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Introduction: Neoadjuvant chemotherapy (CT) for locally advanced colon cancer (LACC) could potentially lead to tumor shrinkage, eradication of micrometastases, and prevention of tumor cell shedding during surgery. This retrospective study investigates the surgical and oncological outcomes of preoperative CT for LACC. Methods: Using the Netherlands Cancer Registry, data of patients with stage II or III colon cancer, diagnosed between 2008 and 2016 was collected. A propensity score matching (PSM; 1:2) was performed and compared patients with clinical tumor (cT) 4 colon cancer who were treated with neoadjuvant CT to patients with cT4 colon cancer treated with adjuvant CT (Fig. 1). Results: A total of 192 patients treated with neoadjuvant CT were compared to 1,954 patients that received adjuvant CT. After PSM, 149 patients in the neoadjuvant group were compared to 298 patients in the control group. No significant differences were found in baseline characteristics after PSM. After neoadjuvant CT, a significant response was observed in 13 (9%) patients with 5 (4%) patients showing a complete response. Complete resection margins (R0) were achieved in 77% in the neoadjuvant group versus 86% in the adjuvant treated group (p = 0.037). Significantly less tumor positive lymph nodes were found in the neoadjuvant group (median 0 vs. 2, p < 0.001). Major complication rates and 5-year overall survival did not differ between both groups (67–65%, p = 0.87). Conclusion: Neoadjuvant CT seems safe and feasible with similar long-term survival compared to patients who are treated with adjuvant CT.

Purpose: Intraoperative image guidance may aid in clinical decision-making during surgical treatment of colorectal cancer. We developed the dual-labeled carcinoembryonic antigen–targeting tracer, [111In]In-DTPA-SGM-101, for pre- and intraoperative imaging of colorectal cancer. Subsequently, we investigated the tracer in preclinical biodistribution and multimodal image-guided surgery studies, and assessed the clinical feasibility on patient-derived colorectal cancer samples, paving the way for rapid clinical translation. Experimental Design: SGM-101 was conjugated with p-isothiocyanatobenzyl–diethylenetriaminepentaacetic acid (DTPA) and labeled with Indium-111 (111In). The biodistribution of 3, 10, 30, and 100 μg [111In]In-DTPA-SGM-101 was assessed in a dose escalation study in BALB/c nude mice with subcutaneous LS174T human colonic tumors, followed by a study to determine the optimal timepoint for imaging. Mice with intraperitoneal LS174T tumors underwent micro-SPECT/CT imaging and fluorescence image–guided resection. In a final translational experiment, we incubated freshly resected human tumor specimens with the tracer and assessed the tumor-to-adjacent tissue ratio of both signals. Results: The optimal protein dose of [111In]In-DTPA-SGM-101 was 30 μg (tumor-to-blood ratio, 5.8 ± 1.1) and the optimal timepoint for imaging was 72 hours after injection (tumor-to-blood ratio, 5.1 ± 1.0). In mice with intraperitoneal tumors, [111In]In-DTPA-SGM-101 enabled preoperative SPECT/CT imaging and fluorescence image–guided resection. After incubation of human tumor samples, overall fluorescence and radiosignal intensities were higher in tumor areas compared with adjacent nontumor tissue (P < 0.001). Conclusions: [111In]In-DTPA-SGM-101 showed specific accumulation in colorectal tumors, and enabled micro-SPECT/CT imaging and fluorescence image–guided tumor resection. Thus, [111In]In-DTPA-SGM-101 could be a valuable tool for preoperative SPECT/CT imaging and intraoperative radio-guided localization and fluorescence image–guided resection of colorectal cancer.