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T.K. Waddell
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ORAL 21 - Biology - Moving Beyond the Oncogene to Oncogene-Modifying Genes (ID 118)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:A. Katz, M.S. Tsao
- Coordinates: 9/08/2015, 10:45 - 12:15, Mile High Ballroom 4a-4f
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ORAL21.05 - p53/KRAS Mutation Status Does Not Predict Sensitivity to Chemotherapy in NSCLC PDXs (ID 2459)
10:45 - 12:15 | Author(s): T.K. Waddell
- Abstract
- Presentation
Background:
The LACE-Bio group assessed the prognostic and predictive values of KRAS and p53 mutations in 1543 completely resected non-small cell lung cancer (NSCLC) tumors. The predictive value of combined KRAS/p53 mutations for survival benefit from adjuvant chemotherapy was evaluated on 49 patients and chemotherapy was deleterious in this group compared to observation (HR 2.49 CI 95% [1.10 – 5.66], p=0.03). Patients with tumors harboring combined KRAS/p53 mutations had a worse outcome when treated with adjuvant chemotherapy compared patient with double wild type (WT) tumors (HR 3.03 (95% CI [1.29 – 7.15], p=0.01, interaction p=0.06). We have compared the chemo-sensitivity of patient derived xenografts (PDXs) with double p53/KRAS mutations, single p53, single KRAS mutation or double WT. 0
Methods:
Surgically resected early stage lung adenocarcinomas (ADC) were implanted into non-obese diabetic severe combined immune deficient (NOD-SCID) mice. Fourteen lung ADC PDXs with various p53/KRAS status were revived and implanted: 11 engrafted and were expanded for comparison of treatment vs control. For each model, 6 replicates were included in treatment and control arms. Chemotherapy (cisplatin 3 mg/kg and vinorelbine 7 mg/kg intraperitoneally weekly) was initiated in the PDXs at tumor volumes of 150 mm[3].
Results:
Four models were p53/KRAS double mutant, 4 p53 mutant, 2 KRAS mutant and 1 double WT. The 4 double mutant PDXs responded to chemotherapy, 2 with reduced (SD) and 2 inhibited (PR) growth. Among the 4 PDXs with p53 mutation only, 2 responded (1 PR and 1 SD) and 2 were resistant. Among the 2 PDXs with KRAS mutation only, 1 had a complete response, but relapsed at treatment arrest and 1 achieved PR. The double WT PDX was highly sensitive to chemotherapy (PR) but also relapsed at treatment arrest.
Conclusion:
Among these 11 PDXs, the p53/KRAS mutation status did not predict chemo-sensitivity to cisplatin/vinorelbine, one of the most active adjuvant chemotherapy regimens in NSCLC. As these PDXs were molecularly profiled, we currently are investigating other biomarkers that might predict their sensitivity or resistance to chemotherapy.
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P2.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 210)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.02-021 - Robotic Pulmonary Resection for Lung Cancer: Analysis of the Learning Curve in a Novel Surgical Program (ID 1730)
09:30 - 17:00 | Author(s): T.K. Waddell
- Abstract
Background:
We present the first Canadian series of robotic pulmonary resection for lung cancer, examining the effects of learning curves associated with new technology on perioperative outcomes.
Methods:
Prospective databases at two institutions were queried for patients who underwent robotic pulmonary resection for lung cancer between October 2011 and February 2015. Data was collected on demographics, comorbidities, perioperative variables and complications. Results are presented as median (range). The learning curve effect was evaluated in temporal tertiles, stratified by surgeon. Differences in perioperative outcomes were evaluated using the Mantel-Cox Log-Rank test.
Results:
Of 116 patients included, 48% were males and median age was 67 (28-88). The majority (88%, 102/116) underwent a robotic lobectomy, 9% (11/116) a segmentectomy, and 3% (3/116) a wedge resection. Five patients (4%) were converted to thoracotomy. Median operative time was 281 minutes (134-650) and length of stay was 4 days (1-19). Total operative time decreased significantly (p<0.01) over the learning curve; tertile 1 (326 min (290-362)), tertile 2 (275 min (261-289)) and tertile 3 (235 min (210-260)). Median time spent on the robotic console also decreased significantly (p<0.01) over tertiles- 195 (144-246), 148 (136-160), and 116 (100-132) minutes, respectively. Across tertiles, there were no differences in the median number of lymph node stations harvested (6, 5, 6; p=0.33), length of stay (4, 4, 4; p=0.25, or the rate of major complications (Clavien-Dindo Class >= III; 5, 1, 4, respectively; p=0.26). There were no mortalities.
Conclusion:
The early Canadian experience with robotic lung cancer resection demonstrates excellent results that are comparable to those of experienced centers in operative times, length of stay and conversion rates. Further improvement was demonstrated by the learning curve effect. A prospective study to examine the outcomes and cost of robotic pulmonary resection compared to video-assisted thoracoscopic surgery should be done in the context of the Canadian healthcare system.
