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Ultrastructural Pathology Mar 2024Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing...
Radiation exposure is a major health concern due to bone involvement including mandible, causing deleterious effects on bone metabolism, and healing with an increasing risk of infection and osteoradionecrosis. This study aims to investigate the radiotherapy-induced microstructural changes in the human mandible by scanning electron microscopy (SEM). Mandibular cortical bone biopsies were obtained from control, irradiated, and patients with osteoradionecrosis (ORN). Bone samples were prepared for light microscopy and SEM. The SEM images were analyzed for the number of osteons, number of Haversian canal (HC), diameter of osteon (D.O), the diameter of HC (D.HC), osteonal wall thickness (O.W.Th), number of osteocytes, and number of osteocytic dendrites. The number of osteons, D.O, D.HC, O.W.Th, the number of osteocytes, and osteocytic dendrites were significantly decreased in both irradiated and ORN compared to controls ( < .05). The number of HCs decreased in irradiated and ORN bone compared to the control group. However, this was statistically not significant. The deleterious effect of radiation continues gradually altering the bone quality, structure, cellularity, and vascularity in the long term (>5 years mean radiation biopsy interval). The underlying microscopic damage in bone increases its susceptibility and contributes further to radiation-induced bone changes or even ORN.
Topics: Humans; Microscopy, Electron, Scanning; Osteoradionecrosis; Osteocytes; Haversian System; Mandible
PubMed: 38115187
DOI: 10.1080/01913123.2023.2295458 -
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 -
International Journal of Oral and... Nov 2023This study aimed to assess preoperative radiological and clinical examinations for identifying bone status and to evaluate survival outcomes in patients undergoing...
This study aimed to assess preoperative radiological and clinical examinations for identifying bone status and to evaluate survival outcomes in patients undergoing marginal mandibulectomy for the primary treatment of oral squamous cell carcinoma. The medical records, enhanced computed tomography (CT) scans, and pathological specimens of these patients were reviewed. Disease-free (DFS), local recurrence-free (LRFS), and osteoradionecrosis-free (ORNFS) survival were analysed. The study included 104 patients. The preoperative CT and clinical examinations achieved a sensitivity of 45.8% and specificity of 100% for judging bone condition. LRFS was 79.6% and DFS was 68.8%. Pathological bone invasion in significantly affected DFS (P = 0.597), while DFS was significantly higher for those with a lower clinical tumour stage (1/2 vs 3/4; P = 0.005) and postoperative radiotherapy (P = 0.011). Among 39 patients receiving postoperative radiotherapy, ORNFS was 75.2%. Postoperative chemotherapy significantly decreased ORNFS (P = 0.009). Tumour subsite (P = 0.003) and the resection site (P = 0.035) significantly affected the remaining bone height. The results indicate that CT and clinical examinations cannot precisely identify superficial bone damage, but work well in selecting patients for marginal resection. Adhering to current indications, this resection approach can guarantee safe bone margins in terms of survival outcomes.
PubMed: 37271626
DOI: 10.1016/j.ijom.2023.05.007 -
International Journal of Radiation... 2024To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for...
BACKGROUND
To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC).
METHODS
Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news.
RESULTS
The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors () and the subgroup of patients re-irradiated more than two years after the first course of irradiation (). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10).
CONCLUSION
Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.
Topics: Humans; Carcinoma, Adenoid Cystic; Re-Irradiation; Carcinoma, Squamous Cell; Neoplasm Recurrence, Local; Head and Neck Neoplasms
PubMed: 37526368
DOI: 10.1080/09553002.2023.2242934 -
International Journal of Particle... 2023To assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to...
PURPOSE
To assess clinical outcomes of adolescents and young adults (AYAs) with head and neck sarcomas (HNSs) treated with pencil beam scanning proton therapy (PBSPT) and to report quality of life (QoL).
MATERIALS AND METHODS
Twenty-eight AYAs (aged 15 to 39 years) with HNS treated between January 2001 and July 2022 at our institution were included. The median age was 21.6 years. Rhabdomyosarcoma (39.3%), Ewing sarcoma (17.9%), chondrosarcoma (14.3%), and osteosarcoma (14.3%) were the most frequent diagnoses. Three (10.7%) patients were metastatic before PBSPT and 13 (46.4%) patients had a tumor with intracranial extension. The median total radiation dose was 63 GyRBE (range, 45 to 74 GyRBE). Thirteen (46.4%) patients received concomitant chemotherapy. Toxicity was reported according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 (US National Institutes of Health, Bethesda, Maryland). Survival was estimated using the Kaplan-Meier method. QoL was assessed using a PEDQOL (Pediatric Quality of Life Questionnaire) questionnaire. Self-reported outcomes were assessed using institutional questionnaires.
RESULTS
With a median follow-up of 57 months (range, 3.7 to 243 months), 5 patients (17.8%) had local failure (LF) only, 2 (7.1%) experienced distant failure (DF) only, and 2 (7.1%) had LF and DF. The estimated 5-year local control (LC) and distant control (DC) rates were 71.8% and 80.5%, respectively. The median times to LF and DF were 13.4 and 22.2 months, respectively. Four (14.3%) patients died, all but one from their HNS. Estimated 5-year overall survival was 90.7%. Six (21.4%) patients developed nonocular grade ≥3 toxicity, which consisted of otitis media (n = 2), hearing impairment (n = 2), osteoradionecrosis (n = 1), and sinusitis (n = 1). Four (14.3%) patients developed cataracts that required surgery. The 5-year freedom from nonocular grade 3 toxicity was 91.1%. No grade 4 or higher toxicity was observed. Adolescents rated their quality of life before treatment worse than their parents did.
CONCLUSION
Excellent outcomes with acceptable late-toxicity rates were observed for AYAs with HNS after PBSPT.
PubMed: 38075481
DOI: 10.14338/IJPT-23-00010.1 -
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 -
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 -
Annals of Translational Medicine Jun 2024
PubMed: 38911558
DOI: 10.21037/atm-24-10 -
The Laryngoscope Jan 2024To report the microorganisms and their antibiotic sensitivity profile from tissue cultures and stains at the time of anterolateral thigh fascia lata (ALTFL) rescue flap...
OBJECTIVE
To report the microorganisms and their antibiotic sensitivity profile from tissue cultures and stains at the time of anterolateral thigh fascia lata (ALTFL) rescue flap for management of mandibular osteoradionecrosis (ORN).
METHODS
Retrospective chart review of patients who underwent ALTFL rescue flap for native mandibular ORN between 2011 and 2022.
RESULTS
Twenty-six cases comprising 24 patients (mean age 65.4 years, 65.4% male) with mandibular ORN from whom tissue cultures and gram stain were obtained at the time of ALTFL rescue flap. 57.7% grew bacterial species, while 34.6% grew fungal species. Multibacterial speciation was noted in 26.9% of cultures. A combination of bacterial and fungal growth was also seen in 15.4% of cases. All gram-positive cocci (GPC) were pansensitive to antibiotics except for one case of Staphylococcus aureus, which was resistant to levofloxacin. Gram-negative bacilli (GNB) species were isolated in 50.0% of cases. All fungal growth was due to Candida species. No growth was noted in 23.1% of cases. Multidrug resistance was noted in 53.8% of cases when GNB was isolated.
CONCLUSION
We report 76.9% of our cases of mandibular ORN had microbial growth from tissue cultures obtained at the time of the ALTFL rescue flap. Fungal growth was noted in a substantial number of cases and should be obtained as a specimen when pursuing culture-driven antibiotic therapy. Most GPCs were pansensitive to antibiotics, while GNBs were often the harbinger of multidrug resistant mandibular ORN.
LEVEL OF EVIDENCE
4 Laryngoscope, 134:166-169, 2024.
Topics: Aged; Female; Humans; Male; Anti-Bacterial Agents; Drug Resistance, Bacterial; Mandible; Mandibular Diseases; Osteoradionecrosis; Retrospective Studies; Surgical Flaps
PubMed: 37401754
DOI: 10.1002/lary.30785 -
Oral Surgery, Oral Medicine, Oral... Aug 2023Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. Despite recent advances, there are patients who fail to...
OBJECTIVES
Osteoradionecrosis (ORN) of the jaw is a potentially devastating consequence of head and neck irradiation. Despite recent advances, there are patients who fail to respond to conventional therapies. Historically, free flaps were reserved for advanced cases requiring segmental resection and composite reconstruction, with early and intermediate disease treated more conservatively. We have adopted a more active surgical approach in selected intermediate cases.
STUDY DESIGN
A retrospective review of patients with intermediate stage ORN who received debridement and either fascio-cutaneous or fascio-periosteal free flap reconstruction was performed. Demographic data, ORN severity, treatment, and outcomes are described.
RESULTS
From 2019, 9 cases in 7 patients were identified. All cases were Notani grade II. There were 6 Epstein stage IIa and 3 Epstein stage IIIa. The mandible was the most common site (n = 8). Of the 7 patients, 2 had oropharyngeal primaries treated with chemoradiation, and 5 had oral cavity primaries treated with surgery and adjuvant radiation therapy. Three patients had prior hyperbaric oxygen therapy, and 2 had pentoxifylline/tocopherol therapy. After debridement, the radial forearm, ulnar artery perforator, and antero-lateral thigh fascio-cutaneous free flaps were each used in 1 case and the temporoparietal fascio-periosteal free flap was used in 6 cases. There was no recurrence or progression of ORN at the site of surgery, but 2 patients developed additional sites of ORN.
CONCLUSIONS
For patients with unresponsive intermediate ORN, debridement and soft tissue free flap reconstruction is an alternative to ongoing conservative management or composite resection and reconstruction.
Topics: Humans; Free Tissue Flaps; Osteoradionecrosis; Mandibular Diseases; Plastic Surgery Procedures; Retrospective Studies; Mandible
PubMed: 36804836
DOI: 10.1016/j.oooo.2022.12.002