Search

Los abejorros sociales del género Bombus son componentes muy importantes de la biodiversidad de México. Son polinizadores de una gran variedad de plantas, muchas de ellas cultivos de gran importancia comercial como los jitomates y los chiles y son componentes fundamentales de los ecosistemas donde habitan. Muchas especies están amenazadas por el crecimiento urbano, el cambio climático y el desarrollo de la agricultura a escala industrial aunque, paradójicamente, algunas especies son indispensables en la agricultura protegida. En este libro se reúne el conocimiento actual sobre las 22 especies nativas de abejorros mexicanos que se reconocen formalmente y sobre una especie introducida, precisamente asociada con la agricultura industrial. Aunque no se puede considerar como una obra definitiva sobre los abejorros mexicanos, es una primera propuesta encaminada a condensar aspectos generales de la biología y la conservación de los abejorros mexicanos, en combinación con un tratamiento taxonómico preciso y detallado, pero accesible a cualquier lector interesado, incluyendo también a los especialistas. Esta obra fue elaborada por un equipo de biólogos conocedores de los abejorros mexicanos y está ricamente ilustrada, con mapas originales de distribución de las especies y con imágenes artísticas magistralmente logradas por dos de los autores. Para todas las especies se presentan ilustraciones científicas por primera vez, lo que hace de este Atlas una obra magnífica y digna de conocer y coleccionar.

Highlights • Breast cancer recurrences deep to pectoralis are very rare after mastectomy. • Post-mastectomy chest wall radiation should exclude deep chest wall structures. • Radiation after immediate implant reconstruction increases complications. • Post-mastectomy radiation should target subcutaneous tissues and pectoralis major., Introduction Most studies report post-mastectomy local recurrences as chest wall recurrences without clarifying whether the recurrence is in the subcutaneous tissue, muscle or underlying rib. Post-mastectomy chest wall radiation is recommended in patients at increased risk of locoregional recurrence. Chest wall radiation-related fibrosis has become an important clinical consideration in the era of immediate implant-based breast reconstruction. In patients with commonly performed subpectoral implant-based reconstruction, the pectoralis major becomes relocated anterior to the implant and just deep to skin, therefore raising the question of value in radiating deep chest wall structures. This study assessed the rate of recurrence in each anatomical region of chest wall in post-mastectomy patients. Methods A comprehensive breast cancer database of 4287 patients at a single regional cancer center from 2006 to 2018 was retrospectively analyzed to identify 1571 mastectomy patients. Recurrences were classified as local skin/subcutaneous, pectoralis muscle (pectoralis major), deep chest wall (pectoralis minor, intercostal muscle or rib) or regional axillary recurrence. Results A total of 26 patients with locoregional recurrence were identified. Most recurrences were in the skin/subcutaneous level. Of 1571 mastectomy patients, only one patient developed a local recurrence posterior to pectoralis major. Our literature search and meta-analysis revealed that local recurrences post-mastectomy are much more likely to be in subcutaneous tissues/pectoralis major versus deeper chest wall. Conclusion A reduced clinical target volume which encompasses skin/subcutaneous and pectoralis muscle layers without treating deep chest wall may be more appropriate to reduce radiation-associated toxicity since avoiding circumferential radiation of an implant may prevent capsular contracture without compromising treatment benefit.

Adjuvant whole-breast radiotherapy (RT) is a significant part of the standard of care treatment after breast cancer (BC) conserving surgery. Modern techniques including intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) have constituted to better target coverage and critical organs sparing. However, BC survivors are at risk of developing radiation-induced cardiac toxicity. Hence, deep-inspiration breath-hold (DIBH) techniques have been implemented at many centers to further reduce cardiac exposure but require compliance. 4D-CT robust optimization can account for heart intrafractional motion per breathing phase. The optimization has been explored in cardiac sparing of breast IMRT compared to DIBH in a small sample size but has not been evaluated in substructures sparing, nor in VMAT. To provide patients who are not compliant to breath-hold with an optimal treatment approach, various heart sparing techniques need to be evaluated for statistical significance and clinical feasibility.This retrospective study aimed to provide an extensive dosimetric heart sparing comparison of free-breathing, 4D-CT-based treatment planning, including robust optimization with DIBH-based treatment planning. Combinations of forward and inverse IMRT and VMAT are also considered.Fifteen early stage left-sided BC standard treatment plans were selected. Breast, lung, left anterior descending artery (LAD), left ventricle (LV), and the whole heart were contoured on each 4D-CT phase and DIBH CT dataset. Each treatment plan was optimized using forward/inverse IMRT and VMAT on the following CT datasets: DIBH, average 4D-CT, and the complete 4D-CT dataset needed for robust optimization. Dose-volume histograms were used to compare VAll RT techniques assessed including 4D robust optimization were clinically feasible. Statistically significant differences in mean heart, LAD and LV dose, max LAD dose, and VThis study demonstrated the clinical feasibility of 4D robust optimization in limiting the cardiac and substructures dose during free-breathing RT with both IMRT/VMAT for patients who are not compliant with breath-hold RT. However, this study also presents that 4D robust optimization can reduce LAD dose but not fully outperform DIBH or conventional 4D-CT-based planning with IMRT/VMAT in heart sparing in treating early staged left-sided BC patients.

Female patients with breast cancer frequently develop arthralgia when treated with aromatase inhibitors (AI). Although the mechanism of AI-induced arthralgia is unknown, potential biomarkers have been identified. The purpose of this study was to investigate the clinical and genetic predictors of AI-induced arthralgia in a prospective cohort of patients with estrogen receptor-positive breast cancer. One hundred and ninety-six patients were enrolled at initiation of AI therapy with either letrozole or anastrozole. Patients completed two validated self-report questionnaires assessing pain, stiffness, and physical function at baseline, and repeated the questionnaires at two and at six months after the initiation of treatment with an AI. Germline DNA of all patients was genotyped for seven single-nucleotide polymorphisms (SNPs) previously identified by genetic screens and genome-wide association studies as associated with AI-induced arthralgia. More than 50% of the study group experienced arthralgia symptoms. Genetic analysis revealed that four SNPs, in CYP19A1 (rs4775936) and ESR1 (rs9322336, rs2234693, rs9340799), were associated with the development of arthralgia (adjusted P = 0.016, 0.018, 0.017, 0.047). High body mass index (BMI) was also associated with the development of arthralgia symptoms (adjusted P = 0.001). Patients prescribed letrozole were significantly more likely to develop arthralgia than patients on anastrozole (P = 0.018), and also more likely to discontinue AI therapy due to arthralgia. The CYP19A1 (rs4775936) SNP was significantly associated with discontinuation of therapy due to intolerable arthralgia. Our results suggested that BMI and AI drug (letrozole versus anastrozole) were clinical predictors of arthralgia, while genetic variants rs4775936, rs9322336, rs2234693, and rs9340799 were genetic predictors of AI-induced arthralgia. Significantly, rs4775936 was also a predictor of discontinuation of therapy.

Background: Guidelines recommend that breast radiation (RT) can be omitted for patients with a low risk of local recurrence (LR) after breast-conserving surgery (BCS) for DCIS. The inability to identify women at low risk of LR ( Methods: Prospective cohort study of women with low/moderate risk pure DCIS treated with BCS. Cases with age 2.5cm, multifocality, or prior breast cancer were excluded. Baseline CPFs, the DS and risk of LR were collected. Pre-assay, the radiation oncologist provided an estimate of 10-year LR risk without RT and a preliminary recommendation for RT. Post-assay, final recommendations were recorded. The primary outcome was change in treatment recommendation by the radiation oncologist. Target sample size was 220 to provide data on 200 evaluable patients with adequate precision. Results: 217 patients were evaluable: mean age, 63 years and mean tumor size, 1.1 cm. Nuclear grade was low in 26 (12%), intermediate in 116 (53%), and high in 75 (35%) of patients. Mean DS = 32; 140 (64%) low (15% in 128 (59%) cases. Post-assay, estimated 10-yr LR risk after BCS was 15% in 49 (22%) (RT recommended in 98%). Conclusion: The use of the DCIS Score combined with CPFs identifies more women with an estimated low ( Table 1.Post-assay 10-yr LR risk15%(N=101)(N= 67)(N=49)Pre-assay estimated 10-yr LR risk• 15% (N=128)424739RT recommended• Yes17 (17%)44 (66%)48 (98%)• No83 (83%)23 (34%)1 (2%) Citation Format: Eileen Rakovitch, Anne Koch, Laval Grimard, Hany Soliman, Christiaan Stevens, Francisco Perera, Iwa Kong, Senti Senthelal, Margaret Anthes, Ericka Wiebe, Jeffrey Cao, Mira Goldberg, Sally Smith, Luciana Spadafora, Sameer Parpia, Timothy Whelan. Refined local recurrence risk estimates based on a multigene expression assay combined with clinicopathological features significantly impacts radiotherapy recommendation in patients with low/intermediate risk DCIS treated with breast-conserving surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-16-01.

Background: Tamoxifen is widely used in patients with hormone sensitive breast cancer in the adjuvant setting to decrease risk of recurrence and metastasis. 5-10 years of tamoxifen has demonstrated a near 50% reduction in recurrence risk. Despite marked interpatient variation in the metabolism of tamoxifen to its active metabolite endoxifen, all patients are prescribed 20 mg daily dose of tamoxifen. Current evidence suggests that patients are at risk for suboptimal benefit if measured endoxifen concentration is below 5.9 ng/ml (~15nM). However, there have been conflicting data on the clinical utility of CYP2D6 genotype testing, and measuring endoxifen plasma concentration as a predictor of breast cancer recurrence. The goal of this prospective study was to determine the impact of endoxifen levels and CYP2D6 genetic variations to clinical outcome among patients with early breast cancer. Methods: Since 2010, as part of Personalized Medicine Program in Oncology, our team has been prospectively enrolling patients on tamoxifen therapy. To date 950 patients have been enrolled and preliminary analysis has been completed in 429. After initial CYP2D6 genotype testing, plasma concentration of tamoxifen and its metabolites were quantified using liquid chromatography-tandem mass spectrometry during each clinic visit. Baseline characteristic are outlined in table 1. Primary outcome assessed was invasive disease-free survival (IDFS) defined as time since start of tamoxifen therapy till an event of interest such as loco-regional recurrence, distant metastasis, new contralateral primary breast cancer, death due to breast cancer and other causes. Patients were censored at their last encounter at our institution (London Health Sciences Centre). Results: IDFS data for 426 patients were obtained. Outcome was stratified by CYP2D6 phenotypes (ultra-rapid, extensive, intermediate and poor metabolizers) and endoxifen levels (>5.9ng/ml or vs< 5.9 ng/ml showed a clear trend towards lower IDFS (hazard ratio = 2.4, (95%CI,1.26-4.77) P=0.0002) among those with endoxifen < 5.9 ng/ml. We note this preliminary data analysis was unadjusted and will undergo further in-depth statistical analysis. Conclusion: Preliminary finding suggests endoxifen concentration, but not CYP2D6 phenotype, may be a predictor of risk for suboptimal benefit during tamoxifen therapy. Detailed statistical analysis is planned for the full cohort, including adjustment for covariates including tumor stage, menopausal status, drug interactions, and use of aromatase inhibitors. To our knowledge, this is the first study of its type to prospectively collect multiple plasma samples for tamoxifen and endoxifen level in real-world patients during tamoxifen therapy, with sufficient sample size and follow-up period for primary clinical outcome. Table 1: Baseline Characteristics of PatientsCharacteristicsCYP2D6-Phenotypes, n=429 (%)Endoxifen concentration, n=429 (%)UM/EMIMPM>5.9ng/ml(~15nm) Citation Format: Veera Durga Sravanthi Panuganty, Denise Keller, Wendy A Teft, John Gordon Lenehan, Kylea Raijann Potvin, Jawaid Younus, Theodorus Anthony Vandenberg, Diane Mary Logan, Karin Hahn, Muriel Brackstone, Phillip Stanley Blanchette, Francisco Perera, Yun-Hee Choi, Richard Brian Kim. Clinical outcomes in early breast cancer patients on adjuvant tamoxifen: Impact of CYP2D6 genotype and observed endoxifen concentrations [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-05.

Purpose The neoadjuvant treatment of breast cancer (NABC) is a rapidly changing area that benefits from guidelines integrating evidence with expert consensus to help direct practice. This can optimize patient outcomes by ensuring the appropriate use of evolving neoadjuvant principles. Methods An expert panel formulated evidence-based practice recommendations spanning the entire neoadjuvant breast cancer treatment journey. These were sent for practice-based consensus across Canada using the modified Delphi methodology, through a secure online survey. Final recommendations were graded using the GRADE criteria for guidelines. The evidence was reviewed over the course of guideline development to ensure recommendations remained aligned with current relevant data. Results Response rate to the online survey was almost 30%; representation was achieved from various medical specialties from both community and academic centres in various Canadian provinces. Two rounds of consensus were required to achieve 80% or higher consensus on 59 final statements. Five additional statements were added to reflect updated evidence but not sent for consensus. Conclusions Key highlights of this comprehensive Canadian guideline on NABC include the use of neoadjuvant therapy for early stage triple negative and HER2 positive breast cancer, with subsequent adjuvant treatments for patients with residual disease. The use of molecular signatures, other targeted adjuvant therapies, and optimal response-based local regional management remain actively evolving areas. Many statements had evolving or limited data but still achieved high consensus, demonstrating the utility of such a guideline in helping to unify practice while further evidence evolves in this important area of breast cancer management.

Summary Background Whole breast irradiation delivered once per day over 3–5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. Methods We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5–8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov , NCT00282035 . Findings Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3–9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9–4·0) in the APBI group and 2·8% (1·8–3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84–1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p Interpretation External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. Funding Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

El presente artículo comparte los impactos bibliométricos de la investigación científica de la Universidad de las Regiones Autónomas de la Costa Caribe Nicaragüense (URACCAN), se ha enfatizado en la producción y publicación, tanto impresa como digital, durante 2013-2017. La investigación se desarrolló bajo el enfoque cuantitativo de corte transversal. Entre los principales resultados sobresalen: i) La producción científica de URACCAN, del 2013-2017 fue de 787 investigaciones, de las que un 78.5% corresponde a investigaciones monográficas, 10.8% a tesis y 10.7% a investigaciones libres de institutos, centros de investigación, docentes investigadores y personal de áreas técnicas; ii) Del 2013 al 2017 la URACCAN publicó un total de 20 números de sus revistas científicas, con 169 artículos, 89 en la revista Ciencia e Interculturalidad y 80 en la Revista Universitaria del Caribe; iii) La publicación científica de la Universidad en formato digital ha sido muy exitosa, desde junio del 2011 a enero del 2018, en tres portales, se hicieron un total de 574,649 descargas de artículos en formato pdf, de estos, 333,488 descargas se hicieron en el Portal de revistas de URACCAN, 205,853 en Lamjol y 35,308 en el Portal de revistas de Nicaragua; iv) En el período de agosto del 2015 a noviembre del 2018, la revista Ciencia e Interculturalidad obtiene el primer lugar en descargas de artículos de las revistas de universidades públicas, yel segundo lugar general de 49 revistas de Nicaragua, Honduras y El Salvador, alojadas en Lamjol.

PURPOSE/OBJECTIVE(S) APBI is the delivery of radiotherapy (RT) to the tumor bed after breast conserving surgery (BCS) often given over a week or less. An attractive approach to deliver APBI is by external beam 3DCRT or IMRT. Previous studies have suggested that external beam APBI delivered twice-a-day can lead to increased late effects and poor breast cosmesis. The objective of our trial was to determine if two doses for APBI given once-a-day over 1-week result in acceptable long-term morbidity. MATERIALS/METHODS Eligible patients were > 50 years with DCIS or invasive breast cancer < 3 cm treated by BCS with negative margins and negative axillary nodes. Consenting patients were planned to receive APBI with 3-5 non-coplanar fields using a 3DCRT or IMRT and randomized to 27.5Gy or 30Gy each given in 5 fractions once-a-day over 5-8 days. Cosmetic evaluation with the EORTC Cosmetic Rating System was performed at baseline and 2 years by: a study nurse directly assessing the breast, and a group of oncologists unaware of RT regimen assessing photographs. Patient assessment of cosmesis was also performed at 3 years. Patients were followed for toxicity using the NCI CTCAE and recurrence. The primary outcome was adverse cosmesis (fair or poor global score) by photographic assessment at 2 years. The rate of adverse cosmesis with standard whole breast irradiation was 17% in our previous trial. Based on this consideration and one-sided α of 5% for each group, the upper bound of a one-sided 95% (two-sided 90%) confidence interval (CI) had to be < 23% for the treatment to be acceptable; 140 patients were required for each group. The proportion of patients with adverse cosmesis at 2 years and cosmetic deterioration from baseline to 2 years (excellent/good to fair/poor) with corresponding two-sided 90% CIs were estimated using the Wilson score method. The proportion of patients with any late breast toxicity (edema, induration, and telangiectasia) grades 2-3 at 2 years and local recurrence (LR) were also determined. RESULTS Of the 281 patients: 139 were randomized to 27.5Gy and 142 to 30.0Gy. Median follow-up was 3 years. The mean age was 65 years; mean tumor size was 1.2cm. With respect to photographic assessment both schedules met our criteria for acceptability (Table 1). Adverse cosmesis assessed by nurse or patient and toxicity appeared to be less for 27.5Gy compared to 30Gy. No LRs were observed for 27.5Gy and one LR was observed for 30Gy. CONCLUSION According to the study design 27.5Gy and 30Gy resulted in acceptable cosmetic outcomes. In light of recent studies, the lower dose may be preferable in terms of late adverse effects but requires further evaluation.

Purpose To evaluate whether concurrent neoadjuvant radiation added to standard chemotherapy could increase the pathologic complete response (pCR) to treatment for locally advanced breast cancer (LABC). Methods and Materials This prospective phase 2 trial recruited 32 LABC patients from 2009 to 2011. Patients received neoadjuvant every-3-weekly 5-fluorouracil (500 mg/m 2 ), epirubicin (100 mg/m 2 ), and cyclophosphamide (500 mg/m 2 ) for 3 cycles, followed by weekly docetaxel (35 mg/m 2 ) for 9 cycles. Regional radiation (45 Gy/25 plus 5.4 Gy/5) was delivered concurrently with docetaxel, then modified radical mastectomy. Patients were matched post hoc by a blinded statistician to a concurrent cohort treated with neoadjuvant chemotherapy, modified radical mastectomy, and adjuvant regional radiation. Results Thirty of 32 patients completed treatment. Twenty-seven were successfully matched by propensity score to 81 control patients by age, stage, and molecular subtype. The concurrent chemoradiation produced a significant increase in pCR (14% vs 22%, P P =.186, hazard ratio 0.51; and 74% vs 89%, P =.162, hazard ratio 0.46). Toxicity included 25% of patients with grade 3 pneumonitis and 25% of patients with dermatitis, and 1 death. Conclusions Concurrent neoadjuvant radiation added to radiosensitizing chemotherapy significantly improved pCR. A prospective randomized clinical trial is warranted to exploit the improved response seen with concurrent therapy but using another radio-sensitizing taxane, to better minimize treatment-related toxicity and determine its impact on overall survival.

Este volumen número 25 comparte la compilación de 13 artículos divididos en 7 sesiones; de estos, 3 están vinculados a la Educación, uno en la sección de Salud, tres artículos en Historia y Actualidad de URACCAN, un artículo en Género e Interculturalidad; un artículo en Autonomía de la Costa Caribe; dos en la sección de Medio Ambiente y Recursos Naturales: y dos en la sesión Agropecuaria.

Palmar-plantar erythrodysesthesia (PPE) is a common dermatologic adverse reaction secondary to capecitabine use, but the skin toxicity rarely involves the genitals. We describe a case of PPE with scrotal and penile involvement secondary to capecitabine chemotherapy concurrent with radiotherapy. The patient presented with pain and erythema involving the penis and scrotum during the fifth week of neoadjuvant chemoradiotherapy with capecitabine for T3c N2b M0 low rectal adenocarcinoma. The onset and severity of symptoms in the genitals were loosely associated with the symptoms in the hands and feet. The pain and erythema were self-limiting and improved 11 days after capecitabine discontinuation and local supportive care.

The aromatase inhibitor (AI) letrozole is a first-line drug in the adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI therapy, including letrozole, remains problematic due to the development of debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation is associated with the development of arthralgia. We enrolled 126 female breast cancer patients initiated on letrozole therapy and prospectively collected blood samples at baseline and two follow-up time points to determine letrozole plasma concentrations and CYP2A6 genotype. At each visit, participants completed two validated questionnaires to assess the severity of arthralgia symptoms. More than half (55%) of patients experienced a significant increase in their arthralgia symptoms after initiation of treatment. The clinical variables of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and positively associated with plasma letrozole concentrations, respectively. CYP2A6 genotype was significantly associated with letrozole levels (P

Compartimos una compilación de poesía de 12 talentos entre los que sobresalen los niños.

Purpose To evaluate the rate of gastrointestinal (GI) toxicity of neoadjuvant chemoradiation with capecitabine, oxaliplatin, and intensity modulated radiation therapy (IMRT) in cT3-4 rectal cancer. Methods and Materials Patients with localized, nonmetastatic T3 or T4 rectal cancer Results Seventy-nine patients were accrued, of whom 68 were evaluable. Sixty-one patients (89.7%) had cT3 disease, and 37 (54.4%) had cN (+) disease. Postoperative chemotherapy was given to 42 of 68 patients. Fifty-eight patients had target contours drawn per protocol, 5 patients with acceptable variation, and 5 patients with unacceptable variations. Thirty-five patients (51.5%) experienced grade ≥2 GI toxicity, 12 patients (17.6%) experienced grade 3 or 4 diarrhea, and pCR was achieved in 10 patients (14.7%). With a median follow-up time of 3.98 years, the 4-year rate of locoregional failure was 7.4% (95% confidence interval [CI]: 1.0%-13.7%). The 4-year rates of OS and DFS were 82.9% (95% CI: 70.1%-90.6%) and 60.6% (95% CI: 47.5%-71.4%), respectively. Conclusion The use of IMRT in neoadjuvant chemoradiation for rectal cancer did not reduce the rate of GI toxicity.

Purpose A retrospectivechart review was conducted to determine whether the time interval from breast-conserving surgery to breast irradiation (surgery-radiation therapy interval) in early stage node-negative breast cancer had any detrimental effects on recurrence rates. Methods and Materials There were 566 patients with T1 to T3, N0 breast cancer treated with breast-conserving surgery and breast irradiation and without adjuvant systemic treatment between 1985 and 1992. The surgery-to-radiation therapy intervals used for analysis were 0 to 8 weeks (201 patients), >8 to 12 weeks (233 patients), >12 to 16 weeks (91 patients), and >16 weeks (41 patients). Kaplan-Meier estimates of time to local recurrence, disease-free survival, distant disease-free survival, cause-specific survival, and overall survival rates were calculated. Results Median follow-up was 17.4 years. Patients in all 4 time intervals were similar in terms of characteristics and pathologic features. There were no statistically significant differences among the 4 time groups in local recurrence ( P =.67) or disease-free survival ( P =.82). The local recurrence rates at 5, 10, and 15 years were 4.9%, 11.5%, and 15.0%, respectively. The distant disease relapse rates at 5, 10, and 15 years were 10.6%, 15.4%, and 18.5%, respectively. The disease-free failure rates at 5, 10, and 15 years were 20%, 32.3%, and 39.8%, respectively. Cause-specific survival rates at 5, 10, and 15 years were 92%, 84.6%, and 79.8%, respectively. The overall survival rates at 5, 10, and 15 years were 89.3%, 79.2%, and 66.9%, respectively. Conclusions Surgery-radiation therapy intervals up to 16 weeks from breast-conserving surgery are not associated with any increased risk of recurrence in early stage node-negative breast cancer. There is a steady local recurrence rate of 1% per year with adjuvant radiation alone.

Este volumen comparte la compilación de 10 artículos estructurados en 4 secciones, las cuales comprenden en la primera sección de Educación el artículo: Actitudes hacia las matemáticas: un estudio en una escuela rural de la Costa Caribe Sur de Nicaragua; Aprendizaje de la circunferencia aplicando el Modelo Van Hiele en estudiantes de undécimo grado de Educación Secundaria de Río San Juan; Experiencia de construcción de referentes curriculares con incorporación tecnológica para la formación del profesorado de América Latina y el Caribe; Construcción de instrumentos de evaluación del desempeño docente universitario desde una perspectiva cualitativa y el artículo Estrategias metodológicas para la enseñanza del uso y manejo de las reglas ortográficas en el Instituto Rubén Darío de Santa Rita, Costa Caribe Norte de Nicaragua. En la segunda sección sobre Ciencias Sociales, comprende los artículos: Derechos laborales de mujeres en institutos de Educación Secundaria de Siuna, Costa Caribe Norte de Nicaragua, y el artículo Identidad cultural de los jóvenes de Siuna, Costa Caribe Norte de Nicaragua. En la tercera sección sobre Recursos Naturales y Medio Ambiente se comparte el artículo Hábitat potencial del Danto (Tapires bairdii) en la Costa Caribe Norte de Nicaragua. En la Cuarta sección Agropecuaria los artículos Sistemas productivos de comunitarios mestizos en la Costa Caribe Norte de Nicaragua y Producción y calidad de forraje con enmiendas orgánicas en pastura (Brachiaria Brizantha), en la Costa Caribe Sur de Nicaragua.

No Resumen

No Resumen

Outcomes for women with locally advanced breast cancer (LABC) remain poor, with a fi ve-year survival of approximately 50%, despite aggressive treatment with a combination of chemotherapy, surgery and radiotherapy, all delivered sequentially [1,2]. Achieving a pathological complete response (pCR) to neoadjuvant systemic therapy (defi ned as no residual disease in the breast or axilla at surgery) is a major favorable prognostic factor [3 – 5]; however, rates of pCR are low: a large meta-analysis demonstrated that 17% of women, on average, achieve a pCR after neoadjuvant treatment [3]. In LABC, concurrent chemoradiotherapy has been associated with higher rates of pCR [4,6]. In an attempt to improve the pCR rate for LABC, a phase II trial was launched to evaluate the effi cacy of a regimen consisting of neoadjuvant docetaxel con-current with locoregional radiotherapy. At the rec-ommendation of the data safety monitoring committee, the trial closed early due to a higher-than-anticipated rate of symptomatic radiation pneumonitis (RP). The goal of this study was to evaluate predictors of symptomatic RP and CT-based radiation-induced lung injury (RILI) in a unique cohort of breast cancer patients treated with concurrent neoadjuvant chemoradiation therapy.

Este volumen, número 23 comparte la compilación de 14 ensayos y dos artículos, todos vinculados a la educación, estos son: 1) ¿Es posible la interculturalidad en contextos multiculturales o solo es un concepto de moda? ¿Cómo se vive desde la educación superior?; 2) La Educación Intercultural pertinente y de calidad: “un derecho en camino”; 3) La educación superior, un reto para las universidades comunitarias interculturales de América Latina; 4) La Universidad Intercultural Amawtay Wasi del Ecuador, un proyecto atrapado en la colonialidad del poder; 5) Interculturalización de la educación superior en Nicaragua: del pensamiento teórico a la realidad; 6) De la educación superior convencional a la educación superior intercultural; 7) Mirar a la diversidad cultural para interculturalizar la educación superior; 8) Reflexión sobre el trabajo de la Universidad de las Regiones Autónomas de la Costa Caribe Nicaragüense (URACCAN) como universidad comunitaria intercultural; 9) Comunidades de aprendizaje y su avance en la interculturalización de la educación superior en URACCAN-Recinto Universitario Bilwi; 10) La formación del profesorado para la práctica de la interculturalidad en educación superior; 11) Innovaciones jurídicas, acceso, colaboración intercultural y pueblos indígenas en la educación superior; 12) Educación superior incluyente: Experiencia de la Universidad de las Regiones Autónomas de la Costa Caribe Nicaragüense; 13) Universidad de las Regiones Autónoma de la Costa Caribe Nicaragüense y su acompañamiento Comunitario; 14) La vinculación comunitaria desde la mirada de URACCAN: Experiencia en la elaboración del estatuto de la comunidad de Sumubila en la Costa Caribe Norte de Nicaragua; 15) La Comunicación Intercultural en la Educación Superior Intercultural, desde los Pueblos Indígenas y Afrodescendientes; 16) Senda recorrida en los procesos de Planificación y Autoevaluación Institucional de la Universidad Comunitaria Intercultural.

Background Whole breast irradiation (WBI) after lumpectomy reduces the risk of local recurrence, thereby avoiding subsequent mastectomy. It is a key component of breast conserving therapy. WBI is usually given in daily fractions over 3-6 weeks. With accelerated partial breast irradiation (APBI), radiation is delivered over a week or less to the surgical cavity with a margin of normal tissue. It was introduced to provide treatment in a shorter more convenient form. 3D-CRT is an attractive approach as it is non-invasive and uses standard techniques for external beam RT that are widely available. The objective of the RAPID trial was to determine if APBI using 3D-CRT was not inferior to WBI following breast conserving surgery (BCS). Methods Women ≥40 years of age with axillary node-negative invasive ductal carcinoma, or ductal carcinoma in situ (DCIS) ≤3cm treated by BCS with clear margins of excision were eligible. Randomization was stratified for age (< or ≥50y), histology (DCIS alone or invasive breast cancer), tumor size (< or ≥1.5cm), ER status (+/-) if invasive disease, and treatment center. Patients were allocated to APBI using 3D-CRT (38.5Gy in 10 fractions delivered twice daily) or WBI (42.5Gy in 16 daily fractions or 50Gy in 25 daily fractions; boost radiation was permitted). The primary outcome was ipsilateral breast tumor recurrence (IBTR). Important secondary outcomes included radiation toxicity and nurse assessed adverse cosmesis (fair or poor on global assessment). The trial was designed to show that the 5-year IBTR rate in the APBI arm was not inferior to the WBI arm by more than 1.5% (hazard ratio [HR] ≤ 2.02) with 85% power and a one-sided alpha of 5%. Results From February 2006 to July 2011, 2135 patients from sites in Canada, Australia, and New Zealand were randomly assigned: 1070 to APBI and 1065 to WBI. The median follow-up was 8.6 years. The mean age of the study population was 61 years; 82% of patients had invasive breast cancer and 18% had DCIS only. For invasive cancers: 60% were < 1.5cm and 90% were ER positive. For DCIS tumors: 68% were < 1.5cm. A total of 65 IBTRs were observed. For the APBI patients, the 5-year and 8-year cumulative rates of IBTR were 2.3% and 3.0%, respectively. The corresponding data for the WBI patients were 1.7% and 2.8%. The HR for APBI versus WBI was 1.27, 90% confidence interval, 0.84 to 1.91. Acute radiation toxicity (occurring within 3 months of treatment start) e.g. radiation dermatitis and breast swelling was less in patients treated with APBI compared with WBI (≥ Grade 2, 28% vs 45%, p Conclusions The APBI regimen used in our trial was non-inferior to WBI in preventing local recurrence. Although it was associated with less acute toxicity, an increase in late normal tissue toxicity and adverse cosmesis was observed with APBI. Citation Format: Whelan T, Julian J, Levine M, Berrang T, Kim D-H, Gu CS, Germain I, Nichol A, Akra M, Lavertu S, Germain F, Fyles A, Trotter T, Perera F, Balkwill S, Chafe S, McGowan T, Muanza T, Beckham W, Chua B, Olivotto I. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-03.

Este estudio muestra el ranking de los artículos más leídos de la Revista Ciencia e Interculturalidad y la Revista Universitaria Caribe; así ha inducir una reflexión interna en las universidades nicaragüenses, con énfasis en la Universidad de las Regiones Autónomas de la Costa Caribe Nicaragüense (URACCAN), sobre las ventajas de la difusión de resultados de investigaciones desde las revistas electrónicas tanto en el uso de acceso abierto y de software de código abierto como Open Journal Systems (OJS).Entre los resultados sobresalen: i) La revista digital Ciencia e Interculturalidad Incorporada en el Portal de Revistas Nacionales de Nicaragua, Portal del Sistema Regional de Información en Línea para revistas científicas de América Latina, el Caribe y Portugal (Latindex) y en el portal de Latin American Journals Online (Lamjol). ii) Ciencia e Interculturalidad, en Latin American Jornal online (Lamjol) recibió un total de 53,757 visitas desde marzo 2011 a octubre 2013; en el Portal de Revistas de Nicaragua recibió un total de 12,522 visitas en revisión a resúmenes y 13,881 para revisar o descargar artículo completo en PDF, del 2012 a noviembre del 2013; y en el Portal de Revistas de URACCAN recibió un total de 18,661 visitas para revisar resúmenes y 32,254 para revisar o descargar artículo completo en pdf, durante junio 2011 a octubre 2013. iii). El Consejo Nicaragüense de Ciencia y Tecnología de Nicaragua (CONICYT), entregó en noviembre del 2013, un reconocimiento a la revista “por su esfuerzo en elevar la calidad y aplicación de los criterios de LATINDEX y lograr visibilidad de la producción científica de Nicaragua en LAMJOL”. SummaryThis study shows the ranking of the most read articles in the Science and Interculturality Magazine and the Caribbean University Magazine, which induce and brought across an internal reflection within Nicaraguan universities, with emphasis on the University of the Autonomous Regions of the Nicaraguan Caribbean Coast (URACCAN), regarding the benefits of disseminating research results from electronic magazines by using both open access and open source software code such as Open Journal Systems (OJS).Among the results we highlight: i) The digital magazine Science and Interculturality, incorporated in the Nicaragua’s National Magazine Portal, Portal Online Regional Information System for scientific magazines of Latin America, the Caribbean and Portugal (Latindex) and the portal Latin American Journals Online (Lamjol). ii) Science and Interculturality in Latin American Journals Online (Lamjol) received a total of 53.757 visitors since March 2011 to October 2013; the Portal of Journals of Nicaragua received a total of 12,522 visits that reviewed abstracts and 13,881 to review or download full article in PDF, from 2012 to November 2013. And the Portal of Journals of URACCAN received a total of 18,661 visits to review abstracts and 32,254 to review or to download full article in PDF during June 2011 to October 2013. iii). The Nicaraguan Council of Science and Technology (CONICYT), delivered in November 2013, a recognition to the magazine "for their efforts in raising the quality and application of the LATINDEX criteria’s and to achieve visibility of scientific production in LAMJOL - Nicaragua". DOI: http://dx.doi.org/10.5377/rci.v13i2.1275

Los antiguos habitantes de Siuna fueron los Sumus, quienes se encontraban principalmente a orillas de los ríos de la zona, teniendo como principal fuente de vida la caza y la pesca, complementando con frutas, platano o banano y posiblemente otros cultivos como la yuca. Según anécdotas de antepasados, en lo que hoy es Siuna, vivía una suma muy bella de nombre Siu, quien por su belleza a todos llamaba la atención, al morir dicha suma y en memoria de ella se le llamó al lugar Siuna. En otra anécdota se cuenta que el nombre de Siuna se debe a que en el siglo pasado el área fue habitada no densamente por Siunas, pobladores sumos, que llevaban este nombre en recuerdo de un audaz guerrero, que se arriesgaba solo a cazar chanchos de monte en la deshabitada e inexplorable selva; pero independientemente cual sea el origen del nombre, la verdad es que nació del pueblo sumu, antiguos habitantes de la zona, cuya influencia es predominante en la toponimia de la zona.

Esta investigación tuvo como propósito adecuar la oferta académica de la URACCAN, basada en las realidades y necesidades de formación profesional en el nivel de grado de la Costa Caribe de Nicaragua para el quinquenio 2014-2018. Se desarrolló en las Regiones Autónomas, específicamente en los municipios donde la Universidad tiene presencia (Bluefields, Laguna de Perlas, Nueva Guinea, El Coral, Almendro, San Miguelito, Siuna, Rosita, Bonanza, Waslala, Bilwi y Waspam). Se trabajó con los estudiantes finalistas de Secundaria (undécimo grado) de todos los centros educativos, incluyendo a los directores de estos colegios. Asimismo, se entrevistaron a autoridades territoriales, gobiernos municipales y regionales. Participaron en el estudio los principales empleadores de nuestros graduados/graduadas de las diferentes carreras, los que dirigen las principales instituciones de gobierno regional, municipal y central, así como el análisis de la Estrategia de Desarrollo de la Costa Caribe y el Plan Nacional de Desarrollo del País.Las carreras más demandadas para ser ofertadas e implementadas en los cuatro Recintos son: Medicina Intercultural, Ingeniería Civil, Ingeniería en Sistema, Derecho con énfasis en Derecho Autonómico y Administración de Empresas. La oferta académica de la Universidad cubre algunas áreas en la formación de profesionales de la estrategia en desarrollo de la Costa Caribe; pero, otras quedan pendientes como: Ordenamiento territorial, seguridad alimentaria, agua y saneamiento, convivencia comunitaria y administración de justicia, protección de los bosques y los ecosistemas, transporte (canal intercostero, construcción de carreteras), energía renovable y agua (hidroeléctricas) y agroforestería comunitaria, por lo que estas deben ser parte fundamental en la nueva oferta académica que llevará a cabo la Universidad en el próximo quinquenio.SummaryThis research was aimed to adjust URACCAN academic offer, based on the realities and needs of professional training in the degree level of the Caribbean Coast of Nicaragua for a period of five years (2014 to 2018). The research was developed in the Autonomous Regions, specifically in the municipalities where the University is present (Bluefields, Pearl Lagoon, Nueva Guinea, El Coral, Almendro, San Miguelito, Siuna, Rosita, Bonanza, Waslala, Bilwi and Waspam). We worked with the finalists high school students (eleventh grade) of all the schools, including the directors of these schools. Likewise, interviewed were applied to authorities of the territorial, municipal and regional governments. The major employers who run the principal institutions of the central, regional and municipal government participated in the study of our graduates from different careers, making an analysis of the development strategy of the Caribbean Coast and the Country National Development Plan.The most demanded careers to be offered and implemented in the four campuses are: Intercultural Medicine, Civil Engineering, System Engineering, and Law with emphasis on Autonomy Law and Business Administration. The academic offer of the University covers some areas in the professional training of development strategy in the Caribbean Coast, but they are others that remain pending as: Land management, food security, water and sanitation, community life and administration of justice, protection of forests and ecosystems, transportation (intercoastal canal or waterway, road construction), renewable energy and water (hydroelectric power) and community agroforestry; so these should be a fundamental part of the new academic offer that the University will carry out during the next five years. DOI: http://dx.doi.org/10.5377/rci.v13i2.1276

Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. However, little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration. Therefore, 196 breast cancer patients on tamoxifen were enrolled in this prospective study over a 24-month period. Blood samples were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites. Regression analysis indicated that besides CYP2D6, the recently described CYP3A4*22 genotype, seasonal variation, and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration. Of note, genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 %. Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence, we set the therapeutic threshold at 18 nM, the 20th percentile for endoxifen level among enrolled patients in this cohort. Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM, while carriers of CYP3A4*22 were twofold less likely to be in sub-therapeutic range. Unexpectedly, endoxifen levels were 20 % lower during winter months than mean levels across seasons, which was also associated with lower vitamin D levels. CYP3A4*22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy. The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration.

Este volumen comparte la compilación de 8 artículos estructurada en 4 secciones, las cuales compren- den en la primera sección de Educación el artículo: Evaluando la calidad en la Maestría Internacional en Comunicación Intercultural con enfoque de Género, de la Red de Universidades Indígenas Interculturales y Comunitarias de Abya Yala (RUIICAY) y el artículo Educar para la vida: Un docente desde la pedagogía del amor. En la segunda sección sobre Educación Superior: Actitudes hacia la estadística en la formación del profesorado para contextos multiculturales y el artículo Comunidades de aprendizaje: una perspectiva de la educación inclusiva. En la tercera sección sobre Historia y Actualidad de URACCAN se comparte el artículo Alta Hooker, galardonada en América Latina por la UNESCO y el artículo Alta Hooker, maestra comunitaria intercul- tural. En la cuarta sección de Medio Ambiente y Recursos Naturales: Acciones para elevar el conocimiento de la educación ambiental en la comunidad Natividad del Municipio La Sierpe y el artículo Conocimientos botánicos de estudiantes de sexto grado, escuela rural del municipio de Fómeque, Cundinamarca.

Introduction The objective of this study was to develop and assess the feasibility of utilizing consensus-based penalty metrics for the purpose of critical structure and organ at risk (OAR) contouring quality assurance and improvement. Methods A Delphi study was conducted to obtain consensus on contouring penalty metrics to assess trainee-generated OAR contours. Voxel-based penalty metric equations were used to score regions of discordance between trainee and expert contour sets. The utility of these penalty metric scores for objective feedback on contouring quality was assessed by using cases prepared for weekly radiation oncology radiation oncology trainee treatment planning rounds. Results In two Delphi rounds, six radiation oncology specialists reached agreement on clinical importance/impact and organ radiosensitivity as the two primary criteria for the creation of the Critical Structure Inter-comparison of Segmentation (CriSIS) penalty functions. Linear/quadratic penalty scoring functions (for over- and under-contouring) with one of four levels of severity (none, low, moderate and high) were assigned for each of 20 OARs in order to generate a CriSIS score when new OAR contours are compared with reference/expert standards. Six cases (central nervous system, head and neck, gastrointestinal, genitourinary, gynaecological and thoracic) then were used to validate 18 OAR metrics through comparison of trainee and expert contour sets using the consensus derived CriSIS functions. For 14 OARs, there was an improvement in CriSIS score post-educational intervention. Conclusions The use of consensus-based contouring penalty metrics to provide quantitative information for contouring improvement is feasible.

Purpose 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is potentially useful in assessing lymph nodes and detecting distant metastases in women with primary breast cancer. Patients and Methods Women diagnosed with operable breast cancer within 3 months underwent FDG-PET at one of five Ontario study centers followed by axillary lymph node assessment (ALNA) consisting of sentinel lymph node biopsy (SLNB) alone if sentinel lymph nodes (SLNs) were negative, SLNB with axillary lymph node dissection (ALND) if SLNB or PET was positive, or ALND alone if SLNs were not identified. Results Between January 2005 and March 2007, 325 analyzable women entered this study. Sentinel nodes were found for 312 (96%) of 325 women and were positive for tumor in 90 (29%) of 312. ALND was positive in seven additional women. Using ALNA as the gold standard, sensitivity for PET was 23.7% (95% CI, 15.9% to 33.6%), specificity was 99.6% (95% CI, 97.2% to 99.9%), positive predictive value was 95.8% (95% CI, 76.9% to 99.8%), negative predictive value was 75.4% (95% CI, 70.1% to 80.1%), and prevalence was 29.8% (95% CI, 25.0% to 35.2%). Using logistic regression, tumor size was predictive for prevalence of tumor in the axilla and for PET sensitivity. PET scan was suspicious for distant metastases in 13 patients; three (0.9%) were confirmed as metastatic disease and 10 (3.0%) were false positive. Conclusion FDG-PET is not sufficiently sensitive to detect positive axillary lymph nodes, nor is it sufficiently specific to appropriately identify distant metastases. However, the very high positive predictive value (96%) suggests that PET when positive is indicative of disease in axillary nodes, which may influence surgical care.

To report pooled overall survival and time to radiological intracranial progression results related to arc-based image-guided radiotherapy for dose-escalation of oligometastatic disease of the brain.Anonymized patient, tumor, and treatment data were pooled from the VU University medical center (VUmc) and the London Regional Cancer Program (LRCP) for patients treated with whole brain radiotherapy (20 Gy/5 VUmc, 30 Gy/10 LRCP) with simultaneous integrated boost (SIB) to individual intracranial lesions (40 Gy/5 VUmc, 35-60 Gy/10 LRCP) to perform survival/intracranial control outcome analyses.A total of 120 patients were treated by both the LRCP (n=70) and VUmc (n=50) between 2005 and 2010. Median lesional dose BED3,10 for the entire cohort of patients were 147 and 72 Gy, respectively. Median follow-up for the entire cohort of patients was 4.7 months with median follow-up of 5.2 months for living patients. On multivariable analysis, primary lung cancer (HR 2.044), presence of systemic metastatic disease (HR 1.937), and lower baseline WHO performance status (HR 1.742) were significant (p0.05) predictors of shorter overall survival. Cumulative brain metastases volume (HR 1.014, p=0.06) was of borderline significance on analysis of intracranial control.This pooled analysis has provided robust outcome data regarding the use of arc-based radiotherapy with SIB.

Background: Taxanes are known to have radiosensitizing properties, by causing cell arrest in the G2 and M phases of the cell cycle. As taxanes have become integrated into routine oncologic use, concerns have arisen over the association between taxanes and radiation toxicities such as pneumonitis. Pneumonitis has been reported to occur both with taxane administration alone or, more commonly, with concurrent or sequential radiation. The purpose of this study is to evaluate radiation pneumonitis from our institutional phase I/II protocol of neoadjuvant FEC chemotherapy followed by weekly docetaxel concurrent with radiotherapy in the treatment of locally advanced breast cancer (LABC). Materials and Methods: Since August 2009, thirty-two LABC patients with stage IIB, IIIA, IIIB, or IIIC invasive breast cancer were enrolled to receive protocol based treatment consisting of 3 cycles of intravenous (IV) fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2 (FEC) every 3 weeks. Following this, weekly IV docetaxel 35 mg/m2 was administered concurrently with locoregional external beam radiotherapy to a total dose of 45 Gy in 25 fractions followed by a boost of 5.4-9 Gy in 3–5 fractions to gross residual disease. Adverse events were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. A linear regression model was built used to evaluate potential parameters predictive of clinical pneumonitis (grade ≥2). Results: Of the 32 patients enrolled on this prospective protocol, 7 were excluded from analysis (n = 6, follow-up < 4 weeks; n = 1, converted to palliative radiotherapy due to metastatic disease). Twenty-five patients remained for analysis. The median age was 48 years (range 26 to 64). Thirteen patients were treated with intensity modulated radiation therapy while 12 were treated using 3D conformal radiotherapy. In total 13 patients (52%) experienced clinical pneumonitis with 6 of these patients (24%) transiently requiring supportive oxygen (grade 3). On linear regression modeling, the use of IMRT (p = 0.08), grade 3 skin toxicity (p = 0.08), and baseline left ventricular ejection fraction (LVEF, p = 0.05) were potentially predictive of symptomatic pneumonitis. Conversely, various heart and lung dose-volume histogram parameters, trastuzumab use, bolus use, disease laterality, total docetaxel dose, were not predictive of symptomatic pneumonitis (p > 0.10). In multivariable modeling, the use of IMRT (p = 0.05) and baseline LVEF (0 = 0.03) remained predictive of symptomatic pneumonitis. Conclusion: The use of concurrent weekly docetaxel-based chemoradiotherapy in LABC is associated with significant symptomatic pneumonitis and may be related to low baseline LVEF and the use of IMRT. However, conventional parameters of low dose volumes of lung and heart irradiated were not predictive of pneumonitis. The relationship of the use of IMRT and taxanes in the development of pnemonitis is likely complex and warrants further investigation. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-11.

Purpose Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. Methods and Materials The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lower dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5–30-Gy (total lesion dose of 35–60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. Results A total of 48 patients received treatment in the 35-Gy ( n = 3), 40-Gy ( n = 16), 50-Gy ( n = 15), 55-Gy ( n = 8), and 60-Gy ( n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. Conclusion The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.

Prólogo

Background Blood levels of the extracellular domain of HER-2/neu (ECD/HER2) have been suggested to have potential as a tumor marker in breast cancer. Our aim was to assess the prognostic value of baseline levels of ECD/HER2, but more importantly changes in levels over time, in women with metastatic breast cancer. Methods Baseline and serial levels of ECD/HER2 were measured in 158 women with newly-diagnosed metastatic breast cancer, in whom we previously performed serial measurement of plasma osteopontin. ECD/HER2 was measured in 1,282 serum samples using a validated ELISA at baseline and every 3–12 weeks during and after therapy until death (median, n = 8 samples per patient). Multivariate time-dependent survival analyses were conducted using models that right-censored patient outcomes 3, 6 and 12 months after last known ECD/HER2 measurement. Results Thirty-four patients (22%) had elevated baseline ECD/HER2 (median 10.2 ng/ml: range 4.1–40.4 ng/ml). In univariate analysis, elevated baseline ECD/HER2 was associated with short survival (P = 0.001). In a multivariate model incorporating standard clinical prognostic factors, baseline ECD/HER2 was significantly associated with survival duration (RR 1.029; P = 0.020). Presence of visceral metastases and ECOG status 2–4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential ECD/HER2 levels, an ECD/HER2 increase of >12 ng/ml at any time was the variable with most prognostic value for poor survival (RR 6.10; P = 0.0003); poor ECOG status also retained significance. Conclusion Increases over time of ECD/HER2 levels were strongly associated with poor survival in this cohort of women with metastatic breast cancer.

Objective There is little information available on the treatment of hot flashes in patients refractory to pharmaceutical interventions. Anecdotal evidence led to the use of oxybutynin for the management of hot flashes in refractory cancer patients; therefore, we performed a retrospective chart review of such patients to determine the effect of oxybutynin in treating hot flashes and to observe the side effects of the drug in these patients. Design A prospective database of all patients treated for hot flashes was started in July 2004 and was retrospectively analyzed as of March 2006. Also included were individual charts preceding July 2004. Fifty-two patient charts were examined. Demographic information was obtained along with baseline severity and frequency of hot flashes, dose and duration of treatment with oxybutynin, patient response to oxybutynin, and side effects. Results More than 90% of patients analyzed were refractory to hot flash treatments before starting oxybutynin. Seventy percent of patients showed a partial or excellent response to oxybutynin. The duration of oxybutynin use ranged from 2 weeks to 5 years with more than half of patients currently on oxybutynin or taking oxybutynin for longer than 6 months. Of those patients who experienced an excellent or partial response to treatment, 12% stopped because of documented oxybutynin-related side effects within 4 weeks. Conclusion Oxybutynin seems promising in the management of hot flashes with tolerable side effects in the majority of refractory patients. A placebo-controlled, randomized study is being developed to look more closely at the effectiveness of oxybutynin in reducing hot flashes.

Este volumen No. 15 muestra la compilación estructurada en 6 secciones, las cuales comprenden en la primera sección: de Género e Interculturalidad con el artículo: Internacionalización e interculturalidad desde la perspectiva de la Red universidades Indígenas, por la Rectora Alta Hooker Blandford; en la temática Educación en la Costa Caribe, comprende los artículos: Estudios literarios en educación a distancia en estudiantes de tercer año, instituto “Cristo Rey”, río San Juan, II semestre del 2013 y Medios didácticos empleados en la disciplina de Lengua y Literatura de octavo grado en Nueva Guinea. En la sección: Medio ambiente y recursos naturales se presenta el artículo: Registros contables en los comités de agua potable y saneamiento (CAPS) en Nueva Guinea, 2014. En la sección de Cultura de la Costa Caribe se presenta el ensayo de la crítica de Arte Hispánico, de Isolda Rodríguez, intitulado: Desencuentros culturales en la novela Columpio al aire del escritor Lisandro Chávez Alfaro. Y el escrito de Henry A. Petrie: Edgar en el alma y el corazón de ACIC. En la sección de Cuentos y leyendas: los cuentos: Letras prohibidas, El árbol de monedas y Zapatitos de un niño. En la sección Poética e Interculturalidad se presenta: Prosemas, y 5 poemas de Delvin Mendoza Olivar¸ Pepitas de palabra del poemario inédito de Alba Rosa; una muestra de poesía denominada: Niños poetas de la Florida, Nueva Guinea, de los autores Dayvin David Espinoza, Javier Gaitán, Ixdalí Antonia Tercero Espinoza, Jendri Lidieth Pérez Amador, Emerson Javier Gaitán, Bertha Lidia Aguilar, Alfredo Heber Masís, Kevin Uriel Ramírez; asimismo poesía de los profesores Gustavo Madrigal y a manera de epílogo se presenta el poema: Si yo hubiera nacido en Sepur Zarco de la poeta guatemalteca Brenda Solís Fong.

Objective: To assess the effect of prognostic factors and their impact on survival in male and female breast cancer. Methods: Medical records for men and women diagnosed with breast cancer referred to the cancer center for treatment were reviewed. Patients with distant metastatic diseases were excluded. Data on prognostic factors including age, nodal status, resection margin, use of hormonal therapy, chemotherapy with and without hormone and radiation therapy (RT), survival, and recurrence were analyzed. Survival estimates were obtained using Kaplan-Meier methodology. The Cox regression interaction was used to compare male and female differences in prognostic factors. Male breast cancer (MBC) and female breast cancer (FBC) were matched according to propensity scores and survival compared using Cox regression. Results: From 1963-2006, there were 75 MBC and 1,313 FBC totaling 1,388 breast cancers. The median age of the cohort was 53 (range: 23-90) years. Median follow-up was 90 (range: 0.4-339) months. Prognostic factors of patients were balanced among the groups after adjusting for propensity scores. A Cox model adjusting for propensity scores showed that overall survival (OS) (HR= 2.52 (1.65, 3.86), P

Purpose: Osteopontin is a malignancy-associated protein measurable in blood and tumor tissue. To evaluate its prognostic value in advanced disease, we conducted a prospective clinical study measuring serial osteopontin plasma levels in women with metastatic breast cancer throughout the course of their disease. Experimental Design: One hundred fifty-eight women with newly diagnosed metastatic breast cancer were enrolled in the study. Plasma osteopontin was measured using our validated ELISA, at baseline and every 3 to 12 weeks during and after therapy until death. Multivariate time-dependent survival analyses were conducted using models that right censored patient outcomes 3, 6, and 12 months after the last known osteopontin measurement. Results: Osteopontin was measured in 1,378 samples (median, 9 per patient). Ninety-nine patients had elevated baseline osteopontin (median, 177 ng/mL; range, 1-2,648 ng/mL). In univariate analysis, elevated baseline osteopontin was associated with short survival (P = 0.02). In a multivariate model incorporating standard prognostic factors, baseline osteopontin was significantly associated with survival duration (relative risk, 1.001; P = 0.038). Metastasis-free interval, visceral metastases, and Eastern Cooperative Oncology Group status 2 to 4 also retained significance. In a multivariate model incorporating standard prognostic factors and changes in sequential osteopontin levels, an osteopontin increase of >250 ng/mL at any time was the variable with the most prognostic value for poor survival (relative risk, 3.26; P = 0.0003), and poor Eastern Cooperative Oncology Group status also retained significance. Conclusions: This is the first study to show that in women with metastatic breast cancer, increases in osteopontin levels over time are strongly associated with poor survival. Sequential monitoring of osteopontin may have use in making treatment decisions for these patients.

This report examines the relationships between measured skin doses and the acute and late skin and soft tissue changes in a pilot study of lumpectomy and high-dose-rate brachytherapy only for breast cancer.Thirty-seven of 39 women enrolled in this pilot study of high-dose-rate brachytherapy (37.2 Gy in 10 fractions b.i.d.) each had thermoluminescent dosimetry (TLD) at 5 points on the skin of the breast overlying the implant volume. Skin changes at TLD dose points and fibrosis at the lumpectomy site were documented every 6 to 12 months posttreatment using a standardized physician-rated cosmesis questionnaire. The relationships between TLD dose and acute skin reaction, pigmentation, or telangiectasia at 5 years were analyzed using the GEE algorithm and the GENMOD procedure in the SAS statistical package. Fisher's exact test was used to determine whether there were any significant associations between acute skin reaction and late pigmentation or telangiectasia or between the volumes encompassed by various isodoses and fibrosis or fat necrosis.The median TLD dose per fraction (185 dose points) multiplied by 10 was 9.2 Gy. In all 37 patients, acute skin reaction Grade 1 or higher was observed at 5.9% (6 of 102) of dose points receiving 10 Gy or less vs. 44.6% (37 of 83) of dose points receiving more than 10 Gy (p0.0001). In 25 patients at 60 months, 1.5% telangiectasia was seen at dose points receiving 10 Gy or less (1 of 69) vs. 18% (10 of 56) telangiectasia at dose points receiving more than 10 Gy (p = 0.004). Grade 1 or more pigmentation developed at 1.5% (1 of 69) of dose points receiving less than 10 Gy vs. 25% (14 of 56) of dose points receiving more than 10 Gy (p0.001). A Grade 1 or more acute skin reaction was also significantly associated with development of Grade 1 or more pigmentation or telangiectasia at 60 months. This association was most significant for acute reaction and telangiectasia directly over the lumpectomy site (p0.001). Grade 1 or more fibrosis, in 25 patients with a 60-month follow-up, occurred in 47.4% (9 of 19) of patients with a volume of 45 cm3 or less covered by the 100% isodose vs. 83.3% (5 of 6) of patients with a larger volume (p = 0.180). Asymptomatic and biopsy-proven fat necrosis occurred in 5 patients. No significant differences in fat necrosis rates according to volume were detected.For high-dose-rate brachytherapy to the lumpectomy site, TLD skin dose was significantly related to acute skin reaction and to pigmentation and telangiectasia at 60 months. An acute skin reaction was also significantly associated with the development of telangiectasia at 60 months. TLD skin dose measurement may allow modification of the brachytherapy implant geometry (dwell times and position) to minimize late skin toxicity.

Purpose In this pilot study of high-dose-rate brachytherapy to the lumpectomy site as the sole radiation, ipsilateral and contralateral breast recurrences are documented with specific attention to the location of recurrence relative to the lumpectomy site. Methods Between March 1992 and January 1996, 39 patients with T1 (32 patients) and T2 breast cancers received 37.2 Gy in 10 fractions (b.i.d.) over 1 week prescribed to a volume encompassing the surgical clips. Thirteen received adjuvant tamoxifen, and 4 received chemotherapy. Follow-up included annual bilateral mammograms and clinical breast examination every 3 to 6 months. Whereas 13 patients had intraoperative implantation of the lumpectomy site, 26 had postoperative implantation. The latter group and 7 of the former group had surgical clips marking the lumpectomy site, which allowed estimates of the distance of any ipsilateral breast recurrence from the lumpectomy site, using the mediolateral and cranio-caudad mammographic views. Results At a median follow-up of 91 months, 33 women are alive, 4 have died of disease, and 2 have died of other causes. The 5-year actuarial rate of ipsilateral breast recurrence was 16.2%. Of 6 ipsilateral recurrences, 2 occurred within the lumpectomy site (in-field recurrences). One of the 2 patients had a 1-mm microscopic margin at initial diagnosis; the recurrence was a 3.5-mm microscopic focus of duct carcinoma in situ . The other patient had a 1.5-cm, high-grade infiltrating mammary carcinoma with no residual at wider resection at first diagnosis; the 5-mm invasive recurrence was also of high grade. Four women developed invasive recurrences at least 1.6 cm or more from the lumpectomy site (out-of-field recurrences). Two of these women had gross multifocal recurrences with two cancers in each patient; 1 of the 2 patients had an extensive intraductal component at initial diagnosis. The estimated nearest distances between the out-of-field recurrences and the surgical clips were 1.6, 5.5, 7.7, and 12.0 cm. All ipsilateral breast recurrences were salvaged by mastectomy (4 patients) or by repeat lumpectomy (2 patients) and whole-breast radiation. The interval postdiagnosis to ipsilateral recurrence ranged from 20 months to 58 months. There were two contralateral breast recurrences at intervals of 34 and 36 months; 1 of these patients also had a multifocal, ipsilateral recurrence at 58 months, as previously described. Among patients with any breast recurrence, 1 patient had a family history of prostate cancer; there was no family history of breast or ovarian cancer. Of 17 patients who received adjuvant systemic therapy, only 1 had a breast recurrence. Conclusions In this pilot study, breast recurrences outside of the lumpectomy site were the predominant pattern of recurrence.

Este volumen comparte la compilación de 10 artículos estructurados en 4 secciones, las cuales comprenden en la primera sección de Educación el artículo: Actitudes hacia las matemáticas: un estudio en una escuela rural de la Costa Caribe Sur de Nicaragua; Aprendizaje de la circunferencia aplicando el Modelo Van Hiele en estudiantes de undécimo grado de Educación Secundaria de Río San Juan; Experiencia de construcción de referentes curriculares con incorporación tecnológica para la formación del profesorado de América Latina y el Caribe; Construcción de instrumentos de evaluación del desempeño docente universitario desde una perspectiva cualitativa y el artículo Estrategias metodológicas para la enseñanza del uso y manejo de las reglas ortográficas en el Instituto Rubén Darío de Santa Rita, Costa Caribe Norte de Nicaragua. En la segunda sección sobre Ciencias Sociales, comprende los artículos: Derechos laborales de mujeres en institutos de Educación Secundaria de Siuna, Costa Caribe Norte de Nicaragua, y el artículo Identidad cultural de los jóvenes de Siuna, Costa Caribe Norte de Nicaragua. En la tercera sección sobre Recursos Naturales y Medio Ambiente se comparte el artículo Hábitat potencial del Danto (Tapires bairdii) en la Costa Caribe Norte de Nicaragua. En la Cuarta sección Agropecuaria los artículos Sistemas productivos de comunitarios mestizos en la Costa Caribe Norte de Nicaragua y Producción y calidad de forraje con enmiendas orgánicas en pastura (Brachiaria Brizantha), en la Costa Caribe Sur de Nicaragua.

To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial.Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assess the association of risk factors for these outcomes among all patients and those treated with APBI only.Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients.In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.

Se presenta el estado del arte de la comunicación intercultural orientada a la protección de los recursos naturales en cuatro comunidades de la laguna de Pahra, Municipio de Puerto Cabezas.