571 resultados para UT MD Anderson Cancer Center
Resumo:
Background. In the past two decades, the incidence of thyroid cancer in the United States (US) has been increasing. There has been debate on whether the increase is real or an artifact of improved diagnostic scrutiny. Methods. We linked SEER9 database with 2000 US Census to obtain county-level SES (Socioeconomic Status) and compared thyroid cancer incidence trends between high and low SES counties. Joinpoint analysis was used to assess the thyroid cancer incidence trends. Annual Percentage Changes (APCs) were calculated to evaluate incidence trends. Results . The thyroid cancer incidence in high SES counties increased moderately (APC1=+2.5*, *P<0.05) before late 1990s and dramatically increased (APC2=+6.3*) after late 1990s, whereas incidence in low SES counties increased moderately (APC=+3.5*) during the entire time period (1980–2008). For smaller tumors (≤4cm), the APCs in high and low SES counties are similar to each other before late 1990s, but the incidence in high SES counties increased dramatically after late 1990s while that in low SES counties continued at a moderate increase. For large tumors (>4cm), the incidence trends in high SES counties are similar to those of low SES counties, which had a steady moderate increase. Conclusion. Our findings indicate that enhanced detection likely contributed to the increased thyroid cancer incidence in the past decades but cannot fully explain the increase, suggesting that a true increase also exists. Efforts should be made on identifying the cause of this observed increased incidence as well as more refined/selected screening and prevention measures.^
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Four basic medical decision making models are commonly discussed in the literature in reference to physician-patient interactions. All fall short in their attempt to capture the nuances of physician-patient interactions, and none satisfactorily address patients' preferences for communication and other attributes of care. Prostate cancer consultations are one setting where preferences matter and are likely to vary among patients. Fortunately, discrete choice experiments are capable of casting light on patients' preferences for communication and other attributes of value that make up a consultation before the consultation occurs, which is crucial if patients are to derive the most utility from the process of reaching a decision as well as the decision itself. The results of my dissertation provide strong support to the notion that patients, at least in the hypothetical setting of a DCE, have identifiable preferences for the attributes of a prostate cancer consultation and that those preferences are capable of being elicited before a consultation takes place. Further, patients' willingness-to-pay for the non-cost attributes of the consultation is surprisingly robust to a variety of individual level variables of interest. ^
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The prevalence of obesity has continued to rise over the last several decades in the United States lending to overall increases in risk for chronic diseases including many types of cancer. In contrast, reduction in energy consumption via calorie restriction (CR) has been shown to be a potent inhibitor of carcinogenesis across a broad range of species and tumor types. Previous data has demonstrated differential signaling through Akt and mTOR via the IGF-1R and other growth factor receptors across the diet-induced obesity (DIO)/CR spectrum. Furthermore, mTORC1 is known to be regulated directly via nutrient availability, supporting its role in the link between epithelial carcinogenesis and diet-induced obesity. In an effort to better understand the importance of mTORC1 in the context of both positive and negative energy balance during epithelial carcinogenesis, we have employed the use of specific pharmacological inhibitors, rapamycin (mTORC1 inhibitor) and metformin (AMPK activator) to target mTORC1 or various components of this pathway during skin tumor promotion. Two-stage skin carcinogenesis studies demonstrated that mTORC1 inhibition via rapamycin, metformin or combination treatments greatly inhibited skin tumor development in normal, overweight and obese mice. Furthermore, mechanisms by which these chemopreventive agents may be exerting their anti-tumor effects were explored. In addition, the effect of these compounds on the epidermal proliferative response was analyzed and drastic decreases in epidermal hyperproliferation and hyperplasia were found. Rapamycin also inhibited dermal inflammatory cell infiltration in a dose-dependent manner. Both compounds also blocked or attenuated TPA-induced signaling through epidermal mTORC1 as well as several downstream targets. In addition, inhibition of this pathway by metformin appeared to be, at least in part, dependent on AMPK activation in the skin. Overall, the data indicate that pharmacological strategies targeting this pathway offset the tumor-enhancing effects of DIO and may serve as possible CR mimetics. They suggest that mTORC1 contributes significantly to the process of skin tumor promotion, specifically during dietary energy balance effects. Exploiting the mechanistic information underlying dietary energy balance responsive pathways will help translate decades of research into effective strategies for prevention of epithelial carcinogenesis.
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The incidence of OSCC in younger population and in those who never smoked or drank has increased since the last decade. This increase may be attributable to increase of infection with HPV. The pro-inflammatory cytokine TNF-&agr; has the role in the pathogenesis of chronic inflammatory diseases and was found to control HPV infection in cervical cancer studies. Our study aimed to investigate the association between the four polymorphisms located in TNF-&agr; promoter region, -308(rs1800629), -857(rs1799724), -863(rs1800630) and -1031(rs1799964), and the risk of HPV-related OSCC. In this hospital-based case-control study, 325 cases and 335 controls were included. We found that HPV 16 seropositivity was associated with an increased risk of oral cancer (OR = 3.1, 95% CI, 2.1–4.6). Each of the polymorphism showed to increase the risk of HPV-related OSCC. And after combining the risk genotypes and using the low-risk group (0–1 combined risk genotypes) and HPV16 seronegativity as the reference group, only the high-risk groups (3–4 combined risk genotypes) and HPV16 seronegativity were associated with a low OR of 1.8 (95% CI, 1.1–2.8), while the low-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.7 (95% CI, 1.3–5.8) and 8.5 (95% CI, 3.7–19.4), respectively. In addition, the joint effects were greater among the young subjects (aged<50), males, never smokers or never drinkers, and patients with oropharyngeal cancer. Overall, the four TNF-&agr; polymorphisms, individually or collectively, would result in a significantly increased risk for HPV16-associated oral cancer in a non-Hispanic white population. More large sized studies are needed for future investigation.^
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Although physician recommendation has been significantly associated with colorectal cancer screening (CRCS), it still does not motivate all patients to get CRCS. Although improved physician recommendation for CRCS has been shown to increase patient CRCS screening, questions remain about what elements of that discussion may lead to screening. The objective of this study is to describe patients' perceptions and interpretations about their physician's recommendation for CRCS during their annual wellness exam. A subset of patients (n=51) participating in a supplement study of a behavioral intervention trial designed to increase CRCS completed a follow-up, open-ended interview two to four weeks after their annual wellness visit. Using qualitative methods, transcripts of these interviews were analyzed. Findings suggest that most patients would follow their physician's recommendation for CRCS despite not engaging in much discussion. Patients may refrain from CRCS discussion because of a commitment to CRCS, awareness of screening guidelines, and trust in physician's honesty and beneficence. Yet many patients left their wellness exams with questions, refraining because of future plans to consult with their physicians, perceived time constraints or a lack of a patient-physician relationship. If patients are leaving their wellness exams with unanswered questions, interventions should prepare physicians for patient reticence, teaching physicians how to assure patients that CRCS is a primary care activity where all questions and concerns, including cost and scheduling, may be resolved.^
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Introduction. Distant metastasis remains the leading cause of death among prostate cancer patients. Several genetic susceptibility loci associated with Prostate cancer have been identified by the Genome Wide Association Studies (GWAS). To date, few studies have explored the ability of these SNPs to identify metastatic prostate cancer. Based on the identification of genetic variants as predictors of aggressive disease, a case comparison study of prostate cancer patients was designed to explore the association of 96 GWAS single nucleotide polymorphisms (SNPs) with metastatic disease. ^ Method. 1242 histologically confirmed prostate cancer patients, with and without metastatic disease, were enrolled into the study. Data were collected from personal interviews, hospital database and abstraction of medical records. Ninety six SNPs identified from GWAS studies based on their associations with prostate cancer risk were genotyped in the study population. Univariate and multivariate logistic regression analyses were used to explore the relationships of the variants with metastatic prostate cancer in Whites and African American men. ^ Results. Four SNPs showed independent associations with metastatic prostate cancer (rs721048 in EHBP1 (2p15), rs3025039 in VEGF (6p12), rs11228565 in Intergenic(11q13.2) and rs2735839 in KLK3(19q13.33)) in the White population. For SNP rs2735839 in KLK3, genotype GA was 1.71 times as likely to be associated with metastatic prostate cancer diagnosis as genotype AA after adjusting for other significant SNPs and covariates (95% CI, 1.12-2.60; p=0.012). In men of African descent, three SNPs: rs1512268 in NKX3-1(8p21.2), rs12155172 in intergenic (7p15.3) & rs10486567 in JAZF1 (7p15.2) were positively associated with metastatic disease in the multivariate analysis. The strongest SNP was rs1512268 heterozygous genotype AG in NKX3-1(8p21.2) which was associated with 3.97-fold increased risk of metastatic prostate cancer diagnosis (95% CI, 1.69-9.34; p =0.002). ^ Conclusion. Genetic variants associated with metastatic prostate cancer were different in Whites and African American men. Given the high mortality rate recorded in men diagnosed with metastatic prostate tumor, further studies are needed to validate associations and establish their clinical application.^
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Trastuzumab is a humanized-monoclonal antibody, developed specifically for HER2-neu over-expressed breast cancer patients. Although highly effective and well tolerated, it was reported associated with Congestive Heart Failure (CHF) in clinical trial settings (up to 27%). This leaves a gap where, Trastuzumab-related CHF rate in general population, especially older breast cancer patients with long term treatment of Trastuzumab remains unknown. This thesis examined the rates and risk factors associated with Trastuzumab-related CHF in a large population of older breast cancer patients. A retrospective cohort study using the existing Surveillance, Epidemiology and End Results (SEER) and Medicare linked de-identified database was performed. Breast cancer patients ≥ 66 years old, stage I-IV, diagnosed in 1998-2007, fully covered by Medicare but no HMO within 1-year before and after first diagnosis month, received 1st chemotherapy no earlier than 30 days prior to diagnosis were selected as study cohort. The primary outcome of this study is a diagnosis of CHF after starting chemotherapy but none CHF claims on or before cancer diagnosis date. ICD-9 and HCPCS codes were used to pool the claims for Trastuzumab use, chemotherapy, comorbidities and CHF claims. Statistical analysis including comparison of characteristics, Kaplan-Meier survival estimates of CHF rates for long term follow up, and Multivariable Cox regression model using Trastuzumab as a time-dependent variable were performed. Out of 17,684 selected cohort, 2,037 (12%) received Trastuzumab. Among them, 35% (714 out of 2037) were diagnosed with CHF, compared to 31% (4784 of 15647) of CHF rate in other chemotherapy recipients (p<.0001). After 10 years of follow-up, 65% of Trastuzumab users developed CHF, compared to 47% in their counterparts. After adjusting for patient demographic, tumor and clinical characteristics, older breast cancer patients who used Trastuzumab showed a significantly higher risk in developing CHF than other chemotherapy recipients (HR 1.69, 95% CI 1.54 - 1.85). And this risk is increased along with the increment of age (p-value < .0001). Among Trastuzumab users, these covariates also significantly increased the risk of CHF: older age, stage IV, Non-Hispanic black race, unmarried, comorbidities, Anthracyclin use, Taxane use, and lower educational level. It is concluded that, Trastuzumab users in older breast cancer patients had 69% higher risk in developing CHF than non-Trastuzumab users, much higher than the 27% increase reported in younger clinical trial patients. Older age, Non-Hispanic black race, unmarried, comorbidity, combined use with Anthracycline or Taxane also significantly increase the risk of CHF development in older patients treated with Trastuzumab. ^
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Retrospective data from the Cameron Country Hispanic Cohort (1) were analyzed to assess the burden of cancer in the Mexican American population living in Brownsville TX. Data provided by the study participants for themselves and their parents and other extended relatives on cancer and related risk factors were used to determine both the prevalence of cancer and these risk factors as well as any associations between them. Lifetime incidence of cancer among the study participants was of 2.8%. Lifetime incidence of cancer among the parents of the study population was calculated for cancer in general and for specific cancer sites to determine the ranking of occurrence of each type of cancer. Some cancer types in this population were ranked higher than what would be expected when compared with national data from Hispanics in the U.S, these were: Liver cancer (3rd vs. 7th nationally in males and 6th vs. 13th nationally in females), stomach cancer (4th vs. 8th nationally in males and 5th vs. 11th nationally in females) and ovarian cancer (3rd vs. 8th nationally in females). A significant association with cancer was found for being born in the United States compared to being born elsewhere (O.R. 1.62, 95% C.I. 1.01–2.60) among study participants and the same association was also found between birth of parents in the United States regardless of gender for cancers in general (O.R. 1.38 95% C.I. 1.12–1.70), stomach cancer (O.R. 1.92 95% C.I. 1.01–3.67) and colorectal cancer (O.R. 2.93 95% C.I. 1.28–6.72). Having been born in the United States and having a family history of cancer was also found to be significantly associated with other risk factors for cancer such as obesity, diabetes and insulin resistance, both among the parents and the participant population, suggesting these interactions are complex. These high rates of cancer and particular prominence of less usual cancer such as liver and ovary in health disparities warrant evaluation of early detection strategies.^
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Complex diseases, such as cancer, are caused by various genetic and environmental factors, and their interactions. Joint analysis of these factors and their interactions would increase the power to detect risk factors but is statistically. Bayesian generalized linear models using student-t prior distributions on coefficients, is a novel method to simultaneously analyze genetic factors, environmental factors, and interactions. I performed simulation studies using three different disease models and demonstrated that the variable selection performance of Bayesian generalized linear models is comparable to that of Bayesian stochastic search variable selection, an improved method for variable selection when compared to standard methods. I further evaluated the variable selection performance of Bayesian generalized linear models using different numbers of candidate covariates and different sample sizes, and provided a guideline for required sample size to achieve a high power of variable selection using Bayesian generalize linear models, considering different scales of number of candidate covariates. ^ Polymorphisms in folate metabolism genes and nutritional factors have been previously associated with lung cancer risk. In this study, I simultaneously analyzed 115 tag SNPs in folate metabolism genes, 14 nutritional factors, and all possible genetic-nutritional interactions from 1239 lung cancer cases and 1692 controls using Bayesian generalized linear models stratified by never, former, and current smoking status. SNPs in MTRR were significantly associated with lung cancer risk across never, former, and current smokers. In never smokers, three SNPs in TYMS and three gene-nutrient interactions, including an interaction between SHMT1 and vitamin B12, an interaction between MTRR and total fat intake, and an interaction between MTR and alcohol use, were also identified as associated with lung cancer risk. These lung cancer risk factors are worthy of further investigation.^
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The ECM of epithelial carcinomas undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How tumors maintain ECM integrity in the face of dynamic biophysical forces is still largely unclear. This study addresses these deficiencies using mouse models of human lung adenocarcinoma. Spontaneous lung tumors were marked by disorganized basement membranes, dense collagen networks, and increased tissue stiffness. Metastasis-prone lung adenocarcinoma cells secreted fibulin-2 (Fbln2), a matrix glycoprotein involved in ECM supra-molecular assembly. Fibulin-2 depletion in tumor cells decreased the intra-tumoral abundance of matrix metalloproteinases and reduced collagen cross-linking and tumor compressive properties resulting in inhibited tumor growth and metastasis. Fbln2 deposition within intra-tumoral fibrotic bands was a predictor of poor clinical outcome in patients. Collectively, these findings support a feed-forward model in which tumor cells secrete matrix-stabilizing factors required for the assembly of ECM that preferentially favors malignant progression. To our knowledge, this is the first evidence that tumor cells directly regulate the integrity of their surrounding matrix through the secretion of matrix-stabilizing factors such as fibulin-2. These findings open a new avenue of research into matrix assembly molecules as potential therapeutic targets in cancer patients.
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In 1941 the Texas Legislature appropriated $500,000 to the Board of Regents of the University of Texas to establish a cancer research hospital. The M. D. Anderson Foundation offered to match the appropriation with a grant of an equal sum and to provide a permanent site in Houston. In August, 1942 the Board of Regent of the University and the Trustees of the Foundation signed an agreement to embark on this project. This institution was to be the first one in the medical center, which was incorporated in October, 1945. The Board of Trustees of the Texas Medical Center commissioned a hospital survey to: - Define the needed hospital facilities in the area - Outline an integrated program to meet these needs - Define the facilities to be constructed - Prepare general recommendations for efficient progress The Hospital Study included information about population, hospitals, and other health care and education facilities in Houston and Harris County at that time. It included projected health care needs for future populations, education needs, and facility needs. It also included detailed information on needs for chronic illnesses, a school of public health, and nursing education. This study provides valuable information about the general population and the state of medicine in Houston and Harris County in the 1940s. It gives a unique perspective on the anticipated future as civic leaders looked forward in building the city and region. This document is critical to an understanding of the Texas Medical Center, Houston and medicine as they are today. SECTIONS INCLUDE: Abstract The Abstract was a summary of the 400 page document including general information about the survey area, community medical assets, and current and projected medical needs which the Texas Medical Center should meet. The 123 recommendations were both general (e.g., 12. “That in future planning, the present auxiliary department of the larger hospitals be considered inadequate to carry an added teaching research program of any sizable scope.”) and specific (e.g., 22. That 14.3% of the total acute bed requirement be allotted for obstetric care, reflecting a bed requirement of 522 by 1950, increasing to 1,173 by 1970.”) Section I: Survey Area This section basically addressed the first objective of the survey: “define the needed hospital facilities in the area.” Based on the admission statistics of hospitals, Harris County was included in the survey, with the recognition that growth from out-lying regional areas could occur. Population characteristics and vital statistics were included, with future trends discussed. Each of the hospitals in the area and government and private health organizations, such as the City-County Welfare Board, were documented. Statistics on the facilities use and capacity were given. Eighteen recommendations and observations on the survey area were given. Section II: Community Program This section basically addressed the second objective of the survey: “outline an integrated program to meet these needs.” The information from the Survey Area section formed the basis of the plans for development of the Texas Medical Center. In this section, specific needs, such as what medical specialties were needed, the location and general organization of a medical center, and the academic aspects were outlined. Seventy-four recommendations for these plans were provided. Section III: The Texas Medical Center The third and fourth objectives are addressed. The specific facilities were listed and recommendations were made. Section IV: Special Studies: Chronic Illness The five leading causes of death (heart disease, cancer, “apoplexy”, nephritis, and tuberculosis) were identified and statistics for morbidity and mortality provided. Diagnostic, prevention and care needs were discussed. Recommendations on facilities and other solutions were made. Section IV: Special Studies: School of Public Health An overview of the state of schools of public health in the US was provided. Information on the direction and need of this special school was also provided. Recommendations on development and organization of the proposed school were made. Section IV: Special Studies: Needs and Education Facilities for Nurses Nursing education was connected with hospitals, but the changes to academic nursing programs were discussed. The needs for well-trained nurses in an expanded medical environment were anticipated to result in significant increased demands of these professionals. An overview of the current situation in the survey area and recommendations were provided. Appendix A Maps, tables and charts provide background and statistical information for the previous sections. Appendix B Detailed census data for specific areas of the survey area in the report were included. Sketches of each of the fifteen hospitals and five other health institutions showed historical information, accreditations, staff, available facilities (beds, x-ray, etc.), academic capabilities and financial information.
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Cancer therapy and tumor treatment remain unsolved puzzles. Genetic screening for tumor suppressor genes in Drosophila revealed the Hippo-signaling pathway as a kinase cascade consisting of five core components. Disrupting the pathway by deleting the main component genes breaks the balance of cell proliferation and apoptosis and results in epithelial tissue tumorigenesis. The pathway is therefore believed to be a tumor suppressor pathway. However, a corresponding role in mammals is yet to be determined. Our lab began to investigate the tumor suppression function of the potent mammalian Hippo pathway by putting floxed alleles into the mouse genome flanking the functional-domain-expressing exons in each component (Mst1, Mst2, Sav1, Lats1 and Lats2). These mice were then crossed with different cre-mouse lines to generate conditional knockout mice. Results indicate a ubiquitous tumor suppression function of these components, predominantly in the liver. A further liver specific analysis of the deletion mutation of these components, as well as the Yap/Taz double deletion mutation, reveals essential roles of the Hippo pathway in regulating hepatic quiescence and embryonic liver development. One of the key cellular mechanisms for the Hippo pathway’s involvement in these liver biological events is likely its cell cycle regulation function. Our work will help to develop potential therapeutic approaches for liver cancer.
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Objective. Weight gain after cancer treatment is associated with breast cancer recurrence. In order to prolong cancer-free survivorship, interventions to manage post-diagnosis weight are sometimes conducted. However, little is known about what factors are associated with weight management behaviors among cancer survivors. In this study, we examined associations of demographic, clinical, and psychosocial variables with weight management behaviors in female breast cancer survivors. We also examined whether knowledge about post-diagnosis weight gain and its risk is associated with weight management behaviors. ^ Methods. 251 female breast cancer survivors completed an internet survey. They reported current performance of three weight management behaviors (general weight management, physical activity, and healthy diet). We also measured attitude, elf-efficacy, knowledge and social support regarding these behaviors along with demographic and clinical characteristics. ^ Results. Multiple regression models for the weight management behaviors explained 17% of the variance in general weight management, 45% in physical activity and 34% in healthy dieting. The models had 9–14 predictor variables which differed in each model. The variables associated with all three behaviors were social support and self-efficacy. Self-efficacy showed the strongest contribution in all models. The knowledge about weight gain and its risks was not associated with any weight management behaviors. However, women who obtained the knowledge during cancer treatment were more likely to engage in physical activity and healthy dieting. ^ Conclusions. The findings suggest that an intervention designed to increase their self-efficacy to manage weight, to be physically active, to eat healthy will effectively promote survivors to engage in these behaviors. Knowledge may motivate women to manage post-diagnosis weight about risk if information is provided during cancer treatment.^
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Early-stage lung cancer incidence among older adults is expected to increase due to demographic trends and CT-based screening, yet optimal treatment of lung cancer in the elderly remains controversial. There are several accepted strategies for treating lung cancer including surgery, conventional radiation, and stereotactic ablative body radiotherapy (SABR). However, there are currently no randomized controlled trials to help distinguish the comparative effectiveness of these various strategies. This is an unfortunate omission as lung cancer causes the most deaths among all cancers in the United States (as well as the entire world). SABR holds particular promise as it is a completely non-invasive, ambulatory technique for achieving cure without an operation, thus avoiding the risks of surgery and the associated pre-operative and post-operative costs. To provide fair view of the potential effect on SABR on controlling lung cancer in the United States, a systematic review of SABR with a focus on its achieved outcomes, toxicities, and comparison to conventional radiation and surgical options is presented. ^
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Background. Cancer cachexia is a common syndrome complex in cancer, occurring in nearly 80% of patients with advanced cancer and responsible for at least 20% of all cancer deaths. Cachexia is due to increased resting energy expenditure, increased production of inflammatory mediators, and changes in lipid and protein metabolism. Non-steroidal anti-inflammatory drugs (NSAIDs), by virtue of their anti-inflammatory properties, are possibly protective against cancer-related cachexia. Since cachexia is also associated with increased hospitalizations, this outcome may also show improvement with NSAID exposure. ^ Design. In this retrospective study, computerized records from 700 non-small cell lung cancer patients (NSCLC) were reviewed, and 487 (69.57%) were included in the final analyses. Exclusion criteria were severe chronic obstructive pulmonary disease, significant peripheral edema, class III or IV congestive heart failure, liver failure, other reasons for weight loss, or use of research or anabolic medications. Information on medication history, body weight and hospitalizations was collected from one year pre-diagnosis until three years post-diagnosis. Exposure to NSAIDs was defined if a patient had a history of being treated with NSAIDs for at least 50% of any given year in the observation period. We used t-test and chi-square tests for statistical analyses. ^ Results. Neither the proportion of patients with cachexia (p=0.27) nor the number of hospitalizations (p=0.74) differed among those with a history of NSAID use (n=92) and those without (n=395). ^ Conclusions. In this study, NSAID exposure was not significantly associated with weight loss or hospital admissions in patients with NSCLC. Further studies may be needed to confirm these observations.^