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El cáncer es uno de los problemas de salud pública en muchos países o regiones del mundo. La incidencia, mortalidad y la prevalencia del cáncer, permiten cuantificar la magnitud de esta patología y orientan las políticas públicas en relación a la prevención y los servicios de salud. El elevado costo económico y social que representa la atención de estos pacientes, hace que la prevalencia, forma de evolución y pronóstico difieran de un país a otro. En el Perú, el cáncer representa la primera causa de muerte. Para el año 2018, según Globocan, se diagnosticaron más de 66 mil nuevos casos y se registraron más de 33 mil muertes por cáncer. Las tres patologías más frecuentes en las mujeres fueron cáncer de mama (19%), cérvix (11%) y cáncer de estómago (7%), en los hombres cáncer de próstata (25%), estómago (10%) y colorrectal (7%); y las principales causas de muerte fueron por cáncer de estómago (13.9%), pulmón (8.6%) y próstata (8.2%). La tasa de incidencia fue de 192.6 y la tasa de mortalidad de 92.9 por 100,000 personas, respectivamente; según la localización del tumor, la tasa de incidencia de cáncer de próstata fue de 47.8, mama 40.0, cérvix 23.2 y de estómago 16.1, y la tasa de mortalidad por cáncer de próstata fue de 15.6, estómago 12.8, mama 10.3 y de cérvix 10.2 por 100,000, respectivamente. La prevalencia estimada a un año fue de 42,849 casos, a tres años 104,007 y a 5 años 150,132 casos; las patologías más prevalentes en los hombres fueron cáncer de próstata, colorrectal y LNH, en las mujeres fueron cáncer de mama, cérvix y tiroides. La razón de mortalidad e incidencia, que permiten cuantificar la letalidad de la enfermedad en nuestro medio, siguen siendo altas en neoplasias como cáncer de hígado, páncreas, estómago y pulmón. La tasa de incidencia y mortalidad por cáncer siguen incrementándose en nuestra población en relación al reporte del período 2012; es posible que estos incrementos sean una consecuencia de los cambios de la estructura de edad de la población, adopción de estilos de vida sedentaria, dieta no saludable y entre otros factores.

Background Infections with human papillomavirus (HPV) types 16 and 18 account for ~70% of invasive cervical cancers but the degree of protection from naturally acquired anti‐HPV antibodies is uncertain. We examined the risk of HPV infections as defined by HPV DNA detection and cervical abnormalities among women >25 years in the Human Papilloma VIrus Vaccine Immunogenicity ANd Efficacy trial's (VIVIANE, NCT00294047) control arm. Methods Serum anti‐HPV‐16/18 antibodies were determined at baseline and every 12 months in baseline DNA‐negative women (N = 2687 for HPV‐16 and 2705 for HPV‐18) by enzyme‐linked immunosorbent assay (ELISA) from blood samples. HPV infections were identified by polymerase chain reaction (PCR) every 6‐months, and cervical abnormalities were confirmed by cytology every 12 months. Data were collected over a 7‐year period. The association between the risk of type‐specific infection and cervical abnormalities and serostatus was assessed using Cox proportional hazard models. Results Risk of newly detected HPV‐16‐associated 6‐month persistent infections (PI) (hazard ratio [HR] = 0.56 [95%CI:0.32; 0.99]) and atypical squamous cells of undetermined significance (ASC‐US+) (HR = 0.28 [0.12; 0.67]) were significantly lower in baseline seropositive vs baseline seronegative women. HPV‐16‐associated incident infections (HR = 0.81 [0.56; 1.16]) and 12‐month PI (HR = 0.53 [0.24; 1.16]) showed the same trend. A similar trend of lower risk was observed in HPV‐18‐seropositive vs ‐seronegative women (HR = 0.95 [0.59; 1.51] for IIs, HR = 0.43 [0.16; 1.13] for 6‐month PIs, HR = 0.31 [0.07; 1.36] for 12‐month PIs, and HR = 0.61 [0.23; 1.61] for ASC‐US+). Conclusions Naturally acquired anti‐HPV‐16 antibodies were associated with a decreased risk of subsequent infection and cervical abnormalities in women >25 years. This possible protection was lower than that previously reported in 15‐ to 25‐year‐old women.

Breast cancer (BC) is a highly prevalent malignancy in Latin American women, most cases being diagnosed at locally advanced or metastatic stages when options for cancer care are limited. Despite its label as a public health problem in the region, Latin American BC patients face several barriers in accessing standard of care treatment when compared with patients from developed countries. In this review, we analyse the landscape of the four main identified barriers in the region: i) high burden of locally advanced/advanced BC; ii) inadequate access to medical resources; iii) deficient access to specialised cancer care and iv) insufficient BC research in Latin America. Unfortunately, these barriers represent the main factors associated with the BC poor outcomes seen in the region. Targeted actions should be conducted independently by each country and as a region to overcome these limitations and create an enhanced model of BC care.

COVID-19 pandemic is the more challenging public health emergency of the century, producing the collapse of health systems and unprecedented levels of morbidity and mortality around the world, especially in low resource settings. Patients with chronic diseases are the most affected, not only due to the high susceptibility to SARS-CoV-2 infection but also due to the decrease in opportunities for timely care. In this dark landscape, telemedicine, before limited to very specific scenarios, has become one of our main tools to manage cancer patients, particularly in Latin America where COVID-19 has had a strong impact on the public health. Telemedicine can provide rapid access to specialized cancer care in a scenario complicated, reducing the exposure of patients and healthcare personnel to the SARS-CoV-2. In this review, we would like to share our experience and our workflow using telemedicine at Oncosalud-AUNA, a private clinic in Peru.

Summary Background Although the risk of human papillomavirus (HPV) infection is greatest in young women, women older than 25 years remain at risk. We present data from the VIVIANE study of the HPV 16/18 AS04-adjuvanted vaccine in adult women after 7 years of follow-up. Methods In this phase 3, double-blind, randomised controlled trial, healthy women older than 25 years were enrolled (age stratified: 26–35 years, 36–45 years, and ≥46 years). Up to 15% in each age stratum had a history of HPV infection or disease. Women were randomly assigned (1:1) to receive HPV 16/18 vaccine or aluminium hydroxide control, with an internet-based system. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or greater (CIN1+) associated with HPV 16/18. We did analyses in the according-to-protocol cohort for efficacy and total vaccinated cohort. Data for the combined primary endpoint in the according-to-protocol cohort for efficacy were considered significant when the lower limit of the 96·2% CI around the point estimate was greater than 30%. For all other endpoints and cohorts, data were considered significant when the lower limit of the 96·2% CI was greater than 0%. This study is registered with ClinicalTrials.gov, number NCT00294047. Findings The first participant was enrolled on Feb 16, 2006, and the last study visit took place on Jan 29, 2014. 4407 women were in the according-to-protocol cohort for efficacy (n=2209 vaccine, n=2198 control) and 5747 women in the total vaccinated cohort (n=2877 vaccine, n=2870 control). At month 84, in women seronegative for the corresponding HPV type in the according-to-protocol cohort for efficacy, vaccine efficacy against 6-month persistent infection or CIN1+ associated with HPV 16/18 was significant in all age groups combined (90·5%, 96·2% CI 78·6–96·5). Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. We also noted significant cross-protective efficacy against 6-month persistent infection with HPV 31 (65·8%, 96·2% CI 24·9–85·8) and HPV 45 (70·7%, 96·2% CI 34·2–88·4). In the total vaccinated cohort, vaccine efficacy against CIN1+ irrespective of HPV was significant (22·9%, 96·2% CI 4·8–37·7). Serious adverse events related to vaccination occurred in five (0·2%) of 2877 women in the vaccine group and eight (0·3%) of 2870 women in the control group. Interpretation In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non-vaccine types HPV 31 and HPV 45 over 7 years of follow-up. Funding GlaxoSmithKline Biologicals SA.

The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p 25 years in this study was similar to that in women 15-25 years in PATRICIA.

To develop intensity-duration-frequency (IDF) curves, it is necessary to calculate annual maximum rainfall intensities for different durations. Traditionally, these intensities have been calculated from the analysis of traces recorded by rain gauges on pluviograph strip charts (PSCs). For many years, these charts have been recorded and analyzed by the personnel who operate and maintain the pluviograph gauges, thus the reliability of the observational analysis depends exclusively on the professional experience of the person performing the analysis. Traditionally, the analyzed PSCs are physically stored in data repository centers. After storing rainfall data on aging paper for many years, the risk of losing rainfall records is very high. Therefore, the conversion of PSC records to digital format is crucial to preserve and improve the historical instrumental data base of these records. We conducted the first &ldquo, Data Rescue Initiative&rdquo, (DRI) for central Chile using a pluviograph strip charts reader (PSCR), a tool that uses a scanner-type device combined with digital image processing techniques to estimate maximum rainfall intensities for different durations for each paper band (&gt, 80,000 paper bands). On the paper bands, common irregularities associated with excess ink, annotations, or blemishes can affect the scanning process, this system was designed with a semi-automatic module that allows users to edit the detected trace to improve the recognition of the data from each PSC. The PSCR&rsquo, s semi-automatic characteristics were designed to read many PSCs in a short period of time. The tool also allows for the calculation of rainfall intensities in durations ranging between 15 min to 1 h. This capability improves the value of the data for water infrastructure design, since intense storms of shorter duration often have greater impacts than longer but less intense storms. In this study, the validation of the PSCR against records obtained from observational analysis showed no significant differences between maximum rainfall intensities for durations of 1 h, 6 h, and 24 h.

Lung cancer is a public health problem worldwide and Latin America (LATAM) cannot escape this reality. This malignant disease has not only a high prevalence in the region, but is also the main cause of cancer related deaths, and in other emerging countries, the incidence rates are still on the rise. Interestingly in most LATAM countries, lung cancer mortality has been decreasing in men but not in women, reflecting smoking patterns in countries such as Chile, Bolivia, and Brazil. Despite the fact that these issues are well known to government agencies, physicians and patients in the region, current efforts still fall behind those needed in order to face this problem of epidemic proportions. Tobacco control and smoking cessation are the most important interventions against lung cancer, but even with their optimal implementation (which is far from reality at this time) the number of cases in the foreseeable future would still be significant. Beyond tobacco control, advances in our understanding of the molecular component of lung cancer have resulted in new targeted therapies and immune check point inhibitors, which have improved clinical outcomes but at a considerably higher financial cost. LATAM has not widely and speedily adopted these strategies, including new technology and approved novel drugs, due to a number of facts, and therefore only a dismal proportion of LATAMs patient population have benefited from these new advances. A keen focus on a heterogeneous education system for caregivers in lung cancer treatment would likely help standardize care and improve future potential gains from domestic research. In this review we discuss the challenges of treatment implementation, focusing on new technologies.

Copyright © 2015 Massachusetts Medical Society. BACKGROUND Ovarian failure is a common toxic effect of chemotherapy. Studies of the use of gonadotropin- releasing hormone (GnRH) agonists to protect ovarian function have shown mixed results and lack data on pregnancy outcomes. METHODS We randomly assigned 257 premenopausal women with operable hormone-receptor- negative breast cancer to receive standard chemotherapy with the GnRH agonist goserelin (goserelin group) or standard chemotherapy without goserelin (chemotherapy- alone group). The primary study end point was the rate of ovarian failure at 2 years, with ovarian failure defined as the absence of menses in the preceding 6 months and levels of follicle-stimulating hormone (FSH) in the postmenopausal range. Rates were compared with the use of conditional logistic regression. Secondary end points included pregnancy outcomes and disease-free and overall survival. RESULTS At baseline, 218 patients were eligible and could be evaluated. Among 135 with complete primary end-point data, the ovarian failure rate was 8% in the goserelin group and 22% in the chemotherapy-alone group (odds ratio, 0.30; 95% confidence interval, 0.09 to 0.97; two-sided P = 0.04). Owing to missing primary end-point data, sensitivity analyses were performed, and the results were consistent with the main findings. Missing data did not differ according to treatment group or according to the stratification factors of age and planned chemotherapy regimen. Among the 218 patients who could be evaluated, pregnancy occurred in more women in the goserelin group than in the chemotherapy-alone group (21% vs. 11%, P = 0.03); women in the goserelin group also had improved disease-free survival (P = 0.04) and overall survival (P = 0.05). CONCLUSIONS Although missing data weaken interpretation of the findings, administration of goserelin with chemotherapy appeared to protect against ovarian failure, reducing the risk of early menopause and improving prospects for fertility.

Summary Chile has a unique geography that provides an extraordinary variety of climatic conditions and availability of water resources. The objective of this manuscript was to describe and analyze the spatial and temporal distribution patterns, as well as the management of water resources, along a country with a narrow distance from the Andes Mountains to the Pacific Ocean. This presents challenges to water governance from data collection and analysis perspectives, and for administration of the resource. The Water Resources Directorate ( Direccion General de Aguas , DGA), is the federal government organization in charge of the water resources of the country. The DGA and other relevant public and private institutions are examined in terms of competition and conflict resolution across different scales and levels of interaction associated with water resources governance. Both monitoring stations (rainfall, streamflow, water quality, groundwater, sediment and snowfall), and the Chilean management and legislation of water resources are also analyzed. Finally, the success (or lack) of the national administration to upgrade its monitoring stations and equalize water resources distribution throughout the country is discussed including the influence of climate change on data collection, and decision making across different scales of water governance.

This study utilized a combination of HPV self-sampling, iFTA elute specimen cards, and long distance transport for centralized processing of specimens to determine the feasibility of large-scale screening in remote and transient populations.This study was performed in two locations in Peru (Manchay and Iquitos). The "Just For Me" cervico-vaginal brush and iFTA elute cards were used for the collection and transport of specimens. Samples were shipped via FedEx to China and tested for 14 types of high-risk HPV using PCR based MALDI-TOF. HPV positive women were treated with cryotherapy after VIA triage, and followed-up with colposcopy, biopsy, ECC, and repeat HPV testing at 6 months.Six hundred and forty three women registered, and 632 returned a sample over a 10 day period. Within 2 weeks, specimens were shipped, samples tested, and results received by study staff. Sixty-eight women (10.8%) tested positive, and these results were delivered over 4 days. Fifty-nine HPV positive women (87%) returned for evaluation and treatment, and 2 had large lesions not suitable for cryotherapy. At 6 months, 42 women (74%) returned for follow-up, and 3 had CIN 2 (all positive samples from the endocervical canal). Ninety eight percent of participants reported that they would participate in this type of program again.Utilizing HPV self-sampling, solid media specimen cards for long distance transport, and centralized high throughput processing, we achieved rapid delivery of results, high satisfaction levels, and low loss to follow-up for cervical cancer screening in remote and transient populations.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.

Cervical cancer is the leading malignant neoplasm in Peruvian women. This malignancy is a public health problem and several efforts were previously performed to develop cancer control plans. Geographical, cultural, structural, infrastructural and procedural barriers can limit the implementation of such strategies. Several previous studies have characterized human papilloma virus (HPV) epidemiology, where prevalence of high-risk HPV in adult females is ~12% and the prevalence in cervical cancer is 90-95%. The predominant barriers for the control of cervical cancer are lack of specialists in remote villages, education/cultural issues, loss of patients in follow-up, lack of access to HPV testing and lack of compliance for HPV vaccination. A good strategy for the prevention and early detection of high-risk HPV, pre-malignant neoplasms and cervical cancer, identified by interventional studies, is the self-sampling test, which assists with overcoming the cultural and geographic barriers. The current cancer control plan, termed 'Plan Esperanza', is performed with massive training of health professionals and social sensitization campaigns leading to filling the gaps regarding education and, in addition, it provides cancer care coverage for poorer individuals. In our experience at Oncosalud-AUNA, with a cohort of ~750,000 affiliates using a pre-paid system with annual screenings for cervical cancer for women, offered free-of-charge, a lower incidence of this malignancy (5.8/100,000) is now observed compared with the national incidence (32.7/100,000). As in other countries, the HPV vaccination can be a cost-utility strategy to reduce the high burdens of cervical cancer in Peru, a rapid and cheap HPV molecular sub-typification is rapidly required.

Background Topoisomerase II-α is a molecular target of anthracyclines; several studies have suggested that topoisomerase II-α expression is related to response to anthracycline treatment. The objective of this study was to evaluate if topoisomerase II-α overexpression predicts response to anthracycline treatment in locally advanced breast cancer patients. Material and methods Topoisomerase II-α, HER2, estrogen receptor (ER) and progesterone receptor (PR) expression were evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded breast tumors from 111 patients presenting with locally advanced breast cancer between 1995 and 2002. The prognostic value of these markers was analyzed using a multivariate proportional hazards regression model and an interaction analysis between topoisomerase II-α status and dose intensity. Results Tumors from 40 patients (36%) showed topoisomerase II-α overexpression, 62 patients (56%) for ER, 39 (35%) for PR and 26 (23%) for HER2. There were no significant correlations between topoisomerase II-α expression and response to therapy, progression-free survival (PFS) or overall survival (OS). Anthracycline dose intensity had a significant impact on PFS and OS in patients overexpressing topoisomerase II-α ( P =0.010 and 0.027, respectively). Negative PR ( P =0.041), positive HER2 ( P =0.013) were identified as risk factors in the multivariate model. The multivariate analysis in patients topoisomerase II-α negative shown no significance (HR=0.92, IC 95% 0.39–2.15, P =0.839) while the multivariate analysis in topoisomerase II-α positive, dose intensity shown to be statistically significant (HR=2.725, IC 95% 1.07–6.95, P =0.036). Conclusions Our data do not support a correlation between topoisomerase II-α expression in breast cancer patients and improved clinical benefit with anthracycline therapy. However, they do suggest that tumors overexpressing topoisomerase II-α may experience better clinical benefit with higher anthracycline dose intensity.

BACKGROUND This study was conducted to determine the prognostic effect hormone receptor (HR) status in early HER2 positive (HER2 +) breast cancer patients, since it has not yet been established whether HR status can be used in the prognosis of patients with (HER2 +) breast cancer. PATIENTS AND METHODS We obtained data from 299 patients with early HER2 + breast cancer who underwent surgery and received standard adjuvant chemotherapy, hormonal therapy and/or radiation between 2000 and 2002 at the Instituto Nacional de Enfermedades Neoplasicas, Peru. Clinical and pathological features were compared. Endpoints analyzed were disease free survival (DFS) and overall survival (OS). RESULTS Overall, 155 patients were HR− positive (HR +) and 144 were negative (HR−). The two groups had similar characteristics except for histologic grade and extracapsular extension. With a median follow-up of 93 months, 5-year DFS was statistically different between the two groups: 65.0% for (HER2 +/ HR−) and 74.6% for the (HER2 +/ HR +) patients ( P = .045). OS at 5 years was not statistically different between the two groups with 75.5% for (HER2 +/ HR−) patients and 82.4% for the (HER2 +/ HR +)( P = .140). CONCLUSIONS Patients with (HER2 +/ HR−) breast cancers treated with surgery and standard adjuvant chemotherapy exhibited a statistically worse DFS compared to those with (HER2 +/ HR +) tumors. However, OS was similar in both groups.

Durante las últimas décadas, una considerable atención científica ha sido puesta en la seguridad de los fluoruros, dada la amplia variedad de fuentes de ingestión a la que la población se encuentra expuesta y los riesgos a la salud de las personas que esto puede acarrear. El objetivo de esta investigación fue determinar si la fluoración del agua a concentraciones de 0,6 a 1 ppm se asocian a una mayor proporción de efectos adversos en la población general al compararlo con concentraciones subóptimas. Se realizó una revisión sistemática de la literatura en MEDLINE, EMBASE, COCHRANE, SCIELO, LILACS, CRD, BBO, PAHO y WHOLIS, limitada desde el 2002 al 2012. Se incluyeron estudios primarios y secundarios en español, inglés y portugués con al menos dos poblaciones comparadas, una con niveles óptimos de flúor en agua (0,6­1 ppm) y otra sin fluoración del agua (0,3 < 0,6 ppm). Dos investigadores de forma independiente realizaron evaluación de la calidad de los artículos seleccionados y que cumplieron los criterios de inclusión. La búsqueda arrojó 1024 artículos de los cuales 24 cumplieron los criterios de inclusión y 10 fueron incluidos como evidencia. Con excepción de fluorosis dental, no hay asociación entre fluoración del agua con fracturas óseas, cáncer u otro efecto adverso. A pesar de la mayor prevalencia de fluorosis en zonas fluoradas, esta fue principalmente del tipo cuestionable a leve y la proporción de fluorosis con daño estético no difiere significativamente de la presente en zonas sin fluoración del agua.

Objective Nonvalvular atrial fibrillation (NVAF) is a risk factor for ischemic stroke and systemic embolism. New oral anticoagulants are currently available. The objective of this study was to assess the incremental cost–utility ratio (ICUR) for apixaban vs. acenocoumarol in patients treated in Chile's public health system. Study Design and Setting We assessed cost–utility from the payer perspective with a lifetime Markov model. Epidemiologic characteristics, costs, and utilities were obtained from a Chilean cohort; data were completed with information from international literature. Results Incremental costs when using apixaban vs. acenocoumarol over a lifetime are CH$2,108,600 with an incremental effectiveness of 0.173 years of life gained (YLG) and 0.182 quality-adjusted life-year (QALY). The ICUR of apixaban vs. acenocoumarol was CH$12,188,439 per YLG and CH$11,585,714 per QALY. One to 3 times gross domestic product (GDP) per capita threshold is acceptable based on World Health Organization (WHO) norms. Chilean GDP per capita was CH$7,797,021 in 2013. The sensitivity analysis shows that these results are sensitive to the ischemic stroke risk with apixaban, and the intracranial hemorrhage risk due to the use of acenocoumarol. Conclusion The use of apixaban in patients with NVAF in moderate-to-high risk of stroke is cost-effective, considering the payment threshold suggested by WHO.

Objectives:Differential pricing, based on countries’ purchasing power, is recommended by the World Health Organization to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage, and accessibility for patients with breast cancer in Latin America (LA).Methods:A Markov model was designed to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs from a healthcare perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country.Results:Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 U.S. dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0 percent probability that trastuzumab is CE if the willingness-to-pay threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3 percent and 26.6 percent, respectively). Trastuzumab price would need to decrease between 69.6 percent to 94.9 percent to became CE in LA.Conclusions:Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries.

Summary. The PML/RARα fusion gene in acute promyelocytic leukaemia (APL) has three subtypes based on the breakpoint site of the PML gene: long (bcr1), short (bcr3) and variable (bcr2) subtypes. The PML/RARα fusion protein is involved in the pathogenesis of APL and the breakpoint site of the PML gene might be associated with aetiological factor(s). Because APL is over-represented in patients that originate in Latin America (Latinos), we evaluated whether the distribution of the PML/RARα fusion mRNA in this population is different to that reported in non-Latinos. Among 52 APL patients (28 from Mexico and Central America diagnosed in Los Angeles and 24 from Peru, South America), bcr1, bcr2 and bcr3 expression was 75%, 10% and 15% respectively. However, bcr1 breakpoints were significantly higher compared with non-Latino patients (340/654, 52%) reported in four studies. Often bcr1 and bcr2 are reported together; 862 (60%) of 1429 non-Latino APL patients reported in nine studies were either bcr1 or bcr2, compared with 44 (85%) in our 52 Latino patients. This difference was also statistically significant when our patients were compared to each of the individual studies from USA and Europe, but not for a small series from China and Japan. These results suggest that the overrepresentation of APL among Latin American patients can be accounted for by an increase of a single subtype – bcr1, and the breakage sites in the PML gene may not be random but possibly influenced by genetic and/or environmental factor(s).

Introduction: In a previous work we found differences in immune gene sets enrichment in NSCLC between genders, regardless their smoking status, where women had higher expression of gene sets associated with immune processes. Based in this fact, we hypothesize fewer benefits from immune checkpoint inhibitors in women patients compared than men patients. Objectives: Evaluate the benefit (in terms of progression-free survival) of women patients from immune checkpoint inhibitors nivolumab and pembrolizumab in published randomized phase III trials. Methods: We evaluated by meta-analysis four randomized phase III studies, two of prembrolizumab (Herbst et al., 2015 and Reck et al., 2016) and two of nivolumab (Borghaei et al., 2015 and Brahmer et al., 2015). We analyzed TCGA data for lung adenocarcinoma to evaluate differences in the expression of PDCD1, CD274 genes (encoding for PD-1 and PD-L1, respectively). Results: For all studies, it was observed an overall HR=0.79 (CI95%:0.71-0.87;P Conclusion: Although there are not differences between genders in the expression of PDCD1 and CD274 genes , such as is previously described for expression for PD-1 and PDL-1 proteins, in our meta-analysis we shown that women have modest benefit from anti immune checkpoint inhibitors. Blockade of PD1 and PD-L1 is a promising therapy in lung cancer; however, a better stratification of patients should be done. Meta-analysis of four phase III randomized studiesStudyAll patientsMenWomenWeightHazard Ratio IV, Fixed, 95% CIWeightHazard Ratio IV, Fixed, 95% CIWeightIV, Fixed, 95% CIReck et al., 201610.6%0.50 [0.37, 0.68]10.4%0.39 [0.26, 0.581]8.0%0.71[0.40, 1.26Brahmer et al., 201513.7%0.63 [0.48, 0.8217.8%0.63 [0.46, 0.86]11.2%0.75[0.46, 1.22]Borghaei et al., 201530.3%0.91 [0.76, 1.0926.6%0.81 [0.63, 1.04]37.8%1.02[0.78, 1.33]Herbst et al., 201545.40.85 [0.73, 0.98]45.2%0.78 [0.64, 0.95]43.0%1.04[0.81, 1.33]Total (95% Cl)100.0%0.79 [0.71, 0.87]100.0%0.71 [0.62, 0.80100.0%0.97[0.82, 1.14]Heterogeneity: Chi2=14.73,df=3 (P=0.002); I2= 80% Test for overall effect: Z= 4.73 (P Citation Format: Joseph A. Pinto, Luis A. Mas, Carlos S. Vallejos, Jhajaira Araujo, Leny Bravo, Alfredo Aguilar, Zaida Morante, Denisse Bretel, Henry L. Gomez, Christian Rolfo. Decrease of benefit from immune checkpoint inhibitors in women with non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2614. doi:10.1158/1538-7445.AM2017-2614

Objective To evaluate the incremental cost-effectiveness ratio (ICER) of the use of ticagrelor as a substitute for clopidogrel for secondary prevention of acute coronary syndrome in Chile. Study Design and Setting Cost-effectiveness analysis based on a Markov model: Safety and effectiveness data of ticagrelor were obtained from a systematic review of the literature. Costs are expressed in Chilean pesos (CLP) as of 2013. The evaluation was conducted from the payer standpoint. A probabilistic sensitivity analysis comprising discount rates and national cost variability was done. A budget impact analysis estimated for 2015 was conducted to calculate the total cost for both treatments. Results The ICER with a discount rate of 6% for ticagrelor vs. clopidogrel was CLP 4,893,126 per quality-adjusted life-year (QALY) gained (=9,689 US$). In the budget impact analysis for the baseline scenario, considering 100% of treatment, coverage, and adherence, ticagrelor represented an additional cost of CLP 5,233,854,272, for 979 QALYs gained compared with clopidogrel. Conclusions Ticagrelor is cost-effective in comparison with clopidogrel for the secondary prevention of acute coronary syndrome. These findings are similar to those reported in other international cost-effectiveness studies.

The purpose of this ongoing study is to determine the response and safety of a combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus doxorubicin as neoadjuvant therapy for stage IIIB breast cancer. Thirty-nine chemotherapy-naive patients were enrolled in the study. The median age was 54 years (range, 32 to 74 years), and the median Karnofsky performance status was 100. Gemcitabine 1,200 mg/m(2) was given on days 1 and 8, and doxorubicin 60 mg/m(2) on day 1, followed by surgery or radiotherapy. Ninety-seven of 117 cycles (83%) were administered at full dose. An overall response rate of 95% was obtained, with a complete response in 18% (seven patients) and a partial response in 77% (30 patients). Twenty-eight patients (72%) underwent breast surgery after a maximum of three cycles of neoadjuvant therapy. World Health Organization grade 3/4 toxicities included leukopenia in nine cycles (8%), neutropenia in 16 cycles (14%), febrile neutropenia in 11 cycles (9%), and anemia in two cycles (2%). The most important nonhematologic toxicity was grade 2/4 mucositis in 16 cycles (14%), and/or grade 2/3 diarrhea in 10 cycles (9%). Neoadjuvant therapy with gemcitabine plus doxorubicin results in a high tumor response rate with moderate oral and hematologic toxicity. Semin Oncol 28 (suppl 10):57-61.

OBJETIVO: Evaluar la correlación entre la asimetría fetal (CC/CA y LF/CA sobre el percentil 95) y la asimetría neonatal (índice ponderal neonatal (IPN) menor del percentil 10). MATERIAL Y MÉTODO: Estudio de seguimiento con datos del SIP del CLAP de fetos clasificados como asimétricos y simétricos según índices biométricos. RESULTADOS: El 1604 casos seleccionados se encontró asociación significativa entre la asimetría fetal y la neonatal. La relación LF/CA > p95 demostró ser un buen predictor de asimetría neonatal después de la semana 33. CONCLUSIONES: La relación CC/CA resultó ser el mejor predictor de asimetría neonatal.

Premature ovarian failure is a devastating long-term toxic effect of chemotherapy for premenopausal women. The survival benefit of adjuvant chemotherapy in young women with operable hormone receptor–negative breast cancer is well known, but concern over becoming infertile may influence the c

We have performed a phase II study to evaluate the activity and toxicity of ifosfamide and cisplatin as first-line treatment for advanced ovarian cancer. Patients were treated with cisplatin 100 mg/m 2 on day 1 and ifosfamide 5 g/m 2 in 18-hr continuous infusion on day 1 or 1.5 g/m 2 bolus on days 1–5. Between August 1988 and March 1990, 30 women were entered in the trial, 26 of them with measurable disease. The overall clinical response rate was 69% (95% CI: 48–85%), including 34.6% complete responses (95% CI:17–55%). Reassessment laparotomy was performed in 12 cases, and 4 (33%) exhibited a pathologic complete response. For all patients, the median duration of progression-free survival was 14 months, and the median overall survival was 25 months. There were no major differences in the response rate or survival between the two ifosfamide administration modalities. Relevant toxicities were grade IV hematologic toxicity in 11/30 patients and grade IV renal toxicity in 2/30 patients. A patient with grade IV encephalopathy developed a trauma-related cerebral hemorrhage and died 2 months later. The combination of ifosfamide and cisplatin is active in first-line therapy in advanced ovarian cancer, although it does not seem to improve the efficacy or toxicity profile of conventional combinations.

Contribution over time of human papillomavirus (HPV) types in human cancers has been poorly documented. Such data is fundamental to measure current HPV vaccines impact in the years to come. We estimated the HPV type-specific distribution in a large international series of invasive cervical cancer (ICC) over 70 years prior to vaccination. Paraffin embedded ICC cases diagnosed between 1940 and 2007 were retrieved from eleven countries in Central-South America, Asia and Europe. Included countries reported to have low-medium cervical cancer screening uptake. Information on age at and year of diagnosis was collected from medical records. After histological confirmation, HPV DNA detection was performed by SPF-10/DEIA/LiPA25 (version1). Logistic regression models were used for estimating the adjusted relative contributions (RC) of HPV16 and of HPV18 over time. Among 4,771 HPV DNA positive ICC cases, HPV16 and HPV18 were the two most common HPVs in all the decades with no statistically significant variations of their adjusted-RC from 1940–59 to 2000–07 (HPV16—from 61.5 to 62.1%, and HPV18—from 6.9 to 7.2%). As well, the RC of other HPV types did not varied over time. In the stratified analysis by histology, HPV16 adjusted-RC significantly increased across decades in adenocarcinomas. Regarding age, cases associated to either HPV16, 18 or 45 were younger than those with other HPV types in all the evaluated decades. The observed stability on the HPV type distribution predicts a high and stable impact of HPV vaccination in reducing the cervical cancer burden in future vaccinated generations.

Objective: Trastuzumab (Herceptin®), a recombinant, humanized, monoclonal antibody targeting HER2 is well established as an effective treatment for HER2-positive breast cancer. Evidence from developed countries showed that trastuzumab was cost-effective; but there are few evidences in developing countries. This study assesses the cost-effectiveness of adjuvant trastuzumab treatment in Colombia. Methods: A Markov health-state transition model was built to estimate clinical and economic outcomes in HER2-positive breast cancer with or without 12 months trastuzumab adjuvant chemotherapy over a lifetime perspective with annual transition cycles. The model incorporated five health states (diseasefree, local recurrence, distant recurrence, cardiac failure, and death). Baseline event rates and 3-year hazard ratio (HR=0.51, IC 95% 0.44-0.59; p

Latin America and the Caribbean have not yet developed strong clinical cancer research programmes. In order to improve this situation two international cancer organisations, the Latin American Society of Clinical Oncology (SLACOM) and the European Society of Medical Oncology (ESMO) worked closely with the Peruvian Cooperative Oncology Group (GECOPERU) and organised a clinical cancer research workshop held in Lima, Peru, in October 2015. Many oncologists from different Latin American countries participated in this gathering. The opportunities for and strengths of clinical oncology research in Latin American and Caribbean countries were identified as the widespread use of the Spanish language, the high cancer burden, growing access to information, improving patient education, access to new drugs for research centres, regional networks and human resources. However, there are still many weaknesses and problems including the long timeline for regulatory approval, lack of economic investment, lack of training and lack of personnel participating in clinical research, lack of cancer registries, insufficient technology and insufficient supplies for the diagnosis and treatment of cancer, few cancer specialists, low general levels of education and the negative attitude of government authorities towards clinical research.

BACKGROUND AND OBJECTIVES We report the 8-year follow-up of 34 patients aged ≥ 69 years old with NHL included in a phase IIb open-label randomized parallel groups study to evaluate the effectiveness of amifostine in preventing the toxicity of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP regime) . PATIENTS AND METHODS Patients were randomized to receive classical CHOP (cyclophosphamide 750 mg/ m 2 , doxorubicin 50 mg/m 2 , vincristine 1.4 mg/m 2 [maximum 2 mg] on day 1 and prednisone 100 mg/day for 5 days) or CHOP plus amifostine (6 cycles of amifostine 910 mg/m 2 on day 1). Efficacy (time to progression, TTP; disease-free survival, DFS; overall survival, OS) and toxicity endpoints were evaluated. RESULTS Thirty-four patients were randomized to A-CHOP (n = 18) or CHOP (n = 16). Patients with A-CHOP vs CHOP had significantly lower toxicity; neutropenia grade 4 ocurred in 13/92 (13%) vs 23/85 (27%, P = 0.007) cycles, febrile neutropenia in 3/92 A-CHOP (3%) vs 8/85 (10%, P = .056) CHOP cycles, hospitalization for toxicity in 4/92 (4%) A-CHOP vs 11/85 (13%, P = .05) CHOP cycles. Median hospitalization stay for toxicity was 5 days with A-CHOP vs 8 days with CHOP ( P = .05). There were no significant differences at 8 years in TTP (A-CHOP, 48.9% vs CHOP, 36.3%; P = .65), DFS (A-CHOP, 72.9% vs CHOP 55.6%; P = .50) and OS (A-CHOP, 44.3% vs CHOP, 54.4%). There was no long-term toxicity of clinical interest. The only prognostic factor identified to 8 years was the International Prognostic Index (IPI low/low intermediate risk vs high intermediate/high risk; HR = 2.98; CI 95%:1.01-8.77; P = .048). CONCLUSION These results show that amifostine can be added to the standard CHOP treatment schedule with less acute toxicity and without influencing the outcome.

El estudio y analisis de las precipitaciones se ha convertido en una herramienta vital para conocer el comportamiento temporal y espacial del recurso hidrico, tanto en terminos de disponibilidad, asi como de los posibles impactos asociados a los eventos extremos. El objetivo de esta investigacion fue evaluar las intensidades maximas (duracion D = 1 h y periodos de retorno T = 5 y 100 anos) y los montos anuales de precipitacion para diferentes latitudes y zonas climaticas de Chile, analizando la informacion de miles de bandas pluviograficas y la pluviometria anual de 49 estaciones de medicion. Ello, porque aun no es claro que las intensidades de precipitacion difieren latitudinalmente en el pais, asi como lo hacen los montos anuales de las lluvias. Asimismo, no hay evidencia cientifica de los rangos y montos de ambas variables. Asi, se utilizo la funcion de Gumbel y formulas matematicas para desarrollar las curvas intensidad-duracion-frecuencia (IDF) de cada estacion. Los valores minimos y maximos de intensidad de precipitacion registrados para T = 100 anos, fueron 8,79 (zona hiperarida) y 40,17 mm h-1 (zona subhumeda-humeda). Respecto al monto anual de precipitaciones, los valores minimos y maximos fueron 43,9 (zona hiperarida) y 3891,0 mm ano-1 (zona humeda) respectivamente. Adicionalmente, la intensidad maxima real registrada en cada estacion fue analizada para determinar su probabilidad de excedencia. Asimismo, se realizaron comparaciones multiples para detectar diferencias significativas entre las estaciones de medicion y las diferentes zonas climaticas, mediante el test no parametrico Kruskal Wallis (alfa = 0,05). Las diferencias entre los valores maximos y minimos registrados en la totalidad de las estaciones analizadas pueden superar las 80 veces, para el caso de los montos anuales de las lluvias, y pueden llegar hasta 4,5 veces para el caso de las intensidades de precipitacion (T = 100 anos). Sin embargo, se encontraron valores maximos similares de intensidad de precipitacion en diferentes latitudes y altitudes del territorio nacional. Por tanto, se concluye que un mayor monto anual de lluvia no necesariamente involucra una mayor intensidad de precipitacion

Summary Background Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. Methods Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. Findings 22 661 paraffin-embedded samples were obtained from 14 249 women. 10 575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90–92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70–72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92–96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6–50·4], 48·2 years [47·3–49·2], 46·8 years [46·6–48·1], and 55·5 years [54·9–56·1], respectively). Interpretation To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45. Funding Spanish grants from Instituto de Salud Carlos III, Agencia de Gestio d'Ajuts Universitaris i de Recerca, Marato de TV3 Foundation, and unrestricted grants from GlaxoSmithKline Biologicals, Sanofi Pasteur MSD, and Merck.

Molecular classification is an excellent prognostic and predictive method in breast cancer (BC). In this study. we evaluated differences in clinicopathologic features and overall survival (OS) in four BC molecular subtypes: luminal A, luminal B, basal cell-like, and HER2/neu.Immunohistochemical evaluation of estrogen receptor (ER), progesterone receptor (PgR), and HER2 was performed using a Peruvian hospital database of 1198 BC patients who were diagnosed between 2000 and 2002. Overall survival was calculated.Out of 1198 patients with invasive BC, 49.3% were luminal A; 13.2%, luminal B; 21.3%, basal-like; and 16.2%, HER2. The mean of age at diagnosis was 51.5 years for luminal A; 49.6 for luminal B; 49.5 for basal-like; and 49.4 for HER2. The HER2 subtype showed 63.7% positive lymph nodes, 42.3% stage III and 9.7% stage IV cases. Basal subtypes showed the highest prevalence of a poorly differentiated phenotype (70.3%). Average follow-up was 60 months. Five-year OS was significantly different between all 4 groups (P.0001); luminal A had the highest OS, followed by luminal B, basal-like; and HER2. Results are compared with other population studies.This study shows significant differences between the distribution of molecular subtypes and clinicopathologic features. Immunohistochemistry is useful in the clinical management of BC patients.