Outcome analysis of HIV-positive patients with anal squamous cell carcinoma.

PURPOSE: With improved antiretroviral therapy, HIV-positive patients are achieving a longer life expectancy. An increased incidence of anal squamous cell carcinomas has been noted in these patients. The purpose of this study was to determine the outcome of HIV-positive patients with anal squamous cell carcinomas. METHODS: We conducted a review based on our tumor registry from 1980 through 1999. We identified 73 patients with anal squamous cell carcinoma treated at the University of Texas Southwestern Medical Center affiliated hospitals; 23 were HIV positive (18 had AIDS). In the HIV-positive group, 9 had in situ squamous carcinomas and 14 had invasive squamous cell carcinomas. Data collected included age, CD4 count, treatment, complications, and survival; these data were analyzed by Student's t-test. RESULTS: All patients were male. Those with squamous cell cancer of the anus were offered radiation therapy and chemotherapy. Beginning in 1998, all patients received highly active antiretroviral therapy before treatment. Seven of 14 anal squamous cell carcinoma patients had their therapy adjusted owing to toxicity. Morbidity included proctocolitis and diarrhea (n = 2) requiring diversion (n = 1), hemorrhagic cystitis (n = 1), neutropenic fever (n = 3), bone marrow suppression (n = 1), and urethral stricture (n = 1). Mean age was 42 years for anal squamous cell carcinoma patients and 36 years for squamous cell carcinoma in situ patients (P = 0.05). Mean CD4 count was 222 cells/ml in patients with infiltrating carcinoma and 200 in the in situ patients (P = NS). One-year and five-year mortality rates, respectively, were 40 percent and 80 percent for infiltrating carcinoma patients and 17 percent and 50 percent for the in situ patients. Both of the in situ patients who died had CD4 counts <20 cells/ml at diagnosis, whereas the rest had CD4 counts >100 cells/ml and are currently without anal disease. Mean CD4 count at diagnosis for all patients who died was 133 cells/ml, whereas for those surviving, it was 261 cells/ml (P = 0.03). Eight (all with infiltrating carcinoma) of the 10 patients who died had persistent anal disease, but none had metastasis. CONCLUSION: HIV-positive patients with in situ carcinomas present at an earlier age than those with infiltrating lesions. In situ patients with CD4 counts as low as 105 cells/ml do well with local excision. A low CD4 count at diagnosis without highly active antiretroviral therapy predicts a poor prognosis. Because these patients appear to succumb to their HIV status and not the anal disease, anal squamous cell carcinoma should be included with cervical squamous cell carcinoma as an AIDS-defining illness. HIV-positive patients, particularly AIDS patients, with invasive anal cancers and without effective antiretroviral therapy obtain little benefit and significant toxicity from current radiation therapy and chemotherapy. Initiation of highly active antiretroviral therapy in HIV-positive patients before radiation therapy and chemotherapy are begun may decrease toxicity and improve survival. Additional clinical trials are warranted to test this theory.

Relationship between colorectal cancer glutathione levels and patient survival: early results.

PURPOSE: Elevated glutathione is a cause of resistance to anticancer agents and x-rays. The purpose of this study was to determine the frequency and clinical significance of glutathione elevation in human colorectal cancer. METHODS: Glutathione levels were measured in 41 colon cancers, 24 rectal cancers, and corresponding normal tissues. The patients were then followed up prospectively for tumor recurrence and survival. Survival was analyzed by the Kaplan-Meir method and Cox proportional hazards regression. RESULTS: Glutathione levels in primary colorectal cancers were significantly higher than in the corresponding normal tissues. Elevated glutathione levels had a significant negative effect on survival in patients with colorectal cancer, whether based on the mean (P = 0.02) or median (P = 0.04) normal tissue levels. A negative effect of glutathione levels on survival was apparent in patients with colorectal cancer, whether or not they were treated with postoperative therapy. The larger the ratio of tumor glutathione to normal tissue glutathione, the poorer the prognosis. When adjusted for other covariates, glutathione was still a significant predictor of survival. CONCLUSIONS: An elevated tumor glutathione level at the time of diagnosis appears to confer a poor prognosis in patients with colorectal cancer. Longer-term study using a larger number of patients will be required to confirm these findings. Knowledge of tumor glutathione content may help identify patients requiring more intensive therapy.

Intratumor variability in prognostic indicators may be the cause of conflicting estimates of patient survival and response to therapy.

The DNA index, percentage of S-phase cells, proliferation fraction, and glutathione (GSH) content were determined at more than 1100 separate sites in 140 human tumors and 140 normal tissues. The study showed that the variability was so great from site to site within a tumor that there was only a 61% chance of identifying an aneuploid tumor clone (when present) if only a single site sample was analyzed for DNA content. Similar broad variability was observed in the percentage of S-phase cells, proliferation fraction, and glutathione content. Since these tumor characteristics are often used to predict the outcome of therapy and patient survival, the inaccuracy and underestimation of the test results may cause conflicting or erroneous predictions. The probability of finding an aneuploid clone or elevated percentage of S-phase cells proliferation fraction and GSH content increased dramatically as the number of sample sites studied per tumor was increased. Statistical analyses indicated that in order to achieve a 90% probability that the test results for these parameters were representative of the whole tumor: (a) all single site testing should be abandoned; (b) assays should be performed on samples taken from 3-7 different sites within each tumor; or (c) samples from each tumor should be pooled and the analyses run on a thoroughly mixed or homogenized aliquot of the multisite sample.