S.H.: Just all right. So, hello everyone, and welcome to our first episode of Five Minute Sarcoma Talk on Onco Daily. I’m Shushan Hovsepian, a pediatric oncologist from Armenia, and I’m thrilled to be your host today. Today, we have the privilege to speak with Professor Leo Kager, who is a world-renowned osteosarcoma expert and heads the Saint Anna Children’s Research Institute and outpatient clinic at Saint Anna Children’s Hospital in Vienna, Austria. Hello, Professor Kager, how are you?

L.K.: Hello, Shushan. Good to see you. It was a great time having you here in Vienna.

S.H.: Thank you. I had the pleasure to work with Professor Kager for a short time in Vienna. He’s an excellent expert in the field and also a wonderful personality. So, let’s start with our questions to shed some light on the challenges of osteosarcoma treatment and research. So, a little bit of history. How has the approach to treating pediatric osteosarcoma evolved in the last three decades?

L.K.: Coming back, the very first important step was the Myers trial in the US, where the advantage of chemotherapy compared to surgery alone was proven. Two years ago, I started working for two years in Memphis, Tennessee, and my former boss, Bill Evans, who became director of Saint Jude, asked me, “Leo, can you tell me your work in the field of osteosarcoma? What have you achieved in the last 15 years?” And actually, I said, “Which drugs do you use?” And I said, “We use MAP and Ifosfamide and VB 16.” And he said, “But that was used 20 years ago.” And I had to confess, “Yes, and now, 22 years later, we still use the same drugs as standard.” So from the systemic treatment approach, there was not much progress. However, when it comes to the local therapy, there was really progress made in radiotherapy because osteosarcoma, compared to Ewing sarcoma, is more radio-resistant. But when you use carbon ions and protons, especially in combination, you can really achieve a local tumor control.

S.H.: Yeah, that’s a little bit frustrating not to have a treatment option for so long. But, we need to work on that to improve the systematic treatment. Building on that point, what are the current critical gaps in the research field that, in your opinion, need special attention?

L.K.: Yeah, I think it’s wise to look at osteoclasts and Ewing sarcomas. So in Ewing sarcomas, we have made progress. So when a treatment intensification is shown by the Koc group, with the addition of ifosfamide vp16 to the standard backbone, that resulted in significant improved survival. The same was true when we did the compressed treatment. So this is now the standard to compress the chemo treatment and local control rate in a five-year event-free survival in patients with Ewing sarcoma and localized disease is about 87% or so. And in osteosarcoma, it’s 60%. So there is a huge gap. And now we have to figure out what is the difference. Why do osteosarcoma cells migrate so often to the lung? What is the difference in comparison to Ewing sarcoma cells? So in Ewing’s, at least in osteosarcoma, when you have a relapse, you have a second chance. In Ewing sarcoma, it’s very hard to become a long-term survival when you relapse. To figure out what are the mechanisms behind that gives rise to such a high number of metastases? I think this is a very important task ahead.

S.H.: Yeah, that’s true. But, is there anything transformative and a breakthrough in the treatment maybe also from the preclinical field, is there something that is really promising for the future?

L.K.: Yeah. There is one group of drugs, the TKIs, especially Cabozantinib. And the CoC is planning or is performing already a trial with frontline Cabozantinib. And here in Europe, we have founded the Foster Consortium to fight osteosarcoma through European research. First time that we have almost all countries in Europe participating in such a consortium. And we are happy that we can also now go into a trial with a chemo backbone, plus Cabozantinib add-on treatment.

S.H.: That’s an incredible progress to have a consortium working specifically on osteosarcoma after this long time. And, I always think that collaborative effort will always pay off. So, hopefully, we will have results very soon. And now, as we are wrapping up our conversation and stepping from research, I would like to ask you about your personal experience. What motivated you initially to specialize in osteosarcoma research and treatment?

L.K.: As I started more than 30 years ago, we had two different wards. One was for solid tumors and the other was for liquid malignancies. And that was why I started to become more involved in solid tumors. And then it was, of course, the fantastic environment of the CoC group and the many other friends throughout the world. And now, it’s kind of I’m close to retirement, and now it’s very important, we can cure many patients already. But now it’s high time to have this also for our osteosarcoma patients. So, very simply, why I came into the field, but why I stick now in the field is to get adequate treatment for the osteosarcoma patients.

S.H.: Thanks. Thank you very much for sharing your perspectives. And also, I think it is very interesting for young oncologists to learn from personal experience of the experts. And thank you for accepting our invitation. Thank you for being with us today. And we hope that our episode, our listeners will find informative and engaging. And let’s continue to learn, grow, and support each other on this journey. Thanks a lot, everyone, for listening.

L.K.: Thank you very much and warmest greetings to all friends in Yerevan.

S.H: Thanks a lot.