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Tumor involvement at the resection margin remains the most important predictor for local recurrence in patients with rectal cancer. A careful description of tumor localization is therefore essential. Currently, endoscopic tattooing with ink is customary, but visibility during laparoscopic resections is limited. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) could be an improvement. In addition to localize tumors, ICG can also be used to identify sentinel lymph nodes (SLNs). The feasibility of this new technique was explored in five patients undergoing laparoscopic low anterior resection for rectal cancer. Intraoperative tumor visualization was possible in four out of five patients. Fluorescence signal could be detected 32±18 minutes after incision, while ink could be detected 42 ± 21 minutes after incision (p = 0.53). No recurrence was diagnosed within three months after surgery. Ex vivo imaging identified a mean of 4.2 ± 2.7 fluorescent lymph nodes, which were appointed SLNs. One out of a total of 83 resected lymph nodes contained a micrometastasis. This node was not fluorescent. This technical note describes the feasibility of endoscopic tattooing of rectal cancer using ICG:nanocolloid and NIR fluorescence imaging during laparoscopic resection. Simultaneous SLN mapping was also feasible, but may be less reliable due to neoadjuvant therapy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Care for patients with colon and rectal cancer has improved in the last twenty years however still considerable variation exists in cancer management and outcome between European countries. Therefore, EURECCA, which is the acronym of European Registration of cancer care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012 the first multidisciplinary consensus conference about colon and rectum was held looking for multidisciplinary consensus. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Experts commented and voted on the two web-based online voting rounds before the meeting (between 4th and 25th October and between the 20th November and 3rd December 2012) as well as one online round after the meeting (4th–20th March 2013) and were invited to lecture on the subjects during the meeting (13th–15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. All sentences that were voted on are available on the EURECCA website www.canceraudit.eu. The consensus document was divided in sections describing evidence based algorithms of diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and stage IV separately. Consensus was achieved using the Delphi method. Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Conclusions: It is feasible to achieve European Consensus on key diagnostic and treatment issues using the Delphi method. This consensus embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe. [Copyright &y& Elsevier]

Abstract: Background: Care for patients with colon and rectal cancer has improved in the last 20years; however considerable variation still exists in cancer management and outcome between European countries. Large variation is also apparent between national guidelines and patterns of cancer care in Europe. Therefore, EURECCA, which is the acronym of European Registration of Cancer Care, is aiming at defining core treatment strategies and developing a European audit structure in order to improve the quality of care for all patients with colon and rectal cancer. In December 2012, the first multidisciplinary consensus conference about cancer of the colon and rectum was held. The expert panel consisted of representatives of European scientific organisations involved in cancer care of patients with colon and rectal cancer and representatives of national colorectal registries. Methods: The expert panel had delegates of the European Society of Surgical Oncology (ESSO), European Society for Radiotherapy & Oncology (ESTRO), European Society of Pathology (ESP), European Society for Medical Oncology (ESMO), European Society of Radiology (ESR), European Society of Coloproctology (ESCP), European CanCer Organisation (ECCO), European Oncology Nursing Society (EONS) and the European Colorectal Cancer Patient Organisation (EuropaColon), as well as delegates from national registries or audits. Consensus was achieved using the Delphi method. For the Delphi process, multidisciplinary experts were invited to comment and vote three web-based online voting rounds and to lecture on the subjects during the meeting (13th–15th December 2012). The sentences in the consensus document were available during the meeting and a televoting round during the conference by all participants was performed. This manuscript covers all sentences of the consensus document with the result of the voting. The consensus document represents sections on diagnostics, pathology, surgery, medical oncology, radiotherapy, and follow-up where applicable for treatment of colon cancer, rectal cancer and metastatic colorectal disease separately. Moreover, evidence based algorithms for diagnostics and treatment were composed which were also submitted to the Delphi process. Results: The total number of the voted sentences was 465. All chapters were voted on by at least 75% of the experts. Of the 465 sentences, 84% achieved large consensus, 6% achieved moderate consensus, and 7% resulted in minimum consensus. Only 3% was disagreed by more than 50% of the members. Conclusions: Multidisciplinary consensus on key diagnostic and treatment issues for colon and rectal cancer management using the Delphi method was successful. This consensus document embodies the expertise of professionals from all disciplines involved in the care for patients with colon and rectal cancer. Diagnostic and treatment algorithms were developed to implement the current evidence and to define core treatment guidance for multidisciplinary team management of colon and rectal cancer throughout Europe. [Copyright &y& Elsevier]

Although optimising rectal cancer treatment has reduced local recurrence rates, many patients develop distant metastases (DM). The current study investigated whether a total neoadjuvant treatment strategy influences the development, location, and timing of metastases in patients diagnosed with high-risk locally advanced rectal cancer included in the Rectal cancer And Pre-operative Induction therapy followed by Dedicated Operation (RAPIDO) trial. Patients were randomly assigned to short-course radiotherapy followed by 18 weeks of CAPOX or FOLFOX4 before surgery (EXP), or long-course chemoradiotherapy with optional postoperative chemotherapy (SC-G). Assessments for metastatic disease were performed pre- and post-treatment, during surgery, and 6, 12, 24, 36, and 60 months postoperatively. From randomisation, differences in the occurrence of DM and first site of metastasis were evaluated. In total, 462 patients were evaluated in the EXP and 450 patients in the SC-G groups. The cumulative probability of DM at 5 years after randomisation was 23% [95% CI 19–27] and 30% [95% CI 26–35] (HR 0.72 [95% CI 0.56–0.93]; P = 0.011) in the EXP and SC-G, respectively. The median time to DM was 1.4 (EXP) and 1.3 years (SC-G). After diagnosis of DM, median survival was 2.6 years [95% CI 2.0–3.1] in the EXP and 3.2 years [95% CI 2.3–4.1] in the SC-G groups (HR 1.39 [95% CI 1.01–1.92]; P = 0.04). First occurrence of DM was most often in the lungs (60/462 [13%] EXP and 55/450 [12%] SC-G) or the liver (40/462 [9%] EXP and 69/450 [15%] SC-G). A hospital policy of postoperative chemotherapy did not influence the development of DM. Compared to long-course chemoradiotherapy, total neoadjuvant treatment with short-course radiotherapy and chemotherapy significantly decreased the occurrence of metastases, particularly liver metastases. • With the experimental treatment, the risk of distant metastases is reduced. • The metastatic pattern of LARC changed after the RAPIDO total neoadjuvant schedule. • The experimental treatment caused a decrease in liver metastases. • This treatment did not change the timing of the diagnosis of DM. • Survival after DM was poorer in the experimental group. [ABSTRACT FROM AUTHOR]

A pathological complete response (pCR) following chemoradiation (CRT) or short-course radiotherapy (scRT) leads to a favourable prognosis in patients with rectal cancer. Total neo-adjuvant therapy (TNT) doubles the pCR rate, but it is unknown whether oncological outcomes remain favourable and whether the same characteristics are associated with pCR as after CRT. Comparison between patients with pCR in the RAPIDO trial in the experimental [EXP] (scRT, chemotherapy, surgery, as TNT) and standard-of-care treatment [STD] (CRT , surgery, postoperative chemotherapy depending on hospital policy) groups. Primary and secondary outcomes were time-to-recurrence (TTR), overall survival (OS) and association between patient, tumour, and treatment characteristics and pCR. Among patients with a resection within six months after preoperative treatment, 120/423 (28%) [EXP] and 57/398 (14%) [STD] achieved a pCR. Following pCR, 5-year cumulative TTR and OS rates in the EXP and STD arms were 8% vs. 7% (hazard ratio 1.04, 95%CI 0.32–3.38) and 94% vs. 93% (hazard ratio 1.41, 95%CI 0.51–3.92), respectively. Besides the EXP treatment (odds ratio 2.70, 95%CI 1.83–3.97), pre-treatment carcinoembryonic antigen (CEA) <5, pre-treatment tumour size <40 mm and cT2 were associated with pCR. Distance from the anal verge was the only characteristic with a statistically significant difference in association with pCR between the EXP and STD treatment (P interaction =0.042). pCR rates did not increase with prolonged treatment time. The doubled pCR rate of TNT compared to CRT results in similar oncological outcomes. Characteristics associated with pCR are the EXP treatment, normal CEA, and small tumour size. • TNT results in a doubled pCR rate compared to CRT. • A pCR following TNT or CRT leads to similar, favourable oncological outcomes. • Α tumour size < 40 mm, CEA < 5, cT2-stage and TNT are associated with achieving pCR. • pCR rates did not increase with prolonged treatment time within each treatment. [ABSTRACT FROM AUTHOR]

Background Several histological high-risk factors are used as an indication for adjuvant therapy in stage II colon cancer. Those and other factors, including lymphatic invasion, perineural invasion (PNI), venous invasion and tumour budding are associated with decreased outcome. In this study, we evaluated the prognostic and predictive values of these biomarkers in a cohort of rectal cancer patients. Materials and methods The trial-based cohort consisted of 221npTNM stage II–III rectal cancer patients, included in the PROCTOR/SCRIPT trial, a multicentre randomised phase III trial. Patients treated with neoadjuvant radiotherapy and TME surgery were randomised between adjuvant chemotherapy or observation. Lymphatic invasion, PNI, extramural venous invasion, intramural venous invasion and tumour budding were determined in standard tissue slides. Results The presence of PNI (HR 3.36; 95% CI 1.82–6.21), extramural vascular invasion (HR 1.93; 95% CI 1.17–3.19) and tumour budding (HR 1.83, 95% CI 1.11–3.03) was associated with a significant worse overall survival. The presence of ≥2 adverse biomarkers resulted in a stronger prediction of adverse outcome in terms of overall survival (HR 2.82; 95% CI 1.66–4.79), disease-free survival (HR 2.27; 95% CI 1.47–3.48), and distant recurrence (HR 2.51; 95% CI 1.56–4.02). None of these markers alone or combined predicted a beneficial effect of adjuvant chemotherapy. Discussion We confirmed that several stage-independent biomarkers were significantly associated with a decreased outcome in rectal cancer patients. More importantly, these markers did not have predictive value and are thus not useful to select for adjuvant therapy in rectal cancer. [ABSTRACT FROM AUTHOR]

Background Preoperative short-term radiotherapy (PRT) in combination with total mesorectal excision (TME) has shown to improve local control in rectal cancer treatment, however without a survival benefit and at the cost of increased morbidity. The current study investigates the long-term health-related quality of life (HRQL) of patients 14 years after treatment in the Dutch TME trial. Methods In the TME trial (1996–1999) 1530 Dutch patients with rectal cancer were treated with TME and randomly assigned to PRT (5 × 5 Gy). In 2012 HRQL was evaluated in surviving patients ( n = 606) using a questionnaire combining EORTC QLQ-C30, EORTC QLQ-CR29 and additional questions. Findings Results were obtained from 478 patients (82%), with a median follow up of 14 years. PRT + TME patients without stoma reported more faecal leakage and higher stool frequency, resulting in increased need of pads. Furthermore, irradiated males reported more erection problems. However, radiotherapy did not have negative effects on overall functioning. Compared with Dutch population, patients in both treatment arms reported a small decrease in overall functioning and males reported less sexual activity, interest and enjoyment and more erection difficulties. Irradiated females reported more vaginal dryness and more pain at intercourse compared with Dutch population. Interpretation Long-term HRQL evaluation shows that treatment-related symptoms are still present 14 years after treatment for rectal cancer. Radiotherapy increased bowel dysfunction in patients without stoma. Compared with the Dutch population, both groups reported increased sexual dysfunction. Despite these treatment-related symptoms, there was no difference in overall functioning and global health between TME and PRT + TME. [ABSTRACT FROM AUTHOR]

Abstract: Aims: Pre-operative radiotherapy has proven to reduce local recurrences after curative surgery for rectal cancer. Radiotherapy is generally well tolerated, although postoperative morbidity and mortality was increased in some patients. Current study was undertaken to analyse whether the interval between preoperative radiotherapy and surgery influences post-operative mortality and recurrence for two cohorts. Methods: All Dutch patients included in the total mesorectal excision (TME)-trial receiving radiotherapy for resectable rectal cancer were included in this study (n =642). The verification set consisted of all patients receiving short-course radiotherapy for resectable rectal cancer in two radiotherapy clinics in The Netherlands (n =600). Univariate and multivariable survival analyses for overall survival, disease-free survival, local recurrence-free survival and non-cancer related survival were calculated. Results: Patients aged 75years and older treated during the TME-trial showed a worse overall and non-cancer-related survival when surgically treated 4–7days after the last fraction of radiotherapy. No differences in survival between the interval groups were found in the verification set. Conclusion: Present study found that elderly patients aged 75years and older operated 4–7days after the last fraction of radiotherapy had a higher chance of dying due to non-cancer-related causes during the TME-trial as compared to patients with an interval of 0–3days. In the verification set similar differences could not be confirmed, which could be due to awareness of the clinicians who avoided delayed surgery after radiotherapy since the results have been presented during congresses. A longer than recommended interval between radiotherapy and surgery should be avoided. Besides, the verification set suggests that radiotherapy duration of 7days is acceptable. [Copyright &y& Elsevier]