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Subjects increasing sperm DNA fragmentation (sDF) during Density Gradient Centrifugation (DGC), a common sperm selection procedure in Assisted Reproduction Techniques (ARTs), experience a 50% lower probability of pregnancy. Hence, identification of these subjects is of clinical importance. Here, we investigated whether such subjects are identified with higher accuracy detecting DNA fragmentation in viable (viable sDF) instead of total spermatozoa (total sDF) and whether swim up, an alternative procedure to DGC, does not increase sDF. With DGC, we identified 10/20 subjects increasing total sDF, and 2 more subjects using viable sDF. With swim up, we identified 8/40 subjects increasing total sDF, and 8 more subjects using viable sDF. In addition, viable sDF reveals more accurately the increase of the damage when it occurs. Finally, a multivariate analysis demonstrated that the proportional increase of sDF was higher after DGC respect to swim up. In conclusion, viable sDF is a more accurate parameter to reveal the increase of the damage by selection both with swim up and DGC. Swim up increases sDF in some samples, although at a lesser extent than DGC, suggesting that it should be used to select spermatozoa for ARTs when possible.

The MITO-END3 trial compared carboplatin and paclitaxel (CP) with avelumab plus carboplatin and paclitaxel (CPA) as first-line treatment in endometrial cancer (EC) patients and demonstrated a significant interaction between avelumab response and mismatch repair status. To investigate prognostic/predictive biomarker, 29 MITO-END3-EC patients were evaluated at pretreatment (B1) and at the end of CP/CPA treatment (B2) for peripheral myeloid-derived suppressor cells (MDSC) and Tregs. At B2, effector Tregs frequency was significantly higher in patients treated with CPA as compared to CP ( p  = 0.038). Both treatments (CP/CPA) induced significant decrease in peripheral M-MDSC (− 5.41%) in TCGA 2-MSI-high as compared to TCGA-category 4 tumors ( p  = 0.004). In accordance, both treatments induced M-MDSCs (+ 5.34%) in MSS patients as compared to MSI-high patients ( p  = 0.001). Moreover, in a subgroup of patients, primary tumors were highly infiltrated by M-MDSCs in MSS as compared to MSI-high ECs. A post hoc analysis displayed higher frequency of M-MDSCs ( p  = 0.020) and lower frequency of CD4+ ( p  < 0.005) at pretreatment in EC patients as compared to healthy donors. In conclusion, the peripheral evaluation of MDSCs and Tregs correlated with molecular features in EC treated with CP/CPA and may add insights in identifying EC patients responder to first-line chemo/chemo-immunotherapy. Graphical abstract

Background: Plasma circulating tumour-specific microRNAs (miRNAs) are promising biomarkers of tumour presence and recurrence, especially for diseases whose best chance of successful treatment requires early diagnosis and timely surgery of an already malignant but not yet invasive tumour, such as colorectal cancer (CRC). Methods: Expression levels of miRNAs previously found to be differently expressed in tumour vs normal colon tissues were investigated by quantitative real-time PCR in plasma from CRC patients and from healthy donors and confirmed in independent case control series. The validated miRNAs were also measured after surgery. Analyses were repeated on the subsets of haemolysis-free samples. Results: We identified four miRNAs differently expressed between the compared groups, two (miR-21 and miR-378) of which were validated. miR-378 expression decreased in non-relapsed patients 4–6 months after surgery and miR-378 ability to discriminate CRC patients from healthy individuals was not influenced by haemolysis levels of plasma samples. Conclusion: The miRNA analysis on plasma samples represents a useful non-invasive tool to assess CRC presence as well as tumour-free status at follow-up. Plasma levels of miR-378 could be used to discriminate CRC patients from healthy individuals, irrespective of the level of haemoglobin of plasma samples.

Colorectal cancer (CRC) is a global health concern, and the incidence of early onset (EO) CRC, has an upward trend. This study delves into the genomic landscape of EO-CRC, specifically focusing on pediatric (PED) and young adult (YA) patients, comparing them with adult (AD) CRC. In this retrospective monocentric investigation, we performed targeted next-generation sequencing to compare the mutational profile of 38 EO-CRCs patients (eight PED and 30 YA) to those of a ‘control group’ consisting of 56 AD-CRCs. Our findings reveal distinct molecular profiles in EO-CRC, notably in the WNT and PI3K-AKT pathways. In pediatrics, we observed a significantly higher frequency of RNF43 mutations, whereas APC mutations were more prevalent in adult cases. These observations suggest age-related differences in the activation of the WNT pathway. Pathway and copy number variation analysis reveal that AD-CRC and YA-CRC have more similarities than the pediatric patients. PED shows a peculiar profile with CDK6 amplification and the enrichment of lysine degradation pathway. These findings may open doors for personalized therapies, such as PI3K-AKT pathway inhibitors or CDK6 inhibitors for pediatric patients. Additionally, the distinct molecular signatures of EO-CRC underscore the need for age-specific treatment strategies and precision medicine. This study emphasizes the importance of comprehensive molecular investigations in EO-CRCs, which can potentially improve diagnostic accuracy, prognosis, and therapeutic decisions for these patients. Collaboration between the pediatric and adult oncology community is fundamental to improve oncological outcomes for this rare and challenging pediatric tumor.

Background Resistance to osimertinib in advanced EGFR- mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications. Methods This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR- mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed. Results Sixty-five advanced EGFR -mutated NSCLC patients treated with osimertinib in first- ( n  = 56) or in second-line ( n  = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification ( n  = 8), EGFR C797S ( n  = 3), and SCLC transformation ( n  = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively. Conclusions Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.

Background: Increasing evidence suggests that diabetes increases the risk of developing different types of cancer. Hyperinsulinemia, hyperglycemia and chronic inflammation, characteristic of diabetes, could represent possible mechanisms involved in cancer development in diabetic patients. At the same time, cancer increases the risk of developing new-onset diabetes, mainly caused by the use of specific anticancer therapies. Of note, diabetes has been associated with a ∼10% increase in mortality for all cancers in comparison with subjects who did not have diabetes. Diabetes is associated with a worse prognosis in patients with cancer, and more recent findings suggest a key role for poor glycemic control in this regard. Nevertheless, the association between glycemic control and cancer outcomes in oncologic patients with diabetes remains unsettled and poorly debated. Purpose: The current review seeks to summarize the available evidence on the effect of glycemic control on cancer outcomes, as well as on the possibility that timely treatment of hyperglycemia and improved glycemic control in patients with cancer and diabetes may favorably affect cancer outcomes.

Abstract Background Infections with antimicrobial-resistant (AMR) organisms significantly worsen outcomes in cancer patients. Since the main cause of AMR is the inappropriate use of antibiotics for prophylactic or empirical treatment, antimicrobial stewardship programmes (ASPs) have been developed. Few papers on ASPs describe prospective audits in oncology settings. In light of this, the Italian Association of Medical Oncology (AIOM) has decided to evaluate the oncologists’ perceptions of this issue with a brief survey. Methods An anonymous 14-item questionnaire was shared online during the XXVI National Congress on the AIOM website. The survey was divided into two sections. The first set of questions collected the hospital organization and practices (Q1–Q6), while the second one was about the clinical practices and antibiotic therapy (Q7–Q14). Results Sixty-four medical oncologists completed the anonymous questionnaire. Seventy-two percent of respondents believe that AMR is a significant issue in cancer patients, and an equal percentage considers it likely that a cancer patient will become infected with a MDR pathogen. Despite these concerns, only 48% (n = 31/64) report having an active ASP in their centre. Just 6% of respondents (n = 4/64) consider themselves very confident in prescribing antibiotic therapy, while most consider themselves fairly or not very confident (n = 34/64, 53%, and n = 26/64, 36%, respectively). Conclusions This survey highlights the urgent need for educating and training oncologists on AMR, as well as the importance of the development of oncology-specific guidelines to mitigate the impact of AMR in this high-risk population.

Chemotherapy is the standard treatment for advanced non-small-cell lung cancer, and myelosuppression is a common side-effect. We aimed to assess whether haematological toxic effects could be a biological measure of drug activity and a marker of efficacy. We analysed data for 1265 patients who received chemotherapy (vinorelbine, gemcitabine, gemcitabine and vinorelbine, cisplatin and vinorelbine, or cisplatin and gemcitabine) within three randomised trials. Primary landmark analyses were restricted to 436 patients who received all six planned chemotherapy cycles and who were alive 180 days after randomisation. Neutropenia was categorised on the basis of worst WHO grade during chemotherapy: absent (grade 0), mild (grade 1–2), or severe (grade 3–4). All statistical analyses were stratified by treatment allocation. Analyses were repeated in the out-of-landmark group (829 patients), stratifying by treatment allocation and number of chemotherapy cycles. The primary endpoint was overall survival. In the landmark group, hazard ratios of death were 0·65 (0·46–0·93) for patients with severe neutropenia and 0·74 (0·56–0·98) for those with mild neutropenia. Median survival after the landmark time of 180 days was 31·4 weeks (95% CI 25·7–39·6) for patients without neutropenia compared with 42·0 weeks (32·7–59·7) for patients with severe neutropenia, and with 43·7 weeks (36·6–66·0) for those with mild neutropenia (severe vs mild vs no neutropenia p=0·0118). Findings were much the same for the out-of-landmark group. Neutropenia during chemotherapy is associated with increased survival of patients with advanced non-small-cell lung cancer, and its absence might be a result of underdosing. Prospective trials are needed to assess whether drug dosing guided by the occurrence of toxic effects could improve efficacy of standard regimens.

Since the mid-1990s, the adoption of combined antiretroviral therapy (cART) has significantly reduced HIV-related mortality and morbidity. Nevertheless, cancer continues to be the leading cause of death in people living with HIV (PLWH). We conducted a survey to assess the knowledge and inter-disciplinarity among the Italian oncologists and infectious disease specialists in the cancer prevention and treatment of PLWH. All the members of AIOM, SIMIT and SITA who are oncologists and infectious disease specialists were invited via email. A survey with 24 queries was administered using a web-based platform. Data were analysed with the chi-square or Fisher exact tests to explore any significant difference between the two specialist subgroups. From April to June 2023, 182 participants filled in the questionnaires. A low rate of respondents from each scientific society was reported (3% for AIOM, 8% from SIMIT and 2% from SITA). All interviewees agreed that HIV infection was a relevant risk factor for cancer (95.1%) and that PLWH had limited access to clinical trials (73.1%). More than a third of oncologists worked in a hospital without an infectious diseases department, using a remote method of communication for interdisciplinary discussion (telephone and Email were used in 64.5% of cases). Eighty-four percent of the oncologists vs 51.4% of the infectious disease specialists had in charge less than 5 patients with HIV during the previous year. The results of this survey underscore the opportunity for education, interdisciplinary collaboration, and organizational support to optimize cancer care for PLWH. A Hub&Spoke model could represent a potential facilitation to build-up in the near future through inter-societal collaboration.

Docetaxel (75 mg m −2 3-weekly) is standard second-line treatment in advanced non-small-cell lung cancer (NSCLC) with significant toxicity. To verify whether a weekly schedule (33.3 mg m −2 for 6 weeks) improved quality of life (QoL), a phase III study was performed with 220 advanced NSCLC patients, ⩽75 years, ECOG PS ⩽2. QoL was assessed by EORTC questionnaires and the Daily Diary Card (DDC). No difference was found in global QoL scores at 3 weeks. Pain, cough and hair loss significantly favoured the weekly schedule, while diarrhoea was worse. DDC analysis showed that loss of appetite and overall condition were significantly worse in the 3-week arm in the first week, while nausea and loss of appetite were more severe in the weekly arm in the third week. Response rate and survival were similar, hazard ratio of death in the weekly arm being 1.04 (95% CI 0.77–1.39). A 3-weekly docetaxel was more toxic for leukopenia, neutropenia, febrile neutropenia and hair loss; any grade 3–4 haematologic toxicity was significantly more frequent in the standard arm (25 vs 6%). The weekly schedule could be preferred for patients candidate to receive docetaxel as second-line treatment for advanced NSCLC, because of some QoL advantages, lower toxicity and no evidence of strikingly different effect on survival.