Urothelial carcinoma predominantly affects older patients, who often exhibit frailty, comorbidities, renal impairment, and reduced physiological reserve. We evaluated overall survival (OS) and progression-free survival (PFS) with first-line immune-based strategies in patients aged ≥65 years with advanced or metastatic urothelial carcinoma. The aim was to characterize treatment effects within this age-defined subgroup, not to determine whether age modifies treatment efficacy compared with younger patients. Methods: We conducted a systematic review and meta-analysis of phase 3 randomized trials published from January 2015 to May 2026 reporting age-specific survival outcomes. Combination regimens were compared with platinum-based chemotherapy using random-effects models. Results: Combination strategies improved OS versus chemotherapy (HR 0.79, 95% CI 0.64–0.96), although heterogeneity was substantial (I2 = 69.7%) and the prediction interval crossed the null (0.48–1.27). Class-specific HRs were 0.56 (95% CI 0.26–1.20) for ADC plus ICI, 0.85 (0.77–0.95) for ICI plus chemotherapy, and 0.91 (0.34–2.42) for dual-checkpoint inhibition. PFS favoured experimental treatment but remained imprecise (HR 0.54, 95% CI 0.27–1.08; I2 = 89.5%). Excluding ADC plus ICI trials attenuated the OS effect (HR 0.88, 95% CI 0.80–0.96), indicating that the pooled estimate was influenced by these trials. ICI monotherapy did not improve OS. Conclusions: First-line immune-based combinations improved survival in selected patients aged ≥65 years, but benefit varied across treatment classes and should not be considered uniform across regimens. These findings do not establish whether age modifies treatment efficacy. Age-specific safety data were insufficient to define the benefit–risk profile of individual strategies.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Over the last decade, the therapeutic landscape of advanced HCC has substantially evolved following the introduction of immune checkpoint inhibitor-based combinations, including anti-programmed death ligand 1 (PD-L1) plus anti-vascular endothelial growth factor (VEGF) agents and dual immune checkpoint blockade strategies targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4). Nevertheless, the optimal timing and integration of locoregional therapies following systemic treatment remain poorly defined, particularly in patients achieving major radiological responses. In this setting, multidisciplinary evaluation is essential to guide individualized therapeutic strategies. CASE SUMMARY: Herein we present the case of a 68-year-old male with advanced HCC. First-line systemic treatment with atezolizumab plus bevacizumab was administered for six cycles, resulting in a major radiological and biochemical response. Following multidisciplinary discussion, selective transarterial embolization (TAE) was performed as consolidative locoregional treatment. At the last follow-up evaluation at 42 months, the patient remained alive with no evidence of disease recurrence. CONCLUSION: Our case highlights the potential role of a multidisciplinary therapeutic strategy in selected patients with advanced HCC. The integration of systemic immunotherapy-based treatment with consolidative locoregional therapy may enable successful downstaging and durable disease control, suggesting a possible role of leftward treatment stage migration in advanced unresectable HCC.

BACKGROUND:Postoperative circulating tumor DNA (ctDNA) is an emerging biomarker for molecular residual disease (MRD) detection in early-stage colorectal cancer (CRC). However, its prognostic value in patients with resected metastatic disease has not been comprehensively assessed. This study aimed to evaluate the association between postoperative ctDNA detection and survival outcomes, including after completion of adjuvant chemotherapy (post-ACT), in patients with metastatic CRC (mCRC) treated with curative intent. METHODS:A systematic search of PubMed/MEDLINE, Scopus, and Embase was conducted up to March 17, 2025. Eligible studies included adults with mCRC undergoing curative intent treatment, reporting hazard ratios (HRs) for time-to-event outcomes according to postoperative ctDNA status. Random-effects meta-analyses were performed to pool HRs for recurrence-free survival (RFS) and overall survival (OS). Risk of bias was assessed using the QUIPS tool. The study followed PRISMA guidelines and was registered in PROSPERO (CRD42024528320). RESULTS:Sixteen studies (N = 1048) were included. Postoperative ctDNA positivity was detected in 409 patients (39.0%) and was associated with significantly worse RFS (16 studies; HR = 4.45, 95% CI, 3.44-5.75; P < 0.0001) and shorter OS (9 studies; HR = 6.23; 95% CI, 3.15-12.33, P = 0.0003). Notably, post-ACT ctDNA positivity (N = 96, 41.4%) remained associated with recurrence (5 studies; HR, 6.08; 95% CI, 4.04-9.16; P < 0.001). CONCLUSIONS:Postoperative ctDNA positivity in mCRC treated with curative intent is strongly associated with increased risk of recurrence and mortality. These findings support its role as a consistent prognostic biomarker and highlight the need for biomarker-guided clinical trials in this setting.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for several solid tumors. Among the mechanisms investigated to explain variability in ICIs efficacy, the potential effect of the time-of-day (ToD) at which ICIs are administered has emerged as an area of interest. This review summarizes the evidence on the impact of ToD administration of ICIs in solid tumors. A comprehensive manual search of two leading international databases, PubMed/MEDLINE and Scopus/ELSEVIER, was conducted to identify relevant studies. An exploratory pooled analysis of the included studies was performed. The pooled effect size was expressed as HR with 95

Characteristics of patients significantly differ between registrational clinical trials (CTs) and Italian real-world practice, with older median age, higher elderly (≥ 65) rate and worse performance status (PS) in the latter, without imbalance in female rate. We compared the same characteristics between registrational phase 2/3 and phase 1 CTs. Data on age, sex and PS were extracted from European Public Assessment Reports of European Medicines Agency. Weighted means and standard deviations were calculated in both groups and differences were described overall, by cancer type and drug class. We collected 103 phase 2/3 and 111 phase 1 CTs, supporting 97 therapeutic indications. Age and sex were compared in 59 indications. Mean median age (SD) was 60.7 (5.1) years in phase 2/3 and 59.7 (5.6) years in phase 1 (p = 0.051). Age difference was greater for skin and breast cancer; no heterogeneity emerged among drug classes. Mean female rate was not statistically significantly lower in phase 2/3 than phase 1 CTs overall, (mean difference − 4.9

Background: Breast cancer remains the leading cause of cancer-related deaths among women despite advances in early detection. Neoadjuvant chemotherapy (NACT) is now standard for early-stage BC, with vitamin D (VD) emerging as a potential prognostic biomarker considering its positive pleiotropic effects. This review and meta-analysis assess the impact of baseline VD levels on outcomes in BC patients undergoing NACT. Methods: Inclusion criteria required patients to be over 18 years of age, have a pathologically confirmed BC diagnosis, and have their VD levels assessed prior to chemotherapy. Studies were included if they reported odds ratios (ORs) for response and/or hazard ratios (HRs) for PFS with 95% confidence intervals (CIs). A comprehensive literature search of PubMed/MEDLINE and Scopus/ELSEVIER (2014–2024) was conducted, and data were analyzed using fixed- and random-effects models, with Forest plots illustrating the results. Study quality and potential biases were assessed using the MINORS, NOS, and RoB2 scales, and statistical heterogeneity was evaluated with I2 statistics and funnel plots. Results: Six studies were included in the analysis. All studies addressed stages II and III, with three also including stage I. The meta-analysis covered data from 722 patients regarding NACT response and 1033 patients for PFS. The results revealed a 22% reduction in the likelihood of non-response to NACT associated with adequate VD levels (low/deficient VD vs. high/sufficient VD; OR: 0.78; 95% CI: 0.30–1.25; p = 0.001) and a 35% reduction in progression risk with sufficient baseline VD levels (low/deficient VD vs. high/sufficient VD; HR: 0.65; 95% CI: 0.33–0.97; p < 0.001). Conclusions: These findings highlight the significance of maintaining adequate vitamin D levels in BC treatment and encourage further studies to unravel the role of VD on cancer biology.

BACKGROUND Squamous cell carcinoma of the head and neck (SCCHN) accounts for 3% of all malignant tumors in Italy. Immune checkpoint inhibitors combined with chemotherapy is first-line treatment for SCCHN; however, second-line treatment options are limited. Taxanes are widely used for combination therapy of SCCHN, as clinical trials have shown their efficacy in patients with this disease, particularly in patients with prior therapy. AIM To perform a multicenter retrospective study on the efficacy and safety of weekly paclitaxel for SCCHN. METHODS All patients were previously treated with at least one systemic therapy regimen, which included platinum-based therapy in the vast majority. No patient received prior immunotherapy. RESULTS Median progression-free survival (mPFS) was 3.4 months and median overall survival (mOS) was 6.5 months. Subgroup analysis was performed according to three principal prognostic factors: Smoking, alcohol consumption, and body mass index. Analysis demonstrated reduced survival, both mOS and mPFS, in the unfavorable prognostic groups, with the biggest deltas observed in mOS. CONCLUSION Weekly paclitaxel provided favorable survival and disease control rates, with low severe adverse events. Paclitaxel is a safe and valid therapeutic option for patients with SCCHN who received prior therapy.

Abstract Background Vitamin D (VD) is implicated in various health conditions, including colorectal cancer (CRC). To investigate potential relationships between pre-chemotherapy VD levels and the time-to-outcome in metastatic CRC patients, we conducted a systematic review and meta-analysis. Methods Following the PRISMA 2020 guidelines, we performed thorough searches in PubMed/MEDLINE and Scopus/ELSEVIER databases (covering the years 2002 to 2022). Inclusion criteria mandated studies to report on individuals aged 18 years and above with histologically confirmed stage IV CRC. Additionally, studies needed to provide data on VD levels before chemotherapy, along with hazard ratios (HR) and 95% confidence intervals (CIs) for overall survival (OS) and/or progression-free survival (PFS). Five articles were identified with the aim of establishing a combined risk estimate for death and progression based on pre-chemotherapy VD levels. Heterogeneity among studies and publication bias were evaluated using Tau2, I2 statistics, and a Funnel plot. Results Although no significant heterogeneity was observed in time-to-outcome among the selected studies, variations in technical assessments and serum VD concentration measurements were noted. The pooled analysis, involving 1712 patients for OS and 1264 patients for PFS, revealed a 47% increased risk of death (HR: 1.47, 95% CI: 1.21–1.79) and a 38% increased risk of progression (HR: 1.38, 95% CI: 1.13–1.70) for patients with lower VD levels, as indicated by fixed-effects models. Conclusions Our results emphasize the adverse effects of low VD concentration on the time-to-outcome in metastatic CRC patients. This underscores the importance of investigating VD supplementation as an innovative approach in this clinical setting to enhance patient outcomes.

We report the case of a patient with a BRAFV600E mutant mCRC, with evidence of acquired 'NeoBRAF wild-type' (wt) state. The patient, longitudinally assessed by liquid biopsy, obtained a remarkable clinical outcome with a multimodal approach including surgery, systemic treatment and targeted therapy. In patients with newly diagnosed RAS and BRAFV600E mutant mCRC, longitudinal assessment with liquid biopsy is not routinely used in clinical practice. We report the case of a patient with a BRAFV600E mutant mCRC, with evidence of acquired 'neoBRAF wild-type' (wt) state. The patient obtained a remarkable clinical outcome and has been longitudinally assessed by liquid biopsy.

Background: Vitamin D (VD) has been implicated in several diseases, including colorectal cancer (CRC). This study aimed to determine whether there is an association between VD levels and time-to-outcome in stage III CRC patients through a systematic review and meta-analysis. Methods: The study adhered to the PRISMA 2020 statement. Articles were searched in PubMed/MEDLINE and Scopus/ELSEVIER. Four articles were selected, with the primary objective of providing a pooled estimate of the risk of death specifically in stage III CRC patients based on pre-operative VD levels. Study heterogeneity and publication bias were analyzed using Tau2 statistics and funnel plots. Results: The selected studies showed significant heterogeneity regarding time-to-outcome, technical assessments, and serum VD concentration measures. The pooled analysis of 2628 and 2024 patients revealed a 38% and 13% increase in the risk of death (HR: 1.38, 95% CI: 0.71–2.71) and recurrence (HR: 1.13; 95% CI: 0.84–1.53), respectively, for random-effects models among patients with lower levels of VD. Conclusions: Our findings suggest that a low concentration of VD has a significant negative impact on time-to-outcome in stage III CRC.

BACKGROUND: Angiosarcoma (AS) of the breast is very rare, accounting for 1% of all soft tissue breast tumors. AS may present as primary tumors of the breast or as secondary lesions usually associated with previous radio-therapy. Commonly, secondary AS affects old-er women (median age 67-71 years) with a clin-ical history of breast cancer. The preferred site of onset of RIAS is the edge of radiation fields, where radiation doses and tumor necrosis may be heterogeneous, resulting in a DNA damage and instability. Radical surgery is the treatment of choice, but no clear consensus exists on sur-gical management of breast AS.CASE REPORT: We describe an atypical case of relapsed RIAS after radical mastectomy, treat-ed with new surgery and, considering the higher risk of recurrence, subsequent adjuvant chemo-therapy with weekly paclitaxel.CONCLUSIONS: The frequency of radiation -in-duced angiosarcomas (RIAS) after breast -con-serving surgery and radiotherapy has been in-creased to 0.14-0.5% among long survivors. Nev-ertheless, even if RIAS continues to be prognos-tically an extremely unfavorable cancer due to a high rate of recurrence, distant spread, and me-dian overall survival (OS) of about 60 months, the benefits of loco-regional breast radiotherapy are clearly higher than the risk in developing angio-sarcoma.

Glioblastoma multiforme is one of the most frequent and aggressive primary tumors in the central nervous system, representing >60% of all brain tumors in adults. Despite treatment, prognosis remains poor with most if not all patients experiencing disease recurrence and a 2-year survival rate of 27%. At present, no confirmed standard treatment exists for recurrent glioblastoma. Regorafenib is one of the few options available, based on results from the REGOMA trial. In the present study, a real-life retrospective investigation on the role of regorafenib in patients with recurrent glioblastoma (>60 years old) from two main Oncological Units in South Italy (Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy and Ospedale Civile San Giovanni di Dio, Frattamaggiore, Naples, Italy), was performed. The primary endpoint was overall survival (OS), whereas progression-free survival (PFS), objective response rate and disease control were secondary endpoints. Survival was then analyzed according to age, isocitrate dehydrogenase (IDH) and methylated methylguanine-DNA-methyltransferase (MGMT) status. A total of 56 patients met the eligibility criteria. The intention to treat population median PFS (mPFS) was 4.1 months and median OS (mOS) was 6.8 months. Age did not appear to have a significant influence on mPFS. mOS in MGMT-methylated patients was improved compared with that of the unmethylated group (7.7 months vs. 5.6 months). Both mOS and mPFS were longer in IDH-mutant patients. The present study was one of the first real life analyses of regorafenib in recurrent glioblastoma. The results were in line with the REGOMA trial. Age did not appear to be a prognostic factor, thus suggesting that treatment choice should not be different in elderly. MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies.

Lung cancer is the leading cause of cancer-related death and the most diagnosed cancer. The treatment of Non-Small Cell Lung Cancer (NSCLC) depends on clinical staging. Surgical radical resection is recommended for patients with stage 1 or 2 of disease and represents the treatment of choice. In the last decades, the surgical approach for lung cancer changed moving from an open approach to a minimally invasive approach, represented by Video Assisted Thoracic Surgery (VATS) and Robot-Assisted Thoracic Surgery (RATS). In this chapter, we illustrate the characteristics of lung cancer, the diagnosis, the classification, the staging and the preoperative evaluation. Then we focus on the surgical treatment of lung cancer and on how it has changed during the years. We explain the open approach represented by the traditional posterolateral thoracotomy and by the muscle-sparing thoracotomy. We illustrate VATS approach and evolution: from the hybrid approach to the pure VATS that can be triportal, biportal or even uniportal. Then, we focus on RATS approach, characterized by the use of multiple ports in the same intercostal space and how it evolved toward the uniportal approach. The objective is to combine the advantage of uniportal VATS (lower postoperative pain, enhanced recovery) and RATS (better visualization, more degrees of movements).

Background Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm, generally arising in the visceral pleura. It rarely originates from other sites such as trachea, orbital cavities, nasal cavities, peritoneum, paranasal sinuses, meninges, salivary glands, thyroid gland, diaphragm, liver, pancreas, lung kidney, adrenal gland, mediastinum, spermatid cord, pericardium, urinary bladder, prostate, uterine cervix, testis, spinal cord, periosteum, skin, soft tissue and bone. Case Description We present a surgical case of a rare primary tracheal tumor. High resolution computed tomography (HRCT) scan of the chest showed a 5 mm hypodense lesion, located on the right lateral wall of the proximal third of trachea; however the tracheal lumen was normal. We performed a rigid bronchoscopy in order to remove the endotracheal tumor with palliative purposes only. For this reason, we did not perform a prior histologic examination. The lesion was easily removed with common biopsy forceps and with standard aspirator. The debulking of the tumor was achieved with the use of laser Nd-YAP, electrocautery was used also for hemostasis to prevent bleeding during the operation. Without complications during the endoscopic treatment, the procedure was well tolerated by the patient. The pathological diagnosis was SFT. Conclusions SFT located in the trachea can be endoscopically resceted. Endoscolical treatment is indicated for patients with poor clinical conditions (heart disease, respiratory failure) that are not elegible for surgical resection.

Glioblastoma multiforme (GBM) is one of the most frequent and aggressive primary tumors in the central nervous system, representing more than 60% of all brain tumors in adults. Primary GBM remains incurable with a poor prognosis both for limited therapeutic alternatives and for a high risk of progression or recurrence. In fact, at recurrence, the few treatment options available, and often characterized by limited effectiveness, have always been an Achilles' heel. The recent approval of second line of regorafenib, a multikinase inhibitor, has given hope after several years of darkness for new therapies in the treatment of GBM. Indeed, in the REGOMA trial, a phase 2 study, regorafenib was the first drug to show a statistically significant improvement in median overall survival compared with lomustine group, usually used in the second-line treatment after temozolomide failure. We report a case of a 43-year-old patient affected by GBM in treatment with regorafenib in third line of therapy with good disease control and long PFS.

In recent years, the advanced knowledge of clinical, biological and molecular features of prostate cancer have led to the introduction of new drugs and have allowed the relocation of old drugs in different settings. In this way, the new concepts of systemic disease arise: high risk or high volume vs. low risk and low volume disease castration sensitive prostate cancer (CSPC), diversifying the use of previously approved drugs (CRPC) and opening new scenarios for sequence therapy. The aim of this review is to integrate new developments into the medical management of systemic prostate cancer.

Abstract OBJECTIVEVideo-Assisted Thoracic Surgery (VATS) resection, of deep-seated and nodules smaller than 3 cm, is very hard.Solitary, small and deep-seated pulmonary nodules are difficult to palpate or to see during VATS. We aimed to evaluated the validity of Intraoperative lung ultrasound (ILU) to visualize solitary and deep-seated pulmonary nodules smaller than 3 cm to enhance knowledge on the ultrasound morphological patterns.RESULTSUS processor was inserted by expert ultrasound surgeon into the chest through the operating hole, and the mediastinal, costal and diaphragmatic surfaces of the lung were explored.VATS- Ultrasound (VATS-US) allows to identify size, localization and Ultrasound (US) pattern of the lesions of interest.Accuracy of Intraoperative Lung Ultrasound for the detection of pulmonary nodules was calculated-comparing the two groups; the first group in which the patients did not undergo intraoperative ultrasound and the second group in which the patients underwent intraoperative ultrasound.Student's t-test (p<0,0001) showed that the accuracy of intraoperative ultrasound by comparing detection time of nodules in the two groups.Intracavitary VATS-US is a reliable, feasible, real-time and effective method of localization of parenchymal lung nodules during selected wedge resection procedures.

Background: Vitamin D exerts multiple beneficial effects in humans, including neuronal, immune, and bone homeostasis and the regulation of cardiovascular functions. Recent studies correlate vitamin D with cancer cell growth and survival, but meta-analyses on this topic are often not consistent. Methods: A systematic search of the PubMed database and the Clinical Trial Register was performed to identify all potentially relevant English-language scientific papers containing original research articles on the effects of vitamin D on human health. Results: In this review, we analyzed the antioxidant and anti-inflammatory effects of vitamin D against acute and chronic diseases, focusing particularly on cancer, immune-related diseases, cardiomyophaties (including heart failure, cardiac arrhythmias, and atherosclerosis) and infectious diseases. Conclusions: Vitamin D significantly reduces the pro-oxidant systemic and tissue biomarkers involved in the development, progression, and recurrence of chronic cardiometabolic disease and cancer. The overall picture of this review provides the basis for new randomized controlled trials of oral vitamin D supplementation in patients with cancer and infectious, neurodegenerative, and cardiovascular diseases aimed at reducing risk factors for disease recurrence and improving quality of life.

Traditionally, lymph node metastases (LNM) evaluation is essential to the staging of colon cancer patients according to the TNM (tumor-node-metastasis) system. However, in recent years evidence has accumulated regarding the role of emerging pathological features, which could significantly impact the prognosis of colorectal cancer patients. Lymph Node Ratio (LNR) and Log Odds of Positive Lymph Nodes (LODDS) have been shown to predict patients' prognosis more accurately than traditional nodal staging and it has been suggested that their implementation in existing classification could help stratify further patients with overlapping TNM stage. Tumor deposits (TD) are currently factored within the N1c category of the TNM classification in the absence of lymph node metastases. However, studies have shown that presence of TDs can affect patients' survival regardless of LNM. Moreover, evidence suggest that presence of TDs should not be evaluated as dichotomic but rather as a quantitative variable. Extranodal extension (ENE) has been shown to correlate with presence of other adverse prognostic features and to impact survival of colorectal cancer patients. In this review we will describe current staging systems and prognostic/predictive factors in colorectal cancer and elaborate on available evidence supporting the implementation of LNR/LODDS, TDs and ENE evaluation in existing classification to improve prognosis estimation and patient selection for adjuvant treatment.

Introduction Video-assisted thoracic surgery (VATS) for ipsilateral reoperations is controversial, because after the first surgical intervention, pleural adhesions occur frequently in the thoracic cavity and/or chest wall. This study assessed the usefulness of preoperative ultrasonography to reduce the incidence of lung injury at the time of the initial port insertion during secondary ipsilateral VATS. Materials and methods This was a retrospective, single-center study. Nine patients who underwent thoracic surgery at Vanvitelli Hospitalfrom September 2019 to February 2022, were scheduled for a second VATS surgeryon ipsilateral lung, because of inconclusive intraoperative histologic examination. All nine patients underwent preoperative ultrasonography to assess the possible presence of pleural adhesions. We evaluated the lung sliding, since the presence of pleural adhesions does not permit to appreciate it. Statistical analysis Hard severe adhesions were observed in all nine patients without sliding lung sign (specificity 100%). In this series, the sensitivity, PPV, and NPV of the sliding lung sign were 93%, 100% and 94% respectively. Results The presence of the lung respiratory changes can be evaluated as the “sliding lung sign” by chest ultrasonography; we believe that the sliding lung sign might also predict intrathoracic adhesion. Conclusions Preoperative detection of pleural adhesions using transthoracic ultrasonography was useful for ipsilateral secondary pulmonary resection patients undergoing VATS. Using preoperative ultrasonography can improve the safety and feasibility of placing the initial port in VATS.