Everybody in our society's life is touched by cancer -- if not personally, then through a loved one, a family member, colleague, friend. And once our lives are touched by cancer, we quickly learn that there are basically three weapons, or three tools, that are available to fight the disease: surgery, radiation and chemotherapy. And once we get involved in the therapeutic decisions, again either personally or with our loved ones and family members, we also very quickly learn the benefits, the trade-offs and the limitations of these tools.
这个社会的每一个成员都会接触到癌症- 有的是本人不幸患病 有的是亲人 同事或者朋友得了癌症 一旦生命中接触到了癌症 我们很快就了解到 治疗癌症的 三种常见治疗手段是: 手术 放疗和化疗 一旦到了 选择治疗手段的时候 不论是自己的治疗 还是亲人朋友的 我们又很快了解到 各种治疗手段的 优劣之处
I'm very thankful to Jay and to Mark and the TEDMED team for inviting me today to describe a fourth tool, a new tool, that we call Tumor Treating Fields. Tumor Treating Fields were invented by Dr. Yoram Palti, professor emeritus at the Technion in Israel. And they use low-intensity electric fields to fight cancer. To understand how Tumor Treating Fields work, we first need to understand what are electric fields.
非常感谢杰和马克 以及TEDMED小组 邀请我 来介绍一种新的治疗手段 我们称做肿瘤治疗电场 肿瘤治疗电场这项技术的发明人是 以色列理工学院的荣誉教授尤兰姆・帕耳提医生 以色列理工学院的荣誉教授尤兰姆・帕耳提医生 他们利用低强度电场 来治疗癌症 来治疗癌症 要理解肿瘤治疗电场的工作原理 我们先来了解一下 什么是电场
Let me first address a few popular misconceptions. First of all, electric fields are not an electric current that is coursing through the tissue. Electric fields are not ionizing radiation, like X-rays or proton beams, that bombard tissue to disrupt DNA. And electric fields are not magnetism. What electric fields are are a field of forces. And these forces act on, attract, bodies that have an electrical charge.
首先澄清 几个常见误区 首先,电场 并不是流经身体组织的电流 并不是流经身体组织的电流 其次,电场 也不是电离辐射 比如X光或者质子光束 它们能攻击细胞组织 来扰乱DNA 第三,电场 也不是磁力 电场 是一种力场 这些力 能吸引和作用于 带电荷的物体
The best way to visualize an electric field is to think of gravity. Gravity is also a field of forces that act on masses. We can all picture astronauts in space. They float freely in three dimensions without any forces acting on them. But as that space shuttle returns to Earth, and as the astronauts enter the Earth's gravitational field, they begin to see the effects of gravity. They begin to be attracted towards Earth. And as they land, they're fully aligned in the gravitational field. We're, of course, all stuck in the Earth's gravitational field right now. That's why you're all in your chairs. And that's why we have to use our muscle energy to stand up, to walk around and to lift things.
最直观的理解方法是 类比重力 重力也是一种力场 它作用于物质 我们来想象一下太空中的宇航员 他们不受重力影响 在三维空间里自由漂浮 但是一旦航天飞机 回到地球 宇航员就进入地球的引力场 他们就开始受重力影响了 受到地球的吸引力 着陆时 重力场则完全作用于他们 当然我们现在正困在地球的重力场里 所以各位才能坐在椅子上 所以我们不得不利用肌肉力量 才能站起来,走动 和提起东西
In cancer, cells rapidly divide and lead to uncontrolled tumor growth. We can think of a cell from an electrical perspective as if it's a mini space station. And in that space station we have the genetic material, the chromosomes, within a nucleus. And out in the cytoplasmic soup we have special proteins that are required for cell division that float freely in this soup in three dimensions. Importantly, those special proteins are among the most highly charged objects in our body. As cell division begins the nucleus disintegrates, the chromosomes line up in the middle of the cell and those special proteins undergo a three-dimensional sequence whereby they attach and they literally click into place end-on-end to form chains. These chains then progress and attach to the genetic material and pull the genetic material from one cell into two cells. And this is exactly how one cancer cell becomes two cancer cells, two cancer cells become four cancer cells, and we have ultimately uncontrolled tumor growth.
恶性肿瘤里 细胞能迅速分裂 肿瘤的增大就一发不可收拾 从电学的角度 我们可以把肿瘤想象成 一个小型的空间站 在这个“空间站”里, 遗传物质染色体 位于细胞核内 细胞核外的细胞质中 有细胞分裂过程中 需要的一种特殊蛋白质 这些蛋白质在细胞质中 自由漂浮 关键的是,这些特殊的蛋白质 是人体中携带大量电荷的部分 是人体中携带大量电荷的部分 细胞分裂前期 细胞核分裂 染色体排列在 细胞中 那些特殊蛋白质物质 经过三维排序 从而能够 端点相连 形成链条 这些链条 就会进一步连上 遗传物质 然后将这些遗传物质 从一个细胞拉进两个细胞里 这就是一个癌细胞分裂生两个的过程 这就是一个癌细胞分裂生两个的过程 两个癌细胞再变成四个 最后变成 无限增长的肿瘤
Tumor Treating Fields use externally placed transducers attached to a field generator to create an artificial electric field on that space station. And when that cellular space station is within the electric field, it acts on those highly charged proteins and aligns them. And it prevents them from forming those chains, those mitotic spindles, that are necessary to pull the genetic material into the daughter cells. What we see is that the cells will attempt to divide for several hours. And they will either enter into this so-called cellular suicide, programmed cell death, or they will form unhealthy daughter cells and enter into apoptosis once they have divided. And we can observe this.
肿瘤处理电场 利用配有一个电场生成器的外置传感器 利用配有一个电场生成器的外置传感器 来人工制造电场 作用于那个“空间站” 当那个细胞“空间站” 位于电场内时 电场就能作用于那些高电荷的物质 将其排序 进而阻碍其形成链条 那些有丝分裂纺锤体 纺锤体是把遗传物质拖放到 子细胞的必要条件 我们就能看到细胞尝试数小时 进行分裂 最后它们要么进入 所谓的细胞自杀 一种程序化的细胞死亡 或者最后形成非正常的子细胞 一旦分裂后 细胞就死亡 我们可以观察到这些
What I'm going to show you next are two in vitro experiments. This is cultures, identical cultures, of cervical cancer cells. And we've stained these cultures with a green florescent dye so that we can look at these proteins that form these chains. The first clip shows a normal cell division without the Tumor Treating Fields. What we see are, first of all, a very active culture, a lot of divisions, and then very clear nuclei once the cells have separated. And we can see them dividing throughout. When we apply the fields -- again, in the identical time-scale to the identical culture -- you're going to see something different. The cells round up for division, but they're very static in that position. We'll see two cells in the upper part of the screen attempting to divide. The one within the circle manages. But see how much of the protein is still throughout the nucleus, even in the dividing cell. The one up there can't divide at all. And then this bubbling, this membrane bubbling, is the hallmark of apoptosis in this cell.
下面我将展示一下 两个体外试验 这是两个完全一样的培养基 培养的子宫癌细胞 我们用绿色萤光染料将 培养基染色 这样我们就能看到这些蛋白质 是如何形成链条的 第一条短片 是一个正常的细胞分裂 没有治疗电场的干涉 我们能看到 首先是一个非常活跃的培养基 大量的分裂 一旦细胞分裂开来 就有非常清晰的细胞核 我们从从头至尾看到分裂过程 然后我们使用了电场- 同样的时间尺度 同样的培养基 你会看到不一样的东西 细胞开始分裂 但是都静止在原来的位置上 我们看到 屏幕上方的两个细胞 尝试分裂 圆圈内的这个分裂了 但是看看有多少蛋白质 仍然贯穿细胞核 甚至是在细胞分裂时 上面的那个根本无法分裂 然后细胞膜就起泡 这是细胞死亡的 一个标志特征
Formation of healthy mitotic spindles is necessary for division in all cell types. We've applied Tumor Treating Fields to over 20 different cancers in the lab, and we see this effect in all of them. Now importantly, these Tumor Treating Fields have no effect on normal undividing cells.
有丝分裂纺锤体的正常形成 对每一种细胞的分裂繁殖 是一个必要的条件 我们已经把肿瘤治疗电场 在实验室中对20种不同的癌细胞进行了试验 实验结果表明 全部有效果 重要的是 肿瘤治疗电场对于 正常不分裂的细胞没有影响
10 years ago, Dr. Palti founded a company called Novocure to develop his discovery into a practical therapy for patients. In that time, Novocure's developed two systems -- one system for cancers in the head and another system for cancers in the trunk of the body. The first cancer that we have focused on is the deadly brain cancer, GBM. GBM affects about 10,000 people in the U.S. each year. It's a death sentence. The expected five year survival is less than five percent. And the typical patient with optimal therapy survives just a little over a year, and only about seven months from the time that the cancer is first treated and then comes back and starts growing again.
十年前 帕尔提医生创立一个公司叫Novocure 致力于把这个发现 变成临床实用的疗法 那时Novocure开发了两个系统 一个针对头部的肿瘤 另一个是针对躯干上的肿瘤 我们针对的第一个癌症 是致命的脑癌GBM(多形性胶质母细胞瘤) 在美国每年有将近一万人 受此病折磨 患上脑癌如同被判死刑 不足百分之五的患者 能够存活到五年 大多数病人 接受了最好的治疗后 也只能撑过一年多一点 首次接受治疗后 仅仅约是七个月 癌症就会复发继续扩大
Novocure conducted its first phase three randomized trial in patients with recurrent GBM. So these are patients who had received surgery, high dose radiation to the head and first-line chemotherapy, and that had failed and their tumors had grown back. We divided the patients into two groups. The first group received second-line chemotherapy, which is expected to double the life expectancy, versus no treatment at all. And then the second group received only Tumor Treating Field therapy. What we saw in that trial is that that the life expectancies of both groups -- so the chemotherapy treated group and the Tumor Treating Field group -- was the same. But importantly, the Tumor Treating Field group suffered none of the side effects typical of chemotherapy patients. They had no pain, suffered none of the infections. They had no nausea, diarrhea, constipation, fatigue that would be expected.
Novocure进行了 第一阶段的三个随即试验 病人都是GBM复发 他们都曾 接受过手术 高强度的头部放疗 和一线化疗 然而这些都失败了,肿瘤复发 我们把病人分成两组 第一组接受二线化疗 对比完全不接受治疗的病人 预期能够延长一倍存活寿命 第二组 只接受肿瘤治疗电场的治疗 在这个实验中 我们看到两组- 放疗组 和肿瘤治疗电场治疗组 预期寿命是一样的 但重要的是 接受肿瘤治疗电场的对照组 没有遭受任何化疗的 副作用 没有疼痛 没有感染 没有恶心或腹泻 便秘或疲劳 这些可能的症状
Based on this trial, in April of this year, the FDA approved Tumor Treating Fields for the treatment of patients with recurrent GBM. Importantly, it was the first time ever that the FDA included in their approval of an oncology treatment a quality of life claim.
基于今年4月的试验 基于今年4月的试验 FDA批准了肿瘤治疗电场法 用于GBM复发病人的 治疗 这是FDA首次 把生命质量的要求 放入对肿瘤治疗的 批准条款
So I'm going to show you now one of the patients from this trial. Robert Dill-Bundi is a famous Swiss cycling champion. He won the gold medal in Moscow in the 4,000 meter pursuit. And five years ago, Robert was diagnosed with GBM. He received the standard treatments. He received surgery. He received high dose radiation to the head. And he received first-line chemotherapy. A year after this treatment -- in fact, this is his baseline MRI. You can see that the black regions in the upper right quadrant are the areas where he had surgery. And a year after that treatment, his tumor grew back with a vengeance. That cloudy white mass that you see is the recurrence of the tumor.
所以我将 展示一位 来自此试验的病人 罗伯特・狄尔邦迪 是著名瑞士自行车赛冠军 他曾在莫斯科 四千米竞赛中获得金牌 五年前 罗伯特被诊断为GBM 他接受了标准疗法 实施了手术 接受了高强度的放疗 也接受了一线化疗 治疗后一年- 这是他的脑部核磁共振成像的基线 右上角的 黑色区域 就是手术的部位 治疗一年后 肿瘤复发 图上大块的白色云状物 就是复发的肿瘤
At this point, he was told by his doctors that he had about 3 months to live. He entered our trial. And here we can see him getting the therapy. First of all, these electrodes are noninvasive. They're attached to the skin in the area of the tumor. Here you can see that a technician is placing them on there much like bandages. The patients learn to do this themselves And then the patients can undergo all the activities of their daily life. There's none of the tiredness. There's none of what is called the "chemo head." There's no sensation. It doesn't interfere with computers or electrical equipment. And the therapy is delivered continuously at home, without having to go into the hospital either periodically or continually.
当时医生告诉他 只有三个多月的寿命了 他加入了我们的试验 这里我们可以看到他在接受治疗 首先这些电极是体外的 它们附着在肿瘤的对应范围内的皮肤上 它们附着在肿瘤的对应范围内的皮肤上 这儿你可以看到 一位技术人员正把绷带模样的东西放上去 病人会自己学习操作 这样一来 病人就可以正常进行日程活动 没有疲乏症状 没有chemo head症状(记忆力减退,思维能力下降等) 感觉不到装置 不需要电脑或电子设备 不需要电脑或电子设备 治疗可以在家中 持续进行 不必不停或者时不时地 往医院跑
These are Robert's MRIs, again, under only TTField treatment. This is a therapy that takes time to work. It's a medical device; it works when it's on. But what we can see is, by month six, the tumor has responded and it's begun to melt away. It's still there. By month 12, we could argue whether there's a little bit of material around the edges, but it's essentially completely gone. It's now five years since Robert's diagnosis, and he's alive, but importantly, he's healthy and he's at work. I'm going to let him, in this very short clip, describe his impressions of the therapy in his own words.
这些是罗伯特仅接受了肿瘤治疗电场法之后 的核磁共振成像图 这个治疗得花上不少时间才能起效 这是个医疗设备 打开时才工作 但是我们看到,第六个月 肿瘤就有了变化 开始缩小 不过还在那儿 12月的时候 可以说 只有周边还有一些残余 但是大部分是消失了 现在是罗伯特被确诊为GBM后的 第五年 他仍然活着 更重要的是,他很健康 还在工作 让他来在这个短片里 亲自介绍一下 他对治疗的感受
(Video) Robert Dill-Bundi: My quality of life, I rate what I have today a bit different than what most people would assume. I am the happiest, the happiest person in the world. And every single morning I appreciate life. Every night I fall asleep very well, and I am, I repeat, the happiest man in the world, and I'm thankful I am alive.
(视频)罗伯特・狄尔邦迪:我现在的 生命质量 我觉得 人们可能意想不到 我是这世上最最开心的人 每个早晨我都感谢生命 每个晚上我都沉沉熟睡 我的确是 世界上最开心的人 我很感激我还活着
BD: Novocure's also working on lung cancer as the second target. We've run a phase two trial in Switzerland on, again, recurrent patients -- patients who have received standard therapy and whose cancer has come back. I'm going to show you another clip of a woman named Lydia. Lydia's a 66 year-old farmer in Switzerland. She was diagnosed with lung cancer five years ago. She underwent four different regimes of chemotherapy over two years, none of which had an effect. Her cancer continued to grow. Three years ago, she entered the Novocure lung cancer trial.
BD:Novocure对肺癌也有效 这是第二目标 我们在瑞士进行了 第二期临床试验 也是针对复发患者 病人都曾接受过标准治疗 而癌症又复发了 我将展示一个视频 来自一位叫莉迪雅的女士 莉迪雅是名66岁的农妇 住在瑞士 五年前 她被诊断为肺癌 她在两年内接受了四种不同的化疗 她在两年内接受了四种不同的化疗 没有一个有效果 她的肿瘤持续增大 三年前 她参加了Novocure的肺癌临床试验
You can see, in her case, she's wearing her transducer arrays, one of the front of her chest, one on the back, and then the second pair side-to-side over the liver. You can see the Tumor Treating Field field generator, but importantly you can also see that she is living her life. She is managing her farm. She's interacting with her kids and her grand kids. And when we talked to her, she said that when she was undergoing chemotherapy, she had to go to the hospital every month for her infusions. Her whole family suffered as her side effect profile came and went. Now she can run all of the activities of her farm. It's only the beginning.
可以看到 她携带着她的传感器设备 一个在胸前一个在背后 另一副并排放在肝部上方 你能看到肿瘤治疗电场的生发器 但更重要的可以看到她仍然照常生活 经营她的农场 她和儿女还有孙子孙女们一起玩乐 我们和她聊天的时候 她说当她接受化疗时 每个月她得去医院接受输液 她的整个家庭因为 她的治疗副作用而遭罪 现在她能自己 从事农场的所有活计 这只是开始
(Applause)
(掌声)
In the lab, we've observed tremendous synergies between chemotherapy and Tumor Treating Fields. There's research underway now at Harvard Medical School to pick the optimum pairs to maximize that benefit. We also believe that Tumor Treating Fields will work with radiation and interrupt the self-repair mechanisms that we have. There's now a new research project underway at the Karolinska in Sweden to prove that hypothesis.
在实验室里,我们观察到了很多 化疗和肿瘤处理场的协同增进效果 这些试验正在哈佛医学院进行 来挑选出最优组合 最大化效果 我们也相信肿瘤治疗电场能和放疗协调工作 从而阻断肿瘤的自我修复机制 这是一项在瑞典的Karolinska 进行的新研究项目 来证实我们的假设
We have more trials planned for lung cancer, pancreatic cancer, ovarian cancer and breast cancer. And I firmly believe that in the next 10 years Tumor Treating Fields will be a weapon available to doctors and patients for all of these most-difficult-to-treat solid tumors. I'm also very hopeful that in the next decades, we will make big strides on reducing that death rate that has been so challenging in this disease.
我们还有更多的临床实验 针对肺癌的 胰腺癌,卵巢癌 还有乳腺癌 我坚信 未来十年里 肿瘤治疗电场 将成为医生和患者的武器 来对付所有顽固的实质固态肿瘤 我也希望 在未来十年 我们能在 减少以上疾病的死亡率上 有更大的进步
Thank you.
谢谢
(Applause)
(掌声)