Publications by authors named "Shailesh M Advani"

20 Publications

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Engaging Patients with Late-Stage Non-Small Cell Lung Cancer in Shared Decision Making about Treatment.

J Pers Med 2021 Oct 1;11(10). Epub 2021 Oct 1.

Department of Medical Oncology, Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.

Few treatment decision support interventions (DSIs) are available to engage patients diagnosed with late-stage non-small cell lung cancer (NSCLC) in treatment shared decision making (SDM). We designed a novel DSI that includes care plan cards and a companion patient preference clarification tool to assist in shared decision making. The cards answer common patient questions about treatment options (chemotherapy, chemotherapy plus immunotherapy, targeted therapy, immunotherapy, clinical trial participation, and supportive care). The form elicits patient treatment preference. We then conducted interviews with clinicians and patients to obtain feedback on the DSI. We also trained oncology nurse educators to implement the prototype. Finally, we pilot tested the DSI among five patients with NSCLC at the beginning of an office visit scheduled to discuss treatment with an oncologist. Analyses of pilot study baseline and exit survey data showed that DSI use was associated with increased patient awareness of the alternatives' treatment options and benefits/risks. In contrast, patient concern about treatment costs and uncertainty in treatment decision making decreased. All patients expressed a treatment preference. Future randomized controlled trials are needed to assess DSI implementation feasibility and efficacy in clinical care.
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October 2021

Association of Breast Density With Breast Cancer Risk Among Women Aged 65 Years or Older by Age Group and Body Mass Index.

JAMA Netw Open 2021 Aug 2;4(8):e2122810. Epub 2021 Aug 2.

Terasaki Institute of Biomedical Innovation, Los Angeles, California.

Importance: Breast density is associated with breast cancer risk in women aged 40 to 65 years, but there is limited evidence of its association with risk of breast cancer among women aged 65 years or older.

Objective: To compare the association between breast density and risk of invasive breast cancer among women aged 65 to 74 years vs women aged 75 years or older and to evaluate whether the association is modified by body mass index (BMI).

Design, Setting, And Participants: This prospective cohort study used data from the Breast Cancer Surveillance Consortium from January 1, 1996, to December 31, 2012, for US women aged 65 years or older who underwent screening mammography. Data were analyzed from January 1, 2018, to December 31, 2020.

Exposures: Breast Imaging Reporting and Data System breast density category, age, and BMI.

Main Outcomes And Measures: The 5-year cumulative incidence of invasive breast cancer by level of breast density (almost entirely fat, scattered fibroglandular densities, or heterogeneous or extreme density) and age (65-74 vs ≥75 years) was calculated using weighted means. Cox proportional hazards models were fit to estimate the association of breast density with invasive breast cancer risk. The likelihood ratio test was used to test the interaction between BMI and breast density.

Results: A total of 221 714 screening mammograms from 193 787 women were included in the study; a total of 38% of the study population was aged 75 years or older. Of the mammograms, most were from women aged 65 to 74 years (64.6%) and non-Hispanic White individuals (81.4%). The 5-year cumulative incidence of invasive breast cancer increased in association with increasing breast density among women aged 65 to 74 years (almost entirely fatty breasts: 11.3 per 1000 women [95% CI, 10.4-12.5 per 1000 women]; scattered fibroglandular densities: 17.2 per 1000 women [95% CI, 16.1-17.9 per 1000 women]; extremely or heterogeneously dense breasts: 23.7 per 1000 women [95% CI, 22.4-25.3 per 1000 women]) and among those aged 75 years or older (fatty breasts: 13.5 per 1000 women [95% CI, 11.6-15.5]; scattered fibroglandular densities: 18.4 per 1000 women [95% CI, 17.0-19.5 per 1000 women]; extremely or heterogeneously dense breasts: 22.5 per 1000 women [95% CI, 20.2-24.2 per 1000 women]). Extreme or heterogeneous breast density was associated with increased risk of breast cancer compared with scattered fibroglandular breast density in both age categories (65-74 years: hazard ratio [HR], 1.39 [95% CI, 1.28-1.50]; ≥75 years: HR, 1.23 [95% CI, 1.10-1.37]). Women with almost entirely fatty breasts had a decrease of approximately 30% (range, 27%-34%) in the risk of invasive breast cancer compared with women with scattered fibroglandular breast density (65-74 years: HR, 0.66 [95% CI, 0.58-0.75]; ≥75 years: HR, 0.73; 95% CI, 0.62-0.86). Associations between breast density and breast cancer risk were not significantly modified by BMI (for age 65-74 years: likelihood ratio test, 2.67; df, 2; P = .26; for age ≥75 years, 2.06; df, 2; P = .36).

Conclusions And Relevance: The findings suggest that breast density is associated with increased risk of invasive breast cancer among women aged 65 years or older. Breast density and life expectancy should be considered together when discussing the potential benefits vs harms of continued screening mammography in this population.
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August 2021

Impartially Validated Multiple Deep-Chain Models to Detect COVID-19 in Chest X-ray Using Latent Space Radiomics.

J Clin Med 2021 Jul 14;10(14). Epub 2021 Jul 14.

Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA.

The COVID-19 pandemic continues to spread globally at a rapid pace, and its rapid detection remains a challenge due to its rapid infectivity and limited testing availability. One of the simply available imaging modalities in clinical routine involves chest X-ray (CXR), which is often used for diagnostic purposes. Here, we proposed a computer-aided detection of COVID-19 in CXR imaging using deep and conventional radiomic features. First, we used a 2D U-Net model to segment the lung lobes. Then, we extracted deep latent space radiomics by applying deep convolutional autoencoder (ConvAE) with internal dense layers to extract low-dimensional deep radiomics. We used Johnson-Lindenstrauss (JL) lemma, Laplacian scoring (LS), and principal component analysis (PCA) to reduce dimensionality in conventional radiomics. The generated low-dimensional deep and conventional radiomics were integrated to classify COVID-19 from pneumonia and healthy patients. We used 704 CXR images for training the entire model (i.e., U-Net, ConvAE, and feature selection in conventional radiomics). Afterward, we independently validated the whole system using a study cohort of 1597 cases. We trained and tested a random forest model for detecting COVID-19 cases through multivariate binary-class and multiclass classification. The maximal (full multivariate) model using a combination of the two radiomic groups yields performance in classification cross-validated accuracy of 72.6% (69.4-74.4%) for multiclass and 89.6% (88.4-90.7%) for binary-class classification.
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July 2021

Impact of Underlying Comorbidities on Mortality in SARS-COV-2 Infected Cancer Patients: A Systematic Review and Meta-Analysis.

Asian Pac J Cancer Prev 2021 May 1;22(5):1333-1349. Epub 2021 May 1.

Cancer Prevention and Control Program, Georgetown University School of Medicine, Georgetown University, Washington DC, USA.

Background: The evidence has shown that SARS CoV-2 infected patients with comorbidities are more likely to have severe disease sequel and mortality. In SARS-CoV-2 infected cancer patients risks associated with other underlying comorbidities might vary from those in non-cancer SARS CoV-2 infected patients. The relative impact of different underlying health conditions among patients with cancer and SARS CoV-2 infection remains yet to be explored. This systematic review aims to explore the prevalence of comorbidities among cancer patients with SARS CoV-2 infection and their impact on mortality.

Methods: Online databases PubMed, Embase, Scopus and Web of science were searched for articles published between 9th July 2019 to July 8th 2020.Studies of cancer patients (>18 years) with diagnosis of SARS CoV-2 infection, published in English were included. A random-effects modelling for the meta-analyses was applied to assess the pooled prevalence and odds ratio for mortality due to comorbidities in SARS CoV-2 infected cancer patients.

Results: Total 31studies with 4086 SARS-CoV-2 infectedcancer patientsmet the inclusion criteria. Most prevalent co-morbidities in cancer patients with SARS CoV-2 infection were hypertension [42.3% (95%CI:37.5- 47.0)], diabetes [17.8% (95% CI: 15.3-20.4)] and cardiovascular diseases [16.7% (95%CI:12.9-20.4)].The risk of mortality (pOR) was significantly higher in individuals with hypertension[1.6(95%CI 1.24-2.00)], cardiovascular diseases [2.2 (95%CI 1.49- 3.27)], chronic obstructive pulmonary diseases [1.4(95% CI 1.05-2.00)] and diabetes [1.35(95%CI 1.06-1.73)].

Conclusion: Our results indicates that the mortality in SARS-CoV-2 infected cancer patients is affected by preexisting non-cancer comorbidities. By identifying the comorbidities predictive for mortality, clinicians can better stratify the risk of cancer patients presenting with SARS-COV-2, on their initial contact with health services.
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May 2021

Disparities in H1N1 Vaccination Rates: a Systematic Review and Evidence Synthesis to Inform COVID-19 Vaccination Efforts.

J Gen Intern Med 2021 06 31;36(6):1734-1745. Epub 2021 Mar 31.

VA Evidence Synthesis Program, VA Portland Health Care System, 3710 SW US Veterans Hospital Rd, Portland, OR, 97239, USA.

Background: Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine uptake, factors contributing to disparities, and interventions to reduce them.

Methods: We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment.

Results: We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (low- to moderate-strength evidence). However, Latinos were more likely than Whites to intend to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (low-strength evidence). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied.

Discussion: Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy.

Primary Funding Source: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development.

Protocol Registration: PROSPERO CRD42020187078.
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June 2021

Prevalence and mortality of lung comorbidities among patients with COVID-19: A systematic review and meta-analysis.

Lung India 2021 Mar;38(Supplement):S31-S40

University of Glasgow, Glasgow, UK; Prince Sultan Military Medical City, Respiratory Care Department, Riyadh, Saudi Arabia.

COVID-19 infections are seen across all age groups, but they have shown to have a predisposition for the elderly and those with underlying comorbidities. Patients with severe COVID-19 infections and comorbidities are more prone to respiratory distress syndrome, mechanical ventilator use, and ultimately succumb to these complications. Little evidence exists of the prevalence of underlying lung comorbidities among COVID-19 patients and associated mortality. We performed a systematic review of the literature including PubMed (Medline), Embase (Ovid), Google Scholar, and Cochrane Library. The last date for our search was April 29, 2020. We included all original research articles on COVID-19 and calculated prevalence of chronic lung disease patients among COVID-19 patients using random effects model. Further, we assessed for mortality rates among COVID-19 patients associated with these lung comorbidities. The authors identified 29 articles that reported prevalence of chronic lung conditions among COVID-19 patients. Among those, 26 were from China and 3 from the United States. The pooled prevalence of lung comorbidities including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer was 3% (95% confidence interval [CI] = 0%-14%), 2.2% (95% CI = 0.02%-0.03%), and 2.1% (95% CI = 0.00%-0.21%), respectively. Mortality rates associated with these comorbidities was 30% (41/137) for COPD and 19% (7/37) for lung cancer respectively. No mortality rates were reported for patients with asthma. This study offers latest evidence of prevalence of chronic lung conditions among patients with COVID-19. Asthma, followed by COPD and lung cancer, was the most common lung comorbidity associated with COVID-19, while the higher mortality rate was found in COPD. Future studies are needed to assess other lung comorbidities and associated mortality among patients diagnosed with COVID-19.
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March 2021

ARID1A Mutation May Define an Immunologically Active Subgroup in Patients with Microsatellite Stable Colorectal Cancer.

Clin Cancer Res 2021 03 7;27(6):1663-1670. Epub 2021 Jan 7.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: AT-rich interactive domain 1A () is commonly mutated in colorectal cancer, frequently resulting in truncation and loss of protein expression. ARID1A recruits MSH2 for mismatch repair during DNA replication. ARID1A deficiency promotes hypermutability and immune activation in preclinical models, but its role in patients with colorectal cancer is being explored.

Experimental Design: The DNA sequencing and gene expression profiling of patients with colorectal cancer were extracted from The Cancer Genome Atlas and MD Anderson Cancer Center databases, with validation utilizing external databases, and correlation between ARID1A and immunologic features. IHC for T-cell markers was performed on a separate cohort of patients.

Results: Twenty-eight of 417 patients with microsatellite stable (MSS) colorectal cancer (6.7%) had mutation. Among 58 genes most commonly mutated in colorectal cancer, mutation had the highest increase with frameshift mutation rates in MSS cases (8-fold, < 0.001). In MSS, mutation was enriched in immune subtype (CMS1) and had a strong correlation with IFNγ expression (Δ score +1.91, < 0.001). Compared with wild-type, statistically significant higher expression for key checkpoint genes (e.g., PD-L1, CTLA4, and PDCD1) and gene sets (e.g., antigen presentation, cytotoxic T-cell function, and immune checkpoints) was observed in mutant cases. This was validated by unsupervised differential expression of genes related to immune response and further confirmed by higher infiltration of T cells in IHC of tumors with mutation ( = 0.01).

Conclusions: The immunogenicity of -mutant cases is likely due to an increased level of neoantigens resulting from increased tumor mutational burden and frameshift mutations. Tumors with mutation may be more susceptible to immune therapy-based treatment strategies and should be recognized as a unique molecular subgroup in future immune therapy trials.
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March 2021

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

Ann Intern Med 2021 03 1;174(3):362-373. Epub 2020 Dec 1.

VA Evidence Synthesis Program, VA Portland Health Care System and Oregon Health & Science University, Portland, Oregon (K.M., K.K.K., S.S., D.K.).

Background: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups.

Purpose: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them.

Data Sources: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020.

Study Selection: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings.

Data Extraction: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence.

Data Synthesis: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence).

Limitations: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies.

Conclusion: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates.

Primary Funding Source: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).
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March 2021

Epidemiology and Molecular-Pathologic Characteristics of CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer.

Clin Colorectal Cancer 2021 06 12;20(2):137-147.e1. Epub 2020 Oct 12.

Division of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Background: CpG island methylator phenotype (CIMP) forms a distinct epigenetic phenotype in colorectal cancer (CRC). Though associated with distinct clinicopathologic characteristics, limited evidence exists of the association of CIMP with patient's reported lifestyle factors and tumor molecular characteristics. We assessed the associations of these characteristics in a pooled analysis of CRC patients.

Patients And Methods: We pooled data from 3 CRC patient cohorts: Assessment of Targeted Therapies Against Colorectal Cancer (ATTACC), biomarker-based protocol (Integromics), and The Cancer Genome Atlas (TCGA). CIMP was measured using the classical 6-gene methylated-in-tumor (MINT) marker panel (MINT1, MINT2, MINT31, p14, p16, and MLH1) in ATTACC and genome-wide human methylation arrays in Integromics and TCGA, respectively. CIMP-High (CIMP-H) was defined as ≥ 3 of 6 methylated markers in ATTACC. In TCGA and Integromics, CIMP-H group was defined on the basis of clusters of methylation profiles and high levels of methylation in tumor samples. Baseline comparisons of characteristics across CIMP groups (CIMP-H vs. CIMP-0) were performed by Student t test or chi-square test for continuous or categorical variables, respectively. Further logistic regression analyses were performed to compute the odds ratio (OR) of these associations.

Results: Pooled prevalence of CIMP-H was 22% across 3 data sets. CIMP-H CRC tumors were associated with older age at diagnosis (OR, 1.02; 95% confidence interval [CI], 1.01, 1.03), microsatellite instability-high (MSI-H) status (OR, 9.15; 95% CI, 4.45, 18.81), BRAF mutation (OR, 7.70; 95% CI, 4.98, 11.87), right-sided tumor location (OR, 2.40; 95% CI, 1.78, 3.22), poor differentiation (OR, 2.94; 95% CI, 1.95, 4.45), and mucinous histology (OR, 2.47; 95% CI, 1.77, 3.47), as reported previously in the literature. CIMP-H tumors were also found to be associated with self-reported history of alcohol consumption (OR, ever vs. never, 1.58; 95% CI, 1.07, 2.34). Pathologically, CIMP-H tumors were associated with the presence of intraepithelial lymphocytes (OR, 3.31; 95% CI, 1.41, 7.80) among patients in the Integromics cohort.

Conclusion: CIMP-H tumors were associated with history of alcohol consumption and presence of intraepithelial lymphocytes. In addition, we confirmed the previously known association of CIMP with age, MSI-H status, BRAF mutation, sidedness, and mucinous histology. Molecular pathologic epidemiology associations help us explore the underlying association of lifestyle and clinical factors with molecular subsets like CIMP and help guide cancer prevention and treatment strategies.
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June 2021

Estimating global injuries morbidity and mortality: methods and data used in the Global Burden of Disease 2017 study.

Inj Prev 2020 10 24;26(Supp 1):i125-i153. Epub 2020 Aug 24.

Department of Pharmacy, Adigrat University, Adigrat, Ethiopia.

Background: While there is a long history of measuring death and disability from injuries, modern research methods must account for the wide spectrum of disability that can occur in an injury, and must provide estimates with sufficient demographic, geographical and temporal detail to be useful for policy makers. The Global Burden of Disease (GBD) 2017 study used methods to provide highly detailed estimates of global injury burden that meet these criteria.

Methods: In this study, we report and discuss the methods used in GBD 2017 for injury morbidity and mortality burden estimation. In summary, these methods included estimating cause-specific mortality for every cause of injury, and then estimating incidence for every cause of injury. Non-fatal disability for each cause is then calculated based on the probabilities of suffering from different types of bodily injury experienced.

Results: GBD 2017 produced morbidity and mortality estimates for 38 causes of injury. Estimates were produced in terms of incidence, prevalence, years lived with disability, cause-specific mortality, years of life lost and disability-adjusted life-years for a 28-year period for 22 age groups, 195 countries and both sexes.

Conclusions: GBD 2017 demonstrated a complex and sophisticated series of analytical steps using the largest known database of morbidity and mortality data on injuries. GBD 2017 results should be used to help inform injury prevention policy making and resource allocation. We also identify important avenues for improving injury burden estimation in the future.
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October 2020

Patient-reported Symptom Outcomes and Microsatellite Instability in Patients With Metastatic Colorectal Cancer.

Clin Colorectal Cancer 2020 03 23;19(1):48-56.e2. Epub 2019 Oct 23.

Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Background: The survival of patients with metastatic colorectal cancer (mCRC) is influenced by the genetic and epigenetic changes that might influence the patient experience of symptom burden. Understanding the association of molecular changes with the symptom burden could help clinicians gain insight into the molecular basis of symptom burden and improve treatment tolerance. To date, no studies have compared the patient-reported symptom burden with these molecular subsets among patients with mCRC.

Patients And Methods: We recruited patients with mCRC that was refractory to ≥ 1 line of therapy who had been enrolled in the Assessment of Targeted Therapies Against Colorectal Cancer trial at The University of Texas MD Anderson Cancer Center. All patients completed a baseline gastrointestinal symptom inventory (MD Anderson Symptom Inventory, gastrointestinal). The symptom burden across key demographic variables and molecular changes, including CRC-associated mutations, microsatellite instability (MSI) status, and the CpG island methylator phenotype (CIMP) were compared using χ tests. Association of the symptom burden with overall survival was examined using Cox regression models.

Results: Patients with an MSI-high (MSI-H) phenotype reported greater pain (odds ratio [OR], 3.06; 95% confidence interval [CI], 1.61-5.84), fatigue (OR, 2.78; 95% CI, 1.41-5.49), sleep (OR, 2.52; 95% CI, 1.32-4.08); and drowsiness (OR, 2.51; 95% CI, 1.32-4.78) compared with microsatellite stable patients. Patients with an MSI-H phenotype also had greater odds of overall symptom burden (OR, 2.48; 95% CI, 1.29-4.74) compared with microsatellite stable patients. The CIMP-high patients experienced greater odds of pain compared with the CIMP-negative patients (OR, 1.72; 95% CI, 1.06-2.80). A greater overall symptom burden was associated with poor overall survival (hazard ratio, 1.42; 95% CI, 0.98-2.06]), although the difference was not significant (P = .06).

Conclusion: Correlation of MSI-H-associated tumor features with the symptom burden could help provide a better understanding of underlying mechanisms associated with our findings.
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March 2020

Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study.

JAMA Oncol 2019 12;5(12):1749-1768

Department of Family and Community Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

Conclusions And Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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December 2019

Smoking cessation interventions for potential use in the lung cancer screening setting: A systematic review and meta-analysis.

Lung Cancer 2019 09 6;135:205-216. Epub 2019 Jul 6.

Georgetown University Medical Center-Lombardi Comprehensive Cancer Center, Cancer Prevention and Control Program, 3300 Whitehaven St. NW, Washington, DC, USA.

Objectives: Current guidelines recommend delivery of smoking cessation interventions with lung cancer screening (LCS). Unfortunately, there are limited data to guide clinicians and policy-makers in choosing cessation interventions in this setting. Several trials are underway to fill this evidence gap, but results are not expected for several years.

Methods And Materials: We conducted a systematic review and meta-analysis of current literature on the efficacy of smoking cessation interventions among populations eligible for LCS. We searched PubMed, Medline, and PsycINFO for randomized controlled trials of smoking cessation interventions published from 2010-2017. Trials were eligible for inclusion if they sampled individuals likely to be eligible for LCS based on age and smoking history, had sample sizes >100, follow-up of 6- or 12-months, and were based in North America, Western Europe, Australia, or New Zealand.

Results: Three investigators independently screened 3,813 abstracts and identified 332 for full-text review. Of these, 85 trials were included and grouped into categories based on the primary intervention: electronic/web-based, in-person counseling, pharmacotherapy, and telephone counseling. At 6-month follow-up, electronic/web-based (odds ratio [OR] 1.14, 95% CI 1.03-1.25), in-person counseling (OR 1.46, 95% CI 1.25-1.70), and pharmacotherapy (OR 1.53, 95% CI 1.33-1.77) interventions significantly increased the odds of abstinence. Telephone counseling increased the odds but did not reach statistical significance (OR 1.21, 95% CI 0.98-1.50). At 12-months, in-person counseling (OR 1.28 95% CI 1.10-1.50) and pharmacotherapy (OR 1.46, 95% CI 1.17-1.84) remained efficacious, although the decrement in efficacy was of similar magnitude across all intervention categories.

Conclusions: Several categories of cessation interventions are promising for implementation in the LCS setting.
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September 2019

Pharmacological management of cachexia in adult cancer patients: a systematic review of clinical trials.

BMC Cancer 2018 Nov 27;18(1):1174. Epub 2018 Nov 27.

Department of Medicine, Division of Oncology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, 77030, USA.

Background: Cachexia is a multisystem syndrome characterized by weight loss, anorexia, loss of muscle mass, systemic inflammation, insulin resistance, and functional decline. Management of cachexia involves addressing multiple underlying biological mechanisms. Previous review on pharmacological management of cancer cachexia identified progestins and corticosteroids as effective agents for treatment of cachexia. However, to date no consensus exists on a single effective or standard treatment for management of cachexia. The aim of this systematic review is to determine the effectiveness of pharmacological treatments used to manage cachexia among adult cancer patients.

Methods: We performed literature searches of PubMed (NLM), Embase (Ovid), and Medline(Ovid) to identify clinical trials focused on pharmacological management of cancer cachexia among adult cancer patients from 2004 to 2018. Three reviewers screened a random selection of abstracts to measure for interrater reliability. After this step, each screener screened two-thirds of all abstracts and 177 studies were identified for full text review. The primary outcome was impact of pharmacological management on change in either weight or lean body mass in cancer patients.

Results: We identified 19 articles (representing 20 RCTs) that focused on pharmacological management of cancer cachexia. Agents showing promising results included Anamorelin and Enobosarm. Anamorelin at 50 or 100 mg per day for 12 weeks showed a consistent benefit across all studies and resulted in significant improvement in weight as compared to baseline among cancer patients. Enobosarm at 1 and 3 mg per day was also effective in improving lean body mass and QOL symptoms among advancer stage cancer patients. Finally, use of combination agents provide evidence for targeting multiple pathways underlying cachexia mechanism to achieve maximum benefit. No agents showed functional improvement in cancer patients.

Conclusion: Anamorelin as a single agent shows promising results in improving cachexia related weight loss among cancer patients. Further research on combination therapies may be helpful to address critical gaps in cachexia management.
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November 2018

Health-Related Quality of Life and Survival Outcomes of Pediatric Patients With Nonmetastatic Osteosarcoma Treated in Countries With Different Resources.

J Glob Oncol 2018 09 24;4:1-11. Epub 2017 Mar 24.

Michael W. Bishop, Catherine A. Billups, and Jami S. Gattuso, St Jude Children's Research Hospital; Michael W. Bishop, University of Tennessee Health Science Center, Memphis, TN; Shailesh M. Advani and Najat C. Daw, The University of Texas MD Anderson Cancer Center, Houston, TX; Milena Villarroel, Cecilia Rivera, and Juan A. Quintana, Luis Calvo McKenna Hospital, Santiago, Chile; Fariba Navid, Children's Hospital of Los Angeles, Los Angeles, CA; and Pamela S. Hinds, Children's National Health System and George Washington University, Washington, DC.

Purpose: Health-related quality of life (HRQOL) improves throughout treatment of patients with nonmetastatic osteosarcoma. We compared HRQOL for patients in the United States and Chile treated on an international trial (OS99) with polychemotherapy and surgery, and we assessed the relationships among HRQOL measures, event-free survival (EFS), and overall survival (OS).

Materials And Methods: Patients with newly diagnosed, localized osteosarcoma and their parents completed three HRQOL instruments (PedsQL v.4, PedsQL Cancer v.3, and Symptom Distress Scale [SDS]). Data were collected at four time points throughout therapy. Repeated measures models were used to investigate the effect of treatment site on instrument scores. The log-rank test examined the impact of treatment site on survival outcomes, and Cox proportional hazards regression models evaluated baseline HRQOL measures as predictors of EFS and OS.

Results: Of 71 eligible patients, 66 (93%) participated in the HRQOL studies in the United States (n = 44) and Chile (n = 22). The median age was 13.4 years (range, 5 to 23 years). Clinical characteristics were similar between treatment sites. US patients reported better scores for physical ( P = .030), emotional ( P = .027), and school functioning ( P < .001). Chilean patients reported poorer scores for worry ( P < .001) and nausea ( P = .007). Patient and parent nausea scores were similar between patients treated in the United States and Chile by the end of therapy. Differences in symptom distress were not observed between the countries. Neither HRQOL measures nor treatment site were associated with EFS or OS.

Conclusion: Although significant differences in HRQOL were observed between countries, outcomes were similar, and HRQOL measures were not associated with prognosis.
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September 2018

Prognostic Implications of Mucinous Differentiation in Metastatic Colorectal Carcinoma Can Be Explained by Distinct Molecular and Clinicopathologic Characteristics.

Clin Colorectal Cancer 2018 12 17;17(4):e699-e709. Epub 2018 Jul 17.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:

Background: The mucinous histologic subtype accounts for 5% to 20% of colorectal cancer (CRC) cases but remains poorly characterized. The present study characterized the baseline characteristics, mutational profile, and clinical outcomes of patients diagnosed with mucinous CRC.

Materials And Methods: We identified 1877 patients with metastatic CRC with available histologic findings and molecular profiling and summarized the baseline clinical and pathologic characteristics and overall survival (OS) stratified by the histologic type. The data from separate cohorts with consensus molecular subtype (CMS) and CpG island methylator information were also summarized.

Results: The mucinous histologic type was found in 277 of the 1877 patients (14.8%) and was associated with an increased prevalence of microsatellite instability (P < .001) and a right-sided primary (P < .001). An increased frequency of CMS1 (microsatellite instability immune) and lower rates of CMS2 (canonical) were identified, with mucinous compared with nonmucinous adenocarcinoma (P < .0001). Mutations in SMAD4 (P < .001), GNAS (P < .001), ERBB2 (P = .02), BRAF (P < .001), and KRAS (P < .001) occurred at greater frequencies in the mucinous CRC cases, and TP53 (P < .001), APC (P < .001), and NRAS mutations (P = .03) were less common. Univariate (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.17-1.63; P < .001) and multivariate analysis (HR, 1.36; 95% CI, 1.12-1.64; P = .002) demonstrated that the mucinous histologic type is associated with worse OS. The features associated with the mucinous histologic subtype were independent predictors for shorter OS, including BRAF (HR, 1.74; 95% CI, 1.35-2.25; P < .001) and KRAS (HR, 1.42; 95% CI, 1.22-1.65; P < .001) mutations, right-sided location (HR, 1.20; 95% CI, 1.04-1.39; P = .01), and synchronous metastases (HR, 2.92; 95% CI, 2.49-3.42; P < .001).

Conclusion: Compared with nonmucinous adenocarcinoma, the mucinous histologic type is associated with a worse prognosis, even when controlling for known prognostic features. This unique biologic behavior should be considered in the treatment and prognostic assessment of patients with CRC.
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December 2018

Clinical, Pathological, and Molecular Characteristics of CpG Island Methylator Phenotype in Colorectal Cancer: A Systematic Review and Meta-analysis.

Transl Oncol 2018 Oct 30;11(5):1188-1201. Epub 2018 Jul 30.

Division of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030. Electronic address:

Background: CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors.

Methods: We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model.

Results: We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatum bacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion.

Conclusion: The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.
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October 2018

Use of non-steroidal anti-inflammatory drugs in US adults: changes over time and by demographic.

Open Heart 2017;4(1):e000550. Epub 2017 Apr 28.

Baylor College of Medicine, USDA/ARS Children's Nutrition Research Center, Houston, Texas, USA.

Objective: Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) are preventive against cardiovascular disease (CVD) and several cancer types, but long-term use has been associated with significant health risks, resulting in conflicting recommendations on NSAID use for prevention of CVD and cancer. Previous research indicates that aspirin use increases with age and CVD risk factors and that a large percentage of the US population regularly use analgesics, including NSAIDs, but there has not been a recent, in-depth assessment of NSAID use prevalence, changes in use over time or predictors of NSAID use in the USA.

Methods: We used the cross-sectional, National Health And Nutrition Examination Survey (NHANES) from 1988 to 1994 and three continuous cycles (1999-2004) to assess regular NSAID use prevalence, changes over time and predictors of regular NSAID use.

Results: Overall, regular NSAID use increased over time and varied by demographic features. Participants over 60 years of age, women, participants with high body mass index, increased waist circumference or heart disease were significantly more likely to be regular NSAID users. By contrast, non-Hispanic African American and Mexican American participants were significantly less likely to regularly use NSAIDs.

Conclusions: This study uses a nationally representative data set (NHANES) to provide an exploration of regular NSAID use patterns over time, highlighting several demographic, lifestyle and clinical conditions associated with regular NSAID use. Understanding who is likely to regularly use NSAIDs enables more targeted messaging both for increasing the preventive benefits and for limiting the toxicities associated with regular use of NSAIDs.
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April 2017

Local Control Modality and Outcome for Ewing Sarcoma of the Femur: A Report From the Children's Oncology Group.

Ann Surg Oncol 2016 10 23;23(11):3541-3547. Epub 2016 May 23.

Department of Orthopaedics, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, UT, USA.

Background: The choice of a local control (LC) modality for Ewing sarcoma (EWS) of the femur is controversial. This study aimed to determine the effect of LC modality on tumor LC and patient outcomes.

Methods: The study reviewed the treatment and outcomes for 115 patients who had EWS of the femur treated with similar chemotherapy in three cooperative group trials. Patient outcomes were analyzed according to the LC modality using the log-rank test and the cumulative incidence of local or distant failure using competing risks regression.

Results: The median age of the patients was 13 years. The most common tumor location was the proximal femur followed by the mid femur. For 55 patients with available data, the tumor was larger than 8 cm in 29 patients and 8 cm or smaller in 26 patients. For 84 patients (73 %), surgery only was performed, whereas 17 patients (15 %) had surgery plus radiation, and 14 patients (12 %) had radiation only. The 5-year event-free survival (EFS) rate was 65 % (95 % confidence interval [CI], 55-73 %), and the 5-year overall survival (OS) rate was 70 % (95 % CI, 61-78 %). Patient outcomes did not differ significantly according to tumor location within the femur (proximal, mid or distal) or tumor size (<8 vs ≥8 cm). The findings showed no statistically significant differences in EFS, OS, cumulative incidence of local failure, or cumulative incidence of distant failure according to LC modality (surgery, surgery plus radiation, or radiation).

Conclusions: The LC modality did not significantly affect disease outcome for EWS of the femur. Further study of treatment complications and functional outcome may help to define the optimal LC modality.
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October 2016

A proposed staging system and stage-specific interventions for familial adenomatous polyposis.

Gastrointest Endosc 2016 Jul 6;84(1):115-125.e4. Epub 2016 Jan 6.

Center for Hereditary Tumors, HELIOS Klinikum Wuppertal, University Witten-Herdecke, Wuppertal, Germany.

Background And Aims: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis.

Methods: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments.

Results: The staging and intervention ratings of the 26 reviewers were highly concordant (ρ = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within ±1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within ±1 level of the mode.

Conclusions: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason.
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July 2016