Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols.

BACKGROUND: To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy. METHODS: This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy. RESULTS: Out of 65 patients with a median age at diagnosis of 8.7 years (0.6-20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2-95.5) and 89.1% (95% CI: 78.4-94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS. CONCLUSIONS: Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.

From Personalized to Precision Medicine in Oncology: A Model-Based Dosing Approach to Optimize Achievement of Imatinib Target Exposure.

Imatinib is a targeted cancer therapy that has significantly improved the care of patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). However, it has been shown that the recommended dosages of imatinib are associated with trough plasma concentration (Cmin) lower than the target value in many patients. The aims of this study were to design a novel model-based dosing approach for imatinib and to compare the performance of this method with that of other dosing methods. Three target interval dosing (TID) methods were developed based on a previously published PK model to optimize the achievement of a target Cmin interval or minimize underexposure. We compared the performance of those methods to that of traditional model-based target concentration dosing (TCD) as well as fixed-dose regimen using simulated patients (n = 800) as well as real patients' data (n = 85). Both TID and TCD model-based approaches were effective with about 65% of Cmin achieving the target imatinib Cmin interval of 1000-2000 ng/mL in 800 simulated patients and more than 75% using real data. The TID approach could also minimize underexposure. The standard 400 mg/24 h dosage of imatinib was associated with only 29% and 16.5% of target attainment in simulated and real conditions, respectively. Some other fixed-dose regimens performed better but could not minimize over- or underexposure. Model-based, goal-oriented methods can improve initial dosing of imatinib. Combined with subsequent TDM, these approaches are a rational basis for precision dosing of imatinib and other drugs with exposure-response relationships in oncology.

Stability of a high-concentrated aqueous solution of idarubicin stored in a polypropylene syringe for transarterial chemoembolization.

Idarubicin (IDA) is an antineoplasic drug commonly used to treat hematologic diseases. Because of its relative lipophilic properties, this anthracycline is also used in transarterial chemoembolization (TACE) as part of hepatocellular carcinoma (HCC) treatment. But TACE requires injected volume to be reduced to restrict systemic diffusion and side effects. The aim of this study was to determine the stability of a highly concentrated aqueous solution of IDA, stored in polypropylene syringes between 2 °C and 8 °C. Analyses were performed with an HPLC system combined with UV detector and mass spectrometer. Forced degradation was used to investigate potential degradation products. This study demonstrated 7 days of stability after storage in previously mentioned conditions. This conservation is long enough to anticipate drug preparation and facilitates pharmacy organization.

Monographic consultation of onconephrology. Rationale and implementation.

The increase in demand for medical care for renal complications associated with neoplastic diseases is a reality in most nephrology departments. In response to this overall situation, the creation of healthcare models such as monographic consultations and develop training programs in Onconephrology could improve the care of these patients. Through an exploratory and descriptive study, we identified current situation of kidney involvement in cancer patients. The objective of the present study is to establish the criteria for specific assistance in the field of Onconephrology. For this, we have reviewed key aspects and analyzed the current situation in our country, through a survey addressed to all nephrologists through the Spanish Society of Nephrology., together with the experience of two Spanish centers. From this information, we have established some requirements and recommendations for the start-up of these consultations.

Monographic consultation of onconephrology. Rationale and implementation. / Consulta monográfica de onconefrología. Justificación y puesta en marcha.

The increase in demand for medical care for renal complications associated with neoplastic diseases is a reality in most nephrology departments. In response to this overall situation, the creation of healthcare models such as monographic consultations and develop training programs in onconephrology could improve the care of these patients. Through an exploratory and descriptive study, we identified current situation of kidney involvement in cancer patients. The objective of the present study is to establish the criteria for specific assistance in the field of onconephrology. For this, we have reviewed key aspects and analyzed the current situation in our country, through a survey addressed to all nephrologists through the Spanish Society of Nephrology, together with the experience of 2 Spanish centers. From this information, we have established some requirements and recommendations for the start-up of these consultations.

Aplasia pura adquirida crônica da série vermelha secundária à quimioterapia em paciente com adenocarcinoma endometrioide invasivo / Chronic acquired pure aplasia of the red series secondary to chemotherapy in a patient with invasive endometrioid adenocarcinoma

O presente relato de caso descreve a apresentação atípica de uma paciente com adenocarcinoma endometrioide invasivo que evoluiu com aplasia pura adquirida crônica da série vermelha secundária à quimioterapia. Paciente de 71 anos, sexo feminino, procurou atendimento médico por quadro de metrorragia com três meses de evolução. A curetagem uterina evidenciou adenocarcinoma endometrioide invasor moderadamente diferenciado. Iniciou-se uma abordagem com esquema quimioterápico composto por Carboplatina e Paclitaxel interrompido ao quinto ciclo para evitar progressão de aplasia medular constatada por biópsia de medula óssea. A possível hematotoxicidade do protocolo Paclitaxel e Carboplatina foi observada na conduta terapêutica da paciente, por sua progressão para uma apresentação atípica de aplasia pura adquirida crônica da série vermelha após administração desta associação de drogas.

The present case report describes the atypical presentation of a patient with invasive endometrioid adenocarcinoma that evolved with chronic acquired pure aplasia of the red series secondary to chemotherapy. A seventy-one-yearold patient, female, sought medical care for a three-month-old metrorrhagia evolution. The uterine curettage showed moderately differentiated invasive endometrioid adenocarcinoma. It was initiated an approach with chemotherapy regimen consisting of Carboplatin and Paclitaxel interrupted at the fifth cycle to prevent progression of spinal aplasia found by bone marrow biopsy. The possible hematoxicity of the patient, for its progression to an atypical presentation of chronic acquired aplasia of the red series after administration of this combination of drugs.

Aflibercept in Combination With FOLFIRI as First-line Chemotherapy in Patients With Metastatic Colorectal Cancer (mCRC): A Phase II Study (FFCD 1302).

BACKGROUND: FOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line. PATIENTS AND METHODS: Patients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H0: 55% and H1= 75%. Data were analyzed in intention to treat. RESULTS: Forty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification. CONCLUSION: Although the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction.

In vitro and computational studies of natural products related to perezone as anti-neoplastic agents.

Many natural phyto-products as perezone (Per) exhibit anti-cancer activities. Using experimental and computational studies, it was described that Poly ADP-ribose polymerase 1(PARP-1) inhibition and the induction of oxidative stress state explain the pro-apoptotic activity of Per. The aim of this study was to evaluate two phyto-products related to Per as anti-cancer agents: hydroxyperezone (OHPer) and its monoangelate (OHPer-MAng). These molecules were structurally characterized employing thermal analysis, IR spectrophotometry and X-ray diffraction techniques. The phyto-compounds evaluated in vitro in six cancer cell lines (K562, MCF-7, MDA-MB-231, HeLa, U373, A549) and non-malignant cells determinate their cytotoxicity, type of induced cell death, ability to avoid cell migration and changes at the redox status of the cell. Using, in vitro and computational studies provided the inhibition of PARP-1 and its potential binding mode. Cell proliferation assays demonstrated that OHPer-MAng treatment significantly induces apoptosis in triple negative breast cancer (TNBC) cell line (MDA-MB-231 IC50 = 3.53 µM), being particularly less cytotoxic to Vero cells (IC50 = 313.92 µM), human lymphocytes (IC50 = 221.46 µM) and rat endothelial cells (IC50=> 400 µM). The treatment of MDA-MB-231 cells with OHPer-MAng showed inhibition of migration by cancer cells. The induction of an oxidative stress state, similar to other quinones and PARP-1 inhibition explains the pro-apoptotic activity of OHPer-MAng. Docking studies showed that OHPer-MAng establishes great non-bonding interactions with the lateral chains of Tyr235, Hys201, Tyr246, Ser203, Asn207, and Gly233 located at the catalytic site of PARP-1, also demonstrating the anti-cancer activity of OHPer-MAng in TNBC cell line.

Oral health status before, during and after antineoplastic treatment at a cancer institute in Barranquilla, Colombia / Estado de salud oral antes, durante y después del tratamiento antineoplásico en un instituto de cáncer en Barranquilla, Colombia

Chemotherapy and radiotherapy are aggressive treatments for cancer management. Both therapies make the stomatogatic system vulnerable to adverse effects on the oral mucosa and hard tissues. This may result in severe oral complications that can affect the quality of life of the oncologic patient. Consequently, oral diagnosis and interdisciplinary management by the stomatologist are critical for cancer treatment, regardless of its location. Objective. To determine the oral health status of cancer patients before, during and after antineoplastic treatment at a cancer institute in the city of Barranquilla, Colombia. Materials and Methods. A descriptive, longitudinal and prospective study of 131 cancer patients, was conducted. The study consisted of initial stomatological assessment of the antineoplastic therapy; classification according to the antineoplastic therapy given by the oncologist; a second stomatological assessment during treatment; and a final stomatological assessment or evaluation forty days after the end of therapy. Descriptive statistics, chi-square and MacNemar test were used to compare and identify variances at the different stages. Results. Female patients accounted for 69%, and breast cancer had 24% prevalence among the included subjects. At the initial stomatological assessment, high frequency lesions were identified, such as generalized biofilm-associated gingivitis in 69% of the cases, followed by oral candidiasis in 61%. The specific prevalence of lesions was 10.65%. In the second stomatological assessment, a greater frequency of periodontal abscesses was observed in 31%, and oral mucositis type II in 18%. The third clinical assessment showed significant changes in oral health status; an increase in the frequency of gingivitis was found in 9.9% (p<0.001); unlike before and during, there was an increment in dental caries of 26.73% (p<0.00000) at this last stage, root remains increased by 39.53% (p<0.00000), and finally, xerostomia increased by 45%. Oral candidiasis was the only lesion that showed improvement. Conclusion. An increase in the number of lesions was observed during and after antineoplastic treatment. The oral cavity is susceptible to antineoplastic treatments; gingivitis, candidiasis, xerostomia, and mucositis were observed, among others conditions.

La quimioterapia y la radioterapia son tratamientos agresivos para el manejo del cáncer, producen susceptibilidad en el sistema estomatogático causando efectos adversos en mucosa bucal y tejidos duros. Esto se traduce a complicaciones bucales agresivas, que afectan la calidad de vida del paciente oncologico, por lo que es fundamental el diagnostic bucal y manejo interdisciplinario que incluya el estomatologo en manejo del cáncer, indistintamente de su localizacion. Objetivo. Determinar el estado de salud bucal antes, durante y después del tratamiento antineoplásico en un instituto oncológico de la ciudad de Barranquilla. Materiales y Métodos. Estudio descriptivo prospectivo longitudinal, con una muestra de 131 pacientes con cáncer. Constó de: valoración estomatológica inicial a la terapia antineoplásica, clasificación según la terapia antineoplásica asignada por el oncólogo, una segunda valoración estomatológica durante los tratamientos, y finalmente una última valoración estomatológica cuarenta días de culminadas las terapias. Se empleó estadística descriptiva, chi cuadrado y prueba de MacNemar para comparar e identificar varianzas en las diferentes fases. Resultados. Un 69% eran del género femenino con frecuencia de cáncer de mama en un 24%. A la valoración estomatológica inicial se identificó alta frecuencia de lesiones como gingivitis asociada a biofilm generalizada en un 69%, seguida de candidiasis oral en un 61%. La prevalencia puntual de lesiones fue de 10,65%. En el segundo examen estomatológico se observó mayor frecuencia de abscesos periodontales en un 31% y mucositis oral tipo II en un 18%, entre otras. La tercera valoración clínica mostró cambios significativos en la salud bucal; se encontró un aumento de la frecuencia de gingivitis en un 9,9% (p<0,001) a diferencia del antes y el durante, igualmente para la caries dental se encontró aumentada en un 26,73% (p<0,00000), restos radiculares aumentó en un 39,53% (p<0,00000) y finalmente la xerostomía aumentando en un 45%, entre otras; la única lesión que mostró mejoria fue la candidiasis oral. Conclusión. Se observó un aumento de las lesiones, durante y después del tratamiento antineoplásico. La cavidad oral es susceptible a los tratamientos antineoplásicos, se relacionan con: gingivitis, candidiasis, xerostomía, mucositis entre otras.

Recognition of taste in patients during antineoplastic therapy with platinum drugs.

Taste changes caused by the use of platinum drugs have been described. However, few studies qualify the impaired tastes and whether these changes are derived exclusively from chemotherapy (QTx). AIMS: Evaluation of changes in sweet, sour, salty, bitter, and umami tastes in patients receiving QTx with platinum drugs was the aim of this study. METHODS: A total of 43 subjects, 21 from the study group and 22 from the control, were studied in two time periods, one before the start of QTx (T0) and another after two cycles of QTx (T1). The usual dietary intake, body mass index (BMI), handgrip strength and fatigue (through the fatigue pictogram) were evaluated to characterize the group studied. Taste Strips tests were performed for all 4 tastes and umami was studied by comparing Likert's scale using monosodium glutamate (GMS) food. Statistical analysis was performed using repeated measures (ANOVA), mixed model, with significance level p≤0.05. RESULTS: Salty and sour were the most affected tastes in the study group (p = 0.001 and 0.05); as well as the ionotropic receptors (p = 0.02) responsible for identifying these tastes. There was a difference between the times for BMI, dynamometry and impact in daily activities, by the fatigue pictogram (p = 0.008, 0.009 and 0.006 respectively). CONCLUSION: These findings suggest an important role in altering taste recognition, mainly in salty and sour tastes, identified by ionotropic receptors, which seems to be related to dietary changes. QTx has demonstrated a contribution to impairment of functionality and fatigue.

Quinoline-derivative coordination compounds as potential applications to antibacterial and antineoplasic drugs.

Quinoline-derivative coordination compounds were synthesized with Zn(II), Al(III), Cu(II), Ru(II) producing 1-4 compounds using 5-nitro-8-hydroxyquinoline and 5-8 compounds using 5-chloro-8-hydroxyquinoline. These coordination compounds were characterized by elemental analysis and 1H NMR, IR, UV-Vis and fluorescence spectroscopies, representing the coherent data matched all compounds. Myelotoxicity data, as well as the biochemical data, depicted the compounds have low cytotoxicity towards the blood cells. All coordination compounds displayed slight antimicrobial activity against E. coli, S. aureus, P. aeruginosa and E. faecalis; [RuCl(NO)(5-chloro-8-oxyquinoline)2] compound (8) represent the best result to inhibitions of Gram-positive and Gram-negative bacteria. Antineoplasic action depicted the [Ru(NO)(5-nitro-8-oxyquinoline)2Cl] compound (4) as a potential chemotherapeutic agent against MCF-7 (a breast cancer cell line), compared to cisplatin (Platistine® CS) and cyclophosphamide (Genuxal®) drugs.

Evaluation of the antioxidant potential of Copaifera multijuga in Ehrlich tumor-bearing mice

Copaifera multijuga, commonly known as copaiba, is popularly used in the form of tea for various conditions due to the presence of antioxidant substances in its composition, which protect cells against damage caused by free radicals. Its oleoresin is also used as an anti-inflammatory and antitumoral agent. The present study investigated the antioxidant effect of the ethanolic extract of copaiba stem bark on Swiss mice inoculated with solid Ehrlich tumors. Mice were inoculated subcutaneously with 1x106 Ehrlich's tumor cells and treated via gavage with ethanolic extract of copaiba for thirty days, with doses varying between 100 and 200 mg kg-1. Biochemical analyses of enzymatic antioxidants [superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST)], non-enzymatic antioxidants [reduced glutathione (GSH) and ascorbic acid (ASA)], substances reactive to thiobarbituric acid (TBARS) and protein carbonylation (carbonyl) in different tissues were significantly affected. The extract administered at 200 mg kg-1 presented higher antioxidant capacity in the liver, increased CAT, GST, GSH and decreased TBARS, as well as increased CAT activity and protein carbonylation in brain tissue. The results showed that the copaiba extract was able to reverse the oxidative stress caused by solid Ehrlich tumor, probably due to the presence of antioxidant compounds, and had potential antineoplasic effect after a 30-day treatment. (AU)

Endophytic Fungus Isolated From Achyrocline satureioides Exhibits Selective Antiglioma Activity-The Role of Sch-642305.

Glioblastoma is the most devastating primary brain tumor. Current treatment is palliative, making necessary the development of new therapeutic strategies to offer alternatives to patients. Therefore, endophytes represent an interesting source of natural metabolites with anticancer potential. These microorganisms reside in tissues of living plants and act to improve their growth. Evidence revealed that several medicinal plants are colonized by endophytic fungi producer of antitumor metabolites. Achyrocline satureioides is a Brazilian medicinal plant characterized by its properties against gastrointestinal disturbances, anticancer and antioxidant effects. However, there are no reports describing the endophytic composition of A. satureioides. The present study proposes the isolation of endophytic fungus from A. satureioides, extract preparation, phytochemical characterization and evaluation of its antiglioma potential. Our data showed that crude extracts of endophyte decreased glioma viability with IC50 values of 1.60-1.63 µg/mL to eDCM (dichloromethane extract) and 37.30-55.12 µg/mL to eEtAc (ethyl acetate extract), respectively. Crude extracts induced cell death by apoptosis with modulation of redox status. In order to bioprospect anticancer metabolites, endophytic fungus extracts were subjected to guided fractionation and purification yielded five fractions of each extract. Six of ten fractions showed selective antiproliferative activity against glioma cells, with IC50 values ranged from 0.95 to 131.3 µg/mL. F3DCM (from eDCM) and F3EtAc (from eEtAc) fractions promoted C6 glioma toxicity with IC50 of 1.0 and 27.05 µg/mL, respectively. F3EtAc fraction induced late apoptosis and arrest in G2/M stage, while F3DCM promoted apoptosis with arrest in Sub-G1 phase. Moreover, F3DCM increased antioxidant defense and decreased ROS production. Additionally, F3DCM showed no cytotoxic activity against astrocytes, revealing selective effect. Based on promising potential of F3DCM, we identified the production of Sch-642305, a lactone, which showed antiproliferative properties with IC50 values of 1.1 and 7.6 µg/mL to C6 and U138MG gliomas, respectively. Sch-642305 promoted arrest on cell cycle in G2/M inducing apoptosis. Furthermore, this lactone decreased glioma cell migration and modulated redox status, increasing superoxide dismutase and catalase activities and enhancing sulfhydryl content, consequently suppressing reactive species of oxygen generation. Taken together, these results indicate that metabolites produced by endophytic fungus isolated from A. satureioides have therapeutic potential as antiglioma agent.

[Advances in the management of cervical lymphadenopathies of unknown primary with intensity modulated radiotherapy: Doses and target volumes]. / Évolutions dans la prise en charge des métastases ganglionnaires cervicales sans cancer primitif retrouvé : doses et volumes cibles de la radiothérapie avec modulation d'intensité.

The definition of nodal and/or mucosal target volumes for radiation therapy for lymphadenopathies of unknown primary is controversial. Target volumes may include all nodal areas bilaterraly and be pan-mucosal or unilateral, selective, including the sole oropharyngeal mucosa. This review presents current recommendations in light of changes in the TNM classification, Human papillomavirus status and therapeutic advances. We conducted a systematic review of the literature with the following keywords: lymphadenopathy; head and neck; unknown primary and radiation therapy. There are no direct comparative studies between unilateral or bilateral nodal irradiation or pan-mucosal and selective mucosal irradiation. Contralateral lymph node failure rates range from 0 to 6% after unilateral nodal irradiation and 0 and 31% after bilateral irradiation. Occurrence of a mucosal primary varies between 0 and 19.2%. Initial clinical presentation and Human papillomavirus status are critical to define mucosal target volumes. Intensity-modulated radiotherapy is recommended (rather than three-dimensional irradiation) to avoid toxicities. Systemic treatments have similar indications as for identified primary head and neck cancers. Failures do not appear superior in case of unilateral nodal irradiation but comparative studies are warranted due to major biases hampering direct comparisons. Human papillomavirus status should be incorporated into the therapeutic strategy and practice-changing TNM staging changes will need to be evaluated.

Is regorafenib providing clinically meaningful benefits to pretreated patients with metastatic colorectal cancer?

Treatment with regorafenib has demonstrated statistically significant improvements in terms of overall survival, progression-free survival and disease control when compared with placebo in pretreated patients with metastatic colorectal cancer in two placebo-controlled, randomized, phase III trials (CORRECT and CONCUR). Similar results were observed in two open-label, single-arm studies (REBECCA and CONSIGN) performed in the real-world setting. But several authors have suggested that the benefit provided by regorafenib may not be clinically meaningful for these patients. Moreover, it has been suggested that not all subgroups of patients might benefit from regorafenib. The intention of this review is to provide an overview of the existing evidence for regorafenib in terms of efficacy, tolerability and quality of life in different subpopulations according to clinical and biological characteristics. Additionally, the magnitude of the clinical benefit provided by regorafenib to these patients has been explored and whether there are poorer outcomes in certain subpopulations.

Glioblastoma: approach to treat elderly patients / Glioblastoma: enfoque no tratamento de pacientes idosos

Treating elderly cancer patients is a challenge for oncologists, especially considering the several therapeutic modalities in glioblastoma. Extensive tumor resection offers the best chance of local control. Adequate radiotherapy should always be given to elderly patients if they have undergone gross total resection and have maintained a good performance status. Rather than being ruled out, chemotherapy should be considered, and temozolomide is the chosen drug. A comprehensive geriatric assessment is a valuable tool to help guiding treatment decisions in elderly patients with glioblastoma.

O tratamento de idosos com câncer é um desafio para a prática oncológica, especialmente no que se refere à terapêutica multimodal do glioblastoma. Nessa população, a ressecção ampla do tumor oferece a melhor chance de controle local e, naqueles pacientes que mantenham um bom performance status, a radioterapia complementar deve sempre ser levada em consideração. A quimioterapia também tem um papel no tratamento, sendo a temozolomida a droga de eleição. Frente à heterogeneidade desses pacientes, uma avaliação geriátrica ampla é um instrumento valioso no auxílio da decisão terapêutica em idosos com glioblastoma.

Early administration of peroxisomicine A1 (T-514 extracted from K. parvifolia seeds) causes necrosis of implanted TC-1 cells without affecting target organs in a murine model / La administración temprana de peroxisomicina A1 (T-514 extraída de las semillas de K. parvifolia)causa necrosis de células TC-1 implantadas sin afectar órganos blanco en un modelo murino

Peroxisomicine A1 (PA1), one of the toxins isolated from seeds of plants of the Karwinskia genus, whose targets organs are the liver, kidney, and lungs. There is a selective toxicity in vitro to cancer-cell lines derived from the lungs, liver, and colon, compared to normal cell lines. PA1 caused apoptosis in several cancer-cell lines in culture. In toxic doses to rodents, it causes extensive apoptosis in the liver, kidney, and lungs. In our study we were interested in evaluating, for the first time, the morphological effects of administration of PA1 to implanted TC-1 cells and in the target organs in vivo. The TC-1 cells were cultured and injected into the hind limb of C57BL-6 mice. The animals were divided into 3 groups; those treated with four doses of 1 mg/kg each of PA1, the untreated control, and the vehicle-control groups. All mice were killed 10 days after cell implantation. Samples were obtained from TC-1 cells at the implantation site and from the liver, kidney, and lungs. The samples were processed for examination under light and electron microscopy. In the PA1-treated group, the TC-1 cells had necrosis, whereas in the control groups the tumor cells were undamaged. The target organs did not show any lesions. We demonstrated for the first time that there is a selective toxic effect of PA1 on the TC-1 cells in vivo.

Peroxisomicina A1 (PA1), una de las toxinas aisladas de las semillas de plantas del género Karwinskia, cuyos órganos blanco son hígado, riñón y pulmón. Hay una toxicidad selectiva in vitro contra líneas celulares cancerosas derivadas de pulmón, hígado y colon, comparadas con líneas celulares normales. PA1 causa apoptosis en varias líneas celulares malignas en cultivo. En dosis tóxicas a roedores, causa extensa apoptosis en hígado, riñón y pulmón. En nuestro estudio, estuvimos interesados en evaluar por primera vez los efectos morfológicos de la administración temprana de PA1 sobre células TC-1 implantadas y los órganos blanco in vivo. Las células TC-1 fueron cultivadas e implantadas en la extremidad posterior de ratones C57BL-6. Los animales fueron divididos en tres grupos: tratado con cuatro dosis de 1 mg/kg de peso de PA1, control sin tratamiento y control vehículo. Todos los animales fueron sacrificados 10 días posterior al implante de las células. Se colectaron muestras del sitio del implante de las células TC-1 y de hígado, riñón y pulmón. Las muestras fueron procesadas para su análisis a microscopía de luz y microscopia electrónica de transmisión. En el grupo tratado con PA1, las células TC-1 presentaron necrosis, mientras que en los grupos control las células tumorales se observaron sin daño. Los órganos blanco no mostraron lesión alguna. Demostramos por primera vez que existe un efecto tóxico selectivo de PA1 sobre las células TC-1 in vivo.

Uso neoadjuvante do mesilato de imatinibe no tratamento de GIST retal volumoso: relato de caso / Neoadjuvant use of imatinib mesylate for treatment of large rectal GIST: case report

Tem sido relevante o papel das drogas que interferem na atividade tirosina-quinase dos receptores c-kit, no tratamento dos tumores derivados do estroma gastrintestinal (GISTs), sobretudo em tumores volumosos. Relata-se o caso de um paciente do sexo masculino, 56 anos, obeso, com quadro de peso retoanal associado a tenesmo e à sensação de evacuação incompleta. Foi diagnosticado volumoso GIST de reto inferior de localização posterior, visualizado por ressonância magnética e confirmado por estudo imunoistoquímico em punção-biópsia parassacral, guiada por tomografia. A impressão inicial foi de necessidade de amputação abdômino-perineal do reto, pois havia importante compressão do canal anal e do aparelho esfincteriano. Optou-se, então, por indicação de neoadjuvância com mesilato de imatinibe (Glivec®) na tentativa de preservação esfincteriana. Após quatro meses de tratamento, apresentava, ao toque retal, redução significativa (cerca de 50 por cento) do volume da massa e em menor grau à ressonância magnética. Paciente foi submetido à excisão total do mesorreto e anastomose colo-anal manual, com ileostomia protetora. Evoluiu com necrose do cólon abaixado, tendo sido realizada ressecção do mesmo e colostomia terminal ilíaca. O paciente recusou a se submeter a uma nova tentativa de abaixamento colo-anal, tendo sido fechada a ileostomia e restabelecido trânsito pela colostomia ilíaca. No tratamento dos GISTs de reto muito volumosos ou irressecáveis, deve-se avaliar a indicação pré-operatória do imatinibe, uma vez que a cirurgia radical deve ser sempre indicada, a fim de minimizar a possibilidade de recorrência local.

The role of drugs that intervene with the tirosine kinase activity on the c-kit receptors in the treatment of gastrointestinal stromal tumors (GISTs) has been considered very important, mainly in large tumors. We report a case of a male patient, 56 years-old, obese, presenting with feeling of rectal pressure and incomplete evacuation. Work-up revealed a large inferior rectal GIST located in the posterior wall, suspected on MRI and confirmed by immunohistochemical study of a parasacral biopsy guided by tomography. The supposed initial approach was an abdominoperineal resection, since tumor was compressing anal canal and sphincter complex. In order to save the sphincters, we have decided to refer patient to neoadjuvant treatment with imatinib mesylate (Glyvec®). After four months of treatment, a down staging of tumor was observed during rectal exam (about 50 percent), which was smaller on pelvic RNM. Patient was undergone to total mesorectal excision with manual coloanal anastomosis and protective ileostomy. He presented necrosis of mobilized left colon and underwent to resection, and terminal iliac colostomy. Subsequently, patient refused to undergo through a new coloanal anastomosis and remain with iliac colostomy after ileostomy takedown. In the treatment of unresectable or large rectal GISTs, the use of imantinib should be strongly considered, since that radical surgery is the main approach to reduce the possibility of local recurrence.

Neoadjuvância sistêmica / Systemic neoadjuvance

A neoadjuvância sistêmica é a aplicação de terapia antineoplásica como primeiro tratamento em pacientes sem evidência de metástases e com intenção plena de controle da doença. É tambem chamada de primária, pré-operatória, perioperatória, basal ou de indução. Cada vez mais pacientes estão sendo tratados com quimioterapia (QT), hormonioterapia (HT) e imunoterapia (IT) antes do tratamento cirúrgico e em estágios mais precoces da doença. A chamada Estratégia de Tratamento Multidisciplinar consiste no tratamento sistêmico primário ou adjuvante associada ao tratamento locorregional, através da cirurgia e radioterapia (RT). O tratamento do câncer de mama, em especial o localmente avançado, é baseado nesse planejamento, e a QT com antracíclicos e taxanos ocupa o papel central. Entretanto, a utilização de dados histológicos e marcadores imuno-histoquimicos relacionados a biologia molecular e a expressão genética tumoral conduzem a individualização do tratamento, que consiste na obtenção do máximo de informações disponíveis sobre o tumor para oferecer o tratamento mais adequado para cada paciente. Em relação à IT, ou terapia alvo, muitos ensaios clínicos tem mostrado bons índices de resposta em pacientes HER 2 positivo com esquemas quimioterapicos contendo Trastuzumab. Outras drogas anti-HER 2 também tem sido testadas. A HT neoadjuvante como tratamento único pode ser uma opção adequada em pós-menopáusicas com receptores hormonais (RH) positivo, e os inibidores da aromatase (IA) são a opção de escolha. As principais vantagens do tratamento sistêmico primario consistem na melhora das condições cirúrgicas, uma melhor avaliação do potencial de resposta tumoral a terapia sistêmica e uma possivel melhora da sobrevida.

Systemic neoadjuvant therapy is the first line treatment in patients without evidence of metastasis and with a good control of the disease. It is also named as primary, preoperative, perioperative, basal or induction. Chemotherapy (CT), hormone therapy (HT) and immunotherapy (IT) have been increasingly used before the surgical treatment and in early stages of the disease. The so-called Multidisciplinary Treatment Strategy consists in a primary or adjuvant systemic treatment associated to locoregional treatment through surgery and radiotherapy (RT). Breast cancer treatment, specially the locally advanced, is mainly based on this planning, and CT with anthracyclics and taxanes has the central role. Nevertheless, histologic data and tumor markers, related to molecular biology and tumor genetic expression, have been used to individualize the treatment for breast cancer, by obtaining the maximum available information about the tumor in order to offer the proper treatment for each patient. There are many clinical trials with IT, or target therapy, demonstrating good response rates in patients HER 2positive who used chemotherapy with Trastuzumab. Other anti-HER 2 drugs have been tested. The neoadjuvant HT as single agent can be used as an option in post-menopausal women with positive hormone receptor, and aromatase inhibitors are the drug of choice. The main advantages of primary systemic treatment are better surgical conditions, better evaluation of the potential of the tumor to respond to systemic therapy and, consequently, a better survival rate.

Intravitreal bevacizumab for choroidal metastasis of lung carcinoma; a case report.

PURPOSE: To report an alternative treatment for metastatic tumors within the eye. CASE REPORT: Five intravitreal injections of bevacizumab (2.5 mg each) were performed in one eye of a 50-year-old woman with choroidal metastasis of lung carcinoma. Tumor size was reduced, pain disappeared, vision improved, and there were no secondary reactions. Vision improved from 20/40 to 20/20 and metamorphopsia decreased. Ten months after initiating treatment, an ultrasonographic study revealed no residual tumor, the choroid was normal in thickness and fluorescein angiography revealed a scar but no mass lesion. CONCLUSION: Intravitreal bevacizumab displayed beneficial effects in reducing tumor size and improving symptoms in this case of choroidal metastasis of lung carcinoma. The antineoplasic properties of this agent make it a viable alternative for treatment of metastatic choroidal tumors.