Alveolar bone histological necrosis observed prior to extractions in patients, who received bone-targeting agents.

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: 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). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: 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.

Trastuzumab combined with pegylated liposomal doxorubicin in patients with metastatic breast cancer. phase II Study of the Hellenic Cooperative Oncology Group (HeCOG) with biomarker evaluation.

OBJECTIVE: Combination of trastuzumab and anthracyclines in metastatic breast cancer (MBC) is precluded due to cardiotoxicity. Pegylated liposomal doxorubicin (PLD) is the least cardiotoxic among the anthracyclines. We performed a phase II study of trastuzumab and PLD with biomarker evaluation. METHODS: Patients with MBC and HER2 overexpression, assessed as 3+ at local laboratories, received trastuzumab 8 mg/kg as loading dose followed by 6 mg/kg in combination with PLD 30 mg/m(2), both given every 3 weeks. To be eligible, patients should have received first-line chemotherapy for MBC or should have relapsed within a year of adjuvant taxane. Tumor tissue blocks were collected for central review and exploratory biomarker evaluation. Left-ventricular ejection fraction (LVEF) was closely monitored by cardiac ultrasound. RESULTS: Among 37 patients, an overall response rate of 22% was observed with a progression-free survival (PFS) of 6.5 months (0.8-31.1, 95% CI 2.7-10.3) and a survival of 18.7 months (1.6-40.8, 95% CI 3.7-33.7). No decline in LVEF was noticed. Overexpression of mTOR and TOP2A gene alterations were associated with better PFS. PTEN gene deletion was associated with resistance to treatment. CONCLUSION: Trastuzumab combined with PLD every 3 weeks is feasible, effective and safe in HER2-positive patients.

Periodontal disease preceding osteonecrosis of the jaw (ONJ) in cancer patients receiving antiresorptives alone or combined with targeted therapies: report of 5 cases and literature review.

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.