这项研究得到台北医科大学医院 (106 tmuh-02) 的支持。

本研究获得台北医科大学联合机构评审委员会批准。
1. SBRT 咨询
<ol><li>通过咨询多学科肿瘤委员会, 评估 SBRT 治疗肝转移瘤患者的资格。 注意: 需要进行局部消融以及手术和其他治疗选择必须由肿瘤委员会评估。我们的选择标准如下: 1) 具有良好表现状态的成年患者 (东方合作肿瘤组 0-1), 2) 通过抗癌药物控制癌症状态, 仅在肝脏 oligometastases, 3) 肝损害数≤3和最大的肿瘤≤6厘米直径, 4) 肝体积 (肝脏不包括总肿瘤) 大于700厘米3, 5), 没有急性肝炎或慢性乙型肝炎在稳定的抗病毒控制。</li>
	<li>讨论 SBRT 及其相关的风险以及 SBRT 与常规放疗之间的差异与患者9,19。</li>
</ol>2. CT 模拟
<ol><li>
把病人放在仰卧位, 头先放在沙发上, 手臂放在头上。
	<ol>
<li>使用系统 (例如, BodyFIX) 来固定病人。将病人放置在一个个性化的, 真空的减压袋中, 用盖子盖住病人。</li>
		<li>应用腹部压缩机 (ac), 并标记交流的深度。 注意: AC 限制患者的呼吸运动;因此, 有些病人可能会在这个过程中产生呼吸困难。应提供通过鼻腔插管补充氧气, 以减轻他们的不适。</li>
		<li>将呼吸跟踪传感器放在胸腔壁上, 并监测呼吸波形。</li>
	</ol>
</li>
	<li>
获得放射治疗计划的 CT 图像。
	<ol>
<li>选择4维 CT 扫描模式, 3 毫米切片厚度。</li>
		<li>进行 surview 扫描 (120 伏, 30 mA), 以获得患者的前后 (AP) 和侧面视图。在屏幕和控制面板上单击"转到"。</li>
		<li>确定 "螺旋扫描" 分页下的 ct 扫描覆盖率, 并在 "肺门扫描" 分页中决定4维 ct 扫描范围。 注: 螺旋扫描的覆盖范围应从肺的顶端延伸到离肝尾缘至少5厘米的距离。肺门扫描的领域, 这是小于螺旋扫描, 应该覆盖肝脏与3-5 厘米延伸从颅和尾部的肝脏。</li>
		<li>监测呼吸波形, 直到它保持稳定3分钟。</li>
		<li>注射100毫升造影剂 (例如, 欧乃派克), 速度为4-5 毫升/秒, 通过18克静脉注射导管进入 antecubital 静脉。</li>
		<li>进行对比螺旋 CT 扫描 (120 kV, 400 mAs/切片), 十五年代后造影注射。</li>
		<li>随后通过点击 "下一个系列" 进行非对比的4维 CT 扫描 (120 伏, 2000 mAs/切片)。</li>
	</ol>
</li>
</ol>3. 放疗治疗计划
<ol><li>
将图像从 CT 模拟和诊断扫描导入计划系统。 注: 诊断图像可能包括正电子发射断层扫描 (pet)/pet-ct, 磁共振图像, 或诊断螺旋 CT 扫描。</li>
	<li>
轮廓转移肿瘤成总肿瘤体积和相邻器官的危险 (桨)。
	<ol>
<li>选择一个器官 (这里, 胃) 和使用刷子, 铅笔,等。在 CT 图像的每个切片中对器官进行轮廓。圈或定义感兴趣的器官。使用 "向上" 和 "向下" 按钮查看每个图像切片。 注: 桨叶包括肺部、胃、十二指肠、脊髓、肝脏、小肠、肋骨和肾脏。</li>
	</ol>
</li>
	<li>
根据动态跟踪图像观察到的器官运动, 对肿瘤的内靶容积 (ITV) 进行轮廓分析。在 ITV 中添加一个5毫米的边距以获得规划目标卷 (PTV)。
	<ol>
<li>选择一个器官 (这里, 胃) 和使用刷子, 铅笔,等。在 CT 图像的每个切片中对器官进行轮廓。圈或定义感兴趣的器官。使用 "向上" 和 "向下" 按钮查看每个图像切片。</li>
	</ol>
</li>
	<li>为相对较大的肿瘤, 在五个馏分中规定辐射剂量为48至三分或 35 PTV。 注: 治疗计划必须考虑因桨而造成的限制;如果桨的辐射剂量在约束范围内 (表 1), 则相对较高的处方剂量是可以接受的。</li>
</ol>4. 治疗分娩
<ol><li>使用每日质量保证确认辐射光束数据, 确保数据在正常范围内。</li>
	<li>使用病人的姓名、出生日期和身份证识别病人。将病人放置在真空袋中, 放置盖板, 并根据 CT 模拟部分所描述的程序固定 AC。</li>
	<li>
获取4D 锥束 CT (总站) 图像, 调整沙发, 使其与在模拟 CT 图像上获得的4维总站图像的目标位置相关联。
	<ol>
<li>选择4D 总站模式并确认安装数据。单击面板上的"转到" 。</li>
	</ol>
</li>
	<li>
4D 总站后, 将获得的4D 总站图像加载到 IGRT 系统中。左上、右下图像均由 CT 模拟作为轮廓和治疗计划。右上角和下左图像来自4D 总站, 每天在每个分数之前执行。
	<ol>
<li>使用软件调整设置。然后, 手动调整沙发上的每个参数。沙发在 X、Y 和 Z 轴上只有3直线运动, 而系统在6中可以调整, 包括旋转、俯仰和滚动。因此, 技术员需要证实调整。</li>
		<li>记录和打印每日调整的参数。 注: 如果肿瘤位置在任何一个六轴上超过5毫米的公差限制, 病人应重新定位。</li>
	</ol>
</li>
	<li>提供放射治疗。确认处理计划和系统配置。单击 "转到" 开始治疗。在整个治疗过程中用实时摄像头监控病人, 以确保病人的安全。</li>
</ol>

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作者没有披露。

呼吸引起的肝畸形和器官运动导致了与辐射传递有关的困难, 以及轮廓 (目标划定) 问题。对器官运动管理技术的改进提高了治疗的准确性和精确度, 这对 SBRT 是至关重要的。目前有几种图像引导技术和呼吸运动管理系统。基准标记植入是目标定位的常用技术。基准标记通常是圆柱形的金籽, 长度为2.5 到5毫米, 直径为0.8 毫米. 在病变附近植入一个基准标记, 使基于 X 射线的图像引导系统能够定位目标。然而, 在 > 30% 的患者中, 使用基准标记 (包括内出血、发热、疼痛、脱位和感染) 的并发症已被报道。患者接受侵入性手术是另一项关注事项12。此外, 空气呼吸协调 (ABC) 和深灵感呼吸保持 (DIBH) 技术经常用于图像引导放疗;这些无创的呼吸控制系统旨在帮助患者屏住呼吸, 从而在放射治疗中使靶固定。尽管在治疗前进行了耐心训练, 但是, 每一个分数的长期治疗时间、呼吸困难和个别的医疗状况限制了 ABC 和 DIBH13、14的使用。
用 AC 进行肺 SBRT 的呼吸相关 ct 和4维 ct 辅助扫描的准确性已被广泛证明15,16。最近的几项研究讨论了这种技术在呼吸相关肝运动中的应用。高桥et al。建议4维 CT 扫描与 AC 实现实质性的呼吸运动管理, 并减少 PTV 边缘 < 5 毫米16。此外, 4 维 CT 积分的肝脏 SBRT 剂量评价已被处理17。Shimohigashi et al。最近报道, 4 d-CT 与 AC 准确地代表肿瘤运动在 SBRT18期间。使用4维 CT 的交流比其他呼吸运动管理技术更有利, 因为该技术是无创的, 并允许自由呼吸。此外, 病人认为这项技术比其他管理技术更方便。医生和治疗师也可能受益于这种技术, 因为它创造了一个方便的工作流程。最近的一些研究报告说, 使用4维 CT 作为一种呼吸管理技术在肝转移 SBRT 期间19,20,21。患者不需要屏住呼吸时, 4 d-CT 与 AC 使用 (不像在病人训练时, DIBH 或 ABC 使用);因此, 4 d-CT 的交流被认为是方便的, 因此通常用于 SBRT 肺和肝脏。然而, 还应强调的是, 在肝脏运动管理中, 4 维 CT 的交流与治疗肺部病变的方法不同。
首先, 虽然规划 ct 扫描的图像质量仍未像 ct 扫描那样高, 但我们仍然建议对比 ct 能够精确地进行肿瘤的轮廓。与肺 SBRT 不同的是, 肺部病变可以很容易地与正常的肺组织区别于肺部 CT 图像。然而, 在 noncontrasted 肝脏图像中, 正常和恶性组织不能很容易区分。第二, 每日4维总站在治疗前对肿瘤部位进行验证, 对于显著提高 intrafractional 准确性至关重要;PTV 边距的3毫米以前被认为是足够的每日4维总站扫描 (尽管我们仍然遵守5毫米的 PTV 保证金标准)18。第三, 慢速 ct 扫描或电影 ct 扫描应在自由呼吸下进行。4维 CT 动态跟踪图像的各个阶段的肿瘤可作为 ITV 的肿瘤运动, 而交流限制器官运动以减少照射量。此外, 应评估肺的辐射剂量。靠近隔膜的肝脏病变可导致肺部辐射剂量增加。放射性肺炎是常见的并发症;然而, i. 级放射性肺炎通常无症状。对整个肺的剂量限制和 CT 扫描不应忽视。
从历史上看, 常规放疗对肝癌的治疗效果极低。然而, 肝脏对辐射剂量的耐受性相对较低, 辐射诱发肝病 (RILD) 可能是致命的。虽然一些研究提出了预防肝细胞癌放疗中 RILD 的预处理评价22, 但使用常规放疗治疗肝脏病变必须谨慎。SBRT 提供改进的肿瘤控制与极小的严重并发症;然而, 只有少数研究报告的风险评估, 以防止 RILD, 同时使用 SBRT 治疗肝转移。此外, 对于接受 SBRT 肝转移瘤患者的资格标准还没有明确定义, 尽管一些研究报告了一些常见的标准4,5。我们的选择标准如下: 1) 具有良好表现状态的成年患者 (东方合作肿瘤组 0-1), 2) 通过抗癌药物控制癌症状态, 仅在肝脏 oligometastases, 3) 肝损害数≤3和最大的肿瘤≤6厘米直径, 4) 肝体积 (肝脏不包括总肿瘤) 大于700厘米3, 5), 没有急性肝炎或慢性乙型肝炎在稳定的抗病毒控制。原癌的组织病理学不需要仅限于结肠、乳房和肺部, 但这些部位是首选。在拟议的议定书中需要进行多学科的肿瘤委员会讨论, 而行动应是第一个选择。其他局部消融疗法可以由肿瘤委员会讨论, 最后的治疗是根据病人的决定。
虽然局部消融包括 SBRT 可以实现局部肿瘤控制和使用 4 d-CT 的 AC 可以促进运动控制, 生存和无进展间隔严重依赖化疗的抗癌作用, 靶向治疗, 或其他系统药物。换言之, 如果没有适当的系统控制, 即使是最合适的局部消融治疗也不会提供任何整体的好处。因此, 回顾全身疗法的效果有助于选择局部消融治疗。此外, oligometastases 控制与无进展生存或整体生存之间的相关性仍需进一步调查。不同的因素, 如 oligometastases 的位置和数量, 原癌的病理组织学, 或治疗-天真的病人, 可能会对结局23产生影响。尽管有上述限制, SBRT, 这是无创的, 并在临床上方便, 作为 4 d-CT 与 AC 呼吸运动管理, 提供了相当大的局部消融作用的肝转移。

传统上, 转移被认为是癌症的末期阶段, 与预后和生存率差有关。但是, 山et al。在1984年报告说, 根据他们20年的经验, 完整的手术切除肺转移导致一个相对较高的存活率, 如果主要肿瘤部位是在系统控制的时候, 手术1。赫尔曼和 Weichselbaum 在1995年首次提出 oligometastases, 一个中间阶段之间的局部病变和系统性疾病与 polymetastases, 这可以治愈使用额外的局部治疗2,3。在过去的几十年中, 早期发现转移, 新的手术方法治疗 oligometastases (后) 和有效的化疗改善了预后的转移。肝脏是实体肿瘤最常见的转移器官之一, 肝 oligometastases 的手术切除可以改善生存。局部消融方法, 包括射频消融, radioembolization 和放疗, 为治疗肝转移已建议一些无法手术的病人, 以实现必要的局部肿瘤控制3,4,5,6,7. 在过去几年中, 一些前瞻性和回顾性的研究报告通过立体定向体放疗 (SBRT), 也称为立体定向消融放疗, 对肝转移瘤进行有效的局部肿瘤控制, 可耐受毒性4,5,8,9。
在病人定位和固定化方法方面已经有了改进;图像采集、整合和转移到放疗系统;呼吸运动管理;高剂量输出和快速辐射输送;以及从靶病变到周围正常组织的陡峭剂量梯度。由于这些进展, SBRT 实现高度精确和精确的放射治疗与极小的严重毒性10,11。呼吸运动管理是 SBRT 的基础, 特别是对肝脏和肺部病变。一种无创、临床方便的呼吸管理技术将极大地提高 SBRT 作为治疗方案的普及程度。本文详细介绍了肝转移的 SBRT 协议, 使用四维计算机断层扫描 (4 d-CT) 与腹部压缩机 (AC) 的图像引导帮助和肝脏运动管理。

<table border="0" cellpadding="0" cellspacing="0" width="875">
	<tbody>
		<tr height="51">
			<td height="51" style="height:51px;width:195px;">CT scan</td>
			<td style="width:188px;">Philips</td>
			<td style="width:265px;">Brilliance&#160;Big Bore&#160;16 Slice&#160;CT, 7387</td>
			<td style="width:228px;">Acquire CT images for contouring and planning</td>
		</tr>
		<tr height="51">
			<td height="51" style="height:51px;width:195px;">CT contrast</td>
			<td style="width:188px;">GE Healthcare</td>
			<td style="width:265px;">Omnipaque 350 mg L/mL</td>
			<td style="width:228px;">Enhence lesion in CT images</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Linear accelerator</td>
			<td>Elekta</td>
			<td>Synergy</td>
			<td>Deliver radiotherapy</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Palnning system</td>
			<td>Pinnacle</td>
			<td>Pinnacle 9.8</td>
			<td>Implement radiotherapy planning</td>
		</tr>
		<tr height="65">
			<td height="65" style="height:65px;width:195px;">Immobilization: BlueBag BodyFix</td>
			<td>Elekta</td>
			<td>900 mm x 2325 mm, P10104840</td>
			<td>Immobilize the patient</td>
		</tr>
		<tr height="66">
			<td height="66" style="height:66px;width:195px;">Immobilization: BodyFix Cover sheet</td>
			<td>Elekta</td>
			<td>2700 mm x 1400 mm, P10102-304</td>
			<td>Immobilize the patient</td>
		</tr>
		<tr height="73">
			<td height="73" style="height:73px;width:195px;">Immobilization: BodyFix abdominal compressor</td>
			<td>Elekta</td>
			<td>diaphragm control, P10102-149</td>
			<td style="width:228px;">Restrict breath motion and organ/lesion motion</td>
		</tr>
		<tr height="57">
			<td height="57" style="height:57px;width:195px;">Immobilization: vacuum pump</td>
			<td>Elekta</td>
			<td>vacuum pump, p2 120V, P10102-110</td>
			<td style="width:228px;">Shape body bag and cover sheet according to the patient</td>
		</tr>
	</tbody>
</table>

treatment of liver metastases using an internal target volume method for stereotactic body radiotherapy

由于有效的化疗和 oligometastatic 手术, 在过去数十年中, 转移性癌症患者的预后有所改善。对于无法手术的病人, 局部消融治疗, 如立体定向体放射治疗 (SBRT), 可以提供有效的局部肿瘤控制和最小的毒性。由于它的高精度和准确性, SBRT 提供了更高的辐射剂量每分数, 是更有效的, 并针对较小的辐射量比常规放疗。此外, 利用 SBRT 实现了靶向病灶向周围正常组织的陡峭剂量梯度;因此, SBRT 提供更有效的肿瘤控制, 并表现出较少的副作用比常规放疗。使用 SBRT 是普遍的治疗颅内病变 (称为立体定向放射外科);然而, 它现在也被用于治疗脊柱和肾上腺转移。由于在图像引导辅助和呼吸运动管理方面的进步, 一些研究已经研究了使用 SBRT 治疗肺或肝肿瘤, 这是作为一个病人呼吸移动。这些研究的结果表明, SBRT 有利控制肿瘤的运动性病变。
四维计算机断层扫描 (4 维 ct) 与腹部压缩机 (AC) 是临床上方便有效的呼吸运动管理。因为这种方法是无创的, 并允许自由呼吸, 它的使用减少并发症。此外, 病人认为这种方法很方便。此外, 它被认为比其他方法的呼吸运动管理的医生和治疗师。应用4维 CT 和 AC 治疗肺部病变也得到了广泛的研究, 该技术正在获得接受治疗肝损害。然而, 使用4维 CT 的交流治疗肝脏病变的协议与治疗肺部病变的方法不同。在本文中, 我们描述了一个新的协议 SBRT 4 维 CT 和交流治疗肝转移。

SBRT 可以通过强调制放疗 (IMRT) (与6辐射束) 或容积式电弧放疗 (VMAT) (连续剂量传递和龙门旋转) 来覆盖所有目标的单一治疗, 因为单一的手术可能<img alt="image" src="/files/ftp_upload/57050/57050imgv2.jpg">不能达到切除所有肿瘤的效果。有代表性的 SBRT 治疗计划表明, 手术不可行时两种肝转移瘤的放疗计划成功。两个转移肿瘤的长度为 3cm (从段4到段 8) 和4.3 厘米 (段 8), 其体积分别为13厘米3和22厘米3。所规定的剂量为5个分数的 50, 而光束被定向以避免桨 (图 1A-c)。复杂的处理计划包括四部分光束弧, 即180°到 50°, 260°到 50°, 335° 35°, 50°到 180° (图 1D)。剂量容积直方图显示了肿瘤的覆盖范围, 100% 的 PTVs 的体积由 > 95% 所规定的剂量;桨的辐射剂量在约束范围内 (图 2)。
<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always"><tbody>
<tr>
<td></td>
			<td>3分数</td>
			<td>5分数</td>
		</tr>
<tr>
<td>覆盖</td>
			<td></td>
			<td></td>
		</tr>
<tr>
<td>PTV</td>
			<td colspan="2">D105% < 15%</td>
		</tr>
<tr>
<td></td>
			<td colspan="2">V100% ≥95%</td>
		</tr>
<tr>
<td>桨</td>
			<td></td>
			<td></td>
		</tr>
<tr>
<td>正常肝脏容量12
</td>
			<td>> 700 厘米3 at < 15</td>
			<td>平均 < 15</td>
		</tr>
<tr>
<td>胃、十二指肠、小肠</td>
			<td>D 3 厘米3 at < 21</td>
			<td>D 0.5 厘米3 at < 32</td>
		</tr>
<tr>
<td>两个肾脏</td>
			<td>V 15 < 35%</td>
			<td>平均 < 12Gy</td>
		</tr>
<tr>
<td>脊髓</td>
			<td>D 1 厘米3 at < 18</td>
			<td>D 0.5 厘米3 at < 28</td>
		</tr>
<tr>
<td>心</td>
			<td>D 1 厘米3 at < 30</td>
			<td>V 32 < 15 cm3</td>
		</tr>
<tr>
<td>两肺</td>
			<td>V 12.4 到 < 1000 cm3
</td>
			<td>V 11.4 到 < 1000 cm3
</td>
		</tr>
<tr>
<td>肋</td>
			<td>D 30 厘米3 at < 30</td>
			<td>零</td>
		</tr>
</tbody></table>表 1: 建议的风险器官剂量限制 (桨).PTV: 计划目标量。桨: 有危险的器官。1总肝脏体积-累计总肿瘤体积。2建议正常肝脏容积为 > 700 厘米3。
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57050/57050fig1.jpg"> 图 1:剂量分布 (-c) 和波束方向 (D)。紫色和淡蓝色线条指示计划目标卷, 而黄色和粉红色的线条分别表示50和 30 (-c)。<a href="/files/ftp_upload/57050/57050fig1large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/57050/57050fig2.jpg"> 图 2:剂量-体积直方图.规划目标卷 (PTV) 1 和 PTV2 是彩色的紫色和浅蓝色。危险器官包括正常肝脏 (橙色), 肋骨 (淡粉色), 心脏 (黄色), 左肺 (荧光绿色), 右肺 (粉红色) 和脊髓 (蓝色)。<a href="/files/ftp_upload/57050/57050fig2large.jpg" target="_blank">请单击此处查看此图的较大版本.</a>

Watch this Scientific Journal Video about Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy at JoVE.com

Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

立体定向体放疗 (SBRT) 需要严格的准确性和精确度, 以提供高辐射剂量每分数到小的治疗量, 以改善肿瘤控制和同时减少毒性。在此, 我们提出了一个无创和临床方便的呼吸运动管理协议 SBRT 肝转移。

内靶容积法治疗肝转移瘤的立体定向体放疗

The prognosis of patients with metastatic cancers has improved in the past decades due to effective chemotherapy and oligometastatic surgery. For ...

treatment-liver-metastases-using-an-internal-target-volume-method-for

Nanyang Technological University

Research

JoVE Journal

Medicine

14.0K 次观看.  Taipei Medical University Hospital. 立体定向体放疗 (SBRT) 需要严格的准确性和精确度, 以提供高辐射剂量每分数到小的治疗量, 以改善肿瘤控制和同时减少毒性。在此, 我们提出了一个无创和临床方便的呼吸运动管理协议 SBRT 肝转移。

视频: Treatment of Liver Metastases Using an Internal Target Volume Method for Stereotactic Body Radiotherapy

Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment2. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure3. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 &mu;l every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without radiation.

The purpose of this article is to describe the use of an orthotopic glioblastoma model for chemoradiation studies. This article will go though cell processing, implanting, and radiotherapy of the mouse using an intracranial model.

在原位小鼠脑肿瘤模型结合放疗

Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors1. In recent years there has been substantial progress in the ...

科研

医学

Stereotactic Radiosurgery for Gynecologic Cancer

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, intricate treatment planning, on-board imaging, and reduced number of ablative radiation doses to cancer targets usually refractory to chemotherapy and conventional radiation. Steep SBRT radiation dose drop-off permits narrow 'pencil beam' treatment fields to be used for ablative radiation treatment condensed into 1 to 3 treatments.
Treating physicians must appreciate that SBRT comes at a bigger danger of normal tissue injury and chance of geographic tumor miss. Both must be tackled by immobilization of cancer targets and by high-precision treatment delivery. Cancer target immobilization has been achieved through use of indexed customized Styrofoam casts, evacuated bean bags, or body-fix molds with patient-independent abdominal compression.1-3 Intrafraction motion of cancer targets due to breathing now can be reduced by patient-responsive breath hold techniques,4 patient mouthpiece active breathing coordination,5 respiration-correlated computed tomography,6 or image-guided tracking of fiducials implanted within and around a moving tumor.7-9 The Cyberknife system (Accuray [Sunnyvale, CA]) utilizes a radiation linear accelerator mounted on a industrial robotic arm that accurately follows patient respiratory motion by a camera-tracked set of light-emitting diodes (LED) impregnated on a vest fitted to a patient.10 Substantial reductions in radiation therapy margins can be achieved by motion tracking, ultimately rendering a smaller planning target volumes that are irradiated with submillimeter accuracy.11-13
Cancer targets treated by SBRT are irradiated by converging, tightly collimated beams. Resultant radiation dose to cancer target volume histograms have a more pronounced radiation "shoulder" indicating high percentage target coverage and a small high-dose radiation "tail." Thus, increased target conformality comes at the expense of decreased dose uniformity in the SBRT cancer target. This may have implications for both subsequent tumor control in the SBRT target and normal tissue tolerance of organs at-risk. Due to the sharp dose falloff in SBRT, the possibility of occult disease escaping ablative radiation dose occurs when cancer targets are not fully recognized and inadequate SBRT dose margins are applied. Clinical target volume (CTV) expansion by 0.5 cm, resulting in a larger planning target volume (PTV), is associated with increased target control without undue normal tissue injury.7,8 Further reduction in the probability of geographic miss may be achieved by incorporation of 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET).8 Use of 18F-FDG PET/CT in SBRT treatment planning is only the beginning of attempts to discover new imaging target molecular signatures for gynecologic cancers.

Stereotactic body radiotherapy (SBRT) involves image-guided, ablative radiation delivered to cancer targets refractory to chemotherapy or to conventional radiation treatment. The robotic-armed Cyberknife SBRT system, using sophisticated target localization, delivers hypofractionated radiation doses capable of sterilizing cancer targets. This article will consider new therapeutic roles of SBRT for gynecological cancers.

妇科肿瘤的立体定向放射外科

Stereotactic body radiotherapy (SBRT) distinguishes itself by necessitating more rigid patient immobilization, accounting for respiratory motion, ...

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both direct and rapid analysis of therapeutic sensitivity and resistance. However, recent evidence suggests that therapeutic response is not exclusive to the inherent molecular composition of cancer cells but rather is greatly influenced by the tumor cell microenvironment, a feature that cannot be recapitulated by traditional culturing methods. Even implementation of tumor xenografts, though providing a wealth of information on drug delivery/efficacy, cannot capture the tumor cell/microenvironment crosstalk (i.e., soluble factors) that occurs within human tumors and greatly impacts tumor response. To this extent, we have developed an ex vivo (fresh tissue sectioning) technique which allows for the direct assessment of treatment response for preclinical and clinical therapeutics development. This technique maintains tissue integrity and cellular architecture within the tumor cell/microenvironment context throughout treatment response providing a more precise means to assess drug efficacy.

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

Established cancer cell lines and xenografts have been the mainstay of cancer research for the past several decades. However, recent evidence suggests that therapeutic response is greatly influenced by the tumor cell microenvironment. Therefore, we have developed an ex vivo analysis of primary tumor specimens for drug development purposes.

原发性肿瘤和/或转移相关的临床前和治疗的临床开发的离体处理响应

The molecular analysis of established cancer cell lines has been the mainstay of cancer research for the past several decades. Cell culture provides both ...

Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic agent melphalan. Briefly, the procedure starts with the setup of a percutaneous veno-venous bypass from the femoral vein to the external jugular vein. Via a laparotomy, catheters are then inserted into the proper hepatic artery and the caval vein. The portal vein and the caval vein, both supra- and infrahepatically, are then clamped. The arterial and venous catheters are connected to a heart lung machine and the liver is perfused with melphalan (1 mg/kg body weight) for 60 min. This way it is possible to locally perfuse the liver with a high dose of a chemotherapeutic agent, without leakage to the systemic circulation.
In previous studies including patients with isolated liver metastases of uveal melanoma, an overall response rate of 33-100% and a median survival between 9 and 13 months, have been reported. The aim of this protocol is to give a clear description of how to perform the procedure and to discuss IHP as a treatment option for liver metastases of uveal melanoma.

Here, we present a protocol how to perform an isolated liver perfusion (IHP) with melphalan and we also discuss IHP as a treatment option for liver metastases of uveal melanoma.

隔离肝脏灌注作为治疗葡萄膜黑色素瘤肝转移

Isolated hepatic perfusion (IHP) is a procedure where the liver is surgically isolated and perfused with a high concentration of the chemotherapeutic ...

Dynamic Lung Tumor Tracking for Stereotactic Ablative Body Radiation Therapy

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable risks for normal tissue injury and the hazards of physical tumor miss. A first-of-its-kind SBRT platform achieves high-precision ablative radiation treatment through a combination of versatile real-time imaging solutions and sophisticated tumor tracking capabilities. It uses dual-diagnostic kV x-ray units for stereoscopic open-loop feedback of cancer target intrafraction movement occurring as a consequence of respiratory motions and heartbeat. Image-guided feedback drives a gimbaled radiation accelerator (maximum 15 x 15 cm field size) capable of real-time &#177;4 cm pan-and-tilt action. Robot-driven &#177;60&#176; pivots of an integrated &#177;185&#176; rotational gantry allow for coplanar and non-coplanar accelerator beam set-up angles, ultimately permitting unique treatment degrees of freedom. State-of-the-art software aids real-time six dimensional positioning, ensuring irradiation of cancer targets with sub-millimeter accuracy (0.4 mm at isocenter). Use of these features enables treating physicians to steer radiation dose to cancer tumor targets while simultaneously reducing radiation dose to normal tissues. By adding respiration correlated computed tomography (CT) and 2-[18F] fluoro-2-deoxy-&#7429;-glucose (18F-FDG) positron emission tomography (PET) images into the planning system for enhanced tumor target contouring, the likelihood of physical tumor miss becomes substantially less1. In this article, we describe new radiation plans for the treatment of moving lung tumors.

Stereotactic ablative body radiation therapy (SBRT) involves the precise delivery of high-dose radiation to cancer tumor targets. A novel SBRT platform offers a first-of-its-kind gimbaled radiation accelerator mounted within a pivoting O-ring gantry capable of dynamic image-guided tumor tracking. Here, we describe dynamic tumor tracking for lung targets.

动态肺肿瘤跟踪烧蚀立体定向放射身体治疗

Physicians considering stereotactic ablative body radiation therapy (SBRT) for the treatment of extracranial cancer targets must be aware of the sizeable ...

An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity is a commonly used model to study both acute lung injury and fibrosis, and multiple methods have been developed for administering bleomycin (and other toxic agents) into the lungs. However, many of these approaches, such as transtracheal instillation, have inherent drawbacks, including the need for strong anesthetics and survival surgery. This paper reports a quick, reproducible method of intratracheal intubation that involves mild inhaled anesthesia, visualization of the trachea, and the use of a surrogate spirometer to confirm exposure. As a proof of concept, 8-12 week old C57BL/6 mice were administered either 2.0 U/kg of bleomycin or an equivalent volume of PBS, and both damage and fibrotic endpoints were measured post-exposure. This procedure allows researchers to treat a large cohort of mice in a relatively short period with little expense and minimal post-procedure care.

This article presents a rapid and simple method for administering bleomycin directly into the mouse trachea via intubation. Key advantages of this method are that it is highly reproducible, easy to master, and does not require specialized equipment or lengthy recovery times.

在小鼠气管插管快速的改进方法

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn unresectable metastases into resectable ones. Some patients however, suffer from side effects or progression under systemic treatment. For patients with metastasized uveal melanoma there are no standard systemic therapy options. For patients without extrahepatic disease, isolated liver perfusion (IHP) may enable local disease control with limited systemic side effects. Previously, this was performed during open surgery with satisfying results, but morbidity and mortality related to the open procedure, prohibited a widespread application. Therefore, percutaneous hepatic perfusion (PHP) with simultaneous chemofiltration was developed. Besides decreasing morbidity and mortality, this procedure can be repeated, hopefully leading to a higher response rate and improved survival (by local control of disease). During PHP, catheters are placed in the proper hepatic artery, to infuse the chemotherapeutic agent, and in the inferior caval vein to aspirate the chemosaturated blood returning through the hepatic veins. The caval vein catheter is a double balloon catheter that prohibits leakage into the systemic circulation. The blood returning from the hepatic veins is aspirated through the catheter fenestrations and then perfused through an extra-corporeal filtration system. After filtration, the blood is returned to the patient by a third catheter in the right internal jugular vein. During PHP a high dose of melphalan is infused into the liver, which is toxic and would lead to life threatening complications when administered systemically. Because of the significant hemodynamic instability resulting from the combination of caval vein occlusion and chemofiltration, hemodynamic monitoring and hemodynamic support is of paramount importance during this complex procedure.

Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver

In this manuscript, we describe percutaneous isolated hepatic perfusion with simultaneous chemofiltration as treatment for unresectable liver metastases. This procedure is performed under general anaesthesia in the angiosuite by an experienced team, consisting of an interventional radiologist, a clinical perfusionist and anaesthesiologist.

经皮肝脏灌注（PHP）与美法仑作为囿于肝脏不能手术切除转移的治疗

Unresectable liver metastases of colorectal cancer can be treated with systemic chemotherapy, aiming to limit the disease, extend survival or turn ...

Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ischemia/reperfusion (I/R) injury with myriad negative consequences. Potential I/R injury in marginal organs destined for liver transplantation contributes to the current donor shortage secondary to a decreased organ utilization rate. A significant need exists to explore hepatic I/R injury in order to mediate its impact on graft function in transplantation. Rat liver hilar clamp models are used to investigate the impact of different molecules on hepatic I/R injury. Depending on the model, these molecules have been delivered using inhalation, epidural infusion, intraperitoneal injection, intravenous administration or injection into the peripheral superior mesenteric vein. A rat liver hilar clamp model has been developed for use in studying the impact of pharmacologic molecules in ameliorating I/R injury. The described model for rat liver hilar clamp includes direct cannulation of the portal supply to the ischemic hepatic segment via a side branch of the portal vein, allowing for direct segmental hepatic delivery. Our approach is to induce ischemia in the left lateral and median lobes for 60 min, during which time the substance under study is infused. In this case, pegylated-superoxide dismutase (PEG-SOD), a free radical scavenger, is infused directly into the ischemic segment. This series of experiments demonstrates that infusion of PEG-SOD is protective against hepatic I/R injury. Advantages of this approach include direct injection of the molecule into the ischemic segment with consequent decrease in volume of distribution and reduction in systemic side effects.

A unique rat liver hilar clamp model was developed for studying the impact of pharmacologic molecules in ameliorating ischemia-reperfusion injury. This model includes direct cannulation of the portal supply to the ischemic liver segment via a branch of the portal vein, allowing for direct hepatic delivery.

直接节段性肝内交付使用大鼠肝门部夹具模型方法

Major hepatic surgery with inflow occlusion, and liver transplantation, necessitate a period of warm ischemia, and a period of reperfusion leading to ...

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated arc therapy (VMAT) plans for patients with head/neck cancer and 4-field box plans for patients with cervical cancer. It is a combination of specially developed in-house software that uses an application programming interface to communicate with a commercial radiotherapy treatment planning system. It also interfaces with a commercial secondary dose verification software. The necessary inputs to the system are a Treatment Plan Order, approved by the radiation oncologist, and a simulation computed tomography (CT) image, approved by the radiographer. The RPA then generates a complete radiotherapy treatment plan. For the cervical cancer treatment plans, no additional user intervention is necessary until the plan is complete. For head/neck treatment plans, after the normal tissue and some of the target structures are automatically delineated on the CT image, the radiation oncologist must review the contours, making edits if necessary. They also delineate the gross tumor volume. The RPA then completes the treatment planning process, creating a VMAT plan. Finally, the completed plan must be reviewed by qualified clinical staff.

Radiation therapy is a highly complex cancer treatment that requires multiple specialists to create a treatment plan and provide quality assurance (QA) prior to delivery to a patient. This protocol describes the use of a fully automated system, the Radiation Planning Assistant (RPA), to create high-quality radiation treatment plans.

放射规划助理-一个流线型的全自动放疗治疗计划系统

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated ...

Predicting Treatment Response to Image-Guided Therapies Using Machine Learning: An Example for Trans-Arterial Treatment of Hepatocellular Carcinoma

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this study was to develop a method to predict response to intra-arterial treatment prior to intervention.
The method provides a general framework for predicting outcomes prior to intra-arterial therapy. It involves pooling clinical, demographic and imaging data across a cohort of patients and using these data to train a machine learning model. The trained model is applied to new patients in order to predict their likelihood of response to intra-arterial therapy.
The method entails the acquisition and parsing of clinical, demographic and imaging data from N patients who have already undergone trans-arterial therapies. These data are parsed into discrete features (age, sex, cirrhosis, degree of tumor enhancement, etc.) and binarized into true/false values (e.g., age over 60, male gender, tumor enhancement beyond a set threshold, etc.). Low-variance features and features with low univariate associations with the outcome are removed. Each treated patient is labeled according to whether they responded or did not respond to treatment. Each training patient is thus represented by a set of binary features and an outcome label. Machine learning models are trained using N - 1 patients with testing on the left-out patient. This process is repeated for each of the N patients. The N models are averaged to arrive at a final model.
The technique is extensible and enables inclusion of additional features in the future. It is also a generalizable process that may be applied to clinical research questions outside of interventional radiology. The main limitation is the need to derive features manually from each patient. A popular modern form of machine learning called deep learning does not suffer from this limitation, but requires larger datasets.

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. A method for predicting response to these therapies is proposed. The technique uses pre-procedural clinical, demographic, and imaging information to train machine learning models capable of predicting response prior to treatment.

用机器学习预测图像引导疗法的治疗反应--肝细胞癌的跨动脉治疗实例

Intra-arterial therapies are the standard of care for patients with hepatocellular carcinoma who cannot undergo surgical resection. The objective of this ...