Is Detection of Relapse by Surveillance Imaging Associated With Longer Survival in Patients With Rhabdomyosarcoma?

Abstract

Background: We investigated whether surveillance imaging had an impact on post-relapse survival in patients with rhabdomyosarcoma (RMS). We hypothesized that relapse detected by imaging (group IM) would be associated with longer survival compared with relapse detected with a clinical sign or symptom (group SS). Materials and Methods: We performed an observational multi-institutional study in 127 patients with relapsed RMS comparing overall survival (OS) after relapse using Kaplan-Meier and Cox proportional hazards analyses. Results: Relapse was detected in 60 (47%) group IM and 67 (53%) SS patients. Median follow-up in survivors was 4 years (range 1.0 to 16.7 y). Four-year OS rates were similar between group IM (28%, 95% confidence interval [CI]: 14%-40%) and SS (21%, 95% CI: 11%-31%) (P=0.14). In multivariable analyses accounting for institution, age at diagnosis, time to relapse, risk group at diagnosis, and primary site, not receiving chemotherapy (hazard ratio [HR]: 6.8, 95% CI: 2.8-16.6), radiation (HR: 3, 95% CI: 1.7-5.3), or surgery (HR: 2.8, 95% CI: 1.6-4.8) after relapse were independently associated with poor OS. Conclusion: These results on whether surveillance imaging provides survival benefit in patients with relapsed RMS are inconclusive. Larger studies are needed to justify current surveillance recommendations. Chemotherapy, radiotherapy and surgery to treat recurrence prolong OS.

Relapse after non‐metastatic rhabdomyosarcoma: The impact of routine surveillance imaging on early detection and post‐relapse survival

“…More work will be needed to further clarify the actual value of surveillance imaging in RMS patients in order to establish the most appropriate follow‐up. This might imply prospective randomized control trial, as suggested by other authors, 40 or large international cooperative observational study, as indicated by others 18 …”

“…It is still hard to establish the real benefit of such off‐therapy imaging. The very few studies that have addressed this issue in the case of RMS 15–19 indicate that most recurrences of RMS are diagnosed on the grounds of clinical symptoms, 15–17 and that surveillance imaging could reveal relapses earlier 16,17 . That said, there was no evidence to suggest that the earlier radiological detection of a relapse, before any clinical symptoms emerge, improves a patient's chances of survival after relapse 15–19 .…”

“…The very few studies that have addressed this issue in the case of RMS 15–19 indicate that most recurrences of RMS are diagnosed on the grounds of clinical symptoms, 15–17 and that surveillance imaging could reveal relapses earlier 16,17 . That said, there was no evidence to suggest that the earlier radiological detection of a relapse, before any clinical symptoms emerge, improves a patient's chances of survival after relapse 15–19 . Also the recently published North American multicenter study on 127 patients with relapsed RMS did not demonstrate a difference in survival when disease recurrence was detected by surveillance imaging or by clinical signs or symptoms 18 …”

“…The real benefit of such routine surveillance imaging in patients treated for RMS has yet to be demonstrated, however. Four published studies on RMS, [15][16][17][18] and one that examined RMS and other childhood sarcomas, 19 all suggested that systematic surveillance imaging may contribute to the earlier detection of recurrences, but has no impact on patients' outcomes.…”

Clinical implementation of plasma cell-free circulating tumor DNA quantification by digital droplet PCR for the monitoring of Ewing sarcoma in children and adolescents

“…ctDNA data will be used as complementary information in routine clinical monitoring of EWS patients. Although two large studies in (127 and 199) patients with recurrence of rhabdomyosarcoma did not show a significantly improved overall survival upon imaging-based early detection of relapse vs. clinical symptom-based detection (36,37), prevention of delay before further molecular and clinical progression occurs, potential additional mutations are acquired, or more metastases are seeded, appear mandatory. As ctDNA recurrence can often be observed before clinical progression/relapse is evident, it might open up a window of opportunity to treat patients while tumor burden and molecular heterogeneity are at their lowest (38)(39)(40)(41).…”