Oncology最新文献

Introduction: Cancer patients often have comorbidities due to the aging population or various other factors. However, clinical trials typically exclude specific severe comorbidities, and no prior study has examined their impact on antiemetic efficacy. Our previous research suggested that antiemetic efficacy might be higher in patients with diabetes mellitus (DM) compared to those without DM because of cortisol and substance P. To further investigate this, the current study analyzed which comorbidities affected chemotherapy-induced nausea and vomiting in patients with esophageal cancer treated with cisplatin-based chemotherapy.

Methods: This retrospective study enrolled Japanese patients with esophageal cancer who received fluorouracil and cisplatin (FP) combination chemotherapy as their initial treatment. The primary endpoint was the total control (TC) rate during the first cycle, defined as no emetic episodes, no nausea, and no rescue medication use over the overall period (0-120 h) measured by patients' diary or medical staff interview. Univariate and multivariate logistic regression models were used to analyze the TC rate, including previously reported risk factors (age, sex, performance status, body mass index, cisplatin dose, and number of prophylactic antiemetic agents). Comorbidities showing significance in the univariate analysis were further assessed in the multivariate analysis. The significance level was set at 5%.

Results: Among the 285 eligible patients, the prevalence of comorbidities was as follows: hypertension (36.8%), DM (17.9%), cardiovascular disease (10.6%), and hyperlipidemia (9.5%). Multivariate analysis revealed a significantly higher TC rate during the overall period in patients with cardiovascular disease (50.0%) compared to those without one (32.5%) (adjusted odds ratio 0.455, 95% confidence interval 0.207-0.999, p = 0.0499).

Conclusions: Antiemetic regimen appeared to be more effective in patients with esophageal cancer and cardiovascular disease during the overall period when compared to patients without one. The clinical trial stratified by whether cardiovascular disease should be conducted in the further.

Introduction: Hepatoblastoma (HB) is the most frequent liver cancer in children, typically occurring before the age of five. Thanks to the combination of chemotherapy and surgery, the 5-year survival rate following diagnosis is approximately 83%. Today, the main challenge is the efficient treatment of high-risk patients, particularly those presenting with lung metastasis or experiencing relapse. To better study HB and validate new therapeutic options, various animal models have been developed in mice, chick and zebrafish. However, none of these models fully recapitulates the complexity and juvenile context of the disease, as observed in very young patients.

Methods: To account for the young age of patients and better mimic the hepatic microenvironment in which HBs develop, we established an innovative orthotopic xenograft model of HB in juvenile mice, which also generates lung metastases. Eleven-day-old immunocompromised mice were injected intrahepatically with Huh6 cells. Tumor progression was monitored through bioimaging and confirmed post-euthanasia by direct examination of the liver and lungs using microscopic imaging and immunohistochemistry. To further validate the model, some implanted mice were treated with cisplatin, and the response of HB cells to this DNA intercalating agent was assessed.

Conclusion: This neonatal orthotopic xenograft model of HB in mice reproduces lung metastases and exhibits sensitivity to cisplatin. It fully mimics the developmental progression of this pediatric tumor and clearly surpasses existing models in adult mice, paving the way for more robust basic research investigations and preclinical studies in whole animals.

Introduction: Azacitidine plus venetoclax (HMA&Ven) is a well-established treatment for acute myeloid leukemia (AML) in older or medically unfit patients, given its favorable efficacy and safety profile. Recently, there has been growing interest in extending its use to younger, fitter patients who are traditionally treated with intensive chemotherapy (IC). However, prior studies comparing HMA&Ven to IC have been limited by small sample sizes and inconclusive results.

Methods: We conducted a propensity score-matched cohort study using the TriNetX database to compare mortality and safety outcomes between HMA&Ven and IC in this population. We included patients aged 60-75 years with a diagnosis of AML who received either HMA&Ven or IC as induction therapy. Patients who underwent bone marrow transplantation or chimeric antigen receptor T-cell therapy following induction were excluded. We matched patients on predetermined variables, such as age, sex, race, comorbidities, medication, socioeconomic status, and healthcare utilization.

Results: The final analysis included 370 patients in each treatment group. At the 1-year follow-up, HMA&Ven demonstrated comparable all-cause mortality to IC (HR: 1.16 [95% CI: 0.93-1.44], p value = 0.186). However, HMA&Ven was associated with significantly lower rates of neutropenia (HR: 0.72 [95% CI: 0.60-0.87], p value <0.001) and sepsis (HR: 0.72 [95% CI: 0.56-0.92], p value = 0.009).

Conclusion: Among AML patients aged 60-75, HMA&Ven showed similar 1-year all-cause mortality compared to IC, while offering a significantly better safety profile with reduced risks of neutropenia and sepsis.

Introduction: Prostate cancer is one of the main types of cancer in men; specifically, in Mexico there is an increasing trend in incidence in the last 2 decades. The lack of targeted therapy in this neoplasm compels us to find new biomarkers that could work as possible drug targets. HER2 is a protein in cell membrane that has been targeted with different types of antibodies in multiple neoplasms, such as breast or gastric cancer. In prostate cancer, there are few reports of HER2 expression; in one study, the incidence of HER2 in prostatic tissue was 15%, mainly with low expression of the protein; in another report that included a total of 2,525 patients, they reported up to 22.5% of HER2 expression, with HER2 1+ and 2+ being the most common report. There are no reports of HER2 expression in Mexican population.

Methods: We identified patients diagnosed with prostate cancer through prostatectomy or transurethral resection of the prostate, between January 2017 and December 2021 in a private hospital in Mexico City, and then performed immunohistochemistry utilizing VENTANA® HER2 (4B5).

Results: A total of 277 patients with prostate cancer were included and finally a total of 194 patients were analyzed, reporting an expression of 21.1% of patients, with expression of HER2 1+ in 20.1%, HER2+ 0.5%, and HER2 3+ in 0.5% of patients. We found an association between the presence of HER2 and the prognostic group according to Gleason score that the patients were allocated in.

Conclusion: Our study shows that expression of HER2 in prostate cancer in Mexican population is similar to that reported in other countries and that this biomarker could be used as a prognostic factor. As well, the overexpression of this protein might be used as a targeted therapy since there is evidence of the use of drugs such as fam-trastuzumab deruxtecan in different types of tumors that have a low expression of HER2, adding a new possible therapeutic weapon in a tumor with limited therapeutic options.

Introduction: Breast cancer is the main cause of cancer-related mortality in women in the developed world. In particular, receptors of luteinizing hormone-releasing hormone (LHRH or GnRH) are overexpressed in this malignant disease. The aim of this study was to develop a new molecular probe [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/nicotinic acid (NA) as a novel molecular imaging agent for breast cancer.

Methods: HYNIC-GSG-LHRH(D-Lys6) was acquired and radiolabeled with [99mTc]Tc. Radiochemical purity and stability under different conditions were evaluated by instant thin-layer chromatography (ITLC) and high-performance liquid chromatography. Lipophilicity was determined by the partition coefficient test. In vitro cell binding studies were performed in different human and mice breast cancer cell lines (MDA-MB-231, MDA-MB-435, MCF-7, BT474, and 4T1) as well as in normal murine fibroblasts (NIH-3T3) and CHO-K1 as a negative control. Biodistribution studies were performed in normal Balb/c mice and 4T1 tumor-bearing Balb/c mice up to 6 h post-injection (pi). SPECT/CT images were performed in 4T1 tumor-bearing Balb/c mice up to 5 h pi.

Results: [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/NA complex was labeled with a high radiochemical purity (>98%) and remained stable for up to 4 h. It exhibited good hydrophilicity (log p = -2.82 ± 0.04) and also demonstrated significant and specific binding across all evaluated breast cancer cell lines. Biodistribution studies showed a high renal clearance and low nonspecific binding (<2% Act/g) in most organs, as well as appreciable tumor uptake (5.8 ± 0.5 % ID/g 1 h pi) and high tumor-to-muscle ratio (maximum of 30.5 ± 11.2 at 1 h pi). SPECT/CT imaging of 4T1-tumor-bearing Balb/c mice revealed results consistent with the biodistribution studies, showing a tumor-to-non-tumor ratio of greater than 3.5 at all evaluated time points. In vivo blocking studies confirmed specificity for the LHRH receptor.

Conclusions: [99mTc]Tc-HYNIC-GSG-LHRH(d-Lys6)/tricine/NA complex has shown significant potential for in vivo visualization of LHRH receptors expression in breast cancer.

Introduction: The use of electronic patient-reported outcome (ePRO) in patients has been demonstrated to improve patient care and symptom management in curative and palliative settings. We examined the electronic and dynamic reporting of wellbeing, symptoms, and cognition in unsupervised patients with solid cancers of bladder, breast, and lung in neoadjuvant, adjuvant, and metastatic therapy settings.

Methods: Participants undergoing immune checkpoint inhibitor treatment were provided a mobile smartphone app for standardized and structured reporting on wellbeing and symptoms according to the CTCAE criteria, as well as cognitive test and vital parameters. Data of 11 patients were available for descriptive analysis.

Results: The eleven patients presented here entered a total of 9,624 symptom ratings and rated their wellbeing 2,983 times. Patients recorded a median number of symptom entries of 453 (IQR 109-1401). 49 different symptoms were reported in total with a median of 8 per patient (IQR 4-15). Of the 24 symptoms that were frequently shared among multiple patients, all are considered clinically relevant and associated with immunotherapeutic interventions. The most commonly patient-reported symptoms were fatigue (82%), diarrhea (45%), limb and muscle pain (45%), sleep problems (45%), and dyspnea (36%). Overall, symptoms severity was reported at grades between 0.1 (very mild) and 9.0 (very severe), at a mean grade of 2.6. The most severely rated unique entry was for limb and muscle pain; edema of limbs showed the highest mean rating (5.9). The median duration of app use was 195 days (IQR 108-472). The descriptive analysis showed a general trend of patients with higher grade symptoms reporting a lower grade of wellbeing but no clear association with cognitive performance.

Conclusion: Unsupervised patients showed high app usage adherence and frequency of data entries, which was comparable to previous reports on supervised patients undergoing immunotherapeutic interventions.

Introduction: Malignant mesothelioma is a rare but aggressive cancer with limited treatment options and poor prognosis. Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) score, reflecting inflammation and nutritional status, is a potential prognostic marker in various cancers. Our study aimed to investigate the prognostic value of the HALP score in mesothelioma.

Methods: This retrospective study included 68 metastatic mesothelioma patients diagnosed between 2015 and 2023. Clinical and laboratory data were collected, and HALP scores were calculated at the time of metastasis. Patients were divided into HALP-low and HALP-high groups based on the median HALP score. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method, and prognostic factors were assessed using univariate and multivariate analyses.

Results: The median HALP score was 24.85. The median OS for the entire cohort was 11.59 months. Patients with low HALP scores had significantly worse OS (7.81 months) compared to those with high HALP scores (16.36 months) (p = 0.01). Similarly, median PFS was significantly shorter in the HALP-low group (7.29 months) compared to the HALP-high group (12.12 months) (p = 0.02). In multivariate analysis, low HALP score (p = 0.02) and de novo metastatic disease (p = 0.01) remained independent prognostic factors for OS.

Conclusion: This study demonstrates that the HALP score is an independent prognostic biomarker in metastatic mesothelioma. Low HALP scores are associated with worse OS and PFS. Given its simplicity and cost-effectiveness, the HALP score may be a valuable tool for risk stratification and treatment decision-making in clinical practice.

Introduction: In this study, we aimed to evaluate the efficacy and safety of the combination therapy with chemotherapy and anlotinib in patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations who exhibit primary resistant to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs).

Methods: Clinical data were collected from patients with advanced NSCLC harboring EGFR mutations and exhibiting primary resistance to EGFR-TKI, who were treated with a combination of chemotherapy and anlotinib. The primary endpoints were overall response rate (ORR), progression-free survival (PFS), disease control rate, overall survival (OS), and treatment-related adverse events (AEs).

Results: A total of 34 patients with advanced NSCLC harboring EGFR mutations and exhibiting primary resistance to EGFR-TKI were enrolled. The ORR and DCR for the treatment with chemotherapy plus anlotinib were 32.35% and 64.71%, respectively. The median PFS and OS were 5 months and 9 months, respectively. Compared to patients with EGFR exon 19 deletion mutations, those with EGFR exon 21 L858R mutations derived greater benefit from the treatment (mPFS = 4.0 months vs. 5.0 months, p < 0.05; mOS = 9.0 months vs. 10.0 months, p < 0.05). The common AEs were myelosuppression, hypertension, proteinuria, and hand-foot syndrome. Most AEs were mild and well tolerated. These findings suggest that chemotherapy combined with anlotinib may be a promising strategy to overcome primary resistance to EGFR-TKIs in patients with advanced NSCLC.

Conclusion: The combination of chemotherapy and anlotinib appears to be an effective and well-tolerated treatment strategy in patients with advanced NSCLC exhibiting primary resistance to EGFR-TKIs. Further studies are warranted to validate these findings and investigate long-term clinical outcomes.

Introduction: Atezolizumab plus bevacizumab (ATZ/BEV) is used for the treatment of unresectable hepatocellular carcinoma (u-HCC). However, there are few reports investigating the predictors of whether or not disease control can be achieved for long periods.

Methods: We enrolled 106 u-HCC patients who were treated with ATZ/BEV as the first-line systemic chemotherapy and were evaluated as nonprogressive disease (non-PD) in their initial assessments. They were divided into two groups: patients who had achieved disease control (non-PD) for more than 6 months, Group-L, and patients who had progressed (PD) within 6 months, Group-S. We investigated the predictors of long-term therapeutic efficacy.

Results: Patients in Group-L had significantly lower neutrophil-to-lymphocyte ratios (NLR) (the ratios of NLR at the start of the second course of ATZ/BEV to their pretreatment levels) than Group-S (p = 0.044), and the optimal cutoff value was 1.129. The patients with an NLR ratio <1.129 had longer progression-free survival (PFS) and overall survival (OS) than those with an NLR ratio ≥1.129 (median: 16 vs. 6 months, p = 0.016 for PFS; not reached vs. 22 months, p = 0.007 for OS). Univariate and multivariate analyses showed that an NLR ratio ≥1.129 was an independent predictor for unfavorable PFS and OS (hazard ratio [HR] 2.03, p = 0.022 for PFS; HR 2.37, p = 0.019 for OS).

Conclusions: In u-HCC patients treated with ATZ/BEV, a lower NLR ratio was associated with a durable response, which led to favorable PFS and OS.

Introduction: Claudins are essential for tight junctions, maintaining cell adhesion, regulating intercellular molecule movement, and preserving cellular polarity. Altered claudin expression can lead to dysfunctions, potentially contributing to oncogenesis in epithelial cancers. The role of CLDN18.2 in rectal cancer is not well understood.

Methods: We analyzed tissue samples from 343 rectal cancer patients who underwent concurrent chemoradiotherapy (CCRT) followed by proctectomy.

Results: Upregulated CLDN18.2 expression was associated with older age (p = 0.016), higher pre-CCRT tumor N stage (p = 0.014), higher post-CCRT tumor T stage (p = 0.005), more vascular invasion (p = 0.008), and worse tumor regression (p < 0.001). Univariate analysis showed high CLDN18.2 expression correlated with worse disease-free survival (p < 0.0001), local recurrence-free survival (p < 0.0001), and metastasis-free survival (p < 0.0001). Multivariate analysis indicated high CLDN18.2 expression was associated with inferior disease-specific survival (p < 0.001) and metastasis-free survival (p < 0.001).

Conclusion: Elevated CLDN18.2 expression is associated with adverse clinical outcomes and pathological features, yet suggests a more unfavorable treatment response in rectal cancer patients undergoing CCRT, indicating its potential as a biomarker.