Progression-free Survival Time Of Patients Research Articles

CURRENT DRUG THERAPY OPTIONS FOR DISSEMINATED HER2-POSITIVE BREAST CANCER AT THE KAZAKH SCIENTIFIC RESEARCH INSTITUTE OF ONCOLOGY AND RADIOLOGY: A CLINICAL CASE

Relevance: Distant outcomes of treatment for Her2neu-positive metastatic breast cancer are improving due to access to innovative drug therapies. The study aimed to demonstrate the initial experience of treating a patient with progressive disseminated hormone receptor-positive breast cancer expressing HER2 (3+) and nearly exhausted options for anti-tumor drug therapy using trastuzumab deruxtecan. Methods: The paper describes a clinical case of a female patient born in 1977 who was diagnosed with Stage IV breast cancer (T1N1M1), invasive ductal carcinoma, and treated at the Kazakh Institute of Oncology and Radiology (Almaty, Kazakhstan). Immunohistochemical luminal subtype “B” with Her2neu (3+) expression. Metastatic involvement of skeletal bones with pain syndrome, lungs, liver, axillary, parasternal, and para-mediastinal lymph nodes. Since June 2023, monoclonal antibody conjugate trastuzumab deruxtecan therapy was initiated. The efficacy of fifth-line therapy was assessed using RECIST 1.1 before and during treatment. According to RECIST 1.1., target lesions included a conglomerate of hyperplastic axillary lymph nodes on the right, measuring 1.6 cm, parasternal lymph node 1.6 cm, a lesion in the parenchyma of the lower lobe of the left lung 1.3 cm, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe 1.8 cm and 3.6 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes SLD 9.9 cm. Results: Pain syndrome was completely relieved after treatment. According to RECIST 1.1. in April 2024, after 11 courses of therapy, target lesions showed size reduction: conglomerate of hyperplastic axillary lymph nodes on the right decreased to 1.0 cm, lesion in the parenchyma of the lower lobe of the left lung increased to 2.7 cm, parasternal lymph node was not visualized, lesions (n=2) in the parenchyma of segment 2 of the left liver lobe measured 1.6 cm and 2.7 cm. Non-target lesion: hyperplastic para-mediastinal lymph nodes were not visualized. Conclusion: According to the clinical study data (DESTINY-Breast02), applying antibody-drug conjugate (ADC) demonstrates better objective response and progression-free survival time in patients previously treated with trastuzumab and taxanes.

Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 − 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Clinical Features and Prognosis of Patients with CD5+ Diffuse Large B-Cell Lymphoma

To analyze the clinical characteristics and prognosis of patients with CD5+ diffuse large B-cell lymphoma (DLBCL). The clinical data of 161 newly treated DLBCL patients in Gansu Provincial Hospital from January 2013 to January 2020 were retrospectively analyzed. According to CD5 expression, the patients were divided into CD5+ group and CD5- group. The clinical characteristics and prognosis of the two groups were statistically analyzed. The median age of patients in CD5+ group was 62 years, which was higher than 56 years in CD5- group (P =0.048). The proportion of women in CD5+ group was 62.96%, which was significantly higher than 41.79% in CD5- group (P =0.043). The proportion of patients with IPI score > 2 in CD5+ group was 62.96%, which was higher than 40.30% in CD5- group (P =0.031). Survival analysis showed that the median overall survival and progression-free survival time of patients in CD5+ group were 27(3-77) and 31(3-76) months, respectively, which were both shorter than 30(5-84) and 32.5(4-83) months in CD5- group (P =0.047, P =0.026). Univariate analysis showed that advanced age, positive CD5 expression, triple or double hit at initial diagnosis, high IPI score and no use of rituximab during chemotherapy were risk factors for the prognosis of DLBCL patients. Further Cox multivariate regression analysis showed that these factors were also independent risk factors except for advanced age. CD5+ DLBCL patients have a worse prognosis than CD5- DLBCL patients. Such patients are more common in females, with advanced age and high IPI score, which is a special subtype of DLBCL.

Abstract PO1-15-07: Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial

Abstract Background: The standard approach of using one-size-fits-all endocrine therapy for hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancers has faced significant challenges due to variations in treatment response among individuals. Consequently, there is still an urgent need to understand the molecular biology of HR+/HER2- breast cancer and explore precision treatment strategy. Methods: We established a multiomics cohort (n = 351), multicenter real-world clinical cohorts (n = 643), a prospective clinical cohort (MULAN trial), and a drug-testing platform containing patient-derived organoids (n = 126) and patient-derived tumor fragments (n = 49) of HR+/HER2- breast cancers. Integrating "bench" and “bedside” data, we conducted comprehensive preclinical and clinical translational research on precision strategies in HR+/HER2- breast cancer. Results: We implemented a comprehensive classification system for HR+/HER2- breast cancer, comprising four distinct subtypes. We further demonstrated the efficacy and mechanisms of subtyping-directed precision treatment strategies through clinical cohort studies, omics analysis and functional assays: endocrine therapy alone for the canonical luminal subtype; the addition of CDK4/6 inhibitor and PARP inhibitor for the proliferative subtype; the immunotherapy for the immunogenic subtype; and tyrosine kinase inhibitors for the receptor tyrosine kinase-driven subtype. Using clinically applicable subtyping methods, we validated that matched precision treatment strategies outperformed unmatched approaches in a real-world cohort, almost doubling the median progression-free survival time for patients with refractory advanced HR+/HER2- breast cancer (9.83 months [95% CI, 5.74-13.93] vs 4.77 months [95% CI, 3.35-6.18]; hazard ratio 0.64 [95% CI, 0.41-0.99]). Importantly, the first-stage analysis of the MULAN phase II umbrella clinical trial (NCT04355858) verified the higher objective response rate (88.9%, 95%CI: 51.7%-99.7%) of the subtyping-directed precision treatment. Conclusion: Our study emphasizes the superiority of subtyping-directed precision treatment strategies for HR+/HER2- breast cancer, refines traditional “one-size-fits-all” therapy, and facilitates the translation of precision treatment strategies from bench to bedside. Overall study design Part 1 Subtype Molecular Characteristics: Molecular features of the four subtypes of HR+/HER2- breast cancer. Part 2 Multidimensional Efficacy Validation: Integrating data from a multiomics cohort, real-world study, drug testing platform and prospective clinical research to validate the subtyping-directed precision treatment strategy in HR+/HER2- breast cancer. Part 3 Subtyping-directed Precision Treatment Strategy: Integrating clinical cohort studies, omics analysis and functional assays revealed the heterogeneity of treatment response in HR+/HER2- breast cancer, and proposed a subtyping-directed precision treatment strategy. CIN, chromosomal instability; RTK, receptor tyrosine kinase; CNA, copy-number alteration; ER, estrogen receptor; HR, hormone receptor; HER2, human epidermal growth factor receptor 2. Citation Format: Xiu-Zhi Zhu, Xi Jin, Hu-Yun-Long Zhang, Xiyu Liu, Yi-Fan Zhou, Yi-Yu Chen, Tong Fu, Ming-Liang Jin, Ya-Xin Zhao, Yi-Fan Xie, Ruo-Xi Wang, Zhong-Hua Wang, Lei Fan, Yi-Zhou Jiang, Zhi-Ming Shao. Subtyping-directed precision treatment refines traditional one-size-fits-all therapy in HR+/HER2- breast cancer: a sub-study of the MULAN umbrella trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-15-07.

Correlation of 1p/16q loss of heterozygosity and 1p gain with clinicopathological characteristics and prognosis in Wilms tumor

Objective: To investigate the relationship between 1p/16q loss of heterozygosity (LOH) and 1p gain in Wilms tumor and their clinicopathologic characteristics and prognosis. Methods: A total of 175 Wilms tumor samples received from the Department of Pathology, Beijing Children's Hospital from September 2019 to August 2022 were retrospectively analyzed. The histopathologic type and presence of lymph node involvement were evaluated by two pathologists. The clinical data including patients'gender, age, tumor location, preoperative chemotherapy, and tumor stage were summarized. Fluorescence in situ hybridization (FISH) was done to detect 1p/16q LOH and 1p gain and their correlation with the clinicopathological features and prognosis were analyzed. Results: Among the 175 samples, 86 cases (49.1%) were male and 89 (50.9%) were female. The mean age was (3.5±2.9) years, and the median age was 2.6 years. There were 26 (14.9%) cases with 1p LOH, 28 (16.0%) cases with 16q LOH, 10 (5.7%) cases of LOH at both 1p and 16q, and 53 (30.3%) cases with 1q gain. 1q gain was significantly associated with 1p LOH (P<0.01) and 16q LOH (P<0.01). There were significant differences (P<0.01) between 1q gain, 1p LOH and 16q LOH among different age groups. The rate of 16q LOH in the high-risk histopathological subtype (50.0%) was significantly higher than that in the intermediate-risk subtype (13.6%, P<0.05). The frequency of 1q gain, 1p LOH, and 16q LOH in children with advanced clinical stages (Ⅲ and Ⅳ) was significantly higher than that in children with early clinical stages (Ⅰ and Ⅱ). 1q gain, 1p LOH, and 16q LOH showed no significant correlation with gender, unilateral or bilateral disease, chemotherapy, or lymph node metastasis. The progression-free survival (PFS) time for patients with 1q gain and 1p LOH was significantly shorter than those without these aberrations (P<0.05). Additionally, the PFS time of patients with 16q LOH was slightly shorter than those with normal 16q, although the difference was not statistically significant. Patients with stage Ⅲ to Ⅳ disease exhibiting 1q gain or 1p LOH had a significantly higher relative risk of recurrence, metastasis, and mortality. Conclusions: 1p/16q LOH and 1q gain are associated with age, high-risk histological type, and clinical stage in Wilms tumor. 1q gain and 1p LOH are significantly correlated with the prognosis of Wilms tumor.

Efficacy and Safety Evaluation of Enteral Nutrition Support Combined with Pemetrexed and Cisplatin in Advanced Lung Adenocarcinoma

This study was designed to probe the efficacy and safety of enteral nutrition support in combination with pemetrexed and cisplatin in advanced lung adenocarcinoma. To this end, patients were divided into two groups: experimental (received cisplatin + pemetrexed chemotherapy regimen + enteral nutritional emulsion) and control (received cisplatin + pemetrexed chemotherapy regimen + routine nutritional intervention). The clinical efficacy of the experimental group was better relative to the control group (P = 0.005). After chemotherapy, the experimental group exhibited a significant reduction of tumor markers, higher hemoglobin and serum albumin levels, higher immune function, and a lower inflammatory reaction relative to the control group. Moreover, the experimental group had a high score on quality of life, a lower total occurrence rate of adverse reactions, and longer overall survival and progression-free survival time than the control group. In summary, enteral nutrition support combined with cisplatin and pemetrexed chemotherapy had a higher efficacy and safety in advanced lung adenocarcinoma therapy, which could improve the overall survival and progression-free survival time of patients and did not elevate the occurrence of adverse reactions in patients.

A biopolymeric mesh enriched with PLGA microparticles loaded with AT101 for localized glioblastoma treatment

Current treatment strategies for glioblastoma (GBM) including surgical resection and adjuvant radio/chemotherapy result in a limited progression-free survival time of patients due to rapidly occurring tumor recurrences. The urgent need for more effective treatments has led to the development of different approaches for localized drug delivery systems (DDSs) offering the advantages of reduced systemic side effects. A promising candidate for the treatment of GBMs is AT101, the R-(-)-enantiomer of gossypol due to its ability to induce apoptosis or trigger autophagic cell death in tumor cells. Here, we present an alginate-based drug-releasing mesh ladened with AT101-loaded PLGA microspheres (AT101-GlioMesh). The AT101-loaded PLGA microspheres were fabricated using an oil-in-water emulsion solvent evaporation method obtaining a high encapsulation efficiency. The drug-loaded microspheres enabled the release of AT101 over several days at the tumor site. The cytotoxic effect of the AT101-loaded mesh was evaluated using two different GBM cell lines. Strikingly, encapsulation of AT101 in PLGA-microparticles and subsequent embedding in GlioMesh resulted in a sustained delivery and more efficient cytotoxic effect of AT101 on both GBM cell lines. Thus, such a DDS holds promise for GBM therapy likely by preventing the development of tumor recurrences.

Comparison of multi-cycle and standard-cycle temozolomide chemotherapies in patients with glioblastoma undergoing surgery and successive radiotherapy

PurposeTo assess the clinical potential of multi-cycle temozolomide (TMZ) chemotherapy in patients with glioblastoma who underwent surgery and successive radiotherapy. MethodsThe clinical data of 68 glioblastoma patients who underwent surgery from January 2015 to December 2019 were collected. A total of 33 patients were treated with multi-cycle (≥9 cycles) TMZ chemotherapy (study group), while 35 patients were treated with standard-cycle (6 cycles) TMZ chemotherapy (control group). Differences in progression-free survival (PFS) and overall survival (OS) between the two groups were analyzed to evaluate the effects of multi-cycle and standard-cycle TMZ chemotherapies. The survival rates of the patients in both groups were analyzed using Kaplan–Meier survival curve. ResultsThe median PFS times were 10.5 months and 7.7 months in the study and control groups, respectively (P = 0.010), while the median OS times were 27.2 and 19.8 months, respectively (P = 0.036). The 1-, 2 -, and 3-year survival rates in the control group were 77.1 %, 42.9 %, and 25.7 % while those in the study group were 87.8 % (P = 0.344), 63.6 % (P = 0.097), and 39.4 % (P = 0.302), respectively. ConclusionsThe multi-cycle TMZ chemotherapy could prolong the OS and PFS time of patients with glioblastoma undergoing surgery and successive radiotherapy. However, it could not significantly elevate the 1 -, 2 -, and 3-year survival rates of these patients.

Prognostic values of immune landscape in Ras-mutant colorectal cancer peritoneal metastases.

e15583 Background: The peritoneal metastasis (PM) in patients with colorectal cancer (CRC) is associated with poor survival, especially in those with Ras mutations. However, knowledge on the mechanism of molecular biology in CRC peritoneal metastasis (CRCPM) is limited, and the impact of tumor immune microenvironment (TME) on PM pathogenesis and the prognosis of CRCPM remain unclear. Therefore, we characterized the TME of CRCPM and evaluated its potential diagnostic and prognostic values. Methods: This study involved 21 patients with metastatic CRC (mCRC), of whom 11 with CRCPM were classified into the experimental group and 10 with mCRC without PM (noCRCPM) were classified into the control group. Formalin-fixed and paraffin-embedded tissue of primary tumors from all patients was examined using the NanoString RNA sequencing system. The clinicopathological variables and TME biomarkers were compared using the chi-square test and Cox regression analysis. According to the results of multivariate analysis, a prognostic nomogram was generated, and its prediction ability was measured using the concordance index (C-index). Survival curves were generated using the Kaplan–Meier method, and survival comparison between groups was conducted using the log-rank test. Results: The TME in the CRCPM and noCRCPM groups was different, especially the expression of NOS2, TNSF9, KIR3DL2, MAGEA12, MRC1, KIR3DL1, and CD244 and the content of DC cells, macrophages, exhausted CD8+T cells, NK CD56dim cells, and M2 macrophages. Univariate analysis revealed that the expression of PTPN11, TIE1, MAGEA4, PDGFB, and PMS2 was significantly correlated with progression-free survival (PFS) time. These genes were subjected to the least absolute shrinkage and selection operator regression analysis and established a risk score model. Multiple Cox regression analysis showed that the risk score was a significant independent prognostic factor. However, considering the particularity of serum carcinoembryonic antigen (CEA), we built a combined model that included the CEA level and risk score. It could perform well in predicting the PFS time in patients with CRCPM (C-index 0.77). Conclusions: The TME of the primary lesion was significantly different between the CRCPM and noCRCPM groups. The model that combined the risk score and CEA level was a better outcome predictor among patients with CRCPM.

Assessment of therapeutic outcome and role of reirradiation in patients with radiation-induced glioma

BackgroundWe sought to clarify the optimal follow-up, therapeutic strategy, especially the role of reirradiation, and the diagnostic impact of isocitrate dehydrogenase (IDH) 1 and 2 mutation status in patients with radiation-induced glioma (RIG).MethodsWe retrospectively reviewed the clinical characteristics and treatment outcomes of 11 patients with high-grade glioma who satisfied Cahan’s criteria for RIG in our database during 2001–2021. IDH 1/2 mutations were analyzed by Sanger sequencing and/or pyrosequencing.ResultsThe RIGs included glioblastoma with IDH 1/2 wild-type (n = 7), glioblastoma not otherwise specified (n = 2), anaplastic astrocytoma with IDH1/2 wild-type (n = 1), and anaplastic astrocytoma not otherwise specified (n = 1). The median period from primary disease and RIG diagnosis was 17 years (range: 9–30 years). All patients underwent tumor removal or biopsy, 5 patients postoperatively received reirradiation combined with chemotherapy, and 6 patients were treated with chemotherapy alone. The median progression-free and survival times were 11.3 and 28.3 months. The median progression-free survival time of patients treated with reirradiation and chemotherapy (n = 5) tended to be longer than that of patients that received chemotherapy alone (n = 6) (17.0 vs 8.1 months). However, the median survival time was similar (29.6 vs 27.4 months). Local recurrence was observed in 5 patients treated with chemotherapy alone, whereas in 2 patients among 4 patients treated with reirradiation and chemotherapy. None of the patients developed radiation necrosis. In one case, the primary tumor was diffuse astrocytoma with IDH2 mutant, and the secondary tumor was glioblastoma with IDH 1/2 wild-type. Based on the difference of IDH2 mutation status, the secondary tumor with IDH 1/2 wild-type was diagnosed as a de novo tumor that was related to the previous radiation therapy.ConclusionsRIG can occur beyond 20 years after successfully treating the primary disease using radiotherapy; thus, cancer survivors should be informed of the long-term risk of developing RIG and the need for timely neuroimaging evaluation. Reirradiation combined with chemotherapy appears to be feasible and has favorable outcomes. Determining the IDH1/2 mutational status is useful to establish RIG diagnosis when the primary tumor is glioma.

Acetylation-induced PCK isoenzyme transition promotes metabolic adaption of liver cancer to systemic therapy.

Sorafenib and lenvatinib are approved first-line targeted therapies for advanced liver cancer, but most patients develop acquired resistance. Herein, we found that sorafenib induced extensive acetylation changes towards a more energetic metabolic phenotype. Metabolic adaptation was mediated via acetylation of the Lys-491 (K491) residue of phosphoenolpyruvate carboxykinase isoform 2 (PCK2) (PCK2-K491) and Lys-473 (K473) residue of PCK1 (PCK1-K473) by the lysine acetyltransferase 8 (KAT8), resulting in isoenzyme transition from cytoplasmic PCK1 to mitochondrial PCK2. KAT8-catalyzed PCK2 acetylation at K491 impeded lysosomal degradation to increase the level of PCK2 in resistant cells. PCK2 inhibition in sorafenib-resistant cells significantly reversed drug resistance in vitro and in vivo. High levels of PCK2 predicted a shorter progression-free survival time in patients who received sorafenib treatment. Therefore, acetylation-induced isoenzyme transition from PCK1 to PCK2 contributes to resistance to systemic therapeutic drugs in liver cancer. PCK2 may be an emerging target for delaying tumor recurrence.

Male Breast Cancer: Clinical, Demographical, and Pathological Features in a Cohort of 41 Patients.

Background and objectiveMale breast cancer (MBC) is a rare malignancy, and it accounts for less than 1% of all cancers in men. The pathogenesis of MBC remains unclear, with most available data obtained from single-center studies and retrospective series. The aim of this study was to share our experiences of MBC cases and to describe the characteristics of MBC patients.Materials and methodsWe retrospectively reviewed the records of 41 MBC cases and recorded the pathological, clinical, and demographic features of the patients. Data on progression-free survival (PFS) and overall survival (OS) were also recorded.ResultsThe mean age of the patients was 64.1 ± 10.0 years. The most common histopathological subtype was invasive ductal carcinoma. Hormone receptor positivity was detected in 39 (95.1%) patients. Human epidermal growth factor receptor 2 (HER2) positivity was present in five (12.2%) patients. Most of the patients had early-stage disease. Surgery was the treatment of choice for most primary tumors. Thirty-nine (95.1%) patients received hormonotherapy, and 21 (51.2%) received systemic chemotherapy. OS was found to be 126.4 months and PFS was 83.2 months. The OS and PFS time in patients with a Nottingham Prognostic Index (NPI) score of <5.4 were longer than those with an NPI score of >5.4.ConclusionThe hormone receptor status of most of the MBC patients was positive, and their HER2 status was negative. A multimodality approach was associated with longer survival, which has been reported in female patients with breast cancer as well. The NPI score is a useful tool for predicting survival time in MBC patients.

Targeted exome sequencing for the identification of common mutational signatures and potential driver mutations for brain metastases and prognosis.

Brain metastases (BMs) are malignancies in the central nervous system with poor prognosis. Genetic landscapes of the primary tumor sites have been extensively profiled; however, mutations associated with BMs are poorly understood. In the present study, target exome sequencing of 560 cancer-associated genes in samples from 52 patients with brain metastasis from various primary sites was performed. Recurrent mutations for BMs from distinct origins were identified. There were both genetic homogeneity and heterogeneity between BMs and primary lung tumor tissues. The mutation rate of the major cancer driver gene, TP53, was consistently high in both the primary lung cancer sites and BMs, while some genetic alterations, associated with DNA damage response deficiency, were specifically enriched in BMs. The mutational signatures enriched in BMs could serve as actionable targets for treatment. The mutation in the primary site of the potential brain metastasis driver gene, nuclear mitotic apparatus protein 1 (NUMA1), affected the progression-free survival time of patients with lung cancer, and patients with the NUMA1 mutation in BMs had a good prognosis. This suggested that the occurrence and clinical outcome of brain metastases could be independent of each other.

Lenvatinib prolongs the progression‑free survival time of patients with intermediate‑stage hepatocellular carcinoma refractory to transarterial chemoembolization: A multicenter cohort study using data mining analysis

Tyrosine kinase inhibitors are considered for use in patients with hepatocellular carcinoma (HCC) refractory to transarterial chemoembolization (TACE). The aim of the present retrospective study was to identify factors associated with progression-free survival (PFS) and to evaluate the indications for lenvatinib treatment in patients with intermediate-stage HCC refractory to TACE using a data-mining analysis. A total of 171 patients with intermediate-stage HCC refractory to TACE were included. All patients were classified into three groups according to their HCC treatment: Lenvatinib (n=45), sorafenib (n=53) and TACE (n=73) groups. PFS time was calculated using the Kaplan-Meier method and analyzed using a log-rank test. Factors associated with PFS time were evaluated using multivariate and decision-tree analyses. The median PFS time was 5.8, 3.2 and 2.4 months in the lenvatinib, sorafenib and TACE groups, respectively (P<0.001). In the Cox regression analysis, lenvatinib treatment and being within the up-to-seven criteria were identified as independent factors for PFS (lenvatinib, P<0.0001; within up-to-seven, P=0.001). The decision-tree analysis revealed that patients beyond the up-to-seven criteria, treated with lenvatinib and with albumin-bilirubin (ALBI) grade 1 had a longer PFS time (245.2±107.9 days) than patients beyond the up-to-seven criteria, treated with lenvatinib and with ALBI grade 2 (147.1±78.6 days). Additionally, lenvatinib was independently associated with longer PFS time in patients with intermediate-stage HCC refractory to TACE. Therefore, lenvatinib may be recommended for patients who have intermediate-stage HCC refractory to TACE, ALBI grade 1 and who are within the up-to-seven criteria.

PAX2 promotes epithelial ovarian cancer progression involving fatty acid metabolic reprogramming.

Ovarian cancer is the fifth most common type of cancer afflicting women and frequently presents at a late stage with a poor prognosis. While paired box 2 (PAX2) expression is frequently lost in high-grade serous ovarian cancer, it is expressed in a subset of ovarian tumors and may play a role in tumorigenesis. This study investigated the expression of PAX2 in ovarian cancer. The expression of PAX2 in a murine allograft model of ovarian cancer, the RM model, led to a more rapidly growing cell line both in vitro and in vivo. This finding was in accordance with the shorter progression-free survival observed in patients with a higher PAX2 expression, as determined in this study cohort by immunohistochemistry. iTRAQ-based proteomic profiling revealed that proteins involved in fatty acid metabolism and oxidative phosphorylation were found to be upregulated in RM tumors expressing PAX2. The expression of two key fatty acid metabolic genes was also found to be upregulated in PAX2-expressing human ovarian cancer samples. The analysis of existing datasets also indicated that a high expression of key enzymes in fatty acid metabolism was associated with a shorter progression-free survival time in patients with serous ovarian cancer. Thus, on the whole, the findings of this study indicate that PAX2 may promote ovarian cancer progression, involving fatty acid metabolic reprograming.

PD-L1 gene promoter methylation represents a potential diagnostic marker in advanced gastric cancer.

Gastric cancer is one of the most prevalent malignant tumors worldwide. Immunological checkpoint inhibitors of the programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) signaling pathway are effective in the treatment of various malignant tumor types, but the potential of such immunotherapeutic techniques for the treatment of gastric cancer is yet to be elucidated. The purpose of the present study was to investigate the methylation of the PD-L1 gene promoter and its clinical significance in advanced gastric cancer, as this may suggest the use of PD-L1 promoter methylation as a novel biomarker for gastric cancer progression. In a total of 70 samples, the methylation rate of the PD-L1 gene promoter region was significantly higher in gastric cancer tissues compared with adjacent tissues. A high level of PD-L1 promoter methylation was associated with lymph node staging, and resulted in poorer prognoses in patients with advanced gastric cancer. A total of 26 patients exhibited highly methylated PD-L1; in this group, the median progression-free survival time of patients receiving platinum/fluorouracil chemotherapy was 4.2 months longer than those receiving paclitaxel/fluorouracil chemotherapy, and the risk of disease progression in patients receiving paclitaxel/fluorouracil chemotherapy was 5.009 times higher compared with patients who received platinum/fluorouracil chemotherapy. Additionally, PD-L1 promoter methylation was significantly correlated with PD-L1 expression, and the progression of advanced gastric cancer. In conclusion, high methylation levels of the PD-L1 promoter region may be a faciliatory mechanism enabling gastric cancer tumorigenesis, and may also represent an independent prognostic factor for chemotherapeutic efficacy in patients with advanced gastric cancer.

LncRNA KCNQ1OT1 is overexpressed in non-small cell lung cancer and its expression level is related to clinicopathology.

The aim of this study was to explore the expression of long non-coding RNA (lncRNA) KCNQ1OT1 in non-small cell lung cancer (NSCLC), and to elucidate its clinical significance. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA KCNQ1OT1 in NSCLC tissues and para-cancer tissues (5 cm or above away from the tumor). The relation between lncRNA KCNQ1OT1 expression and the clinical-pathological data was analyzed by the multivariate logistic regression analysis. Furthermore, the survival analysis was performed by the Kaplan-Meier method. The expression of lncRNA KCNQ1OT1 increased significantly in NSCLC tissues than that of in para-cancer tissues. According to the median expression of lncRNA KCNQ1OT1, NSCLC patients were divided into two groups, including high expression group and low expression group. Meanwhile, the lncRNA KCNQ1OT1 expression was correlated with tumor size, tumor node metastasis (TNM) staging, and lymph node metastasis of NSCLC patients. Both univariate analysis and multivariate analysis indicated that the high expression of lncRNA KCNQ1OT1 was closely related to TNM staging and lymph node metastasis. In addition, the Kaplan-Meier analysis showed that the overall survival and progression-free survival time of patients with higher lncRNA KCNQ1OT1 expression were significantly worse than those with lower lncRNA KCNQ1OT1 expression. LncRNA KCNQ1OT1 might contribute to the development of NSCLC.

Preliminary experience in guiding individualized targeted therapy of advanced metastatic renal cell carcinoma with gene detection technology

Objective To explore the efficacy and tolerance of adverse reactions of gene detection technique in guiding individualized targeted therapy for advanced metastatic renal cell carcinoma. Methods Retrospective analysis was performed on the clinical data of 62 patients with advanced metastatic renal cell carcinoma before and after receiving targeted drug treatment in our department from October 2015 to October 2017. Among the 62 patients, there were 36 males and 26 females, with an average age of (54±13)years old.16 patients were treated with sunitinib, 20 patients were treated with sorafenib and 26 patients were treated with pazopanib. A total of 28 patients (individualized group) were selected to receive targeted drug according to the results of gene detection, and 34 patients were treated with targeted drug empirically (empirical group). In individualized group, there were 17 males and 11 females with the average age of(51.3±15.6) years old. 20 patients accepted the operation. The distant metastasis included bone metastasis in 21 cases, lung metastasis in 7 cases, liver metastasis in 16 cases, epidermal metastasis in 4 cases and lymphatic metastasis in 14 cases. According to risk of MSKCC, the case number of low risk, moderate risk and high risk were 15, 7, 6, respectively. 7 patients were treated with sunitinib, 8 patients were treated with sorafenib and 13 patients were treated with pazopanib. In empirical group, there were 19 males and 15 females with the average age of (56.3±10.1) years old. 22 patients accepted the operation. The distant metastasis included bone metastasis in 20 cases, lung metastasis in 5 cases, liver metastasis in 13 cases, epidermal metastasis in 3 cases and lymphatic metastasis in 15 cases. According to risk of MSKCC, the case number of low risk, moderate risk and high risk were 20, 8, 6, respectively. 9 patients were treated with sunitinib, 12 patients were treated with sorafenib and 13 patients were treated with pazopanib.The baseline characteristics of the two groups of patients, including gender, age, whether operation was performed, site of metastasis, and risk of MSKCC, didn’t show significant difference. Patients in both groups received the standard treatment regimen and the follow-up duration was 4-26 months to observe the efficacy, progression-free survival and tolerance to adverse reactions of the targeted therapy. Results After 12 months of treatment, 13 patients in the individualized group was recorded objective remission. 7 patients in the empirical group was recorded objective remission, as well. The tumor control efficacy of the individualized group was significantly better than that of the empirical group (46.4% vs. 20.6%, P=0.03). Meanwhile, the median progression-free survival time (13.2 months, 3.7-24.2 months) in the individualized group was significantly longer than that in the empirical group (12.1 months, 2.8-22.1 months) (P=0.009). Compared with the empirical group, the higher incidence of targeted treatment-related adverse reactions occurred in the individualized group, including thrombocytopenia(46.4% vs.17.6% P=0.014), leukopenia(46.4% vs.17.6% P=0.005), hypertension(71.4% vs.44.1%, P=0.031) and hypothyroidism(60.7% vs.29.4%, P=0.013). Conclusions Compared with the patients with empirical drugs, the application of gene detection technique to select individualized targeted drugs for the treatment of advanced metastatic renal cancer is obvious curatively effective, and to a certain extent extends the progression-free survival time of patients. Key words: Advanced metastatic renal cell carcinoma; Molecular targeted therapy; Gene detection; Individualized

Observation of clinical efficacy and toxic and side effects of pirarubicin combined with cytarabine on acute myeloid leukemia

Efficacy and toxic and side effects of pirarubicin combined with cytarabine and mitoxantrone combined with cytarabine on the treatment of initially treated acute myeloid leukemia (AML) were compared. A retrospective analysis was performed on the medical records of 76 AML patients who were initially treated in Weifang People's Hospital. Among them, 36 patients (observation group) were treated with pirarubicin combined with cytarabine, and 40 patients (control group) were treated with mitoxantrone combined with cytarabine. The efficacy and toxic and side effects on patients in the two groups were observed. There was no statistically significant difference in the complete response (CR) rate, partial response (PR) rate and overall response (OR) rate of patients between the two groups (P>0.05). Patients in the observation group had significantly lower incidence of cardiotoxicity and alopecia than those in the control group (P<0.05). Patients in the observation group had lower incidence of bone marrow depression (BMD) at grade IV than those in the control group (P<0.05). The median progression-free survival time of patients was 14.5 months in the observation group and 18 months in the control group. The progression-free survival rate of patients was 36.11% in the observation group and 40.00% in the control group, with no difference between the two groups (P>0.05). The median survival time of patients was 22.5 months in the observation group and 24.5 months in the control group. The overall survival (OS) rate of patients was 44.44% in the observation group and 47.50% in the control group, with no difference between the two groups (P>0.05). Both pirarubicin combined with cytarabine and mitoxantrone combined with cytarabine have satisfactory efficacy on initially treated AML. Compared to the latter, the former has lower toxic and side effects.

Impact of prior antibiotic use on the efficacy of nivolumab for non‑small cell lung cancer

Gut microbiota serves an important role in shaping systemic immune responses. Antibiotics cause changes in the gut microbiota that may influence the efficacy of cancer immunotherapy. In the present study, a retrospective analysis of the data from 90 patients treated with nivolumab for non-small cell lung cancer (NSCLC) was conducted. A total of 13 patients were treated with antibiotics prior to nivolumab therapy. The median progression-free survival time in patients treated with antibiotics was 1.2 months [95% confidence interval (CI), 0.5-5.8], while the time for patients who were not treated with antibiotics was 4.4 months (95% CI, 2.5-7.4). The median overall survival time in patients treated with antibiotics was 8.8 months, while it was not reached in those not treated with antibiotics, respectively. The differences between the survival curves with regard to PFS and OS were statistically significant (P=0.04 and P=0.037, respectively). However, in multivariate analysis, no statistically significant association was indicated between survival and prior antibiotic use, although a certain trend concerning the negative influence of antibiotic use was conveyed.