Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time. This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails

First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion

One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full-size liver graft was derived from a 13-year-old, female DCD donor and was end-ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16-year-old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation

TYK2 is a key regulator of the surveillance of B lymphoid tumors

Aberrant activation of the JAK-STAT pathway has been implicated in tumor formation; for example, constitutive activation of JAK2 kinase or the enforced expression of STAT5 induces leukemia in mice. We show here that the Janus kinase TYK2 serves an opposite function. Mice deficient in TYK2 developed Abelson-induced B lymphoid leukemia/lymphoma as well as TEL-JAK2–induced T lymphoid leukemia with a higher incidence and shortened latency compared with WT controls. The cell-autonomous properties of Abelson murine leukemia virus–transformed (A-MuLV–transformed) TYK2(–/–) cells were unaltered, but the high susceptibility of TYK2(–/–) mice resulted from an impaired tumor surveillance, and accordingly, TYK2(–/–) A-MuLV–induced lymphomas were easily rejected after transplantation into WT hosts. The increased rate of leukemia/lymphoma formation was linked to a decreased in vitro cytotoxic capacity of TYK2(–/–) NK and NKT cells toward tumor-derived cells. RAG2/TYK2 double-knockout mice succumbed to A-MuLV–induced leukemia/lymphoma faster than RAG2(–/–)TYK2(+/–) mice. This defines NK cells as key players in tumor surveillance in Abelson-induced malignancies. Our observations provide compelling evidence that TYK2 is an important regulator of lymphoid tumor surveillance