The Vertebrobasilar Trunk and Its Anatomical Variants: A Microsurgical Anatomical Study.

BACKGROUND: The trunk of the basilar artery has not been included in microanatomy studies. Anatomical variants of the perforant branches of the vertebrobasilar trunk and their relationship with neural structures are very important in surgical approaches. Surgical dissection for the treatment of vascular lesions requires a perfect knowledge of the microsurgical anatomy. METHODS: We conducted a descriptive analysis of 50 brains, which were fixed with formalin at 10% for 2 weeks, and the arterial system was injected with colored latex. After microsurgical dissection, it was divided into three segments: the lower portion went from the anterior spinal artery to the anteroinferior cerebellar artery, the middle segment was raised from the upper limit of the lower portion to the origin of the superior cerebellar artery, and the upper segment ranged from the previous portion until the origin of the posterior cerebral artery. RESULTS: The basilar artery had an average length of 30 mm. The average diameter at its junction with the vertebral arteries was 4.05 mm. The average middle segment was 3.4 mm in diameter and 15.2 mm in length. The diameter of the upper segment was 4.2 mm, and its average length was 3.6 mm. The average number of bulbar arteries was three, and their average diameter was 0. 66 mm. The number of caudal perforator arteries were five on average, with a diameter of 0.32 mm. We found three rare cases of anatomical variants in the vertebra-basilar junction. CONCLUSIONS: The basilar artery emits penetrating branches in its lower, middle, and upper portions. The origin of penetrating branches was single or divided after forming a trunk. However, we observed long branches from perforant arteries.

Real-World Experience in Hispanic Patients With Breast Cancer and Brain Metastases Using Different Prognostic Tools.

PURPOSE: Only a small percentage of Hispanic patients have been included in studies that developed prognostic models for breast cancer and brain metastases. Therefore, there is a clear need for tools tailored to this demographic. This study assesses the efficacy of common prognostic tools in a Hispanic population. METHODS AND MATERIALS: We retrospectively analyzed a data set of Hispanic patients with breast cancer and newly diagnosed brain metastases from 2009 to 2023 at a single referral center. For each prognostic tool, Kaplan-Meier curves were built. The performances of the models were compared using the area under the curve (AUC), C-statistic, and Akaike information criteria (AIC). RESULTS: Of 492 patients, the median time from breast cancer to brain metastasis diagnosis was 22.7 months (IQR, 12.1-53.3). The median overall survival was 11.6 months (95% CI, 9.9-13.4). All models were validated as prognostic tools (P < .001). The model with the better performance was the breast graded prognostic assessment (GPA; AIC, 402; AUC, 0.65), followed by the modified GPA (AIC, 406; AUC, 0.64), the disease-specific GPA (AIC, 407; AUC, 0.62), recursive partitioning analysis (AIC, 421; AUC, 0.62), and GPA (AIC, 422; AUC, 0.60). CONCLUSIONS: The breast GPA demonstrated superior accuracy in prognosticating outcomes for Hispanic patients with breast cancer and brain metastases. This underscores the critical importance of incorporating racial and ethnic diversity in creating and validating medical prognostic tools.

Perilesional edema diameter associated with brain metastases as a predictive factor of response to radiotherapy in non-small cell lung cancer.

Background: Different prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD). Aim: The aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT. Methods: Out of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively. Results: Minor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26-10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7-4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4-3.3); p = 0.001]. Conclusion: Higher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.

A brain metastasis prediction model in women with breast cancer.

BACKGROUND: Breast cancer (BC) is a leading cause of mortality and the most frequent malignancy in women, and most deaths are due to metastatic disease, particularly brain metastases (BM). Currently, no biomarker or prediction model is used to predict BM accurately. The objective was to generate a BM prediction model from variables obtained at BC diagnosis. METHODS: A retrospective cohort of women with BC diagnosed from 2009 to 2020 at a single center was divided into a training dataset (TD) and a validation dataset (VD). The prediction model was generated in the TD, and its performance was measured in the VD using the area under the curve (AUC) and C-statistic. RESULTS: The cohort (n = 5009) was divided into a TD (n = 3339) and a VD (n = 1670). In the TD, the model with the best performance (lowest AIC) was built with the following variables: age, estrogen receptor status, tumor size, axillary adenopathy, anatomic clinical stage, Ki-67 expression, and Scarff-Bloom-Richardson score. This model had an AUC of 0.79 (95%CI, 0.76-0.82; p < 0.0001) in the TD. The 10-fold cross-validation showed the good stability of the model. The model displayed an AUC of 0.81 (95%CI, 0.77-0.85; P < 0.0001) in the VD. Four groups, according to the risk of BM, were generated. In the low-risk group, 1.2% were diagnosed with BM (reference); in the medium-risk group, 5.0% [HR 4.01 (95%CI, 1.8 - 8.8); P < 0.0001); in the high-risk group, 8.5% [HR 8.33 (95%CI, 4.1-17.1); P < 0.0001]; and in the very high-risk group, 23.7% [HR 29.72 (95%CI, 14.9 - 59.1); P < 0.0001]. CONCLUSION: This prediction model built with clinical and pathological variables at BC diagnosis demonstrated robust performance in determining the individual risk of BM among patients with BC, but external validation in different cohorts is needed.

Age and sex disparities in Latin-American adults with gliomas: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to identify if there are ethnic differences in the age and sex distribution of gliomas in the Latino adult population. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Databases used were MEDLINE, LILACS, Web of Science, and Scopus. Studies were included if they reported the age and/or sex distribution of gliomas in Latin adults, published in English or Spanish from January 1st, 1985, to December 1st, 2022. The quality of the studies was assessed using the Newcastle-Ottawa Quality Assessment Scale and the NIH Quality Assessment Tool. RESULTS: From 1096 articles, fifteen studies with information on 6,815 patients were selected for the systematic review, and thirteen were selected for the meta-analysis. The mean ages of diagnosis of glioma and glioblastoma were 50.9, 95\%\ CI [47.8-53.9] years and 53.33 years, 95 \% CI [51-55.6], respectively. The male-to-female incidence rate ratio of gliomas was 1.39. CONCLUSION: Our study found mean ages of glioma and glioblastoma were 6 and 10 years lower than those reported in the CBTRUS. Our study suggests disparities in the age and sex distribution of gliomas in Latin America compared to other regions. PROSPERO REGISTRATION NUMBER: CRD42021274423.

Are neurologic symptoms associated with worse QoL in non-CNS cancer patients?

BACKGROUND: The burden of having neurologic symptoms (NS) in cancer patients has scantly been studied; therefore, we performed a study whose purpose was to measure the impact of having clinically active (NS) on the quality of life (QoL) of non-primary CNS cancer patients. METHODS: Patients with systemic cancer (non-primary CNS cancer) sent for neurological evaluation at a single cancer center (INCAN) were prospectively invited to respond the EORTC-QLQ-C30 and BN20 questionnaires. Associations of the questionnairés items were blindly measured for the following groups: NS+ or not (NS-) and having active cancer (AC+) or not (AC-). RESULTS: Of 205 patients aged 55.4 ± 15.4 years, 122 (60%) had NS+ and 107 (52%) AC +. The NS+ group (compared with the NS-) showed a significant worse perception in the following scales/items of the EORTC QLQ-C30: physical functioning (median 86 vs. 92, P = 0.012), role functioning (66 vs. 100, P < 0.001), emotional functioning (75 vs. 83, P = 0.005), cognitive functioning (66 vs. 83, P < 0.001), fatigue (33 vs. 22, P < 0.001), nausea and vomiting (P = 0.021), pain (33 vs. 16, P < 0.001), insomnia (33 vs. 0, P = 0.011), appetite loss (P = 0.021), and global health (66 vs. 75, P = 0.001). CONCLUSION: In patients with systemic (non-CNS) cancer, the QoL is significantly worse for patients with active neurologic symptoms.

Nitroglycerin Plus Whole Intracranial Radiation Therapy for Brain Metastases in Patients With Non-Small Cell Lung Cancer: A Randomized, Open-Label, Phase 2 Clinical Trial.

PURPOSE: Hypoxia has been associated with chemoradioresistance secondary to vascular endothelial growth factor receptor induced by hypoxia-induced factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in tissues, and this may have antiangiogenic, proapoptotic, and antiefflux effects. Particularly, epidermal growth factor-mutated (EGFRm) tumor cell lines have been shown to overexpress both vascular endothelial growth factor and HIF. In this phase 2 study, we evaluated the effect of transdermal NTG plus whole brain radiation therapy (WBRT) in patients with non-small cell lung cancer (NSCLC) with brain metastases (BM). METHODS: This was an open-label, phase 2 clinical trial with 96 patients with NSCLC and BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. The primary endpoint was intracranial objective response rate (iORR) evaluated 3 months posttreatment. NTG was administered using a transdermal 36-mg patch from Monday through Friday throughout WBRT administration (10 days). The protocol was retrospectively registered at ClinicalTrials.gov (NCT04338867). RESULTS: Fifty patients were allocated to the control group, and 46 were allocated to the experimental group (NTG); among these, 26 (52%) had EGFRm in the control group and 21 (45.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response compared with controls (56.5% [n = 26/46 evaluable patients] vs 32.7% [n = 16/49 evaluable patients]; relative risk, 1.73; 95% confidence interval [CI], 1.08-2.78; P = .024). Additionally, patients who received NTG + WBRT had an independently prolonged intracranial progression-free survival (ICPFS) compared with those who received WBRT alone (27.7 vs 9.6; hazard ratio [HR], 0.5; 95% CI, 0.2-0.9; P = .020); this positively affected overall progression-free survival among patients who received systemic therapy (n = 88; HR, 0.5; 95% CI, 0.2-0.9; P = .043). The benefit of ICPFS (HR, 0.4; 95% CI, 0.2-0.9; P = .030) was significant in the EGFRm patient subgroup. No differences were observed in overall survival. A significantly higher rate of vomiting presented in the NTG arm of the study (P = .016). CONCLUSIONS: The concurrent administration of NTG and radiation therapy improves iORR and ICPFS among patients with NSCLC with BM. The benefit in ICPFS is significant in the EGFRm patient subgroup.

Re-irradiation in patients with progressive or recurrent brain metastases from extracranial solid tumors: A novel prognostic index.

BACKGROUND: Most studies evaluating factors associated with the survival of patients with brain metastases (BM) have focused on patients with newly diagnosed BM. This study aimed to identify prognostic factors associated with survival after brain re-irradiation in order to develop a new prognostic index. METHODS: This 5-year retrospective study included patients treated with repeat-radiotherapy for recurrent BM at the "Instituto Nacional de Cancerología" of Mexico between 2015 and 2019. Significant variables in the multivariate Cox regression analysis were used to create the brain re-irradiation index (BRI). Survival and group comparisons were performed using the Kaplan-Meier method and the log-rank test. RESULTS: Fifty-seven patients receiving brain re-irradiation were identified. Most patients were women (75.4%) with a mean age at BM diagnosis of 51.4 years. Lung and breast cancer were the most prevalent neoplasms (43.9% each). Independent prognostic factors for shorter survival after re-irradiation were: Age >50 years (hazard ratio [HR]:2.5 [95% confidence interval [CI], 1.1-5.8]; p = 0.026), uncontrolled primary tumor (HR:5.5 [95% CI, 2.2-13.5]; p < 0.001), lesion size >20 mm (4.6 [95% CI, 1.7-12.2]; p = 0.002), and an interval <12 months between radiation treatments (HR:4.3 [95% CI, 1.7-10.6]; p = 0.001). Median survival (MS) after re-irradiation was 14.6 months (95% CI, 8.2-20.9).MS of patients stratified according to the BRI score was 17.38, 10.34, and 2.82 months, with significant differences between all groups. CONCLUSIONS: The new BRI can be easily implemented for the prognostic classification of cancer patients with progressive or recurrent BM from extracranial solid tumors.

Deep DNA sequencing of MGMT, TP53 and AGT in Mexican astrocytoma patients identifies an excess of genetic variants in women and a predictive biomarker.

PURPOSE: Astrocytomas are a type of malignant brain tumor with an unfavorable clinical course. The impact of AGT and MGMT somatic variants in the prognosis of astrocytoma is unknown, and it is controversial for TP53. Moreover, there is a lack of knowledge regarding the molecular characteristics of astrocytomas in Mexican patients. METHODS: We studied 48 Mexican patients, men and women, with astrocytoma (discovery cohort). We performed DNA deep sequencing in tumor samples, targeting AGT, MGMT and TP53, and we studied MGMT gene promoter methylation status. Then we compared our findings to a cohort which included data from patients with astrocytoma from The Cancer Genome Atlas (validation cohort). RESULTS: In the discovery cohort, we found a higher number of somatic variants in AGT and MGMT than in the validation cohort (10.4% vs < 1%, p < 0.001), and, in both cohorts, we observed only women carried variants AGT variants. We also found that the presence of either MGMT variant or promoter methylation was associated to better survival and response to chemotherapy, and, in conjunction with TP53 variants, to progression-free survival. CONCLUSIONS: The occurrence of AGT variants only in women expands our knowledge about the molecular differences in astrocytoma between men and women. The increased prevalence of AGT and MGMT variants in the discovery cohort also points towards possible distinctions in the molecular landscape of astrocytoma among populations. Our findings warrant further study.

Targeted Therapies and Utility of the Lung-molGPA in Non-Small-Cell Lung Cancer Patients with Brain Metastases.

INTRODUCTION: Therapeutic advances have increased the survival of non-small-cell lung cancer (NSCLC) patients as well as the lifetime risk of being diagnosed with brain metastases (BM). Although BM have historically been associated with poor prognosis, it is unclear whether they remain a strong predictor of reduced survival. This study aimed to evaluate the prognostic value of BM and the utility of the Lung-molGPA. METHODS: This single-center retrospective database analysis included 1,393 NSCLC patients with newly diagnosed BM who registered at the Instituto Nacional de Cancerología of Mexico (INCan) from 2010 to 2020. The Kaplan-Meier method and log-rank test were used for the survival analysis. Survival times were calculated from the date of NSCLC diagnosis (OS), or BM diagnosis, to the date of death or last follow-up. Cox proportional-hazards models were used to calculate the hazard ratio (HR) for death and the significance of the parameters evaluated. RESULTS: Out of 1,058 patients who underwent genetic testing for epidermal growth factor receptor (EGFR) mutations and/or anaplastic lymphoma kinase (ALK) rearrangements, 650 had a positive tumor mutational/rearrangement status (543 had EGFR mutations, 104 had ALK rearrangements, and 3 had both EGFR and ALK alterations). Median OS did not differ between patients with BM and without BM (17.7 months [95% CI, 15.4-19.0] vs. 16.6 months [95% CI, 14.3-19.0]; p = 0.362). In contrast, the presence of BM was associated with worse OS in patients with a negative tumor mutational status (HR: 1.225 [95% CI, 1.041-1.443]; p = 0.015), who did not receive TKI therapy (HR: 1.269 [95% CI, 1.082-1.488]; p = 0.003), or with non-adenocarcinoma histology (HR: 1.582 [95% CI, 1.118-2.238]; p = 0.01). The median survival after BM diagnosis was 4.27, 6.96, 14.68, and 18.89 months for adenocarcinoma patients with Lung-molGPA scores 0-1, 1.5-2, 2.5-3, and 3.5-4, respectively (p < 0.0001). For non-adenocarcinoma patients with Lung-molGPA scores 0-1, 1.5-2, and 2.5-3, the corresponding estimates were 0.95, 2.89, and 9.39 months, respectively (p < 0.0001). CONCLUSIONS: These results show that the prognosis of NSCLC patients with BM is no longer uniformly poor and should be individually assessed. Furthermore, the validity of the Lung-molGPA was confirmed in an independent population from a different geographical region.

Primary Benign Tumors of the Spinal Canal.

Benign tumors that grow in the spinal canal are heterogeneous neoplasms with low incidence; from these, meningiomas and nerve sheath tumors (neurofibromas and schwannomas) account for 60%-70% of all primary spinal tumors. Benign spinal canal tumors provoke nonspecific clinical manifestations, mostly related to the affected level of the spinal cord. These tumors present a challenge for the patient and healthcare professionals, for they are often difficult to diagnose and the high frequency of posttreatment complications. In this review, we describe the epidemiology, risk factors, clinical features, diagnosis, histopathology, molecular biology, and treatment of extramedullary benign meningiomas, osteoid osteomas, osteoblastomas, aneurysmal bone cysts, osteochondromas, neurofibromas, giant cell tumors of the bone, eosinophilic granulomas, hemangiomas, lipomas, and schwannomas located in the spine, as well as possible future targets that could lead to an improvement in their management.

Predict the incidence of Guillain Barré Syndrome and arbovirus infection in Mexico, 2014-2019.

The Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) virus infections have been linked to Guillain-Barré syndrome (GBS). GBS has an estimated lethality of 4% to 8%, even with effective treatment. Mexico is considered a hyperendemic country for DENV due to the circulation of four serotypes, and the ZIKV and CHIKV viruses have also been circulating in the country. The objective of this study was to predict the number of GBS cases in relation to the cumulative incidence of ZIKV / DENV / CHIKV in Mexico from 2014 to 2019. A six-year time series ecological study was carried out from GBS cases registered in the Acute Flaccid Paralysis (AFP) Epidemiological Surveillance System (ESS), and DENV, ZIKV and CHIKV estimated cases from cases registered in the epidemiological vector-borne diseases surveillance system. The results shows that the incidence of GBS in Mexico is positively correlated with DENV and ZIKV. For every 1,000 estimated DENV cases, 1.45 GBS cases occurred on average, and for every 1,000 estimated ZIKV cases, 1.93 GBS cases occurred on average. A negative correlation between GBS and CHIKV estimated cases was found. The increase in the incidence of GBS cases in Mexico can be predicted by observing DENV and ZIKV cases through the epidemiological surveillance systems. These results can be useful in public health by providing the opportunity to improve capacities for the prevention of arbovirus diseases and for the timely procurement of supplies for the treatment of GBS.

Association of the neutrophil-to-lymphocyte ratio with brain metastases in Hispanic breast cancer patients.

BACKGROUND: Breast cancer (BC) is one of the most common cancers and leading cause of cancer-related deaths in women. Metastatic disease, particularly brain metastases (BM), is associated with death in BC patients. The neutrophil-to-lymphocyte ratio (NLR) has been associated with BC prognosis, but it is not usually used in clinical practice and has not been associated with BM. We aimed to determine if there is an association between NLR and BM and if NLR is associated with survival in a Hispanic population. METHODS: A retrospective cohort with a total of 2,104 patients with a confirmed diagnosis of BC at a single referral center were randomly divided into training and validation datasets. Univariable and multivariable analyses were performed to study the association of NLR with BM and/or survival. RESULTS: No significant differences between datasets were identified. A high NLR (> 2.2) was associated with a higher frequency of BM after multivariable adjustment in both datasets. Overall survival was shorter in patients with a high NLR; however, the most important factor associated with outcome was the presence of BM. The interaction NLR/BM was not statistically significant. CONCLUSION: A high NLR at BC diagnosis was associated with a higher frequency of BM, and the presence of BM was associated with worse overall survival in Hispanic BC patients.

Identification of a high-risk group for brain metastases in non-small cell lung cancer patients.

PURPOSE: Identification of a high-risk group of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) could lead to early interventions and probably better prognosis. The objective of the study was to identify this group by generating a multivariable model with recognized and accessible risk factors. METHODS: A retrospective cohort from patients seen at a single center during 2010-2020, was divided into a training (TD) and validation (VD) datasets, associations with BM were measured in the TD with logit, variables significantly associated were used to generate a multivariate model. Model´s performance was measured with the AUC/C-statistic, Akaike information criterion, and Brier score. RESULTS: From 570 patients with NSCLC who met the strict eligibility criteria a TD and VD were randomly assembled, no significant differences were found amid both datasets. Variables associated with BM in the multivariate logit analyses were age [P 0.001, OR 0.96 (95% CI 0.93-0.98)]; mutational status positive [P 0.027, OR 1.96 (95% CI 1.07-3.56); and carcinoembryonic antigen levels [P 0.016, OR 1.001 (95% CI 1.000-1.003). BM were diagnosed in 24% of the whole cohort. Stratification into a high-risk group after simplification of the model, displayed a frequency of BM of 63% (P < 0.001). CONCLUSION: A multivariate model comprising age, carcinoembryonic antigen levels, and mutation status allowed the identification of a truly high-risk group of BM in NSCLC patients.

Role of whole brain radiotherapy in the management of infratentorial metastases from lung and breast cancer.

BACKGROUND: Brain metastases (BM) occur in almost one third of patients with systemic malignancies. Only a small number of studies focus on infratentorial location and whole brain radiotherapy (WBRT) as the main non-surgical management. The aim of the study was to compare the prognosis of patients treated with WBRT among patients with supra- or infratentorial lesions. MATERIALS AND METHODS: At a single center, 263 patients with either breast (BC) or lung (LC) cancer, that had developed BM and received treatment with WBRT, were analyzed during an 8-year period. RESULTS: A total of 152 patients with BC and 111 with LC were analyzed, median age at the time of BM was 50.7 years, systemic activity other than BM was detected in 91%. Newly diagnosed BM were supratentorial in 40%, infratentorial in 10% and 51% in both locations. Median overall survival was 13 months (95% CI: 11.1-14.8 months), without significant difference between supra- or infratentorial location. WBRT alone was administered in 79% of patients, whereas WBRT with chemtoreapy was provided for 21%. CONCLUSION: In patients with BM from LC or BC that were not candidates for surgical resection, palliative WBRT appears to be equally effective in those with supra- or infratentorial locations.

Central nervous system international prognostic index impacts overall survival in diffuse large b-cell lymphoma treated with r-chop in a third level cancer center from Mexico: a survey of 642 patients

Background: Central nervous system international prognosis index (CNS-IPI) is validated in European and the USA cancer databases. However, no validation has been done in Mexican population. Objective: The objective of the study was to assess the impact of the CNS-IPI on central nervous system (CNS) relapse and survival in Mexican patients with diffuse large B-cell lymphoma (DLBCL). Methods: In this retrospective analysis, clinical, biochemical, and histological variables and the CNS-IPI were analyzed. Results: Six hundred and forty-two patients with DBLCL were included in the study. The mean ± SD age was 56.8 ± 14.9 years. Most had an ECOG of 0-1: 75% (n = 484) had absence of B-symptoms and advanced disease (clinical stage: III-IV, n = 433, 67.4%). According to the CNS-IPI, almost one-half were in the low-risk category. According to the CNS-IPI, CNS relapse rate was 1.36% (95% CI: 83.2-92.8), 3.1% (95% CI: 132.4-162.8), and 7.4% (95% CI 61-91) for patients in the low-, intermediate-, and high-risk categories, respectively. The median overall survival in the high-risk group (CNS-IPI) was 22 months, and it has not been achieved after 80 months of follow-up for the other groups. Conclusions: CNS-IPI was associated with survival; therefore, we propose its use as a prognostic tool for prospective validation.

Prophylactic Cranial Irradiation in Patients With High-Risk Metastatic Non-Small Cell Lung Cancer: Quality of Life and Neurocognitive Analysis of a Randomized Phase II Study.

PURPOSE: To this date, studies regarding the use of prophylactic cranial irradiation (PCI) versus standard of care (SoC) for patients with non-small cell lung cancer have shown limited benefit in survival outcomes, in addition to the potential effects on quality of life (QoL) and neurocognitive function (NCF). This randomized, phase II study evaluated the role of PCI in QoL and NCF, in a population comprised of subjects at a high risk for development of brain metastases (BM). METHODS AND MATERIALS: Eligible patients had histologically confirmed non-small cell lung cancer without baseline BM, harboring epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen (CEA) at diagnosis. Participants were assigned to receive SoC or SoC plus PCI (25 Gy in 10 fractions). Primary endpoint was BM at 24 months (BM-24), for which the study was powered. Secondary endpoints included QoL assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the Lung Cancer module (LC13) and NCF assessed using the Mini Mental State Examination (MMSE). Patients were followed every 3 months for a year for QoL and NCF. RESULTS: From May 2012 to December 2017, 84 patients were enrolled in the study, 41 were allocated to PCI while 43 received SoC. Efficacy outcomes are discussed in a separate article. The global health-QoL scores were similar at 3, 6, 9, and 12 months after randomization between both study arms, with no significant differences when comparing by groups. At 1-year postrandomization, median global health QoL scores were 83 (p25-p75: 75-83) and 83 (p25-p75: 75-83) in the control and experimental arms, respectively. There were no significant changes in terms of the mean differences between subjects in either study arm when analyzing the change between baseline and 12-month scores (16.4 ± 19.9 vs 12.9 ± 14.7; P = .385). Seventeen patients were alive at database lockdown in February 2020, without significant differences in median MMSE (30 [p25-75: 29-30] vs 30 [p25-75: 28-30]) or QLQ-C30 scores (75.0 [p25-75: 50-87.2] vs 67.0 [p25-75: 50.0-100.0]). CONCLUSIONS: Among a selected high-risk population for developing BM, PCI did not significantly decrease QoL or neurocognitive function as assessed using the MMSE. Future studies are warranted to assess this observation, using more varied and sensitive tools available to date.

Central Nervous System International Prognostic Index Impacts Overall Survival in Diffuse Large B-cell Lymphoma Treated with R-Chop in a third Level Cancer Center from Mexico: A Survey of 642 Patients.

BACKGROUND: Central nervous system international prognosis index (CNS-IPI) is validated in European and the USA cancer databases. However, no validation has been done in Mexican population. OBJECTIVE: The objective of the study was to assess the impact of the CNS-IPI on central nervous system (CNS) relapse and survival in Mexican patients with diffuse large B-cell lymphoma (DLBCL). METHODS: In this retrospective analysis, clinical, biochemical, and histological variables and the CNS-IPI were analyzed. RESULTS: Six hundred and forty-two patients with DBLCL were included in the study. The mean ± SD age was 56.8 ± 14.9 years. Most had an ECOG of 0-1: 75% (n = 484) had absence of B-symptoms and advanced disease (clinical stage: III-IV, n = 433, 67.4%). According to the CNS-IPI, almost one-half were in the low-risk category. According to the CNS-IPI, CNS relapse rate was 1.36% (95% CI: 83.2-92.8), 3.1% (95% CI: 132.4-162.8), and 7.4% (95% CI 61-91) for patients in the low-, intermediate-, and high-risk categories, respectively. The median overall survival in the high-risk group (CNS-IPI) was 22 months, and it has not been achieved after 80 months of follow-up for the other groups. CONCLUSIONS: CNS-IPI was associated with survival; therefore, we propose its use as a prognostic tool for prospective validation.

Landscape of Germline Genetic Variants in AGT, MGMT, and TP53 in Mexican Adult Patients with Astrocytoma.

Astrocytoma is the most common type of primary brain tumor. The risk factors for astrocytoma are poorly understood; however, germline genetic variants account for 25% of the risk of developing gliomas. In this study, we assessed the risk of astrocytoma associated with variants in AGT, known by its role in angiogenesis, TP53, a well-known tumor suppressor and the DNA repair gene MGMT in a Mexican population. A case-control study was performed in 49 adult Mexican patients with grade II-IV astrocytoma. Sequencing of exons and untranslated regions of AGT, MGMT, and TP53 from was carried in an Ion Torrent platform. Individuals with Mexican Ancestry from the 1000 Genomes Project were used as controls. Variants found in our cohort were then assessed in a The Cancer Genome Atlas astrocytoma pan-ethnic validation cohort. Variants rs1926723 located in AGT (OR 2.74, 1.40-5.36 95% CI), rs7896488 in MGMT (OR 3.43, 1.17-10.10 95% CI), and rs4968187 in TP53 (OR 2.48, 1.26-4.88 95% CI) were significantly associated with the risk of astrocytoma after multiple-testing correction. This is the first study where the AGT rs1926723 variant, TP53 rs4968187, and MGMT rs7896488 were found to be associated with the risk of developing an astrocytoma.

Treatment and outcome in 12 cases of olfactory neuroblastoma at Mexico´s National Cancer Institute: A retrospective clinical analysis and literature review.

INTRODUCTION: Olfactory neuroblastoma (ONB) is a malignant neoplasm that arises from the upper nasal vault. OBJECTIVE: We present a retrospective case series and clinical analysis of 12 ONB cases. MATERIALS AND METHODS: Patients with ONB treated at Mexico´s National Cancer Institute between 2011 and 2018. RESULTS: The Kadish proportion of B, C, and D stage was 16%, 58%, or 25%, respectively. Hyams Grade 1, 2, or 3 was 25%, 50%, and 25%, respectively. The most common surgical approach was the craniofacial in 5 cases (42%), followed by the transfacial in 4 cases (33%), and the endonasal endoscopic approach in 3 cases (25%). Gross total resection was achieved in 8 patients (67%). Five patients (42%) underwent a second operation due to recurrent/progressive disease. The surgical complication rate was 8.3%. Progression-free survival was 41 months and the mean overall survival was 63.6 months. CONCLUSIONS: Surgical resection followed by radiotherapy, and chemotherapy for metastatic and recurrent disease provides the best outcome in terms of survival and recurrence. To the best of our knowledge, this is the first series of cases reported in Mexico.

ANTECEDENTES: El neuroblastoma olfatorio es una neoplasia maligna que se origina en la bóveda nasal superior. OBJETIVO: Presentar una serie de casos y un análisis clínico retrospectivo. MÉTODO: Pacientes con neuroblastoma olfatorio tratados en el Instituto Nacional de Cancerología, de México, entre 2011 y 2018. RESULTADOS: La proporción de Kadish en las etapas B, C y D fue del 16, el 58 y el 25%, respectivamente. Los grados 1, 2 y 3 de Hyams fueron el 25, el 50 y el 25%, respectivamente. El abordaje quirúrgico más frecuente fue el craneofacial, en cinco casos (42%), seguido del transfacial en cuatro (33%) y del abordaje endoscópico endonasal en tres (25%). La resección total macroscópica se logró en ocho pacientes (67%). Cinco pacientes (42%) se sometieron a una segunda operación debido a enfermedad recurrente o progresiva. La tasa de complicaciones quirúrgicas fue del 8,3%. La sobrevida libre de progresión fue de 41 meses y la supervivencia media global fue de 63,6 meses. CONCLUSIONES: La resección quirúrgica seguida de radioterapia y quimioterapia para la enfermedad metastásica y recurrente proporciona el mejor resultado en términos de supervivencia y recurrencia. Hasta donde sabemos, esta es la primera serie de casos reportados en México.