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O6-methylguanine-DNA methyltransferase (MGMT) serves a crucial role in DNA repair by removing alkyl lesions from the O6 position of guanine, maintaining genomic stability. Loss of MGMT expression, often due to promoter methylation, is linked to enhanced sensitivity to chemotherapy. While MGMT methylation has been observed in various cancers, its impact on overall survival (OS) in solid tumors remains uncertain. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, studies were selected from PubMed that examined the impact of MGMT methylation on OS in adult patients with solid tumors. Data were extracted where methylation status was defined, and OS was reported through hazard ratios (HRs) and confidence intervals (CIs) from either univariate or multivariable analyses. R version 4.4.2 and the 'meta' package were employed for the meta-analysis, using both fixed-effects (Mantel-Haenszel method) and random-effects (DerSimonian-Laird method with Hartung-Knapp adjustment) models based on the I2 statistic for heterogeneity. Subgroup analyses were performed by cancer type, and publication bias was assessed through funnel plot inspection and Egger's regression. A total of 21 studies involving 2,946 patients met the inclusion criteria. The fixed-effects model showed a significant association between MGMT promoter methylation and poorer OS (HR=1.27; 95% CI, 1.13-1.42; P<0.0001); however, notable heterogeneity (I²=64.7%) led to a non-significant result under the random-effects model (HR=1.26; 95% CI, 0.97-1.65; P=0.084). Subgroup analyses revealed that MGMT methylation was strongly associated with decreased survival in biliary tract (HR=2.31), cervical (HR=2.50) and duodenal cancers (HR=4.25), whereas melanoma exhibited improved survival (HR=0.32). Other cancer types, including colorectal, esophageal, head and neck, leiomyosarcoma, non-small cell lung cancer and pancreatic neuroendocrine tumors, demonstrated no notable relationship between MGMT methylation and OS. Sensitivity analyses confirmed the stability of these findings despite the inherent heterogeneity. In conclusion, MGMT promoter methylation may be a prognostic biomarker in select solid tumors; however, its impact on OS varies by cancer type. Further studies with standardized methylation assessment methods are warranted to clarify its prognostic and predictive utility, especially on OS.

To assess the impact of Jordanian's Corona Virus Disease (COVID-19) lockdown on visual acuity and macular thickness in patients with macular edema receiving intravitreal injections, and to assess the ethical endeavor of lockdown among serious sight threatening conditions. This retrospective observational study included patients planned for intravitreal injections who did not complete the planned course before the lockdown (ie, before 20th of March 2020). Data included demographics, indication for the intravitreal injection, corrected distance visual acuity (CDVA), and central macular thickness on Optical Coherence Tomography (OCT) before and after the lockdown. One-hundred and sixty-six eyes of 125 patients were studied, 68 (54.4%) patients were males, and the mean (± standard deviation, SD) age was 64.79 (±9.41) years. Mean (±SD) duration of delay in the planned injection was 60.97 (±24.35) days. The change in visual acuity was statistically significant for patients with diabetic macular edema (p= 0.045 improvement), patients with central retinal vein thrombosis (CRVO) (p= 0.05 deterioration), and patients with age-related macular degeneration (AMD) (p= 0.005 deterioration). Of interest, delay of more than 2 months and the previous need for 3 or more injections were significant poor prognostic factors for visual outcome for patients with diabetic macular edema (p=0.027 and 0.045). The impact of delay in the scheduled intravitreal injections resulted in variable outcomes depending on the indication. Triaging the urgency of patients should be based on the indication to support the equity principle of bioethics, where those in need are prioritized against others, depending on potential adverse outcome.

ABSTRACT Objective: Brain metastasis (BM) from bone and soft tissue sarcomas (STS) is very rare and mostly predicts dismal prognosis. Owing to its' rarity, data on optimal therapy including surgical management, chemotherapy, and radiotherapy is scarce. We sought to assess the prevalence, disease characteristics, and outcomes of BM in bone and STS patients treated at a single institution. Methods: A retrospective chart review was performed for consecutive bone and STS patients treated at King Hussein Cancer Center from 2007 to 2020. Patients with BM were identified. Survival was estimated by the Kaplan-Meier method. Factors of possible effect on OS was examined in univariate analysis. Survival comparisons were carried out by the log-rank test. Results: A total of 1,548 bone and STS patients were treated at our center during the eligibility period. We identified 18 patients (1.1%) who had BM at initial presentation (n = 16, 1.0%) or during follow up (n = 2; 0.1%). Fourteen patients (77.8%) were male. The median age was 29.5 years (range: 0.1-60 years). The primary tumor was most commonly located in the extremities (61%). Ten different histopathological subtypes were encountered; Ewing sarcoma (ES) was the most common (n = 4; 28%). Twelve patients (67%) had lung metastasis as the first site of metastatic disease. BM was detected at a median time of 12 months following sarcoma diagnosis (range: 1-71 months). A total of 10 patients (56%) had solitary metastasis and 4 patients (22.2%) had hemorrhagic metastasis. The most common location of brain metastatic lesions was the occipital lobe (n = 4; 22.2%). Thirteen patients received treatment for metastatic brain sarcoma. The most common treatment modality was radiotherapy, received by a total of 10 patients (55.5%), followed by surgical intervention performed in a total of 5 patients (27.7%), The other treatment modalities included combined chemo-radiotherapy (n = 2), targeted therapy plus chemotherapy, and targeted therapy plus radiotherapy (n = 1, each). At a median follow up of 10 months following detection of BM, the median OS was 4.0 months; (95% CI: 2.54-5.46). We did not identify any factor that influenced OS in univariate analysis. Conclusion: Sarcoma BM is exceedingly rare and herald's dismal prognosis. ES was a major histological subtype accounting for BM metastasis in our series.

Objective. To evaluate our experience with intravitreal melphalan chemotherapy as a second-line regimen for RB patients with refractory or recurrent vitreous seeds. Methods. A retrospective case series of 16 eyes from 16 patients with intraocular RB who received intravitreal melphalan chemotherapy using the antireflux injection technique. Data included demographics, stage at diagnosis, treatment modalities, side effects, eye salvage, and survival. Results. The total number of injections was 64 (median, 3 injections per eye; range, 3–8), and the median age at time of injection was 22 months (range, 9–63 months). Nine (56%) patients were males, and 13 (81%) patients had bilateral RB. Complete response was seen in 13 (81%) eyes: in 9 (100%) eyes with focal vitreous seeds and in 4 (57%) eyes with diffuse vitreous seeds (P=0.062). At a median follow-up of 18 months (range, 6–48 months), the eye salvage rate was 81%, local retinal toxicity confined to the site of injection was seen in 2/3 of the eyes, 2 (12%) eyes had cataract, and none of the patients had orbital recurrence and distant metastasis or was dead. Conclusion. Intravitreal melphalan is a promising modality for treatment of vitreous seeds, and the dose of 20–30 μg of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.

Purpose This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region’s adult population, highlighting opportunities to enhance cancer prevention programs. Design We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region. Results The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited. Conclusion The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.

Retinoblastoma presents most commonly as advanced unilateral disease, particularly in developing countries for which primary enucleation has been the preferred method of treatment. However, with the evolution of newer treatment modalities including intravitreal chemotherapy, intra-arterial chemotherapy and newer chemotherapeutic combinations, a trend towards more conservative approaches is being observed. Our aim is to evaluate outcomes of group D eyes following conservative and non-conservative treatment options. The ocular oncology database was used to identify eyes with unilateral retinoblastoma that fulfilled the International Intraocular Retinoblastoma Classification (IIRC) group D criteria from August 2010 to August 2018 and these were retrospectively reviewed. Overall, 39 eyes were identified. Nineteen (49%) eyes underwent primary enucleation and 20 (51%) received eye-conserving treatment. Eye salvage was possible in 15 (75%) eyes in the attempted salvage group. None of the patient revealed signs of metastasis. All eyes received conventional chemotherapy (carboplatin, vincristine, etoposide) and focal laser therapy. Additional treatment modalities offered included intravitreal chemotherapy, intra-arterial chemotherapy and topotecan. Three (11%) eyes in the primary enucleation group showed high-risk features on histopathology and none developed metastasis. The results of the study seem promising and conservative measures can be adopted in selected unilateral group D eyes.

The shift toward a histo‐molecular approach in World Health Organization classification of central nervous system tumors (WHO CNS5) emphasizes the critical role of molecular testing, such as next‐generation sequencing (NGS) and DNA methylation profiling, for accurate diagnosis. However, implementing these advanced techniques is particularly challenging in resource‐constrained countries. To address this, the Asian Oceanian Society of Neuropathology committee for Adapting Diagnostic Approaches for Practical Taxonomy in Resource‐Restrained Regions (AOSNP‐ADAPTR) was initiated to help pathologists in resource‐limited regions to implement WHO CNS5 diagnoses using simpler diagnostic tools, mainly immunohistochemistry. An online survey by this group assessed the in‐house/local availability of diagnostic resources and outsourcing capabilities across the Asian Oceanian region, covering 19 countries. Of 318 responding centers, the availability of molecular techniques in‐house/locally was limited in lower middle‐income countries (LMICs), with 29% having fluorescence in situ hybridization, 10.7% Sanger sequencing, and only 9.4% NGS. DNA methylation was largely unavailable in‐house/locally in of LMICs, while in the whole region, its availability stood at a meager 4.4%. Though outsourcing for all diagnostic tests was an easily accessible alternative, outsourcing for NGS and DNA methylation was uncommon because of the financial burden on patients being a significant obstacle. The survey categorized centers into five resource levels (RLs) based on the in‐house/local access to diagnostic techniques, which highlighted the variability and disparity in diagnostic capabilities across the region. High‐income countries had 80% of centers with advanced RL IV, V resources, in contrast to LMICs, where 70.5% of centers fell into RL I–III. This comprehensive evaluation emphasizes the need for tailored resource level guidelines, with the aim of improving diagnostic accuracy and treatment as well as advocating better healthcare infrastructure in resource‐constrained areas. However, the survey's reliance on responses from better‐resourced centers may underestimate challenges in lower‐resource settings, stressing the need for broader outreach and support. Asian Oceanian Society of Neuropathology‐Adapting Diagnostic Approaches for Practical Taxonomy in Resource‐Restrained Regions survey provides an overview of in‐house/ local and outsourcing resources in Asian Oceanian region for brain tumor diagnostics according to World Health Organization classification of Central Nervous System tumors. It highlights constraints and disparities, especially in lower middle‐income countries, identifies five resource levels, and emphasizes the need to develop tailored resource level guidelines for improving diagnostic accuracy.

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy is an established treatment for several hematological malignancies, with peripheral blood mononuclear cells (PBMCs) serving as the starting material for manufacturing. Cryopreservation of PBMCs may offer logistical flexibility, although its influence on manufacturing outcomes remains incompletely defined. This review aimed to compare the effect of fresh versus cryopreserved PBMC starting material on CAR-T cell manufacturing outcomes, including viability, fold expansion, and transduction efficiency.MethodsA systematic review was conducted following PRISMA guidelines. PubMed and Google Scholar were searched from inception through March 2026 for original studies comparing fresh and cryopreserved PBMCs in human CAR-T cell manufacturing. Methodological quality was assessed using the design-appropriate quality-appraisal tools, and findings were synthesized narratively due to heterogeneity in study design and protocols.ResultsFive studies published between 2019 and 2025 met the inclusion criteria, comprising two clinical and three experimental analyses. Post-thaw viability and recovery of cryopreserved PBMCs ranged between 77% and 97%, slightly lower than fresh material. Fold expansion, transduction efficiency, and cytotoxic activity were generally comparable between groups, although some studies reported transient early differences including prolonged doubling times, mitochondrial dysfunction signals, and increased TIM-3 expression in cryopreserved-derived products.ConclusionCryopreservation can be considered a feasible approach in CAR-T manufacturing, with generally comparable outcomes despite early post-thaw cellular changes. These differences do not seem to consistently compromise the overall manufacturing performance. However, the current evidence remains limited and heterogeneous, and further studies are required to increase confidence in our initial findings.

Background The Middle East and North Africa (MENA) region is expected to witness a significant increase in the burden of cancer. Contrary to Western literature, the burden of psycho-oncology is yet to be established within the MENA region. This study reviews all available evidence characterizing the psychological burden among patients with cancer across the MENA region. Methods We systematically explored the PubMed/MEDLINE, Cochrane/CENTRAL, and Web of Science (WoS) databases for reports on the psychiatric burden among patients with cancer residing within the MENA region from January 2000 until January 2023. Raw proportion were extracted and analyzed using a random-effects model. Findings Eighty-three studies comprised of 16 810 participants, representing 14 countries, met our inclusion criteria. Across the MENA region, the prevalence of depression, anxiety, and distress were 44% (95% CI, 39%-50%), 47% (95% CI, 40%-54%), and 43% (95% CI, 30%-56%), respectively. Prevalence of depression was significantly different across countries, with Palestine (73%; 95% CI, 42%-91%) reporting the highest rate while Morocco (23%; 95% CI, 7%-56%) reported the lowest. Similarly, anxiety significantly differed across MENA nations ranging from 64% (95% CI, 3%-99%) in Morocco to 28% (95% CI, 18%-42%) in Tunisia. Rates of depression and anxiety were significantly different across measurement tools but not between Arabic-speaking versus Persian/Farsi-speaking countries. Meta-regression models showed that neither publication year nor age affected the prevalence of both anxiety and depression (P = .374 and .091 for depression and P = .627, and .546 for anxiety, respectively). Interpretation We report an abnormally high rate of psychiatric burden among patients with cancer in the MENA region. Thus, establishing appropriate psycho-oncologic interventions within the MENA region is of utmost importance. The burden of psycho-oncology is not yet established within the Middle East and North Africa region. This study reviewed all available evidence characterizing the psychological burden among patients with cancer in this region.

The fifth edition of the WHO classification of CNS Tumors (WHO CNS5) has revised the diagnostic and grading criteria for Adult‐type Diffuse Gliomas (ADGs) by integrating molecular parameters with histologic features. Conducting molecular testing for most ADGs is now crucial in fulfilling the WHO CNS5 diagnostic criteria. However, due to additional costs and technical barriers, implementing molecular diagnostics is often not feasible in Low‐Income Countries (LICs) and Lower Middle‐Income Countries (LMICs). Therefore, practical approaches are needed for diagnosis in resource‐restrained settings. Hence, the Asian Oceanian Society of Neuropathology (AOSNP), through the ‘ADAPTR’ (Adapting Diagnostic Approaches for Practical Taxonomy in Resource‐Restrained Regions) initiative, aimed to provide resource‐stratified recommendations for diagnosing ADGs based on available resources while adhering to the WHO guidelines as much as possible. ADAPTR identified different resource levels (RLs) of diagnostic pathology services, ranging from RL I to RL V, with RL I to RL IV being applicable to the LMICs, and provides recommendations for a ‘Histology‐oriented integrated diagnosis format’ for each tumor type at different RLs. In addition, diagnostic flow charts for ADGs have been generated to suit these RLs. The emphasis is mainly on using histopathological approaches with immunohistochemistry, while molecular testing recommendation is categorized as ‘can be considered’, ‘highly recommended’ or ‘obligatory’, to reach the next level diagnosis. In each RL, either a WHO CNS5 diagnosis with an accompanying CNS WHO grade or an ADAPTR descriptive diagnosis with an associated ADAPTR histologic grade is provided, depending on the context. ADAPTR recommendations are therefore a practical adaptation of the WHO CNS5 guidelines that will suit routine diagnostic practices in resource‐restrained regions. ADAPTR recommendations for Adult‐type Diffuse Gliomas in Resource‐restrained settings.