Improving susceptibility of neuroendocrine tumors to radionuclide therapies: personalized approaches towards complementary treatments.

Radionuclide therapies are an important tool for the management of patients with neuroendocrine neoplasms (NENs). Especially [131I]MIBG and [177Lu]Lu-DOTA-TATE are routinely used for the treatment of a subset of NENs, including pheochromocytomas, paragangliomas and gastroenteropancreatic tumors. Some patients suffering from other forms of NENs, such as medullary thyroid carcinoma or neuroblastoma, were shown to respond to radionuclide therapy; however, no general recommendations exist. Although [131I]MIBG and [177Lu]Lu-DOTA-TATE can delay disease progression and improve quality of life, complete remissions are achieved rarely. Hence, better individually tailored combination regimes are required. This review summarizes currently applied radionuclide therapies in the context of NENs and informs about recent advances in the development of theranostic agents that might enable targeting subgroups of NENs that previously did not respond to [131I]MIBG or [177Lu]Lu-DOTA-TATE. Moreover, molecular pathways involved in NEN tumorigenesis and progression that mediate features of radioresistance and are particularly related to the stemness of cancer cells are discussed. Pharmacological inhibition of such pathways might result in radiosensitization or general complementary antitumor effects in patients with certain genetic, transcriptomic, or metabolic characteristics. Finally, we provide an overview of approved targeted agents that might be beneficial in combination with radionuclide therapies in the context of a personalized molecular profiling approach.

The cost of improving nutritional outcomes through food-assisted maternal and child health and nutrition programmes in Burundi and Guatemala.

Evidence on the cost-effectiveness of multisectoral maternal and child health and nutrition programmes is scarce. We conducted a prospective costing study of two food-assisted maternal and child health and nutrition programmes targeted to pregnant women and children during the first 1,000 days (pregnancy to 2 years). Each was paired with a cluster-randomized controlled trial to evaluate impact and compare the optimal quantity and composition of food rations (Guatemala, five treatment arms) and their optimal timing and duration (Burundi, three treatment arms). We calculated the total and per beneficiary cost, conducted cost consequence analyses, and estimated the cost savings from extending the programme for 2 years. In Guatemala, the programme model with the lowest cost per percentage point reduction in stunting provided the full-size family ration with an individual ration of corn-soy blend or micronutrient powder. Reducing family ration size lowered costs but failed to reduce stunting. In Burundi, providing food assistance for the full 1,000 days led to the lowest cost per percentage point reduction in stunting. Reducing the duration of ration eligibility reduced per beneficiary costs but was less effective. A 2-year extension could have saved 11% per beneficiary in Guatemala and 18% in Burundi. We found that investments in multisectoral nutrition programmes do not scale linearly. Programmes providing smaller rations or rations for shorter durations, although less expensive per beneficiary, may not provide the necessary dose to improve (biological) outcomes. Lastly, delivering effective programmes for longer periods can generate cost savings by dispersing start-up costs and lengthening peak operating capacity.