Medication-related osteonecrosis of the jaw in cancer patients: Case series and review of the current literature.

Currently, a large proportion of cancer patients are treated with bone modifying agents (BMA). In this regard, the increase in the prescription of these drugs has lead to concerns in the increment of osteonecrosis of the jaws. This article describes four patients with BMA cancer treatments requested dental evaluation at our institution due to pain and swelling of the mandibular bone after tooth extraction, tooth loss, or unknown risk factor. Oral and radiographic evaluation reveals Medication-related osteonecrosis of the jaw (MRONJ) at different clinical stages according to the American Association of Oral and Maxillofacial Surgeons (AAOMS) classification. Some patients underwent abscess drainage, oral cleaning and antibiotic therapy with complete recovery. Follow-up showed treatment success in all patients. That is why we emphasize the importance of early establishment of appropriate treatment and emphasize the avoidance of dental procedures during BMA therapy.

En la actualidad, una gran cantidad de pacientes con cáncer son tratados con agentes modificadores óseos (AMO). En relación con esto, el aumento en la prescripción de estos fármacos ha generado preocupación por el incremento en la osteonecrosis de los maxilares. Este artículo describe cuatro casos de pacientes con cáncer, tratados con AMO, que acuden a nuestra institución debido a que padecen dolor e inflamación de la mandíbula, después de la extracción dental, así como pérdida de dientes con un factor de riesgo desconocido. La evaluación clínica y radiográfica evidenció osteonecrosis de los maxilares en diferentes etapas clínicas, según la clasificación de la Asociación Estadounidense de Cirujanos Orales y Maxilofaciales (AAOMS). Algunos de los pacientes fueron sometidos a drenaje de abscesos, limpieza bucal y antibioticoterapia con recuperación completa. El seguimiento clínico fue exitoso en todos los pacientes. Es por eso que hacemos énfasis en la importancia de establecer un tratamiento apropiado y evitar procedimientos dentales durante la terapia con AMO.

Physicians' Attitudes, Knowledge, and Perceived Barriers toward Fertility Preservation in Young Breast Cancer Patients in a Developing Country.

BACKGROUND: In Mexico, up to 15% of breast cancer (BC) patients are 40 years or younger. Therefore, fertility preservation and pregnancy after cancer treatment are major concerns in this population. However, no data are available regarding Mexican physicians' knowledge and attitudes toward these issues. OBJECTIVE: The objective of the study was to describe physicians' attitudes, knowledge, and perceived barriers toward fertility preservation among young women with BC (YWBC) in a developing country. METHODS: A cross-sectional study was conducted among physicians attending the 2016 Mexican Society of Oncology (SMeO) Annual Meeting or affiliated to SMeO. Chi-squared tests were used to assess factors associated with a higher likelihood of disclosing infertility risks, discussing fertility preservation methods, referring to specialists, and effective counseling. RESULTS: Of the 314 participants, 83% reported a high sense of responsibility about informing treatment-related infertility risks, 58% always informed patients about those risks, 38% always discussed fertility preservation procedures, 52% always referred interested patients to fertility specialists, and 24% wrongly considered pregnancy and GnRH analogs detrimental in YWBC. Barriers for discussing fertility preservation were costs, lack of specialists, and prognosis. CONCLUSIONS: It is crucial to promote physicians' knowledge and to endorse policies to overcome barriers obstructing universal access to fertility preservation for YWBC in Mexico.

Impact of chemotherapy regimen and sequence on the effectiveness of scalp cooling for alopecia prevention.

PURPOSE: Scalp cooling (SC) is the most reliable method for the prevention of chemotherapy-induced alopecia. However, it remains unclear if its effectiveness is related to the chemotherapy regimen, sequence, and frequency. This study aims to evaluate SC performance among breast cancer patients who received different chemotherapy regimens. METHODS: The medical records of all consecutive patients undergoing curative-intent chemotherapy and receiving at least one SC session using the DigniCap® System from 2016-2020 in a private Mexican hospital were retrospectively reviewed. SC effectiveness according to chemotherapy regimen was analyzed using descriptive statistics. Successful alopecia prevention was defined as grade 0-1 alopecia (< 50% hair loss not requiring the use of a wig or headpiece) according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: SC adequately prevented alopecia in 56/76 (74%) patients. All 12/12 (100%) and 15/17 (88%) patients receiving paclitaxel-only and docetaxel-based chemotherapy, respectively, had effective hair preservation. SC was successful in 7/16 (44%) patients when sequential chemotherapy started with anthracyclines and 22/30 (73%) when paclitaxel was administered upfront. Considering dose-dense regimens, 9/15 (60%) had satisfactory hair retention, and chemotherapy sequence was not clearly related to SC success. CONCLUSION: SC was highly effective in preventing alopecia, particularly with taxane-based regimens. Notably, better outcomes were observed when sequential chemotherapy started with taxanes followed by anthracyclines than when the inverse order was administered, suggesting that the chemotherapy sequence, rather than chemotherapeutic agents per se, might have a more significant impact on the effectiveness of SC for the prevention of alopecia.

Immunotyping of tumor-infiltrating lymphocytes in triple-negative breast cancer and genetic characterization.

Tumor-infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple-negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre-surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller-Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin-eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3+, CD4+ and CD8+. In addition, the gene expression profile of CD3, CD4, CD8, CD20, CD45, forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3+ and CD4+ counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of CD3, CD4, CD8, CD45 and CD20 genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of CD3, CD4, CD8, CD45 and CD20 genes and partial and complete pathological response, compared with the association between high expression and IHC alone.

Successful Implementation of a Quality Improvement Intervention Toward a QOPI-Certified Breast Cancer Center in Mexico.

INTRODUCTION: As part of a quality improvement (QI) project undertaken during the 2018 edition of the American Society of Clinical Oncology's Quality Training Program (QTP), we evaluated our practice's compliance to 70 measures regarding the Core, Symptom/Toxicity and Breast Cancer modules from the Quality Oncology Practice Initiative (QOPI) database. Thirteen measures were identified as being consistently low in documentation rate in our medical records (MR). METHODS: After establishing a multidisciplinary QI team, we defined to accomplish 100% documentation rate of these 13 QOPI measures in ≥ 80% of the monthly new patient MRs during the 6-month QTP. We designed a Microsoft Word MR template and implemented a new pre-consultation process. Monthly Plan-Do-Study-Act cycles were conducted to assess the performance of the intervention. RESULTS: After the 6-month QI intervention, > 80% of our monthly MRs achieved 100% compliance to the aimed-for 13 QOPI measures. Furthermore, our new pre-consultation process proved to be valuable in facilitating the documentation of data without interfering with the oncology appointment. CONCLUSION: The development of a systematic QI approach effectively enhanced our compliance to 13 QOPI measures over a 6-month period. These results led to the standardization of the current model of care at our institution. To our knowledge, Hospital Zambrano Hellion's Breast Cancer Center is the first Mexican cancer center to pursue a QOPI certified practice.

Change in therapeutic management after the EndoPredict assay in a prospective decision impact study of Mexican premenopausal breast cancer patients.

OBJECTIVE: To evaluate the change in adjuvant therapeutic decision in a cohort of young women with breast cancer discussed by a multidisciplinary team, before and after EndoPredict testing. PATIENTS AND METHODS: 99 premenopausal women with hormone receptor-positive, HER2-negative, T1-T2, and N0-N1 breast cancer were included. Clinicopathological characteristics were recorded and cases were presented in a multidisciplinary tumor board. Consensual therapeutic decisions before and after EndoPredict results were registered. Medical records were reviewed at six-month follow-up to determine physicians' adherence to therapeutic recommendations. Pearson chi-square and McNemar's tests were used to analyze differences between groups and changes in treatment recommendations, respectively. RESULTS: Median age at diagnosis was 43 years. The most frequent tumor size was pT2 (53.5%) and 27% of patients had 1-3 positive lymph nodes. 46% of patients had a low-risk EPclin result. Nodal status and tumor grade were significantly associated with EPclin result (p < .00001 and p = .0110, respectively), while Ki67 levels and age ≤40 years were not. A change in chemotherapy decision was registered in 19.2% of patients (p = .066), with the greatest impact in de-escalation (9% net reduction). A change in chemotherapy or endocrine therapy regimen was suggested in 19% and 20% of cases, respectively, after EPclin results were available. A significant difference was found in the median EPclin score between patients with a low- vs. high-intensity chemotherapy and endocrine therapy regimen recommendation (p = 0.049 and p = 0.0001, respectively). Tumor board treatment recommendation adherence with the EndoPredict result was 95% and final treatment adherence to EPclin result was 93%. CONCLUSIONS: The EndoPredict test successfully assisted the clinical decision-making process in premenopausal patients, with a clinically significant change in overall decision-making, with the greatest impact seen in chemotherapy reduction, and a high rate of therapeutic adherence.

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To DNA Mutations.

Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

"Joven & Fuerte": Program for Young Women with Breast Cancer in Mexico - Initial Results.

Despite the high rates of breast cancer among young Mexican women, their special needs and concerns have not been systematically addressed. To fulfill these unsatisfied demands, we have developed "Joven & Fuerte: Program for Young Women with Breast Cancer in Mexico," the first program dedicated to the care of young breast cancer patients in Latin America, which is taking place at the National Cancer Institute of Mexico and the two medical facilities of the Instituto Tecnológico y de Estudios Superiores de Monterrey. The program was created to optimize the complex clinical and psychosocial care of these patients, enhance education regarding their special needs, and promote targeted research, as well as to replicate this program model in other healthcare centers across Mexico and Latin America. From November 2013 to February 2017, the implementation of the "Joven & Fuerte" program has delivered specialized care to 265 patients, through the systematic identification of their particular needs and the provision of fertility, genetic, and psychological supportive services. Patients and families have engaged in pedagogic activities and workshops and have created a motivated and empowered community. The program developed and adapted the first educational resources in Spanish dedicated for young Mexican patients, as well as material for healthcare providers. As for research, a prospective cohort of young breast cancer patients was established to characterize clinicopathological features and psychosocial effects at baseline and during follow-up, as a guide for the development of specific cultural interventions addressing this vulnerable group. Eventually, it is intended that the program's organization and structure can reach national and international interactions and serve as a platform for other countries.

Tumor suppressor miR-29c regulates radioresistance in lung cancer cells.

Radiotherapy is an important treatment option for non-small cell lung carcinoma patients. Despite the appropriate use of radiotherapy, radioresistance is a biological behavior of cancer cells that limits the efficacy of this treatment. Deregulation of microRNAs contributes to the molecular mechanism underlying resistance to radiotherapy in cancer cells. Although the functional roles of microRNAs have been well described in lung cancer, their functional roles in radioresistance are largely unclear. In this study, we established a non-small cell lung carcinoma Calu-1 radioresistant cell line by continuous exposure to therapeutic doses of ionizing radiation as a model to investigate radioresistance-associated microRNAs. Our data show that 50 microRNAs were differentially expressed in Calu-1 radioresistant cells (16 upregulated and 34 downregulated); furthermore, well-known and novel microRNAs associated with resistance to radiotherapy were identified. Gene ontology and enrichment analysis indicated that modulated microRNAs might regulate signal transduction, cell survival, and apoptosis. Accordingly, Calu-1 radioresistant cells were refractory to radiation by increasing cell survival and reducing the apoptotic response. Among deregulated microRNAs, miR-29c was significantly suppressed. Reestablishment of miR-29c expression in Calu-1 radioresistant cells overcomes the radioresistance through the activation of apoptosis and downregulation of Bcl-2 and Mcl-1 target genes. Analysis of The Cancer Genome Atlas revealed that miR-29c is also suppressed in tumor samples of non-small cell lung carcinoma patients. Notably, we found that low miR-29c levels correlated with shorter relapse-free survival of non-small cell lung carcinoma patients treated with radiotherapy. Together, these results indicate a new role of miR-29c in radioresistance, highlighting their potential as a novel biomarker for outcomes of radiotherapy in lung cancer.

Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the "Hispanic paradox".

OBJECTIVE: Sixteen percent of US population is Hispanic, mostly Mexican. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) with non-small-cell lung cancer (NSCLC), even when most Hispanic patients are diagnosed at advanced disease stages and have lower income status. We analyzed the clinical, pathological, and molecular characteristics as well as outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox". MATERIAL AND METHODS: A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007 to 2014 was analyzed. Their clinical-pathological characteristics, the presence of EGFR and KRAS mutations and the prognosis were evaluated. RESULTS: Patients presented with disease stages II, IIIa, IIIb and IV at rates of 0.6, 4.8, 18.4 and 76.3%, respectively. NSCLC was associated with smoking in only 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 27.0% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.5% (10.3% men vs. 10.1% in women p=0.939). The median OS for all patients was 23.0 [95% CI 19.4-26.2], whereas for patients at stage IV, it was 18.5 months [95% CI 15.2-21.8]. The independent factors associated with the OS were the ECOG, disease stage, EGFR and KRAS mutation status. CONCLUSION: The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs.

Platinum-based chemotherapy in triple-negative advanced breast cancer.

The purpose of this study was to evaluate the efficacy of platinum-based chemotherapy (PBC) versus conventional non-PBC regimens in a metastatic triple-negative breast cancer (TNBC) setting. We reviewed the electronic patient records of patients with confirmed metastatic TNBC at four major cancer centres in Canada. All patients were allocated into two groups based on type of chemotherapy received (PBC vs. non-PBC) and line of treatment (first-, second-, or third-line). The primary objective of this study was to evaluate the efficacy of PBC in metastatic TNBC in terms of median duration of overall survival (OS) from diagnosis of distant metastatic disease and compare it with the efficacy of conventional non-platinum-based chemotherapy in metastatic TNBC after controlling for known prognostic factors. A total of 153 metastatic TNBC patients were identified, 58 treated with PBC and 95 with non-PBC. The median time in first-line PBC versus non-PBC was not different between the two groups (2 vs. 2 months, p = 0.9), the median time on treatment in second and third-line therapy was longer for the PBC group compared to the conventional treated group (4 vs. 1 months, p = 0.004; 4 vs. 0.5 months, p = 0.004, respectively). Patients who received PBC had a longer OS compared to those managed conventionally (14.5 vs. 10 months, p = 0.041). This study evaluates the survival outcomes in a homogenous group of TNBC metastatic patients treated with or without PBC. Our results confirmed our hypothesis of a better OS among PBC-treated TNBC patients compared to conventionally managed TNBC patients. Currently ongoing Phase III trials assessing the benefit of PBC versus other chemotherapeutic regimens in advanced TNBC will help define the role of these agents for the management of this breast cancer subtype.

Retinoic acid reduces solvent-induced neuropathy and promotes neural regeneration in mice.

In humans, exposure to organic solvents (OS) is frequent in work activities or as a recreational inhalant, inducing severe neuropathy (secondary to demyelization of peripheral nerves). We have previously shown that all-trans retinoic acid (ATRA) increases local content of neural growth factor (NGF), improving peripheral neuropathy of diverse origins. In this study, we evaluated the effect of ATRA on OS-induced peripheral neuropathy in experimental mice. Two simultaneous experiments were performed. The first one aimed to evaluate ATRA for the prevention of damage induced by OS, the second to test ATRA as an OS-induced neuropathy treatment. Nociceptive threshold latency and NGF concentration in serum and in peripheral nerves were determined. Morphological changes and evidence of sciatic nerve regeneration were evaluated. Mice exposed to OS developed neuropathy and axonal degeneration. ATRA diminished the effects of OS inhalation on sensorial changes and nerve morphology. Treatment with ATRA reversed sensorial and nerve morphological changes of OS-induced neuropathy, and this was associated with increased contents of NGF. Similar to previous experiences on diabetic and toxic neuropathy, ATRA reduced and partially reversed the peripheral neuropathy caused by OS exposure. These favorable effects apparently are due to local production of NGF induced by neural regeneration in response to the administration of retinoic acid.

Usefulness of serum carcinoembryonic antigen (CEA) in evaluating response to chemotherapy in patients with advanced non small-cell lung cancer: a prospective cohort study.

BACKGROUND: High serum carcinoembryonic antigen (CEA) levels are an independent prognostic factor for recurrence and survival in patients with non-small cell lung cancer (NSCLC). Its role as a predictive marker of treatment response has not been widely characterized. METHODS: 180 patients with advanced NSCLC (stage IIIB or Stage IV), who had an elevated CEA serum level (>10 ng/ml) at baseline and who had no more than one previous chemotherapy regimen, were included. CEA levels were measured after two treatment cycles of platinum based chemotherapy (93%) or a tyrosine kinase inhibitor (7%). We evaluate the change in serum CEA levels and the association with response measured by RECIST criteria. RESULTS: After two chemotherapy cycles, the patients who achieved an objective response (OR, 28.3%) had a reduction of CEA levels of 55.6% (95%CI [box drawings light horizontal]64.3 to [box drawings light horizontal]46.8) compared to its basal level, with an area under the ROC curve (AURC) of 0.945 (95%CI 0.91-0.99), and a sensitivity and specificity of 90.2 and 89.9%, respectively, for a CEA reduction of ≥14%. Patients that achieved a decrease in CEA levels ≥14% presented an overall response in 78% of cases, stable disease in 20.3% and progression in 1.7%, while patients that did not attain a reduction ≥14% had an overall response of 4.1%, stable disease of 63.6% and progression of 32.2% (p < 0.001). Patients with stable (49.4%) and progressive disease (22.2%) had an increase of CEA levels of 9.4% (95%CI 1.5-17.3) and 87.5% (95%CI 60.9-114) from baseline, respectively (p < 0.001). The AURC for progressive disease was 0.911 (95%CI 0.86-0.961), with sensitivity and specificity of 85 and 15%, respectively, for a CEA increase of ≥18%. PFS was longer in patients with a ≥14% reduction in CEA (8.7 vs. 5.1 months, p < 0.001). Neither reduction of CEA nor OR were predictive of OS. CONCLUSIONS: A CEA level reduction is a sensitive and specific marker of OR, as well as a sensitive indicator for progression to chemotherapy in patients with advanced NSCLC who had an elevated CEA at baseline and had received no more than one chemotherapy regimen. A 14% decrease in CEA levels is associated with a better PFS.