Cancers

Background: The histopathological assessment is critical in the comprehensive treatment process for patients diagnosed with oral squamous cell carcinoma (OSCC). A detailed and precise specimen characterization is essential to facilitate effective surgeon–pathologist communication. Methods: In response to this need, a user-friendly virtual communication protocol utilizing a 3D scanner has been developed. This study involved 50 patients with OSCC, whose resected tumors were directly scanned in the operating room and subsequently annotated and characterized using available software. Results: The direct application of annotations and descriptions onto the virtual tumor specimens significantly enhanced the quantity and accuracy of information conveyed to the pathologist. Conclusions: The proposed solution’s repeatability and standardized approach make integration into routine clinical practice feasible, thereby establishing a potential new standard in the field.

Purpose: Brain metastases (BM) in sarcomas occur rarely and are associated with poor prognosis. This study is a large retrospective cohort describing the demographic and clinical characteristics of these patients, treatment strategies, and survival outcomes. Methods: In total, 81 patients with BM from sarcomas were identified across five sarcoma centers. Demographic data, clinical presentation, and treatment modalities were analyzed. Results: The most common histologies were leiomyosarcoma (12.3%) and undifferentiated pleomorphic sarcoma (12.3%). The median time from sarcoma diagnosis to brain metastases was 1.9 years. Upon presentation, 88.9% of patients with BM from sarcomas were symptomatic with the most common presenting symptom being focal neurological deficits (37.9%) and headaches (22.1%). Higher-grade sarcomas were more likely to metastasize and were usually preceded by metastases to other sites, most commonly the lungs. One-year overall survival was 31% from initial sarcoma diagnosis, and the median time from diagnosis of BM until death was 6.0 months. For treatment, 60 (74.1%) patients had radiation, 39 (48.1%) patients had systemic therapy, and 29 (35.8%) patients had surgery. In a multivariate analysis, surgery (HR 0.30) and chemotherapy (HR 0.23) were found to be significantly correlated with improved survival outcomes. Although radiation as a whole was not found to significantly correlate with survival, improved outcomes were seen with stereotactic radiosurgery (SRS, mOS 11.6 mo) as opposed to whole-brain radiation therapy (WBRT, mOS 8.3 mo). Additionally, patients with leptomeningeal disease were significantly less likely to survive more than one year compared to patients with brain metastases only. Conclusions: Our findings identify that patients with metastatic sarcoma to the brain have poor prognoses, often have concurrent metastasis, and have a median survival of only 6 months. Additionally, our study found that leptomeningeal metastases is a rare presentation with poor survival outcomes. There are various treatment modalities for sarcomas with BM; however, there are no guidelines, unlike in other malignancies. Further research is necessary to evaluate the role of therapeutic measures in terms of type, timing, and outcomes.

Background: Detecting pathological lymph nodes (LNs) is crucial for establishing the proper clinical approach in patients with head and neck cancer (HNC). Positron emission tomography with [18F] fluorodeoxyglucose (FDG PET) has high diagnostic value, although it can yield false positives since FDG-avid LNs can also occur from non-cancerous diseases. Objectives: To explore if radiomics features from FDG PET can enhance the identification of pathological lymph nodes in head and neck cancer. Materials and methods: This study was carried out on n=51 cervical lymph nodes (26 negative, 25 positive) from a cohort of n=27 subjects, and the standard of reference was fine needle aspiration cytology or excisional biopsy. An initial set of 54 IBSI-compliant radiomics features, which was subsequently reduced to 31 after redundancy elimination, was considered for the analysis. Mann–Whitney U tests were performed to compare each feature between positive and negative LNs. Classification models based on two sets of features, PETBase (SUVmax, MTV and TLG) and PETRad (radiomics features), respectively, were trained using logistic regression, support vector machines and Gaussian naïve Bayes, and their performance was compared. Accuracy was estimated via leave-one-out cross-validation. Results: We identified via univariate analysis 21 features that were statistically different between positive and negative LNs. In particular, dispersion features indicated that positive LNs had higher uptake non-uniformity than the negative ones. AUC, sensitivity, specificity and accuracy obtained with logistic regression were, respectively, 0.840, 68.0%, 89.5% and 80.4% for PETBase and 0.880, 72.0%, 90.0% and 82.4% for PETRad. The other classification models showed the same trend. Conclusions: Radiomics features from FDG PET can improve the diagnostic accuracy of LN status in HNC.

Background: Hepatocellular carcinoma (HCC) is a prevalent type of primary liver cancer and one of the leading causes of cancer-related mortality worldwide. Antivascular Ultrasound (AVUS) is a novel therapy approach that utilizes the mechanical and thermal interactions between ultrasound and microbubbles to disrupt tumor vasculature or potentiate effects of chemotherapy or radiation therapy in a dose-dependent fashion. In this review, we aim to illustrate the mechanisms of AVUS, focusing on the preclinical and clinical evidence of AVUS applications in HCC. Methods: Peer-reviewed publications pertaining to the use of AVUS in HCC were collected and analyzed. Results: 12 preclinical studies and 1 clinical trial were analyzed. At lower energy levels, AVUS can enhance tumor perfusion, facilitating the delivery of chemotherapy agents and resulting in improved therapeutic outcomes. Conversely, at higher energy levels, AVUS can disrupt tumor perfusion, leading to ischemic damage of the tumors. Combining AVUS with other therapeutic approaches, such as chemotherapy, radiation therapy, and transarterial radioembolization (TARE), can synergistically enhance therapeutic outcomes. Conclusions: AVUS is a promising novel treatment modality for HCC. Current evidence suggests that AVUS exhibits a dose-dependent nature, making it a versatile approach that can be effectively combined with other therapeutic regimens. Further clinical studies and long-term follow-ups are needed to establish the optimal clinical protocol and safety profile of AVUS.

Background/Objectives: This retrospective observational study aimed to investigate the perioperative outcome in Malignant Peripheral Nerve Sheath Tumors (MPNSTs) with and without relation to Neurofibromatosis Type 1 (NF1) and to detect possible influencing factors. Methods: Clinical reports, histopathological evaluations, imaging, and treatment characteristics were reviewed in 35 operated MPNSTs in 33 patients. Possible predictive valuables included disease type, preoperative tumor volume, SUV and MIB-1 proliferation index, resection margins, the presence of metastasis, and whether radio-/chemotherapy was received. Results: Patients with NF1 were younger (mean age: 29 ± 13, 8–54 years) than sporadic cases (mean age: 45 ± 13, 24–67 years) and exhibited significantly larger preoperative tumor volumes (mean 299 vs. 18 cm3, p = 0.048). Most tumors were located in the facial/cervical/neck area (34%, n = 12), followed by the trunk (31%, n = 11), lower extremity (17%, n = 6), upper extremity (14%, n = 5), and intraspinal area (3%, n = 1). NF1-associated MPNSTs appeared predominantly on the trunk (39%) and sporadically in the facial/cervical/neck area (50%). Complete resection was possible in 66% and an improvement in or stability of function was achieved in most cases (motor 69%, sensory 74%), as well as a decrease in pain intensity (63%). NF1-associated MPNSTs exhibited more severe pain scores (median VRS scale 2, p = 0.002) compared to sporadic tumors (median VRS scale 0.5). Sporadic MPNSTs located at the head/facial/brachial plexus and upper extremities exhibited better preoperative functions compared to those on the lower extremities. In 12 cases with available [18F]FDG PET, the mean preoperative SUV (9.8 ± 7.2) positively correlated with the mean maximum MIB-1 index (34 ± 26%, p = 0.005) and the mean preoperative tumor volume (474.7 ± 68.6 cm3, p = 0.047). The overall survival (OS) was significantly longer in tumors with higher resection extents (R0, p = 0.01) and without accompanying metastasis (p = 0.046), and tended to be longer, but not significantly so, in sporadic MPNSTs. In six and seven tumors, with R1/R2 resection margins and present metastasis, respectively, solid or combined neo-/adjuvant radio-/chemotherapy led to a significantly shorter OS (p = 0.014). Conclusions: NF1-associated MPNSTs have larger tumor volumes, higher SUVs and MIB-1 proliferation indices, and a shorter overall survival period. Nevertheless, surgery can improve symptoms, particularly medication-resistant pain, and should also be considered in advanced disease for symptom control/improvement.

Cinobufagin (CB), a bufadienolide, has shown promising potential as an anticancer agent, particularly in combating lung cancer. This systematic review synthesizes preclinical evidence on CB’s effects against lung cancer, focusing on its mechanisms of action, efficacy, and potential clinical implications. We analyzed data from various preclinical studies involving both in vitro cell line models and in vivo animal models. The reviewed studies indicate that CB effectively reduces cell viability, induces apoptosis, and inhibits cell proliferation, migration, and invasion across multiple lung cancer cell lines and xenograft models. Specifically, CB was found to decrease cell viability and increase apoptosis in lung cancer cells by modulating key molecular pathways, including Bcl-2, Bax, cleaved caspases, caveolin-1, FLOT2, Akt, STAT3, and FOXO1. In vivo studies further demonstrated significant inhibition of tumor growth with minimal toxicity. However, limitations include reliance on in vitro models, which may not fully represent in vivo tumor dynamics, and a lack of long-term safety data. The studies also vary in their methodologies and cell line models, which may not accurately encompass all lung cancer subtypes or predict human responses. Despite these limitations, CB’s ability to target specific molecular pathways and its promising results in preclinical models suggest it could be a valuable addition to lung cancer treatment strategies. Our review suggests further clinical trials to validate its efficacy and safety in humans. Future research should explore combination therapies and optimize delivery methods to enhance clinical outcomes.

Background/Objectives: Time to treatment initiation (TTI) has been identified as a predictor of survival in many cancers, but its impact on malignant pleural mesothelioma (MPM) is unknown. This study investigates factors influencing TTI in MPM and its association with overall survival. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to obtain data for MPM patients in the United States. TTI was defined as the number of days from diagnosis to initiation of first treatment, and delayed TTI was defined as exceeding the median TTI. Χ2 tests and t-tests compared sociodemographic and clinical differences between early and delayed TTI groups, while Kaplan–Meier and Cox proportional hazards models evaluated relationships between prognostic factors, TTI, and survival. Results: Among 4879 MPM patients, the median TTI was 39 days. Median survival was 10 months among early TTI patients and 13 months among delayed TTI patients. Patients with epithelioid histology were more likely to have delayed TTI, as were patients who received combination therapy or were diagnosed more recently (p < 0.0001). Adjusting for covariates, delayed TTI status remained associated with better survival (HR 0.79, 95% CI: 0.74–0.84). Conclusions: This study presents an important insight into the management of MPM, demonstrating that delayed time to treatment initiation is positively associated with improved overall survival, contrary to findings in most cancers. This finding underscores the importance of comprehensive, multidisciplinary care, as delays due to robust staging evaluations and patient travel to high-volume centers of excellence likely contribute to delays in treatment. Taken together, these results suggest that clinicians should prioritize personalized treatment planning and collaborative care over a push to rapidly initiate treatment to optimize patient outcomes in MPM.

Introduction: Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, despite advances in immune checkpoint inhibitors and targeted therapies. Antibody–drug conjugates (ADCs) represent a promising therapeutic approach by delivering cytotoxic agents specifically to cancer cells, potentially reducing harm to healthy tissues. This study aims to explore the effectiveness and challenges associated with ADCs in NSCLC, with a focus on drug-induced interstitial lung disease (D-ILD). Methods: A comprehensive literature review was conducted across MEDLINE (Ovid), Embase (Elsevier), CENTRAL (Cochrane Library), and other sources up to March 2023, to identify ADCs used in NSCLC treatment and their associated risk of D-ILD. The incidence of ILD was analyzed from clinical trial data, while ADC target expression was examined through RNA and protein levels in normal and tumor lung tissues. Discussion: Our findings highlight the therapeutic potential of ADCs in NSCLC, as evidenced by significant clinical outcomes. However, the occurrence of D-ILD presents a notable challenge, as its incidence was not directly correlated with the expression levels of the target antigens. This suggests that D-ILD may result from factors beyond antigen expression, including the cytotoxic payload and linker characteristics of ADCs. Conclusion: ADCs offer a promising avenue for NSCLC treatment. Nonetheless, the risk of D-ILD necessitates a balanced approach in ADC development, focusing on optimizing linker and payload properties to mitigate this adverse effect. Further research is essential to better understand and manage D-ILD, ensuring the safe and effective use of ADCs in clinical practice.

Background/Objectives: Pentraxin 3 (PTX3), a member of the pentraxin superfamily, plays diverse roles in immunity and inflammation. Its dual role in tumorigenesis, exhibiting both protumoral and antitumoral effects, has been the subject of conflicting reports. High PTX3 expression levels in serum and tumor tissues have been associated with poor prognosis in various malignancies, suggesting its potential as a prognostic biomarker. Through this meta-analysis, we aim to comprehensively assess the prognostic significance of PTX3 protein expression in human malignancies and evaluate its potential as a pan-cancer prognostic marker. Methods: A systematic literature search was conducted across the PubMed, Embase, Web of Science, MEDLINE, and Cochrane Library databases. Studies were included if they assessed the association between PTX3 protein expression and overall survival (OS) in cancer patients. Hazard ratios (HRs) were pooled using a random-effects model. Subgroup analyses were performed based on the method of PTX3 assessment, and publication bias was evaluated using Egger’s and Begg’s tests. Results: Nine studies encompassing 1215 patients were included in the analysis. High PTX3 expression was significantly associated with poorer OS (HR = 1.89, 95% CI = 1.55–2.32, p < 0.01) with no significant heterogeneity (I2 = 0%). Subgroup analysis revealed consistent results across different assessment methods (immunohistochemistry: HR = 1.93, p < 0.01; immunoassay: HR = 1.86, p < 0.01). However, publication bias was detected (Egger’s test, p = 0.03). Conclusions: High PTX3 protein expression is associated with a poor prognosis in various malignancies, supporting its potential as a prognostic biomarker.

Background: Adjuvant trastuzumab is the standard of care for HER2+ breast cancer (BC) patients. However, >50% of patients become resistant. This study aimed at the identification of the molecular factors associated with disease relapse and their further investigation as therapeutically exploitable targets. Methods: Analyses were conducted on formalin-fixed paraffin-embedded tissues of the primary tumors of relapsed (cases) and not relapsed (controls) HER2+ BC patients treated with adjuvant trastuzumab. The nCounter Human Breast Cancer Panel 360 was used. Logistic regression and partitioning around medoids were employed to identify the genes associated with disease recurrence. Cytotoxicity experiments using trastuzumab-resistant cell lines and a network pharmacology approach were carried out to investigate drug efficacy. Results: A total of 52 patients (26 relapsed and 26 not relapsed) were analyzed. We found that a higher expression of HDAC6 was significantly associated with an increased risk of recurrence, with an adjusted OR of 3.20 (95% CI 1.38–9.91, p = 0.016). Then, we investigated the cytotoxic activity of the selective HDAC6 inhibitor Nexturastat A (NextA) on HER2+ cell lines, which were both sensitive and trastuzumab-resistant. A sub-cytotoxic concentration of NextA, combined with trastuzumab, showed a synergistic effect on BC cell lines. Finally, using a network pharmacology approach, we identified HSP90AA1 as the putative molecular candidate responsible for the synergism observed in vitro. Conclusions: Our findings encourage the exploration of the role of HDAC6 as a prognostic factor and the combinatorial use of HDAC6 selective inhibitors combined with trastuzumab in HER2+ BC, in particular for those patients experiencing drug resistance.