An Unknown Foreign laryngeal Object: an exotic complication of skull base osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the skull base is a rare complication after head and neck radiation with a broad variety of subsequent complications. METHODS: A 68-year-old woman with a complex oncological history (right-sided sphenoid meningioma; left-sided neck metastasis of a Cancer of Unknown Primary-CUP) was admitted with a right-sided epi-/ oropharyngeal mass and severe pain exacerbations for further evaluation. CT scan revealed an advanced ORN of the skull base with subsequent abruption of the ventral part of the clivus. This dislocated part of the clivus wedged in the oropharynx for 48 h and then moved towards the larynx, resulting in dyspnea and almost complete airway obstruction. RESULTS: Due to the dangerous airway situation, an urgent exploration and removal of the dislocated clivus was necessary. After a potential cervical spine instability was ruled out, the patient's airway was initially secured with an awake tracheotomy and the clivus was removed transorally. The tracheostomy tube was removed during the ongoing inpatient stay, and the patient was discharged with significant pain relief. CONCLUSIONS: The present case illustrates an orphan complication of skull base ORN resulting in a major airway emergency situation.

Radiologic findings of osteonecrosis, osteoradionecrosis, osteomyelitis and jaw metastatic disease with cone beam CT.

PURPOSE: The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM) and jaw metastatic disease (JM), evaluate the presence and extent of radiologic findings, identify radiologic parameters that may distinguish the four entities and last, introduce a new modified radiographic index (CRIm), in order to contribute to the diagnosis of these conditions. METHODS: Τwo major databases were retrospectively searched for fully documented and diagnosed CBCT scans of MRONJ, ORN, OM and JM from 2006 to 2019. 335 CBCT scans met the inclusion criteria and were assessed under standardized viewing conditions blindly by 2 observers. The CRIm index proposed in this study evaluates: lytic changes, sclerosis, periosteal bone formation, sequestration, non-healing extraction sockets and other findings which included: sinus implication, inferior alveolar canal implication and jaw fracture. Lytic changes, sclerosis, periosteal bone formation, sequestration and non-healing extraction sockets were scored as: absent (0), localized/single (1) and extensive/multiple (2). Each one of other findings were scored individually as: absent (0) and present (1). For statistical analysis t-test, Pearson's r correlation coefficient, one-way ANOVA and Bonferonni were performed. RESULTS: Extensive lytic changes were the most common finding, especially for ORN, where it occurred in all CBCT scans (100%). The mean value of the CRIm index differs significantly between CBCT scans with MRONJ and JM, as well as between those with OM and JM (Bonferroni p < 0.001). CONCLUSIONS: The new modified Composite Radiographic Index introduced in this study, appears to have improved an objective approach to the previously used Composite Radiographic Index by means of cumulative radiologic features. Τhe predominance of certain radiologic features in one or more of these entities may lead the diagnostician towards the correct diagnosis.

Osteoradionecrosis of the lamina papyracea leading to recurrent orbital infections-A case study.

Osteoradionecrosis (ORN) is a well-known complication of radiotherapy (RT) to the sino-nasal cavity and nasopharynx. Here, we report a case of recurrent orbital infections secondary to ORN of the lamina papyracea (LP). A 66-year-old female presented to our unit with right periorbital swelling and pain after having undergone chemotherapy and proton beam irradiation to her ethmoid sinuses for sino-nasal undifferentiated carcinoma (SNUC) 5 years prior. She had also undergone endoscopic sinus surgery for chronic rhinosinusitis about a year prior to the current presentation. Her post-operative course was notable for recurrent episodes of pre-septal cellulitis occurring about 3 months apart that were increasingly severe. Examination revealed right proptosis, and endoscopy showed an exposed and denuded LP with scant crusting of the ethmoid sinuses. Microbial studies did not yield any significant growth, and imaging showed enhancement of the right orbit. The working diagnosis was acute right orbital cellulitis secondary to ORN of the right LP. She was treated with broad spectrum intravenous antibiotics and systemic steroids, but experienced minimal symptomatic improvement. She then underwent endoscopic resection of the right LP, and histopathological examination showed osteonecrosis on an inflammatory background. Post-operatively, all orbital symptoms resolved and she was well at 6 months' follow up. In the discussion, we highlight additional factors in our patient that may have contributed to this clinical presentation, and hope that this report raises awareness of a rare complication of RT to the sino-nasal cavity.

Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma.

INTRODUCTION: Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between osteoradionecrosis and recurrent or progressive disease, as clinical and radiologic features may be similar. Our aim was to compare the clinical presentation and radiologic features of osteonecrosis with those of recurrent or progressive cancer. METHODS: We conducted a single-center case series of 19 patients with head and neck squamous cell carcinoma diagnosed between 2011 and 2019 who subsequently developed clinical and/or radiological suspicion of osteoradionecrosis. The population was a referred sample from head and neck cancer physicians at Northwell Health Cancer Institute. Clinician notes and imaging reports were reviewed to assign a final diagnosis of either cancer, osteonecrosis, or indeterminate. RESULTS: No differences were found in the clinical presentation or radiologic features between groups. Median time between treatment and development of symptoms was longer in patients with a final diagnosis of osteoradionecrosis than recurrent or progressive disease (5 vs. 3 months), but this difference was not statistically significant. Radiation dose and type were not associated with diagnosis. Mean standard uptake value maximums on positron emission tomography/computed tomography were significantly higher in the cancer group (median 14.8 vs. 9.1, p < 0.0152). At 1 year after first suspicion of osteoradionecrosis, 100% of osteoradionecrosis patients were alive, versus 28.6% of cancer patients. DISCUSSION/CONCLUSION: There is significant overlap in clinical and radiologic features of osteoradionecrosis and cancer. Standard uptake maximums may be helpful in predicting diagnosis. Occurrence of symptoms within 6 months of completing chemoradiotherapy should raise the concern for malignancy.

Comparison of maximum and mean standardized uptake values of jaw pathologies with bone SPECT/CT: an especial focus on medication-related osteonecrosis of the jaw.

OBJECTIVES: To investigate the comparison of maximum and mean standardized uptake values (SUVs) of jaw pathologies with bone Single-photon emission computed tomography/computed tomography (SPECT/CT), and a special focus on medication-related osteonecrosis of the jaw (MRONJ). METHODS: Eighty-nine patients with jaw pathologies (63 MRONJ, 13 chronic osteomyelitis, 11 osteoradionecrosis and 2 primary intraosseous carcinoma) underwent bone SPECT/CT scans acquisition at 4 h after intravenous injection of Tc-99m hydroxymethylene diphosphonate in this prospective study. The evaluation of mean and maximum SUVs of jaw pathologies were performed using Q. Metrix and Xeleris workstation and defined the data automatically. Statistical analyses were performed by Pearson's correlation coefficient for comparison of maximum and mean SUVs and Mann-Whitney U-test for SUVs of MRONJ. A P value lower than 0.05 was considered to indicate statistical significance. RESULTS: Maximum SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 17.6 ± 8.4, 21.7 ± 7.1, 11.9 ± 4.8 and 26.6 ± 7.0, respectively. Mean SUVs of MRONJ, chronic osteomyelitis, osteoradionecrosis and primary intraosseous carcinoma were 10.1 ± 4.9, 11.9 ± 3.3, 7.0 ± 2.8 and 10.1 ± 4.5, respectively. The maximum SUV of jaw pathologies was significantly correlated with the mean SUV (Y = 0.494X + 1.228; R2 = 0.786; P < 0.001). Furthermore, maximum and mean SUVs of MRONJ had significant differences in underlying diseases, medication and staging. CONCLUSION: The maximum and mean SUVs with bone SPECT/CT can be an effective tool for the quantitative evaluation of jaw pathologies, especially MRONJ.

Vascular Analysis of Soft Tissues Around the Bone Lesion in Osteoradionecrosis, Medication-Related Osteonecrosis, and Infectious Osteomyelitis of the Jaw.

OBJECTIVE: The histopathological differences of the surrounding soft tissues in osteoradionecrosis of the jaw, medication-related osteonecrosis of the jaw as well as infectious osteomyelitis of the jaw patients were rarely investigated. Here, we focused on the vascular microarchitecture of the soft tissues around bone lesion and compared the microvessel difference of ORNJ, MRONJ, and IOMJ in a quantitative fashion. METHODS: A series of consecutive patients diagnosed as ORNJ, MRONJ, and acute/chronic IOMJ was retrospectively reviewed. All cases received preoperative cone bean computed tomography scans. Immunohistochemistry of CD34 was performed with the streptavidin-peroxidase method and the variables including vascular density, vascular area fraction, mean vessel lumen area, perimeter and diameter of the vessels as well as percentage of lumen less than 400 µm2 were analyzed. RESULTS: The results showed that the vascular-like structures were visible in more cases of acute/chronic IOMJ compared with ORNJ and MRONJ by hematoxylin-eosin staining. Quantitively, our results demonstrated the decreased vascular density, mean perimeter and diameter of the vessels but increased percentage of small vessels in ORNJ and MRONJ patients in contrast with IOMJ patients. CONCLUSIONS: Hypovascularity of surrounding soft tissues could play important roles in the etiology of IOMJ, ORNJ, and MRONJ, and microvessel profile may be a useful pathological diagnostic indicator to differentiate these 3 types of OMJ.

An audit of dental assessments including orthopantomography and timing of dental extractions before radiotherapy for head and neck cancer.

Introduction Head and neck cancer (HNC) patients should receive a dental assessment at an appropriate time before commencing radiotherapy (RT), to prevent complications such as osteoradionecrosis (ORN) if extractions are required. A recent orthopantomogram radiograph (OPG) is part of this assessment.Aim To compare the delivery of pre-RT dental assessment at the Regional Oncology Centre against national guidelines in regard to OPG assessments and timing of extractions.Materials and methods A consecutive cohort of patients treated curatively were selected within two timeframes (January to March 2018 and January to March 2019) using multidisciplinary team records at Liverpool University Hospital. Patient notes, x-ray images and records were examined.Results In total, 145 patients were identified. Eighty-nine percent (129) had an OPG radiograph and 72% (104) had a pre-RT dental assessment. Oral and laryngeal sites had the highest number of missed assessments. Altogether, 54 patients had dental treatment, with 47 undergoing extractions. Extractions were completed a median 13 days before RT started. By November 2020, no patients had been diagnosed with ORN.Conclusions Three-quarters of patients received a pre-RT assessment but there is scope for improvement. OPGs should be part of initial HNC staging and referral to Regional Oncology Centre dental services should be made as part of the pre-RT workup.

18F-FDG PET/CT for early response assessment of jaw osteoradionecrosis after the PENTOCLO protocol: A promising imaging modality.

INTRODUCTION: The Pentoxifylline, Tocopherol and Clodronate protocol (PENTOCLO) showed promising results for jaw osteoradionecrosis (ORN) management. However, the clinical and radiological improvements are often delayed, leading to unwanted long-term treatment, with potential loss of opportunity for more radical surgical treatments. Our objective was to assess the diagnosis performance of 18F-FDG PET/CT to early predict ORN response to the PENTOCLO protocol. MATERIALS AND METHODS: All patients from our center who were treated with the PENTOCLO protocol and with a 18F-FDG PET/CT performed at diagnosis and three months after the end of antibiotherapy were retrospectively included. The PENTOCLO protocol was always combined with prior appropriate antibiotherapy for six weeks. The healing endpoint was divided into healing, stability or worsening, according to the combination of clinical and radiological assessments at the date of last follow-up. For each patient, the difference between the maximal standardized uptake value (ΔSUVmax) of the ORN lesion at three months and baseline were computed. Diagnostic performance of 18F-FDG PET/CT was evaluated by sensitivity, specificity and the area under the receiver operating characteristic curve (ROC-AUC) of ΔSUVmax. RESULTS: 24 patients were included with an average follow-up of 29.3 months. The healing, stability and worsening rate were 25%, 62.5% and 12.5% respectively. The AUC for discriminating worsening vs stability or healing was 0.92 (IC95 [0.81-1.00]). A ΔSUVmax greater than or equal to 0 was predictive of a worsening with a sensitivity and specificity of 84 and 66% respectively. CONCLUSION: 18F-FDG PET/CT imaging could be useful for early prediction of PENTOCLO treatment resistance with appropriate antibiotherapy.

Refining the mandibular osteoradionecrosis rat model by in vivo longitudinal µCT analysis.

Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. Today, our lack of knowledge about the physiopathology restricts the development of new treatments. In this study, we refined the ORN rat model and quantitatively studied the progression of the disease. We tested the impact of radiation doses from 20 to 40 Gy, delivered with incident 4MV X-ray beams on the left mandible of the inbred Lewis Rat. We used micro-computed tomography (µCT) to obtain in vivo images for longitudinal bone imaging and ex vivo images after animal perfusion with barium sulphate contrast agent for vessel imaging. We compared quantification methods by analyzing 3D images and 2D measurements to determine the most appropriate and precise method according to the degree of damage. We defined 25 Gy as the minimum irradiation dose combined with the median molar extraction necessary to develop non-regenerative bone necrosis. µCT image analyses were correlated with clinical and histological analyses. This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures.

Dosimetry-guided virtual surgical planning in the reconstruction of mandibular osteoradionecrosis.

Patients with osteoradionecrosis (ORN) of the mandible pose additional challenges to the attending clinician when it comes to major reconstructive head and neck surgery. We present a novel technique to assist in the virtual surgical planning of mandibular ORN, which involves deforming previously delivered radiation dosimetry data on to the virtual mandible to aid in the assessment of surgical resection margins. This is a retrospective case series of patients whose treatment involved a traditional virtual surgical planning approach or dosimetry-guided virtual surgical planning. All the patients whose treatment involved dosimetry-guided virtual surgical planning had evidence of bony consolidation between the native mandible and fibular free flap. In comparison, only three of the nine patients in the traditional virtual surgical planning group demonstrated bony healing on subsequent imaging. In this known cohort of difficult-to-manage patients, any technique that helps to improve outcomes is a welcome addition to the armamentarium of the surgeon.

Osteoradionecrosis of the hyoid presenting as acute airway compromise.

BACKGROUND: Osteoradionecrosis (ORN) of the mandible is a well-known complication of radiation therapy for head and neck cancer. However, few reports have described hyoid bone ORN and its clinical implications. METHODS: We describe a retrospective case series of previously irradiated patients who were seen with sudden airway compromise, found to have underlying pathological hyoid fractures secondary to osteoradionecrosis. RESULTS: Six patients within postchemoradiation period (3-9 months) for oropharyngeal squamous cell carcinoma were seen with acute-onset dyspnea. Computed topography (CT) imaging was remarkable for severe airway luminal narrowing and pathological hyoid fractures. All six patients required urgent intervention with direct laryngoscopy and tracheostomy. Intraoperatively, five patients were seen with exposed necrotic hyoid bones. CONCLUSION: The hyoid and its associated musculature strongly influence upper airway patency. ORN may compromise its physiological function and leads to acute airway compromise. Hyoid ORN may hold significant and imperative clinical implications in head and neck cancer post-treatment surveillance.

Bone single-photon emission computed tomography-CT peak standardized uptake value for chronic osteomyelitis, osteoradionecrosis and medication-related osteonecrosis of the jaw.

INTRODUCTION: Recently, standardized uptake value (SUV) has been applied for the evaluation of SPECT-CT. This study was performed to investigate the bone SPECT-CT peak SUV for chronic osteomyelitis, osteoradionecrosis and medication-related osteonecrosis of the jaw (MRONJ). METHODS: Sixty-five patients with jaw lesions (12 chronic osteomyelitis, 12 osteoradionecrosis and 41 MRONJ) underwent SPECT-CT after injection of technetium-99m hydroxymethylene diphosphonate. The peak SUV was compared for the chronic osteomyelitis with osteoradionecrosis and MRONJ using GI-BONE software. Statistical analyses for the peak SUV were performed by one-way repeated measures analysis of variance with Tukey's HSD test. A P-value lower than 0.05 was considered as statistically significant. RESULTS: Peak SUV for chronic osteomyelitis (15.6 ± 4.4) was significantly higher than those for osteoradionecrosis (6.7 ± 2.1, P = 0.000) and MRONJ (10.7 ± 6.1, P = 0.019). CONCLUSION: The SPECT-CT peak SUV using GI-BONE software can be useful for the evaluation of jaw lesions, such as chronic osteomyelitis, osteoradionecrosis and MRONJ.

18F-FDG PET/CT in Osteoradionecrosis of the Hyoid.

Osteoradionecrosis (ORN) is a well-documented complication following radiation treatment for head and neck malignancy. Facial bones, mainly the mandible, laryngeal cartilage, and skull, are frequently involved sites for ORN. A rare site for ORN is the hyoid, with very limited cases described in the literature. Recognition of the imaging pattern of hyoid ORN is critical to avoid misdiagnosis of recurrent disease, prompting early treatment.

Osteomyelitis, osteoradionecrosis, or medication-related osteonecrosis of the jaws? Can CBCT enhance radiographic diagnosis?

OBJECTIVE: To attempt defining differential radiographic diagnostic characteristics for osteonecrotic lesions using 2D as opposed to 3D images. MATERIALS AND METHODS: This was a cross-sectional study. Subjects presenting mandibular osteonecrotic lesions (osteomyelitis, osteoradionecrosis, and medication-related osteonecrosis of the jaws) were selected and compared to a group of age- and gender-matched controls, all having both cone-beam computed tomographic images (CBCT) and panoramic radiographs (PANO). Both imaging modalities (predictor variables) were evaluated by two radiologists that scored lesion presence, eight additional radiological features, and a composite severity index (outcome variables). For each pathologic condition, characteristic features were assessed in PANO and CBCT by the Wilcoxon signed-rank test. Regression tree analysis revealed the predictive value of PANO and CBCT (α = 5%). RESULTS: Overall, the predictive value of PANO reached 74%, while for CBCT it became 90%. Regarding the composite severity index, CBCT enabled to detect more subtle lesions. Also, CBCT imaging allowed showing more distinct radiographic diagnostic features as compared to PANO imaging, more specifically when distinguishing osteomyelitis from both other lesions. CONCLUSIONS: Cone-beam computed tomography enabled showing more differences in radiological features between distinct osteonecrosis disease entities. CBCT imaging might be a better contributor for the detection of early lesions and to monitor further pathological developments in the mandible.

Risk assessment of osteoradionecrosis associated with periodontitis using 18F-FDG PET/CT.

PURPOSE: Osteoradionecrosis (ORN) is a serious complication after radiotherapy (RT), even in the era of intensity modulated radiation therapy (IMRT). The purpose of this study was to evaluate whether 18F-FDG PET/CT can predict ORN associated with periodontal disease in patients with oropharyngeal or oral cavity squamous cell carcinoma (OP/OC SCC) undergoing RT. METHODS: One hundred and five OP/OC SCC patients treated with RT who underwent pretreatment 18F-FDG PET/CT between October 2007 and June 2016 were retrospectively reviewed. A post-treatment diagnosis of ORN was made clinically based on presence of exposed irradiated mandibular bone that failed to heal after a period of three months without persistent or recurrent tumor. The maximum standardized uptake value (SUVmax) of periodontal regions identified on PET/CT was measured for all patients. Image-based staging of periodontitis was also performed using American Academy of Periodontology staging system on CT. RESULTS: Among 105 patients, 14 (13.3 %) developed ORN. The SUVmax of the periodontal region in patients with ORN (3.35 ±â€¯1.23) was significantly higher than patients without ORN (1.92 ±â€¯0.66) (P <  .01). The corresponding CT stage of periodontitis in patients with ORN was significantly higher (2.71±0.47) than patients without ORN (1.80±0.73) (P <  .01). ROC analysis revealed the cut-off values of developing ORN were 2.1 in SUVmax, and II in CT stage of periodontitis. The corresponding AUC was 0.86 and 0.82, respectively. CONCLUSIONS: Pretreatment 18F-FDG PET/CT identification of periodontitis may be helpful to predict the future development of ORN in patients with OP/OC SCC undergoing RT.

Cervical spine osteoradionecrosis or bone metastasis after radiotherapy for nasopharyngeal carcinoma? The MRI-based radiomics for characterization.

BACKGROUND: To develop and validate an MRI-based radiomics nomogram for differentiation of cervical spine ORN from metastasis after radiotherapy (RT) in nasopharyngeal carcinoma (NPC). METHODS: A radiomics nomogram was developed in a training set that comprised 46 NPC patients after RT with 95 cervical spine lesions (ORN, n = 51; metastasis, n = 44), and data were gathered from January 2008 to December 2012. 279 radiomics features were extracted from the axial contrast-enhanced T1-weighted image (CE-T1WI). A radiomics signature was created by using the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram model was developed based on the radiomics scores. The performance of the nomogram was determined in terms of its discrimination, calibration, and clinical utility. An independent validation set contained 25 consecutive patients with 47 lesions (ORN, n = 25; metastasis, n = 22) from January 2013 to December 2015. RESULTS: The radiomics signature that comprised eight selected features was significantly associated with the differentiation of cervical spine ORN and metastasis. The nomogram model demonstrated good calibration and discrimination in the training set [AUC, 0.725; 95% confidence interval (CI), 0.622-0.828] and the validation set (AUC, 0.720; 95% CI, 0.573-0.867). The decision curve analysis indicated that the radiomics nomogram was clinically useful. CONCLUSIONS: MRI-based radiomics nomogram shows potential value to differentiate cervical spine ORN from metastasis after RT in NPC.