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Jeffrey Ward
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FP07 - Pathology (ID 109)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Pathology, Molecular Pathology and Diagnostic Biomarkers
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP07.11 - Circulating Tumor DNA (ctDNA) Clearance as a Biomarker in Patients With Locally Advanced NSCLC Following Chemoradiation (ID 1432)
00:00 - 00:00 | Author(s): Jeffrey Ward
- Abstract
- Presentation
Introduction
Circulating tumor DNA (ctDNA) testing has the potential to identify patients at high risk for recurrence following completion of concurrent chemoradiation (CRT) for locally advanced non-small cell lung cancer (LANSCLC). The objective of this analysis is to examine the feasibility of ctDNA testing on a commercially available focused gene panel to predict outcomes in patients with LANSCLC.
Methods
A total of 43 patients were prospectively enrolled between 09/2017 and 10/2019. Plasma for ctDNA testing was collected at the time of CRT initiation (D1), CRT completion (V1), quarterly follow up appointments for 12 months (FU1, 2, 3 and 4 respectively) after CRT completion, and at the time of relapse (R). ctDNA analysis was performed using InVisionFirst®-Lung, to detect the presence of SNVs, indels and CNAs in 37 cancer-related genes. ctDNA clearance was defined as the absence of D1 variants at V1. Patients without detectable D1 variants or in whom V1 samples were not collected were excluded from this analysis.
Results
Nineteen of 43 patients (44%) had detectable variants at D1. In this cohort of 19 patients, the median age at diagnosis was 65 years (range 43 - 82), with the majority of patients being smokers (16/19, 84%). The stage distribution was as follows: IIA (5%), IIIA (37%), IIIB (52%) and IIIC (5%). Nine patients (47%) had squamous cell carcinoma, 7 (37%) had adenocarcinoma, and 3 (16%) had poorly differentiated or NSCLC NOS. A median of 2 mutations per sample (range 1 - 5) were detected with a median of mean allelic frequency (AF) of 0.53 (range 0.05 - 16.28) at D1. Mutations in TP53 were the most commonly detected (17/19, 89%) at D1, followed by mutations in PIK3CA (5/19, 26%), CDKN2A (4/19, 21%), and EGFR (3/19, 16%). Two patients died from non-cancer related causes before FU1 and were excluded from further analysis (1 cleared ctDNA, another did not). All (3/3) patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have not relapsed after a median follow-up of 469 days (range 130-710). Median time to relapse in patients who cleared ctDNA was 217 days (range 53-587 days).
Conclusion
Our results demonstrate that it is feasible to employ ctDNA testing to identify LANSCLC patients who are at high risk for disease recurrence following CRT. This finding requires validation in future studies.
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FP07.13 - Clinical Characteristics and Outcomes in Patients With KRAS G12C Mutated Non-Small Cell Lung Cancer (ID 1415)
00:00 - 00:00 | Author(s): Jeffrey Ward
- Abstract
Introduction
KRAS oncogenic mutations are the most common driver alterations in non-small cell lung cancer (NSCLC). Among these, G12C mutations are the most frequently encountered and targetable with currently available investigational therapies. Understanding the clinical characteristics and outcomes in patients with G12C mutated NSCLC has the potential to inform clinical testing in resource limited settings and facilitate the study of novel combination therapies.
Methods
KRAS-mutant NSCLC patients treated at Washington University in St. Louis were retrospectively identified through review of commercial target hybrid-capture next generation sequencing (NGS) test results (plasma and tissue). Clinical and demographic information was collected from electronic medical records. Patients were categorized into two groups based on the KRAS mutation: G12C and non-G12C. Fisher’s exact test was used for comparing categorical variables and log-rank test was used to test for differences in survival, between these categories.
Results
A total of 169 patients with KRAS mutations were identified for this study. Nearly a third of patients were G12C mutated (n=64,37.6%) (Table 1). The majority of patients in both groups were diagnosed with stage IV disease (68.7% [G12C] and 72.9% [non-G12C]). PD-L1 (22C3 antibody) status was available in 43.7% of patients and PD-L1 status did not significantly differ between both categories (p=0.772). G12C mutations were observed in patients of all races and predominantly in smokers (96.9%). Apart from adenocarcinomas (92.2%), G12C mutations were also observed in large cell carcinomas (n=5), poorly differentiated carcinomas (n=3), NSCLC-NOS (n=1) and combined adenocarcinoma-small cell lung cancer (n=1). Pattern of metastasis at presentation did not differ between G12C and non-G12C patients. Overall, 28 KRAS mutated patients received immunotherapy as single agent or in combination with chemotherapy in the first-line setting (n=10 [G12C] and n=18 [non-G12C]). While no statistically significant difference in PFS and OS were found between these categories (median PFS 6.24 [G12C] vs 6.27 months [non-G12C], log rank p=0.899; median OS 21.0 [G12C] vs 21.8 months [non-G12C], log rank p=0.992), G12C mutated NSCLC was associated with a better PFS than non-G12C NSCLC (p=0.0384), when the analysis was restricted to patients achieving a durable response to immunotherapy (PFS>3.5 months, corresponding to first 4 cycles).
ConclusionTABLE 1. Patients Characteristics
Characteristic
KRAS G12C (n=64)
Non-KRAS G12C (n=105)
p-valuea
Median Age (range)
64.5 (47-89)
63.0 (46-89)
Gender, n (%)
0.626
Male
22 (34.4)
40 (38.1)
Female
42 (65.6)
65 (61.9)
Race, n (%)
0.156
Caucasian
54 (84.4)
82 (78.1)
African American
7 (10.9)
22 (21.0)
Asian
2 (3.1)
1 (1.0)
Hispanic
1 (1.6)
0 (0)
Smoking history, n (%)
0.08
Ever
62 (96.9)
94 (89.5)
Never
2 (3.1)
11 (10.5)
Histology, n (%)
0.146
Adenocarcinoma
59 (92.2)
83 (77.6)
Squamous cell
0 (0)
6 (5.6)
Large cell
5 (8.0)
18 (16.8)
NSCLC-NOS
3 (4.7)
10 (9.5)
Sarcomatoid
0 (0)
3 (2.9)
Poorly differentiated carcinoma
1 (1.6)
0 (0)
Adenosquamous
0 (0)
1 (1.0)
NSCLC with NET differentiation
0 (0)
1 (1.0)
Adenocarcinoma with SCLC component
1 (1.6)
0 (0)
Carcinoma of the lung
0 (0)
1 (1.0)
Clinical stage*, n (%)
0.942
I
6 (9.3)
8 (7.4)
II
4 (6.4)
5 (4.8)
III
10 (15.6)
16 (14.9)
IV
44 (68.7)
78 (72.9)
PD-L1 status, n (%)
0.704
<1%
13 (20.3)
20 (19.0)
1-49%
7 (10.9)
11 (10.5)
>50%
11 (17.2)
12 (11.4)
Missing
33 (51.6)
62 (59.0)
Initial Therapy, n (%)
0.772
Surgery +/- Chemotherapy
10 (18.2)
12 (12.9)
Radiation
5 (9.1)
9 (9.7)
Concurrent chemoradiation
7 (12.7)
14 (15.1)
Chemoimmunotherapy
6 (10.9)
12 (12.9)
Platinum-doublets
14 (25.5)
27 (29.0)
Pembrolizumab
4 (7.3)
6 (6.5)
Docetaxel
1 (1.8)
0 (0)
Vinorelbine
0 (0)
1 (1.1)
Gemcitabine
0 (0)
1 (1.1)
Pemetrexed
6 (10.9)
7 (7.5)
Targeted therapy
0 (0)
3 (3.2)
Clinical Trial
2 (3.6)
1 (1.1)
aFisher’s exact test p-value; NSCLC-NOS: non-small cell lung cancer, not otherwise specified; NET: neuroendocrine tumor; SCLC: small cell lung cancer; *stage at diagnosis; PD-L1: programmed death ligand-1
Although outcomes and demographics in KRAS G12C and non-G12C mutant NSCLCs appear to be largely comparable, our analyses suggest an association between the presence of G12C mutations and durable responses to immunotherapy. These findings will require validation in larger, prospective studies.
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P09 - Health Services Research/Health Economics - Real World Outcomes (ID 121)
- Event: WCLC 2020
- Type: Posters
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P09.26 - Cause of Death in Patients with Squamous Cell Lung Cancer (SCC) Treated with Surgery (ID 2335)
00:00 - 00:00 | Author(s): Jeffrey Ward
- Abstract
Introduction
In patients with early stage squamous cell lung cancer (SCC), the standard of care treatment includes surgical resection followed by adjuvant chemotherapy (CT) in those with tumors greater than or equal to 4 cm or with lymph node involvement. Although large randomized studies report overall and relapse-free survival, there is limited data on the cause of death (COD), particularly within the first 12 months from diagnosis. The purpose of this study is to evaluate the survival and COD among patients with SCC treated with surgery.
Methods
The Surveillance, Epidemiology and End Report (SEER) was queried for patients with SCC stage I to IIIA according to AJCC 7th edition, diagnosed between 1998 and 2016, treated with surgery with or without chemotherapy. Outcomes were subdivided into alive, death from lung cancer, death from another type of cancer, death from non-cancer causes and unknown.
Results
There were 26,530 patients (pts) that met the inclusion criteria, of which 16,757 (63.2%) died during the study period. The most common COD was lung cancer (9,046 pts, 54.0%), followed by death from other non-malignant causes (5,902 pts, 35.2%), and death from other cancers (1,721 pts, 10.3%). COD was unknown in 88 pts (0.5%). A total of 4,518 patients (17.0% of total pts and 26.9% of deaths) died within one year from diagnosis. Lung cancer was the most common COD within 12 months (2,869; 63.5%) followed by non-malignant causes (1,195; 26.4%), other malignancies (306; 6.7%) and unknown causes (24; 0.5%). The most common known causes of non-malignant deaths within one year were cardiovascular disease (422; 35.3%), chronic obstructive pulmonary disease (267; 22.3%), infection (160; 13.4%) and stroke (72; 6.2%).
Conclusion
In the general population represented by the SEER database, 17% of patients with early stage SCC undergoing surgery die within 12 months from diagnosis. Despite the indication for surgery and chemotherapy based on stage at diagnosis, better selection of patients according to co-morbidities and performance status may decrease the early mortality after treatment with curative intent.
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P49 - Small Cell Lung Cancer/NET - Radiotherapy (ID 237)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P49.03 - Chemoradiation with Cisplatin-Etoposide versus Carboplatin-Etoposide in Limited-Stage Small Cell Lung Cancer (ID 3144)
00:00 - 00:00 | Author(s): Jeffrey Ward
- Abstract
Introduction
There are limited data on the comparison between etoposide plus cisplatin or carboplatin in patients with limited-stage small-cell lung cancer (SCLC). Although the guidelines and published randomized trials have included only cisplatin-based chemotherapy, the COCIS (Carboplatin- or Cisplatin-Based Treatment for SCLC) meta-analysis showed no significant differences in efficacy based on platinum drug used for either limited or extensive-stage SCLC (J Clin Oncol 2012; 30: 1692-8). We conducted a retrospective study to compare the outcomes in patients with stage III SCLC treated with thoracic radiation therapy with etoposide and either cisplatin or carboplatin.
Methods
Patients diagnosed with limited-stage SCLC at Washington University between January of 1997 and May of 2019 were retrospectively screened for this study. Those with stage III, who were treated with radiation therapy and chemotherapy, including etoposide plus either cisplatin or carboplatin, were included in this analysis. The Kaplan-Meier method and multivariate Cox Proportional Hazard models were used to estimate progression-free survival (PFS) and overall survival (OS). Fischer exact tests were used to test group differences for categorical variables.
Results
Among the 244 patients evaluated, 150 (61.4%) met the eligibility criteria. 69 patients (28.3%) were excluded due to stage I, II or unavailable, 17 (7.0%) due to lack of radiation therapy, and 8 (3.3%) due to the use of other chemotherapy regimens. Among the 150 patients, 68 were treated with cisplatin and 82 with carboplatin. The median age was 58 years in the cisplatin group and 67 years in the carboplatin group. While most patients were treated with concurrent chemoradiation, more patients received sequential radiation in the carboplatin group when compared to the cisplatin one (18.3% vs. 2.9%, P=0.004). There were no significant differences between the two groups regarding gender, race, or smoking status. At a median follow-up of 19 months, there was no statistical difference in PFS or OS between both groups. The median PFS was 13 months in the cisplatin group and 9 months in the carboplatin group (P=0.33). The median OS was 33 months in the cisplatin group and 26 months in the carboplatin group (P=0.1). On multivariate Cox regression analysis, chemotherapy type was not significantly associated with PFS or OS. However, increasing age at diagnosis and sequential radiation were both independently associated with increased mortality (HR:1.03 [1.00-1.05], P=0.02, and 1.97 [1.03-3.78], P=0.04, respectively).
Conclusion
Our findings suggest that among patients with stage III SCLC treated with chemoradiotherapy, there are no significant differences in outcomes based on the platinum drug used. Although there are no ongoing randomized studies directly comparing the platinum drugs, some allow carboplatin, and their results may further clarify its role in the management of limited-stage SCLC.
