Stage II/III rectal cancer with intermediate response to preoperative radiochemotherapy: Do we have indications for individual risk stratification?

<p>Abstract</p> <p>Background</p> <p>Response to preoperative radiochemotherapy (RCT) in patients with locally advanced rectal cancer is very heterogeneous. Pathologic complete response (pCR) is accompanied by a favorable outcome. However, most patients show incomplete response. The aim of this investigation was to find indications for risk stratification in the group of intermediate responders to RCT.</p> <p>Methods</p> <p>From a prospective database of 496 patients with rectal adenocarcinoma, 107 patients with stage II/III cancers and intermediate response to preoperative 5-FU based RCT (ypT2/3 and TRG 2/3), treated within the German Rectal Cancer Trials were studied. Surgical treatment comprised curative (R0) total mesorectal excision (TME) in all cases. In 95 patients available for statistical analyses, residual transmural infiltration of the mesorectal compartment, nodal involvement and histolologic tumor grading were investigated for their prognostic impact on disease-free (DFS) and overall survival (OS).</p> <p>Results</p> <p>Residual tumor transgression into the mesorectal compartment (ypT3) did not influence DFS and OS rates (p = 0.619, p = 0.602, respectively). Nodal involvement after preoperative RCT (ypN1/2) turned out to be a valid prognostic factor with decreased DFS and OS (p = 0.0463, p = 0.0236, respectively). Persistent tumor infiltration of the mesorectum (ypT3) and histologic tumor grading of residual tumor cell clusters were strongly correlated with lymph node metastases after neoadjuvant treatment (p < 0.001).</p> <p>Conclusions</p> <p>Advanced transmural tumor invasion after RCT does not affect prognosis when curative (R0) resection is achievable. Residual nodal status is the most important predictor of individual outcome in intermediate responders to preoperative RCT. Furthermore, ypT stage and tumor grading turn out to be additional auxiliary factors. Future clinical trials for risk-adapted adjuvant therapy should be based on a synopsis of clinicopathologic parameters.</p

Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study

The aim of this study was to investigate the efficacy and safety of chemoradiation using capecitabine and irinotecan as neoadjuvant therapy for patients with rectal cancer. Conventional radiation was given at daily fractions of 1.8 Gy on 5 days a week for a total dose of 55.8 (50.4+5.4) Gy. Concurrently, irinotecan 40 mg m−2 once weekly and capecitabine continuously at dose levels of 500, 650, 750 and 825 mg m−2 twice daily were administered. Surgery was performed 4–6 weeks following completion of chemoradiation. A total of 28 patients (3 UICC II, 25 UICC III) were enrolled and all received treatment. Dose-limiting toxicity was diarrhoea grade IV and hand–foot syndrome at the 825 mg m−2 dose level. The maximum tolerated dose of capecitabine was 750 mg m−2. Diarrhoea was the most common toxicity: grade III in nine patients. Two patients died, one due to pneumonia and one due to sudden cardiac death. A complete response and only microfocal residual tumour disease was achieved in four and three patients (27%). In all, 25 of 28 patients undergoing surgery, 24 (96%) had R0 resection. Preoperative chemoradiation based on continuous daily capecitabine and weekly irinotecan appears to tolerated and effective in patients with rectal cancer

A multi-centre pathologist survey on pathological processing and regression grading of colorectal cancer resection specimens treated by neoadjuvant chemoradiation

To ascertain the approach and degree of consensus of pathologists in the handling and regression grading of colorectal cancer resection specimens treated with neoadjuvant chemoradiation, a ten-part questionnaire was circulated to 18 gastrointestinal pathologists in eight countries. The questions were specific and addressed pertinent issues related to colorectal cancer with neoadjuvant chemoradiation. There is a lack of consensus on how to handle the specimen, number of sections taken, correlation with pre- and post-operative radiological imaging, and especially, regression grading schema employed. Consensus in the form of guidelines is required so that the pathological assessment of these specimens will provide clinically relevant information for patient management, irrespective of location

Ultrassom anorretal tri-dimensional pode selecionar pacientes com tumor no reto após neoadjuvância para cirurgia de preservação esfincteriana? Can three-dimensional anorectal ultrasound select patients with rectal tumor for sphincter-saving resection after post-chemoradiotherapy

OBJETIVO: Avaliar a resposta pós-quimioradioterapia-QT no tratamento do tumor no reto utilizando ultrassom anorretal tridimensional(US-3-D) visando definir a estratégia cirúrgica adequada. MÉTODO: Avaliou-se prospectivamente 32 pacientes com adenocarcinoma no reto médio e inferior. Realizou-se US-3-D para estadiamento e avaliação quanto à invasão no canal anal ou distância(cm) entre tumor e esfíncter anal interno-EAI: GrupoI-invasão no canal anal; GrupoII-distância menor-ou-igual 2cm, GrupoIII-distância maior 2. Foram encaminhados neoadjuvância e realizado US-3D após 50-55 dias. A escolha da estratégia cirúrgica baseou-se na resposta pós-QT e achados do US-3-D/pós-QT e comparado com histopatológico. RESULTADOS: O US-3-D/pós-QT coincidiu com histopatológico em 31/32, eficácia de 97%. Evidenciou-se 26/27 casos com lesão residual, sensibilidade de 96%, sendo 19(59%) resposta parcial e 07 (22%) sem resposta. Em 5/5 o US-3-D/pós-QT demonstrou resposta completa, especificidade e valor preditivo positivo 100%. Valor preditivo negativo 83% pois um(3%) caso inconclusivo. Realizou-se cirurgia de preservação esfincteriana em 16 pacientes (05 com resposta completa, 10 com resposta parcial e um inconclusivo) com margem maior que 2cm. Confirmados ao histopatológico com margem livre. O índice Kappa na avaliação de linfonodos demonstrou concordância substancial(87,5%). Conclui-se que o US-3D pode ser útil na escolha de pacientes que irão beneficiar-se com a cirurgia de preservação esfincteriana.<br>PROPOSAL: Evaluate the post-chemoradiotherapy response for treatment of rectal tumor using three-dimensional anorectal ultrasound-3D-US to determine the best surgical approach METHODS: 32 patients with lower and middle rectal cancer were prospectively staged using 3D-US to identify anal canal invasion and the distance(cm) between tumor and the internal anal sphincter-IAS, Group l:with anal canal invasion; Group II-with distance =2cm; Group III-with distance >2. They were submitted to neoadjuvant chemoradiation-CRT and the 3-D US was repeated 50-55 days later. The choice of the surgical approach was based on the post-chemoradiation response identified by the 3D-US comparing with pathologic findings. RESULTS: The post-chemoradiation/3D-US findings were concordant with pathologic results in 31/32(97%). It was identified residual tumors in 26/27(96% sensibility), 19(59%) with partial response and 7(22%) without response. Complete response was demonstrated in 5/5 by 3D-US, with specificity and predictive valor in 100%. Negative predictive valor in 83% since one(3%) case was inconclusive. Sphincter-saving resection was performed in 16 patients, 5 with complete response, 10 with partial response and one inconclusive, with distal margin >2cm. The pathologic findings confirmed distal margins without tumor. It was demonstrated high concordance(87.5%) concerning the lymph nodes evaluation(Kappa test). CONCLUSION: 3D-US can be useful to determine the patients who should be submitted to sphincter-saving resections