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Protons and ions in the right amount

Hadron therapy combats tumors more selectively and effectively than conventional radiation therapy

024-025_cancer proton_223in Heidelberg

Proton or carbon ion beams accelerated up to 225,000 meters per second, three-quarters of the speed of light, can penetrate 30 cm inside the human body with almost no damage to the biological tissue through which they travel. Almost all the energy of this flow of electrically charged subatomic particles is directed at the exact time and place in which protons or ions cease to move. This is known as the stopping point, and it can be controlled with pinpoint accuracy and directed at a tumor, which will then receive a dose of concentrated energy greater than the dose currently provided by conventional radiation therapy. In hadron therapy, the name given to this relatively new therapeutic approach against cancer, the probability is great that the tumor cells, and only they, will die due to the ionizing radiation.

“This concentration effect of particle energy at the stopping point is known as the Bragg peak,” says Thomas Haberer, the scientific and technical director of the center for ion beam therapy maintained by the University Hospital of Heidelberg, Europe’s most advanced center using protons and carbon ions for cancer treatment and research. Expensive and available in only about 40 hospitals or medical centers located in Asia, Europe, the United States, and South Africa (Brazil has none), hadron therapy has been used on approximately 112,000 patients in the last 20 years. About 90% of the patients received proton irradiation, which is considered the most promising for the most complicated cases; it is more powerful than that of traditional radiation therapy and has two to three times less energy than carbon ions.

Hadron therapy room in Heidelberg

Heidelberg University HospitalHadron therapy room in HeidelbergHeidelberg University Hospital

Classic radiation therapy uses photons, particles of light, to try to eradicate the cancer. X-rays are the type of light most often used against tumors. They are extremely useful in the fight against the disease, but there is a problem: before the x-rays reach the tumor, they lose part of their energy along the way and damage the DNA of normal cells with which they come in contact. Thanks to the Bragg peak, a physical and radiobiological characteristic peculiar to electrically charged subatomic particles, hadron therapy can be extremely lethal to tumors and, at the same time, almost innocuous to healthy tissue. “Carbon ions are heavier and have less side scatter than protons,” says Italian physicist Marco Durante, director of the Department of Biophysics of the GSI Helmholtz Centre for Heavy Ion Research in Darmstadt, which developed the technology used in Heidelberg. “This makes them more able to conform to the tumors. Their high load increases their biological properties and makes them able to deliver a powerful punch against radiation-resistant tumors.”

Opened in 2009, the center in Heidelberg to date has treated 2,200 patients, half with protons and half with carbon ions. “Since we follow standardized protocols, which recommend a limit on the daily dose of ionizing radiation, patients undergoing proton therapy do not need to be part of a clinical trial. But virtually all subjects treated with carbon ions participate in clinical trials,” says Dr. Haberer. In the realm of cancer treatment, only six places in the world use carbon ions that are heavier and more highly charged than protons. Three centers are in Japan (Chiba, Gunma and Hyogo), which has been doing hadron therapy for 20 years; one is in Lanzhou, China; another is in Pavia, Italy, in addition to the unit in Germany.

670 metric ton structure that directs the particle beams with pinpoint accuracy against tumors

HOSPITAL UNIVERSITÁRIO DE HEIDELBERG670 metric ton structure that directs the particle beams with pinpoint accuracy against tumorsHOSPITAL UNIVERSITÁRIO DE HEIDELBERG

Many patients who have undergone hadron therapy had tumors located in parts of the body that are difficult to access, such as the brain or lungs; many tumors were situated next to organs that could not be irradiated or simply were resistant to conventional treatments. Some forms of pediatric cancers are also likely targets for particle therapy, usually based on protons with less energy than carbon ions. There are studies showing an improved clinical picture and longer survival in patients who underwent particle therapy compared to conventional radiation therapy. But some doctors believe that more research is still needed in this regard. “The treatment is still somewhat controversial and some results require validation in comparative studies,” says João Victor Salvajoli, a radiologist at the São Paulo State Cancer Institute (Icesp) and the Heart Hospital (HCor). “But particle therapy may be more effective in certain selected cases, such as some childhood cancers, chordomas (tumors at the base of the skull) and choroidal melanoma. Brazil should have at least one proton therapy center for selected cases, teaching and research.”

Expensive therapy
To explore the possibilities of this form of radiation therapy, medical centers need a cyclotron or a synchrotron, circular particle accelerators responsible for producing the appropriate proton or ion speed needed for clinical use, and special facilities to house the peripheral equipment that isolates the radiation generated by hadron therapy. The Heidelberg center, which cost €120 million, is located in a three-story building and covers an area of 5,000 square meters. A giant steel structure, which weighs 670 metric tons and is 25 meters long and 13 meters wide, is connected to the synchrotron. It occupies three floors and is used to direct beams of particles with pinpoint accuracy to three therapy rooms.

The United States, where much of the technology and research on hadron therapy began decades ago, today has no treatment center that uses carbon ions, although there are 14 institutions using proton therapy. “It’s more a question of how the health system is funded in the United States, which is different from Europe and Asia,” says Stephen Peggs, a physicist at Brookhaven National Laboratory in New York State, who in February 2014 participated in a meeting to discuss the future of hadron therapy in the United States. “Today the system does not cover the costs of carbon ion therapy, only proton therapy.” Hadron therapy is expensive. In Heidelberg, it costs around R$75,000 to treat a patient.