Molecular Tumour Board (MTB): From Standard Therapy to Precision Medicine.

Background: In the metastatic setting, cancer patients may not benefit from standard care regimes and their diseases undergo drug resistance due to tumour cell heterogeneity and genomic landscape complexity. In recent years, there have been several attempts to personalise the diagnostic-therapeutic path and to propose novel strategies based on not only histological test results but also on each patient's clinical history and molecular biology. Profiling molecular tests allows physicians to investigate the single tumour genomic landscape and to promote targeted approaches. The Molecular Tumour Board (MTB) is a multidisciplinary committee dedicated to selecting individualised and targeted therapeutic strategies appropriate for patients suffering from diseases that present resistance to standard care. Materials and Methods: Our MTB settled in "Azienda Ospedaliero Universitaria delle Marche", Ancona (AN), Italy, and includes oncologists, molecular biologists, geneticists, and other specialists. Clinical cases are referred by physicians to the MTB, through the Cancer and Research Centre of the Marche Region (CORM), through a telemedicine platform. Four possible molecular profiles are available: FoundationOne® CDx e FoundationOne®Liquid CDx and two local Next Generation Sequencing (NGS) panels, with 16 DNA genes and 10 RNA genes respectively. The resulting genetic mutations and their analyses are evaluated by all the members of the Board and a report for each patient is provided with medical recommendations. Results: from June 2021 to May 2023, we collected data from 97 referral patients (M: 49, F: 48). The mean age was 60.6 years (range 22-83 years). 90 cases were approved for testing. Only seven patients were not eligible for genomic profiling. In two patients who were eligible, molecular profiling was not performed because a tissue sample was not available. Off-label therapy was recommended for three patients. 5% of cases (5/88) showed addressable driver mutations associated with an existing targeted therapy and were immediately enrolled. Conclusions: MTB presents a powerful tool for offering precise medical goals. Our Department of Clinical Oncology also takes advantage of the important role of multidisciplinary teams, through the establishment of CORM and MTB meetings, within which there is the chance to perform NGS-based analyses. It will be important in the future to implement the use of genomic profiling to improve personalised care and to guide the choice of suitable therapies and more appropriate management of patients.

Maternal metabolic control and perinatal outcome in women with gestational diabetes treated with regular or lispro insulin: comparison with non-diabetic pregnant women.

OBJECTIVE: To compare maternal glucose levels and neonatal outcome, achieved in women with gestational diabetes (GDM) receiving either regular insulin or insulin lispro, with those of a control group of non-diabetic pregnant women. STUDY DESIGN: We enrolled 49 pregnant women with GDM, randomly allocated to the treatment with either insulin lispro (n=25) or regular insulin (n=24), and 50 pregnant women with normal GCT, matched for age, parity, pre-pregnancy weight and BMI, who formed the control group. All the women were caucasian, non-obese, with a singleton pregnancy and delivered term live born infants. Women of both groups were requested to perform a blood glucose profile (consisting of nine determinations: fasting/pre-prandial, 1 and 2h post-prandial) every week from the time of diagnosis to 38 weeks (study subgroups) or every 2 weeks from 28 to 38 weeks' gestation (control group). RESULTS: Overall pre-prandial blood glucose values in diabetic women were significantly higher than those of controls; at the 1h post-prandial time point, blood glucose values of GDM women receiving insulin lispro were similar to those of controls, whereas in the regular group they were significantly higher. Overall, both the lispro and regular insulin obtained optimal metabolic control at the 2h post-prandial time point, although near-normal blood glucose levels 2h after lunch could be observed only in the lispro group. There were no statistically significant differences between the groups in neonatal outcome and anthropometric characteristics; however, the rate of infants with a cranial-thoracic circumference (CC/CT) ratio between the 10th and the 25th percentile was significantly higher in the group treated with regular insulin in comparison to the lispro and control groups. CONCLUSIONS: Fasting/pre-prandial and 1h post-prandial maternal blood glucose levels in non-diabetic pregnant women fell well below the currently accepted criteria of glycemic normality in diabetic pregnancies. In women with GDM, the use of insulin lispro enabled the attainment of near-normal glucose levels at the 1h post-prandial time point and was associated with normal anthropometric characteristics; the use of regular insulin was not able to blunt the 1h peak post-prandial response to a near-normal extent and resulted in infants with a tendency toward the disproportionate growth. Insulin lispro can be regarded as a valuable option for the treatment of gestational diabetes.

Sonographic evaluation of fetal growth and body composition in women with different degrees of normal glucose metabolism.

OBJECTIVE: To investigate the maternal demographic and metabolic factors contributing to the growth of fetal lean and fat body mass in women whose degree of glucose intolerance is less than that defining gestational diabetes in comparison with women with normal glucose metabolism. RESEARCH DESIGN AND METHODS: Longitudinal sonographic examinations of 66 singleton fetuses without anomalies of nonobese mothers with abnormal oral glucose challenge test (GCT) results and without gestational diabetes (group 1) were compared with those of 123 singleton fetuses without anomalies of nonobese mothers with normal GCT values (group 2). Lean body mass measurements included head circumference, femur length, mid-upper arm, and mid-thigh central areas. Fat body mass measurements included the anterior abdominal wall thickness, the subscapular thickness, and the mid-upper arm and mid-thigh subcutaneous areas. All the women performed a 24-h glucose profile on the day preceding the ultrasound scan. Multivariate logistic regression analysis established best-fit equations for fetal sonographic measurements of fat and lean body mass. Independent variables included groups 1 and 2, maternal age, parity, prepregnancy BMI, gestational age, weight gain during pregnancy, fetal sex, and the following averaged 24-h profile maternal capillary blood glucose values: preprandial, 1-h postprandial, and 2-h postprandial. RESULTS: No difference was found between the two groups with respect to fetal lean body mass parameters; the factors that contributed significantly and most frequently were gestational age and fetal sex (male). With respect to fetal fat body mass, all the measurements were significantly higher in group 1 than in group 2. In all instances, the significantly contributing factors were gestational age and maternal 1-h postprandial glucose values, whereas another frequent contributor was prepregnancy BMI. CONCLUSIONS: Our study suggests the possibility of using sonographically determined fetal fat and lean mass measurements as indicators of body composition. The assessment of these parameters, achievable in a noninvasive and reproducible fashion in pregnancies complicated by glucose intolerance, might enable the real-time detection of fetal overgrowth and disproportion, thus opening the possibility of exploring interventions to limit fetal fat accretion, birth weight, and potential resulting morbidity.