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S. Harden



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    O14 - Radiotherapy - Toxicity and Clinical Trials (ID 105)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      O14.07 - IDEAL CRT: Isotoxic Dose Escalation and Acceleration in Lung Cancer ChemoRadiotherapy - a phase I/II trial of concurrent chemoradiation with dose-escalated radiotherapy in patients with stage II or stage III Non-Small Cell Lung Cancer. (ID 1368)

      11:35 - 11:45  |  Author(s): S. Harden

      • Abstract
      • Presentation
      • Slides

      Background
      The IDEAL-CRT trial uses an individual patient approach to radiotherapy (RT) dose escalation, escalating the dose within a fixed overall treatment time, 6 weeks, by increasing dose per fraction. Isotoxic RT is based on the calculated risk of RT-pneumonitis (RTPN), RT dose being escalated so that all patients are exposed to the same RTPN risk. We investigated the feasibility and safety of individualised, isotoxic dose escalation for once daily RT delivered in 30 once-daily fractions with concurrent chemotherapy.

      Methods
      Eligibility; NSCLC stage II/III, PS 0/1, FEV~1~ (≥40% predicted or ≥1L), DCLO (≥40% predicted). A radiobiological model was used to individualize RT dose-prescription – selecting a dose which, in 30# once daily for 6 weeks, is associated with a 10% risk of grade 3+ RTPN, but limiting prescribed doses to between 63Gy - 73Gy (2Gy dose equivalent α:β=10, 63.5Gy-86Gy). Dose constraints were fixed for spinal cord, heart, brachial plexus. In Arm 1, initially the maximum dose to 1cc oesophageal did not exceed 63Gy. Arm 2 comprised patients in whom oesophageal dose rather than lung dose limited the prescription dose: the oesophageal dose was raised from 65Gy to 68Gy, 71Gy and 73Gy in consecutive cohorts, the prescribed dose lying between 63Gy and 73Gy and being the highest consistent with the oesophageal limit. Dose escalation was determined using a 6+6 design. Dose limiting toxicity (DLT) was defined as Grade 3+ oesophagitis. MTD was determined if grade 3+ oesophagitis >42% (>5/12). Two cycles of Cisplatin-Vinorelbine chemotherapy given concurrently during RT. All contouring and dosimetry on planning CT scans was centrally reviewed. IMRT was introduced in November 2012. Primary endpoints: oesophagitis and RTPN. Serial pulmonary function tests and ECGs performed. Efficacy endpoints: overall survival (OS), progression free survival (PFS), and tumour response.

      Results
      Between October 2010 and February 2013, 84 patients recruited (9 UK centres), 49 patients Arm 1, 35 patients Arm 2 (13 at 65Gy, 12 at 68Gy, 10 at 71Gy; none at 73Gy as the 73Gy upper prescription dose limit was only rarely associated with an oesophageal dose higher than 71Gy). Median follow up was 11 months (range 2,24); median age 66 years (range 43-84); 74% male; 39%/60% WHO 0/1; 30% adenocarcinoma, 54% squamous. Mean GTV 121cc (range 14-602cc). Mean prescribed dose for patients completing RT (n=80) 67.6Gy (range 63-73Gy) in Arm 1 and 70.1 Gy (63-73) in Arm 2. Mean 1cc-oesophageal-dose in Arm 1 55.5Gy (range 14.2-68.0Gy). In Arm 1 grade 3+ oesophagitis was 6% (3/49). In Arm 2, Grade 3+ oesophagitis was 17% (2/12) at 68Gy; no Grade 3+ oesophagitis in 65Gy (0/12) and 71Gy (0/10) cohorts. Grade 3+ RTPN 2% (1/49) in Arm 1 and 6% (2/35) in Arm 2. 1 year OS and PFS rates were 92% and 74% respectively.

      Conclusion
      Isotoxic RT dose escalation was safe and feasible. The MTD for oesophagus was not reached. Acceleration of the IDEAL-CRT schedule to five weeks is under investigation in a second study, currently recruiting.

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    P3.13 - Poster Session 3 - SCLC (ID 202)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.13-005 - CONVERT - the challenges of opening centres and recruiting patients to an international multi-centre chemo-radiotherapy trial in limited-stage small cell lung cancer (ID 1366)

      09:30 - 09:30  |  Author(s): S. Harden

      • Abstract

      Background
      CONVERT is a multicentre, randomised, phase III trial open in Europe and Canada in limited-stage small cell lung cancer. Patients are randomised to twice (45 Gy in 30 fractions) or once-daily radiotherapy (66 Gy in 33 fractions) given concurrently with 4-6 cycles of chemotherapy. This study is funded by Cancer Research UK and involves centres from the UK NCRI, the ‘Groupe Francais de Pneumo-Cancerologie’, the Spanish Lung Cancer Group, the EORTC and NCIC CTG.

      Methods
      To identify and review the challenges in site set-up. To review time taken from site initiation to first patient randomised, number of centres opened that included 0-2 patients and number of centres that recruited the majority of all patients.

      Results
      In June 2013, 519/532 patients had been recruited in 9 countries; 299 from 32 UK centres, 100 from 17 French centres, 39 from 9 Canadian centres, 27 from 6 Spanish centres, 26 from 3 Belgian centres, 13 patients from 1 centre in Slovenia, 9 from 2 centres in The Netherlands and 6 patients from 1 centre in Poland. Figure 1 shows the number of centres open and patients recruited. 96 sites are currently open to recruitment (5 sites opened in 2008, 34 in 2009, 31 in 2010, 17 in 2011, 8 in 2012 & 3 in 2013, 2 sites subsequently closed early) of which 74 (77%) have randomised at least 1 patient. 24 sites (25%) recruited only 1 or 2 patients. 10 sites have recruited 49% of the total number of patients with a single site recruiting 18.5% of all patients randomised. Time taken from site initiation to 1[st] patient randomised ranged from 0–1029 days with a median of 144 days. Time taken to complete the QA exercise from initial information sent to site ranged from 14-1181 days with a median of 290.5 days. Figure 1

      Conclusion
      Recruitment to an academic trial in LS-SCLC is a challenge but accrual has improved considerably since 2008. This can be directly related to the increasing number of sites opened to recruitment. Duration of site set-up and completion of the QA exercise are factors explaining slower than anticipated accrual rates particularly between 2008 and 2010. We anticipate that the study will close to recruitment in July 2013. International participation has been a key factor to the success of the trial and the experience gained will be of value to the design of future radiotherapy studies to ensure target accrual.