Unilateral conjunctival Classic Kaposi Sarcoma following a COVID 19 booster.

Purpose: We describe a case of Classic Kaposi's sarcoma in a functionally monocular patient following a COVID19 vaccine booster and provide compelling evidence that suggests the booster was a relevant co-factor in the initiation of the disease process. Observations: The patient presented with red, irritated conjunctival area described as "bubbling" in her right eye. While her past medical history includes hypercholesterolemia and hypertension, she had no history of a compromised immune system. Her ophthalmologic history is more complex including treatment for glaucoma. The patient has 20/20 uncorrected vision OD and LP OS. Due to her ocular co-morbidities, the patient initially received interferon alpha 2-B qid for 6 weeks. However, topical therapy failed to decrease the size of the conjunctival lesions. After referral to Radiation Oncology, the right eye/orbit was treated with electron beam therapy for 1 month which caused a marked decrease in the size and vascularity of the conjunctival lesions. A slow improvement continued during followup. Conclusion and importance: In that the vaccine booster preceded the cancer, it appears etiologic to the appearance of Kaposi's sarcoma. The patient's monocular vision and glaucoma complicated her treatment. This case expands on current concepts of cofactors needed for the development of Kaposi's sarcoma in that vaccine booster administration was relevant to tumor progression and both clinical and mechanistic evidence is presented to support this hypothesis.

Efficacy and Safety of Glembatumumab Vedotin in Patients With Advanced or Metastatic Squamous Cell Carcinoma of the Lung (PrECOG 0504).

INTRODUCTION: Glycoprotein NMB is a transmembrane protein linked with poor prognosis and is expressed in most squamous lung cancer. Glembatumumab vedotin is an antibody-drug conjugate targeting glycoprotein NMB, administered intravenously every 3 weeks in this phase 1 study to determine the safety, tolerability, and maximum tolerated dose in patients who had progressed on any number of previous therapies. RESULTS: A total of 13 patients were enrolled; adverse events (of any grade) including dyspnea, neutropenia, respiratory failure, anemia, increased aspartate transaminase/alanine transaminase, diarrhea, and hypophosphatemia were seen in 15% of patients. Grade 5 events included two cases of respiratory failure, either completely or partially attributed to cancer progression. The only other grade 5 event was "disease progression." The most common adverse events (23%) were decreased appetite, fatigue, rash, and weight loss.The median overall and progression-free survivals were 5.7 months (90% confidence interval: 2.5-16.8) and 2.5 months (90% confidence interval: 1.6-5.8) respectively. CONCLUSIONS: Glembatumumab vedotin exhibited no serious or unexpected toxicity in this heavily pretreated population, except those caused by disease progression. Modest anticancer activity was observed with a recommendation for a phase 2 dose of 1.9 mg/kg. This portion of the study was not undertaken owing to the company's decision to discontinue drug development.

Risk Stratification of Locally Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with Chemo-Radiotherapy: An Institutional Analysis.

BACKGROUND: The purpose of this study was to determine which factors predicted survival and to derive a risk prediction model for patients with locally advanced non-small cell lung cancer (NSCLC) receiving concurrent chemo-radiotherapy (cCRT). METHODS: This investigation included 149 patients with locally advanced NSCLC who were treated with cCRT at Stony Brook University Hospital between 2007 and 2015. A finite set of demographic, clinical, and treatment variables were evaluated as independent prognostic factors. Kaplan-Meier survival curves were generated, and log rank tests were used to evaluate difference in survival between groups. To derive a risk score for mortality, a machine learning approach was utilized. To maximize statistical power while examining replicability, the sample was split into discovery (n=99) and replication (n=50) subsamples. Elastic-net regression was used to identify a linear prediction model. Youden's index was used to identify appropriate cutoffs. Cox proportional hazards regression was used to examine mortality risk; model concordance and hazards ratios were reported. RESULTS: One-quarter of the patients survived for three years after initiation of cCRT. Prognostic factors for survival in the discovery group included age, sex, smoking status, albumin, histology, largest tumor size, number of nodal stations, stage, induction therapy, and radiation dose. The derived model had good risk predictive accuracy (C=0.70). Median survival time was shorter in the high-risk group (0.93 years) vs the low-risk group (2.40 years). Similar findings were noted in the replication sample with strong model accuracy (C=0.69) and median survival time of 0.93 years and 2.03 years for the high- and low-risk groups, respectively. CONCLUSION: This novel risk prediction model for overall survival in patients with stage III NSCLC highlights the importance of integrating patient, clinical, and treatment variables for accurately predicting outcomes. Clinicians can use this tool to make personalized treatment decisions for patients with locally advanced NSCLC treated with concurrent chemo-radiation.

Severe immune thrombocytopenia induced by a single dose of nivolumab in a patient with advanced non-small cell lung cancer.

Nivolumab-induced immune thrombocytopenia (ITP) is a rare process with few reported cases. We present a 67-year-old man with advanced non-small cell lung cancer who was hospitalized with severe thrombocytopenia. Physical exam was notable for petechiae across his chest and extremities as well as bullae in his oral cavity. The patient initially received high-dose glucocorticoids and intravenous immuno - globulin, but did not respond to treatment. He was then started on weekly rituximab and after three doses, there was complete resolution of his thrombocytopenia. Altogether, his presentation was an extreme case and rare side effect of immune checkpoint therapy, known as nivolumab-induced ITP. Diagnosis of nivolumab-induced ITP is challenging given the lack of specific testing and a wide differential diagnosis. There are few cases reporting severe ITP following nivolumab treatment. We highlight the importance of recognizing and treating this rare complication of immunotherapy.

Survival Outcomes Among Lung Cancer Patients Treated Using a Multidisciplinary Team Approach.

BACKGROUND: Evidence favoring a multidisciplinary team (MDT) approach in the treatment of lung cancer is scarce, especially in the United States. The purpose of the present investigation was to evaluate survival outcomes of lung cancer patients treated with an MDT compared with a traditional care model. PATIENTS AND METHODS: The Stony Brook Cancer Center Registry was used to identify all lung cancer cases diagnosed between 2002 and 2016. We compared survival outcomes among 1956 lung cancer patients participating in our institution's Lung Cancer Evaluation Center's (LCEC) MDT program and 2315 lung cancer patients receiving traditional care. Log-ranks tests were used to evaluate differences in the 1-, 3-, 5-, and 10-year survival outcomes between the 2 groups. To address inherent biases, Cox proportional hazard models were used to estimate the effects on survival outcomes and adjust for possible confounders. Propensity matching was also performed to account for the effects of selection bias. RESULTS: The 5-year survival rates in the propensity-matched sample were one third greater among LCEC patients compared with those receiving a traditional care approach (33.6% vs. 23.0%; P < .001). After adjusting for potential confounders in the multivariable propensity-matched analyses, the LCEC model demonstrated a significant beneficial effect on 5-year survival outcomes compared with the standard treatment model (hazard ratio, 0.65; 95% confidence interval, 0.54-0.77). CONCLUSION: The results of the present investigation suggest an improved survival benefit from usage of an MDT model versus a traditional care model in the treatment of lung cancer. Despite the use of sophisticated statistical methods to mitigate bias in a nonrandomized study, additional research is needed to determine the extent to which an MDT approach for lung cancer influences patient outcomes.

Five-Year Survival Among Stage IIIA Lung Cancer Patients Receiving Two Different Treatment Modalities.

BACKGROUND Five-year survival rates among stage IIIA lung cancer patients range between 2% and 15%, and there is currently no consensus regarding optimal treatment approaches for these patients. The current investigation evaluated survival outcomes among stage IIIA lung cancer patients receiving 2 different treatment modalities, neoadjuvant chemotherapy followed by resection versus chemoradiation alone. MATERIAL AND METHODS This retrospective study is based on 127 patients attending the Lung Cancer Evaluation Center at Stony Brook Cancer Center between 2002 and 2014. Patients were treated either with neoadjuvant chemotherapy followed by resection or a regimen of chemoradiation alone. Kaplan-Meier curves were used to compare survival outcomes between groups and Cox proportional hazard models were used to evaluate treatment effects on survival, while adjusting for possible confounders. RESULTS Approximately one-fourth (n=33) of patients received neoadjuvant chemotherapy followed by surgery, whereas 94 patients received definitive chemoradiation. Patients in the surgical group were found to be significantly younger than those receiving chemoradiation alone (60.1 vs. 67.9 years, respectively; p=0.001). Five-year survival among patients receiving preoperative chemotherapy followed by resection was significantly higher than that among patients receiving chemoradiation alone (63% vs. 19%, respectively; p<0.001), whereas the hazard ratio (HR) was 3-4 times greater in the latter group (HR=3.77, 95% confidence interval=1.87, 7.61). CONCLUSIONS Findings from this study indicate that preoperative chemotherapy followed by resection can improve survival outcomes for stage IIIA lung cancer patients compared with chemoradiation alone. The results reflect a select surgical group of patients; thus, the data highlight the need to develop new therapies that may result in more patients being viable surgical candidates.

Randomized, double-blind, placebo-controlled, multicenter phase II study of the efficacy and safety of apricoxib in combination with either docetaxel or pemetrexed in patients with biomarker-selected non-small-cell lung cancer.

PURPOSE: Overexpression of COX-2 correlates with advanced stage and worse outcomes in non-small-cell lung cancer (NSCLC), possibly as a result of elevated levels of COX-2-dependent prostaglandin E2 (PGE2). Exploratory analyses of studies that used COX-2 inhibitors have demonstrated potentially superior outcome in patients in whom the urinary metabolite of PGE2 (PGE-M) is suppressed. We hypothesized that patients with disease defined by PGE-M suppression would benefit from the addition of apricoxib to second-line docetaxel or pemetrexed. PATIENTS AND METHODS: Patients with NSCLC who had disease progression after one line of platinum-based therapy, performance status of 0 to 2, and normal organ function were potentially eligible. Only patients with a ≥ 50% decrease in urinary PGE-M after 5 days of treatment with apricoxib could enroll. Docetaxel 75 mg/m(2) or pemetrexed 500 mg/m(2) once every 21 days per the investigator was administered with apricoxib or placebo 400 mg once per day. The primary end point was progression-free survival (PFS). Exploratory analysis was performed regarding baseline urinary PGE-M and outcomes. RESULTS: In all, 101 patients completed screening, and 72 of the 80 who demonstrated ≥ 50% suppression were randomly assigned to apricoxib or placebo. Toxicity was similar between the arms. No improvement in PFS was seen with apricoxib versus placebo. The median PFS for the control arm was 97 days (95% CI, 52 to 193 days) versus 85 days (95% CI, 67 to 142 days) for the experimental arm (P = .91). CONCLUSION: Apricoxib did not improve PFS, despite biomarker-driven patient selection.

Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach.

PURPOSE: To determine the effectiveness of bortezomib plus irinotecan and bortezomib alone in patients with advanced gastroesophageal junction (GEJ) and gastric adenocarcinoma. We also sought to explore the effect of these therapeutics on tumor and normal gene expression in vivo. METHODS: Forty-one patients with advanced GEJ (89 %) or gastric (11 %) adenocarcinoma received bortezomib (1.3 mg/m(2) days 1, 4, 8, 11) plus irinotecan (125 mg/m(2) days 1, 8) every 21 days as first line therapy (N = 29), or bortezomib alone as second line therapy (N = 12). The trial was designed to detect a 40 % response rate for the combination, and 20 % response rate for bortezomib alone. Affymetrix HU133A gene chip arrays were used for gene expression studies. RESULTS: Objective response occurred in 3 of 29 patients (10 %, 95 % confidence intervals [CI] 2 %, 27 %) treated with bortezomib plus irinotecan, and in 1 of 12 patients (8 %, 95 % CI 0 %, 39 %) with bortezomib alone. Due to the limited number of responders, there were no significant correlations with response found in the gene expression profiles of 12 patients whose tumors were sampled before and 24 h after therapy with bortezomib alone (N = 2) or the combination (N = 10). CONCLUSIONS: We conclude that bortezomib is not effective for the treatment of advanced adenocarcinoma of the GEJ or stomach, whether used alone or in combination with irinotecan, in an unselected patient population.

Phase II trial of the histone deacetylase inhibitor romidepsin in patients with recurrent/metastatic head and neck cancer.

OBJECTIVES: Patients with advanced squamous cell carcinoma of the head and neck (SCCHN) have limited treatment options. Inhibition of histone deacetylases (HDACs) represents a novel therapeutic approach warranting additional investigation in solid tumors. METHODS: A phase II trial of single agent romidepsin, an HDAC inhibitor, was performed in 14 patients with SCCHN who provided consent for pre- and post-therapy samples of accessible tumor, blood and uninvolved oral mucosa. Romidepsin was administered at 13 mg/m(2) as a 4-h intravenous infusion on days 1, 8 and 15 of 28 day cycles, with response assessment by RECIST every 8 weeks. RESULTS: Objective responses were not observed, although 2 heavily pretreated patients had brief clinical disease stabilization. Observed toxicities were expected, including frequent severe fatigue. Immunohistochemical analysis of 7 pre- and post-treatment tumor pairs demonstrated induction of p21(Waf1/Cip1) characteristic of HDAC inhibition, as well as decreased Ki67 staining. Exploratory microarray analyses of mucosal and tumor samples detected changes in gene expression following romidepsin treatment that were most commonly associated with regulation of transcription, cell cycle control, signal transduction, and electron transport. Treatment with romidepsin did not alter the extent of DNA methylation of candidate gene loci (including CDH1 and hMLH1) in SCCHN tumors. CONCLUSIONS: Single agent romidepsin has limited activity for the treatment of SCCHN but can effectively achieve tumor-associated HDAC inhibition. Although tolerability of romidepsin in this setting may be limiting, further evaluation of other HDAC inhibitors in combination with active therapies may be justified.

Antiangiogenic agents for the treatment of nonsmall cell lung cancer: characterizing the molecular basis for serious adverse events.

Novel agents to reduce angiogenesis by targeting vascular endothelial growth factor and other proangiogenic signaling pathways are being developed for advanced nonsmall cell lung cancer. Antibody-based therapies (e.g., aflibercept) and multitargeted tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, and BIBF 1120) are being evaluated in phase III clinical trials. Some antiangiogenic agents have demonstrated distinct profiles in producing a variety of nonhematologic toxicities, including bleeding/hemorrhage, venous and arterial thromboembolic events, gastrointestinal perforation, hypertension, and proteinuria. Elucidating the molecular basis of these toxicities may lead to clinical benefits by improving patient selection and allowing for the development of effective prevention and management strategies.

Preoperative taxane-based chemotherapy and celecoxib for carcinoma of the esophagus and gastroesophageal junction: results of a phase 2 trial.

PURPOSE: The primary objective of this study was to determine the rate of pathological response after preoperative celecoxib and concurrent taxane-based chemotherapy in patients with cancer of the esophagus and gastroesophageal junction. METHODS: Thirty-nine patients were enrolled in this single-arm, phase II clinical trial. Patients were administered daily celecoxib in combination with two to three cycles of carboplatin and paclitaxel with preoperative intent. Levels of cyclooxygenase (COX)-2 expression in resected tumors were analyzed by immunohistochemistry and correlated with clinical outcome measures. Postoperatively, patients were administered daily celecoxib for 1 year or until documented tumor recurrence. RESULTS: All patients received two to three cycles of chemotherapy plus celecoxib 800 mg/d. Toxicities were as expected. A major clinical response (complete response + partial response) was noted in 22 patients (56%); six patients (15%) had a complete clinical response. Thirty-seven patients underwent esophagectomy. Five patients had a major pathological response (12.8%). Four-year overall and disease-free survivals were 40.9% and 30.3%, respectively. Patients with tumors expressing COX-2 demonstrated a higher likelihood of a major clinical response response (62% versus 50%) and an improved overall survival, compared with patients with COX-2-negative tumors. CONCLUSIONS: Preoperative celecoxib with concurrent chemotherapy demonstrated sufficient effect on pathologic response to warrant further study. Patients with tumors expressing COX-2 demonstrated trends toward improved response to preoperative therapy and improved overall survival compared with nonexpressors.

Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis.

CONTEXT: Venous thromboembolism is one of the leading causes of morbidity and mortality in patients with cancer. Concerns have arisen regarding the risk of venous thromboembolism with the novel antiangiogenic agent bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor that is widely used in cancer treatment. Currently, the role of bevacizumab in venous thromboembolism is controversial. OBJECTIVE: To assess the overall risk of venous thromboembolism associated with the use of bevacizumab, a systematic review and meta-analysis of published randomized controlled trials was performed. DATA SOURCES: The databases of PubMed and Web of Science were searched for articles published in the English language from January 1966 until January 2008 and abstracts presented at American Society of Clinical Oncology conferences held between January 2000 and January 2008 were searched to identify relevant clinical trials. STUDY SELECTION AND DATA EXTRACTION: Eligible studies included prospective randomized controlled trials in which standard antineoplastic therapy was used with and without bevacizumab and data on venous thromboembolism were available. Summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. DATA SYNTHESIS: A total of 7956 patients with a variety of advanced solid tumors from 15 randomized controlled trials were identified and included for analysis. Among those patients receiving bevacizumab, the summary incidences of all-grade and high-grade venous thromboembolism were 11.9% (95% CI, 6.8%-19.9%) and 6.3% (95% CI, 4.8%-8.3%), respectively. Patients treated with bevacizumab had a significantly increased risk of venous thromboembolism with an RR of 1.33 (95% CI, 1.13-1.56; P < .001) compared with controls. The risk was significantly increased for both all-grade and high-grade venous thromboembolism. In addition, the risk was similarly increased for bevacizumab at 2.5 mg/kg per week (low dose; RR, 1.31 [95% CI, 1.08-1.60]; P = .007) and 5 mg/kg per week (high dose; RR, 1.31 [95% CI, 1.02-1.68]; P = .04). CONCLUSION: The use of bevacizumab was significantly associated with an increased risk of developing venous thromboembolism in cancer patients receiving this drug.

Randomized phase II trial of docetaxel/irinotecan and gemcitabine/irinotecan with or without celecoxib in the second-line treatment of non-small-cell lung cancer.

PURPOSE: Trials combining irinotecan/docetaxel and irinotecan/gemcitabine in second-line treatment of non-small-cell lung cancer (NSCLC) have yielded promising results. Preliminary data suggested that the selective cyclooxygenase -2 inhibitor celecoxib (CBX) might enhance efficacy of chemotherapeutic regimens. This multicenter, phase II, randomized trial investigated efficacy and safety of irinotecan and docetaxel and irinotecan and gemcitabine, with or without CBX, in second-line treatment of NSCLC. PATIENTS AND METHODS: Patients 18 years or older were randomly assigned to receive irinotecan 60 mg/m2 and docetaxel 35 mg/m2, or irinotecan 100 mg/m2 and gemcitabine 1,000 mg/m2, with or without CBX 400 mg twice daily, for four cycles. Primary efficacy end points were median and 1-year survival probabilities. Patient-reported symptoms were assessed by the Lung Cancer Symptoms Scale (LCSS). RESULTS: A total of 133 patients were assessable for efficacy and safety. Median survival time was 6.31 months for patients treated with CBX and 8.99 months for those treated with chemotherapy alone. One-year survival rates were 24% and 36% respectively. The overall toxicity rates and LCSS scores were similar between patients treated or not treated with CBX. Four deaths were considered possibly treatment related. CONCLUSION: Survival results for the second-line regimens in this study were similar to results reported for single-agent therapy in this setting. CBX did not appear to enhance efficacy or improve patient-reported symptoms. The addition of high-dose CBX to second-line chemotherapy in NSCLC cannot be recommended.

Surgical resection for residual N2 disease after induction chemotherapy.

BACKGROUND: Induction therapy is a common treatment modality for patients with stage IIIA non-small cell lung cancer (NSCLC). Although mediastinal nodal downstaging after induction therapy is generally considered a favorable prognostic feature, the benefit of resection in the presence of residual N2 disease is controversial. In this study we analyzed our experience with resection after induction chemotherapy in patients with residual N2 disease to more precisely define the role of surgical resection in this group of patients. METHODS: In this retrospective analysis, we reviewed the records of 78 patients with N2 disease who received induction therapy with preoperative intent between 1990 and 2003. All patients had potentially resectable disease. Survival analysis was performed using the Kaplan-Meier method. A Cox proportional hazards regression model was used to evaluate multiple prognostic factors. RESULTS: There were 78 patients (39 men) with a median age of 64 years. Sixty had nonsquamous histology. Resection was performed in 52 patients (47 R0). Hospital mortality was 1.9%. A complete pathologic response occurred in 2 of 52 (3.8%) patients and 19 of 52 (36%) patients had no residual N2 disease. Overall 5-year survival for resected patients was 23%. Overall 5-year survival was 30% for N0-N1 patients and 19% for those with residual N2 disease. Multivariable analysis identified clinical response to therapy (p = 0.0007) and histology (p = 0.01), but not residual N2 disease (p = 0.65), as important prognostic variables. CONCLUSIONS: Surgical resection may be a viable option for patients with residual N2 disease after induction chemotherapy, provided an R0 resection can be performed.

Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342.

PURPOSE: Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer. PATIENTS AND METHODS: Four hundred seventy-four women with metastatic breast cancer who had received one or no prior chemotherapy regimens were randomly assigned to one of three paclitaxel dosing regimens-175 mg/m(2), 210 mg/m(2), or 250 mg/m(2)-each administered as a 3-hour infusion every 3 weeks. Women completed self-administered quality of life and symptom assessment questionnaires at baseline and after three cycles of treatment. RESULTS: No evidence of a significant dose-response relationship was demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21% for the three regimens, respectively. A marginally significant association (P =.04) was seen between dose and time to progression; however, in a multivariate analysis, the difference was even less apparent. No statistically significant difference was seen in survival. Neurotoxicity and hematologic toxicity were more severe on the higher dose arms. There was no significant difference in quality of life on the three arms. CONCLUSION: Higher doses of paclitaxel administered as a 3-hour infusion to women with metastatic breast cancer did not improve response rate, survival, or quality of life. There was a slight improvement in time to progression with higher dose therapy, which was offset by greater toxicity. When a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m(2) should be considered the optimal dose.

Positron emission tomography scanning poorly predicts response to preoperative chemotherapy in non-small cell lung cancer.

BACKGROUND: The ability to accurately predict pathologic response to preoperative chemotherapy may have a significant impact on the treatment strategy for non-small cell lung cancer (NSCLC). The purpose of this study was to examine the accuracy of positron emission tomography (PET) scanning in predicting the pathologic response to preoperative chemotherapy in the primary tumor and draining lymph nodes. METHODS: A total of 25 patients were enrolled in two separate phase II trials investigating induction chemotherapy for NSCLC. All patients underwent pre-treatment and post-treatment PET scans followed by surgical resection. A significant PET scan response was defined as a reduction in the standard uptake value by 50% or more. We defined a major pathologic response as either no disease or microscopic disease only in the primary tumor. The percentage change in standard uptake value was then calculated and correlated with pathologic response in the primary tumor. In addition, the presence or absence of nodal metastases as determined by the postchemotherapy PET scan was compared with final pathologic nodal stage. RESULTS: The positive and negative predictive values for PET detection of major pathologic response in the primary tumor were 43% and 100%, respectively. Positron emission tomography did not accurately predict nodal status in 52% of patients. The positive and negative predictive values of PET to detect node-positive disease were 73% and 64%, respectively. For N2 disease the positive predictive value of PET scans was less than 20%. CONCLUSIONS: Positron emission tomography scanning does not reliably predict pathologic response to preoperative chemotherapy in NSCLC in either the primary tumor or the draining lymph nodes.

A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer.

BACKGROUND: Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers. METHODS: We conducted a randomized, double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas. We randomly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo. We determined the proportion of patients with adenomas, the number of recurrent adenomas, and the time to the development of adenoma between randomization and subsequent colonoscopic examinations. Relative risks were adjusted for age, sex, cancer stage, the number of colonoscopic examinations, and the time to a first colonoscopy. The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis. RESULTS: A total of 517 randomized patients had at least one colonoscopic examination a median of 12.8 months after randomization. One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group (P=0.004). The mean (+/-SD) number of adenomas was lower in the aspirin group than the placebo group (0.30+/-0.87 vs. 0.49+/-0.99, P=0.003 by the Wilcoxon test). The adjusted relative risk of any recurrent adenoma in the aspirin group, as compared with the placebo group, was 0.65 (95 percent confidence interval, 0.46 to 0.91). The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group (hazard ratio for the detection of a new polyp, 0.64; 95 percent confidence interval, 0.43 to 0.94; P=0.022). CONCLUSIONS: Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.