Prediction of tumor control probability in prostate cancer radiotherapy using a biophysical model incorporating cancer stem cell and hypoxia

がん幹細胞と低酸素状態を組み込んだ生物物理モデルを用いた前立腺がん放射線療法における腫瘍制御確率の予測

嵯峨 涼*; 岩森 賢大*; 松谷 悠佑  ; 細川 洋一郎*

Saga, Ryo*; Iwamori, Kenta*; Matsuya, Yusuke; Hosokawa, Yoichiro*

本研究では、前立腺がんの放射線治療効果を精密に予測するため、サイドポピュレーション(SP)を含むがん幹細胞(CSC)の特性と、腫瘍内の酸素効果(OER)を統合した生物物理モデルを開発した。DU145細胞からSPとメインポピュレーション(MP)を分離し、X線照射後のDNA二本鎖切断やコロニー形成による生存率を、低酸素環境(0.1% O)も含めて評価した。これらのデータをMP・SPおよび酸素濃度を考慮したIMKモデルで解析し、分割照射(2、3、7Gy/回)による臨床TCPと比較した。その結果、MP/SP割合、共通のOER、腫瘍内低酸素体積を用いることで、in vitroおよび臨床データを良好に再現できた。さらに、初期DSB生成量が細胞特性と酸素濃度に応じた放射線感受性を決定する主要因であることが示された。開発モデルは、低酸素領域への線量強化など、前立腺がん治療の最適化の貢献が期待できる。

This study developed a biophysical model that integrates the characteristics of cancer stem cells (CSCs), including the side population (SP), and the oxygen enhancement effect (OER) to more accurately predict radiotherapy outcomes in prostate cancer. SP and main population (MP) cells were isolated from the DU145 prostate cancer cell line, and DNA double-strand breaks and survival were evaluated under both normoxic and hypoxic conditions (0.1% O). The obtained data were analyzed using the IMK model incorporating MP, SP, and oxygen concentration, and the predictions were compared with clinical tumor control probability (TCP) under various fractionation regimens (2, 3, and 7 Gy/Fx). As a result, the in vitro and clinical data were well reproduced by considering the MP/SP fraction, a population-independent OER, and the intratumoral hypoxic volume. Furthermore, the initial yield of DSBs was identified as a key determinant of radiosensitivity depending on cell characteristics and oxygen levels. The developed model is expected to contribute to the optimization of prostate cancer radiotherapy, including dose escalation to hypoxic tumor regions.