Andreas Hallqvist1, Stefan Bergström2, Hedvig Björkestrand3, Anna-Maja Svärd4, Simon Ekman3, Erik Lundin5, Erik Holmberg6, Mikael Johansson4, Signe Friesland4, Jan Nyman7. 1. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Blå stråket 2, 413 45 Gothenburg, Sweden. Electronic address: andreas.hallqvist@oncology.gu.se. 2. Department of Oncology, Gävle Hospital, Lasarettsvägen 1, 801 11 Gävle, Sweden. 3. Department of Oncology, Karolinska University Hospital, Karolinska vägen 171 76 Stockholm, Sweden. 4. Department of Radiation Sciences, Umeå University, Daniel Naezéns väg, 907 37 Umeå, Sweden. 5. Department of Oncology, Örebro University Hospital, Södra Grev Rosengatan, 701 85 Örebro, Sweden. 6. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Blå stråket 2, 413 45 Gothenburg, Sweden; Regional Cancer Center in Western Sweden, Medicinaregatan 18G, 413 90 Göteborg, Gothenburg, Sweden. 7. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Blå stråket 2, 413 45 Gothenburg, Sweden.
Abstract
OBJECTIVES:Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. MATERIALS AND METHODS:NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. RESULTS: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. CONCLUSION: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
RCT Entities:
OBJECTIVES: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. MATERIALS AND METHODS:NSCLCpatients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. RESULTS: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. CONCLUSION: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).
Authors: Katherina P Farr; Katrina West; Roland Yeghiaian-Alvandi; David Farlow; Rachel Stensmyr; Andrew Chicco; Eric Hau Journal: Phys Imaging Radiat Oncol Date: 2019-09-20
Authors: Kate Haslett; Neil Bayman; Kevin Franks; Nicki Groom; Susan V Harden; Catherine Harris; Gerard Hanna; Stephen Harrow; Matthew Hatton; Paula McCloskey; Fiona McDonald; W David Ryder; Corinne Faivre-Finn Journal: Int J Radiat Oncol Biol Phys Date: 2020-11-21 Impact factor: 7.038