Cancer treatment and research communications最新文献

Background

Rectal cancer (RC) poses a significant global health challenge, causing substantial morbidity and mortality. This study aims to investigate the survival rates of RC patients and identify the factors that influence their survival. The study considers demographic characteristics, tumor features, and treatment received as the factors under consideration.

Methods

A retrospective analysis was conducted on the medical records of 593 RC patients. Data were collected through a comprehensive review of medical records and conducting telephone interviews. Survival rates were estimated using the life table method, and subgroup comparisons were performed using the log-rank test. Cox regression analysis was utilized to assess the independent associations between RC survival time and various covariates.

Results

The study cohort comprised 593 RC patients, with a predominantly male representation. The mean age at diagnosis was 58.18 years, and the majority of patients (78.6 %) underwent surgical interventions. The median age at symptom onset and diagnosis were 58 and 59 years, respectively. Survival rates at 1st, 3rd, 5th, and 10th years were estimated to be 85 %, 59 %, 47 %, and 36 %, respectively. Statistical analysis revealed several significant prognostic factors, including age, education, symptoms, and cancer stage. In the multivariate Cox proportional-hazards analysis, advanced regional stage (HR = 1.54, 95 % CI, 1.13–2.08), presence of metastasis (HR = 3.73, 95 % CI, 2.49–5.58), and age over 70 (HR = 1.65) were associated with a higher risk of mortality.

Conclusion

Given the alarming prognosis of RC observed in the study area and the significant delay between symptom onset and diagnosis, it is crucial to address this issue and potentially improve the survival rates of RC patients.

Introduction

We have shown in a Phase I trial that immediate adjuvant chemotherapy (IAC) during surgical resection and immediately postoperative is safe and feasible in patients with colon cancer (CC). IAC avoids delays in adjuvant treatment and has the potential to improve survival and quality of life. We aim to determine patients and providers attitudes toward this novel multidisciplinary treatment approach.

Methods

Two web-based surveys were administered to newly diagnosed CC patients, survivors, surgeons and oncologists. Surveys assessed treatment preferences and perceived barriers to IAC. Chi-square tests were conducted to compare differences between patients’ and providers’ responses.

Results

Responses were collected from 35 patients and 40 providers. Patients were more willing to: (1) proceed with IAC to finish treatment earlier thus possibly improving quality of life (p = 0.001); (2) proceed with IAC despite potential side effects (p < 0.001); and (3) proceed with a dose of intraoperative chemotherapy even if on final pathology, may not have been needed (p = 0.002). Patients were more likely to indicate no barriers to collaborative care (p = 0.001) while providers were more likely to cite that it is time consuming, thus a barrier to participation (p = 0.001), has scheduling challenges (p = 0.001), and physicians are not available to participate (p = 0.003).

Conclusions

We observed a discordance between what providers and patients value in perioperative and adjuvant CC treatment. Patients are willing to accept IAC despite potential side effects and without survival benefit, highlighting the importance of understanding patient preference.

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.

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.

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.

Background

In untreated ALK-positive non-small cell lung cancer no randomized controlled trials (RCTs) are available directly comparing next-generation ALK-inhibitors. We conducted a sensitivity analysis using the likelihood of being helped or harmed (LHH).

Methods

Phase III trials comparing ALK-inhibitors to crizotinib were included. Efficacy outcomes were progression-free survival (PFS), objective response rate (ORR), PFS in patients with brain metastases and intracranial ORR. Safety outcomes were grade 3–4 adverse events (AEs), dose reductions and discontinuations.

Results

Six RCTs (1524 patients) were included. Lorlatinib and brigatinib had the lowest NNT for intracranial outcomes. Alectinib demonstrated favourable LHHs for grade 3–4 AEs, dose reductions and discontinuations. Brigatinib LHHs were low for common AEs, mainly laboratory anomalies and hypertension. Ensartinib showed mainly skin toxicity. Lorlatinib LHHs were low for specific grade 3–4 AEs, mainly metabolic alterations.

Conclusions

The four ALK-inhibitors exhibited favourable risk-benefit ratios. Lorlatinib showed the lowest NNT for systemic efficacy and, alongside with Brigatinib, lower NNTs for intracranial efficacy. Alectinib exhibited higher LHHs for AEs.

Registration

PROSPERO registration number: CRD42023389101.

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.

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.