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Abstract：
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-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. 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.
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-dependent radiobiological parameters and model-independent histology-driven optimal SBRT and hypofractionated radiation therapy schemes for early-stage lung ADC and SCC. SCC requires substantially higher radiation doses to maximize tumor control than ADC, plausibly attributed to tumor genetic diversity and microenvironment. The determined optimal SBRT schemes agree well with clinical practice for early-stage lung ADC. 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.
摘要：
目的：组织学是早期非小细胞肺癌（NSCLC）立体定向放疗（SBRT）后局部肿瘤控制概率（TCP）的重要预后因素。在常规临床实践中尚未探索组织学驱动的SBRT方法，并且组织学依赖性分级方案仍然未知。这里,我们分析了作为生物学有效剂量(BED)函数的合并组织学TCP数据,以确定两种主要早期NSCLC组织学亚型腺癌(ADC)和鳞状细胞癌(SCC)的SBRT和大分割放疗的组织学驱动分割方案.
方法：使用最小χ2方法来拟合收集的8510例早期NSCLC患者的组织学TCP数据，以根据临床中的小分割治疗效果（HyTEC）计划确定完善的放射生物学模型的参数。
结果：对组织学TCP数据的拟合得出了早期肺ADC和SCC放疗的独立放射生物学参数集。TCP随着BED急剧增加，并达到渐近最大平台，允许我们确定在1-30个部分中的最小剂量的与模型无关的最佳分级方案，以实现早期肺ADC和SCC的最大肿瘤控制，例如，30、44、48和51Gy的ADC，对于1、3、4和5个馏分的SCC，分别为32、48、54和58Gy，分别。
结论：我们首次确定了组织学依赖的放射生物学参数和模型独立的组织学驱动的最佳SBRT和早期肺ADC和SCC的大分割放射治疗方案。SCC需要比ADC高得多的辐射剂量来最大限度地控制肿瘤，合理地归因于肿瘤遗传多样性和微环境。确定的最佳SBRT方案与早期肺ADC的临床实践非常吻合。这些提出的最佳分割方案为两种主要的早期NSCLC亚型ADC和SCC的基于组织学的个性化放射治疗提供了初步见解。这需要大规模组织学TCP数据的进一步验证。
方法：使用最小χ2方法来拟合收集的8510例早期NSCLC患者的组织学TCP数据，以根据临床中的小分割治疗效果（HyTEC）计划确定完善的放射生物学模型的参数。
结果：对组织学TCP数据的拟合得出了早期肺ADC和SCC放疗的独立放射生物学参数集。TCP随着BED急剧增加，并达到渐近最大平台，允许我们确定在1-30个部分中的最小剂量的与模型无关的最佳分级方案，以实现早期肺ADC和SCC的最大肿瘤控制，例如，30、44、48和51Gy的ADC，对于1、3、4和5个馏分的SCC，分别为32、48、54和58Gy，分别。
结论：我们首次确定了组织学依赖的放射生物学参数和模型独立的组织学驱动的最佳SBRT和早期肺ADC和SCC的大分割放射治疗方案。SCC需要比ADC高得多的辐射剂量来最大限度地控制肿瘤，合理地归因于肿瘤遗传多样性和微环境。确定的最佳SBRT方案与早期肺ADC的临床实践非常吻合。这些提出的最佳分割方案为两种主要的早期NSCLC亚型ADC和SCC的基于组织学的个性化放射治疗提供了初步见解。这需要大规模组织学TCP数据的进一步验证。
