Assessment by a multidisciplinary team conference affects treatment strategy and overall survival in patients with synchronous colorectal liver metastases.

BACKGROUND: The aim of this retrospective observational study was to investigate the geographical or sex differences in patients with synchronous colorectal liver metastases (sCRLM) in terms of assessment by a multidisciplinary team conference (MDT), curative treatment, and overall survival. METHOD: All sCRLM patients in the South-East Health Care Region of Sweden from 2009 to 2015 were included (n = 615). Data were derived from the Swedish Colorectal Cancer Registry, Swedish Registry of Liver and Bile Surgery and medical records. RESULTS: Patients who had a hepatobiliary unit (HBU) at the nearest hospital were more likely to undergo liver surgery (HBU+, 37% (n = 106), compared to HBU-, 22% (n = 60); p = 0.001) and had a better median survival (p < 0.001). No sex differences were observed. In multivariate Cox regression analyses of overall survival, assessment by an MDT that included a liver surgeon was independently linked to better survival (HR 0.574, 0.433-0.760). CONCLUSION: There were no sex differences in access to liver surgery or overall survival, however, there were geographical inequalities, where residency near a hospital with HBU was associated with increased overall survival and the possibility to receive liver surgery. Assessment at MDT with liver surgeon present was associated with greater survival, indicating its important role for treatment.

Preoperative Radiotherapy Decision-Tree for Rectal Cancer Patients: A Real-World Analysis Based on the Swedish Colorectal Cancer Registry.

BACKGROUND: There are 3 widely used preoperative radiotherapy (RT) procedures in rectal cancer treatment including long-course RT (LRT), short-course RT with delayed surgery (SRTW), and short-course RT with immediate surgery (SRT). However, further evidence is required to determine which treatment option results in more optimal patient survival. METHODS: This Swedish Colorectal Cancer Registry-based retrospective study of real-world data included 7766 stage I-III rectal cancer patients, of which 2982, 1089, 763, and 2932 patients received no RT (NRT), LRT, SRTW, and SRT, respectively. The Kaplan-Meier survival curve and Cox proportional hazard multivariate model were used to identify potential risk factors and to examine the independent association of RT with patient survival after adjusting for baseline confounding factors. RESULTS: RT effects on survival differed by age and clinical T stage (cT) subgroups. Subsequent survival analysis by age and cT subgroups confirmed that patients ≥70 years old with cT4 benefited from any RT (P < .001, NRT as reference) and equally from any RT (P > .05 pairwise between RTs). In contrast, for cT3 patients ≥70 years, SRT and LRT were associated with better survival than SRTW (P < .001). In patients <70 years, LRT and SRTW had superior survival benefits in cT4 patients but inferior to SRT (P < .001); SRT was the only effective treatment in the cT3N+ subgroup (P = .032); patients with cT3N0 and <70 years did not benefit from any RT. CONCLUSION: This study suggests that preoperative RT strategies may have varying effects on the survival of rectal cancer patients, depending on their age and clinical stage.

The impact of adjuvant chemotherapy on survival in mucinous and non-mucinous rectal adenocarcinoma patients after TME surgery.

INTRODUCTION: The 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 METHODS: The 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. RESULTS: Patients 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. CONCLUSIONS: There 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.

MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer.

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.

Liver resection is beneficial for patients with colorectal liver metastases and extrahepatic disease.

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.

Assessment of remaining tumour involved lymph nodes with MRI in patients with complete luminal response after neoadjuvant treatment of rectal cancer.

OBJECTIVE: To assess the accuracy of MRI to predict remaining lymph node metastases in patients with complete pathological luminal response (ypT0) after neoadjuvant therapy. METHODS: Data from a national registry were used. 19 patients with histopathologically remaining lymph node metastases (ypT0N+) were identified. Another 19 patients without lymph node metastases (ypT0N0) 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 ypT0N+ group than in the ypT0N0 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 (ypT0N0), these were correctly classified by MRI in 16 of 19 patients. All patients who had MR-identified lymph nodes larger than 8 mm 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 ypT0 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 8 mm 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.

FXYD-3 expression in relation to local recurrence of rectal cancer.

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.

Expression of FXYD-3 is an independent prognostic factor in rectal cancer patients with preoperative radiotherapy.

PURPOSE: FXYD-3 (MAT-8) is overexpressed in several types of cancers; however, its clinical relevance in rectal cancers has not been studied. Therefore, we examined FXYD-3 expression in rectal cancers from the patients who participated in a Swedish clinical trial of preoperative radiotherapy (RT) to determine whether FXYD-3 was overexpressed in rectal cancers and correlated with RT, survival, and other clinicopathologic variables. METHODS AND MATERIALS: The study included 140 rectal cancer patients who participated in a clinical trial of preoperative RT, 65 with and 75 without RT before surgery. FXYD-3 expression was immunohistochemically examined in distant (n = 70) and adjacent (n = 101) normal mucosa, primary tumors (n = 140), and lymph node metastasis (n = 36). RESULTS: In the whole cohort, strong FXYD-3 expression was correlated with infiltrative tumor growth (p = 0.02). In the RT group, strong FXYD-3 expression alone (p = 0 .02) or combined with phosphatase of regenerating liver was associated with an unfavorable prognosis (p = 0.02), independent of both TNM stage and tumor differentiation. In tumors with strong FXYD-3 expression, there was less tumor necrosis (p = 0.02) and a trend toward increased incidence of distant metastasis (p = 0.08) after RT. None of these effects was seen in the non-RT group. FXYD-3 expression in the primary tumors tended to be increased compared with normal mucosa regardless of RT. CONCLUSION: FXYD-3 expression was a prognostic factor independent of tumor stage and differentiation in patients receiving preoperative RT for rectal cancer.