Welcome to the world of sarcoma with the fifth episode of ‘5 Min Sarcoma Talk‘ on OncoDaily. In this episode, host Dr. Hovsepyan and esteemed sarcoma expert Prof. Andrea Ferrari discuss the history and challenges of non-rhabdomyosarcoma soft tissue sarcomas, Prof. Ferrari’s inspiring path to pediatric oncology, and more.

Join us for an educational and inspiring journey into the sarcoma field.

Andrea Ferrari

Professor Andrea Ferrari is a pediatric oncologist working at the Pediatric Oncology Unit of the National Cancer Institute of Milan. His clinical and research interests are focused on adolescents and young adults with cancer. He holds various leadership roles in international childhood cancer study groups and advisory boards.

He is a founding member of the Board of the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) and the Chair of the EpSSG Scientific Committee on Non-rhabdomyosarcoma soft tissue sarcomas. He coordinates the Italian AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Working Group on Soft Tissue Sarcomas concerning pediatric rare tumors.

He also developed the “Youth Project” in Milan. Prof. Ferrari is author or co-author of over 500 papers published in international scientific journals.

Shushan Hovsepyan

Shushan Hovsepyan is a pediatric oncologist and adjunct assistant professor at the Yerevan State Medical University. Currently, she is the Editor-in-Chief of OncoDaily Medical Journal.

She completed her clinical at the National Institute of Cancer in Milan, Italy and at the St. Anna Children’s Research Hospital in Austria Furthermore, she held a research fellowship position at the European Organisation for Research and Treatment of Cancer in Brussels, Belgium.

Dr. Hovsepyan also completed the Postgraduate Harvard Medical School’s Effective Writing for Healthcare program. She is a former co-chair of the SIOP Global Health Network Education and Training Working Group.

00:00 Introduction
1:15 Non-rhabdomyosarcoma soft tissue sarcomas
2:33 Key challenges during NRSTs treatment
4:31 Envisioning the future of clinical trials for NRSTs
7:07 Prof. Ferrari’s journey in oncology
9:33 Advice for young oncologists interested in sarcomas

The Transcript of 5 min Sarcoma Talk with Shushan Hovsepyan and Andrea Ferrari

Shushan Hovsepyan: Hello everyone and Welcome to our five-minute Sarcoma Talk podcast on  OncoDaily. I’m Shushan Hovsepyan, a pediatric oncologist from Armenia and I’m thrilled to be your host today.

Today we have a very special guest, Professor Andrea Ferrari, who is a pediatric oncologist working at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori di Milano. His clinical and research interests are focused on adolescents and young adults with cancer, and he holds various leadership roles in international Childhood Cancer study groups and advisory boards.

He is the chair of NRSTS scientific committee within European Pediatric Soft Tissue Sarcoma Group. And finally, he is my mentor who taught me everything about STS from A to Z and really sparked my interest in Sarcomas. So welcome, Professor Ferrari!

Andrea Ferrari: Thank you, Shushan, for the nice introduction. 

Shushan Hovsepyan: Thank you for being with us today. And let’s start from the background.

What are NRSTS (Non-Rhabdomyosarcoma Soft Tissue Sarcomas)? How would you define this group of tumors?

Andrea Ferrari: Yes, when we talk about NRSTS, we should know that we’re talking about a very heterogeneous group of different tumor types. Under the definition of NRSTS, we include low-grade tumors with a very benign course, but also very highly malignant diseases with a very poor outcome. And this is one of the major problems because under the same definition, we include very, very different tumors.

On a general rule, we can say that NRSTS are characterized by a scarce response to chemotherapy, by the fact that they are rare tumors (less than 3-4% of pediatric cancers), and most of them are more typically found in adults.

This is the main reason why it is difficult to build a clinical trial on NRSTS, just due to their heterogeneity.

Shushan Hovsepyan: Yeah, that’s very important to know because a lot of people don’t know the definition of Non-Rhabdomyosarcoma Soft Tissue Sarcoma, especially taking into account the fact that it has more than 60 subtypes.

And what are the key challenges associated with the treatment of NRSTS? And can you provide us with some historical overview of the treatment during the years?

Andrea Ferrari: One of the main issues is that, up to 2000-2005, NRSTS were really orphan diseases. They were treated all together on the same clinical guideline: low-grade tumors with the same treatment as high-grade tumors.

The treatment was adopted for rhabdomyosarcoma, which is clearly a completely different disease. Just to say that there were no clinical trials, the two largest published series were single-center series: one from the St. Jude Children’s Research Hospital and the other from The Instituto Nazionale dei Tumori in Milan.

The key point of the history of NRSTS is around 2005. Around 2005, the two major Cooperative International trials, the Children’s Oncology Group and the European Pediatric Soft Tissue Sarcoma Study Group, developed, in the same time, two very similar clinical protocols fully dedicated to NRSTS.

The AOST0332 from the Children’s Oncology Group and the EPCG R2005. The two protocols were very similar in philosophy, in the clinical approach, in the risk stratification, and the treatments adopted from the adult history.

And we can say that these two trials really represent today the benchmark for the treatment of NRSTS, and they were able to develop a sort of standard treatment for all the NRSTS types.

Shushan Hovsepyan: Yeah, that’s enlightening to see that during the history, the approach to treat NRSTS changed a lot.

And in your ideal imagination, how do you envision the future of clinical trial design for Pediatric NRSTS, especially in terms of incorporating Innovative therapies and emphasizing also patient-centered outcomes?

Andrea Ferrari: We say that many things change, but we are still treating NRSTS in a few different types of treatment approach. We have the definition of adult-type NRSTS that are dedifferentiated liposarcoma, solitary fibrous tumor, myxofibrosarcoma, epithelioid sarcoma, commentoma, and we treat them according to a risk stratification where we use the tumor grade, tumor size, tumor site to mitigate the degree of initial surgical resection, to define a surgical group, a radiotherapy group, a neo-adjuvant group. But we still continue to treat them according to the same treatment approach.

Ideally, in the future, we should find a way to treat according to the histological or even better, the molecular characteristics of the tumor. The problem is that NRSTS are very rare, are rare in pediatric age, in particular, are rare also in the adult age, and so there is the big problem to think to develop clinical trials just for the molecular target or just for the histology to be more simple. But we don’t have the numbers to do this.

So, the first issue is to try to work together in a transage view, working together with adults. This is not easy because we know that the pediatric community and the adult community are very different for many reasons.

But the situation is changing over the years, and now we are starting to work together, to think protocols together, exactly what you say, to try to incorporate all the novelties that are coming, in particular from the adult group, in terms of better understanding the tumor of the tumors, to find a better molecular characterization, to think of a better risk stratification not based on tumor size, based on molecular characteristics, and to find new targeted therapies that can be incorporated into the treatment.

Shushan Hovsepyan: Yeah, you very well mentioned all the challenges, and I would like to mention one as well, also the funding. Taking into account the fact that NRSTS are very rare, funding is something that is also challenging because there are not many companies that are interested to invest in such rare diseases.

Reflecting on your journey as a pediatric oncologist, how did you start specializing in soft tissue sarcomas? And could you share with us your journey?

Andrea Ferrari: It’s difficult to say when I started to work in soft tissue sarcomas. The major focus was on rhabdomyosarcoma as many of us. But as I said before, I think it was really of great interest for me to see how when we started to work together with other colleagues, NRSTS were really orphan diseases. They were really neglected. There was nothing on NRSTS.

This was the major reason to focus our attention, my attention, on NRSTS, and in particular, to try to change something in terms of thinking outside the box. Where the box at the time was the pediatric world that was really isolated, no relationship with the other worlds, difficult to work together.

And I think that one of the major issues also, when thinking about the way to build new treatment approaches for NRSTS, I think that the real idea was to work together. There is a nice sentence that we use sometimes that says, “When you work with common cancers, do randomized trials. When you work on rare cancers, find friends.”

And so, the idea was really to find friends, to find cooperation, to find people that can help us to build a better treatment approach, better knowledge for these patients that were really neglected. And I think we changed many things. What we are doing together is very different from what we did in the past.

And for the future, we are really thinking to open our mind to worldwide cooperation, transatlantic cooperation, cooperation together between pediatric and other worlds because there are a lot of things to change.

You mentioned the problem of the access to clinical trials and to new drugs for pediatric patients. These are major issues because sometimes the drugs that are available and they can be interesting in the adult soft tissues sarcoma are not available for children. So, there are a lot of things we need to change, and I think we are changing.

Shushan Hovsepyan: Thanks a lot. That’s very inspirational. And lastly, what is your advice to young pediatric oncologists interested in sarcomas?

Andrea Ferrari: I don’t know. I think it’s important that for young oncologists, you need to find your interest and to dedicate yourself to these interests. My impression, looking at my experience but also the experience of other colleagues, is that in current oncology, in current pediatric oncology, you cannot be an expert for everything.

So, it’s important you find your tumor types and you dedicate yourself with all your energy, with all your beauty, with your everything to this kind of tumor for research, for cooperation, for clinical studies, always taking in your mind that we do this for our patients because everything is done for the patients and not just for the value of research that is sometimes the same but sometimes not.

Shushan Hovsepyan: Yeah, that’s very correct. And thank you for sharing your insights and thank you for your time. I know that you are extremely busy.

And to our listeners, I hope you enjoyed our discussion. Join us next time for more conversations about sarcomas. Stay informed and goodbye for now.

Andrea Ferrari: Okay, thank you. Goodbye.

Previous episodes of  5 min Sarcoma Talk with Shushan Hovsepyan

Episode 1: Leo Kager

Episode 2: Rajkumar Venkatramani

Episode 3: Aaron Weiss

Episode 4: Leo Mascarenhas