Excess weight and anti-PD-1 immune checkpoint inhibitor’s outcomes in non-small cell lung cancer

Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs.MethodsWe studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment’s outcome in the study group and in the control group (objective response, and progression-free and overall survival).ResultsIn our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found.ConclusionOur study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy. (AU)

Excess weight and anti-PD-1 immune checkpoint inhibitor's outcomes in non-small cell lung cancer.

PURPOSE: Immune checkpoint inhibitors are one of the most effective treatments available in advanced non-small cell lung cancer. However, at present, there are no clinical or analytical biomarkers that define which patients benefit with certainty from these treatments. In our study, we evaluated whether excess weight could be a good predictive biomarker of benefit from these drugs. METHODS: We studied a population of 79 patients, divided into a study group with 39 patients diagnosed with non-small cell lung cancer treated with immunotherapy and 40 patients in a control group, diagnosed with different advanced cancers, treated with non-immunotherapy treatment. We analyzed according to the presence of excess weight or not, the treatment's outcome in the study group and in the control group (objective response, and progression-free and overall survival). RESULTS: In our study, we detected a better response rate to immunotherapy in patients with excess weight (62.50 vs 26.08%, OR 4.72, p = 0.02), and a better median progression-free survival (14.19 vs 5.03 months, HR 0.50, p = 0.058) and median overall survival (33.84 months vs 20.76 months, HR 0.43, p = 0.01) in the study group. These findings were specific to the immunotherapy group since in the control group, with patients who did not receive immune checkpoint inhibitors, these findings were not found. CONCLUSION: Our study suggests that patients with excess weight who receive anti-PD-1 immune checkpoint inhibitors diagnosed with non-small cell lung cancer have a better outcome. This effect is specific to patients receiving immunotherapy.

Evolución y resultados del tratamiento neoadyuvante en cáncer de mama durante un periodo de 10 años / Progress and oncological outcome of neoadjuvant therapy in breast cancer patients during a 10-year period

Introducción: el cáncer de mama es la neoplasia más frecuente en mujeres españolas. Los continuos avances en su tratamiento han contribuido a mejorar de forma progresiva la supervivencia en estadios precoces. Entre los avances durante los últimos años, hay que destacar el tratamiento neoadyuvante.Material y métodoshemos valorado la evolución temporal de las indicaciones y los resultados del tratamiento neoadyuvante del cáncer de mama durante un periodo de 10 años. Para ello, se han analizado las características clínicas, la respuesta completa patológica (RCp), la supervivencia global (SG) y libre de progresión (SLP) de todos los pacientes con cáncer de mama tratados con neoadyuvancia entre el 1 de enero de 2007 y el 31 de diciembre de 2016.Resultadosse han tratado 212 pacientes con cáncer de mama. A lo largo de los 10 años hemos observado un progresivo aumento en el número de pacientes tratadas con neoadyuvancia, en la edad de los pacientes incluidos (p < 0,001), en los casos de menopausia (p = 0,029), de casos triple negativo y HER2 positivo. También, hemos observado un aumento en el número de casos en los que se ha realizado cirugía conservadora y biopsia selectiva del ganglio centinela.Conclusionesel tratamiento neoadyuvante se utiliza cada vez más en las pacientes con cáncer de mama, sobre todo en los subtipos de mal pronóstico (triple negativo y HER2). La incorporación de nuevos fármacos y el tratamiento de estadios más precoces está contribuyendo a la mejora de las tasas de RCp y las cirugías conservadoras. (AU)

Introduction: Breast cancer is the most frequent tumor in Spanish women. Continuous advances in the treatment of this neoplasm, have contributed to progressively improve survival in early stages. In the last years, neoadjuvant treatment has evolved and changes have occurred in the treatment indication and in the results.Material and methodsWe have assessed the temporal evolution of indications and results of neoadjuvant therapy in breast cancer over a 10-year period. We have analyzed the clinical characteristics, the complete pathological response (CRp), overall survival (OS) and progression-free survival (PFS) of all patients with breast cancer treated with neoadjuvant therapy between January 1st 2007 and December 31st 2016.ResultsDuring the study period, 212 patients were treated.  Throughout the 10-year period, we observed that increasingly older patients had been treated (p < 0.001), a greater number of menopausal patients (p = 0.029), a greater number of triple negative and HER2 positive cases. In addition, a larger number of conservative surgeries and sentinel lymph node biopsies had been performed.ConclusionsNeoadjuvant therapy is increasing in patients with breast cancer, especially in subtypes with poor prognosis (triple negative and HER2). The emerging new drugs and treatment in earlier stages has increased the rate of pCR and breast conserving surgery. (AU)

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC.

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry. As a control group, we studied patients with advanced malignancies before initiating non-immunotherapy treatment. The frequency of PBMCs was correlated with treatment outcome. Patients were categorized as having either high or low expression for each biomarker, defined as those above the 55th or below the 45th percentile of the overall marker expression within the cohort. In the study group, three subpopulations were associated with significant differences in outcome: high pretreatment levels of circulating CD4+CCR9+, CD4+CCR10+, or CD8+CXCR4+ T cells correlated with poorer overall survival (15.7 vs. 35.9 months, HR 0.16, p = 0.003; 22.0 vs. NR months, HR 0.10, p = 0.003, and 22.0 vs. NR months, HR 0.29, p = 0.02). These differences were specific to immunotherapy-treated patients. High baseline levels of circulating T cell subpopulations related to tissue lymphocyte recruitment are associated with poorer outcomes of immunotherapy-treated advanced NSCLC patients.

Effect of excess weight and immune-related adverse events on the efficacy of cancer immunotherapy with anti-PD-1 antibodies.

Immunotherapy is an effective treatment in advanced cancer, although predictors of response are limited. We studied whether excess weight influences the efficacy outcomes of immunotherapy. We have also evaluated the combined prognostic effect of excess weight and immune-related adverse events (irAEs). Efficacy of anti-PD-1 treatment was evaluated with both objective radiological response (ORR) rate and progression-free survival (PFS), and toxicity with irAEs. We studied the association between excess weight and ORR, PFS or irAEs. 132 patients diagnosed with advanced cancer were included. Median body mass index (BMI) was 24.9 kg/m2. 64 patients had normal weight (BMI<25 kg/m2), and 64 patients had excess weight (BMI≥25 kg/m2). Four patients had underweight and were excluded from further analysis. ORR was achieved in 50 patients (38.0%), median PFS was 6 months. 44 patients developed irAEs (33.3%). ORR was higher in excess weight patients than in patients with normal weight (51.6% vs 25.0%; OR 3.45, p = .0009). PFS was improved in patients with excess weight (7.25 months vs 4 months, HR 1.72, p = .01). The incidence of IrAEs was not different in patients with excess weight (54.5% vs 43.2%, p = .21). When high BMI and irAEs were combined, we observed a marked prognostic trend in ORR rate (87.5% vs 6.2%; OR 161.0, p < .00001), and in PFS (14 months vs 3 months; HR 5.89, p < .0001). Excess weight patients with advanced cancer that receive single-agent anti-PD-1 antibody therapy exhibit a significantly improved clinical outcome compared with normal BMI patients. This association was especially marked when BMI and irAEs were considered combined.

A systemic inflammation response index (SIRI) correlates with survival and predicts oncological outcome for mFOLFIRINOX therapy in metastatic pancreatic cancer.

OBJECTIVES: Systemic inflammatory response and survival has not been evaluated as a predictive factor of chemotherapy in metastatic pancreatic cancer. The aim of this study was to evaluate the prognostic and predictive value of a baseline Systemic Inflammation Response Index (SIRI) in metastatic pancreatic cancer. METHODS: Retrospective study of 164 metastatic pancreatic cancer patients. Associations between overall survival (OS), progression free survival (PFS), chemotherapy and SIRI were analyzed. SIRI is defined by neutrophil x monocyte/lymphocyte 109/L. RESULTS: Median age 66 years. 22 (13%) received mFOLFIRINOX, 59 (36%) gemcitabine + nab-paclitaxel, 40 (24%) gemcitabine, 13 (8%) other regimens and 30 (18%) had not received treatment. Patients with SIRI<2.3 × 109/L showed a statistically significant improvement in OS compared to SIRI≥2.3 × 109/L [16 months versus 4.8 months, Hazard Ratio (HR) 2.87, Confidence Interval (CI) 95% 2.02-4.07, p < 0.0001] that was confirmed in multivariate analysis. In addition, patients with SIRI<2.3 × 109 showed a longer PFS (12 versus 6 months, HR 1.92, IC 95% 1.314-2.800, P = 0.001). Furthermore, we observed that patients with SIRI ≥2.3 × 109/L were more likely to benefit from mFOLFIRINOX therapy. Patients with an elevated SIRI treated with mFOLFIRINOX versus gemcitabine plus nab-paclitaxel and gemcitabine showed a clinically and statistically significant difference in median OS of 17 months compared to 6 and 4 months respectively (p < 0.001). Conversely, the difference was not clinically significant in the SIRI<2.3 × 109/L subgroup: 15.9 months versus 16.5 and 16, respectively. CONCLUSION: An elevated SIRI (≥2.3 × 109/L) was an independent prognostic factor for patients with metastatic pancreatic cancer, warranting prospective evaluation.

Safety and Oncological Outcomes of Bevacizumab Therapy in Patients With Advanced Colorectal Cancer and Self-expandable Metal Stents.

BACKGROUND: Malignant bowel obstruction can occur in 18% of cases. Self-expandable metal stents (SEMS) can be an alternative to surgery. Bevacizumab (BV) has been associated with bowel perforation, but data on the safety of SEMS for occlusive colon cancer during BV-containing regimens are lacking. MATERIAL AND METHODS: This is a retrospective analysis of 78 patients with malignant bowel obstruction who underwent placement of SEMS as a palliative intent for stage IV disease. Chemotherapy and BV-containing regimens, stent-related complications, and outcomes were recorded. RESULTS: Overall, major stent-related complications were observed in 27 (35%) patients: Re-obstruction occurred in 14 (52%) patients, and there were 7 (26%) perforations, 4 (15%) minor bleeding, and 2 (7%) migrations. Sixteen patients received BV; 2 (12.5%) had a perforation. No differences were observed between chemotherapy alone and BV in overall complications. Univariate analysis did not show that BV was more likely to develop perforations, although the incidence was higher in this subset of patients. Kaplan-Meier analysis showed a significant association with longer overall survival for patients treated with systemic therapy (27 vs. 11 months; P ≤ .00001). Also, there is a significant benefit of BV compared with chemotherapy alone (43 vs. 39 months; P = .02). CONCLUSION: Placement of SEMS is effective and relatively safe but with an overall complication rate of 35% in the metastatic setting. The major early risk is perforation, which can increase up to 12% during BV treatment. In patients with obstructing advanced colorectal cancer that would benefit from SEMS, we should consider the risks associated with systemic therapies, taking into account the improvement in survival observed with BV.

Psychometric properties of Liverpool Stoicism Scale (LSS) in a cohort of patients with resected cancer in adjuvant treatment / Propiedades psicométricas de la Liverpool Stoicism Scale (LSS) en una cohorte de pacientes con cáncer resecado en tratamiento adyuvante

Stoicism has been used to describe a wide range of behaviors in the face of disease that go from silence, resistance to the adversity, or ‘to make the best of a bad disease’. This study pursued two objectives: 1) analyze the psychometric properties of the Spanish version of the LSS; 2) assess the relation between stoicism and gender, age, and the five-factor personality model. NEOcoping is a prospective, multicenter, observational, non-interventionist study. Patients were recruited consecutively at thirteen Spanish teaching hospitals. The following scales were administered: Liverpool Stoicism Scale (LSS) and Big Five Inventory (BFI-10). A total of 443 patients (250 females) with a mean age of 59.8 years (SD =12.3) were enrolled. Colon cancer was the most common, followed by breast cancer. At the total-scale level, mean LSS was lower than the originally reported British sample. The four-factor structure fitted the data well, had a clear interpretation, and the derived scales showed acceptable reliabilities. The personality trait of introversion predicted 4.1% of the variance of stoicism (p<001). Even though it needs to be improved, the LSS scale demonstrates acceptable psychometric properties to appraise stoicism in the Spanish population with resected cancer (AU)

El estoicismo se ha utilizado para describir una amplia gama de comportamientos frente a la enfermedad que van desde el silencio a la resistencia a la adversidad. Este estudio tiene dos objetivos: 1) analizar las propiedades psicométricas de la versión española del LSS; 2) evaluar la relación entre estoicismo, género, edad y el modelo de los cinco grandes factores de personalidad. NEOcoping es un estudio prospectivo, multicéntrico, observacional, no-intervencionista. Los pacientes fueron reclutados consecutivamente en 13 hospitales universitarios de España. Se aplicó la Liverpool Stoicism Scale (LSS) y el Big Five Inventory (BFI-10). Participaron 443 pacientes (250 mujeres) con una edad media de 59,8 años (SD =12,3). El cáncer de colon y mama fueron los más frecuentes. A nivel de escala total, la puntuación media de la LSS fue inferior a la muestra Británica. La estructura propuesta en cuatro factores proporciona un buen ajuste a los datos, y las puntuaciones en las escalas derivadas presentan fiabilidades aceptables. El rasgo de personalidad de introversión fue capaz de predecir el 4,1% de la variancia de estoicismo (p<001). Aunque debe ser mejorada, la LSS presenta globalmente unas propiedades psicométricas aceptables para evaluar el estoicismo en pacientes españoles con cáncer resecado (AU)

Prognostic Value of BRAF, PI3K, PTEN, EGFR Copy Number, Amphiregulin and Epiregulin Status in Patients with KRAS Codon 12 Wild-Type Metastatic Colorectal Cancer Receiving First-Line Chemotherapy with Anti-EGFR Therapy.

INTRODUCTION: Mutational analysis of RAS is required for anti-epidermal growth factor receptor (EGFR) treatment for patients with metastatic colorectal cancer (mCRC). However, most patients with KRAS wild-type tumors still do not respond. Other molecules downstream of the EGFR may also play a role in resistance to EGFR therapies. OBJECTIVE: Our objective was to investigate the clinical importance of biomarkers in relation to response, progression-free survival, and overall survival in patients with mCRC receiving first-line treatment with anti-EGFR therapy plus chemotherapy. METHODS: We studied the EGFR pathway [EGFR, NRAS, BRAF, PIK3CA, phosphatase and tensin homolog (PTEN), amphiregulin (AREG), and epiregulin (EREG)] in 105 patients with mCRC KRAS codon 12 wild type. We analysed objective response, progression-free survival, and overall survival in molecularly defined subgroups of the patients receiving anti-EGFR therapy plus chemotherapy as first-line treatment. RESULTS: We found a significant association between RAS wild-type, BRAF wild-type, EREG, and AREG overexpression and response to anti-EGFR therapy (p = 0.003, p = 0.015, p = 0.05, and p = 0.009, respectively). Progression-free survival and overall survival were lower in patients with RAS (p = 0.36 and p ≤ 0.001, respectively) or BRAF (p = 0.003 and p = 0.002, respectively) mutant tumors. Patients with EREG and AREG messenger RNA (mRNA) expression had longer survival than those with low-expression tumors; progression-free survival and overall survival were significant for AREG (p = 0.001 and p = 0.05, respectively). Patients with EGFR amplification tumors responded better to treatment and had better survival rates, although this was not significant. PIK3CA and PTEN were not associated with either response or survival. The multivariate logistic regression model for response showed only BRAF as a significant predictor after adjustment for the other covariates (p = 0.04, odds ratio 8.3, 95 % confidence interval 0.81-86.0). CONCLUSIONS: RAS, BRAF, AREG, and EREG predict for efficacy of first-line anti-EGFR therapy in patients with mCRC.