Mutation profile in liquid biopsy tested by next generation sequencing in Mexican patients with non-small cell lung carcinoma and its impact on survival.

Background: Lung cancer represents a significant global health concern, often diagnosed in its advanced stages. The advent of massive DNA sequencing has revolutionized the landscape of cancer treatment by enabling the identification of target mutations and the development of tailored therapeutic approaches. Unfortunately, access to DNA sequencing technology remains limited in many developing countries. In this context, we emphasize the critical importance of integrating this advanced technology into healthcare systems in developing nations to improve treatment outcomes. Methods: We conducted an analysis of electronic clinical records of patients with confirmed advanced non-small cell lung cancer (NSCLC) and a verified negative status for the epidermal growth factor receptor (EGFR) mutation. These patients underwent next-generation sequencing (NGS) for molecular analysis. We performed descriptive statistical analyses for each variable and conducted both univariate and multivariate statistical analyses to assess their impact on progression-free survival (PFS) and overall survival (OS). Additionally, we classified genetic mutations as actionable or non-actionable based on the European Society for Medical Oncology Scale of Clinical Actionability of Molecular Targets (ESCAT) guidelines. Results: Our study included a total of 127 patients, revealing the presence of twenty-one distinct mutations. The most prevalent mutations were EGFR (18.9%) and Kirsten rat sarcoma viral oncogene homolog (KRAS) (15.7%). Notably, anaplastic lymphoma kinase (ALK) [hazard ratio (HR): 0.258, P<0.001], tumor mutation burden (TMB) (HR: 2.073, P=0.042) and brain magnetic resonance imaging (MRI) (HR: 0.470, P=0.032) demonstrated statistical significance in both the univariate and multivariate analyses with respect to PFS. In terms of OS, ALK (HR: 0.285, P<0.001) and EGFR (HR: 0.482, P=0.024) exhibited statistical significance in both analyses. Applying the ESCAT classification system, we identified actionable genomic variations (ESCAT level-1), including EGFR, ALK, breast cancer (BRAF) gene, c-ros oncogene 1 (ROS1), and rearranged during transfection (RET) gene, in 32.3% of the patients. Conclusions: Our findings from massive DNA sequencing underscore that 32.3% of patients who test negative for the EGFR mutation possess other targetable mutations, enabling them to receive personalized, targeted therapies at an earlier stage of their disease. Implementing massive DNA sequencing in developing countries is crucial to enhance survival rates among NSCLC patients and guide more effective treatment strategies.

Acral Melanoma Is Infiltrated with cDC1s and Functional Exhausted CD8 T Cells Similar to the Cutaneous Melanoma of Sun-Exposed Skin.

Acral melanoma (AM) is the most common melanoma in non-Caucasian populations, yet it remains largely understudied. As AM lacks the UV-radiation mutational signatures that characterize other cutaneous melanomas, it is considered devoid of immunogenicity and is rarely included in clinical trials assessing novel immunotherapeutic regimes aiming to recover the antitumor function of immune cells. We studied a Mexican cohort of melanoma patients from the Mexican Institute of Social Security (IMSS) (n = 38) and found an overrepresentation of AM (73.9%). We developed a multiparametric immunofluorescence technique coupled with a machine learning image analysis to evaluate the presence of conventional type 1 dendritic cells (cDC1) and CD8 T cells in the stroma of melanoma, two of the most relevant immune cell types for antitumor responses. We observed that both cell types infiltrate AM at similar and even higher levels than other cutaneous melanomas. Both melanoma types harbored programmed cell death protein 1 (PD-1+) CD8 T cells and PD-1 ligand (PD-L1+) cDC1s. Despite this, CD8 T cells appeared to preserve their effector function and expanding capacity as they expressed interferon-γ (IFN-γ) and KI-67. The density of cDC1s and CD8 T cells significantly decreased in advanced stage III and IV melanomas, supporting these cells' capacity to control tumor progression. These data also argue that AM could respond to anti-PD-1-PD-L1 immunotherapy.

Establishment of triple-negative breast cancer cells based on BMI: A novel model in the correlation between obesity and breast cancer.

Introduction: Obesity has been associated with an increased risk of biologically aggressive variants in breast cancer. Women with obesity often have tumors diagnosed at later stages of the disease, associated with a poorer prognosis and a different response to treatment. Human cell lines have been derived from specific subtypes of breast cancer and have served to define the cell physiology of corresponding breast cancer subtypes. However, there are no current cell lines for breast cancer specifically derived from patients with different BMIs. The availability of those breast cancer cell lines should allow to describe and unravel functional alterations linked to these comorbidities. Methods: Cell cultures were established from tumor explants. Once generated, the triple negative subtype in a patient with obesity and a patient with a normal BMI were chosen for comparison. For cellular characterization, the following assays were conducted: proliferation assays, chemo - sensitivity assays for doxorubicin and paclitaxel, wound healing motility assays, matrix invasion assays, breast cancer cell growth to estradiol by chronic exposure to leptin, induction of endothelial permeability and tumorigenic potential in athymic mice with normo - versus hypercaloric diets with an evaluation of the epithelium - mesenchymal transformation proteins. Results: Two different cell lines, were established from patients with breast cancer: DSG-BC1, with a BMI of 21.9 kg/m2 and DSG-BC2, with a BMI of 31.5 kg/m2. In vitro, these two cell lines show differential growth rates, motility, chemosensitivity, vascular permeability, response to leptin with an activation of the JAK2/STAT3/AKT signaling pathway. In vivo, they displayed distinct tumorigenic potential. In particular, DSG-BC2, presented higher tumorigenicity when implanted in mice fed with a hypercaloric diet. Discussion: To our knowledge, these primary cultures are the first in vitro representation of both breast cancer and obesity. DSG - BC2 presented a more aggressive in vivo and in vitro phenotype. These results support the hypothesis that breast cancer generated in an obese metabolic state may represent a contrasting variant within the same disease. This new model will allow both further comprehension, functional studies and the analysis of altered molecular mechanisms under the comorbidity of obesity and breast cancer.

Prognostic factors in cancer patients infected with SARS-CoV-2: a Latin American country results.

PURPOSE: The aim of this study was to evaluate the demographic characteristics, clinical and pathological factors, and the outcome of cancer and COVID-19 patients in Mexico. PATIENTS AND METHODS: A prospective, multicentric study was performed through a digital platform to have a national registry of patients with cancer and positive SARS-CoV-2 test results through reverse transcription quantitative polymerase chain reaction (RT-qPCR). We performed the analysis through a multivariate logistic regression model and Cox proportional hazard model. RESULTS: From May to December 2020, 599 patients were registered with an average age of 56 years with 59.3% female; 27.2% had hypertension. The most frequent diagnoses were breast cancer (30.4%), lymphoma (14.7%), and colorectal cancer (14.0%); 72.1% of patients had active cancer and 23.5% of patients (141/599) were deceased, the majority of which were men (51.7%). This study found that the prognostic factors that reduced the odds of death were gender (OR = 0.42, p = 0.031) and oxygen saturation (OR = 0.90, p = 0.0001); meanwhile, poor ECOG (OR = 5.4, p = 0.0001), active disease (OR = 3.9, p = 0.041), dyspnea (OR = 2.5, p = 0.027), and nausea (OR = 4.0, p = 0.028) increased the odds of death. In the meantime, the factors that reduce survival time were age (HR = 1.36, p = 0.035), COPD (HR = 8.30, p = 0.004), having palliative treatment (HR = 10.70, p = 0.002), and active cancer without treatment (HR = 8.68, p = 0.008). CONCLUSION: Mortality in cancer patients with COVID-19 is determined by prognostic factors whose identification is necessary. In our cancer population, we have observed that being female, younger, non-COPD, with non-active cancer, good performance status, and high oxygen levels reduce the probability of death.

Incidence and clinical characteristics of thyroid abnormalities in cancer patients treated with immune checkpoint inhibitors.

INTRODUCTION: Immune checkpoint inhibitors (ICI) are a group of drugs that have been used in recent years for the treatment of advanced malignancies such as melanoma, non-small cell lung cancer and other tumors, significantly increasing survival. However, the use of ICI has been associated with an increased risk of autoimmune diseases, with endocrine organs, specifically the thyroid, being highly susceptible to this phenomenon. OBJECTIVE: To describe the incidence and clinical characteristics of patients treated with ICI who develop thyroid disease. METHODS: The medical records of all patients who received ICI treatment within the last three years were retrospectively reviewed, with those who developed thyroid abnormalities being identified. RESULTS: The prevalence of thyroiditis was 7 %, with an incidence of 21.4 % of patients-month. Median time for the development of thyroiditis was 63 days. Most patients had mild or moderate symptoms and did not require hospitalization, although all but one developed permanent hypothyroidism and required hormone replacement therapy with levothyroxine. CONCLUSIONS: Thyroid dysfunction secondary to immunotherapy is a common entity in our population. Clinical presentation is usually mild and does not require treatment discontinuation; however, due to the high incidence of these adverse events, non-oncology specialists must be familiar with the diagnosis and treatment of these alterations in order to provide multidisciplinary management.

INTRODUCCIÓN: Los inhibidores del punto de control inmunológico (IPCi) son utilizados en los últimos años en el tratamiento de neoplasias malignas avanzadas, con ellos se ha logrado un aumento significativo de la supervivencia; sin embargo, su uso se ha asociado a incremento del riesgo de enfermedades autoinmunes. OBJETIVO: Describir la incidencia y las características clínicas de los pacientes tratados con IPCi que desarrollaron tiroidopatía. MÉTODOS: Se revisaron retrospectivamente los expedientes de todos los pacientes que recibieron IPCi en los últimos tres años y se identificaron aquellos que desarrollaron anomalías tiroideas. RESULTADOS: La prevalencia de tiroiditis fue de 7 %, con una incidencia de 21.4 % pacientes/mes. La mediana del tiempo para el desarrollo de tiroiditis fue de 63 días. La mayoría de los pacientes presentó síntomas leves o moderados y no requirió hospitalización, si bien todos menos uno desarrollaron hipotiroidismo permanente y requirieron terapia de reemplazo hormonal con levotiroxina. CONCLUSIONES: La disfunción tiroidea secundaria a inmunoterapia es una entidad común en nuestra población. El cuadro clínico suele ser leve y no requiere suspender el tratamiento; sin embargo, debido a la alta incidencia de este evento adverso, los médicos no oncólogos deben estar familiarizados con su diagnóstico y tratamiento, para brindar un manejo multidisciplinario.

Incidencia y características clínicas de la enfermedad tiroidea en pacientes con neoplasias malignas tratados con inhibidores de punto de control inmunológico / Incidence and clinical characteristics of thyroid abnormalities in cancer patients treated with immune checkpoint inhibitors

Resumen Introducción: Los inhibidores del punto de control inmunológico (IPCi) son utilizados en los últimos años en el tratamiento de neoplasias malignas avanzadas, con ellos se ha logrado un aumento significativo de la supervivencia; sin embargo, su uso se ha asociado a incremento del riesgo de enfermedades autoinmunes. Objetivo: Describir la incidencia y las características clínicas de los pacientes tratados con IPCi que desarrollaron tiroidopatía. Métodos: Se revisaron retrospectivamente los expedientes de todos los pacientes que recibieron IPCi en los últimos tres años y se identificaron aquellos que desarrollaron anomalías tiroideas. Resultados: La prevalencia de tiroiditis fue de 7 %, con una incidencia de 21.4 % pacientes/mes. La mediana del tiempo para el desarrollo de tiroiditis fue de 63 días. La mayoría de los pacientes presentó síntomas leves o moderados y no requirió hospitalización, si bien todos menos uno desarrollaron hipotiroidismo permanente y requirieron terapia de reemplazo hormonal con levotiroxina. Conclusiones: La disfunción tiroidea secundaria a inmunoterapia es una entidad común en nuestra población. El cuadro clínico suele ser leve y no requiere suspender el tratamiento; sin embargo, debido a la alta incidencia de este evento adverso, los médicos no oncólogos deben estar familiarizados con su diagnóstico y tratamiento, para brindar un manejo multidisciplinario.

Abstract Introduction: Immune checkpoint inhibitors (ICI) are a group of drugs that have been used in recent years for the treatment of advanced malignancies such as melanoma, non-small cell lung cancer and other tumors, significantly increasing survival. However, the use of ICI has been associated with an increased risk of autoimmune diseases, with endocrine organs, specifically the thyroid, being highly susceptible to this phenomenon. Objective: To describe the incidence and clinical characteristics of patients treated with ICI who develop thyroid disease. Methods: The medical records of all patients who received ICI treatment within the last three years were retrospectively reviewed, with those who developed thyroid abnormalities being identified. Results: The prevalence of thyroiditis was 7 %, with an incidence of 21.4 % of patients-month. Median time for the development of thyroiditis was 63 days. Most patients had mild or moderate symptoms and did not require hospitalization, although all but one developed permanent hypothyroidism and required hormone replacement therapy with levothyroxine. Conclusions: Thyroid dysfunction secondary to immunotherapy is a common entity in our population. Clinical presentation is usually mild and does not require treatment discontinuation; however, due to the high incidence of these adverse events, non-oncology specialists must be familiar with the diagnosis and treatment of these alterations in order to provide multidisciplinary management.

Biological Landscape of Triple Negative Breast Cancers Expressing CTLA-4.

Patients with triple-negative breast cancer (TNBC) have a poor prognosis, partly because of the absence of targeted therapies. Recognition of the key role of immune responses against cancer has allowed the advent of immunotherapy, focused on the inhibition of negative immune checkpoints, such as CTLA-4. CTLA-4 is also expressed in some cancer cells, but its activity in tumor cells is not completely understood. Thus, the aim of the present work was to determine the biological landscape and functions of CTLA-4 expressed in TNBC cells through preclinical and in silico analysis. Exploration of CTLA-4 by immunohistochemistry in 50 TNBC tumors revealed membrane and cytoplasmic expression at different intensities. Preclinical experiments, using TNBC cell lines, showed that stimulation of CTLA-4 with CD80 enhances activation of the ERK1/2 signaling pathway, while CTLA-4 blockade by Ipilimumab induces the activation of AKT and reduces cell proliferation in vitro. We then developed an analytic pipeline to define the effects of CTLA-4 in available public data that allowed us to identify four distinct tumor clusters associated with CTLA-4 activation, which are characterized by enrichment of distinctive pathways associated with cell adhesion, MAPK signaling, TGF-ß, VEGF, TNF-α, drug metabolism, ion and amino acid transport, and KRAS signaling, among others. In addition, blockade of CTLA-4 induced increased secretion of IL-2 by tumor cells, suggesting that the receptor regulates cellular functions that may impact the immune microenvironment. This is relevant because a deep characterization of immune infiltrate, conducted using public data to estimate the abundancies of immune-cell types, showed that CTLA-4-activated-like tumors present a conditional immune state similar to an escape phenotype exploited by cancer cells. Finally, by interrogating transcriptional predictors of immunotherapy response, we defined that CTLA-4 activation correlates with high immune scores related to good clinical predicted responses to anti-CTLA-4 therapy. This work sheds new light on the roles of activated CLTA-4 in the tumor compartment and suggests an important interplay between tumor CLTA-4-activated portraits and immune-infiltrating cell populations.

Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma.

PURPOSE: The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS: This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS: After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION: Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.

Fibrinolytic Activity of Circulating Microvesicles Is Associated with Progression of Breast Cancer.

The fibrinolytic system plays an important role in breast cancer, favoring progression through extracellular-matrix degradation, angiogenesis, apoptosis and cellular proliferation. The expression of urokinase-type plasminogen activator (uPA) in breast cancer tissue is widely recognized as an unfavorable prognostic factor. However, fibrinolytic activity associated with uPA cannot be reliably measured in the blood because of the rapid inhibition of uPA by plasminogen activator inhibitor-1 (PAI-1). By contrast, circulating microvesicles (Mvs) in peripheral blood protect bound enzymes from inhibition. Mvs are extracellular vesicles, released from various types of cells, and their size fluctuates between 100 and 1,000 nm. Mvs carry DNA, RNA, miRNA, and proteins, thereby serving as a source of horizontal communication between cells. We investigated whether fibrinolytic activity on circulating Mvs reflects breast cancer progression. The study population consisted of 13 patients with breast cancer and 13 healthy women. The cancer patients included 4 patients in remission, 3 patients with locally advanced cancer, and 6 with metastatic disease. Mvs were isolated from peripheral blood, quantified by a protein concentration method, and their fibrinolytic potential was measured by their capacity to generate plasmin. Although the quantity of Mvs found in patients with cancer and healthy individuals was similar, plasmin generated on Mvs was twice the amount in patients with metastasis than in healthy women (P < 0.05), underlying the value of this distinctive parameter. The data suggest that in breast cancer patients, higher fibrinolytic activity of circulating Mvs could be related to progression and metastasis of breast cancer.

Experiencia con el uso de olaparib en pacientes con cáncer de ovario.

INTRODUCTION: More than the twenty percent of ovarian cancers are hereditary, and most have BRCA mutations. The 30% of Mexican patients with the BRCA1 mutation have the BRCA1 gene exon 9-12del deletion founder mutation (BRCA1 ex9-12del). BRCA-mutated tumors are more sensitive to PARP inhibitors such as olaparib. OBJECTIVE: To show the clinical experience on the use of olaparib at Instituto Nacional de Cancerología in Mexico. METHOD: Ovarian cancer patients treated with olaparib from November 2016 to December 2018 were studied, and their characteristics, clinical response, progression-free survival (PFS) and toxicities were described. RESULTS: Nineteen patients were assessed, with BRCA1 mutation being found in 78.9%, out of which 21.1% were carriers of the ex9-12del founder mutation. The median of PFS was 12 months; for patients treated on second and third line it was > 15 months, and for those treated with a fourth and subsequent line it was 8.3 months. Patients with the founder mutation had better results. Toxicities were like those reported in previous studies. CONCLUSIONS: Olaparib offers greater PFS benefit as maintenance therapy after a first and second relapse. Patients with founder mutation have had sustained PFS.

INTRODUCCIÓN: Más del 20 % de los cánceres de ovario puede ser hereditario y la mayoría tiene mutaciones BRCA. El 33 % de las pacientes mexicanas con mutación BRCA1 tiene la mutación fundadora deleción del exón 9-12del del gen BRCA1 (BRCA1 ex9-12del). Los tumores BRCA mutados son más sensibles a inhibidores PARP como olaparib. OBJETIVO: Mostrar la experiencia clínica del uso de olaparib en el Instituto Nacional de Cancerología de México. MÉTODO: Se estudiaron las pacientes con cáncer de ovario tratadas con olaparib de noviembre de 2016 a diciembre de 2018 y se describieron sus características, respuesta clínica, supervivencia libre de progresión y toxicidades. RESULTADOS: Se evaluaron 19 pacientes, 78.9 % presentó mutación BRCA1, del cual 21.1 % era portador de la mutación fundadora ex9-12del. La mediana de supervivencia libre de progresión global fue de 12 meses, para las pacientes tratadas tratadas con olaparib de mantenimiento posterior a segunda y tercera línea fue de > 15 meses y para las de cuarta línea o más fue de 8.3 meses. Las pacientes con mutación fundadora presentaron mejores respuestas. Las toxicidades fueron similares a las de estudios con el uso de olaparib. CONCLUSIONES: Olaparib ofrece mayor beneficio en supervivencia libre de progresión como tratamiento de mantenimiento después de la primera y segunda recaída. Las pacientes con mutación fundadora han tenido respuesta sostenida.

[Clinicopathological features, prognosis and influence in the adjuvant treatment of the risk recurrence groups determined by the 21 gene expression profile, Oncotype Dx®, in early breast cancer]. / Características clinicopatológicas, pronóstico e influencia en el tratamiento adyuvante en los grupos de riesgo de recurrencia determinados por el perfil de expresión de 21 genes, Oncotype Dx®, en cáncer de mama temprano.

BACKGROUND: Adjuvant chemotherapy (ACT) reduces recurrence and mortality in breast cancer (BC); however, not all patients require ACT. Oncotype Dx® (ODX) explores the expression of 21 genes and the risk of recurrence BC. OBJECTIVES: To determine the clinicopathologic characteristics, prognosis, and the prescription for ACT in early BC according to ODX risk groups. METHODS: 36 patients with resected stage I-IIA BC, axillary lymph node-negative or 1-3+, hormonal receptor (HR)-positive, HER2 negative. Three groups were designed by ODX: low (LG), medium (MG) and high-risk groups (HG). RESULTS: LG 23 patients (63.9%), MG eight (22.2%) and HG five (13.9%). We detected high expression of Ki-67 in MG and HG in relation to LG, 21.1 and 32.5 versus 10.1%, respectively (p = 0.007) and lower ER-positive, 85.3, 85.4 and 56.9%, respectively (p = 0.005). Recurrence score: LG 12 (0-18), MG 23 (19-27) and HG 47 (36-57); p < 0.000. Pre-ODX, we planned ACT in 21/36 patients (58.3%) and post-ODX only 9/36 patients (25%) received it. No recurrences or deaths were observed in all groups. CONCLUSIONS: In early BC, 64% have low recurrence risk. High-risk cases presented elevated Ki-67 and lower ER expression. ODX modifies the therapeutic recommendation in 57.2% of cases.

[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.

[PET/CT tomography. Usefulness in oncology]. / La tomografía por emisión de positrones (PET/CT). Utilidad en la oncología.

In order to have optimum results in oncological patients, precise evaluation, diagnosis and staging of the patient is necessary. Positron emission tomography (PET) yields a high negative predictive value through exploration of the entire body. It diagnoses the benign or malignant state of a neoplasm that has been detected by other imaging methods and establishes an extensive diagnosis previous to therapeutic treatment of a known cancer. It identifies residual tumor and changes produced after surgery, chemotherapy or radiotherapy and locates suspicious residual tumor clinically or by elevation of the tumor markers. It allows for a new extension study or re-staging after diagnosis of recurrence and permits early evaluation of response to a therapeutic regime and permits the search for a primary tumor in patients with metastasis of unknown origin. PET leads to a molecular functional imaging of cancer in the entire body.

La tomografía por emisión de positrones (PET/CT): utilidad en la oncología / PET/CT tomography: usefulness in oncology

En oncología es necesario el diagnóstico y estadificación precisos del paciente con cáncer, para tener resultados óptimos en su tratamiento. La tomografía por emisión de positrones (PET) tiene alto valor predictivo negativo mediante la exploración del cuerpo entero. Diagnostica la benignidad o malignidad de una neoplasia detectada por otros métodos de imagen; establece el diagnóstico de extensión previo al planteamiento terapéutico de un cáncer conocido; identifica tumor residual y cambios producidos poscirugía, quimio o radioterapia; localiza recidivas tumorales sospechosas clínicamente o por elevación de marcadores tumorales; permite hacer un nuevo estudio de extensión o reestadificación tras el diagnóstico de una recurrencia; permite valorar tempranamente la respuesta a un esquema terapéutico y la búsqueda del tumor primario en pacientes con metástasis de origen desconocido. PET conduce a una imagenología molecular funcional del cáncer en el cuerpo entero.

In order to have optimum results in oncological patients, precise evaluation, diagnosis and staging of the patient is necessary. Positron emission tomography (PET) yields a high negative predictive value through exploration of the entire body. It diagnoses the benign or malignant state of a neoplasm that has been detected by other imaging methods and establishes an extensive diagnosis previous to therapeutic treatment of a known cancer. It identifies residual tumor and changes produced after surgery, chemotherapy or radiotherapy and locates suspicious residual tumor clinically or by elevation of the tumor markers. It allows for a new extension study or re-staging after diagnosis of recurrence and permits early evaluation of response to a therapeutic regime and permits the search for a primary tumor in patients with metastasis of unknown origin. PET leads to a molecular functional imaging of cancer in the entire body.

Complementary and alternative medicine (CAM) in Mexican patients with cancer.

BACKGROUND: Cancer is the second cause of death in Mexico, most cases are detected at advanced stages and the use of chemotherapy is frequent. At present, more than 300 types of complementary and/or alternative medicine (CAM) treatments are known that offer different therapeutic objectives. Many patients use this type of treatments. OBJECTIVE: To determine the characteristics of the patients that use CAM, to identify the aim of these treatments, the source of information and the potential benefits obtained by the patient. PATIENTS AND METHODS: A questionnaire was applied from February 20 to March 5, 2004 to non-selected patients with cancer in private consultation to determine age, sex, education level, work, use of CAM, type and number of used therapies, potential benefits and monthly cost. Two groups were formed, A for users and B for non-users of CAM. Results between groups were compared and the mentioned variables were correlated with the use of alternative medicine. RESULTS: Group A included 37 patients and group B included 38, with no difference regarding age, education level, work and oncological diagnosis, p > 0.05; a significant trend was found as regards the feminine sex, p = 0.07, neoplasm different from breast cancer, p = 0.08 and evident association with neoplasm advanced stages, p = 0.02. Most patients used between 1 and 3 types of therapies, 97.2%. The most common types of therapies were nutritional and spiritual, 54% and 48.6%, respectively. The source was the patient's family in 56.4% and the physician in 24.3%. Complementary and alternative therapy was considered a success in 57.1%; most of the users mentioned benefits (78.6%) deemed as tranquility (46.4%) or improvement of the physical condition (46.4%). The average monthly cost was $ 345.5 dollars, with a range of $ 13.6 to $ 2,545.5 dollars. CONCLUSIONS: The use of complementary and/or alternative therapy is frequent among young women with advanced cancer and high level of education. The family participates in the decision of using these methods; most users noticed a benefit in their general condition and reported tranquility; these patients may be prone to higher incidence of depression and anxiety. The effectiveness and safety of this type of treatments remain to be determined, as well as the possible interactions with conventional therapy.

Complementary and alternative medicine (CAM) in mexican patients with cancer

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Background. Cancer is the second cause of deathin Mexico, most cases are detected at advancedstages and the use of chemotherapy is frequent. Atpresent, more than 300 types of complementaryand/or alternative medicine (CAM) treatments areknown that offer different therapeutic objectives.Many patients use this type of treatments.Objective. To determine the characteristics of thepatients that use CAM, to identify the aim of thesetreatments, the source of information and the potentialbenefits obtained by the patient.Patients and methods. A questionnaire was appliedfrom February 20 to March 5, 2004 to non-selectedpatients with cancer in private consultation to determineage, sex, education level, work, use of CAM,type and number of used therapies, potential benefitsand monthly cost. Two groups were formed, Afor users and B for non-users of CAM. Results betweengroups were compared and the mentionedvariables were correlated with the use of alternativemedicine.Results. Group A included 37 patients and group Bincluded 38, with no difference regarding age, educationlevel, work and oncological diagnosis, p >0.05; a significant trend was found as regards thefeminine sex, p = 0.07, neoplasm different frombreast cancer, p = 0.08 and evident association withneoplasm advanced stages, p = 0.02. Most patientsused between 1 and 3 types of therapies, 97.2%. Themost common types of therapies were nutritionaland spiritual, 54% and 48.6%, respectively. Thesource was the patient's family in 56.4% and thephysician in 24.3%. Complementary and alternativetherapy was considered a success in 57.1%; most ofthe users mentioned benefits (78.6%) deemed astranquility (46.4%) or improvement of the physicalcondition (46.4%). The average monthly cost was $345.5 dollars, with a range of $ 13.6 to $ 2,545.5 dollars.Conclusions. The use of complementary and/or alternativetherapy is frequent among young womenwith advanced cancer and high level of education.The family participates in the decision of usingthese methods; most users noticed a benefit in theirgeneral condition and reported tranquility; thesepatients may be prone to higher incidence of depressionand anxiety. The effectiveness and safetyof this type of treatments remain to be determined,as well as the possible interactions with conventionaltherapy

Talidomida en cáncer avanzado: estudio en fase I / Thalidomide in advanced cancer: aphase I study

Antecedentes: en 1997, en México se registraron más de 87 mil casos nuevos de cáncer. Las neoplasias más frecuentes fueron: cuello uterino, mama, próstata, ganglios linfáticos y estómago. La angiogénesis es un factor determinante en el crecimiento y proliferación neoplásica, así como para conferir la capacidad metastásica tumoral. La talidomida, que fue vinculada con teratogénesis en los años 50, tiene capacidad de inhibir la angiogénesis, inducir la apoptosis y tiene efectos inmunomoduladores. Objetivo: evaluar la tolerancia y seguridad de la talidomida como agente antiangiogénico, en pacientes con neoplasia avanzada. Pacientes y método: mayores de 18 años, de uno y otro sexos, con neoplasia metastásica multitratada, con resistencia o progresión a terapia convencional, que recibieron talidomida como monoterapia al menos durante un mes. Este fármaco fue administrado a dosis de 100 mg/día, vía oral con ascenso a 200 mg la primera semana y luego cada 15 días hasta 800 mg. Se evaluaron edad, sexo, neoplasia y estirpe histológica, etapa clínica, dosis utilizada, tiempo de uso, efectos secundarios y tiempo de seguimiento. Resultados: 13 pacientes, 3 mujeres y 10 hombres, edad promedio 57.8 + 14.6 años margen de 31 a 76. Correspondían a: 10 tumores sólidos y 3 hematológicos. Se incluyeron 3 hepatocarcinoma, 2 mieloma múltiple, 2 melanoma, 2 pulmón y uno de mama, colon, recto y linfoma no Hodgkin. De las 10 sólidas, 7 en EC IV y 3 EC III; en las hematológicas, 2 etapa II de Durie-Salmon y el linfoma en etapa IV. Ocho pacientes tenían evidencia de actividad metastásica, 61.5 por ciento. Cinco pacientes habían recibido 1 línea de quimioterapia, otros 6 pacientes 2 y 3 más de 3 esquemas. Dosis de talidomida: 4 pacientes emplearon 100 mg/día; 7, 200 mg; 1, 300 mg y 1, 400 mg/día, sólo en 2 pacientes se intentó escalar la dosis. El tiempo promedio de uso 3.15 + 3.8 meses, margen de 1 a 12, mediana 1. Diez pacientes tuvieron efectos secundarios; somnolencia, 8; 6 neuropatía periférica sensitiva, 1 erupción cutánea. Se observaron casos con estabilidad de la enfermedad durante al menos dos meses y ocho casos con progresión. La talidomida fue adecuadamente tolerada a la dosis de 100 a 200 mg/día, su uso se asocia con somnolencia y neuropatía periférica sensitiva de bajo grado, los efectos secundarios se incrementan al elevar la dosis. Se requiere de más estudios para evaluar su efecto antitumoral, dosis óptima y su asociación con quimioterapia o agentes inmunomoduladores