Impact of Treatment Sequencing on Overall Survival in Patients with Transplant-Ineligible Newly Diagnosed Myeloma.

BACKGROUND: Because patients with newly diagnosed multiple myeloma (NDMM) do not always receive any treatment beyond first-line (1L) therapy, it is imperative that patients receive the best treatment in the 1L setting. However, the optimal initial treatment remains to be identified. We performed a clinical simulation to assess potential outcomes with different treatment sequences. PATIENTS AND METHODS: We used a partitioned survival model to compare overall survival (OS) with (1) daratumumab, lenalidomide, and dexamethasone (D-Rd) in 1L followed by a pomalidomide- or carfilzomib-based regimen in second line (2L) versus (2) bortezomib, lenalidomide, and dexamethasone (VRd) in 1L followed by a daratumumab-based regimen in 2L versus (3) lenalidomide and dexamethasone (Rd) in 1L followed by a daratumumab-based regimen in 2L. Probabilities of transition between health states (1L, 2L+, and death) were based on published clinical data and real-world data from the Flatiron Health database. The proportion of patients discontinuing treatment after 1L (attrition rates) in the base case was estimated with a binomial logistic model using data from the MAIA trial. RESULTS: Using D-Rd in 1L conferred a longer median OS compared with delaying daratumumab-based regimens until 2L after VRd or Rd, respectively (8.9 [95% CrI 7.58-10.42] vs. 6.92 [5.92-8.33] or 5.75 [4.50-7.25] years). Results of scenario analyses were consistent with the base case. CONCLUSION: Our simulation, which incorporates clinically representative treatments and attrition rates, supports the use of D-Rd as initial therapy, rather than delaying the use of daratumumab until later lines of therapy, in patients with transplant-ineligible NDMM.

Linfoma testicular primario tipo B de célula grande: aspectos clínicos, histopatológicos, diagnóstico terapéutico y pronósticos / Large cell type B primary testicular lymphoma: clinical, histopathological, therapeutic diagnosis and prognostic aspects

RESUMEN Fundamento: el linfoma testicular constituye entre el 1 y el 9 % de los tumores testiculares, es el tumor testicular maligno más frecuente en los varones mayores de 50 años. El pronóstico es reservado debido a una gran tendencia a la propagación sistémica temprana. La presentación clínica más habitual, dolor testicular a la palpación y espontáneo, con aumento del volumen y de la consistencia testicular. Su tratamiento se sustenta en tres pilares fundamentales: orquiectomía, quimioterapia y radioterapia. Objetivo: describir un enfermo con linfoma testicular tipo B de célula grande. Presentación del caso: paciente masculino de 55 años de edad, hipertenso, fumador 10 cigarrillos al día, bebedor ocasional. Acude a consulta por aumento de volumen testicular izquierdo. En la analítica se observa elevación del lactato deshidrogenasa. Ecografía: teste izquierdo con ecogenicidad muy heterogénea, parénquima desestructurado, sin lesiones nodulares. Engrosamiento difuso del epidídimo. Vascularización incrementada. Se realiza orquiectomía radical inguinal, al ser el diagnóstico anatomopatológico linfoma difuso de células grandes tipo B, en la actualidad ha sido tratado con quimioterapia, por presentar además afectación ósea. Pero ha evolucionado favorablemente. Conclusiones: el linfoma testicular es una enfermedad poco frecuente, a pesar de ser considerado el tumor testicular más común en mayores de 60 años. En su mayoría se trata de linfomas no Hodgkin difusos de grado intermedio alto de malignidad e inmunofenotipo B. El pronóstico siempre es reservado debido a su gran tendencia a la propagación sistémica. El tratamiento está basado en la cirugía (orquiectomía radical inguinal), quimioterapia y radioterapia.

ABSTRACT Background: testicular lymphoma constitutes between 1 and 9 % of testicular tumors; it is the most frequent malignant testicular tumor in men over 50 years of age. The prognosis is reserved due to a great tendency to early systemic spread. The most common clinical presentation is testicular pain on palpation and spontaneous, with increased volume and testicular consistency. Its treatment is based on three fundamental pillars: orchiectomy, chemotherapy and radiotherapy. Objective: to describe a patient with large cell type B testicular lymphoma. Case report: 55-year-old male patient, hypertensive, smoker 10 cigarettes a day, occasional drinker. He goes to consultation due to left testicular volume increase. In the laboratory tests, the lactate dehydrogenase is elevated. Ultrasound Scand: Left testicle with very heterogeneous echogenicity, unstructured parenchyma, no nodular lesions. Diffuse thickening of the epididymis. Increased vascularization. Inguinal radical orchiectomy is performed, the anatomic-pathological diagnosis being diffuse large B cell type lymphoma, it has now been treated with chemotherapy, because he alsopresented bone involvement. But he has evolved favorably. Conclusions: testicular lymphoma is a very rare entity, despite being considered the most common testicular tumor in people over 60 years of age. The majority are diffuse non-Hodgkin lymphomas of high intermediate degree of malignancy and immune-phenotype B. The prognosis is always reserved due to its great tendency to systemic spread. The treatment is based on surgery (radical inguinal orchiectomy), chemotherapy and radiotherapy.

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response.

OBJECTIVE: To evaluate background parenchymal enhancement (BPE) and its characteristics, as well as its behavior before and after neoadjuvant chemotherapy (NAC), in both breasts of patients with unilateral breast cancer. MATERIALS AND METHODS: This was a retrospective, cross-sectional observational study involving a consecutive sample of women with invasive breast cancer who underwent breast magnetic resonance imaging (MRI) between July 2007 and July 2017, as well as undergoing dynamic contrast-enhanced MRI before and after NAC. In both breasts, we evaluated the BPE in accordance with the Breast Imaging Reporting and Data System. We applied logistic regression analysis, and values of p < 0.05 were considered significant. RESULTS: We evaluated 150 women. The mean age was 45.2 years (range, 20-74 years). The variables correlating independently with a high pre-NAC BPE, in the affected and contralateral breasts, were being under 50 years of age (odds ratio [OR] = 6.55; 95% confidence interval [95% CI]: 2.32-18.46, for both breasts) and a post-NAC BPE reduction (OR = 17.75; 95% CI: 4.94-63.73 and OR = 18.47; 95% CI: 5.19-66.49, respectively). CONCLUSION: Patients with invasive unilateral breast cancer who have a high pre-NAC BPE in both breasts tend to be under 50 years of age and to show a post-NAC reduction in BPE.

OBJETIVO: Avaliar o realce de fundo do parênquima (RFP), suas características e seu comportamento pré- e pós-quimioterapia neoadjuvante (QTN) em ambas as mamas em pacientes com câncer de mama unilateral. MATERIAIS E MÉTODOS: Estudo observacional transversal retrospectivo realizado em um serviço acadêmico e um centro especializado em mamas, que incluiu mulheres com câncer de mama invasivo submetidas a QTN e que realizaram exames de ressonância magnética (RM) das mamas com contraste antes e depois da quimioterapia, entre julho de 2007 e julho de 2017. Os exames foram realizados de acordo com protocolo padronizado. O RFP foi avaliado em ambas as mamas de acordo com o ACR BI-RADS, 5ª edição. Foi aplicada análise de regressão logística. O nível de significância adotado para os testes estatísticos foi p < 0,05. RESULTADOS: Foram analisadas 150 mulheres. A idade média foi de 45,2 anos (20­74 anos). Na análise de regressão multivariada, apenas a idade inferior a 50 anos e redução do RFP correlacionaram-se independentemente com o nível alto de RFP em ambas as mamas: mamas afetadas (odds ratio [OR]: 6,55; intervalo de confiança 95% [IC 95%]: 2,32­18,46 e OR: 17,75; IC 95%: 4,94­63,73, respectivamente); mamas contralaterais (OR: 6,55; IC: 95% 2,32­18,46 e OR: 18,47; IC 95%: 5,19­66,49, respectivamente). CONCLUSÃO: Idade abaixo de 50 anos e redução do RFP pós-QTN correlacionaram-se independentemente com maior RFP pré-QTN em ambas as mamas em pacientes com câncer de mama invasivo unilateral submetidas a QTN.

Background parenchymal enhancement: behavior during neoadjuvant chemotherapy for breast cancer and relationship with a pathological complete response / Realce de fundo do parênquima: comportamento durante quimioterapia neoadjuvante para câncer de mama e relação com resposta patológica completa

Abstract Objective: To evaluate background parenchymal enhancement (BPE) and its characteristics, as well as its behavior before and after neoadjuvant chemotherapy (NAC), in both breasts of patients with unilateral breast cancer. Materials and Methods: This was a retrospective, cross-sectional observational study involving a consecutive sample of women with invasive breast cancer who underwent breast magnetic resonance imaging (MRI) between July 2007 and July 2017, as well as undergoing dynamic contrast-enhanced MRI before and after NAC. In both breasts, we evaluated the BPE in accordance with the Breast Imaging Reporting and Data System. We applied logistic regression analysis, and values of p < 0.05 were considered significant. Results: We evaluated 150 women. The mean age was 45.2 years (range, 20-74 years). The variables correlating independently with a high pre-NAC BPE, in the affected and contralateral breasts, were being under 50 years of age (odds ratio [OR] = 6.55; 95% confidence interval [95% CI]: 2.32-18.46, for both breasts) and a post-NAC BPE reduction (OR = 17.75; 95% CI: 4.94-63.73 and OR = 18.47; 95% CI: 5.19-66.49, respectively). Conclusion: Patients with invasive unilateral breast cancer who have a high pre-NAC BPE in both breasts tend to be under 50 years of age and to show a post-NAC reduction in BPE.

Resumo Objetivo: Avaliar o realce de fundo do parênquima (RFP), suas características e seu comportamento pré- e pós-quimioterapia neoadjuvante (QTN) em ambas as mamas em pacientes com câncer de mama unilateral. Materiais e Métodos: Estudo observacional transversal retrospectivo realizado em um serviço acadêmico e um centro especializado em mamas, que incluiu mulheres com câncer de mama invasivo submetidas a QTN e que realizaram exames de ressonância magnética (RM) das mamas com contraste antes e depois da quimioterapia, entre julho de 2007 e julho de 2017. Os exames foram realizados de acordo com protocolo padronizado. O RFP foi avaliado em ambas as mamas de acordo com o ACR BI-RADS, 5ª edição. Foi aplicada análise de regressão logística. O nível de significância adotado para os testes estatísticos foi p < 0,05. Resultados: Foram analisadas 150 mulheres. A idade média foi de 45,2 anos (20-74 anos). Na análise de regressão multivariada, apenas a idade inferior a 50 anos e redução do RFP correlacionaram-se independentemente com o nível alto de RFP em ambas as mamas: mamas afetadas (odds ratio [OR]: 6,55; intervalo de confiança 95% [IC 95%]: 2,32-18,46 e OR: 17,75; IC 95%: 4,94-63,73, respectivamente); mamas contralaterais (OR: 6,55; IC: 95% 2,32-18,46 e OR: 18,47; IC 95%: 5,19-66,49, respectivamente). Conclusão: Idade abaixo de 50 anos e redução do RFP pós-QTN correlacionaram-se independentemente com maior RFP pré-QTN em ambas as mamas em pacientes com câncer de mama invasivo unilateral submetidas a QTN.

Anticancer drug prices and clinical outcomes: a cross-sectional study in Italy.

OBJECTIVE: To investigate whether the prices of new anticancer drugs correlated with their relative benefit despite negotiation. DESIGN: Retrospective cross-sectional study correlating new anticancer drugs prices with clinical outcomes. SETTING: We did a retrospective cross-sectional study including all new anticancer drugs approved by the European Medicines Agency (EMA) (2010-2016) and reimbursed in Italy. MAIN OUTCOMES AND MEASURES: Information on clinical outcomes-in terms of median overall survival (OS), median progression-free survival (PFS) and objective response rate (ORR)-was extracted from pivotal trials as reported in the European Public Assessment Reports available on the EMA website. Cost of a full course treatment was estimated on negotiated official and discounted prices. Regression coefficients ß, their levels of significance p and the coefficients of determination R2 were estimated adjusting by tumour type. RESULTS: Overall, 30 new anticancer drugs (with 35 indications) were available for analysis. Where data on OS were available, we observed no correlation between the improvement in median OS (in weeks) and negotiated price (R2=0.067, n=16 drugs for 17 indications). When the clinical outcomes were expressed as improvements in the median PFS or ORR, 25 drugs (29 indications) were available for the analysis, and again, there was no correlation with prices (R2=0.004 and 0.006, respectively). CONCLUSIONS AND RELEVANCE: Our results suggest that the prices of anticancer drugs in Italy do not reflect their therapeutic benefit. Drug price negotiations, which is mandatory by law in Italy, do not seem to ensure that prices correlate with clinical benefits provided by the cancer drugs. These results call for further efforts to establish the standard determinants of drug prices available at the time of negotiation. These findings need to be confirmed in other countries where price negotiations are in place. Moreover, further investigations may verify whether outcome data obtained after drug marketing would improve the correlation between prices and therapeutic benefit.

Microsatellite instability status determined by next-generation sequencing and compared with PD-L1 and tumor mutational burden in 11,348 patients.

Microsatellite instability (MSI) testing identifies patients who may benefit from immune checkpoint inhibitors. We developed an MSI assay that uses data from a commercially available next-generation sequencing (NGS) panel to determine MSI status. The assay is applicable across cancer types and does not require matched samples from normal tissue. Here, we describe the MSI-NGS method and explore the relationship of MSI with tumor mutational burden (TMB) and PD-L1. MSI examined by PCR fragment analysis and NGS was compared for 2189 matched cases. Mismatch repair status by immunohistochemistry was compared to MSI-NGS for 1986 matched cases. TMB was examined by NGS, and PD-L1 was determined by immunohistochemistry. Among 2189 matched cases that spanned 26 cancer types, MSI-NGS, as compared to MSI by PCR fragment analysis, had sensitivity of 95.8% (95% confidence interval [CI] 92.24, 98.08), specificity of 99.4% (95% CI 98.94, 99.69), positive predictive value of 94.5% (95% CI 90.62, 97.14), and negative predictive value of 99.2% (95% CI, 98.75, 99.57). High MSI (MSI-H) status was identified in 23 of 26 cancer types. Among 11,348 cases examined (including the 2189 matched cases), the overall rates of MSI-H, TMB-high, and PD-L1 positivity were 3.0%, 7.7%, and 25.4%, respectively. Thirty percent of MSI-H cases were TMB-low, and only 26% of MSI-H cases were PD-L1 positive. The overlap between TMB, MSI, and PD-L1 differed among cancer types. Only 0.6% of the cases were positive for all three markers. MSI-H status can be determined by NGS across cancer types. MSI-H offers distinct data for treatment decisions regarding immune checkpoint inhibitors, in addition to the data available from TMB and PD-L1.

Health-related quality of life associated with regorafenib treatment in refractory advanced gastric adenocarcinoma.

BACKGROUND: The INTEGRATE phase II multinational randomized controlled trial demonstrated the activity of regorafenib on progression-free survival (PFS) in patients with refractory advanced gastric adenocarcinoma. We sought to evaluate whether these PFS gains had the potential to be offset by quality of life (QoL) impacts from treatment side effects and to thereby determine the appropriateness of continuing development to phase III. METHODS: QoL was assessed in INTEGRATE at baseline and at each 4 weeks thereafter, until discontinuation of study treatment, using the QLQ-C30, STO22, and EQ-5D questionnaires. The patient disease and treatment assessment (PTDATA) form was also provided to English-speaking participants. Randomized groups were compared on the QLQ-C30, STO22, and EQ-5D scales using a repeated-measures model; the frequency of troublesome symptoms and side effects measured by the PTDATA form; and deterioration-free survival (DFS). The prognostic value of baseline QoL information was also evaluated. RESULTS: Of the 147 eligible randomized patients, 142 consented to participate in the QoL substudy, 136 completed a baseline QoL assessment, and 95 completed at least one post-baseline QoL assessment. The DFS rate was significantly improved with regorafenib, and there was no compelling statistical evidence that regorafenib had a broad negative effect across the spectrum of QoL indices evaluated. Fatigue, anxiety, appetite loss, and pain were among the issues most commonly reported for both randomized groups. Baseline levels of pain, appetite, constipation, and physical functioning were prognostic factors for survival. CONCLUSIONS: Regorafenib improved DFS without an excessively negative effect on QoL. Progressing development to the phase III setting is warranted.

Minimization of olaratumab drug waste using real-world data.

PURPOSE: Results of a study in which population-based body weight and body surface area (BSA) data were used for vial size optimization to reduce drug waste associated with administration of the i.v. anticancer agent olaratumab are reported. METHODS: A retrospective observational study was conducted to determine weight and BSA distributions in a large sample of U.S. oncology patients using data from a large electronic medical record database. Body weight and BSA values at the time of initial systemic anticancer therapy were used to compute olaratumab dose requirements in a cohort of patients with soft tissue sarcoma; those data were analyzed to derive estimates of drug waste likely to result from the use of various proposed olaratumab vial sizes in combination with an existing 500-mg size. Weight and BSA distributions were calculated for additional cohorts of patients with 7 other cancer types. RESULTS: Median weight values in men (n = 1,179) and women (n = 1,078) with soft tissue sarcoma were 82.55 kg (interquartile range [IQR], 72.58-95.53 kg) and 68.69 kg (IQR, 58.51-84.28 kg), respectively. Modeling of olaratumab dosing scenarios indicated that use of the 500-mg vial only would result in estimated average drug waste of 234 mg per patient per administration; analysis of various potential vial size combinations showed that waste could be reduced by 87.6% with the addition of a 190-mg vial size. CONCLUSION: Analysis of real-world patient weight and BSA data allowed olaratumab vial size optimization to enable maximal dosing flexibility with minimal drug waste.

Docetaxel in prostate cancer: a familiar face as the new standard in a hormone-sensitive setting.

The increasing knowledge of prostate cancer is leading to many questions about its natural history and to reconsider conventional therapeutic strategies. Androgen ablation therapy has been the standard therapy in the advanced setting. Although docetaxel has demonstrated increased survival in patients with metastatic prostate cancer who had progressed to hormone treatments, due to its potential toxicity the role of chemotherapy has been relegated to patients who were symptomatic or who had high tumor burden. Several studies have assessed whether docetaxel could have a role in hormone-sensitive disease or even in earlier stages with no distant metastases. In the CHAARTED and STAMPEDE studies, docetaxel provides an unprecedented increase in overall survival (OS). This review summarizes the evidence behind the paradigm shift to strengthening docetaxel as a new standard of treatment that prolongs survival in earlier stages of prostate cancer.

Hepatocellular Carcinoma Treatment With Sorafenib: Real-Life Evaluation of Prognostic Factors and a Practical Clue for Patient Management.

INTRODUCTION: Sorafenib chemotherapy is the first-line therapy for patients with hepatocellular carcinoma (HCC) in an advanced stage. The aim of this study was to evaluate prognostic factors of survival in HCC patients treated with sorafenib, in real-life clinical practice. MATERIAL AND METHODS: Retrospective study of HCC patients who initiated treatment with sorafenib, following assessment and indication from the multidisciplinary group. RESULTS: There were included 36 patients, mostly male (89%) and with a mean age of 65 years. The main etiologies were chronic hepatitis C (44%) and alcoholic liver disease (36%). Twenty patients (56%) were classified as Child-Pugh A and 16 patients (44%) as Child-Pugh B. Half of the patients group were staged as BCLC C and the remaining as BCLC B. Significant adverse events were observed in 15 patients (42%) and were associated with longer survival (21.5 vs. 3.2 months, p < 0.001). The most frequent adverse events were diarrhea and palmar-plantar syndrome. Median survival was 17.3 months for Child-Pugh A versus 3.2 months for Child-Pugh B patients (p = 0.001). Within Child-Pugh A, median OS was 21.5 months for BCLC B patients and 15.7 months for BCLC C patients (p = 0.001). DISCUSSION AND CONCLUSIONS: The main prognostic factors beyond Child-Pugh class and BCLC stage included the occurrence of significant adverse events. Being related to increased time of exposure to the drug, it points out the need of dose reducing instead of discontinuation whenever significant adverse events occur.

INTRODUÇÃO: O tratamento de primeira linha de doentes com carcinoma hepatocelular (HCC) em estadio avançado é a quimioterapia com sorafenib. O objetivo deste estudo foi avaliar os fatores de prognóstico de sobrevivência em doentes com HCC tratados com sorafenib, na prática clínica. MATERIAL E MÉTODOS: Estudo retrospetivo com inclusão dos doentes com HCC que iniciaram tratamento com sorafenib, após avaliação e decisão de grupo em reunião multidisciplinar. RESULTADOS: Foram incluídos 36 doentes, que eram em maioria do género masculino (89%) e com idade média de 65 anos. As principais etiologias eram a hepatite C crónica (44%) e a doença hepática alcoólica (36%). Vinte doentes (56%) foram classificados como Child-Pugh A e 16 doentes (44%) como Child-Pugh B. A amostra apresentava em metade dos casos estadio BCLC C e os restantes BCLC B. Quinze doentes (42%) desenvolveram efeitos adversos significativos, que se associaram com maior sobrevivência (21,5 vs 3,2 meses, p < 0,001). Os efeitos adversos mais frequentes foram diarreia e síndrome palmo-plantar. A sobrevivência global mediana foi de 6,8 meses (IC 95%, 3-10,6). A sobrevivência mediana foi de 17,3 meses nos doentes Child-Pugh A versus 3,2 meses nos casos Child-Pugh B (p = 0,001). Considerando os doentes Child-Pugh A, a sobrevivência mediana foi de 21,5 meses para o estadio BCLC B e 15,7 meses para o estadio BCLC C (p = 0,001). DISCUSSÃO E CONCLUSÕES: Os principais fatores prognósticos, além da classificação de Child-Pugh e do estadiamento BCLC, incluíram a ocorrência de efeitos adversos. Estes, relacionados com o tempo de exposição ao fármaco, assinalam a importância de uma estratégia de redução de dose em vez de descontinuação quando se manifestam efeitos adversos significativos.

Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma.

OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5%) patients of this cohort received rituximab as first-line treatment and nine (7.1%) received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. CONCLUSION: Central nervous system infiltration in this cohort is similar to that of previous reports in the literature. As this was a small cohort with a rare event, only three risk factors were important for this infiltration.

Secondary infiltration of the central nervous system in patients with diffuse large B-cell lymphoma

OBJECTIVE: To investigate the incidence and risk factors of infiltration of the central nervous system after the initial treatment of diffuse large B-cell lymphoma in patients treated at Santa Casa de Misericórdia de São Paulo. METHODS: A total of 133 patients treated for diffuse large B-cell lymphoma from January 2001 to April 2008 were retrospectively analyzed in respect to the incidence and risk factors of secondary central nervous system involvement of lymphoma. Intrathecal prophylaxis was not a standard procedure for patients considered to be at risk. This analysis includes patients whether they received rituximab as first-line treatment or not. RESULTS: Nine of 133 (6.7%) patients developed central nervous system disease after a mean observation time of 29 months. The median time to relapse or progression was 7.9 months after diagnosis and all but one patient died despite the treatment administered. Twenty-six (19.5%) patients of this cohort received rituximab as first-line treatment and nine (7.1%) received intrathecal chemoprophylaxis. Of the nine patients that relapsed, seven (77.7%) had parenchymal central nervous system involvement; seven (77.7%) had stage III or IV disease; one (11.1%) had bone marrow involvement; two (22.2%) had received intrathecal chemoprophylaxis; and 3 (33.3%) had taken rituximab. In a multivariate analysis, the risk factors for this infiltration were being male, previous use of intrathecal chemotherapy and patients that were refractory to initial treatment. ...

Fatores que influenciam o consumo energético de mulheres no tratamento do câncer de mama / Factors associated with changes in energy intake of women after treatment for breast cancer

RESUMO OBJETIVO: Investigar alterações no consumo dietético, bem como a influência das características gerais, dos fatores sociodemográficos, clínicos e nutricionais, e do tratamento antineoplásico sobre as mudanças do consumo energético, em mulheres do sul do Brasil, antes e após a realização de terapia adjuvante para o câncer de mama. MÉTODOS: Ensaio clínico não randomizado, conduzido em hospital da rede pública de saúde, com 53 pacientes. Informações dietéticas foram coletadas com questionário de frequência alimentar. Para avaliar os fatores que influenciaram alterações longitudinais da ingestão energética, usou-se modelo de regressão linear de efeitos mistos. RESULTADOS: Houve aumento significativo no consumo diário de energia, de gorduras, cálcio, ferro, cobre, ácidos graxos poli-insaturados, ômega 6 e ômega 3, e uma diminuição significativa da vitamina B2. O modelo final de regressão mostrou aumento médio de 19,2 kcal/mês. As maiores associações com ingestão energética foram frutas e leguminosas, sendo que cada 100 g de consumo destas, resultou um acréscimo médio de 68,4 e 370,5 kcal, respectivamente. Mulheres com idade compreendida entre 51 e 60 anos consumiram 403,5 kcal menos do que aquelas com idade de 31 a 50 anos. CONCLUSÃO: Observou-se que houve aumento na ingestão energética durante o tratamento e que o aumento na ingestão de frutas e leguminosas foi associado com aumentos significativos na ingestão de energia.

PURPOSE: To investigate changes in the dietary consumption as well as the influence of the general characteristics, of the sociodemographic, clinical and nutritional factors, and of the antineoplastic therapy on the changes in the energy intake of women from southern Brazil, before and after adjuvant therapy for breast cancer. METHODS: A non-randomized clinical study was conducted on 53 patients at a hospital of the public health network. Dietary information was collected with a food frequency questionnaire. A mixed-effects linear regression model was used to evaluate the factors that influenced longitudinal alterations of energy intake. RESULTS: A significant increase was observed in daily energy intake of fats, calcium, iron, copper, polyunsaturated fatty acids, omega 6 and omega 3, and a significant decrease in vitamin B2 intake. The final regression model for the change in energy intake showed an average increase of 19.2 kcal/month. Fruit and legume consumption showed the highest association with energy intake, with each 100 g consumed resulting in an average increase of 68.4 and 370.5 kcal, respectively. Women in the 51 to 60 year age range consumed 403.5 kcal less than those in the 31 to 50 year age range. CONCLUSION: There was an increase in energy intake during treatment and the increase in the ingestion of fruits and legumes was associated with significant increases in energy intake.

Uso de gemtuzumabe ozogamicina combinado com quimioterapia convencional em pacientes com leucemia mieloide aguda / Use of gemtuzumab ozogamycin combined with conventional chemotherapy in patients with acute myeloid leukemia

Objective: To analyze the outcome of patients treated with gemtuzumab ozogamycin combined with conventional therapy treated at Hospital Israelita Albert Einstein. Methods: 14 patients who had high risk features (secondary leukemia, unfavorable cytogenetics, and refractory disease) were treated with gemtuzumab ozogamycincombined with conventional therapy and their outcome was analysed by reviewing their medical records. Results: Overall response rate was 58%, with 43% achieving complete response, with a median followup of 11 months, event-free survival was 3 months. Eleven patients died, 6 of them due to refractory acute myeloid leukemia. Only four patients presented with grade 3 to 4 toxicities and only one patient had sinusoidal obstruction syndrome after bone marrow transplant. Conclusion: gemtuzumab ozogamycin combined with chemotherapy is a feasible treatment regimen in acute myeloid leukemia patients. However, further studies are necessary to clarify which subgroup of patients may benefit from this treatment.

Objetivo: Analisar a evolução de pacientes tratados com gemtuzumabe ozogamicina combinado à terapêutica convencional no Hospital Israelita Albert Einstein. Métodos: 14 pacientes que tinham alto risco (leucemia secundária, citogenética desfavorávele doença refratária) foram tratados com gentuzumabe ozogamicina associado à terapêutica convencional, e sua evolução foi analisada por meio de seus prontuários médicos. Resultados: A taxa total de resposta foi de 58%, com 43% chegando a resposta completa, em acompanhamento médio de 11 meses, e três meses com intervalo de sobrevivência livre. Foram a óbito 11 pacientes, 6 deles por leucemia mieloide aguda. Somente quatro pacientes apresentaram graus 3 a 4 de toxicidade e apenas um paciente teve síndrome de obstrução sinusoidal após transplante de medula. Conclusão: Gemtuzumabe ozogamicina associado à terapêutica quimioterápica convencional éum tratamento factível em pacientes com leucemia mieloide aguda. Contudo, novos estudos são necessários para esclarecer qual o subgrupo de pacientes que pode se beneficiar desse tratamento.

Primary cardiac angiosarcoma: in a patient with a dacron aortic prosthesis.

This is a report of a primary cardiac angiosarcoma in a woman who, several years earlier, had undergone repair of an aortic dissection with a Dacron graft prosthesis. Dacron prostheses have rarely been associated with neoplasia, and this, to our knowledge, is the first reported case of primary cardiac angiosarcoma in association with Dacron. Our patient presented with extensive metastases. If tumors are localized, they can be treated successfully with a combination of surgical resection, chemotherapy, and radiotherapy. Cardiac transplantation can also be beneficial, but the overall prognosis remains poor.

Intervenção coronariana complexa e tardia pós-tratamento quimioterápico / Complex late coronary intervention after chemotherapy

A associação entre o uso de quimioterápicos e a ocorrência de síndromes coronarianas agudas (SCA) ou mesmo infarto agudo do miocárdio (IAM) é rara, todavia constitui complicação por vezes de natureza grave, surpreendendo pacientes em curso de tratamento de uma doença já debilitante. Relata-se um caso dessa ocorrência, representada por um lado pelo uso de paclitaxel (taxol) para o tratamento de câncer de ovário e, do outro, por uma lesão complexa, de bifurcação, tratada percutaneamente.

Although associations between chemotherapy and acutecoronary syndromes or even acute myocardial infarctions are rare, they may result in complications that might even be severe, surprising patients during treatments of diseases that are already debilitating. We present a case study of such an association, represented on the one hand by the use of paclitaxel (Taxol), with a complex coronary lesion (bifurcation) treated percutaneously on the other.

Monitoring imatinib plasma concentrations in chronic myeloid leukemia.

Imatinib has proved to be effective in the treatment of chronic myeloid leukemia, but plasma levels above 1,000 ng/mL must be achieved to optimize activity. Therapeutic drug monitoring of imatinib is useful for patients that do not present clinical response. There are several analytical methods to measure imatinib in biosamples, which are mainly based on liquid chromatography with mass spectrometric or diode array spectrophotometric detection. The former is preferred due to its lower cost and wider availability. The present manuscript presents a review of the clinical and analytical aspects of the therapeutic drug monitoring of imatinib in the treatment of chronic myeloid leukemia. The review includes references published over the last 10 years. There is evidence that the monitoring of plasmatic levels of imatinib is an useful alternative, especially considering the wide pharmacokinetic variability of this drug.

Imatinib resistance: a review of alternative inhibitors in chronic myeloid leukemia.

The development of point mutations in the BCR-ABL kinase domain is the main reason for imatinib resistance in chronic myeloid leukemia. Different detection methods are used in chronic myeloid leukemia monitoring, such as direct sequencing, denaturing high performance liquid chromatography and allele specific polymerase chain reaction. Mutation analysis has become mandatory during patient workup of chronic myeloid leukemia in order for the physician to choose the most suitable tyrosine kinase inhibitor. This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient.