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.
Rak utiče na život svih ljudi u našem društvu, ako ne baš lično, onda je deo priče naših voljenih, članova porodice, kolega, prijatelja. U momentu kada rak prodre u naše živote, veoma brzo naučimo da postoje u osnovi tri tipa oružja, tri alata, kojima se borimo protiv ove bolesti: operacija, zračenje i hemoterapija. U momentu kada postanemo deo donošenja odluka o terapiji bilo baš lično ili preko naših voljenih i članova porodice, veoma brzo shvatimo prednosti, sporedne efekte i ograničenja ovih alata.
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.
Veoma sam zahvalan Džeju i Marku i ekipi TEDMED-a na pozivu da vam danas opišem četvrto oruđe, novo oruđe, koje nazivamo "Polja za tretiranje tumora". Polja za tretiranje tumora je izumeo dr Joram Palti, počasni profesor na Tehnionu u Izraelu. Oni koriste električna polja slabe jačine u borbi protiv raka. Da bismo razumeli kako ova polja rade, moramo prvo shvatiti šta su električna polja.
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.
Prvo bih obrazložio nekoliko opštih pogrešaka. Pre svega, električna polja nisu električna struja koja prolazi kroz tkivo. Električna polja nisu jonizujuće zračenje kao što su X-zraci ili snopovi protona, koji bombarduju tkivo kako bi uništili DNK. Električna polja nisu ni magnetizam. Električna polja su polje sila. Ove sile ispoljavaju svoje dejstvo, deluju protiv tela koja imaju električnu maržu.
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.
Najbojli način da predstavite električno polje je da zamislite gravitaciju. Gravitacija je takođe polje sila koje deluje na masu. Svi možemo da zamislimo astronaute u svemiru. Oni slobodno plutaju u trodimenzionalnom prostoru bez ikakve sile koja deluje na njih. Ali kada se svemirska letelica vrati na Zemlju, i kada astronauti uđu u gravitacioni prostor Zemlje, oni počnu da osećaju uticaj gravitacije. Zemlja počinje da ih privlači. U momentu prizemljenja su u potpunosti pod dejstvom gravitacionog polja. Naravno, svi smo sada privezani gravitacionom silom za Zemlju. Usled toga ste svi u svojim stolicama. Zato moramo da koristimo energiju u mišićima kako bismo ustali, šetali okolo i kako bismo podigli stvari.
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.
U slučaju raka, ćelije se brzo umnožavaju što dovodi do nekontrolisanog rasta tumora. Ćeliju možemo zamisliti sa stanovišta elekricizma kao mini kosmičku stanicu. U toj stanici se nalazi genetički materijal, hromozomi, u jedru. A izvan toga, u citoplazmi se nalaze posebni proteini, koji su neophodni kako bi se ćelije delile, koji slobodno plutaju u tom buljonu u sve tri dimenzije. Značajno je da su ti posebni proteini među najelektrisanijim objektima u našem telu. Kada počne ćelijska deoba dolazi do dezintegracije jedra, hromozomi se poređaju u ravan na sredini ćelije i ovi posebni proteini prolaze kroz seriju događaja pri čemu se prikače i bukvalno se uklope jedan za drugog kako bi formirali lanac. Ovi lanci se potom izdužuju kako bi se prikačili za genetički materijal i razdvojili taj genetički materijal iz jedne u dve ćelije. Upravo na ovaj način od jedne ćelije raka nastanu dve, od dve ćelije raka nastanu četiri, i na kraju dođe do nekontrolisanog rasta tumora.
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.
Ova tehnologija koristi spoljašnje transduktore koji su povezani za generatorom polja kako bi stvorile veštačko električno polje u toj kosmičkoj stanici. Kada je ćelijska kosmička stanica u okviru tog električnog polja ona deluje na te visoko naelektrisane proteine i poređa ih u red. To ih sprečava da naprave te lance, to deobno vreteno, koje je neophodno da bi se genetički materijal razdvojio u dve ćerke ćelije. Uočili smo da ćelije pokušavaju da se podele po nekoliko sati. Ili će doći do takozvanog samoubistva ćelije, to je programirana ćelijska smrt, ili će od njih nastati nezdrave ćerke ćelije koje će ući u proces apoptoze nakon ćelijske deobe. Možemo to uočiti.
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.
Ono što ću vam sada pokazati su dva in vitro eksperimenta. Ovo su kulture, identične kulture, ćelija raka grlića materice. Obeležili smo ove ćelije zelenom fluorescentnom bojom kako bismo mogli da posmatramo proteine koji formiraju te lance. Prvi snimak prikazuje normalnu ćelijsku deobu bez primene "Polja za tretiranje tumora". Možemo uočiti pre svega veoma aktivnu kulturu, mnogo deoba, a potom veoma jasno definisana jedra nakon razdvajanja ćelija. Možemo uočiti ceo proces ćelijske deobe. Kada primenimo polja, ponovo, u istom vremenskom periodu na istovetnu kulturu, videćete nešto drukčije. Ćelije se spreme za deobu, ali su veoma statične u tom momentu. Možemo uočiti dve ćelije u pokušaju ćelijske deobe u gornjem delu ekrana. Ćeliji u okviru kruga to i uspeva. Ali uočite koliko je proteina ostalo u jedru čak i u ćeliji koja se deli. Ova gore ne može da se podeli uopšte. Ovo bubrenje, bubrenje membrane, je zaštitni znak apoptoze kod ćelija.
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.
Formiranje funkcionalnog deobnog vretena je neophodno za deobu svih tipova ćelija. Primenili smo "Polja za tretman tumora" na oko 20 različitih tipova raka u laboratoriji, i uočavamo isti efekat kod svih tipova. Značajno je to da ova "Polja za tretman tumora" nemaju nikakav efekat na ćelije koje nisu u procesu deobe.
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.
Dr. Palti je pre 10 godina osnovao kompaniju "Novocure" kako bi svoje otkriće razvio do nivoa primene u lečenju pacijenata. U tu svrhu "Novocure" je razvio dva sistema - jedan za primenu u slučaju raka mozga, i drugi za lečenja raka trupa tela. Prvi tip raka na koji smo se skoncentrisali je smrtonosni rak mozga, glioblastoma (GBM). Od GBM-a oboli oko 10.000 osoba u SAD-u svake godine. To je smrtna kazna. Verovatnoća za petogodišnje preživljanje je manja od 5 odsto. Tipičan pacijent koji prima optimalnu terapiju će živeti malo duže od godinu dana, i samo sedam meseci od perioda kada je lečenje raka počelo i kada dođe do relapsiranja tumora.
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" je sproveo prvu studiju treće faze uz nasumičan izbor pacijenata sa relapsirajućim GBM-om. To su pacijenti koji su bili podvrgnuti operacijama, visokoj dozi zračenja glave i inicijalnoj hemoterapiji, sve to je bilo bezuspešno i tumor je relapsirao. Podelili smo pacijente u dve grupe. Prva grupa pacijenata je tretirana sekundarnim režimom hemoterapije, koja bi trebalo da udvostruči period preživljavanja, u poređenju sa periodom preživljavanja bez ikakvog tretmana. Druga grupa pacijenata je bila podvrgnuta lečenju "Poljima za tretiranje tumora". Ono što smo uočili u studiji je da je period preživljavanja u slučaju obe grupe, dakle i onih koji su tretirani hemoterapijom, i onih koji su tretirani "Poljima za tretiranje tumora", bio jednak. Međutim, ljudi koji su tretirani poljima koja leče tumor nisu patili ni od jedne kontraindikacije koje su tipične za hemoterapiju. Nisu bili u bolovima, nije došlo do infekcija. Nije bilo mučnine, dijareje, zatvora, zamora što bi bilo očekivano.
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.
Na osnovu ove studije, iz aprila ove godine, Administracija za hranu i lekove je odobrila upotrebu "Polja za tretiranje tumora" za lečenje bolesnika koji pate od relapsirajuće forme GBM-a. Ono što je važno je da je Administracija po prvi put u svojim formularima za odobrenje primene onkološkog tretmana navela kvalitet života kao prednost.
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.
Pokazaću vam sada jednog pacijenta iz studije. Robert Dil-Bandi je poznati švajcarski šampion u biciklizmu. Osvojio je zlatnu medalju u Moskvi u trci na 4.000 metara. Pre pet godina, Robertu je dijagnostikovan GBM. Lečen je standardnim protokolima. Podvrgnut je operaciji. Primio je visoku dozu zračenja glave. I dobio je inicijalnu hemoterapiju. Godinu dana nakon tog tretmana, ovo je ustvari njegov osnovni MR snimak. Ovi crni delovi koje možete videti u gornjem desnom kvadrantu su delovi koji su bili podvrgnuti operaciji. Godinu dana nakon tretmana, tumor se povratio u još agresivnijoj formi. Ova magličasta bela masa koju možete videti je tumor koji se ponovo stvorio.
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.
U tom momentu lekari su mu rekli da mu je ostalo još oko tri meseca života. Uključili smo ga u našu studiju. Ovde ga možemo videti u fazi lečenja. Pre svega, ovo su neinvazivne elektrode. Prikačene su za kožu u predelu tumora. Možete videti ovde tehničara kako ih postavlja na sličan način kao i zavoj. Pacijenti nauče da sami ovo rade. Nakon toga pacijenti mogu nastaviti sa uobičajenim dnevnim aktivnostima. Ne dolazi do zamora. Ne dolazi do sindroma nazvanog "hemo-glava". Ništa se ne oseća. To ne interferira sa računarima ili električnom opremom. Terapija se kontinuirano primenjuje kod kuće i nije potrebno odlaziti u bolnicu, bilo periodično ili stalno.
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.
Ovo su Robertovi MR snimci, ponovo, pri isključivoj primeni terapije polja koja leče tumor. Neophodno je vreme da bi ova terapija delovala. To je medicinski uređaj, radi kada je uključen. Ali možemo da vidimo da već u šestom mesecu dolazi do delovanja na tumor koji počinje lagano da nestaje. Još uvek je tamo. Ovde, u dvanaestom mesecu možemo polemisati da li je preostalo nešto tkiva tumora oko samih ivica ali je u principu nestao potpuno. Prošlo je pet godina od uspostavljanja Robertove dijagnoze i on je živ, i što je važno, on je zdrav i radi. U ovom kratkom filmu će vam on opisati svojim rečima utiske o terapiji.
(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.
(Snimak) Robert Dil-Bandi: Kvalitet mog života, ja ocenjujem ono što danas posedujem malo drukčije u odnosu na ono što bi većina ljudi pretpostavila. Ja sam najsrećnija, najsrećnija osoba na svetu. Svakog jutra ja slavim život. Svake noći lako zaspim, i ja sam, ponavljam, najsrećniji čovek na zemlji, i zahvalan sam što sam živ.
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" takođe radi na raku pluća, to je novi cilj. Sprovodimo drugu fazu studije u Švajcarskoj i to ponovo na pacijentima sa relapsirajućim tumorom, to su pacijenti koji su bili podrvgnuti standardnim tretmanima a rak se ponovo javio. Pokazaću vam još jedan snimak, o ženi koja se zove Lidija. Lidija ima 66 godina i ona je poljoprivrednik u Švajcarskoj. Dijagnostifikovan joj je rak pluća pre pet godina. U toku lečenja primila je četiri različita režima hemoterapije u periodu od dve godine, ni jedan od njih nije pokazao efekat. Njen rak je nastavljao da raste. Pre tri godine je pristupila studiji "Novocure"-a za lečenje raka pluća.
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.
Možete vidti da u njenom slučaju ona nosi provodničke mreže, jednu na grudima, jednu na leđima, i još jedan par koji je postavljen jedan do drugog oko jetre. Možete uočiti i punjač "Polja za tretiranje tumora" ali još važnije možete videti da ona živi svoj život. Ona održava svoje imanje. Druži se sa svojom decom i unucima. U razgovoru nam je rekla da je morala da ide u bolnicu svakog meseca kako bi primila svoju dozu, dok se lečila hemoterapijom. Čitava njena porodica je patila dok je posmatrala nuz-pojave lečenja kako se javljaju i nestaju. Sada može da se bavi svim delatnostima na svom imanju. To je samo početak.
(Applause)
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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.
U laboratoriji smo uočili neverovatne sinergističke efekte hemoterapije i polja koja leče rak. U Školi medicine Harvarda je trenutno u toku istraživanje koje iznalazi najbolje parove terapija koje bi pojačale prednosti tretmana. Takođe verujemo da će "Polja za tretiranje raka" davati dobre rezultate u sinergiji sa zračenjem pri onesposobljavanju mehanizama za reparaciju koje nosimo u sebi. Novi istraživački projekat, koji treba da dokaže tu hipotezu, treba da počne na institutu Karolinska u Švedskoj.
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.
Planirali smo još studija za izučavanje raka pluća, raka gušterače, raka jajnika i raka dojki. Ja zaista verujem da će u narednih deset godina Polja za tretiranje tumora biti dostupno oruđe za lekare i pacijente za sve ove veoma teške forme tumora tvrdog tkiva. Takođe se nadam da ćemo u narednim decenijama učiniti velike pomake u smanjenju stope smrtnosti koja je već toliko dugo istinski izazov kod ove bolesti.
Thank you.
Hvala vam.
(Applause)
(aplauz)