Welcome to the world of sarcoma with the second episode of ‘5 Min Sarcoma Talk’ on OncoDaily. In this episode, host Dr. Hovsepyan and esteemed sarcoma expert Dr. Venkatramani discuss the latest advancements and challenges in rhabdomyosarcoma treatment and research. Discover the promising agents under investigation, Dr. Venkatramani’s inspiring path to pediatric oncology, and more. Join us for an informative and inspiring journey into the sarcoma field.

 About Rajkumar Venkatramani

Dr. Venkatramani is the director of the Rare Tumors Program at Texas Children’s Cancer and Hematology Center. He attended medical school in India and completed his pediatric training at Kings College in London. Furthering his education, he pursued a pediatric residency at the University of Illinois College of Medicine and a pediatric hematology-oncology fellowship at Children’s Hospital Los Angeles. He holds a master’s degree from the University of Southern California and an MBA from the University of Massachusetts. Dr. Venkatramani serves as the scientific chair of the Children’s Oncology Group (COG) Soft Tissue Sarcoma Committee. He has published extensively and received numerous awards for teaching and mentorship.

About Shushan Hovsepyan

Dr. Shushan Hovsepyan is a pediatric oncologist and adjunct assistant professor at the Yerevan State Medical University. She earned her medical degree (M.D.) from the same university’s General Medicine faculty, where she was awarded the Nominal Student Scholarship. Currently, she is a clinical research coordinator at the Yeolyan Hematology and Oncology Center. She completed a clinical fellowship lasting over a year at the pediatric oncology unit of the National Institute of Cancer in Milan, Italy, with a primary focus on pediatric sarcomas and rare tumors. Additionally, she was a clinical observer at the pediatric oncology unit of St. Anna Children’s Research Hospital in Austria for six months. 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, focusing on writing and reviewing medical-scientific manuscripts. Dr. Hovsepyan is a member of the POEM Training Committee and a graduate of the College of the European School of Oncology. She is a former co-chair of the SIOP Global Health Network Education and Training Working Group.

About OncoDaily

OncoDaily.com was founded in 2023. It is a US-based oncology media platform, which features the latest news, insights, and patient stories from the world of oncology. Within a short period, it became one of the leading oncology media platforms globally. OncoDaily gathers content from various sources, including social media posts from renowned oncologists from all over the world, news from oncology societies and cancer centers, patient and survivor stories, and career-related information for professionals. The mission of OncoDaily is to empower patients, survivors, and professionals with the knowledge and inspiration they need to fight cancer. The motto of OncoDaily is “Cancer doesn’t take a day off – neither do we.”

Follow the transcript below

Shushan Hovsepian (S.H.): Good morning. Good evening and good afternoon, everyone. Wherever you are. And welcome back to our second episode of Five Minutes Sarcoma Talk on OncoDaily. I’m Shushan Hovsepian, a pediatric oncologist from Armenia, and I will be your host today. I’m excited to continue our journey, through the world of sarcoma. And today, we are honored to speak with the renowned expert Doctor Rajkumar Venkataramani. 

Rajkumar Venkataramani (R.V.): Thanks for having me, doctor Hovsepyan. It’s it’s my pleasure to be here. Pleasure is all mine. So let’s get started. as the scientific chair of, Children’s Oncology Group, soft tissue sarcoma Committee, what are the main challenges that you usually encounter in conducting clinical trials in patients with sarcomas, particularly within the cooperative groups?

S.H. : So one of the main things it’s both a fortunate and unfortunate thing because we don’t have enough children with, specific diagnosis, for example, rhabdomyosarcoma, we have about 400 patients. Sorry about that. 400 patients a year in, us per year. So we it’s a good thing that not a lot of children develop cancer, but at the same time, it makes it very difficult for us to conduct clinical trials. as you know, we have so many questions we want to answer for us. Each clinical trial takes about a decade.

And, to conduct because of the rarity of the cancers, especially soft tissue sarcomas in children. So that is the major challenge for us. The other major challenge, of course, is lack of new medications directed towards rhabdomyosarcoma or children’s non rhabdoid soft tissue sarcoma. So those are the two challenges because this is a very extremely rare disease. And there is not enough focus to develop medication specifically for these tumors.

R.V. : Yeah. Thank you for sharing your insights. And you mentioned about the lack of, new therapeutic agents. But, delving deeper into that, and specifically for rhabdomyosarcoma, could you share any recent breakthroughs or novel therapeutic targets that are promising in rhabdomyosarcoma patients?

S.H. : So within the field of rhabdomyosarcoma, as most of your listeners know, they’re still the standard of care in at least North America is, vincristine India and cyclophosphamide, the classic whack regimen. And we have had those regimens since 1970s. And we haven’t, even though it has undergone some modification, doesn’t change a lot. And with every decade we have tried to add some new medications or compare with different medications. Still, the whack seems to be the best regimen we have for rhabdomyosarcoma right now.

We are focused on increasing effectiveness of efficacy, but also decreasing toxicity. Is there a specific, patients where we can reduce therapy, and is there a specific patient where we should intensify therapy? So the latest development, which I am excited about is mainly characterization of molecular features in these tumors and prognostication of rhabdomyosarcoma based on molecular features.

So we have the MCI, the Molecular characterization initiative from National Cancer Institute, where we are sequencing every patient rhabdomyosarcoma in the country as long as they enroll in the trial. And every month we are getting more and more data. And this data is being deposited in publicly available database So anyone in the world can get this data. We do whole exome sequencing, methylation fusion testing, ultra panel, and all the data is released to everyone to study.

So our hope is we are on a threshold of, innovation in rhabdomyosarcoma, where a lot more data is going to come and we are going to use big data to get achieve breakthrough issues with regard to specific medications. the latest one we are looking at is Hdac inhibitors. There are some exciting data in there. of course we are always looking at whether we can do cellular therapy, but it’s not prime time yet to use them in patients. So those are the other modalities. I think we have reached the maximum of chemotherapy so I don’t think it’s chemotherapy is going to improve anymore a traditional chemotherapy. So we have to look at other modalities of treatment for rhabdomyosarcoma.

R.V. : Yeah. that’s actually, very promising to hear that, we are going to have new agents and, hopefully the research endeavors that, right now, we are doing, will, pay off. But, another thing regarding the chemotherapy, what is your opinion on maintenance therapy?

S.H. : So, so you have to take maintenance therapy in the context. Okay. So, I know we have in European context, it seems to be helpful, but the back bone used in Europe is different from the backbone of chemotherapy used in us. So we haven’t we actually tested the results are coming. We have presented in a poster format. We have tested maintenance therapy along with our backbone. At least.

Our initial impression is that maintenance doesn’t add to the 42 weeks of chemotherapy we deliver in, US in Europe, the backbone is about 27 weeks of induction. In that context, adding six months of maintenance therapy seems to be helpful. but we still haven’t proved that it’s helpful in the American context or North American context, where we tend to deliver a lot more chemotherapy longer when compared to what the European backbones are.

R.V. : Yeah, that’s very interesting, actually. And with that in mind, moving to the relapsed setting, what are the main challenges and advancements in this, patients?

S.H. : So again, the same we are stuck with the same thing. Right? So whack is our initial therapy. When the relapse depending on the risk group, if they had only two drug therapy which has been promising. And we know that those patients tend to do better, with treatment. But if they have intensive therapy up front, especially if they have metastatic relapse, it’s extremely difficult to cure these patients.

So we do not have any breakthroughs, recent breakthroughs in relapse. We are still using cytotoxic chemotherapy. Of course we always try to enroll this patients on early phase clinical trials if we can so that we can learn more. But right now we do not, unfortunately have effective therapies for relapsed patients with rhabdomyosarcoma.

R.V. : Yeah, unfortunately that’s a real challenge. And especially if you are working in a low middle income country where you cannot enroll that patients into the clinical trials. And, let’s explore another aspect, regarding your, personal experience, what led you to specialize in the field of soft tissue sarcomas? What or who was your inspiration?

S.H. : So I when I did my fellowship, my mentor was Doctor Mascarenhas. he is another well known soft tissue sarcoma plus solid tumor oncologist. So I learned a lot of stuff I know from him. plus, soft tissue sarcoma is an area in need. because, as I explained in the previous five minutes, that we don’t have any effective therapy.

So that’s one of the things which attracted to me to soft tissue sarcomas. And of course, the varied presentation. Even though it is called rhabdomyosarcoma, it can happen from head to foot anywhere in the body. The biology is very, very interesting. Plus it’s an area in need. So that’s why I’m I got attracted and I got considering on soft tissue sarcomas.

R.V. : Yeah that’s very interesting. And actually our next episode will be with Doctor Mascarenhas, so.

S.H. : Oh, great. Yeah. Thank you, Doctor Venkataramani, for sharing your expertise. and your knowledge. thank you for accepting our invitation. It’s a great honor for me. And, with that, I would like to bring this episode, to a close and join us for the next time for another insightful conversation.

R.V. : Thanks. Thank you for having me.