Publications by authors named "David Gómez-Sánchez"

6 Publications

  • Page 1 of 1

Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB harmonization project comparing three NGS panels.

J Immunother Cancer 2021 May;9(5)

H12O-CNIO Lung Cancer Clinical Research Unit, Health Research Institute Hospital 12 de Octubre (imas12) / Spanish National Cancer Research Center (CNIO), Madrid, Spain.

Background: Tumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed.

Methods: We evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined.

Results: Both panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with <1% of cells expressing PD-L1 (PD-L1<1%; N55), and 0.861 (TSO500-FO) and 0.722 (OTML-FO) in tumors with PD-L1≥1% (N=41). Inter-laboratory reproducibility analyses showed higher reproducibility with TSO500. No significant differences were found in terms of immune infiltration versus TMB. Adjusted cut-off values corresponding to 10 muts/Mb with FO needed to be lowered to 7.847 muts/Mb (TSO500) and 8.380 muts/Mb (OTML) to ensure a sensitivity >88%. With these cut-offs, the positive predictive value was 78.57% (95% CI 67.82 to 89.32) and the negative predictive value was 87.50% (95% CI 77.25 to 97.75) for TSO500, while for OTML they were 73.33% (95% CI 62.14 to 84.52) and 86.11% (95% CI 74.81 to 97.41), respectively.

Conclusions: Both panels exhibited robust analytical performances for TMB assessment, with stronger concordances in patients with negative PD-L1 expression. TSO500 showed a higher inter-laboratory reproducibility. The cut-offs for each assay were lowered to optimal overlap with FO.
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May 2021

Identification of Predictive Biomarkers of Response to HSP90 Inhibitors in Lung Adenocarcinoma.

Int J Mol Sci 2021 Mar 3;22(5). Epub 2021 Mar 3.

CIBERONC, Respiratory Tract Tumors Program, 28029 Madrid, Spain.

Heat shock protein 90 (HSP90) plays an essential role in lung adenocarcinoma, acting as a key chaperone involved in the correct functioning of numerous highly relevant protein drivers of this disease. To this end, HSP90 inhibitors have emerged as promising therapeutic strategies, even though responses to them have been limited to date. Given the need to maximize treatment efficacy, the objective of this study was to use isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic techniques to identify proteins in human lung adenocarcinoma cell lines whose basal abundances were correlated with response to HSP90 inhibitors (geldanamycin and radicicol derivatives). From the protein profiles identified according to response, the relationship between lactate dehydrogenase B (LDHB) and DNA topoisomerase 1 (TOP1) with respect to sensitivity and resistance, respectively, to geldanamycin derivatives is noteworthy. Likewise, rhotekin (RTKN) and decaprenyl diphosphate synthase subunit 2 (PDSS2) were correlated with sensitivity and resistance to radicicol derivatives. We also identified a relationship between resistance to HSP90 inhibition and the p53 pathway by glucose deprivation. In contrast, arginine biosynthesis was correlated with sensitivity to HSP90 inhibitors. Further study of these outcomes could enable the development of strategies to improve the clinical efficacy of HSP90 inhibition in patients with lung adenocarcinoma.
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March 2021

Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients: psychometric properties and measurement invariance.

Psicothema 2021 02;33(1):131-138

University of Barcelona.

Background: The aim of this study was to evaluate the psychometric properties, convergent validity, and factorial invariance of the Multidimensional Scale of Perceived Social Support (MSPSS) in cancer patients.

Method: Confirmatory factor analysis (CFA) was conducted to explore the scale's dimensionality and test for strong measurement invariance across sex and age in a cross-sectional, multicenter, prospective study. Patients completed the MSPSS and Satisfaction with Life Scale (SWLS).

Results: A total of 925 consecutive patients were recruited in 13 hospitals between July 2015 and December 2018. The CFA indicated that the original three-factor model was replicated in patients with cancer. The results of the multi-group CFA revealed a strong invariance according to sex and age. The Spanish version of the MSPSS had high estimated reliability with values exceeding .90. The simple sum of the items of each scale was a good indicator of oncology patients' perceived social support. The three MSPSS subscales correlated significantly with the SWLS. Women scored higher on social support by friends than men.

Conclusion: The Spanish version of the MSPSS proved to be a valid, reliable instrument to assess perceived social support in cancer patients.
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February 2021

Psychometric properties of Spanish version of the Mini-Mental Adjustment to Cancer Scale.

Int J Clin Health Psychol 2021 Jan-Apr;21(1):100185. Epub 2020 Jul 2.

Department of Medical Oncology, Hospital Universitario Central of Asturias, Spain.

Background/objective: The aim of the study was to examine the factor structure and psychometric properties of the Spanish version of the Mini-Mental Adjustment to Cancer Scale (Mini-MAC) in a large sample of patients with non-metastatic, resected cancer.

Methods: Prospective, observational, multicenter study for which 914 patients were recruited from 15 Spanish hospitals. Exploratory and confirmatory factor analyses, validity and reliability analyses were conducted.

Results: Factor-analytic results indicated a 4-factor structure of the Spanish version of the Mini-MAC. Three subscales have psychometric properties similar to those of Helplessness, Anxious preoccupation, and Cognitive avoidance of the original the Mini-MAC. The Fighting spirit and the Fatalism subscales were combined on the Positive attitude scale. The four factor-derived scale scores exhibited acceptable accuracy for individual measurement purposes, as well as stability over time in test-retest assessments at 6 months. Validity assessments found meaningful relations between the derived scale scores, and Brief Symptom Inventory depression and anxiety scores and Functional Assessment of Chronic Illness Therapy spiritual well-being scores.

Conclusions: The Spanish version of the Mini-MAC provides reliable and valid measures for patients with non-metastatic, resected cancer, and results corroborate the instrument's cross-cultural validity.
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July 2020

Prospective Clinical Integration of an Amplicon-Based Next-Generation Sequencing Method to Select Advanced Non-Small-Cell Lung Cancer Patients for Genotype-Tailored Treatments.

Clin Lung Cancer 2018 01 23;19(1):65-73.e7. Epub 2017 Jun 23.

Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain; Lung Cancer Group, Clinical Research Program, CNIO (Centro Nacional de Investigaciones Oncológicas) and Instituto de Investigación i+12, Madrid, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.

Introduction: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm.

Patients And Methods: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs.

Results: We analyzed 109 tumors using NGS between December 2014 and January 2016. Fifty-six patients (51%) were treatment-naive and 82 (75%) had lung adenocarcinomas. In 89 cases (82%), we used samples derived from lung cancer diagnostic procedures. We obtained successful sequencing results in 95 cases (87%). As part of our routine lung cancer molecular subtyping protocol, single-gene testing for EGFR, ALK, and ROS1 was attempted in nonsquamous and 3 squamous-cell cancers (n = 92). Sixty-nine of 92 samples (75%) had sufficient tissue to complete ALK and ROS1 immunohistochemistry (IHC) and NGS. With the integration of the gene panel, 40 NSCLCs (37%) in the entire cohort and 30 NSCLCs (40%) fully tested for ALK and ROS1 IHC and NGS had actionable mutations. KRAS (24%) and EGFR (10%) were the most frequently mutated actionable genes. Ten patients (9%) received matched targeted therapies, 6 (5%) in clinical trials.

Conclusion: The combination of IHC tests for ALK and ROS1 and amplicon-based NGS is applicable in routine clinical practice, enabling patient selection for genotype-tailored treatments.
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January 2018