89Zr-Trastuzumab PET/CT Imaging of HER2-Positive Breast Cancer for Predicting Pathological Complete Response after Neoadjuvant Systemic Therapy: A Feasibility Study.

BACKGROUND: Approximately 20% of invasive ductal breast malignancies are human epidermal growth factor receptor 2 (HER2)-positive. These patients receive neoadjuvant systemic therapy (NAT) including HER2-targeting therapies. Up to 65% of patients achieve a pathological complete response (pCR). These patients might not have needed surgery. However, accurate preoperative identification of a pCR remains challenging. A radiologic complete response (rCR) on MRI corresponds to a pCR in only 73% of patients. The current feasibility study investigates if HER2-targeted PET/CT-imaging using Zirconium-89 (89Zr)-radiolabeled trastuzumab can be used for more accurate NAT response evaluation. METHODS: HER2-positive breast cancer patients scheduled to undergo NAT and subsequent surgery received a 89Zr-trastuzumab PET/CT both before (PET/CT-1) and after (PET/CT-2) NAT. Qualitative and quantitative response evaluation was performed. RESULTS: Six patients were enrolled. All primary tumors could be identified on PET/CT-1. Four patients had a pCR and two a pathological partial response (pPR) in the primary tumor. Qualitative assessment of PET/CT resulted in an accuracy of 66.7%, compared to 83.3% of the standard-of-care MRI. Quantitative assessment showed a difference between the SUVR on PET/CT-1 and PET/CT-2 (ΔSUVR) in patients with a pPR and pCR of -48% and -90% (p = 0.133), respectively. The difference in tumor-to-blood ratio on PET/CT-1 and PET/CT-2 (ΔTBR) in patients with pPR and pCR was -79% and -94% (p = 0.133), respectively. Three patients had metastatic lymph nodes at diagnosis that were all identified on PET/CT-1. All three patients achieved a nodal pCR. Qualitative assessment of the lymph nodes with PET/CT resulted in an accuracy of 66.7%, compared to 50% of the MRI. CONCLUSIONS: NAT response evaluation using 89Zr-trastuzumab PET/CT is feasible. In the current study, qualitative assessment of the PET/CT images is not superior to standard-of-care MRI. Our results suggest that quantitative assessment of 89Zr-trastuzumab PET/CT has potential for a more accurate response evaluation of the primary tumor after NAT in HER2-positive breast cancer.

Clinical translation and implementation of optical imaging agents for precision image-guided cancer surgery.

INTRODUCTION: The field of tumor-specific fluorescence-guided surgery has seen a significant increase in the development of novel tumor-targeted imaging agents. Studying patient benefit using intraoperative fluorescence-guided imaging for cancer surgery is the final step needed for implementation in standard treatment protocols. Translation into phase III clinical trials can be challenging and time consuming. Recent studies have helped to identify certain waypoints in this transition phase between studying imaging agent efficacy (phase I-II) and proving patient benefit (phase III). TRIAL INITIATION: Performing these trials outside centers of expertise, thus involving motivated clinicians, training them, and providing feedback on data quality, increases the translatability of imaging agents and the surgical technique. Furthermore, timely formation of a trial team which oversees the translational process is vital. They are responsible for establishing an imaging framework (camera system, imaging protocol, surgical workflow) and clinical framework (disease stage, procedure type, clinical research question) in which the trial is executed. Providing participating clinicians with well-defined protocols with the aim to answer clinically relevant research questions within the context of care is the pinnacle in gathering reliable trial data. OUTLOOK: If all these aspects are taken into consideration, tumor-specific fluorescence-guided surgery is expected be of significant value when integrated into the diagnostic work-up, surgical procedure, and follow-up of cancer patients. It is only by involving and collaborating with all stakeholders involved in this process that successful clinical translation can occur. AIM: Here, we discuss the challenges faced during this important translational phase and present potential solutions to enable final clinical translation and implementation of imaging agents for image-guided cancer surgery.

Carcinoembryonic antigen-specific, fluorescent image-guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer.

This multicentre pilot study investigated the role of peroperative carcinoembryonic antigen (CEA)-specific fluorescence imaging during cytoreductive surgery-hyperthermic intraperitoneal chemotherapy surgery in peritoneal metastasized colorectal cancer. A correct change in peritoneal carcinomatosis index (PCI) owing to fluorescence imaging was seen in four of the 14 included patients. The use of SGM-101 in patients with peritoneally metastasized colorectal carcinoma is feasible, and allows intraoperative detection of tumour deposits and alteration of the PCI. Augmented reality guidance.

[Acute appendicitis or colon cancer? Difference in elderly patients not always clear]. / Acute appendicitis of coloncarcinoom?

Three elderly patients presented with acute abdominal pain in the right lower quadrant and leukocytosis. CT-imaging of the abdomen supported the suspicion of acute appendicitis. The patients underwent appendectomy. After pathological examination, two patients were found to have a colon carcinoma. The third patient had a normal appendix; however, adenocarcinoma of the cecum was found four weeks later. The patients underwent a second operation, a right hemicolectomy, within two months. In patients older than 65 years with symptoms of acute appendicitis, colon cancer should be considered in the differential diagnosis. Distinguishing between appendicitis and colon cancer based on clinical symptoms and imaging is difficult. However, this distinction is important for the prognosis and choice of surgical treatment. If no direct evidence of malignancy is present in elderly patients with symptoms of appendicitis, a colonoscopy should be performed postoperatively to exclude colon cancer.