Histology-driven hypofractionated radiation therapy schemes for early-stage lung adenocarcinoma and squamous cell carcinoma

•Histology was found to be an important prognostic factor for local tumor control probability (TCP) after stereotactic body radiation therapy (SBRT) of early-stage non-small-cell lung cancer (NSCLC). Histology-driven SBRT approach has not been explored in routine clinic practice and histology-dependent fractionation schemes remain unknown.•We analyzed pooled histologic TCP data for early-stage NSCLC patients as a function of biologically effective dose (BED) and determined histology-driven optimal SBRT and hypofrationated radiation therapy schemes of least doses to maximize tumor control in 1–30 fractions for the two predominant histologic subtypes lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC).•The determined SBRT schemes are consistent with clinic practice for ADC, SCC requires substantially higher doses to maximize tumor control than ADC. These histology-driven optimal hypofractionated radiation therapy schemes provide first insights for personalized radiation therapy of two predominant early-stage NSCLC subtypes ADC and SCC. Histology was found to be an important 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-driven fractionation schemes for SBRT and hypofractionated radiotherapy of two predominant early-stage NSCLC histologic subtypes adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The least-χ2 method was used to fit the collected histologic TCP data of 8510 early-stage NSCLC patients to determine parameters for a well-developed radiobiological model per the Hypofractionated Treatment Effects in the Clinic (HyTEC) initiative. A fit to the histologic TCP data yielded independent radiobiological parameter sets for radiotherapy of early-stage lung ADC and SCC. TCP increases steeply with BED and reaches an asymptotic maximal plateau, allowing us to determine model-independent optimal fractionation schemes of least 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. We presented the first determination of histology-depe