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Biomedical subjects

S S Donaldson

Publications and source records attributed to S S Donaldson.

At least 109 records · Page 6Linked to original sources
PubMed1987

Langerhans' cell histiocytosis of the head and neck.

Langerhans' cell histiocytosis has been accepted by many to replace the term Histiocytosis X, describing a poorly defined continuum of diseases involving neoplastic proliferation of histiocytes. Twenty-four cases of histologically confirmed Langerhans' cell histiocytosis with head and neck involvement were seen between the years 1970 to 1986, and charts were reviewed retrospectively. Control of local osseous disease was successful using radiation therapy in 100% of those cases with follow-up. Surgical curettage of bone lesions was successful in a small number of cases. Chemotherapy alone or in combination with radiation appeared to enhance survival in patients with recurrent disease or multisystem involvement. Sixteen of the 24 patients (67%) are disease free with a mean follow-up of 6 years. Prompt diagnosis and careful follow-up are important to improve survival and prevent complications.

Adolescent↗
PubMed1986

Von Willebrand factor levels do not predict or diagnose radiation pneumonitis.

In search for an index of endothelial injury that would provide an early diagnosis of radiation pneumonitis, we investigated the plasma levels of von Willebrand Factor (Factor VIII Related Antigen, FVIII:RAg) in 14 patients undergoing pulmonary irradiation. This study was based on observations indicating that damage to the endothelium-rich pulmonary parenchyma may produce alterations in the synthesis, storage or release of FVIII:RAg, detectable in plasma. There was no correlation between FVIII:RAg levels and radiation pneumonitis, radiation dose, volume of irradiated lung, tumor burden, or time-interval between exposure and sampling. The heterogeneity of the neoplasms and the inconstant effects of radiation in the tumor vasculature are among several variables that may explain this lack of correlation. The plasma levels of FVIII:RAg cannot be used to diagnose or predict radiation pneumonitis.

Adolescent↗
PubMed1986

Rhabdomyosarcoma: the Stanford experience using a TNM staging system.

Seventy-four patients with rhabdomyosarcoma were initially staged according to the Intergroup Rhabdomyosarcoma Study (IRS) grouping classification and then retrospectively using a TNM staging system based on the initial clinical extent of disease. The TNM system includes T1, tumor confined to site or organ of origin; T2, regional extension beyond the site of origin; N0, normal lymph nodes; N1, lymph nodes containing tumor; M0, no evidence of metastases; and M1, distant metastases. All patients received combination chemotherapy, and more than 90% received radiation therapy as part of their initial treatment program with curative intent. Fifty-three of 74 patients (72%) were group III according to the IRS system, indicating unresectable or gross residual tumor. A more uniform distribution was achieved using the TNM system. Freedom from relapse (FFR) was 43% and the actuarial survival rate was 47% for the entire study group at 10 years. All but one relapse occurred within 3 years of initial diagnosis, and only three of 38 relapsed patients were salvaged. All TNM stage I patients are surviving disease free. Among patients having stages II, III, and IV disease by the TNM system, FFR was 53%, 26%, and 11%, and the survival rates were 47%, 36%, and 33%, respectively. Thirty-two of 74 patients (43%) had evidence of lymph node involvement at presentation, and 28 (88%) of these had primary lesions that extended beyond the site of origin (T2 primary). Histologic subtype and primary site had little impact on outcome in a multivariate analysis, and T stage was identified as the single most significant covariate correlated with survival; a model composed of both T stage and M stage was the best one for predicting relapse. The presented data support a study using a prospectively assigned TNM staging system based on the initial clinical extent of disease for use in future therapeutic trials.

Adolescent↗
PubMed1986

Topography of childhood tumors: pediatric coding system.

The importance of a uniform coding system for cancer research, tumor registry, and exchange of information is recognized. However, tumors arising in children differ from those in adults, resulting in lack of precision when one coding system is used for both. Because the topographic code of the International Classification of Disease for Oncology for adult tumors does not lend itself well to pediatric tumors, the International Society of Paediatric Oncology (SIOP) developed a four-digit topographic coding system particularly adapted to childhood tumors. The four digits correspond to anatomic site, general and specific localization, and tissue of origin. An SIOP pilot study demonstrated the usefulness of this code.

Child↗
PubMed1985

The value of adjuvant chemotherapy in the management of sarcomas in children.

Sarcomas of childhood rank fifth in incidence of malignant tumors in children younger than 15 years. Among the soft tissue sarcomas, approximately 50% are rhabdomyosarcomas. The remainder represent a heterogeneous group of diverse sarcomas which are not unique to children and include fibrosarcoma, synoviosarcoma, malignant fibrous histiocytoma, malignant schwannoma, angiosarcoma, leiomyosarcoma, and others. The most common bone cancers in childhood are osteosarcoma and Ewing's sarcoma. Although a multidisciplinary approach utilizing surgery, irradiation, and combination chemotherapy is routinely used in management of virtually all children with solid tumors, the value of adjuvant chemotherapy in select bone and rare soft tissue sarcomas is currently being tested. Multiagent chemotherapy including vincristine, dactinomycin, cyclophosphamide, and Adriamycin (doxorubicin) contribute to cure rates in 65% to 75% of children with localized rhabdomyosarcoma, Stages I to III, when combined with surgery and/or irradiation. Other drugs which hold promise include platinum, DTIC, methotrexate, and VP-16. The efficacy of similar drugs in the rarer pediatric soft tissue sarcomas other than rhabdomyosarcoma and its variants requires prospective randomized trials evaluating histologic grade, tumor size, and nodal status. It has been suggested that the high-grade sarcomas presenting with minimal tumor bulk are most sensitive to combined radiotherapy-chemotherapy, whereas the low-grade sarcomas are more resistant to such therapy. Tumor cell heterogeneity contributes to biologic diversity and response to treatment. Chemotherapy as adjuvant therapy to irradiation is currently recommended and utilized for Ewing's sarcoma with survival rates approaching 80%, and disease-free survival of approximately 75% for those with localized disease. Children with widespread and metastatic disease at presentation fare less well. Although multiple single agents exhibit response rates ranging from 40% to 60%, including cyclophosphamide, Adriamycin, dactinomycin, BCNU, mithramycin, and 5-fluorouracil, new and more effective agents are needed. Controversy regarding the value of multiagent chemotherapy in osteosarcoma has stimulated prospective randomized trials. Evaluation of local control rates as well as sites and occurrence of metastases are essential in assessing the contribution of aggressive combined modality therapy in the pediatric sarcomas. Emphasis on refinement of therapy in determining the risk/benefit ratio from adjuvant chemotherapy in pediatric sarcomas is mandatory. Enhancement of early local reactions is apparent when adjuvant chemotherapy is used with local radiotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Antineoplastic Agents↗
PubMed1985

Radiotherapy of lymphoid diseases of the orbit.

Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. The diagnosis was made by biopsy in all patients and immunophenotyping was done in six cases, of which 5 were monoclonal. Patients were evaluated with a chest radiograph, lymphogram or abdominal CT, bone marrow biopsy and orbital CT. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. There were no relapses in those with localized disease. Two patients developed cataracts. Carefully planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma.

Adult↗
PubMed1985

Intra-arterial infusion of radiosensitizer (BUdR) combined with hypofractionated irradiation and chemotherapy for primary treatment of osteogenic sarcoma.

Combined modality treatment was given in nine patients of osteogenic sarcoma wherein the tumor was unresectable because of location or amputation was refused. This alternative to massive surgery comprised hypofractionated irradiation, intra-arterial infusion of the radiosensitizer 5'-bromodeoxyuridine (BUdR) and adjuvant systemic chemotherapy. Local control was achieved in seven of the nine patients. Four survived, all without evidence of disease at 6, 7.1, 8.8, and 10.5 years after completion of irradiation. Pulmonary metastases developed in six patients--of whom one survives, following high-dose pulmonary irradiation and additional chemotherapy. Significant soft-tissue injury occurred in five patients. On the basis of our experience, we believe that new approaches using modifications of external beam irradiation with different fractionation schedules or better radiosensitizing compounds may hold promise for patients with non-resectable osteosarcoma.

Adolescent↗
PubMed1985

Late relapse among patients treated for Hodgkin's disease.

Of 1360 consecutive patients with Hodgkin's disease treated at Stanford University, 1312 patients (96%) had complete remission, but 424 patients had a relapse. Fifty-five patients had relapses 36 months or more after completion of therapy. The actuarial risk of relapse in patients disease-free 3 years after therapy was 12.9%. The occurrence of late relapse was significantly related to stage I disease and nodular sclerosis histologic subtype. Late relapse was detected in 88% of patients by history, physical findings, or chest radiographs. Most patients with stage III and IV disease had late relapses in previously irradiated nodes or extranodally, but patients with stage I and II disease had late relapses primarily in unirradiated nodes. Disease-free survival after salvage therapy for late relapse was similar to that seen after treatment of earlier relapse. Prolonged surveillance of patients for late relapse is necessary after treatment of patients with Hodgkin's disease.

Adolescent↗
PubMed1984

Thyroid dysfunction after radiotherapy in children with Hodgkin's disease.

Thyroid function was measured in 119 children, 16 years of age or less, after radiotherapy (XRT) for Hodgkin's disease. Thyroid abnormalities developed in 4 of 24 children (17%) who received 2600 rad or less, and in 74 of 95 children (78%) who received greater than 2600 rad to the cervical area, including the thyroid. The abnormality in all but three (one with hyperthyroidism and two with thyroid nodules) included the development of elevated levels of thyroid stimulating hormone (TSH). Age, sex, and administration of chemotherapy were not significant factors in the development of thyroid dysfunction. All children had lymphangiograms (LAG) and no time relationship was noted between thyroid dysfunction and LAG-XRT interval. The mean interval from radiotherapy to documented thyroid dysfunction was 18 months in the low-dose group and 31 months in the high-dose group, with most patients becoming abnormal within 3 to 5 years. Of interest was a spontaneous return of TSH to within normal limits in 20 children and substantial improvement in another 7. This study confirms the occurrence of dose-related occult hypothyroidism in children following external irradiation of the neck.

Adolescent↗
PubMed1984

Acute nonlymphocytic leukemia developing during the course of Ewing's sarcoma.

Two children with Ewing's sarcoma developed acute nonlymphocytic leukemia (ANLL) during the course of their illness. One patient developed ANLL after apparently successful treatment of his primary malignancy with radiation therapy and multiagent chemotherapy. In the second patient, acute leukemia developed before the administration of radiotherapy or systemic chemotherapy. The development of secondary ANLL after Ewing's sarcoma has been reported only twice previously, most likely representing a therapy-induced complication. The occurrence of ANLL in Patient 2 prior to therapy suggests that these two disorders may have a more than treatment-related association. Close follow-up of long-term survivors of Ewing's sarcoma with surveillance for secondary acute leukemia is advised.

Acute Disease↗
PubMed1984

A rational clinical staging system for childhood rhabdomyosarcoma.

There is a need for a rational and useful staging system for childhood rhabdomyosarcoma that predicts prognosis based on the biology and natural history of the disease. Important factors to consider are age, histology, tumor volume, extent of invasion, and lymphatic involvement. A clinical staging system based on a classical tumor/node/metastasis status, and which accounts for natural history as a function of site of primary, local invasion, and lymphatic or hematogenous metastases is presented. This staging system eliminates the requirement that stage is assigned following an initial therapeutic strategy and removing the implication that prognosis is determined by that strategy.

Adolescent↗
PubMed1984

Childhood Hodgkin's disease: patterns of relapse.

One hundred seventy-nine consecutive children with Hodgkin's disease seen at Stanford University Medical Center between the years 1961-1980 have been analyzed for survival and freedom-from-relapse as a function of clinical versus laparotomy staging as well as primary treatment modalities. Of laparotomy-staged patients, 86% are alive at 10 years after primary radiation with chemotherapy reserved for relapse, as compared with 90% managed by planned combined modality therapy (p = 0.62). Patients who were clinically staged and managed with primary radiation have only a 69% survival (p = 0.05). A favorable subgroup of patients with lymphocyte-predominant Hodgkin's disease experienced a low relapse rate regardless of primary treatment modality. Patterns of relapse in clinically staged patients reflect understaging, with most relapses in distant, nonirradiated sites, whereas the less frequent relapses in laparotomy-staged patients usually reflect regional recurrence. It is concluded that laparotomy staging is highly desirable to allow greatest flexibility in optimizing individual therapy. Routine combined modality treatment for all patients would overtreat certain favorable subgroups, who can be managed more conservatively as long as the information derived from surgical staging is available. For young children, in whom bone growth issues are paramount, combined modality treatment using low-dose radiation is recommended. For older children and adolescents, where concerns over chemotherapy-related leukemogenesis and infertility are more important than height considerations, radiation alone may be used for stages I-IIIA with equal overall success.

Adolescent↗
PubMed1984

Protection from radiation nephropathy by WR-2721.

The efficacy of WR-2721 pretreatment against radiation injury to the growing kidney was evaluated in the weanling mouse. Immediately following unilateral nephrectomy, animals received intraperitoneal injections of saline or WR-2721 (220 mg/kg). Thirty minutes later both nonprotected (saline-treated) control animals and protected (WR-2721-treated) animals received 1000-rad single-fraction radiation to the remaining kidney. Other animals received WR-2721 immediately following unilateral nephrectomy but no radiation. Animals were sacrificed at 3 and 24 weeks. Nonirradiated animals treated with WR-2721 only showed normal compensatory renal growth, body growth, and renal function at 24 weeks. The nonprotected, irradiated animals exhibited renal growth inhibition without body growth inhibition, and renal functional abnormalities including elevation of serum BUN and reduction of glomerular filtration rate. Pretreatment with WR-2721 prior to 1000 rad prevented the renal growth inhibition and functional abnormalities seen in the nonprotected irradiated animals. Within the observation period there were no differences in renal morphology by light and electron microscopy between protected and nonprotected groups; only mild glomerular and tubular abnormalities compatible with radiation injury were seen. WR-2721 can modulate renal radiation injury; however, the growth and functional protection is not well correlated with specific histologic change. The dose reduction factor for WR-2721 renal growth protection is between 1.16 and 1.2. WR-2721 may have future clinical utility by increasing radiation tolerance of the kidney.

Amifostine↗
PubMed1983

Cranial nerve involvement in children with leukemia and lymphoma.

Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.

Adolescent↗
PubMed1982

Electrophysiologic evidence of subclinical injury to the posterior columns of the human spinal cord after therapeutic radiation.

Spinal somatosensory conduction velocity (SSCV) was indirectly estimated from cerebral evoked potentials in 15 adults who had received therapeutic radiation (RT) (2000-4380 rad) to the thoracic spinal cord during treatment for lung cancer, and in 15 age-matched normal controls. Thirteen of the patients had also received 4400-5500 rad to the supraclavicular fossae. One-way impulse conduction time in the arm, estimated from F-wave latency, was prolonged in the patients as compared to controls (12.0 +/- 1.2 versus 10.4 +/- 1.0 msec; P less than 0.001) but conduction time in the leg was similar in the two groups (22.4 +/- 2.4 versus 22.0 +/- 2.5 msec; P less than 0.1). SSCV was significantly slower in the patient group (37.9 +/- 13.9 versus 54.5 +/- 12.9 m/sec; P less than 0.001) whereas supraspinal latency (cervical cord to cortex) was identical (5.5 +/- 0.9 versus 5.5 +/- 0.8 msec; P less than 0.1). SSCV in the patient group was not related to total RT dose (r = 0.15; P = 0.2), but was correlated with both treatment time and number of fractions (r = 0.49 and 0.43; P = 0.003 and 0.007, respectively). These findings suggest that RT may produce subclinical spinal cord dysfunction even at conventional dosage schedules, and that it may be possible physiologically to monitor the myelopathic effects of RT in individual patients.

Aged↗
PubMed1982

A prospective randomized clinical trial of total parenteral nutrition in children with cancer.

A prospective randomized clinical trial was undertaken to test the efficacy of total parenteral nutrition (TPN) among previously untreated children receiving abdominal/pelvic irradiation with or without adjuvant chemotherapy who were at risk for weight loss, malnutrition, and complications from treatment. Children were evaluated by weight/height determinations, anthropomorphic measurements, and laboratory studies. TPN was associated with an improved nutritional status during therapy as compared with control patients on ad libitum intake. However, when TPN was discontinued, weight declined and there were no differences among treated and control patients detected at three-month follow-up. Likewise there was no obvious effect from TPN on tolerance to therapy in the adequately nourished child. TPN as initial supportive therapy should be reserved for those children who are malnourished or marginally malnourished at the time of presentation. Close nutritional assessment during treatment is essential since approximately 25% of children undergoing abdominal/pelvic radiotherapy with chemotherapy can be expected to become malnourished during an initial course of therapy.

Adolescent↗