Cancer treatment and research communications最新文献

Background

The most recommended treatment for stage IV EGFR-positive lung cancer is osimertinib monotherapy. The dosage of osimertinib is fixed at 80 mg/day regardless of body surface area (BSA), however some patients withdraw or reduce the dosage due to adverse events (AEs).

Methods

We performed a retrospective cohort study of 98 patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), who received 80 mg osimertinib as the initial treatment. We investigated the impact of BSA on efficacy and safety of osimertinib.

Results

The cut-off value of BSA was estimated using the receiver operating characteristics curve, and was determined to be 1.5 m². There were 44 patients in the BSA < 1.5 group and 54 patients in the BSA ≥ 1.5 group. There was no significant difference in the incidence of AEs (hematologic toxicity of ≥grade 3 or higher, and non-hematologic toxicity of ≥grade 3) between the two groups. However, the incidence of dose reduction due to AEs was significantly higher in the BSA < 1.5 group compared with the BSA ≥ 1.5 group (16 patients vs 5 patients, p = 0.003). The main reasons were fatigue, anorexia, diarrhea, and liver disfunction. Median progression-free survival (PFS) was not significantly different (16.9 months in the BSA < 1.5 group vs 18.1 months in the BSA ≥ 1.5 group, p = 0.869).

Conclusion

Differences in BSA affected the optimal dose of osimertinib. However, the PFS with osimertinib treatment was not affected by BSA. Therefore, when using osimertinib as an initial treatment for patients with EGFR-mutant NSCLC, dose reduction to control AEs should be considered, especially in the BSA<1.5 group.

Background

Colorectal cancer is one of the most common cancers and the leading cause of cancer-related deaths worldwide. The incidence is gradually increasing, and the mortality and recurrence rates of the disease remain high.

Methods

This study was conducted as a cross-sectional study using tissue samples of 106 patients who underwent surgery at Sina Hospital from 2021 to 2022. After histopathological examination and identification of the pathological features of the tumor, the samples were subjected to immunohistochemical staining using a monoclonal antibody against villin.

Results

In this study, we observed a significant association between villin expression and tumor depth, as well as a correlation between villin expression and tumor location (colon or rectum). However, no association was found between villin expression and the number of affected lymph nodes and age, sex, tumor grade, and size. Furthermore, there was no significant association between villin expression and tumor vascular or neural invasion.

Conclusion

The extent of local invasion and metastasis are important factors in disease progression and can lead to treatment failure. Therefore, new biomarkers are needed to identify patients at risk of local and distant metastases and to enable appropriate treatment of patients.

Background

Amivantamab, an EGFR-MET bispecific antibody, is the first approved targeted therapy for patients with EGFR Ex20ins NSCLC after prior platinum-based chemotherapy—a population with historically poor outcomes before amivantamab approval. As antitumor activity in single-arm studies typically focuses on responders, the evaluation of outcomes in patients with stable disease (SD) as best response is of clinical interest.

Patients and methods

Among 114 patients with post-platinum EGFR Ex20ins NSCLC in CHRYSALIS (NCT02609776; data cutoff: March 30, 2021), response was assessed by blinded independent central review via RECIST v1.1. Patients alive and receiving therapy at 12 weeks were grouped by response at this landmark: partial or complete response (PR+), SD, or progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) by response cohort were determined using the Kaplan-Meier method; hazard ratios (HRs) and 95% confidence intervals (CIs) between response cohorts were calculated using Cox proportional hazards regression.

Results

Among patients alive and receiving therapy at 12 weeks (n=107), 42 (39%) had PR+, 52 (49%) had SD, and 13 (12%) had PD. Among patients with PR+ and SD, median PFS was 12.2 and 7.0 months, respectively. A corresponding improvement in OS was observed in patients achieving PR+ (median: not reached; HR vs PD=0.21 [95% CI: 0.08–0.54]) and SD (median: 23.0 months; HR vs PD=0.33 [95% CI: 0.14–0.77]), relative to those with PD (median: 14.0 months).

Conclusion

SD was observed in 49% of patients receiving amivantamab, with corresponding increases in OS that dramatically improved the prognoses of this patient population.

Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), is an enzyme with tyrosine kinase activity that plays a pivotal role in angiogenesis, the process of new blood vessel formation. This receptor is of significant clinical importance as it is implicated in various cancers, particularly non-small cell lung cancer (NSCLC), where its dysregulation leads to uncontrolled cell growth through ligand-induced phosphorylation. While commercially available drugs target VEGFR1, their prolonged use often leads to drug resistance and the emergence of mutations in cancer patients. To address these challenges, researchers have identified the human tyrosine kinase (hTK) domain of VEGFR1 as a potential therapeutic marker for lung malignancies. The 3D crystal structure of the hTK domain, obtained from Protein Data Bank (PDB ID: 3HNG), has provided vital structural insights of hVEGFR1. This study has revealed variations within the hVEGFR1 tyrosine kinase domain, distinguishing between regions associated with phosphorylase kinase and transferase activities. We identified numerous potential phosphorylation sites within the TK domain, shedding light on the protein's regulation and signaling possible. Detailed molecular interaction analyses have elucidated the binding forces between lead molecules and hVEGFR1, including hydrogen bonds, electrostatic, hydrophobic, and π-sigma interactions. The stability observed during molecular dynamics simulations further underscores the biological relevance of these interactions. Furthermore, docked complexes has highlighted localized structural fluctuations, offering insight into potential allosteric effects and dynamic conformational changes induced by lead molecules. These findings not only provide a comprehensive characterization of hVEGFR1 but also pave the way for the development of targeted therapies. Eventually, this study has the potential in identifying drug to combat diseases associated with hVEGFR1 dysregulation, including cancer and angiogenesis-related disorders, contributing to effective treatment strategies.

Colorectal cancer (CRC) continues to be one of the most prevalent and lethal cancers worldwide. Over the past decades, immune checkpoint inhibitors (ICIs) have shown to significantly improve patient outcomes in mismatch repair-deficient metastasized CRC. However, widening the scope of this novel treatment modality has been the object of growing interest. This article will review several landmark trials, while exploring various aspects of this rapidly evolving field, including potential neoadjuvant (or even entirely nonsurgical) and adjuvant indications in localized disease. We will also discuss differences between management of rectal and colon cancer, current and expected challenges (eg. resistance, toxicities, pseudoprogression, biomarkers) and other future opportunities including combinations with other therapeutic agents and the role of ICIs in the treatment of both deficient as well as proficient mismatch repair (dMMR and pMMR respectively) CRC.

Cervical cancer ranks as the fourth most prevalent gynaecological malignancy and is a significant contributor to mortality among women globally. With the exception of HPV-mediated oncogenesis, the molecular etiology of the disease is poorly understood, and there is a critical dearth of knowledge concerning cancer that is not caused by HPV. Moreover, none of the options presently accessible for the treatment of cancers specifically target cervical cancer. In context with this, this research aims to identify the critical genes, regulators, and pathways that contribute to the pathogenesis of cervical cancer, in addition to prospective pharmacological targets and repurposed therapeutic agents that can be directed against the targets. A total of eleven different global gene expression (transcriptome) datasets were subjected to analysis utilizing a variety of in silico tools. The present study reveals a previously unknown correlation between cervical cancer and five genes: SHC1, CBL, GNAQ, GNA14, and PPP2CA. Significant dysregulation was observed in four crucial transcription factors (KLF4, E2F1, FOXM1, and AR) that modulate the expression of numerous genes in cervical cancer. Furthermore, it was observed that AKT1, MAPK1, and MAPK3 ranked the highest among the regulatory genes that hold promise as therapeutic targets in the context of cervical cancer. Additional research, both in vitro and in vivo, is required to validate and establish the therapeutic potential of these crucial genes in the context of cervical cancer.

Objectives

Endometrial cancer is a collection of heterogeneous histologies and molecular subtypes with different risk profiles. High-risk endometrial cancer surveillance regimens vary amongst providers. The National Comprehensive Cancer Network (NCCN) recommends symptom and exam-based surveillance for all endometrial cancers after remission, regardless of cancer stage and histology. Our objective was to identify the first method of detection of recurrence in high-risk endometrial cancers and examine disease recurrence and treatment patterns.

Methods

A retrospective review of patients diagnosed with high-risk endometrial cancer between November 2013 and February 2020 was conducted at a large academic institution. High-risk endometrial cancers were classified by histology and pathologic stage and were categorized by primary method of detection.

Results

Two hundred and twenty-nine patients were identified with high-risk endometrial cancer, 63 (28 %) of whom had a recurrence. Most recurrences were first detected with routine imaging in 31 patients (49.2 %) and symptom surveillance in 24 patients (38.15 %). Regardless of the detection method, most patients underwent systemic treatment. The average survival after recurrence was 2.0 years in the imaging cohort and 1.6 years in the non-imaging surveillance cohort.

Conclusions

The most common site of recurrence in our cohort of high-risk endometrial cancer was in the lung, and most recurrences were identified with asymptomatic imaging. Though there was no statistically significant difference between the survival of those who underwent imaging surveillance vs. standard of care, there was a trend toward survival that deems further exploration with a larger cohort.

Background & Aims

Accumulating evidence showed that inflammation contributes markedly to cancer progression, with C-reactive protein (CRP) being one of the lengthily studied inflammation marker. For breast cancer (BCa), pre-treatment elevated CRP upon diagnosis was linked with increased mortality. This study aimed to identify factors predictive of elevated CRP in pre-treatment BCa population that can serve as potential therapeutic targets to reduce inflammation.

Methods

This is a cross-sectional study using multiple logistic regression to identify predictors of elevated CRP among pre-treatment, newly diagnosed BCa patients. Studied variables were socio-demographic and medical characteristics, anthropometric measurements [body weight, Body Mass Index, body fat percentage, fat mass/fat free mass ratio, muscle mass, visceral fat], biochemical parameters [albumin, hemoglobin, white blood cell (WBC), neutrophil, lymphocyte], energy-adjusted Dietary Inflammatory Index, handgrip strength (HGS), scored Patient Generated-Subjective Global Assessment, physical activity level and perceived stress scale (PSS).

Results

A total of 105 participants took part in this study. Significant predictors of elevated CRP were body fat percentage (OR 1.222; 95 % CI 1.099–1.358; p < 0.001), PSS (OR 1.120; 95 % CI 1.026–1.223; p = 0.011), low vs normal HGS (OR 41.928; 95 % CI 2.155–815.728; p = 0.014), albumin (OR 0.779; 95 % CI 0.632–0.960; p = 0.019), and WBC (OR 1.418; 95% CI 1.024–1.963; p = 0.036).

Conclusion

Overall, predictors of elevated CRP in pre-treatment, newly diagnosed BCa population were body fat percentage, PSS, HGS category, albumin and WBC.

Background

Colorectal (CRC) and lung adenocarcinoma share many genetic and pathological similarities. A circulating tumor DNA (ctDNA) test for CRC may also be useful for detection of lung adenocarcinoma. This study determined if a methylated BCAT1/IKZF1 ctDNA test for CRC can be used for detection of lung adenocarcinoma.

Patients and methods

Circulating cell free DNA (ccfDNA) was extracted from plasma collected prospectively from healthy controls, patients in remission from CRC, patients with lung adenocarcinoma, and patients with isolated metastatic CRC lung lesions. Plasma ccfDNA was bisulfite converted and assessed for methylated BCAT1/IKZF1 by quantitative real-time PCR. Comparisons between the different patient groups for a positive ctDNA test (BCAT1 and/or IKZF1) and ctDNA levels (% of total ccfDNA), as well as any associations with clinicopathological and demographic features, were assessed.

Results

Methylated BCAT1/IKZF1 ctDNA was detected in 18/39 (46.2 %) patients with lung adenocarcinoma, which was significantly (p < 0.001) higher compared to healthy controls (49/606; 8.1 %) and patients in remission from CRC (22/171, 12.9 %). Patients with stage III/IV lung adenocarcinoma had higher BCAT1/IKZF1 ctDNA positivity compared to stage I/II cases (68.2 % vs 17.7 %, p < 0.01), where a significantly higher proportion tested positive for methylated IKZF1 ctDNA alone (54.6 % vs 5.9 %, p < 0.001). There was no difference in BCAT1/IKZF1 ctDNA test positivity between patients with stage IV primary lung adenocarcinoma (n = 17) compared to lung-metastasising CRC cases (n = 17; 70.6 % v 64.3 %).

Conclusion

A ctDNA test measuring methylated BCAT1/IKZF1 can sensitively detect lung adenocarcinoma and may be a promising aid for detection of advanced disease.

Clinical trial registrations

Australian and New Zealand Clinical Trials Registry, www.anzctr.org.au, ACTRN12616001138471, ACTRN12611000318987.

Introduction

Thyroid cancer is an important endocrine malignancy worldwide, including papillary carcinoma, which is responsible for more than 90 % of thyroid malignancies. Human epidermal growth factor receptor 2 (Her-2/neu) overexpression plays a significant act in the development, progression, and invasion of various tumors through effects on the cell cycle, angiogenesis, cell movement, and apoptosis.

Objective and methods

The study was conducted as a cross-sectional study, using tissue samples from 53 patients who underwent lobectomy or total thyroidectomy between 2020 and 2022. For histopathological examination and to determine the pathological features of the tumor, tumor specimens were stained for immunohistochemistry using a monoclonal antibody against Her-2/neu.

Results

In this study, Her-2/neu was expressed in 13.2 % of PTC patients and not expressed in normal thyroid tissue. No significant relationship was established between Her-2/neu expression and tumor histological subtype, as well as tumor size, sex, or tumor focality. Furthermore, there was no significant association between Her-2/neu expression and vascular invasion or extrathyroidal extension of the tumor.

Conclusion

No significant Her-2/neu expression was observed in the malignant thyroid tissue. These findings raise questions about the value of Her-2/neu as a potential prognostic factor or target of a specific anticancer treatment for thyroid cancer.