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The treatment of patients affected by a teratoma with somatic-type malignancy (STM) is challenging, since they are characterized by a poor prognosis, due to chemoresistance to standard cisplatin-based regimens. Only five more case reports were described for melanomatous STM and for which there are no data available for efficacy evidences of immune checkpoint inhibitors in this setting. Here we report the case of a patient with an initial diagnosis of mediastinal pure seminoma at the first biopsy. After four cycles of a standard cisplatin-based regimen and a partial response, a radical surgery was performed, revealing a mediastinal teratoma with triple STM component (melanoma, leiomyoarcoma and primitive neuroectodermal tumor). However, during post-surgical follow-up, he developed distant metastases from the melanomatous component and a first-line treatment with immune checkpoint inhibitors (ICI) was started.

BackgroundImproving prognosis of BC patients has drawn the attention of health care professionals on disease related long-term side effects and on the multiple treatments BC patients must undergo. Despite advances in procedures, surgery still has multiple detrimental effects, including pain, edema, and limited mobility. For this reason, fostering adapted physical activity (APA) and healthy lifestyle (including a balanced diet and weight management) should become an everyday purpose of healthcare professionals. Fencing may be a well-suited activity to counteract fatigue, pain, and limited arm mobility.Method and analysisThe FENICE study is a mono-center, randomized clinical trial targeting women with BC stages I-III within four weeks from BC surgery. Participants in the control arm will receive the usual recommendations based on the good clinical practice guidelines. In the study arm, participants will be treated with the usual clinical and therapeutic recommendations together with APA and correct lifestyle suggestions.ObjectiveThe primary objective of the study is to compare whether implementation of APA and healthy lifestyle in BC patient after surgery will result in an overall improvement of physical and mental status.ConclusionFencing and its early application in postoperative period may represent a feasible strategy to be implemented in the rehabilitation journey of BC patients.Ethics and disseminationThe study protocol FENICE has been approved by an Italian Ethics Committee on May 2023 (R.S 100.23 5th May 2023).

Introduction: Neoadjuvant chemotherapies for breast cancer (BC) are effective but potentially cardiotoxic, and expose long survivors at risk of chemotherapy-related cardiac dysfunction (CTRCD). Unfortunately, early screening for CTRCD has actual diagnostic limits. Myocardial extracellular volume (mECV) is a radiological marker used in cardiac CT scans and cardiac magnetic resonance for diagnosis and follow-up of CTRCD. It can be measured in whole-body CT (WB-CT) scan, routinely performed in patients at high risk of relapse, to evaluate CTRCD occurrence during oncological follow-up. Methods: 82 WB-CT scans were examined at baseline (T0) and during oncological follow-up at first year (T1) and fifth year (T5) after the end of neoadjuvant treatment. mECV was measured at 1 min (PP) and 5 min (DP) after contrast injection. 31 echocardiograms were retrieved in T1 to perform a linear correlation between mECV and left ventricular ejection fraction (LVEF). Results: mECV values in T0 were similar between the two groups both in PP and in DP. Significant results were found for PP values in T1 (37.0 % vs 32 %, p = 0.0005) and in T5 (27.2 % vs 31.2 %, p = 0.025). A cut-off value of 35 % in PP proved significant in T1 (OR = 12.4, p = 0.004), while mECV was inversely correlated with LVEF both in PP (adj-S = −3.54, adj-p = 0.002) and in DP (adj-S = −2.51, adj-p = 0.0002), suggesting a synergistic action with the age at diagnosis (p

The development of large language models (LLMs) is a recent success in the field of generative artificial intelligence (AI). They are computer models able to perform a wide range of natural language processing tasks, including content generation, question answering, or language translation. In recent months, a growing number of studies aimed to assess their potential applications in the field of medicine, including cancer care. In this mini review, we described the present published evidence for using LLMs in oncology. All the available studies assessed ChatGPT, an advanced language model developed by OpenAI, alone or compared to other LLMs, such as Google Bard, Chatsonic, and Perplexity. Although ChatGPT could provide adequate information on the screening or the management of specific solid tumors, it also demonstrated a significant error rate and a tendency toward providing obsolete data. Therefore, an accurate, expert-driven verification process remains mandatory to avoid the potential for misinformation and incorrect evidence. Overall, although this new generative AI-based technology has the potential to revolutionize the field of medicine, including that of cancer care, it will be necessary to develop rules to guide the application of these tools to maximize benefits and minimize risks.

Background: Aromatase inhibitors (AI) are widely used for treating hormone-sensitive breast cancer (BC). Obesity, however, due to aromatase-mediated androgen conversion into estradiol in the peripheral adipose tissue, might impair AI inhibitory capacity. We aimed at identifying a cut-off of body mass index (BMI) with significant prognostic impact, in a cohort of stage I-II BC patients on systemic adjuvant therapy with AI. Methods: we retrospectively evaluated routinely collected baseline parameters. The optimal BMI cut-off affecting disease-free survival (DFS) in AI-treated BC patients was identified through maximally selected rank statistics; non-linear association between BMI and DFS in the AI cohort was assessed by hazard-ratio-smoothed curve analysis using BMI as continuous variable. The impact of the BMI cut-off on survival outcomes was estimated through Kaplan–Meier plots, with log-rank test and hazard ratio estimation comparing patient subgroups. Results: A total of 319 BC patients under adjuvant endocrine therapy and/or adjuvant chemotherapy were included. Curve-fitting analysis showed that for a BMI cut-off >29 in AI-treated BC patients (n = 172), DFS was increasingly deteriorating and that the impact of BMI on 2-year DFS identified a cut-off specific only for the cohort of postmenopausal BC patients under adjuvant therapy with AI. Conclusion: in radically resected hormone-sensitive BC patients undergoing neoadjuvant or adjuvant chemotherapy and treated with AI, obesity represents a risk factor for recurrence, with a significantly reduced 2-year DFS.

Os autores assinalam a importância da classificação de Laurén para os tumores epiteliais do estômago. Tal classificação é atualmente utilizada pelos epidemiologistas com a finalidade de correlacionar o tipo histológico do tumor com os fatôres que predispõem ao seu aparecimento. O trabalho inclui a análise de 181 peças cirúrgicas estudadas pelos autores, classifcadas segundo Laurén, mencionando-se as referências bibliográficas mais recentes sobre o assunto.

Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole‐genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan‐Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine‐learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning.

Gastric cancer (GC) is the third cause of cancer-related mortality worldwide. Nevertheless, because GC screening programs are not cost-effective, most patients receive diagnosis in the advanced stages, when surgical options are limited. Peritoneal dissemination occurs in approximately one-third of patients with GC at the diagnosis and is a strong predictor of poor outcome. Despite the clinical relevance, biological and molecular mechanisms underlying the development of peritoneal metastasis in GC remain poorly defined. Here, we report results of a high-throughput sequencing of transcriptome expression in paired samples of non-neoplastic and neoplastic gastric samples from 31 patients with GC with or without peritoneal carcinomatosis. The RNA-seq analysis led to the discovery of a group of highly upregulated or downregulated genes, including the leukemia inhibitory factor receptor (LIFR) and one cut domain family member 2 (ONECUT2) that were differentially modulated in patients with peritoneal disease in comparison with patients without peritoneal involvement. Both LIFR and ONECUT2 predicted survival at univariate statistical analysis. LIFR and its major ligand LIF belong to the interleukin-6 (IL-6) cytokine family and have a central role in immune system regulation, carcinogenesis, and dissemination in several human cancers. To confirm the mechanistic role of the LIF/LIFR pathway in promoting GC progression, GC cell lines were challenged in vitro with LIF and a LIFR inhibitor. Among several GC cell lines, MKN45 cells displayed the higher expression of the receptor, and their exposure to LIF promotes a concentration-dependent proliferation and epithelial–mesenchymal transition (EMT), as shown by modulation of relative expression of E-cadherin/vimentin along with JAK and STAT3 phosphorylation and acquisition of a migratory phenotype. Furthermore, exposure to LIF promoted the adhesion of MKN45 cells to the peritoneum in an ex vivo assay. These effects were reversed by the pharmacological blockade of LIFR signaling. Together, these data suggest that LIFR might have a major role in promoting disease progression and peritoneal dissemination in patients with GC and that development of LIF/LIFR inhibitors might have a role in the treatment of GC.

Abstract Background Characterization of breast cancer (BC) through the determination of conventional markers such as ER, PR, HER2, and Ki67 has been useful as a predictive and therapeutic tool. Also, assessment of tumor-infiltrating lymphocytes has been proposed as an important prognostic aspect to be considered in certain BC subtypes. However, there is still a need to identify additional biomarkers that could add precision in distinguishing therapeutic response of individual patients. To this end, we focused in the expression of interferon regulatory factor 8 (IRF8) in BC cells. IRF8 is a transcription factor which plays a well-determined role in myeloid cells and that seems to have multiple antitumoral roles: it has tumor suppressor functions; it acts downstream IFN/STAT1, required for the success of some therapeutic regimes, and its expression in neoplastic cells seems to depend on a cross talk between the immune contexture and the tumor cells. The goal of the present study was to examine the relationship between IRF8 with the therapeutic response and the immune contexture in BC, since its clinical significance in this type of cancer has not been thoroughly addressed. Methods We identified the relationship between IRF8 expression and the clinical outcome of BC patients and validated IRF8 as predictive biomarker by using public databases and then performed in silico analysis. To correlate the expression of IRF8 with the immune infiltrate in BC samples, we performed quantitative multiplex immunohistochemistry. Results IRF8 expression can precisely predict the complete pathological response to monoclonal antibody therapy or to select combinations of chemotherapy such as FAC (fluorouracil, adriamycin, and cytoxan) in ER-negative BC subtypes. Analysis of immune cell infiltration indicates there is a strong correlation between activated and effector CD8+ T cell infiltration and tumoral IRF8 expression. Conclusions We propose IRF8 expression as a potent biomarker not only for prognosis, but also for predicting therapy response in ER-negative BC phenotypes. Its expression in neoplastic cells also correlates with CD8+ T cell activation and infiltration. Therefore, our results justify new efforts towards understanding mechanisms regulating IRF8 expression and how they can be therapeutically manipulated.

Abstract Background HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in first-line, and 74 and 10 months in 194 pertuzumab-naïve patients (p = 0.0006 and 0.03 for OS and PFS2, respectively). Conclusions Our data support the hypothesis that the addition of pertuzumab to trastuzumab reduces the amount of available plasma membrane HER2 receptor, limiting the binding of T-DM1 in cancer cells. This may help interpret the less favorable outcomes of second-line T-DM1 in trastuzumab/pertuzumab pre-treated patients compared to their pertuzumab-naïve counterpart.

Objective: To compare perioperative outcomes of the elderly versus non-elderly patients on ERPs undergoing laparotomy for gynecologic surgery. Methods: From January 2016 to June 2017, patients undergoing elective laparotomies for gynecologic surgery were enrolled in a perioperative ERP protocol. Outcomes were compared between the elderly (age ≥ 70 years) and the non-elderly (age ≤ 69 years). Primary outcomes were length of stay and perioperative complication rates. Comparisons were performed using chi-squared tests or Fisher’s exact tests for categorical data and Student’s t-test or Wilcoxon rank-sum tests for continuous variables, with p

Abstract This article reviews radiation chemistry processes induced by high-linear energy transfer (LET) radiation. The first part gives a short historical introduction and defines the essential concepts of radiation chemistry. It is aimed at radiobiologists in search of basics in this discipline, to link to their biological observations. Then, special focus is done on LET effect, oxygen effect and nanoparticles as these parameters can influence the success of radiotherapy. The embraced point of view is the one from a chemist as involved molecular reactions in water are detailed and revealed, for example, how dioxygen can be produced in situ during high-LET irradiations, even in anoxic conditions. A step forward can be reached using nanoparticles in conjunction with radiation beams to enhance their effects. The last part of this review is thus devoted to the description of an original approach combining high-LET projectiles (3-MeV α-rays) and gold nanoparticles. Fluorescence microscopy was used to evaluate the formation yield of radicals in anoxic condition via scavenging by Ampliflu® Red. As with low-LET irradiations, an overproduction of radicals was obtained, encouraging to conduct a broader study and to consider nanoparticles in simulation as an additional source of radicals.

Hormonal therapies for receptor positive-breast and prostate cancer patients have shown clinical efficacy but also several side effects including osteoporosis, loss of bone mass and increased fracture risk. Denosumab represents an anti RANKL (receptor activator of nuclear factor-kB ligand) monoclonal anti-body acting as inhibitor of osteoclasts formation, function, and survival, then increasing bone mass. Herein, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the role of Denosumab in saving bone health in prostate and breast cancer patients receiving respectively androgen deprivation therapy and adjuvant endocrine therapy. Moreover, selected patients have to be treated with Denosumab at the dose of 60 mg every six month or placebo. Outcomes studied included the bone mass density (BMD) increase at 24 and 36 months, BMD loss, reduction of fractures risk (in particular vertebral) at 24 and 36 months and safety (overall, serious adverse events – SAEs and discontinuation rate). Our results showed a reduction of the BMD loss up to 36 months both at the lumbar and femoral level and a BMD increase both at 24 and 36 months. It was also found a reduction in the number of new vertebral and femoral fractures at 24 and 36 months. Finally, our pooled analysis showed that Denosumab did not affect both the SAEs and therapy discontinuation risk. In conclusion, Denosumab administration can be considered effective and safe in the prevention and management of the above mentioned adverse events related to hormonal therapies designed for breast and prostate tumors. Keywords: Breast, Prostate, Cancer, Hormone, Denosumab, Fracture

An amendment to this paper has been published and can be accessed via the original article.

Objectives. The authors reported a retrospective study on myxoid liposarcomas (MLs), evaluating factors that may influence overall survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), and analyzing the metastatic pattern. Methods. 148 MLs were analyzed. The sites of metastases were investigated. Results. Margins (p = 0.002), grading (p = 0,0479), and metastasis (p < 0,0001) were significant risk factors affecting overall survival (OS). Type of presentation (p = 0.0243), grading (p = 0,0055), margin (p = 0.0001), and local recurrence (0.0437) were risk factors on metastasis-free survival (MFS). Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS) and reported 55% extrapulmonary metastases and 45% pulmonary metastases. Conclusion. Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma.