Palliative treatment of epidemic Kaposi sarcoma of the feet.

Limited information is available in the medical literature on epidemic Kaposi sarcoma (EKS) of the foot. Patients with EKS of the foot can experience severe discomfort that makes it difficult to ambulate and even wear shoes. Between 1985 and 1996, 36 patients with EKS of the foot were treated with palliative intent. Most patients were referred for radiation therapy because of foot discomfort or marked difficulty with ambulation. From the pool of 36 patients, data were available at completion of treatment for 46 sites, and at 1 month for 44 sites. Morbidity was assessed for 35 sites. The median follow-up time for the 44 sites with at least 1 month follow-up was 8 months. The most frequently used regimen was a novel fractionation schedule of three fractions a week at 3.5 Gy/fx to a total dose of 21.0 Gy. The overall response rate and complete response rate for the 44 sites with at least 1 month follow-up were 91% and 80%, respectively. The 46 treated sites evaluated at the completion of treatment had a complete response rate of only 13% and an overall response rate of 63%. Of the 35 sites assessed for acute toxicity, 63% experienced discomfort related to the radiation therapy. This discomfort usually resolved without intervention within 2 weeks of completion of radiation therapy. For patients with and without a history of opportunistic infections, complete responses were observed in 8 of 12 sites (67%) and 25 of 27 sites (93%), respectively (p = 0.06). Radiation therapy for EKS of the foot yields excellent response rates, comparable with responses seen in other cutaneous sites with EKS. Appropriate patient education and support are needed because initial responses to radiation therapy are often disappointing and pedal discomfort can be exacerbated transiently. However, the discomfort resolves and complete response occurs in most patients. The 3.5-Gy triweekly fractionation schedule is a convenient and effective regimen and minimizes treatment visits for patients with ambulatory discomfort. A history of opportunistic infections appears to be a poor prognosticator of response to radiation treatments.

Tumor bed brachytherapy with a mesh template: an accessible alternative to intraoperative radiotherapy.

BACKGROUND AND OBJECTIVES: Locally advanced and recurrent malignancies often require adjuvant radiotherapy to achieve tumor control. We report our experience with a technique that uses an intraoperatively placed mesh template for the delivery of radiotherapy. METHODS: from 1988 to 1996, 14 patients were treated with tumor bed brachytherapy using this mesh technique. Sites of involvement included the head and neck region (n = 6), abdomen/pelvis (n = 4), retroperitoneum (n = 3), and the lower extremity (n = 1). During surgery, plastic catheters were evenly placed within a mesh template (Vicryl or Marlex), which was positioned in the tumor bed. The catheters were afterloaded with radioactive sources once the final pathology had been determined and the patient required limited nursing care. Radiation dose was titrated to the surgico-pathologic findings (e.g., margin status). RESULTS: All of the patients tolerated the procedure without experiencing acute or chronic sequelae. The median survival time was 13 months. Local control was achieved in 11 of 13 evaluable patients, with an actuarial local control of 82% at 6 months. CONCLUSION: Tumor bed brachytherapy with a mesh implant is a practical technique to improve tumor control and warrants further investigation.

Palliation of AIDS-related primary lymphoma of the brain: observations from a multi-institutional database.

PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. METHODS: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha-beta value of 10. RESULTS: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS > or = 70 vs. KPS < or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management program that includes cranial irradiation. Young patients with excellent performance status are most likely to respond to treatment. The delivery of higher biologically effective doses of irradiation also may increase the probability of achieving a palliative response.

Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: a multivariate analysis of a multi-institutional experience.

PURPOSE: There is limited information about the outcome of AIDS patients with primary central nervous system lymphoma treated with definitive irradiation. The purpose of this study was to determine factors associated with increased survival in such patients. METHODS: An analysis was performed of 163 patients with AIDS who were evaluated at nine urban hospitals. These patients were treated for primary central nervous system lymphoma after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (> 90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective dose according to the formula Gy10 = Total Dose x (1 + fractional dose/alpha-beta), using an alpha-beta of 10. RESULTS: Longer median survival times were associated with high Karnofsky performance status (KPS > or = 70 vs < or = 60: 181 vs 77 days), young age (< 35 vs > 35: 162 vs 61 days), and high total definitive irradiation doses (> 39 Gy10 vs < 39 Gy10: 162 vs 40 days). Tissue diagnosis, gender, race, number of lesions (solitary vs multiple), and the presence of other cancers did not influence outcome. In multivariate analysis, young age, high Karnofsky performance status, and the delivery of higher biologically effective doses of irradiation retained independent significance relative to the endpoint of survival. CONCLUSIONS: Even at urban tertiary medical centers, few AIDS patients with intracranial lesions undergo biopsies to establish a precise tissue diagnosis. Survival following definitive irradiation is strongly related to two pretreatment factors (young age, high performance status) and one treatment factor (total biologically effective dose of cranial radiotherapy). These variables should be considered in selecting patients for definitive irradiation and in designing future studies.

Treatment of chiasmatic/hypothalamic gliomas of childhood with chemotherapy: an update.

Chiasmatic/hypothalamic gliomas (CHG) of childhood may cause progressive neurological and visual deterioration. Radiotherapy results in at least transient stabilization of tumor growth in most patients but may also have adverse long-term effects, especially in young children. Since 1977, children with progressive CHG under 5 years of age at diagnosis have been treated with combination chemotherapy (actinomycin D and vincristine) without radiotherapy. Twenty-four patients, a median of 1.6 years of age at diagnosis, have been treated and followed for a median of 4.3 years (range, 0.3-10 years). All patients are alive. Nine have developed radiographic or clinical progression, occurring a median of 3 years (range, 2-6.5 years) after initiation of treatment. Fifteen of 24 (62.5%) have remained free of progressive disease and have received no other therapy. Tumor shrinkage was documented in 9 of 24 patients but did not clearly relate to long-term outcome. Full-scale intelligence quotient (IQ) obtained a median of 3.5 years after diagnosis in patients who received only chemotherapy was a mean of 103 (range 84-133). We conclude that chemotherapy can significantly delay the need for radiotherapy in children with CHG and such a delay may be beneficial regarding long-term outcome.

Chiasmatic optic glioma treated with chemotherapy. A preliminary report.

Chiasmatic optic glioma is a rare tumor with an erratic natural history, usually seen in young children. A prior study from this institution demonstrated that these lesions were frequently lethal, despite initial clinical stabilization following radiation therapy, and that visual, intellectual, and late endocrinological disabilities were prevalent. A novel approach was developed in 1977, when an initial clinical response to vincristine was recorded in a child with a recurrent optic glioma. Since then, all children with recurrent optic glioma and all children aged 6 years old and under with newly diagnosed optic glioma have been offered a program of initial therapy with vincristine and actinomycin D for six cycles over 18 months. The four children with recurrent tumor who were treated with that regimen remain clinically stable 13 to 115 months after chemotherapy. Twelve children (eight under 24 months old) with newly diagnosed optic glioma have been treated with this program, and three are still on therapy. Four developed progression while on therapy, and five remain stable from 1 to 60 months posttherapy. The four children who developed progressive disease have been treated with radiation therapy and remain stable. Six of the 12 children showed shrinkage of their tumor on computerized tomography while receiving chemotherapy. This program may serve as an alternative to initial radiation therapy in young children.

Syndrome of inappropriate antidiuretic hormone secretion. A complication of high-dose intravenous melphalan.

Melphalan is now being investigated as an intravenous (IV) bolus chemotherapeutic agent in children with resistant tumors involving the bone marrow. Two patients received 2 mg/kg melphalan, IV bolus; 10 patients received 1 mg/kg. Seven of the ten patients receiving 1 mg/kg had noticeable downward trends in the serum sodium concentrations, whereas both patients receiving 2 mg/kg developed hyponatremia (serum sodium concentration [SNa], mEq/l = 124-125) and inappropriate urinary sodium losses. Syndrome of inappropriate antidiuretic hormone (SiADH) is a previously unreported complication of high dose bolus melphalan therapy.

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.

Prognostic importance of cellular differentiation in medulloblastoma of childhood.

Medulloblastoma is the most common intracranial primitive neuroectodermal malignancy of childhood. Certain parameters are predictive of survival in children with medulloblastoma; however, tumor histology is of unclear prognostic value. A classification system, proposed by Rorke for all central nervous system (CNS) neoplasms composed of primitive neuroepithelial cells, was utilized in a review of 38 consecutive patients with newly diagnosed medulloblastoma. The classification is based on the concept that medulloblastoma is not unique to the cerebellum but is similar to tumors that may arise elsewhere in the CNS consequent to neoplastic transformation of primitive neuroepithelial cells. Cells forming the tumors may remain in the undifferentiated state or they may exhibit differentiation along glial, and/or ependymal, and/or neuronal lines. For purposes of simplification, the cases were divided into two major groups: those primitive neuroectodermal tumors (PNET's) which showed no evidence of cellular differentiation (PNET-U) and those that were differentiated (PNET-D). There were 20 cases in the PNET-U group and 18 in the PNET-D group. The 4-year survival rate was 70% for PNET-U, compared to 32% for PNET-D (p = 0.004). Only one of 10 children with PNET-D with differentiation along more than one cell line survived. Other factors, including age at diagnosis, tumor metastasis (TM) stage, and extent of surgical resection, were analyzed and were of prognostic importance; but histological features remained statistically significant within each subgroup.

Pineal region tumors of childhood.

The incidence, response to treatment, and outcome of children with pineal region neoplasms is poorly characterized. Since 1975, in one institution, 25 consecutive patients with pineal tumors have undergone biopsy prior to further treatment. This constituted 11% (25/234) of all brain neoplasms seen over this time period. Specific tumors diagnosed included pineal parenchymal tumors ( pineoblastomas , pineocytomas ) in eight patients (32%); germ cell tumors (embryonal cell carcinomas, teratomas, germinomas) in eight patients (32%); glial tumors (astrocytoma, ganglioglioma ) in eight patients (32%); and ganglioneuroblastoma in one patient (4%). Clinical parameters, computed tomographic findings and CSF markers (alphafetoprotein and human chorionic gonadotropin) were unreliable in discriminating between specific tumor types. Response to treatment and patterns of disease relapse were dependent on the type of tumor present. Five of eight children with pineal parenchymal tumors had disease recurrence, and in all leptomeningeal dissemination occurred prior to or concurrent with local relapse. Three of eight children with germ cell tumors and two of eight patients with glial tumors suffered a relapse; in all five children recurrence was initially local. Findings suggest that pineal region neoplasms are not infrequent in childhood; that these tumors vary greatly in histologic type; that contrary to other reports germinomas do not constitute the majority of pineal tumors; and that histologic confirmation is necessary prior to treatment for appropriate management.

Enhanced cis-platinum neurotoxicity in pediatric patients with brain tumors.

Eight children were treated with cis-platinum for recurrent brain tumor. Six of these children were fully evaluable. All received cis-platinum (total dose per course 60 to 120 mg/m2; up to three courses) by infusion with mannitol and hydration. All had received one or more courses of cranial irradiation. Five of the six patients had evidence of significant hearing loss after only one cycle of treatment. All six patients demonstrated significant audiometric or symptomatic hearing loss after a total dose of 110-120 mg/m2. In patients further challenged with cis-platinum hearing loss progressed significantly. Two patients developed profound deterioration in neurologic status within 72 h after infusion. These experiences suggest that Ototoxicity is accentuated in patients who have received cranial irradiation. Further treatment may lead to prohibitive hearing loss. Severe neurologic deterioration may occur secondary to drug infusion.

Chiasmatic gliomas of childhood. A reappraisal of natural history and effectiveness of cranial irradiation.

Disagreement exists concerning the natural history and treatment of chiasmatic gliomas (CG) of childhood. We reviewed our experience in 21 cases of surgically verified CG with a median age of 4 years at time of diagnosis, followed for a median of 5.3 years (range 3-14.8 years). Initial treatment included radiation therapy (RT) in 18 patients, chemotherapy in 2, and observation in 1. Disease recurrence, defined as progressive visual or neurological deterioration, was documented in 10 children (48%), occurring at a median of 6 years after diagnosis. 5-year actuarial survival was 89%, but fell to 60% by 10 years. Visual improvement after RT was uncommon, occurring once. Intellectual deficits were noted in 5 of 17 survivors. We compared our results to that of other patients reported and concluded that: (1) CG may act aggressively independent of their location in the visual pathway at time of diagnosis; (2) the beneficial effects of RT are difficult to document; (3) progressive disease may occur late in the course of illness, and (4) intellectual sequelae are common in long-term survivors.

Coexistence of myeloid and lymphoid neoplastic subpopulations in chronic myelogenous leukemia.

Serial cytogenetic studies have been performed on a child with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) and correlated with clinical, morphologic, and cytochemical data in an attempt to elucidate further the natural history of leukemia progression observed in this disease. Once the initial blast crisis had occurred, two genetically different leukemic clones of cells, one presumably having arisen from the other, coexisted throughout the remainder of the patient's course. The initial clone comprised differentiating myeloid cells, while the second clone appeared on morphologic and cytochemical grounds to be lymphoid and blastic. A dynamic equilibrium existed between these two populations of cells, with the balance altered by chemotherapy and/or other selective pressures. The leukemic progression demonstrated in this case is consistent with the concept of clonal evolution of malignant cell populations. In planning therapy, it may be necessary to consider each of these coexistent clones and their different therapeutic requirements.

Polycythemia vera in a child with acute lymphocytic leukemia.

A 10-year-old boy, who had been in an uninterrupted remission of acute lymphocytic leukemia (ALL) for six years, developed polycythemia vera (PV). One and a half months after detection of PV, he was found to have active leukemia. Both the polycythemia and leukemia receded with anti-leukemia therapy. Three possible explanations for the development of PV in a child with ALL are discussed: 1) PV was a part of his original ALL and recurred whtn patient relapsed. The PV phase was detected only during relapse because the patient was under close observation. 2) PV was a second neoplasm independent of ALL. 3) PV was part of a second leukemia which was different from the original leukemia; this new ALL was derived from a pluripotential cell line involving both erythroid and lymphoid elements. A precedent for this explanation has been observed in chronic myelogenous leukemia.

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.

Response to vincristine of recurrent brain tumors in children.

Seventeen children with clinical evidence of a recurrent brain tumor were treated with vincristine 1.5 mg/sq m weekly for 12 weeks with doses on alternate weeks thereafter. Eight of the 16 patients who received four or more doses of vincristine showed significant objective responses; these included patients with high-and low-grade astrocytomas and patients with medulloblastoma. Six of the eight who responded remained asymptomatic for more than 2 years. The toxicity encountered was minimal except for seizures possibly related to vincristine in three children, who were able to resume treatment. Vincristine therapy results in long-term regression in a wide variety of pediatric brain tumors and causes little or no toxicity.