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Purpose: Magnetic resonance imaging-detected extramural venous invasion (mrEMVI) and tumor deposits (TDs) are risk factors for the development of local recurrence and distant metastases (DMs) in rectal cancer. However, little is known about their response to neoadjuvant treatment and its relation to oncologic outcomes. This study evaluated the incidence and features of mrEMVI and TDs before and after neoadjuvant treatment in relation to the development of local recurrence and DMs.Methods and Materials: Patients with cT3/4 rectal cancer without synchronous metastases who underwent surgery in a tertiary referral hospital were retrospectively analyzed. MRI scans were re-evaluated for the presence of mrEMVI, the occurrence of TDs, and response to neoadjuvant therapy (mr-vTRG).Results: In total, 277 patients were included, of whom 163 (58.8%) presented with mrEMVI. TDs were present in 56.4% of mrEMVI-positive and 9.6% of mrEMVI-negative patients (P < .001). The 5-year DM rate was significantly higher in mrEMVI-positive patients with and without TDs (45.2% and 35.9%, respectively) compared with mrEMVI-negative patients (25.7%; P = .012). After neoadjuvant treatment, the 5-year DM rate of patients with mr-vTRG 3-5 was 46.1%, whereas good responders (mr-vTRG 1-2) had a DM rate similar to mrEMVI-negative patients (25.7% and 25.7%, respectively; P = .002). The occurrence of TDs and larger mrEMVI size resulted in a lower likelihood of regression of mrEMVI.Conclusions: The prevalence of mrEMVI and TDs in cT3-4 rectal cancer is high and is associated with worsened oncologic outcomes. mrEMVI regression (mr-vTRG 1-2), which occured in 25% of the cases, leads to oncologic outcomes similar to those in patients without mrEMVI on baseline MRI. (C) 2021 The Author(s). Published by Elsevier Inc.

Introduction: The addition of induction chemotherapy (ICT) to neoadjuvant chemoradiotherapy (CRT) has the potential to improve outcomes in patients with locally advanced rectal cancer (LARC). However, patient selection is essential to prevent overtreatment. This study compared the complete response (CR) rate after treatment with and without ICT of LARC patients with prognostically poor characteristics. Methods: All LARC patients who were treated with neoadjuvant CRT, whether or not preceded by ICT, and who underwent surgery or were considered for a wait-and-see strategy between January 2016 and March 2020 in the Catharina Hospital Eindhoven, were retrospectively selected. LARC was defined as any T4 tumour, or a T2/T3 tumour with extramural venous invasion and/or tumour deposits and/or N2 lymph node status, and/or mesorectal fascia involvement (T3 tumours only). Case-control matching was per -formed based on the aforementioned characteristics. Results: Of 242 patients, 178 (74%) received CRT (CRT-group) and 64 patients (26%) received ICT followed by CRT (ICT-group). In the ICT-group, 3 patients (5%) did not receive the minimum of three cycles. In addition, in this selected cohort, compliance with radiotherapy was 100% in the ICT-group and 97% in the CRT-group. The CR rate was 30% in the ICT-group and 15% in the CRT-group (p = 0.011). After case-control matching, the CR rate was 28% and 9%, respectively (p = 0.013). Conclusion: Treatment including ICT seemed well tolerated and resulted in a high CR rate. Hence, this treatment strategy may facilitate organ preservation and improve survival in LARC patients with prog-nostically poor characteristics. (c) 2021 Elsevier Ltd, BASO -The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

BackgroundCarcinoembryonic antigen is overexpressed in colorectal cancer (CRC), making it an optimal target for fluorescence imaging. A phase I/II study was designed to determine the optimal imaging dose of SGM-101 for intraoperative fluorescence imaging of primary and recurrent CRC.MethodsPatients were included and received a single dose of SGM-101 at least 24 h before surgery. Patients who received routine anticancer therapy (i.e., radiotherapy or chemotherapy) also were eligible. A dedicated near-infrared imaging system was used for real-time fluorescence imaging during surgery. Safety assessments were performed and SGM-101 efficacy was evaluated per dose level to determine the most optimal imaging dose.ResultsThirty-seven patients with CRC were included in the analysis. Fluorescence was visible in all primary and recurrent tumors. In seven patients, no fluorescence was seen; all were confirmed as pathological complete responses after neoadjuvant therapy. Two tumors showed false-positive fluorescence. In the 37 patients, a total of 97 lesions were excised. The highest mean intraoperative tumor-to-background ratio (TBR) of 1.9 (p = 0.019) was seen in the 10-mg dose. This dose showed a sensitivity of 96%, specificity of 63%, and negative predictive value of 94%. Nine patients (24%) had a surgical plan alteration based on fluorescence, with additional malignant lesions detected in six patients.ConclusionsThe optimal imaging dose was established at 10 mg 4 days before surgery. The results accentuate the potential of SGM-101 and designated a promising base for the multinational phase III study, which enrolled the first patients in June 2019.

Background In patients with rectal cancer, enlarged lateral lymph nodes (LLNs) result in increased lateral local recurrence (LLR) and lower cancer-specific survival (CSS) rates, which can be improved with (chemo)radiotherapy ((C)RT) and LLN dissection (LLND). This study investigated whether different LLN locations affect oncological outcomes. Methods Patients with low cT3–4 rectal cancer without synchronous distant metastases were included in this multicentre retrospective cohort study. All MRI was re-evaluated, with special attention to LLN involvement and response. Results More advanced cT and cN category were associated with the occurrence of enlarged obturator nodes. Multivariable analyses showed that a node in the internal iliac compartment with a short-axis (SA) size of at least 7 mm on baseline MRI and over 4 mm after (C)RT was predictive of LLR, compared with a post-(C)RT SA of 4 mm or less (hazard ratio (HR) 5.74, 95 per cent c.i. 2.98 to 11.05 vs HR 1.40, 0.19 to 10.20; P Conclusion Internal iliac LLN enlargement is associated with an increased LLR rate, whereas obturator nodes are associated with more advanced disease with increased distant metastasis and reduced CSS rates. LLND improves local control in persistent internal iliac nodes, and might have a role in controlling systemic spread in persistent obturator nodes. Members of the Lateral Node Study Consortium are co-authors of this study and are listed under the heading Collaborators.

Background: In the West, pre-treatment abnormal lateral lymph nodes (LLN+) in patients with a low locally advanced rectal cancer (AJCC Stage III), are treated with neoadjuvant (chemo)radiotherapy (nCRT), without a lateral lymph node dissection (LLND). It has been suggested, however, that LLN+ patients have higher local recurrence (LR) rates than similarly staged patients with abnormal mesorectal lymph nodes only (LLN-), but no comparative data exist. Therefore, we conducted this international multi-center study in the Netherlands and Australia of Stage III rectal cancer patients with either LLN+ or LLN- to compare oncological outcomes from both groups. Materials and Methods: Patients with Stage III low rectal cancer with (LLN+ group) or without (LLN- group) abnormal lateral lymph nodes on pre-treatment MRI were included. Patients underwent nCRT followed by rectal resection surgery with curative intent between 2009 and 2016 with a minimum follow-up of 2-years. No patient had a LLND. Propensity score matching corrected differences in baseline characteristics. Results: Two hundred twenty-three patients could be included: 125 in the LLN+ group and 98 in the LLN- group. Between groups, there were significant differences in cT-stage and in the rate of adjuvant chemotherapy administered. Propensity score matching resulted in 54 patients in each group, with equal baseline characteristics. The 5-year LR rate in the LLN+ group was 11 vs. 2% in the LLN- group (P = 0.06) and disease-free survival (DFS) was 64 vs. 76%, respectively (P = 0.09). Five-year overall survival was similar between groups (73 vs. 80%, respectively; P = 0.90). Conclusions: In Western patients with Stage III low rectal cancer, there is a trend toward worse LR rate and DFS rates in LLN+ patients compared to similarly staged LLN- patients. These results suggest that LLN+ patients may currently not be treated optimally with nCRT alone, and the addition of LLND requires further consideration.

Background Lateral nodal disease in rectal cancer remains a subject of debate and is treated differently in the East and the West. The predictive value of lateral lymph node and MRI-detected extramural vascular invasion (mrEMVI) features on oncological outcomes was assessed in this study. Methods In this retrospective cohort study, data on patients with cT3–4 rectal cancer within 8 cm from the anal verge were considered over a 5-year period (2009–2013). Lateral lymph node size, malignant features and mrEMVI features were evaluated and related to oncological outcomes. Results In total, 192 patients were studied, of whom 30 (15·6 per cent) underwent short-course radiotherapy and 145 (75·5 per cent) received chemoradiotherapy. A lateral lymph node short-axis size of 10 mm or more was associated with a significantly higher 5-year lateral/presacral local recurrence rate of 37 per cent, compared with 7·7 per cent in nodes smaller than 10 mm (P = 0·041). Enlarged nodes did not result in a higher 5-year rate of distant metastasis (23 per cent versus 27·7 per cent in nodes smaller than 10 mm; P = 0·563). However, mrEMVI positivity was related to more metastatic disease (5-year rate 43 versus 26·3 per cent in the mrEMVI-negative group; P = 0·014), but not with increased lateral/presacral recurrence. mrEMVI occurred in 46·6 per cent of patients with nodes smaller than 10 mm, compared with 29 per cent in patients with nodes of 10 mm or larger (P = 0·267). Conclusion Although lateral nodal disease is more a local problem, mrEMVI mainly predicts distant recurrence. The results of this study showed an unacceptably high local recurrence rate in patients with a short axis of 10 mm or more, despite neoadjuvant (chemo)radiotherapy.

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS &gt, 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p &lt, 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS &lt, 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.