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Frontiers in Oncology 2024The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced...
BACKGROUND
The JAVELIN Bladder 100 phase 3 trial demonstrated the efficacy and safety of avelumab administered as first-line (1L) maintenance treatment in patients with advanced urothelial carcinoma (UC) without disease progression after 1L platinum-based chemotherapy. This study provides the first real-world data from Korea regarding avelumab 1L maintenance treatment, comprising data obtained from a nationwide expanded access program (EAP).
METHODS
This open-label EAP was conducted at five centers from September 2021 until June 2023. Eligible patients had unresectable locally advanced or metastatic UC and were progression free after 1L platinum-based chemotherapy. Patients received avelumab 10 mg/kg intravenously every 2 weeks per local prescribing information. Safety and effectiveness were assessed by treating physicians according to routine practice.
RESULTS
Overall, 30 patients were enrolled. At initial UC diagnosis, 20 patients (66.7%) had stage 4 disease and 12 (40.0%) had visceral metastases. The most common 1L chemotherapy regimen was gemcitabine + cisplatin (21 patients; 70.0%). All but one patient (96.7%) had received 4-6 cycles of 1L chemotherapy. The median interval from end of 1L chemotherapy to start of avelumab was 4.4 weeks. Median duration of avelumab treatment was 6.2 months (range, 0.9-20.7); nine patients (30.0%) received >12 months of treatment. Adverse events related to avelumab occurred in 21 patients (70.0%) and were grade ≥3 or classified as serious in three patients (10.0%). Median progression-free survival was 7.9 months (95% CI, 4.3-13.1). Overall survival was not analyzed because only one patient died.
CONCLUSION
Results from this EAP demonstrated the clinical activity and acceptable safety of avelumab 1L maintenance treatment in Korean patients with advanced UC, consistent with previous studies.
PubMed: 38887229
DOI: 10.3389/fonc.2024.1403120 -
Thoracic Cancer Jun 2024Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential...
BACKGROUND
Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin-2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored.
METHODS
We retrospectively analyzed 191 patients with SCLC (72 with limited-stage [LD] and 119 with extensive-stage) treated using platinum-based chemotherapy. Lipocalin-2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin-2 and neutrophil-to-lymphocyte ratio (NLR) were determined using time-dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia.
RESULTS
In LD-SCLC, high lipocalin-2 expression was associated with worse progression-free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin-2 expression. Patients were stratified into three prognostic groups by combining lipocalin-2 with NLR: low lipocalin-2/low NLR, high lipocalin-2/low NLR or low lipocalin-2/high NLR, and high lipocalin-2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin-2 with the pectoralis muscle index. High lipocalin-2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin-2 in extensive-stage SCLC.
CONCLUSIONS
High lipocalin-2 expression is potentially associated with poorer survival in LD-SCLC. Combining lipocalin-2 with other inflammation-related markers could improve prognostic stratification.
PubMed: 38886905
DOI: 10.1111/1759-7714.15389 -
BMC Medicine Jun 2024Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC).... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Previous studies have shown that the addition of platinum to neoadjuvant chemotherapy (NAC) improved outcomes for patients with triple-negative breast cancer (TNBC). However, no studies have assessed the efficacy and safety of the combination of taxane and lobaplatin. In this study, we conducted a randomized controlled phase II clinical study to compare the efficacy and safety of taxane combined with lobaplatin or anthracycline.
METHODS
We randomly allocated patients with stage I-III TNBC into Arm A and Arm B. Arm A received six cycles of taxane combined with lobaplatin (TL). Arm B received six cycles of taxane combined with anthracycline and cyclophosphamide (TEC) or eight cycles of anthracycline combined with cyclophosphamide and sequential use of taxane (EC-T). Both Arms underwent surgery after NAC. The primary endpoint was the pathologic complete response (pCR). Secondary endpoints were event-free survival (EFS), overall survival (OS), and safety.
RESULTS
A total of 103 patients (51 in Arm A and 52 in Arm B) were assessed. The pCR rate of Arm A was significantly higher than that of Arm B (41.2% vs. 21.2%, P = 0.028). Patients with positive lymph nodes and low neutrophil-to-lymphocyte ratio (NLR) benefited significantly more from Arm A than those with negative lymph nodes and high NLR (P = 0.001, P = 0.012, respectively). There was no significant difference in EFS (P = 0.895) or OS (P = 0.633) between the two arms. The prevalence of grade-3/4 anemia was higher in Arm A (P = 0.015), and the prevalence of grade-3/4 neutropenia was higher in Arm B (P = 0.044).
CONCLUSIONS
Neoadjuvant taxane plus lobaplatin has shown better efficacy than taxane plus anthracycline, and both regimens have similar toxicity profiles. This trial may provide a reference for a better combination strategy of immunotherapy in NAC for TNBC in the future.
Topics: Humans; Triple Negative Breast Neoplasms; Female; Middle Aged; Neoadjuvant Therapy; Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclobutanes; Anthracyclines; Aged; Taxoids; Organoplatinum Compounds; Treatment Outcome; Cyclophosphamide; Bridged-Ring Compounds
PubMed: 38886794
DOI: 10.1186/s12916-024-03474-0 -
MedRxiv : the Preprint Server For... Jun 2024Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showing resistance to platinum-based chemotherapy. While...
Patients with High-Grade Serous Ovarian Cancer (HGSOC) exhibit varied responses to treatment, with 20-30% showing resistance to platinum-based chemotherapy. While hematoxylin-eosin (H&E) pathological slides are used for routine diagnosis of cancer type, they may also contain diagnostically useful information about treatment response. Our study demonstrates that combining H&E-stained Whole Slide Images (WSIs) with proteomic signatures using a multimodal deep learning framework significantly improves the prediction of platinum response in both discovery and validation cohorts. This method outperforms the Homologous Recombination Deficiency (HRD) score in predicting platinum response and overall patient survival. The study sets new performance benchmarks and explores the intersection of histology and proteomics, highlighting phenotypes related to treatment response pathways, including homologous recombination, DNA damage response, nucleotide synthesis, apoptosis, and ER stress. This integrative approach has the potential to improve personalized treatment and provide insights into the therapeutic vulnerabilities of HGSOC.
PubMed: 38883738
DOI: 10.1101/2024.06.01.24308293 -
Journal of Thoracic Disease May 2024The most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various...
BACKGROUND
The most effective method and length of time for administering adjuvant immunotherapy after surgery for non-small cell lung cancer (NSCLC) are still unknown. Various clinical trials have utilized diverse strategies for adjuvant treatment. In this case, we explore the potential benefits of neoadjuvant immunotherapy combined with chemotherapy in managing locally advanced lung squamous carcinoma, which often poses challenges for treatment. This multimodal approach aims to downstage tumors and optimize surgical outcomes.
CASE DESCRIPTION
Following a diagnosis of stage IIIB lung cancer, the patient underwent three cycles of neoadjuvant therapy using sintilimab, Abraxane, and Lobaplatin, resulting in a significant 45% reduction in tumor size. Subsequently, a right lower lobe lobectomy and systematic lymphadenectomy were performed using a uniportal video-assisted thoracic surgery (VATS) approach. Postoperative analysis revealed negative lymph nodes, with only a 5-mm residual tumor in the tumor bed, downstaging the cancer to IA1. Remarkably, the patient experienced a smooth recovery without any postoperative complications. One cycle of adjuvant therapy was administered following the operation to further support the patient's recovery and minimize the risk of disease recurrence. This comprehensive treatment approach underscores the importance of neoadjuvant therapy in optimizing surgical outcomes and improving long-term prognosis for patients with locally advanced lung cancer.
CONCLUSIONS
For patients with stage III locally advanced lung squamous carcinoma, the combination of Sintilimab and Platinum-based drugs can be used as a neoadjuvant therapy which can reduce the difficulty of the operation.
PubMed: 38883681
DOI: 10.21037/jtd-24-522 -
American Journal of Translational... 2024To investigate the independent risk factors for a decreased hemoglobin level in gastric cancer patients undergoing adjuvant chemotherapy.
OBJECTIVE
To investigate the independent risk factors for a decreased hemoglobin level in gastric cancer patients undergoing adjuvant chemotherapy.
METHODS
A retrospective study was conducted on 142 gastric cancer patients who received chemotherapy between May 2017 and May 2021 at the Gansu Provincial Cancer Hospital. All patients were subjected to the same regimen of adjuvant chemotherapy combining platinum/taxane and fluorouracil. The correlation between patients' clinicopathological features and the decreased hemoglobin during adjuvant chemotherapy was analyzed. Logistic and LASSO regression analyses were employed to screen for independent risk factors for decreased hemoglobin during adjuvant chemotherapy.
RESULTS
Univariate analysis revealed that intraoperative bleeding, pre-chemotherapy anemia, and hypoalbuminemia were risk factors for the decreased hemoglobin in patients during adjuvant chemotherapy (all P < 0.05). Both logistic and LASSO regression analyses corroborated these factors as influential factors in the decrease of hemoglobin (P < 0.05). In addition, both logistic and LASSO regression models demonstrated similar performance in this aspect. The nomogram model was subjected to internal validation, resulting in a C-index of 0.712 (0.629-0.796). The calibration curves exhibited satisfactory alignment with the ideal curve.
CONCLUSION
Intraoperative blood loss, pre-chemotherapy anemia, and hypoalbuminemia are independent risk factors for hemoglobin reduction following chemotherapy. Moreover, both the logistic and LASSO regression models exhibited equivalent performance in this context. These findings bear substantial clinical implications, aiding physicians in the management of anemia in patients undergoing chemotherapy.
PubMed: 38883365
DOI: 10.62347/CLLZ7409 -
ACS Omega Jun 2024This study synthesized core/shell gold-platinum nanoparticles and characterized their colorimetric properties; ultraviolet-visible spectroscopy revealed that the...
This study synthesized core/shell gold-platinum nanoparticles and characterized their colorimetric properties; ultraviolet-visible spectroscopy revealed that the synthesized nanoparticles exhibited distinct colors from conventional gold nanoparticles. Furthermore, the nanoparticles were subjected to lateral flow assays using Protein A, and the results revealed that they outperformed conventional spherical gold nanoparticles in terms of color development. This improvement can be attributed to the distinct core/shell structures of our nanoparticles. Further evaluation revealed that these nanoparticles could facilitate the detection of Toxin B visually at an extremely low concentration (1 ng/mL) without the requirement for advanced instrumentation. This substantial improvement in sensitivity can be attributed to the meticulous design and nanoscale engineering of the structure of the nanoparticles.
PubMed: 38882078
DOI: 10.1021/acsomega.4c00722 -
Translational Cancer Research May 2024Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is...
BACKGROUND
Apigenin is a natural flavonoid compound with proven antitumor activity. However, its precise underlying pharmacological mechanism remains unclear. Oxaliplatin (OXA) is commonly utilized for cancer treatment as a platinum-based chemotherapy drug. However, the utilization of low-dose OXA carries the risk of inducing epithelial-mesenchymal transition (EMT) in cancer cells and promoting tumor metastasis, thereby giving rise to potential side effects. The purpose of this study is to investigate the synergistic inhibitory effect of apigenin and OXA and its potential mechanism.
METHODS
HSC-3 cells of oral squamous carcinoma cells (OSCCs) were divided into control, apigenin-treated and co-treated groups. A wound healing assay was conducted to assess alterations in cellular motility and migration, an invasion assay was performed to assess invasiveness, and a three-dimensional culture assay was employed to evaluate angiogenic capacity. Cultured cells were utilized for total DNA extraction, followed by reverse transcription. Relative RNA levels were obtained, and quantitative polymerase chain reaction (qPCR) analysis was conducted to assess the efficiency of LINC00857 expression.
RESULTS
The administration of a low dose of OXA promoted the migratory, invasive, and angiogenic capabilities of HSC-3 cells, while also regulating EMT-associated molecular markers to facilitate the process of EMT. The inhibitory impact on OSCC proliferation was enhanced by the synergistic effect of apigenin and OXA. Furthermore, the tumor-promoting effects induced by low-dose OXA were notably suppressed through LINC00857.
CONCLUSIONS
Evidence from this study indicates that apigenin can effectively suppress the metastasis of OSCC cancer cells induced by low-dose OXA through inhibiting the level of LINC00857, suggesting a promising therapeutic strategy.
PubMed: 38881938
DOI: 10.21037/tcr-23-2335 -
Mediastinum (Hong Kong, China) 2024Thymoma, thymic carcinoma and thymic neuroendocrine tumors originate from the epithelial cells of the thymus and account for the thymic epithelial tumors (TETs).... (Review)
Review
BACKGROUND AND OBJECTIVE
Thymoma, thymic carcinoma and thymic neuroendocrine tumors originate from the epithelial cells of the thymus and account for the thymic epithelial tumors (TETs). Although TETs are uncommon, they are the most frequent tumor type in the anterior mediastinum. Multidisciplinary approach is essential for their correct management. The aim of the present review is to summarize the update management for TETs.
METHODS
For this review, we searched in Excerpta Medica database (EMBASE) and MEDLINE until 6 September 2023. The terms used in the search included thymoma, thymic carcinoma, thymic epithelial tumors, management, immunotherapy, multiple tyrosine kinases inhibitors.
KEY CONTENT AND FINDINGS
The therapeutic approach is based on histology and tumor stage and may involve surgery with or without neoadjuvant or adjuvant treatment. In the metastatic setting, platinum-based chemotherapy is the standard of care and patients who do not respond to first-line treatment have limited treatment options mainly because of the poor efficacy shown in subsequent lines of therapy.
CONCLUSIONS
Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. Immune check point inhibitors, mammalian target of rapamycin (mTOR) and antiangiogenic multikinase inhibitors have also been studied in this clinical setting.
PubMed: 38881809
DOI: 10.21037/med-23-47 -
Radiation Oncology (London, England) Jun 2024Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates,...
Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience.
BACKGROUND
Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population.
METHODS
All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT.
RESULTS
In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81-9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT.
CONCLUSIONS
SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.
Topics: Humans; Radiosurgery; Male; Female; Aged; Middle Aged; Retrospective Studies; Aged, 80 and over; Survival Rate; Urologic Neoplasms; Neoplasm Metastasis; Adult; Urinary Bladder Neoplasms
PubMed: 38880908
DOI: 10.1186/s13014-024-02465-y