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A.A. Konski



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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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      O14.01 - Memory preservation with conformal avoidance of the hippocampus during whole-brain radiotherapy for patients with brain metastases: Preliminary results of RTOG 0933 (ID 2262)

      10:30 - 12:00  |  Author(s): A.A. Konski

      • Abstract
      • Presentation
      • Slides

      Background
      Preclinical and clinical evidence suggests that hippocampal dose during whole-brain radiotherapy (WBRT) plays a role in cognitive decline. This may be preventable by conformally avoiding the hippocampus during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with cognitive function assessments and pre-specified comparison to a historical control of WBRT without hippocampal avoidance.

      Methods
      Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function assessments were performed at baseline, 2, 4, and 6 months. The primary endpoint was change in the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-DR) at 4 months. The historical control consisted of brain metastases patients treated with WBRT on the PCI-P-120-9801 phase III trial, which demonstrated a 30% mean relative loss in HVLT-DR from baseline to 4 months. To detect a minimum relative 50% improvement in this end-point, leading to an absolute 15% or less mean relative loss in HVLT-DR following HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with a one-sided alpha=0.05.

      Results
      113 patients were accrued from April 2011-November 2012; 56 out of 100 eligible patients had non-small cell lung cancer (NSCLC). One grade 3 toxicity of cerebral edema and no grade 4 or higher toxicities were reported. Median survival was 6.9 months (95% confidence interval (95% CI) 4.8-15.2 months). 41 patients were analyzable at 4 months. Mean relative change in HVLT-DR from baseline to 4 months was +3.3% (95%CI: -8.0% to +14.6%), which was significant in comparison to the historical control (p<0.0001) and substantially exceeded the hypothesized -15% value. 28 patients were analyzable at 6 months with a mean relative change in HVLT-DR from baseline to 6 months of +4.6% (95%CI: -8.6% to +17.8%), a finding in dramatic contrast to expected continued deterioration in HVLT-DR scores from other WBRT trials. In terms of patients with NSCLC, 21 patients were analyzable at 4 months, with a mean relative change in HVLT-DR from baseline to 4 months of +10.0% (95%CI: -9.5% to +27.1%). At 6 months, 14 patients with NSCLC were analyzable, with a mean relative change in HVLT-DR from baseline to 6 months of 0.0% (95%CI: -18.5% to +18.5%).

      Conclusion
      Conformal avoidance of the hippocampus during WBRT is associated with memory preservation at 4 and 6 months follow-up in NSCLC patients, who comprised the majority of accrued and analyzable patients on this trial. These promising phase II results warrant further validation in a phase III trial, currently under development in the RTOG.

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    P1.08 - Poster Session 1 - Radiotherapy (ID 195)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P1.08-011 - Dosimetric Predictors of Esophageal Toxicity in Patients with Non-small Cell Lung Cancer Receiving Chemotherapy and Radiotherapy (ID 1507)

      09:30 - 16:30  |  Author(s): A.A. Konski

      • Abstract

      Background
      Esophageal toxicity can be a dose-limiting event in patients with non-small cell lung cancer receiving chemotherapy and radiotherapy necessitating treatment breaks with potential to cause adverse treatment related factors. The objective of this study was to investigate those factors, both clinical and dosimetric, which predict for esophageal toxicity.

      Methods
      Patients (pts) with non-small cell lung cancer prospectively enrolled into an IRB approved database were retrospectively reviewed. Pts with biopsy-proven non-small cell lung cancer treated with radiotherapy alone, sequential or concurrent chemoradiotherapy had maximal esophageal toxicity scored per CTCAE 4.0 criteria. V5, V10, V20, V30, V40, V50, V60, V70, esophageal hot spot, and dose per fraction were the dosimetric variables and age, sex, race, chemotherapy, and stage were the clinical variables investigated. Data were analyzed using SAS (SAS INC, Cary, NC) Version 9.2 software package. Ordinal maximum reported esophageal toxicity was evaluated using logistic regression. A multivariable regression model was fit using important univariate predictors along with a backwards elimination stepwise regression. Probability of esophageal toxicity as a function of absorbed dose in a partial volume was modeled by the method of Lyman, by converting the dose volume histograms into an equivalent fractional volume receiving the maximum dose in the DVH, using the effective volume method of Kutcher and Burman. The parameters in this model (D50, slope m and volume exponent n) were determined by maximum likelihood estimation.

      Results
      A total of 100 pts were enrolled between 7/10 and 12/12 into a prospective database and eligible for analysis. Pts were excluded without a complete dose volume histogram data or were stage I disease leaving 71 eligible for analysis, 43 females and 28 males with a median age of 61 (range: 39-85). 14 pts were treated with radiotherapy alone while 23 received sequential treatment and 34 concurrent treatment. The median delivered dose was 66.6 Gy (range: 27.5-66.6) in a median of 1.8 Gy (range: 1.8-3.0) per fraction. Maximal esophageal toxicity was rated as 0: 12pts, 1: 21 pts, 2: 33 pts, and 3: 5pts. Univariate predictors of > grade 2 esophageal toxicity included, V5-V60 and use of concurrent chemotherapy. The maximum likelihood fit of the Lyman model parameters to patients with ≥ 2 esophageal symptoms were n=0.26 m=0.32, TD50=39.1 Gy when the α/β ratio was assumed to be 10 Gy. The maximal likelihood fit of the Lyman model parameters to patients when the α/β ratio was not set were n=0.26, m=0.32 and TD50 39.3 with the α/β calculated at 7.6 Gy. Patients not having chemotherapy had a higher TD50, 46.4 Gy as compared to patients having chemotherapy, TD50=37.1 Gy, p=0.09.

      Conclusion
      We have shown the TD50 for > grade 2 esophageal toxicity is lower for patients receiving chemotherapy and radiotherapy compared to patients receiving radiotherapy alone. This is first report to show the α/β ratio for esophageal toxicity may be lower than 10. Confirmations of these data are needed in an independent data set.