Estimation methods for computing a branch’s total value added from incomplete annual accounting data. National Bank of Belgium, Working Paper No. 371

Timely monitoring of the economic performance of a particular sector is generally hindered by the fact that not all companies have deposited their annual accounts by the time that an evaluation is made. In view of this, we develop several imputation strategies that each enable predicting a company’s value added based on available information from past and current years for those companies where the value added was not timely reported. For each proposed strategy we discuss the assumptions which must be fulfilled for unbiased estimation and calculate the estimation uncertainty. In particular, the proposed imputation procedures all rely on an assumption of missing at random, namely that the values added in companies that did not yet deposit their annual accounts are similar (in some way) to those in companies with the same characteristics (e.g. the same historical data) that did deposit their accounts by the evaluation date. We show how to retrospectively assess the validity of this assumption, and how to adjust the imputation procedure in case the assumption fails. The importance of the availability of the uncertainty margins should not be underestimated because they will result in faster and higher quality publications. Finally we retrospectively apply each strategy to data from the Belgian Port sector and compare their performance at several evaluation dates. All the proposed methods show good results on these data. The method using (ordinary least squares) regression is preferred because it is very flexible in the use of auxiliary variables, requires weaker assumptions, has smaller estimation uncertainty and is easily automatable

A phase I/II trial of fixed-dose stereotactic body radiotherapy with sequential or concurrent pembrolizumab in metastatic urothelial carcinoma : evaluation of safety and clinical and immunologic response

Background: Current first-line standard of therapy for metastatic urothelial carcinoma is platinum-based combination chemotherapy. Pembrolizumab in phase III has demonstrated a promising overall response rate of 21.1% in patients with progression or recurrence after platinum-based chemotherapy. Preclinical and clinical evidence suggests that radiotherapy has a systemic anti-cancer immune effect and can increase the level of PD-L1 and tumor infiltrating lymphocytes in the tumor microenvironment. These findings gave rise to the hypothesis that the combination of radiotherapy with anti-PD1 treatment could lead to a synergistic effect, hereby enhancing response rates. Methods: The phase I part will assess the dose limiting toxicity of the combination treatment of stereotactic body radiotherapy (SBRT) with four cycles of pembrolizumab (200 mg intravenously, every 3 weeks) in patients with metastatic urothelial carcinoma. The dose of both pembrolizumab and SBRT will be fixed, yet the patients will be randomized to receive SBRT either before the first cycle of pembrolizumab or before the third cycle of pembrolizumab. SBRT will be delivered (24 Gy in 3 fractions every other day) to the largest metastatic lesion. Secondary objectives include response rate according to RECIST v1.1 and immune related response criteria, progression-free survival and overall survival. The systemic immune effect triggered by the combination therapy will be monitored on various time points during the trial. The PD-L1/TIL status of the tumors will be analyzed via immunohistochemistry and response rates in the subgroups will be analyzed separately. A Simon's two-stage optimum design is used to select the treatment arm associated with the best response rate and with acceptable toxicity to proceed to the phase II trial. In this phase, 13 additional patients will be accrued to receive study treatment. Discussion: The progress made in the field of immunotherapy has lead to promising breakthroughs in various solid malignancies. Unfortunately, the majority of patients do not respond. The current trial will shed light on the toxicity and potential anti-tumor activity of the combination of radiotherapy with anti-PD1 treatment and may identify potential new markers for response and resistance to therapy

Toxoplasma gondii-induced brachial plexus neuropathy after allogeneic hematopoietic stem cell transplantation

Brachial plexus neuropathy is a rare, but underdiagnosed condition, characterized by intense analgesic-resistant shoulder pain, followed by brachial plexus paresis and sensory symptoms. We present a case of brachial plexus neuropathy, induced by Toxoplasma gondii (T. gondii) 17 days after allogeneic hematopoietic stem cell transplantation (alloHSCT) in a patient with acute myeloid leukemia. The diagnosis was made based on the clinical presentation, magnetic resonance imaging (MRI) of the brachial plexus, and positive T. gondii polymerase chain reaction (PCR) in cerebrospinal fluid. The patient was treated with pyrimethamine, sulfadiazine, and levofolinic acid during 6 weeks, with a positive outcome