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Simple Summary: There is a noticeable dearth of information regarding chronic myeloid leukemia (CML) within the Gulf region. This study seeks to address this gap by offering comprehensive insights into the status of CML in the Gulf, encompassing aspects such as diagnosis, testing, treatment objectives, toxicities, and discontinuation. Through a survey completed by 15 experts and subsequent discussions, this research sheds light on the management and treatment approaches for CML within the region. Remarkably, the practices observed among these experts closely align with global standards, although unique challenges pertinent to the Gulf region were distinctly identified during the discourse. Studies on chronic myeloid leukemia (CML) in the Gulf region are scarce, consisting of a survey and expert meeting that included 15 experts in 2023 which discussed CML diagnosis, testing, treatment objectives, toxicities, and discontinuation in the Gulf region. Most patients were reported to be in first-line therapy, and the most common treatments were imatinib/imatinib generic in first-line and dasatinib in second- and third-lines. Mutation analysis was not reported to be routinely performed at the time of diagnosis but rather in case of progression to accelerated/blast phase or any sign of loss of response. While all participants were aware that BCR-ABL should be monitored every three months during the first year of treatment, 10% reported monitoring BCR-ABL every six months in practice due to test cost and lab capability. The most important first-line therapy objective was "achievement of major molecular response" (MMR) in younger patients and "overall survival" in older ones. The most important treatment objectives were "MMR" and "early molecular response followed by prolongation of overall survival" in the short term and "treatment-free remission" in the long term. The current practices in CML in the Gulf region appear to be similar to global figures. [ABSTRACT FROM AUTHOR]

Simple Summary: Midline gliomas are tumors that can manifest as either circumscribed or diffuse growths. These tumors typically develop in midline structures, including the thalamus, brainstem, and spinal cord. Other structures along the midline, such as the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum may also be affected. Diffuse midline gliomas (DMGs) are a subtype of midline gliomas and are considered highly aggressive and are most commonly diagnosed in children and young adults. These tumors are difficult to treat due to their location and invasive nature, and their prognosis is generally poor. We aim to describe our experience with midline gliomas, with a focus on DMGs. Midline gliomas are tumors that occur in midline structures and can be circumscribed or diffuse. Classical midline structures include the thalamus, brainstem, and spinal cord. Other midline structures include the corpus callosum, basal ganglia, ventricles, paraventricular structures, and cerebellum. Diffuse midline glioma (DMG) is a diffuse glioma that occurs in the classical midline structures, characterized by a specific genetic alteration, and associated with grim outcome. This study was conducted at King Hussein Cancer Center and reviewed the medical records of 104 patients with circumscribed and diffuse gliomas involving midline structures that underwent biopsy between 2005 and 2022. We included a final cohort of 104 patients characterized by a median age of 23 years and a male-to-female ratio of 1.59-to-1. Diffuse high-grade glioma (DHGG) was the most common pathological variant (41.4%), followed by DMG (28.9%). GFAP was positive in most cases (71.2%). Common positive mutations/alterations detected by surrogate immunostains included H3 K27me3 (28.9%), p53 (25.0%), and H3 K27M (20.2%). Age group, type of treatment, and immunohistochemistry were significantly associated with both the location of the tumor and tumor variant (all; p < 0.05). DMGs were predominantly found in the thalamus, whereas circumscribed gliomas were most commonly observed in the spinal cord. None of the diffuse gliomas outside the classical location, or circumscribed gliomas harbored the defining DMG mutations. The median overall survival (OS) for the entire cohort was 10.6 months. Only the tumor variant (i.e., circumscribed gliomas) and radiotherapy were independent prognosticators on multivariate analysis. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer is the most commonly diagnosed non-skin malignancy in men. Numerous studies have been undertaken to explore the role that genomics plays in prostate cancer initiation and progression. Most of this genomic data comes tumors arising in men with European or Asian ancestry, leaving other ancestry groups understudied. To fill this gap, we investigated the differences in copy number aberrations between prostate cancers arising in men of Middle Eastern ethnicity and those of European, African, or East Asian ethnicities in the hope of better understanding the incidence and risk of prostate cancer in different populations. We identified ancestry-specific gains and deletions, as well as differences in overall genomic instability between ancestry groups. This confirms that ancestry should be considered when investigating and characterizing biomarkers and molecular signatures relative to disease progression, prognosis, and potentially therapeutic targeting. Our knowledge of prostate cancer (PCa) genomics mainly reflects European (EUR) and Asian (ASN) populations. Our understanding of the influence of Middle Eastern (ME) and African (AFR) ancestry on the mutational profiles of prostate cancer is limited. To characterize genomic differences between ME, EUR, ASN, and AFR ancestry, fluorescent in situ hybridization (FISH) studies for NKX3-1 deletion and MYC amplification were carried out on 42 tumors arising in individuals of ME ancestry. These were supplemented by analysis of genome-wide copy number profiles of 401 tumors of all ancestries. FISH results of NKX3-1 and MYC were assessed in the ME cohort and compared to other ancestries. Gene level copy number aberrations (CNAs) for each sample were statistically compared between ancestry groups. NKX3-1 deletions by FISH were observed in 17/42 (17.5%) prostate tumors arising in men of ME ancestry, while MYC amplifications were only observed in 1/42 (2.3%). Using CNAs called from arrays, the incidence of NKX3-1 deletions was significantly lower in ME vs. other ancestries (20% vs. 52%; p = 2.3 × 10−3). Across the genome, tumors arising in men of ME ancestry had fewer CNAs than those in men of other ancestries (p = 0.014). Additionally, the somatic amplification of 21 specific genes was more frequent in tumors arising in men of ME vs. EUR ancestry (two-sided proportion test; Q < 0.05). Those included amplifications in the glutathione S-transferase family on chromosome 1 (GSTM1, GSTM2, GSTM5) and the IQ motif-containing family on chromosome 3 (IQCF1, IQCF2, IQCF13, IQCF4, IQCF5, IQCF6). Larger studies investigating ME populations are warranted to confirm these observations. [ABSTRACT FROM AUTHOR]

Simple Summary: This study was conducted to investigate the prognostic significance of programmed death-ligand 1 (PD-L1) expression in a large cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients and to explore the correlation of PD-L1 and BRAFV600E mutations in PTC tumors and cell lines. We found PD-L1 over-expression in PTC patients and it was significantly associated with aggressive clinico-pathological parameters and BRAF mutation. PTC patients with co-existing PD-L1 over-expression and BRAF mutation had a poor disease-free survival. In vitro studies showed that BRAF inhibition induces PD-L1 expression in BRAF-mutated PTC cell lines via mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) pathway activation. Silencing of PD-L1 in BRAF-mutated cell lines significantly attenuated cell growth. Our data suggest that PD-L1 could represent a useful prognostic marker for risk stratification in Middle Eastern PTC and that a programmed cell death protein 1 (PD-1)/PD-L1 inhibitor could be a potential therapeutic option for aggressive PTC cancers, such as the tall cell variant, BRAF mutation-positive patients that are unresponsive to standard PTC treatment. PD-L1 inhibition is a promising therapeutic target whose efficacy has been demonstrated in several cancers. Immunohistochemistry was performed to assess PD-L1 protein expression in PTC. We further conducted in vitro analysis to investigate the role of PD-L1 in regulating BRAFV600E in PTC cell lines. PD-L1 over-expression was noted in 32.4% (473/1458) of cases and significantly associated with aggressive clinico-pathological parameters. Importantly, PD-L1 was found to be an independent poorer prognostic marker. We also found PD-L1 to be significantly associated with BRAF mutation and patients with co-existing PD-L1 over-expression and BRAF mutation had a poor disease-free survival compared to patients with BRAF mutation alone. In vitro analysis showed high expression of PD-L1 in BRAF-mutated PTC cell lines compared to a BRAF wild-type cell line. Inhibition of BRAF using vemurafenib induced PD-L1 expression in BRAF-mutated cell lines without affecting cell growth. Knockdown of PD-L1 in BRAF-mutated cell lines significantly decreased the cell growth and induced apoptosis. Our data suggest that PD-L1 might represent a useful prognostic marker in Middle Eastern PTC and PD-L1 inhibition could be a potential therapeutic option for aggressive PTC cancers, such as the tall cell variant, BRAF mutation-positive patients that are unresponsive to standard treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor recurrence is a relatively common event in papillary thyroid cancer (PTC). The aim of this study was to analyze the time-varying pattern of recurrence in PTC using annual hazard function and establish a predictive model for early and late recurrences. We found a double-peaked pattern of annual hazard of recurrence, with the risk being highest during the first 5 years after surgery. We also found distinct clinico-pathological parameters that could independently predict the occurrence of early recurrence (first 5 years) as compared to late recurrence (after 5 years). Overall, this study highlights the importance of long-term follow-up of PTC patients. Furthermore, the findings of our study could help in establishing individualized treatment and surveillance plans in PTC patients. Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans. [ABSTRACT FROM AUTHOR]

Simple Summary: In Cyprus, approximately 9% of triple-negative (negative in common breast cancer receptors—estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors) breast cancer (TNBC) patients carry inherited mutations in the BRCA1/2 breast cancer (BC) susceptibility genes. These mutations increase the risk of BC. However, the contribution of other BC susceptibility genes has not yet been determined. To this end, we aimed to investigate the prevalence of mutations in BRCA1/2-negative TNBC patients in Cyprus. Ninety-five cancer susceptibility genes were sequenced for 163 TNBC patients. The frequency of non-BRCA mutations and especially PALB2 in TNBC patients in Cyprus appears to be higher compared to other populations, and half of the mutation-positive patients were diagnosed over the age of 60 years. Based on these results, we believe that PALB2 and TP53 along with BRCA1/2 genetic testing could be beneficial for a large proportion of TNBC patients in Cyprus, irrespective of their age of diagnosis. In Cyprus, approximately 9% of triple-negative (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2-negative) breast cancer (TNBC) patients are positive for germline pathogenic variants (PVs) in BRCA1/2. However, the contribution of other genes has not yet been determined. To this end, we aimed to investigate the prevalence of germline PVs in BRCA1/2-negative TNBC patients in Cyprus, unselected for family history of cancer or age of diagnosis. A comprehensive 94-cancer-gene panel was implemented for 163 germline DNA samples, extracted from the peripheral blood of TNBC patients. Identified variants of uncertain clinical significance were evaluated, using extensive in silico investigation. Eight PVs (4.9%) were identified in two high-penetrance TNBC susceptibility genes. Of these, seven occurred in PALB2 (87.5%) and one occurred in TP53 (12.5%). Interestingly, 50% of the patients carrying PVs were diagnosed over the age of 60 years. The frequency of non-BRCA PVs (4.9%) and especially PALB2 PVs (4.3%) in TNBC patients in Cyprus appears to be higher compared to other populations. Based on these results, we believe that PALB2 and TP53 along with BRCA1/2 genetic testing could be beneficial for a large proportion of TNBC patients in Cyprus, irrespective of their age of diagnosis. [ABSTRACT FROM AUTHOR]