Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility : a Single-Institution Experience

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value. OBJECTIVE: We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s). PATIENTS AND METHODS: From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36-86) and the median number of previous treatment lines was five (range 2-8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%). RESULTS: One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63-3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0-15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80-5.03] vs. 2.13 months [95% CI 1.77-2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17-9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33-10.80] vs. 7.18 months [95% CI 5.63-9.33], respectively, p = 0.06). CONCLUSIONS: This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment

Ultrastruttura dei tessuti dentari affetti da carie iniziale in un campione di bambini in età scolare

Aim of the work. The purpose of this work is twofold: to describe the epidemiological investigation on food habits and oral hygiene of a sample of children and to show images of ultrastructural hard dental tissue modifications during the acid demineralization process and the carious one. The study aim at evaluating the correlation between an incorrect diet and an inadequate dental hygiene, and the consequent clinical and therapeutical implications. Materials and methods. The epidemiological study, carried out on a sample of children, was supported by the use of a scanning electron microscope (SEM) to better observe the effects that an incorrect diet has on hard dental tissues. Results. The microscopic scansion observation of hard dental tissues is objectively the best way to detect even the slightest and sub-clinical morphological alterations. Conclusions. The alterations of hard dental tissues found were the result of acid dissolution due to the activity of the demineralization of food containing a high cariogenic power and to the incorrect oral hygiene habits, which were very common in the sample of children studied

Entrectinib for the treatment of metastatic NSCLC: safety and efficacy

Introduction: Gene fusions are strong driver alterations in various cancers, increasingly diagnosed with multiple testing techniques. ROS1 fusions can be found in 1-2% of non-small cell lung cancer (NSCLC) and several tyrosine kinase inhibitors (TKIs) have been tested in this oncogene-driven disease. NTRK fusions are characteristic of a few rare types of cancer, also infrequently seen in some common cancers including NSCLC. Entrectinib is a newer ROS1 and NTRK inhibitor developed across different tumor types harboring rearrangements in these genes. Entrectinib was granted FDA accelerated approval in August 2019 for the treatment of ROS1+ NSCLC and NTRK-driven solid tumors. Areas covered: This review covers the mechanism of action, safety, and efficacy of entrectinib in patients with metastatic NSCLC. Expert opinion: Entrectinib is an orally bioavailable TKI of TrkA, TrkB, TrkC, and ROS1, with the ability to cross the blood-brain barrier. Entrectinib was effective and well-tolerated in patients harboring ROS1- or NTRK-rearranged NSCLC treated within phase I and II studies. Entrectinib appears to be the most appropriate treatment choice for TKIs-na\uefve patients, especially in those presenting brain metastasis. Conversely, in case of systemic progression with the evidence of acquired resistance mutations in ROS1 or Trk proteins, a sequential therapy with entrectinib could not be successful

A comparison between radiographic and sonographic assessment of hand and wrist bones for the estimation of skeletal age in the child patient.,

Abstract AIM: The purpose of this study was to examine, with a sonographic investigation, the hand and wrist bones of a group of young patients and to compare the results with those obtained with a classical radiographic assessment. MATERIALS AND METHODS: Some 25 subjects, 9-18 years of age, who presented problems concerning their short stature or precocious puberty, were evaluated. Each subject was examined by a standard radiographic assessment and by a sonographic investigation with real-time imaging. Sonographic examination was performed on the metacarpus-phalanx articulation of the first finger in order to locate the sesamoid bone. Sonographic examination was also performed on the second and third phalanxes of the third finger and on the distal portion of the radius to evaluate the characteristics of growth cartilage in the area. RESULTS AND STATISTICS: In all the cases where a sesamoid bone was present, this was correctly identified by the sonogram, even up to the initial appearance of its ossification nucleus. Sensitivity, specificity, and diagnostic accuracy were all 100%. The capping phenomenon seen in radiographs was not detected by sonographic investigation in any of the cases. Sonographic evaluation of the fertile cartilage of the third finger distal phalanx demonstrated a sensitivity of 89%, a specificity of 100% and a diagnostic accuracy of 92%. Sonographic evaluation of the radius cartilage showed a sensitivity of 95%, a specificity of 100% and a diagnostic accuracy of 96%. CONCLUSION: Sonographic evaluation of hand and wrist bones cannot accurately reproduce the results of the classical radiographic evaluation. However, the sonographic investigation may be useful, when integrated in a radiographic investigation