Johan Erlandsson1, Ester Lörinc2, Madelene Ahlberg3, David Pettersson4, Torbjörn Holm5, Bengt Glimelius6, Anna Martling7. 1. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Colorectal Cancer Karolinska University Hospital, Stockholm, Sweden. Electronic address: johan.erlandsson@ki.se. 2. Division of pathology Lund, Department of Pathology and Cytology, Skåne University Hospital, Stockholm, Sweden. Electronic address: lorinc.ester@telia.com. 3. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Colorectal Cancer Karolinska University Hospital, Stockholm, Sweden. Electronic address: madelene.ahlberg@sll.se. 4. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of surgery, Norrtälje Sjukhus, Sweden. Electronic address: david.pettersson@tiohundra.se. 5. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Colorectal Cancer Karolinska University Hospital, Stockholm, Sweden. Electronic address: torbjorn.holm@ki.se. 6. Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Uppsala University, Sweden. Electronic address: bengt.glimelius@igp.uu.se. 7. Department of Molecular Medicine and Surgery, Karolinska Institutet and Department of Colorectal Cancer Karolinska University Hospital, Stockholm, Sweden. Electronic address: anna.martling@ki.se.
Abstract
BACKGROUND AND PURPOSE:Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 × 5 Gy surgery within one week (SRT), 5 × 5 Gy with surgery after 4-8 weeks, and 2 Gy × 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. MATERIAL AND METHODS: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). RESULTS: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. CONCLUSION:SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 × 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.
RCT Entities:
BACKGROUND AND PURPOSE: Neoadjuvant radiotherapy (RT) in rectal cancer induces tumour regression with a possible complete response (pCR). The optimal fractionation and timing to surgery is not established. The Stockholm III trial randomly assigned 840 patients to 5 × 5 Gy surgery within one week (SRT), 5 × 5 Gy with surgery after 4-8 weeks, and 2 Gy × 25 with surgery after 4-8 weeks (LRT-delay). The aim of this substudy was to assess tumour regression and correlation to survival. MATERIAL AND METHODS: All available microscopy slides were assessed by one pathologist, blinded to treatment, regarding tumour regression, graded according to the Dworak system (TRG), TNM-stage and other standard histopathology characteristics. Patients' data were collected from the Swedish ColoRectal Cancer Registry. Outcomes were TRG, pCR-rates, overall survival (OS) and time to recurrence (TTR). RESULTS: 318, 285 and 94 patients were included in the SRT, SRT-delay and LRT-delay groups. Median follow up was 5.7 years. There were significantly lower tumour stages after SRT-delay. pCR was seen in 1 (0.3%), 29 (10.4%) and 2 (2.2%) patients in SRT, SRT-delay and LRT-delay, respectively. The pCR and Dworak grade 4 were associated with superior survival. pCR vs no-pCR Hazard Ratio (95% Confidence Interval) OS: 0.51 (0.26-0.99) p = 0.046, TTR: 0.27 (0.09-0.86) p = 0.027. CONCLUSION: SRT-delay induces pCR in about 10% of the patients and is in this aspect superior to 25 × 2 Gy. A complete tumour response, TRG 4 using the Dworak system, or a pCR, is associated with superior OS and TTR.
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