DOI: 10.1159/000360575 // Published online: March 26, 2014 .
(a)Anthony Turpina / (b)Sohie Taiebb / (a)Nicolas Penela .
(a)Department of Medical Oncology, and (b)Imaging Department, Centre Oscar Lambret,Lille, France .
Key Words :
Myxoid liposarcoma · Trabectedin · Tumor calcification
AbstractIntroduction:
Myxoid/round-cell liposarcoma (MRCL) is a specific histological subtype that accounts for 30–35% of liposarcomas and whose virulence depends on the quantity of round-cells within the tumor. MRCL is associated with specific chromosomal translocations resulting in the formation of CHOP/FUS and CHOP/EWS fusion proteins. A high sensitivity of MRCL to trabectedin was reported.
Case Report:
We report the case of a 63-year-old woman with a bulky and metastatic MRCL, treated with trabectedin 1.5 mg/m2 as a first-line treatment. She experienced a long-lasting clinical benefit. The patients received 14 cycles of trabectedin and achieved a durable partial response to the metastases and a stable disease of the primary tumor, which is a very favorable safety profile. Also noteworthy is that we have observed a calcification of the primary tumor and the metastasis. The response, which lasted 30 months, led to a symptomatic improvement, associated with an excellent general condition and an absence of pain.
Conclusion:
To the best of our knowledge, this is the first report of a MRCL treated with trabectedin that resulted in a calcification of the primary tumor and the metastases, associated with an outstandingly long response. This case suggests that trabectedin may represent a feasible first-line therapeutic option for patients with MRCL, with meaningful clinical benefits and an acceptable safety profile.
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Conclusions :To our knowledge, this is the first report of a MRCL treated with trabectedin that result-ed in a substantial calcification of the primary tumor and metastases. After 14 cycles of trabectedin treatment, a durable partial response on metastases and stable disease on the primary tumor was accompanied with an improvement of symptoms and performance status, and with an acceptable toxicity profile. Therefore, this case emphasizes the role of trabectedin as a viable chemotherapeutic agent which significantly reinforces the therapeu-tic armamentarium in the treatment of MRCL.
In a former prospective multicenter phase II clinical trial, 3 of 23 assessable patients with myxoid liposarcoma, treated with neoadjuvant trabectedin, achieved a pathological complete response, i.e. a complete disappearance of the tumor tissue (histological and molecular absence of cells with the FUS–CHOP translocation) (13%; 95% CI: 3–34) and a good and a moderate histological response was observed in 2 and 10 patients, respectively, as assessed by a central pathological review. Furthermore, 7 out of 29 patients achieved a partial response according to RECIST (24%; 95% CI: 10–44) and 21 patients had a stable disease. Remarkably, no patients had a disease progression starting from the onset of the study treatment to the respective curative surgery.
The high sensitivity of MRCL to the neoadjuvant trabectedin was in line with the findings of a retrospective analysis of 51 patients with MRCL, treated with trabectedin on a compassionate use protocol, where a high response rate (51%) and a progression-free time (PFS) (14 months) were also reported [2]. Additionally, in a long-term follow-up in 32 of these 51 patients, the overall response rate was 50%, with a PFS of 17 months, showing that that the high response rate of MRCL to trabectedin largely translates into a prolonged PFS [3].
In both abovementioned studies, substantial radiological changes in tumor density occurred, accompanied by histological decrement in the cellular and vascular tumor component and a maturation of tumor cells to lipoblasts in both myxoid and myxoid/round cell variants. Recently, it has been reported that the selective mechanism of trabectedin in MRCL is specific and related to its ability to cause a functional inactivation of the oncogenic chimera with a consequent depression of the adypocytic differentiation [1]. In vitro studies suggest that trabectedin induces the maturation of MRCL lipoblasts by inhibiting the fusion protein activity [5].In conclusion, the rarity of response in this 63-year-old woman with MRCL was distin-guished by the long-lasting (>27 months) stable disease observed, even after drug discon-tinuation (15 months) and the presence of massive calcifications of the metastases and theprimary tumor. Physicians should be aware of this exceptional pattern of response in order to avoid inappropriate drug discontinuation.
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