Clinical trials

Adverse events (AEs) with Cabozantinib are frequent (about 40-67% of patients) and often lead to temporary treatment interruptions, dose reductions or permanent discontinuations, potentially reducing dose intensity and sustained exposure. Therefore, strategies are needed to improve tolerability without compromising antitumor activity. Therapeutic drug monitoring (TDM) is particularly suitable for drugs with high interpatient variability, narrow therapeutic windows and defined exposure-response relationships; real world data support this profile for Cabozantinib and suggest that pharmacokinetically guided dosing could help manage toxicity while maintaining efficacy. Based on this evidence, the study proposes a model of individualized pharmacological counselling integrating TDM, pharmacogenetic testing and structured evaluation of pharmacological interactions to optimize Cabozantinib exposure and minimize avoidable toxicity.

The advances in early detection coupled with improvements in treatments have led to an ever-increasing number of breast cancer survivors. New methods to improve outcomes, including strategies aimed at improving the quality of life and reducing the risk of other diseases, may represent valid additions to the currently available treatment options. Interventions targeting diet, weight and physical activity can reduce the risk of cancer occurrence, prevent cancer recurrence, improve survival and the quality of life. This is an observational, prospective study aimed at evaluating the effects of physical activity on the quality of life of patients with early stage hormone receptor positive breast cancer receiving adjuvant hormonal therapy and adhering to a physical activity program lasting for a total of 12 weeks organized by ANDOS onlus (Associazione Italiana Donne Operate al Seno).

This research project builds on a long-standing tradition within our Institute of documenting "free thoughts" and personal reflections shared by adolescent oncology patients and their families. These narratives, collected through "logbooks" in ward rooms and during dedicated events-including those focused on the COVID-19 pandemic-represent a profound tool for patients to reclaim their identity beyond their diagnosis. The aim is to stimulate and collect patient narratives to better understand their emotional and lived experiences. By analyzing these spontaneous writings, the study aims to improve clinical practice, enhance the patient-provider relationship, and optimize the overall healthcare organization.

The study stems from the need to have available effective tools for detecting the anxiety of the cancer patient who has to undergo surgery. The period leading up to surgery, is characterized by strong emotions that create an upheaval in the work, family and social life of the patient as well as concern about the unknown. It would be crucial to ensure a personalized nursing care by having scales of assessment specific to the clinical-surgical oncology setting in order to collect the patient's emotions, concerns and fears. Despite the numerous scales available, many of them have limitations concerning the issues they go to investigate but also concerning the timeframes for compilation, which are often long and laborious so they are difficult to apply. The study aims to validate in the Italian context the Surgical Anxiety Questionnaire (SAQ) questionnaire, already translated and validated in multiple languages, to detect which factors are the most influential in increasing preoperative anxiety, with the aim of implementing education of the patient and implement strategies and interventions that can reduce anxiety.

Reference intervals are an essential tool for the clinical interpretation of laboratory test results. Traditionally, these interval are determined using samples from healthy individuals, a process that is resource-intensive, time-consuming, and require the active recruitment of healthy volunteers. In recent years, due to the increasing availability of electronic health record (EHR) databases and the growing number of laboratory tests, it is possible to determine the reference intervals indirectly. This approach relies on the analysis of routine data acquired in clinical laboratories, eliminating the need for active recruiting healthy subjects and significantly reducing costs. Moreover, the method has the potential to eliminate the selection bias of an ultra-healthy population typical of the direct methods. The indirect methods for determining reference intervals have evolved from simple strategies of isolating the healthy population using sample metadata, to sophisticated statistical models that effectively distinguish normal from pathological distributions. One of the advanced techniques, RefineR, has reached an excellent combination of accuracy, robustness, and computational efficiency, outperforming previous methods. It has been implemented as an open-source R package, facilitating its application in real-world settings. In recognition of these advantages, the IFCC (International Federation of Clinical Chemistry and Laboratory Medicine), through its Committee on Reference Intervals and Decision Limits (C-RIDL), has promoted the adoption of indirect methods for determining reference intervals, highlighting the advantages of this strategy, including greater speed, lower costs, and the absence of a need to recruit healthy donors. Furthermore, a recent study has highlighted age-related physiological variations in hemoglobin levels in elderly population. This underscores the need for defining age-specific reference intervals which are currently absent from most laboratory reports, potentially impacting diagnostic accuracy.

Obesity increases the risk of endometrial cancer, with higher Body Mass Index (BMI) leading to a significant increase in both cancer risk and recurrence. Because of the excellent cancer-specific outcomes and preponderance of obesity-related complications, women with endometrial cancer are more likely to die of cardiovascular disease and other obesity-related illnesses than endometrial cancer itself. This makes an endometrial cancer diagnosis a critical moment to emphasizes the importance of actively managing the underlying issue of obesity in the endometrial cancer survivorship period. Bariatric surgery has shown long-term benefits, including weight loss and reduction of obesity-related comorbidities, and has been linked to a decrease in endometrial cancer incidence. However, bariatric surgery has limitations, such as irreversibility and potential complications. Recent interest in less invasive methods, like bariatric endoscopy, shows promising results in achieving weight loss and improving metabolic profiles. Endoscopic procedures, such as Endomina Endoscopic suture gastroplasty (E-ESG), have shown effectiveness in weight loss and could offer a safer, more accessible alternative to surgery, in particular if associated to a lifestyle modifications program. Efficacy and safety of Bariatric endoscopy has been stressed within the recently published "Guideline of the Italian Society of Surgery of Obesity and Metabolic Diseases on Bariatric Endoscopy in the treatment of obesity and associated complications" that suggest the use of bariatric endoscopy in patients with class I obesity and in patients with class II obesity regardless of the presence of comorbidities, for the treatment of obesity. This study aims to assess the feasibility and safety of the E-ESG procedure in treating obesity in women after curative treatment for endometrial cancer.

Investigator propose the implementation of circulating biomarker monitoring, focusing on molecules related to the progression of gastric atrophy and/or associated with gastric cancer. Monitoring these biomarkers will provide gastroenterologists with timely information on individuals at risk and, if values worsen during follow-up, will alert physicians observing these patients to evaluate them. This monitoring will be offered to individuals who contact the IBO (Immunopatologia e Biomarcatori Oncologici) Unit at CRO (Centro di Riferimento Oncologico) in Aviano requesting an assessment of gastric function through pepsinogen and G17 gastrin level testing. Monitoring these biomarkers will provide a dynamic analysis of patients' gastric status, allowing for timely intervention in case of deviations from normal values. This proactive approach is important for the preventive management of gastric diseases, particularly for the diagnosis and monitoring of gastric atrophy and gastric cancer. The IBO unit of the CRO in Aviano, together with the pathological anatomy and clinical units of gastroenterology, medical oncology, and surgery, will play a role in coordinating and implementing this monitoring program, thus contributing to the promotion of gastric health and the prevention of associated diseases.

Applying Dried Blood Spots (DBS) techniques to pharmacokinetic analysis could significantly streamline the use of Therapeutic Drug Monitoring (TDM) in clinical practice. To establish DBS as a viable alternative sampling method, it is essential to demonstrate that results obtained from DBS analysis are reliable. This validation can be achieved through a cross-validation study. In this protocol, an original validated method, the plasma-based assay, serves as the "reference", while the alternative DBS-based analytical technique is the "comparator." The reliability will be defined analysing patients' samples with the new methods and comparing these results with those obtained with the reference LC-MS/MS (Liquid Chromatography-Mass Spectrometry) methods (in plasma). The possibility to apply DBS technique to pharmacokinetic analysis should largely facilitate the application of TDM to clinical practice.

High-risk meningiomas always require postsurgical radiation treatment. Recent evidence has shown that increased radiation therapy dose may be associated with increased intracranial control of disease. In order to better define the volume of radiation treatment, the addition of PET imaging with somatostatin receptor tracers adds additional information compared to encephalon MRI with MoC alone.The present study aims to investigate whether radiation treatment with higher doses than the standard and defined using PET imaging can be safe and at the same time effective in order to increase progression-free survival in high-risk meningiomas.

Accurate assessment of axillary lymph nodes in patients with breast cancer is essential for prognosis and treatment planning. Staging and surgical management have evolved from axillary lymph node dissection to sentinel lymph node biopsy to minimize morbidity. However, sentinel lymph node biopsy has non-negligible morbidity, and more than 70% of biopsies are negative, calling into question its routine use. Magnetic resonance imaging (MRI) can be used to detect and stage lymph node metastases in situ, but its sensitivity and specificity are moderate to poor. Few studies have employed artificial intelligence to detect lymph node metastases on MRI images, and none have used an integrative multidata approach (IMA), defined as modeling the combination of clinical and laboratory data with multiparametric MRI. The primary objective of this retrospective observational study is to improve the accuracy of detecting lymph node involvement in breast cancer using IMA. The secondary objective is to allow longitudinal monitoring of the effects of neoadjuvant therapy on lymph node involvement

Hepatitis C virus (HCV), which infects more than 185 million people, is a major risk factor. Direct-acting antiviral (DAA) therapy has significantly improved the eradication of the virus, but has not completely eliminated the risk of HCC, so careful surveillance is necessary. The genetic diversity of the natural killer receptor, histocompatibility antigens (HLA) and interferon lambda 4 (INFL4) activity, among other factors, have been found to be crucial in directing disease progression. Importantly, these markers are detectable years before the diagnosis of HCC. In addition, polymorphic variants attributable to the expression of genes involved in innate-type immune response, such as IFNL4 and HLA-E, have been shown to be predictive for the development of HCC and have not yet been extensively studied. The aim of the study is to evaluate novel circulating biomarkers, including the presence of antibodies to specific HCV proteome peptides, IFNL4 expression, and the interaction of specific HLA receptors/ligands in a large cohort of HCV-positive subjects in order to create a screening strategy for the early diagnosis of HCV-associated HCC. Part of the study will be devoted to describing the immune microenvironment associated with the expression of IFNL4 and HLAE, evaluating them as potential prognostic indicators for HCC in HCV-infected subjects undergoing surgery for HCC, as well as in those with advanced/metastatic HCC.

The purpose of the study is to assess the attitudes and the use of research by nurses at the IRCCS-CRO Aviano. Furthermore, it will make it possible to identify attitudes towards the use/non-use of research results, specific training needs and targeted interventions to ensure adequate care for cancer patients along the disease course, derived from a constant updating of nursing skills. The study will involve nurses working in different care settings of the Institute and some patients who will be able to express their care needs and research priorities, making a direct contribution towards development of care centred on the health needs, preferences and values of the cancer patients.

Breast cancer (BC) is the most frequent tumour in women. To date, among the available treatments, the use of Capecitabine, an oral prodrug of fluorouracil, has been shown activity in different setting. In advanced disease, Capecitabine is often used as monotherapy in patients pretreated with anthracycline, taxane or both. One of the most frequent toxicities reported by patients receiving capecitabine is hand-foot syndrome (HFS), with an incidence of grade 3 HFS of 28%. HFS, also known as palmar-plantar erythrodysesthesia syndrome, is initially characterized by palmoplantar numbness, tingling, or burning pain. These symptoms usually coincide with sharply demarcated erythema with or without edema, cracking, or desquamation. In advanced stages, blistering and ulceration may occur. Although HFS is not considered life threatening, it can be painful and interfere with daily activities, thusseriously compromising quality of life (QoL), therefore this toxicity is considered dose limiting.Moreover, consistent with the theory that Capecitabine and its metabolites induce an inflammatory effect, the use of COX-2 inhibitors is an emerging strategies, but more evidence are needed from largest study to confirm their efficacy. Similarly, N-acetylcysteine (NAC), an antioxidant, mucolytic and nephroprotective agent, that affects pathways involved in inflammatory conditions and that has demonstrated to be effective in several dermatologic conditions, could be useful in the management of Capecitabine-induced HFS. From this arises the present study that has the objective of evaluating the role of NAC plus urea-based cream in the prevention of Capecitabineinduced HFS in patient affected by breast cancer.

Radiotherapy key role in pediatric oncology, despite the potential side effects especially in the long term, including the risk of radioinduced second cancers. Very rarely malignant neoplasms typical of children and adolescents may present in adulthood, historically with a worse outcome, but for some of these histologies demonstrated recent results overlapping with those in pediatric age when treated with strategies similar to pediatric protocols and similar radiotherapy. Long-term data on outcome and incidence of potential toxicity late radiation therapy in these populations almost exclusively from epidemiologic studies or retrospective case series. Prospective data are lacking, particularly in patients treated with IMRT and specifically with certain IMRT modalities such as Helical Tomotherapy, for which the CRO pediatric radiotherapy has documented experience. The main objective is to evaluate the short- and long-term toxicity secondary to radiotherapy performed at the Pediatric Radiotherapy of the CRO in Aviano, with specific subgroup analyses aimed at highlighting any differences mainly by age, pathology and radiotherapy technique.

Malignant pleural mesothelioma (MPM) is a tumour that originates from the pleural layers (visceral and parietal) that envelop the lungs and the inner wall of the thoracic cage. In other tumour contexts, numerous studies have demonstrated a synergistic effect between RT and Immune Checkpoint Inhibitors (ICIs), mainly due to immunogenic effects attributed to high doses of RT and ICIs-mediated activation of anti-tumour T lymphocytes. Both treatments, RT and immunotherapy, have demonstrated a survival advantage in MPM, but are associated with non-negligible pulmonary toxicity. Therefore, the combination of these 2 therapeutic approaches requires a careful assessment of risk factors for the occurrence of toxicity. The identification of circulating biomarkers capable of predicting the onset of severe toxicity induced by radical radiation treatment is an important clinical need in MPM. This study aims to monitor circulating biomarkers, such as molecules involved in inflammation and oxidative stress and cellular effectors modulated by radiation treatment and potentially associated with the development of toxicity and/or markers of an immunogenic effect of radiotherapy in the peripheral blood of subjects with malignant pleural mesothelioma for treatment with radical hemithoracic radiotherapy.

Artificial intelligence (AI) undoubtedly represents the main tool currently available in the definition of complex algorithms and its use in the medical field is becoming increasingly strategic.As reported in the literature, it is increasingly difficult to find new therapeutic strategies for neoplasms, especially neurological ones. Molecular characterisation is therefore increasingly essential, as is the use of new predictive methods. With this in mind, the aim of this study is to assess, by means of AI algorithms applied to genomic data, in what percentage molecular alterations are susceptible to potential drug therapies, compared to the literature data that does not consider AI algorithms for this purpose.

In locally advanced rectal cancer the pathological complete response (pCR) to neoadjuvant chemoradiation therapy (nCRT) is associated with a favourable long-term prognosis. The identification of markers predictive of response to therapy would therefore optimise treatment by allowing personalised therapy. It has been shown that the genetic profile of the patient could influence the activation of the immune system in combination with chemoradiation therapy in targeting tumour cells. In addition, genetic features of molecular pathways correlated with response to chemoradiotherapy, may in turn affect the probability of a good response to treatment in these patients, but also the occurrence of adverse events. The main objective of the study is to define the role of genetic markers related to immune system activation and other molecular pathways in predicting the complete pathological response to preoperative chemoradiation therapy in patients with locally advanced rectal cancer.

According to an analysis by Memorial Sloan Kettering Cancer Center patients who receive a target therapy having an oncogenic driver mutation live longer than those who do not receive it. In addition to that, therapies guided by analysis on mutations identified in ct-DNA had a favorable impact, allowing longer survival. All this suggests that the presence of a therapeutically targetable oncogene (oncogene addicted) allows target therapy, resulting in a longer life expectancy. The main objective of this study is to evaluate the frequency of patients with oncogene addiction in a consecutive series of patients with NSCLC afferent to the CRO. Oncogene addiction is defined as being carriers of one of the mutations among EGFR, ALK, RET, KRAS, BRAF, Her2, ROS1, MET or other mutations that become therapeutic targets under investigation.

This study aims to evaluate the activity and safety of the combination of platinum-pemetrexed based chemotherapy plus Lorlatinib in ALK positive Non-Small Cell Lung Cancer (NSCLC) with exclusively extracranial disease progression on Lorlatinib. Platinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.

The association of clinical, pathogenesis and mutational profile of patients affected by ovarian cancer have improved the armamentarium of therapies available for medical doctors. One of most remarkable advancements is represented by the introduction of PARP inhibitors in the front-line setting of advanced ovarian carcinoma. It is necessary to continue with this effort and introduce novel approaches to improve the survival rate as well as predictive biomarkers to approved therapies. Given the absence of predictive biomarkers to standard therapy, patients derived organoid could be a promising platform to test clinically available drugs and/or promising new molecules to explore the tumor sensibility in an ex-vivo model. The aim of this study is to correlate treatment sensibility measured in tumor derived organoids to clinical sensibility seen in real world patients.

This study aims at verifying the overexpression of STARD3 in both early and advanced CRC patients derived tissues, to identify the pathways underpinning tumorigenesis and cancer progression in which STARD3 is involved. Moreover its role as a dynamic biomarker of treatment response and its part in treatment sensitivity will be explored.

Breast radiation treatment is burdened by acute and chronic toxicities, in most cases mild. However, considering the excellent life expectancy of patients with breast cancer, maintaining a low toxicity profile is of primary importance in order to guarantee a satisfactory quality of life. The definition of the molecular and genetic variables related to radiotoxicity and their integration into predictive molecular signatures may allow the risk of toxicity to be individualized. This would provide the clinician with a useful tool in order to personalize the radiation treatment, thus being able to choose the best technique or schedule for each patient.

The goal of this observational study is to learn about relation between vitamin D levels in subjects with head and neck cancer. The main question it aims to answer are: * variation of vitamin D levels in the study population at different time points * relation between therapy side effects and vitamin D level * relation between disease outcome and vitamin D level Participants will be followed as per clinical practice

The advances in early detection coupled with improvements in treatments have led to an ever increasing number of breast cancer survivors. New methods to improve outcomes, including strategies aimed at improving the quality of life and reducing the risk of other diseases, may complement the currently available treatment options. In particular, interventions targeting diet, weight and physical activity can reduce the risk of cancer occurrence, prevent cancer recurrence, and improve survival and the quality of life.This cross-sectional, prospective, observational study aims at evaluating dietary habits and nutritional knowledge in patients with early hormone receptor positive and hormone receptor negative breast cancer.

Re-irradiation in gliomas is a therapeutic option at recurrence before of 2nd-line chemotherapy. The dose of re-irradiation with conventional fractionation is unfortunately limited by the risk of symptomatic radionecrosis that is significant for cumulative doses above 100 Gy. The use of unconventional low dose rate pulsed radiotherapy (pLDRT) can reduce the risk of radiotoxicity while taking advantage of the cellular hyper-radiosensitivity that occurs at low dose-rates. The present study therefore aims at evaluating whether the use of pLDRT in the re-irradiation of recurrences of gliomas allows maintaining a low risk of symptomatic radionecrosis even for cumulative doses greater than 100 Gy.