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International Journal of Radiation... Apr 2024Osteoradionecrosis (ORN) of the mandible remains a significant complication in the intensity modulated radiation therapy (IMRT) era. Dental dose cannot be predicted from...
PURPOSE
Osteoradionecrosis (ORN) of the mandible remains a significant complication in the intensity modulated radiation therapy (IMRT) era. Dental dose cannot be predicted from heterogeneous IMRT dose distributions; mandibular dose metrics cannot guide dentist avulsion decisions in high-risk ORN situations. Using a mapping tool to report dental root dose, avulsions, and ORN sites, we re-examined ORN risk factors in a case-control study.
METHODS AND MATERIALS
From 2008 to 2019, 897 consecutive patients with oral cavity/oropharynx or unknown primary cancer undergoing IMRT were analyzed to identify ORN cases. These were matched (1 ORN/2 controls) retrospectively for tumor location, surgery, and tobacco consumption in a monocentric case-control study. Univariate and multivariate analyses integrated ORN factors and accurate dental dose data (grouped into 4 mandibular sectors). Generalizability was investigated in a simulated population database.
RESULTS
A total of 171 patients were included. The median follow-up was 5.2 and 4.5 years in the ORN and control groups, respectively. The median time to ORN was 12 months. In univariate analysis, post-IMRT avulsions at the ORN site (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 1.5-8.9; P = .005), tumor laterality (HR, 4.4; 95% CI, = 1.4-14, P = .01), mean mandibular dose (HR, 1.1; 95% CI, = 1.01-1.1; P = .018) and mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) correlated with higher ORN risk. In multivariate analysis, mean dose to the ORN site (HR, 1.1; 95% CI, = 1.1-1.2; P < .001) and post-IMRT avulsions at the ORN site (HR, 4.6; 95% CI, = 1.5-14.7; P = .009) were associated with ORN. For each increase in gray in dental dose, the ORN risk increased by 12%. Simulations confirmed study observations.
CONCLUSIONS
Dental dose and avulsions are associated with ORN, with a 12% increase in risk with each additional gray. Accurate dose information can help dentists in their decisions after IMRT.
PubMed: 38685504
DOI: 10.1016/j.ijrobp.2024.04.019 -
Dentistry Journal Mar 2024Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions....
Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.
Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.
PubMed: 38667995
DOI: 10.3390/dj12040083 -
Frontiers in Oncology 2024Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with... (Review)
Review
Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy.
BACKGROUND
Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy.
METHODS
A systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT.
RESULTS
Despite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap-tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications.
CONCLUSION
Flap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.
PubMed: 38665951
DOI: 10.3389/fonc.2024.1379861 -
MedRxiv : the Preprint Server For... Apr 2024Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published...
International Expert-Based Consensus Definition, Staging Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.
PURPOSE
Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 diagnostic/staging systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.
METHODS
The ORAL Consortium comprised 69 international experts, including representatives from medical, surgical, radiation oncology, and oral/dental disciplines. Using a web-based modified Delphi technique, panelists classified descriptive cases using existing staging systems, reviewed systems for feature extraction and specification, and iteratively classified cases based on clinical/imaging feature combinations.
RESULTS
The Consortium ORNJ definition was developed in alignment with SNOMED-CT terminology and recent ISOO-MASCC-ASCO guideline recommendations. Case review using existing ORNJ staging systems showed high rates of inability to classify (up to 76%). Ten consensus statements and nine minimum data elements (MDEs) were outlined for prospective collection and classification of precursor/ORNJ stages.
CONCLUSION
This study provides an international, consensus-based definition and MDE foundation for standardized ORNJ reporting in cancer survivors treated with RT. Head and neck surgeons, radiation, surgical, medical oncologists, and dental specialists should adopt MDEs to enable scalable health information exchange and analytics. Work is underway to develop both a human- and machine-readable knowledge representation for ORNJ (i.e., ontology) and multidisciplinary resources for dissemination to improve ORNJ reporting in academic and community practice settings.
PubMed: 38645105
DOI: 10.1101/2024.04.07.24305400 -
Radiotherapy and Oncology : Journal of... Jul 2024To assess osteoradionecrosis (ORN) incidence in a population of Irish Head and Neck cancer (HNC) patients, and assess precipitating factors that may contribute to ORN...
BACKGROUND AND PURPOSES
To 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 METHODS
Review 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.
RESULTS
ORN 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).
CONCLUSION
This 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.
Topics: Risk Factors; Osteoradionecrosis; Head and Neck Neoplasms; Incidence; Retrospective Studies; Ireland; Oral Hygiene; Humans; Male; Female; Adult; Middle Aged; Aged; Radiotherapy; Mandible
PubMed: 38641259
DOI: 10.1016/j.radonc.2024.110286 -
Periodontology 2000 Feb 2024Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long... (Review)
Review
Exosomes are the smallest subset of extracellular signaling vesicles secreted by most cells with the ability to communicate with other tissues and cell types over long distances. Their use in regenerative medicine has gained tremendous momentum recently due to their ability to be utilized as therapeutic options for a wide array of diseases/conditions. Over 5000 publications are currently being published yearly on this topic, and this number is only expected to dramatically increase as novel therapeutic strategies continue to be developed. Today exosomes have been applied in numerous contexts including neurodegenerative disorders (Alzheimer's disease, central nervous system, depression, multiple sclerosis, Parkinson's disease, post-traumatic stress disorders, traumatic brain injury, peripheral nerve injury), damaged organs (heart, kidney, liver, stroke, myocardial infarctions, myocardial infarctions, ovaries), degenerative processes (atherosclerosis, diabetes, hematology disorders, musculoskeletal degeneration, osteoradionecrosis, respiratory disease), infectious diseases (COVID-19, hepatitis), regenerative procedures (antiaging, bone regeneration, cartilage/joint regeneration, osteoarthritis, cutaneous wounds, dental regeneration, dermatology/skin regeneration, erectile dysfunction, hair regrowth, intervertebral disc repair, spinal cord injury, vascular regeneration), and cancer therapy (breast, colorectal, gastric cancer and osteosarcomas), immune function (allergy, autoimmune disorders, immune regulation, inflammatory diseases, lupus, rheumatoid arthritis). This scoping review is a first of its kind aimed at summarizing the extensive regenerative potential of exosomes over a broad range of diseases and disorders.
Topics: Humans; Exosomes; Regenerative Medicine
PubMed: 38591622
DOI: 10.1111/prd.12561 -
Journal of Contemporary Brachytherapy Feb 2024Brachytherapy (BT) is a validated radiation technique for treatment of early stage tumors of oral cavity and oropharynx. This study aimed to analyze the results of our...
PURPOSE
Brachytherapy (BT) is a validated radiation technique for treatment of early stage tumors of oral cavity and oropharynx. This study aimed to analyze the results of our institute's patients after replacing low-dose-rate (LDR) with pulse-dose-rate (PDR) brachytherapy.
MATERIAL AND METHODS
We retrospectively collected data from all patients treated between 2009 and 2020 for squamous cell carcinoma (floor of the mouth, tongue, and oropharynx) using adjuvant interstitial BT with or without external RT. Primary outcome was local control. Secondary outcomes were regional control rate and toxicity. Statistical analysis of local and regional recurrences were described using Kaplan-Meier method. Prognostic value of each factor for recurrence or toxicity was evaluated with bivariate Fine-Gray model.
RESULTS
Data from 66 patients were analyzed. Local and regional recurrences were reported in 11% and 20% of the patients, respectively. No significant factors were identified in the present study. Grade 2 and 3 acute mucositis were reported in 21% of patients, and were more frequent in the BT only group. Almost half (47%) of the patients described acute pain following BT, and 26% required stage 2 or 3 analgesics. Trophic disorders were observed in 16 patients. Five patients presented with soft tissue necrosis (STN) and required medical treatment, of whom one subsequently required hyperbaric oxygen therapy. No predictive factors were identified for STN risk. Two patients developed osteoradionecrosis.
CONCLUSIONS
Oral and oropharyngeal PDR-BT as adjuvant treatment is safe and effective for well-defined indications.
PubMed: 38584888
DOI: 10.5114/jcb.2024.135626 -
Journal of Stomatology, Oral and... Jun 2024Head and neck cancer squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with around 600,000 new diagnosis each year. Nowadays, in locally...
INTRODUCTION
Head and neck cancer squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with around 600,000 new diagnosis each year. Nowadays, in locally advanced disease, radiotherapy (RT) play an important role, this with or without chemotherapy in organ preservation strategies. More specific for early stage localized disease, RT (or surgery) seems to give similar results on locoregional control (LRC) and choice is made according to the organ preservation issue. Despite the fact that technical improvements have been made to optimize the radiation dose delivery and minimize the normal tissue toxicity, RT is associated with potential early and late toxicities. Osteoradionecrosis of the jaw (ORNJ), especially seen after teeth extraction, is one of the associated toxicities and can significantly impair the patient's quality of life. Because of the fear of developing ORNJ, one is very reluctant to extract or place a dental implant post-radiotherapy, especially in high irradiation dose zones (>40 Gy). Hence, it is important to define teeth at risk of future extraction before initiating RT and to handle those in high-risk irradiation zones. In order to optimise extractions, we created a predictive model of the expected irradiation dose, and thus the need for extraction, to the teeth bearing bones. The aim of this study is to validate our model and to define the potential relationship between the radiation dose received by each tooth and the dental complications observed.
MATERIAL AND METHODS
Between March 2012 and March 2018, patients with HNSCC treated by intensity modulated RT were retrospectively analysed. The mean irradiation dose for each tooth was generated on the administered treatment plan by contouring each tooth separately on each dosimetric scan section using dedicated software (Eclipse, Varian). In order to validate our predictive model, we compared the actual generated/administered teeth irradiation doses with the irradiation doses predicted by our model.
RESULTS
Our predictive model was accurate in 69.6% of the cases. In 12.5% of cases the predicted dose was higher than the calculated dose and lower in 17,8% of the cases. A correct- or over-estimation (is the latter being clinically less worrying than an underestimated dose) was achieved in 82% of cases. For the 18% of cases underfitting, the mean margin of error was 5.7 Gy. No statistically significant association was found between the development of caries and doses to the teeth, doses to the parotid glands or dental hygiene. However, a significant association between dental irradiation at more than 40 Gy and the occurrence of dental fractures (p = 0.0002) were demonstrated.
CONCLUSIONS
Our predictive model seems to be 82% accurate for dose prediction, hence might be helpful for optimizing/minimizing prophylactic extractions. Indeed, following our model, professionals could decide not to extract damaged teeth in areas not at risk of ORNJ, lowering morbidity during and after RT. Contrary to the literature, no relationship was found between the occurrence of dental caries and parotid irradiation and the patient's oral hygiene. However, for the first time, a highly significant correlation between the occurrence of dental fracture and dental irradiation at more than 40 Gy was observed.
Topics: Humans; Retrospective Studies; Osteoradionecrosis; Head and Neck Neoplasms; Male; Female; Middle Aged; Aged; Radiotherapy Dosage; Tooth Extraction; Adult; Squamous Cell Carcinoma of Head and Neck; Aged, 80 and over
PubMed: 38556165
DOI: 10.1016/j.jormas.2024.101858 -
Advances in Radiation Oncology May 2024The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base...
PURPOSE
The purpose of this study was to evaluate the feasibility and safety of dose-escalated proton beam therapy for treating chordomas and chondrosarcomas of the skull base and spine. Methods: A prospective cohort of 54 patients (42 with chordomas and 12 with chondrosarcomas) was enrolled between 2010 and 2018. The primary endpoints were feasibility and <20% rate of acute grade ≥3 toxicity, and secondary endpoints included cancer-specific outcomes and toxicities. Patients were followed with magnetic resonance imaging or computed tomography at 3-month intervals. Proton beam therapy was delivered with doses up to 79.2 Gy using protons only, combination protons/intensity modulated radiation therapy (IMRT), or IMRT only.
RESULTS
Feasibility endpoints were met, with only 2 out of 54 patient radiation therapy plans failing to meet dosimetric constraints with protons, and 4 out of 54 experiencing a delay or treatment break >5 days, none for toxicities related to treatment. There were no grade 4 acute toxicities and 1 grade 3 acute toxicity (sensory neuropathy). The only 2 grade 3 late toxicities recorded, osteoradionecrosis and intranasal carotid blowout (mild and not emergently treated), occurred in a single patient. We report overall survival as 83% at 5 years, with local failure-free survival and progression-free survival rates of 72% and 68%, respectively. Five patients developed distant disease, and among the 9/54 patients who died, 4 deaths were not attributed to treatment or recurrence.
CONCLUSIONS
Our findings suggest that high-dose proton therapy alone or in combination with IMRT is a safe and effective treatment option for chordomas and chondrosarcomas of the skull base and spine.
PubMed: 38550376
DOI: 10.1016/j.adro.2024.101456 -
Clinical and Translational Radiation... May 2024Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased...
OBJECTIVES
Patients with head and neck cancer are routinely screened for dental foci prior to radiotherapy (RT) to prevent post- RT tooth extractions associated with an increased risk of osteoradionecrosis. We evaluated the risk factors for post-RT tooth extraction to personalise dental screening and prevention protocols prior to RT.
MATERIALS AND METHODS
This retrospective cohort study included dentulous patients diagnosed with oropharyngeal cancer who had undergone radiation therapy at doses 60-70 Gy and achieved a disease-free survival of ≥ 1 year (N = 174). Risk factors were assessed using Cox regression models.
RESULTS
The cumulative incidence of post-RT tooth extraction was 30.7 % at 5 years. Main indications for extraction (n = 62) were radiation caries (n = 20) and periodontal disease (n = 27). Risk factors associated (p < 0.05) with radiation caries-related extractions included active smoking, alcohol abuse, poor oral hygiene, parotid gland irradiation, and mandibular irradiation. A high-dose volume in the mandible was associated with periodontal disease events.
CONCLUSION
Post-RT extractions due to radiation caries were influenced by lifestyle factors and RT dose in the mandible and parotid glands. Periodontal disease-related extractions were primarily associated with the mandibular dose. During dental screening these post-RT risk factors should be taken into account to prevent osteoradionecrosis.
PubMed: 38495648
DOI: 10.1016/j.ctro.2024.100759