Rechallenge with Anti-EGFR Treatment in RAS/BRAF wt Metastatic Colorectal Cancer (mCRC) in Real Clinical Practice: Experience of the GITuD Group.

BACKGROUND: There are few third- and fourth-line therapeutic options for metastatic colorectal cancer (mCRC). In RAS/BRAF wild-type (wt) mCRC previously treated with anti-epidermal growth factor receptor (anti-EGFR) (first-line) and relapsed after a good response, retreatment with anti-EGFR (rechallenge) emerges as a therapeutic alternative. OBJECTIVE: The aim was to show the activity and safety of anti-EGFR rechallenge in RAS/BRAF wt mCRC in real-world practice. PATIENTS AND METHODS: A multicenter, retrospective, observational study (six hospitals of the Galician Group of Research in Digestive Tumors) was conducted. Adult patients with RAS/BRAF wt mCRC, evaluated by liquid biopsy, were included. They received anti-EGFR rechallenge (cetuximab, panitumumab) as monotherapy, or combined with chemotherapy, in third- or subsequent lines. Efficacy (overall response rate [ORR], disease control rate [DCR], overall survival [OS], and progression-free survival [PFS]) and safety (incidence of adverse events [AEs]) were assessed. RESULTS: Thirty-one patients were analyzed. Rechallenge (median 6 cycles [range 1-27], mainly cetuximab [80.7%]), started at a median anti-EGFR-free time of 18.4 months (1.7-37.5 months) after two (38.7%) or more (61.3%) lines of treatment; 64.5% of patients received a full dose. Median OS and PFS were 9.8 months (95% confidence interval [CI] 8.2-11.4) and 2.6 months (95% CI 1.7-3.4), respectively. ORR was 10%, and DCR was 30%. The most common AEs were diarrhea (35.5%), anemia (29%), emesis (6.4%), and neutropenia (6.4%); < 5% grade ≥ 3; 48.4% of patients reported anti-EGFR-related skin toxicity (grade > 1). Hypomagnesemia required supplements in 29% of patients. Dose delays (≥ 3 days) and reduction (≥ 20%) were reported in 11 (35.5%) and seven patients (22.6%), respectively. CONCLUSIONS: In RAS/BRAF wt mCRC patients, an anti-EGFR rechallenge provides a feasible therapeutic option with clinical benefit (survival) and a manageable safety profile.

Dynamic perspective of the neutrophil-to-lymphocyte ratio in metastatic gastric cancer.

PURPOSE: The neutrophil-to-lymphocyte ratio (NLR) is an accessible marker from a routine blood test. This study explored the prognostic and predictive value of a change in NLR (c-NLR) after chemotherapy, baseline NLR (bNLR) and chemotherapy response, in metastatic gastric cancer (mGC) patients. METHODS: A total of 116 mGC patients treated between 2009 to 2019 at seven hospitals from Galician Research Group on Digestive Tumors (GITuD) were reviewed in a multicentre, ambispective and observational study. NLR was calculated and the optimal cut-off was defined as NLR=3.96 based on ROC method. NLR was determined at baseline and after two chemotherapy cycles in first line treatment. Change NLR was calculated as NLR after two chemotherapy cycles minus bNLR. The relation of bNLR and c-NLR to overall survival (OS) was evaluated by Kaplan-Meier method and compared by log-rank test. Dynamic Score (DScore) based on c-NLR and baseline NLR were correlated with OS and radiological response. Univariate, multivariate and chi-square analyses were performed. RESULTS: Median patient age was 68.7 years, and 66% were male. Univariate analysis showed OS correlation for bNLR ≥3.96 (5.97 vs 10.87 months, p=0.001), c-NLR increase (6.63 vs 10.34 months, p=0.021) and DScore (12.74 vs 7.68 vs 2.43 months, p<0.001). High DScore was associated with radiological progression after two cycles (x2=10.26, p=0.006). Multivariate analysis: bNLR ≥3.96 (HR=2.16, p=0.003) and c-NLR increase (HR= 2.36, p=0.003) were prognostic factors of poor OS. CONCLUSION: High bNLR and increased NLR after chemotherapy were associated with worse outcome. Dynamic measurement of NLR provides information for stratifying patients to guide optimal treatment.

Do Clinical Trials Meet Current Care Needs? Views of Digestive Oncology Specialists in Galicia (Spain) Using the Delphi Method.

Background: In recent years, abundant scientific evidence has been generated based on clinical trials (CT) in the field of oncology. The general objective of this paper is to find out the extent to which decision making is based on knowledge of the most recent CT. Its specific objectives are to pinpoint difficulties with decision making based on the CT performed and find out the motivations patients and clinicians have when taking part in a CT. Methodology: Combined, prospective study, based on the Delphi method. A lack of correspondence between the people who take part in CT and patients who come for consultation has been identified. A need for training in analysing and interpreting CT has also been identified and a lack of trust in the results of CT financed by the pharmaceutical industry itself has been perceived. Conclusions: There is a difficulty in selecting oncological treatment due to the lack of correspondence between the patients included in the CT and patients seen in consultation. In this process, real world data studies may be highly useful, as they may provide this group with greater training in interpreting CT and their results.

Recurrent primary enterolithiasis with no apparent cause. Presentation of a case / [Enterolitiasis primaria recurrente idiopática. Presentación de un caso]

Enterolithiasis is a rare cause of intestinal obstruction. It occurs with a low frequency and its etiology can be primary or secondary. They present nonspecifically clinically and their resolution is usually surgical. We present a case of a 45-year-old patient who presented two episodes, one year apart, of intestinal obstruction due to enteroliths of unknown cause. The recurrence of this pathology, for no apparent reason, is what makes this publication interesting.

La enterolitiasis es una causa poco frecuente de obstrucción intestinal. Su etiología puede ser primaria o secundaria, según el sitio de formación de los litos. Se presentan clínicamente de manera inespecífica y su resolución es habitualmente quirúrgica. Se presenta un caso de una paciente de 45 años que presentó dos episodios, separados por un año, de obstrucción intestinal por enterolitos de causa desconocida. La recurrencia de esta patología, sin causa de base aparente, es lo que hace interesante esta publicación.

Vitamin D modulation and microRNAs in gastric cancer: prognostic and therapeutic role.

Gastric adenocarcinoma arises after a complex interaction between the host and environmental factors. Tumor location and TNM are the tools that currently guide treatment decisions. Surgery is the only curative treatment, but relapse is common. After relapse or advanced staged disease survival is poor and systemic treatment has modestly improved survival. An association between sun exposure, vitamin D status and gastric cancer (GC) incidence and mortality has been reported. The molecular differences of the histological subtypes and the new molecular classifications account for the great heterogeneity of this disease and are the basis for the discovery of new therapeutic targets. New prognostic and predictive factors are essential and microRNAs (miRNAs) are endogenous small non-coding RNA molecules with a great potential for diagnosis, prognosis and treatment of cancer. There are hundreds of miRNAs with altered expression in tumor gastric tissue when compared to normal gastric tissue. Many of these miRNAs are associated with clinicopathological variables and survival in patients with GC. Furthermore, the expression of some of these miRNAs with prognostic importance in CG is influenced by vitamin D and others are mediators of some of the actions of this vitamin. This review aims to update the evidence on several miRNAs with prognostic value and therapeutic potential in GC, whose expression may be influenced by vitamin D or may regulate vitamin D signaling.

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Depleción crónica de potasio en paciente con derivación biliopancreática / Chronic potassium depletion in patient with biliopancreatic diversion

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Prediction of serious complications in patients with seemingly stable febrile neutropenia: validation of the Clinical Index of Stable Febrile Neutropenia in a prospective cohort of patients from the FINITE study.

PURPOSE: To validate a prognostic score predicting major complications in patients with solid tumors and seemingly stable episodes of febrile neutropenia (FN). The definition of clinical stability implies the absence of organ dysfunction, abnormalities in vital signs, and major infections. PATIENTS AND METHODS: We developed the Clinical Index of Stable Febrile Neutropenia (CISNE), with six explanatory variables associated with serious complications: Eastern Cooperative Oncology Group performance status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), mucositis of grade ≥ 2 (National Cancer Institute Common Toxicity Criteria; 1 point), monocytes < 200 per µL (1 point), and stress-induced hyperglycemia (2 points). We integrated these factors into a score ranging from 0 to 8, which classifies patients into three prognostic classes: low (0 points), intermediate (1 to 2 points), and high risk (≥ 3 points). We present a multicenter validation of CISNE. RESULTS: We prospectively recruited 1,133 patients with seemingly stable FN from 25 hospitals. Complication rates in the training and validation subsets, respectively, were 1.1% and 1.1% in low-, 6.1% and 6.2% in intermediate-, and 32.5% and 36% in high-risk patients; mortality rates within each class were 0% in low-, 1.6% and 0% in intermediate-, and 4.3% and 3.1% in high-risk patients. Areas under the receiver operating characteristic curves in the validation subset were 0.652 (95% CI, 0.598 to 0.703) for Talcott, 0.721 (95% CI, 0.669 to 0.768) for Multinational Association for Supportive Care in Cancer (MASCC), and 0.868 (95% CI, 0.827 to 0.903) for CISNE (P = .002 for comparison between CISNE and MASCC). CONCLUSION: CISNE is a valid model for accurately classifying patients with cancer with seemingly stable FN episodes.

[Predictive capacity of the diagnostic criteria of metabolic syndrome on the insulin-resistance and the coronary risk]. / Capacidad predictiva de los criterios diagnósticos del síndrome metabólico sobre la resistencia a la insulina y el riesgo coronario.

BACKGROUND AND OBJECTIVE: Since at present several diagnostic criteria of the metabolic syndrome (MS) exist, the objective of the study is to verify the utility of the criteria of the International Diabetes Federation (IDF) to diagnose the MS, their agreement with other previous definitions and the insulin resistance (IR). It also studies its relation with the coronary risk (CR). SUBJECTS AND METHOD: Design of a cross-sectional descriptive study in the scope of the primary care of Yecla (Murcia). We studied 317 selected people from a stratified random sampling (age and sex) of 424 from a population of 18,059 with sanitary card and aged > or = 30 years. Socio-demographic, anthropometric and analytical (lipids, microalbuminuria, hemoglobin A1c and insulinemia) variables were registered. Criteria from the World Health Organization (WHO), Third Report of National Cholesterol Education Program (NCEP-III), European Group for the Study of Insuline Resistance (EGIR) and IDF were used to diagnose the MS. We defined IR when index HOMA > or = 3.8. The agreement between definitions of MS was determined by the kappa statistic. The CR was quantified according to Anderson (1991) method. RESULTS: The prevalence of the MS was: WHO, 35.3% (95% confidence interval [CI], 29.8-40.8); NCEP, 20.2% (95% CI, 15.6-24.8); EGIR, 24% (95% CI, 19.1-28.9), and IDF, 28.9% (95% CI, 23.8-34). The prevalence of IR was 27.7% (95% CI, 22.6-32.8). The agreement between the most clinical criteria (NCEP, IDF) and the biochemists (WHO, EGIR, HOMA) was lower (kappa < 0.50). A 58.2% (WHO), 66.1% (NCEP), 50% (EGIR) and 57% (IDF) of subjects with MS presented a CR greater than 20%. CONCLUSIONS: A high prevalence of the MS in Yecla exists, with a good agreement between the most clinical definitions of the syndrome (NCEP and IDF), that are associated with greater CR.

Capacidad predictiva de los criterios diagnósticos del síndrome metabólico sobre la resistencia a la insulina y el riesgo coronario / Predictive capacity of the diagnostic criteria of metabolic syndrome on the insulin-resistance and the coronary risk

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[Prevalence of metabolic syndrome in the adult population of Yecla (Murcia). Degree of agreement between three definitions of it]. / Prevalencia del síndrome metabólico en la población adulta de Yecla (Murcia). Grado de acuerdo entre tres definiciones.

OBJECTIVES: To determine the prevalence of metabolic syndrome (MS), its components and insulin resistance (IR) in the adult population of Yecla. To study the variability between 3 definitions of the syndrome and IR. To identify the variables that predict the presence of IR and to verify the diagnostic validity of several strategies for predicting it. DESIGN: Descriptive, cross-sectional study. SETTING: Primary care, Yecla (Murcia), Spain. PARTICIPANTS: We studied 317 persons (292 with analysis) out of 424 selected by stratified (age and sex) random sampling from 18,059 people > or = 30 years old and possessing a health card. MAIN MEASUREMENTS: We used WHO-98, NCEP III, and EGIR criteria for diagnosing MS, and WHO-99 for defining DM2, impaired basal glucose and impaired glucose tolerance. The following variables were collected: social, demographic and personal details, plasma lipid, glycosylated haemoglobin, microalbuminuria, and insulin levels. IR was defined by the HOMA method at > or = 3.8 or as the highest quartile of basal insulinemia in normoglycaemic persons. RESULTS: MS prevalence was NCEP 20.2% (95% CI, 15.6-24.8), WHO 35.3% (95% CI, 29.8-40.8), EGIR 24% (95% CI, 19.1-28.9), and IR was 27.7% (95% CI, 22.6-32.8). The sensitivity and specificity of NCEP, WHO, and EGIR criteria for detecting IR were (46% and 90%), (78% and 81%), and (73% and 95%), respectively. Insulin resistance was associated significantly with age, basal glycaemia, triglycerides, and waist circumference. CONCLUSIONS: Metabolic syndrome is common in Yecla (more so in men). There is disagreement between several diagnostic criteria for the syndrome, with NCEP criteria less sensitive in determining IR. A generally accepted definition is needed.

Prevalencia del síndrome metabólico en la población adulta de Yecla (Murcia). Grado de acuerdo entre tres definiciones / Prevalence of metabolic syndrome in the adult population of Yecla (Murcia). Degree of agreement between three definitions of it

Objetivos. Detectar la prevalencia del síndrome metabólico (SM), sus componentes y la resistencia a la insulina (RI) en la población adulta de Yecla. Estudiar la concordancia de 3 definiciones del SM entre sí y con la RI. Identificar variables que puedan predecir la presencia de RI y comprobar la validez diagnóstica de varias estrategias para predecirla. Diseño. Estudio descriptivo, transversal. Emplazamiento. Población de Yecla (Murcia). Ámbito de atención primaria. Participantes. Estudiamos a 317 personas (292 aportaron analítica) de 424 seleccionadas mediante muestreo aleatorio estratificado (edad y sexo) de 18.059 con tarjeta sanitaria y edad é 30 años. Mediciones principales. Utilizamos los criterios NCEP III, OMS-98 y EGIR (Grupo Europeo de Estudio de la Resistencia a la Insulina) para diagnosticar el SM y OMS-99 para definir la diabetes mellitus no insulinodependiente, la glucemia basal alterada y la tolerancia alterada a la glucosa. Recogimos variables sociodemográficas y antropométricas, y determinamos la presencia de lípidos, microalbuminuria, HbA1c e insulinemia; definimos RI si el índice HOMA é 3,8 o como cuartil más alto de insulinemia basal en normoglucémicos. Resultados. La prevalencia del SM fue, según los criterios NCEP, del 20,2% (intervalo de confianza [IC] del 95%, 15,6-24,8), OMS del 35,3% (IC del 95%, 29,8-40,8), EGIR del 24% (IC del 95%, 19,1-28,9) y RI del 27,7% (IC del 95%, 22,6-32,8). La sensibilidad y la especificidad de NCEP, OMS y EGIR para detectar RI fueron del 46 y el 90%, del 78 y el 81% y del 73 y el 95%, respectivamente. La edad, la glucemia basal, los triglicéridos y el perímetro de la cintura se asocian significativamente con RI. Conclusiones. Hay una alta prevalencia de SM en el área (mayor en los varones). Hay diferencias entre los diferentes criterios diagnósticos del síndrome, y los de NCEP son menos sensible para determinar la RI. Es necesario establecer una definición universalmente aceptada del SM

Objectives. To determine the prevalence of metabolic syndrome (MS), its components and insulin resistance (IR) in the adult population of Yecla. To study the variability between 3 definitions of the syndrome and IR. To identify the variables that predict the presence of IR and to verify the diagnostic validity of several strategies for predicting it. Design. Descriptive, cross-sectional study. Setting. Primary care, Yecla (Murcia), Spain. Participants. We studied 317 persons (292 with analysis) out of 424 selected by stratified (age and sex) random sampling from 18 059 people >=30 years old and possessing a health card. Main measurements. We used WHO-98, NCEP III, and EGIR criteria for diagnosing MS, and WHO-99 for defining DM2, impaired basal glucose and impaired glucose tolerance. The following variables were collected: social, demographic and personal details, plasma lipid, glycosylated haemoglobin, microalbuminuria, and insulin levels. IR was defined by the HOMA method at >=3.8 or as the highest quartile of basal insulinemia in normoglycaemic persons. Results. MS prevalence was NCEP 20.2% (95% CI, 15.6-24.8), WHO 35.3% (95% CI, 29.8-40.8), EGIR 24% (95% CI, 19.1-28.9), and IR was 27.7% (95% CI, 22.6-32.8). The sensitivity and specificity of NCEP, WHO, and EGIR criteria for detecting IR were (46% and 90%), (78% and 81%), and (73% and 95%), respectively. Insulin resistance was associated significantly with age, basal glycaemia, triglycerides, and waist circumference. Conclusions. Metabolic syndrome is common in Yecla (more so in men). There is disagreement between several diagnostic criteria for the syndrome, with NCEP criteria less sensitive in determining IR. A generally accepted definition is needed

[Analysis of disturbances in carbohydrate metabolism in the adult population of Yecla (Murcia, Spain)]. / Análisis de las alteraciones del metabolismo hidrocarbonado en la población adulta de Yecla (Murcia).

OBJECTIVE: To determine the prevalence of impaired fasting glucose (IFG or GBA), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM2) in the adult population of Yecla. RESEARCH, DESIGN, AND METHODS: We performed a population-based cross-sectional study (on Primary Care Field) with stratified and random sampling (393) from 17 500 residents in Yecla with sanitary card and aged > or =30 years. We studied 286 subjects (107 declining to participate) and 261 of them (125 men and 136 women) underwent an oral glucose tolerance test (OGTT). MAIN MEASUREMENTS: World Health Organization (WHO-99) and American Diabetes Association (ADA-97) criteria were used for diagnosis of unknown DM2, GBA and IGT. Socio-demographic and anthropometric variables were measured. Plasma lipid, glycosylated haemoglobin (HbA1C), microalbuminuria and insulin levels also were measured. Insulin resistance was evaluated by the HOMA method. RESULTS: According ADA-97 criteria the prevalence of DM2 and GBA was 2.65 (CI+/-1.95) and 4.3% (+/-2.5) respectively. Underwent an OGTT, the age-adjusted prevalence of DM2, IGT and GBA (using the Spanish population of July 02) was 6.7 (95%CI, 3,7-9,7); 13.2 (95%CI, 9.1-17.3) and 0.2% (95%CI, 0-1.8) respectively. The known DM2 was 5,9% (95%CI, 3.8-8) and the global prevalence of DM2 was 12.6% (95%CI, 9.6-15.6). The diabetes was associated with overweight, overage and higher insulin, HbA1C and insulin resistance levels. CONCLUSIONS: There is a high prevalence of DM2 in Yecla (known/unknown 0.87/1). The ADA97 criteria only detected 53% of the unknown DM2. The 78% of normoglycemics subjects had overweight or upper-body fat distribution and diabetics people had higher BMI (Body Mass Index), Hypertension, insulinemia, HbA1C and insulin resistance levels than normoglycemics and IGT subjects.