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Jeffrey M Switchenko



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    MA01 - Oligometastatic Disease (ID 114)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Now Available
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      MA01.02 - Lung Stereotactic Body Radiotherapy and Concurrent Immunotherapy: A Multi-Center Safety and Toxicity Analysis (Now Available) (ID 597)

      10:30 - 12:00  |  Author(s): Jeffrey M Switchenko

      • Abstract
      • Presentation
      • Slides

      Background

      Radical treatment of metastases with stereotactic body radiotherapy (SBRT) in patients with advanced malignancies is an emerging treatment paradigm. SBRT is increasingly used in patients receiving immune checkpoint inhibition (ICI); however, limited toxicity data for this treatment approach exists. The purpose of this study was to evaluate the safety and tolerability of lung SBRT with concurrent ICI.

      Method

      Records from a single academic institution were reviewed to identify patients treated with lung SBRT and concurrent (within 30 days) ICI; a contemporaneous cohort receiving lung SABR without ICI were included as a reference cohort. Treatment-related adverse-effects (AE) occurring within 30 days (acute) and 180 days (subacute) of SBRT were graded via CTCAE v5.0.

      Result

      110 patients were included; 47 received SBRT with concurrent ICI (49 SBRT courses, 61 lesions) between August 2015 and January 2019. 63 received SBRT without ICI (68 courses, 79 lesions). For the SBRT+ICI cohort, median age at treatment was 64 years, median follow-up was 6.7 months. 70% were lung, 15% were melanoma, 6.4% were from head and neck primaries. 90% were treated for metastatic consolidation/oligo-progression, 10% received SBRT for locally advanced/recurrent disease. 65.3% of patients received prior RT. 36.7% received prior lung RT, 40% of which were overlapping. 67% received ICI monotherapy, 16% ICI/chemotherapy, and 16% ICI/ICI combinations. 24.5% received ICI between SBRT fractions; 38.8% received ICI both before and after SBRT. Grade 3 (G3) and any grade pneumonitis rates were 8.2% and 30.6%; there were no G4-5 events. ICI was discontinued due to toxicity in 22.4% of patients. Receipt of ICI/ICI combinations increased the risk of any grade pneumonitis (62.5% vs 24.4%, p=0.04); but not G3 pneumonitis. Risk of G3 pneumonitis was higher in the SBRT+ICI vs SBRT alone cohort (8.2 vs 0%, p=0.03); but not any grade pneumonitis (30.6% vs 29.9%, SBRT+ICI vs SBRT p=0.75). Median time to onset was 3.4 months from end of SBRT in both groups. Risk of G3 and any grade pneumonitis was not predicted by ICI agent, timing of ICI administration, prior RT, prior lung RT, lesion centrality, number of target lesions, or smoking status. Overall acute G3+ AE rates were 2% (SBRT+ICI) and 0% (SBRT). Subacute G3+ AEs occurred in 26.5% (SBRT+ICI) and 2.9% (SBRT) of patients.

      Conclusion

      Concurrent ICI, especially ICI/ICI combinations, increased the risk of G3 pneumonitis with lung SBRT. However, SBRT+ICI appears safe and tolerable compared to SBRT alone. Strategies integrating SBRT and ICI warrant additional investigation.

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-03 - Inter-Fraction Variability of 18-FDG PET During Lung SBRT and the Effect of Systemic and Immunotherapy: Results of a Prospective Pilot Study (Now Available) (ID 154)

      09:45 - 18:00  |  Author(s): Jeffrey M Switchenko

      • Abstract
      • Slides

      Background

      18-FDG PET/CT has been used to inform prognosis, response to treatment, adaptive planning, and target volume delineation in NSCLC. Changes in PET characteristics, such as inter-fraction variation of 18-FDG uptake during a course of ablative radiation, and how PET metrics respond to systemic agents during SBRT, are unknown. This study prospectively characterized key metabolic parameters during lung SBRT, an important factor for biology-guided radiotherapy (BgRT).

      Method

      Patients treated with lung SBRT of 50Gy in 5 fractions for early-stage NSCLC or lung metastases were eligible. Three PET/CTs were acquired per protocol: within 2 weeks of treatment start (PET1), between fractions 1 and 2 (PET2), and fractions 4 and 5 (PET3). The primary endpoint was inter-fraction variability. FDG-PET parameters including maximum and mean standardized uptake value (SUVmax, SUVmean), metabolic tumor volume (MTV), and derived metrics were extracted and compared longitudinally; where change between PET1 and PET2 is denoted as PET1-2. PET parameters were extracted using a MIMVISTA (v6.8.3) work station. Lesions were segmented with individualized location-based window settings. The effect of co-variates on each static (PET1, PET2, PET3) and change metric (PET1-2, PET2-3, PET1-3) were determined for each PET parameter. Continuous and categorical variables were compared by non-parametric methods with Spearman and Kruskal-Wallis tests. Clinical trial NCT03493789.

      Result

      14 patients who completed treatment as prescribed, with 17 total target lesions, were included. Treatment indications were: 5 (35.7%) medically-inoperable, 2 (14.3%) medically operable, 1 (7.1%) recurrent, 2 (14.3%) metastatic consolidation, 4 (28.6%) metastatic progression. 7 (50%) received prior systemic therapy, 4 (28.6%) received immunotherapy with 2 (14.3%) given concurrently. In aggregate, SUVmax did not significantly change over the SBRT course. Average SUVmax change from PET1 to PET2 (PET1-2) was -8.2% (p=0.51), -7.0% for PET1-3 (p=0.52), and 1.3% for PET2-3 (p=0.92). SUVmean, [SUVmax/SUVmean], and normalized parameters of [SUVmax/liver SUVmean] and [SUVmean/liver SUVmean] were similarly stable over the treatment course. Multiple PET2, PET1-2, and PET2-3 parameters were significantly related to systemic therapy, immunotherapy, and timing of administration. There were no significant interactions between age, sex, number of target lesions, target location, lesions centrality, smoking status, and static and change metrics for each PET parameter.

      Table 1. Correlation between treatment variables and median SUVmax for each PET/CT study and each inter-fraction SUVmax change between PET/CTs.
      PET1 PET2 PET3 PET1-2 PET1-3 PET2-3
      Co-variates Median SUVmax p-value Median SUVmax p-value Median SUVmax p-value SUVmax change p-value SUVmax change p-value SUVmax change p-value
      Systemic therapy (no vs yes) 7.52 vs 5.76 0.336 8.24 vs 4.91 0.021 6.12 vs 7.26 0.700 0.79 vs -1.46 0.034 0.13 vs -0.40 0.700 -2.46 vs 1.98 0.005
      Immunotherapy (no vs yes) 7.46 vs 5.99 0.752 7.92 vs 4.82 0.058 7.26 vs 3.50 0.461 0.65 vs -3.11 0.027 0.14 vs -1.40 0.598 -1.14 vs 0.58 0.073
      Concurrent administration (no vs yes) 5.99 vs 10.67 0.365 7.44 vs 6.30 0.821 6.12 vs 10.91 0.308 0.58 vs -4.37 0.024 0.10 vs -1.48 0.428 -0.40 vs 4.38 0.113

      Conclusion

      Serial 18-FDG PET imaging during lung SBRT demonstrated minimal variability of key parameters. FDG uptake at PET2, change from baseline, and between fractions, were related to systemic therapy, immunotherapy, and timing of administration. Mechanism of PET parameter variability, and its impact of on oncologic outcomes require investigation; prospective evaluation of BgRT is ongoing.

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