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Journal of Translational Medicine Jun 2023Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer (HNC). However, its etiology and pathogenesis have not been completely...
BACKGROUND
Osteoradionecrosis (ORN) is a serious complication of radiotherapy for head and neck cancer (HNC). However, its etiology and pathogenesis have not been completely elucidated. Recent studies suggest the involvement of the oral microbiota in the development of ORN. The aim of this study was to assess the correlation between oral microbiota and the extent of bone resorption in ORN patients.
MATERIALS AND METHODS
Thirty patients who received high-dose radiotherapy for HNC were enrolled. Tissue specimens were collected from the unaffected and affected sides. The diversity, species differences and marker species of the oral microbial community were determined by 16 S rRNA sequencing and bioinformatics analysis.
RESULTS
The ORN group had greater microbial abundance and species diversity. The relative abundance of f_Prevotellaceaeand, f_Fusobacteriaceae, f_Porphyromonadaceae, f_Actinomycetaceae, f_Staphylococcaceae, g_Prevotella, g_Staphylococcus, s_Endodontalis and s_Intermedia were particular;y increased in ORN, suggesting a potential association between the oral microbiota and ORN. Furthermore, g_Prevotella, g_Streptococcus, s_parvula and s_mucilaginosa were identified as potential diagnostic and prognostic biomarkers of ORN. Association network analysis also suggested an overall imbalance in species diversity and ecological diversity in the oral microbiota of ORN patients. In addition, pathway analysis indicated that the dominant microbiota in ORN may disrupt bone regeneration by regulating specific metabolic pathways that increase osteoclastic activity.
CONCLUSION
Radiation-induced ORN is associated with significant changes in the oral microbiota, and the latter may play a potential role in the etiopathology of post-radiation ORN. The exact mechanisms through which the oral microbiota influence osteogenesis and osteoclastogenesis remain to be elucidated.
Topics: Humans; Osteoradionecrosis; Head and Neck Neoplasms; Health Status
PubMed: 37328857
DOI: 10.1186/s12967-023-04219-y -
European Annals of Otorhinolaryngology,... Aug 2022To systematically present and interpret the current literature on research and treatment perspectives for mandibular osteoradionecrosis (mORN) in the field of... (Review)
Review
OBJECTIVES
To systematically present and interpret the current literature on research and treatment perspectives for mandibular osteoradionecrosis (mORN) in the field of biomaterials.
MATERIAL AND METHODS
A systematic review of the literature using the "Synthesis without meta-analysis" (SWiM) methodology was performed on PubMed, Embase and Cochrane, focusing on the implantation of synthetic biomaterials for bone reconstruction in mORN in humans and/or animal models. The primary endpoints were the composition, efficacy on mORN and tolerance of the implanted synthetic biomaterials.
RESULTS
Forty-seven references were obtained and evaluated in full-text by two assessors. Ten (8 in humans and 2 in animal models) met the eligibility criteria and were included for analysis. Materials most often comprised support plates or metal mesh (5 of 10 cases) in combination with grafts or synthetic materials (phosphocalcic ceramics, glutaraldehyde). Other ceramic/polymer composites were also implanted. In half of the selected reports, active compounds (molecules, growth factors, lysates) and/or cells were associated with the reconstruction material. The number of articles referring to implantation of biomaterials for the treatment of mORN was small, and the properties of the implanted biomaterials were generally poorly described, thus limiting a thorough understanding of their role.
CONCLUSION
In preventing the morbidity associated with some reconstructive surgeries, basic research has benefitted from recent advances in tissue engineering and biomaterials to repair limited bone loss.
Topics: Animals; Biocompatible Materials; Humans; Mandible; Osteoradionecrosis; Prostheses and Implants; Plastic Surgery Procedures
PubMed: 34210630
DOI: 10.1016/j.anorl.2021.06.006 -
Head & Neck Jun 2022To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN).
OBJECTIVES
To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN).
MATERIALS AND METHODS
Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009.
RESULTS
Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94).
CONCLUSIONS
Although recurrence of ORN is rare, surgical complications are common and charges are high. Poorer outcomes and higher charges are associated with preoperative factors.
Topics: Aged; Drainage; Humans; Mandible; Mandibular Osteotomy; Osteoradionecrosis; Retrospective Studies
PubMed: 35238096
DOI: 10.1002/hed.27024 -
ORL; Journal For Oto-rhino-laryngology... 2023Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between...
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.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Osteoradionecrosis; Head and Neck Neoplasms; Positron Emission Tomography Computed Tomography; Osteonecrosis
PubMed: 36455537
DOI: 10.1159/000527261 -
The Cochrane Database of Systematic... Aug 2023This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue.... (Review)
Review
BACKGROUND
This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy.
OBJECTIVES
To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4.
ADVERSE EVENTS
Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence.
MAIN RESULTS
Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I = 74%; 2 RCTs, 158 participants; high-certainty evidence).
AUTHORS' CONCLUSIONS
These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.
Topics: Humans; Hyperbaric Oxygenation; Radiation Injuries; Neoplasms; Osteoradionecrosis; Disease Progression; Pain; Barotrauma
PubMed: 37585677
DOI: 10.1002/14651858.CD005005.pub5 -
European Journal of Radiology Aug 2023The purpose of this study was to assess CBCT scans of patients with medication related osteonecrosis of the jaws (MRONJ), osteoradionecrosis (ORN), osteomyelitis (OM)...
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.
Topics: Humans; Osteoradionecrosis; Bisphosphonate-Associated Osteonecrosis of the Jaw; Retrospective Studies; Sclerosis; Osteonecrosis; Cone-Beam Computed Tomography; Neoplasms; Neoplasms, Second Primary; Osteomyelitis; Jaw
PubMed: 37300936
DOI: 10.1016/j.ejrad.2023.110916 -
Oral Surgery, Oral Medicine, Oral... May 2018The purpose of this study was to evaluate the healing benefit provided by the antioxidant and antifibrotic properties of pentoxifylline-tocopherol or... (Review)
Review
OBJECTIVE
The purpose of this study was to evaluate the healing benefit provided by the antioxidant and antifibrotic properties of pentoxifylline-tocopherol or pentoxifylline-tocopherol-clodronate in combination therapy for osteoradionecrosis.
STUDY DESIGN
We searched for relevant reports in PubMed by using a combination of "osteoradionecrosis" and the following keywords: "pentoxifillyne," "tocopherol," "vitamin E," or "clodronate." We considered articles in English or Spanish, with no limitations on the publication date.
RESULTS
The combination of pentoxifylline plus tocopherol with or without clodronate was found to be effective for the treatment of mandibular osteoradionecrosis, although data were generally scarce and mostly came from retrospective case series.
CONCLUSIONS
This drug therapy is well tolerated and could be promising for the treatment of mandibular osteoradionecrosis, but prospective randomized controlled clinical trials are needed for further clarification.
Topics: Clodronic Acid; Drug Combinations; Head and Neck Neoplasms; Humans; Mandibular Diseases; Osteoradionecrosis; Pentoxifylline; Tocopherols
PubMed: 29550081
DOI: 10.1016/j.oooo.2018.02.004 -
Dental Clinics of North America Jan 2018Oral cancer therapies are associated with orofacial complications that could result in dose-limiting cancer treatment and consequent suboptimal tumor control. Oral... (Review)
Review
Oral cancer therapies are associated with orofacial complications that could result in dose-limiting cancer treatment and consequent suboptimal tumor control. Oral cancer treatment complications include oral mucositis, salivary gland hypofunction, odontogenic infections, pain, dermatitis, neurotoxicity, soft tissue fibrosis, trismus, osteoradionecrosis, and potential cancer recurrence. These complications significantly affect cancer survivorship, quality of life, and psychosocial status. Effective dental management of patients with oral cancer involves the coordination of care among several health care professionals before, during, and after cancer therapy. The goal is to minimize complications, and establish optimal quality of life for survivors.
Topics: Antineoplastic Agents; Dental Care for Chronically Ill; Dental Caries; Drug-Related Side Effects and Adverse Reactions; Humans; Mouth Neoplasms; Neoplasm Recurrence, Local; Osteoradionecrosis; Quality of Life; Radiotherapy; Stomatitis; Stomatognathic Diseases; Trismus; Xerostomia
PubMed: 29126490
DOI: 10.1016/j.cden.2017.08.010 -
Oral Diseases Mar 2017Osteonecrosis of the jaw may be caused by radiation, medication, or infection. Optimal therapy requires a multimodal approach that combines surgery with adjuvant... (Review)
Review
Osteonecrosis of the jaw may be caused by radiation, medication, or infection. Optimal therapy requires a multimodal approach that combines surgery with adjuvant treatments. This review focuses on the use of adjunctive hyperbaric oxygen therapy for this condition. In addition to evidence regarding the basic and clinical science behind hyperbaric oxygen therapy, controversies in the field and economic implications are discussed.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Humans; Hyperbaric Oxygenation; Jaw; Osteonecrosis; Osteoradionecrosis
PubMed: 27062390
DOI: 10.1111/odi.12489 -
Oral Surgery, Oral Medicine, Oral... May 2023The purpose of this manuscript is to review the current literature on osteoradionecrosis of the cervical spine (C-ORN) and to summarize the risk factors, presenting... (Review)
Review
OBJECTIVES
The purpose of this manuscript is to review the current literature on osteoradionecrosis of the cervical spine (C-ORN) and to summarize the risk factors, presenting symptoms and management strategies of this rare condition.
STUDY DESIGN
A systematic review of the literature on C-ORN was completed using PubMed. Nineteen articles met criteria; 97 patient cases were identified. Statistical analysis was completed from the patient cases.
RESULTS
Of the analyzed patients, 72% are male and 28% are female with an average age of 57.7 years. Nasopharyngeal carcinoma was the most common initial diagnosis (72%). Thyroid and other lower neck cancers were associated with a later onset of C-ORN compared with other cancers. C-ORN more commonly occurred in the clivus to C2 (55.3%, P = .004). Onset of C-ORN significantly differed for men (n = 6.99 years) and women (n = 17.5 years) (P = .022).
CONCLUSION
C-ORN can be a devastating complication of head and neck radiation therapy. C-ORN is associated with nasopharyngeal carcinoma, and most commonly affects the area of the clivus to cervical vertebrae C2. Cancers of the lower neck and female sex are associated with later onset. Initial presentation ranges from asymptomatic to severe neurologic deficits; the degree of intervention should be congruent with the severity of presenting symptoms. As long-term survival of patients with head and neck cancer increase, this complication may become more prevalent.
Topics: Female; Humans; Male; Middle Aged; Cervical Vertebrae; Head and Neck Neoplasms; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Osteoradionecrosis; Retrospective Studies
PubMed: 36529672
DOI: 10.1016/j.oooo.2022.08.019