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S S Donaldson

Publications and source records attributed to S S Donaldson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Parameningeal rhabdomyosarcoma: results of an international workshop.

PURPOSE: A retrospective analysis was performed on children with nonmetastatic rhabdomyosarcomas (RMS) involving a parameningeal site treated by one of the four major cooperative groups: Intergroup Rhabdomyosarcoma Study (IRS), International Society of Pediatric Oncology (SIOP), German Cooperative Group (CWS), and Italian Cooperative Group (ICS) to analyse survival and prognostic factors. METHODS AND MATERIALS: Between 1979 and 1989, 230 children (median age 6 years) were treated in the IRS III, SIOP 84, CWS 81, and ICS 79 studies. All patients received chemotherapy, and 203 were irradiated. Radiotherapy doses were similar in the four studies, although treatment volumes were not similar. The SIOP patients had smaller volumes treated. In addition, the SIOP patients with a low risk of meningeal involvement and children under 5 years of age were not irradiated if they had a complete response (CR) to chemotherapy. Time to initiation of irradiation was earlier in the IRS and Italian studies. RESULTS: Median follow-up was 62 months (range 22-140). The 5-year survival and 5-year event-free survival were better for the IRS study (74% and 71%) than for the other study groups (55% and 36% for SIOP, 47% and 47% for CWS, and 39% and 39% for ICS). The low-risk (LR) patients in the IRS study had improved survival. However, patients with high risk of meningeal involvement had similar survival in all four studies. The most significant prognostic factor was the size of tumor (> 5 cm). CONCLUSION: The improved results from the IRS group, especially among the LR patients, could be related to the IRS treatment employed, particularly the systematic use of radiation, to the inclusion of patients with smaller tumors, and to the routine use of quality control of radiation.

Adolescent↗
PubMed1995

Radiation-induced premature menopause: a misconception.

PURPOSE: To disprove the common view that women who have undergone irradiation to fields excluding the pelvis are at risk for radiation-induced premature menopause, we reviewed menstrual function and fertility among women treated with subtotal lymphoid irradiation for Hodgkin's Disease. METHODS AND MATERIALS: Treatment and follow-up records of all women less than age 50 at the time of diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967 to 1985, were reviewed. In addition, patients were surveyed regarding their menstrual status and fertility history. RESULTS: Thirty-six women, aged 10 to 40 years, with normal menstrual function at the time of Hodgkin's diagnosis, were identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The average radiation dose to mantle and paraaortic fields was 40-44 Gy; the calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%) experienced premature menopause. The reported rate of premature menopause in women who have not undergone irradiation is 1-3%; not significantly different than the rate in our study. There is a syndrome whereby antibodies to several endocrine organs occur (including the ovary), which is associated with premature ovarian failure. This syndrome may be associated with prior radiation to the thyroid, such as that given by mantle irradiation for Hodgkin's Disease. We report such a case. CONCLUSION: There is little risk of premature menopause in women treated with radiation fields that exclude the pelvis. Women with presumed radiation-induced premature menopause warrant an evaluation to exclude other causes of ovarian failure, such as autoimmune disorders.

Adolescent↗
PubMed1995

Hyperfractionated radiation in children with rhabdomyosarcoma--results of an Intergroup Rhabdomyosarcoma Pilot Study.

PURPOSE: The Intergroup Rhabdomyosarcoma Study (IRS) Group initiated a pilot study (IRS IV-P) of hyperfractionated radiation (HF XRT) with chemotherapy to test the feasibility and toxicity of this combined modality approach in children with localized but nonresected (group III) and metastatic (group IV) rhabdomyosarcoma. METHODS AND MATERIALS: Using the linear quadratic equation, and an alpha/beta ratio of 10 Gy for acute reacting tumor effect and 3 Gy for late reacting normal tissue effect, a HF XRT protocol was developed giving a total radiation dose of 59.4 Gy, in 1.10 Gy fractions, twice daily at 6-8 h intervals. All patients received chemotherapy in addition to irradiation. The radiation scheme was calculated to increase the biologically effective dose to the tumor by 10% without increasing late effects, when compared to a conventional schedule of 50.4 Gy in 1.8 Gy daily fractions. This protocol also was predicted to cause an increase in acute normal tissue effects. RESULTS: Four hundred forty-nine children age 21 years and younger were eligible for the hyperfractionated radiation study of whom 297 had Group III disease and 152 had Group IV disease. A total of 117 patients were excluded from the feasibility and toxicity analysis because of progressive disease or death prior to scheduled irradiation, surgical resection, major protocol violation, treatment with brachytherapy, or missing data. Thus, 332 children were evaluable for the HF XRT protocol. Twenty-eight of the 332 (8%) were given conventional radiation because of physician preference or young age. Twenty of the 332 (6%) were not irradiated because of young age, anesthesia, or transportation problems. All nonirradiated children were < or = 3 years of age. Thus, 284 children, 86% of the evaluable population, received HF XRT. The radiation dose, number of fractions, number of days, and interfractional interval were scored as appropriate in 93% of cases. Review of radiation portals revealed that in 230 of 284 cases (81%) the radiation fields were appropriate, as per protocol. Thus, the HF XRT was feasible treatment in a multiinstitutional study. Analysis of toxicity revealed that 152 of 204 (75%) of Group III and 52 of 80 (65%) of Group IV patients experienced severe or life-threatening toxicity, explained by the addition of chemotherapy with the radiation. The majority of this toxicity was hematopoietic. Observed organ toxicity, which was potentially explained by the radiation treatment, was greatest at the end of radiation, and improved at the 6-week and 3-month evaluation periods. There were no deaths attributed to radiation toxicity and no instance of toxicity that required alteration of the radiation protocol. Thus, the treatment was not associated with toxicity that was considered excessive or unusual. CONCLUSION: The IRS IV-P study confirms that HF XRT combined with chemotherapy is both feasible and tolerable in children with rhabdomyosarcoma. A prospective randomized trial is underway to test its efficacy as compared to conventional radiation among children also receiving concurrent chemotherapy for rhabdomyosarcoma.

Adolescent↗
PubMed1995

Cost effectiveness and outcome assessment of magnetic resonance imaging in diagnosing cord compression.

BACKGROUND: This study was designed to investigate the costs associated with the use of magnetic resonance imaging (MRI) in the workup of spinal cord compression caused by metastatic disease, an area in which it has proven to be diagnostically useful. METHODS: The study was divided into two parts. Part 1 consisted of a retrospective review of the hospital charts of 46 patients, half of whom were diagnosed with cord compression in the pre-MRI era and the other half diagnosed after MRI availability; costs for these two groups were compared. Part 2 consisted of a review of several major studies comparing the sensitivities and specificities of MRI with alternative imaging techniques, usually myelography. Cost effectiveness and cost/cost ratios were derived for diagnostic usefulness using prevalence, sensitivity, specificity, and cost estimates of MRI and its alternatives, including costs of false-negative and false-positive testing. RESULTS: Our hospital-based experience yielded an average cost of $ 3664 per patient without MRI and $ 2283 per patient when MRI was available (1991 dollar amounts). The cost of diagnosis was 65% more expensive without MRI. Use of the literature-based experience demonstrated that the cost of diagnosis was at least 82% more costly without MRI than when it was available. However, when key variables were altered during sensitivity analysis, this difference of increased cost of diagnosis without MRI ranged from 25% to 98%. CONCLUSION: This work suggests that MRI may result in significant economic benefits in diagnosing metastatic cord compression, but further work is needed on physician behavior and referral patterns with MRI versus myelography as is long term follow-up for potential reductions in patient debility using MRI.

Cost-Benefit Analysis↗
PubMed1995

Response of growing bone to irradiation: a proposed late effects scoring system.

The effect of radiation on epiphyseal bone growth is one of the most important dose-limiting factors in the radiotherapeutic management of children with malignant neoplasms. Clinical and laboratory evidence suggest that many factors may influence the severity of radiation-induced growth arrest. However, the absence of a consistent scoring system for late effects has hampered efforts to analyze the influence of various therapeutic maneuvers or to compare and collate results from different reported series. In this review, laboratory and clinical studies of radiation effects on growing bone are summarized, and a late effects scoring system is proposed.

Bone Development↗
PubMed1995

The Third Intergroup Rhabdomyosarcoma Study.

PURPOSE: The ultimate goal of the Third Intergroup Rhabdomyosarcoma Study (IRS-III, 1984 to 1991) was to improve treatment outcome in children with rhabdomyosarcoma through clinical trials comparing risk-based protocols of surgery and multiagent chemotherapy, with or without irradiation. PATIENTS AND METHODS: One thousand sixty-two previously untreated, eligible patients who were entered onto the study after surgery were randomized or assigned to treatment by clinical group (I through IV), histology (unfavorable or favorable), and site of the primary tumor. Initial responses, progression-free survival (PFS), and survival (S) were the end points used in comparisons between randomized groups and between patients treated in IRS-III and IRS-II (1978 to 1984). RESULTS: The overall outcome of therapy in IRS-III was significantly better than in IRS-II (5-year PFS, 65% +/- 2% v 55% +/- 2%; P < .001 by stratified testing). Patients with group I favorable-histology tumors fared as well on a 1-year regimen of vincristine and dactinomycin (VA), as did a comparable group treated with VA plus cyclophosphamide (C) (5-year PFS, 83% +/- 3% v 76% +/- 4%; P = .18). Results for patients with group II favorable-histology tumors, excluding orbit, head, and paratesticular sites, were inconclusive regarding the benefit from addition of doxorubicin (ADR) to VA. Patients with group III tumors, excluding those in special pelvic, orbit, and other selected nonparameningeal head sites, fared much better on the more intensive regimens of IRS-III than on pulsed VAC or VAC-VADRC in IRS-II (5-year PFS estimates, 62% +/- 3% v 52% +/- 3%; P < .01); however, there were no significant differences in outcome among the groups treated in IRS-III. Patients with metastatic disease at diagnosis (clinical group IV) did not benefit significantly from the more complex therapies evaluated in IRS-III. CONCLUSION: Intensification of therapy for most patients in IRS-III, using a risk-based study design, significantly improved treatment outcome overall. The largest gain from this strategy was realized in patients with gross residual tumor after biopsy (clinical group III). It was also possible to decrease therapy for selected patient subsets without compromising survival.

Adolescent↗
PubMed1994

Hodgkin's disease in the very young.

PURPOSE: A retrospective review of patients with Hodgkin's disease treated at Stanford University Medical Center was undertaken to determine if, within the pediatric population, children < or = 10 years of age have a unique prognosis and response to treatment. METHODS AND MATERIALS: Records of all patients treated for Hodgkin's disease at SUMC between 1961 and 1991 were reviewed. RESULTS: Of 2238 patients with Hodgkin's disease, 91 (4%) were < or = 10 years of age. There is a predominance of male patients (80%) and a higher percentage of mixed cellularity (33%) and lymphocyte predominance (13%) histologies among the very young patients compared to adolescents and adults. The 5 and 10-year survival is 94 +/- 3% and 92 +/- 3%, respectively, for children < or = 10 vs. 93 +/- 2% and 86 +/- 3% for adolescents and 84 +/- 1% and 73 +/- 1% for adults. Five and 10-year freedom from relapse is also higher in the youngest children (88 +/- 4% and 85 +/- 4%, respectively) compared to adolescents (78 +/- 3% and 74 +/- 3%, respectively) and adults (70 +/- 1% and 67 +/- 1%, respectively). Actuarial survival at 25 years for children < or = 10 years is 78%, which is slightly better than for adolescents (67%) and significantly better than for adults (41%) (p = 0.001). Actuarial 25-year freedom from relapse is also significantly better for children < or = 10 (78%) compared to adolescents (74% [p = 0.05]) and adults (65% [p = 0.001]). For all stages of disease, children < or = 10 fare similarly to or slightly better than adolescents and substantially better than adults. For those with Stage I or II disease, survival at 5, 10, and 25 years is 98 +/- 2%, 93 +/- 4% and 73%, respectively, for children aged < or = 10; 98 +/- 1%, 91 +/- 3%, and 79%, respectively, for adolescents and 89 +/- 1%, 80 +/- 1%, and 45%, respectively, for adults. The greatest difference between age groups is seen for Stage III and IV patients. Those aged < or = 10 have an 89 +/- 5% 5 and 10-year survival, and 89% actuarial 25-year survival compared to 87 +/- 4%, 80 +/- 5%, and 28%, respectively, for adolescents and 77 +/- 2%, 64 +/- 2%, and 41%, respectively, for adults. Of patients < or = 10 years of age, 28 (31%) were treated with primary external beam radiotherapy, and 59 (65%) received combined modality therapy consisting of low-dose radiation and chemotherapy. With a median follow-up of 11 years, freedom from relapse is 64% and survival 75% for the radiotherapy group, compared to 97% (p = 0.000) and 93% (p = 0.21) for those treated with combined modality therapy. CONCLUSION: Results indicate that young age is a favorable prognostic factor in Hodgkin's disease. Combined modality therapy has led to improved freedom from relapse and survival rates for all stages of disease and is currently the treatment of choice for the majority of very young children.

Adolescent↗
PubMed1994

Radiation induced height impairment in pediatric Hodgkin's disease.

PURPOSE: To quantitate the impairment in skeletal growth from radiation treatment, we reviewed height measurements among children with Hodgkin's disease irradiated at Stanford University Medical Center between 1965 and 1986. METHODS AND MATERIALS: One hundred and twenty-four children with Hodgkin's disease, in whom long-term follow-up data were available, became the subjects for this analysis. They all had baseline height measurements within 1 year of radiation treatment, a final height measurement beyond age 15 for boys and 13 for girls, and a minimum time interval between baseline and final measurement of 2 years. A baseline and final percent height, as compared to a reference standard, was calculated for each patient. The difference between these two figures was used to assess height impairment. The study group was divided into age and treatment groups and a comparative analysis between these groups was performed. RESULTS: Height impairment was most severe among children who were given high dose radiation to the entire spine when pre-pubertal in age. These patients demonstrated a 7.7% (p < 0.0001) average height impairment, which equates to a height loss of 13 cm or two standard deviations of the U.S. population mean. Pubertal and post-pubertal patients given similar heavy treatment as well as pre-pubertal patients given light treatment also demonstrated some impairment of skeletal growth, however, the loss was not deemed clinically significant. Comparison of standing versus sitting height impairment did not show evidence of disproportionate final growth impairment. CONCLUSION: Treatment regimens that use low doses of radiation for pediatric Hodgkin's disease are thus not associated with clinically significant impairment of skeletal growth, as measured by standing and sitting heights.

Adolescent↗
PubMed1994

Acute myeloid leukemia in patients treated for rhabdomyosarcoma with cyclophosphamide and low-dose etoposide on Intergroup Rhabdomyosarcoma Study III: an interim report.

The early occurrence of five cases of acute myeloid leukemia (AML) in children treated for primary rhabdomyosarcoma on the Intergroup Rhabdomyosarcoma Study III (IRS III) has prompted this report. These patients received cyclophosphamide and four received etoposide in addition to other agents. There were 1,062 eligible patients entered on IRS III between 1984 and 1991. Following surgery, treatment consisted of multiagent chemotherapy and radiotherapy in select clinical groups. Median follow-up time is 3.7 years (range 0-7.4 years). Incidence densities and odds ratios for AML were calculated for various treatment groups. Five cases of secondary AML have been reported through August 1992. A single case of osteogenic sarcoma was reported in the same period and a patient with myelodysplastic syndrome has occurred since that time. Median time to development of AML was 39 months. Incidence density of AML for patients receiving neither cyclophosphamide nor etoposide was 0, for those receiving cyclophosphamide but no etoposide it was 7.6, and when both agents were given, it was 51.6. The odds ratios of AML for the latter two groups indicated a risk of AML which was seven times higher in the patients who received both agents. A history of breast cancer was present in all five families of patients with AML and several other cancers had occurred in three families. Preliminary analysis suggests a possible causal role for low-dose etoposide in addition to that assumed for cyclophosphamide in the early development of AML among pediatric patients treated for rhabdomyosarcoma.

Adolescent↗
PubMed1994

Prognostic features of Ewing's sarcoma on radionuclide bone scan after initial treatment.

OBJECTIVE: To study short-term changes in the radiopharmaceutical bone scan (BS) appearance of Ewing's sarcoma for indicators of decreased survival or future disease progression. METHODS: One-hundred and four patients with non-metastatic Ewing's sarcoma were evaluated at three time points: time of diagnosis (pre-biopsy), after induction chemotherapy (13 weeks) and after radiation therapy (20 weeks). Radiographs, computed tomograms (CTs) and BSs were obtained at each interval. Primary lesion activity and size on BS were evaluated and compared to radiographic and CT findings. RESULTS: No significant relationship was found at any time point between absolute radiopharmaceutical activity within the primary lesion and either disease progression or patient survival. Relative changes in BS activity between time points were also not significantly related to disease progression or survival despite a significant decrease in activity among the three time points. The size of the BS abnormality compared to the CT abnormality at the primary lesion site was related to both survival and disease progression at the post-induction chemotherapy time point (P = 0.025 and P = 0.014, respectively) with larger BS abnormalities indicating worse prognosis and survival. This relationship lost its significance at the post-radiation time point. No other significant relationship between the relative size of the BS abnormality and the size of the plain radiographic or CT abnormality was detected. CONCLUSION: Our data suggest that BS imaging of the primary lesion of Ewing's sarcoma provides little information in terms of predicting long-term survival or disease progression in patients with non-metastatic Ewing's sarcoma.

Adolescent↗
PubMed1994

ABVD/MOPP and low-dose involved-field radiotherapy in pediatric Hodgkin's disease: the Stanford experience.

PURPOSE: We reported previously that treatment with six cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) chemotherapy and 15 to 25 Gy irradiation was effective in curing children with Hodgkin's disease, but was associated with a 6.5% 10-year risk of development of secondary leukemia. Based on the results of that study, a successor study was designed with the objective to maintain treatment efficacy while decreasing adverse effects, particularly the occurrence of secondary leukemia. PATIENTS AND METHODS: Fifty-seven children with a chronologic and/or bone age less than 16 years were enrolled onto this study between May 1982 and October 1990. Treatment consisted of six cycles of combination chemotherapy--three of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and three of MOPP--and low-dose irradiation (15 Gy) of involved fields. Boosts of 10 Gy were given to areas of bulky disease and to those that did not respond completely after two cycles of chemotherapy. RESULTS: With a median follow-up duration of 6.7 years, the projected 10-year survival and event-free survival (EFS) rates are 96% (SE 2.5%) and 93% (SE 3.5%) for the entire cohort of 57 patients, and 85% (SE 10%) and 69% (SE 12.8%), respectively, for 13 patients with stage IV disease. No patient has developed a second malignancy. Growth and development have progressed normally. No patients have symptomatic cardiac, pulmonary, or thyroid disease. Subclinical abnormalities of pulmonary function were detected in 32% and chemical hypothyroidism in 16%. CONCLUSION: This therapy was highly efficacious in children with Hodgkin's disease without unacceptable toxicity. Future efforts should be directed toward further reducing therapy for favorable early-stage patients and improving treatment efficacy for those with stage IV disease.

Adolescent↗
PubMed1993

Lessons from our children.

While the incidence of cancer is increasing among both children and adults, mortality rates have decreased for children, while they have increased for adults. Of children diagnosed with cancer today, 80% are predicted to be long-term survivors. Although there are differences between children and adults with respect to the tumor types, biology, and outcome, there are common lessons which we can learn from our children regarding the genetics of cancer, its management and treatment, and the importance of longitudinal studies of the survivors. Specific pediatric cancers, such as retinoblastoma, have led to the recognition of tumor suppressor genes, now also observed among adult tumors including sarcomas, breast, lung, and bladder cancer. The presence of the tumor suppressor gene provides an understanding for the incidence of second malignant tumors among patients with heritable diseases. Furthermore, cancer prone families, such as those with the Li-Fraumeni syndrome, also carry the p 53 tumor suppressor gene; the presence of which greatly increases the risk of developing invasive cancer. Childhood cancer is rare; it represents only 1% of the total US cancer problem. However, 53% of all children with cancer, but only 2% of all adults, are studied via the NCI cooperative group mechanism. For some specific childhood tumors such as rhabdomyosarcoma and Wilms' tumor, as many as 70-85% of all cases are managed via NCI sponsored trials. Essentially all pediatric cancer is treated by interdigitating radiation with surgical resection and systemic chemotherapy. This approach has contributed to high cure rates. Finally, our understanding of the late effects of being a cancer survivor have come from longitudinal studies of children. The most severe long-term effects related to radiation in childhood pertain to growth and development, infertility, and second malignant tumor induction. Here the children treated for Hodgkin's disease have taught us the dose and volume effects on axial skeletal and soft tissue growth. Infertility issues are also treatment-related and may often be obviated by using gonadal shielding. The risk of secondary leukemia is related to dose and class of specific chemotherapeutic agents administered; it is 5.5% among children receiving 6 cycles of MOPP. There is a 22-fold risk at 30 years of age of solid tumor induction following radiotherapy for children with Hodgkin's disease. These serious concerns have been offset by current therapeutic approaches of using lower doses and smaller volumes of radiation with fewer cycles of less toxic chemotherapeutic agents. Childhood cancer ranks high among number of person-years of potential life saved annually.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Radiotherapy is successful treatment for orbital lymphoma.

PURPOSE: To describe the clinical presentation, treatment technique, outcome and complications in a large single institutional experience using radiotherapy for treatment of orbital lymphoma. METHODS AND MATERIALS: Twenty-five patients with lymphoma of the orbit or ocular adnexa were treated with radiotherapy at Stanford University Medical Center during the fourteen year period, 1977-1991. Patients were staged using the Ann Arbor criteria with chest x-ray, computerized tomography of abdomen and orbits, lymphangiogram, and bone marrow biopsy. Patients with disease localized to the orbits as well as those with disseminated disease and symptomatic orbital lesions were treated. Thirty-one involved eyes were treated. Mean radiotherapy dose was 35.3 Gy, with a range of 28 Gy to 40.2 Gy. Lens protection was used in all cases. Two patients with diffuse large cell lymphoma also received chemotherapy as part of their initial treatment. Follow-up ranged from 10 months to 13 years, with a mean follow-up time of 4 years. RESULTS: Twenty patients had disease confined to one or both orbits (Stage I). One patient had a monoclonal atypical infiltrate, while the remainder had a histologic diagnosis of malignant lymphoma: diffuse small lymphocytic, 13; follicular mixed, 3; diffuse small cleaved, 3; diffuse large cell, 2; follicular small cleaved, 1; follicular and diffuse small cleaved, 1; undifferentiated, 1. Two local relapses occurred; the actuarial 5-year freedom from local relapse is 89%. Actuarial 5-year freedom from distant relapse, freedom from any relapse and overall survival are 77%, 70%, and 93%, respectively. Acute complications of treatment were mild. Late complications included transient cystoid macular edema (one patient), asymptomatic subcapsular and medial sector cataract formation (two patients), retinopathy (two patients), mild eyelid retraction (one patient), and dry eye with secondary conjunctivitis (one patient). CONCLUSION: Carefully planned radiotherapy with lens shielding is an effective and safe treatment in the management of orbital lymphoma. We recommend megavoltage radiation doses of 30-35 Gy in 180-200 cGy fractions for low grade lesions, and 36-40 Gy for intermediate and high grade lesions.

Adult↗