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Pancreatic adenocarcinoma is the seventh leading cause of cancer death in the world and the most common type pf pancreatic cancer. Unfortunately, less than 20% of patients are surgically resectable and the great majority of cases are treated with palliative chemotherapy with unsatisfactory results. No targeted agents or personalized approaches have been validated in the last decades. On the other side, neuroendocrine neoplasms of the pancreas are generally considered indolent tumours. However, high-grade neuroendocrine carcinoma is a rare subtype of neuroendocrine neoplasm of the pancreas (accounting up to 10% of the neuroendocrine neoplasms of the pancreas), with particularly aggressive behaviour and poor prognosis. Even in this case, the treatment is represented by palliative chemotherapy with dismal results and no personalized therapies are available, so far. Notably, the quality of life of these patients is disappointingly low and the future perspectives of more personalized diagnostic and therapeutic strategies are scarce. In this review, we discuss relevant and current information on epidemiology, pathology, diagnosis, clinical presentation, treatment and ongoing clinical trials of these two entities, in order to illustrate the two sides of the moon.

Environmental and occupational exposures have been associated with an increased risk of different types of cancers, although the exact mechanisms of higher carcinogenesis risk are not always well understood. Lung cancer is the leading cause of global cancer mortality, and, also, genitourinary neoplasms are among the main causes of cancer-related deaths in Western countries. The purpose of this review is to describe the main environmental and occupational factors that increase the risk of developing lung and genitourinary cancers and to investigate carcinogenesis mechanisms that link these agents to cancer onset. Further objectives are to identify methods for the prevention or the early detection of carcinogenic agents and, therefore, to reduce the risk of developing these cancers or to detect them at earlier stages.

164 Background: ARSI [enzalutamide (ENZA) and abiraterone (ABI)] demonstrated to be efficacious as a first-line therapy for mCRPC, showing a median progression-free survival of 16 and 20 months (mos) in pivotal trials, respectively. Nevertheless, some pts of daily clinical practice show exceptionally prolonged disease control with very long duration of treatment. The present study aimed at identifying the characteristics of LTR pts who received one ARSI as a first-line for mCRPC. Methods: We retrospectively reviewed the clinical records of a consecutive series of 647 pts treated in the daily clinical practice with one ARSI as first-line mCRPC in four Italian high-volume Institutions. Pts who had previously received docetaxel in castration-sensitive setting were excluded. Pts received standard AA or ENZA doses (1,000 mg po daily plus prednisone 10 mg po daily or 160 mg po daily, respectively). ARSI were administered until progression and were followed according to each Institution policy. For each pt we recorded pre and post-ARSI clinical history, baseline characteristics, treatment details and clinical outcomes. Pts were considered as LTR in presence of an ARSI exposure ≥ 36 mos. LTR were compared to the progressed pts with an ARSI exposure < 36 mos. On-treatment pts with an ARSI exposure < 36 mos were not considered. Results: We identified 81 LTR pts (53 treated with ENZA and 28 treated with ABI). The median age was 76 yrs (range 56-89). The median treatment duration was 46.1 mos (range 36.4-88.6) and 52 pts were still on treatment. LTR were compared to no-LTR 415 pts (233 treated with ENZA and 182 treated with ABI). Compared to no-LTR, LTR pts showed longer PSA doubling time (PSADT) (PSADT) (p = 0.001) and time to mCRPC (p < 0.0001), lower levels of basal PSA (p = 0.01), and alkaline phosphatase (ALP) (p = 0.01), better ECOG PS (p = 0.01), lower Gleason score (p = 0.01), and less pain level (p = 0.04). ECOG PS, ALP, time to mCRPC and PSADT were all identified as independent predictors of time to treatment interruption in multivariate analysis. LTR showed an 89% decreased risk of death compared to no-LTR (HR = 0.11 IC95% 0.06-0.18). Conclusions: In our experience, several variables, which are usually considered as having a prognostic value, demonstrated to be able to predict the probability of prolonged disease control in mCRPC pts treated with first-line ARSI.

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase (KIT) exon 11 PV were included in the study. We analyzed the type and codon location of the PV according to clinicopathological characteristics and clinical outcome; the metastatic sites in relapsed patients were also investigated. Results: Tumors harboring a KIT exon 11 deletion or deletion/insertion involving the 557 and/or 558 codons, showed a more aggressive clinical behavior compared with tumors carrying deletion/deletion/insertion in other codons, or tumors with duplication/insertion/single-nucleotide variant (SNV) (7-year RFS: 50% versus 73.1% versus 88.2%, respectively; p

Neuroendocrine neoplasms (NENs) represent a rare and heterogeneous group of malignancies which can develop in many different sites of our body. They originate from the cells of the diffuse neuroendocrine system. Gastroenteropancreatic NENs were classified in four categories, including NETs G1 (WD with 20% Ki-67), and NECs (PD with >20% Ki-67) in accordance with the 2019 WHO classification (IARC WHO Classification of the digestive system tumors, on 11th July 2019). Lung NENs, in accordance with the latest WHO classification, 2015 edition, are distinguished in small cell lung cancer (SCLC), large cell neuroendocrine carcinoma (LCNEC), atypical carcinoid (AC), and typical carcinoid (TC).

Soft tissue sarcomas (STSs) represent a rare and heterogeneous group of solid tumors derived from mesenchymal progenitors and account for 1% of all adult malignancies. Although in the last decade anthracycline-based chemotherapy single agent or in combination has been able to improve clinical benefits, prognosis is still poor, and STSs represent an important unmet medical need.

The primitive neoplasms of the central nervous system (CNS) are a rare and heterogeneous group of malignancies. Brain metastases (BMs) are the most frequent intracranial tumor, and their incidence is rising in the last few decades. Primary tumors more often complicated by BMs are lung cancer, breast cancer, and melanoma. Neuroimaging techniques, mainly magnetic resonance imaging (MRI), play a key role for the diagnosis of BMs. The management of BMs is based on a multimodal approach, including symptomatic treatment, local treatment, such as surgery, stereotactic radiosurgery (SRS), and whole brain radiotherapy (WBRT), and systemic therapy, such as chemotherapy, target therapy, or immunotherapy. Despite active treatment, however, BMs still have an adverse impact on survival and quality of life.

Simple Summary Non-small cell lung cancer (NSCLC) with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation comprises a specific subgroup of patients who are particular in terms of several clinical and molecular aspects. Indeed, there is a clear medical need to find specific and effective treatments for these patients, since KRAS mutation positive NSCLC has demonstrated to be—in some cases—less responsive to standard therapies. For many years, targeting KRAS mutations has been considered an impossible challenge. The scenario is further complicated by the possible role of co-mutations that could influence both tumour microenvironment and drug response. However, some promising preclinical and clinical data are expected to change the treatment landscape of this hard-to-treat disease. Indeed, tumors harbouring G12C mutations could now be effectively targeted with specific inhibitors based on clinical trial results. This review aims to provide a clinical update on potential therapies for advanced NSCLC with KRAS mutations other than the more common G12C, for which good results have already been achieved, particularly focusing on clinical trials, molecules and mechanisms currently under investigation. Abstract Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) gene mutations are among the most common driver alterations in non-small cell lung cancer (NSCLC). Despite their high frequency, valid treatment options are still lacking, mainly due to an intrinsic complexity of both the protein structure and the downstream pathway. The increasing knowledge about different mutation subtypes and co-mutations has paved the way to several promising therapeutic strategies. Despite the best results so far having been obtained in patients harbouring KRAS exon 2 p.G12C mutation, even the treatment landscape of non-p.G12C KRAS mutation positive patients is predicted to change soon. This review provides a comprehensive and critical overview of ongoing studies into NSCLC patients with KRAS mutations other than p.G12C and discusses future scenarios that will hopefully change the story of this disease.

Background Neuroendocrine neoplasms (NENs) are a group of heterogeneous neoplasms which can be treated with different therapies: in well differentiated (WD) NENs analogs of somatostatin (SSA) can be used considering their proved antineoplastic and antisecretory effects. This is a multicenter study to investigate the safety of high doses (HDD) analogs of somatostatin (SSA) in WD NENs with particular attention for patients over 70 years of age. Methods We collected clinical data from 13 Italian NENs dedicated Units. Patients with WD NENs, in progression on previous treatments, included SSA, and subsequently treated with HDD-SSA, were considered. Results 170 pts were included: 61.76% male, 38.24% female. The median age at the diagnosis was 58.83. Regarding the site of origin, the most frequent was gastro-intestinal system (54.71%), followed by pancreas (27.06%) and lung (8.24%). G1 NENs were 54.11%, G2 42.94% and typical lung carcinoid 2.95%; 31.76% were affected by a carcinoid syndrome or clinical conditions such as gastrinoma, insulinoma and Zollinger-Ellison. The median PFS was 20.18 months. Side effects (SEs) were registered in 25 pts (14.71%), the most frequent were cholecystitis (4%), G1 asthenia (12%), G1 hyperglycemia (8%), G1 steatorrhea (76%). We divided patients in 4 groups considering the age at the diagnosis: lower than 60 years, 61-70, 71-80 and more than 81 years. With the increase of age there was a higher percentage of SEs (Tab.1) with a maximum percentage of 20.41% in the group with an age of 71-80 years. The treatment was well tolerated without life-threatening side effects also in the group of patients with an age > 70 years. Tab. 1 Table: 520P . Age at the diagnosis (years) % side effects 10,00% 61-70 13,73% 71-80 20,41% >81 20,00% Conclusions We concluded that in this setting of patients, with an age >70 and a WD NEN in progression to standard doses of SSA, HD-SSA represents a safe and effective second line therapy with a median PFS of 20.80 months. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.