2085 - Histology-Driven Hypofractionated Radiotherapy Schemes for Early-Stage Lung Adenocarcinoma and Squamous Cell Carcinoma

F. Liu¹, M. Farris², J. D. Ververs¹, R. T. Hughes¹, and M. T. Munley¹; ¹Department of Radiation Oncology, Wake Forest University School of Medicine, Winston Salem, NC, ²Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC

Purpose/Objective(s): Histology was found to be an important and independent prognostic factor for local tumor control probability (TCP) after stereotactic body radiotherapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). A histology-driven SBRT approach has not been explored in routine clinical practice and histology-dependent fractionation schemes remain unknown. Here, we analyzed pooled histologic TCP data as a function of biologically effective dose (BED) to determine histology-dependent radiobiological parameters and histology-drive optimal fractionation schemes for SBRT and moderate hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Materials/

Methods: We collected 1-, 2-, 3-, and 5-year histologic TCP data of 8510 early-stage NSCLC patients treated from conventional radiation therapy to SBRT. The least-chi-square method was used to fit the collected TCP data to determine the radiobiological parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative.
Results: A simultaneous fit to the histologic TCP data determined two sets of histology-dependent radiobiological parameters for radiotherapy of early-stage lung ADC and SCC, respectively. TCP increases steeply with BED and reaches an asymptotic maximal plateau, which allows us for the first time to determine model-independent and histology-drive optimal fractionation schemes of least prescription doses in 1-30 fractions to achieve maximal tumor control for early-stage lung ADC and SCC, e.g., 30, 44, 48, and 51 Gy for ADC, and 32, 48, 54, and 58 Gy for SCC in 1, 3, 4, and 5 fractions, respectively.
Conclusion: We presented the first determination of histology-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. The proposed optimal fractionation schemes for ADC agree well with current clinical practice for SBRT of early-stage NSCLC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. Current clinical hypofractionation schemes of 3-5 Gy/fraction are not optimal to achieve maximal tumor control for early-stage lung ADC and SCC, higher radiation doses are required. These proposed optimal fractionation schemes provide first insights for histology-based personalized radiotherapy of two predominant early-stage NSCLC subtypes ADC and SCC, which require further validation with large-scale histologic TCP data.