Thomas E. Goffman

Long-term follow-up on national cancer institute phase I/II study of glioblastoma multiforme treated with iododeoxyuridine and hyperfractionated irradiation

PURPOSEnWe report the results of the final phase I/II program in glioblastoma (GBM) multiforme patients using only hyperfractionated irradiation and intravenous iododeoxyuridine (IdUrd).nnnMETHODSnFor a decade we investigated halogenated pyrimidine radiosensitizers in an effort to exploit the potential for differential uptake of thymidine analogs between proliferating tumor and normal brain tissues. Trials began with bromodeoxyuridine (BrdUrd) but were changed to IdUrd when the latter proved less photosensitizing. A series of dose-escalating pilot trials led to treatment at a maximum-tolerated dose (MTD) of IdUrd of 1,000 mg/m2/d for two separate 14-day courses, one during the initial radiation field and one during the cone down. The radiotherapy also evolved over time and was hyperfractionated in all cases reported. Over 5 years we accrued 45 patients into the final hyperfractionated, 1,000 mg/m2/d scheme. We report here results on only the patients with minimum follow-up of 1 year (90% had at least 2 years of follow-up) or until death.nnnRESULTSnThe results do not indicate a significant benefit for use of sensitizers, as compared with other contemporary and aggressive types of radiation treatment. The median survival has been 11 months, with a 2-year actuarial survival of 9%. As yet, there are no survivors at 3 years. Tumor biopsies at craniotomy showed relatively low sensitizer incorporation.nnnCONCLUSIONnThe failure of radiosensitizers combined with radiation therapy to show major benefit may be due to patient selection but appears also to be related to the combined problems of poor drug penetration/uptake into tumor, tumor-cell heterogeneity, and a high inherent cellular radioresistance of GBM.

Persistent or recurrent acromegaly. Long-term endocrinologic efficacy and neurologic safety of postsurgical radiation therapy

As in other clinics, pituitary surgery was definitive treatment in less than 50% of cases of acromegaly treated at one institution over several decades. From 1965 to 1989, 24 acromegalic patients who had noncurative pituitary surgery received radiation therapy at the National Institutes of Health, with a basal human growth hormone level of greater than 5 ng/ml as the criterion for active disease. Using megavoltage irradiation, more than 60% of these patients stabilized at a normal hormonal range, and the overwhelming majority had decreasing growth hormone levels with time. No major side effects of irradiation were encountered except panhypopituitarism of varying degrees. The authors evolved a policy of surgery as the first option, followed by irradiation for patients with postoperative growth hormone levels more than 5 ng/ml.

Esophageal carcinoma following irradiation for breast cancer

A patient previously irradiated for inner‐quadrant breast cancer developed a midesophageal stricture that on repeated biopsies showed pathologic changes consistent with acute and chronic radiation injury. Eventually a focus of well‐differentiated esophageal carcinoma was found in the stricture. The patient was the second in a series of 20 patients treated at Georgetown University Hospital, Medical Oncology Division, 1973–1978, for esophageal cancer, who gave a history of previous irradiation for breast carcinoma. This finding led to the review of related case reports, follow‐up studies on irradiated spondylitic patients, and data from the Connecticut Tumor Registry on esophageal cancer following breast carcinoma. These data suggest that the modest increase in risk for esophageal cancer reported in studies of atomic bomb survivors is of clinical significance to patients receiving therapeutic radiation, and, that specifically, women irradiated for inner‐quadrant breast cancer, in which the dose of radiation to the esophagus can be large, may be at risk for subsequent esophageal carcinoma.

Intensity-Modulated Radiation Therapy

Abstract Goffman, T. E. and Glatstein, E., Intensity-Modulated Radiation Therapy. Radiat. Res. 158, 115–117 (2002). Intensity-modulated radiation therapy (IMRT) is an increasingly popular technical means of tightly focusing the radiation dose around a cancer. As with stereotactic radiotherapy, IMRT uses multiple fields and angles to converge on the target. The potential for total dose escalation and for escalation of daily fraction size to the gross cancer is exciting. The excitement, however, has greatly overshadowed a range of radiobiological and clinical concerns.

CNS lymphoma: back to the drawing board.

In this issue, Nelson et al. from the RTOG report on primary CNS lymphoma and show treatment results that can only be described as disheartening. They are of significant importance as they represent a sizable number of cases with good follow-up of approximately 44 years. Median survival was only 11.6 months from start of radiotherapy. Perhaps only the relative historic rarity of primary CNS lymphoma has kept us from acknowledging the extraordinary challenge this disease represents. For adults, offering a 10% 5-year survival is generous. Although a doseresponse appears to exist (2, 6), even at the upper end, local control is rarely durable. For other cancers of brain, such as high grade gliomas, we at least can find rationales for treatment failure: Workers have shown radioresistance in cell culture, increasing radioresistance with grade, and even variable radioresistance within the same tumor lines (4, 7, 8).

Renal Cell Carcinoma Causing a Selective Mineralocorticoid Insufficiency

AbstractWe report on a patient with metastatic renal cell carcinoma in whom adrenal insufficiency developed and initially was mistaken for the debility of advanced cancer. Laboratory data revealed a discrete mineralocorticoid deficiency. Autopsy documented replacement of the adrenal glands with metastatic carcinoma. The problem of adequately screening for mineralocorticoid as well as glucocorticoid insufficiency in cancer patients is discussed.