We are please to announce taht our manuscript entitled : Metronomic chemotherapy for children in low- and middle-income countries: survey of current practice and opinion of pediatric oncologists by Revon-Rivière Gabriel, Banavali Shripad, Heississen Laila, Gomez Garcia Wendy, , Abdolkarimi Babak, Vaithilingum Manickavallie, Chi-Kong Li, Leung Ping Chung, Prabhat Malik, Pasquier Eddy, Epelman Sidney, Chantada Guillermo, André Nicolas from the following institutions :

 Department of Pediatric Hematology-Oncology, APHM, La Timone Hospital, Marseille France,

 Metronomics Global Health Initiative, Marseille, France, Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India, Homi Bhabha National Institute, Mumbai, India,

 Department of Pediatric Hematology-Oncology, Rabat Children Hospital, University Mohamed V, Rabat, Morocco,

 Department of Pediatric Hematology-Oncology, Dr Robert Reid Cabral Children’s Hospital, Santo Domingo, Dominican Republic,

 Department of Pediatrics, Lorestan University of Medical Science, Khoramabad, Iran

 Netcare Parklands Hospital, Durban, South Africa, Departments of Pediatrics, Prince of Wales Hospital, Chines University of Hong Kong, Hong Kong, China

 Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

 State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong

 Department of Medical Oncology, Dr. BRAIRCH, All India Institute of Medical Sciences, New Delhi, India,

 Centre de Recherche en Cancérologie de Marseille CNRS, INSERM, Aix-Marseille Université, Institut Paoli-Calmettes, Marseille, France,

 Department or Pediatric Oncology, Santa Marcelina Hospital, Sao Paulo, Brazil

 Department of Hematology-Oncology, Hospital JP Garrahan, Buenos Aires, Argentina

has been accepted for publication in Journal of Global Oncology.

PURPOSE: Low and Middle Income Countries (LMIC) experience the burden of 80% of new childhood cancer cases worldwide, with cure rates as low as 10% in some countries. Metronomics combines low-dose chemotherapy in frequent administrations with drug repurposing, which consists in using already-approved drugs for new medical applications. With wide availability, limited costs and little infrastructure needs, metronomics can be part of constraint-adapted regimens in these resource-limited settings. Our study aims at describing experience, practices, opinions and needs in metronomics of physicians working in LMIC. METHODS: Online questionnaire was sent to more than 1200 physicians in pediatric oncology networks of developing countries. Items included type of center, physician’s demographics, experience in pediatric oncology, experience and current knowledge about metronomics. Opinions and perspectives were explored by MAQ and open questions. RESULTS: 17% of physicians responded. 54,9% of respondents declared they had already used a metronomic regimen. Most frequently cited repositioned drugs were celecoxib (44%) followed by propranolol and valproic acid (17%). Respondents pointed the advantages of outpatient use (20%) and expected low toxicity (24%). Considering drawbacks of metronomics, 47% of responses highlighted the lack of scientific evidence or guidelines, 33% the availability or affordability of drugs and 18% the problem of acceptance or compliance. 79% of physicians believed that metronomics use will spread in LMIC in the upcoming years and 98% of them were willing to participate to international metronomic protocols or registries. CONCLUSION: Metronomics is already used in LMIC and is a potential answer to unmet needs in pediatric oncology. There is room for improvement in availability of drugs and a necessity to develop collaborative protocols and research to generate level A evidence.