Classic Kaposi's sarcoma associated with human herpesvirus 8 infection in a 13-year-old male: a case report.

PURPOSE: Classic Kaposi's sarcoma (KS) is rare in children. Although its etiology is not fully understood, human herpesvirus 8 (HHV-8) is present in the angiogenic lesions. We report an HIV-negative, 13-year-old patient of Sicilian descent with HHV-8-associated classic KS to facilitate the diagnosis and treatment of this entity in children. EXPERIMENTAL DESIGN: DNA was extracted from the skin specimen of the patient and analyzed via PCR assay and Southern blot hybridization for HHV-8 DNA. The amplified HHV-8 DNA was cloned, sequenced, and compared with the prototype HHV-8-KS330/BAM. RESULTS: The patient presented with purpuric lesions on the distal lower extremities and the tip of his nose, associated with thrombocytopenia and leukopenia, suggesting an immune-mediated cytopenia. While on prednisone, he developed marked vascular proliferation in the groins. Biopsy of the skin lesions showed KS, and HHV-8 was detected in the tissues by PCR. Sequence analysis of the amplified DNA was homologous to the prototype HHV-8-KS330/BAM. His HHV-8 strain was the A subgroup, the type associated with Mediterranean classic KS. Stopping prednisone and treatment with IFN-alpha and IgG resulted in regression of the groin lesions. CONCLUSIONS: This report emphasizes the importance of recognizing classic KS in children and avoiding immunosuppressive therapies in indolent classic KS. The diagnostic and therapeutic strategies were effective and well tolerated.

Breast cancer occurred after treatment for Hodgkin's disease: analysis of 133 cases.

PURPOSE: To assess the clinical and histological characteristics of breast cancer (BC) occurring after Hodgkin's disease (HD) and give possible therapies and prevention methods. MATERIALS AND METHODS: In a retrospective multicentric analysis, 117 women and two men treated for HD subsequently developed 133 BCs. The median age at diagnosis of HD was 24 years. The HD stages were stage I in 25 cases (21%), stage II in 70 cases (59%), stage III in 13 cases (11%), stage IV in six cases (5%) and not specified in five cases (4%). Radiotherapy (RT) was used alone in 74 patients (63%) and combined modalities with chemotherapy (CT) was used in 43 patients (37%). RESULTS: BC occurred after a median interval of 16 years. TNM classification (UICC, 1978) showed 15 T0 (11.3%), 44 T1 (33.1%), 36 T2 (27.1%), nine T3 (6.7%), 15 T4 (11.3%) and 14 Tx (10.5%). Ductal infiltrating carcinoma and ductal carcinoma in situ (DCIS) represented 81.2 and 11.3% of the cases, respectively. Among the infiltrating carcinoma, the axillary involvement rate was 50%. Seventy-four tumours were treated by mastectomy without (67) or with (ten) RT. Forty-four tumours had lumpectomy without (12) or with (32) RT. Another four received RT alone, and one CT alone. Sixteen patients (12%) developed isolated local recurrence. Thirty-nine patients (31.7%) developed metastases and 34 died; 38 are in complete remission whereas five died of intercurrent disease. The 5-year disease-specific survival rate was 65.1%. The 5-year disease-specific survival rates for the pN0, pN1-3 and pN>3 groups were 91, 66 and 15%, respectively (P<0.0001), and 100, 88, and 64% for the TIS, T1 and T2. For the T3 and T4, the survival rates decreased sharply to 32 and 23%, respectively. These secondary BC are of two types: a large number of aggressive tumours with a very unfavourable prognosis (especially in the case of pN>3 and/or T3T4), and many tumours with a 'slow spreading' such as DCIS and microinvasive lesions. These lesions developed especially in patients treated exclusively by RT. CONCLUSIONS: The young women and girls treated for HD should be carefully monitored in the long-term by clinical examination, mammography and ultrasonography. We suggest that a baseline mammography is performed 5-8 years after supradiaphragmatic irradiation (complete mantle or involved field) in patients who were treated before 30 years of age. Subsequent mammographies should be performed every 2 years or each year, depending on the characteristics of the breast tissue (e.g. density) and especially in the case of an association with other BC risk factors. This screening seems of importance due to excellent prognosis in our T(1S)T(1) groups, and the possibility of offering these young women a conservative treatment.

Management of craniopharyngioma.

PURPOSE: The management of craniopharyngioma does not have a consensus. Extensive surgery may be associated with major complications. The purpose of this study was to evaluate local tumor control and survival after limited surgery and postoperative radiotherapy. METHODS AND MATERIALS: Thirty patients with craniopharyngioma were treated at SUNY Upstate Medical University in Syracuse, NY from 1967 to 2000. The group consisted of 13 males and 17 females, and the median age was 35 years. The median follow-up was 71 months. Only two patients underwent complete tumor resection. Eighteen patients underwent subtotal resection, and 10 underwent decompressive surgery (ventriculoperitoneal shunt or cyst aspiration). Most (20/ 28) patients who had less than total resection received immediate postoperative radiotherapy. Four patients received conventional radiotherapy for recurrence. Gamma knife radiosurgery was used as part of the primary treatment in two patients and at the time of local tumor recurrence in three patients. RESULTS: The local control rate, including after salvage treatment, was 91% and 83% at 5 and 10 years, respectively. Salvage was radiotherapy, gamma knife or surgery. Ultimate local tumor control appeared better for patients who underwent subtotal resection (100% and 89% at 5 and 10 years, respectively) than for those who did not undergo resection (61% and 61% at 5 and 10 years, respectively). The overall survival was 93% and 83% at 5 and 10 years, respectively. Two patients underwent gross total resection, and one patient experienced recurrence 6 years after the surgery and was treated by gamma knife radiosurgery. Both patients are well without recurrence at 3 and 7 years after the initial surgery. Survival also appeared to be improved for the group who underwent subtotal resection (100% and 90% at 5 and 10 years, respectively) versus those who did not undergo surgery (73% and 73% at 5 and 10 years, respectively). The dose of radiotherapy > or = 50 Gy had no impact on local control or survival. Ten patients experienced surgery-related complications, and five had radiotherapy-related complications, including visual, cranial nerve, motor, and endocrine deficits. CONCLUSION: The extent of surgery appears to be an important prognostic factor for predicting outcome, although this may represent selection bias. Long-term disease control is excellent after subtotal resection and postoperative radiotherapy. Encouraging initial results have been seen with gamma knife radiosurgery, and the potential for gamma knife radiosurgery to replace more extensive surgical resection should be further explored.

Aggressive radiotherapy adjuvant to peripheral blood stem cell transplant for relapsed Hodgkin's disease.

The role of radiotherapy in conjunction with high-dose chemotherapy and autologous bone marrow transplant for relapsed Hodgkin's disease remains to be clearly defined. Although there is substantial evidence that radiotherapy enhances local tumor control, prospective trials in the transplant setting have not been reported, and the potential toxicity of radiotherapy need to be considered. However, certain patients are at high risk of posttransplant tumor recurrence, most notably those with tumors unresponsive to pretransplant chemotherapy. We report the use of aggressive radiotherapy in three high-risk patients, including the first reported case of whole lung irradiation after a high-dose carmustine-based chemotherapy regimen. Two of these patients received repeat partial lung irradiation, including one patient with carmustine-related pulmonary toxicity. Radiotherapy (30-34.5 Gy; 1.5 Gy/fraction) was tolerated well without significant acute or late toxicity, and all patients remain disease free 40 to 62 months after irradiation without severe sequelae. We conclude that radiotherapy may be of benefit for patients at high risk of local tumor relapse, and should be considered in such cases despite potential toxicity.

Hematologic toxic reaction to radiation therapy adjuvant to autologous peripheral blood stem cell transplantation for recurrent or refractory Hodgkin disease.

PURPOSE: To evaluate the hematologic toxic reaction to external-beam radiation therapy after high-dose chemotherapy with peripheral blood stem cell (PBSC) support in patients with Hodgkin disease. MATERIALS AND METHODS: A retrospective study of 30 cases of Hodgkin disease in patients who underwent high-dose carmustine, etoposide, and cyclophosphamide chemotherapy with PBSC support was performed. Thirteen patients underwent radiation therapy (28.8-39.0 Gy) a median of 45 days after PBSC repeat infusion. RESULTS: Radiation therapy was delivered as planned, without interruption, in all patients. Five patients developed thrombocytopenia (one with grade 1 thrombocytopenia; two, grade 2; and two, grade 3) and included three with progressive disease prior to radiation therapy and two with a history of prior irradiation. None developed a bleeding complication or required transfusion support. Five patients who underwent irradiation had thrombocytopenia (three with grade 1 and two with grade 2) 100 days after PBSC repeat infusion, compared with three patients (two with grade 1 and one with grade 3) who did not undergo posttransplantation irradiation. At the most recent follow-up, no patient without evidence of disease had a platelet count of less than 100 x 10(9)/L. CONCLUSION: External-beam radiation therapy was well tolerated in the posttransplantation setting in patients with Hodgkin disease. Thrombocytopenia was common but was not related to clinical complications.

Resection and permanent I-125 brachytherapy without whole brain irradiation for solitary brain metastasis from non-small cell lung carcinoma.

We assessed a treatment plan of local therapy (resection and placement of permanent low dose-rate I-125 seeds) without whole brain irradiation in 15 patients with solitary brain metastasis (SBM) from primary non-small cell lung cancer between January, 1991 and May, 1996. Thirteen lesions were confirmed as solitary by MRI scan, and 2 patients had CT scan only. With median follow up of 14 months, 3 patients remain alive at 6, 33, and 62 months post-resection. Median survival is 14 months for all patients and 26 months for patients with SBM as the only site of disease. Five tumors failed in the brain: 2 solitary recurrences adjacent to the site of SBM, 2 multiple metastases outside the primary site, and 1 multiple recurrence including the primary site. No failures were seen with SBM <2.5 cm. Only 2 of 13 patients with SBM confirmed with MRI experienced relapses elsewhere in the brain. Recurrence rates both adjacent and outside the area of the initial brain lesion are similar to studies employing resection plus whole brain irradiation (WBI), and the patient is spared the acute and potential late toxicity of WBI. This approach may be considered for selected patients with solitary brain metastases (SBMs), although further experience with larger patient numbers is needed.

High-dose hemithorax irradiation in a patient with recurrent thymoma: a study of pulmonary and cardiac radiation tolerance.

Malignancy spread throughout a hemithorax without distant metastasis poses a difficult therapeutic challenge. Irradiation is often not considered because of the risk of pulmonary and cardiac toxicity. We report on a patient with thymoma recurrent throughout the left pleural cavity. Disease progressed despite chemotherapy, and subsequently a radical course of radiotherapy (6,600 cGy) was delivered to the entire hemithorax. Tumor regressed markedly by the completion of radiotherapy. Although tumor regrowth was noted 1 year after radiotherapy, the patient remained markedly improved symptomatically until shortly before her death 2 years after radiotherapy. Pulmonary function tests at 1 year (forced expiratory volume of the first second and forced vital capacity) were similar to pretreatment values, and cardiac function at 2 years remained essentially normal. High-dose hemithorax irradiation may be a consideration in select cases.

Phase II trial of weekly paclitaxel and concurrent radiation therapy for locally advanced non-small cell lung cancer.

We conducted a prospective Phase II study to determine the response rate, toxicity, and 2-year survival rate of concurrent weekly paclitaxel and radiation therapy (RT) for locally advanced unresectable non-small cell lung cancer. The weekly paclitaxel regimen was designed to optimize the radiosensitizing properties of paclitaxel. Thirty-three patients with unresectable stage IIIA and IIIB non-small cell lung cancer from six institutions were entered into the study between March 1994 and February 1995. Weekly i.v. paclitaxel (60 mg/m2; 3-h infusion) plus concurrent chest RT (60 Gy over 6 weeks) was delivered for 6 weeks. Twenty-nine patients were evaluable for response. Three patients achieved a complete response (10%), and 22 patients (76%) achieved a partial response, for an overall response rate of 86% (95% confidence interval, 68-96%). One patient progressed during the therapy, and three patients had stable disease. Esophagitis was the principal toxicity. Grade 3 or 4 esophagitis occurred in 11 patients (37%). One patient died of pneumonia after completion of therapy. Additional grade > or =3 toxicities included pneumonitis (12%) and neutropenia (6%). One patient had a grade 3 hypersensitivity reaction. The median overall survival duration for all 33 patients who entered the study was 20 months, and 1-, 2-, and 3-year overall survival rates were 60.6%, 33.3%, and 18.2%, respectively. The median progression-free survival duration for all 33 patients was 10.7 months, and 1-, 2-, and 3-year progression-free survival rates were 39.4%, 12.1%, and 6.1%, respectively. Weekly paclitaxel plus concurrent RT is a well-tolerated outpatient regimen. The survival outcome from this regimen is encouraging and seems to be at least equivalent to that of other chemotherapy/radiation trials. These findings warrant further clinical evaluation of weekly paclitaxel/RT in Phase II trials in the neoadjuvant setting and in combination with other cytotoxic agents.

The value of gallium imaging after therapy for Hodgkin's disease.

BACKGROUND: Although it is used widely, the value of gallium imaging in managing Hodgkin's disease remains unclear. METHODS: A retrospective review of gallium imaging and treatment outcome in 60 patients with Hodgkin's disease treated between January 1990 and July 1995 was conducted. The minimum follow-up was 1 year. RESULTS: Based on gallium imaging, 46 patients were in complete remission (CR) after initial treatment, 10 were in partial remission (PR), and 4 had persistent or progressive disease (NR). Ten of 29 patients (34%) with gallium CR after chemotherapy subsequently recurred, compared with no recurrences in 17 patients receiving initial radiotherapy or combined chemoradiation. Eight of ten patients received further therapy after gallium PR, and nine patients remained disease free at last follow-up. Survival did not differ in patients achieving a gallium CR or PR. CONCLUSIONS: Gallium-67 imaging may help confirm the presence of active Hodgkin's disease, but was unreliable in defining disease remission after chemotherapy in this study population. Patients with a gallium PR may still have a good prognosis after additional therapy.

Increased risk of breast cancer in splenectomized patients undergoing radiation therapy for Hodgkin's disease.

PURPOSE: Second malignancies have been reported among patients who were treated by radiation therapy or chemotherapy alone or in combination. Studies have implied an increased risk of breast cancer in women who received radiotherapy as part of their treatment for Hodgkin's disease. This review was performed to determine if there is an association between splenectomy and subsequent breast cancer. METHODS AND MATERIALS: One hundred and thirty-six female patients with histologically proven Hodgkin's disease were seen in the Division of Radiation Oncology between 1962 and 1985. All patients received mantle or mediastinal irradiation as part of their therapy. The risk of breast cancer was assessed and multiple linear regression analysis was performed on the following variables: patient age, stage, dose and extent of radiation field, time after completing radiation therapy, splenectomy, and chemotherapy. RESULTS: Breast cancer was observed in 11 of 74 splenectomized patients and in none of 62 patients not splenectomized. The mean follow-up was 13 years in splenectomized patients and 16 years, 7 months in nonsplenectomized patients. Nine patients developed invasive breast cancer and two developed ductal carcinoma in situ. Splenectomy was the only variable independently associated with an increased risk of breast cancer (p < 0.005) in multiple linear regression analysis; age, latency, and splenectomy considered together were also associated with an increased risk of breast cancer (p < 0.01). CONCLUSION: Our data show an increased risk of breast cancer in splenectomized patients who had treatment for Hodgkin's disease. A multiinstitutional survey may better define the influence of splenectomy relative to developing breast cancer in patients treated for Hodgkin's disease. The risk of breast cancer should be considered when recommending staging laparotomy, and we recommend close follow-up examination including routine mammograms for female patients successfully treated for Hodgkin's disease.