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Background: Head and neck cancer (HNC) mortality differs by race, ethnicity, and socioeconomic status (SES). However, it is unclear whether the relationship between race/ethnicity and HNC-specific mortality varies according to the residence-level SES. Methods: Data from the Surveillance Epidemiology and End Results database included participants with primary HNC between 2006 and 2017 (followed through 2018) to assess the joint association of race/ethnicity and census-tract level SES Yost-index groups (quintiles) with all-cause and HNC-specific mortalities. Relative survival rates at 1, 5, and 10 years were calculated. Multivariable Cox proportional hazard regression models estimated hazard-ratios and 95% confidence intervals for all-cause mortality, and Fine-Gray subdistribution hazard models for HNC-specific mortality. Cumulative incidence curves for HNC-specific deaths were estimated. Results: 76,095 patients were included in the analysis: 63.2% were Conclusions: NH-Black patients of all SES strata had significantly worse outcomes. Other factors, such as healthcare quality, may be associated with persistent disparities. Impact: The study highlights the persistence of significant racial disparities in HNC survival across socioeconomic categories. There is need to consider additional factors underlying these disparities.

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]).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.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 with200 mmOur study showed that some clinical features may indicate greater chances of recurrence after treatment and MT of OPMD.

Figure S1 shows flowchart of study participant selection.

Table S3 shows demographic and clinical characteristics of patients with primary head and neck cancer by socioeconomic status.

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.

Purpose To assess the safety and efficacy of prophylactic extraoral photobiomodulation (PBM) for the prevention of oral and oropharyngeal mucositis (OM) on clinical outcomes and survival in patients with oral cavity and oropharyngeal squamous cell carcinoma (OOPSCC). Methods OOPSCC patients who received radiotherapy (RT) were prospectively randomized to two groups: prophylactic extraoral PBM and placebo. OM grade (NCI), pain (VAS), analgesia, and anti-inflammatory prescriptions were assessed weekly. Quality of life questionnaires (QoL) were performed at the first and last day of RT. Following RT, participants were evaluated quarterly for oncological outcomes follow-up. Results Fifty-five patients met the inclusion criteria. The first occurrence of OM was observed at week 1, for the placebo group (p = 0.014). Later, OM onset and severity was observed for the PBM group, with first occurrence at week 2 (p = 0.009). No difference in severe OM incidence was observed (p > 0.05). Lower mean pain score was noted at week 7 for the PBM group (2.1) compared to placebo group (4.5) (p = 0.009). Less analgesics (week 3; p = 0.009/week 7; p = 0.02) and anti-inflammatory prescription (week 5; p = 0.0346) were observed for the PBM group. Better QoL scores were observed for the PBM group at last day of RT (p = 0.0034). No difference in overall survival among groups was observed in 1 year of follow-up (p = 0.889). Conclusion Prophylactic extraoral PBM can delay OM onset, reduce pain, and reduce analgesic and anti-inflammatory prescription requirements. Extraoral PBM was associated with better QoL. There was no evidence of PBM impact on oncological outcomes. Trial registration TRN:RBR-4w4swx (date of registration: 01/20/2020). Supplementary Information The online version contains supplementary material available at 10.1007/s00520-021-06625-8.

Objective This article reviews the literature and evidence of the association of medication-related osteonecrosis of the jaw with tumor necrosis factor-α inhibition. Methods A systematic review was performed using electronic databases (PubMed, MEDLINE, and Embase) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Key terms were used in the search. No restrictions were placed on publication status. Selection criteria comprised all levels of available evidence. Articles in the English language were selected up to and including July 2020. Reference lists of relevant studies were searched for additional articles. Articles were selected on the basis of inclusion and exclusion criteria. Findings from eligible studies were extracted by one reviewer and confirmed by a second. Disagreements were settled through discussion. Results The initial search of the key terms yielded 2107 articles. There were 1192 articles remaining after removal of duplicates and addition of 6 articles that were hand-selected from among reference lists of relevant studies. There were 12 eligible articles after screening. The full texts were read, and 5 articles were included on the basis of inclusion and exclusion criteria. Conclusions Further research is required to determine an association of medication-related osteonecrosis of the jaw and tumor necrosis factor-α inhibition.

Purpose: To characterize oral and oropharyngeal squamous cell carcinoma (OOPSCC) patients with dental needs before cancer treatment and to correlate their baseline characteristics with cancer treatment-related toxicities. Methods: A prospective cohort study that recruited OOPSCC patients referred to the Dental Oncology Service at the Instituto do Câncer do Estado de São Paulo, Brazil, for dental treatment between November/2019 and December/2020. Comorbidities, sociodemographic data, medication in use, treatment-related toxicities and altered laboratory tests results were correlated. Results: 110 patients were included. The most common comorbidities reported and altered laboratory results were respectively hypertension, dyslipidemia, diabetes and C-reactive protein, hemoglobin, and hematocrit. Toxicities were progressive over time. There was no correlation between the comorbidities and cancer treatment-related toxicities. There was a positive correlation between medications in use and oral mucositis (OM) and a negative correlation between medications and dysgeusia. OM was associated with altered laboratory findings, including thyroxine (T4) and free thyroxine (FT4) starting at D15; calcium at D5/10/30; urea at D25/30/33-35; creatinine at D15/30; alkaline phosphatase at D20/25; syphilis at D15/30. Family income and housing were OM predictors. Oral candidiasis (OC) was associated with syphilis and HIV at D20. Conclusion: Laboratory findings including altered T4, FT4, urea, calcium, alkaline phosphatase, creatinine, and syphilis may be useful clinical predictors of OM. Syphilis and HIV may also be considered reliable predictors of OC secondary to OOPSCC treatment. Despite the high frequency of comorbidities and abnormal laboratory results, dental treatment before cancer treatment resulted in no adverse events in our sample.

To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3–4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy. There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

New advances in cancer immunotherapy have been flooding the market at a rapid rate. Pembrolizumab (Keytruda), a programmed cell death protein 1 inhibitor, introduced in 2014, has been used to treat several cancers. Immune-related adverse events associated with pembrolizumab and other immune checkpoint inhibitors are now well-described complications. We describe the case of a 65-year old female with severe oral lichenoid lesions occurring after treatment with pembrolizumab for bladder cancer. To the best of our knowledge, this is the first report of a biopsy-proven oral erosive lichenoid reaction confirmed through direct immunofluorescence.

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). 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. 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

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.

To characterize oral sites affected by radiation-induced oral mucositis (OM) and related clinical outcomes in oral cancer patients subjected to prophylactic photobiomodulation therapy (PBMT). This study included advanced oral squamous cell carcinoma (OSCC) patients treated with prophylactic PBMT for OM. The site distribution of OM, OM grading (CTCAE NCI, Version 4.0, 2010), OM-related pain (VAS), analgesic protocol (WHO Analgesic Ladder), and use of enteral nutrition were evaluated weekly during treatment. Data analysis was performed using descriptive statistics expressed as median values and percentages. A total of 145 OSCC patients were included. OM most frequently affected the lateral border of the tongue (44.1%), buccal mucosa (37.2%), and labial mucosa (33.8%). Keratinized oral mucosa sites, including the tongue dorsum (6.21%), retromolar trigone (8.3%), and hard palate (2.76%), were less frequently affected. Peak OM scores were observed at weeks 5, 6, and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed at the sixth week, and 13.8% of the patients required feeding support. This study showed, compared with studies that did not provide PBMT, reduced severity of mucositis, reduced pain and analgesic use, and reduced tube feeding in patients treated with PBMT. OM involving keratinized and non-keratinized surfaces should be included in the prophylactic PBMT to reduce severe OM in future studies.

We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA).Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken.Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p .0007). BTAs1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050).Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.

High-risk (HR) human papillomavirus (HPV) infection is recognized as a primary etiologic factor of anogenital cancers and more recently of a subgroup of oropharyngeal squamous cell carcinomas (OPSCC). The incidence of HPV-related OPSCC has increased dramatically in several developed countries in the past 3 decades and is currently the most common cancer caused by HR-HPV in the United States and Germany, surpassing cervical cancer. Consequently, the patient's demographic and clinicopathologic profile has shifted to nonsmoking and nondrinking younger men with higher schooling level and with a history of multiple oral sex partners. Patients with HPV-related OPSCC often show better treatment outcomes and higher survival rates than their HPV-unrelated counterparts, which has led to a change in tumor staging for HPV-related cases. HPV vaccination is emerging as an effective primary prevention strategy, and systematic screening of HPV DNA in blood and salivary oral rinse samples of HR patients is being examined to determine if it may provide a surveillance method and support early diagnosis of HPV-related OPSCC. In this context, a narrative review was conducted to provide an overview of the state-of-the-art of HPV-related OPSCC, including epidemiology, risk factors, clinicopathologic and molecular features, screening, prevention, management, and prognosis.

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.

It is well reported that severe cases of COVID-19 frequently need critical care in the ICU to manage respiratory complications, often requiring orotracheal intubation (OTI). Due to complex systemic conditions, the patient may remain intubated for a long period of time and be placed in prone position. This positioning and the pressure of the intubation device on the lips may lead to the development of traumatic injuries. Oral care and the use of photobiomodulation (PBM) can be successfully implemented to promote oral mucosa healing and prevent soft tissue necrosis. We describe the outcomes of the management protocol that was routinely used by the ICU oral medicine team, leading to the implementation of a preventive protocol for the OTI-related oral injuries. We retrospectively analyzed the records of 472 patients with COVID-19 in the ICU from May 2020 to February 2021. 60/472 patients developed traumatic injuries and were managed with the oral care protocol and PBM, to prevent the progress to lip necrosis. When appropriated, in addition to oral care and PBM, other measures were taken to prevent further local trauma (lip hydration, changes in tube fixation). The proposed oral care protocol associated with PBM successfully prevented the progress of traumatic lesions, ulceration, necrosis, and loss of tissue associated with IOT. The quality of life of patients in the ICU and after their recovery was preserved.

Photobiomodulation therapy (PBMT) has been considered an effective method for preventing and managing certain cancer-related toxicities in head and neck cancer (HNC) patients treated with radiotherapy and chemotherapy. However, the potential effects of PBMT on pain control and analgesia resulting from these toxicities is still controversial. The aim of this systematic review was to compile available evidence of the effects of PMBT on pain control and reduced use of analgesics in HNC patients. We searched three indexed databases: MEDLINE/PubMed, Embase, and Scopus. The databases were reviewed up to and including December 2018. Only human clinical studies in English language were selected. Information was only available for mucositis and radiodermatitis. Fifteen out of 1112 studies met the inclusion criteria (14 for oral mucositis (OM) and 1 for radiodermatitis). From the 14 studies involving the prevention and treatment of OM, 10 had the study subjects compared to a placebo group. Of these 10 studies, all but 1 showed statistically significant difference related to pain control favoring the PBMT group. The study that compared PBMT with other treatment modality showed better results in pain control with PBMT. It appears that PBMT application frequency and potency impact on pain control. The only study involving the prevention and treatment of radiodermatitis was compared to placebo arm and showed statistically significant difference related to pain control favoring the PBMT group. Seven studies compared the need of analgesic medication between PBMT and placebo groups. Of these, five studies showed that the use of analgesic medication was significantly higher in the placebo group. The current evidence supports that PBMT is effective in pain control resulting from OM and radiodermatitis and may also reduce the need for analgesics. The evidence is not yet available of the effects of PBMT in other HNC treatment-related toxicities.

Photobiomodulation therapy (PBMT), also known as low-level laser therapy (LLLT), has been increasingly used for the treatment of toxicities related to cancer treatment. One of the challenges for the universal acceptance of PBMT use in cancer patients is whether or not there is a potential for the light to stimulate the growth of residual malignant cells that evaded oncologic treatment, increasing the risk for tumor recurrences and development of a second primary tumor. Current science suggests promising effects of PBMT in the prevention and treatment of breast cancer-related lymphedema and oral mucositis, among other cancer treatment toxicities. Nevertheless, this seems to be the first systematic review to analyze the safety of the use of PBMT for the management of cancer-related toxicities. Scopus, MEDLINE/PubMed, and Embase were searched electronically. A total of 27 articles met the search criteria. Selected studies included the use of PBMT for prevention and treatment of oral mucositis, lymphedema, radiodermatitis, and peripheral neuropathy. Most studies showed that no side effects were observed with the use of PBMT. The results of this systematic review, based on current literature, suggest that the use of PBMT in the prevention and management of cancer treatment toxicities does not lead to the development of tumor safety issues.

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.

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.

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.

Drug-induced sarcoidosis-like reaction (DISR) is a condition almost indistinguishable from sarcoidosis, both clinically and microscopically, consisting of granulomatous tissue reaction associated with a specific therapy. Commonly affected sites are the lungs, hilar lymph nodes, and skin. This report aimed to describe a very uncommon case of DISR with an unique involvement of the oral cavity. A 63-year-old female with a history of rheumatoid arthritis, who was treated with a TNF-α antagonist (adalimumab), presented multiple ulcerative nodules on the hard palate. Laboratory tests and imaging studies failed to show any other alterations. The biopsy specimen demonstrated multiple noncaseating granulomas. Histochemical reactions were negative for acid-fast bacilli and fungi, and immunohistochemical assessment highlighted the presence of normal lymphocytes and histiocytes. With the diagnosis of DISR, adalimumab was discontinued, and complete clinical resolution of the lesions was achieved after 14 months. Although uncommon, DISR should be considered in differential diagnoses of oral granulomatous reactions, especially in cases where the patient is being treated with TNF-α antagonists.

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.

We performed a systematic review of the current literature addressing the safety and efficacy of photobiomodulation therapy (PBMT) in cancer patients. In this systematic review, the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were used. In vitro, in vivo, and clinical studies, which investigated the effect of PBMT on cell proliferation/differentiation, tumor growth, recurrence rate, and/or overall survival were included. The Medline/PubMed, EMBASE, and Scopus databases were searched through April 2020. A total of 67 studies met the inclusion criteria with 43 in vitro, 15 in vivo, and 9 clinical studies identified. In vitro studies investigating the effect of PBMT on a diverse range of cancer cell lines demonstrated conflicting results. This could be due to the differences in used parameters and the frequency of PBM applications. In vivo studies and clinical trials with a follow‐up period demonstrated that PBMT is safe with regards to tumor growth and patient advantage in the prevention and treatment of specific cancer therapy‐related complications. Current human studies, supported by most animal studies, show safety with PBMT using currently recommended clinical parameters, including in Head & Neck cancer (HNC) in the area of PBMT exposure. A significant and growing literature indicates that PBMT is safe and effective, and may even offer a benefit in patient overall survival. Nevertheless, continuing research is indicated to improve understanding and provide further elucidation of remaining questions regarding PBM use in oncology., We performed a systematic review of the current literature addressing the safety and efficacy of photobiomodulation therapy (PBMT) in cancer patients. A significant and growing literature indicates that PBMT is safe and effective, and may even offer a benefit in patient overall survival. Nevertheless, continuing research is indicated to improve understanding and provide further elucidation of remaining questions regarding PBM use in oncology.

Drug-induced sarcoidosis-like reaction (DISR) is a condition almost indistinguishable from sarcoidosis, both clinically and microscopically, consisting of granulomatous tissue reaction associated with a specific therapy. Commonly affected sites are the lungs, hilar lymph nodes, and skin. This report aimed to describe a very uncommon case of DISR with an unique involvement of the oral cavity. A 63-year-old female with a history of rheumatoid arthritis, who was treated with a TNF-α antagonist (adalimumab), presented multiple ulcerative nodules on the hard palate. Laboratory tests and imaging studies failed to show any other alterations. The biopsy specimen demonstrated multiple noncaseating granulomas. Histochemical reactions were negative for acid-fast bacilli and fungi, and immunohistochemical assessment highlighted the presence of normal lymphocytes and histiocytes. With the diagnosis of DISR, adalimumab was discontinued, and complete clinical resolution of the lesions was achieved after 14 months. Although uncommon, DISR should be considered in differential diagnoses of oral granulomatous reactions, especially in cases where the patient is being treated with TNF-α antagonists.

Background: Adverse drug/device reactions (ADRs) can result in severe patient harm. We define very serious ADRs as being associated with severe toxicity, as measured on the Common Toxicity Criteria Adverse Events (CTCAE)) scale, following use of drugs or devices with large sales, large financial settlements, and large numbers of injured persons. We report on impacts on patients, clinicians, and manufacturers following very serious ADR reporting. Methods: We reviewed clinician identified very serious ADRs published between 1997 and 2019. Drugs and devices associated with reports of very serious ADRs were identified. Included drugs or devices had market removal discussed at Food and Drug Advisory (FDA) Advisory Committee meetings, were published by clinicians, had sales > $1 billion, were associated with CTCAE Grade 4 or 5 toxicity effects, and had either >$1 billion in settlements or >1,000 injured patients. Data sources included journals, Congressional transcripts, and news reports. We reviewed data on: 1) timing of ADR reports, Boxed warnings, and product withdrawals, and 2) patient, clinician, and manufacturer impacts. Binomial analysis was used to compare sales pre- and post-FDA Advisory Committee meetings. Findings: Twenty very serious ADRs involved fifteen drugs and one device. Legal settlements totaled $38.4 billion for 753,900 injured persons. Eleven of 18 clinicians (61%) reported harms, including verbal threats from manufacturer (five) and loss of a faculty position (one). Annual sales decreased 94% from $29.1 billion pre-FDA meeting to $4.9 billion afterwards (p

This communication discusses the current challenges of oral mucositis (OM) management during the pandemic COVID-19 outbreak and reflects about an extraoral photobiomodulation protocol as an optimal alternative for preventing and treating OM in advanced cancer patients while minimizing the risk of infection by avoiding intraoral manipulation.

To identify and summarize the evidence on the cost-effectiveness of photobiomodulation (PBM) therapy for the prevention and treatment of cancer treatment-related toxicities.This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE). Scopus, MEDLINE/PubMed, and Embase were searched electronically.A total of 1490 studies were identified, and after a two-step review, 4 articles met the inclusion criteria. The included studies analyzed the cost-effectiveness of PBM therapy used in the context of lymphedema for breast cancer and oral mucositis (OM) induced by chemotherapy and radiotherapy. Better outcomes were associated with PBM therapy. The incremental cost-effectiveness ratio ranged from 3050.75 USD to 5592.10 USD per grade 3-4 OM case prevented. PBM therapy cost 21.47 USD per percentage point reduction in lymphedema in comparison with 80.51 USD for manual lymph drainage and physical therapy.There is limited evidence that PBM therapy is cost-effective in the prevention and treatment of specific cancer treatment-related toxicities, namely, OM and breast cancer-related lymphedema. Studies may have underreported the benefits due to a lack of a comprehensive cost evaluation. This suggests a wider acceptance of PBM therapy at cancer treatment centers, which has thus far been limited by the number of robust clinical studies that demonstrate cost-effectiveness for the prevention and treatment of toxicities.

Oral mucositis (OM) is one of the most impacting oral complications negatively affecting the quality of life of cancer patients being treated with high-dose chemotherapy and radiation of the head and neck. It is an acute adverse effect that can be devastating and could affect cancer prognosis. Prevention and management strategies have not been successful. Photobiomodulation is a form of light therapy delivered to human tissues by lasers, light-emitting diodes, and even broadband light. It interferes in the way human cells repair tissues in a nonthermal and nonionizing fashion. There is mounting evidence that photobiomodulation (PBM or low-level laser therapy) can be effective in preventing OM and/or reducing the severity of this important complication. This chapter describes current modeling of the pathobiology and clinical characteristics of OM, the burden on the cancer patient, and the use of PBM as a preventative and/or therapeutic management of this oral complication.

Introduction: Adverse drug/device reactions (ADRs) can result in severe patient harm. We operationally define titanic ADRs as Common Toxicity Criteria Adverse Events grade 4 or 5 that follow use of drugs or devices that have large sales, large safety financial settlements, and affect large numbers of persons. We report on the impact of titanic ADRs identified between 1997 and 2019. Methods: We reviewed clinician reported titanic ADRs. Data sources included Food and Drug Advisory (FDA) Advisory Committee transcripts, news reports, and medical journals. We reviewed data on timing of titanic ADR reports, Boxed warnings, product withdrawals, and impacts on patients, clinicians, and manufacturers. Results: Overall, twenty titanic ADRs involved 15 drugs and 1 device. Legal settlements totaled $38.4 billion for 874,000 persons reportedly developing titanic ADRs. Five clinicians reported receiving threats from manufacturers’ employees, one clinician lost a university faculty position, and five clinicians were not invited to FDA meetings where their safety findings were discussed. Annual sales for 9 still patented drugs and 1 device decreased 78% from $21.3 billion pre-ADR report to $3.9 billion afterwards. Following FDA approval, the median time to titanic ADRs reporting was 7.5 years. Fourteen drugs received Box warnings a median of 7.5 years following titanic ADR reporting. Six drugs and 1 device were withdrawn from marketing (median of 5 years after titanic ADR reporting). Conclusion: Overall, 874,000 persons were purportedly injured by fifteen drugs and one device that caused titanic ADRs, reputational harms were reported by eleven clinicians , and $38.4 billion in legal settlements were paid . Because titanic ADRs impacts are so large, and investigative processes not always transparent, policy makers should develop an independently funded drug safety board. Funding Statement: This work received support from the National Cancer Institute (1R01 A102713 (CLB), https://www.nih.gov/about-nih/what-we-do/nih-almanac/national-cancer-institute-nci; the American Cancer Society (IRG-13-043-01), https://www.cancer.org/; and an unrestricted grant from Doris Levkoff Meddin. Declaration of Interests: The authors have declared that no competing interests exist.

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.

Patients undergoing radiation therapy for the head and neck are susceptible to a significant and often abrupt deterioration in their oral health. The oral morbidities of radiation therapy include but are not limited to an increased susceptibility to dental caries and periodontal disease. They also include profound and often permanent functional and sensory changes involving the oral soft tissue. These changes range from oral mucositis experienced during and soon after treatment, mucosal opportunistic infections, neurosensory disorders, and tissue fibrosis. Many of the oral soft tissue changes following radiation therapy are difficult challenges to the patients and their caregivers and require life‐long strategies to alleviate their deleterious effect on basic life functions and on the quality of life. We discuss the presentation, prognosis, and management strategies of the dental structure and oral soft tissue morbidities resulting from the administration of therapeutic radiation in head and neck patient. A case for a collaborative and integrated multidisciplinary approach to the management of these patients is made, with specific recommendation to include knowledgeable and experienced oral health care professionals in the treatment team.

Background Photobiomodulation therapy (PBMT) has increasingly been used to manage oral toxicities secondary to cancer treatment; however, its impact on the stimulation of malignant cells is currently unknown. Objective This 4-arm, double-blind, phase III randomized controlled clinical trial (RBR-4w4wwx) was designed to assess the impact of prophylactic PBMT for oral and oropharyngeal mucositis (OM) in the survival rates of patients with oral and oropharyngeal squamous cell carcinoma (OPSCC). Methods Patients were randomly allocated to 4 groups: intraoral prophylactic PBMT (G1), placebo intraoral PBMT (G2), extraoral prophylactic PBMT (G3), and placebo extraoral PBMT (G4). OM grade (NCI) and OM-associated pain (EVA scale) were assessed weekly during OPSCC treatment. Tumor outcomes were evaluated quarterly during 12 months. Data analysis was performed using descriptive statistics. Results A total of 45 OPSCC patients were included. OM peak ulcerations (grade 2 or higher) were observed at week 3 for G1, G2, and G4 and at week 5 for G3. Placebo groups had the highest levels of pain when compared with the treatment/intervention groups (P Conclusions No negative impact of prophylactic PBMT for OM could be detected in terms OPSCC treatment outcomes.

Background Photobiomodulation therapy (PBMT) is recommended for the prevention of radiation-induced oral mucositis (OM) in head and neck patients. It is unclear to what extent the delivered PBMT therapy effectively provides an adequate uniform dose to the at-risk tissues. Objective To characterize oral sites affected by radiation-induced OM and its clinicopathologic outcomes in oral squamous cell carcinoma (OSCC) patients subjected to prophylactic PBMT. Methods The site distribution of OM, OM grading (NCI, Version 4.0), OM-related pain (visual analog scale), analgesic protocol (WHO), and use of enteral nutrition were evaluated weekly during treatment for OSCC patients with prophylactic PBMT. Data analysis was performed using descriptive statistics. Results One hundred forty-five OSCC patients were included. The most frequently affected sites by OM included lateral tongue (44.1%) and buccal mucosa (37.2%). Keratinized oral mucosae sites, including the tongue dorsum (6.21%) and retromolar trigone (8.3%), were also affected. Peak OM scores were observed at weeks 5, 6 and 7, with severe OM (NCI grades 3 and 4) rates of 11%, 20%, and 25%, respectively. The cumulative occurrence of severe OM was 23%, which developed as early as week 3 and as late as week 7. The highest mean value of OM-related pain (2.7) was observed in the sixth week, and 13.8% of the patients required feeding support. Conclusions Compared to previously published studies that did not provide PBMT, OM, pain and analgesia and tube feeding use reduction was seen. Keratinized surfaces should also be included in the prophylactic PBMT for OM aiming to reduce severe OM.

Medication-related osteonecrosis of the jaw is an oral complication in cancer patients being treated with either antiresorptive or antiangiogenic drugs. The first reports of MRONJ were published in 2003. Hundreds of manuscripts have been published in the medical and dental literature describing the complication, clinical and radiographic signs and symptoms, possible pathophysiology, and management. Despite this extensive literature, the pathobiological mechanisms by which medication-related osteonecrosis of the jaw develops have not yet been fully delineated. The aim of this manuscript is to present current knowledge about the complication ragarding to the definition, known risk factors, and clinical management recommendations. Based on this current state of the science, we also propose research directions that have potential to enhance the management of future oncology patients who are receiving these agents.