R. Lor Randall, MD, FACS, is the David Linn Endowed Chair for Orthopedic Surgery and chair of the Department of Orthopedic Surgery as well as a professor at the University of California Davis.

R. Lor Randall, MD, FACS, The David Linn Endowed Chair for Orthopaedic Surgery, professor and chair, Department of Orthopaedic Surgery, University of California Davis Health, discusses the evolution of limb salvage technologies in bone sarcomas.

Cemented stem and press-fit implants were useful limb salvage technologies initially; however, over time, stress shielding causes many of these endoprostheses to become loose at the stem interface, Randall explains. This loosening eventually causes the limb to fail and cause pain, fractures, and other morbid complications.

Before the integration of neoadjuvant and adjuvant chemotherapy, patients with bone sarcomas were likely to succumb to their disease, so short-term benefits from limb salvage technology were usually sufficient. However, chemotherapy had prolonged survival so that patients were outliving their disease, Randall says. Therefore, limb salvage technologies that caused eventual orthopedic disease needed to be improved upon.

As such, compressive osseointegration is a novel technique that harnesses Wolff’s law to allow the bone to adapt and grow in response to physical force, Randall concludes.

Videos

R. Lor Randall, MD, FACS, discusses the evolution of limb salvage technologies in bone sarcomas.  



Dr. Randall on the Evolution of Limb Salvage Technologies in Bone Sarcomas 

R. Lor Randall, MD, FACS, professor and The David Linn Endowed Chair for Orthopaedic Surgery and professor and chair of the Department of Orthopaedic Surgery, University of California Davis Health, discusses initial considerations when treating patients with desmoid tumors, a type of soft tissue sarcoma.

It is important to establish up front whether a patient with a diagnosed desmoid tumor harbors an 

 mutation, which would put them at risk for Gardner syndrome, multiple desmoid fibromatosis, and polyps, Randall explains. Patients with Gardner syndrome need to be monitored aggressively because they tend to have multiple relapses at multiple sites because they have several desmoids. As such, genetic counseling should be strongly considered for patients with a solitary desmoid tumor, particularly if they have a family history of colon cancer, Randall says.

Additionally, it is critical to weigh the risks and benefits of treatment for patients with desmoid tumors to ensure the treatment doesn’t cause more harm to the patient than surveillance, Randall says. Notably, not all patients with a desmoid tumor require aggressive local treatment, which was standard of care historically. In the past, some patients would be disfigured from aggressive treatment with the goal of negative margins; however, their disease likely didn’t require such interventions.

This concept has been observed in patients with desmoid tumors of the chest wall or breast implant–associated desmoid tumors, Randall explains. Moreover, treating patients with desmoid tumors with aggressive surgery and radiation therapy can lead to disfigurement, identity issues, and pain. Therefore, it is critical to get insight from a provider who has substantial experience in managing desmoid tumors before making treatment decisions for patients, Randall adds.

Historically, patients with desmoid tumors who required treatment underwent surgery with or without radiation therapy. Although surgery still plays an important role in the management of desmoid tumors, it has become less prominent. As such, the guidelines now are to monitor patients when their tumor is not progressing. If they have progressive disease, several noncytotoxic and cytotoxic therapies can be considered, Randall concludes.

Funding from SpringWorks Therapeutics/Content Developed Independently by OncLive

R. Lor Randall, MD, FACS, discusses initial considerations when treating patients with desmoid tumors.



Dr. Randall on Initial Considerations When Treating Patients With Desmoid Tumors 

R. Lor Randall, MD, FACS, professor and The David Linn Endowed Chair for Orthopaedic Surgery and professor and chair of the Department of Orthopaedic Surgery, University of California Davis Health, discusses the evolution of orthopedic surgery in sarcoma.

Surgical intervention for patients with sarcoma requires a technical, two-step process, says Randall. The first step is to remove the cancer, and the second step is to replace the patient’s anatomy with something functional at the site of surgery. Ablative approaches, such as amputation, are reserved for rare circumstances. 

The development of limb-salvage surgical techniques has eliminated the need to build custom prosthetics for patients with bone and soft tissue sarcoma, Randall says. The technology evolved to offer more off-the-shelf modular erector sets that can reconstruct patients’ limbs. 

Additionally, improved imaging from radiographs to CT scans and MRIs allowed for more anatomic detail to be captured on an image. Improved imaging led to refined approaches that enabled surgeons to remove smaller amounts of tissue while sparing the joint, concludes Randall.

R. Lor Randall, MD, FACS, discusses the evolution of orthopedic surgery in sarcoma.  


Dr. Randall on the Evolution of Orthopedic Surgery in Sarcoma 

R. Lor Randall, MD, FACS, professor and The David Linn Endowed Chair for Orthopaedic Surgery and professor and chair of the Department of Orthopaedic Surgery, University of California Davis Health, discusses the SAFETY trial (NCT03944798) in soft tissue sarcoma.

The SAFETY trial will evaluate the effectiveness of chest computerized tomography (CT) versus chest radiograph in patients with primary extremity sarcoma that has metastasized to the lungs. Currently, when soft tissue sarcoma metastasizes to the lungs, patients undergo chest imaging via a chest radiograph or a chest CT scan; however, it is unknown whether the imaging should be done every 3 months or every 6 months and whether a chest radiograph or CT scan is best.

While a chest radiograph provides results more quickly and exposes patients to less radiation, a chest CT scan provides a more detailed image, says Randall. This trial may shed light on whether a chest CT is needed or whether patients could be spared unnecessary radiation, concludes Randall.

R. Lor Randall, MD, FACS, discusses the SAFETY trial (NCT03944798) in soft tissue sarcoma.

Dr. Randall on the SAFETY Trial in Soft Tissue Sarcoma

R. Lor Randall, MD, FACS, professor and The David Linn Endowed Chair for Orthopaedic Surgery, University of California Davis Health, discusses ongoing research in sequencing the tumors of patients with primary bone or tissue sarcomas.

Research is looking into deep sequencing tumors to look for mutations that can be targeted with the cadre of biotargeting agents in primary bone and tissue sarcomas, explains Randall. Patients with these tumors eligible for chemotherapy will receive it in a conventional form. If they fail conventional chemotherapy, they will move on to more targeted agents, says Randall.

At the University of California Davis Health, when sarcoma is diagnosed based on biopsy, some of the original tumor is stored for precision medicine treatments, concludes Randall.

R. Lor Randall, MD, FACS, discusses ongoing research in sequencing the tumors of patients with primary bone or tissue sarcomas.

Dr. Randall of Tumor Sequencing Research in Sarcomas

R. Lor Randall, MD, FACS, professor and The David Linn Endowed Chair for Orthopaedic Surgery, University of California Davis Health, discusses the use of pexidartinib (Turalio), which was recently 

, in the treatment of patients with tenosynovial giant cell tumor (TGCT).

In TGCT, there are 2 subclasses: pigmented villonodular synovitis and giant cell tumor of the tendon sheath, says Randall. For the most part, these are benign conditions that grow very aggressively around the knee and other areas, which can be very debilitating for patients, he explains.

Until recently, the standard of care for patients with TGCT has been surgical removal, but over a period of time the tumor grows back, adds Randall. The phase III ENLIVEN trial showed that pexidartinib, a CSF1R inhibitor, can target this disease and shrink the tumor. Pexidartinib does not entirely eliminate the tumor, but it can help reduce its size and assist with symptom reduction, concludes Randall.

R. Lor Randall, MD, FACS, discusses using pexidartinib to treat tenosynovial giant cell tumor.

R. Lor Randall, MD, FACS

Articles

Dr. Randall on the Evolution of Limb Salvage Technologies in Bone Sarcomas

Dr. Randall on Initial Considerations When Treating Patients With Desmoid Tumors

Dr. Randall on the Evolution of Orthopedic Surgery in Sarcoma

Dr. Randall on the SAFETY Trial in Soft Tissue Sarcoma

Dr. Randall of Tumor Sequencing Research in Sarcomas

Dr. Randall on Using Pexidartinib to Treat Tenosynovial Giant Cell Tumor