(P 145) A RETROSPECTIVE CASE SERIES ANALYSIS OF 22 RHABDOMYOSARCOMA PATIENTS WITH SPINDLE-CELL/SCLEROSING MORPHOLOGY

Objective: RMS with spindle cell/sclerosing morphology (ssRMS) comprise rare variants of rhabdomyosarcoma (RMS) which formerly were often included amongst embryonal RMS. In particular, spindle-cell RMS was recently recognized as an entity associated to genetic aberrations, involving VGLL, MYOD1, TFCP2.There is no standard treatment for RMS other than embryonal and alveolar, while the few published series provide discrepant results.
We report on a case series analysis of RMS patients with spindle cell/sclerosing morphology, observed over more than 10 years at a sarcoma reference centre and a collaborative professional sarcoma network.

Methods: We searched for all consecutive patients treated for a RMS with spindle cell/sclerosing morphology at the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, and within the Italian Rare Cancer Network since 2010. Data on patients’ demographics, clinical presentation, treatment, and outcome were collected and analyzed. Responses were retrospectively evaluated according to RECIST 1.1. Survival analyses were performed using the Kaplan-Meier method.

Results: Since 2010, 22 patients (8 F, 14 M) with a median age of 38 years (range 11-66) were identified. At the diagnosis, 19 patients (86%) had a localized disease, 3 were metastatic. The primary site was the head and neck in 13 patients (60%), the trunk in 6 (27%), the limbs in 2 (9%), and the viscera in 1 (4%). The mean size of the tumor was 4,7 cm (range 1,6 – 10,5). Twelve cases had a spindle-cell morphology, 4 sclerosing, 6 mixed. At a median follow-up of 43 months, overall survival was undefined, and 5y-OS was 65%.
Twenty/22 (90%) patients underwent surgery of the primary tumor: R0 in 11 patients, R1 in 5 patients, R2 in 4 patients (3 of whom re-resected to R0). Thirteen/22 patients received peri-operative radiation. All patients with localized disease at the onset received peri-operative chemotherapy: doxorubicin/epirubicin + ifosfamide/cyclophosphamide associations were the most common regimens (17/19 patients). Ten patients received neoadjuvant, 9 adjuvant chemotherapy. Three/10 patients (30%) who received neoadjuvant anthracycline+ifosfamide chemotherapy had a PR, 4 (40%) a SD, 3 a PD (30%).
RFS in localized patients was 35 months (range 0.9-115+). Most of the events (90%) occurred within the first 18 months of follow-up. Five patients developed a local relapse, 4 of them after R1 surgery and peri-operative radiation. Median RFS in patients responding and progressing to neoadjuvant chemotherapy was not reached and 2.1 months, respectively.
Twelve/22 patients received palliative chemotherapy for metastatic disease (3 at the onset, 9 at relapse). The median number of lines was 2. Four patients received gemcitabine-based, 4 irinotecan-based, 3 anthracycline-based chemotherapy, 2 pazopanib. Among all, only a PR was seen, on epirubicin + ifosfamide, all others being PD. Median overall survival from first chemotherapy line was 14 months, 1y-OS was 20%.

Conclusion: In this series, though retrospective in nature and still not corroborated by molecular characterization (which is ongoing on cases with available samples), we observed a high-risk of local relapse after R1 surgery (80%), regardless of peri-operative radiation. A relatively low-probability of response to chemotherapy was seen, essentially limited to anthracycline-containing regimens (ORR 33%). However, patients experiencing a PR or a SD to neoadjuvant chemotherapy seemed to have a better prognosis compared to progressing patients. The risk of relapse was higher within the first two years of follow-up. Prognosis was poor in the advanced setting. Overall, these data would suggest a clinical behavior diverging from typical embryonal/alveolar RMS under several respects. Difficult though they may be, given the rarity of these histologies, prospective studies focusing on specific molecularly-assessed rare RMS variants are needed.