Comparison of quality of life after stereotactic body radiotherapy and surgery for early-stage prostate cancer

Background: As the long-term efficacy of stereotactic body radiation therapy (SBRT) becomes established and other prostate cancer treatment approaches are refined and improved, examination of quality of life (QOL) following prostate cancer treatment is critical in driving both patient and clinical treatment decisions. We present the first study to compare QOL after SBRT and radical prostatectomy, with QOL assessed at approximately the same times pre- and post-treatment and using the same validated QOL instrument. Methods: Patients with clinically localized prostate cancer were treated with either radical prostatectomy (n = 123 Spanish patients) or SBRT (n = 216 American patients). QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) grouped into urinary, sexual, and bowel domains. For comparison purposes, SBRT EPIC data at baseline, 3 weeks, 5, 11, 24, and 36 months were compared to surgery data at baseline, 1, 6, 12, 24,and 36 months. Differences in patient characteristics between the two groups were assessed using Chi-squared tests for categorical variables and t-tests for continuous variables. Generalized estimating equation (GEE) models were constructed for each EPIC scale to account for correlation among repeated measures and used to assess the effect of treatment on QOL. Results: The largest differences in QOL occurred in the first 1-6 months after treatment, with larger declines following surgery in urinary and sexual QOL as compared to SBRT, and a larger decline in bowel QOL following SBRT as compared to surgery. Long-term urinary and sexual QOL declines remained clinically significantly lower for surgery patients but not for SBRT patients. Conclusions: Overall, these results may have implications for patient and physician clinical decision making which are often influenced by QOL. These differences in sexual, urinary and bowel QOL should be closely considered in selecting the right treatment, especially in evaluating the value of non-invasive treatments, such as SBRT.

Dificultad en la comunicación del riesgo de padecer cáncer hereditario.

Diferentes estudios han demostrado que, en ocasiones, los pacientes tienen dificultades a la hora de entender lo que el médico quiere comunicarles. El presente artículo intenta reflexionar sobre cuáles son los determinantes que pueden influir en el proceso de comunicación del riesgo en pacientes que tienen antecedentes familiares de cáncer y acuden a las Unidades de Consejo Genético en busca de asesoramiento. Existen estudios que señalan que los pacientes con antecedentes familiares de cáncer se preocupan por padecer dicha enfermedad. Sólo algunos de ellos han explorado cómo los pacientes entienden y perciben el concepto de riesgo y los posibles sesgos asociados a él. Como primeras aproximaciones, creemos que es necesario utilizar un lenguaje sencillo, claro y fácil de entender por parte de los pacientes, huyendo del lenguaje epidemiológico o médico. Del mismo modo es importante diseñar programas de formación psicoeducativos y material de soporte adecuado, así como el correcto manejo del counselling como herramienta principal de trabajo por parte de los profesionales y fomentar futuras investigaciones en este área determinada.

Sobre tránsitos, identidades y crecimiento postraumático en cáncer hereditario

A lo largo de la historia de la psico-oncología los conceptos de personalidad e identidad de los pacientes oncológicos se han utilizado frecuentemente tanto para explicar la aparición de la enfermedad como los cambios personales inducidos por la misma. Ya sea históricamente vinculado a los orígenes y causas en forma de personalidad que predispone al enfermar, o como transformación identitaria una vez el sujeto ha superado la enfermedad, las formas de ser constituyen también punto de arranque y destino de una parte importante del trabajo psicoterapéutico. Tras analizar las teorías socio-cognitivas de Janoff-Bulman y de Tedeschi y Calhoun sobre el fenómeno denominado crecimiento postraumático los autores se interrogan sobre el posible impacto de los modelos identarios y de crecimiento personal aplicados al ámbito del cáncer hereditario y el consejo genético.

Adenocarcinoma da próstata: a alteração hipoecogênica difusa da próstata é um achado ultra-sonográfico importante?

Avaliar se há associação entre a observação de alteração hipoecogênica difusa da próstata, com perda da demarcação entre a zona periférica e a glândula interna, e o diagnóstico de adenocarcinoma de próstata na biópsia prostática transretal. MATERIAIS E MÉTODOS: Avaliamos 143 homens com nível sérico de antígeno prostático específico maior do que 4 ng/ml. Todos os pacientes foram submetidos à ultra-sonografia endorretal e biópsia randomizada da próstata. RESULTADOS: Foi diagnosticado adenocarcinoma de próstata em 36,4% dos pacientes. A alteração hipoecogênica difusa da próstata, caracterizada por perda da demarcação entre a zona periférica e a glândula central, foi observada em 22 pacientes e correspondeu ao diagnóstico de adenocarcinoma de próstata em 21 deles (95,4%). CONCLUSÃO: A alteração hipoecogênica difusa da próstata constituiu um critério de suspeita ultra-sonográfica de adenocarcinoma de próstata altamente significativo, já que em 95,4% das próstatas que apresentavam essas características a biópsia foi positiva para adenocarcinoma de próstata

Localized prostate cancer in Norway, the United States, and Spain: between-country differences of variables before treatment among patients eligible for curative treatment

Between-country differences in medical and sociodemographic variables, and patient-related outcomes (PROs) before treatment might explain published variations of side effects after radical prostatecomy (RP) or radiotherapy (RAD) for prostate cancer (PCa). This hypothesis was tested among 1908 patients from the United States, Spain, and Norway. Significant between-country differences were observed for most factors investigated before treatment. The observations should be considered in comparison of the frequency and severity of internationally published studies. Background: In men with PCa, large variations of PROs after RP or high-dose RAD might be related to betweencountry differences of medical and sociodemographic variables, and differences in PROs before treatment in the sexual and urinary domains. Patients and Methods: In 1908 patients with localized PCa from Norway, the United States, or Spain, the relation between medical (prostate-specific antigen, Gleason score, cT-category) and sociodemographic variables (age, education, marital status) before treatment was investigated. Using the Expanded Prostate Cancer Index Composite questionnaire, PROs before treatment within the sexual and urinary domains were also considered. Results: Compared with the European patients, American patients were younger, fewer had comorbid conditions, and more had a high education level. Fifty-three percent of the US men eligible for RP had low-risk tumors compared with 42% and 31% among the Norwegian and the Spanish patients, respectively. Among the Spanish RAD patients, 54% had had low-risk tumors compared with 34% of the American and 21% of the Norwegian men planned for RAD, respectively. Compared with the European patients, significantly fewer US patients reported moderate or severe sexual dysfunction and related problems. In most subgroups, the number of patients with sexual or urinary dysfunction exceeded that of patients with bother related to the reported dysfunction. Conclusion: Statistically significant between-country differences were observed in medical and sociodemographic variables, and in PROs before treatment within the sexual and urinary domains. Large differences between reported dysfunction and related problems within the sexual and urinary domains indicate that dysfunction and bother should be reported separately in addition to calculation of summary scores. The documented differences, not at least regarding PROs, might in part explain the large variation of side effects after treatment evident in the medical literature

Metástase de câncer gástrico simulando neoplasia primária de pulmão: relato de caso e revisão da literatura

O adenocarcinoma gástrico apresenta, freqüentemente, disseminação por extensão direta para órgãos vizinhos. Metástases para sítios distantes, como o pulmão, são menos freqüentes, sugerindo usualmente outras doenças. O objetivo deste artigo é apresentar o caso de um paciente de 47 anos de idade, cujos exames de imagem (radiografias simples e tomografia computadorizada de tórax) apresentaram características sugestivas de neoplasia pulmonar primária e com diagnóstico simultâneo de câncer gástrico evidenciado pela endoscopia digestiva alta. A biópsia, guiada por fibrobroncoscopia, da massa torácica confirmou o diagnóstico de metástase pulmonar de adenocarcinoma gástrico. Além da apresentação do caso, é feita uma revisão do padrão de disseminação do câncer gástrico.

O perfil da mulher que se submete a mamografia em Goiânia: uma contribuição a "Bases para um programa de detecção precoce do câncer de mama"

Foi estudado o perfil de 2.000 mulheres que se submeteram a mamografia em um hospital público e uma clínica privada de Goiânia, GO. Os dados foram coletados em entrevista. As mulheres tinham, em média, 49 anos de idade, a maioria procedia da própria cidade, 11,5% nunca tinham amamentado e dois terços tinham amamentado por mais de seis meses. Terapia de reposição hormonal era utilizada por mais de 20%, e um quinto destas não havia se submetido a mamografia previamente. História de câncer de mama familiar foi relatada por 13,3% das examinadas no hospital público e por 7,5% das examinadas na instituição privada. Destas, 28,67% e 33,33%, respectivamente, não tinham mamografia preliminar. Rastreamento do câncer mamário foi a maior motivação para o exame. Grande parte das entrevistadas não havia se submetido a mamografia anteriormente, por falta de solicitação médica ou por a considerarem desnecessária na época do pedido.

Allosteric conversation in the androgen receptor ligand-binding domain surfaces

Androgen receptor (AR) is a major therapeutic target that plays pivotal roles in prostate cancer (PCa) and androgen insensitivity syndromes. We previously proposed that compounds recruited to ligand-binding domain (LBD) surfaces could regulate AR activity in hormone-refractory PCa and discovered several surface modulators of AR function. Surprisingly, the most effective compounds bound preferentially to a surface of unknown function [binding function 3 (BF-3)] instead of the coactivator-binding site [activation function 2 (AF-2)]. Different BF-3 mutations have been identified in PCa or androgen insensitivity syndrome patients, and they can strongly affect AR activity. Further, comparison of AR x-ray structures with and without bound ligands at BF-3 and AF-2 showed structural coupling between both pockets. Here, we combine experimental evidence and molecular dynamic simulations to investigate whether BF-3 mutations affect AR LBD function and dynamics possibly via allosteric conversation between surface sites. Our data indicate that AF-2 conformation is indeed closely coupled to BF-3 and provide mechanistic proof of their structural interconnection. BF-3 mutations may function as allosteric elicitors, probably shifting the AR LBD conformational ensemble toward conformations that alter AF-2 propensity to reorganize into subpockets that accommodate N-terminal domain and coactivator peptides. The induced conformation may result in either increased or decreased AR activity. Activating BF-3 mutations also favor the formation of another pocket (BF-4) in the vicinity of AF-2 and BF-3, which we also previously identified as a hot spot for a small compound. We discuss the possibility that BF-3 may be a protein-docking site that binds to the N-terminal domain and corepressors. AR surface sites are attractive pharmacological targets to develop allosteric modulators that might be alternative lead compounds for drug design.

Polymorphisms in DNA-repair genes in a cohort of prostate cancer patients from different areas in Spain: heterogeneity between populations as a confounding factor in association studies

Background: Differences in the distribution of genotypes between individuals of the same ethnicity are an important confounder factor commonly undervalued in typical association studies conducted in radiogenomics. Objective: To evaluate the genotypic distribution of SNPs in a wide set of Spanish prostate cancer patients for determine the homogeneity of the population and to disclose potential bias. Design, Setting, and Participants: A total of 601 prostate cancer patients from Andalusia, Basque Country, Canary and Catalonia were genotyped for 10 SNPs located in 6 different genes associated to DNA repair: XRCC1 (rs25487, rs25489, rs1799782), ERCC2 (rs13181), ERCC1 (rs11615), LIG4 (rs1805388, rs1805386), ATM (rs17503908, rs1800057) and P53 (rs1042522). The SNP genotyping was made in a Biotrove OpenArrayH NT Cycler. Outcome Measurements and Statistical Analysis: Comparisons of genotypic and allelic frequencies among populations, as well as haplotype analyses were determined using the web-based environment SNPator. Principal component analysis was made using the SnpMatrix and XSnpMatrix classes and methods implemented as an R package. Non-supervised hierarchical cluster of SNP was made using MultiExperiment Viewer. Results and Limitations: We observed that genotype distribution of 4 out 10 SNPs was statistically different among the studied populations, showing the greatest differences between Andalusia and Catalonia. These observations were confirmed in cluster analysis, principal component analysis and in the differential distribution of haplotypes among the populations. Because tumor characteristics have not been taken into account, it is possible that some polymorphisms may influence tumor characteristics in the same way that it may pose a risk factor for other disease characteristics. Conclusion: Differences in distribution of genotypes within different populations of the same ethnicity could be an important confounding factor responsible for the lack of validation of SNPs associated with radiation-induced toxicity, especially when extensive meta-analysis with subjects from different countries are carried out.