PURPOSE: Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas (LASTS), although not standard, represents a promising option for resectable tumours. Current lack of biological predictors of chemotherapy response led us to establish a relationship between Topoisomerase II-alpha (Topo2A), HER2, excision repair cross-complementing group 1 (ERCC1) protein expression, histological response and clinical outcomes of LASTS patients. PATIENTS AND METHODS: A retrospective study based on clinical data and archival paraffin-embedded tumour tissue at diagnosis from 78 consecutive LASTS patients treated with neo-adjuvant chemotherapy in our institution enabled analysis of ERCC1, HER2 and Topo2A protein expression by immuno-histochemistry. RESULTS: Disease free survival (DFS) and overall survival (OS) were 48% and 64%, respectively. The annual risk of relapse increased with a higher percentage of residual identifiable cells (RIC). A higher Topo2A protein was associated with an improved rate of good HR (r=0.416) and with a decreased risk of relapse. Median DFS decreased with low Topo2A (p⩽0.042). The ERCC1 status had no impact on histological response while ERCC1 positive tumours correlated with a favourable OS (p ≤ 0.058). Patients with LASTS co-expressing Topo2A and ERCC1 had a significant better outcome (p=0.018). Topo2A was the only independent variable linked to a good HR (p ≤ 0.017); histological grade 3 was the only independent adverse prognostic variable linked to both DFS (p ≤ 0.04) and OS (p ≤ 0.004). CONCLUSIONS: While histological response predicts better DFS, Topo2A protein expression correlates with histological response and better DFS. The combination of an early predictive factor for chemosensitivity (Topo2A) and for survival (ERCC1) highlights the possibility to develop individualised therapeutic approaches (CONTICANET program).
PURPOSE: Neoadjuvant chemotherapy for locally advanced soft tissue sarcomas (LASTS), although not standard, represents a promising option for resectable tumours. Current lack of biological predictors of chemotherapy response led us to establish a relationship between Topoisomerase II-alpha (Topo2A), HER2, excision repair cross-complementing group 1 (ERCC1) protein expression, histological response and clinical outcomes of LASTS patients. PATIENTS AND METHODS: A retrospective study based on clinical data and archival paraffin-embedded tumour tissue at diagnosis from 78 consecutive LASTS patients treated with neo-adjuvant chemotherapy in our institution enabled analysis of ERCC1, HER2 and Topo2A protein expression by immuno-histochemistry. RESULTS: Disease free survival (DFS) and overall survival (OS) were 48% and 64%, respectively. The annual risk of relapse increased with a higher percentage of residual identifiable cells (RIC). A higher Topo2A protein was associated with an improved rate of good HR (r=0.416) and with a decreased risk of relapse. Median DFS decreased with low Topo2A (p⩽0.042). The ERCC1 status had no impact on histological response while ERCC1 positive tumours correlated with a favourable OS (p ≤ 0.058). Patients with LASTS co-expressing Topo2A and ERCC1 had a significant better outcome (p=0.018). Topo2A was the only independent variable linked to a good HR (p ≤ 0.017); histological grade 3 was the only independent adverse prognostic variable linked to both DFS (p ≤ 0.04) and OS (p ≤ 0.004). CONCLUSIONS: While histological response predicts better DFS, Topo2A protein expression correlates with histological response and better DFS. The combination of an early predictive factor for chemosensitivity (Topo2A) and for survival (ERCC1) highlights the possibility to develop individualised therapeutic approaches (CONTICANET program).
Authors: Ramesh K Ramanathan; Glen J Weiss; Richard G Posner; N V Rajeshkumar; Gayle Jameson; Meraj Aziz; Antje Hoering; Vanessa Bolejack; Anirban Maitra; Monica Fulk; Edward C Stites; William S Hlavacek; Zoran Gatalica; Joanne Xiu; Manuel Hidalgo; Daniel D Von Hoff; Michael T Barrett Journal: J Gastrointest Oncol Date: 2017-12
Authors: Sujana Movva; Wenhsiang Wen; Wangjuh Chen; Sherri Z Millis; Zoran Gatalica; Sandeep Reddy; Margaret von Mehren; Brian A Van Tine Journal: Oncotarget Date: 2015-05-20
Authors: John M Kane; Anthony Magliocco; Qiang Zhang; Dian Wang; Alex Klimowicz; Jonathan Harris; Jeff Simko; Thomas DeLaney; William Kraybill; David G Kirsch Journal: Sarcoma Date: 2018-02-28
Authors: Mina Nikanjam; David Arguello; Zoran Gatalica; Jeff Swensen; Donald A Barkauskas; Razelle Kurzrock Journal: Int J Cancer Date: 2019-10-01 Impact factor: 7.396