Osteoradionecrosis - an old problem with new consequences.

PURPOSE OF REVIEW: Osteoradionecrosis (ORN) is a devasting complication of radiation therapy (RT), especially in head and neck cancers (HNC), and is still poorly understood. The aim of this review is to report its incidence and consider the risk factors associated with ORN to highlight prevention strategies to decrease its incidence. RECENT FINDINGS: The average incidence of ORN is between 2% and 23%, with incidence decreasing in more recent years with the introduction of modern RT technology and better oral health care. Smoking, diabetes mellitus, oropharyngeal and oral cavity cancers, pre- and post-RT dental extractions and a total radiation dose of over 60 Gy were all identified as risk factors for ORN. In prevention, strategies were mainly structured around minimising risk factors or targeting possible mechanisms of ORN's pathophysiology. SUMMARY: At present, the controversy surrounding the risk factors and pathogenesis of ORN makes it difficult to establish a set of prevention guidelines for its incidence. In order to achieve this, more research examining its aetiology must be conducted as well as a universal staging system within which ORN may be classified.

Effects of systemic Anatolian propolis administration on a rat-irradiated osteoradionecrosis model.

OBJECTIVE: Radiotherapy after head and neck cancer is associated with the risk of osteonecrosis development. This study aims to investigate the effectiveness of systemic propolis application to prevent the disease as it has no definite treatment protocol despite the proposed treatment methods and significantly decreases individuals' quality of life. METHODOLOGY: In total, 29 male Wistar-Albino rats were divided into control, 35 Gy irradiation (Group 1), 35 Gy irradiation+100 mg/kg/ml propolis administration (Group 2), and 35 Gy irradiation+200 mg/kg/ml propolis administration groups (Group 3). Propolis was first applied on the day after radiotherapy, except for the control group. Right first and second molars were extracted from all rats three weeks following radiotherapy. Samples were collected seven weeks after radiotherapy. Osteoblast and osteoclast counts were calculated by histomorphometric analysis. Immunohistochemical analysis determined bone morphogenic protein-2 (BMP-2) and transforming growth factor beta-3 (TGFß-3). RESULTS: Group comparison found non-significant differences regarding osteoblast (p=0.130) and osteoclast (p=0.063) counts. However, Group 1 showed the lowest mean osteoblast (OBL: 82.63 [±13.10]) and highest mean osteoclast counts (OCL: 12.63 [±5.55]). OBL/OCL ratio showed significant differences between groups (p=0.011). Despite the significant difference between the Control and Groups 1 (p=0.006) and 2 (p=0.029), Group 3 showed a non-significant difference (p=0.091). For BMP-2 and TGFB3, the control group showed significant differences with the other two groups (p<0.001), except for Group 3. CONCLUSION: Anatolian propolis showed beneficial effects in a radiotherapy-mediated osteonecrosis model, highlighting its potential as a promising intervention.

Hyperbaric oxygen therapy for late radiation tissue injury.

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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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.

Implication of dental insurance status on patterns of pre-radiation dental extraction and risk of osteoradionecrosis of the jaw in head-and-neck cancer patients.

Oral toxicities such as osteoradionecrosis can be minimized by dental screening and prophylactic dental care prior to head and neck (HN) radiation therapy (RT). However, limited information is available about how dental insurance interacts with prophylactic dental care and osteoradionecrosis. To address this gap in knowledge, we conducted a cohort study of 2743 consecutive adult patients treated with curative radiation for HN malignancy who underwent pre-radiation dental assessment and where required, prophylactic dental treatment. Charts were reviewed to determine patient demographics, dental findings, dental treatment and development of osteoradionecrosis following radiation. Three insurance cohorts were identified: private-insured (50.4 %), public-insured (7.3 %), being patients with coverage through government-funded disability and welfare programs, and self-pay (42.4 %). More than half the public-insured patients underwent prophylactic pre-radiation dental extractions, followed by self-pay patients (44 %) and private-insured patients (26.6 %). After a median follow-up time of 4.23 years, 6.5 % of patients developed osteoradionecrosis. The actuarial rate of osteoradionecrosis in the public-insured patients was 14.7 % at 5-years post-RT, compared to 7.5 % in private-insured patients and 6.7 % in self-pay patients. On multivariable analysis, dental insurance status, DMFS160, age at diagnosis, sex, tumor site, nodal involvement, years smoked and gross income were all significant risk factors for tooth removal prior to HN radiation. However, only public-insured status, tumor site and years smoked were significant risk factors for development of osteoradionecrosis. Our findings demonstrate that lack of comprehensive dental coverage (patients who self-pay or who have limited coverage under public-insured programs) associates strongly with having teeth removed prior to HN RT. Nearly 1 in 6 patients covered under public-insurance developed osteoradionecrosis within 5 years of completing their treatment. Well-funded dental insurance programs for HN cancer patients might reduce the number of pre-RT extractions performed in these patients, improving quality of life post-RT.

The role of hyperbaric oxygen in osteoradionecrosis-a prophylactic insight.

BACKGROUND: Osteoradionecrosis (ORN) is an uncommon and debilitating consequence of head and neck radiotherapy and hyperbaric oxygen therapy (HBOT) has been advocated for prophylaxis prior to performing dentoalveolar procedures. The aim of this study was to evaluate a prophylactic HBOT protocol and describe the outcomes of susceptible individuals. METHODS: A retrospective audit of adults who attended the Oral and Maxillofacial Surgery department at the Royal Adelaide Hospital (South Australia) who received dental extractions with a history of radiotherapy to the jaws from 2008 to 2020. Data including demographic information and outcomes of osteoradionecrosis and delayed healing was recorded. RESULTS: A total of 121 individuals were eligible for case note review; 68.6% of individuals were male and 55.4% were aged over 67 years. Osteoradionecrosis occurred in 9.1% of individuals and delayed healing for 3.3%; fifteen individuals (12.4%) were unable to complete the HBOT protocol. The individuals who were diagnosed with ORN had a significant association with age (P = 0.006) and binary analysis showed alcohol consumption to be a significant predictor. CONCLUSIONS: Prophylactic HBOT protocol had a lower proportion of individuals diagnosed with ORN and those who were diagnosed were more likely to be younger males and have current alcohol consumption.

An umbrella review exploring the effect of radiotherapy for head and neck cancer patients on the frequency of jaws osteoradionecrosis.

OBJECTIVE: Efforts have been made to reduce epidemiological indicators of osteoradionecrosis in patients with head and neck cancer over recent years. This umbrella review aims to synthesize the information of the systematic reviews/meta-analyses investigating the effect of radiotherapy in patients with head and neck cancer on the frequency of osteoradionecrosis and to identify and analyze the gaps in current scientific literature. MATERIAL AND METHODS: A systematic review of systematic reviews with and without meta-analysis of intervention studies was conducted. Qualitative analysis of the reviews and their quality evaluation were performed. RESULTS: A total of 152 articles were obtained, and ten of them were selected for the final analysis, where six were systematic reviews and four were meta-analysis. According to the guide Assessing the Methodological Quality of Systematic Reviews (Amstar), eight articles included were of high quality and two of medium quality. These descriptive systematic reviews/meta-analyses included a total of 25 randomized clinical trials, showing that radiotherapy has positive effects on the frequency of osteoradionecrosis. Even though a reduction in the incidence of osteoradionecrosis was observed back in the history, in systematic reviews with meta-analysis, overall effect estimators were not significant. CONCLUSIONS: Differential findings are not enough to demonstrate that there is a significant reduction in the frequency of osteoradionecrosis in patients with head and neck cancer treated by radiation. Possible explanations are related to factors such as the type of studies analyzed, indicator of irradiated complication considered, and specific variables included in the analysis. Many systematic reviews did not address publication bias and did identify gaps in knowledge that require further clarification.

The use of liquid formulation pentoxifylline and vitamin E in both established and as a prophylaxis for dental extractions "at risk" of osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the jaws remains one of the most debilitating complications of radiotherapy (RT) in patients with head and neck cancer (HNC). Liquid pentoxifylline and vitamin E (PVe) presents an alternative formulation to tablets for patients with dysphagia or enteric feeding. OBJECTIVE: This study aimed to assess the clinical outcomes of using a liquid formulation of PVe for both established ORN and as a prophylaxis to avoid its occurrence after dental extractions. A secondary objective was to determine patient-reported side effects in relation to the liquid formulation of PVe. STUDY DESIGN: The clinical records of 111 patients with HNC who were prescribed liquid PVe were reviewed retrospectively (66 with established ORN and 45 as prophylaxis before an invasive dental procedure). RESULTS: In established ORN, 44% healed, and 41% were stable. In the prophylaxis group, 96% of surgical sites healed completely, with 4% (n = 2) developing ORN. Most patients (89%) were able to tolerate liquid PVe. Of the 11% (n = 12) who could not tolerate this regime, the most commonly reported side effect was gastric irritation (n = 5/12), whereas no more than 1 patient reported dizziness, malaise, and bleeding. CONCLUSIONS: This retrospective review suggests that liquid PVe is efficacious for both established ORN and as a prophylaxis. Side effects reported were similar to those recognized for the tablet formulation.

The dental management of patients irradiated for head and neck cancer.

Patients undergoing radiotherapy for head and neck cancers are prone to a range of dental complications, including mucositis, trismus, xerostomia, radiation caries and osteoradionecrosis. Specific considerations include the preventive, restorative and rehabilitative management of such patients, and the prevention and treatment of complications. This article aims to highlight the current understanding and management of dental needs for patients who have had or will undergo radiotherapy.

Can the prophylactic use of pentoxifylline and tocopherol before dental extractions prevent osteoradionecrosis? A systematic review.

PURPOSE: This systematic review aimed to determine whether the pentoxifylline and tocopherol (PENTO) protocol effectively reduce the risk of osteoradionecrosis (ORN) in patients undergoing tooth extraction after head and neck radiotherapy. METHODS: We searched PubMed, SCOPUS, LILACS, EMBASE, Web of Science, and Cochrane databases up to August 2022. We considered only studies that included patients diagnosed with head and neck cancer undergoing tooth extraction with PENTO prophylaxis after radiotherapy. RESULTS: Of the 642 studies identified, 4 were included. Across the included studies, 387 patients had 1871 teeth extracted while on PENTO prophylaxis. The interval of the PENTO protocol differed among the studies included. Overall, a total of 12 (3.1%) patients had ORN, whereas at the individual tooth level analysis the ORN rate was 0.9%. CONCLUSIONS: Insufficient evidence exists to promote using the PENTO protocol before dental extractions to prevent ORN.

Systematic dosimetric evaluation of risk of osteoradionecrosis (DERO): First results of dose reporting for preventing teeth osteoradionecrosis after head and neck irradiation.

PURPOSE: OsteoRadioNecrosis (ORN) is a late complication of radiation for head and neck cancer. Predicting ORN is a major challenge. We developed DERO (Dosimetric Evaluation of Risk of ORN), a semi-automatic tool which reports doses delivered to tooth-bearing sectors, to guide post-therapeutic dental care. We present the method and the first results of a 125-patient prospective cohort. MATERIAL AND METHODS: Dosimetric data of patients treated with IMRT for head and neck cancer were prospectively segmented to the DERO algorithm. Four arches corresponding to 8-tooth sectors were semi-automatically generated. Thirty-two cylindrical Regions Of Interest (ROI) corresponding to each tooth and surrounding periodontium were created by linear interpolation. Mean doses (Dmean) of ROI were extracted and included in a database, along with data about primary tumor site, laterality and dose values from organs at risk. Dmean to tooth sectors were computed for molar sectors, (teeth X5 to X8) and anterior sectors (teeth X1 to X4). An individual dose map was generated and delivered to patients and dentists. RESULTS: Dosimetric data from 125 patients treated with Tomotherapy® were prospectively collected and analyzed: 9 parotid tumors (PA), 41 Sub-Hyoid tumors (larynx, hypopharynx) (SH), 43 Oropharynx tumors (OR), 32 Oral Cavity tumors (OC). Irradiation was unilateral for 100% of PA tumors (9), 12% of OR tumors (5) and 47% of OC tumors (15). For unilateral cervical irradiation, Dmean in ipsilateral molar sectors was 54Gy for OC tumors, 45Gy for OR tumors, 20Gy for PA tumors. For Oral Cavity bilateral irradiation, Dmean was high in all tooth sectors, 49 to 55Gy. For SH tumors, Dmean in molar sectors was 27Gy. A dose gradient of 10 to 20Gy was observed between molar and anterior sectors whether radiation was uni or bilateral. CONCLUSION: Mandibular molar sectors of Oropharynx and Oral Cavity tumors were exposed to high Dmean of 40 to 50Gy. On the other hand, tooth sectors received lower doses for SH radiation. The DERO tool guide post-radiation dental care with a personalized dosimetric cartography to patient. With data update and patient follow-up, we will be able to determine ORN risk after head and neck radiation.

Time required for prophylactic oral care in head and neck cancer patients scheduled for radiotherapy: A single center, prospective cohort study.

BACKGROUND: Prophylactic oral care (POC) before radiotherapy (RT) is an adjunct but an integral process toward preparing patients for RT, however, time to be invested in POC remains unexplored. METHODS: Prospective treatment records were maintained in head and neck cancer patients, who received POC following a standardized protocol with definite timelines. Data collected for oral treatment time (OTT), interruption in RT due to oro-dental issues, future extraction(s), and incidence of osteoradionecrosis (ORN) up to 18 months after treatment were analyzed. RESULTS: Three hundred thirty-three patients, 275 males and 58 females, mean age 52.45 ± 11.2 years were included. Mean OTT was 21.0 ± 6.2 days and was influenced significantly with the number of extractions (p < 0.00). There was no interruption in RT schedule due to oro-dental issues. Five patients were diagnosed with ORN. CONCLUSION: Performing POC as demonstrated aid in timely removal of nidus of infection(s), perform RT as scheduled, and maintain satisfactory oral health through the survivorship of patients.

Pentoxifylline and tocopherol for prevention of osteoradionecrosis in patients who underwent oral surgery: A clinical audit.

PURPOSE: Osteoradionecrosis (ORN) of the jaw is a severe and debilitating complication of the head and neck radiotherapy which frequently occurrs after oral surgery. This clinical audit aims aevaluate the effectiveness of combined use of pentoxifylline and tocopherol (PENTO) in prevention ORN onset in patient who underwent oral surgery after head and neck radiotherapy (RT). MATERIAL METHOD: In this clinical audit Pentoxifylline 400 mg, twice a day, and Tocopherol 800 IU once a day (PENTO protocol) have been prescribed. Patients started the protocol 1 week before the surgical procedure and continued for 8 weeks after. RESULTS: Twenty-nine patients were included. They received 75 surgical interventions under PENTO protocol: 71 surgical procedures of dental extraction (single or multiple dental extractions in each session) and four implant placements. A total of 152 dental extractions were carried out: 64 surgical extractions which required the raising of mucoperiosteal flap, and 88 simple extractions. Four out of 29 patients developed ORN after surgical procedures: four cases of ORN occurred after dental extractions (5.6%) and one case of ORN after implant placement (25%). CONCLUSION: PENTO is a useful ORN preventive protocol, low-cost and clinically feasible, safe and well tolerated by patients. Further studies should focus on better defining the effectiveness PENTO, independently from the antibiotic therapy.

Effect of preradiation dental intervention on incidence of osteoradionecrosis in patients with head and neck cancer: A systematic review and meta-analysis.

BACKGROUND: The purpose of this systematic review was to examine whether dental intervention involving bone or soft-tissue manipulation preradiotherapy (pre-RT) is associated with lower rates of osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer (HNC). TYPES OF STUDIES REVIEWED: The authors included relevant studies from MEDLINE, Embase, and Cochrane Library, including observational studies published from 2007 through 2021 and involving adults who underwent dental intervention pre-RT for HNC. Authors assessed evidence certainty by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Random-effects models were used to calculate pooled relative risk estimates and hazard ratios. When meta-analysis was not possible, study-level measures of association and narrative summaries of the evidence were reported. RESULTS: Twenty-two studies were included. From the pooled, unadjusted analysis, patients undergoing pre-RT extractions may have a 55% increased risk of experiencing ORNJ (relative risk, 1.55; 95% CI, 0.85 to 2.86; very low certainty); the unadjusted pooled hazard ratio was 3.19 (95% CI, 0.99 to 10.31; very low certainty), corresponding to a possible increased hazard of developing ORNJ (very low certainty). Findings for other pre-RT procedures manipulating bone or tissue relied on limited, observational studies with low or very low certainty evidence. CONCLUSIONS: Mostly very low certainty evidence suggests that patients with HNC who need pre-RT dental intervention may have an increased risk of developing ORNJ compared with those who do not. PRACTICAL IMPLICATIONS: Maintaining optimal oral health may help reduce the need for urgent pre-RT dental treatment, potentially reducing ORNJ risk and minimizing delay of oncologic treatment in patients with HNC.

[The role of maxillofacial prosthodontics in the prevention of radiation]. / Place de la prosthodontie maxillo-faciale dans la prévention du patient irradié.

Tumors of the upper aerodigestive tract (ADT) are the most frequent tumors in the world, and among the tumors of the ENT sphere, the frequency of cancers of the oral cavity occupies the third place after that of the larynx and oropharynx. The treatment of these pathologies is heavy and complex. It is the result of a combination of several interventions, namely surgery, radiotherapy and chemotherapy. Among the consequences of radiotherapy, we can mention the embrittlement of dental tissues, osteoradionecrosis, stenosis of muscular tissues or radiomucitis of oral mucosal tissues. All these complications encourage the preparation of the patient before radiotherapy in order to mitigate the consequences and prevent complications. Through this work, we illustrate the place of maxillofacial prosthodontics in the prevention of the irradiated patient, through several prosthetic, medical or medicinal means.

To extract or not extract teeth prior to head and neck radiotherapy? A systematic review and meta-analysis.

PURPOSE: Teeth with poor prognosis are generally recommended to be extracted prior to head and neck radiotherapy (RT) to reduce the risk of developing osteoradionecrosis (ORN), although controversies have been reported. The present systematic review aimed to determine whether tooth extraction prior to head and neck RT may be associated with a reduced risk of developing ORN compared to dental extraction during or after RT. METHODS: The review protocol was registered in PROSPERO (CRD42021241631). The review was reported according to the PRISMA checklist and involved a comprehensive search of PubMed, Scopus, Embase, Cochrane Library, LILACS, and Web of Science, in addition to the gray literature. The selection of studies was performed in two phases by two reviewers independently. The risk of bias of individual studies was analyzed using the Joanna Briggs Institute checklist for cross-sectional studies, and the certainty of evidence was assessed using the GRADE tool. RESULTS: Twenty-eight observational studies were included in the qualitative synthesis, which showed substantial heterogeneity regarding the association between the timing of tooth extraction and ORN development. Twenty-seven of 28 studies were pooled in a meta-analysis that demonstrated a significant association between an increased risk of ORN and post-RT tooth extraction (odds ratio: 1.98; 95% CI: 1.17-3.35; p = 0.01). CONCLUSION: It was confirmed with moderate certainty that dental extractions should be performed prior to the start of head and neck RT to reduce the risk of ORN.

Frequency of osteoradionecrosis of the lower jaw after radiotherapy of oral cancer patients correlated with dosimetric parameters and other risk factors.

OBJECTIVES: Osteoradionecrosis (ORN) of the lower jaw is a serious late complication after radiotherapy in patients with oral cavity cancer. The aim of this study is to generate more insight into which patient- and treatment-related factors are associated with the development of ORN in oral cavity cancer patients undergoing postoperative radiotherapy. MATERIAL AND METHODS: Retrospective evaluation and comparison of 44 patients with ORN (event group 1) matched according to 45 patients without ORN (control group 2) who received postoperative radiotherapy of oral cavity squamous cell carcinoma at our institution between 2012 and 2020. Dosimetric factors that favor the occurrence of ORN should be detected. The cumulative occurrence rate of ORN was calculated according to the Kaplan-Meier method and analyzed by Cox regression and log-rank test. RESULTS: The median time to develop ORN was 18 months (3-93 months) after radiotherapy. Dental status before radiotherapy (RT) treatment (HR 4.5; 1.8-11.5) and dosimetric parameters including Dmean > 45 Gy (HR 2.4; 1.0-5.7), Dmax > 60 Gy (HR 1.3; 1.1-2.8) and planning target volume (PTV) proportion > 40% intersection with the lower jaw (HR 1.1; 1.0-1.1) were significantly associated with ORN. CONCLUSION: The results of this retrospective study reveal that oral cavity cancer patients who underwent pre-RT dental surgery as well as dosimetric parameters using Dmax > 60 Gy, higher mean doses > 45 Gy and more than 40% PTV intersection with the lower jaw bone are independent risk factors for ORN. These findings can assist in the management of patients undergoing RT for head and neck cancer regarding ORN prevention. CLINICAL RELEVANCE: Poor oral hygiene and desolate dental status as well as high radiation doses to the mandibular bone significantly increase the risk of developing osteoradionecrosis. Before irradiating a patient with oral cavity cancer, an appointment with the dentist should be made and teeth sanitized if necessary. Likewise, maximum radiation doses to the lower jaw should be minimized.

Autologous platelet concentrates in extraction sockets for the prevention of osteoradionecrosis: a systematic review of controlled clinical trials.

This systematic review aimed to assess whether the use of autologous platelet concentrates immediately after tooth extraction would prevent ORN in patients treated with radiotherapy (RT) for head and neck cancer (HNC). MEDLINE, Embase, Ovid, Scopus, Web of Science, CENTRAL Cochrane, and OpenGrey databases were searched (up to, and including, June 2021) by two independent reviewers to identify studies, followed by further manual search. As inclusion and exclusion criteria for the studies, only controlled clinical trials (randomized or not) were considered. The risk of bias of each included study was assessed using the Cochrane Risk of Bias Tool. Of the 129 potentially eligible studies, only 2 were included, both randomized controlled clinical trials; however, one used platelet-rich plasma and another leukocyte- and platelet-rich fibrin. Overall, both autologous platelet concentrates had no effect on the outcome assessed. The use of autologous platelet concentrates seems not to be beneficial for ORN prevention following tooth extractions in HNC patients treated with RT; however, according to the available evidence, a reliable statement cannot be made.

Prophylactic pentoxifylline and vitamin E use for dental extractions in irradiated patients with head and neck cancer.

OBJECTIVE: Osteoradionecrosis (ORN) of the jaw is preceded by dental extractions in up to 10% of cases. We present a case series of post-radiotherapy patients undergoing dental extractions who have received the prophylactic antifibrotic agents pentoxifylline and vitamin E (PVe) to prevent ORN. STUDY DESIGN: A retrospective review was conducted of 219 patients with head and neck cancer (HNC) undergoing 1079 dental extractions between 2009 and 2020. Data regarding oncological treatment, prophylactic drug regimen, dental history, and clinical outcome was collected. RESULTS: Twelve patients developed ORN at 17 extraction sites (ORN rates, 1.6% and 5.5% at tooth level and patient level, respectively). PVe regimen compliance significantly decreased ORN rates at the patient level (3.4% vs 11.5%; P < .03) and the tooth level (1.0% vs 3.5%; P < .01) compared with no PVe. Regimen compliance significantly reduced ORN rates in patients with oropharyngeal cancer (P < .01); in those with mandibular (P < .005) molar (P < .003), and flapless extractions (P < .04); in patients with radiation regions >40 Gy (P < .0009); and in those who underwent primary closure (P < .03). Machine learning analysis identified almost all these factors as influential at a tooth level for ORN. CONCLUSIONS: PVe regimen compliance decreased dental extraction ORN rates more than the literature base rates of 7% at the patient level and 2% at the tooth level. Given its success in managing existing ORN, PVe could be extended prophylactically for dental extractions in irradiated patients with head and neck cancer.

Overview and Emerging Trends in the Treatment of Osteoradionecrosis.

OPINION STATEMENT: Osteoradionecrosis (ORN) of the mandible is a rare but devastating complication which occurs following radiation therapy for head and neck malignancies. Left untreated, ORN often results in pathologic fracture of the mandible leading to pain, trismus, difficulty eating, and overall poor quality of life. Historically, early intervention relied on hyperbaric oxygen and local debridement. Patients whose disease progressed despite therapy required segmental resection of the mandible with osseous free flap reconstruction, a highly invasive operation. Patients that presented with a moderate disease without pathologic fracture were often doomed to fail non-operative management, ultimately leading to disease progression and fracture. The traditional dichotomous treatment paradigm left a void of options for patients with moderate disease. The ideal intervention for this category of patients would provide renewed vascularity to the diseased tissue bed allowing for the osteogenesis and reestablishment of strong, load-bearing bone. The innovative technique termed the vascularized fascia lata "rescue flap" has proven to be an effective treatment for moderate ORN and will likely transform dated treatment algorithms.

Clinical practice guidelines for dental management prior to radiation for head and neck cancer.

PURPOSE: Limited evidence exists linking the specific preventative dental care provided prior to radiation therapy (RT) for head and neck cancer to outcomes like osteoradionecrosis (ORN). This study utilized expert consensus to develop tooth-specific dental treatment pathways for head and neck cancer patients prior to radiation. MATERIALS AND METHODS: Dental oncologists from across a single nation were engaged in a Modified Delphi process. Three rounds of questionnaires were performed followed by an in-person meeting. Domains included radiation dose, timing of dental treatment, and treatment of dental caries, periodontal disease and third molars. RESULTS: The response rate from the 32 participants between rounds was > 70%. Consensus was reached for all but 4 questions. The radiation dose at which participants would prophylactically remove teeth to prevent ORN was established as 70 Gy in the maxilla and 60 Gy in the mandible. Treatment pathways were developed for maxillary and mandibular anterior/premolar and molar teeth receiving a dose at or above this threshold. Risk factors were established for carious, periodontally involved and third molar teeth. In general, periodontally involved teeth and mandibular molars were most frequently recommended for extraction. Only symptomatic third molars were recommended for extraction when adequate healing time was available prior to commencement of RT. CONCLUSION: Tooth-level clinical practice guidelines were developed using expert consensus via the modified Delphi process. The treatment pathways developed in this study will be prospectively tested to evaluate the outcomes associated with tooth-specific dental treatments.