Browsing by Subject "SOFT-TISSUE SARCOMA"

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  • Cooperative Weichteilsarkom; Scheer, Monika; Vokuhl, Christian; Blank, Bernd; Jahnukainen, Kirsi; Koscielniak, Ewa (2019)
    Background To evaluate optimal therapy and potential risk factors. Methods Data of DSRCT patients Results Median age of 60 patients was 14.5 years. Male:female ratio was 4:1. Tumors were abdominal/retroperitoneal in 56/60 (93%). 6/60 (10%) presented with a localized mass, 16/60 (27%) regionally disseminated nodes, and 38/60 (63%) with extraperitoneal metastases. At diagnosis, 23/60 (38%) patients had effusions, 4/60 (7%) a thrombosis, and 37/54 (69%) elevated CRP. 40/60 (67%) patients underwent tumor resection, 21/60 (35%) macroscopically complete. 37/60 (62%) received chemotherapy according to CEVAIE (ifosfamide, vincristine, actinomycin D, carboplatin, epirubicin, etoposide), 15/60 (25%) VAIA (ifosfamide, vincristine, adriamycin, actinomycin D) and, 5/60 (8%) P6 (cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide). Nine received high-dose chemotherapy, 6 received regional hyperthermia, and 20 received radiotherapy. Among 25 patients achieving complete remission, 18 (72%) received metronomic therapies. Three-year event-free (EFS) and overall survival (OS) were 11% (+/- 8 confidence interval [CI] 95%) and 30% (+/- 12 CI 95%), respectively, for all patients and 26.7% (+/- 18.0 CI 95%) and 56.9% (+/- 20.4 CI 95%) for 25 patients achieving remission. Extra-abdominal site, localized disease, no effusion or ascites only, absence of thrombosis, normal CRP, complete tumor resection, and chemotherapy with VAIA correlated with EFS in univariate analysis. In multivariate analysis, significant factors were no thrombosis and chemotherapy with VAIA. In patients achieving complete remission, metronomic therapy with cyclophosphamide/vinblastine correlated with prolonged time to relapse. Conclusion Pleural effusions, venous thrombosis, and CRP elevation were identified as potential risk factors. The VAIA scheme showed best outcome. Maintenance therapy should be investigated further.
  • Kolberg, Matthias; Bruun, Jarle; Murumagi, Astrid; Mpindi, John P.; Bergsland, Christian H.; Holand, Maren; Eilertsen, Ina A.; Danielsen, Stine A.; Kallioniemi, Olli; Lothe, Ragnhild A. (2017)
    Patients with malignant peripheral nerve sheath tumor (MPNST), a rare soft tissue cancer associated with loss of the tumor suppressor neurofibromin (NF1), have poor prognosis and typically respond poorly to adjuvant therapy. We evaluated the effect of 299 clinical and investigational compounds on seven MPNST cell lines, two primary cultures of human Schwann cells, and five normal bone marrow aspirates, to identify potent drugs for MPNST treatment with few side effects. Top hits included Polo-like kinase 1 (PLK1) inhibitors (volasertib and BI2536) and the fluoronucleoside gemcitabine, which were validated in orthogonal assays measuring viability, cytotoxicity, and apoptosis. DNA copy number, gene expression, and protein expression were determined for the cell lines to assess pharmacogenomic relationships. MPNST cells were more sensitive to BI2536 and gemcitabine compared to a reference set of 94 cancer cell lines. PLK1, RRM1, and RRM2 mRNA levels were increased in MPNST compared to benign neurofibroma tissue, and the protein level of PLK1 was increased in the MPNST cell lines compared to normal Schwann cells, indicating an increased dependence on these drug targets in malignant cells. Furthermore, we observed an association between increased mRNA expression of PLK1, RRM1, and RRM2 in patient samples and worse disease outcome, suggesting a selective benefit from inhibition of these genes in the most aggressive tumors.
  • Homsy, Pauliina; Blomqvist, Carl; Heiskanen, Ilkka; Vikatmaa, Leena; Tukiainen, Erkki; Numminen, Kirsti; Sampo, Mika; Leppäniemi, Ari; Albäck, Anders; Kantonen, Ilkka; Vikatmaa, Pirkka (2020)
    Objective: Radical excision of retroperitoneal or intra-abdominal soft tissue sarcomas may necessitate vessel resection and reconstruction. The aim of this study was to assess surgical results of retroperitoneal or intra-abdominal sarcomas involving major blood vessels. Methods: This was a retrospective single centre cohort study and a comprehensive review of literature. Patients with retroperitoneal or intra-abdominal sarcomas treated by the oncovascular team in Helsinki University Hospital from 2010 to 2018 were reviewed for vascular and oncological outcomes. A comprehensive literature review of vascular reconstructions in patients with retroperitoneal sarcoma was performed. Results: Vascular reconstruction was performed in 17 patients, 11 of whom required arterial reconstructions. Sixteen of the operations were sarcoma resections; the post-operative diagnosis for one patient was thrombosis instead of the presumed recurrent leiomyosarcoma. Early graft thrombosis occurred in two venous and one arterial reconstruction. Late thrombosis was detected in three (18%). The median follow up was 27 (range 0-82) months. Of the patients with sarcoma resections 5 (31%) died of sarcoma and further 4 (25%) developed local recurrence or new distant metastases. The comprehensive review of literature identified 37 articles with 110 patients, 89 of whom had inferior vena cava reconstruction only. Eight arterial reconstructions were described. Late graft thrombosis occurred in 14%. The follow up was 0-181 months, during which 57% remained disease free and 7% died of sarcoma. Conclusion: Vascular reconstructions enable radical resection of retroperitoneal and intra-abdominal sarcomas in patients with advanced disease. The complex operations are associated with an acceptable rate of serious perioperative complications and symptomatic thrombosis of the repaired vessel is rare. However, further studies are needed to assess the performance of the vascular reconstructions in the long term.
  • Cuppens, Tine; Annibali, Daniela; Coosemans, An; Trovik, Jone; ter Haar, Natalja; Colas, Eva; Garcia-Jimenez, Angel; Van de Vijver, Koen; Kruitwagen, Roy P. M.; Brinkhuis, Mariel; Zikan, Michal; Dundr, Pavel; Huvila, Jutta; Carpen, Olli; Haybaeck, Johannes; Moinfar, Farid; Salvesen, Helga B.; Stukan, Maciej; Mestdagh, Carole; Zweemer, Ronald P.; Massuger, Leonardus F.; Mallmann, Michael R.; Wardelmann, Eva; Mints, Miriam; Verbist, Godelieve; Thomas, Debby; Gomme, Ellen; Hermans, Els; Moerman, Philippe; Bosse, Tjalling; Amant, Frederic (2017)
    Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive biomarkers are available so far to guide choice and modality of treatment. Experimental Design: We investigated the expression of several druggable targets (phospho-S6(S240) ribosomal protein, PTEN, PDGFR-alpha, ERBB2, and EGFR) in a large cohort of human uterine sarcoma samples (288), including leiomyosarcomas, low-grade and high-grade endometrial stromal sarcomas, undifferentiated uterine sarcomas, and adenosarcomas, together with 15 smooth muscle tumors of uncertain malignant potential (STUMP), 52 benign uterine stromal tumors, and 41 normal uterine tissues. The potential therapeutic value of the most promising target, p-S6(S240), was tested in patient-derived xenograft (PDX) leiomyosarcoma models. Results: In uterine sarcomas and STUMPs, S6S240 phosphorylation (reflecting mTOR pathway activation) was associated with higher grade (P = 0.001) and recurrence (P = 0.019), as shown by logistic regression. In addition, p-S6(S240) correlated with shorter progression-free survival (P = 0.034). Treatment with a dual PI3K/mTOR inhibitor significantly reduced tumor growth in 4 of 5 leiomyosarcoma PDX models (with tumor shrinkage in 2 models). Remarkably, the 4 responding models showed basal p-S6(S240) expression, whereas the nonresponding model was scored as negative, suggesting a role for p-S6(S240) in response prediction to PI3K/mTOR inhibition. Conclusions: Dual PI3K/mTOR inhibition represents an effective therapeutic strategy in uterine leiomyosarcoma, and p-S6(S240) expression is a potential predictive biomarker for response to treatment. (C)2017 AACR.
  • Grünewald, Thomas G. P.; Alonso, Marta; Avnet, Sofia; Banito, Ana; Burdach, Stefan; Cidre-Aranaz, Florencia; Di Pompo, Gemma; Distel, Martin; Dorado-Garcia, Heathcliff; Garcia-Castro, Javier; Gonzalez-Gonzalez, Laura; Grigoriadis, Agamemnon E.; Kasan, Merve; Koelsche, Christian; Krumbholz, Manuela; Lecanda, Fernando; Lemma, Silvia; Longo, Dario L.; Madrigal-Esquivel, Claudia; Morales-Molina, Alvaro; Musa, Julian; Ohmura, Shunya; Ory, Benjamin; Pereira-Silva, Miguel; Perut, Francesca; Rodriguez, Rene; Seeling, Carolin; Al Shaaili, Nada; Shaabani, Shabnam; Shiavone, Kristina; Sinha, Snehadri; Tomazou, Eleni M.; Trautmann, Marcel; Vela, Maria; Versleijen-Jonkers, Yvonne M. H.; Visgauss, Julia; Zalacain, Marta; Schober, Sebastian J.; Lissat, Andrej; English, William R.; Baldini, Nicola; Heymann, Dominique (2020)
    Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.