Improving the care of children with advanced cancer by using an electronic patient-reported feedback intervention : results from the PediQUEST randomized controlled trial.

This study aimed to determine whether feeding back patient-reported outcomes (PROs) to providers and families of children with advanced cancer improves symptom distress and health-related quality of life (HRQoL).

My road ahead study protocol: a randomised controlled trial of an online psychological intervention for men following treatment for localised prostate cancer

There is a need for psychosocial interventions for men with prostate cancer to promote adaptive coping with the challenges and distress associated with diagnosis, treatment and recovery. In addition, interventions are needed that help to overcome barriers to psychosocial treatment such as limited face-to-face psychosocial support services, a shortage of adequately trained professionals, geographical distance, perceived and personal stigma and a preference for consumer-centric and self-directed learning. My Road Ahead is an online cognitive behaviour therapy (CBT) intervention for prostate cancer. This protocol describes a randomised controlled trial (RCT) that will evaluate the efficacy of this online intervention alone, the intervention in combination with a moderated online forum, and the moderated online forum alone.

PET imaging of tumours with a 64Cu labeled macrobicyclic cage amine ligand tethered to Tyr3-octreotate

The use of copper radioisotopes in cancer diagnosis and radionuclide therapy is possible using chelators that are capable of binding Cu(II) with sufficient stability in vivo to provide high tumour-to-background contrast. Here we report the design and synthesis of a new bifunctional chelator, 5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid (MeCOSar), that forms copper complexes of exceptional stability by virtue of a cage amine (sarcophagine) ligand and a new conjugate referred to as SarTATE, obtained by the conjugation of MeCOSar to the tumour-targeting peptide Tyr(3)-octreotate. Radiolabeling of SarTATE with (64)Cu(II), a radioisotope suitable for positron emission tomography (PET), was fast (~20 min), easily performed at room temperature and consistently resulted in high radiochemical purity (>99%). In vitro and in vivo evaluation of (64)CuSarTATE demonstrated its high selectivity for tumour cells expressing somatostatin receptor 2 (sstr2). Biodistribution and PET imaging comparisons were made between (64)CuSarTATE and (64)Cu-labeled DOTA-Tyr(3)-octreotate ((64)CuDOTATATE). Both radiopharmaceuticals showed excellent uptake in sstr2-positive tumours at 2 h post-injection. While tumour uptake of (64)CuDOTATATE decreased significantly at 24 h, (64)CuSarTATE activity was retained, improving contrast at later time points. (64)CuSarTATE accumulated less than (64)CuDOTATATE in the non-target organs, liver and lungs. The uptake of (64)CuSarTATE in the kidneys was high at 2 h but showed significant clearance by 24 h. The new chemistry and pre-clinical evaluation presented here demonstrates that MeCOSar is a promising bifunctional chelator for Tyr(3)-octreotate that could be applied to a combined imaging and therapeutic regimen using a combination of (64)Cu- and (67)CuSarTATE complexes, owing to improved tumour-to-non-target organ ratios compared to (64)CuDOTATATE at longer time points.

Postchemotherapy and tumor-selective targeting with the La-specific DAB4 monoclonal antibody relates to apoptotic cell clearance

Early identification of tumor responses to treatment is crucial for devising more effective and safer cancer treatments. No widely applicable, noninvasive method currently exists for specifically detecting tumor cell death after cytotoxic treatment and thus for predicting treatment outcomes.

The ProCaSP study: quality of life outcomes of prostate cancer patients after radiotherapy or radical prostatectomy in a cohort study urological oncology

Background: This study describes and compares health-related quality of life (HRQOL) of prostate cancer patients who received either radical prostatectomy (nerve-sparing, nsRP, or non-nerve-sparing, nnsRP) or radiotherapy (external RT, brachytherapy, or both combined) for treatment of localised prostate cancer. Methods: The prospective, multicenter cohort study included 529 patients. Questionnaires included the IIEF, QLQ-C30, and PORPUS-P. Data were collected before (baseline), three, six, twelve, and twenty-four months after treatment. Differences between groups' baseline characteristics were assessed; changes over time were analysed with generalised estimating equations (GEE). Missing values were treated with multiple imputation. Further, scores at baseline and end of follow-up were compared to German reference data. Results: The typical time trend was a decrease of average HRQOL three months after treatment followed by (partial) recovery. RP patients experienced considerable impairment in sexual functioning. The covariate-adjusted GEE identified a significant - but not clinically relevant - treatment effect for diarrhoea (b∈=∈7.0 for RT, p∈=∈0.006) and PORPUS-P (b∈=∈2.3 for nsRP, b∈=∈2.2 for RT, p∈=∈0.045) compared to the reference nnsRP. Most of the HRQOL scores were comparable to German norm values. Conclusions: Findings from previous research were reproduced in a specific setting of a patient cohort in the German health care system. According to the principle of evidence-based medicine, this strengthens the messages regarding treatment in prostate cancer and its impacts on patients' health-related quality of life. After adjustment for baseline HRQOL and other covariates, RT patients reported increased symptoms of diarrhoea, and nnsRP patients decreased prostate-specific HRQOL. RP patients experienced considerable impairment in sexual functioning. These differences should be taken into account by physicians when choosing the best therapy for a patient.

Implementing novel models of posttreatment care for cancer survivors: Enablers, challenges and recommendations

AIM: The American Society of Clinical Oncology and US Institute of Medicine emphasize the need to trial novel models of posttreatment care, and disseminate findings. In 2011, the Victorian State Government (Australia) established the Victorian Cancer Survivorship Program (VCSP), funding six 2-year demonstration projects, targeting end of initial cancer treatment. Projects considered various models, enrolling people of differing cancer types, age and residential areas. We sought to determine common enablers of success, as well as challenges/barriers. METHODS: Throughout the duration of the projects, a formal "community of practice" met regularly to share experiences. Projects provided regular formal progress reports. An analysis framework was developed to synthesize key themes and identify critical enablers and challenges. Two external reviewers examined final project reports. Discussion with project teams clarified content. RESULTS: Survivors reported interventions to be acceptable, appropriate and effective. Strong clinical leadership was identified as a critical success factor. Workforce education was recognized as important. Partnerships with consumers, primary care and community organizations; risk stratified pathways with rapid re-access to specialist care; and early preparation for survivorship, self-management and shared care models supported positive project outcomes. Tailoring care to individual needs and predicted risks was supported. Challenges included: lack of valid assessment and prediction tools; limited evidence to support novel care models; workforce redesign; and effective engagement with community-based care and issues around survivorship terminology. CONCLUSION: The VCSP project outcomes have added to growing evidence around posttreatment care. Future projects should consider the identified enablers and challenges when designing and implementing survivorship care.

Pseudomonas aeruginosa genotypes acquired by children with cystic fibrosis by age 5-years

BACKGROUND: We describe Pseudomonas aeruginosa acquisitions in children with cystic fibrosis (CF) aged ≤5-years, eradication treatment efficacy, and genotypic relationships between upper and lower airway isolates and strains from non-CF sources. METHODS: Of 168 CF children aged ≤5-years in a bronchoalveolar lavage (BAL)-directed therapy trial, 155 had detailed microbiological results. Overall, 201/271 (74%) P. aeruginosa isolates from BAL and oropharyngeal cultures were available for genotyping, including those collected before and after eradication therapy. RESULTS: Eighty-two (53%) subjects acquired P. aeruginosa, of which most were unique strains. Initial eradication success rate was 90%, but 36 (44%) reacquired P. aeruginosa, with genotypic substitutions more common in BAL (12/14) than oropharyngeal (3/11) cultures. Moreover, oropharyngeal cultures did not predict BAL genotypes reliably. CONCLUSIONS: CF children acquire environmental P. aeruginosa strains frequently. However, discordance between BAL and oropharyngeal strains raises questions over upper airway reservoirs and how to best determine eradication in non-expectorating children.

Childhood cancer in Argentina: survival 2000–2007

 Introduction: Information on the epidemiology of childhood cancer in Latin America is limited. The Argentinean Oncopaediatric Registry (ROHA) is a population-based registry active since 2000. This paper describes the 3-year survival experience of children diagnosed with cancer in Argentina during 2000–2007 by major morphological subgroup, age, sex, and geographical region of residence.
Methods: Newly diagnosed paediatric cancer cases are registered in ROHA (estimated coverage is 93% of the country’s cases). Three-year overall survival was estimated using Kaplan–Meier methods. Univariate Cox models were used to compare subgroup survival.
Results: Between 2000 and 2007, a total of 10,181 new cancer diagnoses in children aged 0–14 years were reported to the registry. Three-year overall survival (95%CI) for all cancers was 61.7% (60.7; 62.7). Specific survival for the most frequent morphological types was: leukaemias 63.3% (61.6; 64.9), lymphomas and related neoplasms 75.3% (72.7; 77.7), brain neoplasms 46.3% (43.9; 48.7), soft-tissue sarcomas 52.3% (48.0; 56.5), neuroblastomas 49.6% (44.6; 54.3), renal tumours 76.7% (72.2; 80.6), and malignant bone tumours 47.2% (42.3; 51.9). Overall survival was associated with age but not sex and varied by geographical region. Compared to other regions, patients who resided in the capital city had a significantly higher survival: 69.6% (65.8; 73.0) versus 63.5% (59.4; 67.4) in Patagonia, 63.2% (61.9; 64.5) in the central region, 58.0% (54.2; 61.7) in Cuyo, 55.6% (52.5; 58.6) in the north-east, and 55.4% (52.4; 58.2) in the north-west (all P values <0.005).
Conclusions: Of children diagnosed with cancer in Argentina, 62% survived at least 3 years after diagnosis. Even though this figure is lower than that reported for more developed countries, survival patterns by diagnosis, age and sex were quite similar. Survival was lower in the two northern regions, which are areas with higher poverty levels.

Predictors of adherence to a 12-week exercise program among men treated for prostate cancer: ENGAGE study

Understanding the factors that influence adherence to exercise programs is necessary to develop effective interventions for people with cancer. We examined the predictors of adherence to a supervised exercise program for participants in the ENGAGE study - a cluster randomized controlled trial that assessed the efficacy of a clinician-referred 12-week exercise program among men treated for prostate cancer. Demographic, clinical, behavioral, and psychosocial data from 52 participants in the intervention group were collected at baseline through self-report and medical records. Adherence to the supervised exercise program was assessed through objective attendance records. Adherence to the supervised exercise program was 80.3%. In the univariate analyses, cancer-specific quality of life subscales (role functioning r = 0.37, P = 0.01; sexual activity r = 0.26, P = 0.06; fatigue r = -0.26, P = 0.06, and hormonal symptoms r = -0.31, P = 0.03) and education (d = -0.60, P = 0.011) were associated with adherence. In the subsequent multivariate analysis, role functioning (B = 0.309, P = 0.019) and hormonal symptoms (B = -0.483, P = 0.054) independently predicted adherence. Men who experienced more severe hormonal symptoms had lower levels of adherence to the exercise program. Those who experienced more positive perceptions of their ability to perform daily tasks and leisure activities had higher levels of adherence to the exercise program. Hormonal symptoms and role functioning need to be considered when conducting exercise programs for men who have been treated for prostate cancer.

Patterns of surgical treatment of breast cancer in Victoria

We analysed data on admissions to Victorian public hospitals for surgical treatment of breast cancer over the period July 1985 to December 1988. Of the 2993 women admitted, 28.7% received breast-preserving surgery. The probability of a woman being treated conservatively was dependent on age, with women aged less than 50 or more than 70 years more likely to receive breast-preserving surgery than women aged 50-69. There was an age-specific change, of marginal statistical significance, in the proportion of women receiving breast-preserving surgery over the period. The public hospitals admissions database is a potentially useful means of monitoring patterns of surgical treatment.

Contribuição ao estudo das hepatectomias parciais com oclusão do fluxo sanguíneo aferente

O tratamento cirúrgico dos tumores hepáticos tem sido um grande desafio na história evolutiva da cirurgia. No passado, as altas taxas de morbidade e mortalidade limitavam sua aplicação como opção terapêutica. O refinamento da técnica de ressecção hepática está associado a menores índices de mortalidade e morbidade peri-operatória e, embora, a mortalidade tenha sido reduzida a menos de 10% nos serviços especializados, a morbidade ainda é bastante significativa, sendo que a hemorragia grave e a embolia aérea permanecem como complicações graves das hepatectomias. O controle da perda sanguínea é o objetivo primordial durante este tipo de cirurgia. As técnicas descritas, com a finalidade de conter a hemorragia transoperatória, são aquelas associadas à redução do fluxo sanguíneo ao fígado, seja através da oclusão vascular aferente ou manobra de Pringle por clampeamento do pedículo hepático, seja por exclusão vascular total do órgão. Hepatectomias parciais podem ser realizadas com pequeno sangramento e, mesmo quando associadas a períodos prolongados de isquemia tecidual, não foram identificadas lesões parenquimatosas ou falência hepática persistente. A redução na necessidade de reposição de sangue, no período peri-operatório, está associada a menor morbidade e à diminuição significativa na incidência de sepse abdominal. O objetivo deste estudo foi o de avaliar uma série de hepatectomias parciais com oclusão do fluxo sanguíneo aferente, em pacientes portadores de patologias benignas e neoplasias malignas. Foram analisadas 60 hepatectomias em 59 pacientes com oclusão do fluxo sanguíneo aferente quanto a possíveis fatores de risco para morbidade e mortalidade, bem como a relação entre o tempo de isquemia hepática e a variação das transaminases, tempo de protrombina e bilirrubinas, e destes, com a evolução pós-operatória. A prevalência de complicações pós-operatórias foi de 43,3% e a mortalidade de 6,7%. O fator de risco significativo para mortalidade foi tempo cirúrgico mais prolongado, quando comparado com os pacientes que não foram a óbito. Para a morbidade pós-operatória, foram identificados como fatores de risco a idade acima de 60 anos, cirurgia por neoplasia maligna, parênquima hepático anormal, ou seja, presença de cirrose, esteatose ou colestase, perda sanguínea necessitando reposição de mais de uma unidade de sangue e outros procedimentos cirúrgicos concomitantes. Na análise multivariada por regressão logística, estes fatores de risco foram reduzidos, apenas, para presença de cirrose, esteatose ou colestase. O tempo de isquemia não apresentou relação com a morbi-mortalidade pós-operatória. A variação das transaminases foram mais acentuadas nos casos com maior tempo de isquemia, porém, retornaram aos níveis pré-operatórios em, aproximadamente, uma semana. Não houve variação de tempo de protrombina e bilirrubinas quanto ao tempo de isquemia. A variação de AST e ALT não foram diferentes entre os pacientes com e sem morbidade pós-operatória.

Prevalência da expressão imunoistoquímica da proteína p21 em adenocarcinoma do esôfago

INTRODUÇÃO: No mundo ocidental, a prevalência de adenocarcinoma da junção esofagogástrica vem crescendo nas últimas décadas. Atualmente, é aceito que o adenocarcinoma do esôfago se desenvolve de uma lesão pré-maligna: esôfago de Barrett. Este carcinoma é de difícil diagnóstico nos seus estágios iniciais, o que resulta em uma mortalidade significativa. O estudo da biologia molecular tem demonstrado que grande parte dos tumores malignos tem origem na interação entre o componente hereditário e influências externas, que em indivíduos predispostos podem ocasionar alterações genéticas que influenciem o controle da diferenciação e crescimento celular. O p21 (WAF1/CIP1) tem um papel fundamental na regulação do ciclo celular, e sua expressão imunoistoquímica tem sido estudada em diversos tumores, mostrando influência no prognóstico de várias neoplasias. OBJETIVO: Verificar a prevalência da expressão da proteína p21 em pacientes com adenocarcinoma de esôfago diagnosticados nos últimos cinco anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre (GCEE/HCPA). METODOLOGIA: A população em estudo foi constituída de 42 pacientes com adenocarcinoma de esôfago diagnosticados no GCEE/HCPA entre janeiro de 1998 e dezembro de 2002. A expressão da proteína p21 foi realizada por meio de imunoistoquímica, com anticorpo primário, p21, clone SX118, código M7202 da DAKO, e avaliada de acordo com o Sistema de Escore de Imunorreatividade (Immunoreactive scoring system – IRS). RESULTADOS: Foram estudados 42 pacientes. 83,3% eram do sexo masculino, com idade superior a 40 anos. Destes, 56,2% foram submetidos a procedimentos cirúrgicos com intenção curativa: Gastrectomia total e Esofagogastrectomia transiatal. Os demais foram submetidos à cirurgia paliativa ou não sofreram tratamento cirúrgico. Apenas cinco pacientes receberam tratamento adjuvante com quimioterapia e radioterapia, isoladas ou combinadas. Quanto ao estadiamento, 78,6% dos pacientes apresentavam doença avançada, estádios III e IV. Apenas 9 apresentaram positividade para o p21, quando considerado o Sistema de Escore de Imunorreatividade (em que p21+ é ³ 3). CONCLUSÃO: A proteína p21 esteve expressa em 9 dos 42 pacientes (21,4%) com adenocarcinoma de esôfago diagnosticados nos últimos cinco anos no Grupo de Cirurgia de Esôfago e Estômago do Hospital de Clínicas de Porto Alegre. Nessa casuística, o acúmulo de p21 não se mostrou essencial no processo de carcinogênese do adenocarcinoma esofágico.

Expressão de p53 e relação clínico-patológica no adenocarcinoma de reto

O adenocarcinoma colorretal é um dos tumores malignos mais freqüentes no mundo ocidental. Sua incidência varia mundialmente; nos Estados Unidos (EUA), é o terceiro câncer mais comum entre os homens e o segundo mais comum entre as mulheres, sendo a segunda causa de morte por câncer, superada apenas pelo tumor de pulmão. No Brasil, está entre as seis neoplasias mais freqüentes, ocupando a quarta posição em mortalidade. Os principais indicadores prognósticos do adenocarcinoma colorretal incluem a diferenciação histológica, profundidade de invasão e ocorrência de metástases. Recentemente, têm sido realizados diversos estudos usando técnicas de biologia molecular objetivando a identificação de novos parâmetros prognósticos. Entre estes, os fatores que regulam o ciclo celular influenciando no crescimento e mecanismo de apoptose têm demonstrado resultados promissores. O p53 é um gene supressor de tumores, localizado no braço curto do cromossomo 17; produz uma proteína chamada p53. Sua principal função é controlar pontos de checagem do ciclo celular, promover o reparo do DNA através do estímulo de outras proteínas (p21, por exemplo) e estimular a apoptose. Mutações deste gene produzem uma proteína p53 inativa que acumula nas células tumorais. A expressão desta proteína alterada é detectada em 30 a 70% dos tumores de reto e pode estar relacionada a mau prognóstico. O p53 é um dos genes mais comumente mutados no câncer humano. O objetivo deste estudo foi correlacionar a expressão imuno-histoquímica da proteína p53 com variáveis clínico-patológicas do adenocarcinoma de reto e sobrevida. Foram estudados 83 casos de pacientes operados no Hospital de Clínicas de Porto Alegre entre 1985 e 1997 através de reação imunohistoquímica utilizando anticorpo monoclonal Pab-1801 em amostras biológicas fixadas em formalina e armazenadas em blocos de parafina. Com um ponto de corte de 5%, 44 pacientes (53%) demonstraram expressão imunohistoquímica da proteína p53 maior que 5% e, com um ponto de corte de 20%, 36 pacientes (43,4%) demonstraram a expressão maior que 20%. Não houve associação estatisticamente significativa entre a expressão de p53 e as variáveis idade, gênero, localização, tamanho do tumor e comprometimento circunferencial. Encontramos associação entre p53 e óbito, recidiva local, metástases e recidiva total quando utilizado o ponto de corte de 20%, indicando um pior prognóstico nos pacientes com p53 positivos. Na análise multivariada em relação à sobrevida, o p53 teve poder prognóstico independente em relação às variáveis da classificação Astler- Coller e grau de diferenciação histológica da neoplasia.