Nivolumab Plus Ipilimumab Versus EXTREME Regimen as First-Line Treatment for Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck: The Final Results of CheckMate 651.

PURPOSE: CheckMate 651 (ClinicalTrials.gov identifier: NCT02741570) evaluated first-line nivolumab plus ipilimumab versus EXTREME (cetuximab plus cisplatin/carboplatin plus fluorouracil ≤ six cycles, then cetuximab maintenance) in recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). METHODS: Patients without prior systemic therapy for R/M SCCHN were randomly assigned 1:1 to nivolumab plus ipilimumab or EXTREME. Primary end points were overall survival (OS) in the all randomly assigned and programmed death-ligand 1 combined positive score (CPS) ≥ 20 populations. Secondary end points included OS in the programmed death-ligand 1 CPS ≥ 1 population, and progression-free survival, objective response rate, and duration of response in the all randomly assigned and CPS ≥ 20 populations. RESULTS: Among 947 patients randomly assigned, 38.3% had CPS ≥ 20. There were no statistically significant differences in OS with nivolumab plus ipilimumab versus EXTREME in the all randomly assigned (median: 13.9 v 13.5 months; hazard ratio [HR], 0.95; 97.9% CI, 0.80 to 1.13; P = .4951) and CPS ≥ 20 (median: 17.6 v 14.6 months; HR, 0.78; 97.51% CI, 0.59 to 1.03; P = .0469) populations. In patients with CPS ≥ 1, the median OS was 15.7 versus 13.2 months (HR, 0.82; 95% CI, 0.69 to 0.97). Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), objective response rate was 34.1% versus 36.0%, and median duration of response was 32.6 versus 7.0 months. Grade 3/4 treatment-related adverse events occurred in 28.2% of patients treated with nivolumab plus ipilimumab versus 70.7% treated with EXTREME. CONCLUSION: CheckMate 651 did not meet its primary end points of OS in the all randomly assigned or CPS ≥ 20 populations. Nivolumab plus ipilimumab showed a favorable safety profile compared with EXTREME. There continues to be a need for new therapies in patients with R/M SCCHN.

Frequency of BRAF V600E Mutation in the Mexican Population of Patients With Metastatic Melanoma.

PURPOSE: The BRAF V600E mutation has been described in melanomas occurring in the Caucasian, European, and Asian populations. However, in the Mexican population, the status and clinical significance of BRAF mutation has not been researched on a large scale. METHODS: Consecutive BRAF-tested Mexican patients with metastatic melanoma (n = 127) were analyzed for mutations in exon 15 of the BRAF gene in genomic DNA by real-time polymerase chain reaction technology for amplification and detection. The results were correlated with the clinical-pathologic features and the prognosis of the patients. RESULTS: The frequency of somatic mutation V600E within the BRAF gene was 54.6% (43 of 127 patients). Nodular melanoma was the most prevalent subtype in our population, with BRAF mutations in 37.2% (16 of 55 patients). In contrast, superficial spread had a frequency of 18.6% BRAF mutation (eight of 24). Other clinicopathologic features were assessed to correlate with the mutation status. CONCLUSION: This study searched for the most prevalent BRAF V600E mutation type in melanoma in a heterogeneous population from Mexico. Nodular melanoma was found to be the most prevalent in metastatic presentation and the presence of BRAF V600E mutation, perhaps related to the mixed ancestry; in the north, ancestry is predominantly European and in the south, it is predominantly Asian. The outcomes of the mutation correlations were similar to those found in other populations.

A meta-analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma.

Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, MMP19, apolipoprotein L6, C-X-C motif chemokine ligand (CXCL)8, basic, immunoglobulin-like variable motif containing and CXCL16. These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.

Propiedades psicométricas de la Escala Hospitalaria de Ansiedad y Depresión (HADS) en una población de pacientes oncológicos mexicanos / Psychometric properties of the Hospital Anxiety and Depression Scale (HADS) in a Mexican population of cancer patients

ANTECEDENTES: La sintomatología ansiosa y depresiva es parte de los principales problemas de salud mental en pacientes oncológicos, lo cual afecta la calidad de vida y la adhesión al tratamiento, además de que se asocia con mayor número de síntomas y estancia hospitalaria. Mediante instrumentos de tamizaje válidos y confiables, como la Escala hospitalaria de ansiedad y depresión (HADS), ha sido posible detectar posibles casos en pacientes hospitalarios. Sin embargo, hasta ahora no se habían caracterizado las propiedades psicométricas en pacientes oncológicos en población mexicana.OBJETIVO: Determinar las propiedades psicométricas de la HADS en una muestra de pacientes oncológicos.MÉTODO: Participaron 400 pacientes del Instituto Nacional de Cancerología, de los cuales 226 eran mujeres (56.5%) y 174 eran hombres (43.6%); la edad promedio fue de 47.4 ± 14.1 años. Los participantes contestaron, además de la HADS, los siguientes inventarios: depresión de Beck, ansiedad de Beck, termómetro de distrés.RESULTADOS: Un análisis factorial ajustado a dos factores presentó un instrumento con 12 reactivos, similar a la versión original. La consistencia interna de la escala global mostró un índice satisfactorio (a=0.86). Los alfas de Cronbach de cada subescala tuvieron un valor de .79 y .80 que explicaron el 48.04% de la varianza. La validez, por medio de correlación con las medidas concurrentes, mostró resultados significativos (r de Pearson de .51 a .71, p<0.05).DISCUSIÓN Y CONCLUSIÓN: La HADS en pacientes con cáncer en población mexicana presentó adecuadas características psicométricas. La relevancia de los resultados obtenidos radica en que se trata de una población que puede llegar a requerir atención oportuna en salud mental en etapas tempranas de su tratamiento. La detección de sintomatología ansiosa y depresiva por medio de la HADS deriva en beneficios para la población oncológica y en estrategias funcionales de atención adecuada y costo-efectivas.

BACKGROUND: Symptoms of anxiety and depression are among the major mental health problems in cancer patients. These symptoms affect the quality of life and treatment adherence, and are associated with other symptoms and longer hospital stays. Valid and reliable screening instruments such as the Hospital Anxiety and Depression Scale (HADS), have made possible the detection of possible cases of depression and anxiety in medically ill patients. However, the psychometric properties of this instrument have not been documented in different types of cancer diagnoses in the Mexican population.OBJECTIVE: To determine the psychometric properties of the HADS in a sample of patients with cancer from the Mexican population.METHOD: Four hundred patients from the National Cancer Institute participated, of which 226 were women (56.5%) and 174 men (43.6%), with a mean age of 47.4 ±14.1 years. Participants completed concurrently the HADS as well as the following inventories: 1. Beck Depression, 2. Beck Anxiety and 3. Distress Thermometer.RESULTS: A factor analysis adjusted to two factors explained 48.04% of the variance, with 12 items loading on these two factors in a way similar to the original version. The internal consistency of the overall scale was satisfactory (α=0.86). Cronbach's alphas for each subscale were .79 and .80. The concurrent validity assessed by way of correlations with concurrent measures showed significant associations (Pearson r=51-71, p<0.05).DISCUSSION AND CONCLUSION: The HADS has adequate construct validity, internal consistency and concurrent validity for its use in cancer patients from the Mexican population. The relevance of these results is a cost effective tool to provide timely mental health care early in oncological treatment for those in need. Detecting anxiety and depression symptoms through the HADS may benefit cancer patients by ensuring appropriate care that may increase their quality of life and treatment adherence, and reduce their hospital stays.

[First Mexican consensus on recommendations of the multidisciplinary care of patients with glioblastoma multiforme (GBM): Mexican Interdisciplinary Group on Neuro-Oncology Research (GIMINO)]. / Primer consenso mexicano sobre recomendaciones de la atención multidisciplinaria del paciente con glioblastoma multiforme (GBM). Grupo Interdisciplinar Mexicano de Investigación en Neurooncología (GIMINO).

Glioblastoma multiforme is one of the most aggressive central nervous system tumors and with worse prognosis. Until now,treatments have managed to significantly increase the survival of these patients, depending on age, cognitive status, and autonomy of the individuals themselves. Based on these parameters, both initial or recurrence treatments are performed, as well as monitoring of disease by imaging studies. When the patient enters the terminal phase and curative treatments are suspended, respect for the previous wishes of the patient and development and implementation of palliative therapies must be guaranteed.

Propiedades psicométricas del inventario de ansiedad de beck (BAI) en pacientes con cáncer / Psychometric properties of the beck anxiety inventory (bai) for patients with cancer

La sintomatología ansiosa es uno de los principales problemas psicológicos en pacientes oncológicos. La Escala de Ansiedad de Beck (BAI) ha demostrado ser un instrumento válido y confiable. Sin embargo, hasta ahora no se había documentado su comportamiento psicométrico en población oncológica en México. Objetivo: Determinar las propiedades psicométricas de la Escala de Ansiedad de Beck (BAI) en una muestra de pacientes con cáncer. Material y Método: participaron 250 pacientes del Instituto Nacional de Cancerología, de los cuales 138 eran mujeres (55,2%) y 112 eran hombres (44,8%); la edad promedio fue de 46,6 ± 14,3 años. Los participantes contestaron además del BAI, la Subescala de ansiedad de la Escala de Ansiedad y Depresión (HADS-A). Resultados: El análisis factorial varimax con 21 reactivos presentó una estructura con 4 factores: Subjetivo, Neurofisiológico, Autonómico y Síntomas vasomotores que explicaron el 46,38% de la varianza. La consistencia interna de la escala global mostró un índice satisfactorio (α=0,82). La validez por medio de correlación con el HADS-A mostraron resultados significativos (r de Pearson de 0,58, p <0,05) y el ECOG (r de Pearson de -0,36 p <0,05). Conclusiones: el BAI en pacientes con cáncer en población mexicana presentó adecuadas características psicométricas. La detección de sintomatología ansiosa a través del BAI deriva en beneficios para la población oncológica y en estrategias funcionales de atención adecuada y costo-efectivas

Introduction: Depressive symptomatology is a major mental health problem in cancer patients. The Beck Anxiety Scale (BAI) has proven to be a reliable and valid instrument. However, until now has not been documented it’s psychometric properties in Mexican population with cancer. Objetives: Determine the psychometric properties of the Beck Anxiety Scale BAI in a sample of cancer patients. Material and methods: Involved 250 patients from the National Cancer Institute, of which 112 were women (55.2%) were male and 138 (44.82%); the average age was 46.6 ± 14.3 years. Participants answered the BAI, and also the Anxiety Sub-scale of HADS. Results: A varimax factor analysis with 21 items show a structure of 4 factors: Subjective, Neurophysiological, Autonomic and vasomotor symptoms that explain 46.38% of the variance. The internal consistency of the overall scale was satisfactory (α=0.82). The validity through correlations with the HADS-A showed significant associations (Pearson r=0.58, p <0.05) and ECOG (Pearson -0.36, p <0.05). Conclusions: The BAI in Mexican population with cancer showed adequate psychometric characteristics. Detection of anxiety symptoms through BAI provides benefits to the cancer population and facilitates the development of adequate and cost-effective care strategies

Ansiedad, depresión y afrontamiento en pacientes con cáncer testicular en tratamiento y periodo de seguimiento / Anxiety, depression and coping in patients with testicular cancer treatment and follow-up period

Introducción: El cáncer de testículo (CT) constituye la neoplasia más común entre los 15 y 39 años. Debido a su incidencia cada vez mayor y a su alta tasa de supervivencia, la literatura se ha centrado en el impacto que puedan tener las secuelas del tratamiento a mediano y a largo plazo. El CT y su asociación con la ansiedad y la depresión constituyen problemas psicológicos frecuentes durante el tratamiento y periodo de seguimiento, en este contexto el afrontamiento ante la enfermedad puede representar un mecanismo de mejor adaptación psicológico. Objetivo: Identificar y comparar los niveles de ansiedad y depresión en pacientes en tratamiento y periodo de seguimiento; así como su relación con los diferentes estilos de afrontamiento positivo. Método: 49 pacientes en tratamiento y 84 en periodo de seguimiento del Instituto Nacional de Cancerología. Se empleo un diseño transversal, no experimental y ex-post-facto. Se utilizaron los Inventarios de Ansiedad de Beck –BAI–, el Inventario de Depresión de Beck –BDI–, y el Instrumento de afrontamiento al estrés de Lazarus y Folkman. Resultados: Se identificaron mayores niveles de ansiedad y depresión en el grupo de pacientes en tratamiento. Se identificó una relación inversamente proporcional entre los estilos de afrontamiento positivos y menores niveles de sintomatología ansiosa y depresiva en ambos grupos. Conclusiones: Se corrobora la asociación entre los estilos de afrontamiento positivos y niveles bajos de ansiedad y depresión. Se recomienda promover en el paciente con CT afrontamiento positivo durante el tratamiento y periodo de seguimiento (AU)

Background: Testicular cancer is the most common malignancy between 15 and 39 years old. Due to the increasing incidence and high survival rate of patients with testicular cancer (CT), literature has focused on the impact that may have the aftermath of medium and long term treatment. The CT and its association with anxiety and depression are common psychological problems, in this context, active coping with this disease may represent a psychological best adaptation mechanism. Objective: To identify and compare the levels of depression and anxiety in patients in treatment and follow-up period; as well as his relationship with positive coping styles. Participants and methods: 49 patients in treatment and follow-up period 84 in the National Cancer Institute follow-up period. It is a transversal, retrospective, not experimental and ex-post-facto. The inventories of Beck Depression –BDI– (1961), the Beck anxiety inventory –BAI– (1988) and the instrument of Lazarus and Folkman (1985) for coping with the stress. Results: Higher levels of anxiety and depression in patients in treatment. If you can identify an inversely proportional relationship between positive coping styles and lower levels of anxious and depressive symptoms in both groups. Conclusions: Is confirmed the association between positive coping styles and low levels of depression and anxiety. It is recommended to promote in patients with CT positive coping during treatment and follow-up period (AU)

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"]. / Tercer Consenso Nacional de Cáncer de Ovario 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM".

INTRODUCTION: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. CONCLUSIONS: In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

[The first Mexican consensus of endometrial cancer. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México]. / Primer consenso Mexicano de cancer de endometrio.

INTRODUCTION: Endometrial cancer (EC) is the second most common gynecologic malignancy worldwide in the peri and postmenopausal period. Most often for the endometrioid variety. In early clinical stages long-term survival is greater than 80%, while in advanced stages it is less than 50%. In our country there is not a standard management between institutions. GICOM collaborative group under the auspice of different institutions have made the following consensus in order to make recommendations for the management of patients with this type of neoplasm. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of four days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: Screening should be performed women at high risk (diabetics, family history of inherited colon cancer, Lynch S. type II). Endometrial thickness in postmenopausal patients is best evaluated by transvaginal US, a thickness greater than or equal to 5 mm must be evaluated. Women taking tamoxifen should be monitored using this method. Abnormal bleeding in the usual main symptom, all post menopausal women with vaginal bleeding should be evaluated. Diagnosis is made by histerescopy-guided biopsy. Magnetic resonance is the best image method as preoperative evaluation. Frozen section evaluates histologic grade, myometrial invasion, cervical and adnexal involvement. Total abdominal hysterectomy, bilateral salpingo oophorectomy, pelvic and para-aortic lymphadenectomy should be performed except in endometrial histology grades 1 and 2, less than 50% invasion of the myometrium without evidence of disease out of the uterus. Omentectomy should be done in histologies other than endometriod. Surgery should be always performed by a Gynecologic Oncologist or Surgical Oncologist, laparoscopy is an alternative, especially in patients with hypertension and diabetes for being less morbid. Adjuvant treatment after surgery includes radiation therapy to the pelvis, brachytherapy, and chemotherapy. Patients with Stages III and IV should have surgery with intention to achieve optimal cytoreduction because of the impact on survival (51 m vs. 14 m), the treatment of recurrence can be with surgery depending on the pattern of relapse, systemic chemotherapy or hormonal therapy. Follow-up of patients is basically clinical in a regular basis. CONCLUSIONS: Screening programme is only for high risk patients. Multidisciplinary treatment impacts on survival and local control of the disease, including surgery, radiation therapy and chemotherapy, hormonal treatment is reserved to selected cases of recurrence. This is the first attempt of a Mexican Collaborative Group in Gynecology to give recommendations is a special type of neoplasm.