Frontiers in Oncology最新文献

Head and neck squamous cell carcinoma (HNSCC) is a type of head and neck cancer that is aggressive, difficult to treat, and often associated with poor prognosis. HNSCC is the sixth most common cancer worldwide, highlighting the need to develop novel treatments for this disease. The current standard of care for HNSCC usually involves a combination of surgical resection, radiation therapy, and chemotherapy. Chemotherapy is notorious for its detrimental side effects including nausea, fatigue, hair loss, and more. Radiation therapy can be a challenge due to the anatomy of the head and neck area and presence of normal tissues. In addition to the drawbacks of chemotherapy and radiation therapy, high morbidity and mortality rates for HNSCC highlight the urgent need for alternative treatment options. Immunotherapy has recently emerged as a possible treatment option for cancers including HNSCC, in which monoclonal antibodies are used to help the immune system fight disease. Combining monoclonal antibodies approved by the US Food and Drug Administration, such as cetuximab and pembrolizumab, with radiotherapy or platinum-based chemotherapy for patients with locally advanced, recurrent, or metastatic HNSCC is an accepted first-line therapy. Targeted radionuclide therapy can potentially be used in conjunction with the first-line therapy, or as an additional treatment option, to improve patient outcomes and quality of life. Epidermal growth factor receptor is a known molecular target for HNSCC; however, other targets such as human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, programmed cell death protein 1, and programmed death-ligand 1 are emerging molecular targets for the diagnosis and treatment of HNSCC. To develop successful radiopharmaceuticals, it is imperative to first understand the molecular biology of the disease of interest. For cancer, this understanding often means detection and characterization of molecular targets, such as cell surface receptors, that can be used as sensitive targeting agents. The goal of this review article is to explore molecular targets for HNSCC and dissect previously conducted research in nuclear medicine and provide a possible path forward for the development of novel radiopharmaceuticals used in targeted radionuclide therapy for HNSCC, which has been underexplored to date.

Objective: Tubo-ovarian carcinosarcomas are rare, extremely aggressive malignant tumors that contain both carcinomatous and sarcomatous components. Due to the disease's rarity, developing an effective treatment strategy for ovarian carcinosarcomas has been challenging. A study was conducted to investigate the clinicopathologic and molecular features of this rare disease.

Methods: We enrolled all patients diagnosed with tubo-ovarian carcinosarcomas from January 2007 to December 2022. The clinical and pathological data were gathered from medical records. Kaplan-Meier curves were plotted to calculate OS and PFS. The Log-rank test and Cox regression model were utilized to explore the relationship between clinicopathological parameters and survival. Patients with cancer tissues available had sequencing with a 242-gene panel done to investigate the mutational landscape and signature of the disease.

Results: In total, 65% of the patients were diagnosed with advanced-stage cancer. The median PFS and OS of this cohort were 27 and 40 months, respectively, and there was no significant difference in survival between the homologous and heterologous components of sarcoma. Unexpectedly, staging did not have effects on prognosis. All patients had surgical attempts, and suboptimal debulking status was correlated with poorer PFS and OS. MSI was identified in 0% with low Tumor mutation burden (TMB) indicating a poor response to immunotherapy. Low HER2 expression is controversial, according to previous reports, and gives us limited choices with this rare and aggressive disease. We surprisingly found the homologous recombination deficiency (HRD)-positive status was identified in 64% of OCS, which is significantly higher than UCS and other types of epithelial ovarian cancer. The fact that all patients in our cohort who received olaparib as maintenance therapy had survived over 30 months and two had no evidence of recurrence at the latest follow-up might further validate the role of poly (ADP-ribose) polymerase inhibitors (PARPi) in the management of OCS.

Conclusion: OCS patients seemed to respond to carboplatin/paclitaxel with optimal PFS and OS. Cytoreduction with no residuals proved to be the sole independent prognostic factor. WES should be done to assess the prognosis and assist with the targeted therapy, especially the HRD test, which might help select potential patients who benefit from PARPi.

Tumor Treating Fields (TTFields) therapy is an anti-cancer treatment modality that is delivered noninvasively to the tumor site via skin-placed arrays. The therapy is US Food and Drug Administration (FDA) approved and Conformité Européenne (CE) marked for adults with newly diagnosed and recurrent glioblastoma (GBM) (grade 4 glioma in the European Union). To date, there are limited data on the safety and efficacy of TTFields therapy in patients with implanted cardiac pacemakers. Herein, we report a case of a 79-year-old male patient with GBM receiving TTFields therapy with a prior medical history of cardiac events necessitating a cardiac pacemaker. The patient presented to the emergency department in May 2021 with newly onset left-sided weakness along with seizures. Based on an initial evaluation and results of the initial computed tomography (CT) scans (May 2021), the patient was clinically diagnosed with a high-grade glioma which was later confirmed as IDH wildtype following a biopsy. He was treated with radiotherapy (40 Gy in 15 fractions), followed by adjuvant temozolomide (TMZ) (75 mg/m²). TTFields therapy was initiated alongside maintenance TMZ (150 mg/m²). Average TTFields therapy usage was 67% throughout the duration of treatment. Follow-up CT scans (February and May of 2022) indicated stable disease. CT scans in August 2022 showed an increase in size of a mass with heterogeneous contrast enhancement and the patient subsequently passed away in October 2022. The patient's last cardiac tests demonstrated that the pacemaker was operational with adequate cardiac function. This report suggests that TTFields therapy concomitant with an implanted electronic device may be safe in patients with GBM.

Background: The triple combination of programmed cell death protein-1 (PD-1) inhibitors plus anti-angiogenesis tyrosine kinase inhibitors (TKIs) with or without transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) enhance the effect of treatment for unresectable hepatocellular carcinoma (uHCC). The present study compared the efficacy and safety of PD-1 plus TKI with or without transarterial chemo(embolization) for uHCC.

Methods: The meta-analysis was conducted using data acquired from PubMed, EMBASE, the Cochrane Library, Ovid, Web of Science, and Clinical Trials.gov from the inception date to December 2023. All clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The hazard ratio (HR) and risk ratio (RR) with 95% confidence intervals (CIs) were used to measure the pooled effect. In addition, subgroup analysis was conducted to determine the specific patient population that benefited.

Results: The OS (HR = 0.47; 95% CI: 0.39-0.56, P <  0.05), PFS (HR = 0.52; 95% CI: 0.45-0.60, P < 0.05), and ORR (RR = 1.94; 95% CI: 1.60-2.35, P < 0.05) were significantly better in TACE/HAIC+TKI+PD-1(TACE/HAIC TP) group than TKI+PD-1(TP) group. The incidence of AEs was acceptable.

Conclusion: The triple therapy of TACE/HAIC TP had better efficacy for uHCC than TP, with acceptable security.

Systematic review registration: PROSPERO, identifier CRD42023475953.

Purpose: The goal of the study was to create a nomogram based on clinical risk factors to forecast the rate of locoregional recurrence-free survival (LRFS) in patients with esophageal squamous cell carcinoma (ESCC) who underwent radiotherapy (RT).

Methods: In this study, 574 ESCC patients were selected as participants. Following radiotherapy, subjects were divided into training and validation groups at a 7:3 ratio. The nomogram was established in the training group using Cox regression. Performance validation was conducted in the validation group, assessing predictability through the C-index and AUC curve, calibration via the Hosmer-Lemeshow (H-L) test, and evaluating clinical applicability using decision curve analysis (DCA).

Results: T stage, N stage, gross tumor volume (GTV) dose, location, maximal wall thickness (MWT) after RT, node size (NS) after RT, Δ computer tomography (CT) value, and chemotherapy were found to be independent risk factors that impacted LRFS by multivariate cox analysis, and the findings could be utilized to create a nomogram and forecast LRFS. the area under the receiver operating characteristic (AUC) curve and C-index show that for training and validation groups, the prediction result of LRFS using nomogram was more accurate than that of TNM. The LRFS in both groups was consistent with the nomogram according to the H-L test. The DCA curve demonstrated that the nomogram had a good prediction effect both in the groups for training and validation. The nomogram was used to assign ESCC patients to three risk levels: low, medium, or high. There were substantial variations in LRFS between risk categories in both the training and validation groups (p<0.001, p=0.003).

Conclusions: For ESCC patients who received radiotherapy, the nomogram based on clinical risk factors could reliably predict the LRFS.

Somatic mutations within the exonuclease proofreading domain (EDM) of the DNA polymerase Pol ϵ (POLE) gene are increasingly being discovered in ovarian, colorectal, urological, and, especially, endometrial carcinoma (EC), where these are found in up to 10% of the cases. In EC, there are five confirmed pathogenic somatic POLE-EDM mutations that are located at codons 286, 411, 297, 456, and 459, and these are called "hotspot" mutations. POLE mutant tumors are ultramutated entities with a frequency of base substitution mutations that is among the highest in human tumors. Interestingly, these mutations are associated with excellent clinical outcome in EC. An additional six "non-hotspot" POLE-EDM EC mutations are also considered pathogenic, and they also confer a favorable prognosis. Currently, de-escalation of adjuvant treatment is recommended for patients with EC with stage I-II tumors involving any of these 11 EDM mutations, even in patients with other clinicopathological risk factors. The high tumor mutational burden and the consequent increased infiltration of immune cells due to the overexpression of different neoantigens are probably responsible for the improved prognosis. Ongoing studies are examining POLE hotspot mutations among many non-gynecologic tumors, although the impact of such mutations on clinical outcomes is still a topic of debate. Therapeutic modalities for these hypermutated tumors are also an important consideration, including the need for or de-escalation of adjuvant treatments and the response to immune therapy. This review addresses the critical role of POLE mutations in gynecologic oncology and oncology in general, focusing on definitions, variants, underlying pathogenic mechanisms, upcoming developments in the field, and the clinic behavior associated with such mutations.

Objectives: The aim of this research is to discuss the research status, hotspots, frontiers, and development trends in the field of small bowel adenocarcinoma based on bibliometrics and visual analysis by CiteSpace software.

Methods: The relevant research articles on SBA from 1923 to 2023 were retrieved from the Web of Science Core Collection database. CiteSpace software was used to form a visual knowledge map and conduct analysis for the countries/regions, journals, authors, keywords, clusters, research hotspots and frontiers of the included articles.

Results: There were 921 articles included, and the number of articles published during 1923-2023 is increasing. The country with the highest number of articles published was the United States (443, 38.76%), followed by Japan (84, 9.12%) and France (72, 7.82%). The author with the highest number of publications is Ansell, Overman MJ (33, 3.58%), and the author with the highest co-citation frequency is Overman MJ (218). Journal of Clinical Oncology is the journal with the highest publication frequency. The top five cluster groups were "chemotherapy", "inflammatory bowel disease", "celiac disease", "tumor" and "small intestine". The related disease, chemotherapy drugs, and treatment regimens of SBA form the main research fields, and prognosis and diagnosis are the research hotspots and trends.

Conclusion: The global research field in SBA has expanded in the past 100 years. The prognosis and new diagnosis of SBA are hotspots in this field and require further study in the future.

Squamous cell carcinoma (SCC) of the head and neck originates from the mucosal lining of the upper aerodigestive tract, including the lip, tongue, nasopharynx, oropharynx, larynx and hypopharynx. In this review, we summarise what is currently known about the potential function of primary cilia in the pathogenesis of this disease. As primary cilia represent a key cellular structure for signal transduction and are related to cell proliferation, an understanding of their role in carcinogenesis is necessary for the design of new treatment approaches. Here, we introduce cilia-related signalling in head and neck squamous cell carcinoma (HNSCC) and its possible association with HNSCC tumorigenesis. From this point of view, PDGF, EGF, Wnt and Hh signalling are discussed as all these pathways were found to be dysregulated in HNSCC. Moreover, we review the clinical potential of small molecules affecting primary cilia signalling to target squamous cell carcinoma of the head and neck area.

Background: This study aimed to retrospectively analyse the pathological response and safety of combining albumin-bound paclitaxel (nab-paclitaxel) or docetaxel with anti-HER2 therapy as a neoadjuvant treatment for HER2-positive breast cancer.

Methods: From June 2020 to August 2023, 225 HER2-positive breast cancer patients who underwent radical surgery following neoadjuvant treatment were enrolled in this study. The patients were divided into two groups based on the drugs they received: the nab-paclitaxel group (n=166, receiving nab-paclitaxel + platinum along with trastuzumab and pertuzumab) and the docetaxel group (n=59, receiving docetaxel + platinum along with trastuzumab and pertuzumab). The pathological response and adverse events related to the drugs were collected and evaluated in both groups.

Results: In the nab-paclitaxel group, the rates of breast and total pathological complete response (bpCR and tpCR) were significantly greater than those in the docetaxel group (69.27% vs. 47.45%, P=0.003; 68.67% vs. 45.76%, P=0.002). For patients who did not achieve pCR after chemotherapy, the pathological response of chemotherapy was analysed using MP grading and RCB grading. The results showed that there was a statistically significant difference between the two groups (P<0.05). Multivariate analysis revealed that therapeutic drugs, clinical stage, ER status, and Ki-67 level were independent predictors of pCR. The nab-paclitaxel group had a significantly greater proportion of patients with peripheral sensory neuropathy than did the docetaxel group (58.43% vs. 38.98%, P=0.035), while the docetaxel group had a greater proportion of patients with allergies and elevated ALT (31.93% vs. 69.49%, P=0.000; 23.49% vs. 40.68%, P=0.021).

Conclusions: Our real-world study revealed that nab-paclitaxel combined with anti-HER2 therapy was an effective neoadjuvant therapy for HER2-positive breast cancer. The multivariate analysis revealed that chemotherapy drugs, clinical stage, ER status, and Ki-67 level was the significant factor influencing treatment outcome. These findings offer a valuable reference for the neoadjuvant treatment of patients with HER2-positive breast cancer.

Introduction: Donor-specific antibodies (DSAs) correspond to anti-HLA antibodies of the recipient that are specifically directed to a mismatched antigen of the donor. In the setting of solid organ transplantation DSAs are associated with rejection. Their role is still debated in allogeneic cell transplantation. International guidelines recommend testing patients for DSA before transplant, and if possible, choosing a donor with negative screening.

Methods: We collected clinical data of 236 recipients of alloSCT, performed at our institution from March 2019 to October 2023, to evaluate their impact on engraftment. Serum from all patients was tested for DSA.

Results: 186 patients (79%) achieved sustained myeloid engraftment within day 30 post alloSCT. Thirty-two out 236 (13%) patients engrafted after day 30 post alloSCT. The median times to neutrophil engraftment and platelet engraftment were respectively 21 days (range 11-121 days) and 19 days (range 10-203 days). Fourteen out 236 patients (6%) experienced PrGF. .Twenty-nine patients (12 %) were DSA-positive. Among 29 patients with DSA positivity, 17 had a haploidentical donor and 12 had a UD donor. DSA positivity directly correlates respectively with neutrophil and platelets engraftment failure at 30 days after alloSCT (p=0.01 and p= 0.0004). Univariate Cox analysis showed that factors, including DSAs positivity, disease type, disease status, donor type, conditioning regimen, patient's age, and CD34+ were correlated with neutrophil and platelet engraftment failure at 30 days after alloSCT. Younger patients with DSA negativity, with acute leukemia, in complete response at the time of transplant, who received a higher dose of CD34+ cells from a sibling donor after a myeloablative conditioning regimen, have a reduced risk of neutrophil and platelet engraftment failure at day +30 post alloSCT.Multivariate analysis confirmed the impact of the presence of DSA only for platelet engraftment, confirming the role of type and status disease, donor type, recipient age, and CD34+ cells infused on engraftment. DSA presence has no impact on TRM, DFS, and OS.

Discussion: PrGF has a multifactorial pathogenesis, where DSA is not the only player, but its impact could vary depending on the transplant platform. Thus patient screening may be helpful to choose the best donor and transplant strategy.