Development of randomized trials in adults with medulloblastoma - the example of EORTC 1634-BTG/NOA-23

Simple Summary Medulloblastoma is rare after puberty. Among several molecular subgroups that have been described, the sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal population and can be targeted with smoothened (SMO) inhibitors. However, no practice-changing prospective clinical trials have been published in adults to date. Tumors often recur, and treatment toxicity is relevant. Thus, the EORTC 1634-BTG/NOA-23 trial for post-pubertal patients with standard risk medulloblastoma will aim to increase treatment efficacy and to decrease treatment toxicity. Patients will be randomized between standard-dose vs. reduced-dosed radiotherapy, and SHH-subgroup patients will also be randomized between the SMO inhibitor sonidegib (Odomzo(TM,), Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone. In ancillary studies, we will investigate tumor tissue, blood and cerebrospinal fluid samples, magnetic resonance images, and radiotherapy plans to gain information that may improve future treatment. Patients will also be monitored long-term for late side effects of therapy, health-related quality of life, cognitive function, social and professional live outcomes, and reproduction and fertility. In summary, EORTC 1634-BTG/NOA-23 is a unique multi-national effort that will help to council patients and clinical scientists for the appropriate design of treatments and future clinical trials for post-pubertal patients with medulloblastoma. Medulloblastoma is a rare brain malignancy. Patients after puberty are rare and bear an intermediate prognosis. Standard treatment consists of maximal resection plus radio-chemotherapy. Treatment toxicity is high and produces disabling long-term side effects. The sonic hedgehog (SHH) subgroup is highly overrepresented in the post-pubertal and adult population and can be targeted by smoothened (SMO) inhibitors. No practice-changing prospective randomized data have been generated in adults. The EORTC 1634-BTG/NOA-23 trial will randomize patients between standard-dose vs. reduced-dosed craniospinal radiotherapy and SHH-subgroup patients between the SMO inhibitor sonidegib (Odomzo(TM), Sun Pharmaceuticals Industries, Inc., New York, USA) in addition to standard radio-chemotherapy vs. standard radio-chemotherapy alone to improve outcomes in view of decreased radiotherapy-related toxicity and increased efficacy. We will further investigate tumor tissue, blood, and cerebrospinal fluid as well as magnetic resonance imaging and radiotherapy plans to generate information that helps to further improve treatment outcomes. Given that treatment side effects typically occur late, long-term follow-up will monitor classic side effects of therapy, but also health-related quality of life, cognition, social and professional outcome, and reproduction and fertility. In summary, we will generate unprecedented data that will be translated into treatment changes in post-pubertal patients with medulloblastoma and will help to design future clinical trials.Neurolog

Foraging of a hypogaeic army ant: a long neglected majority

Army ants have been studied thoroughly for more than a century. The conduction of column and swarm mass raids, featured by epigacicly active species, is believed to be a central characteristic of army ant behavior. Most army ant species, however, lead a hypogaeic life. Due to the difficulties to observe them, nothing is known about their hypogacic behavior in the field. Using palm oil baits, trail excavations, and laboratory observations, the hypogaeic foraging of Dorylus (Dichthadia) laevigatus was observed in Malaysia. D. laevigatus was found to construct stable hypogaeic trunk trail systems providing quick and easy access to all parts of its foraging area. Small column raids were conducted throughout the ground stratum and above the ground surface. These raids were caste specific, with the smallest workers predominantly following existing cracks and tunnels in the soil. In case of food location, larger workers were recruited from nearby trunk trails. Exploratory trails leading to prey had to be widened before larger workers could gain access and help to process the food. Bulky food sources such as baits or termite mounds could be exploited over several weeks to months. Besides raiding in columns, D. laevigatus came occasionally to the ground surface at night to conduct swarm raids. This combination of swarm and column raids with the use of trunk trails has never been demonstrated for a classical army ant species. The omnipresence of D. laevigatus within its foraging area stands in sharp contrast to epigaeicly active species, characterized by a very localized and temporary presence at foraging sites. D. laevigatus stayed in the same foraging area for several weeks to months. Having a broad diet and the ability to exploit bulky food sources over long periods of time, D. laevigatus seems to follow a sustainable use of the soil fauna. Summing up these particularities demonstrates a remarkable divergence of the hypogacic foraging of D. laevigatus from that of epigacicly foraging army ant species