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The effects of mound building ants on soil and vegetation have been described worldwide; however, few studies have explored their effects in salt marsh communities. Here, we studied the effects of the black fire ant Solenopsis richteri on the cordgrass Spartina densiflora in a southwestern Atlantic salt marsh. We found that S. richteri nests are more abundant in the high marsh than in the low marsh and in the terrestrial environment. Sediment characteristics were examined in the above-ground and below-ground portions of nests, and in the surrounding soil apart from them. Nests' sediment had lower organic matter content, lower bulk density and higher pH values than the non-nest soil. These differences were in general more marked in the above-ground portion of nests. Grain size distribution was biased towards coarser grain particles in nests, with the smallest particles being more abundant in the non-nest soil. Ammonium content was higher in the nests than in the non-nest soil, despite nitrate and dissolved inorganic nitrogen were not different. Phosphate content was higher in the below-ground portion than in the above-ground portion of nests. Samplings and transplant experiments showed that plants growing in contact with mounds grew longer, had wider stems and higher root biomass than plants apart from mounds. These results indicate that by affecting sediment characteristics, ants indirectly and positively affect plants condition, with potential cascading up effects on community structure and dynamics. Because mounds are relocated every ~3.5 months, bioturbation impacts may extend over time through the whole high marsh, highlighting the role that black fire ants may have in the ecology of southwestern Atlantic marshes. • Black fire ants inhabit southwestern Atlantic salt marshes. • Ant nests are more abundant in the high than low marsh and terrestrial environment. • Ants modify the physico‐chemical characteristics of the marsh sediment. • Plants in contact with ant mounds perform better than plants apart from mounds. • Bioturbation effects may extend over time through the marsh due to mound relocation. [ABSTRACT FROM AUTHOR]

Holocene climate reconstructions are useful for understanding the diverse features and spatial heterogeneity of past and future climate change. Here we present a database of western North American Holocene paleoclimate records. The database gathers paleoclimate time series from 184 terrestrial and marine sites, including 381 individual proxy records. The records span at least 4000 of the last 12 000 years (median duration of 10 725 years) and have been screened for resolution, chronologic control, and climate sensitivity. Records were included that reflect temperature, hydroclimate, or circulation features. The database is shared in the machine readable Linked Paleo Data (LiPD) format and includes geochronologic data for generating site-level time-uncertain ensembles. This publicly accessible and curated collection of proxy paleoclimate records will have wide research applications, including, for example, investigations of the primary features of ocean–atmospheric circulation along the eastern margin of the North Pacific and the latitudinal response of climate to orbital changes. The database is available for download at 10.6084/m9.figshare.12863843.v1 (Routson and McKay, 2020). [ABSTRACT FROM AUTHOR]

This study evaluates the impact of breast cancer (BC) in health related quality of life (HRQL) and in psychological distress (PD) during the initial phases of the disease and looks for contributing factors. A multicentric case-control study, EpiGEICAM, was carried out. Incident BC cases and age- and residence- matched controls were included. Clinical, epidemiological, HRQL (SF-36) and PD information (GHQ-28) was collected. We used multivariable logistic regression models to estimate OR of low HRQL and of PD in cases compared to controls, and to identify factors associated with low HRQL and with PD. Among 896 BC cases and 890 control women, cases had poorer scores than both, the reference population and the control group, in all SF-36 scales. BC women with lower education, younger, active workers, never smokers, those with comorbidities, in stage IV and with surgical treatment had lower physical HRQL; factors associated with low mental HRQL were dissatisfaction with social support, being current smoker and having children. Cases had a fivefold increased odds of PD compared to controls. Managing comorbidities and trying to promote social support, especially in younger and less educated women, could improve well-being of BC patients. [ABSTRACT FROM AUTHOR]

Violence seems deeply rooted in human nature and an endemic potential for such is today frequently associated with differing ethnic, religious or socio-economic backgrounds. Ethnic nepotism is believed to be one of the main causes of inter-group violence in multi-ethnic societies. At the site of Els Trocs in the Spanish Pyrenees, rivalling groups of either migrating early farmers or farmers and indigenous hunter-gatherers collided violently around 5300 BCE. This clash apparently resulted in a massacre of the Els Trocs farmers. The overkill reaction was possibly triggered by xenophobia or massive disputes over resources or privileges. In the present, violence and xenophobia are controlled and sanctioned through social codes of conduct and institutions. So that, rather than representing an insurmountable evolutionary inheritance, violence and ethnic nepotism can be overcome and a sustainable future achieved through mutual respect, tolerance and openness to multi-ethnic societies. [ABSTRACT FROM AUTHOR]

Although the frequency of pastoral activities involving vertical sheep mobility has decreased over the last century, this is a herding strategy still used in the Ebro basin, where animals move from overwintering valley locations up to the Pyrenees from late spring to early autumn. Such practice allows herders to avoid the worst climatic conditions, seasonally balancing the great contrast between ecological zones in this region, from dry lowland Mediterranean steppe to wet mountain subalpine grasslands. As recent regional archaeological works have suggested, the altitudinal movement of flocks may have begun with the first early Neolithic groups settled in this territory. Here we investigate through stable isotope analyses one of the last flocks that still performs this activity. Sheep specimens were analyzed by sequential analyses (δ13C and δ18O) in bioapatite of tooth enamel, allowing detection of seasonal changes. Tooth series are interpreted according to rainfall distribution, seasonal patterns in δ 18O of meteoric water, vegetation changes and δ13C values in pastures along the altitudinal gradient in the area. Vertical movements in sheep sequential series are recognized by an inverse relationship between δ13C and δ18O values. Monthly δ18O values in meteoric water obtained in valley and mountain locations describe the same type of seasonal oscillation, with high values during the warm months and low values during the cold months. Pastures analyzed along the altitudinal gradient showed a decrease in δ13C values with altitude, linked to the seasonal availability of precipitation and vegetation differences among locations. These results define a new analytical and conceptual framework for the interpretation of archaeological samples in this region. [ABSTRACT FROM AUTHOR]

Background: A regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) is superior to a regimen of fluorouracil, doxorubicin, and cyclophosphamide (FAC) when used as adjuvant therapy in women with node-positive breast cancer. The value of taxanes in the treatment of node-negative disease has not been determined. Methods: We randomly assigned 1060 women with axillary-node–negative breast cancer and at least one high-risk factor for recurrence (according to the 1998 St. Gallen criteria) to treatment with TAC or FAC every 3 weeks for six cycles after surgery. The primary end point was disease-free survival after at least 5 years of follow-up. Secondary end points included overall survival and toxicity. Results: At a median follow-up of 77 months, the proportion of patients alive and disease-free was higher among the 539 women in the TAC group (87.8%) than among the 521 women in the FAC group (81.8%), representing a 32% reduction in the risk of recurrence with TAC (hazard ratio, 0.68; 95% confidence interval [CI], 0.49 to 0.93; P=0.01 by the log-rank test). This benefit was consistent, regardless of hormone-receptor status, menopausal status, or number of high-risk factors. The difference in survival rates (TAC, 95.2%; FAC, 93.5%) was not significant (hazard ratio, 0.76; 95% CI, 0.45 to 1.26); however, the number of events was small (TAC, 26; FAC, 34). Rates of grade 3 or 4 adverse events were 28.2% with TAC and 17.0% with FAC (P<0.001). Toxicity associated with TAC was diminished when primary prophylaxis with granulocyte colony-stimulating factor was provided. Conclusions: As compared with adjuvant FAC, adjuvant TAC improved the rate of disease-free survival among women with high-risk, node-negative breast cancer. (Funded by GEICAM and Sanofi-Aventis; ClinicalTrials.gov number, NCT00121992.) N Engl J Med 2010;363:2200-10. [ABSTRACT FROM AUTHOR]

Purpose: The randomized study aimed to determine the efficacy of psychological intervention consisting of relaxation and guided imagery to reduce anxiety and depression in gynecologic and breast cancer patients undergoing brachytherapy during hospitalization. Methods and materials: Sixty-six patients programmed to receive brachytherapy in two hospitals in Barcelona (Spain) were included in this study. The patients were randomly allocated to either the study group (n=32) or the control group (n=34). Patients in both groups received training regarding brachytherapy, but only study group patients received training in relaxation and guided imagery. After collection of sociodemographic data, all patients were given a set of questionnaires on anxiety and depression: the Hospital Anxiety and Depression Scale (HADS), and on quality of life: Cuestionario de Calidad de Vida QL-CA-AFex (CCV), prior to, during and after brachytherapy. Results: The study group demonstrated a statistically significant reduction in anxiety (p=0.008), depression (p=0.03) and body discomfort (p=0.04) compared with the control group. Conclusions: The use of relaxation techniques and guided imagery is effective in reducing the levels of anxiety, depression and body discomfort in patients who must remain isolated while undergoing brachytherapy. This simple and inexpensive intervention enhances the psychological wellness in patients undergoing brachytherapy. State: This study has passed Ethical Committee review. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Introduction: In 2006 Spain approves Law 39/2006 of December 14 named "_Promotion of Personal Autonomy and Care for people in dependency situations._" This law represents an advance in individuals' life and families who have a dependent member. "_In 2014 there were, in Spain, 18'1% of dependent people over 65 years old while in Catalonia there was 18,3%_" (Idescat, 2015). Given the large number of people over 65 years old that are dependent in Barcelona City, Barcelona City Council together with Association for Independent Living create a program named Functional adaptation at home for dependent and elderly / or disabled people. This program is being carried out from 2.011 to the present, and it's a program for people over 65 years without economic resources and it's a priority that they live alone or with a dependent person. Objectives: The program objectives are: - Improving the quality of life of this collective: providing autonomy maintaining physical and mental activity while the activity is performed in activities of daily living. It also improves accessibility and security at home, while they are promoting more time in their homes and avoid institutionalization. - Provide the discharge of the caregiver in order to avoid the physical and mental impairment. Project overview: Program: Functional adaptation at home for dependent and elderly / or disabled people is done through requests made by Social Workers from Barcelona's City Council Social Services Centers and Primary Care Centers in the area of Barcelona as well as coordinators of the service of home care services. Independent Living Center (CVI) professionals: physiotherapist, occupational therapist and speech therapist, value the person's functional limitations at home. All adaptations are done based on this evaluation, usually with support products and, in exceptional cases, arrangements to improve accessibility at home. In arrangements visits also collaborates an expert accessibility engineer. During the assessment, the person also visits CVI, where professionals evaluate which are the best products for the person while learns how to use the prescribed items. Once the functional adaptation is done, the professionals value the person's satisfaction and his/her caregiver satisfaction. We specifically re-evalue the autonomy's capacity in those daily tasks that they could not perform: to take a shower, sitting down and standing up from the sofa... by a new scaling. The number of beneficiaries that has been attended during the period taken from 2011 to 2015 is approximately 3,200 people. 2015 is approximately 3,200 people. Project results: Two months after the interventions are finished, CVI professionals track the actions taken to beneficiaries through a satisfaction survey of the products and their use. 86% of users said they feel more independent and 95% of them said they feel safer than before. Project results: Two months after the interventions are finished, CVI professionals track the actions taken to beneficiaries through a satisfaction survey of the products and their use. 86% of users said they feel more independent and 95% of them said they feel safer than before. "_For every euro invested in support products annual savings ranging between 2.74 and 3.71 euros_, _taking into account the smaller needs of grants to third parties, and prevention of different types of drops. The repayment of the investment would be lower than 5 months in any case_ " "_This study also confirmed the efficiency of preventive policies in order to address future situations of dependency aggravations_" Funding: Funding is made through a collaboration agreement that's been annually signed between Barcelona City Council and Association for Independent Living (AVI), the entity that manages CVI. Improvement proposal: There must be a drawing hand, in order to amend the current care model (more on an assistance and reagent way) to a different system, where social services politics are conceived on a more preventive and active nature. We believe that should be an enhancement interdisciplinary social network (Social Worker, Home Care Service) and healthcare network (physiotherapist, nurse ...) in which could promote comprehensive care person. Barriers of the implementations process: Starting this project back in 2.011 was hard work as we were in the middle of the economic crisis and it was a revolutionary program that had never been done before in Barcelona. We start all work during 2.010 (meetings with different departments from the City Council, meetings with support products suppliers, etc.) in order to get everything ready to be able to start the program in April 2.011. [ABSTRACT FROM AUTHOR]

Summary The Iberian Peninsula in southwestern Europe represents an important test case for the study of human population movements during prehistoric periods. During the Last Glacial Maximum (LGM), the peninsula formed a periglacial refugium [ 1 ] for hunter-gatherers (HGs) and thus served as a potential source for the re-peopling of northern latitudes [ 2 ]. The post-LGM genetic signature was previously described as a cline from Western HG (WHG) to Eastern HG (EHG), further shaped by later Holocene expansions from the Near East and the North Pontic steppes [ 3–9 ]. Western and central Europe were dominated by ancestry associated with the ∼14,000-year-old individual from Villabruna, Italy, which had largely replaced earlier genetic ancestry, represented by 19,000–15,000-year-old individuals associated with the Magdalenian culture [ 2 ]. However, little is known about the genetic diversity in southern European refugia, the presence of distinct genetic clusters, and correspondence with geography. Here, we report new genome-wide data from 11 HGs and Neolithic individuals that highlight the late survival of Paleolithic ancestry in Iberia, reported previously in Magdalenian-associated individuals. We show that all Iberian HGs, including the oldest, a ∼19,000-year-old individual from El Mirón in Spain, carry dual ancestry from both Villabruna and the Magdalenian-related individuals. Thus, our results suggest an early connection between two potential refugia, resulting in a genetic ancestry that survived in later Iberian HGs. Our new genomic data from Iberian Early and Middle Neolithic individuals show that the dual Iberian HG genomic legacy pertains in the peninsula, suggesting that expanding farmers mixed with local HGs. Video Abstract Highlights • Iberian hunter-gatherers show dual Late Pleistocene genetic ancestry • Dual hunter-gatherer ancestry is the result of admixture from different refugia • This mixed Late Pleistocene ancestry can be traced in Iberian Neolithic farmers Villalba-Mouco et al. generate genome-wide data from prehistoric Iberian hunter-gatherers and early farmers and show that two lineages of Late Pleistocene ancestry survived in Iberian foragers, likely as a result of admixture from different southern refugia. Newly arrived Neolithic farmers retain this genetic signature, suggesting local admixture. [ABSTRACT FROM AUTHOR]

Objectives: Adherence to healthy lifestyle recommendations has been reported to improve health-related quality of life (HRQL) in breast cancer (BC) patients, but the influence of long-term behavioral changes remains unknown. We evaluated the association between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations and HRQL both, at BC diagnosis and the change 7-12 years later., Design: Prospective cohort study., Settings and Participants: A total of 406 breast cancer survivors, from the EpiGEICAM study, were recruited in 16 Spanish hospitals., Measurements: Epidemiological, clinical, dietary, physical activity and HRQL information was collected both at recruitment and 7-12 years later. A 7-item score to measure compliance with recommendations was assessed according to the 2018 WCRF/AICR scoring criteria. HRQL was evaluated using SF-36 questionnaire. Linear mixed models for longitudinal data were used to assess the cross-sectional and longitudinal association between adherence score and the physical and mental component summary scores., Results: At diagnosis, for each unit increase in WCRF/AICR score adherence, the HRQL physical domain increased 0.78 points (95%CI: -0.04 to 1.60; P trend:0.06). The mean change in physical HRQL from diagnosis to follow-up per unit increase in within-subject adherence score was 0.73 points (95%CI: -0.18 to 1.65; P trend: 0.12). For the mental domain, no association was observed with compliance with the recommendations at diagnosis, nor with changes in adherence over time., Conclusions: Our results suggest that Increased adherence to WCRF/AICR cancer prevention recommendations over time could contribute to slightly improved long-term physical HRQoL in BC survivors., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Germline and tumor BRCA testing constitutes a valuable tool for clinical decision-making in the management of epithelial ovarian cancer (EOC) patients. Tissue testing is able to identify both germline (g) and somatic (s) BRCA variants, but tissue preservation methods and the widespread implementation of NGS represent pre-analytical and analytical challenges that need to be managed. This study was carried out on a multicenter prospective GEICO cohort of EOC patients with known gBRCA status in order to determine the inter-laboratory reproducibility of tissue sBRCA testing. The study consisted of two independent experimental approaches, a bilateral comparison between two reference laboratories (RLs) testing 82 formalin-paraffin-embedded (FFPE) EOC samples each, and a Ring Test Trial (RTT) with five participating clinical laboratories (CLs) evaluating the performance of tissue BRCA testing in a total of nine samples. Importantly, labs employed their own locally adopted next-generation sequencing (NGS) analytical approach. BRCA mutation frequency in the RL sub-study cohort was 23.17%: 12 (63.1%) germline and 6 (31.6%) somatic. Concordance between the two RLs with respect to BRCA status was 84.2% (g BRCA 100%). The RTT study distributed a total of nine samples (three commercial synthetic human FFPE references, three FFPE, and three OC DNA) among five CLs. The median concordance detection rate among them was 64.7% (range: 35.3-70.6%). Analytical discrepancies were mainly due to the minimum variant allele frequency thresholds, bioinformatic pipeline filters, and downstream variant interpretation, some of them with consequences of clinical relevance. Our study demonstrates a wide range of concordance in the identification and interpretation of BRCA sequencing data, highlighting the relevance of establishing standard criteria for detecting, interpreting, and reporting BRCA variants.

Purpose: We aimed to evaluate the current situation of electronic health records (EHRs) and patient registries in the oncology departments of hospitals in Spain., Methods: This was a cross-sectional study conducted from December 2018 to September 2019. The survey was designed ad hoc by the Outcomes Evaluation and Clinical Practice Section of the Spanish Society of Medical Oncology (SEOM) and was distributed to all head of medical oncology department members of SEOM., Results: We invited 148 heads of oncology departments, and 81 (54.7%) questionnaires were completed, with representation from all 17 Spanish autonomous communities. Seventy-seven (95%) of the respondents had EHRs implemented at their hospitals; of them, over 80% considered EHRs to have a positive impact on work organization and clinical practice, and 73% considered that EHRs improve the quality of patient care. In contrast, 27 (35.1%) of these respondents felt that EHRs worsened the physician-patient relationship and conveyed an additional workload (n = 29; 37.6%). Several drawbacks in the implementation of EHRs were identified, including the limited inclusion of information on both outpatients and inpatients, information recorded in free text data fields, and the availability of specific informed consent. Forty-six (56.7%) respondents had patient registries where they recorded information from all patients seen in the department., Conclusion: Our study indicates that EHRs are almost universally implemented in the hospitals surveyed and are considered to have a positive impact on work organization and clinical practice. However, EHRs currently have several drawbacks that limit their use for investigational purposes., Clinical Trial Registration: Not applicable., (© 2021. The Author(s).)

Purpose: To evaluate the effect of boost radiotherapy on ipsilateral breast tumor recurrence (IBTR) for ductal carcinoma in situ (DCIS) after breast-conserving surgery and whole breast radiotherapy (WBRT) with or without boost., Methods and Materials: Retrospective, multicentre study of 622 patients (624 tumors) diagnosed with pure DCIS from 1993-2011., Results: Most tumors (377/624; 60.4%) received a boost. At a median follow-up of 8.8 years, IBTR occurred in 64 cases (10.3%). A higher percentage of patients with risk factors for IBTR received a boost (p < 0.05). Boost was not associated with lower rates of IBTR than WBRT alone (HR 0.75, 95% CI 0.42-1.35). On the univariate analyses, IBTR was significantly associated with tumor size (11-20 mm, HR 2.32, 95% CI 1.27-4.24; and > 20 mm, HR 2.10, 95% CI 1.14-3.88), re-excision (HR 1.76, 95% CI 1.04-2.96), and tamoxifen (HR 2.03, 95% CI 1.12-3.70). Boost dose > 16 Gy had a protective effect (HR 0.39, 95% CI 0.187-0.824). Multivariate analyses confirmed the independent associations between IBTR and 11-20 mm (p = 0.02) and > 20 mm (p = 0.009) tumours, and re-excision (p = 0.006). On the margin-stratified multivariate analysis, tamoxifen was a poor prognostic factor in the close/positive margin subgroup (HR 4.28 95% CI 1.23-14.88), while the highest boost dose ( > 16 Gy) had a significant positive effect (HR 0.34, 95% CI 0.13-0.86) in the negative margin subgroup., Conclusions: Radiotherapy boost did not improve the risk of IBTR. Boost radiotherapy was more common in patients with high-risk disease. Tumor size and re-excision were significant independent prognostic factors.

Background: The influence of nutrition on breast cancer prognosis is still inconclusive and therefore dietary interventions incorporating dietary biomarkers are needed to confirm compliance with dietary goals and clarify biological mechanisms. The present study assessed whether a lifestyle intervention in breast cancer survivors could affect dietary biomarkers of fruit and vegetables and fatty acids., Methods: In this phase II single-arm trial, 37 overweight/obese early stage breast cancer patients completed a 12-week diet and exercise intervention. The intervention involved 1-h weekly diet sessions delivered by a dietician and 75-min bi-weekly physical activity sessions of moderate-to-high intensity led by trained monitors. Before and after the intervention, three 24-h dietary recalls were carried out to calculate nutrient intakes and, in addition, blood samples were taken to measure plasma carotenoids, vitamin E and retinol concentrations and erythrocyte membrane fatty acid (EFA) composition. Wilcoxon signed rank tests were used to assess changes in dietary and biomarkers measurements over the intervention period., Results: After the intervention, there was a significant increase in the intake of dietary carotenoids (+15.1% compared to baseline) but not plasma carotenoids levels (+6.3%). Regarding the EFA levels, we observed a significant decrease in percentage of saturated fatty acids (-1.4%) and n-6 polyunsaturated fatty acids (-2.9%) and an increase in monounsaturated fatty acids (1.7%) and total and long-chain n-3 polyunsaturated fatty acids (by 13.1% and 13.7%, respectively). A favourable decrease in the ratio of long-chain n-6 to n-3 polyunsaturated fatty acids (-9.1%) was also observed., Conclusions: After a short-term diet and exercise intervention in overweight/obese breast cancer survivors, we observed significant changes in dietary nutrients and fatty acid biomarkers, suggesting positive dietary changes that could be relevant for breast cancer prognosis., (© 2019 The British Dietetic Association Ltd.)

This study analyzes the association of excessive energy intake and caloric restriction with breast cancer (BC) risk taking into account the individual energy needs of Spanish women. We conducted a multicenter matched case-control study where 973 pairs completed lifestyle and food frequency questionnaires. Expected caloric intake was predicted from a linear regression model in controls, including calories consumed as dependent variable, basal metabolic rate as an offset and physical activity as explanatory. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. The association with BC risk, overall and by pathologic subtype, was evaluated using conditional and multinomial logistic regression models. While premenopausal women that consumed few calories (>20% below predicted) had lower BC risk (OR = 0.36; 95% CI = 0.21-0.63), postmenopausal women with an excessive intake (≥40% above predicted) showed an increased risk (OR = 2.81; 95% CI = 1.65-4.79). For every 20% increase in relative (observed/predicted) caloric intake the risk of hormone receptor positive (p-trend < 0.001) and HER2+ (p-trend = 0.015) tumours increased 13%, being this figure 7% for triple negative tumours. While high energy intake increases BC risk, caloric restriction could be protective. Moderate caloric restriction, in combination with regular physical activity, could be a good strategy for BC prevention.

Adiposity and physical activity are modifiable factors that could be important determinants of breast cancer (BC) prognosis through their effects on endogenous reproductive hormones, chronic inflammation and metabolic changes. Therefore, it is necessary to evaluate whether offering lifestyle interventions to BC survivors could affect the levels of certain biomarkers involved in these mechanisms. We designed a pre-post intervention study offering diet and exercise sessions over 12 weeks to 42 overweight/obese BC survivors. Before and after the intervention, we obtained dietary information, anthropometry and cardiorespiratory fitness (CRF) measurements and blood samples to measure metabolic risk, insulin resistance and adipokines biomarkers. Wilcoxon signed-rank tests and Spearman partial correlation coefficients were used to compare pre- and post-measurements and assess the correlations between changes in biomarkers and changes in anthropometry and CRF. Breast cancer survivors showed significant improvements in metabolic risk biomarkers and insulin resistance indicators along with a non-significant leptin decrease and a significant adiponectin decrease. The improvements in metabolic risk biomarkers, insulin resistance indicators and leptin were moderately correlated (0.32 ≤ |r| ≤ 0.55) with the decrease in body mass index and the increase in CRF. Diet and exercise interventions implemented in overweight/obese BC survivors may improve metabolic risk, insulin resistance and leptin biomarkers., (© 2018 John Wiley & Sons Ltd.)

Purpose: Hormone receptor-positive (HR + ) breast cancer is clinically and biologically heterogeneous, and subgroups with different prognostic and treatment sensitivities need to be identified. Experimental Design: Research-based PAM50 subtyping and expression of additional genes was performed on 63 patients with HR + /HER2 - disease randomly assigned to neoadjuvant multiagent chemotherapy versus endocrine therapy in a phase II trial. The biology associated with treatment response was used to derive a PAM50-based chemoendocrine score (CES). CES's predictive ability was evaluated in 4 independent neoadjuvant data sets ( n = 675) and 4 adjuvant data sets ( n = 1,505). The association of CES, intrinsic biology, and PAM50 risk of relapse (ROR) was explored across 6,007 tumors. Results: Most genes associated with endocrine sensitivity were also found associated with chemotherapy resistance. In the chemotherapy test/validation data sets, CES was independently associated with pathologic complete response (pCR), even after adjusting for intrinsic subtype. pCR rates of the CES endocrine-sensitive (CES-E), uncertain (CES-U), and chemotherapy-sensitive (CES-C) groups in both data sets combined were 25%, 11%, and 2%, respectively. In the endocrine test/validation data sets, CES was independently associated with response. Compared with ROR, >90% of ROR-low and ROR-high tumors were identified as CES-E and CES-C, respectively; however, each CES group represented >25% of ROR-intermediate disease. In terms of survival outcome, CES-C was associated with poor relapse-free survival in patients with ROR-intermediate disease treated with either adjuvant endocrine therapy only or no adjuvant systemic therapy, but not in patients treated with (neo)adjuvant chemotherapy. Conclusions: CES is a genomic signature capable of estimating chemoendocrine sensitivity in HR + breast cancer beyond intrinsic subtype and risk of relapse. Clin Cancer Res; 23(12); 3035-44. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Purpose: Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice., Methods: A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status., Results: Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p < 0.05)., Conclusions: Though this study does not include evaluation of the impact of GEP on long-term outcomes, it was found that GEP results influenced the treatment decisions of medical oncologists and their confidence in adjuvant therapy selection. Patients' anxiety about the selected adjuvant therapy decreased with use of the GEP.

Background: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC)., Methods: Gene expression and clinical-pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated., Results: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55-81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival., Conclusions: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not.

Dihydropyrimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with life-threatening toxicity following exposure to the fluoropyrimidine drugs 5-fluorouracil (5-FU) and capecitabine (CAP), widely used for the treatment of colorectal cancer and other solid tumors. The most prominent loss-of-function allele of the DPYD gene is the splice-site mutation c.1905+1G>A. In this study we report the case of a 73-year old woman with metastatic colorectal cancer who died from drug-induced toxicity after the first cycle of 5-FU-containing chemotherapy. Her symptoms included severe neutropenia, thrombocytopenia, mucositis and diarrhea; she died 16 days later despite intensive care measures. Post-mortem genetic analysis revealed that the patient was homozygous for the c.1905+1G>A deleterious allele and several family members consented to being screened for this mutation. This is the first report in Spain of a case of 5-FU-induced lethal toxicity associated with a genetic defect that results in the complete loss of the DPD enzyme. Although the frequency of c.1905+1G>A carriers in the white population ranges between 1 and 2%, the few data available for the Spanish population and the severity of this case prompted us to design a genotyping procedure to prevent future toxic effects of 5-FU/CAP. Since our group had previously developed a high-resolution melting (HRM) assay for the simultaneous detection of KRAS, BRAF, and/or EGFR somatic mutations in colorectal and lung cancer patients considered for EGFR-targeted therapies, we included the DPYD c.1905+1G>A mutation in the screening test that we describe herein. HRM provides a rapid, sensitive, and inexpensive method that can be easily implemented in diagnostic settings for the routine pre-therapeutic testing of a gene mutation panel with implications in the pharmacologic treatment.

Background: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting., Patients and Methods: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging., Results: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT., Conclusions: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.

Background: Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices., Methods: We describe a high resolution melting (HRM) assay for mutation detection in EGFR exons 19-21, KRAS codon 12/13 and BRAF V600 using formalin-fixed paraffin-embedded samples. Somatic variation of KRAS exon 2 was also analysed by massively parallel pyrosequencing of amplicons with the GS Junior 454 platform., Results: We tested 120 routine diagnostic specimens from patients with colorectal or lung cancer. Mutations in KRAS, BRAF and EGFR were observed in 41.9%, 13.0% and 11.1% of the overall samples, respectively, being mutually exclusive. For KRAS, six types of substitutions were detected (17 G12D, 9 G13D, 7 G12C, 2 G12A, 2 G12V, 2 G12S), while V600E accounted for all the BRAF activating mutations. Regarding EGFR, two cases showed exon 19 deletions (delE746-A750 and delE746-T751insA) and another two substitutions in exon 21 (one showed L858R with the resistance mutation T590M in exon 20, and the other had P848L mutation). Consistent with earlier reports, our results show that KRAS and BRAF mutation frequencies in colorectal cancer were 44.3% and 13.0%, respectively, while EGFR mutations were detected in 11.1% of the lung cancer specimens. Ultra-deep amplicon pyrosequencing successfully validated the HRM results and allowed detection and quantitation of KRAS somatic mutations., Conclusions: HRM is a rapid and sensitive method for moderate-throughput cost-effective screening of oncogene mutations in clinical samples. Rather than Sanger sequence validation, next-generation sequencing technology results in more accurate quantitative results in somatic variation and can be achieved at a higher throughput scale.

Objectives: Gemcitabine has well-recognized activity in the treatment of ovarian cancer. Fixed-dose rate (FDR) delivery has been proposed as a more rationale way to administer gemcitabine, to avoid saturation of the enzyme that catalyzes its intracellular transformation into the active metabolites, difluorodeoxycitidine biphosphate, and triphosphate. Our aim was to assess clinical activity of gemcitabine delivered by FDR infusion in patients with platinum resistant ovarian cancer., Materials and Methods: Patients with platinum-resistant ovarian cancer received gemcitabine 1000 mg/m(2) over 120 minutes on days 1 and 8 of each cycle. Cycles were repeated every 3 weeks, and up to 6 cycles were delivered., Results: Forty-eight patients were included in the study. Among 41 patients evaluable for response, 9 clinical responses (1 complete response and 8 partial responses) were observed, achieving a global response rate of 22%. Grade 3 to 4 hematological toxicity consisted of anemia (15% of patients), neutropenia (24%), and thrombopenia (10%). One patient died due to septic shock. The main grade 3 to 4 nonhematological toxicity was asthenia (7 patients, 17%)., Conclusion: Activity of gemcitabine administered by FDR infusion in patients with platinum-resistant ovarian cancer seems similar to that achieved using 30-minute infusions, with higher toxicity.

Purpose: In clinical practice, it is possible to classify breast tumors according to estrogen receptor (ER), progesterone receptor (PgR), and HER2 overexpression: ER negative, PgR negative, and HER2 overexpressing; ER negative, PgR negative, and HER2 negative; ER positive, PgR positive, and HER2 negative; ER positive, PgR positive, and HER2 overexpressing; and the less frequent remaining 4 combinations. The aim of this study was to determine the percentage of pathologic complete response (pCR) in patients with locally advanced breast cancer (LABC) treated with neoadjuvant or primary chemotherapy with anthracyclines and taxanes grouped according to ER, PgR, and HER2 status., Patients and Methods: Patients with LABC treated with primary chemotherapy including anthracyclines and taxanes were grouped according to ER, PgR, and HER2 status; pCR rates were analyzed using the chi(2) test; and correlations with a P value of < or = 0.05 were considered statistically significant., Results: A total of 103 patients were treated. Only 100 patients were included for the analysis of pCR. Eighteen patients exhibited pCR. The pCR rate for each subgroup was as follows: 39.1% (9 of 23) had ER-negative, PgR-negative, and HER2-negative disease (P < 0.01); 35.7% (5 of 14) had ER-negative, PgR-negative, and HER2-overexpressing disease; 33.3% (3 of 9) had ER-positive, PgR-positive, and HER2-overexpressing disease; and 2.8% (1 of 36) had ER-positive, PgR-positive, and HER2-negative disease (P < 0.01)., Conclusion: In patients with LABC, grouping breast tumors according to ER, PgR, and HER2 status can help predict pCR to primary chemotherapy.

Background: The aim of the study was to analyse the toxicity and health related quality of life (HRQoL) of breast cancer patients treated with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) and TAC (docetaxel, doxorubicin, cyclophosphamide) with and without primary prophylactic G-CSF (PPG)., Patients and Methods: This was a phase III study to compare FAC and TAC as adjuvant treatment of high-risk node-negative breast cancer patients. After the entry of the first 237 patients, the protocol was amended to include PPG in the TAC arm due to the high incidence of febrile neutropenia. A total of 1047 evaluable patients from 49 centres in Spain, two in Poland and four in Germany were included in the trial. Side-effects and the scores of the EORTC QLQ-C30 and QLQ BR-23 questionnaires were compared in the three groups (FAC, TAC pre-amendment and TAC post-amendment)., Results: The addition of PPG to TAC significantly reduced the incidence of neutropenic fever, grade 2-4 anaemia, asthenia, anorexia, nail disorders, stomatitis, myalgia and dysgeusia. Patient QoL decreased during chemotherapy, more with TAC than FAC, but returned to baseline values afterwards. The addition of PPG to TAC significantly reduced the percentage of patients with clinically relevant Global Health Status deterioration (10 or more points over baseline value) at the end of chemotherapy (64% versus 46%, P<0.03)., Conclusions: The addition of PPG significantly reduces the incidence of neutropenic fever associated with TAC chemotherapy as well as that of some TAC-induced haematological and extrahaematological side-effects. The HRQoL of patients treated with TAC is worse than that of those treated with FAC but improves with the addition of PPG, particularly in the final part of chemotherapy treatment.

Purpose: Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability., Patients and Methods: Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added., Results: A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (hazard ratio [HR] = 0.87; 95% CI, 0.49 to 1.54; P = .62). However, the intensive strategy was associated with higher overall survival in patients with stage II tumors (HR = 0.34; 95% CI, 0.12 to 0.98; P = .045) and in those with rectal lesions (HR = 0.09; 95% CI, 0.01 to 0.81; P = .03), mainly due to higher rate of resectability for recurrent tumors. Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumor recurrence in the intensive arm., Conclusion: A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors. Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up, at least.

Background: The purpose of this study was to assess the toxicity and efficacy of the combination of docetaxel and gemcitabine every 2 weeks as first-line therapy in metastatic breast cancer., Patients and Methods: We selected patients between the ages of 18 years and 70 years with a Karnofsky performance status of > or = 60 to receive docetaxel 65 mg/m(2) followed by gemcitabine 2500 mg/m(2) on day 1 every 14 days for 10 cycles. Patients could receive more cycles at the discretion of investigator., Results: Of the 52 patients entered, 48 were evaluable for efficacy and toxicity. The overall response rate was 75% (95% confidence interval, 60%-86%), with 8 patients (17%) exhibiting a complete response. The median time to progression was 10.7 months, and the median survival was 32.2 months. The predominant grade 3/4 hematologic toxicity was neutropenia (44% of patients), and the predominant grade 3/4 nonhematologic toxicity was asthenia (15% of patients). Other grade 3/4 toxicities, such as anemia, nausea/vomiting, and diarrhea, were present but infrequent (< or = 10% of patients). The relative dose intensities of both drugs were > 88%., Conclusion: The combination of docetaxel/gemcitabine once every 2 weeks is active and well tolerated in patients with untreated advanced breast carcinoma. This chemotherapy regimen might be useful in advanced breast cancer when anthracycline combinations are not preferred, such as cases previously treated with adjuvant anthracycline chemotherapy.

Background: The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma., Patients and Methods: Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL)., Results: Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis., Conclusions: Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

Introduction: This phase II study was designed to evaluate the efficacy of vinorelbine in combination with estramustine in patients with chemotherapy-naïve hormone-refractory prostate cancer., Material and Methods: Patients received vinorelbine (i.v. 25 mg/m2) on days 1 and 8 every 3 weeks and estramustine (oral, 600 mg/m2) daily. Eligible patients were required to have progressive metastatic disease following the first hormonal manipulation., Results: Of the 51 patients enrolled (median age = 69 years), 84% presented bone involvement and 75% had at least two organs involved at the time of study entry and 47 were evaluable for treatment efficacy. Prostate specific antigen (PSA) response (> or =50% decrease) which was the primary efficacy criterion was reported in 21 patients (41.2%) in the intent-to-treat (ITT) population and in 20 patients (48.8%) in the per protocol (PP) population. Of the 7 patients with measurable disease, 2 achieved partial response. Median progression-free survival and overall survival were 4.7 months (range: 1.9-8.6) and 14.3 months (range: 4.2-21.2), respectively. Grade 3-4 neutropenia was reported in 6.1% of patients and in 1% of cycles. The incidence of complicated neutropenia (febrile neutropenia reported in 1 patient and septic shock with severe neutropenia reported in 2 patients) was 5.8%. The most frequent grade 3-4 non-haematological events (% of patients > or =5%) included anorexia (10%), thrombosis/embolism (8%), vomiting and hypotension (6% each). There were 3 toxic deaths (5.9 %) resulting from pulmonary embolism, angina pectoris, and septic shock. The impact of combined chemotherapy on the quality-of-life (QL) of the patients was assessed between baseline and the first evaluation scheduled at 6 weeks indicated a marked reduction in pain while the rest of the symptoms remained stable. Overall, health status improved slightly over the treatment period., Conclusions: This study confirmed that the combination of vinorelbine and estramustine is an active regimen in patients with hormone-resistant prostate cancer who had not been treated previously with chemotherapy. Main toxicities included complicated neutropenia even though the incidence of severe neutropenia was low. We observed a higher incidence of toxic deaths which could have been related to the regimen of estramustine used in the study.

The purpose of this study was to assess the toxicity and efficacy of gemcitabine and docetaxel administered every other week as first-line therapy in metastatic breast cancer. Fifty-one patients with histologically confirmed metastatic breast cancer were enrolled. Patients received docetaxel 65 mg/m(2) followed by gemcitabine 2,500 mg/m(2), both on day 1 of a 14-day cycle, for 10 cycles without granulocyte-colony stimulating factor support. Thirty-five patients were evaluable for toxicity and 32 for efficacy. Median age was 65 years (range, 37 to 72 years), and median performance status was 90 (range, 60 to 100). The number of disease sites was 2 or > or =3 in 39% and 44% of patients, respectively, with visceral involvement in the liver and/or lung in 44% of patients. A total of 45% had received prior adjuvant chemotherapy. So far, 267 cycles have been administered. Twenty-five percent of the docetaxel and gemcitabine doses were reduced or delayed due primarily to neutropenia, giving a median dose intensity of 90% of the planned dose for both drugs. Grade 3/4 toxicities were mainly hematologic, with neutropenia in 46% of patients (two patients experienced neutropenic fever). Other toxicities were asthenia, diarrhea, transaminase elevation, and nausea. Overall response rate was 66% (four complete responses, 17 partial responses), with 22% of patients achieving stable disease. Responses were observed in all disease sites, including lung (60%) as well as liver (37.5%). In conclusion, preliminary evaluation from our phase II study shows that the combination of docetaxel and gemcitabine given every 2 weeks is a tolerable and highly active combination in patients with metastatic breast cancer. These data compare favorably with those obtained with other docetaxel schedules.

Background: A prospective randomized clinical trial was implemented to assess whether the concomitant or the sequential addition of tamoxifen to chemotherapy provides improved clinical benefit in the adjuvant treatment of breast cancer in postmenopausal patients., Patients and Methods: Four-hundred and eighty-five patients with node-positive operable disease were randomized to receive tamoxifen (20 mg/day) concomitantly (CON) or sequentially (SEQ) to EC chemotherapy (epirubicin 75 mg/m(2) + cyclophosphamide 600 mg/m(2) on day 1, every 21 days for four cycles)., Results: In the 474 fully evaluable patients there were 96 events; eight being second neoplasms and 88 being related to the breast cancer. Of these, 48 of 88 occurred in the CON arm and 40 of 88 in the SEQ arm. The Kaplan-Meier estimation of disease-free survival (DFS) at 5 years was 70% in the CON and 75% in the SEQ group (log-rank test, P = 0.43). Adjusted hazard ratio for treatment was 1.11 (95% confidence interval 0.71-1.73; P = 0.64)., Conclusion: This study fails to show an advantage of one treatment arm over the other, but a trend, albeit non-significant, appears to favor the sequential addition of tamoxifen to epirubicin + cyclophosphamide and, as such, warrants further investigation.

Aims: This phase II multicentric study evaluates a modified preoperative chemoradiotherapy schedule., Methods: Patients <75 years with potentially resectable neoplasm were eligible. Treatment included an initial course of CDDP 100 mg/m2 (Day 1) and 5-FU CI 5000 mg/m2 (Days 1-5) followed by 45 Gy (Days 28-63) and 5-FU CI 5000 mg/m2 (Days 28-33), CDDP 75 mg/m2 (Day 56) and 5-FU CI 3750 mg/m2 (Days 56-61). Regional lymph nodes were irradiated., Results: Nineteen patients were studied. Oesophagectomy was performed in 17. Clear margins were achieved in 16 of these. Eight patients showed a pathologic complete response (pCR). One patient died of infection during the preoperative treatment and four died due to acute surgical complications. The study was closed prematurely because of excessive mortality. Median follow-up was 19 months. Local and regional relapse occurred in one and three patients, respectively. Median time and actuarial 3-year of overall survival and progression free rates were 18.6 months and 28%, and 12.7 months and 10.4%, respectively., Conclusions: This schedule showed a high pCR, resectability and local control rate. Treatment-related mortality limits its clinical applicability, but further investigations are warranted.

Background: The aim of this study was to assess the outcome in patients with lung cancer., Patients and Methods: Prospective study in 93 patients with lung cancer in 3 community hospitals. In each evaluation (4-6 weeks) the following results were obtained: a) questionnaire on the quality of life or performance status (QoL/PS), based on different instruments (Karnofsky Performance Scale [KPS], ECOG, QLQ-C30, and the Nottingham Health Profile [NHP], and b) a clinical questionnaire. Active follow-up was for 18 months and survival tracking was to five years. A descriptive analysis of the outcome variables and a survival analysis (Kaplan-Meier) were done. The prognostic value of each instrument (Cox) and the correlation between the instruments (Spearman) were also evaluated., Results: The mean values recorded at the time of diagnosis between 60% and 70% of the maximum value possible. Mean survival was 12.4 months; accumulated survival was 30% to one year and 4% to 55 months. Only 17% of patients presented any disease-free period. Toxicity of treatment was almost always irrelevant. The correlation between the KPS, the QLQ-30 and the NHP was acceptable and their initial values were important prognostic factors. The QoL/PS scores for the survivors were similar to their initial values, but the global values were 11%., Conclusions: The outcomes measures used in this study provide very useful information, although registration and analysis of the necessary data should be systematic. The KPS was comparable to the other QoL/PS indicators used, but it is shorter, more acceptable and easier to use. Better QoL/PS measurement instruments are needed to evaluate outcomes in the practice of clinical oncology.

Background: Protracted oral administration of tegafur (TG) and leucovorin (LV) attempts to simulate the continuous infusion of 5-fluorouracil, with a higher intracellular folate pool. In a prior dose-finding study with a fixed TG dose of 0.75 g/m2/day for a period of 21 days and continuous oral LV, the recommended dose of LV was 45 mg/day in 28-day cycles., Methods: Thirty-nine patients with histologic confirmation of adenocarcinoma of the colon or rectum, either advanced or metastatic disease, and who were not candidates for radical treatment were included in a Phase II study using this schedule., Results: One hundred sixty-three cycles of chemotherapy were delivered (median, 4 cycles per patient). Toxicity was observed in the form of diarrhea, which was severe in 12 patients (30.7%). Grade 3 (according to the World Health Organization criteria) oral mucositis was recorded in 7 patients (18%). Asthenia was severe in 10% of the patients. Recuperation from toxicity was rapid and managed primarily on an outpatient basis. Two complete (5.1%) and 13 partial (33.3%) responses were observed, with a global response index of 38.5% (95% confidence interval, 23.2-53.6%). The median overall survival was 11.3 months., Conclusions: The results of this study show that an all-oral regimen of tegafur and leucovorin can obtain biochemical modulation, with a significant response rate, in patients with advanced colorectal carcinoma. Randomized trials are needed to assess the possible advantage of this regimen over intravenous schedules.