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Bassam Ghabach, MD
Targeted Molecular Therapeutic Options for Hepatocellular Carcinoma.
Crit Rev Oncog. 2020;25(1):47-55
Authors: Sridhar S, Sharma I, Sankpal UT, Ghabach B, Narra K, Neerukonda L, Basha R
Liver cancer is the 6th leading cause of cancer related deaths in the US even though it ranks 14th in incidence. More men are diagnosed with liver cancer than women, and the number of projected deaths among men (20,020) is almost double that among women (10,140) in the US. Infections like hepatitis and metabolic conditions like obesity are believed to be major risk factors for the onset of liver cancer. Hepatocellular carcinoma (HCC), the most common type of liver cancer, accounts for 75% of all cases. Chemotherapy has not been effective in treating HCC. Targeted therapies are being used in advanced HCC patients due to a better survival and less side effects when compared to traditional chemotherapy. Therapeutic agents targeting the regulators of growth factor signaling pathways and the mediators of downstream signaling-for example, inhibitors of the tyrosine kinase receptor-are used as targeted molecular therapies. Kinase inhibitors that modulate growth signals, such as sorafenib and lenvatinib, are commonly employed in targeted molecular therapy for HCC patients. This review covers these agents, highlighting modes of action and providing details on clinical trials.
PMID: 32865910 [PubMed - as supplied by publisher]
Current Perspectives in Immunotherapy for Liver Cancer.
Crit Rev Oncog. 2020;25(1):31-46
Authors: Lambring CB, Ghabach B, Narra K, Basha R
Liver cancer is a particularly aggressive group of malignancies with historically low survival rates. Despite advancements in cancer treatments in general in the last few decades, incidence and mortality have not changed. Even though some phase 1 and 2 studies have shown promising results, many medication have failed to reach a sustainable level of efficacy to move into the clinical setting. Immunotherapy drugs have shown impressive results in the treatment of specific immunogenic cancers, prompting the possibility of their use in liver cancers. Immunotherapy medications approved for other cancers have received FDA accelerated approval for treatment of hepatocellular carcinoma. But, these approvals are contingent upon verification and description of clinical benefit in confirmatory trials. With more treatments in development involving cancer vaccines and natural killer cell-mediated therapy, liver cancer treatment is being reinvigorated with a broad array of new treatment angles. In this review article, we discuss these treatments, focusing on mechanism of action and clinical trials. Much needed advancements in treating late- and early-stage liver cancers will require new and innovative immunotherapeutic treatments.
PMID: 32865909 [PubMed - as supplied by publisher]
Smoking cessation and survival among people diagnosed with non-metastatic cancer.
BMC Cancer. 2020 Aug 05;20(1):726
Authors: Barnett TE, Lu Y, Gehr AW, Ghabach B, Ojha RP
BACKGROUND: We aimed to estimate the effects of smoking cessation on survival among people diagnosed with cancer.
METHODS: We used data from a Comprehensive Community Cancer Program that is part of a large urban safety-net hospital system. Eligible patients were diagnosed with primary invasive solid tumors between 2013 and 2015, and were current smokers at time of diagnosis. Our exposure of interest was initiation of smoking cessation within 6 months of cancer diagnosis. We estimated inverse probability weighted restricted mean survival time (RMST) differences and risk ratio (RR) for all cause 3-year mortality.
RESULTS: Our study population comprised 369 patients, of whom 42% were aged < 55 years, 59% were male, 44% were racial/ethnic minorities, and 59% were uninsured. The 3-year RMST was 1.8 (95% CL: - 1.5, 5.1) months longer for individuals who initiated smoking cessation within 6 months of cancer diagnosis. The point estimate for risk of 3-year mortality was lower for initiation of smoking cessation within 6 months of diagnosis compared with no initiation within 6 months (RR = 0.72, 95% CL: 0.37, 1.4).
CONCLUSIONS: Our point estimates suggest longer 3-year survival, but the results are compatible with 1.5 month shorter or 5.1 longer 3-year overall survival after smoking cessation within 6 months of cancer diagnosis. Future studies with larger sample sizes that test the comparative effectiveness of different smoking cessation strategies are needed for more detailed evidence to inform decision-making about the effect of smoking cessation on survival among cancer patients.
IMPLICATIONS FOR CANCER SURVIVORS: The benefits of smoking cessation after cancer diagnosis may include longer survival, but the magnitude of benefit is unclear.
PMID: 32758159 [PubMed - in process]
Adult Cancer Survivors' Engagement and Interest in Patient-Centered Research.
Cancer Epidemiol Biomarkers Prev. 2019 Nov 18;:
Authors: Lubas MM, Lu Y, Gehr AW, Ghabach B, Tanna B, Narra K, Brinkman TM, Ojha RP
BACKGROUND: Limited information is available about the representativeness of survivors engaging in patient-centered research, despite the potential for threats to generalizability. We thus aimed to assess the representativeness of survivors engaged or interested in research development.
METHODS: We used data from the Health Information National Trends Survey, nationally representative survey, to identify survivors of adult cancers. Our outcomes of interest were based on responses to questions about engagement or interest in developing patient-centered research. We estimated the ratio of relative frequencies (RRFs) and corresponding 95% confidence limits (CL) of sociodemographic and survivorship characteristics between survivors engaged or interested in patient-centered research and the overall survivor population.
RESULTS: Our study population comprised 934 survivors, of whom 5% reported being engaged in patient-centered research and 26% reported an interest in participating. Relative frequencies of characteristics were discordant for engaged survivors but largely similar for interested survivors compared with all survivors. In particular, engaged survivors had a higher relative frequency of individuals aged 50 - 64 years (RRF=1.7, 95% CL:1.1, 2.5), Hispanic (RRF=2.9, 95% CL:1.2, 6.9), non-Hispanic Black (RRF=2.9, 95% CL:1.1, 2.5), and unemployment (RRF=4.7, 95% CL: 1.4, 16).
CONCLUSIONS: We observed several meaningful differences in the characteristics of survivors engaged in patient-centered research compared with all survivors, which raises concerns about the generalizability of findings from such studies.
IMPACT: Patient-centered research may not benefit the broader survivor community if survivors engaging in research development are not representative of all survivors. Greater attention to recruiting mechanisms is necessary to avoid creating disparities.
PMID: 31740520 [PubMed - as supplied by publisher]
Affordable Care Act and cancer stage at diagnosis in an underserved population.
Prev Med. 2019 Jun 10;:
Authors: Lu Y, Jackson BE, Gehr AW, Cross D, Neerukonda L, Tanna B, Ghabach B, Ojha RP
The Patient Protection and Affordable Care Act (ACA) has increased insurance coverage among underserved individuals, but the effect of ACA on cancer diagnosis is currently debated, particularly in Medicaid non-expansion states. Therefore, we aimed to assess the effect of ACA implementation on stage at diagnosis among underserved cancer patients in Texas, a Medicaid non-expansion state. We used data from the institutional registry of the JPS Center for Cancer Care, which serves an urban population of underserved cancer patients. Eligible individuals were aged 18 to 64 years and diagnosed with a first primary invasive solid tumor between 2008 and 2015. We used a natural experiment framework and interrupted time-series analysis to assess level (i.e. immediate) and slope (over time) changes in insurance coverage and cancer stage at diagnosis between pre- and post-ACA periods. Our study population comprised 4808 underserved cancer patients, of whom 51% were racial/ethnic minorities. The prevalence of uninsured cancer patients did not immediately change after ACA implementation but modestly decreased over time (PR = 0.94; 95% CL: 0.90, 0.98). The prevalence of early- and advanced-stage diagnosis did not appreciably change overall or when stratified by screen-detectable cancers. Our results suggest that ACA implementation decreased the prevalence of uninsured cancer patients but had little effect on cancer stage at diagnosis in an underserved population. Given that Texas is a Medicaid non-expansion state, Medicaid expansion and alternative approaches may need to be further explored to improve earlier cancer diagnosis among underserved individuals.
PMID: 31195020 [PubMed - as supplied by publisher]
A population-based study of incidence and patient survival of small cell carcinoma in the United States, 1992-2010.
A population-based study of incidence and patient survival of small cell carcinoma in the United States, 1992-2010.
BMC Cancer. 2015 Mar 27;15:185
Authors: Dores GM, Qubaiah O, Mody A, Ghabach B, Devesa SS
BACKGROUND: In contrast to the well-described epidemiology and behavior of small cell lung carcinoma (SCLC), little is known about extrapulmonary small cell carcinoma (EPSCC).
METHODS: Using data from the Surveillance, Epidemiology and End Results (SEER) Program (1992-2010), we calculated age-adjusted incidence rates (IRs), IR ratios (IRRs), annual percent change (APC), relative survival (RS), RS ratios (RSRs), and the respective 95% confidence intervals (95% CI) of SCLC and EPSCC according to primary site. We used the SEER historic stage variable that includes localized (confined to the organ of origin), regional (direct extension to adjacent organ/tissue or regional lymph nodes), and distant (discontinuous metastases) stages and combined localized and regional stages into "limited" stage.
RESULTS: The incidence of SCLC (IR = 76.3/million person-years; n = 51,959) was 22-times that of EPSCC (IR = 3.5; n = 2,438). Of the EPSCC sites, urinary bladder, prostate, and uterine cervix had the highest incidence (IRs = 0.7-0.8); urinary bladder (IRR = 4.91) and stomach (IRR = 3.46) had the greatest male/female disparities. Distant-to-limited stage site-specific IRRs of EPSCC were significantly elevated for pancreas (IRR = 6.87; P < 0.05), stomach, colon/rectum, ovary, and prostate (IRRs = 1.62-2.42; P < 0.05) and significantly decreased for salivary glands, female breast, uterine cervix, and urinary bladder (IRRs = 0.32-0.46). During 1992-2010, significant changes in IRs were observed for EPSCC overall (APC = 1.58), small cell carcinoma of the urinary bladder (APC = 6.75), SCLC (APC = -2.74) and small cell carcinoma of unknown primary site (APC = -4.34). Three-year RS was significantly more favorable for patients with EPSCC than SCLC for both limited (RSR = 2.06; 95% CI 1.88, 2.26) and distant stages (RSR = 1.55; 95% CI 1.16, 2.07). Among limited stage small cell carcinoma, RS was most favorable for salivary glands, female breast, and uterine cervix (RS = 52-68%), whereas RS for nearly all sites with distant stage disease was <10%.
CONCLUSION: EPSCC comprises a heterogeneous group of diseases that appears, at least in part, etiologically distinct from SCLC and is associated with more favorable stage-specific patient survival.
PMID: 25885914 [PubMed - indexed for MEDLINE]