Search

Medication-Related Osteonecrosis of the Jaw (MRONJ) is defined as a complication, which affects the jawbone of patients that meet all of the following criteria: (a) patients were in the past or are now on treatment with bone targeting agents (BTAs) and/or antiangiogenics, (b) they have exposed bone or bone that can be probed through an intraoral or extraoral fistula for more than 8 weeks, and (c) they have no history of radiotherapy or obvious metastatic disease to the jaws. Since the first reports, in 2003, plethora of articles on MRONJ significantly increased our knowledge of this potentially serious complication. However, controversies about the definition and clinical presentation, risk factors, radiological findings, staging and early diagnosis, prevention and treatment may affect the successful management and the quality of life of cancer patients. The purpose of this article is to present the current knowledge about MRONJ and the recent advances to best clinical practice and treatment. Important questions will be discussed, including the following: (1) Should we wait for 8 weeks when a patient on antiresorptive therapy, presents with exposed necrotic jawbone? (2) Can we exclude the diagnosis of osteonecrosis if a patient presents without exposed bone? (3) Is the dental extraction a risk factor for MRONJ? (4) Should we perform the dental extraction, when a patient on antiresorptives, presents with a symptomatic tooth? (5) What is the role of dental or periodontal infection? (6) Shall we re-start the antiresorptives following healing of previous MRONJ?

Objectives: To prospectively evaluate the imaging characteristics of Medication-Related Osteonecrosis of the Jaw (MRONJ), observed in the Orthopantomogram (OPG) and in Cone Beam Computed Tomography (CBCT), in patients with cancer. Materials and Methods: Cancer patients, who received Bone Targeting Agents (BTAs) and developed MRONJ, were prospectively included in the study. MRONJ was staged following the American Association of Oral and Maxillofacial Surgery (AAOMS) 2014 criteria. Four predefined radiological findings, osteolytic changes, sclerosis, periosteal reaction, and sequestration were assessed and were scored as “absent”, “localized”, “extensive” and “beyond the alveolar bone”. Results: Ninety-eight cancer patients were enrolled. Eighty patients (81.6%) received BTAs for over a year; 19 (19.4%) received BTAs between 13 to 24 months and 61 patients (62.2%) received BTAs for over 24 months. The majority of the patients (n=58, 59.2%) had stage 2 MRONJ and 35 (35.7%) were at MRONJ stage 3.Fifty-two (53.06%) patients were assessed with OPG and 89 (90.81%) with CBCT and CBCT was found more effective in detecting sclerosis and sequestration than OPG.Forty-three (43.87%) patients were assessed with both OPG and CBCT and were available for comparisons between OPG and CBCT. CBCT was significantly more accurate than OPG in interpreting the “beyond the alveolar bone” osteolytic changes, sclerosis, periosteal reaction and sequestration, in all MRONJ stages. P-value was 0.0002

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.

Background: Globally 43.8 million people live with cancer. A 60% increase of cancer cases is estimated by 2040, with 29.4 million patients per year requiring therapy. Optimization of cancer management, using digital innovation, is urgently needed. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms, and communicate with physicians. We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. Methods: Patients from 9 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible, and patients and HCPs were satisfied. Patients were successful to report information on their demographics, disease and treatment characteristics. They also disclosed the need to visit non-oncology HCPs during their cancer treatment and other socioeconomic issues. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

Purpose: We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms and communicate with physicians.Methods: Patients from 18 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible and patients and HCPs were satisfied. File uploading changed to become more user friendly. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

The aim of this systematic review was to update the clinical practice guidelines for the use of anti-inflammatory agents in the prevention and/or treatment of oral mucositis. A systematic review was conducted by the Multinational Association of Supportive Care in Cancer/ International Society of Oral Oncology (MASCC/ISOO) subcommittee on mucositis guideline update. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the clinical practice guidelines published in 2014. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guidelines. A total of 11 new papers across five interventions were examined. The recommendation for the use of benzydamine mouthwash for the prevention of radiotherapy-induced mucositis remained unchanged. New suggestion for the use of the same for prevention of mucositis associated with chemoradiotherapy was made. No guideline was possible for any other anti-inflammatory agents due to inadequate and/or conflicting evidence. Of the anti-inflammatory agents studied for oral mucositis, the evidence supports the use of benzydamine mouthwash in the specific populations listed above. Additional well-designed research is needed on other (class of agents) interventions and in other cancer treatment settings.

Purpose: The aim of this study was to update the clinical practice guidelines for the use of basic oral care (BOC) interventions for the prevention and/or treatment of oral mucositis (OM). Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention in each cancer treatment setting was assigned an evidence level. The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. Results: A total of 17 new papers across six interventions were examined and merged with a previous database. Based on the literature, the following guidelines were possible. The panel suggests that the implementation of multi-agent combination oral care protocols is beneficial for the prevention of OM during chemotherapy, head and neck (H&N) radiation therapy (RT), and hematopoietic stem cell transplantation (Level of Evidence III). The panel suggests that chlorhexidine not be used to prevent OM in patients undergoing H&N RT (Level of Evidence III). No guideline was possible for professional oral care, patient education, saline, and sodium bicarbonate, and expert opinion complemented these guidelines. Conclusions: The evidence supports the use of multi-agent combination oral care protocols in the specific populations listed above. Additional well-designed research is needed on the other BOC interventions prior to guideline formulation.

Background Patients, who receive radiotherapy (RT) for head and neck cancer, develop chronic functional abnormalities and survive with reduced quality of life. Purpose We aimed to study patients with oral cancer, who received post-operative radiotherapy or chemoradiotherapy. Patients Ten patients (mean age 63.8 years) were included. Methods Oral mucositis, pain and xerostomia, maximum mouth opening (MMO) and functional abnormalities before and after RT were recorded. The 35 mm MMO or less was accepted as trismus. Patients completed the EORTC QLQ C-30 and Head/Neck35 questionnaires. Results Mean RT dose was 64.3 Gray. Six patients received chemoradiotherapy. Severe mucositis, pain and xerostomia were recorded in 6 and 5 patients respectively. MMO was reduced in all patients. The mean MMO (34 mm) reached the level of trismus. The total number of symptoms increased from 3.1 to 6.3 in C-30 and from 3.1 to 8.8 per patient in the H/N35. Severe fatigue, pain, limitations at work, weakness, sad feelings, family problems, sleeping problems, anorexia, financial difficulties, tense/irritable, constipation, nausea, vomiting and depression were most often reported with C-30. Most patients reported low to moderate quality of life. Severe oral, jaw and neck pain, swallowing problems, taste alterations, sticky saliva, dry mouth, coarseness, dental problems, feeling sick and reduced interest in life/sex were the most common symptoms reported with N/H35. Conclusions The observed trismus, 2- to 3-fold increase of symptoms and poorer quality of life highlighted the need for support of oral cancer patients, who receive postoperative radiotherapy or chemoradiotherapy.

Objective We present clinical and radiologic data of periodontal tissue involvement preceding the appearance of osteonecrosis of the jaw (ONJ) in 5 patients with solid tumors, who received antiresorptives alone or in combination with targeted therapies. Study Design Five patients with osteonecrosis before dental extraction were studied. Results Periodontal involvement was evidenced by pain, bleeding, fistula, purulence, swelling, periodontal pocket, and tooth mobility. Combined endoperiodontal lesions were considered in 1 patient. Duration of symptoms before ONJ diagnosis lasted 8 to 24 weeks. Routine therapy was performed in 2 of 5 patients. Widening of the periodontal ligament was observed in 4 patients, and dense alveolar bone was seen in 1 patient. Local complications of ONJ required dental extractions in 4 of 5 patients. Spontaneous tooth exfoliation was observed in 1 patient. Alveolar bone biopsies, after the extraction in 2 patients, confirmed osteonecrosis. Osteonecrosis healed in 2 patients—1 after the dental extraction and 1 after 3 dental extractions and surgical debridement. Postextraction socket healed in 1 patient, and the area with exposed bone remained asymptomatic. Osteonecrosis progressed in 2 patients. Conclusions Clinical and radiologic signs of periodontal tissue involvement, before dental extraction in patients treated with antiresorptives alone or in combination with targeted therapy, may represent developing osteonecrosis.

The reporting of osteonecrosis of the jaw (ONJ) related to anticancer agents without known antiresorptive properties (non-antiresorptives), such as antiangiogenics, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, immune checkpoint inhibitors, and cytotoxic chemotherapy is increasing. To review characteristics of ONJ in cancer patients receiving non-antiresorptives. A systematic review of the literature between 2009 and 2017 was conducted by the Bone Study Group of MASCC/ISOO. Of 6249 articles reviewed and from personal communication, 42 ONJ cases related to non-antiresorptives were identified. No gender predilection was noted. Median age was 60 years and ONJ stage 2 was most common, with predilection for posterior mandible. Exposed bone, pain, and infection were common at diagnosis. In comparison to bone targeting agents (BTAs), radiology, histology, and management were similar, with medication often discontinued. Delayed diagnosis (median 8 weeks) was noted. Important differences included earlier time to ONJ onset (median 20 weeks), absence of trigger event (40%), and greater likelihood of healing and shorter healing time (median 8 weeks) as compared to BTA-related ONJ. Gastrointestinal cancers predominated, followed by renal cell carcinomas compared to breast, followed by prostate cancers in BTA-related ONJ, reflecting different medications. Data about non-antiresorptive-related ONJ is sparse. This type of ONJ may have better prognosis compared to the BTA-related ONJ, suggested by greater likelihood of healing and shorter healing time. However, the delay in diagnosis highlights the need for more education. This is the first attempt to characterize ONJ associated with different non-antiresorptives, including BRAF and immune checkpoint inhibitors.

Introduction: Mucormycosis is a rare fungal infection, with high morbidity and mortality. Palatal ulceration may suggest a number of differential diagnoses, one of which is rhinocerebral/craniofacial mucormycosis and for which it may be the first presenting clinical finding. We report a case of sinus mucormycosis in a patient with chronic myelomonocytic leukaemia‐2 (CMML‐2), now classified in the myelodysplastic/myeloproliferative neoplasms, presenting with dental pain and palatal ulcer. Case presentation: A 72‐year‐old female with CMML‐2 presented with pain of the left maxillary molar and a dark‐brown necrotic ulcer with a white irregular border on the hard palate. Invasive fungal infection was included in the differential diagnosis. Computerized tomography disclosed inflammatory lesions in the left nasal, ethmoid and frontal sinuses. Histological examination of the ulcer showed fungal hyphae typical of agents of mucormycosis. Rhizopus arrhizus was isolated from the culture. Liposomal amphotericin B was introduced, combined with haematological support and maxillectomy. Mucormycosis was controlled, but the patient died of progressive acute myeloid leukaemia and multiple bacteraemias. A literature review of rhinocerebral mucormycosis with palatal involvement disclosed 109 cases; palatal involvement was present among other presenting signs in 34 patients and as the presenting sign leading to diagnosis in nine cases, including the present case. Six of the nine patients (66.6 %) survived the infection, compared with 43 of 101 (42.6 %) with other signs at presentation. Conclusion: Palatal ulcer may represent an early sign of sinus mucormycosis. Awareness by healthcare professionals is critical for the prompt diagnosis of this rapidly developing and life‐threatening infection.