Alberto Farolfi1, Emanuela Scarpi2, Andrea Rocca3, Anita Mangia4, Nicoletta Biglia5, Lorenzo Gianni6, Amelia Tienghi7, Maria Rosaria Valerio8, Giampietro Gasparini9, Laura Amaducci10, Marina Faedi3, Editta Baldini11, Alessandra Rubagotti12, Roberta Maltoni3, Angelo Paradiso13, Dino Amadori3. 1. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. Electronic address: alberto.farolfi@irst.emr.it. 2. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 3. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 4. Functional Biomorphology Laboratory, Istituto Tumori "Giovanni Paolo II"-IRCCS, Bari, Italy. 5. Obstetrics and Gynaecology Unit, University of Torino Medical School, Torino, Italy. 6. Department of Oncology, Per gli Infermi Hospital, Rimini, Italy. 7. Oncology Unit, S. Maria delle Croci Hospital, Ravenna, Italy. 8. Department of Medical Oncology, AUOP Palermo, Italy. 9. Department of Oncology, San Filippo Neri Hospital, Roma, Italy. 10. Oncology Unit, Degli Infermi Hospital, Faenza, Italy. 11. Oncology Unit, S. Luca Hospital, Lucca, Italy. 12. Department of Internal Medicine of the University of Genoa and Academic Unit of Medical Oncology, AOU San Martino-IST, Genoa, Italy. 13. Clinical Experimental Oncology Laboratory, Istituto Tumori "Giovanni Paolo II"-IRCCS, Bari, Italy.
Abstract
AIM: To evaluate the optimal time interval from definitive surgery to commencing chemotherapy in early breast cancer (EBC). PATIENTS AND METHODS: The relationship between time to initiation of adjuvant chemotherapy (TTC), calculated in weeks, and disease-free (DFS) or overall survival (OS), was assessed in 921 EBC patients with rapidly proliferating tumours (thymidine labelling index >3% or G3 or Ki67 >20%), randomised in a phase III clinical trial (NCT01031030) to receive chemotherapy with or without anthracyclines (epirubicin→cyclophosphamide, methotrexate and fluorouracil (CMF) versus CMF→epirubicin versus CMF). DFS, OS and 95% confidence intervals (95% confidence interval (CI)) were calculated by the Kaplan-Meier method. Multivariate Cox analysis was performed in relation with nodal involvement, oestrogen receptor and human epidermal growth factor receptor 2 (HER2) status, Ki67 value, type of adjuvant chemotherapy, menopausal status and tumour size. RESULTS: At a median follow-up of 105 months (range 2-188), a prolonged TTC resulted in a significant increase in the risk of relapse: hazard ratio (HR) 1.15 (95% CI 1.02-1.30, p=0.019). Using a backward elimination procedure, TTC, tumour size and nodal involvement remained significantly associated with DFS. A time-dependent receiver-operating characteristic (ROC) curve analysis was subsequently utilised to evaluate the best cut-off for TTC, identifying 7 weeks as the best threshold for longer OS (p=0.043): 8-year OS 88% (95% CI 85-90) for patients with a TTC <7 weeks and 78% (95% CI 68-87) for the other group. CONCLUSIONS: Our results confirm that a shorter TTC may reduce relapses and possibly also improve clinical outcome in patients with highly proliferating EBC.
RCT Entities:
AIM: To evaluate the optimal time interval from definitive surgery to commencing chemotherapy in early breast cancer (EBC). PATIENTS AND METHODS: The relationship between time to initiation of adjuvant chemotherapy (TTC), calculated in weeks, and disease-free (DFS) or overall survival (OS), was assessed in 921 EBC patients with rapidly proliferating tumours (thymidine labelling index >3% or G3 or Ki67 >20%), randomised in a phase III clinical trial (NCT01031030) to receive chemotherapy with or without anthracyclines (epirubicin→cyclophosphamide, methotrexate and fluorouracil (CMF) versus CMF→epirubicin versus CMF). DFS, OS and 95% confidence intervals (95% confidence interval (CI)) were calculated by the Kaplan-Meier method. Multivariate Cox analysis was performed in relation with nodal involvement, oestrogen receptor and human epidermal growth factor receptor 2 (HER2) status, Ki67 value, type of adjuvant chemotherapy, menopausal status and tumour size. RESULTS: At a median follow-up of 105 months (range 2-188), a prolonged TTC resulted in a significant increase in the risk of relapse: hazard ratio (HR) 1.15 (95% CI 1.02-1.30, p=0.019). Using a backward elimination procedure, TTC, tumour size and nodal involvement remained significantly associated with DFS. A time-dependent receiver-operating characteristic (ROC) curve analysis was subsequently utilised to evaluate the best cut-off for TTC, identifying 7 weeks as the best threshold for longer OS (p=0.043): 8-year OS 88% (95% CI 85-90) for patients with a TTC <7 weeks and 78% (95% CI 68-87) for the other group. CONCLUSIONS: Our results confirm that a shorter TTC may reduce relapses and possibly also improve clinical outcome in patients with highly proliferating EBC.
Authors: Danielle K DePeralta; Takuya Ogami; Jun-Min Zhou; Michael J Schell; Benjamin D Powers; Pamela J Hodul; Mokenge P Malafa; Jason B Fleming Journal: HPB (Oxford) Date: 2019-09-25 Impact factor: 3.647
Authors: Rajiv Dave; Rachel O'Connell; Tim Rattay; Zoe Tolkien; Nicola Barnes; Joanna Skillman; Paula Williamson; Elizabeth Conroy; Matthew Gardiner; Adrian Harnett; Ciara O'Brien; Jane Blazeby; Shelley Potter; Chris Holcombe Journal: BMJ Open Date: 2016-10-07 Impact factor: 2.692
Authors: E Heeg; J X Harmeling; B E Becherer; P J Marang-van de Mheen; M T F D Vrancken Peeters; M A M Mureau Journal: Br J Surg Date: 2019-08-06 Impact factor: 6.939