Thomas Goffman

Topical application of nitroxide protects radiation-induced alopecia in guinea pigs

We have recently found that treatment of Chinese hamster V79 cells with the stable nitroxide radical TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) afforded significant protection against superoxide, hydrogen peroxide, and X-ray mediated cytotoxicity. Radiation-induced alopecia is a common radiotherapeutic problem. Topical application of TEMPOL was evaluated for possible protective effects against radiation-induced alopecia using guinea pig skin as a model. For single acute X-ray doses up to 30 Gy, TEMPOL, when topically applied 15 min prior to irradiation provided a marked increase in the rate and extent of new hair recovery when compared to untreated skin. TEMPOL was detected in treated skin specimens with electron paramagnetic resonance (EPR) spectroscopy. Similar measurements of blood samples failed to show any signal resulting from topical application, nor could TEMPOL be detected in brain tissue after application on the scalp. TEMPOL represents a new class of compounds with potential for selective cutaneous radioprotection without systemic absorption.

NATIONAL CANCER INSTITUTE (PHASE II) STUDY OF HIGH-GRADE GLIOMA TREATED WITH ACCELERATED HYPERFRACTIONATED RADIATION AND IODODEOXYURIDINE: RESULTS IN ANAPLASTIC ASTROCYTOMA

PURPOSE We report the outcome of a Phase II study of a cohort of patients with high-grade glioma treated with accelerated hyperfractionated radiation and the radiation sensitizer, iododeoxyuridine (IdUrd). METHODS AND MATERIALS Between January 1988 and December 1990, 39 consecutive patients with high-grade glioma were enrolled and treated on a Phase II protocol including hyperfractionated radiation and IdUrd. Thirty-two patients were male and seven were female. Age range was 19 to 71 years with a median age of 38 years. IdUrd (1000 mg/m2 per day) was administered in two separate 14-day courses, the first during the initial radiation field and the second during the final cone-down field. All patients were treated consistently with partial brain technique and received 1.5 Gy/fraction twice daily to a mean total dose of 71.25 Gy (range 66-72 Gy excluding one patient who did not complete treatment). The initial field was treated to 45 Gy followed by a cone-down field covering the tumor volume plus a 1-cm margin to the final dose. Patients were assessed for acute and long-term morbidity and followed for outcome. Two patients had biopsies during the course of treatment. Flow cytometry and high performance liquid chromatography was used to evaluate the labeling index and the percent replacement of IdUrd in the biopsy specimen. RESULTS Thirty-eight of 39 patients completed therapy. One patient died on treatment at 48 Gy and is included in the survival analysis. No patient was lost to follow-up. Twenty-one patients had Grade 3 (anaplastic astrocytoma) tumors and 18 patients had Grade 4 (glioblastoma multiforme). Median survival for the entire cohort was 23 months. For the glioblastoma multiforme patients, median survival was 15 months. The median survival of the anaplastic astrocytoma patients has not yet been reached. In the patients assessed, the range of IdUrd tumor cell incorporation was only 0-2.4%. CONCLUSION Accelerated hyperfractionated radiation therapy with IdUrd was administered with acceptable acute toxicity. The major acute side effects of mucositis and thrombocytopenia were related to IdUrd infusion and were dose-dependent. There were no unacceptable acute toxicities referable to the radiation as delivered. With a median potential follow-up of 51 months, the actuarial median survival of the glioblastoma multiforme patients is comparable with the best previously published reports. The outcome of patients with anaplastic astrocytoma compares very favorably with even the most aggressive multi-modality approaches in the recent literature with a minimum of acute morbidity.

The caucus race: Regionalism in the treatment of Hodgkin's disease

Patient and physician expectation is that Hodgkin’s disease is not only consistently curable but consistently treated. Unfortunately, neither hope is true. National, state, metropolitan, and institutional variations exist for the treatment of lymphoma, and there is no greater regionalism than in the radiotherapy of difficult subsets of Hodgkin’s disease. In fact, the main reason for confusion and controversy in the management of Hodgkin’s disease is precisely the fact that there are several alternatives, none of which is overwhelmingly superior. The comparison of results from different centers, with different treatment traditions, different historical results, different relations with medical and surgical colleagues, and different ancillary facilities, makes dictation of a “one and only” right way to treat Hodgkin’s disease presumptuous if not impossible. Two articles in this issue of the Journal highlight this issue. In a large series followed for more than a decade, Drs. Lee et al. confirm and extend earlier data from Stanford suggesting that more extensive irradiation is more effective for more aggressive disease (2). TN1 with liver irradiation in Stage IIIA and whole-lung irradiation in cases involving hila or large mediastinal disease appeared to improve relapse-free survival and ablate the need for chemotherapy up front. In a much smaller series, Drs. Hartsell et al. show results consistent with other centers of similar practice: that III Al disease can be frequently well-handled with mantle para-aortic therapy alone (1). Perhaps more specifically, for those who choose to subset by histology and splenic nodule number, patients with favorable histology“minimal” splenic disease-tend to have excellent diseasefree survival with radiotherapy alone. A logic for such treatment has been that more aggressive radiotherapy has conferred greater toxicity in some centers, especially when salvage chemotherapy has been required. Unstated in such regimens is that more advanced Stage III cases have not fared as well with radiation alone. Chemotherapy has been increasingly utilized. Although there are differences in the intensity and ingredients of chemotherapy regimens, these pale before the subtleties of schools of thought for Hodgkin’s disease radiotherapy. This should not be confused with inequities in training, but differing experience with outcome over several decades in differing institutions. We resemble a surgical more than a medical subspeciality. Uniformity of methodology presumes all science and no individuality; why should we ask it of our art? The long-term experience of Lee et al. is well documented but it also raises critical questions for those centers that plan on attempting treatment with irradiation alone in disease advanced by nature of stage or thoracic bulk. The Minnesota experience represents a large mature series in which the superiority of the more recent cohort (“radical radiotherapy”) may in part represent a number of confounding variables, including better imaging with CT and in turn better parenchymal, hilar. and mediastinal staging. In these later years in many centers, increasing numbers of patients with obvious massive mediastinal disease are pre-selected before radiotherapeutic consultation for combined modality therapy. Also, the complications in the later group may have yet to be fully ex-