State of art of advanced triple negative breast cancer.

Advanced triple negative breast cancer (TNBC) is an aggressive disease (high probability of visceral metastasis) with poor outcome. Triple negative breast cancer is characterized by lack of expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2), high histologic grade, and high mitotic rate. Chemotherapy remains the primary systemic treatment, with international guidelines supporting the use of single-agent taxanes (with or without bevacizumab) or anthracyclines as first-line therapy, with a median overall survival of approximately 18 months or less. Given the suboptimal outcomes with chemotherapy, new targeted therapies for advanced TNBC are urgently needed. This review summarizes the current status of treatment, and future challenges of using new treatment options for advanced TNBC, such as poly-adenosine-diphosphate-ribose-polymerase inhibitors (olaparib and talazoparib) and immune checkpoint inhibitors (eg atezolizumab) as monotherapy or in combination with chemotherapy.

Low total pathologic complete response rate to preoperative chemotherapy in patients with invasive lobular carcinomaof the breast.

INTRODUCTION: Total pathologic complete response (tpCR; ypT0/is ypN0) after preoperative chemotherapy (PCT) is associated with better outcome in locally advanced breast cancers. However, the tpCR rate according to histology is not usually considered in trials. MATERIAL AND METHODS: Patients with invasive lobular breast carcinoma (ILC), who were included in three phase II trials (AT, ATX, and TXH), were eligible. Expression of markers and clinical phenotypes (CPh) were determined by immunohistochemistry. The primary endpoint was tpCR rate in patients with ILC. Secondary endpoints were breast-conserving surgery rate (BCSR), event-free survival (EFS), and overall survival (OS). RESULTS: In the subgroup of patients with ILC (n = 16) the median age was 50 years, 56.25% were premenopausal, median tumour size was 5 cm, and 68.75% had clinically node involvement. Six patients (37.5%) had clinical stage II, and 10 (62.5%) had clinical stage III. Hormone receptor-positive disease was present in 93.75% of the patients, and median Ki-67 was 25%. CPh were Luminal A-like in 37.5%, Luminal B-like in 50%, HER2-positive in 6.25%, and triple negative in 6.25% of tumours. Only one patient (6.25%) had a tpCR, and another patient had a pathologic complete response (pCR) only in the breast. With a median follow-up of 146 months, median EFS was 120 months (95% CI: 68-139), and median OS was not reached. Ten-year EFS and OS probability were 47% and 60%, respectively. BCSR was only 12.5%. CONCLUSIONS: PCT in patients with ILC is associated with low tpCR rate because the majority of these patients have Luminal tumours with low chemo-sensitivity.

Opioids for management of episodic breathlessness or dyspnea in patients with advanced disease.

BACKGROUND: Episodic breathlessness (EB) or dyspnea is a common symptom with a very negative impact on the quality of life of patients with cancer and with non-oncological advanced diseases, mainly cardiorespiratory and neurological. OBJECTIVE: The purpose of this non-systematic review is to ascertain the role played by opioids in the management of episodic breathlessness. METHODS: A non-systematic literature review was done in the databases MEDLINE, COCHRANE, and DATABASE, and articles of greater scientific rigor, mainly reviews or prospective studies/randomized clinical trials published to date (August 2015), were selected. Terms used in the search included episodic breathlessness, acute breathlessness, episodic dyspnea, opioids, morphine, fentanyl, oxycodone, and breakthrough dyspnea. CONCLUSIONS: Although the pathophysiology and mechanism of action of opioids for management of breathlessness, and specifically EB, are not fully known, there is scientific evidence, and particularly great clinical evidence, of the benefit of this drug class for dyspnea management. It is important to differentiate hospitalized patients from outpatients because venous or subcutaneous access is easier in hospitalized patients, but use of transmucosal fentanyl, especially in faster formulations like intranasal application, opens up new possibilities to manage outpatients due to its fast onset of action. The main problem is the lack of data available and the multitude of unanswered questions about opioid type, administration route, safety, and dose titration.

Update on thymic epithelial tumors: a narrative review.

Background and Objective: Thymoma, thymic carcinoma and thymic neuroendocrine tumors originate from the epithelial cells of the thymus and account for the thymic epithelial tumors (TETs). Although TETs are uncommon, they are the most frequent tumor type in the anterior mediastinum. Multidisciplinary approach is essential for their correct management. The aim of the present review is to summarize the update management for TETs. Methods: For this review, we searched in Excerpta Medica database (EMBASE) and MEDLINE until 6 September 2023. The terms used in the search included thymoma, thymic carcinoma, thymic epithelial tumors, management, immunotherapy, multiple tyrosine kinases inhibitors. Key Content and Findings: The therapeutic approach is based on histology and tumor stage and may involve surgery with or without neoadjuvant or adjuvant treatment. In the metastatic setting, platinum-based chemotherapy is the standard of care and patients who do not respond to first-line treatment have limited treatment options mainly because of the poor efficacy shown in subsequent lines of therapy. Conclusions: Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. Immune check point inhibitors, mammalian target of rapamycin (mTOR) and antiangiogenic multikinase inhibitors have also been studied in this clinical setting.

Update on the management of older patients with pancreatic adenocarcinoma: a perspective from medical oncology.

In the context of pancreatic cancer, surgical intervention is typically recommended for localized tumours, whereas chemotherapy is the preferred approach in the advanced and/or metastatic setting. However, pancreatic cancer is closely linked to ageing, with an average diagnosis at 72 years. Paradoxically, despite its increased occurrence among older individuals, this population is often underrepresented in clinical studies, complicating the decision-making process. Age alone should not determine the therapeutic strategy but, given the high comorbidity and mortality of this disease, a comprehensive geriatric assessment (CGA) is necessary to define the best treatment, prevent toxicity, and optimize older patient care. In this review, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica, SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours (Grupo Español de Tratamiento de los Tumores Digestivos, TTD), and the Multidisciplinary Spanish Group of Digestive Cancer (Grupo Español Multidisciplinar en Cáncer Digestivo, GEMCAD) have assessed the available scientific evidence and propose a series of recommendations on the management and treatment of the older population with pancreatic cancer.

ALK-mutated non-small-cell lung cancer: a new strategy for cancer treatment.

The anaplastic lymphoma kinase (ALK) tyrosine kinase (TK) receptor has emerged recently as a potentially relevant biomarker and therapeutic target in solid and hematologic tumors. A variety of alterations in the ALK gene, such as mutations, overexpression, amplification, translocations, or other structural rearrangements, have been implicated in human cancer tumorigenesis. In this article we review the potential role that ALK may have in lung tumor origin, the methodology to detect the different molecular alterations, and the most important clinical aspects of ALK alterations in NSCLC patients.

Biomarkers of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Beyond PD-L1.

Immunotherapy has markedly improved the survival rate of patients with non-small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Based on the current clinical trials, the aim of the present study was to review the biomarkers for immune checkpoint inhibition that may have the potential to predict the response to immunotherapy in patients with lung cancer. A non-systematic literature review was done. We searched for eligible randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2015 to January 2021. The keywords included biomarkers, immunotherapy, immune checkpoint inhibition, programmed death ligand 1 (PD-L1), and non-small cell lung cancer. Additional biomarkers beyond PD-L1 that have been shown to have predictive capacity include tumor mutational burden, microsatellite instability, lung immune prognostic index, gut microbiome, and certain alterations in genes (eg, STK11 deletion, LKB1 kinase mutation, MDM2/4 amplification) that confer immunoresistance. The biomarkers reviewed in this article could help us better select the appropriate immunotherapy treatment for patients with NSCLC.

Review of risk of COVID-19 in cancer patients and their cohabitants.

BACKGROUND: Patients with a history of active malignancy are at increased risk of infection and COVID-19-related complications. Sanitary protection measures are not specifically recommended within households. This study examined the risk of seroconversion in cancer patients according to their household exposure. PATIENTS AND METHODS: This seroprevalence study was a prevalence study conducted in Torrejon de Ardoz (Spain). It analysed the seroprevalence of IgM and IgG antibodies in 104,299 volunteers (participation rate of 74.8% of population) from 29 May to 05 June 2020. Personal authorisation was requested to collect by questionnaire the test results from cancer patients, who attended the Outpatient Department of the University Hospital of Torrejón, and their cohabitants between 01-19 June 2020. RESULTS: A total of 229 cancer patients were included in the study. Sixty-four of the 229 individuals tested positive for SARS-CoV-2 IgG antibodies (27.9%) and 22 were positive for SARS-CoV-2 IgM antibodies (9.6%). The overall seroprevalence (IgG or IgM positive) was 31.4% (general population seroprevalence was 10% in Spain). Of 72 seropositive patients, 54.2% had intrafamilial exposure vs 45.8% who did not. Among seronegative patients, 30.6% had seropositive cohabitants. The probability of seropositivity for a cancer patient was significantly related to intrafamilial exposure (OR 2.684, 95% CI 1.51-4.76, p = 0.001). CONCLUSIONS: Cancer patients are a high-risk group for SARS-CoV-2 infection. Recommendations against virus transmission need to be implemented even in a household scenario, as it was the main factor significantly related to seroconversion.

Anti-EGFR Antibody Plus Chemotherapy Treatment in a Patient with Synchronous Merkel Cell Carcinoma and Colorectal Cancer.

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy. During early stages, surgery is the primary treatment followed by radiotherapy in patients at high risk of recurrence. Definitive radiation therapy is an alternative for patients who are not surgical candidates, reserving chemotherapy for metastatic disease. We present a case of a male patient diagnosed with MCC and stage IV colorectal cancer and we focus on the skin tumor shrinkage after specific colorectal cancer treatment.

[The role of iron in the interaction between host and pathogen]. / Papel del hierro en la interacción entre el huésped y el patógeno.

Iron is essential for both pathogenic microbes and their host. Iron status may influence the occurrence and outcome of infections. For many microorganisms, iron is essential for growth, survival, and synthesis of virulence factors. However, because circulating iron is mostly transported bound to proteins and the level of free serum iron is therefore very low, some pathogens have developed complex systems to acquire iron efficiently. Understanding these systems is essential in the design of pharmaceutical agents and vaccines targeting pathogens with iron-linked virulence. In this review, we examine current data on the role of iron in the struggle between host and pathogen to regulate levels of this essential element. We hope that, in the near future, treatments aimed at reducing iron overload will improve the response to current therapies, and help control infection.

High-Dose 8% Capsaicin Patch in Treatment of Chemotherapy-Induced Peripheral Neuropathy. A Systematic Review.

INTRODUCTION: This is a review of the evidence from studies of the efficacy and tolerability of topically applied and high-concentration (8%) capsaicin in chemotherapy-induced peripheral neuropathy. METHODS: For this review, we searched EMBASE and MEDLINE to June 20, 2020. The terms used in the search included capsaicin, capsaicin 8% patch, chemotherapy-induced peripheral neuropathy, and cancer. RESULTS: A total of 98 studies were obtained, but only five were selected for the final analysis, with a total of 95 patients included. Three of the studies are prospective and two retrospective, including less than 30 patients per study. Capsaicin 8% patch provides significant pain relief in chemotherapy-induced peripheral neuropathy in all of them. However, the small number of studies (and patients) evaluated require caution with these results. CONCLUSION: Additional clinical trials are required to establish the definitive role of the capsaicin patch in the future.

Seroprevalence of SARS-CoV-2-specific antibodies in cancer outpatients in Madrid (Spain): A single center, prospective, cohort study and a review of available data.

BACKGROUND: Coronavirus disease in 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a global pandemic. Published data suggests that patients with a history of or active malignancy are at increased risk of infection and developing COVID-19 related complications. To date, the published data has analyzed the seroprevalence of COVID-19 infection in the general population, but not in cancer patients. Here we present the results of prevalence of IgG and IgM antibodies against SARS-CoV-2 in cancer patients from the University Hospital of Torrejón (Torrejón de Ardoz, Madrid, Spain). METHODS: SARS-CoV-2 IgG and IgM antibodies was assessed using a commercially available rapid test (Testsealabs® IgG/IgM Rapid Test Cassette) and collect the result from cancer outpatients who attended the medical oncology consult at University Hospital of Torrejón between June 1st and June 19th, 2020. FINDINGS: We analyzed the serological test results of 229 cancer patients. We estimated an overall seroprevalence (IgG or IgM positive) of 31.4%. The probability of SARS-CoV-2 seropositivity was similar between men and women, type of treatment and cancer stage. The probability of seropositivity was significantly higher in cancer patients with pneumonia compared with cancer patients without pneumonia (Odds Ratio (OR) 7.65 [95% confidence interval (CI) 1,85-31,58]). INTERPRETATION: Our results show a higher rate of SARS-CoV-2 antibodies in cancer patients than in the general population. The role of those antibodies in the immune response against the virus infection is unclear.

International recommendations for the prevention and treatment of venous thromboembolism associated with cancer.

Venous thromboembolism (VTE) is a common complication and a leading cause of death in oncological patients. Recent guidelines have been established for the treatment and prevention of VTE in oncological patients in various clinical situations. These guidelines recommend: (a) prophylactic anticoagulation in all hospitalized oncological patients in whom there are no contraindications; (b) prophylactic anticoagulation in patients scheduled for major oncological surgery in whom there are no contraindications; (c) prolonged (>or=6 months) anticoagulant therapy in oncological patients with manifest VTE in order to prevent a new episode; (d) no routine prophylactic anticoagulation in ambulatory patients without VTE receiving chemotherapy, except when they are receiving treatment with anti-cancer agents with a high risk of thrombogenicity, such as thalidomide- or lenalidomide-based chemotherapeutic regimens; and (e) no use of prophylactic anticoagulants to improve survival in patients with cancer without manifest VTE. Although vitamin K antagonists, unfractionated heparin and in some cases fondaparinux sodium could be used for the treatment of VTE, low molecular weight heparins are recommended for initial and continuous anticoagulant treatment in oncological patients with VTE, as well as for its prevention.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia: Review of the Literature and a Single-center Experience.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder that is commonly underdiagnosed. In 2015, it was recognized by the World Health Organization (WHO) classification of lung tumors as a premalignant lesion. DIPNECH syndrome is characterized by cough, exertional dyspnea, wheezing, and, less frequently, hemoptysis. We report the clinical and histological features and imaging findings in four cases of DIPNECH from our institution (Torrejon University Hospital, Madrid, Spain) between the years 2012 and 2019. DIPNECH represents a rare and poorly understood pulmonary disorder. Our limited single-center experience shows the slow and stable evolution of the disease. However, some exceptional cases may progress poorly if distant metastases occur.

[Microbiota, cancer and immune therapy]. / Microbiota, cáncer e inmunoterapia.

The relationship between cancer and microbes is complex and not entirely known. The objective of this manuscript is to review the scientific evidence on the relationship between the microbiome, cancer and immunotherapy. A non-systematic literature review was done in the databases MEDLINE, COCHRANE, and DATABASE, and articles of greater scientific rigor, mainly reviews or prospective studies/randomized clinical trials published to date (May 2018), were selected. Terms used in the search included: microbiome, microbiota, cancer, immune checkpoint inhibitors, PD-L1, PD-1 and CTLA-4.

La relación entre el cáncer y la microbiota es compleja y no del todo conocida. El objetivo de esta publicación es revisar la evidencia científica sobre la relación existente entre el microbioma, el cáncer y la inmunoterapia. Para ello se ha realizado una revisión no sistematizada de la literatura por medio de la consulta de la base de datos de MEDLINE, COCHRANE y DATABASE y se han seleccionado los artículos de mayor rigor científico, principalmente revisiones y estudios prospectivos/ensayos clínicos randomizados publicados hasta mayo de 2018. Los términos utilizados en la investigación fueron microbioma, cáncer, inmunoterapia, inhibidores de immune checkpoints, PD-L1, PD-1 y CTLA-4.

Tumoral angiogenesis: review of the literature.

Tumoral angiogenesis is necessary for the growth of neoplasms and the production of metastasis. The vascular endothelial growth factor (VEGF) is a homodimeric heparin-binding glycoprotein that binds to VEGF-receptors and can induce endothelial cell mitosis, invasion, and eventually capillary tube formation. Bevacizumab, a humanized monoclonal antibody against VEGF, inhibits tumoral angiogenesis and may also improve the delivery of chemotherapy to the tumor mass. Some new antiangiogenic agents, called multi-kinase inhibitors (sorafenib and sunitinib), have also activity against other receptors, such as epidermal growth factor-receptor or platelet-derived growth factor-receptor. A new schedule of treatment (metronomic chemotherapy) also has antiangiogenic activity.

Metastatic triple negative breast cancer: Optimizing treatment options, new and emerging targeted therapies.

Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab. In patients with advanced TNBC, responses to chemotherapy occur, but are often of short duration and it is associated with poor prognosis. The median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed. This review summarizes the clinical efficacy, perspectives and future challenges of using new treatment options for metastatic TNBC, such as poly-ADP-ribose-polymerase inhibitors, antiandrogen therapies and immune checkpoint inhibitors (antiprogrammed death receptor-1/PD-L1 monoclonal antibodies).

Metastatic Thymic Carcinoma with Long Survival After Treatment with Sunitinib.

Thymic carcinomas are the most aggressive histological subtype of thymic tumors with limited data to guide correct management. No standard treatments are available for patients with advanced thymic carcinoma after progressing while on platinum-based chemotherapy. We present a case of a patient with metastatic thymic carcinoma with an unusual response and favorable evolution after receiving treatment with sunitinib, obtaining a progression-free survival of 23 months, much higher than reported to date. We review the literature on the efficacy of sunitinib in metastatic thymic carcinoma after progression to first-line treatment with platinum combinations.

[Effectivity of thalidomide and dexamethasone for the treatment of refractory multiple myeloma: a retrospective study of 36 consecutive cases]. / Efectividad de la talidomida y la dexametasona en el tratamiento del mieloma múltiple resistente al tratamiento: estudio retrospectivo de 36 casos consecutivos.

BACKGROUND AND OBJECTIVE: Multiple myeloma (MM) is a plasm-cell neoplasm characterized by a monoclonal protein in the serum or urine. Thalidomide is effective as second line treatment. PATIENTS AND METHOD: We performed a retrospective study of 36 consecutive patients with refractory MM treated with thalidomide and dexamethasone as second line therapy, with the objective of analyzing the rate of response (primary end point), progression-free survival (PFS) and toxicity profiles (second end points). RESULTS: In our study the overall response rate was 55.6%, with a median of PFS of 12.6 months (95% confidence interval: 4-21 months). PFS at 6, 12 and 18 months was 61.11%, 50% and 22.22% respectively. 30.6% of the patients had neuropathy, 11.11% had rash and 5.55% had deep vein thrombosis. CONCLUSIONS: The combination of thalidomide and dexamethasone is an effective and safe second line treatment for refractory MM, with a manageable toxicity.

[Palliative chemotherapy in metastatic adrenal carcinoma beyond the first line: a case report and literature review]. / Quimioterapia paliativa tras progresión a la primera línea en el carcinoma suprarrenal metastásico: caso clínico y revisión de la literatura.

There are no approved therapeutic regimes for adrenal carcinoma following progression to a first line of chemotherapy/mitotane although a high percentage of patients are candidates to receive them. In the present article we review the possible therapeutic alternatives after the progression to a first line of treatment in patients with adrenal carcinoma and we report a case in which a prolonged overall survival is achieved, much higher than expected, probably in relation to the multidisciplinary management of the case and the use of most of the therapeutic arsenal available.

En el carcinoma suprarrenal metastásico no existen esquemas de tratamiento aprobados tras la progresión a una primera línea de quimioterapia/mitotane, si bien un alto porcentaje de pacientes son candidatos a recibirlos. En este artículo realizamos una revisión sobre las posibles alternativas terapéuticas tras la progresión a una primera línea de tratamiento en pacientes con carcinoma suprarrenal metastásico. A propósito de la misma, se presenta un caso clínico en el que se consigue una prolongada supervivencia global, mucho mayor de la esperable, probablemente debido al manejo multidisciplinario del caso y a la utilización de la mayor parte del arsenal terapéutico disponible.