolescent↗
PubMed2004

Genetic effects of radiotherapy for childhood cancer: gonadal dose reconstruction.

PURPOSE: To estimate the doses of radiation to organs of interest during treatment of childhood cancer for use in an epidemiologic study of possible heritable diseases, including birth defects, chromosomal abnormalities, cancer, stillbirth, and neonatal and premature death. METHODS AND MATERIALS: The study population was composed of more than 25,000 patients with cancer in Denmark and the United States who were survivors of childhood cancer and subsequently had nearly 6,500 children of their own. Radiation therapy records were sought for the survivors who parented offspring who had adverse pregnancy outcomes (>300 offspring), and for a sample of all survivors in a case-cohort design. The records were imaged and centrally abstracted. Water phantom measurements were made to estimate doses for a wide range of treatments. Mathematical phantoms were used to apply measured results to estimate doses to ovaries, uterus, testes, and pituitary for patients ranging in age from newborn to 25 years. Gonadal shielding, ovarian pinning (oophoropexy), and field blocking were taken into account. RESULTS: Testicular radiation doses ranged from <1 to 700 cGy (median, 7 cGy) and ovarian doses from <1 to >2,500 cGy (median, 13 cGy). Ten percent of the records were incomplete, but sufficient data were available for broad characterizations of gonadal dose. More than 49% of the gonadal doses were >10 cGy and 16% were >100 cGy. CONCLUSIONS: Sufficient radiation therapy data exist as far back as 1943 to enable computation of gonadal doses administered for curative therapy for childhood cancer. The range of gonadal doses is broad, and for many cancer survivors, is high and just below the threshold for infertility. Accordingly, the epidemiologic study has >90% power to detect a 1.3-fold risk of an adverse pregnancy outcome associated with radiation exposure to the gonads. This study should provide important information on the genetic consequences of radiation exposure to humans.

Adolescent↗
PubMed2004

Cyclophosphamide dose intensification during induction therapy for intermediate-risk pediatric rhabdomyosarcoma is feasible but does not improve outcome: a report from the soft tissue sarcoma committee of the children's oncology group.

PURPOSE: More than half of pediatric rhabdomyosarcoma cases have intermediate-risk features and suboptimal outcome (3-year failure-free survival estimates, 55 to 76%). Dose intensification of known active agents may improve outcome. EXPERIMENTAL DESIGN: This pilot study evaluated the feasibility of dose intensification of cyclophosphamide in previously untreated patients ages < 21 years with intermediate-risk rhabdomyosarcoma. Induction therapy comprised four 3-week cycles of VAC: vincristine (V) 1.5 mg/m2 on days 0, 7, and 14; actinomycin D (A) 1.35 mg/m2 on day 0; and dose-intensified cyclophosphamide (C) on days 0, 1, and 2. The three cyclophosphamide dose levels tested were as follows: (a) 1.2 g/m2/dose; (b) 1.5 g/m2/dose; and (c) 1.8 g/m2/dose. Continuation therapy comprised nine additional cycles of VAC with 2.2 g/m2/cycle of C. Radiotherapy was administered at week 0 (parameningeal tumors with intracranial extension) or week 12 or 15 (all others). RESULTS: Between October 1996 and August 1999, 115 eligible patients were enrolled. Three of 15 patients treated at dose level 2 experienced life-threatening dose-limiting toxicity (typhlitis +/- other severe toxicity). Dose level 1 was the maximum-tolerated dose, and 91 evaluable patients were treated at this level. The 3-year failure-free and overall survival estimates for patients treated at the maximum-tolerated dose were 52% (95% confidence interval, 41-64%) and 67% (95% confidence interval, 56-77%), respectively, at a median follow-up of 3 years. CONCLUSIONS: A 64% increase in the standard cyclophosphamide dosage during induction (to 3.6 g/m2/cycle) was tolerated. However, outcomes were similar to those observed at lower dosages, suggesting that alkylator dose intensification does not benefit patients with intermediate-risk rhabdomyosarcoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

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.

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.

Central Nervous System Diseases↗
PubMed2004

Treatment of metastatic Ewing's sarcoma or primitive neuroectodermal tumor of bone: evaluation of combination ifosfamide and etoposide--a Children's Cancer Group and Pediatric Oncology Group study.

PURPOSE: One hundred twenty patients with metastatic Ewing's sarcoma or primitive neuroectodermal tumor (PNET) of bone were entered onto a randomized trial evaluating whether the addition of ifosfamide and etoposide to vincristine, doxorubicin, cyclophosphamide, and dactinomycin improved outcomes. METHODS: Thirty-two patients had metastases to lungs only, 12 patients had metastases to bone marrow or bones only, 64 patients had metastases in multiple sites, and five patients had metastases in other sites; seven patients could not be assessed precisely. Treatment comprised 9 weeks of chemotherapy before local control and 42 weeks of chemotherapy; thereafter, regimen A consisted of vincristine 2 mg/m(2), cyclophosphamide 1,200 mg/m(2), and either doxorubicin 75 mg/m(2) or dactinomycin 1.25 mg/m(2). Regimen B consisted of regimen A alternating every 3 weeks with ifosfamide 1,800 mg/m(2)/d for 5 days and etoposide 100 mg/m(2)/d for 5 days. RESULTS: Patients treated on regimen B did not have significantly better survival than those treated on regimen A. The event-free survival (EFS) and survival (S) at 8 years were 20% (SE, 5%) and 32% (SE, 6%), respectively, for those treated on regimen A and 20% (SE, 6%) and 29% (SE, 6%), respectively, for those treated on regimen B. Patients who had only lung metastases had EFS and S of 32% (SE, 8%) and 41% (SE, 9%), respectively, at 8 years. There were six toxic deaths (5%), four from cardiac toxicity and two from sepsis (four treated on regimen B and two treated on regimen A). Two had second malignant neoplasms. CONCLUSION: Adding ifosfamide and etoposide to standard therapy does not improve outcomes of patients with Ewing's sarcoma or PNET of bone with metastases at diagnosis.

Adolescent↗
PubMed2004

Failure pattern and factors predictive of local failure in rhabdomyosarcoma: a report of group III patients on the third Intergroup Rhabdomyosarcoma Study.

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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Ewing sarcoma: radiation dose and target volume.

BACKGROUND: The outcome of children and adolescents with Ewing sarcoma is impacted by many prognostic factors and often measured by estimates of: event-free, relapse-free, disease-free, or overall survival. However, the preferred assessment following radiation therapy is local control. PROCEDURE: A review of large group experiences over the past several decades was undertaken to assess the optimal radiation dose and volume for patients with localized, osseous Ewing sarcoma. New approaches and techniques to improve local control were also investigated. RESULTS: With multidisciplinary therapy, 5-year overall local control rates range from 58 to 93%. Following definitive irradiation, they are 53-86%. Recommended radiation therapy doses are 55.8-60.0 Gy. In the postoperative setting, gross disease requires 55.8 Gy; microscopic disease requires 45 Gy. Altered fractionation schemes have not improved local control. The appropriate irradiated volume is an involved field to the pretreatment tumor volume plus 2.0-2.5 cm margin, followed by a boost to the post-induction chemotherapy tumor volume with margin. Good radiation quality control with central review improves local control. Use of an involved radiation field requires accuracy in defining tumor volume. Techniques to improve local control include risk-adapted multidisciplinary therapy, intraoperative boost radiation, and high radiation doses as delivered by 3-dimensional conformal radiation. Intensity modulated and proton beam radiotherapy may offer an advantage at special sites. CONCLUSIONS: Innovative uses of radiation in the multidisciplinary setting will continue to provide excellent local control, improved function, and quality of life for young patients with localized Ewing sarcoma of bone.

Child↗