Are there socio-economic inequalities in utilization of predictive biomarker tests and biological and precision therapies for cancer? A systematic review and meta-analysis.

BACKGROUND: Novel biological and precision therapies and their associated predictive biomarker tests offer opportunities for increased tumor response, reduced adverse effects, and improved survival. This systematic review determined if there are socio-economic inequalities in utilization of predictive biomarker tests and/or biological and precision cancer therapies. METHODS: MEDLINE, Embase, Scopus, CINAHL, Web of Science, PubMed, and PsycINFO were searched for peer-reviewed studies, published in English between January 1998 and December 2019. Observational studies reporting utilization data for predictive biomarker tests and/or cancer biological and precision therapies by a measure of socio-economic status (SES) were eligible. Data was extracted from eligible studies. A modified ISPOR checklist for retrospective database studies was used to assess study quality. Meta-analyses were undertaken using a random-effects model, with sub-group analyses by cancer site and drug class. Unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each study. Pooled utilization ORs for low versus high socio-economic groups were calculated for test and therapy receipt. RESULTS: Among 10,722 citations screened, 62 papers (58 studies; 8 test utilization studies, 37 therapy utilization studies, 3 studies on testing and therapy, 10 studies without denominator populations or which only reported mean socio-economic status) met the inclusion criteria. Studies reported on 7 cancers, 5 predictive biomarkers tests, and 11 biological and precision therapies. Thirty-eight studies (including 1,036,125 patients) were eligible for inclusion in meta-analyses. Low socio-economic status was associated with modestly lower predictive biomarker test utilization (OR 0.86, 95% CI 0.71-1.05; 10 studies) and significantly lower biological and precision therapy utilization (OR 0.83, 95% CI 0.75-0.91; 30 studies). Associations with therapy utilization were stronger in lung cancer (OR 0.71, 95% CI 0.51-1.00; 6 studies), than breast cancer (OR 0.93, 95% CI 0.78-1.10; 8 studies). The mean study quality score was 6.9/10. CONCLUSIONS: These novel results indicate that there are socio-economic inequalities in predictive biomarker tests and biological and precision therapy utilization. This requires further investigation to prevent differences in outcomes due to inequalities in treatment with biological and precision therapies.

Cost-effectiveness analysis comparing "PARP inhibitors-for-all" to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer.

OBJECTIVES: Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy. METHODS: The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained. RESULTS: PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance. CONCLUSIONS: This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.

The PLCE1 rs2274223 variant is associated with the risk of laryngeal squamous cell carcinoma.

Background: Laryngeal squamous cell carcinoma (LSCC) ranks second in the mortality rate in respiratory malignant tumors and has potential similarity in genomic alterations with the esophageal squamous cell carcinoma (ESCC). The PLCE1 rs2274223 variant is the most significant susceptibility loci identified in ESCC. Whether it is also associated with LSCC susceptibility is still unclear. Materials and Methods: A total of 331 LSCC patients and 349 healthy controls were recruited in this study. The PLCE1 rs2274223 variant was genotyped by using the Taqman SNP Genotyping Assay. Association between PLCE1 rs2274223 variant and LSCC risk was estimated by logistic regression analysis, which was performed using SAS software. Results: The PLCE1 rs2274223 variant was identified to be significantly associated with the susceptibility of LSCC in the additive model (OR = 1.40, 95% CI: 1.06-1.86, P=0.019). Compared with the wild-type (AA) carriers, the risk genotype (GG) carriers had a 2.8-fold risk of LSCC (95% CI: 1.13-7.06, P=0.026). Stratified analysis showed that the association between rs2274223 and LSCC risk was with higher significance in individuals above 60 (P = 0.027) males (P = 0.030) or non-smokers (P = 0.026). Conclusion: The PLCE1 rs2274223 variant was significantly associated with risk of LSCC, which may be a potential biomarker and therapeutic target for the LSCC.

Perspectives on the integration of Immuno-Oncology Biomarkers and drugs in a Health Care setting.

Immunotherapies, specifically checkpoint inhibitors, are becoming an important component in cancer care with the most application now in melanoma and lung cancer patients. Some drawbacks that converge with this new evolution are the rather low response rates to these drugs and their high cost with a significant economic impact on the health care system. These major challenges can likely be circumvented by implementing a "personalized immuno-oncology" approach to accomplish a selection of optimal responders based on biomarkers. In this paper we first discuss the legal framework for the development of valuable in vitro diagnostics. Based on a case study in lung cancer, the clinical validity and utility requirements of predictive immuno-oncology biomarkers is highlighted and an overview is given on the evolution towards multiplex or omics-based assays together with its challenges and pitfalls. Finally, some initiatives between the public and private sector are pinpointed to sustain the future access to innovative medicines in cancer therapy at a reasonable cost.

The path to routine use of genomic biomarkers in the cancer clinic.

It has been almost 15 years since the first microarray-based studies creating multigene biomarkers to subtype and predict survival of cancer patients. This Perspective looks at why only a handful of genomic biomarkers have reached clinical application and what advances are needed over the next 15 years to grow this number. I discuss challenges in creating biomarkers and reproducing them at the genomic and computational levels, including the problem of spatio-genomic heterogeneity in an individual cancer. I then outline the challenges in translating newly discovered genome-wide or regional events, like trinucleotide mutation signatures, kataegis, and chromothripsis, into biomarkers, as well as the importance of incorporating prior biological knowledge. Lastly, I outline the practical problems of pharmaco-economics and adoption: Are new biomarkers viewed as economically rational by potential funders? And if they are, how can their results be communicated effectively to patients and their clinicians? Genomic-based diagnostics have immense potential for transforming the management of cancer. The next 15 years will see a surge of research into the topics here that, when combined with a stream of new targeted therapies being developed, will personalize the cancer clinic.

Incorporating Biomarkers into the Primary Prostate Biopsy Setting: A Cost-Effectiveness Analysis.

PURPOSE: We performed a cost-effectiveness analysis using the PHI (Prostate Health Index), 4Kscore®, SelectMDx™ and the EPI (ExoDx™ Prostate [IntelliScore]) in men with elevated prostate specific antigen to determine the need for biopsy. MATERIALS AND METHODS: We developed a decision analytical model in men with elevated prostate specific antigen (3 ng/ml or greater) in which 1 biomarker test was used to determine which hypothetical individuals required biopsy. In the current standard of care strategy all individuals underwent biopsy. Model parameters were derived from a comprehensive review of the literature. Costs were calculated from a health sector perspective and converted into 2017 United States dollars. RESULTS: The cost and QALYs (quality adjusted life-years) of the current standard of care, which was transrectal ultrasound guided biopsy, was $3,863 and 18.085, respectively. Applying any of the 3 biomarkers improved quality adjusted survival compared to the current standard of care. The cost of SelectMDx, the PHI and the EPI was lower than performing prostate biopsy in all patients. However, the PHI was more costly and less effective than the SelectMDx strategy. The EPI provided the highest QALY with an incremental cost-effectiveness ratio of $58,404 per QALY. The use of biomarkers could reduce the number of unnecessary biopsies by 24% to 34% compared to the current standard of care. CONCLUSIONS: Applying biomarkers in men with elevated prostate specific antigen to determine the need for biopsy improved quality adjusted survival by decreasing the number of biopsies performed and the treatment of indolent disease. Using SelectMDx or the EPI following elevated prostate specific antigen but before proceeding to biopsy is a cost-effective strategy in this setting.

Cost-Effectiveness of Urinary Biomarker Panel in Prostate Cancer Risk Assessment.

PURPOSE: SelectMDx (MDxHealth®) is a panel of urinary biomarkers used in conjunction with traditional risk factors to individualize risk prediction for clinically significant prostate cancer. In this study we sought to characterize the effectiveness of SelectMDx in a population of American men with elevated prostate specific antigen. MATERIALS AND METHODS: We developed a Markov decision analytical model to simulate the chain of events and downstream outcomes associated with ultrasound guided prostate biopsy and a strategy in which the biomarker panel is implemented prior to biopsy. The primary outcome was health outcomes, measured in QALYs (quality-adjusted life years). The secondary outcome was health care costs from the Medicare payer perspective. Multiple 1-way sensitivity analyses were performed to characterize model robustness. RESULTS: The expected mean QALYs per patient under the current standard was 10.796 at a cost of $11,060 during an 18-year horizon. Incorporating the urinary biomarker panel resulted in an expected mean of 10.841 QALYs per patient and a mean cost of $9,366, representing an average of 0.045 QALYs gained at a cost savings of $1,694 per patient. When extrapolating these data to a conservative estimate of 311,879 men per year undergoing biopsy, one would expect that the biomarker panel would result in an incremental 14,035 QALYs gained at a cost savings of $528,323,026 in each yearly cohort. The biomarker panel strategy dominated the current standard across a wide range of sensitivity analyses. CONCLUSIONS: Routine use of the SelectMDx urinary biomarker panel to guide biopsy decision making improved health outcomes and lowered costs in American men at risk for prostate cancer. This strategy may optimize the value of prostate cancer risk assessment in an era of increasing financial accountability.

Modelling cost-effectiveness of a biomarker-based approach to neoadjuvant chemotherapy for muscle-invasive bladder cancer.

OBJECTIVES: To model the cost-effectiveness of a biomarker-based approach to select patients for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: We obtained data from the most recent clinical studies on patients with locally advanced MIBC treated by RC, including stage distributions, overall survival (OS) estimates, associated costs, and utilisation/response to NAC. Additionally, we estimated the putative efficacy of three biomarkers to select patients for NAC: DNA-repair gene panel [ataxia telangiectasia mutated (ATM), retinoblastoma 1 (RB1), and Fanconi anaemia complementation group C (FANCC)], excision repair cross-complementation group 2 (ERCC2), and ribonucleic acid (RNA) subtypes. A decision analysis model was developed to evaluate the cost-effectiveness of biomarker-based approaches to select patients with MIBC for NAC. Comparison of cost-effectiveness included RC alone, unselected NAC plus RC, and NAC based on the three aforementioned biomarkers. RESULTS: The DNA-repair gene panel-based approach to NAC was the most cost-effective strategy (mean OS of 3.14 years, $31 482/life year). Under this approach, 38% would undergo NAC, about twice the number of patients who are currently receiving NAC for MIBC. Such an approach would improve mean OS by 5.2, 1.6, and 4.4 months compared to RC alone, a hypothetical scenario where all patients received NAC, and compared to current estimates of NAC utilisation, respectively. CONCLUSIONS: A biomarker-based strategy to identify patients with MIBC who should undergo NAC was more cost-effective than unselected use of NAC or RC alone. As further data becomes available, such a model may serve as a basis for incorporating biomarkers into clinical decision making.

Use of Tumor Markers in Gastrointestinal Cancers: Surgeon Perceptions and Cost-Benefit Trade-Off Analysis.

BACKGROUND: Gastrointestinal cancers constitute the third most common cancers worldwide. Tumor markers have long since been used in the postoperative surveillance of these malignancies; however, the true value in clinical practice remains undetermined. OBJECTIVE: This study aimed to evaluate the clinical utility of three tumor markers in colorectal and esophagogastric cancer. METHODS: A systematic review of the literature was undertaken to elicit the sensitivity, specificity, statistical heterogeneity and ability to predict recurrence and metastases for carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9 and CA125. European surgeons were surveyed to assess their current practice and the characteristics of tumor markers they most valued. Data from the included studies and survey were combined in a cost-benefit trade-off analysis to assess which tumor markers are of most use in clinical practice. RESULTS: Diagnostic sensitivity and specificity were ranked the most desirable characteristics of a tumor marker by those surveyed. Overall, 156 studies were included to inform the cost-benefit trade-off. The cost-benefit trade-off showed that CEA outperformed both CA19-9 and CA125, with lower financial cost and a higher sensitivity, and diagnostic accuracy for metastases at presentation (area under the curve [AUC] 0.70 vs. 0.61 vs. 0.46), as well as similar diagnostic accuracy for recurrence (AUC 0.46 vs. 0.48). CONCLUSIONS: Cost-benefit trade-off analysis identified CEA to be the best performing tumor marker. Further studies should seek to evaluate new tumor markers, with investigation tailored to factors that meet the requirements of practicing clinicians.

Decisions on Further Research for Predictive Biomarkers of High-Dose Alkylating Chemotherapy in Triple-Negative Breast Cancer: A Value of Information Analysis.

OBJECTIVES: To inform decisions about the design and priority of further studies of emerging predictive biomarkers of high-dose alkylating chemotherapy (HDAC) in triple-negative breast cancer (TNBC) using value-of-information analysis. METHODS: A state transition model compared treating women with TNBC with current clinical practice and four biomarker strategies to personalize HDAC: 1) BRCA1-like profile by array comparative genomic hybridization (aCGH) testing; 2) BRCA1-like profile by multiplex ligation-dependent probe amplification (MLPA) testing; 3) strategy 1 followed by X-inactive specific transcript gene (XIST) and tumor suppressor p53 binding protein (53BP1) testing; and 4) strategy 2 followed by XIST and 53BP1 testing, from a Dutch societal perspective and a 20-year time horizon. Input data came from literature and expert opinions. We assessed the expected value of partial perfect information, the expected value of sample information, and the expected net benefit of sampling for potential ancillary studies of an ongoing randomized controlled trial (RCT; NCT01057069). RESULTS: The expected value of partial perfect information indicated that further research should be prioritized to the parameter group including "biomarkers' prevalence, positive predictive value (PPV), and treatment response rates (TRRs) in biomarker-negative patients and patients with TNBC" (€639 million), followed by utilities (€48 million), costs (€40 million), and transition probabilities (TPs) (€30 million). By setting up four ancillary studies to the ongoing RCT, data on 1) TP and MLPA prevalence, PPV, and TRR; 2) aCGH and aCGH/MLPA plus XIST and 53BP1 prevalence, PPV, and TRR; 3) utilities; and 4) costs could be simultaneously collected (optimal size = 3000). CONCLUSIONS: Further research on predictive biomarkers for HDAC should focus on gathering data on TPs, prevalence, PPV, TRRs, utilities, and costs from the four ancillary studies to the ongoing RCT.

The Kallikrein Panel for prostate cancer screening: its economic impact.

BACKGROUND: Current diagnostic testing for prostate cancer results in numerous unnecessary biopsy procedures and creates a substantial financial burden. A statistical prediction model for prostate cancer has been developed, based on four Kallikrein markers in blood. This systematic review and meta-analysis examines the aggregated results from published studies of the Kallikrein Panel. METHODS: Literature searches to identify relevant studies were conducted. A meta-analysis of the results was performed using inverse variance, mean difference with corresponding 95% confidence intervals (CI). The results of the meta-analysis were used to assess the Kallikrein Panel's effect on healthcare costs. RESULTS: The Kallikrein Panel has been evaluated in more than 8,500 patients (2,780 with prostate cancer and 598 with high grade prostate cancer). Meta-analysis demonstrates a statistically significant improvement of 8-10% in predictive accuracy. In addition, 48% to 56% of current prostate biopsies could be avoided. Use of the Kallikrein Panel could result in annual US savings approaching $1 billion. CONCLUSIONS: The Kallikrein Panel has the potential to improve patient outcomes and reduce costs. The panel provides significantly improved specificity. Because the Kallikrein Panel has been studied in a range of clinical settings, it is a test that could be readily and widely used in practice.

Thyroid nodules with indeterminate cytology: molecular imaging with 99mTc-methoxyisobutylisonitrile (MIBI) is more cost-effective than the Afirma gene expression classifier.

PURPOSE: To compare the cost-effectiveness of (99m)Tc-methoxyisobutylisonitrile (MIBI) thyroid scintigraphy and the Afirma gene expression classifier for the assessment of cytologically indeterminate thyroid nodules. METHODS: A decision tree model was used. Costs were calculated from the perspective of the German health insurance system. The robustness of the results was assessed with probabilistic sensitivity analyses using a Monte Carlo simulation. RESULTS: Life expectancy was 34.3 years (estimated costs per patient €1,459 - €2,224) for the MIBI scan and 34.1 years (estimated costs €3,560 - €4,071) for the molecular test. These results were confirmed by the Monte Carlo simulation. CONCLUSION: MIBI thyroid scintigraphy is more cost-effective than the gene expression classifier.

Modelling the benefits of early diagnosis of pancreatic cancer using a biomarker signature.

Pancreatic cancer (PC) has a poor prognosis, with a 5-year survival of 3-4%. This is mainly due to late diagnosis because of diffuse symptoms, where 80-85% of the patients are inoperable. Consequently, early diagnosis would be of significant benefit, resulting in a potential 5-year survival of 30-40%. However, new technologies must be carefully evaluated concerning effectiveness and healthcare costs. We have developed a framework for modelling cost and health effects from early detection of PC, which for the first time allowed us to analyse its cost-effectiveness. A probabilistic cohort model for estimating costs and quality adjusted life-years (QALY) arising from screening for PC, compared to a "wait-and-see"-approach, was designed. The test accuracy, Swedish survival and costs by tumour stage, expected life gain from early detection and pretest probabilities in risk groups, were retrieved from previous investigations. In a cohort of newly diagnosed diabetic patient (incidence 0.71%) the incremental cost per QALY gained (ICER) was €13,500, which is considered cost-effective in Europe. Results were mainly sensitive to the incidence with the ICER ranging from €315 to €204,000 (familial PC 35% and general population 0.046%, respectively). This is the first study focusing on clinical implementation of advanced testing and what is required for novel technologies in cancer care to be cost-effective. The model clearly demonstrated the potential of multiplexed proteomic-testing of PC and also identified the requirements for test accuracy. Consequently, it can serve as a model for assessing the possibilities to introduce advanced test platforms also for other cancer indications.

A Cost-Effectiveness Analysis of Lung Cancer Screening With Low-Dose Computed Tomography and a Diagnostic Biomarker.

Background: The Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines. Methods: We evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical noninvasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodules' size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses. Results: A lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs $250 or less, is cost-effective with an incremental cost-effectiveness ratio lower than $100 000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing $750 or more is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively. Conclusions: Lung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.

Real-World Utilization of Biomarker Testing for Patients with Advanced Non-Small Cell Lung Cancer in a Tertiary Referral Center and Referring Hospitals.

The continued introduction of biomarkers and innovative testing methods makes already complex diagnosis in patients with stage IV non-small-cell lung cancer (NSCLC) even more complex. This study primarily analyzed variations in biomarker testing in clinical practice in patients referred to a comprehensive cancer center in the Netherlands. The secondary aim was to compare the cost of biomarker testing with the cost of whole-genome sequencing. The cohort included 102 stage IV NSCLC patients who received biomarker testing in 2017 or 2018 at the comprehensive cancer center. The complete biomarker testing history of the cohort was identified using linked data from the comprehensive cancer center and the nationwide network and registry of histopathology and cytopathology in the Netherlands. Unique biomarker-test combinations, costs, turnaround times, and test utilization were examined. The results indicate substantial variation in test utilization and sequences. The mean cost per patient of biomarker testing was 2259.92 ± 1217.10 USD, or 1881.23 ± 1013.15 EUR. Targeted gene panels were most frequently conducted, followed by IHC analysis for programmed cell death protein ligand 1. Typically, the most common biomarkers were assessed within the first tests, and emerging biomarkers were tested further down the test sequence. At the cost of current biomarker testing, replacing current testing with whole-genome sequencing would have led to cost-savings in only two patients (2%).

[Economic aspects of using selected biomarkers in cervical cancer screening]. / Aspekt ekonomiczny wykorzystania wybranych biomarkerów w badaniach przesiewowych raka szyjki macicy.

Increasing knowledge about the cervical cancer etiology, combined with the development of molecular diagnostics technology using DNA matrix and mRNA matrix, introduced a new quality in cervical cancer screening. Moving the diagnostics from the cellular level into the molecular level allowed not only to identify the existing precancerous states, but also to foresee these pathologies in the stage of cellular or molecular changes using oncogenesis biomarkers. The new diagnostic tools give hope for the improvement of effectiveness of cervical cancer screening and for a significant reduction of costs.

Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy.

INTRODUCTION: Biomarkers which can predict disease progression and serve as prognostic indicators are necessary for better management of oral cancer. Studies have shown that Cholinesterase plays an important role in cellular proliferation, differentiation and may have a possible involvement in tumor growth. AIM AND OBJECTIVE: The present study is aimed to determine the utility of serum Butyrylcholinesterase (BChe) levels as a marker for progression of oral squamous cell carcinoma (OSCC) in relation to the grade of the tumor and to determine if any variation occurred in the levels of BChe before and after therapy. MATERIALS AND METHODS: A total of 120 patients were included in the study and divided into two groups as Group A-30 patients (healthy individuals) and Group B-90 cases of histopathologically diagnosed OSCC. The blood sample was collected before surgery, re-collected after the completion of radiotherapy (i.e., 3 and 6 months postsurgery) and analyzed biochemically for the concentration of BCh. STATISTICAL ANALYSIS: Paired t-test, ANOVA, and post hoc test (Bonferroni) were used for determining the statistical significance. RESULTS: BChe levels were lower in OSCC (2940.32-1405.50 u/l when compared with controls (11149.60-11243.07 unit/l) and this difference was statistically significant. Postoperatively at 3 months, the serum BChe levels of OSCC patients increased almost two-fold compared to the preoperative values, and this difference was also statistically significant (P = 0.000) After 6 months, these levels further increased but did not reach those of controls. CONCLUSION: BChe can be used as an inexpensive, easy to use, noninvasive biomarker for the evaluation of disease-free survival in OSCC patients.

Ascitic Calprotectin as an early predictor of hepatocellular carcinoma in patients with cirrhotic ascites.

BACKGROUND: Calprotectin is a heterodimer formed by S100A8 and S100A9 proteins which are enhanced during hepatic carcinogenesis and the increased expression of both proteins promotes malignant progression of hepatocellular carcinoma. The potential correlation between ascitic Calprotectin and HCC was not studied. METHODS: 100 patients were stratified into a case group which enrolled 50 patients with cirrhotic ascites and documented HCC and a control group consisted of 50 patients with cirrhotic ascites without HCC. They were evaluated by liver function tests, abdominal ultrasound and routine ascitic fluid examination including ascetic Calprotectin and results were validated in another group (n = 100). RESULTS: Calprotectin level was significantly higher in the HCC group with insignificant difference regarding total cell count, PNLs, ascitic albumin, LDH, CEA and SAAG. It correlated with serum creatinine (r = 0.245, p = 0.014) and number of focal hepatic lesions (r = 0.309, p = 0.002). In the validation group, 28 patients had elevated ascitic Calprotectin of which 21 patients had developed HCC (75%) after a mean period of 3.8 ± 1.54 months. A cut of value 126 ng/ml was accurate to predict HCC in liver cirrhosis with ascites with a sensitivity of 93.3% specificity 94%, AUC 0.950, Youden's J value = 0.873, p = 0.0001. CONCLUSION: Ascitic Calprotectin may offer an easy, affordable marker that can predict the early occurrence of HCC.

Can Biomarkers Guide the Use of Neoadjuvant Chemotherapy in T2 Bladder Cancer?

Current guidelines recommend cisplatin-based neoadjuvant chemotherapy prior to radical cystectomy as the preferred treatment of muscle-invasive bladder cancer. Nevertheless, for multiple reasons compliance with this guideline recommendation is low. This is particularly evident in clinical T2 bladder cancer, where controversy exists regarding the role of proceeding with radical cystectomy alone. Novel biomarkers such as molecular phenotype and DNA damage repair and response gene alterations may be able to predict who will respond to cisplatin-based neoadjuvant chemotherapy. This clinical problem is discussed, and a recommendation is made given the current state of the art. PATIENT SUMMARY: Neoadjuvant chemotherapy improves survival for patients with muscle-invasive bladder cancer. In the future, perhaps validated biomarkers may predict who should and should not receive this treatment.