EGFR-targeted fluorescence molecular imaging for intraoperative margin assessment in oral cancer patients: a phase II trial.

Inadequate surgical margins occur frequently in oral squamous cell carcinoma surgery. Fluorescence molecular imaging (FMI) has been explored for intraoperative margin assessment, but data are limited to phase-I studies. In this single-arm phase-II study (NCT03134846), our primary endpoints were to determine the sensitivity, specificity and positive predictive value of cetuximab-800CW for tumor-positive margins detection. Secondary endpoints were safety, close margin detection rate and intrinsic cetuximab-800CW fluorescence. In 65 patients with 66 tumors, cetuximab-800CW was well-tolerated. Fluorescent spots identified in the surgical margin with signal-to-background ratios (SBR) of ≥2 identify tumor-positive margins with 100% sensitivity, 85.9% specificity, 58.3% positive predictive value, and 100% negative predictive value. An SBR of ≥1.5 identifies close margins with 70.3% sensitivity, 76.1% specificity, 60.5% positive predictive value, and 83.1% negative predictive value. Performing frozen section analysis aimed at the fluorescent spots with an SBR of ≥1.5 enables safe, intraoperative adjustment of surgical margins.

Assessment of Bone Lesions with 18F-FDG PET Compared with 99mTc Bone Scintigraphy Leads to Clinically Relevant Differences in Metastatic Breast Cancer Management.

It is unknown whether assessment of potential bone lesions in metastatic breast cancer (MBC) by 18F-FDG PET instead of 99mTc bone scintigraphy (BS) supports clinically relevant changes in MBC management. Therefore, we retrospectively compared management recommendations based on bone lesion assessment by 18F-FDG PET plus contrast-enhanced CT (ceCT) or BS plus ceCT, for patients with newly diagnosed MBC. Methods: Baseline ceCT, BS, and 18F-FDG PET for all patients included in the IMPACT-MBC study (NCT01957332) at the University Medical Center Groningen were reviewed for bone lesions. If bone lesions were found by any imaging modality, virtual MBC management recommendations were made by a multidisciplinary expert panel, based on either 18F-FDG PET plus ceCT or BS plus ceCT. The panel had access to standard clinicopathologic information and baseline imaging findings outside the skeleton. Clinically relevant management differences between the 2 recommendations were defined either as different treatment intent (curative, noncurative, or unable to determine) or as different systemic or local treatment. If no bone lesions were found by any imaging modality, the patients were included in the analyses without expert review. Results: In total, 3,473 unequivocal bone lesions were identified in 102 evaluated patients (39% by ceCT, 26% by BS, and 87% by 18F-FDG PET). Additional bone lesions on 18F-FDG PET plus ceCT compared with BS plus ceCT led to change in MBC management recommendations in 16% of patients (95% CI, 10%-24%). BS also changed management compared with 18F-FDG PET in 1 patient (1%; 95% CI, 0%-5%). In 26% (95% CI, 19%-36%) of patients, an additional 18F-FDG PET exam was requested, because BS provided insufficient information. Conclusion: In this exploratory analysis of newly diagnosed MBC patients, 18F-FDG PET versus BS to assess bone lesions resulted in clinically relevant management differences in 16% of patients. BS delivered insufficient information in over one fourth of patients, resulting in an additional request for 18F-FDG PET. On the basis of these data, 18F-FDG PET should be considered a primary imaging modality for assessment of bone lesions in newly diagnosed MBC.

Integrating molecular nuclear imaging in clinical research to improve anticancer therapy.

Effective patient selection before or early during treatment is important to increasing the therapeutic benefits of anticancer treatments. This selection process is often predicated on biomarkers, predominantly biospecimen biomarkers derived from blood or tumour tissue; however, such biomarkers provide limited information about the true extent of disease or about the characteristics of different, potentially heterogeneous tumours present in an individual patient. Molecular imaging can also produce quantitative outputs; such imaging biomarkers can help to fill these knowledge gaps by providing complementary information on tumour characteristics, including heterogeneity and the microenvironment, as well as on pharmacokinetic parameters, drug-target engagement and responses to treatment. This integrative approach could therefore streamline biomarker and drug development, although a range of issues need to be overcome in order to enable a broader use of molecular imaging in clinical trials. In this Perspective article, we outline the multistage process of developing novel molecular imaging biomarkers. We discuss the challenges that have restricted the use of molecular imaging in clinical oncology research to date and outline future opportunities in this area.

Diagnostic accuracy of point-of-care fecal calprotectin and immunochemical occult blood tests for diagnosis of organic bowel disease in primary care: the Cost-Effectiveness of a Decision Rule for Abdominal Complaints in Primary Care (CEDAR) study.

BACKGROUND: Fecal biomarker tests that differentiate between organic bowel disease (OBD) and non-OBD in primary care patients with persistent lower-abdomen complaints could reduce the number of unnecessary referrals for endoscopy. We quantified the accuracy of fecal calprotectin and immunochemical occult blood (iFOBT) point-of-care (POC) tests and a calprotectin ELISA in primary care patients with suspected OBD. METHODS: We performed biomarker tests on fecal samples from 386 patients with lower-abdomen complaints suggestive for OBD. Endoscopic and histological diagnosis served as reference. RESULTS: OBD was diagnosed in 99 patients (prevalence 25.9%); 19 had adenocarcinoma, 53 adenoma, and 27 inflammatory bowel disease. Sensitivity for OBD was 0.64 (95% CI 0.54-0.72) for calprotectin POC, 0.56 (0.46-0.66) for iFOBT POC, and 0.74 (0.65-0.82) for calprotectin ELISA; specificities were 0.53 (0.48-0.59), 0.83 (0.78-0.87), and 0.47 (0.41-0.53), respectively. Negative predictive values (NPVs) were 0.81 (0.74-0.86), 0.85 (0.80-0.88), and 0.84 (0.78-0.89); positive predictive values (PPVs) varied from 0.32 (0.26-0.39) and 0.33 (0.27-0.39) (calprotectin tests) to 0.53 (0.44-0.63) (iFOBT POC). Combining the 2 POC tests improved sensitivity [0.79 (0.69-0.86)] and NPV [0.87 (0.81-0.91)] but lowered specificity [0.49 (0.44-0.55)] and PPV [0.35 (0.29-0.42)]. When adenomas ≤1 cm were considered non-OBD, the NPV of all tests improved to >0.90 [combined POC tests, 0.97 (0.93-0.99)]. CONCLUSIONS: Diagnostic accuracy of the tests alone or combined was insufficient when all adenomas were considered OBD. When only adenomas >1 cm were considered OBD, all tests could rule out OBD to a reasonable extent, particularly the combined POC tests. The tests were less useful for inclusion of OBD.

Retroperitoneal endoscopic versus conventional open adrenalectomy: a cost-effectiveness analysis.

BACKGROUND: A retrospective cost-effectiveness analysis was carried out, comparing retroperitoneal endoscopic and conventional adrenalectomy, which is based on a large group of patients, restricted in tumor size for the purpose of ensuring comparability. MATERIALS AND METHODS: Between 1990 and 2004, 61 patients underwent either an endoscopic or open adrenalectomy for tumors smaller than 6 cm. A short-term, base cost-effectiveness analysis was performed to evaluate costs per day prevented, and a sensitivity analysis was calculated. RESULTS: Average recovery time, postoperative stay, and resumption to oral intake were significantly shorter in the endoscopic group, whereas operative time was longer. No major complications occurred in either group. In 3 endoscopic procedures conversion was indicated. The base cost-effectiveness ratio was 15.41 per day postoperative stay prevented by the endoscopic approach. The number needed to treat with endoscopic adrenalectomy to prevent 1 week of postoperative stay is 2. CONCLUSION: Retroperitoneal endoscopic adrenalectomy may be considered a cost-effective procedure, compared to the conventional open adrenalectomy.