Kirsten Sundby Hall1, Øyvind S Bruland2, Bodil Bjerkehagen3, Olga Zaikova4, Jacob Engellau5, Oskar Hagberg6, Lina Hansson7, Hans Hagberg8, Marie Ahlström9, Heidi Knobel10, Karin Papworth11, Maja Zemmler12, Dorota Goplen13, Henrik C F Bauer14, Mikael Eriksson15. 1. Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: ksh@ous-hf.no. 2. Department of Oncology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: OSB@ous-hf.no. 3. Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. Electronic address: BOB@ous-hf.no. 4. Division of Orthopaedic Surgery, Oslo University Hospital, Oslo, Norway. Electronic address: OLGAZ@ous-hf.no. 5. Department of Oncology, Skåne University Hospital and Lund University, Lund, Sweden. Electronic address: Jacob.Engellau@med.lu.se. 6. Regional Cancer Centre South, Lund, Sweden. Electronic address: oskar.hagberg@skane.se. 7. Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: lina.hansson@vgregion.se. 8. Department of Oncology, Uppsala University Hospital, Uppsala, Sweden. Electronic address: hans.hagberg@akademiska.se. 9. Department of Oncology, Skåne University Hospital and Lund University, Lund, Sweden. Electronic address: Marie.Ahlstrom@skane.se. 10. Department of Oncology, St Olav University Hospital, Trondheim, Norway. Electronic address: Heidi.Knobel@stolav.no. 11. Department of Oncology, Norrlands University Hospital, Umeå, Sweden. Electronic address: Karin.Papworth@vll.se. 12. Department of Oncology, Linköping University Hospital, Linköping, Sweden. Electronic address: Maja.Zemmler@regionostergotland.se. 13. Department Musculo-Skeletal Tumour Service/Oncology, Haukeland University Hospital, Bergen, Norway. Electronic address: dorota.goplen@helse-bergen.no. 14. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. Electronic address: Henrik.Bauer@karolinska.se. 15. Department of Oncology, Skåne University Hospital and Lund University, Lund, Sweden. Electronic address: Mikael.Eriksson@med.lu.se.
Abstract
PURPOSE: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. METHODS: High-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. RESULTS: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. CONCLUSIONS: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.
PURPOSE: To investigate the outcome following adjuvant doxorubicin and ifosfamide in a prospective non-randomised study based on a soft tissue sarcoma (STS) patient subgroup defined by specific morphological characteristics previously shown to be at a high-risk of metastatic relapse. The expected 5-year cumulative incidence of metastases in patients with this risk profile has previously been reported to be about 50% without adjuvant chemotherapy. METHODS: High-risk STS was defined as high-grade morphology (according to the Fédération Nationale des Centres de Lutte Contre le Cancer [FNCLCC] grade II-III) and either vascular invasion or at least two of the following criteria: tumour size ≥8.0 cm, infiltrative growth and necrosis. Six cycles of doxorubicin (60 mg/m2) and ifosfamide (6 g/m2) were given. Postoperative accelerated radiotherapy was applied and scheduled between cycles 3 and 4. RESULTS: For the 150 eligible patients, median follow-up time for metastases-free survival was 3.9 years (range 0.2-8.7). Five-year metastases-free survival (MFS) was 70.4% (95% confidence interval [CI]: 63.1-78.4) with a local recurrence rate of 14.0% (95% CI: 7.8-20.2). For overall survival (OS), the median follow-up time was 4.4 years (range: 0.2-8.7). The five-year OS was 76.1% (95% CI: 68.8-84.2). Tumour size, deep location and reduced dose intensity (<80%) had a negative impact on survival. Toxicity was moderate with no treatment-related death. CONCLUSIONS: A benefit of adjuvant chemotherapy, compared to similar historical control groups, was demonstrated in STS patients with defined poor prognostic factors. Vascular invasion, tumour size, growth pattern and necrosis may identify patients in need of adjuvant chemotherapy.
Authors: Thomas Gp Grünewald; Marta Alonso; Sofia Avnet; Ana Banito; Stefan Burdach; Florencia Cidre-Aranaz; Gemma Di Pompo; Martin Distel; Heathcliff Dorado-Garcia; Javier Garcia-Castro; Laura González-González; Agamemnon E Grigoriadis; Merve Kasan; Christian Koelsche; Manuela Krumbholz; Fernando Lecanda; Silvia Lemma; Dario L Longo; Claudia Madrigal-Esquivel; Álvaro Morales-Molina; Julian Musa; Shunya Ohmura; Benjamin Ory; Miguel Pereira-Silva; Francesca Perut; Rene Rodriguez; Carolin Seeling; Nada Al Shaaili; Shabnam Shaabani; Kristina Shiavone; Snehadri Sinha; Eleni M Tomazou; Marcel Trautmann; Maria Vela; Yvonne Mh Versleijen-Jonkers; Julia Visgauss; Marta Zalacain; Sebastian J Schober; Andrej Lissat; William R English; Nicola Baldini; Dominique Heymann Journal: EMBO Mol Med Date: 2020-10-13 Impact factor: 12.137