Neratinib as Extended Adjuvant Treatment of HER2-Positive/HR-Positive Early Breast Cancer Patients in Germany, Austria, and Switzerland: Interim Results of the Prospective, Observational ELEANOR Study.

Prognosis of patients diagnosed with HER2+ early breast cancer (eBC) has substantially improved, but distant recurrences impacting quality of life and survival still occur. One treatment option for extended adjuvant treatment of patients with HER2+/HR+ eBC is neratinib, available in Europe for patients who completed adjuvant trastuzumab-based therapy within 1 year. The ELEANOR study is investigating the real-world use of neratinib in Germany, Austria, and Switzerland. Results from an interim analysis of the first 200 patients observed for ≥3 months are reported. The primary objective of this prospective, multicenter, observational study is to assess patient adherence to neratinib (defined as the percentage of patients taking neratinib on ≥75% prescribed days). Secondary objectives are patient characteristics and treatment outcomes. At cut-off (May 2, 2022), a total of 202 patients had been observed for ≥3 months, with neratinib treatment documented for 187 patients (median age: 53.0 years; 67.9% at increased risk of disease recurrence). In total, 151 (80.7%) patients had received prior neoadjuvant treatment; of these, 82 (54.3%) patients achieved a pathologically complete response. Neratinib was initiated at a median 3.6 months after trastuzumab-based treatment, with 36.4% starting at a dose <240 mg/day. Treatment is ongoing for 46.0% of patients, with median treatment duration of 11.2 (interquartile range 0.9-12.0) months. Diarrhea was the most common adverse event (78.6% any grade, 20.3% grade ≥3); pharmacologic prophylaxis was used in 85.6% of patients. The pattern of anti-HER2 pretreatment observed reflected the current treatment for HER2+/HR+ eBC in Germany, Austria, and Switzerland. These interim results suggest that neratinib as an extended adjuvant is a feasible option after various anti-HER2 pretreatments and that its tolerability can be managed and improved with proactive diarrhea management

Radiomics biopsy signature for predicting survival in patients with spinal bone metastases (SBMs)

STUDY DESIGN: Retrospective analysis of a registered cohort of patients treated and irradiated for metastases in the spinal column in a single institute. OBJECTIVE: This is the first study to develop and internally validate radiomics features for predicting six-month survival probability for patients with spinal bone metastases (SBM). BACKGROUND DATA: Extracted radiomics features from routine clinical CT images can be used to identify textural and intensity-based features unperceivable to human observers and associate them with a patient survival probability or disease progression. METHODS: A study was conducted on 250 patients treated for metastases in the spinal column irradiated for the first time between 2014 and 2016, at the MAASTRO clinic in Maastricht, the Netherlands. The first 150 available patients were used to develop the model and the subsequent 100 patient were considered as a test set for the model. A bootstrap (B = 400) stepwise model selection, which combines both the forward and backward variable elimination procedure, was used to select the most useful predictive features from the training data based on the Akaike information criterion (AIC). The stepwise selection procedure was applied to the 400 bootstrap samples, and the results were plotted as a histogram to visualize how often each variable was selected. Only variables selected more than 90 % of the time over the bootstrap runs were used to build the final model. A prognostic index (PI) called radiomics score (radscore) and clinical score (clinscore) was calculated for each patient. The prognostic index was not scaled, the original values were used which can be extracted from the model directly or calculated as a linear combination of the variables in the model multiplied by the respective beta value for each patient. RESULTS: The clinical model had a good discrimination power. The radiomics model, on the other hand, had an inferior performance with no added predictive power to the clinical model. The internal imaging characteristics do not seem to have a value in the prediction of survival. However, the Shape features were excluded from further analyses in our study since all biopsies had a standard shape hence no variability

Radiomics biopsy signature for predicting survival in patients with spinal bone metastases (SBMs)

Study design: Retrospective analysis of a registered cohort of patients treated and irradiated for metastases in the spinal column in a single institute. Objective: This is the first study to develop and internally validate radiomics features for predicting six-month survival probability for patients with spinal bone metastases (SBM). Background data: Extracted radiomics features from routine clinical CT images can be used to identify textural and intensity-based features unperceivable to human observers and associate them with a patient survival probability or disease progression. Methods: A study was conducted on 250 patients treated for metastases in the spinal column irradiated for the first time between 2014 and 2016, at the MAASTRO clinic in Maastricht, the Netherlands. The first 150 available patients were used to develop the model and the subsequent 100 patient were considered as a test set for the model. A bootstrap (B = 400) stepwise model selection, which combines both the forward and backward variable elimination procedure, was used to select the most useful predictive features from the training data based on the Akaike information criterion (AIC). The stepwise selection procedure was applied to the 400 bootstrap samples, and the results were plotted as a histogram to visualize how often each variable was selected. Only variables selected more than 90 % of the time over the bootstrap runs were used to build the final model.A prognostic index (PI) called radiomics score (radscore) and clinical score (clinscore) was calculated for each patient. The prognostic index was not scaled, the original values were used which can be extracted from the model directly or calculated as a linear combination of the variables in the model multiplied by the respective beta value for each patient. Results: The clinical model had a good discrimination power. The radiomics model, on the other hand, had an inferior performance with no added predictive power to the clinical model. The internal imaging characteristics do not seem to have a value in the prediction of survival. However, the Shape features were excluded from further analyses in our study since all biopsies had a standard shape hence no variability

A comparison study between single- and dual-energy CT density extraction methods for neurological proton monte carlo treatment planning

Monte Carlo proton dose calculations requires mass densities calculated from the patient CT image. This work investigates the impact of different single-energy CT (SECT) and dual-energy CT (DECT) to density conversion methods in proton dose distributions for brain tumours. Material and methods: Head CT scans for four patients were acquired in SECT and DECT acquisition modes. Commercial software was used to reconstruct DirectDensity((TM)) images in Relative Electron Densities (RED, ) and to obtain DECT-based pseudo-monoenergetic images (PMI). PMI and SECT images were converted to RED using piecewise linear interpolations calibrated on a head-sized phantom, these fits were referred to as "PMI2RED" and "CT2RED". Two DECT-based calibration methods ("Hunemohr-15it" and "Saito-15it") were also investigated. images were converted to mass-densities () to investigate differences and one representative patient case was used to make a proton treatment plan. Using CT2RED as reference method, dose distribution differences in the target and in five organs-at-risk (OARs) were quantified. Results: In the phantom study, Saito-15it and Hunemohr-15it produced the lowest root-mean-square error (0.7%) and DirectDensity((TM)) the highest error (2.7%). The proton plan evaluated in the Saito-15it and Hunemohr-15it datasets showed the largest relative differences compared to initial CT2RED plan down to -6% of the prescribed dose. Compared to CT2RED, average range differences were calculated: -0.1 +/- 0.3 mm for PMI2RED; -0.8 +/- 0.4 mm for Hunemohr-15it, and -1.2 +/- 0.4 mm for Saito-15it. Conclusion: Given the wide choice of available conversion methods, studies investigating the density accuracy for proton dose calculations are necessary. However, there is still a gap between performing accuracy studies in reference phantoms and applying these methods in human CT images. For this treatment case, the PMI2RED method was equivalent to the conventional CT2RED method in terms of dose distribution, CTV coverage and OAR sparing, whereas Hunemohr-15it and Saito-15it presented the largest differences

A three-month, open-label, single-arm trial evaluating the safety and pharmacokinetics of oral lithium in patients with chronic spinal cord injury

Objectives: Lithium has recently been found to enhance neuronal regeneration and differentiation. This arouses its potential use to treat spinal cord injury patients. The safety and pharmacokinetics of lithium are not verified for this group of patients as their internal organ functions may change. This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of lithium in spinal cord injury patients.Methods: A total of 20 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was given in divided dose to maintain the serum lithium level 0.6-1.2 mmol l -1 for 6 weeks. Safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored.Results: No severe adverse event was documented. All blood parameters remained stable. Nausea and vomiting were the most common complaints but tolerance was improved in 2 weeks for most subjects. A wide range of oral doses was required to maintain serum lithium level at the targeted range. However, the dose for individual subject was relatively constant.Conclusion: This phase 1 clinical trial is the first report indicating the safety of lithium in chronic spinal cord injury patients. It is well tolerated after the first 2 weeks. Individual titration of lithium is essential to maintain an optimal serum lithium level but once the desirable level is achieved, the oral dose remains relatively unchanged for maintenance. © 2011 International Spinal Cord Society All rights reserved.link_to_subscribed_fulltex