Search

The publisher regrets that at the time the article was published the name of the author N. La Verde was mistakenly abbreviated as N.L. Verde. This has now been corrected. The publisher would like to apologise for any inconvenience caused.

Background: The presence of KRASG12C mutation in metastatic colorectal cancer (mCRC) correlates with poor outcome. Although different selective inhibitors are under clinical development, the optimal treatment remains uncertain. Thus, we conducted a retrospective analysis in a large cohort of patients with KRASG12C mCRC treated in 12 Italian oncology units. Patients and methods: Patients with unresectable mCRC harboring KRASG12C mutation receiving a first-line chemotherapy doublet or triplet between 2011 and 2021 were included in the study. Evaluation of overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) analysis was carried out. Results: A total of 256/6952 (3.7%) patients with mCRC displayed KRASG12C mutation; of these, 111 met the inclusion criteria. The ORR of first-line therapy was 38.7% (43/111). Median PFS (mPFS) was 9 months [95% confidence interval (CI) 7.5-10.5 months]. After progression, only 62% and 36% of the patients are fit to receive second or third lines of treatment, with limited clinical benefit. Median OS (mOS) was 21 months (95% CI 17.4-24.6 months). In patients receiving first-line triplet chemotherapy, ORR was 56.3% (9/16), mPFS was 13 months (95% CI 10.3-15.7 months) and mOS was 32 months (95% CI 7.7-56.3 months). For irinotecan-based doublets, ORR was 34.5 (10/29), mPFS was 9 months (95% CI 6.4-11.6 months) and mOS was 22 months (95% CI 16.0-28.0 months). With oxaliplatin-based doublets ORR was 36.4% (24/62), mPFS was 7 months (95% CI 4.6-9.4 months) and mOS was 18 months (95% CI, 13.6-22.4 months). Conclusion: Patients with KRASG12C-mutant mCRC had a disappointing response to standard treatments. Within the limitations of a retrospective study, these results suggest that first-line chemotherapy intensification with FOLFOXIRI is a valid option in fit patients.

Merkel cell carcinoma (MCC) is a rare and highly aggressive cutaneous neuroendocrine carcinoma. The MCC incidence rate has rapidly grown over the last years, with Italy showing the highest increase among European countries. This malignancy has been the focus of active scientific research over the last years, focusing mainly on pathogenesis, new therapeutic trials and diagnosis. A national expert board developed 28 consensus statements that delineated the evolution of disease management and highlighted the paradigm shift towards the use of immunological strategies, which were then presented to a national MCC specialists panel for review. Sixty-five panelists answered both rounds of the questionnaire. The statements were divided into five areas: a high level of agreement was reached in the area of guidelines and multidisciplinary management, even if in real life the multidisciplinary team was not always represented by all the specialists. In the diagnostic pathway area, imaging played a crucial role in diagnosis and initial staging, planning for surgery or radiation therapy, assessment of treatment response and surveillance of recurrence and metastases. Concerning diagnosis, the usefulness of Merkel cell polyomavirus is recognized, but the agreement and consensus regarding the need for cytokeratin evaluation appears greater. Regarding the areas of clinical management and follow-up, patients with MCC require customized treatment. There was a wide dispersion of results and the suggestion to increase awareness about the adjuvant radiation therapy. The panelists unanimously agreed that the information concerning avelumab provided by the JAVELIN Merkel 200 study is adequate and reliable and that the expanded access program data could have concrete clinical implications. An immunocompromised patient with advanced MCC can be treated with immunotherapy after multidisciplinary risk/benefit assessment, as evidenced by real-world analysis and highlighted in the guidelines. A very high consensus regarding the addition of radiotherapy to treat the ongoing focal progression of immunotherapy was observed. This paper emphasizes the importance of collaboration and communication among the interprofessional team members and encourages managing patients with MCC within dedicated multidisciplinary teams. New insights in the treatment of this challenging cancer needs the contribution of many and different experts.

The Italian Association for Medical Oncology (AIOM) recommends preventive treatment of skeletal-related events in order to improve survival and the quality of life of patients with advanced malignancies. The aim of the study was to evaluate whether routine clinical practice is in agreement with recommendations about the use of denosumab.A survey was carried out in Italy in the oncological setting.The answers to the survey showed that a large proportion of patients with metastases from solid tumors receive treatment; almost all oncologists administered denosumab every 4 weeks but for a shorter period of time than recommended.This survey showed that Italian oncologists favor the use of bone-targeted therapy to prevent skeletal-related events in patients affected by metastatic breast, prostate or lung cancer, in agreement with current recommendations.

Rossana Berardi, Francesca Morgese, Silvia Rinaldi, Mariangela Torniai, Giulia Mentrasti, Laura Scortichini, Riccardo Giampieri Clinica Oncologica, Università Politecnica delle Marche, Azienda Ospedaliera Universitaria Ospedali Riuniti di Ancona, Ancona, ItalyCorrespondence: Rossana BerardiClinica Oncologica, Università Politecnica Delle Marche, AOU Ospedali Riuniti Di Ancona via Conca 71, Ancona 60126, ItalyTel +39 071 596-5715Fax +39 071 5965053Email r.berardi@univpm.itAbstract: Over the years, a growing body of literature has confirmed as beneficial the implementation of a multidisciplinary approach in the so-often-intricate scenario of cancer patients’ management. Together with the consolidation of tumor-board experience in clinical practice, certain aspects have emerged as controversial and a source of current debate. In this systematic literature review, we focused our attention on the impact of multidisciplinary tumor boards, assessing benefits and limitations as a result of the dissemination of such approaches. On the bright side, adherence to clinical guidelines, treatment outcomes, and overall improvement in decision-making processes have been recognized as advantages. On the other side, our analysis highlights a few limitations that should be taken into account to optimize cancer patients’ management. Of note, some issues, such as costs, legal responsibility, geographic barriers, and treatment delays, have yet to be resolved. In order partly to address this matter, software platforms and novel methods of computational analysis may provide the needed support. Therefore, the aim of our analysis was to describe the multidisciplinary approach in cancer care in terms of adherence to clinical guidelines, treatment outcomes, and overall improvement in decision-making processes through a systematic review of the literature.Keywords: multidisciplinary, tumor board, cancer patients, benefits, limitations

Contains fulltext : 229846.pdf (Publisher’s version ) (Closed access) BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68.0 years (61.8-75.0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1.88, 95% 1.00-3.62), being a current or former smoker (4.24, 1.70-12.95), receiving treatment with chemotherapy alone (2.54, 1.09-6.11), and the presence of any comorbidities (2.65, 1.09-7.46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3.18, 95% CI 1.11-9.06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.

Giulia Mentrasti,* Laura Scortichini,* Mariangela Torniai, Riccardo Giampieri, Francesca Morgese, Silvia Rinaldi, Rossana Berardi Clinica Oncologica, Università Politecnica delle Marche, AOU Ospedali Riuniti Di Ancona, Ancona, Italy*These authors contributed equally to this workCorrespondence: Rossana BerardiClinica Oncologica, Università Politecnica delle Marche, AOU Ospedali Riuniti Di Ancona, Via Conca 71, Ancona 60126, ItalyTel +39 071 5965715Fax +39 071 5965053Email r.berardi@univpm.itAbstract: Hyponatremia, defined as serum sodium concentration < 135 mEq/l, is the most common electrolyte balance disorder in clinical practice. Many causes are listed, but syndrome of inappropriate antidiuretic hormone secretion (SIADH) is certainly the most relevant, mainly in oncological and hospitalized patients. In this review, the pathophysiological and clinical aspects are described in detail. Patients’ extensive medical history and structured physical and biochemical tests are considered the milestones marking the way of the SIADH management as to provide early detection and proper correction. We focused our attention on the poor prognostic role and negative effect on patient’s quality of life of SIADH-induced hyponatremia in both malignant and non-malignant settings, stressing how optimal management of this electrolyte imbalance can result in improved outcomes and lower health costs.Keywords: SIADH, hyponatremia, prognosis, neoplasms, lung cancer

Recent breakthroughs in high-throughput technolo- gies have enabled the development of a better understanding of the functionalities of rho-associated protein kinases (ROCKs) under various physiological and pathological condi- tions. Since their discovery in the late 1990s, ROCKs have attracted the attention of interdisciplinary researchers due to their ability to pleiotropically modulate a myriad of cellular mechanisms. A rapidly growing number of published studies have started to shed light on the mechanisms underlying the regulation of ROCK1 and ROCK2 via long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in different types of cancer. Detailed analyses have suggested that lncRNAs may be characteristically divided into oncogenic and tumor suppressor lncRNAs. Several exciting recent discoveries have also indicated how different lncRNAs and circRNAs modulate ROCK1/2 and mediate multistep cancer onset and progression. The present review chronicles the major advances that have been made in our understanding of the regulatory role of ROCK1/2 in different types of cancer, and how wide-ranging lncRNAs and circRNAs potentiate ROCK-driven signaling by blocking the targeting activities of tumor suppressor microRNAs. © 2022 Spandidos Publications. All rights reserved.

Protecting cultural heritage from water-soil interaction related threats is a current issue and the prediction of the effects induced on buildings by landslides is very challenging. The main difficulties lie in the lack of detailed information about landside movements as well as in the modeling of soil-structure interaction. This paper study the effects of a particular category of slow-moving landslides, namely active rotational and translational slides with movement rates of the order of some mm/year, on buildings of historical and cultural interest such as churches. Three case studies located in the Liguria region (Italy) were analyzed by performing FEM and LEM numerical analyses on sections representative of the slope.

Contrary to the idea that most of the fragments of ancient authors have been already collected and edited, a scholar interested in Hellenistic history and literature may find it surprising that a collection of fragments of Hellenistic orators – or oratory – is not something we could at the moment find on the shelves of a library. For a discipline like ancient literature, which is fragmentary at its core, this seems a surprising gap: we can find collections of fragments for poets of all sorts, for dramatists, historians, geographers, orators (Attic, Roman), and for so many more literary genres that it would be natural to assume that, if we do not have a collection of fragments for a certain genre in a certain period, it must be because nothing at all of it has survived. But fortunately, this is not the case with Hellenistic oratory: the present work constitutes a first attempt to fill this gap and aims at providing the first edition of the fragments of Hellenistic oratory (i.e. of named orators, but also of rhetorical exercises on papyrus), followed a commentary. It will hopefully constitute a first step in the direction of the creation of a comprehensive edition of fragments of Hellenistic orators and oratory, including commentaries on the testimonia (which are here not edited but used as sources for biographies), and on those fragments that for reasons of space (and according to the criteria stated below) could not be included in the present work. I have been able to establish a large corpus of testimonia and fragments, both in Greek and in Latin, for 84 orators. For 29 of them, there are fragments, either quoted or paraphrased, from an impressive variety of Greek and Latin sources. To these fragments, I have added 13 rhetorical papyri. All identified named Hellenistic orators are ordered alphabetically. For those who only have testimonia and no fragments, I provide a succinct but comprehensive biography. For orators who have fragments, I provide a critical text. Depending on the length of each fragment, I choose either to comment line by line (for longer texts) or to give a general commentary on the possible nature of the oration it belonged to (for shorter ones). The same has been done for rhetorical papyri. The commentary on these texts also varies according to the nature of the papyrus: observations on the palaeography or the material aspects are discussed extensively only when relevant to establishing the nature of the text contained in the papyrus or to re-establishing its date; otherwise, just general information is given on these aspects. For longer papyri, I provide a general introduction to the content and the nature of the text, followed by a sentence-by-sentence commentary, while for shorter or badly damaged fragments I only discuss their content and general features. I have not attempted exhaustive commentaries on all the papyri, as if these were editiones principes, especially for texts where extenstive discussions already exist (e.g. P.Berol. 9781, on which I do not comment line by line but on block of lines, following Kremmydas), but I chose to discuss issues of reading and supplement, on the basis of my examination of originals or pictures, and offer material relevant to connections with fourth-century oratory. Finally, the issues arising from the commentary on these texts have enabled me to underline some key topics that constitute different sections of a large introduction to this work, where my editorial criteria and my methodology are also explained.

Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Results From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33–83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1–7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4–58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). Conclusions The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

ispartof: ESMO Open vol:6 issue:3 pages:100137- ispartof: location:England status: published

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR)

Wealth of information has revolutionized our understanding related to the genetics and functional genomics of this heterogeneous disease. Keeping in view the heterogeneity of ovarian cancer, long-term survival might be achieved by translation of recently emerging mechanistic insights at the cellular and molecular levels to personalize individual strategies for treatment and to identify biomarkers for early detection. Importantly, the motility and invasive properties of ovarian cancer cells are driven by a repertoire of signaling cascades, many components of which have been experimentally verified as therapeutic targets in preclinical models as well as in clinical trials. Scientific evidence garnered over decades of research has deconvoluted the highly intricate intertwined network of intracellular signaling pathways which played fundamental role in carcinogenesis and metastasis. In this review we have provided a compendium of myriad of signaling cascades which have been documented to play critical role in the progression and metastasis of ovarian cancer. We have partitioned this multi-component review into different sections to individually discuss and summarize the roles of TGF/SMAD, JAK/STAT, Wnt/β-Catenin, NOTCH, SHH/GLI, mTORC1/ mTORC2, VEGFR and Hippo/YAP pathways in ovarian cancer metastasis. Copyright: © 2021 by the C.M.B. Association. All rights reserved.

The central dogma of molecular biology, has remained a cornerstone of classical molecular biology. However, serendipitously discovered microRNAs (miRNAs) in nematodes paradigmat-ically shifted our current knowledge of the intricate mechanisms during transitions from transcrip-tion to translation. Thediscovery of miRNA captured considerable attention and appreciation, and we had witnessed an explosion in the field of non-coding RNAs. Ground-breaking discoveries in the field of non-coding RNAs have helped in better characterization of microRNAs and long non-coding RNAs (LncRNAs). There is an ever-increasing list of miRNA targets that are regulated by MALAT1 to stimulate or repress the expression of target genes. However, in this review, our main focus is to summarize mechanistic insights on MALAT1-mediated regulation of oncogenic signaling pathways. We have discussed how MALAT1 modulated TGF/SMAD and Hippo pathways in various cancers. We have also comprehensively summarized how JAK/STAT and Wnt/β-catenin pathways stimulated MALAT1 expression and consequentially how MALAT1 potentiated these signaling cascades to promote cancer. MALAT1 research has undergone substantial broadening. However, there is still a need to identify additional mechanisms. MALAT1 is involved in the multi--layered regulation of multiple transduction cascades, and detailed analysis of different pathways will be advantageous in getting a step closer to individualized medicine. © 2021 Bentham Science Publishers.

Background Overcoming resistance to anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) in patients with KRAS wildtype (WT) metastatic colorectal cancer (mCRC) could help meet the needs of patients with limited treatment options. Methods In this phase 1b study, patients with N/KRAS WT, MET-positive mCRC who had progressed following anti-EGFR mAb treatment received escalating oral doses of capmatinib (150, 300, and 400 mg) twice daily plus weekly intravenous cetuximab (at the approved dose). The primary objective was to establish a recommended dose for expansion (RDE) of capmatinib in combination with cetuximab. Safety, preliminary activity, pharmacokinetics, and pharmacodynamics were also explored. Results Thirteen patients were enrolled. No patients experienced a dose-limiting toxicity at investigated doses; the RDE was established as capmatinib 400 mg twice daily plus cetuximab. All patients experienced adverse events (AEs) suspected to be related to the study treatment. Five patients (38.5%) reported study-drug-related AEs of grade 3/4 in severity. No patients achieved a complete or partial response according to RECIST v1.1; however, tumor shrinkage of 29-44% was observed in 4 patients. Conclusions Capmatinib plus cetuximab was well tolerated. Preliminary signs of activity were observed. Further investigation is warranted to obtain efficacy data and refine predictive biomarkers of response. Clinical trial registration NCT02205398.

Riccardo Giampieri, Michela Del Prete, Luca Cantini, Maria Giuditta Baleani, Alessandro Bittoni, Elena Maccaroni, Rossana Berardi Oncology Clinic, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy Abstract: Although advances in medical treatment for gastric cancer (GC) have been made, surgery remains the mainstay of cure for patients with localized disease. Improvement in surgical modalities leads to increased chance of cure for resected patients, but a non-negligible number of patients eventually relapse. On this basis, it has been hypothesized that the addition of complementary systemic or local treatments (such as chemotherapy and radiotherapy) could help in improving patients’ survival by reducing the risk of recurrence. Several studies have tried to identify the best approach in localized GC: some of them have assessed the role of perioperative chemotherapy [CT] with different drug combinations, while others have focused on the benefit obtained by addition of radiotherapy, whose role is still under investigation. In particular, the role of chemoradiotherapy, both in adjuvant and neoadjuvant settings, is still uncertain. In the last few years, several clinicopathological and molecular factors have been investigated and identified as potential prognostic markers in GC. Many of these factors could have influenced the outcome of patients receiving combined treatments in the abovementioned studies. Patients have not been generally distinguished by the site of disease (esophageal, gastric and junctional cancers) and surgical approach, making data difficult to be interpreted. The purpose of this review was to shed light on these highly controversial topics. Keywords: gastric cancer, chemotherapy, radiotherapy, adjuvant, neoadjuvant, prognostic factors

Gianluca Moroncini,1,* Elena Maccaroni,2,* Ilaria Fiordoliva,2 Chiara Pellei,2 Armando Gabrielli,1 Rossana Berardi2 1Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona, Italy; 2Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi, Ancona, Italy *These authors contributed equally to this work Abstract: Lartruvo® (olaratumab) is a fully human immunoglobulin G subclass 1 (IgG1) monoclonal antibody that inhibits platelet-derived growth factor receptor alpha (PDGFRα). The antitumor activity of olaratumab has been tested in vitro and in vivo, and inhibition of tumor growth has been observed in cancer cell lines, including glioblastoma and leiomyosarcoma cells. It represents the first-in-class antibody to be approved by regulatory authorities for the treatment of advanced soft-tissue sarcomas (STSs) in combination with doxorubicin, based on the results of the Phase Ib/II trial by Tap et al. The median progression-free survival (PFS), which was the primary end point of the study, was improved for patients treated with olaratumab plus doxorubicin compared to those treated with doxorubicin monotherapy (6.6 vs 4.1months, respectively; HR 0.672, 95% CI 0.442–1.021, p=0.0615). Moreover, final analysis of overall survival (OS) showed a median OS of 26.5months with olaratumab plus doxorubicin vs 14.7months with doxorubicin, with a gain of 11.8months (HR 0.46, 95% CI 0.30–0.71, p=0.0003). In October 2016, olaratumab was admitted in the Accelerated Approval Program by the US Food and Drug Administration (FDA) for use in combination with doxorubicin for the treatment of adult patients with STSs. In November 2016, the European Medicines Agency (EMA) granted conditional approval for olaratumab in the same indication under its Accelerated Assessment Program. A double-blind, placebo-controlled, randomized Phase III study (ANNOUNCE trial, NCT02451943) is being performed in order to confirm the survival advantage of olaratumab and to provide definitive drug confirmation by regulators. The study is ongoing, but enrollment is closed. The purpose of this review was to evaluate the rationale of olaratumab in the treatment of advanced STSs and its emerging role in clinical practice. Keywords: anti-PDGFR antibodies, soft-tissue sarcoma, PDGFRα, doxorubicin, olaratumab

N/A

Aims and background Women's adherence to mammography and PAP test screening guidelines is a fundamental topic regarding women's health. The aim of the study was to evaluate the knowledge and compliance to breast and cervical cancer screening programs in women living in three Italian towns, where a public screening program, consisting of free mammography every two years and free PAP test every three years, is ongoing. Methods An anonymous survey was mailed to a random sample of women. Eight 120-min focus discussions with groups of women exploring perceptions, knowledge and practices were carried out after analysis of the returned surveys. Results Replies were received from 1345 women (response rate, 27%). Almost every woman knew of the screening program, but women's practice of mammography was age-dependent: up to 72% of the women performed it before the age of 50. Conversely, the age of the first PAP test was rather late: up to 70% of the women performed it at over 30 years of age. Women with a lower educational level reported being screened less than those with a higher level. During the group discussions, women's perceptions, knowledge and beliefs regarding cancer and screening, together with aspects of the health care system, appeared to strongly influence the preventive practices. Many women deplored being infrequently instructed by health professionals. Conclusions Despite the limitations of the study due to the low response rate, we believe that health professionals should invest on encouraging factors and reduce the deterring factors to optimize screening practices.

Background: Lung cancer seems to have different epidemiological, biomolecular and clinical characteristics in females than in males, with a better prognosis for women. The aim of the study is to determine gender differences in lung adenocarcinoma in terms of androgen (AR), estrogen (ER)α and progesterone (PgR) receptors expression and their impact on outcome. Results: Overall survival was significantly better in ERα and in PgR positive lung adenocarcinoma patients (median survival 45 vs. 19 months). Eight out of 62 patients showed positive expression of nuclear (n) AR and 18 of cytoplasmic (c) AR with a significantly better survival (49 vs. 19 and 45 vs. 19 months, respectively). There was a significant difference in survival between patients with vs. without c-AR expression (30 vs. 17 months). Finally, in the subgroup of women, median survival was greater in positive expression of c-AR than for women with negative c-AR (45 vs. 21 months). Materials and Methods: We conducted an analysis on a cohort of 62 patients with advanced NSCLC treated at our institution. We investigated the immunohistochemical expression of n/c AR, ERα and PgR in 62 NSCLC and we correlated it with patients’ clinic-pathologic characteristics and with prognosis. Conclusions: Our results showed that the positive expression of one hormonal receptor could represent a prognostic factor. Furthermore our study suggests that AR should become object of close examination in a larger series of lung adenocarcinoma patients, also for selection of the patients with best prognosis that can perform more chemotherapy lines.

Angiogenesis and immunosuppression work hand-in-hand in the renal cell carcinoma (RCC) microenvironment. Tumor growth is associated with impaired antitumor immune response in RCC, which involves T cells, natural killer cells, dendritic cells (DCs) and macrophages. Vascular endothelial growth factor receptor (VEGFR), such as sorafenib, sunitinib, pazopanib and axitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus and everolimus, do exert both antiangiogenic and immunomodulatory functions. Indeed, these agents affect neutrophil migration, as well as T lymphocyte-DC cross-talk, DC maturation and immune cell metabolism and reactivity. In this review, we overview the essential role of innate and adaptive immune response in RCC proliferation, invasion and metastasis and the relationship between tumor-associated immune cells and the response to targeted agents approved for the treatment of metastatic RCC.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the outcome of patients treated with everolimus for mRCC.METHODS: Ninety-seven patients with mRCC were treated with everolimus till April 2013 in our institutions. Patients were stratified in two groups with NLR >3 (Group A) vs

Introduction. Bone metastases are an emerging clinical problem in colorectal cancer patients probably related to survival increase. There are no data in literature about the role of BPs in the treatment of bone disease from colorectal cancer. We present the final data of a large Italian multicenter retrospective analysis. Methods. 264 colorectal cancer patients with occurrence of bone metastases have been included in the study. All patients were dead due to cancer at the moment of the study inclusion. Patients characteristics, Skeletal Related Events (SRE) data and median survival after bone metastases appearance have been collected in a master data base and statistically analyzed. The primary efficacy endpoint was time to first SRE; secondary endpoint was median survival. 31 patients have been analysed as control group. Results. In 107 patients bisphosphonates data were not available. A total of 157 patients have been included for zoledronic efficacy analysis. A total of 126 patients received zoledronic acid (4 mg) via a 15-minute infusion every 4 weeks until performance status worsening or death. The median time to first SRE in the whole population was 2 mths (1.04-3.45). The median time to first SRE in the zoledronic treated patients was 3.168 mths (0.49- 2.19) compared with 1.71 mths (0.41-0.90) in the control group (p = 0.009). The median survival after skeletal progression was 7 mths (5.75-8.704). The median survival in the zoledronic treated group was 10 mths (8.08-11.91) compared with 6 mths (4.45- 7.54) (p = 0.161). Conclusions. Complete results of statistical analysis will be presented during the meeting. The present analysis represent the efficacy demonstration of a bisphosphonate in bone metastases from colorectal cancer patients. B13 LENOGRASTIM IN PREVENTING

This report describes a 5-year-old girl, mildly mentally retarded, with the following characteristics: macrocephaly; severe obesity; ocular abnormalities (right optic disk coloboma and left choroidal coloboma); short stature; and recurvation of the femur. The case is sporadic with no consanguinity between the parents. The condition was diagnosed tentatively as MOMO syndrome (Macrosomia, Obesity, Macrocephaly, and Ocular Abnormalities) (MIM, 157980), because of the presence of short stature, in contrast with the large stature of the only two previously described cases. It is the third possible example of this rare syndrome to be described in the literature, with some new clinical findings presented.

Summary Background Preclinical data have suggested a synergistic effect of cetuximab combined with gemcitabine and cisplatin and clinical data have shown a substantial improvement in response and survival when gemcitabine is combined with a platinum analogue compared with gemcitabine alone. The aim of this study was to assess the activity and feasibility of a combination of cetuximab with gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone for the treatment of advanced pancreatic cancer. Methods In a multicentre, randomised phase II trial, 84 patients with advanced pancreatic cancer were randomly assigned to either 250 mg/m 2 cetuximab weekly, after a loading dose of 400 mg/m 2 , plus 1000 mg/m 2 gemcitabine and 35 mg/m 2 cisplatin on days 1 and 8 of a 21-day cycle or to the same chemotherapeutic regimen without cetuximab. The primary endpoint was objective response (defined as the proportion of patients whose best response was either partial response or complete response). Secondary endpoints included disease control (defined as the proportion of patients whose best response was either partial response, complete response, or stable disease), progression-free survival, and overall survival. All assessments of response at each site were done blindly by a local experienced radiologist who was not directly involved in the trial. Responses were measured according to an intention-to-treat analysis. This trial is registered with the Clinical Trial registry, number NCT00536614. Findings 29 men and 13 women were randomly assigned to cetuximab plus gemcitabine and cisplatin (median age 61 years [range 38–78]) and 22 men and 20 women were randomly assigned to gemcitabine and cisplatin (median age 64 years [range 40–76]). Seven of 40 (17·5%) patients had an objective response in the cetuximab group (95% CI 7·3–32·8) and five of 41 (12·2%) patients had an objective response in the non-cetuximab group (95% CI 4·1–26·2). No significant difference was noted between the groups both for objective response (5·3% higher in the cetuximab group [95% CI −16·5 to 27·1]; χ 2 test=0·360; p=0·549) or for disease control (3·5% higher in the non-cetuximab group [−34·0% to 27·0%]; 0·446; p=0·504). Overall median follow-up was 11·8 months (range 2·5–18·5). No significant differences between the groups were noted in median progression-free survival (hazard ratio 0·96, 95% CI 0·60–1·52, p=0·847) or in median overall survival (0·91, 0·54–1·55, p=0·739): median progression-free survival was 3·4 months (95% CI 2·4–5·1) in the cetuximab group and 4·2 months (2·6–5·4) in the non-cetuximab group; median overall survival was 7·5 months (5·1–8·8) and 7·8 months (5·3–15·0), respectively. 33 patients from both groups had at least one grade 3–4 toxic effect. Interpretation The addition of cetuximab to a combination of gemcitabine and cisplatin does not increase response or survival for patients with advanced pancreatic cancer. Although toxic effects were not increased by cetuximab, this combination should not be further assessed in phase III trials.

CONTEXT: In Italy, the surveillance of congenital hypothyroidism (CH) is performed by the Italian National Registry of Infants with CH (INRICH). Up to now, about 3600 infants with CH are recorded in the INRICH, and a high number of twins are included. OBJECTIVE: Our objective was to estimate the risk of CH in multiple and single deliveries and to compare neonatal features of CH twins with twins from the general population. DESIGN: The Italian population of CH infants recorded in the INRICH from 1989-2000 was investigated. RESULTS: A more than 3-fold higher frequency of twins was found in the CH population than in the general population, and for the first time, it was possible to estimate the CH incidence in multiple (10.1 in 10,000) and single deliveries (3.2 in 10,000 live births). Significantly higher frequencies of in situ gland as well as lower TSH mean level at screening were found in twin than in singleton CH babies. The concordance rate for permanent CH was very low (4.3%) and due to only three concordant couples. However, a high recurrence risk for CH was estimated in siblings of affected babies recorded in the INRICH, including twins considered as siblings. CONCLUSIONS: The high CH incidence observed in twins is worthy of interest for the high number of induced pregnancies in Italy as well as in other Western countries. Moreover, the low concordance rate for CH among twins together with a high recurrence risk for the disease among siblings indicates that environmental risk factors may act as a trigger on a susceptible genetic background in the etiology of the disease

Objective To determine the efficacy and toxicity of danusertib (formerly PHA-739358) administered i.v. over two different dosing schedules with equivalent dose intensity in patients with metastatic castration-resistant prostate cancer with progressive disease after docetaxel-based treatment. Patients and Methods In this open-label, multicentre phase II trial 88 patients were randomly assigned (1: 1 ratio) to receive either danusertib 330 mg/m(2) over 6 h i.v. on days 1, 8 and 15 (arm A, n=43) or 500 mg/m(2) over 24 h i.v. on days 1 and 15 (arm B, n = 38), every 4 weeks. The primary endpoint chosen for this exploratory study was PSA response rate at 3 months. Results Sixty patients (31/43 in arm A and 29/38 in arm B) were evaluable for the primary endpoint. Median progression-free survival was 12 weeks in both arms. PSA response occurred in one patient in each arm; best overall response was stable disease in eight (18.6%) and 13 (34.2%) patients in arms A and B, respectively. Eleven out of 81 (13.6%) treated patients had stable disease for >= 6 months. Danusertib was generally well tolerated; the most common grade 3 and 4 drug-related adverse event was neutropenia which occurred in 37.2% (arm A) and 15.8% (arm B) of the patients. Conclusion Danusertib monotherapy shows minimal efficacy in patients with castration-resistant prostate cancer. Further studies are required to establish specific biomarkers predictive for either response or prolonged disease stabilization.

Insulin-like growth factor receptor 1 (IGF-1R) with its ligands and intracellular pathway is involved in cell growth and survival control. Many studies have shown how IGF-1R is over-expressed in various tumor cell lines and histological samples. In recent years many trials have been conducted investigating IGF-1R as a possible cancer therapy, with major efforts focusing on the use of monoclonal antibodies and small molecules directed against the IGF-1R-driven pathway. Several drugs are currently under intense investigation and in different experimental phases. Available data suggest that this class of drugs is well tolerated with mild to moderate side effects, when used alone or in combination with other therapeutic agents. The efficacy profile seems to be promising. However, further studies are needed to define the exact role of IGF-1R inhibitors in clinical practice.

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country. The aim of the Register is to monitor efficiency and effectiveness of neonatal screening, to provide disease surveillance and to allow identification of possible aetiological risk factors for the disease. During the past twenty years the active and continuous collaboration between the Register and the Italian Screening and Follow up Centres for Congenital Hypothyroidism allowed to perform a standardization of screening procedures and considerable improvements in the time at starting treatment and in the dose of therapy. Furthermore, the large amount and the high quality of information collected in the Register provided a unique opportunity for research into the disease. This because data collected in the Register are highly representative as referred to the entire Italian population with congenital hypothyroidism. The results derived from the epidemiological studies performed in these years, by using the Register database, contributed to deepen the knowledge of congenital hypothyroidism, to start identifying the most important risk factors for the disease, and to orient molecular studies aimed at identifying new genes involved in the aetiology of this condition.