Oral and cutaneous immune-related adverse events in cancer patients: Prevalence and overall survival.

OBJECTIVES: To assess the prevalence of cutaneous and oral immune-related adverse events (irAEs) in cancer patients, risk factors for its development, and overall survival (OS). MATERIALS AND METHODS: This retrospective observational study which included 748 medical records of cancer patients who received immune checkpoint inhibitors (ICIs). Demographic and clinicopathological characteristics were collected and analyzed. RESULTS: Most patients were male (59.4%), with stage IV cancer (65%) and received pembrolizumab (46.7%). Four hundred fourteen (55.34%) patients developed cutaneous lesions, 84 (11.2%) developed oral mucosal lesions, and 70 (9.3%) developed xerostomia. The median time for irAEs development was 11 weeks for cutaneous and oral mucosal lesions, and 21.5 weeks for xerostomia. Patients who received PD-1 + CTLA-4 had a higher risk for developing cutaneous irAEs (p = 0.001), while those who underwent ICI and concurrent chemotherapy had a higher risk (p = 0.008) for developing oral mucosal lesions. Patients who presented oral and cutaneous irAEs had better OS than those who did not present (p = 0.0001). CONCLUSION: Cutaneous effects affected more than half of the patients, while oral effects and xerostomia were found in around 11% and 9% of patients, respectively. Concurrent chemotherapy and PD-1 + CTLA-4 were more associated with oral and cutaneous irAEs, respectively. Patients who developed such irAEs had better overall survival.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Glandular odontogenic cyst misdiagnosed and treated as a periapical inflammatory lesion for 6 years in an older adult.

OBJECTIVES: To document the case of a patient who underwent several endodontic treatments due to a glandular odontogenic cyst misdiagnosed as an inflammatory periapical lesion. BACKGROUND: Glandular odontogenic cysts behave more aggressively, while others have an indolent course. There is limited information on this cyst in the gerodontologic literature. MATERIALS AND METHODS: A 76-year-old male patient presented with an asymptomatic expansive lesion in the anterior mandible resistant to several endodontic treatments. Cone-beam computed tomography revealed a multilocular osteolytic lesion measuring 6.0 × 4.0 cm, with cortical bone perforation. RESULTS: Histopathological analysis of a biopsy specimen was consistent with glandular odontogenic cyst. The patient underwent marginal mandibulectomy with preservation of the base of the mandible. CONCLUSION: A strict diagnostic process is important to avoid unwanted consequences, particularly in the geriatric population.

Window therapeutic of extraoral photobiomodulation for prevention of oral mucositis in HSCT patients: additional arm.

PURPOSE: This study aimed to evaluate the efficacy of 1W extraoral photobiomodulation (EOPBM) and to compare with our previous results of 2W EOPBM and intraoral photobiomodulation (IOPBM) protocols in the management of oral mucositis (OM) related to hematopoietic stem cell transplantation (HSCT). METHODS: A total of 30 patients underwent autologous or allogenic HSCT. Experimental protocol of 1W EOPBM was performed daily beginning in the first day of the conditioning regimen until 5 days after transplantation. The application areas included six points on the face and three points on the cervical area. Additional application of IOPBM was performed if patients had ulcered mucositis. Its severity was assessed daily according to WHO (World Health Organization) and NCI (National Cancer Institute) scales. Oral and oropharynx pains were scored daily by visual analogue scale (VAS). RESULTS: The 1W EOPBM protocol was well tolerated without any complaints. Of total, 13 patients were male and 17 were female and the mean age was 49.3 years old. Most patients (21 patients - 70%) received autologous HSCT, and 24 patients (80%) underwent myeloablative conditioning (MAC) regime and 6 patients (20%) reduced intensive conditioning regime. Nineteen patients (63.3%) developed OM according to WHO criteria, 3 patients grade I, 10 grade II and 6 grade III. NCI mucositis grades were similar to WHO grades. OM outcomes of 1W EOPBM were similar when compared to our previous groups and no significant differences were observed. No differences were found between pain and the protocols (1W EOPBM, IOPBM and 2W EOPBM). CONCLUSION: This 1W EOPBM protocol seemed to be as effective as IOPBM and 2W EOPBM in the prevention of OM in HSCT patients. In addition, we might assume that there is a window of application on EOPBM.

Oral manifestations of immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.

Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment over the past decade, improving survival rates in numerous advanced cancers. Immune-related adverse events (irAEs) are common and can affect any organ system, with many of these toxicities being well-characterized with clear grading criteria and management approaches. There has been less emphasis on oral manifestations of irAEs. This review provides an overview of oral manifestations of irAEs, including mucosal and salivary gland toxicities, and proposes a grading system and management guidelines. irAEs are common treatment-related toxicities in patients treated with ICIs. Oral irAEs can range from asymptomatic white reticulations to life-threatening mucocutaneous reactions requiring aggressive management with corticosteroids and/or permanent discontinuation of ICIs. Oral healthcare providers should be prepared to identify and manage oral irAEs in collaboration with oncologists and other specialists.

Is serum C-terminal telopeptide cross-link of type 1 collagen a reliable parameter for predicting the risk of medication-related osteonecrosis of the jaws? A systematic review and meta-analysis of diagnostic test accuracy.

OBJECTIVE: To determine the usefulness of Serum C-terminal telopeptide cross-link of type 1 collagen (sCTX) as a preoperative marker for predicting the risk of developing medication-related osteonecrosis of the jaws (MRONJ) after invasive oral surgery in patients on antiresorptive medication. MATERIALS AND METHODS: Two authors independently searched four electronic databases up to March 25, 2021, for case-control studies and prospective and retrospective cohort studies that assessed preoperative sCTX levels in patients taking antiresorptive medication who underwent oral surgery procedures. The main outcome was the number of MRONJ cases in patients with an sCTX value lower and higher than 150 pg/mL. Qualitative and quantitative data was extracted in tables and the risk of bias was assessed using the QUADAS-2 tool. Estimates of diagnostic accuracy were expressed as sensitivity, specificity, negative and positive likelihood ratio (LR - and LR +), and diagnostic odds ratio (DOR), with a 95% confidence interval (95%CI). The data were combined using random-effects models based on the inverse variance method. RESULTS: Seven studies were included in the meta-analysis. The results were as follows: sensitivity 57% (95%CI: 41-71%), specificity 72% (95%CI: 64-79%), LR + 2 (95%CI: 1.3-3.1), LR - 0.6 (95%CI: 0.4-0.9), and DOR 3.4 (95%CI: 1.5-7.7). CONCLUSIONS: The low overall performance of sCTX indicates that this parameter is not suitable for predicting MRONJ risk in patients on antiresorptive medication who need an oral surgery procedure. CLINICAL RELEVANCE: sCTX should not be considered a reliable preoperative marker to predict MRONJ development.

Intraoral versus extraoral photobiomodulation therapy in the prevention of oral mucositis in HSCT patients: a randomized, single-blind, controlled clinical trial.

To compare the efficacy of intraoral and extraoral photobiomodulation (PBM) protocols for the prevention of oral mucositis (OM) in hematopoietic stem cell transplantation (HSCT) patients. A total of 60 patients was randomized into intraoral PBM (IOPBM) and extraoral PBM (EOPBM) groups. Both PBM protocols were well tolerated and no side effects were observed. EOPBM session times were one fourth of IOPBM durations. Of 60 patients, 35 (58.3%) developed ulcerated OM between day +3 and day +12. No intergroup difference was observed in OM healing times (p = 0.424). The lateral border of the tongue was the most common site affected in both groups. However, the incidence of mucositis on buccal mucosa was significantly reduced in the EOPBM group (p = 0.021). Young patients (OR.5.35, 95%CI 0.94-30.4, p = 0.058) and those who had received myeloablative conditioning (OR.55.1, 95%CI 2.69-1129.3, p = 0.009) were more likely to develop ulcerated OM, whereas autologous HSCT recipients (OR 0.079, 95% CI 0.009-0.67, p = 0.021) had a lower probability of developing ulcerated OM independent of PBM protocol. EOPBM protocol was as effective as IOPBM in the management of OM in HSCT patients, with the advantage of shorter treatment sessions. Trial registration number: RBR-7nww56. Date of trial registration submission: 30th September 2019.

Epidemiological profile and clinical implications of oral squamous cell carcinoma adjacent to dental implants.

OBJECTIVES: Describe the epidemiological profile of patients with oral squamous cell carcinoma (OSCC) around dental implants (DI), investigate the spectrum of clinical and pathological characteristics, and discuss the implications of diagnosis delay of these lesions. METHODS: Retrospective analysis of patients treated of OSCC adjacent to DI at A.C. Camargo Cancer Center between 2009 and 2020. RESULTS: Thirty one patients were identified, being women the majority (58.1%). The mean age of the patients was 68.8 years. Never smoker corresponds to 46.9% and never alcohol consumer to 54.9% of the sample. OPMD was reported in 45.2% of patients, affecting mainly women (78.5%). Leukoplakia (63.7%) followed by oral lichen planus (36.3%) was the most common OPMD found in women. OSCC adjacent to DI occurred in the inferior gingiva/alveolar mucosa in 48.3% of cases, and ulceration was the most common clinical appearance (87%). Peri-implantitis (PI) was initial clinical diagnosis in 16.1% of cases. CONCLUSIONS: Oral squamous cell carcinoma adjacent to DI was more common in women over 70 years old, non-smokers and non-drinker, and the majority had oral leukoplakia before the diagnosis of OSCC. OSCC may present clinical and radiographic features that resemble PI which can delay the diagnosis and impair the prognosis.

Evaluation of cortical mandibular bone in patients with oral squamous cell carcinoma.

OBJECTIVES: The aim of the study was to evaluate the mandible cortical bone changes in patients with oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Twenty patients who underwent some mandibular bone removal as part of the treatment of OSCC had bone samples collected in two parts: in the proximity of the tumor (BPT) and in the surgical margin (BEP). Cortical microarchitecture was analyzed trough micro-computed tomography, together with texture analysis, followed by microcrack evaluation in histological sections and gene expression of RANK, RANKL, OPG, and sclerostin by quantitative polymerase chain reaction. RESULTS: Bone surface was higher in BPT (0.005 ± 0.002 vs 0.004 ± 0.002, p = 0.01) compared with BEP. In BPT, the subset of patients without bone invasion presented higher anisotropy (0.83 ± 0.07) compared with the ones with bone invasion (0.70 ± 0.14) (p = 0.04). RANK, RANKL, OPG, and sclerostin were found to be downregulated in the majority of cases in both parts. There were significant correlations between the parameters of microarchitecture and gene expression analysis (p < 0.001 to p < 0.05), most of them related with OPG levels. CONCLUSION: The cortex in the mandible in the proximity of the tumor reveals more bone surface than the bone in the surgical margin, and the tumor invasion causes a decrease in anisotropy. RANK, RANKL, OPG, and sclerostin are downregulated in mandible, in both parts analyzed. Correlation tests revealed the association between cortical thickness, bone surface, anisotropy, porosity, bone mineral density, and OPG levels. CLINICAL RELEVANCE: The mandible cortical bone microarchitecture changes in the proximity of the squamous cell carcinoma lesion.

Variability of high-dose melphalan exposure on oral mucositis in patients undergoing prophylactic low-level laser therapy.

The present study outlines the clinical impact and risk factors of oral mucositis in 79 patients with multiple myeloma following high-dose melphalan for autologous transplant. All patients underwent daily prophylactic low-level indium gallium aluminum phosphate diode laser therapy (660 nm, 15 mW, 3.75 J/cm2, 10 s per point) from the beginning of the conditioning regimen up to day +2. Oral mucositis assessments were made daily until hospital discharge. For analysis, oral mucositis was divided into two groups according to severity: group 1, patients with oral mucositis grade

Knowledge and attitudes of Brazilian dental students and dentists regarding bisphosphonate-related osteonecrosis of the jaw.

PURPOSE: The aim of this study was to evaluate the knowledge of Brazilian dentists (DEN) and dental students (DS) about bisphosphonates (BP) and bisphosphonate-related osteonecrosis of the jaw (BRONJ). METHODS: A convenience sample of 104 DEN and 100 DS was randomly selected and invited to answer a questionnaire. The questionnaire was structured on the basis of the main information about BP and the risk factors associated with the development of BRONJ. The data obtained were analyzed by the chi-square and Fisher's exact tests, considering significance of 5%. RESULTS: Seventy-five (72.1%) DEN and 75 (75%) DS did not know the BP cited in the questionnaire (p < 0.0001), and their commercial brand names were not recognized by 88 (84.6%) DEN and 86 (86%) DS (p < 0.0001). In the same way, 62 (59.6%) DEN (p = 0.04) and 58 (58%) DS (p < 0.0001) did not recognize BRONJ as an oral side effect of BP or point out oral conditions that were not associated with the use of BP. CONCLUSIONS: Practical initiatives, such as free lectures and workshops, must be taken to broaden the knowledge of DEN and DS about BP and thus contribute to the prevention of BRONJ.

Surgical Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw: Six-Year Experience of a Single Institution.

PURPOSE: Bisphosphonates are drugs commonly used to treat osteoporosis, hypercalcemia of malignancy, and bone metastases. In some cases, its administration has been associated with osteonecrosis of the jaws. The management of medication-related osteonecrosis of the jaw (MRONJ) has not been completely elucidated, and its treatment can vary from no or limited surgery to more extensive surgery. The objective of the present study was to evaluate the efficacy of surgical therapy for patients presenting with MRONJ. PATIENTS AND METHODS: A retrospective study was conducted that evaluated all MRONJ cases resulting from bisphosphonate use and treated by surgery from 2006 to 2012. All patients underwent surgery under general anesthesia. RESULTS: A total of 33 patients with 46 MRONJ sites were evaluated. Most of the patients were women, with an age range of 39 to 83 years (mean 65.6 ± 10.6). Complete healing of the MRONJ region was observed in 40 of the 46 sites (87%), with partial improvement (symptom control and reduction of the exposed bone area) observed in 3 sites (6.5%), for a 93.5% clinical benefit rate. Of the remaining regions, 2 showed no significant changes, and 1 presented with a worse aspect compared with the patient's preoperative condition. Such cases were located in the posterior mandible region. The number of applications and type of bisphosphonate did not influence the treatment response. CONCLUSION: The surgical approach to treating MRONJ showed a high rate of clinical control. Therefore, surgery should be considered as a therapy for some cases of this condition.

Syphilis related to atypical oral lesions affecting an elderly man. a case report.

OBJECTIVE: To present a case of oral syphilis in an old patient. BACKGROUND: Syphilis seems to be resurging mainly in the young. However, in the last twenty years, the elderly have become more susceptive to infectious diseases due to a more frequent use of sildenafil. CLINICAL REPORT: An 83-year-old man was referred to our clinic complaining of burning mouth. His medical history revealed papular lesions on chest and penis glans, which had been diagnosed and treated as scabiosis 2 months prior to our assessment. The intra-oral examination showed erosive and patch lesions on the bilateral lip commissures, the palate and the border of the tongue. Initially, oral herpes was suspected. However, both the serological test and the cytology were negative. Therefore, syphilis was hypothesised. Non-treponemic (VDRL) and treponemic tests (FTA-ABS) were reagent and secondary syphilis was confirmed. The treatment consisted of penicillin G benzathine 2.4 million IU/IM for 4 weeks. Both oral and skin lesions had complete remission. CONCLUSION: The present case illustrates that syphilis should be suspected in old patients with oral atypical lesions.

Oral evaluation and procedures performed by dentists in patients admitted to the intensive care unit of a cancer center.

BACKGROUND: Most of the oral problems affecting patients in the ICU (intensive care unit) are conditions resulting from their general health status/immunosuppression, medications, and trauma due to tracheal intubation. Furthermore, microorganisms present in the oral cavity and oropharynx may be transported into the lungs resulting in pneumonia. PURPOSE: The objectives of this study were to evaluate the oral problems in patients in the ICU of a cancer center and describe the procedures performed by the dentists in such patients. METHODS: The sample consisted of 116 patients and 329 procedures performed in the period between May 2007 and July 2011 at A.C. Camargo Cancer Center. RESULTS: Oral mucositis was the main problem (20.3 %), especially in immunosuppressed patients (p < 0.001). Other most prevalent problems were candidiasis (16.6 %), bacterial biofilm (14.9 %), and xerostomia (7.18 %). The main procedures performed were clinical evaluation and medication prescription corresponding to 35.10 and 27.81 %, respectively. CONCLUSIONS: In conclusion, most of the patients presented oral problems related to side effects of oncological treatment. The dentist's participation in the ICU is important for the prevention, diagnosis, and treatment of oral problems.

Peri-implant medication-related osteonecrosis of the jaw mimicking endodontic disease in a cancer patient: A case report.

Medication-related osteonecrosis of the jaw (MRONJ) is a progressive condition that can cause significant bone loss and its diagnosis can be challenging. A 68-year-old man with a diagnosis of hepatocellular carcinoma, undergoing treatment with atezolizumab, bevacizumab and zoledronic acid, complained of spontaneous pain in the right lower second premolar. Oral examination revealed no dental changes and implants in the right jaw. A patient history and thorough clinical and radiographic examinations mimic endodontic disease. The implant crowns were removed, bleeding on probing, and peri-implant pockets were observed. The main hypothesis was MRONJ Stage 2, and the surgical treatment was performed. The pain ceased and signs of MRONJ were not observed within 3 months. MRONJ should be considered as a hypothesis in the case of odontalgia and a patient's history of antiresorptive and antiangiogenic therapies. Furthermore, monitoring patients with dental implants in the mandible through detailed clinical and imaging evaluation is required.

Evaluation of socket healing in patients undergoing bisphosphonate therapy: experience of a single Institution.

OBJECTIVE: To assess the clinical features of exodontias performed in cancer patients who have been receiving intravenous bisphosphonates (BPs). STUDY DESIGN: This is a retrospective cohort study using a sample of 20 patients receiving BPs who had 62 teeth extracted. An univariate analysis was applied to calculate socket healing time (HT), comparing among exodontias performed according to cause, such as periodontal disease or caries, type of BP, and use of corticosteroid. In order to analyze the influence of each variable on HT, multiple statistical analyses were performed through logistic multiple regression. RESULTS: From the 62 tooth extractions performed, 5 exodontias had evolved to 4 sites of bisphosphonate-related osteonecrosis of the jaws (BOJ). Of another 57 exodontias without development of BOJ, HT was significantly better for tooth extraction performed in patients receiving corticosteroid (p= .01), for tooth extracted due to caries (p= .04), and for extractions under pamidronate (p= .03). Sockets after exodontias due to periodontal diseases had OR= 5.22 (95% CI 1.73-133.66, p=0.01) for delayed HT, exodontias performed under corticosteroid use had OR=0.04 (95% CI 0.01-0.40, p<0.001), and exodontias performed under zoledronate had OR=0.31 (95% CI 0.08-1.25, p=0.10). CONCLUSIONS: Exodontias performed in patients under BP therapy had a low rate of BOJ occurrence. Zoledronate and periodontal diseases influence delayed socket healing. Adjuvant antibiotics could be relevant procedures aimed at reducing the risk of BOJ development.