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Biomedical subjects

P Littman

Publications and source records attributed to P Littman.

At least 19 recordsLinked to original sources
PubMed1990

Day 7 marrow response and outcome for children with acute lymphoblastic leukemia and unfavorable presenting features.

The percent of marrow blasts on day 7 of therapy was determined for 128 children with previously untreated acute lymphoblastic leukemia and white blood count (WBC) greater than or equal to 50,000/microliters and/or lymphomatous features enrolled in the Childrens Cancer Study Group trial of the Berlin Frankfurt Munster 76/79 regimen (CCG-193P). Patients received four-drug induction therapy including vincristine, prednisone, l-asparaginase, and daunomycin. Ninety-seven patients had fewer than 25% marrow blasts on day 7. Of these, 94 survived and maintained remission through day 28 and were designated early responders. Thirty-one patients had greater than 25% marrow blasts on day 7. Of these, 28 survived and achieved remission on day 28 and were designated late responders. The outcome of patients who underwent a day 7 marrow aspiration was similar to those who did not. Early responders had a 77.4% +/- 4.5% (standard deviation) 3-year estimated disease free survival, while late responders had 47.3% +/- 9.8% (P less than 0.001). Early responders had a superior outcome both in the subset with an initial WBC less than 50,000/microliters (P = 0.025) and in the subset with a WBC greater than or equal to 50,000/microliters (P = 0.01). The day 7 marrow response had prognostic value in this population of children with unfavorable presenting features who received four-drug remission induction therapy.

Adolescent↗
PubMed1988

A comparison of preoperative radiotherapy regimens for bladder carcinoma. The University of Pennsylvania experience.

Between 1976 and 1985, 155 patients from the Hospital of the University of Pennsylvania, the Philadelphia Veterans Administration Hospital, and the Fox Chase Cancer Center were divided into groups, each of which was treated with one of three preoperative radiotherapy regimens to be followed by cystectomy. Patients initially were treated with 4000 cGy during 4 weeks followed by cystectomy (16 patients). Beginning in 1978, patients received 2000 cGy in 1 week prior to surgery (70 patients). Since 1982, 40 patients were treated with 500 cGy on the day prior to surgery with postoperative radiation therapy reserved for patients with either involved margins of resection, advanced stage or high grade. A fourth group of 20 patients was either not offered or refused preoperative radiation. Nine patients received only postoperative radiation therapy. The 5-year actuarial disease-free survival for pathologic Stages B2, C, and D lesions (T3-4, N0-2), was 63% for those who had received high-dose radiation versus 21% for those that had low-dose or no radiation. Patients with advanced pathologic stage disease who had received greater than 2000 cGy had a reduced rate of local failure (11% versus 27% for those who had received less treatment). Patients with abnormal upper tracts as shown on the intravenous pyelograms (IVP) had a reduced 5-year determinate survival of 23% versus 65% for patients with normal upper tracts. This condition did not independently affect survival, but rather reflected advanced stage. Patients with abnormal creatinine levels had a decreased survival that was independent of stage. Computed tomography was found to have low sensitivity for determining extravesical extension (39%) and metastatic lymphadenopathy (12%). Patients with clinical Stage B2 and C disease (T3) that were downstaged had a 63% 5-year survival versus 18% of those that were not downstaged. The incidence of both ureteroenteral strictures and stomal complications was found to be higher in the 2000 cGy group than in those patients treated with the other regimens. The overall incidence of complications in that group was also significantly greater. We conclude that there is a continuing role for adjuvant radiotherapy in invasive bladder carcinoma to improve both pelvic control and survival. The 500 cGy radiotherapy "sandwich" regimen was equal in terms of pelvic control and survival to the other regimens and showed less overall morbidity. The 2000 cGy regimen was associated with the greatest incidence of morbidity and did not substantially improve pelvic control.

Aged↗
PubMed1988

Interstitial radiation therapy in the treatment of childhood soft-tissue sarcomas.

Between 1971 and 1985, 12 children and adolescents aged 0.7 to 19 years (median 4.7 years) with localized residual soft-tissue sarcomas (STS) underwent interstitial radiation therapy (IRT) at our institution. Eight received IRT as a component of initial therapy, and four were treated for recurrent or persistent disease. Tumor sites were head and neck (6), pelvis (4), extremity (1), and retroperitoneum (1). The radionuclides employed were Iridium-192 (9), Iodine-125 (2), and Californium-252 (1). The median prescribed dose in the Iridium-192 group was 3960 cGy (1955-7300). Seven of eight children receiving IRT during initial therapy have maintained local control, and six remain without evidence of disease for a median follow-up time of 5.8 years (2.0-16.0). One of the four patients treated for recurrent disease is free of disease after salvage surgery, and the other three are dead of disease. Multidisciplinary evaluation of the nine patients with more than 2 years of follow-up revealed functional and cosmetic effects of IRT to be minimal. IRT can be an effective method of delivering high dose irradiation in childhood sarcomas while reducing the deleterious effects in adjacent normal tissues.

Adolescent↗
PubMed1988

Treatment of bladder cancer with interstitial iridium-192 implantation and external beam irradiation.

Although interstitial implantation of invasive carcinoma of the bladder has been shown to be an effective treatment in Europe, there has been little experience with this method in the U.S. During the past 6 years, 14 patients at the Hospital of the University of Pennsylvania with single bladder tumors less than 5 cm and no evidence of carcinoma in situ on random bladder biopsies have been treated by a combination of external beam radiation and iridium wire implant. The iridium wire is inserted by an afterloading technique following tumor exposure via suprapubic cystotomy. Following delivery of the prescribed dose, the sources are removed percutaneously. Three patients with recurrent or high grade T1 lesions and 11 patients with T2-T3A lesions have been treated. With a median follow-up of 22 months (range 17 to 65 months), 9 patients are currently NED, 4 patients have died of disease, and 1 patient has died of intercurrent disease. There have been two isolated bladder recurrences, both non-invasive, one having been treated with cystectomy and one being treated locally. In addition, one patient developed regional failure, two developed distant metastases only, and one developed local recurrence following distant failure. The 2-year actuarial local control rate is 84%, with an overall 2-year actuarial survival of 66%. Complications have been minimal. Bladder implantation by this method is technically simple and produces excellent local control with acceptable morbidity.

Adult↗
PubMed1987

Malignant ovarian tumors in children and adolescents.

Eighteen patients aged 4 to 18 years (median, 10 years) were treated at the Children's Cancer Research Center of The Children's Hospital of Philadelphia (CHP) from September 1973 to September 1983 for malignant ovarian tumors. The pathologic categories were endodermal sinus tumor (eight patients), embryonal carcinoma (three patients), pure dysgerminoma (three patients), adenocarcinoma (three patients), and malignant granulosa-cell tumor (one patient). In 1973 and 1975, respectively, two patients with endodermal sinus tumors were treated with surgical removal with or without radiation therapy (RT) and chemotherapy with vincristine (Vc) and actinomycin D+ cyclophosphamide + Adriamycin (Adria Laboratories, Columbus, OH) (ACAdr); both developed local recurrence within 12 months and died of tumor. Since 1977, four of six patients with endodermal sinus tumors have been managed successfully with surgery followed by chemotherapy with cisplatin (P), bleomycin (B), vinblastine (Vb), and ACAdr; none received RT. One died of recurrent tumor and the other died of congestive heart failure attributed to Adriamycin (Adr). All three patients with embryonal carcinoma were well after surgical excision alone (one patient) or surgery and chemotherapy with cisplatin + bleomycin + vinblastine (PBVb) + ACAdr (two patients). Treatment of the remaining seven patients included excision alone (two patients) or excision and chemotherapy (five patients) with various combinations of Vc, ACAdr, and P. One patient with granulosa-theca cell tumor also received whole abdominal RT (3000 rad by external beam), and died of congestive heart failure attributed to Adr. The other six children were free of detectable tumor 16 months to 8 years from diagnosis. Chemotherapy with PBVb and actinomycin D + cyclophosphamide (AC) should be used in the postoperative management of young persons with malignant ovarian tumors. Adr is of doubtful value and may be considerably toxic. RT is of limited use and usually is not indicated.

Adenocarcinoma↗
PubMed1987

Treatment of children with neurogenic sarcoma. Experience at the Children's Hospital of Philadelphia, 1958-1984.

Twenty-four children aged 3 months to 18 years (median, 12 years) were treated for neurogenic sarcoma at the Children's Hospital of Philadelphia Cancer Research Center from 1958 through 1984. Sixteen patients had neurofibromatosis (NF). The tumors arose in an extremity or in the trunk (15 patients), the retroperitoneum-pelvis (6), or other sites (3). Twelve children underwent grossly complete excision of localized sarcoma; of them, five had no known residual tumor and seven had proven microscopic residual disease. Ten of the remaining 12 patients had grossly visible, residual localized disease, and two had lung metastases. After operation, nine were treated on a protocol with local radiation therapy (4000-6000 rad) plus vincristine, actinomycin D, and cyclophosphamide with or without Adriamycin (doxorubicin). The other 15 were treated variably. At 3 years, the proportion of tumor-free survivors was 9 of 24 (37.5%). The significant favorable factors were the initial surgical removal of all gross tumor (9 of 12 with tumor excision were tumor-free survivors at 3 years compared to none of 12 with gross residual sarcoma; P less than 0.01), and a tumor mitotic rate under one per high-power field. No significant correlation was found between tumor-free survival expectancy and age, race, sex, the presence of NF, the site and size of the primary tumor, or use of the chemoradiotherapy regimen. More effective treatment programs are needed for children with neurogenic sarcoma, especially for those with unresectable tumors.

Adolescent↗
PubMed1987

Central nervous system (CNS) prophylaxis in children with low risk acute lymphoblastic leukemia (ALL).

Five hundred four children with low risk acute lymphocytic leukemia (previously untreated, age 3 to 6 years with white blood counts less than 10,000/mm3 at diagnosis) were randomized into two different central nervous system prophylaxis regimens. One regimen (250 patients) consisted of cranial radiation and intrathecal methotrexate (IT MTX). The second regimen (254 patients) consisted of IT MTX only. Median follow-up time for surviving patients is currently 54 months from randomization. Life table analysis of central nervous relapse, marrow relapse, disease-free survival, and survival shows very similar outcome for both treatment groups. The results indicate that maintenance IT MTX as described in this report can be substituted for cranial radiation in children with low risk ALL.

Central Nervous System↗
PubMed1987

Nonsurgical management of children with recurrent or unresectable fibromatosis.

At The Children's Hospital of Philadelphia, since 1971, six children 3 months to 17 years of age with fibromatosis have been treated with a combination of vincristine, actinomycin D, and cyclophosphamide (VAC). The first three patients also received radiation therapy (5,500 rads). Locally recurrent tumors developed in four of the children after previous operative removal; the other two had tumors that could not be removed initially. The tumors arose in the neck (three patients), pelvis (two patients), or foot (one patient). In the three patients treated with VAC alone, complete disappearance of tumor was confirmed at second operation in two, and greater than 75% shrinkage on CT scans occurred in the third, all at 4 to 6 months after VAC was started. In two of the three patients who received VAC plus radiation therapy, complete disappearance of tumor occurred at 13 and 16 months; the third had no response. Five of the six patients are free of recurrent fibromatosis at 1, 2, 4, and 11 years after VAC was begun; the sixth has required multiple operations during the last 6 years. We conclude that combination chemotherapy with VAC can produce regression of fibromatosis in some children with recurrent or unresectable lesions. The administration of VAC should be considered for children with fibromatosis in whom operative removal is not feasible, would prove mutilating, or is unlikely to produce long-term control of the disease.

Adolescent↗
PubMed1986

Malignant fibrous histiocytoma of soft tissue in childhood.

Seven children aged 6 months to 11 years with malignant fibrous histiocytoma, a type of sarcoma of soft tissues, have been treated at the Children's Hospital of Philadelphia from January 1975 through July 1983. The primary tumor arose in the head and neck region in three patients, the chest wall in two patients and the pelvis or buttock in one patient each. Operative management consisted of complete tumor removal in the two patients with chest wall tumors, and biopsy only in the remaining five children. Afterward, all seven patients were treated with a multiple-agent chemotherapy program consisting of vincristine, dactinomycin, and cyclophosphamide for two years, with or without Adriamycin (doxorubicin). The five patients with residual tumor also received radiation therapy (RT) in doses of 1500 to 5500 rad. The two children with localized, completely excised sarcoma are continuously free of tumor at 1.4 and 9 years after initiation of treatment. Of the five with residual sarcoma, three had a complete response to radiation and chemotherapy, and two of them are free of recurrence at 4 and 5 years, respectively. In the three remaining children, the tumor spread regionally into the central nervous system or distantly into the lungs, subcutaneous tissues, and liver. Childhood malignant fibrous histiocytoma of soft tissue appears to be similar to childhood rhabdomyosarcoma in its modes of spread and response to management. Operative removal is the key to successful therapy. The roles of multiple-agent chemotherapy and RT remain to be defined. Adriamycin appears to be the most promising single agent. In the absence of concrete data, it seems prudent to follow the same guidelines for irradiation as those used for other soft tissue sarcomas of childhood.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature.

Twenty children with soft tissue sarcomas of the head and neck, treated at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania from 1972 to 1981, were evaluated for the late deleterious effects of treatment. All patients received radiation therapy and combination chemotherapy with vincristine, dactinomycin, and cyclophosphamide; certain patients also received Adriamycin (doxorubicin). All had ophthalmologic, otologic, growth, and cosmetic evaluations; 15 also had dental and maxillofacial examinations. The median age at diagnosis was 6 years (range, 7 months-13 years). Median follow-up from time of diagnosis was 5.5 years with a minimum of 3 years in all but four patients. The major problems encountered were related to the eyes (xerophthalmia and cataracts), ears (hearing loss), teeth (maleruption and caries), glandular structures (xerostomia, hypopituitarism), and development (craniofacial deformity). It is concluded that children treated for soft tissue sarcomas of the head and neck with combined modality therapy, including radiation enhancers, may show a variety of late treatment-related adversities. These children require close multidisciplinary follow-up for detection of late effects in order that appropriate prophylactic or symptomatic treatment can be instituted to minimize their consequences.

Adolescent↗
PubMed1986

Primary site as a prognostic variable for children with pelvic soft tissue sarcomas.

From 1974 to 1983 we treated 16 children between 1 and 16 years old for soft tissue sarcoma arising in the pelvis, bladder or prostate. An incisional biopsy was obtained in every patient. Each child then was treated with a combination chemotherapy program, incorporating vincristine, actinomycin D and cyclophosphamide with or without doxorubicin, cis-platinum and etoposide. Of the 16 patients 13 (81 per cent) also received radiation therapy. In 8 children with urinary obstruction or hematuria sarcomas arose in the bladder or bladder-prostate region, including 7 who had localized tumors and 1 who had lung metastases at diagnosis. The median tumor diameter in these patients was 5 cm. Of these 8 patients 3 eventually required total cystectomy and prostatectomy to eradicate persistent local tumor, and 6 are alive and remain free of recurrent sarcoma for 1 to 9 years after initiation of therapy. The 8 other children had a pelvic mass at diagnosis, which arose adjacent to but outside of the bladder or prostate, and 2 had lung metastases at diagnosis. The median tumor diameter in these patients was 15 cm. Only 3 of these 8 children are alive and remain free of sarcoma for 1 to 8 years after initiation of therapy. In only 1 of these children was complete tumor excision ever possible despite the use of local radiation therapy and aggressive chemotherapy. Sarcomas arising in the bladder-prostate region are found when relatively small, perhaps because they soon produce overt signs, and they appear to have a better prognosis than those arising in the retroperitoneum-pelvis outside the bladder. Better treatment strategies are needed for the latter group of tumors that often are locally uncontrollable.

Adolescent↗
PubMed1985

Oligodendroglioma of the posterior fossa in childhood.

Oligodendrogliomas are uncommon intracranial tumors of childhood, especially when these tumors arise in the posterior fossa. Oligodendrogliomas are usually treated with local radiation therapy. The authors report four children, median age 7.5 years, cared for over a 7-year period, who had oligodendrogliomas (all histologically malignant) of the cerebellar region. Three patients received local radiation therapy and all had recurrent disease at a median of 11 months posttreatment outside their radiation field; at the time of relapse, disease at the primary tumor site was stable. One child treated with craniospinal and local radiation therapy is disease-free 15 months after diagnosis. These results suggest that oligodendrogliomas of the posterior fossa should be considered potentially malignant lesions and treated with local plus presymptomatic craniospinal radiation therapy.

Adolescent↗
PubMed1985

Brain stem necrosis after preradiation high-dose methotrexate.

Both cranial radiation therapy (RT) and high-dose systemic methotrexate (MTX) are used to treat intracranial neoplasmas, but both may cause neurologic damage. MTX may be less neurotoxic if given before rather than after radiotherapy. We cared for a 5-year-old girl with a pineocytoma who had progressive brain stem dysfunction 4 months after MTX therapy, followed by local radiation therapy. CT studies were consistent with radiation necrosis that was confirmed at autopsy. MTX used in conjunction with cranial irradiation can result in severe neurotoxicity, even if the drug is given first.

Brain Diseases↗
PubMed1985

The role of surgery in localized neuroblastoma.

A 30-year experience with 83 patients, median age two years, with Children's Cancer Study Group (CCSG) Stages I, II, and III localized neuroblastoma was studied to determine factors that influence outcome. In addition, histology was reclassified in all patients based on the Shimada system, which is divided into five subtypes according to age and cytohistologic criteria. A multivariant survival analysis was carried out and patients were considered to have failed if they relapsed or died from any cause. Initial analysis determined that CCSG stage, Shimada histologic classification, and presence of disease in lymph nodes were statistically significant predictors of failure. Histology was the most important factor with Shimada subtypes 1, 2, and 4 having good outcome and 3 and 5 poor outcome. The latter three variables were combined to create four prognostic groups that had distinctly different rates of survival. Further analysis showed that after controlling for prognostic groups, extent of surgery was a statistically significant predictor. Patients who had more complete surgical resection had better disease-free survival.

Adolescent↗
PubMed1984

Intracranial embryonal cell carcinoma.

Intracranial embryonal cell carcinoma (ECC) is a germ cell tumor most frequently found in the pineal region. However, little is known about the incidence, pattern of growth, or response to treatment of ECC. Between 1975 and 1983, 16 consecutive patients younger than age 18 with tumors of the pineal region have had biopsies performed prior to treatment, and 5 (31%) have had primary intracranial ECC. One other child had ECC in the suprasellar region. The clinical, radiographic, and histologic features of the six patients with ECC are presented and contrasted with the findings in children with other pineal region neoplasms. Pathologic confirmation is necessary to distinguish ECC from other intracranial tumors. Three patients were treated with radiation therapy (RT) plus adjuvant chemotherapy; two patients were treated with chemotherapy followed by RT; and one was treated with RT only. All patients initially responded to therapy, but only one has survived for longer than 1 year. It is concluded that biopsy is necessary for the diagnosis of ECC; that ECC is more common than currently believed; and that current treatment for intracranial ECC is unsatisfactory. Biopsy of pineal region tumors is necessary if progress is to be made in their management.

Adolescent↗
PubMed1984

The somnolence syndrome in leukemic children following reduced daily dose fractions of cranial radiation.

A group of children with acute lymphocytic leukemia was studied to investigate if a reduction in daily dose fraction of cranial radiation would reduce the incidence of somnolence syndrome. Thirty-one evaluable patients received 100 rad X 18 cranial radiation therapy. Sixty-six similar evaluable patients were given 180 rad X 10. Both groups received the same chemotherapy including intrathecal methotrexate. Clinically detectable somnolence appeared in 58% of ech group without significant differences in the overall frequency or severity of somnolence (p greater than 0.5). This study failed to substantiate a radiation dose fraction size dependence for somnolence syndrome in children with acute lymphocytic leukemia.

Brain↗
PubMed1983

Management of Hodgkin's disease in children and adolescents.

Between 1970 and 1980, 66 children or adolescents with Hodgkin's disease were treated at the Children's Hospital of Philadelphia. Since 1977, prepubertal patients and postpubertal patients with Stage IIA massive mediastinal disease or Stage IIB-IVB disease were clinically staged and treated with six courses of chemotherapy and 2000 rad involved-field irradiation. Postpubertal patients with Stage IA or IIA disease were staged pathologically and treated with 3600-4400 rad extended-field irradiation. At four years, actuarial survival in 27 patients with Stage IA or IIA disease is 100%; relapse-free survival is 86% in 16 patients treated with combined modality and 70% in 11 patients treated with irradiation. Among 39 patients with Stage IIB-IVB disease, 34 received combined modality; at five years, survival is 86% and relapse-free survival is 60%. In the majority of cases relapses in patients treated with combined modality could be better explained by chemotherapy failure rather than by insufficient radiation. Clinical staging and combined modality therapy may offer advantages for prepubertal patients and those postpubertal patients at high risk of relapse when treated with irradiation alone. The complications of laparotomy and splenectomy are avoided; however, with 2000 rad and limited-field irradiation, hypothyroidism does occur and growth disturbances may appear.

Adolescent↗