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.

Nivolumab in patients with rare head and neck carcinomas: A single center's experience.

Immunotherapy (IO) with anti-PD1 inhibitors is available for the treatment of recurrent/metastatic squamous cell carcinomas of the head and neck (SCCHD) since 2016. Both nivolumab and pembrolizumab were tested in phase 3 randomized trials in adults progressing on or after platinum-based therapy and were found to confer an overall survival benefit compared to investigator's choice. However, very limited data exist concerning IO use in rare subtypes of head and neck carcinoma, like salivary gland carcinoma. We retrospectively collected clinical data of all patients diagnosed with rare subtypes of head and neck carcinoma, who were treated with immune checkpoint inhibitors in our department during the last 5 years. We analyzed safety and efficacy of these therapies. We identified six patients who received nivolumab for recurrent or metastatic head and neck carcinomas, between 31 and 57 years old. All patients had received at least one line of platinum-chemotherapy, as well as radiation therapy. Treatment was administered every 2 weeks, at a dose of 3 mg per kilogram of body weight. Number of nivolumab cycles varied between 2 and 18. Progression-free survival varied from 1 to 12 months and overall survival from 4 to 24 months. Tolerance was very good, except for one case of diabetes and hypothyroidism requiring medication. There is currently insufficient evidence regarding the optimal treatment of the rare non-squamous cell carcinoma of the head and neck. Our case series supports a role for immunotherapy in these patients. However, larger collaborative studies are needed to evaluate this treatment.

Subcutaneous Trastuzumab Combined with Pertuzumab and Docetaxel as First-line Treatment of Advanced HER2-positive Breast Cancer.

BACKGROUND/AIM: Subcutaneous (s.c.) trastuzumab was introduced in the (neo)adjuvant setting, based on the non-inferiority results and patient preference. In the advanced setting, preliminary safety data have only been reported. We conducted an observational study of s.c. trastuzumab in combination with i.v. pertuzumab and docetaxel in the first-line setting of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. PATIENTS AND METHODS: In this single-institution study, patients received 600 mg s.c. trastuzumab in combination with 840 mg pertuzumab for the first cycle and 420 mg for the following cycles, and 75-100 mg/m2 docetaxel, followed by maintenance with s.c. trastuzumab and pertuzumab until disease progression or unacceptable toxicity. Endpoints were efficacy and safety. RESULTS: Forty patients were enrolled. The median number of cycles with docetaxel was six, while the median number of maintenance cycles was 21. With a median follow-up of 37 months, median progression-free survival and overall survival were 24 and 35 months. CONCLUSION: Subcutaneous trastuzumab in combination with pertuzumab and docetaxel is well tolerated and effective in HER2-positive advanced breast cancer.

Metachronous and synchronous primary lung cancers: diagnostic aspects, surgical treatment, and prognosis.

The average lifelong rate of developing a new primary lung cancer approximates 1% and 6% per year after radical therapy for non-small-cell lung cancer and small cell lung cancer, respectively. The frequency of recorded synchronous and metachronous lung cancers has been increasing in the recent years because of the development of early detection techniques and advances in cancer therapy. The distinction between multiple synchronous or metachronous primary lung cancers and intrapulmonary metastases is based on established clinicopathological criteria, however it is often difficult, although of great importance for the management and prognosis of these patients. Newly developed molecular and genomic methods are expected to contribute to a more solid and clear differentiation. Surgical treatment, whenever feasible, is considered the modality of choice for the management of patients with second primary lung cancers, as opposed to those with metastases. The type and extent of surgery are under discussion. The prognosis of patients with second primary lung cancers largely depends on the time of detection and the stage and location of the second cancer, thus surveillance after surgical resection of the initial tumor is mandatory.

Polymorphisms of uridine glucuronosyltransferase gene and irinotecan toxicity: low dose does not protect from toxicity.

Uridine glucuronosyltransferase (UGT) gene polymorphisms have been linked to irinotecan toxicity. Our purpose was to study the association between UGT1A1*28, UGT1A7*2, and UGT1A7*3 polymorphisms and irinotecan toxicity in Greek patients receiving low-dose weekly irinotecan. Blood samples were collected for 46 patients. DNA was extracted and UGT1A1 promoter and UGT1A7 exon 1 genotyping was carried out. Laboratory tests and physical examination were performed on regular basis for the assessment of toxicity. UGT1A1*28 was significantly correlated with both haematologic and non-haematologic toxicity. Moreover, patients carrying UGT1A7 polymorphisms had significant incidence of toxicity. To conclude, UGT polymorphisms play a role in the toxicity of irinotecan, even if the drug is administered in low doses. The genotyping test may be a useful tool for the management of patients who are going to receive irinotecan.