Prolongation of overall treatment time as a cause of treatment failure in early breast cancer: an analysis of the UK START (Standardisation of Breast Radiotherapy) trials of radiotherapy fractionation

AbstractBackgroundTests of tumour treatment time effect in patients prescribed post-operative radiotherapy for early breast cancer have focussed on time to start of radiotherapy rather than overall treatment time. The START randomised trials of radiotherapy fractionation provide an opportunity to directly estimate the effect of treatment acceleration.MethodsBetween 1986 and 2002, a total of 5861 women with early breast cancer were recruited into the UK START pilot (START-P), START-A and START-B randomised trials. START-P and START-A tested 13 fractions of 3.0–3.3Gy against 25 fractions of 2.0Gy with a fixed treatment duration of 5weeks for all schedules; START-B tested 15 fractions of 2.67Gy in 3weeks against 25 fractions of 2.0Gy over 5weeks. Estimates of the effect of length of treatment for local–regional relapse and for a measure of late normal tissue effects (change in photographic breast appearance, for patients following breast conserving surgery) were obtained from Cox proportional hazards regression analyses stratified according to trial.ResultsAt a median follow-up of 10years, 444/5831 (7.6%) patients with data available had a local–regional relapse, and 1135/3185 (35.6%) had mild or marked change in photographic breast appearance by 5years. Adjusting for prognostic factors, the estimate of the overall treatment time effect for local–regional relapse was 0.60Gy/day (95%CI 0.10 to 1.18Gy/day, p=0.02), and 0.14Gy/day (95%CI −0.09 to 0.34Gy/day, p=0.29) for change in photographic breast appearance.ConclusionsCombined analysis of the START trials generates the hypothesis that overall treatment time is a significant determinant of local cancer control after adjuvant whole breast radiotherapy, with approximately 0.6Gy per day ‘wasted’ in compensating for tumour cell proliferation

Relative validity of a web-based food frequency questionnaire for patients with type 1 and type 2 diabetes in Denmark

BACKGROUND: Diet has an important role in the management of diabetes. However, little is known about dietary intake in Danish diabetes patients. A food frequency questionnaire (FFQ) focusing on most relevant nutrients in diabetes including carbohydrates, dietary fibres and simple sugars was developed and validated. OBJECTIVES: To examine the relative validity of nutrients calculated by a web-based food frequency questionnaire for patients with diabetes. DESIGN: The FFQ was validated against a 4-day pre-coded food diary (FD). Intakes of nutrients were calculated. Means of intake were compared and cross-classifications of individuals according to intake were performed. To assess the agreement between the two methods, Pearson and Spearman's correlation coefficients and weighted kappa coefficients were calculated. SUBJECTS: Ninety patients (64 with type 1 diabetes and 26 with type 2 diabetes) accepted to participate in the study. Twenty-six were excluded from the final study population. SETTING: 64 volunteer diabetes patients at the Steno Diabetes Center. RESULTS: Intakes of carbohydrates, simple sugars, dietary fibres and total energy were higher according to the FFQ compared with the FD. However, intakes of nutrients were grossly classified in the same or adjacent quartiles with an average of 82% of the selected nutrients when comparing the two methods. In general, moderate agreement between the two methods was found. CONCLUSION: The FFQ was validated for assessment of a range of nutrients. Comparing the intakes of selected nutrients (carbohydrates, dietary fibres and simple sugars), patients were classified correctly according to low and high intakes. The FFQ is a reliable dietary assessment tool to use in research and evaluation of patient education for patients with diabetes

Isolation and characterization of microsatellite markers in the spiny lobster, Panulirus echinatus Smith, 1869 (Decapoda: Palinuridae) by Illumina MiSeq sequencing.

The isolation and characterization of 17 polymorphic microsatellite loci from the spiny lobster Panulirus echinatus (Decapoda: Palinuridae) by Illumina MiSeq sequencing is described..

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation

Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of Tpot in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1–N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88±4%) than in the CF (57±9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60±10% vs 46±9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. Tpot showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of Tpot as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between Tpot and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively

Caracterização da estrutura genética do pinhão manso (Jatropha curcas L.): isolamento de fragmentos de dna enriquecidos com sequências de microssatélites.

O pinhão manso (Jatropha curcas) é uma planta oleaginosa que vem se destacando por apresentar um alto potencial na produção de biocombustíveis. Por este motivo o interesse em sua exploração comercial vem aumentado consideravelmente. Assim, torna-se imprescindível o desenvolvimento de tecnologias moleculares de monitoramento e seleção de populações naturais e cultivares. Nesse contexto, marcadores moleculares como os microssatélites são amplamente utilizados. No entanto, os genomas de organismos eucariontes são muito amplos e, assim, o isolamento de seqüências de microssatélites específicas, que possam atuar como marcadores, torna-se uma tarefa complexa. O presente trabalho teve como objetivo estabelecer um protocolo para isolar fragmentos de DNA específicos contendo loci de microssatélites. Este procedimento tem por finalidade aumentar a incidência das seqüências alvo para futura clonagem. Foram testadas diferentes enzimas de restrição e sondas de DNA para o reconhecimento e captura de fragmentos contendo seqüências de microssatélites. Os resultados obtidos mostraram que a enzima RsaI apresentou o melhor padrão de digestão do DNA, enquanto as melhores sondas foram as compostas pelas repetições (AATG)6, (AAAC)6, (AATC)6 e (AAAG)6. Estes procedimentos constituem etapas fundamentais no processo de isolamento de microssatélites e contribuirão para a caracterização da estrutura genética do pinhão manso. Com isto, será possível avaliar quais os estoques mais adequados para seleção de linhagens viáveis para o cultivo, visando ganhos na produtividade