Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.

Novel ion exchange chromatography method for nca arsenic separation.

A high-performance liquid chromatography (HPLC) device equipped with an anion exchange column was used to isolate nca 77As from reactor irradiated natGeO2 targets. The oxidation states of the isotope 77As during the process was verified by thin layer chromatography. The radionuclidic purity of the separated fractions was checked by gamma measurements and it was found to be 99.91% for the As fraction. The elaborated method was applied to separate the isotope 74As from cyclotron irradiated natGeO2 targets too.

Study of excitation function of deuteron induced reactions on nat Kr up to 20 MeV.

In the frame of a systematic study of the activation cross-sections of deuteron induced reactions on different elements, excitation functions on (nat)Kr were investigated up to 20 MeV. The excitation functions for production of (81 m,81 mg,82 g,83,84 m,84 mg,86 mg)Rb, (79,85 m,87)Kr and (77,82)Br radionuclides were measured for the first time using stacked gas cell irradiation technique and gamma-ray spectrometry. The measured data were compared with the results of the theoretical model codes.

Optimization of source-sample-detector geometries for bulk hydrogen analysis using epithermal neutrons.

The advantages and limitations of epithermal neutrons in qualification of hydrocarbons via their H contents and C/H atomic ratios have been investigated systematically. Sensitivity of this method and the dimensions of the interrogated regions were determined for various types of hydrogenous samples. Results clearly demonstrate the advantages of direct neutron detection, e.g. by BF(3) counters as compared to the foil activation method in addition to using the hardness of the spectral shape of Pu-Be neutrons to that from a (252)Cf source.

An improved method for bulk hydrogen analysis using epithermal neutrons.

The advantages of direct detection of thermalized neutrons as compared to the activation method used for bulk hydrogen analysis have been investigated. In both cases samples of 10 cm diameter and 8 cm height dimensions were used. It was found that the new method based on a small BF(3) counter placed along the central line of the cylindrical samples renders the determination of hydrogen contents routinely possible using a few minutes measuring time and a low intensity ( approximately 18.5 GBq) neutron source. A preliminary investigation has shown that the direct detection of neutrons can be used for analysis of samples as large as about 20l. Details of this technique and its applications will be discussed in the next paper.

A comparison of the neutron thermalization and reflection methods used for bulk hydrogen analysis.

The advantages and limitations of the slowing down of epithermal neutrons and the thermal neutron reflection methods were compared for bulk hydrogen analysis. In both cases, the same sample dimensions were used, i.e. 10cm diameter and 8cm height. It was found that the sensitivity of the slowing down method is higher by a factor of approximately 20 in average and the matrix effect can be neglected as compared to the neutron reflection technique. The simultaneous application of the two methods renders the determination of the H content and the C/H atomic ratio possible. The effect of spatial distribution of hydrogen in the matrix to be investigated on the number of reflected neutrons was also studied.

Determination of hydrogen content in bulk samples using the neutron activation method.

The applicability of a new irradiation facility for bulk hydrogen analysis based on the activation method using thermal and epithermal neutrons has been tested for cylindrical samples of 8 cm diameter and 10 cm high. A definite correlation was found between the relative excess flux values, R and the total hydrogen contents, N(H) of the samples. Analytical expressions obtained for R vs. N(H) function indicate the possible use of this method even in the case of approximately kg weight and liter sample dimensions. The large sample has a special advantage if the determination of the hydrogen concentration, C(H) is in question.

Investigations on landmine detection by neutron-based techniques.

Principles and techniques of some neutron-based methods used to identify the antipersonnel landmines (APMs) are discussed. New results have been achieved in the field of neutron reflection, transmission, scattering and reaction techniques. Some conclusions are as follows: The neutron hand-held detector is suitable for the observation of anomaly caused by a DLM2-like sample in different soils with a scanning speed of 1m(2)/1.5 min; the reflection cross section of thermal neutrons rendered the determination of equivalent thickness of different soil components possible; a simple method was developed for the determination of the thermal neutron flux perturbation factor needed for multi-elemental analysis of bulky samples; unfolded spectra of elastically backscattered neutrons using broad-spectrum sources render the identification of APMs possible; the knowledge of leakage spectra of different source neutrons is indispensable for the determination of the differential and integrated reaction rates and through it the dimension of the interrogated volume; the precise determination of the C/O atom fraction requires the investigations on the angular distribution of the 6.13MeV gamma-ray emitted in the (16)O(n,n'gamma) reaction. These results, in addition to the identification of landmines, render the improvement of the non-intrusive neutron methods possible.