Utilization of Target Lesion Heterogeneity For Treatment Efficacy assessment in Late Stage Lung Cancer

RATIONALE: Recent studies have discovered several unique tumor response subgroups outside of response classification by Response Evaluation Criteria for Solid Tumors (RECIST), such as mixed response and oligometastasis. These subtypes have a distinctive property, lesion heterogeneity defined as diversity of tumor growth profiles in RECIST target lesions. Furthermore, many cancer clinical trials have been activated to evaluate various treatment options for heterogeneity-related subgroups (e.g., 29 trials so far listed in clinicaltrials.gov for cancer patients with oligometastasis). Some of the trials have shown survival benefit by tailored treatment strategies. This evidence presents the unmet need to incorporate lesion heterogeneity to improve RECIST response classification. METHOD: An approach for Lesion Heterogeneity Classification (LeHeC) was developed using a contemporary statistical approach to assess target lesion variation, characterize patient treatment response, and translate informative evidence to improving treatment strategy. A mixed effect linear model was used to determine lesion heterogeneity. Further analysis was conducted to classify various types of lesion variation and incorporate with RECIST to enhance response classification. A study cohort of 110 target lesions from 36 lung cancer patients was used for evaluation. RESULTS: Due to small sample size issue, the result was exploratory in nature. By analyzing RECIST target lesion data, the LeHeC approach detected a high prevalence (n = 21; 58%) of lesion heterogeneity. Subgroup classification revealed several informative distinct subsets in a descending order of lesion heterogeneity: mix of progression and regression (n = 7), mix of progression and stability (n = 9), mix of regression and stability (n = 5), and non-heterogeneity (n = 15). Evaluation for association of lesion heterogeneity and RECIST best response classification showed lesion heterogeneity commonly occurred in each response group (stable disease: 16/27; 59%; partial response: 3/5; 60%; progression disease: 2/4; 50%). Survival analysis showed a differential trend of overall survival between heterogeneity and non-heterogeneity in RECIST response groups. CONCLUSION: This is the first study to evaluate lesion heterogeneity, an underappreciated metric, for RECIST application in oncology clinical trials. Results indicated lesion heterogeneity is not an uncommon event. The LeHeC approach could enhance RECIST response classification by utilizing granular lesion level discovery of heterogeneity

Clinical Efficacy and Predictive Molecular Markers of Neoadjuvant Gemcitabine and Pemetrexed in Resectable Non-small Cell Lung Cancer

BackgroundA trial of neoadjuvant gemcitabine and pemetrexed (GP) chemotherapy in patients with resectable non-small cell lung cancer was conducted. The goal was to achieve a disease response rate of 50% and to determine if the expression levels of genes associated with GP metabolism are predictive of response.MethodsPatients had staging with a computed tomography scan, whole body F-18 fluorodeoxyglucose positron emission tomography, and mediastinoscopy. Four biweekly cycles of GP were given. Patients were restaged, and those with resectable stage IB-III disease had thoracotomy. Fresh frozen tumor specimens were collected before and after chemotherapy and the mRNA levels of 14 target genes determined by real-time reverse transcription polymerase chain reaction.ResultsFifty-two patients started therapy. The radiographic disease response rate was 35% (95% confidence interval 21.7-49.6%), and the progression rate was 6%. Forty-six patients had a thoracotomy. The complete tumor resection rate was 77% (40/52). There were no perioperative deaths or deaths related to chemotherapy. Tumor response to chemotherapy was inversely correlated with the level of expression of RRM1 (p < 0.001; regulatory subunit of ribonucleotide reductase) and TS (p = 0.006; thymidylate synthase); i.e., the reduction in tumor size was greater in those with low levels of expression.ConclusionsNeoadjuvant GP is well tolerated and produces an objective response rate of 35%. Tumoral RRM1 and TS mRNA levels are predictive of disease response and should be considered as parameters for treatment selection in future trials with this regimen

Nursing care for patient with Crohn's disease in the surgical department

U radu se prikazuje vanjskotrgovinska razmjena Republike Hrvatske od 2012. do 2016. godine. Glavne komponente vanjskotrgovinske razmjene su, izvoz i uvoz, a njihov odnos iskazuje se na vanjskotrgovinskoj bilanci, u pozitivnom iznosu kao suficit, u negativnom kao deficit. Rad prikazuje kretanje izvoza i uvoza u apsolutnim iznosima i strukturu vanjskotrgovinske bilance te daje pregled vanjskotrgovinske razmjene s najvažnijim zemljama partnerima Republike Hrvatske. Činjenica je da sve zemlje teže ostvarivanju suficita, stoga se u radu naglašava važnost i mogućnosti stimuliranja izvoza u Republici Hrvatskoj. Metodom intervjua, na primjeru iz prakse jednog izvoznika, prikazani su problemi s kojima se susreće u poslovanju.This thesis discusses foreign trade in the Republic of Croatia since 2012 until 2016. Relations in the foreign trade are determined by Croatia's foreign trade policy. Key foreign trade components have been defined, as well as import and export. Their relations are shown in the foreign trade balance, in the positive amount as surplus and in the negative as deficit. This thesis shows the movement of exports and imports in absolute terms and structure of foreign trade balance and it gives an overview of foreign trade with the most important Croatia's partner countries. It is a fact that all countries seek to achieve a surplus, therefore, the importance and the possibility of export stimulation has been emphasized. This paper shows, in an interview, all the problems that a Croatian exporter has had during his business experience

Quality of Available Mates, Education and Intra-Household Bargaining Power

This paper further explores the role of sex ratios on spouses bargaining power, by focusing on educational attainment in order to capture the qualitative aspect of mate availability. Using Census and Current Population Survey data for U.S. metropolitan areas in year 2000, a quality sex ratio is constructed by education brackets to test the effect on the intra-household bargaining power of couples in the corresponding education bracket. We argue that a relative shortage of suitably educated women in the spouses potential marriage market increases wives bargaining power in the household while it lowers their husbands. Additionally, we test the prediction that this bargaining power effect is greater as the assortative mating order by education increases. We consider a collective labor supply household model, in which each spouses labor supply is negatively related to their level of bargaining power. We find that higher relative shortage of comparably educated women in the couples metropolitan area reduces wives labor supply and increases their husbands. Also, the labor supply impact is stronger for couples in higher education groups. No such effects are found for unmarried individuals, which is consistent with bargaining theory

Treatment Strategies for Non-Small Cell Lung Cancer with Common EGFR Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data

The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations

Treatment Strategies for Non-Small Cell Lung Cancer with Common <i>EGFR</i> Mutations: A Review of the History of EGFR TKIs Approval and Emerging Data

The development of targeted therapies over the past two decades has led to a dramatic change in the management of EGFR-mutant non-small cell lung cancer (NSCLC). While there are currently five approved EGFR tyrosine kinase inhibitors (TKIs) for treating EGFR-mutant NSCLC in the first-line setting, therapy selection after progression on EGFR TKIs remains complex. Multiple groups are investigating novel therapies and drug combinations to determine the optimal therapy and treatment sequence for these patients. In this review, we summarize the landmark trials and history of the approval of EGFR TKIs, their efficacy and tolerability, and the role of these therapies in patients with central nervous system metastasis. We also briefly discuss the mechanisms of resistance to EGFR TKIs, ongoing attempts to overcome resistance and improve outcomes, and finalize by offering treatment sequencing recommendations

Longitudinal cohort study to determine effectiveness of a novel simulated case and feedback system to improve clinical pathway adherence in breast, lung and GI cancers

OBJECTIVES: This study examined whether a measurement and feedback system led to improvements in adherence to clinical pathways. DESIGN: The M-QURE (Moffitt—Quality, Understanding, Research and Evidence) Initiative was introduced in 2012 to enhance and improve adherence to pathways at Moffitt Cancer Center (MCC) in three broad clinical areas: breast, lung and gastrointestinal (GI) cancers. M-QURE used simulated patient vignettes based on MCC's Clinical Pathways to benchmark clinician adherence and monitor change over three rounds of implementation. SETTING: MCC, located in Tampa, Florida, a National Cancer Institute Comprehensive Cancer Center. PARTICIPANTS: Three non-overlapping cohorts at MCC (one each in breast, lung and GI) totalling 48 providers participated in this study, with each member of the multidisciplinary team (composed of medical oncologists, radiation oncologists, surgeons and advanced practice providers) invited to participate. INTERVENTIONS: Each participant was asked to complete a set of simulated patient vignettes over three rounds within their own cancer specialty. Participants were required to complete all assigned vignettes over each of the three rounds, or they would be excluded from this study. PRIMARY OUTCOME MEASURE: Increased domain and overall provider care adherence to clinical pathways, as scored by blinded physician abstractors. RESULTS: We found significant improvements in pathway adherence between the third and first rounds of data collection particularly for workup and treatment of cancer cases. By clinical grouping, breast improved by 13.6% (p<0.001), and lung improved by 12.1% (p<0.001) over baseline, whereas GI showed a decrease of 1.4% (p=0.68). CONCLUSIONS: Clinical pathway adherence improved in a short timeframe for breast and lung cancers using group-level measurement and individual feedback. This suggests that a measurement and feedback programme may be a useful tool to improve clinical pathway adherence

Phase II study of sunitinib malate (SM) in subjects with metastatic and/or surgically unresectable non-GIST soft tissue sarcomas

10535 Background: Metastatic soft tissue sarcoma represents a diverse collection of disease types. Sunitinib malate is a multitargeted tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor, with proven efficacy in imatinib mesylate-refractory or intolerant gastrointestinal stromal tumors (GIST). This study was designed to evaluate the efficacy and tolerability of sunitinib malate in four non-GIST sarcoma subytpes (liposarcoma, malignant fibrous histiocytoma, fibrosarcoma and leiomyosarcoma). Methods: Eligibility criteria included tissue documented metastatic soft tissue sarcomas, measurable disease (by RECIST criteria), and a maximum of three prior lines of therapy for metastatic disease. Treatment was with sunitinib malate 50 mg orally daily in 6 week cycles (4 weeks on/ 2 weeks off). Results: Thirty-six subjects have been accrued to date, 12 patients with leiomyosarcoma, 12 with liposarcoma, 11 with..