PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114).

BACKGROUND: The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease. METHODS: Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis. RESULTS: Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%. CONCLUSIONS: Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis. TRIAL REGISTRATION: The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792.

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.

Planning cancer control in Latin America and the Caribbean.

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.

Unfolding the role of the PI3K/AKT/MTOR pathway in male breast cancer: A pragmatic appraisal.

Breast cancer in men is rare, but a relevant public health issue, yielding a 25% higher risk of mortality comparing to female counterparts. The representation of males in clinical trials has been scarce and treatment decisions are based mainly on extrapolations from data in females. In the setting of estrogen-dependent metastatic disease, the use of everolimus has been seldom reported, although the PI3K/AKT/mTOR pathway seems to be a critical oncogenic driver. This paper dissects hallmark biological features of ER+/HER2-advanced male breast cancer, setting a comprehensive basis to promote personalized care, focusing on the potential of targeting the PI3K/AKT/mTOR pathway.

Immune Checkpoint Inhibitors in Breast Cancer: A Narrative Review.

Breast cancer is the most frequently diagnosed malignancy in patients worldwide and the main cause of cancer-related death. Though still incurable, metastatic breast cancer's prognosis has been considerably improved in the past 10 years due to the introduction of new targeted agents, such as immune checkpoint inhibitors (ICI). However, these medications are associated with unique side effects known as immune-mediated adverse events (irAE). In this paper, we review the clinical evidence for the use of ICIs in breast cancer, in both the metastatic as well as neoadjuvant/adjuvant setting, followed by a review of irAE most commonly seen, and the medications used to treat them. Our opinion is that any cancer specialist treating patients with breast cancer should be aware of these side effects for early detection and management, and oncologists should be the leaders of the multidisciplinary team that will take care of them.

PET/CT in Patients with Breast Cancer Treated with Immunotherapy.

Significant advances in breast cancer (BC) treatment have been made in the last decade, including the use of immunotherapy and, in particular, immune checkpoint inhibitors that have been shown to improve the survival of patients with triple negative BC. This narrative review summarizes the studies supporting the use of immunotherapy in BC. Furthermore, the usefulness of 2-deoxy-2-[18F]fluoro-D-glucose (2-[18F]FDG) positron emission/computerized tomography (PET/CT) to image the tumor heterogeneity and to assess treatment response is explored, including the different criteria to interpret 2-[18F]FDG PET/CT imaging. The concept of immuno-PET is also described, by explaining the advantages of mapping treatment targets with a non-invasive and whole-body tool. Several radiopharmaceuticals in the preclinical phase are referred too, and, considering their promising results, translation to human studies is needed to support their use in clinical practice. Overall, this is an evolving field in BC treatment, despite PET imaging developments, the future trends also include expanding immunotherapy to early-stage BC and using other biomarkers.

Endocrine therapy-based treatments in hormone receptor-positive/HER2-negative advanced breast cancer: systematic review and network meta-analysis.

BACKGROUND: Several endocrine therapy (ET)-based treatments are available for patients with advanced breast cancer. We assessed the efficacy of different ET-based treatments in patients with hormone receptor-positive/HER2-negative advanced breast cancer with endocrine-sensitive or endocrine-resistant disease. METHODS: We searched Medline and Cochrane Central Register of Controlled Trials up to 15 October 2019 and abstracts from major conferences from 2016 to October 2019. We included phase II/III randomised trials, comparing ≥2 ET-based treatments. Progression-free survival (PFS) and overall survival (OS) were analysed by network meta-analyses using MTC Bayesian models based on both fixed-effect and random-effect models; relative treatment effects were measured as HRs and 95% credibility intervals (CrI). All statistical tests were two-sided. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and this systematic review is registered in the PROSPERO database. RESULTS: 55 publications reporting on 32 trials (n=12 293 patients) were included. Regarding PFS in the endocrine sensitive setting (n=5200; 12 trials), the combination of cyclin-dependent kinases (CDK)4/6-inhibitors (CDK4/6i)+fulvestrant 500 mg (F500) was likely the most effective treatment (surface under the cumulative ranking curve (SUCRA)=97.3%), followed by CDK4/6i+aromatase inhibitor ±goserelin; there was no significant difference between them (HR 0.82; 95% CrI 0.54-1.25). Regarding OS (n=2157; five trials), the most effective treatment was probably CDK4/6i+F500 (SUCRA=97.3%); comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.63-0.95). Regarding PFS in the endocrine-resistant setting (n=6635; 20 trials), CDK4/6i+F500 was likely the most effective treatment (SUCRA=95.7%), followed by capivasertib+F500, without significant difference between them (HR 0.91; 95% CrI 0.60-1.36). For OS (n=4377; 11 trials), the most effective treatments were capivasertib+F500 (SUCRA=84.7%) and CDK4/6i+F500 (SUCRA=69.9%). Comparing CDK4/6i+F500 versus F500 held a HR of 0.77 (95% CrI 0.67-0.89). CONCLUSIONS: CDK4/6i+F500 is likely the best treatment option in both endocrine-sensitive and endocrine-resistant diseases for PFS, and in endocrine-sensitive patients for OS. Concerning OS in endocrine-resistant patients, capivasertib+F500 and CDK4/6i+F500 are likely the best treatments. PROSPERO REGISTRATION NUMBER: CRD42018104628.

First-line Treatment of Metastatic Renal Cell Carcinoma in the Immuno-oncology Era: Systematic Review and Network Meta-analysis.

Combination treatments with immuno-oncology (IO) agents and IO agents plus a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) have been approved for first-line treatment of patients with metastatic renal cell carcinoma (mRCC). No direct comparisons have been performed among these treatment options. We performed a systematic review and network meta-analysis to compare and rank the available regimens for first-line treatment in terms of survival benefit and efficacy. In accordance with the Preferred Reporting Items for Systematic Review statement, a systematic search of reported studies was performed in MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE up to May 31, 2019. Network meta-analysis models were adjusted using the Bayesian method. Four randomized clinical trials, with a total of 3758 patients, met the inclusion criteria. Considering systemic therapy, 1880 patients had received sunitinib and 550, 432, 442, and 454 patients had received ipilimumab plus nivolumab (ipi + nivo), pembrolizumab plus axitinib (pembro + axi), avelumab plus axitinib (avelu + axi), and atezolizumab plus bevacizumab (atezo + bev). No difference was found in overall survival between ipi + nivo and pembro + axi for the intention to treat population (hazard ratio [HR], 1.34; 95% credible interval [CrI], 0.92-1.97). No difference was found in progression-free survival among the treatments. The overall response rate (ORR) was superior with pembro + axi and avelu + axi compared with the ORR with the other treatments (atezo + bev vs. pembro + axi: HR, 0.66; 95% CrI, 0.52-0.84; ipi + nivo vs. pembro + axi: HR, 0.73; 95% CrI, 0.59-0.90; atezo + bev vs. avelu + axi: HR, 0.55; 95% CrI, 0.43-0.71; avelu + axi vs. ipi + nivo: HR, 1.66; 95% CrI, 1.31-2.12), with no differences across them (HR, 1.21; 95% CrI, 0.95-1.53). In the present indirect comparison, for an intention to treat population, we found no survival differences between pembro + axi and ipi + nivo. All treatments showed better progression-free survival compared with sunitinib that was similar among them. The combination of an IO agent (pembrolizumab or avelumab) and axitinib seemed to be the most effective therapy for the ORR.

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in BRCA1 Mutation Carriers.

PURPOSE: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. RESULTS: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. CONCLUSIONS: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.

Efficacy of Anti-HER2 Agents in Combination With Adjuvant or Neoadjuvant Chemotherapy for Early and Locally Advanced HER2-Positive Breast Cancer Patients: A Network Meta-Analysis.

BACKGROUND: Several (neo)adjuvant treatments for patients with HER2-positive breast cancer have been compared in different randomized clinical trials. Since it is not feasible to conduct adequate pairwise comparative trials of all these therapeutic options, network meta-analysis offers an opportunity for more detailed inference for evidence-based therapy. METHODS: Phase II/III randomized clinical trials comparing two or more different (neo)adjuvant treatments for HER2-positive breast cancer patients were included. Relative treatment effects were pooled in two separate network meta-analyses for overall survival (OS) and disease-free survival (DFS). RESULTS: 17 clinical trials met our eligibility criteria. Two different networks of trials were created based on the availability of the outcomes: OS network (15 trials: 37,837 patients); and DFS network (17 trials: 40,992 patients). Two studies-the ExteNET and the NeoSphere trials-were included only in this DFS network because OS data have not yet been reported. The concept of the dual anti-HER2 blockade proved to be the best option in terms of OS and DFS. Chemotherapy (CT) plus trastuzumab (T) and lapatinib (L) and CT + T + Pertuzumab (P) are probably the best treatment options in terms of OS, with 62.47% and 22.06%, respectively. In the DFS network, CT + T + Neratinib (N) was the best treatment option with 50.55%, followed by CT + T + P (26.59%) and CT + T + L (20.62%). CONCLUSION: This network meta-analysis suggests that dual anti-HER2 blockade with trastuzumab plus either lapatinib or pertuzumab are probably the best treatment options in the (neo)adjuvant setting for HER2-positive breast cancer patients in terms of OS gain. Mature OS results are still expected for the Aphinity trial and for the sequential use of trastuzumab followed by neratinib, the treatment that showed the best performance in terms of DFS in our analysis.

Expressed Gene Fusions as Frequent Drivers of Poor Outcomes in Hormone Receptor-Positive Breast Cancer.

We sought to uncover genetic drivers of hormone receptor-positive (HR+) breast cancer, using a targeted next-generation sequencing approach for detecting expressed gene rearrangements without prior knowledge of the fusion partners. We identified intergenic fusions involving driver genes, including PIK3CA, AKT3, RAF1, and ESR1, in 14% (24/173) of unselected patients with advanced HR+ breast cancer. FISH confirmed the corresponding chromosomal rearrangements in both primary and metastatic tumors. Expression of novel kinase fusions in nontransformed cells deregulates phosphoprotein signaling, cell proliferation, and survival in three-dimensional culture, whereas expression in HR+ breast cancer models modulates estrogen-dependent growth and confers hormonal therapy resistance in vitro and in vivo Strikingly, shorter overall survival was observed in patients with rearrangement-positive versus rearrangement-negative tumors. Correspondingly, fusions were uncommon (<5%) among 300 patients presenting with primary HR+ breast cancer. Collectively, our findings identify expressed gene fusions as frequent and potentially actionable drivers in HR+ breast cancer.Significance: By using a powerful clinical molecular diagnostic assay, we identified expressed intergenic fusions as frequent contributors to treatment resistance and poor survival in advanced HR+ breast cancer. The prevalence and biological and prognostic significance of these alterations suggests that their detection may alter clinical management and bring to light new therapeutic opportunities. Cancer Discov; 8(3); 336-53. ©2017 AACR.See related commentary by Natrajan et al., p. 272See related article by Liu et al., p. 354This article is highlighted in the In This Issue feature, p. 253.

Differential side effects profile in patients with mCRPC treated with abiraterone or enzalutamide: a meta-analysis of randomized controlled trials.

BACKGROUND: Abiraterone and enzalutamide are currently approved for mCRPC patients. Both drugs have distinct mechanisms of action and may have different toxicity profile. There are limited data comparing the side effects of abiraterone and enzalutamide. We performed a meta-analysis of randomized controlled trials (RCT) to better characterize the risk of adverse events associated with both drugs. METHODS: We performed a literature search on MEDLINE for studies reporting abiraterone and enzalutamide side effects from January 1966 to July 31, 2015. Abstracts presented at ASCO meetings from 2004 to 2015 were selected manually. Phase III RCT were included in analysis. We assessed the risk of adverse events reported in RCT by performing two meta-analyses: abiraterone-prednisone vs. placebo-prednisone (2,283 pts) and enzalutamide vs. placebo (2,914 pts). Summary of incidence, relative-risks (RR), and 95% confidence intervals (CI) were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. RESULTS: Overall, enzalutamide was not associated with all-grade (RR 1.06 - 95% CI 0.67-1.65) or grade ≥3 (RR 0.81 - 95% CI 0.28-2.33) cardiovascular events, but was associated with increased risk of all-grade fatigue (RR 1.29 - 95% CI 1.15-1.44). On the other hand, abiraterone was associated with increased risk of all-grade (RR 1.28 - 95% CI 1.06-1.55) and grade ≥3 (RR 1.76 - 95% CI 1.12-2.75) cardiovascular events, but was not associated with all-grade (RR 0.85 - 95% CI 0.58-1.23) or grade ≥3 (RR 1.07 - 95% CI 0.97-1.19) fatigue. CONCLUSIONS: In this meta-analysis, abiraterone was associated with an increased risk of cardiovascular events, while enzalutamide was associated with an increased risk of fatigue.

Estimation of Premature Deaths From Lack of Access to Anti-HER2 Therapy for Advanced Breast Cancer in the Brazilian Public Health System.

PURPOSE: Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic tumors treated in the public health system in Brazil do not have access to trastuzumab. This study aimed to estimate the impact of the lack of access to anti-HER2 therapies on the mortality of these patients. METHODS: On the basis of published data, the number of patients with HER2-positive advanced breast cancer in 2016 who should receive anti-HER2 targeted therapy was estimated. Three different treatment groups were considered for this hypothetical cohort: chemotherapy alone, chemotherapy plus trastuzumab, and chemotherapy plus trastuzumab and pertuzumab. The number of patients alive after 2 years of follow-up was estimated on the basis of the efficacy results of the pivotal trials considering these interventions. RESULTS: It was calculated that 2,008 women will be diagnosed with advanced HER2-positive breast cancer in Brazil in 2016. It was estimated that only 808 women would be alive in 2018 if they receive only chemotherapy (which is the treatment offered by the public health system). On the other hand, the bar rises to 1,408 women alive in 2018 if they receive chemotherapy plus trastuzumab and 1,576 women alive in 2018 if they receive the gold standard of chemotherapy plus trastuzumab and pertuzumab. CONCLUSION: Trastuzumab is included in the WHO's list of essential medications, but the Brazilian public health system does not yet provide this treatment to its population with advanced disease. The introduction of trastuzumab and pertuzumab would have a positive effect, preventing premature deaths in women with metastatic HER2-positive breast cancer in Brazil.

Inhaled corticosteroid treatment and growth of asthmatic children seen at outpatient clinics.

OBJECTIVE: To ascertain the effect of inhaled corticosteroid use on gain in height and weight of asthmatic pediatric outpatients. METHODS: A one-year prospective cohort study was carried out with 124 asthmatic children aged 3 to 16 years who were prescribed inhaled corticosteroids for at least 12 months, evaluating z-scores for height/age, weight/age, body mass index and parental target height for current age. Exclusion criteria were: birth weight less than 2,500 g, malnutrition, chronic diseases and systemic corticoid use for more than 7 consecutive days. RESULTS: The mean +/- standard deviation for z-scores for initial and final height/age were 0.06+/-1.2 and 0.01+/-1.2 (95%CI 0.05-0.11), respectively; for initial and final weight/age z-scores they were 0.6+/-1.5 and 0.5+/-1.5 (95%CI 1.84-6.6), respectively. These figures did not differ significantly (p = 0.199 and p = 0.808). There was also no loss in stature when children were stratified into well and poorly controlled asthma or into pubescent and non-pubescent groups. CONCLUSIONS: In comparison with the NCHS (National Center for Health Statistics) growth curves, there was no compromise to the height or body weight of children/adolescents using inhaled corticosteroids for more than 1 year at the doses recommended for asthma prevention.

Recomendações para a proteção da privacidade do paciente / Recommendations for the protection of patient privacy / Recomendaciones para la protección de la privacidad del paciente

Resumo A preocupação sobre aspectos bioéticos da privacidade do indivíduo e da privacidade dos dados de seus atendimentos é crescente no meio médico. Processos propedêuticos e terapêuticos atuais requerem envolvimento multidisciplinar de uma série de indivíduos, especialmente em se tratando de internações hospitalares. A transmissão e o armazenamento das informações clínicas e laboratoriais dos pacientes envolvem diferentes mídias, com problemas inerentes de acessibilidade e proteção da informação. Os autores sugerem situações hipotéticas que exemplificam problemas comumente abordados na atuação de comitê de bioética clínica, contextualizando-os no Brasil e no mundo, e sugerindo passos para minimizar potenciais problemas de quebra de privacidade e confidencialidade.

Abstract Concerns regarding the bioethical aspects of the privacy of the individual and the confidentiality of their medical treatment data is increasing in the medical community. The current preliminary clinical and therapeutic processes require the multidisciplinary involvement of a number of individuals, especially in the case of hospitalization. The transmission and storage of clinical and laboratory patient information involves different media, with inherent problems of accessibility and protection of information. The authors describe hypothetical situations that exemplify issues commonly addressed in the work of a clinical bioethics committee, contextualizing these problems in Brazil and globally, and suggest steps to minimize potential problems of the breaching of privacy and confidentiality.

Resumen La preocupación sobre los aspectos bioéticos de la privacidad del individuo y de la confidencialidad de los datos de su asistencia está aumentando en la comunidad médica. Los actuales procesos clínicos y terapéuticos requieren la participación multidisciplinar de una serie de personas, especialmente en el caso de las internaciones hospitalarias. La transmisión y el almacenamiento de informaciones clínicas y de laboratorio de los pacientes implican diferentes canales de comunicación, con los problemas inherentes de accesibilidad y protección de la información. Los autores aluden a situaciones hipotéticas que ejemplifican problemas comúnmente tratados en el desempeño de un comité de bioética clínica, contextualizándolos en Brasil y en el mundo, y sugiriendo medidas para minimizar los posibles problemas de violación de la privacidad y de la confidencialidad.

Rituximab monotherapy for splenic marginal zone lymphoma with villous lymphocytes: report on long-term disease control for two patients with recurrence after splenectomy.

CONTEXT: Splenic marginal zone lymphoma (SMZL) is a lymphoproliferative B-cell disorder that has a favorable prognosis, with estimated overall five-year survival of 70%. The majority of symptomatic patients undergo splenectomy, while a few receive first-line chemotherapy, especially with purine analogues. There are no specific treatment guidelines for patients for whom splenectomy fails to provide a cure. It is still unclear whether these patients should undergo cytotoxic chemotherapy, considering they have now a relapsed lymphoma (which is theoretically more aggressive), or whether they should be spared from treatments of greater toxicity, given that their disease usually develops with a more indolent course, even when it recurs. CASE REPORT: Here, we present two patients whose disease recurred after splenectomy and for whom rituximab monotherapy provided satisfactory treatment. From these cases, it can be suggested that postponement of cytotoxic treatments may be possible in at least some situations. It needs to be emphasized that the evidence to support this approach is based only on case reports, since there are no randomized clinical trials on this subject.

Rituximab monotherapy for splenic marginal zone lymphoma with villous lymphocytes: report on long-term disease control for two patients with recurrence after splenectomy / Monoterapia com rituximab no linfoma da zona marginal esplênico com linfócitos vilosos: relato de dois casos de pacientes com controle prolongado da doença depois de recidiva após esplenectomia

CONTEXT: Splenic marginal zone lymphoma (SMZL) is a lymphoproliferative B-cell disorder that has a favorable prognosis, with estimated overall five-year survival of 70 percent. The majority of symptomatic patients undergo splenectomy, while a few receive first-line chemotherapy, especially with purine analogues. There are no specific treatment guidelines for patients for whom splenectomy fails to provide a cure. It is still unclear whether these patients should undergo cytotoxic chemotherapy, considering they have now a relapsed lymphoma (which is theoretically more aggressive), or whether they should be spared from treatments of greater toxicity, given that their disease usually develops with a more indolent course, even when it recurs. CASE REPORT: Here, we present two patients whose disease recurred after splenectomy and for whom rituximab monotherapy provided satisfactory treatment. From these cases, it can be suggested that postponement of cytotoxic treatments may be possible in at least some situations. It needs to be emphasized that the evidence to support this approach is based only on case reports, since there are no randomized clinical trials on this subject.

CONTEXTO: Os linfomas da zona marginal esplênicos constituem uma desordem linfoproliferativa de células B que apresenta um prognóstico favorável, com sobrevida global de cinco anos estimada em 70 por cento. A maioria dos pacientes sintomáticos é submetida a esplenectomia enquanto alguns recebem quimioterapia terapêutica de primeira linha, especialmente com análogos de purinas. Não existem diretrizes específicas para o tratamento dos pacientes que falham à esplenectomia: ainda é incerto se deveriam ser tratados com quimioterapia citotóxica, em virtude de apresentarem um linfoma recidivado (e teoricamente mais agressivo) ou se deveriam ser poupados de um tratamento mais tóxico pelo fato de apresentarem uma doença que usualmente se desenvolve de forma mais indolente, mesmo quando recidivada. RELATO DE CASO: Nesta publicação, são apresentados dois casos nos quais a doença recidivou após esplenectomia e que foram satisfatoriamente tratados com monoterapia com rituximabe. A observação desses casos sugere que a postergação de tratamentos citotóxicos pode ser possível pelo menos em algumas situações. Cabe ressaltar que a evidência para essa conduta é embasada apenas em relatos de caso, uma vez que não existem ensaios clínicos randomizados a respeito desse tema.

Corticosteróides inalatórios e crescimento em crianças asmáticas ambulatoriais / Inhaled corticosteroid treatment and growth of asthmatic children seen at outpatient clinics

OBJETIVO: Verificar o efeito do uso de corticosteróides inalatórios no aumento estatural e ponderal de crianças asmáticas tratadas ambulatorialmente MÉTODOS: Foi realizado um estudo de coorte prospectivo de 1 ano, no qual 124 crianças asmáticas com 3 a 16 anos de idade que haviam recebido prescrição para uso de corticosteróides inalatórios há pelo menos 12 meses foram avaliadas quanto aos escore z altura/idade, peso/idade, índice de massa corporal e altura alvo parental estimada para a idade atual. Os critérios de exclusão foram: peso de nascimento menor que 2.500 g, desnutrição, doenças crônicas e uso de corticóide sistêmico por mais de 7 dias consecutivos. RESULTADOS: A média ± desvio padrão dos escores z altura/idade inicial e final foi, respectivamente, de 0,06±1,2 e 0,01±1,2, (IC95 por cento 0,05-0,11); dos escores z peso/idade inicial e final foi de 0,6±1,5 e 0,5±1,5, respectivamente (IC95 por cento 1,84-6,6). Esses valores não diferiram significativamente (p = 0,199 e p = 0,808). Quando estratificados em grupos bem e mal controlados da asma, púberes e não-púberes, também não houve perda estatural. CONCLUSÃO: Em relação às curvas NCHS (National Center for Health Statistics), não houve prejuízo na estatura e peso corporal de crianças/adolescentes que utilizaram corticosteróides inalatórios por mais de 1 ano nas doses preconizadas para prevenir asma.