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V. Kavadi
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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
- Moderators:G. Pratt, S.K. Vinod
- Coordinates: 10/29/2013, 10:30 - 12:00, Parkside Ballroom A, Level 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 - 10:40 | Author(s): V. Kavadi
- Abstract
- Presentation
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.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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PL03 - Presidential Symposium Including Top Rated Abstracts (ID 85)
- Event: WCLC 2013
- Type: Plenary Session
- Track:
- Presentations: 1
- Moderators:M. Boyer, K. Fong
- Coordinates: 10/29/2013, 08:15 - 09:45, Plenary Hall, Ground Level
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PL03.05 - An intergroup randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) chemoradiotherapy (CRT) +/- cetuximab (cetux) for stage III non-small cell lung cancer (NSCLC): Results on cetux from RTOG 0617 (ID 1424)
08:59 - 09:11 | Author(s): V. Kavadi
- Abstract
Background
The two primary objectives of RTOG 0617 were to compare the overall survival(OS) differences of 1) standard-dose(SD)(60Gy) versus high-dose(HD)(74Gy) radiotherapy (RT) with concurrent chemotherapy(CT); and 2) the addition of cetux to standard CRT. Cetux is a monoclonal Ab targeting EGFR with activity when combined with CT in metastatic NSCLC and head and neck cancer (HNC), and with RT in locally advanced HNC.Methods
This Phase III Intergroup trial randomized pts in a 2 x 2 factorial design. Concurrent CRT included weekly paclitaxel(45 mg/m2) & carboplatin(AUC=2). Pts randomized to cetux received a 400 mg/m2 loading dose on Day 1 followed by weekly doses of 250 mg/m2. All pts were to receive 2 cycles of consolidation CT. This is the initial report of survival outcome based on cetux. The trial was designed for 450 evaluable patients with 80% power and a 1-sided alpha of 0.0125 to detect a 29% reduction in OS failure for each comparison (RT and cetux).Results
544 pts were accrued, and 419 and 465 are eligible for RT and cetux analyses. Median follow up is 18.7 months. Cetux delivery was acceptable in both the concurrent and consolidation phases. Therapy related ≥Grade 3 non-hematologic toxicity was higher in the cetux group; 70.5% vs 50.7% (p<.0001). Grade 4 and 5 events were 35.8% and 28.2%, respectively. Median survival was 23.1 vs 23.5 months, & 18-month OS rates were 60.8% vs 60.2% on the cetux vs non-cetux arms, respectively (p=0.484, HR=0.99), which crossed a protocol-specified futility boundary for early reporting. As previously reported, median survival times and 18-month OS rates for SD and HD arms were 28.7 vs 19.5 months, and 66.9% vs 53.9% respectively (p=0.0007, HR=1.56). There was no significant interaction between RT dose and the use of cetux. The OS rates for the 4 arms of this trial are shown in Table. An H-score analysis, a measure EFGR positivity, is forthcoming.Table: Overall Survival Rates with 95% CI (pts accrued while all 4 arms were open)
Time 60 Gy 74 Gy 60 Gy + Cetux 74 Gy + Cetux 12m 78.4% (68.9, 85.4) 62.6% (51.7, 71.6) 80.0% (70.8, 86.6) 74.7% (64.9, 82.2) 18m 67.9% (57.6, 76.2) 52.3% (41.5, 62.0) 67.1% (56.8, 75.5) 58.0% (47.6, 67.1) Conclusion
In pts receiving CRT for Stage III NSCLC, 74 Gy is not superior to and may be worse than 60 Gy in terms of OS. Cetux provides no survival benefit in the setting of CRT for Stage III NSCLC.
