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K. Stephans
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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MA 09.04 - Increasingly Abnormal Pre-Treatment Diffusion Capacity Is Associated with Greater Local Failure After Lung SBRT (ID 7391)
11:25 - 11:30 | Author(s): K. Stephans
- Abstract
- Presentation
Background:
We hypothesized that impaired pulmonary functions tests might predict for altered lung density which would interfere with the efficacy of radiotherapy. We therefore sought to determine if there are associations between pre-treatment [preTx] forced expiratory volume in 1 second (FEV1, in L and as % predicted [%p]) and diffusion capacity (DLCO, as %p) with local failure (LF) rates seen with lung stereotactic body radiotherapy (SBRT) for medically inoperable lung cancer.
Method:
From an IRB-approved institutional prospective SBRT registry of 1330 patients, we identified 557 treated definitively for medically inoperable early stage T1-T3N0M0 non-small cell lung cancer (NSCLC) between 2003 and 2016 for whom both preTx FEV1 and DLCO were available. Lung SBRT dose/fractionation for a given pt was at the discretion of the treating physician. LF was defined as progressive and increasing CT scan abnormalities confirmed by progressive and incremental increases in lesion SUVs on serial PET imaging, with or without biopsy. Predictors of LF were determined using competing risks regression and rates of local control were determined from cumulative incidence analysis.
Result:
Pt characteristics included: female gender (52.6%); median age 74 years (range 42-95); median KPS 80 (range 50-100); median preTx FEV1 and DLCO: 1.39L (range 0.26-3.87), 60 %p (range 13-151) and 52 %p (range 10-143), respectively. Tumor characteristics included: median diameter 2.2 cm (range 0.7-7.2); median PET SUVmax 7.7 (range 0.8-56); % as T stage 1a, 1b, 2a, 2b, 3: 40.2; 35.5; 18.9; 4.5; 0.9, respectively; “central” location (per RTOG 0813) 22.6%. Median follow up was 18.3 months. At analysis, 46.9% pts were alive. Treatment characteristics included 50 Gy/5 fractions (fx) for 235 pts (42.2%), 60 Gy/3 fx for 167 pts (30%), and other schedules for 155 pts (27.8%), with the latter excluded from analysis due to variability in schedules, leaving 402 pts (72.2%). Only dose was significantly associated with LF on multivariable analysis [p=0.0057; HR =3.416, 95% CI 1.429-8.166]. Three-year cumulative incidence of LF post-SBRT for 50 Gy/5fx and 60 Gy/3 fx was 15.2% and 2.3% [p=0.024], respectively. In subset analysis of the 50 Gy/5 fx, DLCO was significant for LF both as a continuous variable and as a categorical variable. The significant cut-off for DLCO was 45%p, such that 3-year LF at <45 was 24.7% (95% CI 13.6-35.8) and at > 45 was 10.6% (95% CI 5.3-16.0), [p=0.0234; HR =0.441, %95 CI 0.217-0.895[CR1] ]. There were no significant associations between LF and pulmonary functions tests for 60 Gy/3 fx.
Conclusion:
As preTx DLCO drops below 45 %p, our findings suggest local failure increases when lung SBRT is delivered as 50 Gy/5 fx for early stage NSCLC. This warrants validation in prospective series.
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MA 13 - New Insights of Diagnosis and Update of Treatment (ID 674)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:S. Ishikura, H. Nakayama
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 311 + 312
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MA 13.08 - Long Term Follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): a Randomized Phase II Study of 2 SBRT Schedules for Lung Cancer (ID 7390)
16:25 - 16:30 | Author(s): K. Stephans
- Abstract
- Presentation
Background:
NRG Oncology RTOG 0915/NCCTG N0927 was a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction (arm 1) versus 48 Gy in 4 fractions (arm 2) designed to select the better of the 2 regimens by comparing them at 1 year (yr): first by rates of pre-specified protocol-specified adverse events (psAEs), then by primary tumor control for each arm. 34 Gy emerged as the least toxic yet equally efficacious regimen. Herein, we update those results with long-term follow-up.
Method:
This phase II North American multicenter study of patients aged 18 yrs or older with medically inoperable non-small cell lung cancer with biopsy-proven peripheral (≥2 cm from the central bronchial tree) T1 or T2, N0 (clinically node negative by positron emission tomography), M0 tumors was designed to detect 1-yr psAEs rates >17% as primary endpoint. Primary tumor failure (PTF) (either infield or marginal failure) and local failure (either infield, marginal, or involved lobe failure) [with death without failure considered as a competing event]; overall survival (OS); disease-free survival (DFS) and progression-free survival (PFS) were secondary endpoints, but the study was not designed for statistical comparisons of these outcomes. The study opened in September 2009 and closed in March 2011. Updated data were analyzed through November 14, 2016.
Result:
Ninety four patients were accrued, with 86 eligible for analysis: 41 in arm 1 and 45 in arm 2, after 8 cases were excluded. Median follow-up time was 3.8 yrs for all patients, and 5.1 yrs for those alive at analysis. The grade 3 and higher treatment-related toxicity profile was unchanged since previous report, with specifically no new high grade chest wall or grade 5 events. Four of 48 Gy patients had subsequent grade 3 changes in spirometry since meeting the primary endpoint. Medians (in yrs) for 34 Gy and 48 Gy were: 4.1 vs. 4.0 for OS, and 2.6 vs. 2.8 for DFS, respectively. Five-yr outcomes as % (95% CI) for 34 Gy and 48 Gy were: PTF rate of 7.9 (2.0, 19.5) vs. 6.8 (1.7, 16.9); OS of 28.8 (15.4, 43.8) vs. 40.2 (24.9, 55.0); PFS of 19.1 (8.5, 33.0) vs. 31.8 (18.6, 45.9); and second primary rate of 15.5 (6.1, 28.9) vs. 13.3 (5.3, 25.1), respectively. Distant failure as the sole failure or a component of first failure was numerically higher in the 34 Gy arm (7 (46.7%)), but in the 48 Gy arm, rate of second primary development was higher (7 (43.8%)). Approximately 1/3 of patients’ causes of death was unknown, and another 1/3 was related to causes other than cancer or treatment.
Conclusion:
No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 yrs were similar by arm. Median survival times of 4 yrs for each arm suggest similar efficacy pending any larger studies appropriately powered to detect survival differences.
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MA 17 - Locally Advanced NSCLC (ID 671)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:S. Jheon, Georgios Stamatis
- Coordinates: 10/17/2017, 15:45 - 17:30, F203 + F204 (Annex Hall)
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MA 17.11 - Prediction of Response to Trimodality Therapy Using CT-Derived Radiomic Features in Stage III Non-Small Cell Lung Cancer (NSCLC) (ID 10336)
16:55 - 17:00 | Author(s): K. Stephans
- Abstract
- Presentation
Background:
There are no clinically validated biomarkers to identify patients with locally advanced NSCLC who benefit from trimodality therapy (TMT) (i.e. neoadjuvant chemoradiation (NAT) followed by surgery). In this study, we evaluate radiomic (i.e. computer extracted imaging) features of tumor phenotype as potential predictors of pathological response.
Method:
123 patients with stage III NSCLC who received TMT were selected for this study. Of these, 33 patients including those with distant metastasis at presentation and those without baseline pre-NAT CT scans were excluded. Lung tumors were retrospectively contoured on 3D SLICER software by an expert reader. A total of 1542 radiomic features (textural and shape) were extracted from intra and peritumoral region using the MATLAB® 2016a platform (Mathworks, Natick, MA). A random forest (RF) machine classifier was trained with the most predictive features identified on the training set (n=45) and then validated on an independent test set (n=45). The primary endpoint of our study was pathological response defined as the percentage of the residual viable tumor.
Result:
90 patients with NSCLC were included for analysis with a median age of 64 years (38−88), and 54.4 % men. Tumor histology was predominantly adenocarcinoma (71.1%), stage IIIA (94.4%), with positive N2 nodes (91.1%). Pathological response was achieved in 36 (40%) patients; labeled responders (R) and the rest 54 (60%) were labeled non-responders (NR). No statistically significant difference was found in clinical characteristics. We identified five radiomic features (intratumoral and peritumoral textural patterns) predictive of pathological response (Area under Receiver Operating Characteristic (ROC) Curve = 0.7806, RF classifier). Figure 1
Conclusion:
Texture features extracted from within and around the lung tumor on CT images were predictive of pathological response to NAT. Additional validation of these quantitative image-based biomarkers is warranted for accurate early identification of responders who could be potentially spared surgery.
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