Radiation Therapy for Malignancies in the Setting of HIV Disease

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

Experience With Radiotherapy at Saint Vincents Comprehensive CancerCenter

When my colleagues and I first published the 1990 USCF data on 187 patientswith Kaposi's sarcoma (KS) treated with radiotherapy,[1] there was a strongrationale for using a single 8-Gy fraction as palliative treatment. Withthe introduction of newer antiviral therapies, and as mean CD4 counts roseand viral loads dropped, patients were living longer and appearing to tolerateradiotherapy better. Our current dose/fractionation schedule in New YorkCity is now similar to that currently employed in San Francisco: 20 to24 Gy in 8 to 12 fractions. We deliver three to four fractions per week,which allows for closer monitoring of possible acute reactions, althoughsuch reactions occur significantly less often than was noted 5 to 10 yearsago.

As Dr. Swift points out, the mechanism for increased radiosensitivityhas never been elucidated, although patients with lower viral loads andhigher 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 interestingto speculate that these agents may afford a certain amount of radioprotection.

We recently contributed to a database of 163 patients with AIDS whowere treated for primary central nervous system (CNS) lymphoma.[2] Recentanalysis of the data for independent predictors of survival revealed thatpatients with a Karnofsky performance status more than 70, age less than35 years, and higher total radiotherapy dose ( 39 or more Gy/10 fractions),had longer median survival times. Our current policy is to enroll as manyof these patients as possible in the National Intergroup Trial or to treatthe 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 tothat reported by Dr. Swift. Our recent publication[3] revealed that, despiteincreased toxicity, all patients treated with combined-modality therapywere able to complete treatment, with seven of nine patients achievinga complete response and six of nine achieving durable disease-free survival.

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

Impact of Protease Inhibitors and Combination Therapies

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

The data in Table 1 show a break pointin July 1996, when we began to notice a dramatic decrease in both AIDSadmissions and KS referrals. This time point coincides with the introductionand 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 departmenthas 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 inother solid tumors. As the "natural history" of HIV infectionchanges, so should the treatment approach with respect to management ofmalignant disease. Keeping up to date with the newest antiviral regimenswill enable us to best serve our patients.

References:

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

2. Corn BW, Donahue BR, Rosenstock JG, et al: Performance status andage as independent predictors of survival among AIDS patients with primaryCNS 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 carcinomaof the anus in HIV-positive patients. Dis Colon Rectum 37(9):861-865, 1994.