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In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: Nodal stage is a strong prognostic factor of oncological outcome of rectal cancer. To compensate for the variation in total number of harvested nodes, calculation of the lymph node ratio (LNR) has been advocated. The aim of the study was to compare the impact, on the long-term oncological outcome, of the LNR with other predictive factors, including the quality of total mesorectal excision (TME) and the state of the circumferential resection margin., Method: Consecutive patients having elective surgery for nonmetastatic rectal cancer were extracted from a prospectively maintained database. Retrospective uni- and multivariate analyses were performed based on patient-, surgical- and tumour-related factors. The prognostic value of the LNR on overall survival (OS) and on overall recurrence-free survival (ORFS) was assessed and a cut-off value was determined., Results: From 1998 to 2013, out of 456 patients, 357 with nonmetastatic disease were operated on for rectal cancer. Neoadjuvant radiochemotherapy was administered to 66.7% of the patients. The mean number of lymph nodes retrieved was 12.8 ± 8.78 per surgical specimen. A lower lymph node yield was obtained in patients who received neoadjuvant chemoradiotherapy (11.8 vs 14.2; P = 0.014). The 5-year ORFS was 71.8% and the 5-year OS was 80.1%. Multivariate analysis confirmed LNR, the quality of TME and age to be independent prognostic factors of OS. LNR, age and perineural infiltration were independently associated with ORFS. Low- and high-risk patients could be discriminated using an LNR cut-off value of 0.2., Conclusion: LNR is an independent prognostic factor of OS and ORFS. In line with the principles of optimal surgical management, the quality of TME and lymph node yield are essential technical requirements., (Colorectal Disease © 2016 The Association of Coloproctology of Great Britain and Ireland.)

Our goal was to optimize the radiosensitizing potential of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, when given concomitantly with preoperative radiotherapy in KRAS wild-type locally advanced rectal cancer (LARC). Based on pre-clinical studies conducted by our group, we designed a phase II trial in which panitumumab (6 mg/kg/q2 weeks) was combined with preoperative radiotherapy (45 Gy in 25 fractions) to treat cT3-4/N + KRAS wild-type LARC. The primary endpoint was complete pathologic response (pCR) (H0 = 5%, H1 = 17%, α = 0.05, β = 0.2). From 19 enrolled patients, 17 (89%) were evaluable for pathology assessment. Although no pCR was observed, seven patients (41%) had grade 3 Dworak pathological tumor regression. The regimen was safe and was associated with 95% of sphincter-preservation rate. No NRAS, BRAF, or PI3KCA mutation was found in this study, but one patient (5%) showed loss of PTEN expression. The quantification of plasma EGFR ligands during treatment showed significant upregulation of plasma TGF-α and EGF following panitumumab administration (p < 0.05). At surgery, patients with important pathological regression (grade 3 Dworak) had higher plasma TGF-α (p = 0.03) but lower plasma EGF (p = 0.003) compared to those with grade 0-2 Dworak. Our study suggests that concomitant panitumumab and preoperative radiotherapy in KRAS wild-type LARC is feasible and results in some tumor regression. However, pCR rate remained modest. Given that the primary endpoint of our study was not reached, we remain unable to recommend the use of panitumumab as a radiosensitizer in KRAS wild-type LARC outside a research setting.

Background and Purpose: Quality assurance (QA) for radiation treatment has become a priority since poorly delivered radiotherapy can negatively influence patient outcome. Within a national project we evaluated the feasibility of a central review platform and its role in improving uniformity of clinical target volume (CTV) delineation in daily practice., Material and Methods: All Belgian radiotherapy departments were invited to participate and were asked to upload CTVs for rectal cancer treatment onto a secured server. These were centrally reviewed and feedback was given per e-mail. For each five consecutive patients per centre, the overlap parameter dice coefficient (DC) and the volumetric parameters volumetric ratio (RV) and commonly contoured volume (VCC) were calculated., Results: Twenty departments submitted 1224 eligible cases of which 909 were modified (74.3%). There was a significant increase in RV and VCC between the first ten patients per centre and the others. This was not seen for DC. Statistical analysis did not show a further significant improvement in delineation over the entire review period., Conclusion: Central review was feasible and increased the uniformity in CTV delineation in the first ten rectal cancer patients per centre. The observations in this study can be used to optimize future QA initiatives., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Quality of health care is a hot topic, especially with regard to cancer. Although rectal cancer is, in many aspects, a model oncologic entity, there seem to be substantial differences in quality of care between countries, hospitals and physicians. PROCARE, a Belgian multidisciplinary national project to improve outcome in all patients with rectum cancer, identified a set of quality of care indicators covering all aspects of the management of rectal cancer. This set should permit national and international benchmarking, i.e. comparing results from individual hospitals or teams with national and international performances with feedback to participating teams. Such comparison could indicate whether further improvement is possible and/or warranted.

The aim of the present study was to perform a rectal cancer practice survey in order to re-assess in 2005 the Belgian state of the art. A questionnaire based on the past 1999 peer review, supplemented with general questions, was circulated to 16 radiotherapy centres in Belgium. A case was also proposed for treatment planification. In 2005, a formal multidisciplinary team was in place in all visited centres. Endorectal ultrasound, colonoscopy, CEA and an initial pathological diagnosis were standard procedure in all centres. For T1-2N0, the majority of centres do not perform a preoperative treatment; for T3N0, a majority proposes a preoperative radiochemotherapy. For all T3-4 any N, or any T-N involved, a neoadjuvant preoperative treatment is prescribed. Fractionation is conventional (1.8 Gy/d, five times a week). Analysing the practical case, the mean value for CTV and PTV volume was 393 (SD: 126) and 781 cm3 (SD: 105), respectively. Mean D(min) and D(max) of 92 and 106.5%, respectively, were measured in the PTV. From clinical point of view, standards concepts are emerging and spreading for staging and for treatment options. Nevertheless, there is still a need for standardization of volumes and delineation standards.

Purpose: To characterize the molecular pathways activated or inhibited by cetuximab when combined with chemoradiotherapy (CRT) in rectal cancer and to identify molecular profiles and biomarkers that might improve patient selection for such treatments., Patients and Methods: Forty-one patients with rectal cancer (T3-4 and/or N+) received preoperative radiotherapy (1.8 Gy, 5 days/wk, 45 Gy) in combination with capecitabine and cetuximab (400 mg/m2 as initial dose 1 week before CRT followed by 250 mg/m2 /wk for 5 weeks). Biopsies and plasma samples were taken before treatment, after cetuximab but before CRT, and at the time of surgery. Proteomics and microarrays were used to monitor the molecular response to cetuximab and to identify profiles and biomarkers to predict treatment efficacy., Results: Cetuximab on its own downregulated genes involved in proliferation and invasion and upregulated inflammatory gene expression, with 16 genes being significantly influenced in microarray analysis. The decrease in proliferation was confirmed by immunohistochemistry for Ki67 (P = .01) and was accompanied by an increase in transforming growth factor-alpha in plasma samples (P < .001). Disease-free survival (DFS) was better in patients if epidermal growth factor receptor expression was upregulated in the tumor after the initial cetuximab dose (P = .02) and when fibro-inflammatory changes were present in the surgical specimen (P = .03). Microarray and proteomic profiles were predictive of DFS., Conclusion: Our study showed that a single dose of cetuximab has a significant impact on the expression of genes involved in tumor proliferation and inflammation. We identified potential biomarkers that might predict response to cetuximab-based CRT.

Background: To assess the safety and preliminary efficacy of concurrent radiotherapy, capecitabine, and cetuximab in the preoperative treatment of patients with rectal cancer., Patients and Methods: Forty patients with rectal cancer (T3-T4, and/or N+, endorectal ultrasound) received preoperative radiotherapy (1.8 Gy, 5 days/week for 5 weeks, total dose 45 Gy, three-dimensional conformal technique) in combination with cetuximab [initial dose 400 mg/m(2) intravenous given 1 week before the beginning of radiation followed by 250 mg/m(2)/week for 5 weeks] and capecitabine for the duration of radiotherapy (650 mg/m(2) orally twice daily, first dose level; 825 mg/m(2) twice daily, second dose level)., Results: Four and six patients were treated at the first and second dose level of capecitabine, respectively. No dose-limiting toxicity occurred. Thirty additional patients were treated with capecitabine at 825 mg/m(2) twice daily. The most frequent grade 1/2 side-effects were acneiform rash (87%), diarrhea (65%), and fatigue (57%). Grade 3 diarrhea was found in 15%. Three grade 4 toxic effects were recorded: one myocardial infarction, one pulmonary embolism, and one pulmonary infection with sepsis. Two patients (5%) had a pathological complete response., Conclusions: Preoperative radiotherapy in combination with capecitabine and cetuximab is feasible with some patients achieving pathological downstaging.

Background: Preoperative radiotherapy has been shown to decrease the local recurrence rate of patients with locally advanced rectal cancer. Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer and have radiosensitizing properties. Therefore, these drugs would be expected to improve effectiveness of preoperative radiotherapy in terms of local control and prevention of distant metastases., Patients and Methods: Forty patients with rectal cancer (T3-T4 and/or N+) received radiotherapy (1.8 Gy, 5 days a week over 5 weeks, total dose 45 Gy, 3D conformational technique) in combination with intravenous oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation. Surgery was performed 6-8 weeks after completion of radiotherapy. The main end points were safety and efficacy as assessed by the pathological complete response (pCR)., Results: The most frequent grade 3/4 adverse event was diarrhea, occurring in 30% of patients. pCR was found in five (14%) patients. According to Dworak's classification, good regression was found in six (18%) additional patients., Conclusions: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer.