Non-cancer Control Group Research Articles

Venous-thromboembolism and associated health care utilization in elderly patients with diffuse large B cell lymphoma.

Patients with lymphoma have an increased risk of venous thromboembolism (VTE). The authors examined the risk of VTE and subsequent health care utilization in elderly patients with diffuse large B cell lymphoma (DLBCL). A total of 5537 DLBCL patients ≥66 years old enrolled in Medicare from the Surveillance, Epidemiology, and End Results registry and a noncancer control group of Medicare beneficiaries (n = 5537) were identified. Cumulative incidence function to examine the risk of VTE 12 months after DLBCL diagnosis was used. Fine and Gray method was used to examine the risk factors associated with VTE risk in multivariable models. Total number of hospitalizations, outpatient visits, and Medicare spending were compared in DLBCL patients with and without VTE. VTE was diagnosed in 8.3% DLBCL patients and 1.5% controls, yielding an 8.6-fold higher risk of VTE in DLBCL in adjusted analysis (95% confidence interval [CI], 6.62-11.20; P < .001). Multivariable regression analysis showed that precancer VTE history was associated with an increased risk of developing VTE after a DLBCL diagnosis (hazard ratio [HR], 5.39; 95% CI, 4.39-6.63), and Asian individuals were associated with a lower risk (HR, 0.54; 95% CI, 0.29-1.00). Patients newly diagnosed with VTE after lymphoma had a 1.7-fold higher rate of hospitalization and a 1.2-fold higher rate of outpatient visits compared to those without, resulting in excess Medicare spending of $22,208 in the first year after DLBCL diagnosis. Elderly patients with DLBCL have an elevated risk of VTE resulting in excess health care utilization. VTE history before DLBCL was associated with increased risk of post-DLBCL VTE, and Asian individuals were associated with a lower risk of VTE.

Cancer's Lasting Financial Burden: Evidence From a Longitudinal Assessment.

The purpose of this study was to conduct a longitudinal analysis of out-of-pocket expenditure (OOPE) trajectories for the assessment of cancer's lasting financial impact. We identified newly diagnosed cancer patients and constructed matched control group of noncancer participants from the 2002-2018 Health and Retirement Study. Outcomes included monthly OOPE for prescription drugs (RX-OOPE_MONTHLY) and OOPE for medical services other than drugs in the past 2 years (non-RX-OOPE_2YR), consumer debt, and new individual retirement account (IRA) withdrawals. Generalized linear models were used to compare OOPEs between cancer and matched control groups. Logistic regressions were used to compare household-level consumer debt or early IRA withdrawal. Subgroup analysis stratified patients by age, health status, and household income, with the low-income group stratified by Medicaid coverage. All statistical tests were 2-sided. The study cohort included 2022 cancer patients and 10 110 participants in the matched noncancer control group. Mean non-RX-OOPE_2YR of cancer patients was similar to that of participants in the matched control group before diagnosis but statistically significantly higher at diagnosis ($1157, P < .001), 2 ($511, P < .001) years, 4 ($360, P = .006) years, and 6 ($430, P = .01) years after diagnosis. A similar pattern was observed in RX-OOPE_MONTHLY. A statistically significantly higher proportion of cancer patients incurred consumer debt at diagnosis (34.5% vs 29.9%; P < .001) and 2 years after (32.5% vs 28.2%; P = .002). There was no statistically significant difference in new IRA withdrawals. Patients experienced lasting financial consequences following cancer diagnosis that were most pronounced among patients aged 65 years and older, in good-to-excellent health at baseline, and with low income, but without Medicaid coverage. Policies to reduce costs and expand insurance coverage options while reducing cost-sharing are needed.

Providers' mediating role for medication adherence among cancer survivors.

We conducted a mediation analysis of the provider team's role in changes to chronic condition medication adherence among cancer survivors. We used a retrospective, longitudinal cohort design following Medicare beneficiaries from 18-months before through 24-months following cancer diagnosis. We included beneficiaries aged ≥66 years newly diagnosed with breast, colorectal, lung or prostate cancer and using medication for non-insulin anti-diabetics, statins, and/or anti-hypertensives and similar individuals without cancer from Surveillance, Epidemiology, and End Results-Medicare data, 2008-2014. Chronic condition medication adherence was defined as a proportion of days covered ≥ 80%. Provider team structure was measured using two factors capturing the number of providers seen and the historical amount of patient sharing among providers. Linear regressions relying on within-survivor variation were run separately for each cancer site, chronic condition, and follow-up period. The number of providers and patient sharing among providers increased after cancer diagnosis relative to the non-cancer control group. Changes in provider team complexity explained only small changes in medication adherence. Provider team effects were statistically insignificant in 13 of 17 analytic samples with significant changes in adherence. Statistically significant provider team effects were small in magnitude (<0.5 percentage points). Increased complexity in the provider team associated with cancer diagnosis did not lead to meaningful reductions in medication adherence. Interventions aimed at improving chronic condition medication adherence should be targeted based on the type of cancer and chronic condition and focus on other provider, systemic, or patient factors.

Immune checkpoint blocking impact and nomogram prediction of COVID-19 inactivated vaccine seroconversion in patients with cancer: a propensity-score matched analysis

BackgroundPatients with cancer on active immune checkpoint inhibitors therapy were recommended to seek prophylaxis from COVID-19 by vaccination. There have been few reports to date to discuss the impact of...

Reproduction-related cognitive processing and distress among young adult women: the role of personal breast cancer history

Breast cancer diagnosis can threaten fertility and biological motherhood in women of reproductive age due to the gonadotoxic effects of treatments. Much evidence documents these women fertility-related concerns and distress, but no study has attempted to understand how implicit cognitive processes can contribute to this maladjustment. In this research, we explored whether reproduction-related stimuli interfere with cognition among cancer survivors with infertility risk using an emotional Stroop task. Furthermore, we investigated the relationship between reproduction-related cognitive processing and psychological morbidity. Young cancer survivors aged 18-40years who received anticancer treatments and an age-matched non-cancer control group without known fertility problems were compared. Color-naming times and error rates were assessed. Participants in both groups were slower naming the color of reproduction-related words in comparison to unrelated negative valence words. Although in the same direction, this difference did not reach statistical significance for positive and neutral unrelated word lists. Further analysis suggested that biased attention toward reproduction-related information was associated with higher depression levels in young women with personal breast cancer history, but not in healthy women. These findings suggest that biased processing of reproduction-related cues might be a vulnerability factor after a breast cancer diagnosis. Additionally, this study puts in evidence the potential usefulness of using experimental tasks to investigate attentional bias in a context where fertility is at risk.

P64.01 MiRNAs in Exosomes Isolated From the Blood of Non-Small Cell Lung Cancer Patients: Biomarkers for Lung Cancer Prediction and Prognosis

Non-small cell lung cancer accounts for about 80% of lung cancer, and about 75% of patients have been found in advanced stages, and their survival rate is very low. However, sensitive and simple diagnostic tests for NSCLC and highly-targeted therapeutic biomarkers are still clinically unusable. The aim of this study was to investigate the expression profiles and clinical significance of miRNAs in platelet-derived exosomes in peripheral blood as biomarkers for NSCLC. The fasting blood samples of 102 patients with NSCLC and 89 healthy people were collected. The exosomes were obtained from platelets using ExoQuick Precipitation Kit. The expression of miR-223 in exosomes from platelets were determined by QRT-PCR. Furthermore, we explored its mechanism in the tumor progress by cell migration assay. First, we found that the levels of miR-223 in platelets and P-MVs were significantly up-regulated in lung cancer patients compared with the non-cancer control group. Second, in vitro assays using qRT-PCR showed that platelet miR-223 was rapidly delivered into cancer cells by P-MVs. Third, platelet-derived exogenous miR-223 reduces the protein level of the tumor suppressor EPB41L3, thereby promoting the invasion of lung cancer cells. The effect of P-MV on the reduction and enhancement of tumor cell invasion by EPB41L3 was largely eliminated by consumption of miR-223, indicating that miR-223 plays a key role in these processes. This study provides additional evidence that functional miRNAs in MVs secreted by cells can serve as biomarkers for lung cancer prediction and prognosis.

Microbiome Related Cytotoxically Active CD8+ TIL Are Inversely Associated With Lung Cancer Development.

Lung cancer is the most common cancer type around the world. Although major advances in cancer therapy, lung cancer has been the largest proportion of all cancer-related deaths. The respiratory tract contains many types of bacteria and a distinct lung microbiome in lung cancer patients was described in many studies. The specific roles of these lung microorganisms in lung cancer progression remain unclear. In this study, we evaluated the effect of inhalation of bronchoalveolar fluid (BAL) in the lung cancer cell growth. The microbiome-based immune and carcinogenesis was examined in tumor-bearing mouse model. We found that inhalation of BAL collected from non-small cell lung cancer (NSCLC) patients altered the lung microbiota and inhibited tumor cell growth. The inhibitory effect was due to the infiltration of CD3 and CD8+ T cells and decrease of M2 macrophages in lungs. The microbial communities of NSCLC BAL inhalation group were dominated by Pasteurella, whereas the microbial communities of non-cancer control and PBS inhalation group were dominated by Delftia. Linear discriminant analysis (LDA) indicated that the genera Pasteurella, Pseudomonas, and Chryseobacterium were increased in NSCLC BAL inhalation group, while genera Delftia, Ezakiella, Blautia, Cloacibacterium, and Microvirga et al. were increased in PBS and Non-cancer group. We demonstrated a significant positive correlation between Pasteurella and cytotoxic CD8+ TIL and a negative correlation with M2 macrophages. Coriobacteriaceae was positively correlated with M2 macrophages and negatively correlated with CD8+ cells. The abundance of Pasteurella was negatively correlated with tumor cell growth. Our findings provide a promising strategy that can be used as a therapeutic vaccine for lung cancer patients.

Risk of osteoporosis and fracture in long-term breast cancer survivors.

High incidence of osteoporosis has been reported in breast cancer patients due to early menopause triggered by adjuvant treatment and temporary ovarian function suppression. In this study, we sought to determine whether long-term breast cancer survivors had an elevated risk of low bone density compared to the general population. Long-term breast cancer survivors who had been treated for more than 5 years were selected for this study. Data were obtained from medical records and using a questionnaire from the Korea National Health and Nutrition Examination Survey (KNHANES). An age-matched non-cancer control group was selected from the KNHANES records. Incidence of fracture and bone mineral density (BMD) were compared between the two groups. In total, 74 long-term breast cancer survivors and 296 non-cancer controls were evaluated. The incidence of fracture did not differ between the two groups (P=0.130). No differences were detected in lumbar BMD (P=0.051) following adjustment for body mass index, while hip BMD was significantly lower in breast cancer survivors (P=0.028). Chemotherapy and endocrine treatment were not related to low BMD in breast cancer survivors. In more than half of the survivors, the 10-year risk of osteoporotic fracture was less than 1%. Long-term breast cancer survivors had low bone density but a comparable risk of fracture compared to non-cancer age-matched controls. Further studies on the factors related to low bone density in long-term breast cancer survivors are required.

Association of Nijmegen Breakage Syndrome 1 Genotypes With Bladder Cancer Risk

We aimed to examine the association of the genotypes of Nijmegen breakage syndrome 1 (NBS1), a critical gene in DNA double strand break repair machinery, with bladder cancer risk in Taiwan. NBS1 rs1805794 genotypes among 375 bladder cancer patients and 375 non-cancer healthy controls were determined via the polymerase chain reaction-restriction fragment length polymorphism methodology and their association with bladder cancer risk were evaluated. The results showed that the percentages of GG, CG and CC of NBS1 rs1805794 genotypes were 45.4%, 43.7% and 10.9% in the bladder cancer patient group and 47.2%, 43.2% and 9.6% in the non-cancer control group, respectively (p for trend=0.7873). The analysis of allelic frequency distributions showed that the variant C allele of NBS1 rs1805794 does not contribute to an increased bladder cancer susceptibility (p=0.5066). The genotypes of NBS1 rs1805794 are not closely associated with personal susceptibility to bladder cancer.

Sal-Like Protein 4 Transcription Factor: A Significant Diagnostic Biomarker Involved in Childhood ALL Resistance and Relapse.

PurposeSal‐like protein 4 transcription factor (SALL4) is a stem cell transcription factor that plays an essential role in the maintenance and self-renewal of embryonic and hematopoietic stem cells, functioning as an oncogene in several cancers. However, the role of SALL4 in the biological behavior of childhood acute lymphoblastic leukemia and its relationship with multidrug resistance and relapse has remained largely unknown.Patients and MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was used to characterize the expression pattern of SALL4 in the bone marrow samples of 43 patients with Philadelphia negative ALL and 18 children in the non-cancer control group. The presence of minimal residual disease was measured a year after the initial therapy using SSCP (single-strand conformation polymorphism). In addition, the correlation between the expression of SALL4 and ABCA3 in relapsed patients was analyzed statistically.ResultsResults showed an overexpression of SALL4 in de novo patients compared with the control group (P=0.0001, AUC= 0.93), indicating the importance of this gene in the induction of leukemia. A significant increase in the ABCA3 expression levels was revealed in the relapsed patients, in comparison with the drug-sensitive group (P = 0.0005). The leukemogenetic effect of SALL4 can be related to the effect of this gene on the maintenance of pluripotency in cancer stem cells. Results also suggest that the expression of SALL4 can be considered as a diagnostic marker for pediatric ALL. Moreover, SALL4 expression levels in the minimal residual disease positive (mrd+) ALL group was significantly higher than those in the mrd− group (p=0.0001, AUC= 0.92).ConclusionThese data demonstrate the prognostic impact of SALL4 in childhood ALL. Our findings also indicated a direct correlation between the mRNA expression levels of SALL4 and ABCA3 transporter in the relapsed group of ALL patients (r=0.7). These results describe a possible mechanism by which SALL4 may lead to the development of multidrug resistance.

Comparison of bowel dysfunction between colorectal cancer survivors and a non-operative non-cancer control group.

Low anterior resection syndrome (LARS) detrimentally affects quality of life in colorectal cancer survivors. This study assessed the prevalence for LARS in colorectal cancer survivors and the same symptoms in a matched control group. Validated instruments, the LARS score and Short Form Survey 12, used to collect functional and quality of life outcomes from patients who had undergone distal colorectal resection at Auckland Hospital (2008-2015) or Dunedin Hospital (2008-2017). A matched non-operative control group was drawn from patients undergoing surveillance colonoscopy. The response rate was 79%. Cross-sectional prevalence of major LARS in rectal cancer patients was 52% at a median follow-up of 52months. Major LARS prevalence in the sigmoid cancer resection and non-cancer control groups was similar (25% vs 26%, P=0.6). On univariate analysis anastomotic height [risk ratio (RR) for low anterior resection4.6, P<0.001; ultralow anterior resection RR=15.5, P<0.001], radiotherapy (RR=2.6; P=0.009), stoma (RR=3.6; P=0.001) and J pouch reconstruction (vs straight anastomosis, RR=4.6; P=0.008) were associated with major LARS for rectal cancer patients. These factors were not significant when the analysis was stratified for anastomotic height. Despite correlation between LARS and Short Form Survey 12 outcomes (physical ρ=-0.2; mental ρ=-0.2) there was no difference in quality of life outcomes between the groups. Bowel dysfunction after low anterior resection affects the majority of rectal cancer patients. The high background rate of bowel dysfunction must be considered when assessing the prevalence of LARS.

Abstract 106: Targeting tumor associated pH regulators: Effective therapeutic strategy in ovarian cancer

Abstract The cancer cell survival relies on the over-expression of pH regulators that pump out excess protons/lactic acid, in turn acidifying the tumor microenvironment (TME) which further promotes immune suppression and metastasis. Targeting the pH regulatory molecules can neutralize the TME acidification and inhibit cancer growth. Vacuolar ATPase (V-ATPase) proton pump is the primary pH regulator. V-ATPase ‘V0a2’ subunit, a major pH sensing unit, is over-expressed on cancer cells in a wide array of tumor types including ovarian cancer (OVCA). Here, we examined the clinical relevance of V-ATPase ‘V0a2’ subunit in OVCA patient samples and its therapeutic potential in controlling tumor growth in pre-clinical mouse model. The gene data from Cancer Genome Atlas (TCGA) showed a high frequency of V-ATPase gene alterations in OVCA patients (74%, 448/606 patients). Specifically, the V0a2 gene was highly expressed in all stages of OVCA patients indicating its importance in a centralized physiological mechanism of pH regulation. Across the different OVCA grades, the V0a2 gene expression significantly increased with the tumor grade (Grade 1&amp;lt; Grade2 &amp;lt;Grade 3). Immuno-histochemical and confocal analysis confirmed V0a2 overexpression in both Type I (IHC score= 5.8±1.6; n=46) and Type II (IHC score=7.3±1.8; n=22) OVCA patient tissues compared to non-cancer control group (IHC score=2.0±1.2; n=10). In addition to cancer cells, V0a2 was also expressed on the immune infiltrated cells recruited to TME using CD68 (macrophages) and neutrophil elastase (neutrophil) markers that co-localized with V0a2 staining. Monoclocal antibody against V0a2 (anti-V0a2; MAb) effectively inhibited the proton pump activity, MMPs activation and migration of OVCA cells in vitro. In vivo anti-V0a2 treatment (300µg in PBS; i.p) resulted in delayed tumor growth (3.8 fold, p&amp;lt; 0.05) compared to control, with no apparent in vivo toxicity in athymic nude mice xenograft model. Histological staining of anti-V0a2 treated tumor tissues revealed higher immune-infiltration and a marked decrease in cancer cell numbers compared to control tissues. We observed an increased total leukocyte population (CD45), macrophages (F4/80) and a higher anti-tumor response in anti-V0a2 treated tumors. These results show that V-ATPase-V0a2 is overexpressed in tumor microenvironment and its inhibition impairs ovarian cancer growth by interfering with tumor acidification and activation of anti-tumor responses. In conclusion, the study demonstrates that targeting V-ATPase pH regulators is an effective treatment strategy in ovarian cancer. Citation Format: Arpita Kulshrestha, Gajendra K. Katara, Safaa A. Ibrahim, Alexandria N. Young, Shayna Levine, Valerie E. Riehl, Mahmood Bilal, Alice Gilman-Sachs, Kenneth Beaman. Targeting tumor associated pH regulators: Effective therapeutic strategy in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 106.

Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA): A Potential New Tool for Early Detection of Ovarian Cancer.

Objectives: To conduct a comprehensive glycopeptide spectra analysis of serum between cancer and non-cancer patients to identify early biomarkers of epithelial ovarian cancer (EOC). Methods: Approximately 30,000 glycopeptide peaks were detected from the digested serum glycoproteins of 39 EOC patients (23 early-stage, 16 advanced-stage) and 45 non-cancer patients (27 leiomyoma and ovarian cyst cases, 18 endometrioma cases) by liquid chromatography mass spectrometry (LC–MS). The differential glycopeptide peak spectra were analyzed to distinguish between cancer and non-cancer groups by employing multivariate analysis including principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA) and heat maps. Results: Examined spectral peaks were filtered down to 2281 serum quantitative glycopeptide signatures for differentiation between ovarian cancer and controls using multivariate analysis. The OPLS-DA model using cross-validation parameters R2 and Q2 and score plots of the serum samples significantly differentiated the EOC group from the non-cancer control group. In addition, women with early-stage clear cell carcinoma and endometriomas were clearly distinguished from each other by OPLS-DA as well as by PCA and heat maps. Conclusions: Our study demonstrates the potential of comprehensive serum glycoprotein analysis as a useful tool for ovarian cancer detection.

Associations of cell cycle genetic variants with aggressive prostate cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.

175 Background: The need to differentiate patients at risk for developing aggressive prostate cancer (CaP) from those at risk for less aggressive disease has led to efforts to identify genetic markers to predict disease course and personalize treatment. A study with participants from Johns Hopkins Medical Institutions (JHMI) and Washington University (WU) found single nucleotide polymorphisms (SNPs) in cell cycle genes were associated with risk of aggressive CaP. We sought to replicate those results in the European-American population of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Methods: We focused on variants associated with aggressive CaP in the JHMI and WU cohorts, which included 13 SNPs in 12 genes ( CCNC, CCND3, CCNG1, CCNT2, CDK2, CDK6, MDM2, SKP2, TERF2, WEE1, YWHAB, YWHAH). Variants were genotyped using the Pyrosequencing assay. Patients were classified into high risk (Gleason≥8, pT3b, N+, M+), low risk (Gleason≤7, ≤pT3a, N0, M0) or non-cancer control groups based on clinicopathologic characteristics. Logistic regression analysis was used to compare genotype frequencies of each variant between groups using the dominant model. Results: There were 108 aggressive and 1080 non-aggressive CaP patients, and 1155 controls . CDK6 ( rs8) was associated with increased risk of any CaP (OR 1.2, 95% CI 1.02-1.42; p = 0.032) and high risk disease (OR 1.63, 95% CI 1.09-2.42; p = 0.017) vs. controls. In contrast, the JHMI and WU cohort found CDK6 variants to be protective against aggressive CaP. CCNG1 ( rs11541970) approached significance (p = 0.052) between high risk and control groups, and CCNC conferred a protective effect consistent with the prior study, but did not reach significance (p = 0.101). No associations with any cell cycle gene variants were detected when comparing high and low risk patients. Conclusions: Our study did not replicate the results from the JHMI and WU cohorts. CDK6 predicted an increased risk of developing any CaP and high risk CaP. However, directionality was opposite to the prior study, indicating that this variant is unlikely to be a true predictor of increased risk of or protection from aggressive CaP.

Asymptomatic Endometrial Thickening of 8 mm or Greater on Postcontrast Computed Tomography in Postmenopausal Women Is a Predictor of Endometrial Cancer.

The aim of this study was to assess the value of opportunistic endometrial thickness measurement on postcontrast computed tomography (CT) as a predictor of endometrial cancer in asymptomatic postmenopausal women. For this Health Insurance Portability and Accountability Act-compliant, institutional review board-approved retrospective study with waiver of informed consent, our institution's tumor board database was searched for postmenopausal patients, diagnosed with endometrial cancer between August 2003 and December 2016 and who had a postcontrast pelvic CT within 12 months prior to the cancer diagnosis (while they were asymptomatic)-"cancer group." Same number of age-matched patients who had postcontrast pelvic CT constituted the noncancer control group. Endometrial thickness was measured on sagittal postcontrast CT images. After applying exclusion criteria, 22 asymptomatic patients who were diagnosed with endometrial cancer within 1 year after the CT comprised the cancer group, and 22 age-matched patients comprised the control group. Average endometrial thickness was 18.7 ± 14.8 mm (range, 2-70 mm) in the cancer group and 3.6 ± 2.5 mm (range, 1.8-10 mm) in the control group (P < 0.0001). Endometrial thickness 8 mm or greater predicted endometrial cancer with 86% sensitivity and 91% specificity in these asymptomatic patients. Area under the receiver operating characteristic curve for endometrial thickness as a predictor of endometrial cancer was 0.92. Endometrial thickness 8 mm or greater on sagittal postcontrast CT was shown to have high sensitivity in opportunistic detection of endometrial cancer in asymptomatic postmenopausal women.

Contribution of MMP2 Promoter Genotypes to Oral Cancer Susceptibility, Recurrence and Metastasis in Taiwan.

Metalloproteinase 2 (MMP2) is a multi-functional protein which has been shown to be up-regulated in patients with oral cancer, especially those with lymph node metastasis. However, the association of MMP2 genotype with oral cancer risk or metastatic behavior is unknown. This study aimed to evaluate the role of MMP2 promoter 1306 and -735 genotypes in the risk of oral cancer and metastasis. In this case-control study, MMP2 promoter 1306 (rs243865) and -735 (rs2285053) genotypes and their interaction with consumption of areca, cigarettes, and alcohol in determining oral cancer risk were investigated among 788 patients with oral cancer and 956 gender-matched healthy controls. In addition, their role in oral cancer metastasis were also examined. The distribution of CC, CT and TT for MMP2 promoter 1306 genotype was 79.0, 20.1 and 0.9% in the oral cancer group and 68.7, 29.2 and 2.1% in the non-cancer control group, respectively (p for trend=4.3E-6). The allelic frequency distributions showed that the variant T allele of MMP2 promoter 1306 conferred lower oral cancer susceptibility than the wild-type C allele (odds ratio=0.61, 95% confidence interval=0.50-0.75, p=1.1E-6). As for the MMP2 -735 genotypes, there was no differential distribution in genotypic or allelic frequencies. The variant CT and TT genotypes were also associated with lower metastasis rates within 5 years among the patients with oral cancer (odds ratio=0.34, 95% confidence interval=0.15-0.80, p=0.0102). The CT and TT genotypes of MMP2 promoter 1306 may have a protective effect on oral cancer susceptibility and metastasis risk within 5 years for Taiwanese. They may serve as predictive markers for oral cancer in precise medical practice.

Pre-existing Symptoms and Healthcare Utilization Prior to Diagnosis of Neuroendocrine Tumors: A SEER-Medicare Database Study

The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, their prevalence and impact on resource utilization and costs are largely unknown. We identified 9,319 elderly patients diagnosed with NETs between 1/2003 and 12/2011 from the Surveillance, Epidemiology and End Results (SEER)-Medicare. We examined the patients’ conditions potentially associated with NET, resource utilization and costs during the year before diagnosis. We found that NET patients were more likely to have diagnoses of hypertension (63.8% vs. 53.3%), abdominal pain (22.2% vs. 7.6%), heart failure (11.7% vs. 8.0%), diarrhea (5.8% vs. 1.8%), peripheral edema (5.4% vs. 3.8%) and irritable bowel syndrome (1.2% vs. 0.5%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 22.1 vs. 17.2), percentage with ER visits (20.9% vs. 11.6%), and hospitalizations (28.4% vs. 17.0%). Similarly, NET patients incurred significantly higher total (mean: $14602 vs. $9464), outpatient (mean: $5987 vs. $4253), and inpatient costs (mean: $8615 vs. $5211). This first population-based study on the pre-diagnosis symptoms and healthcare utilization found that NET patients were more likely to have certain conditions and incur higher resource utilizations and costs.

Costs of Cancer Care for Elderly Patients with Neuroendocrine Tumors.

The incidence and prevalence of neuroendocrine tumors (NETs) have been steadily rising. NETs can arise in various parts of the body and have distinct pathogenesis, clinical manifestations, treatment, and survival compared to other neoplasms. The magnitude of the economic burden of NETs is largely unknown. This study aimed to estimate the cost of illness for NETs among elderly patients based on a large amount of observational data. We estimated the direct medical costs by phase of care using the Surveillance, Epidemiology, and End Results-Medicare data, including claims from January 1, 2002 through to December 31, 2012. Patients' care was categorized into three phases: initial phase (first year after diagnosis), terminal phase (last year of life), and continuing phase (the period between). We estimated the cost of illness by calculating the difference in medical costs between NET patients and a matched sample from a non-cancer control group. Our study sample included 8409 elderly NET patients in the initial phase, 9218 patients in the continuing phase, and 7897 in the terminal phase. The mean cost of care for the initial phase was $46,462 in 2016 US dollars; mean cost of care for the terminal phase with a cancer-related death was $122,702; while the mean cost of care for the continuing phase was $10,457. The mean 5-year cost was $87,079. This population-based study showed that NET patients had substantial continuing phase costs and 5-year costs. Among elderly NET patients, those with pancreas as the primary cancer site had the highest costs.

Incidence of comorbidities in women with breast cancer treated with tamoxifen or an aromatase inhibitor: an Australian population-based cohort study.

BackgroundThe development of comorbidities has become increasingly relevant with longer-term cancer survival.ObjectiveTo assess the pattern of comorbidities among Australian women with breast cancer treated with tamoxifen or an aromatase inhibitor.DesignRetrospective cohort study using Pharmaceutical Benefits Scheme (PBS) data (10% sample) from January 2003 to December 2014. Dispensing claims data were used to identify comorbidities and classified with the Rx-Risk-V model. The breast cancer cohort had tamoxifen or an aromatase inhibitor dispensed between 2004 and 2011 with no switching between types of endocrine therapy. Comparisons were made between the breast cancer cohort and specific control groups (age- and sex-matched at 1:10 ratio without any dispensing of anti-neoplastic agents during the study period) for the development of five individual comorbidities over time using Cox regression models.ResultsWomen treated with tamoxifen had a higher incidence of cardiovascular conditions, diabetes, and pain or pain-inflammation, but a lower incidence of hyperlipidaemia compared with non-cancer control groups, as indicated by PBS data. Women treated with aromatase inhibitors were more likely to develop cardiovascular conditions, osteoporosis, and pain or pain-inflammation compared with non-cancer control groups. The risks of hyperlipidaemia and osteoporosis were significantly lower among tamoxifen users compared with aromatase inhibitor users.ConclusionsWomen with hormone-dependent breast cancer treated with an endocrine therapy had a higher risk of developing specified comorbid conditions than women without cancer, with different comorbidity profiles for those on tamoxifen versus aromatase inhibitors. Further research into the causes and mechanism of development and management of comorbidities after cancer is needed.

Contribution of Matrix Metalloproteinase-7 Genotypes to the Risk of Non-solid Tumor, Childhood Leukemia.

The matrix metalloproteinases (MMPs) are important in inflammation and carcinogenesis, and the genotypic role of MMP7 has never been examined in leukemia to date. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP7 (A-181G and C-153T) to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan. In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology. The distribution of AA, AG and GG for MMP7 promoter A-181G genotype was 83.5, 12.0 and 4.5% in the childhood ALL group and 89.8%, 9.4 and 0.8% in the non-cancer control group, respectively (p for trend=0.0134), significantly differentially distributed between childhood ALL and control groups. The comparisons in allelic frequency distribution also support the findings that G appears to be the risky allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP7 A-181G GG and AG+GG genotypes had 9.05- and 2.45-fold odds ratios (ORs) (p=0.0135 and 0.0142, respectively) for childhood ALL compared to those carrying wild-type AA genotype. But these differences were not found in girls. Analysis of genotype interaction with age of onset age showed those aged less than 3.5 years at onset carrying the GG or AG+GG genotypes also had elevated ORs of 8.79- and 2.04-fold (p=0.0150 and 0.0413, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more. Our results indicate that the MMP7 A-181G genotype interacts with age and gender and may serve as an early and predictive biomarker for childhood ALL.