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P2.01 - Poster Session with Presenters Present (ID 461)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
P2.01-088 - Prenylation Inhibitors in Lung Adenocarcinoma: Comparison of Zoledronic Acid and a Novel Lipophilic Bisphosphonate (ID 5640)
14:30 - 15:45 | Author(s): C. Aigner
The prenylation inhibitor zoledronic acid is a standard-of-care therapeutic option in bone metastasis. Recent studies suggest that prenylation inhibition using novel lipophilic bisphosphonates might be active against various malignancies outside the bone metastatic setting. Since prenylation is an important posttranslational modification in RAS protein function we explored the sensitivity of a panel of lung adenocarcinoma cells representing various oncogenic driver mutations.
8 human lung adenocarcinoma cell lines were investigated in vitro to assess the short-term viability and long-term clonogenic potential following zoledronic acid and BPH-1222 treatments. The eight lung cancer cell lines represented wild type (HCC78, CALU3), EGFR- (H1650, H1975) KRAS- (A549, H358), BRAF- (CRL5885) and BRAF + NRAS double mutant (CRL5922) molecular subtypes. Effect on short and long term proliferation were measured with a SRB based photometric assay.
Neither short-term nor long-term treatment showed significant differences between the proliferation inhibitory effect of the hydrophilic zoledronic acid and novel lipophilic bisphosphonate BPH-1222. Interestingly, we found that the two KRAS mutant lung adenocarcinoma cell lines were more sensitive in the long-term bisphosphonate treatment assays than non-KRAS mutant cell lines. BRAF or EGFR mutations did not show a differential response against these inhibitors.
In vitro proliferation inhibitory efficacies of hydrophilic and lipophilic bisphosphonates were not different in lung adenocarcinoma cells. Nevertheless, due to the different bone accumulation properties of zoledronic acid and lipophilic bisphosphonates further in vivo preclinical studies are warranted to evaluate the inhibitory effect in a more physiological setting.
SC20 - Small is Beautiful: Impact of Surgical Approach (ID 344)
- Event: WCLC 2016
- Type: Science Session
- Track: Surgery
- Presentations: 1
SC20.01 - Muscle-Sparing Thoracotomy: Can It Still Be Considered a Standard? (ID 6681)
16:00 - 17:30 | Author(s): C. Aigner
Muscle sparing thoracotomy has been a standard approach in thoracic surgery for a long time. Minimal invasive approaches have gained a widespread acceptance recently and were included in the treatment guidelines for early stage NSCLC by several societies. Prospective randomized trials comparing minimal invasive approaches versus muscle sparing thoracotomy in stage I NSCLC have already been performed more than twenty years ago and demonstrated equal morbidity and mortality. Nevertheless it took until 2013 that the American College of Chest Physician guidelines recommended a VATS approach for clinical stage I NSCLC over a thoracotomy in experienced centers (1). No recommendation is made for more advanced stages. When analyzing national registry data still a high percentage of procedures in performed in an open way. This means that in current practice thoracotomy is still used as a standard approach by many surgeons. Minimal invasive approaches – both videothoracoscopic and robotic – are not different operations but different approaches towards performing an operation. It has been proven in several studies that in early stage lung cancer minimal invasive approaches in its various form lead at least to equivalent or even better oncologic outcome compared to an open approach. Nevertheless in more advanced stages this proof is lacking. Experienced centers reported individual series of minimal invasive approaches towards advanced procedures such as sleeve resection, pneumonectomy, chest wall resection and Pancoast tumor resection. While this is technically feasible no data on long-term outcome of larger patient cohorts are available and an open approach is considered standard in these cases. Thus for tumors with invasion of hilar structures or sleeve resection a muscle sparing thoracotomy currently remains a standard approach. Perceived advantages of minimal invasive approaches – VATS as well as RATS – include less pain, fewer complications, shorter length of stay, faster return to normal activity and higher rate of adjuvant chemotherapy compliance. There are a few single center studies challenging these assumptions (2,3) as well as a recent analysis of Danish national data (4), however the majority of studies are in favor of minimal invasive approaches. In summary muscle sparing thoracotomy remains a standard approach for advanced stage tumors, whereas early stage lung cancer should be treated minimally invasive in experienced centers. References 1) Detterbeck FC1, Lewis SZ, Diekemper R, Addrizzo-Harris D, Alberts WM. Executive Summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013 May;143(5 Suppl):7S-37S. 2) Rizk NP, Ghanie A, Hsu M, Bains MS, Downey RJ, Sarkaria IS, Finley DJ, Adusumilli PS, Huang J, Sima CS, Burkhalter JE, Park BJ, Rusch VW. A prospective trial comparing pain and quality of life measures after anatomic lung resection using thoracoscopy or thoracotomy. Ann Thorac Surg. 2014 Oct;98(4):1160-6. 3) Kuritzky AM, Aswad BI, Jones RN, Ng T. Lobectomy by Video-Assisted Thoracic Surgery vs Muscle-Sparing Thoracotomy for Stage I Lung Cancer: A Critical Evaluation of Short- and Long-Term Outcomes. J Am Coll Surg. 2015 Jun;220(6):1044-53 4) Licht PB, Schytte T, Jakobsen E. Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy. Ann Thorac Surg. 2014 Aug;98(2):411-5
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