Análisis coste-efectividad sobre la realización de mastectomía contralateral profiláctica en pacientes con edad igual o menor de 60 años diagnosticadas de cáncer de mama unilateral no portadoras de mutación germinal en los genes BRCA1/2

Las tasas de realización de mastectomía contralateral profiláctica en mujeres diagnosticadas de cáncer de mama unilateral se han incrementado en los últimos años. Sin embargo, no esta claro si esta técnica aporta beneficio en términos de supervivencia o si es coste-efectiva.El objetivo de este estudio analítico, unicéntrico, retrospectivo es analizar si la realización de mastectomía contralateral profiláctica en pacientes con 60 años de edad o menos, diagnosticadas de cáncer de mama unilateral en estadio precoz y no portadoras de mutación germinal en BRCA1/2 es coste-efectiva.En este estudio también se ha comparado la supervivencia libre de evento entre las mujeres que optan por la realización de mastectomía contralateral profiláctica y las que optan por cirugía unilateral. Además, se han determinado qué factores se relacionan con la elección de mastectomía contralateral profiláctica y se ha realizado un estudio comparativo de los costes asociados a la mastectomía contralateral profiláctica y la cirugía unilateral.<br /

Genetic and functional homologous repair deficiency as biomarkers for platinum sensitivity in TNBC: A case report

HRD-biomarkers; Pathological complete response; Triple-negative breast cancerBiomarcadores HRD; Respuesta patológica completa; Cáncer de mama triple negativoBiomarcadors HRD; Resposta patològica completa; Càncer de mama triple negatiuTriple-negative breast cancer is the most aggressive subtype of mammary carcinoma. In the early stage, neoadjuvant chemotherapy (NAC) is the standard of care for prognostic stratification and the best adjuvant treatment strategy. A 30-year-old female presented in the emergency room because of a gigantic right breast associated with an ulcerated lump at the upper quadrants. The right axillary nodes were palpable. An ultrasound was performed, showing the ulcerated neoformation with enlarged right axillary lymph nodes observed to level III. A core biopsy of the breast lesion was performed, and the pathological examination revealed a nonspecial type, grade 3, invasive, triple-negative breast cancer. No distant disease was found in the PET-CT scan. A germline genetic panel by next-generation sequencing identified a likely pathogenic variant in RAD51D (c.898C>T). Assessment of the functionality of the DNA homologous recombination repair pathway by RAD51 foci in the tumor revealed a profile of homologous recombination deficiency. NAC consisting of weekly carboplatin and paclitaxel followed by dose-dense doxorubicin/cyclophosphamide was performed with a complete metabolic response achieved in the PET-CT scan. The patient underwent a modified radical mastectomy plus axillary lymphadenectomy with a pathological complete response in the breast and axilla and remains disease-free after 2 years of follow-up. We report a young female with a triple-negative breast cancer stage cT4bN3M0 and a hereditary pathogenic mutation in RAD51D. The tumor was highly proliferative and homologous recombination-deficient by RAD51. The patient received platinum-based NAC, achieving a pathologic complete response. More effort should be made to identify predictive functional biomarkers of treatment response, such as RAD51 foci, for platinum sensitivity

How could antibiotics, probiotics, and corticoids modify microbiota and its influence in cancer immune checkpoint inhibitors: a review

Immunotherapy has become a new paradigm in oncology, improving outcomes for several types of cancer. However, there are some aspects about its management that remain uncertain. One of the key points that needs better understanding is the interaction between immunotherapy and gut microbiome and how modulation of the microbiome might modify the efficacy of immunotherapy. Consequently, the negative impact of systemic antibiotics and corticosteroids on the efficacy of immunotherapy needs to be clarified.Peer reviewe

Characterisation of T cell receptor repertoire in non-small cell lung cancer patients treated with immunotherapy

Abstract from the 2022 World Conference on Lung Cancer 6-9 August 2022, Vienna, Austria.-- EP16.01-033.Non-small cell lung cancer (NSCLC) therapy has experienced important changes in survival benefit and durable anti-tumor responses due to immune checkpoint blockers (ICBs). However, ICBs show some major limitations including low response rate and drug resistance in unselected patients. Despite the development of new predictive biomarkers, such as PD-L1 expression, microsatellite instability (MSI), or tumor mutation burden (TMB), there is an urgent need for biomarkers that identify which patients will benefit more from ICBs and define the reasons for failure of the treatment. Analysis of peripheral blood T cell receptor beta chain (TCR-β) repertoire and other serum biomarkers may provide information about the immune response in ICBs treated NSCLC patients.Peer reviewe

Intratumoral versus circulating lymphoid cells as predictive biomarkers in lung cancer patients treated with immune checkpoint inhibitors: Is the easiest path the best one?

This article belongs to the Special Issue Cancer Immunology: From Molecular Mechanisms to Therapeutic Opportunities.The molecular and cell determinants that modulate immune checkpoint (ICI) efficacy in lung cancer are still not well understood. However, there is a necessity to select those patients that will most benefit from these new treatments. Recent studies suggest the presence and/or the relative balance of specific lymphoid cells in the tumor microenvironment (TEM) including the T cell (activated, memory, and regulatory) and NK cell (CD56dim/bright) subsets, and correlate with a better response to ICI. The analyses of these cell subsets in peripheral blood, as a more accessible and homogeneous sample, might facilitate clinical decisions concerning fast prediction of ICI efficacy. Despite recent studies suggesting that lymphoid circulating cells might correlate with ICI efficacy and toxicity, more analyses and investigation are required to confirm if circulating lymphoid cells are a relevant picture of the lung TME and could be instrumental as ICI response biomarkers. This short review is aimed to discuss the recent advances in this fast-growing field.J.P. reports research funding from BMS and Gilead and speaker honoraria from Gilead and Pfizer. E.M.G. reports research funding from BMS and Gilead. J.P. and E.M.G. are funded by FEDER (Fondo Europeo de Desarrollo Regional, Gobierno de Aragón (Group B29_17R), Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación (SAF2017-83120-C2-1-R), Fundacion Inocente Inocente, ASPANOA and Carrera de la Mujer de Monzón. J.P. is supported by ARAID Foundation

Microbiota and lung cancer. Opportunities and challenges for improving immunotherapy efficacy

The advances in molecular biology and the emergence of Next Generation Sequencing (NGS) have revealed that microbiome composition is closely related with health and disease, including cancer. This relationship affects different levels of cancer such as development, progression, and response to treatment including immunotherapy. The efficacy of immune checkpoint inhibitors (ICIs) may be influenced by the concomitant use of antibiotics before, during or shortly after treatment with ICIs. Nevertheless, the linking mechanism between microbiote, host immunity and cancer is not clear and the role of microbiota manipulation and analyses in cancer management has not been clinically validated yet. Regarding the use of microbiome as biomarker to predict ICI efficacy it has been recently shown that the use of biochemical serum markers to monitor intestinal permeability and loss of barrier integrity, like citrulline, could be useful to monitor microbiota changes and predict ICI efficacy. There are still many unknowns about the role of these components, their relationship with the microbiota, with the use of antibiotics and the response to immunotherapy. The next challenge in microbiome research will be to identify individual microbial species that causally affect lung cancer phenotypes and response to ICI and disentangle the underlying mechanisms. Thus, further analyses in patients with lung cancer receiving treatment with ICIs and its correlation with the composition of the microbiota in different organs including the respiratory tract, peripheral blood and intestinal tract could be useful to predict the efficacy of ICIs and its modulation with antibiotic use.JP reported research funding from BMS and Gilead and speaker honoraria from Gilead and Pfizer. EG reported research funding from BMS and Gilead. JP and EG were funded by FEDER (Fondo Europeo de Desarrollo Regional, Gobierno de Aragón (Group B29_17R), Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación (SAF2017-83120-C2- 1-R), Fundacion Inocente Inocente, ASPANOA and Carrera de la Mujer de Monzón. JP was supported by ARAID Foundation. DI reported consultation honoraria from AbbVie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche, Merck, MSD, Novartis, Pierre Fabre, Pfizer, and Takeda. DI reported speaker honoraria from Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann-La Roche, MSD, Novartis, Pierre Fabre, and Pfizer. DI reported research grant from AstraZeneca, BMS, F. Hoffmann-La Roche, MSD, and Pierre Fabre.Peer reviewe

From tumor mutational burden to blood T cell receptor: Looking for the best predictive biomarker in lung cancer treated with immunotherapy

2 tables.Immune control inhibitor drugs (anti-PD1/PD-L1/CTLA-4) (ICIs) are showing efficacy in the treatment of lung cancer. Currently the only biomarker with clinical utility for ICIs, such as the expression of PDL1, does not appear to be perfect or effective. Our working group is conducting a pilot study in lung cancer patients receiving ICIs with the aim of analyze the factors that affect the sensitivity of the immunotherapy in lung Cancer. Tumor Mutational Burden (TMB) and the sequencing of the T Cell Receptor (TCR) repertoire in peripheral blood have been postulated as predictive biomarkers of efficacy of immunotherapy. The review focusses on the predictive value of TMB for clinical responses to ICIs and discusses its clinical need after a discussion of the limitations. TCR CDR3 beta analysis and parameters such as clonality and TCR convergence may be good alternatives. For the moment, the combination of biomarkers may be the optimal tool.Despite therapeutic advances, lung cancer (LC) is one of the leading causes of cancer morbidity and mortality worldwide. Recently, the treatment of advanced LC has experienced important changes in survival benefit due to immune checkpoint inhibitors (ICIs). However, overall response rates (ORR) remain low in unselected patients and a large proportion of patients undergo disease progression in the first weeks of treatment. Therefore, there is a need of biomarkers to identify patients who will benefit from ICIs. The programmed cell death ligand 1 (PD-L1) expression has been the first biomarker developed. However, its use as a robust predictive biomarker has been limited due to the variability of techniques used, with different antibodies and thresholds. In this context, tumor mutational burden (TMB) has emerged as an additional powerful biomarker based on the observation of successful response to ICIs in solid tumors with high TMB. TMB can be defined as the total number of nonsynonymous mutations per DNA megabases being a mechanism generating neoantigens conditioning the tumor immunogenicity and response to ICIs. However, the latest data provide conflicting results regarding its role as a biomarker. Moreover, considering the results of the recent data, the use of peripheral blood T cell receptor (TCR) repertoire could be a new predictive biomarker. This review summarises recent findings describing the clinical utility of TMB and TCRβ (TCRB) and concludes that immune, neontigen, and checkpoint targeted variables are required in combination for accurately identifying patients who most likely will benefit of ICIs.Peer reviewe