Journal of the Egyptian National Cancer Institute最新文献

Background: Health-related quality of life has emerged as a significant component in pediatric oncology research during the last several decades. Measures of health-related quality of life provide a thorough assessment of the child's response to medical therapy, disease course, and adjustment outcomes in the context of pediatric oncology.

Methods: The aim of the present study was to assess the cancer-specific health-related quality of life in cancer pediatric patients and to evaluate the contribution of its domains and some of the anthropometric, sociodemographic, and treatment-related variables on the overall quality of life, by using the PedsQL™ 3.0 Cancer Module.

Results: The study included 110 cases. The mean value of the PedsQL™ 3.0 Cancer Module score was 49.3 ± 12.0. The lowest mean score of quality of life was for the "procedure anxiety" (8.7 ± 23.9), followed by the "worry" domains (16.6 ± 28.5). Higher "frequency of hospital visits" was associated with increased feeling of pain and treatment anxiety yet decrease in suffering from nausea and vice versa. The longer period of hospital admission for more than half of the recommended treatment period was associated with reduced pain suffering on the expense of increase in feeling of worry as well as communication problems. The perceived physical appearance was better among those patients who spent a treatment period for 3-6 months when compared to those who spent a treatment period less than 3 months or more than 6 months. There was a highly significant association between all the eight-cancer-specific quality-of-life domains except the pain domain- and the overall quality-of-life log scores. Nausea problem followed by worry and cognitive problems was the most effective domains on the overall quality-of-life score.

Conclusion: Cancer pediatric patients suffered low quality of life especially for anxiety procedure and worry domains with special consideration for the impact of nausea, worry, and cognitive problems on their perception of quality of life.

Background: Gastric cancer is a dominant source of cancer-related death around the globe and a serious threat to human health. However, there are very few practical diagnostic approaches and biomarkers for the treatment of this complex disease.

Methods: This study aimed to evaluate the association between differentially expressed genes (DEGs), which may function as potential biomarkers, and the diagnosis and treatment of gastric cancer (GC). We constructed a protein-protein interaction network from DEGs followed by network clustering. Members of the two most extensive modules went under the enrichment analysis. We introduced a number of hub genes and gene families playing essential roles in oncogenic pathways and the pathogenesis of gastric cancer. Enriched terms for Biological Process were obtained from the "GO" repository.

Results: A total of 307 DEGs were identified between GC and their corresponding normal adjacent tissue samples in GSE63089 datasets, including 261 upregulated and 261 downregulated genes. The top five hub genes in the PPI network were CDK1, CCNB1, CCNA2, CDC20, and PBK. They are involved in focal adhesion formation, extracellular matrix remodeling, cell migration, survival signals, and cell proliferation. No significant survival result was found for these hub genes.

Conclusions: Using comprehensive analysis and bioinformatics methods, important key pathways and pivotal genes related to GC progression were identified, potentially informing further studies and new therapeutic targets for GC treatment.

Background: Driver molecular aberrations, such as epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement, play an important role in the oncogenesis and progression of non-squamous non-small-cell lung cancers (NSCLC). Therefore, this study aimed to detect the incidence of driver mutations among non-squamous NSCLC.

Patients and methods: This was a retrospective-prospective cohort study on 131 patients with non-squamous NSCLC. Data on age, smoking status, chest symptoms, method of lung cancer diagnosis, molecular testing, including EGFR mutations in formalin-fixed paraffin-embedded (FFPE) tumor tissue and serum circulating tumor DNA using next-generation sequencing and ALK gene rearrangement by FFPE tumor tissue, and follow-up data regarding treatment modalities and outcomes were collected.

Results: The median age of the patients was 57 years (range: 32-79 years). Out of 131 patients, 97 were males (74%), and 90 (68.7%) were smokers. Among 128 patients tested, 16 (12.5%) had EGFR mutations detected with either technique by formalin-fixed paraffin-embedded (FFPE) tumor tissue or/and serum circulating tumor DNA using next-generation sequencing, and 6 (4.7%) had ALK rearrangement by FFPE tumor tissue. The majority (62.6%) presented with metastatic disease. Among the 102 patients who received first-line systemic therapy, the objective response rate was 50.0% in mutated NSCLC versus 14.6% in non-mutated (p < 0.001). Among the eight mutated patients who received first-line tyrosine kinase inhibitors (TKIs), 7 patients achieved either complete response or partial response. Among the 22 mutated patients, the median overall survival was 3 months in those who did not receive targeted therapy versus not reached in those who received any type of targeted therapy (p < 0.001).

Conclusion: Screening patients with newly diagnosed non-squamous NSCLC for driver mutations is essential for major prognostic and therapeutic implications. Early administration of TKIs in mutated patients significantly improves disease outcomes.

Background: We previously reported that in highly metastatic breast cancer cells, doxorubicin (DOX) at non-toxic concentrations promoted cell migration and invasion. Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavonoid glycoside isolated from citrus/lemon plant that possesses a cytotoxic effect in several cancer cells. In this study, we investigate whether DOX efficacy is enhanced by hesperidin (Hsd) and the molecular pathway involved in highly metastatic breast cancer, 4T1.

Methods: Combined cytotoxicity of Hsd and DOX was evaluated with MTT assay and was analyzed using Chou-Talalay's method. To better understand the underlying mechanism, several factors, including apoptosis and cell cycle arrest were analyzed by flow cytometry. In addition, antimigration activity was evaluated by scratch wound healing assay, MMP-9 expression by ELISA and gelatin zymography, and Rac-1 protein level using western blot. The data on survival rate and expression level of MMP-9 and Rac-1 were obtained from Gene Expression OMNIBUS (GEO).

Results: Under MTT assay, Hsd showed a cytotoxic effect in a concentration-dependent manner with an IC50 value of 284 µM on 4T1 cells. Hsd synergistically enhanced the cytotoxic effect of DOX which seemed to correlate with an increase in apoptotic cell death, G2/M cell cycle arrest and blocked the migration of 4T1 cells. At 10 nM, doxorubicin induced lamellipodia formation, and increased the level of Rac-1 and metalloproteinase-9 (MMP-9) expression. Interestingly, combined treatment of DOX and Hsd dramatically downregulated the expression of MMP-9 and Rac-1. These results indicated that Hsd block the cell migration induced by DOX under in vitro studies.

Conclusion: These findings strongly suggest that Hsd possesses a potential synergistic effect that can be developed to enhance the anticancer efficacy of DOX and reduce the risks of chemotherapy use in highly metastatic breast cancer.

Background: Multi-parametric magnetic resonance imaging may improve the detection of prostate cancer. The aim of this work is to compare between PI-RADS 3-5 and PI-RADS 4-5 as a threshold for targeted prostatic biopsy.

Methods: This is a prospective clinical study that included 40 biopsy-naïve patients referred for prostate biopsy. Patients underwent prebiopsy multi-parametric (mp-MRI), followed by 12-core transrectal ultrasound-guided systematic biopsy and cognitive MRI/TRUS fusion targeted biopsy from each detected lesion. The primary endpoint was to assess the diagnostic accuracy of the PI-RAD 3-4 versus PI-RADS 4-5 lesion by mpMRI for prostate cancer detection in biopsy-naive men.

Results: The overall prostate cancer detection rate and the clinically significant cancer detection rate were 42.5% and 35%, respectively. Targeted biopsies from PI-RADS 3-5 lesions showed a sensitivity of 100%, specificity of 44%, positive predictive value of 51.7%, and negative predictive value of 100%. Restricting targeted biopsies to PI-RADS 4-5 lesions resulted in a decrease in sensitivity and negative predictive value to 73.3% and 86.2%, respectively, while specificity and positive predictive value were increased to 100% for both parameters which was statistically significant (P value < 0.0001 and P value = 0.004, respectively).

Conclusions: Limiting the TBs to PI-RADS 4-5 lesions improves the performance of mp-MRI in the detection of prostate cancer especially aggressive tumors.

Background: Radiotherapy (RT) is an important part of the treatment of many tumors. Radiotherapy causes oxidative damage in all cellular compartments, including lipid membrane, on a random basis. Toxic lipid peroxidation accumulation has only lately been linked to a regulated type of cell death known as ferroptosis. Iron is required for ferroptosis sensitization in cells.

Aim of the work: This work aimed to study ferroptosis and iron metabolism before and after RT in BC patients.

Subjects and methods: Eighty participants were included divided into two main groups: group I: 40 BC patients treated with RT. Group II: 40 healthy volunteers' age and sex matched as control group. Venous blood samples were collected from BC patients (prior to and after RT) and healthy controls. Glutathione (GSH), malondialdehyde (MDA), serum iron levels and % of transferrin saturation were measured by colorimetric technique. Ferritin, ferroportin, and prostaglandin-endoperoxide synthase 2 (PTGS2) levels were assessed by ELISA.

Results: Serum ferroportin, reduced glutathione, and ferritin showed significant decrease after radiotherapy in comparison to before radiotherapy. However, there was significant increase in serum PTGS2, MDA, % of transferrin saturation and iron levels after radiotherapy in comparison to before radiotherapy.

Conclusion: Radiotherapy induced ferroptosis in breast cancer patients as a new cell death mechanism and PTGS2 is a biomarker of ferroptosis. Iron modulation is a useful approach for the treatment of BC especially if combined with targeted therapy and immune-based therapy. Further studies are warranted to be translated into clinical compounds.

Introduction: Laryngeal cancer is the ninth commonest cancer among Asian males. Global and regional epidemiological analyses have shown varying patterns in the incidence and risk factors for laryngeal cancer. Therefore, we aimed to analyse the trends in the incidence and histological patterns of laryngeal cancers for the first time in Sri Lanka.

Methods: We used the population-based Sri Lanka cancer registry data and pooled all newly diagnosed patients with laryngeal malignancies from 2001 to 2019 (a 19-year study period). The WHO age-standardised incidence rates (ASR) were calculated using the WHO standard pollution. We used the Joinpoint regression software to calculate the estimated annual percentage change (EAPC) and analysed the trends in the incidence by different age categories and sex.

Results: From 2001 to 2019, 9808 new cases of laryngeal cancers (males = 8927, 91%, mean age = 62 years) were registered. The incidence of laryngeal cancers was greatest in the 70-74-year followed by 65-69-year age groups. Around 7.9% were reported as carcinoma not otherwise specified (NOS). Squamous cell carcinoma (90.1%) was the commonest documented histology type. A rise in the WHO-ASR was noted from 1.91 per 100,000 in 2001 [95% confidence interval (95% CI): 1.69-2.12] to 3.59 per 100,000 in 2017 [(95% CI: 3.34-3.84); EAPC: 4.4 (95% CI: 3.7-5.2), p < 0.05 for trend] followed by a decrease in the incidence [2.97 per 100,000 in 2019 (95% CI: 2.74-3.2), EAPC: - 7.2 (95% CI: - 21.1-9.1, p > 0.05)]. From 2001 to 2017, the proportional increase in incidence was greater in males than females [EAPC: 4.9 (95% CI: 4.1-5.7 vs. 3.7 (95% CI: 1.7-5.6)].

Conclusions: We identified an increasing incidence of laryngeal cancer in Sri Lanka from 2001 to 2017 followed by a slight decrease. Further studies are essential to identify the aetiological factors. Development of laryngeal cancer prevention and screening programmes for high-risk populations may be considered.

Background: Childhood parotid neoplasms appear to have different characteristics from adults. This point, in addition to the rarity of these tumors, reflects the challenges faced in diagnosing and treating parotid neoplasms in children.

Patients and methods: This retrospective study included all children who presented to the Children's Cancer Hospital Egypt (CCHE, 57357) with parotid masses from January 2008 to December 2020.

Results: Twenty-one patients were included. Malignant neoplasms were found in 12 (57.1%) of which mucoepidermoid carcinoma was the most common. Benign neoplasms were found in 6 (28.6%) all of them were pleomorphic adenoma, and non-neoplastic lesions were found in 3 (14.3%). Superficial, deep, or total parotidectomy was performed according to the involved lobes. The facial nerve was sacrificed in three cases because of frank invasion by the tumor. Neck dissection was considered in clinically positive lymph nodes and/or T3/4 masses. Complications occurred in 7 (33.3%) all were of the malignant cases. Adjuvant radiotherapy was restricted to high-risk cases (7 cases). Recurrence occurred in two cases, and one patient died of distant metastasis. Fine needle aspiration cytology (FNAC) showed 88.9% sensitivity and 100% specificity for diagnosing malignant neoplasms. The correlation of radiological and pathological staging was fair (66.74% for overall staging).

Conclusions: Parotidectomy is the backbone treatment for benign and malignant pediatric parotid tumors. Neck nodal dissection should be considered after preoperative FNAC of suspicious nodes. Adjuvant radiotherapy is considered only in high-risk tumors. Preoperative FNAC of parotid masses and clinically suspicious lymph nodes is highly recommended.

Background: The prevalence of head and neck cancer (HNC) is increasing rapidly, and the prognosis is poor in the advance stage. For the patient suffering from advance stage HNC, the improvement in quality of life and decrease mortality remain as the mainstay of treatment. The aim was to assess the change in quality-adjusted life-years (QALYs) in recurrent or metastatic HNC patients receiving cetuximab plus cisplatin and cetuximab plus cisplatin-paclitaxel.

Methods: It was a single-centric prospective-observational study. Patients were divided into two cohorts based on the chemotherapy regimens they were prescribed. Patients in cohort 1 were prescribed with cetuximab and cisplatin and in cohort 2 were prescribed with cetuximab, cisplatin, and paclitaxel. The QALYs were the primary outcome of the study, and it was calculated using EQ-5D-5L instrument. Patients were followed until the completion of the therapy, i.e., six chemotherapy cycles. The statistical analysis was carried out using SPSS for descriptive and inferential analysis.

Results: Amongst 175 patients screened, 100 patients were enrolled which further distributed in cohorts 1 and 2 equally. The mean QALYs were 0.016 and 0.017 at the time of diagnosis, i.e., before initiation of chemotherapy for patients in cohorts 1 and 2, respectively. At every chemotherapy cycle, the QALYs were calculated. After the completion of six chemotherapy cycles, the mean QALYs were 0.029 and 0.032 for patients in cohorts 1 and 2, respectively.

Conclusion: The three-drug therapy consisting of cetuximab, cisplatin, and paclitaxel has shown significant improvement in patients' QALYs compared to two-drug regimens of cetuximab and cisplatin. Thus, if the therapy consisted of three-drug regimen is used instead of two-drug regimen, it will have a positive impact on humanistic outcome in recurrent or metastatic HNC patients.

Hypothesis: Biological response modifiers (immunotherapy) in combination to chemotherapy are superior to that of chemotherapy in treatment of breast cancer (triple-negative/HER-2 ( +)), multiple myeloma, and non-small-cell lung cancer.

Methods: This review article consists of a total of eighteen independent randomized controlled clinical trials ranging from phases one to three. Patients were randomly selected for immunomodulatory treatment or chemotherapy and assessed for a specific mutation expression that the immunomodulatory agent targets. Kaplan-Meier plots, swimmer plots, and bar graphs depict overall/progression-free survival, objective response, and clinical response rates. The data collected was assessed by using 95% confidence interval and a p value of 0.05. Patients were treated until disease progression.

Results: Biological response modifiers (immunotherapy) resulted in significantly longer median progression-free survival in PD-L1-positive breast cancer (7.5 months compared to 5.0 months in control group), multiple myeloma (60.7% compared to 26.9% in the daratumumab and placebo groups, respectively), and in non-small-cell lung cancer (median progression-free survival was 10.3 months in the pembrolizumab group compared to 6.0 months in the chemotherapy group): higher complete responses in multiple myeloma (79% and 66% in the elotuzumab and control groups, respectively) and lower disease progression in PD-L1-positive non-small-cell lung cancer (62.1% of pembrolizumab versus 50.3% of chemotherapy patients had no disease progression at 6 months).

Conclusion: Combination biological response modifiers (immunotherapy) and chemotherapy displayed benefit in overall/progression-free survival, response rate, duration of response, clinical benefit, and invasive disease-free survival in triple-negative/HER2-2( +) breast cancer, multiple myeloma, and non-small-cell lung cancer.