Fertility discussions and concerns in childhood cancer survivors, a systematic review for updated practice.

PURPOSE: To provide ways to improve the clinical practice of fertility preservation (FP) for children, adolescents, and young adults (AYA) with cancer. DESIGN: A systematic research of online databases was undertaken in March 2020 following the PRISMA criteria, including Medline and Web of Science. RESULTS: Fifty-nine articles were included. Surveys, interviews, and focus groups were used to collect data from patients, parents, and health care providers (HCPs). Four themes worth exploring emerged: (a) what do patients and professionals think of and know about FP? (b) what makes the fertility discussion happen or not? (c) what, retrospectively, led to FP being pursued or not? and (d) how do patients and HCPs feel about fertility issues? CONCLUSION: A minority of AYAs preserve their fertility (banking assay for 45% of boys and 23% of girls). Yet fertility concerns have a significant impact on the quality of life of young cancer survivors. Although recommendations and guidelines regarding FP are available internationally, there are no specific guidelines as to how to conduct fertility counseling for children and adolescents. Some barriers are not removable, such as a poor prognosis of an obvious severe disease, time constraints for starting treatment, and cultural and religious beliefs. In response to aspects hindering patients and families to be receptive to any discussion at the time of diagnosis, psychological support could reduce the level of emotional distress and help restore a degree of open-mindedness to open a window for discussion. Moreover, as the lack of knowledge of professionals about fertility is frequently pointed out as a limiting factor for fertility discussion, reinforcing professional training regarding FP could be proposed to promote fertility discussion and eventually referral for FP.

Antiangiogenic therapy: Markers of response, "normalization" and resistance.

Currently in cancer treatment, one premise is to use antiangiogenic therapies in association with chemotherapy or radiotherapy to augment their efficacy by benefiting from the vascular "normalization" induced by antiangiogenic therapy. This concept defines the time during which the tumor blood vessels adopt normal-like morphology and functionality, i.e. the blood vessels become more mature, the perfusion augments and hypoxia decreases. To date, there is such a diversity of treatment protocols where the type of antiangiogenic to adopt, its dose and duration of administration are different, that knowing when and how to treat is problematic. In this review, we analyzed thoroughly preclinical and clinical studies that use antiangiogenic treatments to benefit from the "normalization" and showed that the effects depend on the type of antiangiogenic administrated (anti-VEGF, anti-VEGFR, Multi-Kinase Inhibitor) and on the duration of treatment. Finally, biomarkers of "normalization" and resistance that could be used in the clinic are presented.

A new algorithm for a better characterization and timing of the anti-VEGF vascular effect named "normalization".

Antiangiogenics are widely used in cancer treatment in combination with chemotherapy and radiotherapy for their vascular effects. Antiangiogenics are supposed to induce morphological and functional changes in the chaotic tumor vasculature that would help enhance the therapeutic efficacy of chemotherapy and radiotherapy through the amelioration of the drug delivery or the oxygenation in the tumor, respectively. However, finding the best treatment sequence is not an easy task to achieve and no consensus has yet been established because of the lack of knowledge regarding when and for how long the vascular network is ameliorated. The aim of this work was to develop a dedicated image processing algorithm able to analyze the vascular structures on optical microscopy images of the vascular network and to follow its fine modifications in vivo, over time. We applied this algorithm to follow the evolution of the vascular parameters (vascularized tissue surface, branches, sprouts and length), in response or not to anti-VEGF therapy (10 mg/kg/day) and determine precisely whether there is really a vascular "normalization" with anti-VEGF therapy in comparison with the parameters extracted from healthy vascular networks. We found that for this determination, the choice of region of interest to analyze is critical as it is important to compare only microcirculation areas and avoid areas with arteriole-venule-capillary hierarchy. The algorithm analysis allowed us to define a vascular "normalization" in treated tumors, between 8 and 12 days of bevacizumab treatment that was confirmed by standard immunohistochemical analysis, microvascular permeability assessment and immunohistological blood perfusion assessment.