Navigating the complexities and controversies of medication-related osteonecrosis of the jaw (MRONJ): a critical update and consensus statement.

OBJECTIVES: To provide a critical update identifying the knowledge gaps and controversies in medication-related osteonecrosis of the jaw (MRONJ) within the Belgian healthcare context and outline opportunities for improvement and research in these areas. METHODS: A literature review was performed to identify guidelines from international clinical societies in oncology or oral and maxillofacial surgery on diagnosing, preventing, and treating MRONJ. The recommendations were critically assessed in light of recent developments in the field and confronted with the clinical experience of experts. RESULTS: Despite progress in the diagnostic criteria of MRONJ, the continued need for an 8-week timeout period should be reconsidered. Furthermore, 3D imaging techniques should be introduced to improve diagnosis and staging. The staging system remains ambiguous regarding Stage 0 MRONJ, and ongoing confusion exists regarding the term non-exposed MRONJ. The prevention of MRONJ should be tailored, considering the individual patient's risk of MRONJ, frailty, and life expectancy. More research seems needed into the efficacy and safety of drug holidays, considering the risks of rebound remodeling on fractures. With renewed interest in surgical and adjunct management techniques, adequately designed clinical studies are needed to help translate trial outcomes into universally applicable treatment guidelines taking into account individual patient characteristics. CONCLUSIONS: Important knowledge gaps remain and hamper the development of clinical guidelines. Several controversies were identified where consensus is lacking, and further harmonization between stakeholders is necessary. Finally, the need for randomized controlled comparative clinical trials in MRONJ resonates harder than ever to identify the best treatment for individual patients.

Dual time point imaging in locally advanced head and neck cancer to assess residual nodal disease after chemoradiotherapy.

BACKGROUND: FDG-PET/CT has a high negative predictive value to detect residual nodal disease in patients with locally advanced squamous cell head and neck cancer after completing concurrent chemoradiotherapy (CCRT). However, the positive predictive value remains suboptimal due to inflammation after radiotherapy, generating unnecessary further investigations and possibly even surgery. We report the results of a preplanned secondary end point of the ECLYPS study regarding the potential advantages of dual time point FDG-PET/CT imaging (DTPI) in this setting. Standardized dedicated head and neck FDG-PET/CT images were obtained 12 weeks after CCRT at 60 and 120 min after tracer administration. We performed a semiquantitative assessment of lymph nodes, and the retention index (RI) was explored to optimize diagnostic performance. The reference standard was histology, negative FDG-PET/CT at 1 year, or > 2 years of clinical follow-up. The time-dependent area under the receiver operator characteristics (AUROC) curves was calculated. RESULTS: In total, 102 subjects were eligible for analysis. SUV values increased in malignant nodes (median SUV1 = 2.6 vs. SUV2 = 2.7; P = 0.04) but not in benign nodes (median SUV1 = 1.8 vs. SUV2 = 1.7; P = 0.28). In benign nodes, RI was negative although highly variable (median RI = - 2.6; IQR 21.2), while in malignant nodes RI was positive (median RI = 12.3; IQR 37.2) and significantly higher (P = 0.018) compared to benign nodes. A combined threshold (SUV1 ≥ 2.2 + RI ≥ 3%) significantly reduced the amount of false-positive cases by 53% (P = 0.02) resulting in an increased specificity (90.8% vs. 80.5%) and PPV (52.9% vs. 37.0%), while sensitivity (60.0% vs. 66.7%) and NPV remained comparably high (92.9% vs. 93.3%). However, AUROC, as overall measure of benefit in diagnostic accuracy, did not significantly improve (P = 0.62). In HPV-related disease (n = 32), there was no significant difference between SUV1, SUV2, and RI in malignant and benign nodes, yet this subgroup was small. CONCLUSIONS: DTPI did not improve the overall diagnostic accuracy of FDG-PET/CT to detect residual disease 12 weeks after chemoradiation. Due to differences in tracer kinetics between malignant and benign nodes, DTPI improved the specificity, but at the expense of a loss in sensitivity, albeit minimal. Since false negatives at the 12 weeks PET/CT are mainly due to minimal residual disease, DTPI is not able to significantly improve sensitivity, but repeat scanning at a later time (e.g. after 12 months) could possibly solve this problem. Further study is required in HPV-associated disease.

Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography After Concurrent Chemoradiotherapy in Locally Advanced Head-and-Neck Squamous Cell Cancer: The ECLYPS Study.

Purpose To assess the standardized implementation and reporting of surveillance [18F]fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan of the neck in locoregionally advanced head-and-neck squamous cell carcinoma (LAHNSCC) after concurrent chemoradiotherapy (CCRT). Patients and Methods We performed a prospective multicenter study of FDG-PET/CT scanning 12 weeks after CCRT in newly diagnosed patients with LAHNSCC (stage IVa/b) that used standardized reconstruction and Hopkins reporting criteria. The reference standard was histology or > 12 months of clinical follow-up. The primary outcome measure was the negative predictive value (NPV) of FDG-PET/CT scans and other supporting diagnostic test characteristics, including time dependency with increasing follow-up time. Results Of 152 patients, 125 had adequate primary tumor control after CCRT and entered follow-up (median, 20.4 months). Twenty-three (18.4%) had residual neck disease. Overall, NPV was 92.1% (95% CI, 86.9% to 95.3%; null hypothesis: NPV = 85%; P = .012) with sensitivity of 65.2% (95% CI, 44.9% to 81.2%), specificity of 91.2% (95% CI, 84.1% to 95.3%), positive predictive value of 62.5% (95% CI, 45.5% to 76.9%), and accuracy of 86.4% (95% CI, 79.3% to 91.3%). Sensitivity was time dependent and high for residual disease manifesting up to 9 months after imaging but lower (59.7%) for disease detected up to 12 months after imaging. Standardized reporting criteria reduced the number of equivocal reports (95% CI for the difference, 2.6% to 15.0%; P = .003). Test characteristics were not improved with the addition of lymph node CT morphology criteria. Conclusion FDG-PET/CT surveillance using Hopkins criteria 12 weeks after CCRT is reliable in LAHNSCC except for late manifesting residual disease, which may require an additional surveillance scan at 1 year after CCRT to be detected.

Perforator free flaps in head and neck reconstruction: a single-center low-volume experience.

OBJECTIVE: The aim of this article is to investigate the results of free-flap reconstructions in the head and neck area in a secondary low-volume institution and compare these with the literature. STUDY DESIGN: A retrospective study was performed of all patients who underwent free-flap reconstructive surgery in our institution from January 9, 2011, to July 12, 2015, by one young surgeon in a one-team approach. The types of flaps applied, defect sites, pathology, anastomotic details, success and complication rates, lengths of stay, and patients' ages and comorbidities were analyzed. RESULTS: A total of 97 patients received 100 free flaps. Perforator flaps comprised 85% of the total (63% anterolateral thigh, 22% fibular). Thirty-six percent of free flaps were performed in patients who received previous chemotherapy radiation to the head and neck. Free-flap survival was 96%. CONCLUSION: From our data, it seems that free-flap surgery not only is a safe and successful technique in tertiary academic hospitals, but also can be performed in smaller institutions, even in salvage situations and in patients with comorbidities. Therefore, we believe that free tissue transfer is predictable in all centers when performed by skilled microsurgeons and well-trained nursing teams.