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E. Parsons



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    MINI 07 - ChemoRT and Translational Science (ID 110)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      MINI07.11 - Isotoxic Dose Escalation and Acceleration in Lung Cancer Chemoradiotherapy (ID 1522)

      17:45 - 17:50  |  Author(s): E. Parsons

      • Abstract

      Background:
      RTOG 0617 investigated standard dose radiotherapy (RT) versus higher dose in the context of concurrent chemoRT with no advantage to higher dose treatment. IDEAL CRT investigated an alternative RT dose-escalation strategy with concurrent chemoRT in locally advanced NSCLC. Dose-per-fraction-escalation was used to achieve intensification without treatment prolongation. The trial would determine the maximum tolerable dose (MTD) deliverable to esophagus, and assess toxicity and early clinical outcomes for the schedule.

      Methods:
      Patients were enrolled to 2 groups, depending on maximum esophageal dose. Tumor doses were determined by esophageal constraints in Group 1 and other normal tissue constraints in Group 2. Patients received 63-73Gy in 30 once-daily fractions / 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. Group 1 esophageal dose-escalation followed a 6+6 design, increasing maximum dose to 1cc esophagus from 65Gy, 68Gy then 71Gy in successive cohorts, defining MTD by early and late toxicity. Efficacy endpoints were overall survival (OS), progression-free survival (PFS) and tumor response.

      Results:
      8 centres recruited 84 patients, treating 13, 12 and 10 in 65Gy, 68Gy and 71Gy group 1 cohorts. Prescribed RT doses are shown in figure 1. Median follow-up 24 months. 57 patients (68%) were stage IIIa and 21 (25%) IIIb. 5 grade 3 esophagitis events observed across both groups and 3 grade 3 pneumonitis. Following 1 fatal esophageal perforation in the 71Gy cohort, 68Gy was declared as esophageal MTD. Overall Survival (OS) and Progression Free Survival (PFS) were 87.8% and 72.0% at 1 year, and 67.1% and 50.4% at 2 years, median OS 39.3 months. OS is shown in figure 2. Figure 1 Figure 2





      Conclusion:
      Acceptable toxicity rates and promising survival were achieved. The isotoxic design proved practical, allowing significant treatment intensification and definition of MTD with relatively few patients. Results from longer follow-up are required and will be presented at the meeting.