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.

Long-term safety of photobiomodulation therapy for oral mucositis in hematopoietic cell transplantation patients: a 15-year retrospective study.

Photobiomodulation therapy (PBMT) has demonstrated efficacy in the prevention and treatment of oral mucositis (OM) in hematopoietic cell transplantation (HCT). However, based on the cell stimulation properties, its long-term safety has been questioned, mainly in relation to risk for secondary malignancies in the oral cavity. The aim of this study was to investigate if different PBMT protocols for OM control have association with immediate and late adverse effects in HCT patients. Data on autologous and allogeneic transplantation, conditioning regimen, PBMT protocols, and OM severity were retrospectively collected from medical and dental records. Presence of secondary malignancies in the oral cavity was surveyed during a 15-year follow-up. Impact of OM on overall survival was also analyzed. Different PBMT protocols for prevention and treatment of OM were recorded over the years. Severe OM (grades 3 and 4) was infrequently observed. When present, we observed a significant decrease of the overall survival. No immediate adverse effect and secondary malignancy was associated to PBMT. In conclusion, the PBMT protocols used in the study were considered safe. The low frequency of severe OM observed encourages the implementation of this technique, with a special emphasis on the dosimetry adjustments focused on the HCT context.

Strategic use of obturator prostheses for the rehabilitation of oral cancer patients during the COVID-19 pandemic.

During the current pandemic scenario, maxillofacial rehabilitation specialists involved with supportive care in cancer must transform its practice to cope with COVID-19 and improve protocols that could quickly return the oral function of complex cancer patients who cannot wait for surgical complex rehabilitation. This includes the role of the maxillofacial prosthodontist for the rehabilitation of surgically treated patients with maxillary cancers by the means of filling obturator prostheses that are considered an optimal scientific-based strategy to reduce hospital stay with excellent pain control, oral function (speech, swallowing, mastication, and facial esthetics), psychologic and quality of life outcomes for the patients following intraoral cancer resection. Therefore, the aim of this commentary was to bring new lights to the strategic use of obturator prostheses for the rehabilitation of oral cancer patients during the COVID-19 pandemic as well as to present a protocol for managing such cases.

Salivary alpha-1-antitrypsin and macrophage migration inhibitory factor may be potential prognostic biomarkers for oncologic treatment-induced severe oral mucositis.

AIMS: Evaluate the abundance of the selected targets, alpha-1-antitrypsin (A1AT) and macrophage migration inhibitory factor (MIF), and correlate these findings with the risk of developing severe oral mucositis (OM). MATERIALS AND METHODS: Head and neck squamous cell carcinoma (HNSCC) patients submitted to radiotherapy (RT) or chemoradiotherapy (CRT) were assessed. OM grade and pain were evaluated daily during treatment. Two protein targets, A1AT and MIF, were evaluated, using selected reaction monitoring-mass spectrometry (SRM-MS), in whole saliva, collected prior to oncologic treatment. The results obtained from the targeted proteomic analysis were correlated with OM clinical outcomes. RESULTS: A total of 27 patients were included, of whom 21 (77.8%) had locally advanced disease (clinical stage III or IV). Most patients (70.4%) received CRT. OM grades 2 (40.8%) and 3 (33.3%) were the most prevalent during RT with a mean highest reported OM-related pain of 3.22 through the visual analogue scale (VAS). The abundance of A1AT and MIF correlated significantly with severe (grades 3 or 4, p < 0.02) compared with moderate-low (grades 1 or 2, p < 0.04) OM grade. CONCLUSIONS: There is a correlation between the abundance of salivary A1AT and MIF and oncologic treatment-induced OM. The correlation of MIF expression with severe OM appears to be compatible with its physiological pro-inflammatory role. These results open up great possibilities for the use of salivary MIF and A1AT levels as prognostic markers for effective therapeutic interventions, such as photobiomodulation therapy, patient-controlled analgesia, or personalized medicaments.

Cilostazol and Tocopherol in the Management of Medication-Related Osteonecrosis of the Jaw: New Insights From a Case Report.

Several treatment protocols for medication-related osteonecrosis of the jaw (MRONJ) have been published. Despite the efficacy of surgical therapy of approximately 90% as primary therapy, the role of other agents, such as drug administration, should not be underestimated. Based on previous experience with osteoradionecrosis, the association of pentoxifylline and tocopherol has shown encouraging results in MRONJ patients. Despite the need for long-term use of the combination, compliance has been good. However, studies in breast cancer patients revealed that pentoxifylline can require dose reduction or discontinuation due to nausea and epigastric pain. Cilostazol has been used as a substitute for pentoxifylline in peripheral artery disease. Herein we report a case in which cilostazol replaced pentoxifylline at a dose of 100mg, 2 times/day with tocopherol 500UI, 2 times/day, in a 77-year-old female patient that could not tolerate pentoxifylline for the management of MRONJ. After an uneventful 22 months of follow-up, a cone-beam computed tomography revealed complete bone formation and no signs of recurrence. Cilostazol may be a useful and safe alternative to pentoxifylline as part of MRONJ management protocols.

The impact of radiation caries in the quality of life of head and neck cancer patients.

PURPOSE: The objective of this multicentre study was to verify the relationship between the scores of quality of life (QoL) and the decayed, missing and filled teeth (DMFT) and radiation caries (RC) in patients treated with radiation therapy (RT) for head and neck cancer, and through this to determine if RC is capable of causing a significant decrease in the QoL. METHODS: One hundred patients were divided into 2 groups: patients with at least 1 year of RT completion who developed RC (study group, n = 50); and patients with at least 1 year of RT completion who did not develop RC (control group, n = 50). All patients answered the Brazilian-Portuguese version of the University of Washington quality of life (UW-QoL) questionnaire, which was divided into physical and social-emotional functioning domains and evaluated the DMFT index score. RESULTS: The mean score of QoL was 927.2 in the control group and 878.1 in the study group (P = 0.24). The mean score of DMFT was 30.5 in the study group and 20.7 in the control group (P = 0.001). The items recreation and saliva, which belong to the physical function domain, showed a statistically significant difference between the study and control groups (P = 0.031 and P = 0.047, respectively). Saliva was the item with the higher number of patient complaints in both groups. CONCLUSION: RC had a negative impact on the QoL of HNC patients.

Prospective Cohort Study Identifies Medical Predictors of Treatment-Related Oral Toxicities in Oral and Oropharyngeal Cancer Patients.

The dental treatment of patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC) may be challenging for dentists. This study aimed to characterize systemic changes in patients with OOPSCC undergoing dental treatment prior to cancer therapy, with a specific focus on laboratory assessments. The primary objectives included identifying potential adverse events, such as infections or bleeding, resulting from dental procedures. Additionally, the study aimed to correlate baseline patient characteristics with treatment-related toxicities. This was a prospective cohort study that included 110 OOPSCC patients referred to the Dental Oncology Service at São Paulo State Cancer Institute, Brazil, between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, cancer treatment-related toxicities, and altered laboratory tests results were correlated. The most common comorbidities and altered laboratory results were hypertension, dyslipidemia, diabetes, as well as elevated levels of C-reactive protein, hemoglobin, and hematocrit. Toxicities exhibited a progressive pattern over time, encompassing oral mucositis (OM), xerostomia, dysphagia, dysgeusia, trismus, and radiodermatitis. No correlation between comorbidities and cancer treatment-related toxicities, a positive correlation between medications in use and OM, and a negative correlation between medications and dysgeusia were found. OM was associated with altered thyroxine (T4) and free thyroxine (FT4), calcium, urea, creatinine, alkaline phosphatase, and syphilis. Family income and housing were OM predictors. Altered T4/FT4/urea/calcium/alkaline phosphatase/creatinine/syphilis may be useful clinical predictors of OM. Despite the elevated prevalence of comorbidities and abnormal laboratory findings, dental treatment prior to cancer treatment yielded no adverse events.

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.

Oral Complications in Cancer Patients-Medication-Related Osteonecrosis of the Jaw (MRONJ).

Medication-Related Osteonecrosis of the Jaw (MRONJ) was first reported in 2003. Despite the progress in the understanding of this oral complication in cancer patients for the past 18 years, there is still discussion about the best way to define MRONJ, prevent the complication, how to diagnose, and the options of treatment available. The initial reports associated MRONJ to bisphosphonates and denosumab, medications that work as bone-modifying agents. Later, other agents such as the antiangiogenics, have also been reported to cause the oral complication, either alone or in combination with antiresorptives. Initially, these medications were prescribed to patients with osteoporosis and cancers patients with bone metastasis. Today, because of the effect of the medications in the bone remodeling system, patients with several other diseases such as giant cell tumors, rheumatoid arthritis, Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, are managed with these medications, significantly increasing the population of individuals at risk for developing MRONJ. This mini review focused on the cancer patient. It updates the dental clinician on the recent scientific literature about MRONJ and provides information on how to diagnose and manage patients being treated with these medications, suggests protocols to prevent the development of MRONJ, and present ways to manage those patients who develop the oral complication.

Over 300 Radiation Caries Papers: Reflections From the Rearview Mirror.

Radiation caries (RC) is an aggressive oral toxicity in head and neck cancer survivors, which develops 6 to 12 months after head and neck radiotherapy. It initially affects the tooth cervical/incisal surfaces, and if not promptly diagnosed/managed, progresses to dental crown amputation and risk of osteoradionecrosis. It results from a multidimensional cluster of treatment-induced oral symptoms, including hyposalivation, dietary changes, and oral hygiene impairment. Although recognized as a frequent complication of radiotherapy and extensively assessed by a myriad of retrospective, in vitro, and in situ studies, RC patients are still orphans of clinically validated methods for risk prediction, prevention, and treatment of early lesions. This review provides a historical overview of science-based concepts regarding RC pathogenesis and treatment, emphasizing the growing demand for interventional clinical studies (randomized trials).

Clinical predictors of malignant transformation and recurrence in oral potentially malignant disorders: A systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review dedicated to pooling evidence for the associations of clinical features with malignant transformation (MT) and recurrence of 3 oral potentially malignant disorders (OPMDs) (actinic cheilitis [AC], oral leukoplakia [OL], and proliferative verrucous leukoplakia [PVL]). STUDY DESIGN: We selected studies that included clinical features and risk factors (age, sex, site, size, appearance, alcohol intake, tobacco use, and sun exposure) of OL, PVL, and AC associated with recurrence and/or MT. RESULTS: Based on the meta-analysis results, non-homogeneous OL appears to have a 4.53 times higher chance of recurrence after treatment. We also found 6.52 higher chances of MT of non-homogeneous OL. Another clinical feature related to higher MT chances is the location (floor of the mouth and tongue has 4.48 higher chances) and the size (OL with >200 mm2 in size has 4.10 higher chances of MT). Regarding habits, nonsmoking patients with OL have a 3.20 higher chance of MT. The only clinical feature related to higher chances of MT in patients with PVL was sex (females have a 2.50 higher chance of MT). CONCLUSIONS: Our study showed that some clinical features may indicate greater chances of recurrence after treatment and MT of OPMD.

Oral medicine (stomatology) in Brazil: the first 50 years and counting.

This review outlines the historical perspective, status, and future challenges of oral medicine (stomatology) in Brazil based on the records of the Brazilian Society of Stomatology and Oral Pathology (SOBEP) and the Brazilian Federal Dental Council as well as expert evidence input from academic leaders from 3 different generations of Brazilian oral medicine specialists. The beginning of oral medicine in Brazil dates to 1969, followed by the organization of SOBEP in 1974; however, official recognition as an independent specialty was achieved more recently within the Brazilian Federal Dental Council in 1992. After a 50-year maturation period of oral medicine in Brazil in terms of specialty crystallization across dentistry, medicine, and research, it is now time to follow the historical trends of the specialty internationally and establish a standard curriculum at a post-graduate level that will lead to uniformity of training for oral medicine in Brazil.

Awareness of the risk of radiation-related caries in patients with head and neck cancer: A survey of physicians, dentists, and patients.

OBJECTIVES: Radiation-related caries (RRC) is one of the most aggressive complications of radiotherapy (RT) in survivors of head and neck cancer (HNC). Lack of RRC awareness may contribute to the occurrence of this oral cavity complication. RRC may be considered a "forgotten oral complication" by patients with HNC, oncologists, and dentists. The present study aimed to assess the level of awareness of RRC among physicians, dentists, and patients. STUDY DESIGN: Physicians (group 1, G1), dentists (group 2, G2), and patients with HNC undergoing RT (group 3, G3) answered questionnaires concerning their awareness of RRC. Physicians (G1) were divided into group 1A (oncological experience) and group 1B (general physicians/other specialties). Dentists (G2) were divided into group 2A (oncological experience) and group 2B (general dentists/other specialties). Personalized questionnaires were designed for each group. RESULTS: Recruitment was as follows: physicians (n = 124): 1A (n = 64), 1B (n = 60); dentists: (n = 280), 2A (n = 160), 2B (n = 120). In addition, 58 patients answered the questionnaire. In terms of RRC awareness, 46.77% of physicians, 81.78% of dentists, and 24.13% of patients had some knowledge of the problem. CONCLUSION: Patient awareness of RRC was poor. The heterogeneity of answers among physicians and dentists suggests an opportunity to improve patient education and prevention of this serious oral complication of RT.

Successful denosumab treatment for central giant cell granuloma in a 9-year-old child.

BACKGROUND: Denosumab is a nonsurgical treatment option for central giant cell granulomas (CGCG), especially in aggressive lesions. CASE REPORT: We describe a 9-year-old girl with an aggressive maxillary CGCG successfully treated with denosumab, avoiding a mutilating surgery after intralesional corticosteroid injections failed, and the lesion continued to rapidly grow. During denosumab treatment, she developed a self-limiting area of osteonecrosis in the maxillary alveolar bone, which rapidly resolved after antibiotic therapy. Six months after denosumab discontinuation, a maxillary surgical recontour was performed. Two weeks after surgery, the patient presented vomiting, pallor, dehydration, but no fever. Blood tests revealed severe hypercalcemia and acute renal dysfunction. After discarding thyroid, parathyroid, and adrenal alterations, a diagnosis of severe rebound hypercalcemia after denosumab treatment was made. Treatment consisted of hyperhydration, calcium pamidronate, and methylprednisolone, restoring calcium levels to normal. CONCLUSION: After 2 years of follow-up, she remains on orthodontic treatment, with no recurrences or other episodes of hypercalcemia.

Oral lesions in patients with SARS-CoV-2 infection: could the oral cavity be a target organ?

Several viruses transmitted through saliva, such as herpes simplex virus, cytomegalovirus, and Zika virus, are capable of infecting and replicating in the oral mucosa, leading to painful oral ulcers. Few studies have described the oral manifestations of coronavirus disease 2019 (COVID-19). There is growing evidence that angiotensin-converting enzyme 2 (ACE2), the main host cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is highly expressed on the epithelial cells of the tongue and of the salivary glands, which may explain the development of dysgeusia in patients with COVID-19. Hence, it is important to understand if SARS-CoV-2 can infect and replicate in oral keratinocytes and fibroblasts, causing oral ulcerations and superficial necrosis. Here, we report a series of 8 cases of COVID-19 infection, with oral necrotic ulcers and aphthous-like ulcerations which developed early in the course of disease after the development of dysgeusia and affected the tongue, lips, palate, and oropharynx. A short review of the literature regarding the important role of ACE2 in SARS-CoV-2 cellular entry is also provided, bringing new insights into oral keratinocytes and minor salivary glands as potential targets.

Antimicrobial photodynamic and photobiomodulation adjuvant therapies for prevention and treatment of medication-related osteonecrosis of the jaws: Case series and long-term follow-up.

BACKGROUND: Medication-Related Osteonecrosis of the Jaws (MRONJ) incidence are increasing among elderly. Treatment can be challenging. Prevent or treatment protocols that control evolution of the lesion are warranted. OBJECTIVE: To observe long-term outcomes of two protocols based on photonics [antimicrobial photodynamic therapy (aPDT) and photobiomodulation (PBM)] for prevention and treatment of MRONJ lesions. METHODS: In a prospective study, patients who needed oral surgery and had been exposed to antiresorptive drugs were long-term followed-up. For MRONJ prevention, immediately after tooth extraction aPDT was applied. For aPDT a 0.01 % methylene blue solution was applied inside socket for 5 min followed by irradiation with a diode laser [660 nm, 0.028cm2, 0.1 W, 3.57 W/cm2, 90 s and 9 J per point, 321 J/cm2, at least at in 3 points (laser probe was placed at central, and two equidistant points) and total energy of 27J]. Irradiation was repeated weekly until total tissue repair. MRONJ treatment included preoperative aPDT sessions until signs and symptoms of infection had reduced. Then, after necrotic bone removal, aPDT was applied inside surgical wounds and re-applied weekly until healing. Antibiotics were administered pre or postoperatively for no longer than 7 days. PBM therapy was applied with 808 nm diode laser, 0.028cm2, 0.1 W, 3.57 W/cm2, 30 s, 107 J/cm², 3 J and total energy of 12 J until evidence of remission. RESULTS: Eighteen patients underwent preventive protocol, and none presented signs of MRONJ after a follow-up of at least 6 months. Seventeen patients presented with MRONJ underwent aPDT protocol and sixteen of them showed total regression of lesions. PRACTICAL IMPLICATIONS: aPDT and PBM therapy protocols appear to be effective as adjuvant approach not only for preventing MRONJ development due to tooth extraction but for treating MRONJ lesions at early stages with no adverse effects.

Radiation-related caries: current diagnostic, prognostic, and management paradigms.

OBJECTIVE AND STUDY DESIGN: This narrative review summarizes the current state of art of radiation-related caries (RC), an aggressive disease that affects approximately 30% of post-head and neck radiotherapy (HNRT) patients. RESULTS: RC mainly affects the tooth cervical areas and incisal/cuspal tips and develops 6 to 12 months after HNRT. Early RC signs include black/brownish tooth discoloration and enamel cracks, which progress to enamel delamination, exposing underlying dentin to a highly cariogenic oral environment and rapid tooth destruction/dental crown amputation. As RC advances and renders the tooth nonrestorable, it may lead to osteoradionecrosis spontaneously or upon extraction if the tooth is in a highly irradiated field of the oral cavity. This requires aggressive treatment, which would have a negative impact on a cancer survivor's quality of life and contribute to the incremental cost of cancer care. Chlorhexidine mouth rinses and topical fluoride applications are effective agents used in RC prevention; however, there are no well-established treatment protocols. Once RC progresses, dental restorations should be performed with adhesive materials in association with systematic fluoride application as illustrated in the clinical case presented in this review. Post-HNRT patients should be closely followed up for optimal RC prevention, early diagnosis, and prompt treatment. CONCLUSIONS: Future clinical studies are necessary to establish a contemporary, clinically validated protocol for RC management.

Radiographic patterns of multiple myeloma in the jawbones of patients treated with intravenous bisphosphonates.

BACKGROUND: The purpose of this study was to evaluate whether intravenous (IV) bisphosphonate (BP) therapy can change the radiographic patterns of multiple myeloma (MM) in the jawbones. METHODS: The authors evaluated panoramic radiographs obtained from 188 patients with MM for the presence of solitary osteolytic lesions, multiple osteolytic lesions, diffuse osteoporosis, diffuse sclerosis, lamina dura abnormalities, nonhealing alveolar sockets, and bone sequestration. The authors compared results obtained from patients treated with IV BPs with those obtained from patients who had never been exposed to BPs. RESULTS: Multiple osteolytic lesions (P = .001), diffuse osteoporosis (P = .001), and diffuse sclerosis (P = .0036) occurred more often in the mandible in both groups. Solitary osteolytic lesions occurred less frequently in the BP group (P = .0078). Lamina dura abnormalities (P = .0006) and nonhealing alveolar sockets (P = .0021) were associated with BP treatment. CONCLUSIONS: IV BP therapy changes the radiographic patterns of MM in the jawbones. PRACTICAL IMPLICATIONS: The effect of BPs in the maxillofacial area is a matter of concern for health practitioners because this type of medication causes several alterations of the jawbones in patients with cancer.

Intravenous bisphosphonate therapy does not thicken cementum or change periodontal ligaments of cancer patients.

OBJECTIVE: To test the hypothesis that intravenous (IV) bisphosphonate (BP) therapy thickens or alters the micromorphology of cementum and periodontal ligament (PDL) in cancer patients. STUDY DESIGN: Thirty-two teeth extracted from 24 cancer patients and separated into test (patients who have undergone IV BP therapy, n = 16) and control (patients naive to BP therapy, n = 16) groups were studied. Cementum thickness was measured in 3 different areas of the dental root with polarized light microscopy. PDL was assessed by optical light microscopy and the immunohistochemical expression of periostin. RESULTS: No significant difference was detected in cementum thickness (apical, P = .06; medium, P = .16; cervical, P = .18) between groups. The numbers of fibroblasts in PDL (P = .56), incremental lines of cementum (P = .51) and the immunohistochemical patterns of periostin expression in PDL (P = .68) did not differ between groups. CONCLUSION: IV BP therapy does not thicken cementum or change the micromorphology of PDL.