Dear EditorWe sincerely appreciate the nice comments by Drs. P.V. da Costa Ghignatti and R. Pereira de Lima 1 concerning our recent meta-analysis assessing the effects of physical exercise interventions on cardiovascular endpoints in childhood cancer survivors 2. They are quite right to remain that even non-significant improvements in cardiorespiratory fitness (CRF) might be clinically relevant. Indeed, we still do not know if CRF increments of a theoretically low magnitude (, <1 metabolic equivalent) might have a prognostic value in the context of pediatric cancer and treatment-associated cardiotoxicity. We also agree that unsupervised exercise interventions are unlikely to be as effective as tailored programs, especially because the latter allow for intensity to being adequately controlled and thus gradually increased. It is indeed our opinion, after long years of experience working with children with cancer as well as with other debilitated clinical populations, that there is always room for physiological improvement and ideally loads should be gradually improved instead of remaining stable.© Georg Thieme Verlag KG Stuttgart · New York.