Effective radiotherapy in palliating mammalgia associated with gynecomastia after DES therapy.

Between 1977 and 1986, 11 patients with painful gynecomastia after DES therapy were referred for palliative radiotherapy. The treatment regimens varied from 20 Gy in 5 fractions to 40 Gy in 20 fractions. All 11 patients had satisfactory pain relief on follow-up. All 7 patients who had more than 6 months follow-up had complete relief of mammalgia. The average interval between completion of radiotherapy to complete relief of mammalgia was 3.6 months. This study revealed that radiotherapy is highly effective in palliating mammalgia associated with gynecomastia after DES therapy in prostate cancer patients.

Cisplatin and 5-fluorouracil chemotherapy in advanced or recurrent squamous cell carcinoma of the head and neck.

Fifty-three patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with bolus cisplatin (CDDP) and 96-hour infusion of 5-fluorouracil (5-FU). Twenty-six patients with advanced disease (21 T4 and/or N3) and no prior therapy (NPT) received 2 to 3 cycles of chemotherapy prior to surgery and/or radiation. There were four complete responses (CR) and 12 partial responses (PR) to chemotherapy for an overall response rate of 61%. In 20 patients with locally recurrent or disseminated disease there was one CR and six PR for an overall response rate of 35%. All but one responding patient in both groups showed clear evidence of tumor response after the initial cycle of chemotherapy. Two of the five complete responders required at least three courses to achieve CR. Disease-free survival was poor: only five of 26 patients in the NPT group remain alive and free of disease 8 to 28 months from initial therapy. CDDP and 5-FU is an active combination for SCCHN, but survival benefit remains to be proven.

Differential cytotoxicity of cis-platinum and blenoxane against human carcinoma KBE cells in multicellular spheroids of different ages: response at different temperatures.

Human KBE epidermoid carcinoma cells were reproducibly grown in suspension as multicellular spheroids (MCS). Initial aggregation at 48 hours is followed by a rapid diameter increase until day 10. The size increase then continues with daily refeedings, under the growth conditions used, but at a slower rate. When cells are treated in MCS with either blenoxane (bleomycin) or cis-diamminedichloroplatinum (II) (cis-platinum), the survival of cells (by cloning efficiency (CE) essay) varied from that of surface attached (SA) cells. The survival was dependent on the age of the MCS as well as their size; the age response was significantly different for cis-platinum and blenoxane. Hyperthermic incubation of KBE cells in MCS at different ages for 1 hour (40-43 degrees C) resulted in cell killing similar to that observed after hyperthermic incubation of surface attached cells. In combined hyperthermia/chemotherapy experiments, simultaneous treatment with blenoxane resulted in little or no increase in MCS cell toxicity at 40 degrees C; at 42.5 degrees C, there was increased toxicity. The increase in toxicity was similar for MCS of different ages. Upon simultaneous cis-platinum treatment, an increase in toxicity was observed at 40 degrees C, but only in older MCS. At 42.5 degrees C, an increased toxicity (relative to treatment at 37 degrees C) was observed in MCS of all ages. These results are, in general, similar to those described for other in vitro and in vivo systems, but emphasize the differences in the survival response which can result for treatment of human cancer cells in MCS of different ages over even a small size range (up to 1 mm diameter). This is much smaller than clinically detectable tumors. This reproducible human cancer cell multicellular spheroid model has great potential for representing the variability likely to be present in micrometastases of different sizes, and in small regions of solid tumors, and therefore for assisting in preliminary evaluation of combined modality protocols.

Leg function after radiotherapy for Ewing's sarcoma.

Twenty-nine patients with Ewing's sarcoma of the lower extremity who survived for two or more years following therapy (5000 rad locally and systemic chemotherapy) were studied to assess functional status of the affected leg. Twenty-two of twenty-nine were alive and were reexamined; the deceased patients were evaluated by record review. Twenty-two of the twenty-nine had serial radiographs, which were reviewed to assess growth change induced by radiation. The living patients were divided on the basis of clinical examination into four functional groups with Group I comprising patients with minor functional limitations and leg length discrepancy 1.5 cm or less. Group II patients had moderate functional limitations with 2.5-cm leg-length discrepancy or less. Group III patients had severe functional limitations with up to 4-cm leg length discrepancy. Group IV patients had severe complications, sufficient enough to warrant amputation. Thirteen of twenty-two patients were classified as functional Group I, five as Group II, three as Group III, and one as Group IV. Radiographic changes in growing bone did not correlate with functional results. Although a femoral fracture and an age less than 16 years at diagnosis were found to be less favorable prognostic factors for the functional treatment result, these results show that neither femoral location nor young age justify primary amputation for Ewing's sarcoma of the lower leg extremity.

Ewing's sarcoma: an autopsy study.

An autopsy study of 26 cases of Ewing's sarcoma treated with radiation to the primary site plus adjuvant chemotherapy has shown metastatic tumor in 23 cases. Metastases were found typically in lungs, pleura, bones and regional lymph nodes. In three cases no tumor could be found at autopsy, and death was due to complications of treatment. Tumor was found in the irradiated primary site in 13 of the 20 cases in which the primary site was examined at autopsy. Histologically, the tumor at autopsy frequently had increased pleomorphism and increased numbers of bizarre giant cells; however, these changes did not affect the presence of glycogen in tumor cells, thus reaffirming the importance of intracytoplasmic glycogen in the diagnosis of Ewing's sarcoma.

Leukocyte migration inhibition in patients with Ewing's sarcoma by 3-M potassium chloride extracts of fresh and tissue-cultured Ewing's sarcomas.

Leukocyte migration inhibition (LMI) assays were performed to detect cell-mediated immune reactions against tumor-associated antigens (TAA) of Ewing's sarcoma. With the use of crude antigen preparations obtained by 3M KCl extractions of fresh Ewing's sarcoma or of tissue culture cells derived from a pleural effusion of a Ewing's sarcoma patient, assays were performed with leukocytes from these patients, patients with other cancers, and normal donors. The results demonstrated approximately 60% or greater positive LMI reactivity in Ewing's sarcoma patients, as compared to less than 10% reactivity of normal donors, with the use of extracts of either fresh or tissue-cultured Ewing's sarcoma cells. A lower proportion of positive reactivity was observed in patients with breast and lung cancer. Further specificity tests indicated that a smaller proportion of patients with Ewing's sarcoma had LMI reactivity with KCl extracts of tissue-cultured cells derived from breast cancer of fresh lung cancer cells than did patients with the homologous disease. The results indicate that many patients with Ewing's sarcoma have cell-mediated immunity toward TAA on Ewing's sarcomas. Inasmuch as all the LMI assay were performed with allogeneic extracts, the data also suggested that different Ewing's sarcomas possess common antigens and that some breast and lung cancers may share some TAA with Ewing's sarcoma.

Combined modality treatment of American Burkitt's lymphoma.

Fifteen American patients with Burkitt's lymphoma were treated in a clinical trial employing chemotherapy, radiotherapy, and immunotherapy. Two patients died during induction, and 13 achieved complete responses. Eight patients relapsed at a median of 11 weeks from initial treatment, and seven of these have died. The remaining patient has enjoyed a prolonged third remission following intensive chemotherapy and bone marrow autograft. Five patients remain in their first remission in excess of 1 year. The major therapeutic goal in the management of Burkitt's lymphoma is the prevention of relapse; the identification of risk factors and various strategies to achieve this goal are discussed.

Diagnosis of radiosensitive hypothalamic tumors without craniotomy: endocrine and neuroradiologic studies of intracranial atypical teratomas.

Three patients with intracranial atypical teratomas presented with symptoms of endocrine dysfunction (diabetes insipidus, hyperprolactinemia, and anterior hypopituitarism) suggestive of a hypothalamic disorder. Computer-assisted tomography done in two of the three cases enabled us to document the presence of a mass and institute radiotherapy, without prior neurosurgical exploration. Computer-assisted tomography also provided a safe and effective method of assessing the effects of radiotherapy.

Pretreatment serum lactate dehydrogenase predicting metastatic spread in Ewing's sarcoma.

We measured serum lactate dehydrogenase levels in 36 patients with localized Ewing's sarcoma before treatment. The results were evaluated to determine if the levels served as a prognostic indicator for metastatic spread. After adjusting for primary site of disease and adjuvant chemotherapy, the pretreatment serum lactate dehydrogenase proved an extremely good predictor of which patients would ultimately develop metastatic disease. The median serum lactate dehydrogenase of the total group was between 201 and 214 IU/litre. Three of 18 patients presenting with serum levels of this enzyme of less than or equal to 201 IU/litre ultimately developed metastases, while 16 of 18 patients who presented with serum levels of greater than or equal to 214 IU/litre developed metastases (P less than 0.001).

Combined modality therapy of Ewing's sarcoma.

Since 1964, 66 consecutive patients with Ewing's sarcoma have been treated at the National Cancer Institute with local irradiation of the primary site combined with adjuvant regimens of progressively more intensive systemic chemotherapy. Actuarial survival rates for the total series show a 56% 2-year and 35% 5-year survival. The 43 patients without clinically detectable metastases at diagnosis have 64% 2-year and 52% 5-year survival rates. The current protocol, alternating high-dose pulses of adriamycin and cyclophosphamide-vincristine, is providing improved disease-free survival as compared to previous protocols, and indicates further progress toward the ultimate goal of complete tumor eradication. In addition to the problems of diagnostic accuracy in evaluating treatment results, other major factors influencing prognosis include initial metastatic disease, site of the primary tumor, age at diagnosis, and presence of systemic symptoms. At least these, and probably others, must be taken into account in developing randomized prospective trials for determination of optimal adjuvant therapy.