The IKZF1 gene is formed by 8 exons and encodes IKAROS, a transcription factor that regulates the expression of genes that control cell cycle progression and cell survival. In general, 15-20% of the patients with preB acute lymphoblastic leukemia (preB ALL) harbor IKZF1 deletions, and the frequency of these deletions increases in BCR-ABL1 or Ph-like subgroups. These deletions have been associated with poor treatment response and the risk of relapse. The aim of this descriptive study was to determine the frequency of IKZF1 deletions and the success of an induction therapy response in Mexican pediatric patients diagnosed with preB ALL in 2 hospitals from 2017 to August 2018. Thirty-six bone marrow samples from patients at the Instituto Nacional de Pediatría in Mexico City and the Centro Estatal de Cancerología in Tepic were analyzed. The IKZF1 deletion was identified by MLPA using the SALSA MLPA P335 ALL-IKZF1 probemix. Deletions of at least 1 IKZF1 exon were observed in 7/34 samples (20.6%): 3 with 1 exon deleted; 1 with 2 exons, 1 with 5 exons, 1 with 6 exons, and 1 patient with a complete IKZF1 deletion. This study was descriptive in nature; we calculated the frequency of the IKZF1 gene deletion in a Mexican pediatric population with preB ALL as 20.6%.

PURPOSE: The incidence of pneumonitis reported in previous trials in patients with advanced cancer and use of programmed cell death protein 1 (PD-1) immunotherapy inhibitors was 2.7-3.6%. However, none of these trials included Mexican populations.
METHODS: This was a retrospective analysis involving 87 patients with advanced cancer who received PD-1 inhibitors as part of their therapy. The primary outcome was the incidence of pneumonitis after using PD-1 inhibitors. The secondary outcomes were major risk factors and radiological patterns of pneumonitis.
RESULTS: We found 13 cases of pneumonitis, giving an overall incidence of 15%; three of the cases were high-grade (grade 3). A ground-glass pattern was the major form found by chest computed tomography scans. We did not find any significant risk factor for pneumonitis.
CONCLUSION: The incidence of pneumonitis secondary to treatment with PD-1 inhibitors in our Mexican population was 15%, which is 5 times higher than that found in other studies. No risk factor was identified for this increased incidence of drug-induced pneumonitis following the use of PD-1 inhibitors.

BACKGROUND: Although acute lymphoblastic leukemia (ALL) 5 years survival in minors has reached 90%, socioeconomic differences have been reported among and within countries. Within countries, the difference has been related to the socioeconomic status of the parents, even in the context of public health services with universal coverage. In Mexico, differences in the mortality of children with cancer have been reported among sociodemographic zones. The Instituto Mexicano del Seguro Social (IMSS), the country's main social security institution, has reported socioeconomic differences in life expectancy within its affiliated population. Here, the socioeconomic inequalities in the survival of children (< 15 years old) enrolled in the IMSS were analyzed.
METHODS: Five-year survival data were analyzed in cohorts of patients diagnosed with ALL during the period 2007-2009 in the two IMSS networks of medical services that serve 7 states of the central region of Mexico. A Cox proportional risk model was developed and adjusted for the socioeconomic characteristics of family, community of residence and for the clinical characteristics of the children. The slope of socioeconomic inequality of the probability of dying within five years after the diagnosis of ALL was estimated.
RESULTS: For the 294 patients studied, the 5 years survival rate was 53.7%; the median survival was 4.06 years (4.9 years for standard-risk diagnosis; 2.5 years for high-risk diagnosis). The attrition rate was 12%. The Cox model showed that children who had been IMSS-insured for less than half their lives had more than double the risk of dying than those who had been insured for their entire lives.
CONCLUSIONS: We did not find evidence of socioeconomic inequalities in the survival of children with ALL associated with family income, educational and occupational level of parents. However, we found a relevant gradient related social security protection: the longer children's life insured by social security, the higher their probability of surviving ALL was. These results add evidence of the effectiveness of social security, as a mechanism of wealth redistribution and a promoter of social mobility. Extending these social security benefits to the entire Mexican population could promote better health outcomes.

Multiple myeloma (MM) is characterized by bone pain, pathologic fractures, bone destruction, and secondary hypercalcemia, all these conditions impact on health-related quality of life of patients. The objective was to evaluate the global health state and health-related quality of life in a group of patients with MM who attended a tertiary health-care center of the Instituto Mexicano del Seguro Social in Mexico, through the questionnaires designed by European Organization for Research and Treatment of Cancer (EORTC) quality of life group. Exploratory cross-sectional study in patients with MM treated in a Department of Hematology in a High-Specialty Medical Unit was conducted. Patients older than 18 years of age, men and women, were selected, and their informed written consent was obtained. We included all consecutive cases treated from January 2012 to December 2014. Questionnaires EORTC QLQ-C30, EORTC QLQ-MY20, and EORTC IN-PATSAT-32 were used. We studied 37 patients, 19 (51%) men and 18 women. The mean age was 61.9 years. Twenty-two (59.46%) patients presented with clinical stage III. The mean time for diagnosis was 33.11 months. The most used first-line treatment schedule was melphalan/prednisone/thalidomide (15; 40%). The global health median was 66.67, and symptoms showed a median score of 22.22. Treatment side effects score was 16.67; for general satisfaction, the median score was 75. In conclusion, the patients showed an advanced clinical stage and poor prognosis but had scores higher than 50 in functional scales and lower than 50 for symptom scales. The scores for symptom scales were related to age, renal failure, and disease-free survival. Identification of quality of life and satisfaction of care markers allow for early therapeutic intervention and efficiency and enable a change in quality of life and perception of care in Health Services.

PURPOSE: US Hispanics are more likely to be diagnosed with advanced cancer as parents than their non-Hispanic white counterparts but little is known about Hispanic parents' willingness to discuss a terminal cancer diagnosis with dependent children, potentially resulting in suboptimal child coping. Therefore, we investigated Hispanic mothers' willingness to communicate with dependent children about her actual or hypothetical advanced cancer diagnosis.
METHODS: Two focus groups (n = 6 participants) and three one-on-one interviews (n = 3) were conducted in either Spanish or English among adult, Mexican-American mothers with a current cancer diagnosis of any stage residing in US-Mexico border communities. Participants reported their perceived concerns, parenting challenges, and openness to discussing an incurable cancer diagnosis with a dependent child. Audio files were transcribed into English and qualitatively coded using content analysis.
RESULTS: Participants, most with breast cancer, ranged in age from 25 to 47. Five had considered the possibility of their own death from advanced cancer and three had previously discussed this with their children. While many expected their children would carry on well without them, seven expressed concern for the emotional/spiritual well-being of their children. Mothers anticipated physical and time-based parenting challenges but wanted the opportunity to focus on themselves and their children in advance of death. All but one would be willing to discuss an advance cancer diagnosis with dependent children; four expressed the value of doing so or the potential harm of abdicating this responsibility.
CONCLUSIONS: If faced with an advanced cancer diagnosis, Mexican-American mothers are open to communicating with dependent children.

BACKGROUND: Heterozygous germline TP53 gene mutations result in Li-Fraumeni Syndrome (LFS). Breast cancer (BC) is the most frequent tumor in young women with LFS. An important issue related to BC in the Mexican population is the average age at diagnosis, which is approximately 11 years younger than that of patients in the United States (U.S.) and Europe. The aim of this study was to determine the prevalence of germline mutations in TP53 among young Mexican BC patients.
METHODS: We searched for germline mutations in the TP53 gene using targeted next-generation sequencing (NGS) in 78 BC patients younger than 45 years old (yo) who tested negative for BRCA1/2 mutations. A group of 509 Mexican women aged 45yo or older without personal or family BC history (parents/grandparents) was used as a control.
RESULTS: We identified five patients with pathogenic variants in the TP53 gene, equivalent to 6.4% (5/78). Among patients diagnosed at age 36 or younger, 9.4% (5/55) had pathogenic TP53 mutations. Three of these variants were missense mutations (c.844C > T, c.517G > A, and c.604C > T), and the other two mutations were frameshifts (c.291delC and c.273dupC) and had not been reported previously. We also identified a variant of uncertain clinical significance (VUS), c.672G > A, which causes a putative splice donor site mutation. All patients with TP53 mutations had high-grade and HER2-positive tumors. None of the 509 patients in the healthy control group had mutations in TP53.
CONCLUSIONS: Among Mexican BC patients diagnosed at a young age, we identified a high proportion with germline mutations in the TP53 gene. All patients with the TP53 mutations had a family history suggestive of LFS. To establish the clinical significance of the VUS found, additional studies are needed. Pathogenic variants of TP53 may explain a substantial fraction of BC in young women in the Mexican population. Importantly, none of these mutations or other pathological variants in TP53 were found in the healthy control group.

OBJECTIVE: To describe the methods of a study aimed at evaluating high risk-HPV (hrHPV)-based screening and cervical cytology as triage compared to conventional cervical cytology as primary screening in the detection of grade 2+ cervical intraepithelial neoplasia in the National Cancer Screening Program (NCSP) of Mexico.
MATERIALS AND METHODS: We will use information originated from the Womens Cancer Information System of Mexico regarding cervical cancer from 2008 to 2018. The database includes cytology results, diagnostic confirmation by histopathology and/or treatment colposcopy. We will then carry out statistical analyses on approximately 15 million hrHPV.
RESULTS: We will evaluate the overall performance of hrHPV-based screening as part of the NCSP and compare hrHPV-based to cytology-based screening under real-life conditions. To guarantee an unbiased comparison between hrHPV with cytology triage and conventional cytology we will use propensity score matching.
CONCLUSIONS: ytology we will use propensity score matching. Conclusion. Decision makers may use our results to identify areas of opportunity for improvement in NCSP processe.

OBJECTIVE: To evaluate the effectiveness of a combined strategy of human papillomavirus virus (HPV) vaccination and high-risk HPV screening to reduce the occurrence of anogenital and oropharyngeal neoplasms among men who have sex with men, people with HIV, homeless people, transgender women, female sex workers and rape victims.
MATERIALS AND METHODS: This mixed methods study evaluates the effectiveness of a combined vaccination-screening strategy to reduce HPV prevalence/incidence and occurrence of cervical intraepithelial neoplasms grade 2+ and/or anal intraepithelial neoplasms grade 2+, using Kaplan-Meier. The time-to-event method will evaluate time from positive results for specific anogenital HPV to incidence of anogenital lesions containing that HPV type.
RESULTS: People vaccinated against HPV and screened for HPV as a primary test will have lower prevalence and incidence of HPV infection and consequently lower frequency of HPV-related anogenital and oropharyngeal lesions.
CONCLUSIONS: Thisstudy will generate scientific evidence on effectiveness of a combined vaccination-screening strategy to reduce the burden of HPV-associated neoplasms.

BACKGROUND: Carotid body tumors (CBTs) are rare neoplasms located in the carotid bifurcation. The majority of these tumors are unilateral; bilateral CBTs represent approximately 5% of all affected patients, and the recommended treatment is to surgically remove them in staged-planned surgeries. We describe the experience, outcomes, and the surgical management of bilateral CBTs in our institution.
METHODS: A retrospective review of CBTs patients was completed; patient demographics, comorbidities, lesion location, anatomic characteristics, surgical techniques, complications, reinterventions, and other factors that may influence outcomes were evaluated.
RESULTS: A total of 109 patients with CBTs were treated surgically; of these, 8 had bilateral CBTs (7%); the mean age was 56 years, and 7 (87%) were females. Thirteen surgical resections were performed, and in 2 of the cases, the pathology report was malignant (15%). Five were classified as Shamblin I (31%), 5 as Shamblin II (31%), and remaining 6 as Shamblin III (38%). The mean time between the first and second procedure was of 10.7 months. Complications included one case of neck hematoma requiring evacuation and postoperative neurologic complications occurred in three patients (one patient with facial and two with vocal cord palsies). None of the studied individuals had a family history of CBT, and all of them lived in altitude areas higher than 2000 meters above mean sea level (mamsl). The mean tumor size was 3.55 cm and 2.75 cm for right and left CBTs, respectively.
CONCLUSIONS: A better understanding of the clinical characteristics of patients with bilateral CBTs may lead to a more standardized and optimal management with fewer complications and a better quality of life afterward.

The chronic inflammation and damage to the gastric epithelium induced by Helicobacter pylori (H. pylori) are the main risk factors for gastric cancer development. Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) induce chronic inflammation and have been found in gastric tumors. The objectives this observational study were to determine the frequency of multiple infections by Helicobacter pylori, Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) and to relate the infection by EBV and HCMV with H. pylori vacA/cagA genotypes in patients with chronic gastritis or gastric cancer. DNA from H. pylori, EBV and HCMV was detected by PCR in biopsies from 106 Mexican patients with chronic gastritis and 32 from gastric cancer. The cagA status and the vacA genotypes of H. pylori were determined by PCR. In chronic gastritis and gastric cancer EBV was found in 69.8% and 87.5%, HCMV in 52.8% and 53.1%, and H. pylori in 48.1% and 40.6%, respectively. In chronic gastritis, 53% of H. pylori patients were EBV and 33% were both EBV/HCMV; in gastric cancer, 92.3% of H. pylori-infected individuals were EBV and 46.1% were EVB/HCMV. All the intestinal- and mixed-type tumors and the 83.3% of diffuse-type tumors were EBV. No significant differences were found between single infections or coinfections with the diagnosis or the cancer type. The H. pylori genotypes were not related to EBV or HCMV infection. The frequency of dual infections by H. pylori, EBV and HCMV is higher in patients from southwest Mexico than other populations. It is likely that these pathogens act synergistically to induce inflammation and gastric cancer.

BACKGROUND: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation. The aim was to analyze CDH1 somatic alterations in Mexican patients with diffuse and mixed gastric cancer.
METHODS: We searched for mutations in the CDH1 gene in tumor DNA from DGC (n = 13) and MGC (n = 7) patients by next generation sequencing (NGS). Validation of findings was performed using Sanger sequencing. LOH was analyzed using dinucleotide repeat markers surrounding the CDH1 gene, and methylation was investigated by DNA bisulfite conversion and sequencing. E-cadherin protein deficiency was analyzed by immunohistochemistry.
RESULTS: Seventeen point variants were identified by NGS, 13 of them were validated by Sanger sequencing. Only 1/13 had not been previously reported (c.-137C > A), and 12/13 were already reported as polymorphisms. Two DGC cases presented LOH at the locus 16q22.1 (13.3%). CDH1 promoter methylation was positive in (7/11) 63.6% and (4/6) 66.6% of the cases with DGC and MGC, respectively. E-cadherin protein deficiency was observed in 58.3% of DGC cases while 100% in MGC cases.
CONCLUSIONS: While no pathogenic somatic mutations were found that could explain the diffuse histology of gastric cancer in DGC and MGC, methylation was the most common somatic inactivation event of the CDH1 gene, and LOH was rare. The previously unreported c.-137C > A variant modify the CDH1 gene expression since it alters the binding sites for transcription factors.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

Background: In colorectal cancer (CRC), regional lymphadenectomy provides prognostic information and guides management. The current consensus states that at least 12 lymph nodes (LN) should be evaluated. The aims of this study were to identify whether the number of LN is a predictor for survival and recurrence, and to reveal the role of LN ratio (LNR) and perineural invasion (PNI) in predicting prognosis after curative resection of CRC.
Methods: We included all patients who underwent surgery for CRC between 2000 and 2016 in an academic medical center in Mexico. The LNR cutoff value was 0.25. We analyzed two groups according to the number of LN retrieved: Group 1 (≥ 12 LN) and Group 2 (< 12 LN).
Results: We included 305 patients, 13.8% in Stage I, 45.6% in Stage II, and 40.6% in Stage III. The male: female ratio was 1.1. The mean age was 62.6 ± 14 years (range, 19-92). In 233 patients (76.4%), ≥ 12 LN were obtained. Recurrence rates in Groups 1 and 2 were 20.2% versus 26.4%, respectively (p = 0.16). PNI was present in 34 patients (13.2%). An LN harvest < 10 increased local and distant recurrences (p = 0.03). Stage III patients with an LNR ≥ 0.25 had higher overall recurrence rates (p = 0.012) and mortality (p = 0.029). In a multivariate Cox regression analysis, PNI-negative tumors were an independent prognostic factor for disease-free survival (p = 0.011, hazard ratio = 2.78, 95% confidence interval = 1.26-6.16).
Conclusions: An LN retrieval < 10 increased local and distant recurrence rates. LNR was an independent prognostic factor for survival in Stage III tumors. PNI was the only significant independent prognostic factor affecting disease-free survival in our patients.

BACKGROUND: Cervical cancer (CC) is caused by a persistent infection of high-risk human papillomavirus (HR-HPV). While most HPV infections are transient, persistent HPV infections are a significant health problem in Mexico. With an estimated HPV prevalence of 10% among women in reproductive age, approximately 25% of these women present at least a positive result in triage test, which according to previous studies is expected to be confirmed as positive CIN-2/3. The immune system has a key role in the natural history of HPV infection; alterations in the cellular immune response are responsible for the failure to eliminate HPV. The objective of this project is to assess the prognostic value of detecting immune markers (IL-10, IL-4, TGFβ1, IFNγ, IL-6, and TNFα), the expression of HPV-HR E6/E7 proteins, and the viral load at the cervical level with respect to the persistence or clearance of HR-HPV infection, and the regression or progression of a cervical premalignant lesion.
METHODS: A dynamic cohort study is being conducted in women with colposcopic, cytological, and histopathological results negative for squamous intraepithelial lesion (SIL) in the cervix and a positive HPV test; the subjects will be followed-up for 5 years, period from which 3 years have already elapsed, with yearly studies (colposcopy, cytology, and histopathology diagnosis, along with molecular HPV test, quantification of viral load and of IL-10, IL-4, TGFβ1, INFγ, IL-6, and TNFα levels, along with the expression of the HR-HPV E6/E7 proteins in the cervix as a viral marker. The outcome will be categorized as viral persistence or clearance; and as SIL persistence, progression, or regression. Binomial and/or multinomial regression models adjusted for potential confounders will be used, associating the relative risk of the outcome with the immune and viral markers evaluated.
DISCUSSION: This research will generate knowledge about immune markers with predictive value for the persistence and clearance of HPV, which will improve the triage of positive HPV women and thus reduce the economic burden for the Mexican health system imposed by the management of high-grade SIL and CC cases, which are still detected in late stages.

Background & objectives: Human papillomavirus (HPV) infections play a crucial role in the aetiology of cervical cancer (CC), and HPV16 is the primary viral genotype associated with CC. A number of variants of the HPV16 E6 gene are involved in the progression of CC, differing in their prevalence and biological and biochemical properties. This study was designed to determine the frequency of HPV types 16/18 and to identify the presence of HPV16 E6-variants in asymptomatic Mexican women.
Methods: A total of 189 cervical Pap smears were collected from women attending public health services in three different cities in Sinaloa, Mexico. Viral DNA was identified by amplification of E6 viral gene fragments using polymerase chain reaction (PCR). Identification of variants was done by sequencing a DNA fragment (321bp) of the HPV16 E6 gene.
Results: More than half of the women tested were HPV-positive (52.38%), with HPV16 being the most frequent genotype (21.16%), followed by HPV18 (8.99%). Sequence analysis of the E6-HPV16 PCR products showed that in all cases, the viruses corresponded to European variants. It was further observed that the E350G intra-variant was the most common (>76%).
Interpretation & conclusions: This study showed a predominance of European lineage variants of HPV16 among asymptomatic women from Sinaloa, Mexico, predominantly with of the E350G variant. This variant has been shown to be associated with an increased risk of early development of CC. The use of molecular identification of carcinogenic HPV and Pap test screening may be a good strategy for monitoring women to prevent CC.

Uterine sarcomas are infrequent and heterogeneous mesenchymal tumours, associated with aggressive characteristics and a poor clinical outcome. The aim of the study is to describe the prognostic factors associated with uterine sarcomas. The clinical records between 2000 and 2014 of women diagnosed with uterine sarcomas and initially treated surgically were reviewed. A histological comparison was performed. The overall survival (OS) and disease-free survival (DFS) were calculated and compared. Seventy-three women had surgery (12.3% had endometrial stromal sarcomas, 24.7% undifferentiated endometrial sarcomas, 49.3% leiomyosarcomas and 13.7% other subtypes). Complete cytoreduction had a mean DFS of 25.1 months, while the incomplete cytoreduction averaged in a DFS of 4.33 months (p = .04). The median five-year OS with a complete cytoreduction was not reached; the incomplete cytoreduction OS was 10.1 months (p = .002). Our data suggests that undifferentiated endometrial sarcomas have the lowest DFS (p = .004); while OS was negatively influence by stage IV (p < .001). Impact statement What is already known about this subject? Uterine sarcomas compared with the more common endometrial carcinomas (epithelial neoplasms), behave aggressively and are associated with a poorer prognosis. The rarity of uterine sarcoma has made it difficult to perform large studies to identify risk factors. What do the results of this study add? Complete cytoreduction improves the DFS and OS and may be a valuable prognostic factor. Poorer DFS and OS prognosis was observed in undifferentiated endometrial sarcomas. What are the implications of these findings for clinical practice and/or further research? Our results demonstrate the importance of an early diagnosis, and thus an early identification of disease that benefits from complete cytoreduction regardless of histology. For the advanced clinical stage of uterine sarcomas further research is necessary and participation in clinical trials should be encouraged.

Childhood Lymphoblastic leukemia's (ALL) early mortality (EM) is an undesirable treatment outcome for a disease for which >90% long term success is achievable. In the Western world EM constitutes no >3%; yet, in Chiapas, Mexico, remains around 15%. With the objective of improving on EM, we determined associated elements in 28 ALL who died within 60 days of arriving at Hospital de Especialidades Pediátricas in Chiapas (HEP), by comparing them to those in 84 controls who lived beyond the first 90 days. χ, t test, and binary logistic regression (BLR) were used to determine significant individual and multiple variables associated to outcome. On arrival, fever, liver and spleen enlargement, active bleeding, lower albumin, less platelets, higher creatinine, and uric acid, more diploid and less hyperdiploid cases were associated with EM cases. Time to diagnosis, nutritional status, risk group and leukocyte count were not related. Antileukemic treatment approach was similar in both groups. The BLR model including fever, active bleeding, liver enlargement, <10,000 platelets/µL, and >2X upper normal lactic dehydrogenase, determined outcome in 66.7% EM and 90.2% controls. To improve on EM in ALL, patients with characteristics defined here ought to be treated differently at HEP.

The National Cancer Institute's (NCI) Radiation Research Program (RRP) is endeavoring to increase the relevance of preclinical research to improve outcomes of radiation therapy for cancer patients. These efforts include conducting symposia, workshops and educational sessions at annual meetings of professional societies, including the American Association of Physicists in Medicine, American Society of Radiation Oncology, Radiation Research Society (RRS), Radiosurgery Society, Society of Nuclear Medicine and Molecular Imaging, Society for Immunotherapy of Cancer and the American Association of Immunology. A symposium entitled "Radiation-Drug Combinations to Improve Clinical Outcomes and Reduce Normal Tissue Toxicities" was conducted by the NCI's RRP during the 63rd Annual Meeting of the RRS on October 16, 2017 in Cancun, Mexico. In this symposium, discussions were held to address the challenges in developing radiation-drug combinations, optimal approaches with scientific evidence to replace standard-of-care, approaches to reduce normal tissue toxicities and enhance post-treatment quality-of-life and recent advances in antibody-drug conjugates. The symposium included two broad overview talks followed by two talks illustrating examples of radiation-drug combinations under development. The overview talks identified the essential preclinical infrastructure necessary to accelerate progress in the development of evidence and important challenges in the translation of drug combinations to the clinic from the laboratory. Also addressed, in the example talks (in light of the suggested guidelines and identified challenges), were the development and translation of novel antibody drug conjugates as well as repurposing of drugs to improve efficacy and reduce normal tissue toxicities. Participation among a cross section of clinicians, scientists and scholars-in-training alike who work in this focused area highlighted the importance of continued discussions to identify and address complex challenges in this emerging area in radiation oncology.

BACKGROUND: Organizations that issue guidance on breast cancer recommend the use of immunohistochemistry (IHC) for providing appropriate and precise care. However, little focus has been directed to the identification of maximum allowable turnaround times for IHC, which is necessary given the diversity of hospital settings in the world. Much less effort has been committed to the development of digital tools that allow hospital administrators to monitor service utilization histories of their patients.
METHODS: In this retrospective cohort study, we reviewed electronic and paper medical records of all suspected breast cancer patients treated at one secondary-care hospital of the Mexican Institute of Social Security (IMSS), located in western Mexico. We then followed three years of medical history of those patients with IHC testing.
RESULTS: In 2014, there were 402 breast cancer patients, of which 30 (7.4% of total) were tested for some IHC biomarker (ER, PR, HER2). The subtyping allowed doctors to adjust (56.7%) or confirm (43.3%) the initial therapeutic regimen. The average turnaround time was 56 days. Opportune IHC testing was found to be beneficial when it was available before or during the first rounds of chemotherapy.
CONCLUSIONS: The use of data mining tools applied to health record data revealed that there is an association between timely immunohistochemistry and improved outcomes in breast cancer patients. Based on this finding, inclusion of turnaround time in clinical guidelines is recommended. As much of the health data in the country becomes digitized, our visualization tools allow a digital dashboard of the hospital service utilization histories.

La mortalidad por cáncer en niños mexicanos no ha disminuido a los niveles informados en países desarrollados. Una explicación frecuentemente declarada es el alto porcentaje (57.3 %) de pacientes diagnosticados en estadios avanzados (III/IV), atribuible a errores en la sospecha o en la metodología empleada, consideración dudosa si se toma en cuenta que el tiempo de diagnóstico y la proporción de estadios avanzados en México son semejantes a los de países desarrollados. En la mayoría de los niños con cáncer, los días transcurridos desde el primer síntoma a momento del diagnóstico oncológico no correlacionan con el estadio clínico y tampoco con la probabilidad de supervivencia. El éxito en la supervivencia depende en gran medida del tratamiento integral (específico y de la atención a las complicaciones). Esta visión obliga a estrategias dirigidas principalmente a invertir más recursos en opciones terapéuticas eficaces y eficientes, capacitación oncológica integral del equipo de salud (médicos, enfermeras, técnicos), tecnologías diagnósticas, fomento a la colaboración interinstitucional e internacional y apoyo socioeconómico a las familias durante el proceso terapéutico.
Cancer mortality in Mexican children has not decreased to the levels reported in developed countries. A commonly proposed explanation is the high percentage (53.7%) of patients diagnosed at advanced stages (III/IV), which is attributed to erroneous assumptions or mistakes in the diagnostic approach –a questionable consideration taking into account that both time to diagnosis and the proportion of advanced stage cases in Mexico are similar to those in developed countries. In most cancer cases in children, the number of days elapsed from the moment of the first symptom to the cancer diagnosis is not correlated with clinical stage, and neither with the probability of survival. Survival success largely depends on comprehensive treatment (specific and for the care of complications). This view calls for strategies mainly aimed at spending more resources on efficacious and efficient therapeutic strategies, comprehensive oncology training of healthcare personnel (physicians, nurses and technicians), diagnostic technologies, promotion of interinstitutional and international collaboration and socioeconomic support to families during the therapeutic process.

INTRODUCTION:: Acral lentiginous melanoma (ALM) is an aggressive variant of melanoma; the incidence, prevalence, and prognosis differ among populations. We analyzed clinicopathological features and survival in Hispanics, a population with high ALM prevalence.
MATERIAL AND METHODS:: From 1144 patients with melanoma, we analyzed 715 ALMs and 429 non-ALMs from the National Referral Cancer Centre and compared survival.
RESULTS:: Of the ALM group, 62.8% were female; the median age was 58 years. The mean Breslow thickness was 3.56 ± 7.16 mm. ALM patients showed an estimated 5-year disease-specific survival (DSS) of 53.3%, 52.7%, and 40.8% for stage I, II, and III, respectively. For non-ALM patients, the DSS rates were 66%, 60.8%, and 48.4% for stage I, II, and III disease, respectively. Overall, the 1-, 3-, and 5-year DSS rates for patients with ALM were 85.1%, 59.4%, and 46.3%, respectively; for non-ALM patients, they were 81.3%, 64.8%, and 55.7%, respectively ( P = .168). In the multivariate analysis, factors associated with decreased DSS were high Breslow thickness, recurrence, ulceration, male sex, and advanced stage.
CONCLUSIONS:: The 1-, 3-, and 5-year DSS rates of patients with ALM were not statistically different from those of non-ALM patients. In addition to known adverse prognostic factors, male sex was also associated with worse survival.

PURPOSE: To review incidence, treatment and outcome of pediatric pituitary adenomas (PAs).
METHODS: A follow-up study patients with the age of ≤19 years old who were treated from 1995 to 2015 in Mexico.
RESULTS: Out of 1244 diagnosed PA, 43 patients were children (35 females, 8 males) with a mean age of 17.2 years. The majority were macroadenomas (70%) with prolactinomas (PRL) dominating (63%) followed by non-functioning adenomas (21%). In total, 40% were diagnosed as invasive. Growth hormone (GH) secreting adenomas, adrenocorticotropic hormone secreting and mixed GH-PRL secreting were rare. The treatment modalities were dopamine agonists and surgery. The average treatment time was 44 months with an average follow-up period of 104 months. Sixty-eight percent (27/40) of the patients had complete response after long time follow-up. Thirty-one percent did not respond to treatment whereof three patients died due to advanced disease and late intervention. The principal causes for treatment failure were treatment resistance, late intervention and poor patient compliance.
CONCLUSIONS: Sixty eight percent had complete treatment response without any sign of disease, while ~31% did not respond to treatment or did not comply to follow up/treatment. Optimized early diagnose, treatment methods with early intervention, long time follow-up and with better measures for patient compliance should improve outcomes.

BACKGROUND: The incidence of basal cell carcinoma (BCC) in younger individuals has increased in recent decades. However, the characteristics of BCCs in this population, especially in Ibero-Latin American countries, have not been completely defined.
OBJECTIVE: To describe the demographic, clinical, and histopathological characteristics of BCCs in patients younger than 40 treated with Mohs Micrographic Surgery (MMS).
MATERIALS AND METHODS: A multicenter, retrospective study conducted between January 2009 and December 2014, in five Ibero-American countries, included biopsy-proven BCCs in patients younger than 40 that were treated with MMS. Demographic, clinical, histopathological, and surgical characteristics were described.
RESULTS: The study included 301 tumors in 241 patients, of whom 61% were female. The most common Fitzpatrick phototype was III. The most common histological subtypes were nodular (37.5%) and infiltrative (18.9%). Perineural invasion was encountered in 1.7%, and tumor clearance was achieved in 87.4% within two stages of MMS.
CONCLUSIONS: This is the first Ibero-Latin American transnational study describing the characteristics of BCCs in young patients treated with MMS. Despite darker skin phototypes in this population, BCCs can occur in early ages and may present with aggressive features. Therefore, MMS may be considered an appropriate first-line treatment option in this population.

BACKGROUND: Pigmented lesions on acral sites are common; clinical differentiation of nevi and early melanoma can be challenging. In these cases, dermoscopy can provide a more accurate diagnosis. Most dermoscopic patterns on acral skin have been described in Asian and European populations, while there are few studies in Latin American populations.
OBJECTIVES: To determine the frequency of pigmented lesions in volar skin and their dermoscopic patterns in a Mexican population. Methods: An observational, descriptive, cross-sectional study was performed in Hispanic patients with the presence of at least one pigmented lesion on acral skin. Clinical and dermoscopic images were obtained. These were subsequently evaluated independently by two dermatologists trained and experienced in dermoscopy.
RESULTS: A total of 582 pigmented lesions on volar skin were diagnosed in 321 patients. Overall, prevalence of acral pigmented lesions on volar skin was 6.8%. For both observers, parallel furrows were the most frequent pattern described, but for observer 2, a lattice-like pattern was prevalent on the toes and a homogeneous pattern on the sides of the feet. There was lower inter-observer agreement, with a kappa index of 0.144.
STUDY LIMITATIONS: The lesions were not biopsied, so clinical-histological correlation could not be performed. The study did not correlate dermoscopic patterns with age.
CONCLUSIONS.: As previously reported by other authors, parallel furrows were the most frequently found dermoscopic pattern on palmoplantar skin.

OBJECTIVE: Mature B-cell non-Hodgkin lymphoma (B-NHL) comprises more than 50% of all non-Hodgkin lymphoma (NHL) in children and adolescents. An official report published by the Mexican National Center for the Control and Prevention of Cancer in the Pediatric and Adolescent Populations, reported a lymphoma OS of 71% (including all Hodgkin and NHL). The Mexican Association of Pediatric Oncology and Hematology conducted a retrospective study to analyze the clinical characteristics and outcomes of children with diagnosis of B-NHL in Mexico, in order to perceive the main areas of improvement in the health care.
METHODS: From 1 January 2000 to 31 December 2016, 166 pediatric patients were diagnosed with B-cell NHL at the participant institutions.
RESULTS: According to histology the outcomes were 5-year EFS 63%, for BL/BLL, and 80% DLBCL, (P = .051), 5-year PFS 81%, for BL/BLL, and 91% for DLBCL, (P = .126), and 5-year OS 71%, for BL/BLL, and 83% for DLBCL, (P = .095).
DISCUSSION: Overall, 18 patients died due to acute treatment toxicity, resulting in a cumulative incidence of toxic death of 10.84% and an early death rate of 7.23%, defined as <30 days after initial treatment. In conclusion, there is an urgent need to establish an academic collaboration to create strategies to improve pediatric cancer care according to our resources, especially in diseases with expected excellent prognosis as B-NHL. These strategies must include comprehensive supportive care, early referral, and the creation of easy communication between pediatric and adults centers as well as late-effects clinics.

BACKGROUND: Thyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women.
METHODS: To assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models.
RESULTS: Higher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR)
CONCLUSIONS: There is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.

Background: Central nervous system (CNS) tumors are a group of neoplasms that originate from various cells in the CNS. The increasing incidence and prevalence of this type of tumor in developing countries are striking; however, there are few current studies in Latin America including Mexico estimating the impact of these pathological entities on the general population.
Objective: The objective of the study was to study the characteristics of primary CNS tumors over a period of 52 years.
Methods: A review of records from patients with a histopathological diagnosis of CNS neoplasm over a period of 52 years was conducted at a tertiary-care academic medical center. Patients were grouped by sex, age, and the tumor's anatomical location.
Results: A sample of 9615 patients with tumor lesions was obtained; 51% were female, 49% were male, and their mean age was 42 years. The tumors with the highest prevalence were neuroepithelial tumors (38.6%), followed by meningeal tumors (22.8%). Neuroepithelial tumors accounted for 64% in the group of patients under 40 years of age and 56% among those above 40 years of age. The most frequently involved location was supratentorial, in 78.9% of cases.
Conclusions: Although retrospective in nature and based on a small sample, this study reports the epidemiology and characteristics of primary brain tumors in the Mexican population.

AIM: To describe delay intervals, their impact on clinical stage and initiation of first oncologic treatment, and evaluate associated factors in breast cancer patients in Yucatan, Mexico, a low-density population region.
PATIENTS & METHODS: A retrospective analysis was done of 92 medical records, and bivariate and multivariate models applied to identify associations between healthcare delay and several factors.
RESULTS: System delay accounted for most of the delay (median: 86 days; 61% of delay). Socioeconomic status and delivery to tertiary-care hospital predicted delay. Clinical stage determined initiation of first oncologic treatment.
CONCLUSION: Delay in treatment was largely due to system delay. Only a few variables explained this delay. Clinical stage had the strongest effect on initiation of first oncologic treatment.

Introducción: La terapia sistémica para el cáncer de mama afecta la calidad de vida de las mujeres y sus familias. Se analizó la influencia de los factores personales sobre la percepción de calidad de vida de mujeres en tratamiento para el cáncer mamario. Métodos: Participaron noventa y cinco asistentes a la consulta de un hospital público del noreste de México. Se aplicaron dos Cuestionarios de la Organización Europea para la Investigación y Tratamiento del Cáncer (EORTC QLQ-C30 y EORTC QLQ-BR23). Resultados: La edad promedio fue de 55 años ( DE = 9.24). Las participantes destacaron por presentar valores altos para el estado de salud global y niveles bajos en funcionamiento ( rango = 11.71 a 18.42). El insomnio y el impacto económico fueron las áreas más afectadas. Con el incremento de la edad, se observó menor afectación por síntomas mamarios, función y el disfrute sexual ( r = -.273, -.349 y -.304 respectivamente, p < .01). Conclusión: La situación laboral, estado civil, paridad y lugar de procedencia promovieron afectación diferencial en algunos síntomas incluyendo la imagen corporal. La aplicación de estos cuestionarios permitiría la identificación de necesidades de cuidado físico u emocional en la práctica clínica.