Impressive long-term response with pertuzumab and trastuzumab in HER2-positive breast cancer with brain metastasis

This is a case report of a 40-year-old woman who, after conservative breast cancer treatment, developed a HER2 positive solitary brain metastasis in the left temporal lobe, without extracranial disease. She underwent surgery resection followed by stereotactic radiotherapy and, because of early brain progression, she was submitted to the first line therapy with pertuzumab, trastuzumab and weekly paclitaxel. After six months of treatment, a brain magnetic resonance imaging revealed a complete disappearance of brain recurrence, which persisted for more than 24 months

Collagenated heterologous cortico-cancelleus bone mix stimulated dental pulp derived stem cells

Collagenated heretologous cortico-cancelleus bone mix (CHCCBM) is largely employed in maxillary and dental surgery for regeneration procedures, and is similar to human bone from chemical and physical point of view and promotes osteogenesis. In order to get more inside how this biomaterial induces osteoblast gene expression to promote bone formation, the mRNA levels of bone related genes were compared in human osteoblasts and dental pulp stem cells, using real time RT-PCR. The obtained results demonstrated that CHCCBM enhance stem cells differentiation and deposition of matrix by the activation of osteoblast related genes SP7, FOSL1 and SPP1

Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer. Efficacy in combination with hormonal therapy

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not.Results: Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev.Conclusion: Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents

Association between oral cleft and transcobalamin 2 polymorphism in a sample study from Nassiriya, Iraq

Orofacial clefts are common congenital defects whose prevalence differs between geographical regions and ethnic groups. The inheritance is complex, involving the contribution of both genetic and environmental factors. The involvement of genes belonging to the folate pathway is still matter of debate, with strong evidences of association and conflicting results. After demonstrating the contribution, for a sample from the Italian population, of common mutations mapping on three genes of the folate pathway, our group tried to unravel their contribution in independent sample studies with different ethnicity. In the present investigation a set of 34 triads with oral cleft from Nassiriya, Iraq, has been genotyped for rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS polymorphisms. Association analysis evidenced a decreased risk of cleft for children carrying the 667G allele at TCN2 gene (P = 0.02). This evidence further supported the relationship between polymorphisms of folate related genes and oral clefts, and outlined the relevance of studying populations having different ethnicity

A rare case of pituitary melanoma metastasis: a dramatic and prolonged response to dabrafenib-trametinib therapy

Introduction: Pituitary metastases (PM) are rare events and to date only very few cases of melanoma PM have been described in literature up to now. Case Presentation: We describe the clinical history of a 33-year-old male patient who underwent surgical excision of an inter-scapular melanoma in 2008. The subsequent follow-up was negative for ~10 years. In September 2018, due to the onset of a severe headache, the patient underwent a brain magnetic resonance imaging, which showed an expansive mass in the saddle and suprasellar region with a maximum diameter of 17 mm. Pituitary function tests and visual field were normal. Worsening of the headache and the appearance of a left eye ptosis led the patient to surgical removal of the lesion in October 2018. The histological examination unexpectedly showed metastasis of the melanoma. Post-operative hormonal assessment showed secondary hypothyroidism and hypoadrenalism, which were both promptly treated, and a mild hypogonadism. Three months after surgery, a sellar MRI showed a persistent, increased pituitary mass (3 cm of diameter); fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) detected an increased radiopharmaceutical uptake in the sellar region. Due to the persistence of the disease and the evidence of a BRAF V600E mutation, in February 2019, the patient underwent a combined treatment with dabrafenib (a BRAF inhibitor) and trametinib (mitogen-activated extracellular signal-regulate kinase inhibitor). Sellar MRI performed 6 months later showed no evidence of mass in the sellar region. The patient was in a good clinical condition and did not complain of headaches or other symptoms; there were no significant side-effects from the anticancer therapy. After 13 months of treatment, the patient showed no recurrence of the disease on morphological imaging. Anticancer therapy was confirmed, replacement therapies with hydrocortisone and levothyroxine continued and the pituitary-gonadal axis was restored. Conclusion: This is a very interesting case, both for the rarity of the pituitary melanoma metastasis and for the singular therapeutic course carried out by the patient. This is the first case of a pituitary melanoma metastasis with BRAF mutation, successfully treated with the combination of dabrafenib and trametinib after incomplete surgical removal

Non-syndromic cleft palate: Association analysis on three gene polymorphisms of the folate pathway in Asian and Italian populations

Periconceptional folic acid supplementation can reduce the risk of inborn malformations, including orofacial clefts. Polymorphisms of MTHFR, TCN2, and CBS folate-related genes seem to modulate the risk of cleft lip with or without cleft palate (CL/P) in some populations. CL/P and cleft palate only (CPO) are different malformations that share several features and possibly etiological causes. In the present investigation, we conducted a family-based, candidate gene association study of non-syndromic CPO. Three single nucleotide polymorphisms, namely, rs1801133 of MTHFR, rs1801198 of TCN2, and rs4920037 of CBS, were investigated in a sample that included 129 Italian and 65 Asian families. No evidence of association between the three genotyped polymorphisms and CPO was found in the Italian and Asian cases, indeed the transmission disequilibrium test did not detect any asymmetry of transmission of alleles. This investigation, although with some limitation, further supports that CL/P and CPO diverge in their genetic background

progression free survival pfs benefit from first line endocrine based therapies in postmenopausal women with hr her2 metastatic breast cancer mbc according to different prognostic subgroups a combined analysis of data from paloma 2 monaleesa 2 monarch 3 falcon swog and fact trials

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Exploring CT Texture Parameters as Predictive and Response Imaging Biomarkers of Survival in Patients With Metastatic Melanoma Treated With PD-1 Inhibitor Nivolumab: A Pilot Study Using a Delta-Radiomics Approach

In the era of artificial intelligence and precision medicine, the use of quantitative imaging methodological approaches could improve the cancer patient’s therapeutic approaches. Specifically, our pilot study aims to explore whether CT texture features on both baseline and first post-treatment contrast-enhanced CT may act as a predictor of overall survival (OS) and progression-free survival (PFS) in metastatic melanoma (MM) patients treated with the PD-1 inhibitor Nivolumab. Ninety-four lesions from 32 patients treated with Nivolumab were analyzed. Manual segmentation was performed using a free-hand polygon approach by drawing a region of interest (ROI) around each target lesion (up to five lesions were selected per patient according to RECIST 1.1). Filtration-histogram-based texture analysis was employed using a commercially available research software called TexRAD (Feedback Medical Ltd, London, UK; https://fbkmed.com/texrad-landing-2/) Percentage changes in texture features were calculated to perform delta-radiomics analysis. Texture feature kurtosis at fine and medium filter scale predicted OS and PFS. A higher kurtosis is correlated with good prognosis; kurtosis values greater than 1.11 for SSF = 2 and 1.20 for SSF = 3 were indicators of higher OS (fine texture: 192 HR = 0.56, 95% CI = 0.32–0.96, p = 0.03; medium texture: HR = 0.54, 95% CI = 0.29–0.99, p = 0.04) and PFS (fine texture: HR = 0.53, 95% CI = 0.29–0.95, p = 0.03; medium texture: HR = 0.49, 209 95% CI = 0.25–0.96, p = 0.03). In delta-radiomics analysis, the entropy percentage variation correlated with OS and PFS. Increasing entropy indicates a worse outcome. An entropy variation greater than 5% was an indicator of bad prognosis. CT delta-texture analysis quantified as entropy predicted OS and PFS. Baseline CT texture quantified as kurtosis also predicted survival baseline. Further studies with larger cohorts are mandatory to confirm these promising exploratory results

Should all patients with HR-positive HER2-negative metastatic breast cancer receive CDK 4/6 inhibitor as first-line based therapy? A network meta-analysis of data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT trials

Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (−) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach. Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed. Results: First-line treatment options in HR+/HER2− MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53–0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53–0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47–0.86 for abemaciclib + AI) and patient’s characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors. Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics

Custom made/patient specific alloplastic total temporomandibular joint replacement in immature patient: a case report and short review of literature

OBJECTIVE: Temporomandibular joint reconstructive surgery in a growing patient represents a challenging situation. Autogenous and alloplastic reconstructive options are being studied in literature; however, there are still some limitations. The objective of this case report is to evaluate a novel custom-made prosthetic system in a 12-year-old TMJ ankylosis patient. CASE PRESENTATION: The patient had complaints of temporomandibular joint ankylosis and hypoplasia. The patient had already been operated two times with autogenous grafts. Swelling and tumefaction were apparent on the right side of the face. Mouth opening was 1.5 centimeters, with limitations in lateral and protrusive movements of the jaws. Hypertonic muscles and pain upon palpation were registered. There were no signs of luxation, fracture, or traumatic avulsion. After examination, unilateral TMJ ankylosis was apparent on TC scans. Revision surgery was planned with the use of true plastic temporomandibular joint customized prosthesis. The patient underwent a TMJ reconstruction surgery using CADCAM custom-made patient specific prosthesis. The follow up period of this patient was 46 months and showed successful healing with no complications. CONCLUSIONS: Replacement of TMJ with custom made alloplastic material that is reported can be considered as a safe and useful option for growing young individuals in selected cases