Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and aggressive cancer, classified as a type of sarcoma that develops in the body’s bones and soft tissues. Understanding DSRCT involves recognizing its unique characteristics and the specialized approaches required for its management. This article provides an overview of DSRCT, covering its origins, diagnosis, treatment strategies, and ongoing research.
What is DSRCT?
DSRCT is a rare soft tissue sarcoma that originates in the peritoneum, the membrane lining the abdominal and pelvic cavities. It primarily affects children, adolescents, and young adults, with a notable prevalence in males (approximately 80% of patients). Diagnosis typically occurs between ages 18 and 22, though cases range from 4 to 62.
DSRCT is caused by a specific chromosomal translocation, t(11;22)(p13;q12), which creates the EWS-WT1 fusion gene. This genetic error involves a piece of chromosome 11 exchanging places with a piece of chromosome 22, resulting in the fusion of the EWSR1 gene from chromosome 22 and the WT1 gene from chromosome 11. The resulting EWS-WT1 fusion protein drives tumor growth. Its presence is a characteristic molecular marker for definitive diagnosis.
Symptoms and Diagnosis
DSRCT often presents with few early warning signs; patients may appear healthy as tumors grow within the abdominal cavity. The most common symptom is a hard, noticeable mass or swelling in the abdomen. Patients may also experience abdominal pain or cramps, changes in bowel habits (such as constipation or diarrhea), nausea, vomiting, or unexplained weight loss. These symptoms can be non-specific, leading to misdiagnosis given the disease’s rarity.
Diagnosis begins with a physical examination to identify palpable abdominal masses, followed by imaging tests. CT, MRI, and PET scans are used to visualize tumors, determine their size and location, and assess if the cancer has spread. A definitive diagnosis relies on obtaining a tissue sample through a biopsy, acquired via needle or during surgery.
Pathologists examine the tissue under a microscope, looking for characteristic small round cells surrounded by a dense, fibrous (desmoplastic) stroma. Specialized laboratory tests are then performed, including immunohistochemistry (identifying specific proteins) and molecular genetic testing. These molecular tests confirm the EWS-WT1 fusion gene, a hallmark of DSRCT that distinguishes it from other similar-appearing cancers.
Treatment Approaches
Treating DSRCT involves an intensive, multi-faceted strategy due to its aggressive nature and tendency to spread throughout the abdominal cavity. This complex approach combines chemotherapy, surgery, and radiation therapy. Given the rarity and complexity of DSRCT, treatment is best managed at major cancer centers with specialized expertise in sarcomas.
Chemotherapy serves as the initial step, using an aggressive, multi-agent regimen to shrink tumors before surgery. One common protocol, adapted from Ewing sarcoma treatments due to molecular similarities, is the P6 protocol. This regimen includes drugs such as cyclophosphamide, doxorubicin, vincristine, etoposide, and ifosfamide. Chemotherapy aims to reduce the tumor burden, making subsequent surgical removal more feasible.
Following chemotherapy, aggressive cytoreductive surgery is performed to remove all visible tumor masses. This is often a complex and extensive operation, as DSRCT frequently presents with numerous tumor nodules dispersed throughout the peritoneal lining. The extent of surgical removal, aiming for optimal reduction of disease, has been associated with improved survival outcomes.
Radiation therapy is frequently used after surgery to target any remaining cancer cells in the abdomen and pelvis. Whole abdomino-pelvic irradiation (WAPI) may be employed for residual disease, with reports indicating it can improve local control. Some patients may also be considered for additional treatments like hyperthermic intraperitoneal chemotherapy (HIPEC), where heated chemotherapy solution is circulated directly within the abdominal cavity during surgery.
Prognosis and Ongoing Research
DSRCT is recognized as a challenging cancer with a serious outlook. Despite aggressive multi-modal treatment, the disease often recurs, and the five-year survival rate ranges from 15% to 30%. Survival outcomes are more favorable when the disease is confined to the abdomen and pelvis without distant metastases to organs like the liver or spleen.
The medical community is actively engaged in ongoing research to develop more effective treatments for DSRCT. A significant area of focus is the development of targeted therapies that specifically attack the EWS-WT1 fusion protein, the primary driver of this cancer. Researchers are exploring compounds that could inhibit this fusion protein or pathways it activates, such as the cyclin D–CDK4/6–RB axis. For instance, studies indicate that CDK4/6 inhibitors like Palbociclib may reduce cell growth in DSRCT models.
Immunotherapy, which harnesses the body’s own immune system to fight cancer, is also being investigated for DSRCT. Although sarcomas like DSRCT typically have a low tumor mutational burden, making them less responsive to traditional immunotherapies, recent findings suggest the possibility of targeting DSRCT-specific “neopeptides” derived from the fusion protein or surface markers like B7-H3. Dedicated efforts in the scientific community continue to drive the search for novel and more effective treatments to improve the lives of those affected by this rare disease.