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Radiation Therapy for Malignancies in the Setting of HIV Disease

Radiation Therapy for Malignancies in the Setting of HIV Disease

The article by Dr. Swift provides an excellent, comprehensive review of malignancies in the setting of HIV and their management with radiation. It is important for clinicians to have an understanding of the current antiviral management of HIV disease, as well as its implications for patient longevity. This information, in the context of an individual patient's history, is crucial in determining whether treatment will be "palliative" or "curative," and therefore, which radiation dose/fractionation schedule will be employed. With improved antiviral therapies and increasing longevity, the late effects of radiotherapy, as well as recall phenomena (recurrent radiation effects), with the subsequent use of chemotherapeutic agents, must now be considered.

Experience With Radiotherapy at Saint Vincents Comprehensive Cancer Center

When my colleagues and I first published the 1990 USCF data on 187 patients with Kaposi's sarcoma (KS) treated with radiotherapy,[1] there was a strong rationale for using a single 8-Gy fraction as palliative treatment. With the introduction of newer antiviral therapies, and as mean CD4 counts rose and viral loads dropped, patients were living longer and appearing to tolerate radiotherapy better. Our current dose/fractionation schedule in New York City is now similar to that currently employed in San Francisco: 20 to 24 Gy in 8 to 12 fractions. We deliver three to four fractions per week, which allows for closer monitoring of possible acute reactions, although such reactions occur significantly less often than was noted 5 to 10 years ago.

As Dr. Swift points out, the mechanism for increased radiosensitivity has never been elucidated, although patients with lower viral loads and higher CD4 counts appear to be more tolerant of radiotherapy. In addition, many HIV-positive persons today are using high doses of oral antioxidants, including N-acetyl-l-cysteine (the glutathione precursor). It is interesting to speculate that these agents may afford a certain amount of radioprotection.

We recently contributed to a database of 163 patients with AIDS who were treated for primary central nervous system (CNS) lymphoma.[2] Recent analysis of the data for independent predictors of survival revealed that patients with a Karnofsky performance status more than 70, age less than 35 years, and higher total radiotherapy dose ( 39 or more Gy/10 fractions), had longer median survival times. Our current policy is to enroll as many of these patients as possible in the National Intergroup Trial or to treat the whole brain to 30 Gy in 10 fractions with a boost to the primary tumor.

Our experience with squamous cell carcinoma of the anus is similar to that reported by Dr. Swift. Our recent publication[3] revealed that, despite increased toxicity, all patients treated with combined-modality therapy were able to complete treatment, with seven of nine patients achieving a complete response and six of nine achieving durable disease-free survival.

We have a relatively large series of HIV-positive patients with squamous cell carcinoma of the head and neck. A recent review of 17 patients treated with surgery and/or radiotherapy revealed a 25% incidence of severe complications and a poorer-than-expected 1-year survival.[unpublished data] Of six patients with stage I or II laryngeal tumors treated with definitive radiotherapy (60 to 68 Gy), three had severe late complications, including laryngeal hemorrhage requiring total laryngectomy, chondronecrosis, and persistent glottic edema with airway compromise. Of five patients with locally advanced disease treated with radiotherapy, with or without chemotherapy, all experienced significant acute reactions, and only one survived 1 year. This patient subsequently developed a second primary lung cancer.

Impact of Protease Inhibitors and Combination Therapies

The introduction of protease inhibitors and combination therapies has led to a drastic decline in the number of HIV-related admissions to our hospital. The average daily census has decreased from 104 in 1995 to 79 in 1996 to an estimated 64 in 1997. Along with this decline in admissions, there has been a decrease in the number of outpatients with symptomatic KS referred for palliative radiotherapy.

The data in Table 1 show a break point in July 1996, when we began to notice a dramatic decrease in both AIDS admissions and KS referrals. This time point coincides with the introduction and increased use of the first three protease inhibitors on the market, which are clearly having an impact on the clinical course of the infection.

The dramatic decrease in the number of KS patients seen in our department has not yet been observed in HIV-positive people with other malignancies. It may be that there is a lag time effect and that the "prophylactic" effects of the new antiviral therapies will take longer to manifest in other solid tumors. As the "natural history" of HIV infection changes, so should the treatment approach with respect to management of malignant disease. Keeping up to date with the newest antiviral regimens will enable us to best serve our patients.

References

1. Berson AM, Quivey JM, Harris JW, et al: Radiation therapy for AIDS-related Kaposi's Sarcoma. Int J Radiat Oncol Biol Phys 19:569-575, 1990.

2. Corn BW, Donahue BR, Rosenstock JG, et al: Performance status and age as independent predictors of survival among AIDS patients with primary CNS lymphoma: A multivariate analysis of a multi-institutional experience. The Cancer Journal from Scientific American, 1997 (in press)

3. Chadha M, Rosenblatt EA, Malamud S, et al: Squamous-cell carcinoma of the anus in HIV-positive patients. Dis Colon Rectum 37(9):861-865, 1994.

 
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