Katz D, Palmerini E, Pollack SM. More than 50 subtypes of soft tissue sarcoma: paving the path for histology-driven treatments. Am Soc Clin Oncol Educ Book. 2018;38:925–38. https://doi.org/10.1200/EDBK_205423.

Article  PubMed  Google Scholar 

Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumour. Lancet. 2013;382(9896):973–83. https://doi.org/10.1016/S0140-6736(13)60106-3.

Article  CAS  PubMed  Google Scholar 

Ayodele O, Razak ARA. Immunotherapy in soft-tissue sarcoma. Curr Oncol. 2020;27(Suppl 1):17–23. https://doi.org/10.3747/co.27.5407.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stacchiotti S, Frezza AM, Blay JY, Baldini EH, Bonvalot S, Bovee J, et al. Ultra-rare sarcomas: a consensus paper from the Connective Tissue Oncology Society community of experts on the incidence threshold and the list of entities. Cancer. 2021;127(16):2934–42. https://doi.org/10.1002/cncr.33618.

Article  PubMed  Google Scholar 

Gamboa AC, Gronchi A, Cardona K. Soft-tissue sarcoma in adults: an update on the current state of histiotype-specific management in an era of personalized medicine. CA Cancer J Clin. 2020;70(3):200–29. https://doi.org/10.3322/caac.21605.

Article  PubMed  Google Scholar 

Savina M, Le Cesne A, Blay JY, Ray-Coquard I, Mir O, Toulmonde M, et al. Patterns of care and outcomes of patients with METAstatic soft tissue SARComa in a real-life setting: the METASARC observational study. BMC Med. 2017;15(1):78.

Article  PubMed  PubMed Central  Google Scholar 

Tawbi HA, Burgess M, Bolejack V, Van Tine BA, Schuetze SM, Hu J, et al. Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. The Lancet Oncology. 2017;18(11):1493–501. https://doi.org/10.1016/S1470-2045(17)30624-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Seddon B, Strauss SJ, Whelan J, Leahy M, Woll PJ, Cowie F, Rothermundt C, Wood Z, Benson C, Ali N, Marples M, Veal GJ, Jamieson D, Küver K, Tirabosco R, Forsyth S, Nash S, Dehbi HM, Beare S. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial. The Lancet Oncology. 2017;18(10):1397–410. https://doi.org/10.1016/S1470-2045(17)30622-8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Judson I, Verweij J, Gelderblom H, Hartmann JT, Schoffski P, Blay JY, et al. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. Lancet Oncol. 2014;15(4):415–23. https://doi.org/10.1016/S1470-2045(14)70063-4.

Article  CAS  PubMed  Google Scholar 

Meyer M, Seetharam M. First-line therapy for metastatic soft tissue sarcoma. Curr Treat Options Oncol. 2019;20(1):6.

Article  PubMed  Google Scholar 

D’Angelo SP, Mahoney MR, Van Tine BA, Atkins J, Milhem MM, Jahagirdar BN, et al. Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): two open-label, non-comparative, randomised, phase 2 trials. The Lancet Oncology. 2018;19(3):416–26. https://doi.org/10.1016/S1470-2045(18)30006-8.

Article  PubMed  PubMed Central  Google Scholar 

Kim JR, Moon YJ, Kwon KS, Bae JS, Wagle S, Kim KM, Park HS, Lee H, Moon WS, Chung MJ, Kang MJ, Jang KY. Tumor infiltrating PD1-positive lymphocytes and the expression of PD-L1 predict poor prognosis of soft tissue sarcomas. PLoS One. 2013;8(12):e82870. https://doi.org/10.1371/journal.pone.0082870.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Movva S, Wen W, Chen W, Millis SZ, Gatalica Z, Reddy S, et al. Multi-platform profiling of over 2000 sarcomas: identification of biomarkers and novel therapeutic targets. Oncotarget. 2015;6(14). https://doi.org/10.18632/oncotarget.3498.

Pollack SM, He Q, Yearley JH, Emerson R, Vignali M, Zhang Y, Redman MW, Baker KK, Cooper S, Donahue B, Loggers ET, Cranmer LD, Spraker MB, Seo YD, Pillarisetty VG, Ricciotti RW, Hoch BL, McClanahan TK, Murphy E, et al. T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas. Cancer. 2017;123:3291–304. https://doi.org/10.1002/cncr.30726.

Schroeder BA, LaFranzo NA, LaFleur BJ, Gittelman RM, Vignali M, Zhang S, et al. CD4+ T cell and M2 macrophage infiltration predict dedifferentiated liposarcoma patient outcomes. J Immunother Cancer. 2021;9(8). https://doi.org/10.1136/jitc-2021-002812.

Goff PH, Riolobos L, LaFleur BJ, Spraker MB, Seo YD, Smythe KS, et al. Neoadjuvant therapy induces a potent immune response to sarcoma, dominated by myeloid and B cells. Clin Cancer Res. 2022. https://doi.org/10.1158/1078-0432.CCR-21-4239.

Zhang S, Kohli K, Black RG, Yao L, Spadinger SM, He Q, Pillarisetty VG, Cranmer LD, van Tine BA, Yee C, Pierce RH, Riddell SR, Jones RL, Pollack SM. Systemic interferon-gamma increases MHC class I expression and T-cell infiltration in cold tumors: results of a phase 0 clinical trial. Cancer Immunol Res. 2019;7(8):1237–43. https://doi.org/10.1158/2326-6066.CIR-18-0940.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pollack SM, Ingham M, Spraker MB, Schwartz GK. Emerging targeted and immune-based therapies in sarcoma. Journal of Clinical Oncology. 2018;36(2):125–35. https://doi.org/10.1200/JCO.2017.75.1610.

Article  CAS  PubMed  Google Scholar 

Chawla SP, Van Tine BA, Pollack SM, Ganjoo KN, Elias AD, Riedel RF, et al. Phase II randomized study of CMB305 and atezolizumab compared with atezolizumab alone in soft-tissue sarcomas expressing NY-ESO-1. J Clin Oncol. 2022;40(12):1291–300. https://doi.org/10.1200/JCO.20.03452.

Article  CAS  PubMed  Google Scholar 

Ben-Ami E, Barysauskas CM, Solomon S, Tahlil K, Malley R, Hohos M, Polson K, Loucks M, Severgnini M, Patel T, Cunningham A, Rodig SJ, Hodi FS, Morgan JA, Merriam P, Wagner AJ, Shapiro GI, George S. Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: results of a phase 2 study. Cancer. 2017;123(17):3285–90. https://doi.org/10.1002/cncr.30738.

Article  CAS  PubMed  Google Scholar 

Somaiah N, Conley AP, Parra ER, Lin H, Amini B, Solis Soto L, Salazar R, Barreto C, Chen H, Gite S, Haymaker C, Nassif EF, Bernatchez C, Mitra A, Livingston JA, Ravi V, Araujo DM, Benjamin R, Patel S, et al. Durvalumab plus tremelimumab in advanced or metastatic soft tissue and bone sarcomas: a single-centre phase 2 trial. The Lancet Oncology. 2022;23:1156–66. https://doi.org/10.1016/S1470-2045(22)00392-8.

Nathenson M, Choy E, Carr ND, Hibbard HD, Mazzola E, Catalano PJ, et al. Phase II study of eribulin and pembrolizumab in patients (pts) with metastatic soft tissue sarcomas (STS): report of LMS cohort. J Clin Oncol. 2020;38(15_suppl):11559. https://doi.org/10.1200/JCO.2020.38.15_suppl.11559.

Article  Google Scholar 

Petitprez F, de Reynies A, Keung EZ, Chen TW, Sun CM, Calderaro J, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020. https://doi.org/10.1038/s41586-019-1906-8.

Italiano A, Bessede A, Pulido M, Bompas E, Piperno-Neumann S, Chevreau C, et al. Pembrolizumab in soft-tissue sarcomas with tertiary lymphoid structures: a phase 2 PEMBROSARC trial cohort. Nat Med. 2022;28(6):1199–206. This reference is of importance because it underscores the presence of intratumoral tertiary lymphoid structures as a potential predictive biomarker to improve patient selection for pembrolizumab and pembrolizumab combination therapies. https://doi.org/10.1038/s41591-022-01821-3.

Article  CAS  PubMed  Google Scholar 

Judson I, Verweij J, Gelderblom H, Hartmann JT, Schöffski P, Blay J-Y, Kerst JM, Sufliarsky J, Whelan J, Hohenberger P, Krarup-Hansen A, Alcindor T, Marreaud S, Litière S, Hermans C, Fisher C, Hogendoorn PC, dei Tos A, van der Graaf W, European Organisation and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: a randomised controlled phase 3 trial. The Lancet Oncology. 2014;15(4):415–23. https://doi.org/10.1016/S1470-2045(14)70063-4.

Article  CAS  PubMed  Google Scholar 

Ryan CW, Merimsky O, Agulnik M, Blay J-Y, Schuetze SM, Tine BAV, et al. PICASSO III: a phase III, placebo-controlled study of doxorubicin with or without palifosfamide in patients with metastatic soft tissue sarcoma. J Clin Oncol. 2016;34(32):3898–905. https://doi.org/10.1200/JCO.2016.67.6684.

Article  CAS  PubMed  Google Scholar 

Tap WD, Papai Z, Van Tine BA, Attia S, Ganjoo KN, Jones RL, et al. Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial. The Lancet Oncol. 2017;18(8):1089–103. https://doi.org/10.1016/S1470-2045(17)30381-9.

Article  CAS  PubMed  Google Scholar 

Tap WD, Wagner AJ, Schoffski P, Martin-Broto J, Krarup-Hansen A, Ganjoo KN, et al. Effect of doxorubicin plus olaratumab vs doxorubicin plus placebo on survival in patients with advanced soft tissue sarcomas: the ANNOUNCE randomized clinical trial. JAMA. 2020;323(13):1266–76. https://doi.org/10.1001/jama.2020.1707.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weiss GJ, Waypa J, Blaydorn L, Coats J, McGahey K, Sangal A, Niu J, Lynch CA, Farley JH, Khemka V. A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus). Br J Cancer. 2017;117(1):33–40. https://doi.org/10.1038/bjc.2017.145.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pollack SM, Redman MW, Baker KK, Wagner MJ, Schroeder BA, Loggers ET, et al. Assessment of doxorubicin and pembrolizumab in patients with advanced anthracycline-naive sarcoma: a phase 1/2 nonrandomized clinical trial. JAMA Oncol, 82. 2020;6(11):1778 This reference is of importance because it highlights that the combination of doxorubicin with pembrolizumab is promising and worthy of further study, especially in UPS and dedifferentiated LPS.

Livingston MB, Jagosky MH, Robinson MM, Ahrens WA, Benbow JH, Farhangfar CJ, Foureau DM, Maxwell DM, Baldrige EA, Begic X, Symanowski JT, Steuerwald NM, Anderson CJ, Patt JC, Kneisl JS, Kim ES. Phase II study of pembrolizumab in combination with doxorubicin in metastatic and unresectable soft-tissue sarcoma. Clin Cancer Res. 2021;27(23):6424–31. https://doi.org/10.1158/1078-0432.CCR-21-2001.

Article  CAS  PubMed  Google Scholar 

Rosenbaum E, Qin L-X, Thornton KA, Movva S, Nacev BA, Dickson MA, et al. A phase I/II trial of the PD-1 inhibitor retifanlimab (R) in combination with gemcitabine and docetaxel (GD) as first-line therapy in patients (Pts) with advanced soft-tissue sarcoma (STS). J Clin Oncol. 2022;40(16_suppl):11516. https://doi.org/10.1200/JCO.2022.40.16_suppl.11516.

Article  Google Scholar 

Padron LJ, Maurer DM, O’Hara MH, O’Reilly EM, Wolff RA, Wainberg ZA, et al. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022;28(6):1167–77. https://doi.org/10.1038/s41591-022-01829-9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jones RL, Herzog TJ, Patel SR, von Mehren M, Schuetze SM, Van Tine BA, et al. Cardiac safety of trabectedin monotherapy or in combination with pegylated liposomal doxorubicin in patients with sarcomas and ovarian cancer. Cancer Med. 2021;10(11):3565–74. https://doi.org/10.1002/cam4.3903.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze SM, Staddon A, Milhem M, Elias A, Ganjoo K, Tawbi H, van Tine BA, Spira A, Dean A, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel SR. Efficacy and safety of trabectedin or dacarbazine for metastatic liposarcoma or leiomyosarcoma after failure of conventional chemotherapy: results of a phase III randomized multicenter clinical trial. J Clin Oncol. 2016;34(8):786–93. https://doi.org/10.1200/JCO.2015.62.4734.

Article  CAS  PubMed  Google Scholar 

Kawai A, Araki N, Sugiura H, Ueda T, Yonemoto T, Takahashi M, Morioka H, Hiraga H, Hiruma T, Kunisada T, Matsumine A, Tanase T, Hasegawa T, Takahashi S. Trabectedin monotherapy after standard chemotherapy versus best supportive care in patients with advanced, translocation-related sarcoma: a randomised, open-label, phase 2 study. The Lancet Oncology. 2015;16(4):406–16. https://doi.org/10.1016/S1470-2045(15)70098-7.

Article