The Risk of Deep Vein Thrombosis and Optimal Timing of Breast Cancer Surgery After COVID-19 Infection.

PURPOSE: The aim of this study was to assess the risk of postoperative deep vein thrombosis (DVT) in breast cancer patients with coronavirus disease 2019 (COVID-19) to determine the optimal timing for surgery in the era of "post COVID-19 pandemic." METHODS: This prospective study included breast cancer patients who contracted COVID-19 and underwent surgery from December 20th, 2022, to March 20th, 2023 (n = 577). A control group comprised patients who underwent surgery from May 1st, 2019, to October 1st, 2019 (n = 327) and had not contracted COVID-19 prior to surgery. Patients were categorized based on the timing of their surgery relative to their COVID-19 infection. Data were analyzed using logistic regression. RESULTS: Patients with COVID-19 had a higher incidence of postoperative DVT compared to those without COVID-19 (3.64% vs. 1.21%). Multivariable logistic regression analysis indicated that the timing of surgery was significantly associated with the risk of DVT (odds ratio [OR], 2.795; 95% confidence interval [CI], 0.692-11.278; p = 0.024). Patients who underwent surgery within two weeks of COVID-19 infection experienced the highest DVT rates (OR, 10.556; 95% CI, 1.095-303.313; p = 0.003). However, the incidence decreased to 2.85% when surgery was delayed until two weeks or more after infection. The median follow-up period was 10 months, all patients with DVT after surgery were recovered without serious complications or death. There were no adverse effects on subsequent anti-tumor therapy. CONCLUSION: Caution is advised when performing breast cancer surgery within two weeks after a COVID-19 infection. Although the risk of DVT remains somewhat elevated even after two weeks, surgery can be considered safe given the urgency of treatment, favorable complication outcomes, and lack of impact on subsequent adjuvant therapy.

Optimal management of breast cancer with physical exam negative/radiological abnormal axilla.

For breast cancer patients with physical exam node negative but radiological finding node abnormal (cN0/rNa), the NCCN and ASCO guidelines recommend sentinel lymph node biopsy (SLNB) as the first-line axillary staging. However, patients who undergo surgery firstly may be upstaged to pathological II-III status, and these patients happen to be the adaptive population of neoadjuvant therapy (NAT). There is no consensus on the optimal management of cN0/rNa patients. The aim is to explore the optimal management strategy of these patients. We performed a retrospective real-world study of 1414 cN0/rNa patients from June 2014 to October 2022. There were 1003 patients underwent surgery first and 411 patients underwent surgery after NAT. We analyzed the real-world conditions of these patients, compared axilla tumor burden between these two groups. In addition, we compared benefit ratio of axillary surgery and regional nodal irradiation (RNI) de-escalation under the two strategies. Among 1003 patients underwent surgery first, the positive and negative rates of fine needle aspiration (FNA) were 18.5% and 81.5%, respectively. There were 66.1% had ≤ 2 lymph nodes+. There were 40.8% of FNA+ patients could be exempted from ALND underwent surgery first. In 411 patients underwent surgery after NAT, the FNA positive and negative rates were 60.8% and 49.2%, respectively. There were 54.4% of FNA+ patients achieved axilla pathologic complete response (apCR) and could omit ALND after NAT. The apCR was 67.3% in HER2+/TNBC subtypes. According to the NSABP-B51 trial, there were 0 and 54.4% of FNA+ patients could omit RNI among surgery first and after NAT, respectively. Among 1-2 sentinel lymph node (SLN)-positive patients underwent surgery first, with a median follow-up 49 months, there was no difference of survival benefit between SLNB-only and SLNB-ALND. Compared with 1-2 SLN+ patients without RNI, RNI could bring better invasive disease-free survival (97.38% vs. 89.36%, P = 0.046) and breast cancer special survival (100% vs. 94.68%, P = 0.020). It is safe to perform SLNB omitting ALND when detected 1-2 positive SLNs in cN0/rNa patients. Patients with HER2+/TNBC subtypes underwent surgery after NAT had more chance to benefit from dual de-escalation, including axillary surgery and RNI de-escalation.

Polyphenolic truxillic acid crosslinked sodium alginate film with notable antimicrobial and biodegradable properties for food packaging.

This work demonstrated an innovative antimicrobial and biodegradable food packaging film CBDA-10-SA which was prepared by crosslinking a natural polyphenolic truxillic acid (cyclobutane-dicarboxylic acid, CBDA-10) and sodium alginate (SA). The CBDA-10-SA film exhibited improved tensile strength (148 MPa) and UV shielding capabilities. The maximum thermal decomposition temperature was achieved of 249 °C. Compared to SA film, CBDA-10-SA showed increased antibacterial activities. In food packaging test, the CBDA-10-SA inhibited the rapid growth of potential of hydrogen (pH) value, slowed down the weight loss, reduced total plate count (TPC) value of pork, and delayed the spoilage process of pork. Notably, CBDA-10-SA displayed remarkable degradability in soil, with 60 % degrading in four weeks. In this study, CBDA-10-SA showed enhanced physicochemical and mechanical properties compared to traditional SA film. Those improvements make it anticipated to be used in not only food packaging but also mechanical, pharmaceutical, and agricultural fields.

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistance, including on-target mechanisms and off-target mechanisms, as well as changes in the tumor histology and tumor microenvironment (intrinsic mechanisms). Additionally, we summarized current therapeutic approaches aiming at circumventing TKI resistance, including the development of next-generation TKIs and combination therapies. We also discussed emerging strategies such as the use of dual-targeted antibodies and PROteolysis Targeting Chimeras. Furthermore, we explored future directions in TKI-targeted therapy, including the methods for detecting and monitoring drug resistance during treatment, identification of novel targets, exploration of dual-acting kinase inhibitors, application of nanotechnologies in targeted therapy, and so on. Overall, this review provides a comprehensive overview of the challenges and opportunities in TKI-targeted therapy, aiming to advance our understanding of resistance mechanisms and guide the development of more effective therapeutic approaches in cancer treatment.

Case report: A case of Savolitinib in the treatment of MET amplification mutation advanced lung adenocarcinoma with rare bilateral breast metastasis.

Background: The distant metastasis of lung cancer primarily occurs in the bones, liver, brain, and lungs, while the breast is an extremely rare site of metastasis. There is very limited literature on the occurrence of breast metastasis from lung cancer, and metastatic lesions in the breast are prone to being misdiagnosed as primary breast cancer, requiring careful attention and differentiation in the clinical diagnostic and treatment process. Case summary: The patient, a 63-year-old female, initially presented with an EGFR exon 21 L858R mutated left lung adenocarcinoma in 2017, treated successfully with surgical resection and subsequent monitoring. The relapse of disease occurred in January 2020. Despite maintaining a prolonged progression-free survival (PFS) with first-generation EGFR-TKI Afatinib, disease progression occurred in 2022 without detectable resistance mutations. Transition to second-generation TKI Furmonertinib resulted in poor control, with rapid progression including unusual bilateral breast metastases that exhibited inflammatory breast cancer-like peau d'orange changes. Standard chemotherapy achieved only short-term stability. Upon detecting a MET amplification mutation, treatment with Savolitinib was initiated. Remarkably, this led to significant clinical and radiographic improvement, notably resolving the peau d'orange appearance and reducing multiple lesions across the body. Conclusion: This case underscores the importance of continuous genetic profiling and tailored treatment approaches in managing advanced lung adenocarcinoma, particularly when presenting with rare metastatic sites and complex genetic landscapes. The successful application of Savolitinib following the identification of a MET amplification mutation highlights its potential in overcoming resistance mechanisms in NSCLC, providing a significant therapeutic option for similarly challenging cases.

The feasibility of targeted axillary dissection for breast cancer axillary surgery de-escalation after neoadjuvant therapy: A prospective cohort study.

PURPOSE: Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. METHODS: From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). RESULTS: The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3 mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). CONCLUSION: Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

SHR-A1811 (antibody-drug conjugate) in advanced HER2-mutant non-small cell lung cancer: a multicenter, open-label, phase 1/2 study.

A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0-57.9), and a disease control rate of 95.3% (95% CI 84.2-99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1-15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.

Application of indocyanine green-labeled fluorescence technology in laparoscopic total extra-peritoneal inguinal hernia repair surgery:a preliminary study.

BACKGROUND: Laparoscopic Total Extra-peritoneal Inguinal Hernia Repair(TEP) presents escalated risks of surgical complications, notably bleeding, particularly in European Hernia Society (EHS) types 3 and recurrent inguinal hernia. In this study, we introduced an innovative technique using indocyanine green-labeled fluorescence laparoscopy to mitigate intraoperative complications, including bleeding and rupture of the hernial sac. METHODS: This retrospective study reviewed records of 17 patients who underwent TEP repair at Anqing Municipal Hospital between July and August 2023. Intraoperatively, fluorescence imaging was utilized to trace the pathway of the spermatic vessels and outline the boundaries of the hernia sac to facilitate a thorough dissection. RESULTS: The procedure was successfully completed in all 17 patients, with a median operation time of 42 min (range: 30-51 min). Median intraoperative blood loss was 5 ml (range: 3-8 ml). Complete dissection of the hernia sac was achieved in each case without any incidents of sac rupture. Hemodynamic parameters of blood flow within the spermatic artery on postoperative day 1 showed no statistically significant deviations from the preoperative values. Furthermore, during the 7-month follow-up period, there were no cases of seroma formation or hernia recurrence. CONCLUSION: Our findings suggest that employing indocyanine green-labeled fluorescence technology in TEP repair significantly reduces intraoperative complications, notably bleeding and rupture of the hernial sac. This technique demonstrated a negligible impact on the hemodynamic parameters of the spermatic artery and reduced the overall surgical time.

Naringin inhibits cisplatin resistance of ovarian cancer cells by inhibiting autophagy mediated by the TGF-ß2/smad2 pathway.

Background: Resistance to cisplatin (DDP) in patients with ovarian cancer (OC) poses a great challenge to improving the quality of life of patients. Past reports have revealed that naringin can induce apoptosis of OC cells and delay the occurrence of drug resistance in OC cells. However, the molecular role by which naringin inhibits DDP resistance in OC has not been definitively proven by researchers. The objective of this study is to investigate the effect of naringin on DDP resistance in OC cells and the specific mechanism of naringin mediating autophagy. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were selected to evaluate the role of naringin or DDP on the proliferation and apoptosis of human OC cells (SKOV3/A2780). The protein levels of Sequestosome 1 (SQSTM1/p62, hereinafter referred to as p62), microtubule-associated protein 1 light chain 3 (LC3), transforming growth factor-ß2 (TGF-ß2) and SMAD family member 2 (smad2) were detected with Western blotting assay. Immunofluorescence assay was also used to evaluate the level of LC3 in different groups of cells. Besides, functional analyses were performed in vivo. Results: Naringin was shown to promote DDP sensitivity and apoptosis of human OC DDP-resistant cell line (SKOV3/A2780-DDP cells). Significantly increased p62 expression and reduced LC3 expression were found in naringin-treated cells. The autophagy agonist, rapamycin, reversed the effect of naringin on the resistance of SKOV3-DDP cells to DDP. Naringin inhibited levels of TGF-ß2/smad2 pathway-related proteins, and regulated autophagy in SKOV3-DDP cells. In vivo experiments demonstrated that injection of naringin inhibited DDP resistance and autophagy in mice xenograft model. Conclusions: In summary, naringin inhibits DDP resistance in OC cells by inhibiting autophagy mediated by the TGF-ß2/smad2 pathway.

Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.

PURPOSE: Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China. METHODS: TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety. RESULTS: As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low. CONCLUSION: Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.

Evaluation of the clinical value of 10 estimating glomerular filtration rate equations and construction of a prediction model for kidney damage in adults from central China.

Objectives: This study aimed to evaluate 10 estimating glomerular filtration rate (eGFR) equations in central China population and construct a diagnostic prediction model for assessing the kidney damage severity. Methods: The concordance of 10 eGFR equations was investigated in healthy individuals from central China, and their clinical effectiveness in diagnosing kidney injury was evaluated. Subsequently, relevant clinical indicators were selected to develop a clinical prediction model for kidney damage. Results: The overall concordance between CKD-EPIASR-Scr and CKD-EPI2021-Scr was the highest (weightedκ = 0.964) in healthy population. The CG formula, CKD-EPIASR-Scr and CKD-EPI2021-Scr performed better than others in terms of concordance with referenced GFR (rGFR), but had poor ability to distinguish between rGFR < 90 or < 60 mL/min·1.73 m2. This finding was basically consistent across subgroups. Finally, two logistic regression prediction models were constructed based on rGFR < 90 or 60 mL/min·1.73 m2. The area under the curve of receiver operating characteristic values of two prediction models were 0.811 vs 0.846 in training set and 0.812 vs 0.800 in testing set. Conclusion: The concordance of CKD-EPIASR-Scr and CKD-EPI2021-Scr was the highest in the central China population. The Cockcroft-Gault formula, CKD-EPIASR-Scr, and CKD-EPI2021-Scr more accurately reflected true kidney function, while performed poorly in the staging diagnosis of CKD. The diagnostic prediction models showed the good clinical application performance in identifying mild or moderate kidney injury. These findings lay a solid foundation for future research on renal function assessment and predictive equations.

Nomograms for metastasis of non-sentinel lymph nodes or more than three lymph nodes in patients with one or two positive sentinel lymph nodes.

Purpose: The purpose of this study was to provide advice for the indication of regional nodal irradiation (RNI) in patients with one to two positive sentinel lymph nodes (SLNs) without axillary lymph node dissection (ALND). Methods: We conducted a retrospective study in Shandong Cancer Hospital, Fudan University Shanghai Cancer Center, and West China Hospital. Logistic analysis was performed in order to explore the influencing factors of positive non-SLNs (NSLNs) and >3 positive nodes among patients with one to two SLNs+. Then, nomograms were constructed. Results: Between May 2010 and 2020, among the 2,845 patients with one to two SLNs+ undergoing ALND (1,992 patients in the training set and 853 patients in the validation set), there were 34.3% harbored NSLNs+ and 15.6% harbored >3 positive nodes. Multivariate analysis showed that cN stage, the number of positive/negative SLN, pathological tumor stage, lympho-vascular invasion (LVI), multicenter, and molecular subtypes were significantly associated with NSLN metastasis. Similarly, multivariate analysis also showed that cN stage, the number of positive/negative SLNs, pathological tumor stage, and LVI could be independent predictors of >3 positive nodes. Then, nomograms for NSLN metastasis and >3 positive nodes were constructed using these parameters, respectively. Conclusions: The nomograms will be useful in estimating positive NSLNs and >3 positive nodes, and they might provide advice for the optimization of RNI.

Ivonescimab Plus Chemotherapy in Non-Small Cell Lung Cancer With EGFR Variant: A Randomized Clinical Trial.

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

Immunotherapy for patients with advanced non-small cell lung cancer harboring oncogenic driver alterations other than EGFR: a multicenter real-world analysis.

Background: The administration of immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC) with oncogenic driver alterations other than epidermal growth factor receptor (EGFR) aroused a heated discussion. We thus aimed to evaluate ICI treatment in these patients in real-world routine clinical practice. Methods: A multicenter, retrospective study was conducted for NSCLC patients with at least one gene alteration (KRAS, HER2, BRAF, MET, RET, ALK, ROS1) receiving ICI monotherapy or combination treatment. The data regarding clinicopathologic characteristics, clinical efficacy, and safety were investigated. Results: A total of 216 patients were included, the median age was 60 years, 72.7% of patients were male, and 46.8% had a smoking history. The molecular alterations involved KRAS (n=95), HER2 (n=42), BRAF (n=22), MET (n=21), RET (n=14), ALK (n=14), and ROS1 (n=8); 56.5% of patients received immunotherapy in the first-line, and the rest 43.5% were treated as a second-line and above. For the entire cohort who received immunotherapy-based regimens in the first-line, the median progression-free survival (PFS) was 7.5 months and the median overall survival (OS) was 24.8 months. For the entire cohort who received immunotherapy-based regimens in the second-line and above, the median PFS was 4.7 months and median OS was 17.1 months. KRAS mutated NSCLC treated with immunotherapy-based regimens in the first-line setting had a median PFS and OS were 7.8 and 26.1 months, respectively. Moreover, the median PFS and OS of immunotherapy-based regimens for KRAS-mutant NSCLC that progressed after chemotherapy were 5.9 and 17.1 months. Programmed death ligand 1 (PD-L1) expression level was not consistently associated with response to immunotherapy across different gene alteration subsets. In the KRAS group, PD-L1 positivity [tumor proportion score (TPS) ≥1%] was associated with better PFS and OS according to the multivariate Cox analysis. No statistically significant association was found for smoking status, age, or gender with clinical efficacy in any gene group analyses. Conclusions: KRAS-mutant NSCLC could obtain clinical benefits from ICIs either for treatment-naive patients or those who have experienced progression after chemotherapy, and PD-L1 positive expression (TPS >1%) may be a potential positive predictor. For NSCLC with ALK, RET and ROS1 rearrangement, MET exon 14 skipping mutation, or BRAF V600E mutation, effectiveness of single or combined ICI therapy remains limited, therefore, targeted therapies should be considered prior to immunotherapy regimens. Future studies should address the investigation of better predictive biomarkers for immunotherapy response in oncogene-driven NSCLC.

Advances in regional nodal management of early-stage breast cancer.

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node (SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment (systemic/radiotherapy) that may result from de-escalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging node-positive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy (SLNB), the regional nodal management of breast cancer should adhere to the concept of "updating ideas, making bold assumptions, and carefully seeking proof", make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the "net benefit" of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

Evolution of neoadjuvant therapy for breast cancer regimens over 12 years and pathologic response rates according to tumor subtypes and clinical stage: A single-center retrospective study.

BACKGROUND AND PURPOSE: Given the evolution of neoadjuvant therapy (NAT) for breast cancer, this study aimed to analyze trends in NAT regimens over time and patients' pathological responses, tumor stages, and subtypes. MATERIALS AND METHODS: Data were analyzed for 548 patients with cT1-4N0-3M0 breast cancer who received NAT at Shandong Cancer Hospital between 2011 and 2022. The 12-year study period was divided into six 2-year periods termed P1 to P6. RESULTS: From P1 to P6, the proportion of stage II patients treated with NAT increased from 6.4% to 33.8% compared with same-stage operable breast cancer (r = 0.228, P < 0.001), while the proportion of the full-course group increased from 50.0% to 99.0% (r = 0.354, P < 0.001). The pathologic complete remission (pCR) rate in the full-course group increased from 30.8% to 54.6% (r = 0.248, P < 0.001). In the full-course human epidermal growth factor receptor-2 positive (HER2+) group, the proportion of chemotherapy combined with inhibition therapy increased from 33.3% to 100% (r = 0.530, P < 0.001). Furthermore, dual inhibition therapy increased from 0 to 98.9%. The proportion of the nonanthracycline group (dual inhibition) increased from 56.0% at P5 to 76.6% at P6 (r = 0.190, P = 0.042). In the full-course Triple-Negative Breast Cancer (TNBC) group, the proportion of platinum therapy increased from 0 to 41.9% (r = 0.324, P < 0.001) and immune drugs increased from 0 to 53.2% (r = 0.500, P < 0.001). CONCLUSION: Overall, the results indicate an increasing proportion of patients receiving NAT therapy over time. Furthermore, there were increases in HER2 + patients receiving inhibition therapy (especially dual inhibition) and TNBC patients receiving platinum and immune therapy as part of NAT. Notably, these changes were associated with improved outcomes.

Phase I pharmacokinetic, safety, and preliminary efficacy study of tiragolumab in combination with atezolizumab in Chinese patients with advanced solid tumors.

PURPOSE: Tiragolumab is an immunoglobulin G1 monoclonal antibody targeting the immune checkpoint T cell immunoreceptor with immunoglobulin and immunoreceptor ITIM domains. Targeting multiple immune pathways may improve anti-tumor responses. The phase I YP42514 study assessed the pharmacokinetics (PK), safety, and preliminary efficacy of tiragolumab plus atezolizumab in Chinese patients with advanced solid tumors. METHODS: Adult patients from mainland China with Eastern Cooperative Oncology Group performance score 0/1, life expectancy of ≥ 12 weeks, and adequate hematologic/end organ function were eligible. Patients received tiragolumab 600 mg and atezolizumab 1200 mg intravenous every 3 weeks. Key endpoints were PK (serum concentrations of tiragolumab and atezolizumab) and safety. Results from this study were compared with the global phase I study, GO30103 (NCT02794571). RESULTS: In this study, 20 patients received a median of five doses of tiragolumab plus atezolizumab. Median age was 57.5 years, 85.0% of patients were male and the most common tumor type was non-small cell lung cancer. Exposures in Chinese patients were comparable to the global GO30103 population: geometric mean ratio was 1.07 for Cycle 1 tiragolumab area under the concentration-time curve0-21 and 0.92 and 0.93 for Cycle 1 peak and trough atezolizumab exposure, respectively. Treatment-related adverse events were consistent across the Chinese and global populations. Two patients (10.0%) in this study achieved a partial response. CONCLUSION: In this study, tiragolumab plus atezolizumab was tolerable and demonstrated preliminary anti-tumor activity. There were no meaningful differences in the PK or safety of tiragolumab plus atezolizumab between the Chinese and global populations. CLINICAL TRIAL REGISTRATION NUMBER: China Clinical Trial Registry Identifier CTR20210219/YP42514. Date of registration 16 March 2021.

Study on Viscoelastic Properties of Various Fiber-Reinforced Asphalt Binders.

This study analyzed the viscoelastic properties of asphalt binders reinforced with various fibers, such as modified asphalt binder, modified asphalt binder reinforced with lignin fibers (LFs), polyester fibers (PFs), and polypropylene fibers (PPFs), using dynamic shear rheological (DSR) testing. Then, the experiment generated data on the dynamic modulus and phase angle, which described the dynamic rheological characteristics at varying temperatures. The generalized Maxwell model was employed to select the appropriate element, and the test curve was fitted into a discrete time spectrum based on the time-temperature equivalence principle (TTSP). The master curves of the relaxation modulus and creep compliance were established to predict the relaxation and creep properties of various asphalt binders. The analysis indicated that fiber-reinforced binders offer superior resistance to high temperatures and long-term deformation, while being less sensitive to temperature and having a more significant elastic characterization. The binders reinforced with PPFs and LFs exhibited superior performance in high-temperature settings and long-term durability, respectively. On the other hand, the binder reinforced with PFs displayed exceptional high-temperature elastic properties. Additionally, based on the experimental data and corresponding discussion, it appears that the 13-element GM model is more appropriate for fitting the data.