Lung Cancer

PV QA 4 - Poster Viewing Q&A 4

TU_32_3636 - Functional Imaging Demonstrates that Immune Parameters Modulate the Radiosensitivity of Locally Advanced Non-small Cell Lung Cancer

Tuesday, October 23
2:45 PM - 4:15 PM
Location: Innovation Hub, Exhibit Hall 3

Functional Imaging Demonstrates that Immune Parameters Modulate the Radiosensitivity of Locally Advanced Non-small Cell Lung Cancer
A. Pirlamarla1, C. Zhu2, C. Guha3, and N. Ohri3; 1Albert Einstein College of Medicine, Bronx, NY, 2Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, 3Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY

Purpose/Objective(s): Accumulating evidence demonstrates that the immune system plays a critical role in cancer therapy. In this study, we utilized functional imaging (FDG-PET) to quantify radiosensitivity in patients treated with definitive radiotherapy (RT) for locally advanced non-small cell lung cancer (NSCLC) and evaluated associations between immune parameters and radiosensitivity.

Materials/Methods: We identified patients with locally-advanced (stage IIB-III) NSCLC who were treated with definitive RT at our institution, underwent FDG-PET within three months before RT and within five months after RT, and underwent tumor PD-L1 testing by immunohistochemistry. A radiosensitivity score (RSS) was defined as the natural logarithm of the maximum standardized uptake value (SUVmax) within all target lesions before RT divided by the SUVmax after RT. Clinical factors (time from completion of RT to post-treatment FDG-PET/CT, RT dose, pre-treatment SUVmax, and use of concurrent chemotherapy) and immune parameters (PD-L1 tumor proportion score and pre-treatment neutrophil-to-lymphocyte ratio [NLR]) were tested as predictors of RSS using linear regressions.

Results: Twenty-five patients met all eligibility criteria. The median RT dose was 60 Gy (range: 52.5 to 65 Gy), given with a median daily fraction size of 2.1 Gy (range: 1.8 to 2.75 Gy). Twenty-one patients (84%) received concurrent chemotherapy. Seven patients (28%) had high (≥50%) PD-L1 expression, and median NLR was 2.8 (range: 1.3 to 9.9). Median pre-treatment SUVmax was 11.9 (range: 5.5 to 23.6), and median post-treatment SUVmax was 4.2 (range: 2.3 to 12.0). The mean RSS was 0.89 (range: -0.36 to 2.04). RT dose and post-treatment PET timing were not statistically significant predictors of RSS. The use of concurrent chemotherapy was associated with high RSS, with a mean RSS of 1.04 for patients treated with concurrent chemotherapy and a mean RSS of 0.41 for patients treated without concurrent chemotherapy (p=0.041). PD-L1 expression was not associated with RSS, with a mean RSS of 0.78 for patients with PD-L1 expression of at least 50% and a mean RSS of 1.00 for other patients (p=0.405). High NLR was associated with an inferior response to RT, with a mean RSS of 0.67 for patients with NLR above 2.8 and a mean RSS of 1.18 for patients with NLR below 2.8 (p=0.028). In a multivariable model adjusting for concurrent chemotherapy use and pre-treatment SUVmax, high NLR was associated with reduced RSS (-0.43, 95% CI: -0.79 to -0.07, p=0.021).

Conclusion: Using functional imaging to quantify radiosensitivity in patients with locally advanced NSCLC, we have demonstrated that high NLR is associated with diminished radiosensitivity. Validation studies in other datasets are ongoing. Modulation of the immune system should be pursued as a strategy to enhance the efficacy of radiotherapy.

Author Disclosure: A. Pirlamarla: None. C. Zhu: None. C. Guha: Translational Research Program, Gastrointestinal O; RTOG. N. Ohri: None.

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