Cost avoided in drugs derived from theparticipation of patients in oncologyclinical trials

Introduction: Cancer is the second leading cause of death globally. About one in six deaths is due to this disease. The economic impact of cancer is increasing and has a high prevalence leading to high economic burden for the Health System mainly related to oncologic pharmacotherapies. The objective of this study is to calculate pharmaceutical expenditure savings as a consequence of patient’s involvement in Oncology Clinical Trials.Material and methods: Retrospective observational study. In order to determine savings in oncology drugs, cancer treatments of patients participating in oncology clinical trials in April 2018 in a tertiary hospital in Spain were analyzed. Taking into account that the sponsor of the clinical trial provides the study medication free of charge, the costs savings were calculated comparing with the cost that would have supposed to treat the patient if they would have been received was standard regime for the type of tumor under study in clinical practice.Results: The cost avoided in the 50 oncology clinical trials analyzed was 1,564,943.59 euros. The average avoided cost per OCT was 31,298.87 euros, and the average avoided cost per patient was 10,096.41 euros.Conclusions: The participation of patients in oncology clinical trials provides an important economic saving, since it reduces the costs in the acquisition of medicines when they are provided free of charge by the sponsor of the study. (AU)

Introducción: El cáncer es la segunda causa de muerte a nivel mundial. Aproximadamente una de cada seis muertes se debe a esta enfermedad. El cáncer es una enfermedad de alta incidencia y el impacto derivado de la atención a pacientes oncológicos supone una importante carga económica para el Sistema Sanitario. El objetivo de este trabajo es calcular el coste evitado en medicamentos derivado de la participación de pacientes en Ensayos Clínicos de Oncología.Material y métodos: Estudio observacional retrospectivo. Se realiza un corte de datos en abril de 2018, se seleccionan todos los EECC activos en oncología y se incluyen los pacientes que habían participado en los mismos independientemente de la fecha de inclusión.Para determinar el coste evitado se calculó la diferencia entre el coste del esquema de tratamiento que el paciente está recibiendo dentro del EC con aportación gratuita de los medicamentos en investigación, y el coste que supondría el esquema de tratamiento que hubiese recibido en el supuesto de no haber participado en dicho EC.Resultados: El coste evitado en los 50 EECC analizados fue de 1.564.943,59 euros. El coste evitado medio por EC fue de 31.298,87 euros, y el coste evitado medio por paciente fue de 10.096,41 euros.Conclusiones: La participación de pacientes en EECC de oncología proporciona un importante ahorro económico, ya que reduce los costos en la adquisición de medicamentos cuando son proporcionados gratuitamente por el promotor del estudio. (AU)

Ytrrium-90 transarterial radioembolization in patients with gastrointestinal malignancies

Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies.

Ytrrium-90 transarterial radioembolization in patients with gastrointestinal malignancies.

Transarterial radioembolization (TARE) with yttrium-90 (Y90) is a promising alternative strategy to treat liver tumors and liver metastasis from colorectal cancer (CRC), as it selectively delivers radioactive isotopes to the tumor via the hepatic artery, sparring surrounding liver tissue. The landscape of TARE indications is constantly evolving. This strategy is considered for patients with hepatocellular carcinoma (HCC) with liver-confined disease and preserved liver function in whom neither TACE nor systemic therapy is possible. In patients with liver metastases from CRC, TARE is advised when other chemotherapeutic options have failed. Recent phase III trials have not succeeded to prove benefit in overall survival; however, it has helped to better understand the patients that may benefit from TARE based on subgroup analysis. New strategies and treatment combinations are being investigated in ongoing clinical trials. The aim of this review is to summarize the clinical applications of TARE in patients with gastrointestinal malignancies.

Novel molecular targeted therapies for patients with neurofibromatosis type 1 with inoperable plexiform neurofibromas: a comprehensive review.

Neurofibromatosis type 1 (NF1) is a genetic disorder that carries a higher risk of tumor development. Plexiform neurofibromas (PNs) are present in 50% of NF1 and cause significant morbidity when surgery is not feasible. Systemic therapies had not succeeded to reduce PN tumor volume until 2016 when the first trial with an MAPK/extracellular-signal-regulated kinase (MEK) inhibitor was published. We performed a systematic research on novel targeted therapies for patients with NF1 and PNs in PubMed, EMBASE, and conference abstracts with the last update in February 2021. Since 2016, seven trials have reported positive results with MEK inhibitors and other molecular targeted therapies (cabozantinib). Selumetinib has shown an overall response rate of 68% in children with NF1 and symptomatic inoperable PNs, and was associated with pain improvement and a manageable adverse events profile. This led to Food and Drug Administration (FDA) approval of selumetinib in May 2020. Recently, cabozantinib and mirdametinib have also proven their efficacy in adult population. Other MEK inhibitors such as trametinib and binimetinib have also communicated promising preliminary results. Ongoing trials in different populations and with intermittent dosing strategies are underway.

Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy.

BACKGROUND: The prognostic value of neutrophil-to-lymphocyte ratio (NLR) has been extensively studied in cancer patients. However, the performance of NLR as an early marker of efficacy of immune checkpoint inhibitors (ICI) is still understudied. We studied the utility of NLR at baseline (bNLR), before the second dose of immunotherapy (NLR2) and the NLR trend for predicting efficacy outcomes. METHODS: We included all patients with advanced cancer treated with ICI from June 2013 to April 2019 at La Paz University Hospital, Madrid (Spain). We examined bNLR, NLR2 and NLR trend and explored the association with progression-free survival (PFS) at 6 months, median PFS and overall survival (OS). RESULTS: We included 211 patients. PFS and OS were significantly longer in the low bNLR group than in the high bNLR group [HR 0.71 (95% CI 0.60-0.84) and HR: 0.66 (95% CI 0.55-0.79), respectively]. Regarding NLR2, patients with low NLR2 had significantly longer PFS and OS than patients with high NLR2 [HR 0.67 (95% CI 0.57-0.79) and HR: 0.60 (95% CI 0.50-0.72), respectively]. Finally, for NLR trend, PFS and OS for patients with NLR trend < 1 were significantly longer than those patients with NLR trend ≥ 1 [HR 0.59 (95% CI 0.43-0.82) and HR 0.63 (95% CI 0.44-0.90), respectively]. At the multivariate analysis for PFS and OS, bNLR, NLR2 and NLR trend were all independent prognostic factors for PFS and OS. CONCLUSIONS: bNLR, NLR2 and NLR trends are independent prognostic factors for survival in patients on immunotherapy. The dynamics of NLR in patients on immunotherapy is a promising marker that needs further investigation.

Efficacy of capecitabine when used concomitantly with proton pump inhibitors in cancer patients: a systematic review.

BACKGROUND: Capectiabine is an oral antineoplastic drug used in multiple malignancies. Proton pump inhibitors (PPI) have been proven to interact with other oral antineoplastic agents. In this systematic review we will summarize the clinical evidence on the efficacy of capecitabine when used concomitantly with PPI. MATERIALS AND METHODS: We performed a systematic literature search on the main databases up to November 2019. RESULTS: Nine studies met our inclusion criteria: 8 retrospective studies and 1 phase II clinical trial. Patients with colorectal, breast and gastroesophageal were represented. Four out of the 9 studies reported a shorter efficacy outcome in uni- or multivariate analysis when capecitabine was taken concomitantly with PPI than alone. CONCLUSIONS: Up to date, the clinical evidence reported on the use of capecitabine concomitantly with PPI is scarce and shows conflicting results. While awaiting further data, avoiding misuse of PPI in cancer patients taking capecitabine is recommended.

Carcinoma de células de Merkel: diagnóstico y tratamiento en atención especializada dermatológica. Guía de práctica clínica de la Academia Española de Dermatología y Venerología / Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology

Antecedentes y objetivo: El carcinoma de células de Merkel es un tipo de cáncer de piel infrecuente y agresivo. Hay una gran variación en su manejo y las diferentes guías extranjeras que existen cubren parcialmente los problemas identificados como principales. El objetivo de la presente guía es servir de referencia a los dermatólogos españoles para mejorar aspectos controvertidos del diagnóstico, estadificación y tratamiento del carcinoma de células de Merkel. Materiales y métodos: Se empleó el método ADAPTE: se escogió a miembros del Grupo Español de Dermato-Oncología y Cirugía (GEDOC) con experiencia en el tratamiento de estos tumores y con interés en participar en la elaboración de la guía. Tras resumir el proceso de atención y elaborar las preguntas clínicas relevantes, se hizo una búsqueda de guías, que se seleccionaron según su puntuación mediante el instrumento Appraisal of Guidelines for Research and Evaluation (AGREE II). Tras la búsqueda de las respuestas en dichas guías, se elaboraron posteriormente las recomendaciones. Por último, se sometió la guía a revisión externa. Resultados: Las guías con mejor puntuación fueron las de National Comprehensive Cancer Network, la European consensus-based interdisciplinary guideline, Alberta Healthservices Clinical practice guideline, American Cancer Society y Cutaneous Oncology Group of the French Society of Dermatology. Se obtuvieron en total 9 preguntas clínicas, contestadas a partir de estas guías. Conclusiones: Esta guía responde a preguntas habituales en la práctica clínica diaria y sirve a los dermatólogos como referencia en la toma de decisiones, siempre teniendo presentes los recursos y preferencias del paciente

Background and objective: Merkel cell carcinoma is a rare, aggressive skin cancer that is managed in a great variety of ways. However, international clinical practice guidelines give only partial coverage to issues considered major problems.The recommendations presented here aim to provide Spanish dermatologists with a guide to improving disputed aspects of diagnosis, staging, and treatment of localized Merkel cell carcinomas. Material and methods: The ADAPTE process was used. Members of the Spanish Group of Oncologic Dermatology and Surgery (GEDOC) with experience in treating Merkel cell carcinoma and interest in drafting these guidelines were selected. The group described the care process and listed the most important clinical questions. They then searched for guidelines and assessed them with the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. After consulting the guidelines for answers to their clinical questions, the group drafted the present statementand sent it for external review. Results: The guidelines that scored highest in the AGREE II assessment step were the consensus-based interdisciplinary guideline of the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer, and those of the Comprehensive Cancer Network, the Alberta Health Services in Canada, the American Cancer Society, and the Cutaneous Oncology Group of the French Society of Dermatology. A total of 9 clinical questions were answered based on these guidelines. Conclusions: The guidelines presented here answer clinical questions that arise in routine practice. They can provide dermatologists with a starting point for decision-making, although available resources and patient preferences must always be borne in mind

Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology. / Carcinoma de células de Merkel: diagnóstico y tratamiento en atención especializada dermatológica. Guía de práctica clínica de la Academia Española de Dermatología y Venerología.

BACKGROUND AND OBJECTIVE: Merkel cell carcinoma is a rare, aggressive skin cancer that is managed in a great variety of ways. However, international clinical practice guidelines give only partial coverage to issues considered major problems.The recommendations presented here aim to provide Spanish dermatologists with a guide to improving disputed aspects of diagnosis, staging, and treatment of localized Merkel cell carcinomas. MATERIAL AND METHODS: The ADAPTE process was used. Members of the Spanish Group of Oncologic Dermatology and Surgery (GEDOC) with experience in treating Merkel cell carcinoma and interest in drafting these guidelines were selected. The group described the care process and listed the most important clinical questions. They then searched for guidelines and assessed them with the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. After consulting the guidelines for answers to their clinical questions, the group drafted the present statementand sent it for external review. RESULTS: The guidelines that scored highest in the AGREE II assessment step were the consensus-based interdisciplinary guideline of the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer, and those of the Comprehensive Cancer Network, the Alberta Health Services in Canada, the American Cancer Society, and the Cutaneous Oncology Group of the French Society of Dermatology. A total of 9 clinical questions were answered based on these guidelines. CONCLUSIONS: The guidelines presented here answer clinical questions that arise in routine practice. They can provide dermatologists with a starting point for decision-making, although available resources and patient preferences must always be borne in mind.

Clinical guideline SEOM: hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A-B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with "washout" in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications (AU)

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Clinical guideline SEOM: hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the second leading cause of cancer-related death worldwide. Surveillance with abdominal ultrasound every 6 months should be offered to patients with a high risk of developing HCC: Child-Pugh A-B cirrhotic patients, all cirrhotic patients on the waiting list for liver transplantation, high-risk HBV chronic hepatitis patients (higher viral load, viral genotype or Asian or African ancestry) and patients with chronic hepatitis C and bridging fibrosis. Accurate diagnosis, staging and functional hepatic reserve are crucial for the optimal therapeutic approach. Characteristic findings on dynamic CT/MR of arterial hyperenhancement with "washout" in the portal venous or delayed phase are highly specific and sensitive for a diagnosis of HCC in patients with previous cirrhosis, but a confirmed histopathologic diagnosis should be done in patients without previous evidence of chronic hepatic disease. BCLC classification is the most common staging system used in Western countries. Surgical procedures, local therapies and systemic treatments should be discussed and planned for each patient by a multidisciplinary team according to the stage, performance status, liver function and comorbidities. Surgical interventions remain as the only curative procedures but both local and systemic approaches may increase survival and should be offered to patients without contraindications.

Breast cancer stem cell hypothesis: clinical relevance (answering breast cancer clinical features)

The cancer stem cells hypothesis arises from observation of normal tissue hierarchy and the demonstration of stem cells in normal tissues. Scientists continue to debate whether the putative cancer cells derive from the transformation of normal tissue stem cells or from more differentiated cells. The existence of a subpopulation of tumour cells with stem-cell-like characteristics, including very slow replication and resistance to standard chemotherapy, posses a novel therapeutic challenge. This review summarises the state of development of normal and cancer breast cells and the clinical and therapeutic relevance (AU)

Colonic anastomosis and colonic polyp mucosal metastasis of signet ring cell gastric adenocarcinoma

The mucosal metastasis of adenocarcinomas located in colonic mucosa is not infrequent. We present a clinical report of a patient diagnosed with a gastric multifocal signet ring cell adenocarcinoma without any evidence of visceral dissemination with the exception of mucosal infiltration of signet ring cell adenocarcinoma in a colonic polyp and in the mucosa of previous colonic anastomosis. The histopathological study of suspect lesions in the colonic mucosa is necessary to correctly approach the treatment of these patients (AU)

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Descriptive analysis of clinical factors affecting terminally ill cancer patients.

GOALS OF WORK: To make a descriptive analysis of clinical and laboratories parameters in advanced neoplastic patients. MATERIALS AND METHODS: We interviewed 406 terminally ill cancer patients to study demographic and neoplastic data, 24 graded symptoms, 21 analytical parameters and scales to evaluate general condition, quality of life and independence in daily activities. MAIN RESULTS: An average of 9.3 symptoms per patient were detected and median survival was 26.5 days. Most frequent symptoms were asthenia (96.8%), anorexia (94.8%), weight loss (88.1%) and pain (80.5%). Principal laboratory abnormalities were high blood sedimentation rate (96%), high cytolysis and cholestasis enzyme levels (50-77%), anemia (81.5%), low protein (66%) and low albumin levels (67%). Symptom prevalence was different according to age, gender, primary tumour, location of metastasis, laboratory parameters, performance status, quality of life or independence in daily-living activities. CONCLUSIONS: We should know more frequent symptoms affecting terminal cancer patients and any factor contributing to it to provide more comfort in the final phases of life.

Correlation of p53 oncoprotein expression with chemotherapy response in small cell lung carcinomas.

p53 oncoprotein expression was investigated in small cell lung carcinomas (SCLC) using immunohistochemical staining with antibodies against p53. A total of 50 pre-treatment biopsies were examined. We analyzed the relationship between p53 expression and these patients' relevant clinical characteristics, response to chemotherapy, time to progression, and overall survival. We found p53 overexpression in 46% of the samples but no association with clinical data or overall survival. Our results show a strong correlation of p53 staining with chemotherapy response. Multivariate analysis selected p53 as an independent predictive factor of chemotherapy response.

Beta-catenin expression pattern in small cell lung cancer: correlation with clinical and evolutive features.

Beta-catenin expression in small cell lung carcinomas (SCLC) was investigated by immunohistochemical method using antibodies against beta-catenin. 50 pre-treatment biopsies were examined and the relationship between beta-catenin expression and the patients' relevant clinical characteristics, response to chemotherapy, time to relapse or progression, and overall survival, were analyzed. Beta-catenin expression exhibited different intensity within each sample, predominantly localized in the cytoplasm, and no sample showed nuclear expression. There was cytoplasmic hyperexpression in 14 cases, hypoexpression in 15 cases, and normal expression in 21 cases. We did not find any association between beta-catenin expression and clinical data. Our results show, however, correlation between beta-catenin cytoplasmic hyperexpression with a shorter time to progression (p=0.0437) as well as with a shorter overall survival (p=0.0253). Beta-catenin hyperexpression could have prognostic significance in SCLC.

Circulating cancer cells in peripheral blood. A case report.

BACKGROUND: Carcinocythemia, the presence of circulating cancer cells in peripheral blood, is a rare complication of solid neoplasms. When the number of such cells is very high, they can be detected during routine laboratory tests. They are associated with a dismal prognosis. CASE REPORT: Carcinocythemia occurred in a patient with disseminated breast cancer. Eighteen cases were identified from a review of the literature. The most common neoplasms associated with circulating cancer cells in peripheral blood were breast adenocarcinoma, small cell lung carcinoma and rhabdomyosarcoma. All the patients had stage IV disease at the time of diagnosis, and all had involvement of the reticuloendothelial system. Patients survived for an average of a few days or weeks. CONCLUSION: Circulating cancer cells in peripheral blood are an unusual manifestation of disseminated neoplasms that occurs as a terminal event.

Pregnancy in a breast cancer patient treated with a LHRH analogue at ablative doses.

A 36-year-old female diagnosed of breast cancer was treated with surgery, chemotherapy, radiotherapy and goserelin. After 17 months of uninterrupted therapy with this LHRH analogue at hormone suppressive doses, a 16-week gestation foetus was detected and the treatment was withdrawn. Although the drug was administered throughout the first 4 months of pregnancy it resulted in the term delivery of a healthy infant, and no foetal adverse effects were detected. A review of the influence of hormonal treatment for breast cancer on fertility and birth defects has been performed.

[Screening for colorectal cancer predisposition]. / Detección de la predisposición al cáncer colorrectal.

In the last years the advantages in molecular biology have developed a variety of useful tests in order to detect genetic mutations. These mutations are associated to a susceptibility of suffering a colo-rectal cancer. The genetic tests are designed to screen the disease although many problems can emerge when they are offered to the population. In this article, we will try to analyze the advantages, disadvantages and the present indications for genetic testing in colo-rectal cancer, particularity in cases of familial adenomatous polyposis and nonpolyposis inherited colon cancer.