Time-dependent endpoints as predictors of overall survival in multiple myeloma.

BACKGROUND: Supporting health care sector decisions using time-dependent endpoints (TDEs) such as time to progression (TTP), progression-free survival (PFS), and event-free survival (EFS) remains controversial. This study estimated the quantitative relationship between median TDE and median overall survival (OS) in multiple myeloma (MM) patients. METHODS: Studies (excluding allogeneic transplantation) published from 1970 to 2011 were systematically searched (PubMed). The nonparametric Spearman's rank correlation coefficient measured the association between median TDE and OS. The quantitative relationship between TDEs and OS was estimated with a two-step approach to a simultaneous Tobit model. RESULTS: We identified 153 studies: 230 treatment arms, 22,696 patients and mean study duration of 3.8 years. Mean of median TDEs was 22.5 months and median OS was 39.1 months. Correlation coefficients of median TTP, PFS, and EFS with median OS were 0.51 (P = 0.003), 0.75 (P < 0.0001), and 0.84 (P < 0.0001), respectively. We estimate a 2.5 month (95% confidence interval, 1.7-3.2) increase in median OS for each additional month reported for median TDEs. There was no evidence that this relationship differed by type of surrogate. CONCLUSION: TDEs predict OS in MM patients; this relationship may be valuable in clinical trial design, drug comparisons, and economic evaluation.

The validity of the Patient-Generated Subjective Global Assessment Short-form© in cancer patients undergoing chemotherapy.

BACKGROUND & AIMS: The high prevalence of malnourished cancer patients highlights the importance of sensitive and specific tools for nutritional risk and status assessment screening, namely the Patient-Generated Subjective Global Assessment (PG-SGA®). This study aimed to assess whether the short-form version of the PG-SGA® (PG-SGA© SF) would be appropriate to identify the nutritional risk of patients when compared with the final global score of PG-SGA© (long-form version). METHODS: This transversal and observational study comprised a convenience sample of cancer patients undergoing chemotherapy at the Champalimaud Clinical Centre between December 2016 and February 2018. Clinical data and anthropometric parameters were collected in order to apply PG-SGA® and PG-SGA© SF. The data was statistically analysed through SPSS version 22 (SPSS Inc, Chicago, IL, USA). RESULTS: In this study 355 patients were enrolled and PG-SGA© SF results showed that 69.3% (n = 246) of the population presented at least one risk factor for malnourishment (Σ (box A) ≥1). Additionally, PG-SGA® revealed that 50% of patients (n = 177) have a risk of developing malnourishment or are already malnourished (B and C classification). The concordance of results showed to be high (coefficient k = 0.62; p < 0.001), meaning that PG-SGA SF© has a good sensibility (95%) and specificity (67%) for the identification of nutritional risk and assessment of nutritional status when compared with the complete version of PG-SGA©. CONCLUSIONS: According to our results, PG-SGA© SF is a useful and sufficient tool, representing an easier and faster way to identify at-risk or malnourished patients.

Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.

The 2018 Ocular Oncogenesis and Oncology Conference was held through a partnership of the Association for Research in Vision and Ophthalmology (ARVO) and the Champalimaud Foundation. Twenty-one experts from international ocular oncology centers, from the Champalimaud Clinical Centre and the Champalimaud Foundation Cancer Research Program, and from patient advocacy organizations, delivered lectures on subjects that ranged from global ocular oncology, to basic research in mechanisms of ocular malignancy, to clinical research in ocular cancers, and to anticipated future developments in the area. The scientific program of the conference covered a broad range of ocular tumors-including uveal melanoma, retinoblastoma, ocular surface tumors, and adnexal and intraocular lymphomas-and pathogenesis and management were deliberated in the context of the broader systemic cancer discipline. In considering the latest basic and clinical research developments in ocular oncogenesis and oncology, and providing the opportunity for cross-talk between ocular cancer biologists, systemic cancer biologists, ocular oncologists, systemic oncologists, patients, and patient advocates, the forum generated new knowledge and novel insights for the field. This report summarizes the content of the invited talks at the 2018 ARVO-Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.

Long-term follow-up of lymphocyte populations and cellular cytokine production in patients with chronic graft-versus-host disease treated with extracorporeal photopheresis.

We studied lymphocyte populations and cytokine-expression profiles of ten patients with chronic graft-versus-host disease who at least transiently responded to photoimmunotherapy. The numbers of lymphocytes, monocytes and dendritic cells rose in most cases. Th1 cells always increased during therapy, supporting the hypothesis that a more favorable immune balance contributes to clinical responses.

Incidence and characteristics of CD4(+)/HLA DRhi dendritic cell malignancies.

BACKGROUND AND OBJECTIVES: Recent reports suggest that CD4(+)/CD56(+)/lineage(-) hematopoietic neoplasias are aggressive types of malignancies involving lymphoplasmacytoid/DC2 dendritic cells (DC). Here, we report on the incidence of DC malignancies and their clinical, biological, phenotypic and cytogenetic characteristics. DESIGN AND METHODS: From a large series of 392 patients with acute myeloblastic leukemia (AML) and 739 with non-Hodgkin's lymphoma (NHL), five cases (three presenting as acute leukemia and two as NHL) showed clinical, morphologic and phenotypic features compatible with a DC malignancy. RESULTS: The overall incidence of DC malignancies among all AML and NHL cases was 0.76% and 0.27%, respectively. At presentation, these patients displayed cutaneous nodules, splenomegaly and lymph node involvement with variable levels of peripheral blood (PB) and/or bone marrow (BM) infiltration in association with anemia and thrombocytopenia. Cytologic studies showed immature appearing blast cells with negative cytochemistry reactions for both myeloperoxidase and esterases. A highly suggestive DC phenotype based on co-expression of CD123(hi)/HLADR(+)/lin(-)/CD56(+)/CD45(dim) associated with a germline configuration of both the IgH and TCRgamma genes was found in all except one patient who was CD56(-). Expression of other markers compatible with a DC origin was found in all cases. INTERPRETATION AND CONCLUSIONS: We show that DC-derived malignancies can present as either cutaneous lymphoma or acute leukemia, although their incidence is extremely low (<< >1%). While most of these DC neoplasias probably correspond to the malignant counterpart of DC2/lymphoplasmacytoid DC, neoplasias of myeloid DC might also exist, chemotherapy followed by consolidation with ASCT is apparently the most effective strategy for achieving a durable remission in these individuals.

[Cost of cancer care in Portugal]. / Custo do tratamento do cancro em Portugal.

INTRODUCTION: Cancer is the second most important cause of death in Portugal, following cardiovascular diseases (CVD), and shows a constant progressive increase in the proportional share of total deaths. In Portugal, as in most countries, the health care budget is under constant cost-containment pressures. In this context it is necessary to verify if enough resources have been allocated to the disease in terms of health care expenditure. The main objective of this study is to estimate the cost of cancer care in Portugal and to compare it to similar data in Europe and the United States of America (USA), to the cost of CVD. The secondary objective is to evaluate the cost of pharmaceuticals used in the treatment of cancer in Portugal, both in relation to total pharmaceutical expenditure and to other therapeutic areas. METHODS: Three main sources of information were used: comprehensive literature review, primary and secondary data sources, and a modified Delphi Panel, which was used to fill in gaps in the information derived from the data sources and the literatura review. The burden of cancer was measured through the Disability-adjusted life-year (DALY) and, in order to determine the costs of cancer, detailed information on the costs of medical visits and of inpatient episodes based on Diagnosis Related Groups (DRG), in 2006, was used. To estimate the total cost of cancer, we used a combination of top down (breaking global expenditure data to specific levels) and bottom up methodology (based on the sum of different components). RESULTS: Based on 2006 data on direct medical care expenditures in Portugal, we found that 565 million euro were spent on cancer in comparison to 1 320 million on CVD representing 3.91% and 9.14% of total cost on health respectively. When we break down total expenditure on drugs by therapeutic area we find that CVD drugs represent about 21.6% of total drug costs in Portugal and cancer drugs represent about 5.6% of the total. Oncology drugs represent 32% of the total expenditure on cancer, while CVD drugs represent 54% of the total expenditure on CVD. In comparison, in terms of BoD in Portugal, 18.6% of DALY's were associated with CVD and 15.3% with cancer. CONCLUSION: Considering the burden of disease (BoD) of CVD and cancer in Portugal, we can state that the expenditure allocated to cancer is significantly lower than expected. Using the criterion of expenditure according to need, we observed that there is an imbalance of expense/BoD in oncology indicating that cancer seems to be underfunded in Portugal. Even considering that this shouldn't be the only criterion to determine the volume of expense in a certain therapeutic area, the differential observed in this study is sufficiently high to deserve attention from the decision-makers.

[Biosimilars in oncology]. / Biossimilares em oncologia.

The development of biotechnology drugs represents one of the great advances in medical therapy and it was observed an exponential growth in its use. The resource to these drugs in Oncology and Hematology is no exception and it soon became an essential element of an integrated and directed therapy strategy. The expiry of the first biotechnology drugs patents has opened the door for the development and marketing of biosimilars, which entry in the Portuguese market was recently approved. This article was built on the analysis of the available state-of-the-art information on biotechnology drugs, biosimilars and current legislation and it expresses the opinion of Oncology and Hematology experts about the substituition of biological drugs by biosimilars in clinical practice.

[Use of granulocyte growth factors: recommendations of the Portuguese Society of Hematology]. / Uso de factores de crescimento de granulócitos: recomendações da Sociedade Portuguesa de Hematologia.

The administration of cytotoxic chemotherapy may be complicated by the emergence of neutropenia and febrile neutropenia, frequently determining hospital admission and intravenous treatment with broad spectrum antibiotics. Frequently, it is necessary to reduce the dose or to delay the administration of the cytotoxic drugs reducing the relative dose intensity of the chemotherapy regimen. Granulocyte growth factors stimulate the proliferation and differentiation of neutrophils and reduce the number of days of severe neutropenia and febrile neutropenia associated with cytotoxic chemotherapy. They are also indicated for the collection of hematopoietic progenitors for autologous and allogeneic transplantation, as well as in non malignant diseases associated with chronic neutropenia. This article reviews the evidence supporting the use of granulocyte growth factors in Hematology.