Activity and safety of avelumab in high-grade neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas progressive after chemotherapy (AveNEC trial).

Background: Neuroendocrine neoplasias grade 3 (NEN G3) are rare tumors with poor prognosis and no established second-line therapy. The role of immune checkpoint blockade in these aggressive tumors remains unclear.

Methods: The phase II AVENEC study evaluated the effect of avelumab (AVE, 10 mg/kg IV Q2W) in 60 patients with well-differentiated high-grade neuroendocrine tumors (NET G3, N=22) or poorly differentiated neuroendocrine carcinomas (NEC, N=38) progressing after ≥ one prior chemotherapy (excluding Merkel cell and small-cell lung cancer).

Efficient Rejoining of DNA Double-Strand Breaks despite Increased Cell-Killing Effectiveness following Spread-Out Bragg Peak Carbon-Ion Irradiation.

Radiotherapy of solid tumors with charged particles holds several advantages in comparison to photon therapy; among them conformal dose distribution in the tumor, improved sparing of tumor-surrounding healthy tissue, and an increased relative biological effectiveness (RBE) in the tumor target volume in the case of ions heavier than protons. A crucial factor of the biological effects is DNA damage, of which DNA double-strand breaks (DSBs) are the most deleterious. The reparability of these lesions determines the cell survival after irradiation and thus the RBE.