J Maguire1, I Khan2, R McMenemin3, N O'Rourke4, S McNee4, V Kelly5, C Peedell6, M Snee7. 1. Liverpool Heart and Chest Hospital, Liverpool and Clatterbridge Cancer Centre Wirral, UK. Electronic address: drjoemag@hotmail.com. 2. CRUK & UCL Cancer Trial Centre, UK. 3. Northern Centre for Cancer Care, Freeman Hospital, Newcastle, UK. 4. Beatson West of Scotland Cancer Centre, Glasgow, UK. 5. Liverpool Heart and Chest Hospital, Liverpool and Clatterbridge Cancer Centre Wirral, UK. 6. James Cook University Hospital, Middlesbrough, UK. 7. St James' Institute of Oncology, Leeds, UK.
Abstract
BACKGROUND:Cure of lung cancer is impossible without local tumour control. This can be compromised by accelerated repopulation of tumour cells during radiotherapy and chemotherapy. A strategy to minimise accelerated repopulation might improve local control. We investigated whether concurrent chemo-radiotherapy could be given safely over four weeks. METHODS: We conducted a randomised phase II trial in which patients with inoperable Stage III Non-Small Cell Lung Cancer (NSCLC) received a radical radiation dose over four weeks rather than conventional fractionation. Treatment was given either sequentially or concurrently with three to four cycles of cisplatinum and vinorelbine. 130 patients with inoperable stageIII NSCLC and PS 0-1 were randomised to receive cisplatinum and vinorelbine with either sequential or concurrent chemo-radiation using 55Gy in 20 fractions over four weeks. The primary end-point was treatment related mortality. Secondary end-points were toxicity and survival. FINDINGS: Treatment related mortality was: 2.9% (exact 95% confidence interval [CI] 0.36-10.2%) and 1.7% (exact 95% CI 0.043-9.1%) for the Concurrent and Sequential group respectively; relative risk (RR) 1.25; (95% CI 0.55, 2.84). Toxicity was similar between arms; grade 3 or worse oesophagitis was 8.8% versus 8.5%; RR 1.02 (95% CI 0.58, 1.79). OS HR was 0.92; 95% CI (0.60-1.39; p=0.682). The 2 year overall survival rates were: 50% versus 46%; RR 1.06 (95% CI 0.77, 1.46) for Concurrent versus Sequential. INTERPRETATION: A strategy to minimise the effects of accelerated repopulation using accelerated hypofractionated radiotherapy with chemotherapy is feasible, and reasonably safe for patients with stage III NSCLC. The reported two year survival is promising and suggests that a four week regime of radiotherapy should be compared with conventionally fractionated radiotherapy in an adequately powered randomised controlled phase III trial.
RCT Entities:
BACKGROUND: Cure of lung cancer is impossible without local tumour control. This can be compromised by accelerated repopulation of tumour cells during radiotherapy and chemotherapy. A strategy to minimise accelerated repopulation might improve local control. We investigated whether concurrent chemo-radiotherapy could be given safely over four weeks. METHODS: We conducted a randomised phase II trial in which patients with inoperable Stage III Non-Small Cell Lung Cancer (NSCLC) received a radical radiation dose over four weeks rather than conventional fractionation. Treatment was given either sequentially or concurrently with three to four cycles of cisplatinum and vinorelbine. 130 patients with inoperable stage III NSCLC and PS 0-1 were randomised to receive cisplatinum and vinorelbine with either sequential or concurrent chemo-radiation using 55Gy in 20 fractions over four weeks. The primary end-point was treatment related mortality. Secondary end-points were toxicity and survival. FINDINGS: Treatment related mortality was: 2.9% (exact 95% confidence interval [CI] 0.36-10.2%) and 1.7% (exact 95% CI 0.043-9.1%) for the Concurrent and Sequential group respectively; relative risk (RR) 1.25; (95% CI 0.55, 2.84). Toxicity was similar between arms; grade 3 or worse oesophagitis was 8.8% versus 8.5%; RR 1.02 (95% CI 0.58, 1.79). OS HR was 0.92; 95% CI (0.60-1.39; p=0.682). The 2 year overall survival rates were: 50% versus 46%; RR 1.06 (95% CI 0.77, 1.46) for Concurrent versus Sequential. INTERPRETATION: A strategy to minimise the effects of accelerated repopulation using accelerated hypofractionated radiotherapy with chemotherapy is feasible, and reasonably safe for patients with stage III NSCLC. The reported two year survival is promising and suggests that a four week regime of radiotherapy should be compared with conventionally fractionated radiotherapy in an adequately powered randomised controlled phase III trial.
Authors: Catarina Veiga; Edward Chandy; Joseph Jacob; Natalie Yip; Adam Szmul; David Landau; Jamie R McClelland Journal: Radiother Oncol Date: 2020-03-30 Impact factor: 6.280
Authors: D Franceschini; F De Rose; L Cozzi; P Navarria; E Clerici; C Franzese; T Comito; A Tozzi; C Iftode; G D'Agostino; M Sorsetti Journal: Strahlenther Onkol Date: 2017-02-06 Impact factor: 3.621
Authors: Anna Merlotti; Alessio Bruni; Paolo Borghetti; Sara Ramella; Vieri Scotti; Marco Trovò; Rita Chiari; Frank Lohr; Umberto Ricardi; Emilio Bria; Giovanni L Pappagallo; Rolando M D'Angelillo; Stefano Arcangeli Journal: Radiol Med Date: 2021-05-05 Impact factor: 3.469
Authors: Noëlle van der Voort van Zyp; Masoma Hashimzadah; Erik Kouwenhoven; Carmen Liskamp; Christa Gadellaa-van Hooijdonk; Ellen Pouw; Jose Belderbos; Klaartje Maas; Paul van de Vaart; Mirjam Mast Journal: Clin Transl Radiat Oncol Date: 2022-07-07
Authors: James J Urbanic; Xiaofei Wang; Jeffrey A Bogart; Thomas E Stinchcombe; Lydia Hodgson; Steven E Schild; Lyudmila Bazhenova; Olwen Hahn; Ravi Salgia; Everett E Vokes Journal: Int J Radiat Oncol Biol Phys Date: 2018-01-31 Impact factor: 7.038