Tumor Control Probability Modeling for Radiation Therapy of Keratinocyte Carcinoma

Abstract

Summary: Skin cancer patients may be treated definitively using radiation therapy (RT) with electrons, kilovoltage, or megavoltage photons depending on tumor stage and invasiveness. This study modeled tumor control probability (TCP) based on the pooled clinical outcome data of RT for primary basal and cutaneous squamous cell carcinomas (BCC and cSCC, respectively). Four TCP models were developed and found to be potentially useful in developing optimal treatment schemes based on recommended ASTRO 2020 Skin Consensus Guidelines for primary, keratinocyte carcinomas (i.e. BCC and cSCC).

Background: Radiotherapy (RT) with electrons or photon beams is an excellent primary treatment option for keratinocyte carcinoma (KC), particularly for non-surgical candidates. Our objective is to model tumor control probability (TCP) based on the pooled clinical data of primary basal and cutaneous squamous cell carcinomas (BCC and cSCC, respectively) in order to optimize treatment schemes.

Methods: Published reports citing crude estimates of tumor control for primary KCs of the head by tumor size (diameter: ≤2 cm and >2 cm) were considered in our study. A TCP model based on a sigmoidal function of biological effective dose (BED) was proposed. Three-parameter TCP models were generated for BCCs ≤2 cm, BCCs >2cm, cSCCs ≤2 cm, and cSCCs >2 cm. Equivalent fractionation schemes were estimated based on the TCP model and appropriate parameters.

Results: TCP model parameters for both BCC and cSCC for tumor sizes ≤2 cm and >2cm were obtained. For BCC, the model parameters were found to be TD₅₀ = 56.62 ± 6.18 × 10^-3 Gy, k = 0.14 ± 2.31 × 10^-2 Gy^-1 and L = 0.97 ± 4.99 × 10^-3 and TD₅₀ = 55.78 ± 0.19 Gy, k = 1.53 ± 0.20 Gy^-1 and L = 0.94 ± 3.72 × 10^-3 for tumor sizes of ≤2 cm and >2 cm, respectively. For SCC the model parameters were found to be TD₅₀ = 56.81 ± 19.40 × 10⁴ Gy, k = 0.13 ± 7.92 × 10⁴ Gy^-1 and L = 0.96 ± 1.31 × 10^-2 and TD₅₀ = 58.44 ± 0.30 Gy, k = 2.30 ± 0.43 Gy^-1 and L = 0.91± 1.22 × 10^-2 for tumors ≤2cm and >2 cm, respectively. The TCP model with the derived parameters predicts that radiation regimens with higher doses, such as increasing the number of fractions and/or dose per fraction, lead to higher TCP, especially for KCs >2 cm in size.

Conclusion: Four TCP models for primary KCs were developed based on pooled clinical data that may be used to further test the recommended kV and MV x-ray and electron RT regimens from the 2020 ASTRO guidelines. Increasing both number of fractions and dose per fraction may have clinically significant effects on tumor control for tumors >2 cm in size for both BCC and cSCC.

Keywords: basal cell/carcinoma; biological effective dose (BED); dose response modeling; squamous cell carcinama; tumor control probability (TCP).

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Diagram. Schematic depicting the literature review process for the development of basal and cutaneous squamous cell carcinoma (BCC and cSCC, respectively) tumor control probability (TCP) models. Created based on Moher D, A Liberati, J Tetzlaff and DC Altman, 2009 [ref (7)].

Figure 2

Fitting of a tumor control probability (TCP) model to reported clinical data for basal cell carcinoma (BCC) of size (A) ≤2 cm and (B) >2 cm, and cutaneous squamous cell carcinoma (cSCC) of size (C) ≤2 and (D) >2 cm. The abscissa is the biological effective dose calculated using the linear quadratic model with α/β = 10 Gy (BED₁₀), while the ordinate is the TCP. HM06, Hernández-Machin et al., 2006 (10) (circle); S05, Schulte et al., 2005 (12) (square); VH10, van Hezewijk et al., 2010 (13) (diamond); L01, Locke et al., 2001 (5) (pentagram); P87, Petrovich et al., 1987 (11) (hexagram); Co12, Cognetta et al., 2012 (4) (upward pointing triangle); D16, Duinkerken et al., 2016 (14) (right pointing triangle); T16, Terra et al., 2016 (15) (left pointing triangle).