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We read the letter from Dr. Fusco and colleagues with great interest, and we would like to thank them for the stimulating comments regarding our paper “Medication-Related Osteonecrosis of the Jaws and CDK4/6 Inhibitors: A Recent Association” [...]

Background: To prevent excessive compression of the cortical layer, which can lead to marginal bone loss, various companies have introduced specialized drills. However, these drills often lack the necessary precision, as the operator’s hand may neither be stable enough to prevent ovalization and over-widening nor precise enough to maintain coaxial alignment. Therefore, the aim of this study was to develop a device capable of achieving calibrated cortical preparation in terms of both dimension and coaxiality. Methods: A machining technology based on drilling principles was employed to create the device. Results: Nine blades were incorporated between the transmucosal neck and the implant threads, enabling the blades to cut the cortical bone coaxially during the implant insertion process. Conclusions: The primary goal of this study was to develop an implant capable of achieving calibrated cortical bone preparation, ensuring both precise dimensional control and coaxial alignment. This design incorporates integrated blades that allow for controlled cortical decompression, helping to manage radial compressive stresses during implant placement. Although the experimental studies cited were conducted independently of this research, they validate the functional efficacy of this implant design, demonstrating its ability to promote osseointegration and preserve marginal bone. The results suggest that this implant configuration holds the potential for improving clinical outcomes, particularly in cases where bone quality or density poses challenges to implant stability.

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.

The goal of this investigation was to identify potential risk factors to predict the onset of medication-related osteonecrosis of the jaw (MRONJ). Through the identification of the multiple variables positively associated to MRONJ, we aim to write a paradigm for integrated MRONJ risk assessment built on the combined analysis of systemic and local risk factors. The characteristics of a cohort of cancer patients treated with zoledronic acid and/or denosumab were investigated; beyond the set of proven risk factors a new potential one, the intake of new molecules for cancer therapy, was addressed. Registered data were included in univariate and multivariate logistic regression analysis in order to individuate significant independent predictors of MRONJ; a propensity score-matching method was performed adjusting by age and sex. Univariate logistic regression analysis showed a significant effect of the parameters number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01–1.05; p = 0.008) and chemotherapy (OR = 0.35; 95% CI = 0.17–0.71; p = 0.008). The multiple logistic regression model showed that breast, multiple myeloma, and prostate cancer involved a significantly higher risk compared to lung cancer; a significant effect of the combined variables number of doses of zoledronic acid and/or denosumab (OR = 1.03; 95% CI = 1.01–1.06); p-value = 0.03) and exposure to novel molecule treatment (OR = 34.74; 95% CI = 1.39–868.11; p-value = 0.03) was observed. The results suggest that a risk assessment paradigm is needed for personalized prevention strategies in the light of patient-centered care.

Mucoepidermoid carcinoma (MEC) can have a variety of clinical outcomes, but prognosis seems to be related to the tumor grade. The system proposed by Auclair and Goode is useful, and our data lend further support to its application and validity in clinical practice. We have clinicopathologically reviewed 108 cases of MEC originating in major (MASG) and minor (MISG) salivary glands that were treated at the National Cancer Institute of Milan between 1975 and 1995. Following the methods of Auclair and Goode, a quantitative grading system was used. The relationships between clinical and pathologic characteristics and survival rate were investigated. Twenty-six (44%) cases located in MASG and 19 (39%) cases in MISG were categorized as high-grade tumors. In patients with MASG tumors, the 5-year disease-free survival rate was 22.5% when the tumor was high grade and 97.0% if the tumor was low grade (P <.0001). For patients with a tumor of the MISG, the percentages were 35.3% for high-grade and 80.0% for low-grade tumors (P =.0066). Our study confirms that in MEC, tumor grade, subdividing cases into low and high grade by using the criteria delineated by Auclair and Goode, correlates well with prognosis.

Background/Objectives. Head and neck mucosal melanoma (HNMM) is a rare, aggressive malignancy with poor outcomes and limited evidence to guide prognostication and treatment. A detailed assessment of long-term survival and prognostic factors is needed to inform clinical management and staging. This work aimed to describe outcomes and prognostic factors in HNMM patients treated over 45 years. Methods. This was a retrospective observational cohort study of consecutive patients treated at a tertiary referral center in Italy from 1975 to 2020. Random-forest-based screening informed covariate selection for Cox models. Endpoints were overall survival (OS), disease-free survival (DFS), and post-recurrence DFS (prDFS). Associations with clinical and pathological variables were evaluated using Kaplan–Meier estimates, log-rank tests, and multivariable Cox regression. Results. Among 112 patients (median follow-up, 121.1 months), 3-/5-year OS was 42.8%/28.0%, DFS 20.5%/13.2%, and 1-/3-year prDFS 36.7%/10.9%. Ulceration was associated with worse OS (HR 2.12; 95% CI 1.05–4.26) and DFS (HR 2.23; 95% CI 1.16–4.28). Male sex showed a trend toward poorer OS and DFS. Regional lymph-node treatment correlated strongly with OS and prDFS (overall p < 0.001), with neck dissection indicating unfavorable risk (OS HR 5.22; 95% CI 2.39–11.40). Conclusions. HNMM remains a high-mortality disease with frequent recurrence. Ulceration and nodal involvement were key adverse prognostic factors, while surgery was associated with improved survival. The findings support incorporating ulceration into future staging and highlight the potential for durable control through salvage surgery. Further investigation of treatment intensification, biomarkers, and multimodal strategies is warranted.

Clinical data of ri-SGCs patients treated between 2015 and 2019 at a tertiary cancer center and a national hadron therapy facility were reviewed. Latent time (LT) from first RT to ri-SGCs diagnosis, overall (OS), and disease-free survival (DFS) were assessed. Thirteen patients developed 14 ri-SGCs (one patient had 2 synchronous ri-SCGs), after a median LT of 23 years (range 16–34). Parotid was the primary site in 8 cases (57%) and salivary duct carcinoma was the most frequent histotype (29%). Nine patients (69%) underwent surgery (Sx). Among them, 4 patients (31%) underwent Sx alone, 5 received post-operative treatments: 3 (23%) photon-based (X) reRT, one (8%) protons and carbon ions, one (8%) carbon ions only. One patient (8%) received definitive XRT. The remaining 3 patients (23%) received androgen deprivation therapy. With a median follow-up of 48 months (range 24–72), median OS and PFS were 74 and 24 months, respectively. In the subgroup of AR+ ri-SGCs, median PFS and OS were 12 and 74 months, respectively. Given the rarity of ri-SGCs, this work adds further knowledge to the paucity of literature. The management of these malignancies is extremely complex requiring a multidisciplinary treatment approach.

To analyze the patterns of locoregional failure following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) at our institution, as part of an internal quality assurance program. We aimed to investigate the potential existence of a correlation between any part of the IMRT process and clinical outcome. A total of 106 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a sequential or simultaneous integrated boost approach at the total prescribed dose of 66-70 Gy (2.00-2.12 Gy per fraction). MRI studies of recurrences were recorded with the planning computed tomography studies to identify volume of failure. Recurrence-related characteristics were analyzed with respect to the original treatment. Failures were classified as 'in-field , 'marginal or 'out-field if at least 95, 20-95 or less than 20% of the volume of failure, respectively, was within 95% of the total prescription dose. With a median follow-up of 43.4 months, 5-years local control, regional control, locoregional control and overall survival rates were 87.7, 88.0, 83.5 and 81.3% respectively. A total of 21 failures were registered in 15 patients. In particular, ten failures (47.6%) were classified as 'in-field (seven local failures and three regional failures [RFs]), nine failures (42.9%) as 'marginal (five local failures and four RFs) and only two failures (9.5%) as 'out-field (both RFs). The most relevant causes of failures were suboptimal target definition and target coverage as well as a longer than planned overall treatment time. IMRT determines excellent outcome in NPC patients. However, great attention in all IMRT steps is necessary to reduce potential causes of failure.

We report a fourth case of papilliferous keratoameloblastoma, with a 6-year followup. A 62-year-old man underwent resection of a right mandibular neoplasm infiltrating bone and soft tissues. Microscopically, there were cysts lined by papillary projections and containing necrotic debris. Cribriform, solid, and tubular patterns were also present. No regional or distant metastases were found. A local recurrence, developed 3 years later, showed a predominance of the lesser differentiated patterns and focal granular cell ameloblastomatous features. The patient died soon after surgery of unrelated causes, with a further local relapse. The tumor coexpressed cytokeratins and vimentin, and SOO protein (the latter focally in the relapse). It was instead unreactive for Alcian blue, actin, maspin, and GFAP. We suggest that papilliferous keratoameloblastoma be renamed “papillary ameloblastic carcinoma.”