Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. MATERIALS AND METHODS: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. RESULTS: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. CONCLUSIONS: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Observation versus neck dissection for positron-emission tomography-negative lymphadenopathy after chemoradiotherapy.

OBJECTIVES/HYPOTHESIS: To analyze outcomes among patients with residual positron-emission tomography (PET)-negative lymphadenopathy after chemoradiotherapy for head and neck cancer based on whether or not they underwent neck dissection. STUDY DESIGN: Retrospective review. METHODS: Fifty-five patients with stage III/IV squamous cell carcinoma of the head and neck were identified with residual PET-negative lymphadenopathy based on standardized uptake value of <3. All patients had been treated with chemoradiotherapy to a median dose of 70 Gy (range, 60-4 Gy). RESULTS: With a median follow-up of 30 months (range, 6-67 months), the 3-year overall survival (85% vs. 81%, P = .57), progression-free survival (88% vs. 88%, P = .42), and local-regional control (96% vs. 100%, P = .68), did not differ between patients treated by neck dissection or observation. CONCLUSIONS: Omission of neck dissection appears to be reasonable for patients with residual lymphadenopathy but negative PET after chemoradiotherapy for head and neck cancer. LEVEL OF EVIDENCE: 4.

Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster.

The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds.

Rhodiola: a promising anti-aging Chinese herb.

Using the fruit fly, Drosophila melanogaster, we investigated the effects of Rhodiola on life-span. Rhodiola is a plant root used in traditional Chinese medicine that may increase an organism's resistance to stress. It has been proposed that Rhodiola can extend longevity and improve health span by alleviating oxidative stress. Rhodiola supplied every other day at 30 mg/mL significantly increased the lifespan of Drosophila melanogaster. When comparing the distribution of deaths between Rhodiola-supplemented and control flies, Rhodiola-fed flies exhibited decelerated aging. Although the observed extension in lifespan was associated with statistically insignificant reductions in fecundity, correcting for a possible dietary restriction effect still did not eliminate the difference between supplemented and control flies, nor does the effect of Rhodiola depend on dietary manipulation, strongly suggesting that Rhodiola is not a mere dietary restriction mimetic. Although this study does not reveal the causal mechanism behind the effect of Rhodiola, it does suggest that the supplement is worthy of continued investigation, unlike the other Chinese herbals, Lu Duo Wei (LDW), Bu Zhong Yi Qi Tang (BZYQT), San Zhi Pian (SZP, Three Imperial Mushrooms), Hong Jing Tian (Rhodiola) that were evaluated in this study.

Pioglitazone: an anti-diabetic compound with anti-aging properties.

Insulin and Insulin-Growth-Factor-like (IGF) signaling pathways are well known longevity pathways in nematodes, insects and mammals. To our knowledge, there are no systematic pharmacological studies evaluating the anti-aging properties of medications that target this pathway in Drosophila. Although there are no published data implicating an anti-aging role for these compounds in Drosophila, we hypothesized that their promising pharmacological profile might decrease mortality. However, the decrease in mortality could be due to a number of potential artifacts and confounds such as fecundity depression, decrease in metabolic rate, or CNS depression. Therefore, the mere finding that a compound decreases mortality does not qualify it as an anti-aging compound. In this study, we evaluated the anti-aging properties of four compounds that might target the insulin signaling pathway in Drosophila. Once it was established that the compound decreased mortality, we proceeded to evaluate possible confounding factors that could have contributed to the mortality reduction. We show that only piolglitazone displayed anti-aging properties. At present, we do not have a mechanistic explanation for this pharmacological disparity.