bims-myxlip Biomed News
on Myxoid Liposarcoma
Issue of 2020‒12‒06
eight papers selected by
Laura Mannarino
Mario Negri Institute


  1. Case Rep Orthop. 2020 ;2020 8873185
    Tamiya H, Sabe H, Yamashita K, Imura Y, Wakamatsu T, Takenaka S.
      Adriamycin-based chemotherapy is commonly used for malignant soft tissue sarcoma including myxoid liposarcoma. However, in the case of unavailability or failure of the adriamycin-based regimen, trabectedin or eribulin can produce a good antitumor effect for myxoid liposarcoma. We relate the experience of a 64-year-old female with myxoid liposarcoma, who noticed a nodule on her left thigh and visited our institute. At initial presentation, the tumor was 18.7 cm in diameter, and the magnetic resonance imaging (MRI) showed a malignant lipomatous tumor with a myxoid component. We recommended that she undergo treatment; however, she refused. Three years later, the tumor had grown larger, so she finally decided to undergo treatment. A needle biopsy revealed a myxoid liposarcoma. The tumor massively involved the neurovascular structures; we thus determined that hip disarticulation was inevitable. Two years later, metastases in the right thigh, left lung, right ileum, and abdominal space were pointed out and chemotherapy was initiated. Adriamycin was unusable due to cardiac dysfunction, so trabectedin was administered; however, the tumors progressed. Eribulin was subsequently started and has been considerably effective for more than 2 years without severe adverse effects. In conclusion, we experienced a case showing the remarkable and long-lasting effect of eribulin against trabectedin-resistant myxoid liposarcoma.
    DOI:  https://doi.org/10.1155/2020/8873185
  2. Cancers (Basel). 2020 Nov 29. pii: E3568. [Epub ahead of print]12(12):
    de Groot S, Röttgering B, Gelderblom H, Pijl H, Szuhai K, Kroep JR.
      Insulin-like growth factor-1 receptor (IGF1R) inhibitors are effective in preclinical studies, but so far, no convincing benefit in clinical studies has been observed, except in some rare cases of sustained response in Ewing sarcoma patients. The mechanism of resistance is unknown, but several hypotheses are proposed. In this review, multiple possible mechanisms of resistance to IGF-targeted therapies are discussed, including activated insulin signaling, pituitary-driven feedback loops through growth hormone (GH) secretion and autocrine loops. Additionally, the outcomes of clinical trials of IGF1-targeted therapies are discussed, as well as strategies to overcome the possible resistance mechanisms. In conclusion, lowering the plasma insulin levels or blocking its activity could provide an additional target in cancer therapy in combination with IGF1 inhibition. Furthermore, because Ewing sarcoma cells predominantly express the insulin receptor A (IRA) and healthy tissue insulin receptor B (IRB), it may be possible to synthesize a specific IRA inhibitor.
    Keywords:  Ewing sarcoma; GH; IGF1; IGF1R; IGF2; INSR; IRA; IRB; insulin; resistance
    DOI:  https://doi.org/10.3390/cancers12123568
  3. J Surg Oncol. 2020 Dec 01.
    Klemen ND, Kelly CM, Bartlett EK.
      Clinicians caring for patients with sarcoma founded the field of cancer immunotherapy. Despite this, contemporary success with immunotherapy for sarcoma has been limited. Here, we review immunotherapy for sarcoma including Coley's toxins, interleukin-2, adoptive cell transfer, and checkpoint blockade. We detail recent and ongoing efforts to combine checkpoint blockade with other immune modulators, surgery, or radiation. These results, along with ongoing investigations, have identified immunotherapeutic approaches as a promising avenue for progress in advanced sarcomas.
    Keywords:  bone sarcoma; checkpoint inhibition; immunotherapy; sarcomas; soft-tissue sarcoma
    DOI:  https://doi.org/10.1002/jso.26306
  4. Am J Surg. 2020 Nov 23. pii: S0002-9610(20)30764-9. [Epub ahead of print]
    Littau MJ, Kulshrestha S, Bunn C, Agnew S, Sweigert P, Luchette FA, Baker MS.
      BACKGROUND: Prior studies evaluating the impact of adjuvant or neoadjuvant radiotherapy on clinical outcomes in retroperitoneal liposarcoma have been underpowered.METHODS: We queried the National Cancer Database for patients undergoing resection of retroperitoneal liposarcoma from 2004 to 2016. Cox proportional hazards modeling stratified by tumor size was used to identify factors associated with overall survival.
    RESULTS: 4018 patients met inclusion criteria. 251 had small (<5 cm), 574 intermediate (5-10 cm), and 3193 large (>10 cm) tumors. Positive surgical margins were correlated with risk of death across all tumor size categories (<5 cm HR 2.33, CI [1.20, 4.55]; 5-10 cm HR 1.49, CI [1.03, 2.14]; >10 cm HR 1.30, CI [1.12, 1.51]). Adjuvant radiotherapy was associated with improved survival for patients with large tumors only (HR 0.75, CI [0.64, 0.89]).
    CONCLUSIONS: In retroperitoneal liposarcoma, adjuvant radiation is associated with improved survival only for patients with tumors larger than 10 cm. Radiation should be used sparingly in patients with smaller tumors.
    SUMMARY: The use of radiotherapy in the management of retroperitoneal sarcoma remains controversial. We isolated retroperitoneal liposarcomas only and identified a survival benefit from radiotherapy treatment only in tumors larger than 10 cm and only in the adjuvant setting.
    Keywords:  Liposarcoma; Radiotherapy; Retroperitoneal sarcoma
    DOI:  https://doi.org/10.1016/j.amjsurg.2020.11.041
  5. Int J Mol Sci. 2020 Nov 22. pii: E8842. [Epub ahead of print]21(22):
    Boichuk S, Bikinieva F, Nurgatina I, Dunaev P, Valeeva E, Aukhadieva A, Sabirov A, Galembikova A.
      Activation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is well documented for a broad spectrum of human malignancies supporting their growth and progression. Accumulating evidence has also implicated AKT as a potent modulator of anti-cancer therapies via regulation of DNA damage response and repair (DDR) induced by certain chemotherapeutic agents and ionizing radiation (IR). In the present study, we examined the role of AKT signaling in regulating of Rad51 turnover and cytotoxic effects of topoisomerase II inhibitor, doxorubicin (Dox) in soft tissue sarcomas (STS) and gastrointestinal stromal tumors (GIST) in vitro. Blocking of AKT signaling (MK-2206) enhanced cytotoxic and pro-apoptotic effects of Dox in vast majority of STS and GIST cell lines. The phosphorylated form of Akt co-immunoprecipitates with Rad51 after Dox-induced DNA damage, whereas Akt inhibition interrupts this interaction and decreases Rad51 protein level by enhancing protein instability via proteasome-dependent degradation. Inhibition of Akt signaling in Dox-treated cells was associated with the increased number of γ-H2AX-positive cells, decrease of Rad51 foci formation and its colocalization with γ-H2AX foci, thereby revealing unsuccessful DDR events. This was also in consistency with an increase of tail moment (TM) and olive tail moment (OTM) in Dox-treated GIST and STS cells cultured in presence of Akt inhibitor after Dox washout. Altogether, our data illustrates that inhibition of AKT signaling is STS and GIST might potentiate the cytotoxic effect of topoisomerase II inhibitors via attenuating the homology-mediated DNA repair.
    Keywords:  AKT signaling; Rad51 recombinase; apoptosis; gastrointestinal stromal tumors (GIST); homology-mediated DNA repair; sensitization; soft tissue sarcomas (STS)
    DOI:  https://doi.org/10.3390/ijms21228842
  6. J Biol Regul Homeost Agents. 2019 Nov-Dec;33(6 Suppl. 3):33(6 Suppl. 3): 0-. Congress of the Italian Orthopaedic Research Society
    , Perisano C, Vitiello R, Sgambato A, Greco T, Cianni L, Ragonesi G, Malara T, Maccauro G, Martini M.
      Sarcomas are a heterogeneous group of rare tumours. Improvements in immunotherapy and the important role of PD1 and PD-L1 expression in advancement and prognosis have opened new fields of research for the treatment of these neoplasia. We evaluated the immunohistochemistry of PD1 and PD-L1 expression in 60 adults' patients affected by high-grade sarcomas of the limbs. PD1 expression was 65% while PD-L1 was 68.3%. PD-L1 expression seems to correlate to Ki67 in liposarcomas, fibrosarcoma's and pleomorphic sarcomas, while it does not show any correlation to chondrosarcomas, while in rhabdomyosarcomas there is a correlation but, given the small sample size, it was not possible to perform a statistic analysis. Our study shows positivity among the different subgroups of positive PD1 lymphocytes infiltration and PD-L1 expression in high-grade sarcomas of the limbs.
    Keywords:  PD; PD-L1; immunotherapy; programmed cell death receptor; sarcoma
  7. Cancer Epidemiol. 2020 Nov 26. pii: S1877-7821(20)30191-0. [Epub ahead of print]70 101857
    Snow A, Ring A, Struycken L, Mack W, Koç M, Lang JE.
      BACKGROUND: Previous studies have noted the incidence of radiation-induced sarcomas (RIS) but have not investigated the relative risk (RR) of developing RIS based on primary tumor organ disease site. By examining data from the Surveillance, Epidemiology, and End Results (SEER) database, we hypothesized that breast cancer would have a higher incidence of RIS compared to seventeen other primary cancer sites.METHODS: This was a retrospective cohort study that examined patients from SEER registries between 1973 and 2013. We included patients aged 18 years or older who were diagnosed with cancer and those diagnosed with a cancer who subsequently developed a sarcoma. We excluded patients with missing information on initial radiotherapy treatment or stage. RIS was defined as those who developed a secondary sarcoma near the site of their original malignancy and after a 24-month latency period.
    RESULTS: Our patients had a mean age of 60 years and follow up time of 9.2 years. Breast cancer comprised the majority with 693,701(36.8%) patients of which 161 (0.02%) had a secondary sarcoma. Of the 359 patients with secondary sarcomas, 242 (67.4%) had RIS. Breast cancer had the highest number of RIS patients at 126 compared to all combined non-breast cancer sites at 116. The RR of RIS in breast cancer versus 19 other primary cancer sites was 1.21 (CI: 1.01-1.45, p < 0.03, adjusted for age at primary diagnosis, gender, and latency).
    CONCLUSIONS: Our study demonstrated that breast cancer has a higher risk of developing RIS compared to other solid cancers.
    Keywords:  Breast cancer; Epidemiology; Radiation therapy; Radiation-induced sarcoma; Radiotherapy; SEER; Secondary sarcoma; Surveillance; and end results
    DOI:  https://doi.org/10.1016/j.canep.2020.101857