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El documento que aquí reproducimos fue elaborado por un grupo de expertos a propuesta de las dos delegaciones andaluzas del Colegio Oficial de Psicólogos (COP). El trabajo se terminó en diciembre de 1990 y ba sido posteriormente utilizado en diversas reuniones y jornadas organizadas por el COP. Con su publicación íntegra en Apuntes de Psicología, se pretende extender el conocimiento de la posición del COP en Andalucía respecto a la temática abordada y, con ello, ser un instrumento útil tanto para los psicólogos cuya práctica profesional se realiza dentro del sistema sanitario, como para la administración sanitaria (desarrollo de programas de atención sanitaria y de salud mental) y para la administración universitaria (desarrollo de programas de formación pre y postgraduada).

The typical meteorological year (TMY) based on daily rainfall data was calculated in the parish of Nanegalito; 12 years were considered, from 2004 to 2015, including both years. For the establishment of the TMY, the Finkelstein-Schafer (FS) statistical equation was chosen, together with the calculation of the cumulative distribution function for each month of each year considered. The weighted sum, calculated from the FS values, was used to finally choose the months that best represent the climatic characteristics of the period analyzed by applying the root mean square deviation (RMSD). Once these values were obtained, the TMY of Nanegalito was estimated based on the precipitation. The determination of Nanegalito TMY may be useful for the management of several processes, in this and other surrounding parishes, as an example, Pacto, such as irrigation planning in crops, analysis in drought risk scenarios, and if other variables are analyzed in the future, they could serve as tools for the study of possible renewable energies.

En la Reserva de Producción de Fauna Cuyabeno, sectores Laguna Grande y río Cuyabeno, se han construido hoteles ecológicos, para atender la demanda turística, los mismos que generan aguas residuales. El Ministerio de Ambiente, responsable de la conservación de la biodiversidad, ha dispuesto la implementación de biodigestores, para el tratamiento de estas aguas. Después de tres años de implementación del sistema, se propone evaluar la calidad de estas aguas, a través del análisis de parámetros físico-químicos: temperatura, conductividad, pH, sulfatos, nitratos y nitritos, detergentes, DQO, DBO5, aceites y grasas; y microbiológicos: coliformes fecales; cuyos resultados fueron comparados con la legislación ambiental vigente: TULSMA “Límites de descarga a un cuerpo de agua dulce”. La toma de muestras se sujetó a lo que establece la Norma INEN 2 169:2013 y se muestreó en la época de alta y de baja pluviosidad. Los resultados determinaron que los biodigestores únicamente cumplen la norma en tres parámetros: nitratos y nitritos; sulfatos y temperatura; e incumplen la norma en: DBO5, DQO y pH; mientras que en los cuatro parámetros restantes, existe una variación de los resultados. En conclusión todos los biodigestores, incumplen con la normativa, al menos en uno de los parámetros.

In the Cuyabeno Wildlife Reserve near Laguna Grande and Cuyabeno river, several ecological hotels have been built to meet the touristic demand; therefore these eco-lodges generate wastewaters. The Ministry of Environment, responsible for biodiversity conservation, has ordered the implementation of biodigesters for the treatment of these waters. After three years of implementing the system, it is proposed to check the quality of these waters, through the analysis of physical-chemical parameters: temperature, conductivity, pH, sulfates, nitrates and nitrites, detergents, COD, BOD5, oils and fats; and microbiological such as faecal coliforms. These results were compared with the current environmental legislation: TULSMA "Limits discharged to a body of fresh water." Sampling was subject to the provisions of standard Regulation INEN 2 169: 2013 and sampled at the time of high and low rainfall. The results determined that biodigesters only meet the standard regulations in three parameters: nitrates and nitrites; sulfates and temperature; and violate the following regulations: BOD5, COD and pH; while in the remaining four parameters, there is a variation among the results. In conclusion all digesters violate the regulations, at least on one of the parameters., En la Reserva de Producción de Fauna Cuyabeno, sectores Laguna Grande y río Cuyabeno, se han construido hoteles ecológicos, para atender la demanda turística, los mismos que generan aguas residuales. El Ministerio de Ambiente, responsable de la conservación de la biodiversidad, ha dispuesto la implementación de biodigestores, para el tratamiento de estas aguas. Después de tres años de implementación del sistema, se propone evaluar la calidad de estas aguas, a través del análisis de parámetros físico-químicos: temperatura, conductividad, pH, sulfatos, nitratos y nitritos, detergentes, DQO, DBO5, aceites y grasas; y microbiológicos: coliformes fecales; cuyos resultados fueron comparados con la legislación ambiental vigente: TULSMA “Límites de descarga a un cuerpo de agua dulce”. La toma de muestras se sujetó a lo que establece la Norma INEN 2 169:2013 y se muestreó en la época de alta y de baja pluviosidad. Los resultados determinaron que los biodigestores únicamente cumplen la norma en tres parámetros: nitratos y nitritos; sulfatos y temperatura; e incumplen la norma en: DBO5, DQO y pH; mientras que en los cuatro parámetros restantes, existe una variación de los resultados. En conclusión todos los biodigestores, incumplen con la normativa, al menos en uno de los parámetros.

Oligodendroglioma is characterized by unique clinical, pathological, and genetic features. Recurrent losses of chromosomes 1p and 19q are strongly associated with this brain cancer but knowledge of the identity and function of the genes affected by these alterations is limited. We performed exome sequencing on a discovery set of 16 oligodendrogliomas with 1p/19q co-deletion to identify new molecular features at base-pair resolution. As anticipated, there was a high rate of IDH mutations: all cases had mutations in either IDH1 (14/16) or IDH2 (2/16). In addition, we discovered somatic mutations and insertions/deletions in the CIC gene on chromosome 19q13.2 in 13/16 tumours. These discovery set mutations were validated by deep sequencing of 13 additional tumours, which revealed seven others with CIC mutations, thus bringing the overall mutation rate in oligodendrogliomas in this study to 20/29 (69%). In contrast, deep sequencing of astrocytomas and oligoastrocytomas without 1p/19q loss revealed that CIC alterations were otherwise rare (1/60; 2%). Of the 21 non-synonymous somatic mutations in 20 CIC-mutant oligodendrogliomas, nine were in exon 5 within an annotated DNA-interacting domain and three were in exon 20 within an annotated protein-interacting domain. The remaining nine were found in other exons and frequently included truncations. CIC mutations were highly associated with oligodendroglioma histology, 1p/19q co-deletion, and IDH1/2 mutation (p < 0.001). Although we observed no differences in the clinical outcomes of CIC mutant versus wild-type tumours, in a background of 1p/19q co-deletion, hemizygous CIC mutations are likely important. We hypothesize that the mutant CIC on the single retained 19q allele is linked to the pathogenesis of oligodendrogliomas with IDH mutation. Our detailed study of genetic aberrations in oligodendroglioma suggests a functional interaction between CIC mutation, IDH1/2 mutation, and 1p/19q co-deletion.

Epigenetic silencing of the MGMT gene through promoter methylation correlates with improved survival in Glioblastoma Multiforme (GBM) patients receiving concurrent chemoradiotherapy. Although the clinical benefit is primarily seen in patients with methylated MGMT promoter, some unmethylated patients also respond to Temozolomide. One possible explanation may be intratumoral heterogeneity. This study was designed to assess the methylation status of the MGMT promoter in different areas of GBM and determine if methylation status varied depending on the fixation technique (paraffin-embedding versus fresh frozen) used to store tissue. Using intraoperative navigation, biopsies were obtained from three distinct regions: the enhancing outer area, the non-enhancing inner core, and an area immediately outside the enhancing region. Only patients with GBM were included for evaluation and analysis. Samples taken from each area were divided with half stored by flash freezing and the other half stored using paraffin fixation. Methylation Specific-PCR (MS-PCR) was used for analysis of MGMT promoter methylation. Thirteen patients were included. Ten were male with a median age of 62 years. In each patient, samples were taken from the enhancing rim and the necrotic centre. However, it was not considered safe or feasible to obtain samples from the area immediately adjacent to the enhancing tumor rim in one case. All patients were homogeneous for methylation status throughout their tumor and tissue taken adjacent to it when frozen tissue was used. However, four patients had discrepancies in the MGMT promoter status between the frozen and paraffin-embedded blocks and one patient was not homogeneous within the tumor when paraffin-embedded tissue was used. MGMT promoter methylation status was homogeneous in all GBM tumors. Our observation that methylation status varied depending if the DNA was extracted from paraffin-embedded versus frozen tissue is concerning. Although the reason for this is unclear, we postulate that the timing from resection to fixation or the process of fixation itself may potentially alter methylation status in paraffin-embedded tumors.

Objective. A multidisciplinary approach is increasingly used in NeuroOncology clinics. Although this model has several advantages, patients report feeling overwhelmed by the complexity of their treatment protocol and staff feel rushed because each provider must evaluate the patient within the limited clinic hours. We hypothesized that the presence of a pharmacist in clinic could address these concerns by (1) reviewing all treatment protocols and side-effect management with patients, (2) being available to address questions outside of clinic and (3) answering staff related medication questions. Methods. The pharmacist met with consenting patients at the initial clinic visit and followed up by telephone two additional times. The pharmacist was available to answer questions outside of clinic hours. Surveys were developed and given to patient and staff to evaluate their experience. Results. Over 4 months, 13 patients were enrolled. The pharmacist interacted with each patient an average of 9 times with 55% of interactions occurring outside scheduled visits and two-thirds of pharmacist interventions directly involving patient care. A total of 85% of patients and staff responded to the evaluation survey and 90% of respondents indicated that the pharmacist should remain part of the NeuroOncology team. Patients reported less stress related to their treatment and clinical staff experienced improved clinical efficiency directly as a result of the presence of the pharmacist. Conclusion. Based on these results, a clinical pharmacist should become a permanent member of the outpatient NeuroOncology clinic. J Oncol Pharm Practice (2009) 15: 79—85.

To determine the response rate, time to disease progression, survival, and toxicity of intravenous carboplatin and chronic oral high-dose tamoxifen in patients with recurrent malignant gliomas. Patients with histological confirmation of recurrent malignant gliomas were eligible for this multicenter phase II trial. Treatment consisted of 400 mg/m2 carboplatin intravenously every 4 weeks and oral high dose chronic tamoxifen (80 mg bid in women and 100 mg bid in men). Twenty seven patients met the eligibility criteria and were evaluable for response. The histological subtypes were: 16 (59%) glioblastoma multiforme (GBM), malignant astrocytoma (5 patients), malignant mixed glioma (5 patients), and glioblastoma/gliosarcoma (1 patient). Twenty-two patients (82%) had an ECOG performance status of 0 or 1. No complete responses were observed, 4 patients (15%) achieved a partial response, and 14 patients (52%) had stable disease. Median time to progression was 3.65 months (95%CI 2.56, 4.83). Median overall survival was 14.09 months (95%CI 7.06, 19.91). One patient with a recurrent GBM had a sustained partial response and is progression free 81 months since starting treatment. Another patient with mixed malignant oligoastrocytoma also had a prolonged partial response (lasting 63 months) and is alive 84 months after treatment for recurrence. The most frequently reported grade 3 or 4 toxicities were fatigue (19%), nausea (11%) and anorexia (11%). Carboplatin and high dose tamoxifen has similar response rates to other regimens for recurrent malignant gliomas and are probably equivalent to those found using tamoxifen as monotherapy. Long-lasting periods of disease free survival in some patients (particularly those with malignant mixed oligo astrocytomas) were found.

Meningiomas are usually cured by surgical resection. However, approximately 10% are characterized by more aggressive clinical behavior and higher risk of recurrence. Typically, recurrent meningiomas require further surgical resection followed, in some cases, by radiotherapy. To date, no chemotherapeutic agent has proven to be effective in either preventing or treating recurrence. The alkylating chemotherapeutic agent, Temozolomide (TMZ) has shown to increase overall survival in patients with glioblastoma (GBM) but its effectiveness for other types of brain tumor is less known. The clinical benefit of TMZ seems to be limited to those GBM tumors with promoter methylation of the MGMT gene. In this study, we assessed if a biologic rationale exists to support the use of TMZ as a treatment for meningiomas by assessing the MGMT promoter methylation status in these tumors using methylation specific PCR. We investigated the MGMT promoter methylation status in 36 tumors (32 newly diagnosed; 4 recurrent). Histologically, the majority were grade I. Patients were primarily female (64%) with a mean age of 52. None of the meningiomas in our series showed MGMT gene promoter methylation. Based on these data, we conclude that there is no biological rational to suggest that TMZ might have significant anti-meningioma activity.

Treatment for newly diagnosed anaplastic oligodendroglial tumors is controversial. Radiotherapy (RT) alone and in combination with chemotherapy (CT) are the most well studied strategies. However, CT alone is often advocated, especially in cases with 1p19q codeletion. We retrospectively identified 1013 adults diagnosed from 1981-2007 treated initially with RT alone (n = 200), CT + RT (n = 528), CT alone (n = 201), or other strategies (n = 84). Median overall survival (OS) was 6.3 years and time to progression (TTP) was 3.1 years. 1p19q codeletion correlated with longer OS and TTP than no 1p or 19q deletion. In codeleted cases, median TTP was longer following CT + RT (7.2 y) than following CT (3.9 y, P = .003) or RT (2.5 y, P < .001) alone but without improved OS; median TTP was longer following treatment with PCV alone than temozolomide alone (7.6 vs. 3.3 y, P = .019). In cases with no deletion, median TTP was longer following CT + RT (3.1 y) than CT (0.9 y, P = .0124) or RT (1.1 y, P < .0001) alone; OS also favored CT + RT (median 5.0 y) over CT (2.2 y, P = .02) or RT (1.9 y, P < .0001) alone. In codeleted cases, CT alone did not appear to shorten OS in comparison with CT + RT, and PCV appeared to offer longer disease control than temozolomide but without a clear survival advantage. Combined CT + RT led to longer disease control and survival than did CT or RT alone in cases with no 1p19q deletion. Ongoing trials will address these issues prospectively.

This study aimed to evaluate the impact of hemoglobin level on clinical outcome (local response, progression-free survival, and overall survival) in patients with carcinoma of the anal canal treated with definitive chemoradiotherapy.This is a retrospective study of patients with anal cancer treated between 1992 and 2005 with definitive chemoradiotherapy at Tom Baker Cancer Centre. Patient treatment, laboratory, and outcome data were extracted from the chart.Seventy-two patients treated with definitive chemoradiotherapy were identified. The median age was 56 years, the male-to-female ratio was 1:2, and the median tumor size was 3.5 cm. At 6 weeks after the completion of chemoradiotherapy, 62% of patients (38/61) had complete clinical response, and 34% (21/61) had achieved a partial clinical response. At 3 months after treatment, complete clinical response was observed in 78% (49/63) and a partial response in 16% (10/63). The median pretreatment hemoglobin level was 138.5 g/L, and the median on-treatment hemoglobin level was 129 g/L. Distant relapse was associated with hemoglobin levels in the lowest quartiles, pretreatment and on-treatment (P = .007 and P = .008, respectively). Hemoglobin levels were not associated with response at 6 weeks or 3 months. A pretreatment hemoglobin level of130 g/L was associated with worse progression-free and overall survival (P.0001, both). A hemoglobin on-treatment level of121 g/L was associated with progression-free and overall survival (P.0001 and P = .019, respectively), when stratified by gender.Hemoglobin status was correlated with progression-free and overall survival, and distant relapse, but not clinical response, in patients with carcinoma of the anal canal treated with chemoradiotherapy. The clinically relevant cut point, and the value of correcting hemoglobin levels before or during treatment, remains to be elucidated.

Introduction:Chemoradiotherapy followed by monthly temozolomide (TMZ) is the standard of care for patients with glioblastoma multiforme (GBM). Case reports have identified GBM patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression.Methods:We retrospectively evaluated the incidence of radiographic pseudoprogression in a population-based cohort of GBM patients and determined its relationship with outcome and MGMT promoter methylation status.Results:Out of 43 evaluable patients, 25 (58%) exhibited radiographic progression on the first MRI after concurrent treatment. Twenty of these went on to receive adjuvant TMZ, and subsequent investigation demonstrated radiographic pseudoprogression in 10 cases (50%). Median survival (MS) was better in patients with pseudoprogression (MS 14.5 months) compared to those with true radiologic progression (MS 9.1 months, p=0.025). The MS of patients with pseudoprogression was similar to those who stabilized/responded during concurrent treatment (p=0.31). Neither the extent of the initial resection nor dexamethasone dosing was associated with pseudoprogression.Conclusions:These data suggest that physicians should continue adjuvant TMZ in GBM patients when early MRI scans show evidence of progression following concurrent chemoradiotherapy, as up to 50% of these patients will experience radiologic stability or improvement in subsequent treatment cycles.

In glioblastoma (GBM), promoter methylation of the DNA repair gene MGMT is associated with benefit from chemotherapy. Because MGMT promoter methylation status can not be determined in all cases, a surrogate for the methylation status would be a useful clinical tool. Correlation between methylation status and magnetic resonance imaging features has been reported suggesting that non-invasive MGMT promoter methylation status detection is possible. In this work, a retrospective analysis of T2, FLAIR and T1-post contrast MR images in patients with newly diagnosed GBM is performed using L1-regularized neural networks. Tumor texture, assessed quantitatively was utilized for predicting the MGMT promoter methylation status of a GBM in 59 patients. The texture features were extracted using a space-frequency texture analysis based on the S-transform and utilized by a neural network to predict the methylation status of a GBM. Blinded classification of MGMT promoter methylation status reached an average accuracy of 87.7%, indicating that the proposed technique is accurate enough for clinical use.

In glioblastoma (GBM), promoter methylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT) is associated with benefit from chemotherapy. Correlations between MGMT promoter methylation and visually assessed imaging features on magnetic resonance (MR) have been reported suggesting that noninvasive detection of MGMT methylation status might be possible. Our study assessed whether MGMT methylation status in GBM could be predicted using MR imaging. We conducted a retrospective analysis of MR images in patients with newly diagnosed GBM. Tumor texture was assessed by two methods. First, we analyzed texture by expert consensus describing the tumor borders, presence or absence of cysts, pattern of enhancement, and appearance of tumor signal in T2-weighted images. Then, we applied space-frequency texture analysis based on the S-transform. Tumor location within the brain was determined using automatized image registration and segmentation techniques. Their association with MGMT methylation was analyzed. We confirmed that ring enhancement assessed visually is significantly associated with unmethylated MGMT promoter status (P=0.006). Texture features on T2-weighted images assessed by the space-frequency analysis were significantly different between methylated and unmethylated cases (P

Background:The purpose of this study was to determine incidence, survival rate, and prognostic factors as well as the frequency of Collins’ Law Violators (CLVs) in an unselected population of medulloblastoma patients. Collins’ Law dictates that ’cure’ of a child with a tumor occurs after a period that includes the child’s age at diagnosis plus 9 months.Methods:Using the Alberta Cancer Registry a population-based review identified 49 patients with medulloblastoma (19 adults, 30 children) diagnosed from 1975-96. Pathology was reviewed in all cases. All patients had surgical resection, followed by radiotherapy in 47 patients and chemotherapy in 17.Results:The overall 5-year survival was 50%. There was a trend for the extent of resection to be associated with a longer survival (Long rank test, p< 0.06) but this was not significant. Tumor recurrence occurred a median of 22.4 months (range, 6.4-192.3) after diagnosis and median survival after recurrence was 9.3 months (range, 0.4-64.9). The survival curve did not appear to plateau but was affected by tumor-related deaths in 3 (21.4%) of the 21 long-term survivors diagnosed in childhood. These three patients had recurrences a mean of 11.7 years after diagnosis and are designated as CLVs.Conclusions:The survival rate in an unselected population of patients with medulloblastoma is poor. Aggressive resection of the tumors prolongs survival. The Collins’ Law Violators were relatively common and we suggest this concept be abandoned in medulloblastoma.

Background: Some patients with low-grade glioma have extraordinarily long survival times; current, early treatment does not prolong their lives. For this reason, therapies that sometimes have neurologic side effects are often deferred intentionally. Methods: In a study of oligodendrogliomas, we used a quantitative method of MR analysis based on the S-transform to investigate whether codeletion of chromosomes 1p and 19q, a marker of good prognosis, could be predicted accurately by measuring image texture. Results: Differences in texture were seen between tumors with codeletion of chromosomes 1p and 19q and those with intact 1p and 19q alleles on contrast-enhanced T1-weighted and T2-weighted MR images. Quantitative MR texture on T2 images predicted codeletion of chromosomes 1p and 19q with high sensitivity and specificity. Conclusions: This new method of MR image interpretation may have the potential to augment the diagnostic assessment of patients with suspected low-grade glioma.

Reovirus is an oncolytic virus with activity in in vivo models of malignant gliomas (MGs). The primary aims were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of intratumoral administration of reovirus in patients with recurrent MGs. Response, survival, and time to progression (TTP) were secondary aims. Patients were adults, had Karnofsky Performance scoreor = 60, received prior radiotherapy with or without chemotherapy, and had up to the third recurrence of MG. Reovirus was administered intratumorally stereotactically at 1 x 10(7), 1 x 10(8), or 1 x 10(9) tissue culture infectious dose 50 (TCID50) in a volume of 0.9 ml. Twelve patients were treated at three dose levels (3, 6, and 3 patients, respectively). Seven were men, median Karnofsky Performance score was 80, and median age was 53.5 years. There were no grade III or IV adverse events (AEs) definitely or probably related to treatment. Ten patients had tumor progression, one had stabilization, and one was not evaluable for response. Median survival was 21 weeks (range, 6-234), and one is alive 54 months after treatment. Median TTP was 4.3 weeks (range, 2.6-39). An MTD was not reached. The intratumoral administration of the genetically unmodified reovirus was well tolerated using these doses and schedule, in patients with recurrent MG.

Introduction Elderly patients have glioblastomas (GBM) that are aggressive and poorly responsive to treatment. They are also prone to the side effects of treatment of GBM. Methods To shed light on the treatment of elderly patients with GBM, we reviewed the treatment toxicities and survival of patients 65 years of age or older who were treated with chemoradiotherapy, which is the new standard of care for GBM in younger patients. Results Thirty-nine patients at a single cancer center in Canada met the eligibility criteria for this retrospective study. Nineteen patients were treated initially with TMZ and radiotherapy and 20 others were treated with radiotherapy alone (only two had TMZ subsequently). Eight patients in the chemoradiotherapy group (42%) experienced Grade III or IV toxicity versus none in the radiotherapy group. The median overall survival in the chemoradiotherapy group was 8.5 months (range, 2.0–24.7 months) versus 5.2 months (range, 1.5–14.2 months) in the radiotherapy group, an apparent benefit which may have been due to an imbalance in age at diagnosis, extent of resection and performance status. In this series of GBM cases, methylation of the MGMT gene promoter was not associated with longer survival, either overall, or within the chemoradiotherapy treated subset. Conclusions Elderly patients with GBM treated with chemoradiotherapy can be expected to experience significant toxicity. Large randomized trials will be necessary to determine whether chemoradiotherapy prolongs the survival of elderly patients and whether MGMT promoter status predicts benefit from temozolomide in this subset of patients.

Introduction: BRCA1 expression is downregulated in a third of sporadic breast cancers (SBC). Most of the tumors in which BRCA1 function is diminished do not express estrogen receptor alpha (ER). Recent studies suggest that the inhibitor of DNA binding (ID)-4 could participate in the hormonal regulation of BRCA1 expression. Objective: To study the relationship between tumoral expression of BRCA1, ER and ID4 in SBCs. Patients and methods: Forty patients with pathologic confirmation of SBC were included in this study. The mRNA expression of BRCA1, ER and ID4, determined by reverse transcription and polymerase chain reaction (RT-PCR), was correlated with the expression of gliceraldehid-3-phosphate-dehydrogenase (GAPDH). The results were analyzed using two-sided nonparametric tests (Chi-square and Spearman’s rank correlation test) with α < 0.05. Results: Most of the tumors that expressed BRCA1 mRNA were ER-positive (p < 0.0001). In addition, a positive correlation was observed between the level of expression of these mRNAs (rs = 0.75 95% CI = 0.57-0.86; p < 0.0001). An inverse association was observed between the mRNA expression of BRCA1 and ID4 (p = 0.024) and a negative correlation between their levels of expression (rs = -0.35 95% CI -0.59 a -0.04; p = 0.028). Moreover, a negative correlation was stated between the level mRNAs of ER and ID4 (rs = - 0.45 95% CI -0.66 a -0.16; p = 0.0039). Discussion: In this study we demonstrate an association between the tumoral expression of BRCA1, ER and ID4 in patients with SBC. These results are in concordance with previous studies, however, to our knowledge, no other reports have described a relationship between the expression of ID4 and ER at the mRNA level in human breast cancers. These results suggest that ID4 participates in the molecular events that regulate BRCA1 and ER expression, suggesting its role as a tumor marker or potential therapeutic target.

425 Background: HPV status is an important prognostic factor for outcome in head and neck cancers, with improved survival noted in HPV-positive vs -negative tumors. However, this effect has not been studied in anal cancer. Challenges exist in defining reliable and methods of detecting the presence of high-risk HPV virus or the expression of HPV-related proteins. Purpose: To determine p16 expression and HPV16 status, in association with HPV subtyping, in pre-treatment anal cancers, and to correlate marker status with clinical outcome. Methods: This retrospective study evaluated anal cancer patients treated between 1992-2005 with definitive RT or CRT at a single institution (Tom Baker Cancer Centre, Calgary, Canada). HPV subtyping, p16 protein expression via conventional immunohistochemistry (IHC) and automated quantitative IHC (AQUA), and HPV16 in-situ hybridization (CISH) was performed in a subset of patient tumors with sufficient pretreatment tumor specimen. The correlation between results using these different techniques and association of HPV markers with clinical outcome was evaluated. Results: 89 patients were identified; M:F 1:2; median age 57 years. Median tumor size was 3.5 cm. All patients were treated with radical external beam RT with curative intent; 81% received concurrent chemotherapy. Clinical CR was observed in 73% of patients at 3 months post-treatment. Median OS was 82 months. Of tumor specimens analyzed for HPV subtype, 78% (28/36) were HPV16. Using conventional IHC (DAB), 80% (28/35) of tumors over-expressed p16 (score 3). HPV16 CISH was positive in 81% (34/42). P16 AQUA™ score correlated with HPV16 subtyping, CISH for HPV16, and p16 DAB. With HPV16 subtyping as the gold standard for HPV16 infection, false positive and false negative rates were 8% and 4% with DAB, and 10% and 13% with CISH. In univariate analysis only p16 AQUA score > 244 (upper 15%) was associated with PFS (p= 0.006-95% CI 8.4 [1.8-38.6]) and OS (p= 0.013-95% CI 4.5 [1.4-15]). Conclusions: p16 expression via quantitative IHC correlates with other methods, including HPV16 subtyping, and appears more reliable for defining HPV16 status than CISH. Only quantitative IHC identified a subset of patients with worse outcome. No significant financial relationships to disclose.

2054 Background: Elderly patients have glioblastomas (GBM) that are aggressive and poorly responsive to treatment. They are also prone to the side effects of treatment of GBM. Methods: To shed light on the treatment of elderly patients with GBM, we reviewed the treatment toxicities and survival of patients 65 years of age or older who were treated with chemoradiotherapy, which is the new standard of care for GBM in younger patients. Results: Thirty-nine patients at a single cancer center in Canada met the eligibility criteria for this retrospective study. Nineteen patients were treated initially with TMZ and radiotherapy and 20 others were treated with radiotherapy alone (only two had TMZ subsequently). Eight patients in the chemoradiotherapy group (42%) experienced grade III or IV toxicity versus none in the radiotherapy group. The median overall survival in the chemoradiotherapy group was 8.5 months (range, 2.0–24.7 months) versus 5.2 months (range, 1.5–14.2 months) in the radiotherapy group, an apparen...

Background:Leptomeningeal disease (LMD) is a late complication of malignant glioma, mostly of glioblastoma, that usually responds poorly to treatment and is rapidly fatal. A long surviving case led us to review our experience with LMD in patients with oligodendrogliomas.Methods:A 15-year retrospective chart review was performed. Patients with both oligodendroglial tumors and LMD were identified. A single neuro-pathologist reviewed all histological sections, a single neuro-radiologist reviewed all available images and lp/19q status was assessed.Results:Seven out of 145 patients with oligodendroglioma were diagnosed with LMD. Six were male. Median age at tumor diagnosis was 41 years (range, 28-50). None had radiographic or pathological evidence of leptomeningeal or subependymal tumor at initial diagnosis. Most patients had pure anaplastic oligodendrogliomas (4/7); 6/7 had 1p/19q co-deletion. The median time to first relapse was 41 months (range, 19-127). The median time to LMD was 76 months (range, 19-151) from initial diagnosis and 28 months (range, 0-36) from first relapse, respectively. Leptomeningeal disease treatments included spinal radiation and intrathecal and systemic chemotherapy. After progression, some patients with LMD remained stable clinically. The median survival from initial diagnosis was 104 months (range, 19-183) and from LMD diagnosis was 32 months (range, 2-43).Conclusion:Leptomeningeal disease is a complication of oligodendroglioma that may occur preferentially in long surviving patients with 1p/19q co-deletion. Leptomeningeal disease in patients with oligodendrogliomas appears to be relatively indolent which may have implications for their treatment and be related to 1p/19q status.

1563 Background: Reovirus is an oncolytic virus which replicates preferentially in transformed cells possessing activated Ras signaling pathways. Promising activity was found in in vivo models of MGs and in a phase I trial in patients (pts.) with cutaneous metastases from systemic cancer. We performed this dose-escalation trial of i.t. administration of reovirus to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in pts. with recurrent MG. Response, survival and time to progression (TTP) were secondary aims. Methods: Pts. were ≥ 18 yrs old, had a KPS ≥ 60, received prior radiotherapy ± chemotherapy, a histologically proven recurrence of MG and recurred ≤ 3 times. Reovirus was administered i.t. stereotactically at one of three dose levels (1 × 107, 1 × 108 or 1 × 109 TCID50) in a volume of 0.9 mls. Results: Twelve pts. were treated at 3 dose levels; seven were men, the median (mdn) KPS was 80, mdn age was 53.5 yrs, 10 had glioblastoma multiforme, one anaplastic astrocytoma and another anaplastic oligoastrocytoma. There were the 1st, 2nd or 3rd recurrences in 6, 5 and 1 pts., respectively. During i.t. viral administration all pts. were treated with prophylactic anticonvulsants and 6 (50%) were receiving corticosteroids. The 1st, 2nd and 3rd cohorts contained 3, 6 and 3 pts., respectively. There were no grade 3 or 4 adverse events definitely or probably related to the administration of reovirus. A transient increase in GGT was possibly related to reovirus administration and a patient experienced grade 3 motor weakness that could be related to post-injection edema. Viral shedding and systemic immune responses were examined but results are pending. There were no CR, or PR; a pt. had SD, 10 PD and one was not evaluable. The mdn survival was 20 weeks (range, 6–171), 6 pts. survived > 6 months and 3 are alive 6, 7 and 40 months from the reovirus injection. The mdn TTP was 4.3 weeks (range: 3.4–39). Conclusions: A MTD was not reached. The intratumoral administration or reovirus was well tolerated in patients with recurrent MGs. Phase 2 studies in MGs are planned. [Table: see text]

In this population-based study, we determined the frequency and clinical characteristics of leptomeningeal disease (LMD) developing in the context of oligodendroglial tumors (oligodendrogliomas and oligoastrocytomas). LMD occurred in only 3.9% (8/204) of oligodendroglial tumors and in patients with more recurrences [mean 2.88 vs. 1.27 in LMD and non-LMD, respectively (p = 0.001)]. In contrast to LMD from systemic solid tumors, the median survival following the diagnosis of LMD in oligodendroglial tumors was surprisingly long at 22 months (95% CI 11–33 months). Treatment with oral chemotherapy seemed as effective as more aggressive treatments (e.g. repeat RT or intrathecal chemotherapy) in these patients.