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Abraham J. Wu
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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 | Author(s): Abraham J. Wu
- 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.
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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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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MA25.04 - Discussant - MA 25.01, MA 25.02, MA 25.03 (ID 14600)
13:45 - 14:00 | Presenting Author(s): Abraham J. Wu
- Abstract
- Presentation
Abstract not provided
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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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: 3
- 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): Abraham J. Wu
- 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.
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P1.17-13 - The Role of Post-Operative Radiation Therapy in Patients with Locally Advanced NSCLC after Nodal Down-Staging with Systemic Chemotherapy (ID 14251)
16:45 - 18:00 | Author(s): Abraham J. Wu
- Abstract
Background
Post-operative Radiation Therapy (PORT) has been shown to improve local-regional control and overall survival in patients with non-small cell lung cancer (NSCLC) undergoing surgical resection with pathologic N2 nodal involvement. It is unclear if PORT is needed in patients with clinical N2 involvement who are downstaged with neoadjuvant chemotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
The National Cancer Database was queried for patients diagnosed between 2006-2015 with clinical N2, Stage IIIA NSCLC and treated with neoadjuvant chemotherapy followed by R0 surgical resection with either a lobectomy or pneumonectomy. Patients were included if they were alive for at least 3 months following their diagnosis.
Kaplan Meier method was used for overall survival (OS) analysis.
4c3880bb027f159e801041b1021e88e8 Result
A total of 1,174 patients were evaluated. The median age was 65 years (range: 33-89). Most patients were treated with lobectomy (90%). The median radiation (RT) dose was 50.4 Gy (range: 45-54 Gy). Pathologic downstaging and OS rates with and without PORT are demonstrated in Table and Figure.
Survival Rates ypN STAGE PORT (N=303) No PORT (N=871) p-value ypN0 (N=477)
Median OS
1 yr OS
2 yr OS
5 yr OSN=63
73.1 months
100%
89.9%
62.6%N=414
67.5 months
93.6%
78.2%
52.6%0.089 ypN1 (N=182)
Median OS
1 yr OS
2 yr OS
5 yr OSN=39
71.0 months
89.7%
68.6%
58.7%N=143
43.8 months
82.4%
67.0%
38.3%0.172 ypN2 (N=512)
Median OS
1 yr OS
2 yr OS
5 yr OSN=198
46.1 months
89.9%
71.5%
39.5%N=314
39.8 months
84.8%
63.2%
35.9%0.072 All patients (N=1,174)
Median OS
1 yr OS
2 yr OS
5 yr OSN=303
55.0 months
91.7%
74.8%
46.9%N=871
50 months
88.6%
71.3%
44.3%0.211
8eea62084ca7e541d918e823422bd82e Conclusion
Our data demonstrate a trend for improved OS with PORT. Although this is a population-based study, this lack of statistical significance may be attributable to a small sample size as the OS curves indicate a consistent benefit with PORT.
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P1.17-14 - Outcomes of Hypofractionated Radiation Therapy (HFRT) with Concurrent Chemotherapy in Patients with Stage III Non Small Cell Lung Cancer (NSCLC) (ID 14250)
16:45 - 18:00 | Author(s): Abraham J. Wu
- Abstract
Background
Patients with unresectable locally advanced NSCLC are often treated with concurrent chemoradiation. HFRT regimens are becoming increasingly common due to convenience and healthcare costs. A database analysis was performed to evaluate the outcomes of HFRT with concurrent chemotherapy.
a9ded1e5ce5d75814730bb4caaf49419 Method
The National Cancer Database (NCDB) was queried for patients with stage III NSCLC who received RT (50 Gy-80 Gy) with concurrent chemotherapy without surgery from 2004-2015. Patients were defined as receiving concurrent chemotherapy if chemotherapy was started within 3 weeks of the start of radiation. Patients received conventionally fractionated RT (CFRT): 180-200 cGy/fraction (fx) or HFRT: 210-400 cGy/fx. Baseline characteristics were compared. Kaplan Meier method was used for overall survival (OS) and Cox-proportional hazards were used for uni- and multivariable analyses (UVA/MVA).
4c3880bb027f159e801041b1021e88e8 Result
A total of 54,559 patients were evaluated: 50,938 CFRT and 3,621 HFRT. Patients treated with HFRT were more likely to receive RT at an academic center (32.6% vs. 27.2%, p<0.01), more likely to have higher T-stage (cT3/T4: 56.5 vs. 49.2%, p<0.01) but lower N-stage (cN2/3: 77.6% vs. 81.4%, p<0.01). There was no difference in age (median 66 yo), sex, race, insurance, education, Charlson-Deyo Comorbidity Score (CDCS), tumor location, or grade. For the CFRT and HFRT groups, the median RT dose, Biologic Equivalent Dose (BED) and dose/fx were 64 Gy; 76.4; 185 cGy/fx and 65 Gy; 80.5; 235 cGy/fx, respectively.
The median and 2-yr rates of OS were 19.8 mos and 43.2% for CFRT vs 16 mos and 36.1% for HFRT (p<0.01).
On UVA and MVA, (data shown for MVA: HR, p-value), age (1.01, <0.01), male gender (1.2, <0.01), white race (1.09, <0.01), Medicare (1.04, <0.01), urban dwelling (0.93, <0.01), distance from treatment center (0.999, <0.01), treatment at an academic center (0.91, <0.01), CDCS (1: 1.11, <0.01, 2: 1.21, <0.01, 3: 1.29, <0.01), diagnosed 2010-2014 (0.85, <0.01), upper lobe location (0.89, <0.01), T3/T4 stage (1.15, <0.01), N2/N3 stage (1.12, <0.01), stage IIIB (1.11, <0.01), HFRT (1.26, <0.01) and BED (0.99, 0.01) were associated with OS.
8eea62084ca7e541d918e823422bd82e Conclusion
Patients who received HFRT had slightly inferior OS rates, which may be due to toxicity (not captured in the NCDB) or unaccounted confounders such as baseline performance status and aggressiveness of disease.
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