Cancer Management and Research最新文献

Pancreatic cancer (PC) remains one of the most challenging malignancies to treat. Current therapeutic options are unsatisfactory, and there is an urgent need for more effective and less toxic drugs to improve the dismal prognosis of PC. In recent years, drug repurposing (DR) has emerged as an attractive strategy to identify novel treatments for PC by leveraging existing drugs approved for other indications. Through the use of electronic medical records, Artificial Intelligence, study of metabolic pathways, signalling pathways, and many other approaches, it has become much easier in recent years to identify potential novel uses for old drugs. Although policy, funding and research attention in this area are steadily growing, major challenges to efficient and effective patient-centric DR in PC need to be addressed. These include but are not limited to regulatory, financial and funding barriers and the lack of coordination and collaboration among several sectors and stakeholders. To explore the opportunities and challenges associated with DR in PC, a one-day multi-stakeholder meeting was held on 14^th of November 2024 in Brussels, Belgium as part of the REMEDi4ALL project. This meeting provided a platform for researchers, clinicians, industry representatives, funders, regulatory experts, and patient advocates to discuss and propose actions to optimize and accelerate DR in PC. Insights from this meeting support the potential of DR to enhance PC treatment options while highlighting the importance of systemic and supportive changes in the regulatory, policy and funding landscapes, interdisciplinary collaboration, data sharing, and patient involvement in driving therapeutic innovation. This summary highlights key outcomes and recommendations from the meeting in informing future efforts to advance DR initiatives in the context of PC.

Background: Real-world data on treatment patterns and survival outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) remain limited. This study aims to characterize treatment sequencing, duration across lines of therapy, and survival outcomes in patients with mHSPC.

Methods: This single-center, retrospective, non-interventional study included men newly diagnosed with mHSPC at King Abdullah Medical City Cancer Center between 2016 and 2023. Treatment patterns, including sequencing and duration of therapy, were described. Kaplan-Meier methods were used to estimate overall survival (OS) from mHSPC diagnosis to death or censoring at the end of follow-up.

Results: Among 102 patients, the mean age was 70 years, BMI of 26, with 53% having a performance status of 2. Comorbidities included hypertension (51%), diabetes (45%), and cardiovascular disease (20.6%). Nearly half (48%) had a Gleason score of nine, with 62.7% presenting with bone metastases. Novel hormonal therapy (NHT) was the predominant first-line treatment (86%), with abiraterone used in 43% of cases. Second- and third-line treatments were received by 34% and 13% of patients, respectively. The median durations of first-, second-, and third-line therapies were 21, 5, and 2.6 months, respectively. Median OS from diagnosis was 24 months.

Conclusion: Despite the predominant use of novel hormonal therapy (NHT), patients in this cohort exhibited aggressive disease and poor survival outcomes. These findings highlight a critical need for more intensive and tailored treatment strategies for mHSPC.

Background: Gastric cancer (GC) is among the most lethal malignancies worldwide. Due to the substantial heterogeneity of GC, more accurate molecular typing systems are desperately required to enhance the prognosis of GC patients.

Methods: The major immune cell subclusters in GC were identified by a single-cell RNA sequencing (scRNA-seq) dataset. High-dimensional weighted gene coexpression network analysis (hdWGCNA) and multiple bioinformatics methods were utilized to classify the molecular subtypes of GC and further investigate the differences among the subtypes. Based on the module genes and differentially expressed genes (DEGs), random survival forest analysis was applied to identify the key prognostic genes for GC, and the roles and functional mechanisms of the key genes in GC were explored by clinical samples and cellular experiments.

Results: Two distinct GC molecular subtypes (C1 and C2) associated with neutrophils were identified, with C1 associated with better prognosis. Compared with C2 subtype, C1 subtype has significant differences in immune infiltration, immune checkpoint expression, signaling pathway regulation, tumor mutation burden, and immunotherapy and chemotherapeutic drug sensitivity. Three new key genes (VIM, RBMS1 and RGS2) were revealed to be highly correlated with the prognosis of GC patients. In addition, the expression and cellular functions of key genes RBMS1 and RGS2 in gastric carcinogenesis were verified.

Conclusion: We identified two neutrophil-related molecular GC subtypes with different prognostic outcomes and clinical significance. VIM, RBMS1 and RGS2 were identified as potential prognostic markers and therapeutic targets for GC. These findings provide a new perspective for the molecular typing and personalized treatment of GC.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for 85% of all cases, with a poor 5-year survival rate of less than 20%. The majority of NSCLC patients are diagnosed at an advanced stage, contributing to the low survival rate. Platinum-based chemotherapy, including cisplatin and carboplatin, remains the cornerstone of treatment for advanced NSCLC. However, DNA repair mechanisms often hinder treatment efficacy, notably Base Excision Repair (BER), mediated by the X-ray Repair Cross Complementing 1 (XRCC1) protein. This review aims to investigate the role of XRCC1 polymorphisms in platinum resistance, focusing on their impact on DNA repair efficiency. XRCC1's involvement in the BER pathway is critical for repairing DNA damage caused by platinum agents, and polymorphisms in XRCC1 have been linked to altered repair capacity, influencing clinical outcomes and resistance to platinum-based chemotherapy in NSCLC patients.

Objective: To evaluate the clinical efficacy of nab-paclitaxel based chemotherapy in the treatment of advanced epithelioid hemangioendothelioma (EHE).

Methods: Since March 2022, chemotherapy has been recommended for patients with advanced EHE characterized by large tumors (liver tumors > 10 cm or tumors in other organs > 3 cm), rapid tumor progression, severe symptoms, serosal effusion, and treatment failure. Two chemotherapy regimens were administered: nab-paclitaxel plus bevacizumab and nab-paclitaxel plus sirolimus. Clinical data and outcomes were retrospectively analyzed.

Results: From March 2022 to August 2024, 21 patients with histologically confirmed EHE who received nab-paclitaxel based chemotherapy were included. At baseline, 18 patients (85.7%) presented with tumor-related symptoms, and serosal effusion was detected in 12 patients (57.1%). Among patients with hepatic EHE, six (28.6%) had tumors > 10 cm, while six (28.6%) with EHE at other sites had tumors > 3 cm. Partial response and stable disease were achieved in 5 (23.8%) and 12 (57.1%) patients, respectively, resulting in a disease control rate of 80.9%. Symptom relief was observed in 15 of 18 patients (83.3%), and decreased serosal effusion was noted in 6 of 12 patients (50.0%). The 1- and 2-year progression-free survival rates were 50.7% and 13.5%, respectively, while the 1- and 2-year overall survival rates were 70.6% and 51.5%, respectively.

Conclusion: Nab-paclitaxel based chemotherapy may offer an effective treatment option for patients with advanced EHE exhibiting adverse prognostic factors. However, further clinical trials are required to confirm its efficacy.

Objective: Primary spinal cord Glioblastoma multiforme (IV grade WHO), also known as Primary Spinal Cord Astrocytoma (SCA), accounts for 6-8% of primary spinal cord tumors and up to 1.5% of all spinal cord tumors. However, owing to their rarity, no large studies or management consensus are available. Gross total resection (GTR) is the best advisable approach; however, in primary spinal tumors, this procedure is not always safe or feasible. Higher radiation doses with conventional radiotherapy (RT) are limited by the spinal cord's radiation tolerance. Stereotactic radiosurgery (SRS) is an effective and safe alternative when administered with adequate real-time simulation and planning to minimize setup errors with risks to the normal spinal cord.

Case presentation: Herein we present the case of a 32-year-old woman with primary grade IV glioblastoma (GBM) of the spinal cord at cervical C3-C6 (C3-C6) vertebrae level who underwent subtotal resection. The patient presented with neurological impairment in the neck, shoulder, and limbs. Sphincteric dysfunction and hyperaesthesia on the chest were also recorded. As adjuvant therapy, SRS with a dose of 14 Gy to the PTV was administered, ensuring a Dmax of 12 Gy to the spinal cord. Patient was treated in the same day of simulation and planning; hence, no set-up discrepancies were recorded on Cone Beam CT (CBCT) images during the RT delivery. Two days after SRS, the patient's neurological symptoms improved with recovery of neck and shoulder motor functions followed by weak upper limb activity. Afterwards, 6 cycles of temozolomide were administered.

Conclusion: We described a case of grade IV glioblastoma multiforme after partial resection, that was safely treated with adjuvant SRS in real-time with simulation and planning. This modality could improve the safety of SRS in the treatment of such tumors.

Idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are two chimeric antigen receptor T cell (CAR T) therapies approved for use in patients with relapsed/refractory multiple myeloma (MM). Initially approved for late line MM (>4 prior lines), these were recently approved for use in MM with 1-2 prior lines of therapy in April 2024. As their use outside of the pivotal clinical trials continues to expand, it is important to critically evaluate the safety and efficacy of these therapies. Further, it is important to identify patients that would be most likely to benefit from the use of CAR T in earlier lines of therapy. Cilta-cel was initially studied in the phase-I LEGEND-2 study, followed by CARTITUDE-1 and CARTITUDE-4 trials, demonstrating remarkable efficacy. A recent large real-world study also demonstrated similar efficacy, in a mostly pivotal trial ineligible patient population. Based on these impressive results, cilta-cel is currently being studied in trials for newly diagnosed as well as smoldering multiple myeloma. Cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) are known toxicities of cilta-cel (and other CAR Ts), however movement and cognitive disorders (delayed neurotoxicity) and second primary malignancies are an evolving concern. In this article we discuss safety and efficacy data from existing cilta-cel studies. We propose that all patients with MM who have received ≥4 prior lines of therapy should be considered for CAR T. Earlier line use of CAR T should be restricted to patients with a high-risk disease phenotype (eg, functional high-risk disease). This disease phenotype has historically shown poor outcomes with standard triplet regimens and would be most likely to benefit from earlier use of CAR T: considering the availability of other safe and highly effective therapies, and potential high-risk toxicities of CAR T.

Purpose: The purpose of this scoping review was to investigate which viruses other than HPV and EBV-associated with OPMDs and investigate whether viruses are linked solely to the etiology of OPMDs, their malignant transformation (MT), or both.

Methods: A scoping review following PRISMA-ScR methodological framework was used during the process. We conducted thorough searches in the EBSCOhost and PubMed databases. The inclusion criteria were publications that described viruses in OPMDs and identified pertinent research published between 2014 and 2023. The articles included underwent a thorough analysis and synthesis process to map out viruses in OPMDs. Pertinent characteristics such as research domains, publication dates, authors, type of research studies, sample sizes, gender ratios, types of OPMDs lesions, detected viruses, and methodological detection approaches were incorporated into the analysis.

Results: A total of twenty-eight articles were eligible for inclusion. The prevalence of viruses detected in OPMDs was found to be 78.57%. Viruses detected in this study, including HPV (0% to 86.6%), EBV (8% to 95.7%), hepatitis B virus (HBV) (6.71%) and herpes simplex virus (HSV) (1%). The biggest risk factor for OPMDs found in this study was tobacco use.

Conclusion: Given that 90% of oral cancers worldwide are attributable to OSCC, it is crucial to understand the role of viruses such as HPV, EBV, HBV, and HSV, along with unhealthy risk factors like tobacco and alcohol, which may contribute to the etiology and progression of lesions into OPMDs. Global data indicate that these viruses play varying roles in the etiology of OPMDs, with significant geographic variability, co-infections, and interactions with lifestyle factors influencing their oncogenic potential. Although this study found that virus positivity rates were higher in the malignant stage (OSCC) than in OPMDs and that there is a high prevalence of viruses in OPMDs, further research is needed to clarify the direct causality of virus-induced malignant transformation in OPMDs.

Introduction: Liposarcomas are malignant soft tissue tumours with heterogeneous features and variable prognosis. Each entity comprised in this group displays distinct morphology and harbours specific genetic alterations, which correlate with clinical behaviour and therapy response. The aim of this study is to analyse the clinical and histopathological features that can influence the prognosis of liposarcoma. We also present a newly designed scoring system that could be useful for predicting the risk of disease progression and death in patients with different liposarcoma subtypes.

Materials and methods: We carried out a retrospective multicentric study on 77 liposarcomas diagnosed between 2009 and 2023 that were followed up to assess the presence of metastases and survival of the patients. We evaluated the age, gender, tumour location and dimensions, histological subtype, mitotic index, presence and percentage of necrosis, and their association with disease progression and survival.

Results: In this respect, progression-free survival was positively associated with lower mitotic index, somatic soft-tissue localization, well-differentiated and myxoid subtypes and absence of necrosis. Overall survival was negatively influenced by older age, higher mitotic index, dedifferentiated and pleomorphic subtypes and the presence of necrosis. Therefore, several clinical and histopathological features of liposarcomas, such as tumour location, mitotic index, and tumour necrosis can strongly predict the disease evolution.

Discussion: This study focuses on developing a new scoring system that considers histologic subtype, mitotic index, and tumour necrosis as indicators that could predict the risk of disease progression and overall survival in patients with liposarcoma. The system classifies liposarcomas of any histological subtype into low-risk and high-risk tumours. Diagnosing liposarcomas using this two-tiered system could be useful for providing personalized therapy, in order to avoid relapses, metastases and improve the disease's prognosis.

Background: The prognostic value of negative surgical margins in soft tissue sarcomas in terms of disease course is well known. However, there is a lack of consensus in the literature regarding the impact of preoperative radiological surgical margins on recurrence rates and overall survival The aim of the present study was to determine whether soft tissue density at the margin of abdominal sarcomas using Hounsfield Unit (HU) measurement on CT is associated with recurrence after tumor resection.

Material and methods: Seventeen patients who underwent resectional surgery for abdominal sarcoma between May 2014 and May 2024 were retrospectively analyzed. Patients were compared with their preoperative CT scans for postoperative local recurrence according to soft tissue density at the margins of the sarcomas.

Results: Of the 17 patients, nine (52.9%) had recurrence. No significant difference was found for gender in terms of recurrence (p>0.05). As the median age decreases, recurrence increases significantly. (60 years (23-70) vs 73 years (44-79); p= 0.044). Increased preoperative tissue density (width 3 to 5 cm) at sarcoma margin measured by CT was significantly associated with recurrence after tumor resection (with at margin: 3cm; p=0.047, 4cm; p=0.019, 5 cm; p=0.018). The cut-of value of density measured by preoperative CT for soft tissue at sarcoma margin with recurrence was -98.8 hounsfield Unit (HU), whereas cut-of value of density was -109.6 hU with a 91.5% sensitivity, 58.9% specificity, 23.2% positive predictive value (PPV), 76.8% negative predictive value (NPV), and 0.83 accuracy, respectively.

Conclusion: Study results suggest that the risk of recurrence after tumor resection can be predicted by measuring soft tissue density at the sarcoma margin on preoperative CT scans.There appears to be a linear relationship between increased preoperative soft tissue density at the sarcoma margin and recurrence after tumor resection. This measurement method offers a perspective that reveals a new approach to this subject. Multicenter studies consisted of larger patient populations are needed to reach a definitive conclusion.