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Biomedical subjects

P Littman

Publications and source records attributed to P Littman.

At least 37 records · Page 2Linked to original sources

Prolonged second remissions in childhood acute lymphocytic leukemia: a report from the Childrens Cancer Study Group.

To date, median duration of second and subsequent remissions in childhood acute lymphocytic leukemia (ALL) has been short, with most studies reporting median remission duration less than 6 months. In May 1979, the Childrens Cancer Study Group (CCSG) undertook a pilot study to assess the efficacy of a vincristine, methotrexate, and L-asparaginase regimen (modified Capizzi) for maintenance in children with ALL in second or subsequent remission. Thirty patients were treated with this maintenance regimen. By life table analysis, predicted median duration of hematologic remission was 57 weeks. Ten patients (33%) were in continuous hematologic remission at 1 year and three (10%) continue in remission greater than 2 years from maintenance onset. Major toxicity included leukoencephalopathy in four patients, three of whom had experienced at least one central nervous system relapse prior to study entry. Allergic reactions to Escherichia coli L-asparaginase were common. Nine of 30 patients experienced at least one CNS relapse during therapy. We conclude that a modified Capizzi regimen is the most effective regimen reported to date for maintaining second and subsequent remission in childhood ALL. CCSG is currently utilizing this regimen in an ongoing open study.

Asparaginase↗

Radiation-induced pneumothorax.

Pneumothorax is an uncommon complication of radiation therapy to the chest. The proposed pathogenesis is radiation-induced fibrosis promoting subpleural bleb formation that ruptures resulting in pneumothorax. We report on two young patients with primary sarcomas without pulmonary metastases who developed spontaneous pneumothorax after irradiation. Neither patient had antecedent radiographic evidence of pulmonary fibrosis.

Adolescent↗

Soft-tissue sarcomas of the head and neck in children.

Thirty-two children aged three months to 17 years (median six years) were diagnosed with soft-tissue sarcoma of the head and neck and treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1971 to 1981. Thirty-one received chemotherapy and all received radiation therapy (RT). Twenty-five patients had pre-treatment computed tomography (CT) scans, which were used for staging and treatment planning. Doses of radiation therapy ranged from 3000 to 7300 rad to the primary tumor (median 5000 rad). The overall five-year survival of the entire group of 32 patients was 75%. Ten of the 32 patients had invasive cranial parameningeal disease as demonstrated by bony erosion at the skull base, seen on CT in eight and plain radiographs in two patients. Eight of these 10 patients have developed recurrent sarcoma: four in the meninges, two locally, one regionally and one distantly. Five of these 10 children with invasive cranial parameningeal sarcoma received 3000 rad of prophylactic cranial irradiation, begun within the first 12 days of chemotherapy, and none developed meningeal disease. In contrast, only one of the 22 patients without invasive cranial parameningeal disease has relapsed (local recurrence). The data suggest that soft-tissue sarcomas of the head and neck in children without invasion into the base of the skull (invasive cranial parameningeal disease) are usually cured. CT scans are essential for staging. Patients with invasion of the base of the skull may be protected from meningeal relapse by early cranial irradiation, although they still are at high risk for relapse in other sites.

Adolescent↗

Results of radiation therapy given after radical hysterectomy.

Two hundred twelve patients with carcinoma of the cervix, Stage I (193 patients) and Stage II (19 patients), were treated by radical hysterectomy at the Hospital of the University of Pennsylvania during the period from 1955-1977. Pathology reports were evaluated for the presence of the following factors thought to indicate an unfavorable prognosis: (1) positive pelvic lymph nodes (31 patients); (2) parametrial extension (22 patients); and (3) infiltration of the margin of resection (14 patients). Fifty-one high risk patients (HR) with one or more of these pathologic findings have five and ten year survivals of 55% and 30%, respectively. This compares with five- and ten-year survivals of 87% and 85%, respectively, for patients without these findings. Local recurrences were noted in 20/50 (40%) HR patients versus 23/159 (13.2%) non-HR patients (P less than .001). A retrospective analysis revealed that 21 of 50 evaluable HR patients received adjunctive postoperative pelvic irradiation (HR-XRT). Although the reduction in local recurrence in the treated group approached statistical significance, 5/21 versus 15/29 (0.1 greater than P greater than 0.05), the five- and ten-year survival did not differ significantly. Twenty-four patients initially treated with surgery received definitive radiation therapy for local recurrence. The five- and ten-year survivals for the time of recurrence were 22% and 15%. Our findings suggest that postoperative irradiation may be beneficial in controlling local disease in a subgroup of radical hysterectomy patients who are at high risk for recurrence. Since the ultimate incidence of extra pelvic metastasis for the high risk and the recurrent group is 32% and 67%, respectively, however, it appears that improved survival awaits the development of effective systemic adjuvant therapy.

Adenocarcinoma↗

Sanctuary therapy: a randomized trial of 724 children with previously untreated acute lymphoblastic leukemia: A Report from Children's Cancer Study Group.

Between 1972 and 1974, Childrens Cancer Study Group enrolled 724 children with newly diagnosed acute lymphoblastic leukemia on a single randomized clinical trial. Study CCG-101 was designed to test four types of presymptomatic central nervous system and sanctuary therapies consisting of (a) 2400-rad craniospinal radiation therapy (RT) plus 1200-rad extended-field RT, which included the liver, spleen, kidneys, lower abdomen, and gonads; (b) 2400-rad craniospinal RT; (c) 2400-rad cranial RT plus intrathecal methotrexate (i.t. MTX); and (d) i.t. MTX alone. Patients all received a 28-day induction course of vincristine, prednisone, and L-asparaginase and were maintained subsequently on a regimen consisting of daily 6-mercaptopurine, weekly MTX, and monthly pulses of vincristine and prednisone. Patients treated with six doses of i.t. MTX alone had a significantly higher incidence of central nervous system relapse than did patients treated with 2400-rad craniospinal RT plus 1200-rad abdominal RT, 2400-rad craniospinal RT, or 2400-rad cranial RT plus i.t. MTX. There was no significant differences in marrow remission duration or survival of the treatment groups. There appears to be a benefit with regard to length of bone marrow remission and survival for patients with initial white blood counts greater than or equal to 20,000/cu mm treated with cranial RT plus i.t. MTX. The majority of the patients remaining on study have now discontinued maintenance therapy. The 8-year overall estimated survival rate on this study is 56%, and the disease-free survival rate is 52%.

Antineoplastic Agents↗

Declines in IQ scores and cognitive dysfunctions in children with acute lymphocytic leukaemia treated with cranial irradiation.

Intellectual and other neuropsychological dysfunctions have been observed in survivors of childhood acute lymphocytic leukaemia (ALL). The possible relationship of therapy to these dysfunctions was investigated in a prospective study of children with newly diagnosed ALL seen at the Children's Hospital of Philadelphia. They were evaluated with standardised intelligence tests during the first month of treatment and periodically thereafter. There were two therapy schedules--one using standard drugs for induction and maintenance, the other a more intensive schedule. Central-nervous-system prophylaxis (2400 rad cranial radiation and six doses of intrathecal methotrexate) was given to all. Significant reductions were found in overall IQ score for the majority of children, younger patients being most affected. More extensive testing of surviving children, with and without decline in IQ, all of whom were normal on the first test, revealed patterns of functional deficits and residual strengths that could not be characterised with IQ testing alone. These deficits, which could affect learning and academic performance, were not seen in six children studied years after receiving similar chemotherapy that included intrathecal and oral methotrexate but not cranial irradiation.

Adolescent↗

Treatment strategies for infants with malignant sacrococcygeal teratoma.

Twelve children with malignant sacrococcygeal teratoma containing embryonal carcinoma, were treated at the Children's Hospital of Philadelphia between 1971 and 1980. Their ages at diagnosis ranged from 2 days to 23 mo; 8 of the 12 (67%) were girls. Five of the 12 patients presented with localized tumors which were grossly completely excised. Four received no further therapy, and all 4 recurred with histologically documented embryonal carcinoma. Despite subsequent treatment with radiation therapy (RT) and chemotherapy (vincristine, actinomycin D, and cyclophosphamide, collectively called VAC, in all 4 plus adriamycin in 3, only 1 has survived free of disease, 8 yr from diagnosis. The other 3 died of tumor (2) or pneumonia after pulmonary RT (1). The fifth patient in this group received VAC with adriamycin (total dose, 350 mg/sq m) and died of autopsy-proven cardiotoxicity without tumor. The remaining 7 patients presented with either unresectable local tumor (3) or distant metastases (4). One of these 7 died 6 days after biopsy with massive liver metastases. The other 6 children were treated after operation with VAC (5) or vincristine and actinomycin D (1) chemotherapy, and 5 also received RT to the pelvis. One has survived free of disease at 6 yr after treatment with VAC and adriamycin and pelvic RT, but the other 5 died of tumor (2) or of pneumonia after pulmonary RT (3). Surgery alone is inadequate for successful management of children with malignant sacrococcygeal teratoma. Chemotherapy with VAC, with or without adriamycin, can be effective when combined with radiation, but fatal pulmonary toxicity can result from such combined therapy. The optimal therapeutic program for children with malignant sacrococcygeal teratoma is still evolving.

Coccyx↗

Improved relapse-free survival in medulloblastoma utilizing modern techniques.

Between 1969 and 1979, 22 patients with medulloblastoma were treated by the same surgical group and radiation therapy group. The patients were divided into two groups because of the clinical availability in December 1974 of the computed tomographic (CT) scanner and of the operating microscope used in the initial surgical procedure. There were 11 patients in each group. The percentage of patients with a relapse-free survival in the group treated between 1969 and 1974 (Group 1) was 38% at 4 years. The survival in the 11 patients treated between 1974 and 1979 (Group 2) was 84% at 4 years. This improvement is statistically significant (P less than or equal to 0.001). All patients received the same dose of radiation. Efforts to minimize the tumor burden by total surgical resection did not increase postoperative morbidity or mortality. These results are discussed, along with the relative impact of the CT scan, total resection at operation, and increased focus for radiation therapy on the improved outcome.

Cerebellar Neoplasms↗

Radiation therapy in the neonate.

Radiation therapy (RT) is frequently used in the management of children with cancer, but neonatal neoplasms are rare. Newborns represent 1.5% of the children with malignant diseases in the Tumor Registry at the Children's Hospital of Philadelphia over the last 30 years. Thus, occasionally the pediatrics radiation therapist must consider treating the very young infant. The specific radiation effects on growth and development must be weighed in reaching a therapeutic decision. All children are vulnerable to the late effects of radiation therapy, but the neonates may be more susceptible because of the immaturity of important organs such as the brain, lung, liver, kidney, and bone. In general, radiation therapy, should be avoided during the first several weeks of life because of the potential increased sensitivity of the liver and kidneys during that period. If radiation therapy is used at all during infancy, the benefits must be weighed against the possibility of significant late effects. Increasing knowledge of pediatric neoplasms has shown that some tumors (such as mesoblastic nephroma) require no treatment except for surgical excision; and other tumors, such as Stage IV-S neuroblastoma, may require very little treatment. In those tumors that require radiation therapy, the use of chemotherapy may allow reduction of the radiation dose. Furthermore, alterations of time-dose-fractionation schemes and careful attention to tumor volume with the use of special techniques, such as "shrinking fields," may decrease the late adverse effects of treatment.

Brain↗

Pediatric brain stem gliomas.

Sixty-two pediatric patients with brain stem glioma diagnosed between 1964 and 1978 have been reviewed. Posterior fossa eploration was performed on 53% of the patients. Pathology was obtained by biopsy in 58% of those explored. Fifty-four patients had definitive radiation therapy with a median dose of 5000 rads. The actuarial five-year survival for the entire group is 30%. A pathologic diagnosis was available from necropsy or biopsy on 36 of the 62 patients. One-half had malignant tumors, and none survived more than 16 months. The remaining patients with well-differentiated gliomas had five-year actuarial survival of 55%. The use of computed tomography (CT) has been found to be valuable in diagnosis and follow-up, as well as in the design of radiation therapy portals. The data demonstrate no dose response curve. We recommend local radiation therapy of 5000 to 5500 rads to the tumor area as defined by CT.

Actuarial Analysis↗

Computed tomography of brain stem gliomas in children.

In 24 CT studies in children with brain stem gliomas, the CT appearance was seen to vary with the tumor's physical characteristics. Infiltrative tumors produce diffuse enlargement of the brain stem; they are isodense with brain parenchyma or of decreased density and may show partial enhancement. Some gliomas grow focally as an expansile mass or as a large exophytic lesion. These have heterogeneous density and show prominent enhancement. Early diagnosis depends on appreciation of displacement of the fourth ventricle and compression and distortion of the cisterns. The use of diagnostic studies and surgical and therapeutic results in the 24 cases are compared to 45 such cases diagnosed prior to the use of CT.

Adolescent↗

Treatment of advanced Hodgkin's disease in pediatric patients.

From 1970 to 1976, twenty patients with stage II E or II B to IV B Hodgkin's disease were treated at Children's Hospital of Philadelphia. Initially, four of the stage II or III patients received planned total nodal irradiation (TNI) alone; three patients developed progressive disease during irradiation, and one relapsed after 18 months. These results with TNI led to the use of combined modality therapy. Sixteen patients (4, stage II E or B; 8, stage III; 4, stage IV) were treated with COPP (cyclophosphamide, Oncovin, prednisone, and procarbazine) and radiation therapy. In 14 patients treatment was started with COPP. Patients with disease below L2 received TNI; the rest received involved field (IF) or extended field (EF) irradiation. No patient treated with combination therapy encountered life-threatening toxicity. Relapse-free survival in 12 stage II or III patients is 100% with a median follow-up of 28 months (range, 24 to 91 months). Only one of four stage IV patients is alive. Combined modality therapy is effective, tolerable therapy for children with stage II B--III Hodgkin's disease. No relapses occurred in 10 patients given less that potentially curative radiation. Smaller radiation fields and lower doses are planned for the future.

Adolescent↗

Radiation myelitis following craniospinal irradiation with concurrent actinomycin-D therapy.

Two patients are presented who developed radiation myelitis as a complication of treatment for medulloblastoma. These patients had been entered onto a pilot study to evaluate the therapeutic efficacy of combined treatment with radiation therapy and actinomycin-D (AMD). AMD is a known radiation enhancer in all tissues but the nervous system. Both of these patients received a full course of cranio-spinal irradiation plus AMD 15 mcg/kg for the first five days of therapy. One patient developed myelitis at 4 months, and the other at 12 months after treatment. Both patients are surviving three years posttreatment without any evidence of recurrent disease. The myelitis in one patient has improved, and it is stable in the other patient. It is concluded that AMD enhances the effect of radiation therapy on the central nervous system. This has never been reported but is important to note now, since radiation enhancers are included in multimodal treatment regimens for a variety of malifnant conditions. Reduction of radiation dose may be necessary when large volumes of the nervous system are treated.

Adolescent↗

Computed tomography of pediatric craniofacial sarcoma.

Review of the clinical and roentgenographic findings in 16 children with craniofacial sarcomas has revealed that CT is the most accurate method for delineation of the sarcomas and is indispensable for proper therapy planning and post therapy evaluation. The patients were examined and treated according to a protocol which required a CT examination before any type of therapy and after each mode of therapy, chemotherapy and radiotherapy. Chemotherapy alone was noted to produce marked reduction in tumor volume. The orbital sarcomas, which are most frequent, are small tumors without bone destruction. On the other hand, the nasopharyngeal, paranasal sinus and middle ear sarcomas are large tumors frequently associated with extensive bone destruction.

Adolescent↗