Center for Radiological Research, Columbia University Irving Medical Center, New York, New York.
Center for Radiological Research, Columbia University Irving Medical Center, New York, New York.
Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):272-278. doi: 10.1016/j.ijrobp.2019.02.025. Epub 2019 Feb 16.
Treatment of fast-growing, human papillomavirus-negative, head and neck cancers (HNCs) remains challenging from the perspectives of both tumor control and late sequelae. In this study, we use systematic radiobiological optimization to identify fractionation schemes that markedly improve the radiotherapeutic effectiveness balance between tumor control probability (TCP) and late normal tissue complication probability (LNTCP), as compared with standard fractionation.
We track the development after each treatment fraction of both tumor control and late sequelae. Toward the end of the treatment, accelerated repopulation of fast-growing HNC tumors means that further fractions minimally improve TCP but result in major LNTCP increases, providing the potential for optimization of the TCP-LNTCP balance. We used a recent improved model of accelerated repopulation, calibrated with extensive HNC clinical trials data, to identify optimally effective treatment regimens that both increase TCP and significantly decrease LNTCP. For comparison, we also used standard repopulation models.
An optimized hypofractionated schedule of 18 × 3.0 Gy is predicted to substantially increase TCP, particularly for late-stage HNC tumors (eg, ∼35% to 49% for late-stage tumors) while decreasing high-grade LNTCP (eg, ∼13% to <2%), as compared with a standard 35 × 2.0 Gy protocol. In addition, the treatment time is reduced from 47 to 24 days. Twice-daily treatments of 1.8 Gy per fraction provide still better outcomes. The hypofractionation predictions are robust, being almost independent of the details of the repopulation model.
Hypofractionation or its close variant, accelerated hyperfractionation, efficiently overcomes tumor repopulation in fast-growing tumors and can be optimized toward the end of treatment when repopulation causes the TCP to increase only very slowly while LNTCP increases rapidly. Radiobiological modeling suggests that optimized 3.0 Gy per fraction hypofractionation (or 1.8 Gy per fraction, 2 fractions per weekday, accelerated hyperfractionation) is considerably more effective for HNC tumor control and for reduction of late effects than standard 2.0-Gy fractionation.
从肿瘤控制和晚期后遗症的角度来看，治疗生长迅速、人乳头瘤病毒阴性的头颈部癌症（HNC）仍然具有挑战性。在这项研究中，我们使用系统放射生物学优化来确定分割方案，与标准分割相比，这些方案可显著改善肿瘤控制概率（TCP）和晚期正常组织并发症概率（LNTCP）之间的放射治疗效果平衡。
我们跟踪每次治疗后肿瘤控制和晚期后遗症的发展情况。在治疗结束时，快速生长的 HNC 肿瘤的加速再增殖意味着进一步的分割对 TCP 的改善很小，但会导致 LNTCP 的大幅增加，从而为 TCP-LNTCP 平衡的优化提供了潜力。我们使用最近改进的加速再增殖模型，该模型经过广泛的 HNC 临床试验数据校准，以确定既能增加 TCP 又能显著降低 LNTCP 的最佳有效治疗方案。为了进行比较，我们还使用了标准的再增殖模型。
与标准的 35×2.0 Gy 方案相比，预测 18×3.0 Gy 的优化超分割方案将显著增加 TCP，特别是对于晚期 HNC 肿瘤（例如，晚期肿瘤的约 35%至 49%），同时降低高级别 LNTCP（例如，约 13%至<2%）。此外，治疗时间从 47 天缩短到 24 天。每次分割 1.8 Gy，每日两次的治疗效果更好。超分割的预测结果是稳健的，几乎独立于再增殖模型的细节。
超分割或其密切变体加速超分割有效地克服了快速生长肿瘤中的肿瘤再增殖，并且可以在治疗结束时进行优化，此时再增殖导致 TCP 仅非常缓慢增加，而 LNTCP 迅速增加。放射生物学模型表明，与标准的 2.0 Gy 分割相比，优化的 3.0 Gy 分割（或 1.8 Gy 分割，每周工作日 2 次分割，加速超分割）对头颈部肿瘤控制和减少晚期效应更为有效。
