IntroductionThe value of adjuvant chemotherapy for rectal cancer patients is debated and varies in different subgroups. One such subgroup is mucinous adenocarcinoma (MAC), which is more treatment resistant compared to non-mucinous adenocarcinoma (NMAC). To date, mucinous histology is not taken into account when deciding on adjuvant treatment strategy. This is the first study to exclusively include patients with rectal cancer, then separate MAC and NMAC and compare the survival in patients that had or did not have adjuvant chemotherapy. Material and methodsThe study included retrospective register data from 365 Swedish patients with stage II-IV rectal adenocarcinoma, 56 patients with MAC and 309 patients with NMAC. All patients were considered curative, had surgery with total mesorectal excision in 2004-2013, and were followed up until death or 2021. ResultsPatients with MAC that had adjuvant chemotherapy had better overall survival (OS, HR 0.42; CI 95%: 0.19-0.93; p = 0.032) and a trend towards better cancer-specific survival (CSS, HR 0.41 CI 95%: 0.17-1.03; p = 0.057) compared to patients without chemotherapy (HR 0.42; CI 95%: 0.19-0.93; p = 0.032). The difference in OS was still significant even after adjusting for sex, age, stage, differentiation, neoadjuvant chemotherapy and preoperative radiotherapy (HR 0.40; CI 95%: 0.17-0.92; p = 0.031). There was no such difference in the NMAC patients except in the stage-by-stage subgroup analyses where patients in stage IV had better survival after adjuvant chemotherapy. ConclusionsThere may be a difference in treatment response to adjuvant chemotherapy between MAC and NMAC patients. Patients with MAC could possibly benefit from adjuvant chemotherapy in stages II-IV. Further studies are however needed to confirm these results.

Background: Liver metastases are the most common cause of death for patients with colorectal cancer and affect up to half of the patients. Liver resection is an established method that can potentially be curative. For patients with extrahepatic disease (EHD), the role of liver surgery is less established. Methods: This is a retrospective study based on data from the national quality registry SweLiv. Data were obtained between 2009 and 2015. SweLiv is a validated registry and has been in use since 2009, with coverage above 95%. Patients with liver metastases and EHD were analyzed and cross-checked against the national death cause registry for survival analysis. Results: During the study period, 2,174 patients underwent surgery for colorectal liver metastases (CRLM), and 277 patients with EHD were treated with resection or ablation. The estimated median survival time for the entire cohort from liver resection/ablation was 40 months (95% CI, 32-47). The survival time for patients treated with liver resection was 45 months compared to 26 months for patients treated with ablation (95% CI 38-53, 18-33, P=0.001). A subgroup analysis of resected patients revealed that the group with pulmonary metastases had a significantly longer estimated median survival (50 months; 95 % CI, 39-60) than the group with lymph node metastases (32 months; 95% CI, 7-58) or peritoneal carcinomatosis (28 months; 95% CI, 14-41) (P=0.022 and 0.012, respectively). Other negative prognostic factors were major liver resection and nonradical liver resection. Conclusions: For patients with liver metastases and limited EHD, liver resection results in prolonged survival compared to what can be expected from chemotherapy alone.

Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.

Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.

Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).

Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.

Objective: To assess the accuracy of MRI to predict remaining lymph node metastases in patients with complete pathological luminal response (ypTO) after neoadjuvant therapy. Methods: Data from a national registry were used. 19 patients with histopathologically remaining lymph node metastases (ypTON+) were identified. Another 19 patients without lymph node metastases (ypTONO) were used as matched controls. Two radiologists blinded to all patient information evaluated staging and restaging MRI that was compared to histopathological findings of the resected specimen. Results: The average size of the largest lymph node on restaging MRI was significantly larger (4.5 mm) in the ypTON+ group than in the ypTONO group (2.6 mm) (p = 0.04). Presence of ypN+ was correctly predicted by MRI in 7 of 19 patients. In patients without lymph node metastases (ypTONO), these were correctly classified by MRI in 16 of 19 patients. All patients who had MR-identified lymph nodes larger than 8mm at restaging were ypTN+. The sensitivity, specificity, positive predictive value and negative for prediction of remaining lymph node metastasis with MRI were 37, 84, 70 and 57%. Conclusion: In patients with ypTO in rectal cancer after neoadjuvant treatment, remaining regional lymph node metastases cannot safely be predicted by restaging MRI alone using presently known criteria. Presence of a lymph node over 8mm on restaging MRI strongly indicates yPN+. Advances In knowledge: This is one of the first studies on MRI lymph node assessment after chemo- radiotherapy (CRT) in luminal complete response.

Purpose: In a previous study, the transmembrane protein FXYD-3 was suggested as a biomarker for a lower survival rate and reduced radiosensitivity in rectal cancer patients receiving preoperative radiotherapy. The purpose of preoperative irradiation in rectal cancer is to reduce local recurrence. The aim of this study was to investigate the potential role of FXYD-3 as a biomarker for increased risk for local recurrence of rectal cancer.

Materials and Methods: FXYD-3 expression was immunohistochemically examined in surgical specimens from a cohort of patients with rectal cancer who developed local recurrence (n = 48). The cohort was compared to a matched control group without recurrence (n = 81).

Results: Weak FXYD-3 expression was found in 106/129 (82%) of the rectal tumors and strong expression in 23/129 (18%). There was no difference in the expression of FXYD-3 between the patients with local recurrence and the control group. Furthermore there was no difference in FXYD-3 expression and time to diagnosis of local recurrence between patients who received preoperative radiotherapy and those without.

Conclusion: Previous findings indicated that FXYD-3 expression may be used as a marker of decreased sensitivity to radiotherapy or even overall survival. We were unable to confirm this in a cohort of rectal cancer patients who developed local recurrence.

Background: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. Method: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colorectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with amp;gt;4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. Results: Complete eradication of the luminal tumor, ypTO was found in 161 patients (8%). In 83% of the ypTO the regional lymph nodes were tumor negative (ypTONO), 12% had 1-3 positive lymph nodes (ypTON1) and 4% had more than three positive lymph nodes (ypTON2). There was significantly greater survival with ypTO compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypTONO compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypTO, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypTO compared to 5.1% in the group without chemotherapy (p amp;lt; 0.00004). Conclusion: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status. (C) 2016 Elsevier Ltd. All rights reserved.

Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.

Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.

Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.

Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.

Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.