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Keith Cengel
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MA05 - Update on Clinical Trials and Treatments (ID 123)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:Seiki Hasegawa, Enrico Ruffini, Angel Artal
- Coordinates: 9/08/2019, 13:30 - 15:00, Melbourne (1991)
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MA05.10 - Pembrolizumab in the Treatment of Patients with Malignant Pleural Mesothelioma Following Progression After Initial Chemotherapy (Now Available) (ID 2788)
13:30 - 15:00 | Presenting Author(s): Keith Cengel
- Abstract
- Presentation
Background
Checkpoint inhibitor (CPI) therapies have demonstrated clinical benefit in patients (pts) with malignant pleural mesothelioma (MPM) and are now included in the NCCN guidelines as an acceptable treatment option. Herein, we report our initial experience treating pts with MPM in the palliative second line or greater setting.
Method
Between January 2016 and November 2018, 74 pts with biopsy proven MPM were treated with pembrolizumab every three weeks until confirmed disease progression or unacceptable toxicity. Progression-free survival (PFS) and OS were defined as the time from first pembrolizumab dose to recurrence and death, respectively, or to last contact. Response rates (RR) were measured by a dedicated thoracic radiologist using modified RECIST 1.1 criteria. Adverse events were routinely recorded/scored at each follow up visit. according to CTCAE 4.0 with level of attribution to pembrolizumab.
Result
Demographics of the 74 pt cohort are shown in table 1. Twently-nine (39%) of pts experienceda total of 39 grade 1-2 adverse events, possibly or definitely related to therapy (Table 2). There was one grade 4pneumonitis that resulted in new requirement for oxygen, which resolved with steroids; and one patient experienced leukoencephalopathy that resulted in death. The overall response rate (including only partial responses by modified RECIST 1.1) for the entire cohort was 26%. Median progression free survival and overall survival for the entire cohort were 2.8 months and 7.9 months, respectively.
Table 2: Adverse Events
CTCAE 4.0 Grade
AE Description
1-2
3-4
5
hypothroid
5
arthralgias
8
colitis
3
diarrhea
2
lip lesion
1
pneumonitis
2
1
SICCA syndrome
1
thrombocytopenia
1
dermatitis
1
hypopigmentation
1
nephritis
1
fatigue
1
abdominal pain
1
uveitis
1
transaminitis
1
elvated alk phos
1
leukoencephalopathy
1
pruritis
3
hypercalcemia
3
rash
2
Table 1: Demographics
Age in Years
median (range)
Min
73
(52-92)
Gender
Patients (N=74)
Female
29
39%
Male
55
74%
Histology
Epithelial
58
78%
Sarcomatoid
6
8%
Biphasic
10
14%
# of chemotherapy courses
0
3
4%
1
42
57%
2
22
30%
3-4
7
9%
# of radiotherapy courses
0
42
57%
1
30
41%
2-3
6
8%
Surgical Resection
Have EPD
24
32%
Did not have EPD
50
68%
PDL1
Negative
21
28%
Positive
12
16%
Not Determined
42
57%
Conclusion
Pembrolizumab in the Tx of MPM was reasonably well tolerated in this large, single institution experience. RR, PFS and OS appear remarkably similar to recent published data from a registry study of off-label use of pembrolizumab in pts with MPM in Switzerland and Australia (include reference). Ongoing studies include analysis of PDL-1 and other potential immunotherapy response biomarkers.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-65 - Temporal Changes of Radiation-Induced Lung Injury Following Proton Therapy for Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 1715)
10:15 - 18:15 | Author(s): Keith Cengel
- Abstract
Background
Proton therapy (PT) is increasingly being used in locally advanced non-small cell lung cancer (NSCLC), but is there currently a limited understanding of its radiation-induced lung injury pattern that can cofound radiologic interpretation. Here we characterize imaging of radiation-induced lung injury on CT (computed tomography) and FDG-PET (18F-deoxy-glucose-positon emission tomography) following PT.
Method
After institutional IRB approval, longitudinal imaging from adult NSCLC patients undergoing PT over a 5-year period at our institution were retrospectively analyzed by two thoracic radiologists. Tumor size and FDG standard uptake value max (SUVmax) were recorded. In addition, early (<12 months after PT) and late (>12 months) radiation-induced lung injuries were quantified (0-3 Likert score), including consolidation, ground glass, interlobular septal thickening, bronchiectasis and pleural effusion, on all serial imaging.
Result
19 consecutive locally advanced NSCLC patients (mean age 69.3 yrs) had PT during the study period and had serial images available for review. The mean imaging follow-up period from PT start was 30 months. Five patients developed local failure. In the remaining 14 patients, tumor size and FDG avidity steadily decreased over time (mean SUVmax = 10.8 at baseline and 2.5 at 12 months). Ground glass and interlobular septal thickening presented as early changes, increasing through months 6-12 and 9-12 respectively but generally resolved by 24 months. 68% of patients developed a pleural effusion (< 2 years), increasing in severity over the 1st 18 months.
Consolidation consistently increased in severity throughout the observation period (max >48 months) Among 11 tumors, 8 achieved maximum severity in late changes of band-like or mass-like consolidation within 24 months and then typically plateaued. Late development of a pleural effusion, mass-like fibrosis, increased tumor caliber and increased FDG avidity were associated with local tumor recurrence.
Conclusion
Radiation-induced lung injury follows a predictable temporal pattern on CT. Knowledge of expected timeline of the imaging findings may prevent unnecessary imaging and/or biopsies. We are currently analyzing a larger cohort of 100 NSCLC patients to compare post radiation changes in local recurrence and local control.
