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Polymers Jun 2024It is well-established that the structural, morphological and performance characteristics of nanoscale materials critically depend upon the dispersion state of the... (Review)
Review
It is well-established that the structural, morphological and performance characteristics of nanoscale materials critically depend upon the dispersion state of the nanofillers that is, in turn, largely determined by the preparation protocol. In this report, we review synthetic strategies that capitalise on the generation of nanoparticles on and within polymeric materials, an approach that relies on the chemical transformation of suitable precursors to functional nanoparticles synchronous with the build-up of the nanohybrid systems. This approach is distinctively different compared to standard preparation methods that exploit the dispersion of preformed nanoparticles within the macromolecular host and presents advantages in terms of time and cost effectiveness, environmental friendliness and the uniformity of the resulting composites. Notably, the -generated nanoparticles tend to nucleate and grow on the active sites of the macromolecular chains, showing strong adhesion on the polymeric host. So far, this strategy has been explored in fabrics and membranes comprising metallic nanoparticles (silver, gold, platinum, copper, etc.) in relation to their antimicrobial and antifouling applications, while proof-of-concept demonstrations for carbon- and silica-based nanoparticles as well as titanium oxide-, layered double hydroxide-, hectorite-, lignin- and hydroxyapatite-based nanocomposites have been reported. The nanocomposites thus prepared are ideal candidates for a broad spectrum of applications such as water purification, environmental remediation, antimicrobial treatment, mechanical reinforcement, optical devices, etc.
PubMed: 38891556
DOI: 10.3390/polym16111611 -
Radiation Oncology (London, England) Jun 2024This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant...
OBJECTIVE
This retrospective study aimed to investigate the factors influencing the occurrence of neutropenia in patients with endometrial cancer (EC) following adjuvant chemoradiotherapy (CRT).
METHODS
Retrospective analysis of EC patients who underwent adjuvant CRT from January 2012 to June 2023 in the Department of Gynecology and Oncology of the First Affiliated Hospital of Shandong First Medical University. Neutropenia was defined as an Absolute Neutrophil Count (ANC) of peripheral blood neutrophils below 2 × 10/L. Factors affecting neutropenia in EC patients treated with CRT using Generalized Estimating Equation (GEE), and Logistic regression was used to further analyze the effect of adding radiotherapy to different chemotherapy cycles on neutropenia, so that patients receive optimal adjuvant CRT while the risk of neutropenia is appropriately controlled.
RESULTS
A total of 144 patients met the inclusion criteria. They underwent 330 cycles of adjuvant chemotherapy, of whom 96 (66.7%) developed neutropenia, which occurred 140 times. The results of one-way GEE analysis showed that before CRT, White Blood Cell (WBC) (OR = 0.827; 95%CI, 0.701-0.976), ANC (OR = 0.749; 95%CI, 0.586-0.957), Absolute Monocyte Count (AMC) (OR = 0.047; 95%CI, 0.008-0.283), Blood Urea Nitrogen (BUN) (OR = 0.857; 95%CI, 0.741-0.991), platinum and docetaxel (platinum/docetaxel) dosing regimen (OR = 2.284; 95%CI, 1.130-4.618) were associated with neutropenia with adjuvant CRT for EC (p < 0.05), results of multifactorial GEE analysis showed that before adjuvant CRT ANC (OR = 0.552; 95%CI, 0.973-2.231), AMC (OR = 0.047; 95%CI, 0.004-0.052), platinum/docetaxel (OR = 2.437; 95%CI, 1.087-5.464) were an independent influence on neutropenia in adjuvant CRT for EC (p < 0.05). Multifactorial Logistic regression shows addition of radiotherapy to the first cycle of chemotherapy (OR = 4.413; 95%CI, 1.238-18.891) was an independent influence of neutropenia (p < 0.05).
CONCLUSIONS
Patients with low pre-CRT ANC and AMC, platinum/docetaxel dosing regimens need to be closely monitored during each cycle of CRT. Also, the concurrent addition of radiotherapy should be avoided during the first cycle of chemotherapy.
Topics: Humans; Female; Retrospective Studies; Endometrial Neoplasms; Neutropenia; Middle Aged; Aged; Chemoradiotherapy, Adjuvant; Adult; Antineoplastic Combined Chemotherapy Protocols; Prognosis; Docetaxel; Risk Factors
PubMed: 38890652
DOI: 10.1186/s13014-024-02469-8 -
World Journal of Surgical Oncology Jun 2024Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer...
BACKGROUND
Whether programmed cell death-1/ligand-1 (PD-1/PD-L1) blockade-based neoadjuvant treatment may benefit locally advanced oncogene-mutant non-small cell lung cancer (NSCLC) patients remains controversial. This retrospective study was designed to observe the efficacy and safety of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy versus chemotherapy and corresponding tyrosine kinase inhibitors (TKIs) in patients with resectable oncogene-positive NSCLC.
METHODS
Patients with potential resectable NSCLC harbouring oncogene alterations who had received neoadjuvant treatment were retrospectively recruited, and an oncogene-negative cohort of patients who received neoadjuvant PD-(L)1 blockade-based neoadjuvant treatment was reviewed for comparison during the same period. The primary aim was to observe the treatment efficacy and event-free survival (EFS) of these agents. Safety profile, molecular target, and immunologic factor data, including PD-L1 expression and tumour mutational burden (TMB), were also obtained.
RESULTS
A total of 46 patients were recruited. Thirty-one of them harboured oncogene alterations, including EGFR, KRAS, ERBB2, ROS1, MET, RET, ALK, and FGFR3 alterations. Among the oncogene-positive patients, 18 patients received neoadjuvant PD-(L)1 blockade immunotherapy plus chemotherapy (oncogene-positive IO group), 13 patients were treated with neoadjuvant chemotherapy and/or corresponding TKIs or TKIs alone (oncogene-positive chemo/TKIs group), and the other 15 patients were oncogene negative and received neoadjuvant PD-(L)1 blockade plus chemotherapy (oncogene-negative IO group). The pathological complete response (pCR) and major pathological response (MPR) rates were 22.2% (4 of 18) and 44.4% (8 of 18) in the oncogene-positive IO group, 0% (P = 0.120) and 23.1% (3 of 13) (P = 0.276) in the oncogene-positive chemo/TKIs group, and 46.7% (7 of 15) (P = 0.163) and 80.0% (12 of 15) (P = 0.072) in the oncogene-negative IO group, respectively. By the last follow-up, the median EFS time had not reached in the oncogene-positive IO group, and was 29.5 months in the oncogene-positive chemo/TKIs group and 38.4 months in the oncogene-negative IO group.
CONCLUSION
Compared with chemotherapy/TKIs treatment, neoadjuvant treatment with PD-(L)1 blockade plus platinum-based chemotherapy was associated with higher pCR/MPR rates in patients with partially resectable oncogene-mutant NSCLC, while the pCR/MPR rates were lower than their oncogene-negative counterparts treated with PD-(L)1 blockade-based treatment. Specifically, oncogene alteration types and other predictors of response to immunotherapy should be taken into account in clinical practice.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Female; Male; Lung Neoplasms; Middle Aged; Neoadjuvant Therapy; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Aged; B7-H1 Antigen; Immune Checkpoint Inhibitors; Follow-Up Studies; Survival Rate; Adult; Prognosis; Oncogenes; Protein Kinase Inhibitors; Mutation; Programmed Cell Death 1 Receptor
PubMed: 38890622
DOI: 10.1186/s12957-024-03434-1 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal...
OBJECTIVES
First-line pemetrexed-platinum chemotherapy + osimertinib(Pem-Plat-Osi) improves progression-free survival as compared to osimertinib alone in advanced epidermal growth factor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, many patients are hesitant to commence chemotherapy upfront. We describe outcomes to Pem-Plat-Osi after first-line osimertinib failure.
MATERIALS AND METHODS
Patients with advanced EGFR-mutated (ex19del/L858R) NSCLC who had Pem-Plat-Osi between 1/7/2018-30/9/2023 after progression on first-line osimertinib at National Cancer Centre Singapore, Prince of Wales Hospital and Chinese University of Hong Kong were identified. Key endpoints were time to treatment failure (TTF) and overall survival (OS).
RESULTS
A total of 60 patients were included. Median age at diagnosis was 62, 53.3 % (32/60) were male and 76.7 % (46/60) were never smokers. Ex19del comprised 56.7 % (34/60) and L858R 43.3 % (26/60). Baseline central nervous system (CNS) metastases were present in 66.7 % (40/60). Median TTF on osimertinib (TTF1) was 14.4 months(m) and median time to initiation of Pem-Plat-Osi was 41 days(d) (range 0-652) after progression on osimertinib. Partial response (PR) or stable disease to Pem-Plat-Osi was achieved in 81.7 %(49/60). Intracranial disease control was achieved in 90.6 % (29/32) of patients with measurable CNS metastases, including those who did not undergo brain radiotherapy. At median follow up of 31.2 m, median TTF on Pem-Plat-Osi (TTF2) was 6.6 m. Median TTF1 + TTF2 was 23.4 m and median OS was 34.2 m. Survival outcomes were similar comparing ex19del and L858R (median TTF1 + TTF2 21.8 m vs 23.5 m, p = 0.90; median OS 34.2 m vs 36.8 m, p = 0.37) and in patients without/with baseline CNS metastases (median TTF1 + TTF2 21.8 m vs 23.4 m, p = 0.44; median OS 36.2 m vs 31.9 m, p = 0.65). TTF1 duration was not significantly associated with TTF2 (p = 0.76). Patients who started Pem-Plat-Osi within 20d of progression on osimertinib had significantly longer TTF2 as compared to patients who started after 20d (median 8.4 m versus 6.0 months, p = 0.03), which remained statistically significant on multivariable analysis.
CONCLUSIONS
Our real-world data supports the efficacy of Pem-Plat-Osi after progression on first-line osimertinib, including L858R and baseline CNS metastases. Chemotherapy initiation within 20d of Osi progression was predictive of superior TTF2.
PubMed: 38889498
DOI: 10.1016/j.lungcan.2024.107856 -
Cureus Jun 2024Immunotherapy has been shown to provide clinical benefit in selected patients with head and neck squamous cell carcinoma (HNSCC), regardless of human papillomavirus...
Immunotherapy has been shown to provide clinical benefit in selected patients with head and neck squamous cell carcinoma (HNSCC), regardless of human papillomavirus (HPV) infection, and including recurrent/metastatic (R/M) platinum refractory tumors. Hyperprogression is an uncommon negative outcome of treatment with immunotherapy. We present the case of a patient with HPV+ HNSCC who presented hyperprogression after immunotherapy and a rare metastasis location with peritoneal carcinomatosis and subcutaneous nodules. HPV+ HNSCC is related to distant recurrence after a longer interval of time and more diverse metastasis sites compared with HPV- disease. However, the literature on peritoneal metastasis in HNSCC remains limited, with few documented cases. To the best of our knowledge, this is the first case reporting peritoneal carcinomatosis after hyperprogression in HNSCC.
PubMed: 38887752
DOI: 10.7759/cureus.62509 -
Cureus May 2024Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at...
Survival of Metastatic Human Papillomavirus (HPV)-Related Head and Neck Cancer Receiving Platinum-Based Triplet Induction Chemotherapy and Relevance of Circulating Tumor HPV DNA.
Objectives We aimed to examine the effectiveness of platinum-based triplet induction chemotherapy in metastatic squamous cell carcinoma of the head and neck (HNSCC) at diagnosis in terms of tumor human papillomavirus (HPV) status and the clinical relevance of circulating tumor HPV DNA (ctHPVDNA) during induction chemotherapy. Methods Twenty-one patients were included. ctHPVDNA was longitudinally quantified using optimized digital PCR in a subset of patients. Results HPV-related HNSCC patients (N=7) had a significantly better response to induction chemotherapy than HPV-unrelated HNSCC patients (N=14) (complete or partial response rate, 100% vs. 36%, = 0.007). Following induction chemotherapy, more HPV-related HNSCC patients than HPV-unrelated patients received radiotherapy (86% vs. 36%, = 0.06). With a median follow-up of 26 months in surviving patients, the two-year overall survival was 86% in HPV-related HNSCC patients and 43% in HPV-unrelated HNSCC patients ( = 0.04). In two patients, ctHPVDNA levels drastically decreased after the first cycle of induction chemotherapy but turned to continuous increase after the second cycle, suggesting the acquisition of drug resistance by the end of the second cycle. Radiographic imaging after induction chemotherapy failed to identify the drug resistance. In one patient, ctHPVDNA decreased gradually but remained detectable after induction chemotherapy despite no radiographic residual disease. ctHPVDNA became undetectable during radiotherapy. Conclusion HPV-related HNSCC patients with distant metastasis at diagnosis should be treated definitively. The ctHPVDNA level reflects real-time disease activity. ctHPVDNA monitoring during induction chemotherapy could help the decision-making of the therapeutic strategy.
PubMed: 38887331
DOI: 10.7759/cureus.60547 -
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