Noam Yarom

Aim: Antibody-drug conjugates (ADCs) are an emerging class of anti-cancer therapies, designed to specifically target cancer cells while minimizing impact on healthy tissues; however, they are associated with a broad spectrum of toxicities. The goal of this paper is to review the current knowledge about ADC-associated oral toxicities with a focus on the oral mucosa. Methods: A literature search of PubMed and Google Scholar from inception through June 2026 was conducted, supplemented by official FDA pharmaceutical drug information. The review encompasses oral mucosal toxicity, dry mouth, xerostomia, and dysgeusia associated with ADCs. Findings were qualitatively assessed and compared with established guidelines for cancer therapy-associated mucositis. Results: ADC-associated oral mucosal toxicity (OMT) presents as erosions or ulcers, often causing moderate to severe pain. OMT typically occurs early in ADC treatment, with high prevalence rates and varying severity, depending on the ADC type, dose, and treatment cycles. ADC-associated dry mouth can worsen OMT, and ADC-associated dysgeusia may complicate oral intake. OMT management involves a multidisciplinary approach, focusing on basic oral care, pain management, and adequate oral intake tailored to severity. Limited evidence is available regarding steroid-based mouthwashes and cryotherapy, and their efficacy is unclear. Severe OMT may require ADC therapy adjustments, such as dose reduction, cycle spacing, or temporary discontinuation. Conclusions: ADC-associated oral toxicities manifest in various tissues. These toxicities may arise from on-target, off-target, or immune-mediated mechanisms. They require a multidisciplinary approach for management. Further research is needed to establish effective protocols for the prevention and treatment of ADC-associated oral toxicities.

Background: Aspiration pneumonia is the leading cause of morbidity and mortality in oculopharyngeal muscular dystrophy (OPMD), yet non‐muscular contributors to aspiration risk are poorly defined. Thick saliva is frequently reported but has never been quantitatively characterised. Objectives: The primary objective was to compare salivary kinematic viscosity in genetically confirmed patients vs. household controls. Secondary hypothesis‐generating exploratory objectives were to examine associations between viscosity, dysphagia severity, and aspiration risk. Methods: In this observational, cross‐sectional study, we compared genetically confirmed OPMD patients with matched household controls. Salivary kinematic viscosity was the primary outcome. Exploratory assessments examined associations between viscosity and validated dysphagia measures (Swallowing Disturbance Questionnaire, Penetration–Aspiration Scale, Functional Oral Intake Scale) and oral health (number of decayed, missing, and filled teeth). Results: Among 57 participants (30 OPMD, 27 controls), salivary viscosity was higher in patients (difference 0.85 cSt; 95% CI 0.27–1.44; p = 0.007) and remained independently associated with the disease status after adjustment for age, oral health, and “xerogenic” medications. Higher viscosity was independently associated with higher aspiration risk (adjusted OR 2.5 per 1 cSt; 95% CI 1.1–6.1; p = 0.040), and discriminated patients with high risk for aspiration (Area Under the Curve of 0.76 and a positive likelihood ratio of 10.0). Salivary flow rates were preserved, indicating a compositional rather than hyposecretory rheological shift. Conclusion: Oculopharyngeal muscular dystrophy is associated with a flow‐independent shift in salivary rheology quantitatively linked to dysphagia severity and aspiration risk. These cross‐sectional findings nominate salivary viscosity as a non‐invasive candidate biomarker warranting prospective validation for clinical application.

Objective: Acyclovir‐resistant herpes simplex virus infections pose a significant challenge in immunosuppressed patients. This study aimed to characterize the clinical features, treatment outcomes, and mortality associated with acyclovir‐resistant herpes simplex virus infection. Materials and Methods: A retrospective analysis was conducted on 18 patients diagnosed with acyclovir‐resistant herpes simplex virus. Diagnosis was confirmed via plaque reduction assay. Data on demographics, underlying conditions, oral and systemic manifestations, management, and outcomes were retrieved and analyzed. Results: The cohort was comprised of 10 women and eight men with a median age of 41.5 years. Acute myeloid leukemia was the most common underlying medical condition ( n = 5), and 17 patients had undergone allogeneic hematopoietic cell transplantation. Oral lesions were observed in all 18 cases, primarily on the tongue ( n = 12) and lips ( n = 11). Acyclovir resistance was detected after a median of 151.5 days (range: 30–1736 days), after which foscarnet became the primary treatment. Despite therapy, 11 patients died after a median survival of 3 months post‐diagnosis. Conclusions: Acyclovir‐resistant herpes simplex virus infections are associated with considerable morbidity and mortality in immunocompromised patients. These findings highlight the need for heightened awareness, alternative antiviral therapies, and improved prophylactic strategies to manage these patients more effectively. Clinical Relevance: Dentists play a key role in detecting acyclovir resistance through persistent oral HSV lesions, emphasizing early recognition, referral, and supportive care.

Purpose: The MASCC/ISOO Clinical Practice Statement (CPS) endeavors to develop a succinct instrument for clinicians, encapsulating essential practical information requisite for the management of oral complications in oncology patients. This CPS specifically addresses the management of oral complications associated with immunotherapy. Methods: This CPS was formulated through a rigorous literature review, followed by a structured discussion among a consortium of leading experts, members of the Oral Care Study Group of MASCC/ISOO. Immunotherapeutic agents were identified utilizing PubMed, and then they were matched with the National Cancer Institute’s compendium of Food and Drug Administration-approved immunotherapy drugs. The statement integrated information from the literature about the management of oral immune-related adverse events (irAEs), extrapolation from literature about the management of similar oral diseases, and the working group’s clinical experience. The information is systematically presented in concise bullet points and tables, thereby creating a succinct manual delineating the optimal standard of care. Results: Oral irAEs encompass a range of mucosal and gingival conditions, dysgeusia, dysphagia, and xerostomia/hyposalivation. The management of oral toxicities is contingent upon the severity of the symptoms. Topical steroids and immunomodulators are frequently utilized as first-line therapies for oral mucosal toxicities, and topical anesthetics are employed for pain management. Treatment strategies for dysgeusia primarily focus on symptom management. This CPS also provides a guide for oral and dental care for patients undergoing immunotherapy. Conclusion: The management of oral toxicities induced by immunotherapy is intended to mitigate patient discomfort, enhance healing, and regain oral function. Optimal management practices necessitate a collaborative approach between medical professionals and oral health specialists.

Purpose: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise resource for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS focuses on the use of imaging and clinical laboratory tests for the diagnosis, staging, monitoring, treatment decision, and prediction of medication-related osteonecrosis of the jaw (MRONJ) in cancer patients. Methods: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group (OCSG) of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. Results: Radiographs, cone beam computerized tomography (CT), conventional CT, magnetic resonance imaging (MRI), and nuclear imaging are often utilized in patients with MRONJ. The CPS describes the considerations for selecting each imaging modality. Laboratory workup in patients with MRONJ is often derived by comorbidities, with immune status and bleeding tendency being the key considerations. Conclusion: Imaging and lab tests have an important role in the diagnosis and management of MRONJ. The imaging modality and specific laboratory tests should be tailored to the patient’s needs.

Introduction: Medication-related osteonecrosis of the jaw (MRONJ) and jaw metastasis might share similar clinical and radiographic characteristics, with both demonstrating F-18 fluorodeoxyglucose (FDG) uptake on PET-CT. Prostate-specific membrane antigen (PSMA) PET-CT is used to demonstrate prostate cancer dissemination. Unlike FDG PET-CT, PSMA PET-CT is more specific to cancer than to inflammation. Therefore, we hypothesized that it might be a useful tool to differentiate between MRONJ and jaw metastasis. Methods: All files of prostate cancer patients diagnosed with MRONJ and with available PSMA PET-CT studies were retrieved. A similar number of solid cancer patients with MRONJ and with available FDG PET-CT studies served as a second study group. All studies were reviewed by 2 blinded co-investigators (L.D. and M.F.). Results: Seventeen patients who underwent PSMA PET-CT (24 studies) and 15 patients who underwent FDG PET-CT (29 studies) met the inclusion criteria. All patients with FDG PET-CT studies showed pathological uptake at the site of MRONJ in at least one of their studies versus only 23.5% of patients in the PSMA PET-CT group (P < .001). FDG PET-CT studies showed pathological uptake in 89.6% of the studies compared with only 20.8% in the PSMA PET-CT group (P < .001). The mean standardized uptake value (SUVmax) and the mean uptake volume in the FDG PET-CT group were significantly higher compared with the PSMA PET-CT group (P < .001 and P < .005, respectively). The interclass correlation coefficient for all parameters was higher than 0.95. Conclusions: PSMA PET-CT is useful to differentiate between MRONJ and jaw metastasis.

Purpose: A MASCC/ISOO Clinical Practice Statement (CPS) is aimed at generating a concise tool for clinicians that concentrates practical information needed for the management of oral complications of cancer patients. This CPS raises awareness to the prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with breast cancer treated with adjuvant bone-modifying agents (BMA). Methods: This CPS was developed based on a critical evaluation of the literature followed by a structured discussion of a group of leading experts, members of the Oral Care Study Group of MASCC/ISOO. The information is presented in the form of succinct bullets and tables to generate a short manual about the best standard of care. Results: In patients treated with adjuvant BMA, dento-alveolar surgery poses a moderate risk for MRONJ that ranges between the high risk for MRONJ in patients with metastatic breast cancer and the low risk for MRONJ in patients with osteoporosis. Existing MRONJ guidelines serve as a starting point for adjuvant BMA use. Urgent procedures should be delivered without delay using the accepted precautions to prevent MRONJ. If elective surgery is considered, the individual risk for MRONJ following surgery should be assessed according to common risk factors. Conclusion: Prevention of MRONJ in primary breast cancer patients treated with adjuvant BMA requires risk–benefit assessment; collaboration between the medical team, dental professional, and patient; and patient-specific tailored dental treatment planning. The patient should be informed about this risk. Additional research is needed to define optimal MRONJ care for this population.