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Idris Bahce
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MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:Mireia Serra-Mitjans, Thomas A. D'Amico
- Coordinates: 9/08/2019, 10:30 - 12:00, Interlaken (1988)
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MA02.02 - Toxicity of Lung SABR in Patients with Coexisting Interstitial Lung Disease (Now Available) (ID 586)
10:30 - 12:00 | Author(s): Idris Bahce
- Abstract
- Presentation
Background
Patients with lung tumors and coexisting interstitial lung disease (ILD) are at increased risk of toxicity following stereotactic ablative radiotherapy (SABR). We report on our institutional experience with SABR in such patients.
Method
Institutional patients undergoing lung SABR with coexisting ILD were identified. ILD subtypes were determined by a pulmonologist specializing in ILD. From late 2015, patients were routinely counseled about the increased treatment risks. Magnetic resonance (MR-)guided SABR was used to reduce target volumes from 2016. Overall and progression-free survival (OS, PFS) were estimated using the Kaplan-Meier method, and dosimetric predictors of radiation pneumonitis (RP) were analyzed based on total lung minus planning target volumes (PTV).
Result
Twenty-four SABR patients treated for lung cancer (n=22) or metastasis (n=2) between 2007-2018 were identified. Median patient age was 74 years, and the commonest ILD diagnosis was idiopathic pulmonary fibrosis. The commonest fractionation schemes were 60 Gy in 8 fractions (n=11), or 55 Gy in 5 fractions (n=6), and SABR was delivered on a Linac (n=17) to a motion-encompassing internal target volume, or with MR-guided SABR (n=7). At median follow-up of 36.9 months (95% CI, 15.8 to not reached), median OS and PFS were 16.6 and 13.3 months, respectively, and 12-month local control was 88.9%. Five patients (20.8%) developed grade ≥3 RP, of which 3 (12.5%) were fatal. Patients with grade ≥3 RP had a higher total lung V20Gy, and a higher ipsilateral and total mean lung dose (MLDEQD2; Fig. 1) than those without (p <.05).
Conclusion
Our findings confirm that ILD patients have a poor prognosis and are at high risk for developing severe RP following SABR. Treatment should be preceded by patient counseling by an experienced ILD team. Careful attention must be given to limiting lung doses, and MR-guided SABR is our preferred approach in such patients.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-12 - Tumor Uptake and Biodistribution of 89Zr-Labeled Pembrolizumab in Patients with Metastatic Non-Small-Cell Lung Cancer (Now Available) (ID 2429)
09:45 - 18:00 | Author(s): Idris Bahce
- Abstract
Background
Pembrolizumab, a monoclonal antibody targeting PD-1, is approved as monotherapy for the treatment of advanced NSCLC, depending on tumor PD-L1 (T-PD-L1) expression level. However, T-PD-L1 expression correlates moderately with response to pembrolizumab treatment. Therefore, there is need for biomarkers that accurately discriminate between responders and non-responders. Whole body 89Zr-pembrolizumab PET/CT allows to quantify pembrolizumab uptake in tumor lesions and to study pembrolizumab biodistribution in non-malignant tissues.
Method
Patients with advanced stage NSCLC and eligible for pembrolizumab monotherapy were enrolled. Following tracer injection (standard dose: 2mg 89Zr-pembrolizumab, 37 MBq), the first 3 patients received whole body PET/CT-scans at 1h, 72h, 120h and 168h post-injection. Subsequent 10 patients were scanned at 72h and 144h post-injection. Biodistribution and tumor uptake were assessed visually by an experienced nuclear physician. Quantitative uptake was calculated as SUVpeak for delineable lesions and correlated to T-PD-L1/PD-1 IHC and response. A tumor biopsy after the last line of prior treatment was required to assess T-PD-L1/PD-1 IHC status (22C3 assay). Response was defined as partial or complete, after 6 months, according to RECIST criteria.
Result
Thirteen patients (5 ≥50%, 4 1-49%, 4 negative by PD-L1 IHC) were enrolled (6 first line, 7 second/third line treatment). One patient experienced grade 3 myalgia after tracer injection. 89Zr-pembrolizumab biodistribution was comparable to 89Zr-nivolumab biodistribution with relatively high uptake in the spleen, likely due to binding to PD-1 receptors on lymphocytes/dendritic cells, and in the liver likely due to catabolism of the tracer. Imaging revealed tumor uptake in all patients, but not in all lesions. Visual assessment confirmed 70 lesions (including non-malignant lymph nodes) at 72h post-injection (SUVpeak range 1.7-13.0). Not all tumor lesions showed tracer uptake and uptake was heterogeneous within and between patients. In 3 patients response was observed. Pretreatment T-PD-L1≥50% was predictive for response (p=0.023). SUVpeak was higher in responding patients than in non-responding patients (median SUVpeak of all visible lesions 8.0 vs 5.5, p=0.033). In line with these results, responding lesions (n=10) had a higher SUVpeak compared to non-responding lesions (n=24, median 8.1 vs 5.5, p=0.025). Tumor tracer uptake did not correlate with PD-1 expression (low PD-1 expression SUVpeak 6.0 vs high PD-1 expression SUVpeak 7.7, p=0.3).
Conclusion
89Zr-pembrolizumab injection was safe with only one grade 3 possibly related adverse event. Tumor 89Zr-pembrolizumab uptake correlated with response to pembrolizumab treatment. Further research is needed to study the value of this biomarker as standalone biomarker or as added information to T-PD-L1 expression by immunohistochemistry.
