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Summary Background Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding Cancer Research UK.

Submitted by Wiqlifi Bruno de Freitas Melo (wbruno@ufersa.edu.br) on 2018-12-04T21:14:42Z No. of bitstreams: 1 ArthurASO_DISSERT.pdf: 1294160 bytes, checksum: d619a981dc40e2eeb43c658c084c12ac (MD5) Approved for entry into archive by Vanessa Christiane (referencia@ufersa.edu.br) on 2019-02-15T11:46:35Z (GMT) No. of bitstreams: 1 ArthurASO_DISSERT.pdf: 1294160 bytes, checksum: d619a981dc40e2eeb43c658c084c12ac (MD5) Approved for entry into archive by Vanessa Christiane (referencia@ufersa.edu.br) on 2019-02-15T11:46:53Z (GMT) No. of bitstreams: 1 ArthurASO_DISSERT.pdf: 1294160 bytes, checksum: d619a981dc40e2eeb43c658c084c12ac (MD5) Made available in DSpace on 2019-02-15T11:47:11Z (GMT). No. of bitstreams: 1 ArthurASO_DISSERT.pdf: 1294160 bytes, checksum: d619a981dc40e2eeb43c658c084c12ac (MD5) Previous issue date: 2018-08-17 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES fósforo remanescente mede a quantidade de P que permanece na solução de equilíbrio em resposta a uma concentração de P adicionada ao solo. No Brasil, a determinação do P remanescente é feita utilizando uma solução de CaCl2 a 0,01 mol L-1 contendo 60 mg L-1 de P numa relação solo/solução de 1:10. Entretanto, essa concentração pode ser elevada e inadequada para os solos da região Nordeste do Brasil, uma vez que os mesmos possuem baixa capacidade de sorção de fósforo, quando comparados aos solos das demais regiões do Brasil. Neste trabalho, objetivou-se avaliar o efeito de diferentes concentrações iniciais de P da solução de equilíbrio utilizada para a análise do P-rem em 52 solos da região Nordeste do Brasil. Foram testadas concentrações iniciais de 20, 30, 40, 50 e 60 mg L-1 de P da solução de equilíbrio, para a determinação do P-rem em 52 amostras de solos representativos da região Nordeste do Brasil. A determinação do P remanescente seguiu a metodologia proposta por Alvarez et al. (2000). Os solos com maiores teores de argila apresentaram baixos valores de P remanescente, isso provavelmente por esses solos apresentarem maior CMAP em relação aos demais. Nos solos estudados, o aumento da concentração inicial de P na solução de equilíbrio aumentou a média dos valores de P-rem encontrados e, consequentemente, diminuiu o coeficiente de variação (CV) desses valores. Os valores de CV para os solos estudados diminuíram em quase 1% para cada aumento de 1 mg L-1 de P na solução de equilíbrio. Nos solos estudados, o aumento da concentração inicial de P na solução de equilíbrio aumentou a média dos valores de P-rem encontrados e, consequentemente, diminuiu o coeficiente de variação desses valores. Portanto recomenda-se a concentração inicial de P na solução de equilíbrio de 60 mg L-1 de P, para a determinação do P remanescente em solos da região Nordeste do Brasil The remaining phosphorus measures the amount of P remaining in the equilibrium solution in response to a P concentration added to the soil. In Brazil, determination of the remaining P is done using a solution of 0.01 mol L-1 CaCl2 containing 60 mg L-1 of P in a soil / solution ratio of 1:10. However, this concentration may be high and unsuitable for the soils of the Northeast region of Brazil, since they have low phosphorus sorption capacity when compared to the soils of the other regions of Brazil. The objective of this work was to evaluate the effect of different initial concentrations of P of the equilibrium solution used for P-rem analysis in 52 soils of the Northeast region of Brazil. Initial concentrations of 20, 30, 40, 50 and 60 mg L-1 of P of the equilibrium solution were tested for the determination of Prem in 52 representative soil samples from the Northeast region of Brazil. The determination of the remaining P followed the methodology proposed by Alvarez et al. (2000). Soils with higher clay contents showed low values of P remaining, probably because these soils presented higher CMAP in relation to the others. In the studied soils, the increase in the initial concentration of P in the equilibrium solution increased the mean P-values found and consequently decreased the coefficient of variation (CV) of these values. The CV values for the studied soils decreased by almost 1% for each increase of 1 mg L-1 of P in the equilibrium solution. In the studied soils, the increase of the initial concentration of P in the equilibrium solution increased the mean of the P-values found and, consequently, the coefficient of variation of these values decreased. Therefore, the initial concentration of P in the equilibrium solution of 60 mg L-1 of P is recommended for the determination of the remaining P in soils of the Northeast region of Brazil