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J. Bissonnette



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    MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MO17.08 - TCP modeling in Stereotactic Body Radiotherapy for early stage non small cell lung cancer: is a dose-volume effect present? (ID 2205)

      17:00 - 17:05  |  Author(s): J. Bissonnette

      • Abstract
      • Presentation
      • Slides

      Background
      In early stage non-small cell lung cancer (NSCLC) stereotactic body radiotherapy (SBRT) has become standard of care for inoperable patients. Tumor size >3cm was reported to be a predictor of local recurrence (LR), suggesting a dose-volume effect. Recently, the dose effect relation was questioned[1]. We used a Tumor-Control-Probability (TCP) model on a large pooled multi-center cohort to test this.

      Methods
      850 patients were analyzed from our five institutes. Patients received a 4D CT-scan and plans were inversely optimized using advanced dose calculation algorithms. Treatment was delivered using online cone-beam CT guidance. Immobilization, margins, dose prescription and treatment planning was performed according to institute specific protocols. Median tumor diameter was 2.2 cm (range:0.7-8.0), median prescribed dose was 54 Gy (range:18-64) and median number of fractions were 3 (range:1-10). LRs were either biopsy proven or defined as a FDG-PET positive growing mass on CT-scan. The Web-Nahum TCP-model[2] was fitted to LR-data using maximum-likelihood estimation by optimizing its parameters: α representing the population-average radio-sensitivity, σ~α~ representing the population-variation in α and ρ the clonogen density. Input variables were the patient specific Gross Tumor Volume (estimated from the tumor diameter), for the dosimetric parameter PTV-D~min~, D~max~, D~mean~, D~1~, D~99~ were evaluated after conversion to Biological-Effective-Dose (BED) using the LQ-model with α/β=10Gy. We tested the optimized TCP model against a random model in which TCP was fixed independent of dose and volume. The optimal model was selected based on the Akaike-Information-Criterion (AIC).

      Results
      After a median follow up (FU) of 17 months (range:0-93), 43 LRs (5%) were diagnosed at 14 months FU (range:2-56), of which 25 tumors were biopsy proven and 18 recurrences diagnosed on PET-CT. The PTV-BED~mean~ based TCP model showed the best fit with parameters α=0.43Gy[-1] (CI:0.33–0.75) and σ~α~=0.17 Gy[-1] (CI:0.11–0.37). The model-fit was insensitive to ρ and set to literature values: 10[7]/cm[3]. The AIC of the optimal model was 12 units higher than the random model indicating a clear dose-volume-effect. At high PTV~mean~-BEDs, however, the volume effect is modest. Additionally, the AIC of the BED corrected model was 9.4 units higher than the BED uncorrected model. Figure 1

      Conclusion
      A dose-volume-effect relation in SBRT for early stage NSCLC for local control was derived in a large cohort of patients. This dose-effect relation requires validation in independent datasets and prospective trials. 1.van Baardwijk,Rad.Onc.,2012. 2.Web&Nahum,PMB,1993.

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    P2.08 - Poster Session 2 - Radiotherapy (ID 198)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P2.08-005 - 4D-PET/CT-based adaptive dose escalated radiotherapy (RT) in locally advanced non-small cell lung cancer (LA-NSCLC) (ID 1171)

      09:30 - 09:30  |  Author(s): J. Bissonnette

      • Abstract

      Background
      There has been recent interest in dose escalation in LA-NSCLC, with the aim to improve both loco-regional control and overall survival. Attempts to dose escalate CT-defined volumes for radiotherapy (RT) for LA-NSCLC have been limited due to organ at risk (OAR) toxicity. We investigated the potential for adaptive dose-escalation to PET-defined volumes, using 4DPET/CT scans acquired prior to and during a course of radical chemo/RT (CRT).

      Methods
      This single institution study prospectively enrolled patients with NSCLC receiving CRT to a dose ≥60Gy, delivered in daily 2Gy treatments. 4DPET/CT scans were acquired prior to (week 0) and at weeks 2 and 4 during RT. RT was delivered using the intensity modulated RT (IMRT) plan developed from the week 0 scans. Three alternative dose escalated IMRT plans were developed offline based on the week 0, 2 and 4 scans. The PET avid primary (PET-T) and nodal disease (PET-N) volumes were auto-contoured using the 50%SUV~max~ metric. PET-T and PET-N were dose escalated to as high as possible while respecting OAR constraints and ensuring coverage of the clinical plan PTV. The D95% and D~max~ of the PET-T and PET-N were calculated and compared between week 0-2-4.

      Results
      Thirty-two patients were recruited, with 27 completing all scans. Sixteen patients were stage IIIA (60%), 9 were IIIB (33%) and 2 were IIA (7%). Eight patients (30%) had been prescribed a clinical dose of 60 Gy, 17 (63%) had 66 Gy, 1 patient 70Gy and 1 patient 74Gy. 25 patients (93%) were boosted successfully above the clinical plan doses at week 0; this reduced to 23 (85%) at week 2 and 20 (74%) at week 4. For all weeks combined, the D95 for PET-T was higher than that delivered to clinical PTV by a median of 16.2 Gy (4.2-37.4Gy). The D95 for PET-N exceeded that delivered to clinical PTV by 13.4Gy (6.8-29.7Gy). The median D95% to the PET-T at week 0, 2 and 4 were 74.4 Gy, 75.3Gy and 74.1Gy respectively. The median D~max~ to PET-T at week 0, 2 and 4 were 85.9Gy, 83.8Gy and 81.2Gy. The median D95% to PET-N at week 0, 2 and 4 was 74.3Gy, 71.0Gy and 69.5Gy. The median D~max~ to PET-N at week 0, 2 and 4 were 82.7Gy, 82.5Gy and 78.9Gy.

      Conclusion
      Using 4DPET/CT derived volumes, it is feasible to dose escalate a majority of patients, either at the onset or during RT. Though the PET-T was able to be escalated to higher doses than PET-N, nodal disease can still be boosted to significant doses. More patients were able to be dose escalated at the onset of RT; however mid-RT dose escalation allows the additional potential for adaptation.