INTRODUCTION:This study aimed to develop radiomics-based multivariate classifiers able to non-invasively decipher the tumor immune microenvironment (TIME) in resected Non-small cell lung cancer (NSCLC) patients. METHODS:Tumor-infiltrating lymphocytes (TILs) subpopulations and PD-L1 TPS were immunohistochemically assessed. Radiomic features (RFs) were extracted from preoperative CT scans using the PyRadiomics platform. Six machine learning-based models were built to predict distinct TIME-related endpoints: PD-L1 (M1), CD8/CD3 ratio (M2), PD1/CD8 ratio (M3), CD3+ TILs (M4), CD4+ TILs (M5), CD8+ TILs (M6). Except for PD-L1 (classified as positive vs negative), patients were dichotomized into high versus low groups based on median values. Model development relied on Random Forest classifiers with sequential feature selection and internally validated through Leave-One-Out Cross-Validation splitsResults:A total of 98 patients with stage I-IIIA resected NSCLC were included. From 1702 initially extracted RFs per scan, 231 non-redundant features (116 tumor and 115 peritumoral) were retained after correlation filtering. Final models incorporated between 3 and 7 RFs derived from both tumor and peritumoral regions. Model performance showed accuracy, precision, sensitivity, receiver operating curve (ROC) Area under the Curve (AUC) and precision-recall curve (PRC) AUC values ranging from 70% to 80%, with slightly lower performance for M2. Specificity ranged from 55% to 77%, with the highest value observed in the CD8+ TILs model (M6). Feature selection varied across models, although one peritumoral feature (HLL-wavelet GLCM Correlation) was consistently selected in four models (M1, M2, M4, M5). CONCLUSIONS:Tumoral and peritumoral CT-based radiomics might effectively intercept TIME features, thus suggesting a potential non-invasive approach in resected NSCLC patients.
BACKGROUND:Process mining (PM) is a powerful approach for analysing and optimising complex workflows. Radiation therapy (RT) involves multiple steps and resources, making it well suited for PM analysis.This study aims to apply a PM approach to characterise the real-world workflow of a high-volume RT department, with the goal of identifying critical transitions and bottlenecks, quantifying their impact on treatment timelines, and exploring the main factors associated with treatment suspensions and cancellations. MATERIAL AND METHODS:Patients treated with RT at our centre between January 2017 and December 2021 were included. All patient-related events were extracted from the institutional database. A first-order Markov model was used to analyse event sequences and identify anomalies, while the Kruskal-Wallis test compared median completion times across stratified sub-cohorts. RESULTS:The study analysed 43,183 events associated with 8608 treatments. The pathway diagram depicted key events, such as Prescription, Scheduling, CT simulation, RT start, RT cancelled, RT suspension, and RT end. Statistical analysis revealed a significant difference in terms of median time in case of suspension event during the path, leading to a delay in the start of RT treatment (p<0.05). The analysis of the employed time from Prescription to RT start demonstrated a significant impact of suspension on the time interval for breast, genitourinary, gastrointestinal, metastatic, head and neck, gynaecological, thoracic, and skin cancer (p<0.05). CONCLUSIONS:This study illustrates the applicability of PM as a methodological framework for analysing care pathways. By demonstrating how PM can identify delays, interruptions, and workflow inefficiencies, it highlights its potential to support process evaluation and optimisation.
The increasing complexity of precision medicine has highlighted the limitations of traditional randomized clinical trials (RCTs) when applied to highly stratified populations and biologically heterogeneous diseases. In this context, master protocols represent an evolution towards integrated experimental infrastructures, capable of simultaneously evaluating multiple interventions or molecular subgroups within a single methodological framework.These designs redefine the role of randomization in complex settings. Conventional RCTs remain indispensable as confirmatory studies, thanks to their methodological rigor and the robustness of the evidence they generate.Future developments will depend on the capacity to ensure statistical rigor, transparent governance, data protection and equitable access to experimental infrastructures and advanced molecular screening. In this evolving landscape, master protocols emerge not as a methodological trend, but as one of the most convincing tools for making evidence generation faster, more flexible, and more sustainable without giving up the scientific standards required by contemporary clinical research.
INTRODUCTION:Circumferential pharyngolaryngectomy (CPL) may result in extensive posterior pharyngeal defects for which standard reconstructive strategies are insufficient. Chimeric flaps from the thoracodorsal system (TDSF) offer independently vascularized components that may address both posterior coverage and luminal restoration. We report what appears to be the first use of a chimeric TDSF for reconstruction following extended CPL. CASE REPORT:A 68-year-old man with cT4aN1 squamous cell carcinoma of the right oro-hypopharyngeal wall underwent neoadjuvant chemotherapy followed by extended CPL, bilateral neck dissection and total thyroidectomy. Resection included the entire posterior rhino-oro-hypopharyngeal mucosa, creating an approximately 18-cm defect. A chimeric TDSF was harvested in supine position, combining a serratus anterior myofascial component for resurfacing the prevertebral fascia and a latissimus dorsi myocutaneous component to recreate the neopharyngeal circumference. Postoperative recovery was uneventful, with no fistula or stenosis. Oral feeding resumed on postoperative day 15, and the patient was discharged on day 20. Histopathology showed pT4aN3b disease with negative margins, enabling timely adjuvant chemoradiotherapy. CONCLUSION:Chimeric TDSF reconstruction provided reliable posterior protection and functional pharyngeal restoration in a defect not amenable to standard techniques. This approach may represent a valuable option for selected complex CPL cases.
Few innovative treatments were developed for patients with non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) in the past decades. The paper describes the OCTOPUS project (Optimising Combination Therapy fOr Paediatric, adolescent and yoUng adult patients with non-rhabdomyosarcoma soft tissue Sarcomas), a master protocol and includes an adaptive platform trial comprising different sub-trials, a real-world data registry, translational studies, and overarching study questions assessing local therapy issues and patient reported outcome measures (PROMs). The OCTOPUS consortium will provide an operational framework including a legal consortium structure, a network of national coordinating centres (NCCs) and sites within the EpSSG (European paediatric Soft tissue sarcoma Study Group) and ITCC (Innovative Therapies for Children and adolescents with Cancer) network. The overarching aim of the platform is to improve outcome and quality of life for patients with NRSTS by providing access to innovative treatments. Every sub-trial will have a unique design, tailored to the needs of the patients, the characteristics of the disease, and the stage of development of the experimental compound(s). Depending on the medical need in a specific patient population and the expected activity of a compound (or a combination), the innovative treatment(s) will be offered to patients with relapsed/refractory disease or placed in frontline treatment when appropriate.
PURPOSE:The present study aims to investigate the feasibility and therapeutic potential of intravesically administered interleukin-12 mRNA-loaded lipid nanoparticles (IL-12 mRNA LNPs) for treatment of orthotopic bladder cancer. METHODS:Fluc-mRNA LNPs and IL-12 mRNA LNPs were prepared using microfluidic technology and characterized in terms of particle size, zeta potential, encapsulation efficiency, and stability. The in vivo transfection efficiency of the Fluc-mRNA LNPs were assessed by bioluminescence imaging. The antitumor efficacy of IL-12 mRNA LNPs was valuated in orthotopic bladder cancer mice models which were established with Luc-MB49 cells. RESULTS:Fluc-mRNA LNPs and IL-12 mRNA LNPs were successfully prepared via microfluidics, which had uniform particle size (101.6 nm and 104.4 nm), near-neutral surface charge (-3.39 mV and -8.34 mV), high encapsulation efficiency (89.01% and 98.87%), and good stability. Efficient intravesical transfection and robust protein expression were confirmed in mouse bladders using an in vivo bioluminescence imaging. In orthotopic bladder cancer-bearing mice, intravesical instillation of IL-12 mRNA LNPs significantly inhibited tumor growth. CONCLUSIONS:Intravesical delivery of IL-12 mRNA LNPs represents an effective and promising strategy for local immunotherapy of bladder cancer. These findings provide experimental evidence supporting the potential clinical translation of mRNA-LNPs-based intravesical regimens for the treatment of bladder cancer.
AIM:This review aims to describe the literature on mental adaptation to cancer and to examine how coping strategies influence psychological outcomes among cancer patients. RESEARCH QUESTIONS:What coping strategies related to mental adaptation to cancer are reported among patients with breast, lung, colorectal, prostate, and bladder cancers? DESIGN:Systematic review reported according to the PRISMA guidelines. METHODS:A comprehensive literature search was conducted in the PubMed database. Study methodological quality was evaluated using the Joanna Briggs Institute critical appraisal tools, and the certainty of evidence was assessed according to the Oxford Centre for Evidence-Based Medicine. Article selection, quality assessment, and risk-of-bias evaluation were conducted independently by two reviewers. RESULTS:The search identified 173,274 records, of which 42 studies met the eligibility criteria after screening. Most studies were cross-sectional and conducted in hospital oncology departments, outpatient clinics, rehabilitation programs, or community follow-up services. Findings indicate that the diagnostic and early treatment phases represent the most psychologically vulnerable periods for cancer patients. Maladaptive coping strategies, particularly helplessness-hopelessness and anxious preoccupation, were associated with increased psychological distress, including anxiety and depression. Sociodemographic factors such as age, gender, education, income, and social support also influenced psychological outcomes. CONCLUSION:Early psychological assessment and psychosocial interventions during the first months after diagnosis may improve mental health outcomes. Further research should explore digital health tools and remote support systems to enhance psychological care for cancer patients.
PURPOSE:Adolescents and young adults (AYA; 15-39 years) represent a distinct oncology population with specific biological and psychosocial needs. Despite growing awareness, AYA patients often face fragmented care between pediatric and adult settings, resulting in diagnostic delays, limited clinical trial access, and inadequate psychosocial support. In 2021, the AIOM-AIEOP AYA Working Group was established in Italy to promote awareness and address these challenges. METHODS:An anonymous, voluntary online survey was designed by the AIOM-AIEOP AYA Working Group and distributed during the AIOM National Congress (November 2024). Using iPads at a dedicated booth, oncologists and other healthcare professionals completed a questionnaire exploring knowledge, perceptions, and access to AYA-focused services. Data were analyzed using descriptive statistics. RESULTS:Ninety-seven professionals participated (median age 34 years; 75% female; 56% medical oncologists). Although 86% reported access to genetic counseling and 84% to fertility preservation services, only 18% had AYA-dedicated spaces and 21% employed trained AYA-specific staff. Forty-four percent felt competent in assessing hereditary cancer syndromes, and fewer than 25% were aware of AYA-focused research or trials. Psychological support was commonly available, whereas educational coaching and peer support groups were rare (5% each). Lifestyle counseling was frequent, but structured survivorship care and long-term follow-up were limited. CONCLUSIONS:This survey reveals substantial gaps in AYA oncology services in Italy, particularly regarding dedicated staff, infrastructure, and training. National coordination and implementation of standardized frameworks, such as through the AIOM-AIEOP network, are essential to ensure equitable, comprehensive care for AYA patients.
BACKGROUND:Issues related to end-of-life decisions (ELDs) generate impassioned debates in society. Our study aimed at investigating attitudes in care of cancer patients at the end-of-life (EOL); ascertaining the opinion of healthcare professionals (HCPs), patients, and caregivers. METHODS:An anonymous and self-administered questionnaire was delivered to HCPs (physicians, nurses, psychologists, and social workers), patients and family caregivers at Veneto Institute of Oncology, Italy, and 425 questionnaires were collected (136 HCPs, 171 patients, 118 caregivers). RESULTS:Withholding life-sustaining treatment (LST) was declared by 11.3% of physicians and nurses and withdrawing by 19.4%, whereas 46.8% declared starting LST, and 48.4% did not discontinue LST. Most HCPs (75.7%) were in favor of patient's right to anticipate EOL, and 86.4% of withholding/withdrawing LST upon patient's request, with 62.4% HCPs agreeing on lethal drug doses to be allowed upon request of the patient. The majority (80.1%) disagreed that "life is an unavailable asset and there is no right to die". For patients and caregivers, in ELDs greater value was given to self-determination first, with family members and trustees' subsequent involvement. A considerable number of HCPs reported feeling inadequate to communicate bad news. CONCLUSION:Despite the limitations imposed by the cross-sectional nature, this study adds information with regard to EOL in oncology setting in Italy. Our study shows that an attitude to prolonging patient's life in ELDs is still prevalent among HCPs in an Italian oncological setting, although there are signs of change. Communicating bad news emerges as an issue, along with HCPs' awareness that they need more education and training.
For decades, the surgical management of non-small cell lung cancer (NSCLC) has been predominantly guided by anatomical staging. However, this traditional approach often overlooks the "fourth dimension" of cancer biology: time. This narrative review explores how circadian and circannual rhythms act as silent drivers of oncological prognosis, deeply influencing the interaction between host immunity and tumor behavior. Evidence suggests that the integrity of the molecular clock, regulated by genes such as TIMELESS and RORA, is not merely a biochemical detail but a critical determinant of survival and metastatic potential. Furthermore, environmental cues like Vitamin D synthesis and photoperiodism introduce seasonal fluctuations in patient resilience, creating specific "windows of vulnerability" during surgical stress. Moving toward a "time-aware" oncology opens the possibility of synchronizing clinical interventions-from the hour/season of surgery to immunotherapy scheduling-with the patient's biological rhythms. Such an approach represents a promising, cost-effective frontier to further personalize the therapeutic journey and optimize long-term outcomes in resectable NSCLC.
Hereditary cancer genetics is increasingly recognized as an integral component of cancer care, contributing to treatment, early detection, and risk reduction strategies for patients and their relatives. In this context, several hereditary cancer programs, databases, recommendations, and guidelines have been implemented within the Italian National Health System and at hospital level. However, independent and specific quality indicators for hereditary tumor management are still lacking, limiting the ability to evaluate activities across individual centers. To address this gap, AIFET (Associazione Italiana Familiarità ed Ereditarietà Tumori) has established a dedicated scientific committee for the development of such quality indicators. Here, for the first time to our knowledge, we present a set of 37 quality indicators derived from a national Italian survey. The indicators were organised into four sections: General indicators (applicable to all syndromes), specific to hereditary breast and ovarian cancer, specific to colorectal cancer and polyposis, specific to melanoma predisposition. By promoting consistency across centres, this model may not only enhance the quality of care nationally but also foster collaboration with European institutions toward shared standards in hereditary cancer management.
The follow up in early breast cancer represented a major challenging in oncology practice. Current guidelines are supported by evidence demonstrating no benefit of intensive surveillance.Despite evidence, many oncologists still practice a more intensive follow-up, prompting studies to evaluate and improve real-world effectiveness: the effectiveness of routine screening is further questioned by the varied relapse patterns across breast cancer subtypes. Rethinking surveillance as a calibrated clinical choice, rather than an automatic procedure, is a scientific and civic duty in the era of personalized and sustainable healthcare.
BACKGROUND:Synovial sarcoma (SS) is molecularly defined by the pathognomonic SS18::SSX fusion, a master epigenetic driver. While NTRK gene fusions are high-priority tissue-agnostic targets for TRK inhibitors like larotrectinib, their co-occurrence with established lineage-defining drivers in sarcomas is exceptionally rare and presents a therapeutic paradox. CASE PRESENTATION:A 78-year-old female was diagnosed with metastatic biphasic SS. Molecular profiling via targeted RNA sequencing identified a pathogenic PDE3A-NTRK2 fusion (Tier 1A) alongside the canonical SS18 rearrangement. Despite the presence of this usually actionable target, second-line treatment with larotrectinib resulted in rapid clinical deterioration and "explosive" tumor growth, signifying absolute primary resistance to TRK inhibition. The disease followed an aggressive course typical of chemorefractory SS, leading to the patient's death ten months after initial diagnosis. CONCLUSION:This case provides critical clinical evidence of the "driver versus passenger" phenomenon in precision oncology. It demonstrates that the epigenetic dominance of the SS18::SSX fusion can override the therapeutic relevance of a concurrent NTRK fusion. Our findings serve as a cautionary note: actionable targets detected via next-generation sequencing must be interpreted within the tumor's canonical biological context, as lineage-defining translocations may render secondary kinase alterations therapeutically inert.
Purpose: Liquid biopsy has emerged as a valuable tool for detecting therapeutic targets and resistance mechanisms. This study evaluated the analytical performance and clinical utility of TruSight Oncology 500 ctDNA (TSO500) compared to the FDA-approved Guardant360 CDx (G360) in detecting actionable alterations in non-small cell lung cancer (NSCLC) patients progressing on targeted therapies. Patients and methods: We analyzed 44 plasma samples from 36 consecutive metastatic NSCLC patients with known molecular drivers ( EGFR and BRAF mutations, ALK and RET fusions) progressing on targeted therapy. The comparative analysis included 31 paired samples from 27 patients. Valid results were obtained from G360 in 42/44 cases (95.45%) and TSO500 in 32/44 samples (72.8%). Results: TSO500 demonstrated high sensitivity for G360-identified variants (81.02% overall; 85.26% for pathogenic/likely pathogenic variants). Concordance was particularly high for ESCAT I alterations (95.2% sensitivity), including 100% sensitivity for gene fusions (five detected fusions). TSO500 identified 102 additional variants not detected by G360. Among nine patients with concurrent tissue biopsy, TSO500 detected 16 potentially actionable mutations absent in tissue samples. Both assays identified resistance mutations in 12/26 patients (46.2%), with TSO500 detecting all but three G360-identified alterations. High correlation was observed between variant allele frequencies (Pearson's r = 0.89). Conclusions: TSO500 demonstrates high concordance with G360 for detecting actionable alterations and robust fusion identification. Its ability to detect additional variants and resistance mutations not found in tissue highlights its potential value in guiding personalized treatment decisions for NSCLC patients.
BACKGROUND:Soft tissue and bone sarcomas may carry a considerable symptom burden, which typically worsens in the final weeks of life. To help clarify personalized palliative care needs, we investigated discrepancies in end-of-life management between patients with sarcoma and those with the most common carcinomas. PATIENTS AND METHODS:This retrospective cohort study enrolled all sarcoma patients who died between 1 January 2018 - 31 October 2023, either in the palliative care unit or in medical oncology units, at a large cancer hospital in northern Italy. Each patient with sarcoma was matched with up to three randomly selected patients with carcinoma. Matching was based on age, year of death and unit. Electronic health records were reviewed. RESULTS:Thirty-six patients with sarcoma were matched with 96 patients with carcinoma (44 lung cancer, 40 breast cancer and 12 colorectal cancer). Patients with sarcoma had a significantly higher chance of palliative sedation compared with patients with carcinoma (OR=32.5). The most common refractory symptom in patients with sarcoma was dyspnea (50%), followed by pain (26%). The average opioid dose difference between patient groups during sedation was as high as 220 mg. The final recorded Richmond Agitation-Sedation Scale score (RASS) was on average -4.4 for patients with sarcoma who died in hospice compared to -2.5 for those who died in an oncology unit. CONCLUSIONS:In our series, patients with sarcoma had a substantially higher risk of experiencing refractory symptoms requiring palliative sedation compared to patients with the most common cancers. Pain and dyspnea were the most common refractory symptoms in patients with sarcoma, resulting in higher dosages of opioids and possibly impacting sedation deepness. This study suggests that patients with sarcoma may pose special challenges to end-of-life care.
Despite innovations in diagnosis and treatment that have increased our ability to control cancer, it remains the second leading cause of death in Europe and is the principal cause in the under-65s. According to Eurostat, cancer accounted for 30.6% of all deaths in this age group in 2021, 40.6% for women and 25.6% for men.
Accurate preoperative imaging is essential for determining operability, guiding surgical planning, and optimizing outcomes in the treatment of non-small cell lung cancer (NSCLC). This paper outlines thoracic surgeons' expectations from radiologists in the preoperative evaluation of NSCLC, aiming to enhance multidisciplinary collaboration and improve radiologic reporting standards. A narrative review of imaging modalities-including CT, PET-CT, and MRI-was conducted to identify key radiologic parameters relevant to surgical decision-making. The paper integrates current Tumor, nodes, metastasis (TNM) staging criteria, tumor morphology, anatomical localization, and invasion patterns, with practical surgical implications. Radiologists are expected to provide precise measurements of tumor size and morphology, assess nodal involvement and metastatic spread, and identify critical anatomical relationships and variations. Imaging should detail tumor invasion into adjacent structures such as the chest wall, mediastinum, and vascular or airway components. The paper also emphasizes the importance of imaging in evaluating suitability for minimally invasive surgery, guiding lesion localization, and assessing underlying lung pathology and post-induction therapy response. A standardized, surgeon-oriented imaging report enhances surgical planning, reduces intraoperative risks, and supports personalized treatment strategies. This paper serves as a practical guide for radiologists to align imaging assessments with thoracic surgical needs, ultimately improving patient outcomes.
BACKGROUND:Alectinib, a second-generation ALK inhibitor, is used in first-line and adjuvant treatment for ALK-rearranged NSCLC, and has proven to be both effective and well tolerated. Gastrointestinal (GI) perforation is an extremely rare but potentially life-threatening complication, with only sporadic cases reported in the literature. METHODS:We describe, to the best of our knowledge, the largest case series to date of GI perforations that occurred during alectinib treatment in patients with ALK-rearranged NSCLC. Clinical features, management strategies, and outcomes were analyzed and integrated with available literature. RESULTS:Three female patients developed GI perforation after variable durations of alectinib treatment, ranging from one month to over three years. Two cases were associated with pre-existing diverticulosis, while one occurred in the absence of any known GI comorbidities. Management included conservative treatment with intravenous antibiotics in two cases and surgical intervention in one. Alectinib was permanently discontinued in all patients. Subsequent therapeutic strategies included lorlatinib or brigatinib, with heterogeneous tolerability and outcomes. Literature review identified other reports of GI perforation or severe toxicity under alectinib. CONCLUSIONS:Although rare, GI perforation, represents a clinically relevant adverse event associated with alectinib, particularly in patients with diverticulosis or other predisposing conditions. It is essential to optimize safety and long-term disease control by raising awareness of early warning symptoms, conducting a baseline GI evaluation in high-risk patients and carefully sequencing therapy after discontinuation.
Multiparametric Whole-Body Magnetic Resonance Imaging (WB-MRI) may enhance bone metastasis detection in metastatic breast cancer (mBC) patients. We report preliminary results from a prospective clinical trial investigating WB-MRI utility in BC patients with bone-predominant lesions, equivocal imaging findings or oligometastatic disease (OMD). Fifty-nine consecutive patients underwent baseline staging with standard imaging techniques (SIT), followed by WB-MRI. WB-MRI led to treatment-plan modifications in 40% of cases; 83% of lobular carcinoma cases exhibited additional metastases on WB-MRI. Among the 23 patients who underwent at least one reassessment by WB-MRI and SIT, the concordance rate was 69.6%. Among 18 OMD patients, WB-MRI led to the redefinition of the disease status in 44.4% of cases. These findings underscore the value of WB-MRI in BC.
