"Expert Q&A" with Dr. Zhu Jia: Can Targeted Drugs Be Used to Treat Rhabdomyosarcoma?  

"Expert Q&A" with Dr. Zhu Jia: Can Targeted Drugs Be Used to Treat Rhabdomyosarcoma?  

Source: Sunflower Children's Hospital  

Author: Professional Team  

Editor: Chen L  

Date: June 23, 2023  

Disclaimer:  

The online Q&A is not a recommendation for treatment plans. As we cannot understand the patient's detailed condition and cannot perform face-to-face diagnoses, expert opinions are for reference only. For specific treatment plans, please visit a formal hospital.  

In this edition of the "Expert Q&A" column, we invite Dr. Zhu Jia, Deputy Chief Physician of the Pediatric Oncology Department at the Sun Yat-sen University Cancer Prevention and Treatment Center, to answer your questions.  

Dr. Zhu is a member of the Children's Oncology Professional Committee of the China Anti-Cancer Association and a postdoctoral researcher at the MD Anderson Cancer Center in the United States. She specializes in the comprehensive diagnosis and treatment of pediatric lymphoma, leukemia, neuroblastoma, soft tissue sarcomas, and more.  

01  

Q: A 3-year-old boy was diagnosed with rhabdomyosarcoma in the bladder area after a biopsy. The tumor measures 3 cm in diameter, and he has undergone chemotherapy twice. Further treatment will be evaluated after the fourth chemotherapy session.  

Is there a targeted drug for rhabdomyosarcoma? If so, would the targeted drug be more effective?  

A: Rhabdomyosarcoma is mainly divided into three subtypes: embryonal, alveolar, and pleomorphic. It is more common in children and is a malignant tumor that is generally sensitive to chemotherapy and radiotherapy. Chemotherapy, radiotherapy, and surgery are the primary treatment modalities. A small portion may have genetic mutations that make them sensitive to corresponding targeted drugs, such as ALK, ROS1 inhibitors, mTOR inhibitors, HER2 inhibitors, PDGF-a, VEGF inhibitors, and TRK inhibitors. The prerequisite is that the corresponding target mutations must be detected, and the mutations should be tumor driver genes.  

02  

Q: A 4-year-old girl underwent surgery in July 2022 to remove a mass on the outer side of her left knee, which was diagnosed as embryonal rhabdomyosarcoma. After surgery, she began chemotherapy with a high-risk phase IV regimen. Additionally, a subpleural shadow with an indeterminate nature was found. At the end of 2022, she underwent a wide excision surgery, which was pathologically negative. However, a single nodule was found subpleurally post-operation, and she will undergo surgical removal soon. Genetic testing revealed a germline TP53 mutation, with CCND1 and FGFR1 amplification, and loss of PTEN and SMARCB1.  

Should we choose radiotherapy or not? After the surgery for the subpleural nodule, should the pleural area also receive radiotherapy? If radiotherapy is needed, should we choose photon therapy or proton therapy?  

A: The patient has a germline TP53 mutation, which indicates she has Li-Fraumeni syndrome. Radiotherapy may increase the risk of a second tumor in patients with TP53 germline mutations. However, radiotherapy is an important treatment method for embryonal rhabdomyosarcoma, making the decision to radiate or not quite difficult. The rapid occurrence of pleural metastasis indicates a poor prognosis. Based on the current tumor condition, we lean towards radiotherapy. Proton therapy can be used for pleural radiotherapy.  

03  

Q: A boy, now 2 and a half years old, had a left parapharyngeal space mass excised along with lymph node dissection at 18 months of age. There was residual disease, and he was diagnosed with embryonal rhabdomyosarcoma, with a genetic mutation of FGFR4 V550L and lymph node metastasis. He received alternating VAC and VI chemotherapy for the first seven cycles with a weight of 8.5 kg, using Vincristine at 0.72 mg. The chemotherapy was effective, and imaging after the second cycle showed no mass, eliminating the need for a second surgery. After the sixth cycle of chemotherapy, he underwent radiotherapy. During the radiotherapy, it was found that there was skull base invasion at the time of diagnosis. Therefore, both the primary site and the skull base were irradiated. After the seventh cycle of radiotherapy, imaging showed no evidence of tumor, and during the radiotherapy, the chemotherapy dosage was not reduced. The eighth cycle began using the 2016 central nervous system regimen, calculating the dosage based on a weight of under 12 kg, which was 9.5 kg and 85 cm tall, with Vincristine at 0.48 mg.  

Is the dosage too low? We are about to enter the 16th cycle; was the medication for the first seven cycles too light for the intermediate-risk group?  

Should we add chemotherapy or maintenance therapy?  

A: If there was skull base invasion at the onset, the risk level is considered high. A corresponding high-risk chemotherapy regimen should be followed. The child's weight is below 12 kg, so the dosage needs to be appropriately reduced. Given the high risk of recurrence, maintenance therapy is recommended after concluding chemotherapy.