Journal of the Egyptian National Cancer Institute最新文献

Background: Comparison of acute adverse events (acute skin reaction, acute breast pain and lung toxicities) in early-stage breast cancer using 2 different fractionation schedules: ultra-hypofractionation versus hypofractionation radiotherapy.

Methods: Ninety-two patients were recruited and assessed using RTOG criteria for acute skin reactions at the end of radiotherapy, 1 month after, and 3 months after.

Results: There have been no statistically significant differences in acute skin adverse events in 1 month after WBI, there have been neither G3 acute skin toxicity nor G2 skin reactions as were in the fast trial, and milder than skin adverse events in the FAST-FORWARD trial. Acute breast pain at the end of radiotherapy has been statistically significantly lower in arm 1 vs arm 2. Acute breast pain at 1-month follow-up has been comparable between the study arms, with no statistically significant difference. At the 3-month follow-up, acute breast pain was similar in both arms. In all arms, no acute lung toxicities have been reported.

Conclusion: Acute adverse events have been comparable between ultra-hypofractionation and hypofractionation.

Background: Recent statistical analyses indicate a rapid increase in the incidence of breast and colon cancer in Egypt. Although invasive techniques have been widely employed for early detection, diagnosis, and intervention of those cancers, they are associated with inherent risks and limitations, which often result in various complications. Therefore, noninvasive screening methods are inevitable due to their accessibility, cost-effectiveness, and high patient compliance rates. The enzyme L-asparaginase catalyzes the conversion of L-asparagine to L-aspartic acid: key metabolite for tumor cell division, thereby demonstrating anticancer potential. However, the prolonged use of bacterial L-asparaginase may cause allergic reactions and side effects such as diabetes, leukopenia, and co-agglutination disorders. Exploring the anticancer properties of L-asparaginase from different species such as yeast and fungi has been proposed to mitigate these adverse effects.

Objectives: This study aimed at extracting and optimizing the expression of L-asparaginase from the eukaryotic Cladosporium species, as to assess its anticancer potential against breast and colon cancer cell lines.

Method: Cladosporium species were identified morphologically and then cultured on modified Czapek-Dox Agar (mCDA) medium supplemented with L-asparagine to induce L-asparaginase production. Submerged fermentation was employed to optimize enzyme production. The enzyme activity was quantified using the Nesslerization method, and its cytotoxicity against colon and breast cancer cell lines was assessed using the (MTT) assay.

Results: Among the Cladosporium isolates, 18.4% exhibited positive plate assay test, with enzyme activities ranging from 255 to 428 U/mL. Immunoblotting using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed single protein band of approximately 37 kDa, consistent with L-asparaginase activity. Cytotoxicity assay of purified L-asparaginase showed significant antiproliferative effects against breast cancer cell lines MCF-7 and MDA-MB-231, with IC₅₀ values of 36.26 and 45.7 µg/mL, respectively.

Conclusion: Certain eukaryotic Cladosporium strains are potential sources for the anticancer L-asparaginase production.

Background: The cyclophospamide, doxorubicin, vincristine, and prednisone/prednisolone (CHOP) regimen, a standard treatment for aggressive non-Hodgkin lymphoma (NHL), is effective but linked to chemotherapy-induced cardiotoxicity (CDIC), such as heart failure and left ventricular dysfunction. Anthracyclines like doxorubicin are key contributors to CDIC. This study examines left ventricular dysfunction and structural abnormalities in NHL patients receiving CHOP therapy with cumulative doxorubicin doses ≥ 250 mg/m², aiming to improve early CDIC detection and guide timely cardioprotective interventions.

Methods: This prospective cohort study was conducted at Dr. Soetomo Regional General Hospital, Surabaya, from June to October 2023. We included NHL patients aged 18-60 years at any stage, treated with CHOP regimens containing cumulative doxorubicin doses ≥ 250 mg/m², who completed at least four chemotherapy cycles, had baseline left ventricular ejection fraction (LVEF) ≥ 50%, and good echocardiographic window quality. Data were collected from medical records, biochemical tests, and echocardiography. Wilcoxon and paired T-tests were used for statistical analyses. The primary outcome was cardiac function, evaluated by reductions in LVEF, increased left ventricular strain, new structural abnormalities, and elevated high-sensitivity (HS) troponin and NT-proBNP levels post-chemotherapy.

Results: A total of 32 patients, aged 46.62 ± 16.64 years, were included, with the colli region and stage 2 NHL being the most common. Significant differences were observed in all parameters between pre- and post-chemotherapy. LVEF decreased by - 2.40% ± 1.79 (p < 0.001), while global longitudinal strain (GLS) declined by 2.25 ± 1.36 (p < 0.001). HS troponin I levels showed a significant increase of 17.27 ± 36.29 (p < 0.001), and NT-proBNP levels rose by 321.23 ± 85.34 (p < 0.001). The study also identified a higher risk of cardiotoxicity in patients over 50 years of age.

Conclusion: The CHOP regimen poses significant risks of subclinical cardiac dysfunction and structural abnormalities in NHL patients, with cumulative doxorubicin dosage being a key contributor. Early detection using sensitive biomarkers like GLS and NT-proBNP is crucial for identifying cardiotoxicity and enabling timely interventions.

Extracellular vesicles (EVs) have emerged as key cell-to-cell communication mediators and play significant roles in both physiological and pathological processes. In EVs, exosomes represent a distinct subpopulation of EVs that have been found to be involved in cancer initiation and therapeutic resistance. Exosomes transfer a diverse spectrum of molecular cargos that have significant effects on the tumor microenvironment (TME), thereby enabling cancer initiation, metastasis, and therapeutic resistance. Exosomes have recently been of interest in cancer therapy due to their role as important mediators of treatment resistance. The exosomal molecular content-proteins, miRNAs, and lncRNAs-allows exosomes to perform functions including drug efflux and detoxification, cell death pathway modulation, induction of epithelial-to-mesenchymal transition (EMT), and suppression of the immune system. In addition to facilitating immune and stromal cell interactions, exosomes cause extracellular matrix remodeling and induce tumor heterogeneity, making it more difficult to respond to therapy. This review covers intricate roles of exosomes in cancer therapy resistance with regard to their biogenesis, molecular content, and functional impact in the TME. Along with this, we also discuss new therapeutic strategies to overcome exosome-mediated resistance including utilizing exosome inhibitors, designed exosome therapy, and combination with conventional therapies. While exosomes hold promise in prediction and diagnosis through their biomarker function, their heterogeneous origins and cryptic functions make it difficult to target interventions. This review emphasizes that research on exosome-mediated pathways is urgently required to develop new therapeutic strategies that can improve cancer treatment outcomes.

Background: The high incidence of primary and recurrent ovarian cancer after surgery imposes a significant economic burden. Cytoreductive Surgery combined with Hyperthermic Intraperitoneal Chemotherapy (CRS + HIPEC) shows promise as a treatment for epithelial ovarian cancer (EOC). This study aims to evaluate CRS + HIPEC's potential to improve survival outcomes, such as overall survival (OS) and progression-free survival (PFS) while reducing adverse events and enhancing cost-effectiveness.

Method: A literature review was conducted using the PRISMA framework on databases including Scopus, ProQuest, and PubMed, with quality assessment through the Newcastle-Ottawa Scale (NOS) and Risk of Bias (RoB) 2.0. Quantitative analysis employed RevMan 5.4.1 with a pooled randomized effect model using log [hazard ratio].

Result: From 15 studies involving 1982 participants, OS analysis showed significantly higher survival in the CRS + HIPEC group (HR = 0.67, p < 0.0004). Although PFS was higher in this group, the result was not statistically significant (HR = 0.86, p = 0.46). Adverse events were more likely in the intervention group compared to control group (OR = 1.81, p < 0.0001). Cost analysis revealed that the Incremental Cost-effectiveness Ratio per Quality-Adjusted Life Year (ICER/QALY) remains below Indonesia's GDP threshold.

Conclusion: CRS + HIPEC shows potential benefits in EOC management, particularly in OS and PFS improvement, alongside manageable adverse events and favorable cost-effectiveness. However, study design heterogeneity, differences in HIPEC protocols, and variations in patient populations limit the generalization of outcomes. The difference in response to HIPEC between primary and recurrent EOCs still needs further explanation.

Background: Lung cancer is the leading cause of cancer-related mortality worldwide. Approximately 15-20% of newly diagnosed individuals with primary lung cancer have small cell lung cancer, and more than 60% of patients have advanced-stage small cell lung cancer at the time of diagnosis. Patients with advanced-stage small-cell lung cancer may benefit from thoracic radiation therapy. This comprehensive meta-analysis was conducted to determine whether adding thoracic radiation to systemic chemotherapy increases 1-year and 2-year survival in patients with advanced-stage small-cell lung cancer.

Methods: The Science Direct, PubMed, Embase, and Wanfang databases were comprehensively searched from 1980 to 2022. The inclusion criteria for studies were as follows: (1) all patients had advanced-stage small cell lung cancer; (2) a group receiving thoracic radiation therapy combined with chemotherapy was compared with a group receiving only chemotherapy; and (3) 1-year and 2-year overall survival data were provided. Pooled relative risks (RRs) and risk differences (RDs) were calculated, publication bias was evaluated, and sensitivity analysis was conducted.

Results: Ten studies met the inclusion criteria. These studies included 922 patients (534 patients in the chemotherapy combined with thoracic radiation therapy (ChT/TRT) group and 388 patients in the chemotherapy (ChT) group). The results of the meta-analysis revealed that the addition of thoracic radiotherapy to chemotherapy increased the 1-year overall survival rate to 52%, whereas the 1-year overall survival rate was 32.2% when chemotherapy alone was used. The addition of thoracic radiotherapy to chemotherapy also increased the 2-year survival rate to 18.7%, compared with 10% in the ChT group. The ChT/TRT group had a significantly better 1-year overall survival rate than the ChT group, with a pooled RR of 1.61 (95% CI, 1.36-1.90, P < 0.00001) and a pooled RD of 0.2 (95% CI, 0.13-0.26, P < 0.00001). The ChT/TRT group also had a significantly better 2-year overall survival rate than the ChT group, with a pooled RR of 1.90 (95% CI, 1.34-2.68, P = 0.0003) and a pooled RD of 0.09 (95% CI, 0.05-0.13, P < 0.0001).

Conclusion: This study revealed that adding thoracic radiation therapy to chemotherapy increases both 1-year and 2-year survival in patients with extensive-stage small-cell lung cancer.

Background: Cytarabine is a prodrug which is activated to cytarabine triphosphate (Ara-CTP) through a series of phosphorylation steps. For considerable leukemic cell death, high level of Ara-CTP is required. Sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) and Nucleotide diphosphate kinase-2 (NME2) are genes involved in Ara-CTP metabolism. To best of our knowledge, there are no similar studies focused on the association of different polymorphisms involved Ara-C metabolism on the response to induction chemotherapy among adult AML Egyptian patients. Therefore, the aim of this study was to determine the effect of SAMHD1 rs28372906 and NME2 rs3744660 polymorphisms on AML complete remission rate (CR), overall survival (OS), and disease-free survival (DFS) among adult AML Egyptian patients, after Ara-C based induction therapy.

Methods: This study was a retrospective conducted at the National Cancer Institute, Cairo University, Egypt. The patient group included 136 adult patients with newly diagnosed AML, while the control group included 48 healthy subjects. The clinical history of all studied patients was collected from patient records. Patients and controls were genotyped for NEM2 (rs3744660) and SAMHD1 (rs28372906) by using Taq Man Genotyping assay and Taq Man genotyping master mix (REF: 4,371,353, Applied Biosystems, USA). Real-time PCR assay was performed on Thermo Fisher Quant Studio™ 3. The Statistical Package for Social Science version 21.0 was used to analyze our data.

Results: Regarding the SAMHD1 (rs28372906) polymorphism, we did not find any genotype variations between patient, and control groups, where all of them were AA genotype. Regarding NME2 (rs3744660) polymorphism the statistical analysis reported significant association between D28 blasts and OS (P-value = 0.043), while the remaining initial patient characteristics and response to induction were not associated with OS.

Conclusion: CR, DFS, and OS were not significantly associated to SAMHD1 rs28372906 and NME2 rs3744660 polymorphisms.

Background: Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Between 35 and 45% of these patients do not respond to standard chemotherapeutic treatments, resulting in a very low 5-year survival rate of only 5-20%. This resistance often leads to treatment failure and unfavorable prognoses, highlighting the critical need for new therapeutic targets to improve treatment strategies. Autophagy-related gene 4 B (ATG4B) is a crucial cysteine protease for autophagosome formation. It is overexpressed and correlates with poor prognosis in various cancers. However, the relationship between ATG4B expression and angiogenesis in OS remains unexplored. This study investigated the expression levels of ATG4B and VEGF in OS and their correlation with clinicopathological data.

Materials and methods: This study included 67 paraffin-embedded OS tissue samples. ATG4B and VEGF expression levels were assessed via immunohistochemistry, and their associations with clinicopathological variables were statistically analyzed. Additionally, ATG4B gene expression in OS was examined via GEO datasets from https://www.ncbi.nlm.nih.gov .

Results: ATG4B and VEGF were expressed in 79.1% and 74.6% of the osteosarcoma samples, respectively. There was a significant positive correlation between ATG4B expression and tumor size, tumor stage, and histological response to neoadjuvant chemotherapy, with p values of 0.013, 0.008, and 0.022, respectively. VEGF expression was also significantly correlated with tumor size, tumor stage, and the presence of distant metastasis at diagnosis, with p values of 0.022, 0.044, and 0.013, respectively. A notable positive correlation between ATG4B and VEGF expression levels was observed (p=0.002), which was supported by the GEO dataset analysis. High ATG4B and VEGF overexpression were significantly associated with worse overall survival by univariate analysis.

Conclusions: The results suggest that ATG4B acts as a tumor promoter in OS, indicating its potential as a therapeutic target to inhibit tumor growth. Elevated ATG4B levels may also serve as a marker for poor prognosis. Additionally, VEGF overexpression is linked to a greater likelihood of pulmonary metastasis and a worse overall prognosis. The positive correlation between ATG4B and VEGF suggests that the absence of both markers could be indicative of a better chemotherapy response, offering insights into potential new treatment approaches.

Background: Desmoplastic small round cell tumor (DSRCT) poses a diagnostic challenge, initiating with imaging techniques like ultrasound, CT, MRI, and PET scans, with CT being the primary choice for abdominal tumor visualization. Despite advances, the absence of a standardized staging system complicates the diagnostic process.

Methods: A comprehensive literature review and search strategy, encompassing databases like PubMed and Cochrane was performed.

Results: Systemic chemotherapy, notably the P6 regimen, is the cornerstone of DSRCT treatment, while other options, including CDK4/6 inhibitors, antibody-drug conjugates, and anlotinib present varying efficacy. A novel chemotherapeutic agent, ONC-201, exhibits promise, inhibiting tumor growth in preclinical models. Surgical management, encompassing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), reveals improved survival rates, particularly when combined with chemotherapy. Whole abdomen radiotherapy (WART) emerges as a post-chemotherapy treatment option, despite potential complications. A study employing whole abdominopelvic intensity-modulated radiation therapy (WAP-IMRT) suggests reduced radiation toxicity compared to conventional WART. Immunotherapy, targeting receptors such as B7-H3, GD2, EGFR, HER2, tyrosine kinase inhibitors, and androgen receptors is a promising avenue, especially in younger populations, given its favorable long-term effects. Additionally, the inclusion of CCDN1 genomic alterations further informs potential targeted therapies for DSRCT.

Discussion: This comprehensive review provides a current understanding of DSRCT diagnosis and treatment modalities, highlighting the ongoing challenges and promising avenues for future research. The integration of personalized approaches, novel chemotherapeutic agents, and evolving immunotherapy strategies holds the potential to enhance outcomes for individuals with DSRCT.

Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Due to the advanced stage in which HCC presents, most patients are only eligible for transarterial chemoembolization (TACE) or radioembolization (Y⁹⁰). The purpose of this study is to examine the differences in survival and health-related quality of life (HRQOL) in patients diagnosed with HCC and treated with TACE or Y⁹⁰.

Methods: Two hundred thirty-four patients with HCC were enrolled in studies examining HRQOL between 2003-2009. HRQOL was evaluated using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep). Between-group differences were examined using chi-square and ANOVA. Survival was assessed using Kaplan-Meier and Cox regression analyses.

Results: Significant baseline differences between patients treated with TACE versus Y⁹⁰ were found. Patients who received Y⁹⁰ tended to be older (p < 0.001), female (p < 0.001), had fewer lesions (p = 0.03), had smaller tumors (p = 0.03), and were less likely to have vascular invasion (p = 0.04). After adjusting for demographic and disease-specific factors, no significant differences in HRQOL were observed at 3 months (p = 0.79) or 6 months (p = 0.75). Clinically meaningful differences were found, with the TACE group reporting greater physical, social, and emotional well-being at 3 and 6 months and greater overall HRQOL at 6 months. No significant differences in survival were found.

Conclusions: Treatment with TACE and Y⁹⁰ was similar with regard to survival. However, TACE showed statistically and clinically meaningful benefits in physical, social/family, and emotional well-being. Further research is warranted to identify profiles of patients who may demonstrate a preferential response to either TACE or Y⁹⁰.