Persistent ethnicity-associated disparity in anti-tumor effectiveness of immune checkpoint inhibitors despite equal access.

We reviewed response to immune checkpoint inhibitors (ICI) of 207 patients with diagnoses of lung or head and neck cancer treated with chemotherapy/ICI combination therapy and ICI monotherapy between 2015 and 2020 at one of three clinical pavilions associated with the Dan L. Duncan Comprehensive Cancer Center at Baylor College of Medicine. Two of these pavilions (Harris Health System and the Michael E. DeBakey Veterans Affairs Medical Center) serve large minority populations and provide equal access to care regardless of means. 174 patients had a diagnosis of lung cancer (non-small cell or small cell) and 33 had a diagnosis of head and neck squamous cell carcinoma (HNSCC). 38% self-identified as Black, 45% as non-Hispanic White, and 18% as Hispanic. The objective response rate (ORR) was similar for lung cancer (35.057%) and HNSCC patients (30.3%) (p=0.894). The ORR for Hispanic and Black patients was lower compared to non-Hispanic White patients (H 27.0%, B 32.5%, W 38.7%; H vs. W p=0.209; B vs. W p=0.398). When considering only patients treated with ICI monotherapy, the ORR for Hispanic patients dropped further to 20.7% while the ORR of Black and non-Hispanic White patients remained about the same (B 29.3% and W 35.9%, H vs. W p=0.133; B vs. W p=0.419). Immune related adverse events were the lowest in the Hispanic population occurring in only 30% of patients compared to 40% of patients in the Black cohort and 50% of the non-Hispanic White cohorts.

Benefits and harms of CT screening for lung cancer: a systematic review.

CONTEXT: Lung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer. OBJECTIVE: To conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline. DATA SOURCES: MEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012). STUDY SELECTION: Of 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation. DATA EXTRACTION: Critical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus. RESULTS: Three randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare. CONCLUSION: Low-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.

High-dose fenretinide in oral leukoplakia.

We previously showed that low-dose fenretinide (200 mg/d) had limited activity in retinoid-resistant oral leukoplakia (34% response rate) possibly because serum drug levels were insufficient to induce retinoid receptor-independent apoptosis. Therefore, we designed the single-arm phase II trial reported here to investigate whether higher-dose fenretinide would improve leukoplakia response over that of our previous study. Leukoplakia patients received fenretinide (900 mg/m(2) twice daily) in four 3-week cycles (1 week on drug followed by 2 weeks off). At week 12, clinical responses were determined and blood samples were collected for serum drug level assessments. A planned interim futility analysis led to early trial closure after the initial 15 (of 25 planned) patients because only 3 (20%) had a partial response (stopping rule:

Randomized trial of adjuvant 13-cis-retinoic acid and interferon alfa for patients with aggressive skin squamous cell carcinoma.

PURPOSE: To conduct a phase III trial of adjuvant 13-cis-retinoic acid (13cRA) plus interferon alfa (IFN-alpha) for preventing tumor recurrence and second primary tumors (SPTs) of skin squamous cell carcinoma (SCC) among patients with aggressive skin SCC. PATIENTS AND METHODS: Sixty-six patients with aggressive skin SCC were randomly assigned to receive either 6 months of combined 13cRA (1 mg/kg/d orally) and IFN-alpha (3 x 10(6) U subcutaneously three times per week) or no adjuvant therapy (control group) after SCC surgery and/or radiation. RESULTS: At 21.5 months median follow-up, treatment did not improve the time to tumor recurrence and SPT versus control (hazard ratio [HR], 1.13; 95% CI, 0.53 to 2.41), time to tumor recurrence (HR, 1.08; 95% CI, 0.43 to 2.72), or time to SPT (HR, 0.89; 95% CI, 0.27 to 2.93). Adjuvant 13cRA and IFN-alpha was moderately tolerable; 29% of patients in the treatment arm required dose reductions for grade 3 or 4 toxicities. CONCLUSION: Results of this phase III trial do not support 13cRA plus IFN-alpha for adjuvant therapy of aggressive skin SCC. With high rates of tumor recurrence and SPTs, patients with aggressive skin SCC continue to have an unmet medical need, with devastating mortality, morbidity, and financial consequences. Promising agents with preclinical and early clinical results relevant to aggressive skin SCC deserve a high priority for future clinical drug development.

Clinical model of lifetime cost of treating bladder cancer and associated complications.

OBJECTIVES: To estimate the lifetime cost of bladder cancer and the contribution of complications to the total costs. METHODS: We reviewed the medical records of a retrospective cohort of 208 patients with bladder cancer who registered at our comprehensive cancer center from 1991 to 1999. We multiplied the number of resources used during management of bladder cancer by their unit charges. We converted charges into costs using the Medicare cost-to-charge ratio and inflated these to 2005 U.S. dollars. We estimated future costs by creating two extreme hypothetical scenarios. In the best-case scenario, we assumed patients with superficial disease developed recurrences at the cohort's mean rate and that patients with muscle-invasive disease were disease free after definitive therapy. Survival was based on the U.S. life expectancy in both cases. In the worst-case scenario, we assumed patients with superficial disease developed muscle-invasive disease and that all patients subsequently died of bladder cancer. RESULTS: The average cost of bladder cancer was 65,158 dollars among the cohort patients. Sixty percent of this cost (39,393 dollars) was associated with surveillance and treatment of recurrences, and 30% (19,811 dollars) was attributable to complications. The lifetime cost of bladder cancer was lower for the worst-case scenario (99,270 dollars) than for the best-case scenario (120,684 dollars). However, a greater proportion of the costs were attributable to complications with the worst-case scenario (43%, 42,290 dollars) compared with the best (28%, 34,169 dollars). CONCLUSIONS: The management of bladder cancer and its associated complications results in a major economic burden. More cost-effective surveillance strategies and approaches for preventing complications are crucial to minimizing the disease's clinical and economic consequences.

Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group Study.

PURPOSE: Epidemiologic and clinical data suggest that selenium could prevent prostate cancer, but it has not been shown that supplemental selenium leads to an increased concentration of selenium in prostate tissue compared with adjacent tissue. EXPERIMENTAL DESIGN: We conducted a randomized, controlled, short-term trial of l-selenomethionine (SeMet) versus observation in men with organ-confined prostate cancer. The primary endpoint was the measurement of selenium concentration in prostate tissue and seminal vesicle (SV). We assessed baseline selenium levels in serum and in toenail specimens (reflecting long-term intake) and post-intervention selenium levels in serum, and in prostate and SV tissues using hydride generation atomic fluorescence spectroscopy. RESULTS: Sixty-six eligible patients were randomly assigned to the SeMet (n = 34) or observation (n = 32) arm; both arms had similar baseline patient characteristics. Baseline serum selenium was similar in the two groups (P = 0.64). Baseline toenail selenium levels were slightly higher in the SeMet group than in the control group (P = 0.07). After the intervention, the mean serum selenium level increased 15% in the SeMet arm and was higher than in the observation arm (P = 0.001). The selenium concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in the observation arm (n = 25; 1.80 versus 1.47 ppm; P = 0.003, Wilcoxon rank sum test) and remained significantly higher after adjusting for chronic selenium intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups (P = 0.384) and was lower than in prostate tissue. CONCLUSIONS: The present study is the first to show that selenium taken as oral supplementation accumulates preferentially in the human prostate gland as opposed to the SV. These findings support the hypothesis that oral selenium supplementation may contribute to the cancer preventive effects of selenium.

Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer.

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status.

COX-2 inhibitors and other nonsteroidal anti-inflammatory drugs in genitourinary cancer.

Selective cyclooxygenase (COX)-2-inhibiting and other nonsteroidal anti-inflammatory drugs (NSAIDs) show promise for preventing and treating bladder and prostate cancers. In contrast to the strong NSAID epidemiology in colorectal cancer, the epidemiologic data on NSAIDs and genitourinary (GU) cancers are limited and mixed. However, a substantial body of preclinical in vitro and in vivo animal model data shows consistent NSAID activity in treating, and in some cases preventing, GU cancers and begins to address the mechanisms behind this activity (eg, involving Akt and ERK2 in the prostate). Many preclinical and clinical NSAID studies currently under way are helping to resolve the best type (selective or nonselective COX inhibitors or non-COX inhibitors), dose and duration of NSAID treatment for prevention in the GU setting. Future studies likely will focus on clarifying the NSAID mechanisms behind and developing NSAID combinations for both treating and preventing GU cancers.