Luke V. Selby, MD MS FACS FSSO
Assistant Professor of Surgery
University of Kansas Medical Center
Leawood, Kansas, United States
Taylor Williams, MD
Fellow
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Taylor Cusick, BS (she/her/hers)
Medical Student
University of Kansas Medical Center
Kansas City, Kansas, United States
Jill Haley, DPT
Department of Surgery, University of Kansas Medical Center
Kansas City, Kansas, United States
Marium Husain, MD
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
David Liebner, MD
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Benjamin C. Powers, MD
Associate Professor
University of Kansas Cancer Center
Kansas City, Kansas, United States
Isuru P. Ratnayake, PhD
Education Assistant Professor
University of Kansas Medical Center
Kansas City, Kansas, United States
Prabhakar Chalise, PhD
Associate Professor
Department of Biostatistics & Data Science, University of Kansas Medical Center
Kansas City, Kansas, United States
Joal D. Beane, MD
Assistant Professor
Department of Surgery, The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Gabriel Tinoco, MD
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Valerie P. Grignol, MD
Associate Professor of Surgery
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Aubrey C. Swilling, DO, MS
Resident Physician
Department of Surgery, University of Kansas Medical Center
Kansas City, Missouri, United States
Retroperitoneal liposarcomas (RPS) are treated primarily with surgery, yet recurrence is common, and often lethal, following surgery. Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown therapeutic benefit in unresectable and advanced RPS and their adjuvant use may delay the time to subsequent treatment. This multi-institutional series further evaluates the use of adjuvant CDK 4/6 inhibitors to delay recurrence in completely resected RPS.
Methods:
Institutional databases from two high-volume RPS centers were utilized. Patients with primary or recurrent RPS who underwent curative-intent comprehensive complete gross resection were included. Patients were individually evaluated for CDK4/6 inhibition postoperatively. Patients who received adjuvant CDK4/6 inhibitors (palbociclib or abemaciclib) for prevention of tumor recurrence (treatment arm) were compared to patients who underwent active surveillance following surgery (control). We analyzed the impact of adjuvant CDK4/6 inhibition on all patients with grade 2 or 3 tumors as well as patients with primary RPS whose post-op sarculator 5-year risk of recurrence was > 35%. The primary outcome was time to recurrence. Time-to-event analysis was performed and Kaplan-Meier curves were stratified by treatment group.
Results:
Overall, 69 patients with a median age of 65 years old underwent a total of 79 surgeries, 53 (67%) of which were primary resection. Of the 79 surgeries, 24 were grade 2 and 23 were grade 3. In total, 11/24 (46%) patients with grade 2 RPS and 10/23 (44%) patients with grade 3 were selected for adjuvant CDK4/6 inhibition. Age and median tumor size did not differ between groups. The treatment group had significantly better recurrence-free survival at one year (70.4% vs 35%, p=0.01). Median time to recurrence was 18.5 months for the treatment group and 9.1 months for the control.
Of the 53 patients who underwent primary resection, 33 had a sarculator 5-year recurrence risk of >35% (a < 65% predicted disease free recurrence). Of these, 13 were selected to receive adjuvant CDK4/6 inhibition. Again, the treatment arm was associated with improved 1-year recurrence rates (91.7% vs 40.8%, p< 0.01) and medial time to recurrence (23.8 vs 9.8 months).
Conclusions:
In this multi-institution series, the use of adjuvant CDK 4/6 inhibition is associated with delayed recurrence following comprehensive resection of high-risk retroperitoneal liposarcoma. These findings warrant evaluation in a prospective randomized trial.