Detection of enhanced neutrophil adhesion to parainfluenza-infected airway epithelial cells using a modified myeloperoxidase assay in a microtiter format.

Despite growing evidence that respiratory virus infections precipitate episodes of airway obstruction and airway hyper-responsiveness in young children and in asthma, little information is available on the mechanisms by which virus infections alter the airway physiology. Airway inflammatory changes (including influx of inflammatory cells such as neutrophils) have been described during episodes of airway hyper-responsiveness in both animal models and human subjects. Neutrophil damage to several cell types has been shown to require adhesion as a primary step. In order to examine the potential interactions between virus-infected airway epithelial cells and neutrophils, we have studied the ability of neutrophils to adhere to virus-infected airway epithelial cell cultures. Neutrophil adherence was determined indirectly, using myeloperoxidase as a marker for adherent neutrophils in an assay system described here. Airway epithelial cell cultures (both primary human tracheal epithelial cells, and two permanent cell lines, A549 and BEAS-2B) were grown in 96-well tissue culture plates and infected with human parainfluenza virus type 2. Infected airway epithelial cell cultures supported significantly enhanced levels of neutrophil adherence (up to 50-75% of neutrophils added to the wells) compared to uninfected control cultures. Moreover, this adherence occurred in a virus dose-dependent fashion, with increasing levels of adherence noted at increasing viral multiplicities of infection. The assay system described allows the detection of small numbers of adherent neutrophils (as few as 1000 neutrophils) in a 96-well format.

Spinal cord compression in widely metastatic Wilms' tumor. Paraplegia in two children with anaplastic Wilms' tumor.

Spinal cord compression in Wilms' tumor is a rare event, generally caused by invasion of the canal by paraspinal lesions or metastatically involved vertebral bodies. This case report reviews the clinical presentation, radiologic evaluation, and emergent therapy in two cases of spinal cord compromise involving patients with widely metastatic Wilms' tumor. One of these is the only known report of intradural metastasis in a child with this malignancy. Both cases illustrate the importance of anticipating and rapidly responding to neurologic complications that may arise in patients with aggressively metastatic Wilms' tumor.

CT-assisted assessment of bladder and rectum dose in gynecological implants.

Eight patients who received gynecological implants with Fletcher-Suit type applicators were involved in this study. An orthogonal pair of films and computed tomographic scans were obtained for each patient. In the CT study, judicious use of contrast materials and selective window and level settings permitted clear delineation of the bladder and the rectum boundaries relative to the implanted applicators. In comparison to reference organ doses derived from the orthogonal film pair method, the maximum organ doses estimated from the CT-assisted evaluation were considerably higher, by approximately twofold on the average. The differences between the values estimated from the two methods vary from patient to patient, being highly dependent on the individual anatomy and the geometry of the implanted sources. These preliminary results point to the inaccuracy of the conventional method of estimating organ doses. CT-assisted evaluation may be necessary to accurately calculate organ doses in gynecological applications.

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery: final report of an RTOG study.

This randomized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6-7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks (XRT + BCNU). One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks, radiation therapy to 60 Gy and BCNU (MISO + XRT + BCNU). Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics was comparable among the treatment groups. The median survival for XRT + BCNU was 55.0 weeks, and for MISO + XRT + BCNU 46.0 weeks (p = 0.35). With patients on a minimum dose of dexamethasone of 3 mg/d, misonidazole neurotoxicity included 8.8% peripheral neuropathy, 2.7% CNS toxicity, and a 0.68% ototoxicity. BCNU pulmonary toxicity occurred in 9.3% of patients who received 902-2062 mg/m2 of BCNU.

Psychological aspects of primary radiation therapy for breast carcinoma.

Fifty-one patients who received primary radiation therapy as an alternative to radical mastectomy for the treatment of early breast cancer were studied in depth. They chose radiation therapy to avoid the disfigurement, difficulty with emotional adjustment, and adverse effects on their sexual lives they anticipated from mastectomy. Most of these women (median age 49) were leading active sexual lives in which their breasts play an important role. Their breasts also played an important role in enabling them to feel feminine, attractive, and sexually desirable. Forty-three percent of the patients who had had suicidal ideation because of feelings about breast cancer no longer were troubled by suicidal thoughts after learning about primary radiation therapy and the fact that they would not have to have a mastectomy. Recent reports that radiation therapy causes more psychic distress than other forms of cancer treatment appear to be incorrect in this particular population.

A randomized comparison of misonidazole sensitized radiotherapy plus BCNU and radiotherapy plus BCNU for treatment of malignant glioma after surgery; preliminary results of an RTOG study.

A randomized prospective study was performed to evaluate misonidazole radiosensitized radiation therapy in the treatment of malignant glioma. The control arm, Group A, consisted of conventional radiation therapy (6000 cGy/6-7 weeks) to the whole brain plus BCNU (80 mg/m2 on day 3, 4, 5, and then repeated q 8 weeks for 2 years). The BCNU schedule was identical in both arms. In the experimental arm, Group B, misonidazole 2.5 gm/m2 was given once a week for six weeks, to a total dose of 15 gm/m2. It was given orally four hours prior to 400 cGy on Mondays. On Tuesdays, Thursdays and Fridays, 150 cGy was delivered to a total of 5100 cGy/6 weeks. An additional 900 cGy/5F/1 week was given without misonidazole. Patients were stratified according to the prognostic factors of age, performance status, and histology. Distribution of these characteristics among the treatment groups was comparable. As of March 1, 1982, 245 patients were randomized with follow-up information available on 202 patients. The median follow-up is 12 months (range 3-39 months). There is no significant difference in the survival of the two groups. The median survival for Group A was 12.6, and for Group B, 10.7 months. Misonidazole toxicity included an 11% peripheral neuropathy and a 3% central nervous system toxicity. BCNU toxicity included severe hematologic toxicity in 25%, including one death, and significant pulmonary toxicity in 6 out of 55 patients who received a minimum total dose of 960 mg/m2 of BCNU.

The effect of dose rate and adriamycin on the tolerance of thoracic radiation in mice.

Radiation damage to the lung may be a predisposing factor in the development of interstitial pneumonitis in patients undergoing total body radiation and subsequent bone marrow transplantation in the treatment of leukemia. Adriamycin has been used in conjunction with bone marrow transplantation, and has also been shown to interact with radiation. This experiment was designed to study the effects of pre-administration of adriamycin on the radiation tolerance of the lung and esophagus. Since total body radiation is usually administered at low dose rates in order to spare the gastrointestinal tract preferentially as compared to the bone marrow, we investigated whether such a dose rate effect was present for the lung and if so, whether this pulmonary and esophageal dose rate effect would be ameliorated by pre-treatment with adriamycin. Mice were irradiated at 5 rad; 15 rad or 70 rad per minute to the upper body, 24 hours or 7 days after adriamycin. Oral esophageal death occurred within one month; thus deaths within 30 days were ascribed to this mechanism. In comparison, deaths because of pulmonary toxicity occurred later. Those between 30 and 160 days were ascribed to this mechanism. In the absence of adriamycin, a dose rate effect was found for the lung and confirmed for the upper gastrointestinal tract. The dose of radiation necessary to give pulmonary and gastrointestinal toxicity was markedly reduced when adriamycin was administered 24 hours before radiation. If seven days were allowed between adriamycin and radiation there was still an effect seen only at the high dose rate for the esophagus while for the lung at the high dose rate and for both systems at low dose rate no significant drug effects were noted. The dose rate effect is still seen after the drug, but it is reduced. These studies indicate that adriamycin given shortly before can significantly increase the oral esophageal and pulmonary toxicity of radiation and can practically abrogate the sparing effect of dose rate. This must be considered when clinically using total body radiation and adriamycin in preparation for bone marrow transplantation.

Radiation therapy for soft tissue sarcoma.

Soft tissue sarcomas can be adequately treated with wide local excision and postoperative irradiation, rather than the amputation of the affected extremity. Local control and good function can be achieved in the great majority of patients treated with radiation therapy, with particularly good results (95% local control) obtained for lesions of the distal extremity i.e., below the elbow or knee. The most common site of failure is distant metastasis, and the outstanding prognostic indicator is histologic grade. Disease-free survival correlates strongly with grade, with 85%, 51%, and 17% 2-yr disease-free survival for grades 1, 2, and 3, respectively. Lymph node metastasis is an uncommon first site of failure, and prophylactic nodal irradiation or lymphadenectomy is not recommended. The value of chemotherapy or immunotherapy is not firmly established as far as enhancing local control. It is hoped that distant metastasis can be prevented by the use of such adjuvant therapy. Locally advanced, nonresectable sarcoma may be better treated with high linear energy transfer (LET) radiation, and promising results have been reported with fast neutron treatment.

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.

Results of total body irradiation in the treatment of advanced non-Hodgkin's lymphomas.

Total body irradiation (TBI) was used as primary therapy for 58 previously untreated patients with Stage III or IV non-Hodgkin's lymphoma (NHL). 150 rad was administered, with 15 rad fractions twice a week, with careful monitoring of hematologic status. Thrombocytopenia was the most frequent complication, which resolved in all except 4 patients. Survival at 8 years was 52%, with 14% relapse-free survival. Patients with nodular histology had a more favorable prognosis than those with diffuse histology (median relapse-free survival of 24 vs. 12 months). There were 2 cases of erythroleukemia, which occurred after combination chemotherapy was given for relapse. Though TBI can offer complete remission and extended survival in advanced NHL, most patients eventually relapse and it should not be considered as a curative mode of therapy.

The role of radiation therapy in the treatment of pediatric non-Hodgkin's lymphomas.

Between 1971 and 1976, 64 patients less than 18 years of age with non-Hodgkin's lymphoma were treated at Boston's Children's Hospital Medical Center-Joint Center for Radiation Therapy. A multimodality approach was used, consisting of radiation therapy (3500--4500 rad), surgery, and chemotherapy. Since 1973, all patients have received a regimen initially comprising Adriamycin, Prednisone, 6-Mercaptopurine, Vincristine, and L-Asparaginase. Methotrexate was substituted for Adriamycin following a cumulative total dose of 450 mg/m2. The 5-year actuarial survival for all patients was 61% while relapse-free survival was 54%. The actuarial and relapse-free survival for patients presenting with localized disease was 75% and 72%, respectively. Median follow-up was 40 months and all relapses occurred within 24 months of initial therapy. A multidisicplinary approach, such as the current regimen, offers a good prognosis for this disease.