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Chunyu Wang
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MA01 - Early Stage Lung Cancer: Questions and Controversies (ID 894)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 202 BD
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MA01.10 - Toxicity and Local Control in “Ultra-Central” Lung Tumors Treated With SBRT or High-Dose Hypofractionated RT (ID 13969)
11:35 - 11:40 | Presenting Author(s): Chunyu Wang
- Abstract
- Presentation
Background
Stereotactic body radiation therapy (SBRT) for central lung tumors has been associated with higher rates of severe toxicity. Data suggests that tumors with specific high-risk features, namely GTV abutting proximal bronchial tree (PBT), trachea or PTV intersecting esophagus (“ultra-central” tumors), are at risk of severe complications. We sought to evaluate toxicity and efficacy for high-risk lung tumors treated with SBRT in our institution.
a9ded1e5ce5d75814730bb4caaf49419 Method
All patients treated with SBRT for central lung tumors during 2008 to 2017 were reviewed to identify ultra-central tumors. Patients who received more than 4 Gy per fraction and BED10≥84 were included in the analysis. The primary endpoint was grade 3+ adverse events potentially attributable to RT, based on CTCAE 4.0. Secondary endpoints were local control (LC) and overall survival (OS) for primary lung cancer patients, Kaplan-Meier analysis was used to estimate LC and OS.
4c3880bb027f159e801041b1021e88e8 Result
We identified 88 patients who met the inclusion criteria (76 with abutment of PBT, 8 with abutment of trachea, 22 with overlap of esophagus, and 17 with multiple structures at risk). The median follow-up was 21.5 (95%CI, 12.5 to 30.5) months. Forty-six patients had primary NSCLC, 7 had locally recurrent NSCLC and 35 had lung metastases. The prescription doses were 400cGy x 15 (n=21), 750cGy x 8 (n=13), 1000cGy x 5 (n=29) and 900cGy x 5 (n=25). Eight patients (9.1%), all abutting the PBT, experienced fatal complications potentially related to RT. Four patients developed fatal pulmonary hemorrhage. Maximum point doses to PBT were 54.9Gy, 51.4Gy, 49.4Gy (in 5 fractions) and 63.8Gy (8 fractions) and 2 of them had received bevacizumab in close proximity to RT. Four patients developed fatal pneumonia/radiation pneumonitis (all had pre-existing COPD). No Grade 4 toxicity was identified. Grade 3 overall toxicity rate was 12.5%. Only 3 of 22 (13.6%) patients whose PTV overlapped with esophagus had Grade 3 toxicity. The 1-year and 2-year LC for the whole cohort were 87.5% and 79.1%, respectively. The 1, 2-year OS for primary NSCLC patients were 77.8% and 62.6%, respectively.
8eea62084ca7e541d918e823422bd82e Conclusion
To our knowledge, this is the largest reported series of patients who received SBRT for ultra-central tumors. RT achieves high rates of local control in these patients, but the rate of severe or fatal toxicity is substantial. Further studies are needed to establish the relationship between SBRT and toxicity in these patients.
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MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Oligometastatic NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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MA25.07 - Effectiveness of Systemic Therapy Combined with Thoracic Radiotherapy for Patients with Oligometastatic NSCLC: A Pooled Analysis (ID 12572)
14:10 - 14:15 | Presenting Author(s): Chunyu Wang
- Abstract
- Presentation
Background
Local therapy combined with systemic therapy for oligometastases or oligo-recurrence (≤ 5 lesions) in NSCLC has become one of the hottest spots in recent years. At present , there is lack of results from randomised phase III trial in this regard. Therefore, we performed a pooled analysis, aiming to evaluate the effectiveness of the combination of systemic therapy and local thoracic radiotherapy for patients with oligometastatic NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Method
Computerized search of the Pubmed database was performed using the following key words: non-small cell lung cancer, metastasis, stage IV, thoracic radiation. Abstracts were ruled out. In addition, we also reviewed the references listed in the identified articles and included eligible studies for integrity of the literature search. Combination therapeutic modality should include systemic therapy (chemotherapy or targeted therapy) and thoracic radiotherapy. Authors with more than 1 publication involving the same study population were included only once, and the one with most relevant and complete data were included. Literature retrieval was terminated by April 2018. All the analysis was performed in the Stata/SE 12.0.
4c3880bb027f159e801041b1021e88e8 Result
A total of 32 articles with full text were retrieved in our initial literature search. After reviewing these articles and corresponding references, 16 studies (9 retrospective studies vs. 7 prospective phase II studies) with a total of 791 oligometastatic NSCLC patients were finally identified as eligible for this analysis. The median progression free survival (PFS) ranged from 6.6 to 16.0 months and median overall survival OS ranged from 10.0 to 27.1 months. Four studies involving 256 patients reported the post-radiotherapy response, resulting in a pooled objective response (CR + PR) rate of 58% (95% CI: 0.41, 0.76). A total of 3 studies involving 168 patients provided comparison data on PFS between systemic therapy alone and systemic therapy plus thoracic radiotherapy, leading to a pooled hazard ratio (HR) of 0.42 (95% CI: 0.28, 0.64) for the combined modality group.
8eea62084ca7e541d918e823422bd82e Conclusion
Consolidative thoracic radiotherapy in addition to systemic therapy may offer significant outcome benefits for oligometastatic NSCLC, leading to a numerically comparable response and survival to locally advanced NSCLC. Results from phase III randomized controlled trials are awaited.
6f8b794f3246b0c1e1780bb4d4d5dc53Only 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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P1.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 949)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.17-08 - Genetic Predictors of Response to Chemoradiation in Stage III Non-Small-Cell Lung Cancer (ID 12804)
16:45 - 18:00 | Author(s): Chunyu Wang
- Abstract
Background
Radiation with platinum-based doublet chemotherapy is the standard of care for patients with unresectable stage III non-small-cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic alterations are associated with response to therapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation, who had undergone tumor molecular profiling through an institutional next-generation sequencing platform. This platform is an FDA-approved, targeted-DNA-sequencing panel that contains 341 (now expanded to 468) somatic mutations and other genetic alterations. Basic patient and tumor characteristics, clinical outcomes including loco-regional recurrence, distant recurrence, and overall survival, were collected. Overall and recurrence-free survivals were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to investigate association between clinical outcome and genetic alterations.
4c3880bb027f159e801041b1021e88e8 Result
We identified 110 patients with stage III NSCLC who were treated with definitive radiation between 2013 and 2017 and underwent tumor molecular profiling. Fifty-one patients (46%) had stage IIIA disease and 59 patients (54%) had stage IIIB disease. Median radiation dose delivered was 60Gy in 30 fractions (range 48.6Gy to 74Gy). Either concurrent or sequential chemotherapy was given in 104 patients (95%) with 83 patients (75%) receiving concurrently. One patient received induction crizotinib and one patient died before start of chemotherapy. With a median follow-up time of 15.3 months, the median overall survival was 31.2 months. Several genetic mutations were significantly associated with worse overall survival after therapy, including AKT2 any mutation (Hazard ratio 13.71, p<0.001), KMT2C truncating mutations (HR 13.42, p<0.001), KMT2D truncating mutations (HR 6.97, p<0.001), ARID1A frameshift mutations (HR 8.54, p<0.001), and FLT1 any mutation (HR 6.62, p<0.001). These genes were also associated with increased loco-regional recurrence. Mutation in the PIK3C2G gene was significantly associated with improved overall survival. Association of other common genetic alterations such as EGFR mutation with response to therapy was not observed.
8eea62084ca7e541d918e823422bd82e Conclusion
This study coupled multiplex targeted sequencing with clinical outcome information to identify several potential genetic predictors of response to chemotherapy and radiation in locally advanced NSCLC. KMT2C and KMT2D encode two subunits of a histone methyltransferase, and mutations of KMD2 have been shown to correlate with worse survival in locally advanced and advanced NSCLC patients. Further studies including in vitro validations are necessary to confirm the findings.
6f8b794f3246b0c1e1780bb4d4d5dc53
