Tumor genotyping is becoming crucial to optimize the clinical management of patients with advanced differentiated thyroid cancer (DTC); however, its implementation in clinical practice remains ...undefined. We herein report our single-center experience on molecular advanced DTC testing by next-generation sequencing approach, to better define how and when tumor genotyping can assist clinical decision making.
We retrospectively collected data on all adult patients with advanced DTC who received molecular profiling at the IRCSS Sant’Orsola-Malpighi Hospital from 2008 to 2022. The genetic alterations were correlated with radioactive iodide refractory (RAI-R), RAI uptake/disease status, and time to RAI resistance (TTRR) development.
A significant correlation was found between RAI-R development and genetic alterations (P = 0.0001). About 48.7% of RAI-R cases were positive for TERT/TP53 mutations (as both a single event and comutations with other driver gene alterations, such as BRAF mutations, RAS mutations, or gene fusions), while the great majority of RAI-sensitive cases carried gene fusions (41.9%) or were wild type (WT; 41.9%). RAI uptake/disease status and time to TTRR were significantly associated with genetic alterations (P = 0.0001). In particular, DTC with TERT/TP53 mutations as a single event or as comutations displayed a shorter median TTRR of 35.4 months (range 15.0-55.8 months), in comparison to the other molecular subgroups. TERT/TP53 mutations as a single event or as comutations remained independently associated with RAI-R after Cox multivariate analysis (hazard ratio 4.14, 95% CI 1.51-11.32; P = 0.006).
Routine testing for genetic alterations should be included as part of the clinical workup, for identifying both the subset of more aggressive tumors and the subset of tumors harboring actionable gene fusions, thus ensuring the appropriate management for all patients with advanced DTC.
•RAI resistance and time to RAI-R development in advanced DTC are significantly correlated with genetic profiling.•Genetic testing allows for identifying the subset of more aggressive advanced DTC and those with actionable gene fusions.•Genetic testing should be included as part of the clinical workup and carried out as early as possible in all advanced DTCs.
Herein is described the case of a 64-year-old patient affected by metastatic clear-cell carcinoma, with exclusive bone disease, subjected after the initial cytoreductive nephrectomy to 3 successive ...lines of medical treatment (sunitinib, everolimus, and sorafenib) and multiple locoregional treatments (spinal surgery, radiation therapy, and selective arterial embolization), resulting in a surprisingly long survival of over 75 months. In the era of target therapy, integration strategies, including additional locoregional treatment to medical therapy, are essential to optimize the clinical benefit, to maximize treatment duration overcoming focal progressive disease, and to improve the quality of life. In this context, we would highlight that selective transcatheter embolization of bone metastases from renal cell carcinoma should be considered as an effective and safe option in the palliative setting for patients with bone metastasis, especially for pain relief.
At present no reports on gene expression profiling of liver metastases from colorectal cancer are available. We identified two different signatures using Affymetrix platform: epidermal growth factor ...receptor pathway was upregulated in metachronous lesions, whereas the pathway mainly related to angiogenesis was in synchronous lesions. Synchronous or metachronous liver metastases could be treated differently on the basis of different molecular pathways.
Summary In the last ten years, the development of several novel targeted drugs and the refinement of state of the art technologies such as the genomics and proteomics and their introduction to ...clinical practice have revolutionized the management of patients affected by cancer. However, everyday practice points out several clinical questions: the difficulty of response assessment to new drugs especially using standard RECIST criteria that do not provide information on biological, vascular or metabolic variations; the inadequate selection of patients who are likely to benefit from a targeted therapy excluding those with breast cancer and gastrointestinal stromal tumours; the need to know the global biological background of diseases especially in metastatic setting using repeatable non-invasive procedures. Molecular imaging could provide information on in vivo distribution of biological markers in response to targeted therapy and could improve the selection of patients before therapies. The aim of this review is to analyze the current role of conventional and innovative positron emission tomography (PET) radiotracers in clinical practice and to explore the promising perspectives of molecular imaging in cancer research.
The epidermal growth factor receptor (EGFr) is one of the most studied molecules as a target for cancer therapy. Over these last few years, several studies attempting to identify predictive ...biomarkers of treatment response, such as the receptor status or other molecules related to the downstream signalling pathway, have been conducted. However, from a clinical point of view, the information obtained from ex vivo analyses still has various limitations that may be overcome by the combination with molecular imaging technologies which may provide a noninvasive, global, in vivo evaluation of the molecular tumour background. The aim of this review is to report the preclinical results of all positron emission tomography (PET) tracers synthesized until now for in vivo detection of EGFr in cancer. Two classes of PET compounds have been developed: labelled small molecules such as tyrosine kinase inhibitors and labelled monoclonal antibodies. The in vitro and in vivo results of these PET tracers are very different depending on the chemical properties, positron emission radionuclide, or animal models. As a consequence, various critical questions are still open, and the implications of a translation in the clinical setting for EGFr imaging in cancer patients is discussed.
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. The main treatment for localized gastrointestinal stromal tumors is surgical resection. ...Unresectable or advanced GIST are poorly responsive to conventional cytotoxic chemotherapy but the introduction of tyrosine kinase inhibitors (TKIs) marked a revolutionary step in the treatment of these patients, radically improving prognosis and clinical benefit. Historically GIST has been considered radiation-resistant, and the role of radiotherapy in the management of patients with GIST is currently restricted to symptomatic palliation in current treatment guidelines.
Here we report two patients affected by metastatic GIST, treated with radiotherapy and radiosurgery in combination with TKIs, achieving an unexpected objective response in the first case and a significant clinical benefit associated with a local tumor control of several months in the second case.
These and other successful experiences that are progressively accumulating, open up new scenarios of use of radiation therapy in various settings of treatment. GIST is not universally radioresistant and radiotherapy, especially if combined with molecularly targeted therapy, can improve the outcomes for patients diagnosed with GIST.
The JT-60SA is a fusion experiment designed to contribute to the early realization of fusion energy, by providing support to the operation of ITER, by addressing key physics issues for ITER and DEMO ...and by investigating how best to optimize the operation of the next fusion power plants that will be built after ITER. It is a combined project of the JA-EU Satellite Tokamak Program under the Broader Approach (BA) Program and JAEA's Program for National Use, and it is to be built in Naka, Japan, using the infrastructure of the existing JT-60U experiment. This paper describes in detail the design of the JT-60SA Toroidal Field magnet and shows the strong points of each foreseen solution. Additional information about manufacturing procedures is given and technological issues are reported and critically analysed.
The release of biocontrol agents for the management of arthropod pests on greenhouse tomatoes is an increasingly widespread technique in Europe. The predatory mirid Macrolophus pygmaeus was initially ...used for control of the greenhouse whitefly, Trialeurodes vaporariorum, but its range of application expanded when it was found to have the potential for management of the tomato leafminer, Tuta absoluta. One of the constraints that still limits the use of this beneficial in Sardinian greenhouse crops is its slow population growth, frequently responsible for unsatisfactory control of target pests. To evaluate the effects of two innovative release methods on the establishment and population build-up of M. pygmaeus in tomato crops, experiments were carried out under semi-field and field conditions. The two techniques tested for the introduction of the mirid were pre-plant release and release in confined areas. Pre-plant releases were done in the nursery, while confined area releases were done in the production greenhouse where the mirid was introduced on plants covered with a non-woven film for six weeks and provided with a food source (Ephestia kuehniella eggs). In both cases, approximately 0.8 adult mirids per plant were released. The experiments were conducted in glasshouses where spring tomato crops were grown for up to four months. The method that achieved the most promising results in terms of mirid population build-up (up to 9.6 individuals per plant) was the introduction in confined areas. However, when the insects used were purchased through ordinary retail channels, insufficient population growth and inadequate control of target pests were observed. The pre-plant release method failed to significantly enhance the build-up of M. pygmaeus population, and the peak density observed by eight weeks after its introduction was 1.1 individuals per plant for predators introduced in both a heated and unheated nursery.
Identification of sex in the sea urchin, Paracentrotus lividus, has thus far been achieved through gamete analysis, often using lethal, stressful and generally invasive methods. In this study, we ...developed a noninvasive technique to identify the sex of P. lividus based on the secondary sexual characteristics of genital papillae. This method was evaluated with fully and nonfully sexually mature individuals that were collected during both reproductive and nonreproductive seasons. Each individual was examined under a stereomicroscope, and the genital papillae were classified according to morphological features such as male characteristics (conical protuberances) or female characteristics (flat papillae, sometimes sunk below the body surface). Subsequently, the reliability of the method was verified through gamete observation. Regardless of the season, the methodology resulted in reliable results for approximately 95% of fully mature individuals, while it was somewhat less reliable (approximately 73% accuracy) in nonfully sexually mature sea urchins. The observation of genital papillae morphology is thus a noninvasive, nonlethal (100% survival of animals), that is seasonally independent and inexpensive, and allows the number of animals used during experiments to be minimized, thus promoting animal welfare. This methodology is therefore expected to allow gender identification to be conducted year-round, with significant positive impacts in research and actual aquaculture operations.
•Genital papillae disproves the traditional idea that sea urchin gender could be obtained exclusively with gamete analysis.•The genital papillae sex identification method is reliable for approximately 95% of fully mature individuals.•The genital papillae sex identification method is noninvasive, nonlethal, seasonally independent and inexpensive.•The seasonally independent genital papillae methodology makes possible the gender identification year-round.
Since its first detection in Sardinia (Italy), Tuta absoluta (Meyrick) has been reported as a major pest of greenhouse tomatoes. In recent years, however, a tendency toward a progressive reduction of ...tomato borer infestation levels has been observed. The reasons behind this decline are probably diverse, including both the increase in growers' ability to manage the pest and the adaptation of native predators and parasitoids to the new prey/host. In order to assess the species composition of the parasitoid complex associated with T. absoluta larvae in Sardinian greenhouse tomatoes, a two-year (2010/11) survey was conducted in one of the island's major horticultural areas (Pula, Cagliari). An estimate of the levels of parasitism caused by native wasps was also carried out. The occurrence of larval parasitoids of T. absoluta was detected in approximately half of the crops monitored. The average parasitism rate recorded in tomato plants infested by tomato borer larvae was 1.3%. Moreover, while no parasitism was observed in 76.4% of the samples collected, only 3.0% of the samples showed a parasitism rate exceeding 10%. The highest rates were recorded in spring and summer, with a peak in July (4.8%). Of 159 adult parasitoids recovered from infested leaves, 62.9% were found to belong to a Necremnus sp. near artynes (Walker), 34.6% to a Necremnus sp. near tidius (Walker), and 2.5% to Neochrysocharis formosa (Westwood) (Hymenoptera: Eulophidae). These results show that some native parasitoids have adapted to T. absoluta in the study area. Although parasitoid abundance in tomato crops appeared to be low, their contribution for the control of tomato borer infestation could possibly be enhanced through the application of conservation biological control measures.
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