Osteoradionecrosis Risk Factors in Patients Undergoing Maxil-lofacial Radiotherapy – a Systematic Review

Natural History and Clinical/Dosimetric Determinants of Osteoradionecrosis in a Large Cohort of Head and Neck Cancer Following Curative Radiotherapy: Debunking the Myth of Decreased Rates of Osteoradionecrosis in the Modern Radiotherapy Era

e18057 Background: We aimed to identify the incidence and risk factors for osteoradionecrosis (ORN) in head and neck cancer (HNC) patients. We also compared frequency of severity scores across different ORN grading systems. Methods: Retrospective review was conducted for HNC patients who were managed at our institution (2011-2018) with curative-intent definitive, pre- or post-operative intensity-modulated radiation therapy (IMRT) with 45Gy, and underwent pre-IMRT dental evaluation. Jaw ORN was defined based on: 1) clinical signs (exposed bone, bone spicules, sequestra, infection and fistula), 2) radiological finding (abnormal bone pattern, radiographic sequestra and pathological fracture), and 3) treatment required and response to therapy, either conservative (chlorhexidine rinse, antibiotics, PENTOCLO, and hyperbaric oxygen) or surgical (sequestrectomy, debridement, and jaw resection). ORN events were retrospectively graded using 6 different grading systems. Pre-IMRT periodontal condition (PC) was classified by universal multi-dimensional staging system based on number of teeth and bone loss (stages 0 to IV). Multivariable analysis (MVA) using logistic regression was applied to identify risk factors of ORN. Results: A total of 2735 HNC patients were included; median age 61 years, 30% (n = 807) current/ex-smokers, 72% (n = 1914) had moderate to severe PC (stage II-IV), 53% (n = 1459) oral cavity/oropharynx (OC/OP) primary tumor. The median IMRT dose was 70Gy/35 fractions, 43% (n = 1170) received concurrent chemotherapy, and 37% (n = 1006) underwent surgery. A total of 227 patients (8.3%) developed ORN. There was discrepancy in different grading system for capturing and reporting the degree of severity (i.e. grade) of ORN (table). On MVA, risk factors for ORN were: current/ex-smoker (OR 1.5, 95% CI: 1.12-2, p< 0.01), stage II-IV PC (OR 1.7, 95% CI: 1.17-2.36, p< 0.01), primary OC/OP tumor (OR 4.4, 95% CI: 3.08-6.29, p< 0.001], and IMRT dose prescription ≥60Gy (OR 3.5, 95%CI: 1.11-11.33, p< 0.01). Conclusions: ORN is relatively uncommon in HNC patients, however it can be under-reported by different grading systems. Risk factors for ORN were: smoking history, pre-IMRT poor PC condition, OC/OP primary tumor, and higher dose (≥60Gy) IMRT.[Table: see text]

Denture use and dental risk factors associated developing osteoradionecrosis after head and neck radiotherapy: A retrospective analysis of hospital records

Background: The project aimed at determining the incidence of mandibular osteoradionecrosis (ORN) after radiotherapy, possible risk factors, and mandibular dose-volume effects in a large cohort of head and neck cancer patients (HNC).Methods: The cohort consisted of 1224 HNC patients treated with 66–68 Gy in 2007–2015 predominantly with IMRT. ORN cases were defined from clinical observations at follow-up and through hospital code diagnostics after oral-maxillofacial surgery and cross-checked with the national Danish Head and Neck Cancer database. In a nested case–control study, patients with ORN cases were matched with two controls (1:2) and pre-RT dental procedures including surgery to the mandible were documented. Multivariable Cox regression analysis was applied using demographic and treatment variables including dental procedures, smoking and tumor characteristics, and combined with dosimetric data. Mean mandibular dose (Dmean) was pre-selected for the multivariable model.Results: ORN was recorded in 56 cases (4.6%) with a median time to event of 10.9 months (range 1.8–89.7) after RT, 90% occurred within 37.4 months. Median follow-up time was 22 months (0.3–95). Average Dmean was significantly higher in the ORN event cohort and significant dose-volume differences were observed for population mean DVH doses between 30 Gy and 60 Gy. In univariable analysis, smoking (HR = 1.69; CI 1.14–2.5), pre-RT surgery/tooth extraction (HR = 2.76; 1.48–5.14), and several dosimetric parameters including Dmean (HR = 1.05, 1.02–1.08) were all significantly associated with ORN. Dmean and surgery/tooth extraction remained significant predictors of ORN in multivariable analysis, HR = 1.04 (CI 1.01–1.07) and HR = 2.09 (CI 1.1–3.98), respectively, while smoking only retained its significance in an interaction analysis with pre-RT dental procedures.Conclusion: The onset of ORN of the mandible was early (median 10.8 months) and the incidence low (4.6%) after IMRT in HNC cancer patients. Surgery to the mandible and pre-RT tooth extraction, tobacco smoking, and treatment dose were associated with the development of ORN.

Background and PurposesTo assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN development to aid prevention. Materials and MethodsReview of 1050 HNC patients attending the Dental Oncology Clinic, CUDSH between 2010 and 2021 identified 47 cases of ORN. Medical, dental and radiotherapy records of these forty-seven patients were retrospectively reviewed. Patient-, tumour-, and treatment-related variables were investigated in association with osteoradionecrosis development. Analysis conducted using SPSS, Pearson’s Chi-square test (p < 0.05), and ordinal regression model. ResultsORN incidence was 4.4 %. Median time from radiotherapy (RT) to ORN development was 9.5 months (range 1–98.5 months). ORN development within the mandibular surgical site was significant (p <.001), presenting at a higher Notani grade (p =.002), in mid-mandibular body region (p =.028), at radiation doses ≥ 60 Gy (p =.035), due to induced causes (p =.029), and without resolution (p =.019). ConclusionThis is the first retrospective study of ORN in HNC patients in Ireland over 10-year period. ORN incidence was extremely low (4.4%). As patients reported high smoking/alcohol use and poor dental attendance pre-diagnosis, this suggests intensive dental intervention pre/post-diagnosis contributed to low ORN rates. Mandibular surgery pre-RT increased risk of developing ORN at the surgical site. Therefore, we recommend future treatment planning should contour the surgical site, designating it an organ at risk (OAR), assigning a dose constraint, where oncologically possible, with emphasis on reducing the hot-spot to this region; findings reinforce importance of life-long expert dental care to reduce ORN incidence.

Simple SummaryTeeth extractions before or after radiotherapy (RT) could be procedures at high risk for osteoradionecrosis (ORN) onset. This systematic review was performed to investigate the ORN incidence following teeth extractions during and after RT for head and neck (H&N) cancer and to evaluate any other possible risk factor. The results highlight how post-RT teeth extractions are a major risk factor for ORN onset (ORN incidence of 5.8%), especially in the mandible, with a diminishing trend in the last years.Teeth extractions before or after radiotherapy (RT) could be procedures at high risk for osteoradionecrosis (ORN) onset. This systematic review was performed to investigate the ORN incidence following teeth extractions during and after RT for head and neck (H&N) cancer and to evaluate any other possible risk factor. Methods: This systematic review was conducted according to PRISMA protocol, and the PROSPERO registration number was CRD42018079986. An electronic search was performed on the following search engines: PubMed, Scopus, and Web of Science. A cumulative meta-analysis was performed. Results: Two thousand two hundred and eighty-one records were screened, and nine were finally included. This systematic review revealed an ORN incidence of 5.8% (41 patients out of 462, 95% CI = 2.3–9.4); 3 ORN developed in the maxilla. No other clinical risk factors were detected. Conclusion: Post-RT teeth extractions represent a major risk factor for ORN development, especially in the mandible, with a diminishing trend in the last years. Further research on other possible risk factors might improve this evidence.

Factors Influencing the Development of Pneumonia in Patients With Head and Neck Cancer: A Meta-analysis.

ABSTRACTIntroduction: Radiotherapy is a cancer therapy that uses ionizing radiation to damage cancer cells. Ionizing radiation in the head and neck area can disrupt the function and integrity of the oral mucosa and cause oral mucositis. In Bandung, the prevalence and risk factors of oral mucositis in head and neck cancer (HNC) patients undergoing radiotherapy have not been studied. Some textbooks claim that the prevalence of radiotherapy-induced oral mucositis in HNC patients occurs at almost 100%. Various risk factors associated with oral mucositis have been studied, giving significantly different results. This research analyzes the correlation between risk factors and mucositis oral in head and neck cancer patients undergoing radiotherapy. Methods: This research is a cross-sectional retrospective study with secondary data from medical records of HNC patients at RSHS from January 2015 until December 2019. A consecutive sampling method was used to collect the data that match the Inclusion criteria, including diagnosis of HNC(ICD-10), receiving radiotherapy from the first cycle until the last cycle; having a complete medical record following variables (location of HNC coding by ICD-10, gender, age, education level, smoking habit, the cycle of radiotherapy, oral treatment, body mass index, and comorbid disease). All data were then analyzed using Spearman correlation. Result: 171 medical records showed 59 patients had oral mucositis after radiotherapy. 26.9% male and 7.6% female, with susceptible age 40-60 years. Analysis of the Spearman correlation, there is a significant relationship between body mass index (BMI) (ρ = 0,001), smoking habits (ρ = 0,001), and radiotherapy cycles (ρ = 0.001). Conclusion: There is a correlation between risk factors of oral mucositis in HNC patients undergoing radiotherapy in RSHS, including body mass index (BMI), smoking habits, and radiotherapy cycles.Keywords: Head and neck cancer; oral mucositis; prevalence; risk factor; retrospective study

To address the contradictory information on the role of delay in diagnosis on head and neck cancer survival. Systematic review and meta-analysis. Search on MEDLINE (1966 to March 2011), EMBASE (1980 to March 2011) and ISI proceedings (from inception to March 2011). The terms used were ('Head and neck cancers') AND ('delay'OR'prognostic'OR'survival') both in MeSH terms and free-text words. The reference lists of the retrieved articles were also revised manually to identify other potentially relevant papers. All searches were independently undertaken by two clinicians and one epidemiologist, and the results merged. Primary and specialised care levels. Meta-analysis of data from papers on the subject published from 1966 to 2011. Survival. After search in Medline and other databases, we computed pooled relative risks (RR) and 95% confidence interval (95%CI) from the 10 studies retrieved. The estimate of the relative risk of mortality related to any diagnostic delay (either patient or professional delay) was 1.34 (95%CI 1.12-1.61). Referral delay was associated with a three-fold increase in mortality. Total delay was marginally related to mortality (RR: 1.04, 95%CI: 1.01-1.07). By anatomic location, pharynx cancer shows the highest association (RR: 1.68, 95%CI: 1.22-2.31). Diagnostic delay is a moderate risk factor of mortality from head and neck cancer. However, part of the effect observed may be due to residual confounding (confounding from unknown variables that are not eliminated by adjustment).

The aim of this study was to investigate the association of different dental prophylactic modalities and osteoradionecrosis (ORN) and determine the risk of ORN under different timing periods of scaling, with the use chlorhexidine mouth rinse after surgery and with different strategies of fluoride gel application in head and neck cancer (HNC) participants. A cohort of 18,231 HNC participants, including 941 ORN patients and 17,290 matched control cases, were enrolled from a Longitudinal Health Insurance Database for Catastrophic Illness Patients (LHID-CIP) in Taiwan. Based on different dental prophylactic modalities before radiotherapy, including chlorhexidine mouth rinse, scaling, and fluoride gel, all HNC subjects were stratified into different groups. The Cox proportional hazard regression was used to compare ORN incidences under different dental prophylactic modalities. The results revealed that scaling and chlorhexidine mouth rinse were significantly related to ORN risk (P = 0.004 and P < 0.0001). Chlorhexidine mouth rinse was highly correlated to ORN occurrence (hazard ratio [HR], 1.83–2.66), as exposure increased the risk by 2.43-fold among oral cancer patients, regardless of whether they had received major oral surgery or not. Oral cancer patients receiving scaling within 2 wk before radiotherapy increased their incidence of ORN by 1.28-fold compared with patients who had not undergone scaling within 6 mo. There is no significance of fluoride application for dental prophylaxis in increasing ORN occurrence. In conclusion, dental prophylaxis before radiotherapy is strongly correlated to ORN in HNC patients. Chlorhexidine exposure and dental scaling within 2 wk before radiotherapy is significantly related to ORN risk, especially in oral cancer patients. The use of 1.1% NaF topical application did not significantly increase the risk of ORN in HNC patients. An optimal dental prophylaxis protocol to reduce ORN should concern cancer location, cautious prescription of chlorhexidine mouth rinse, and proper timing of scaling.

Comparison of Machine Learning and Deep Learning Methods for the Prediction of Osteoradionecrosis Resulting from Head and Neck Cancer Radiation Therapy

IntroductionTo identify potential risk factors for the development of jaw osteoradionecrosis (ORN) after 3D-conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) among patients with newly diagnosed head and neck cancer.Material and methodsThis study included 776 patients who underwent 3D-CRT or IMRT for head and neck cancer at the Department of Radiotherapy at the University Hospital Halle-Wittenberg between 2003 and 2013. Sex, dental status prior to radiotherapy, tumor site, bone surgery during tumor resection, concomitant chemotherapy, and the development of advanced ORN were documented for each patient. ORN was classified as grade 3, 4, or 5 according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer classification or grade 3 or 4 according to the late effects in normal tissues/subjective, objective, management, and analytic scale. The cumulative incidence of ORN was estimated. Cox regression analysis was used to identify prognostic risk factors for the development of ORN.ResultsFifty-one patients developed advanced ORN (relative frequency 6.6 %, cumulative incidence 12.4 %). The highest risk was found in patients who had undergone primary bone surgery during tumor resection (hazard ratio [HR] = 5.87; 95 % confidence interval [CI]: 3.09–11.19) and in patients with tumors located in the oral cavity (HR = 4.69; 95 % CI: 1.33–16.52). Sex, dentition (dentulous vs. edentulous), and chemotherapy had no clinically relevant influence.Discussion and conclusionIn contrast to most previous studies, we noted a low cumulative incidence of advanced ORN. Patients with tumors located in the oral cavity and those who undergo bone surgery during tumor resection prior to RT may be considered a high-risk group for the development of ORN.

To evaluate osteoradionecrosis (ORN) incidence in a cohort of patients undergoing tooth extraction (TE) before radiotherapy (RT) for head and neck cancers. The study protocol was approved by the Ethics Committee of Università Cattolica del Sacro Cuore (ID-2132) and registered at clinicaltrials.gov (ID: NCT04009161). TE was performed in case of signs of pericoronitis, periapical lesions, restorative impossibility, severe periodontitis. ORN was defined as exposed bone at an unhealed post-extraction socket in the absence of oncological recurrence. The RT plans were reviewed, and each post-extractive socket was contoured to calculate the received radiation dose. In total, 156 patients with 610 TE were enrolled. The mean follow-up was 567 days. ORN was diagnosed in four patients (2.6% of patients and 0.7% of TE). Need for osteotomy and radiation dose at the extraction site were associated with ORN (OR for osteotomy: 21.9, 95% CI: 2.17-222.2, p = 0.009; OR for RT dose: 1.1, 95% CI: 1-1.15, p = 0.05). TE appears to be a significant risk factor for ORN, particularly when osteotomy is required, and post-extraction sockets receive a high RT dosage. This study proposes a decision-making algorithm for TE and outlines a straightforward surgical protocol.

Defining the optimal radiation thresholds for Stratifying jaw osteoradionecrosis risk in head and neck cancer.

Osteoradionecrosis and Trismus Following Radiotherapy Is Genotype Dependent