LUNG CANCER AND HADRONTHERAPY

Methodology and its advantages

The most advanced front of Radiotherapy (RT) is now represented by Hadrontherapy (HT), which uses a beam of heavy subatomic particles with positive charge: protons or carbon ions (C).

Protons have charge + corresponding to hydrogen atoms deprived of their single electron. Carbon ions, heavier than protons, are charged ++ because they derive from the carbon released by its two electrons.

Protons and C ions have the ability to interact with the DNA molecule (in the nucleus of the tumor cell) despite the strong chemical bonds that characterizes this nucleic acid. The impact between protons or C ions and DNA is “rough”, “αδρος” in ancient Greek, which led to the definition of “Hadrontherapy” (HT) the procedure using these positively charged particles.

Instead, traditional radiotherapy (RT) uses X-rays, i.e. photons, quanta of an energy that is not corpuscular but ectromagnetic.

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From a physical point of view, a beam (‘Beam’ in the graph above) of protons or C ions (blue area) during the crossing of a biological organism (‘Penetration Depth’ in cm) releases into healthy tissues a much smaller amount of energy (‘Radiation Dose’) than a beam of photons used by RT (hazelnut-colored area). In the site to be treated (‘Tumor’), the RT arrives energetically de-upgraded, while the HT is pre-programmed so as to discharge, right in the area of clinical interest, all its energy by the so-called “Bragg peak.” At this complete release point, the radiation with ions is exhausted (‘Proton STOP’), while the X radiation of the RT continues to release energy in the healthy tissue tract that separates the cancer site from the exit point from the patient’s body.

Given this different property of energy transfer, protons or C ions have a therapeutic effect against the tumour target with an effectiveness three times higher than the photons used by the RT, such as a depth bomb which explodes in the sea at the predetermined distance from the surface.

Furthermore, in HT the volume of healthy tissue that the radiation must pass through to reach the neoplastic target, is reduced compared to RT.

The side effects are greater with RT because its photons release the maximum amount of energy already to the skin of the patient (point 0 cm in the graph) and in the subcutaneous, tissues that are instead substantially respected by protons and C ions. Therefore, positive ions are called more “selective” than RT X-rays.

RT in the lung can cause, as an unwanted effect, the so-called “ray pneumonia” for a recall of inflammatory cells in the tract of healthy lung parenchyma crossed by X radiation, such as to exclude it from respiratory function and to affect significantly the survival. With the progress of RT (by use of several X-ray emission points along the axial circumference of the patient’s body, all converging on the tumour site), pneumonia by radiation has become rarer, but not the exclusion from the ventilatory function of the tissue crossed by X-rays, which remains a serious drawback for patients with respiratory failure.

HT in these circumstances would be more effective and less likely to aggravate dyspnea.

 

Where

In Italy, HT is provided, at the expense of the national health system, in Pavia city about 30 km south of Milan, in the National Centre for Oncological Hadrontherapy (CNAO). It is one of the six European centres for treatment with protons and one of the three European centres for treatment with C ions. Among the latter three centres that use C ions is Lyon, with which CNAO is collaborating for two years in an international study aimed mainly at refining clinical indications and treatment protocols.

 

Lung cancer

In oncological practice, after chemotherapy the lung cancer is often treated with a cycle of radiant therapy.

In this phase, HT is mainly indicated for the treatment of neoplasms resistant to traditional RT, among which there are sarcomas.  Sarcomas are rare, originally develop in places other than the respiratory system, but often affect the lungs during their evolution, metastatically.

Instead, for tumors originating from the epithelium of the bronchi (bronchogenic carcinomas), we may find some patients at an early stage, but not operable for a number of reasons including a general poor state or advanced age. In these cases, radiant therapy is as effective as surgery if it does not produce heavy side effects, i.e. if it uses positive ions rather than X-rays. The 5-year survival of these patients is five percentage points higher with HT than with RT.

A particular condition that falls into this category is diffuse pulmonary interstitial disease. The fibrotizing thickening of the pulmonary three-dimensional network that supports the alveoli, in fact, contraindicates the surgical exeresis of the tumour in itself and, at the same time, limits the effectiveness of chemotherapy, with greater difficulty reaching the cancer site. In these conditions HT may be the most appropriate solution.

If the bronchogenic carcinoma is adjacent to the heart, the problem of the toxicity of radiant therapy on that organ is a critical element. It has been calculated that women with breast cancer treated with conventional RT have a risk of developing coronary artery disease with a probability of 7.4% for each Gray (measurement unit of radiotherapy) received from the heart. Even chemotherapy, usually taken before or during the cycle of radiant therapy, is not without a certain degree of cardiotoxicity. In theory, HT should also limits the cardiotoxicity of radiant treatment.

Finally, a study carried out on the involvement of lymph nodes located in the center of the chest, invaded by neoplastic cells from lung or esophageal cancer, has revealed the greater effectiveness of radiotherapy with C ions compared to protons and X-rays of conventional RT. A control status of isolated lymph node recurrences, with C ions is achieved wih the rate of 94% after 3 years from the end of treatment.

All these observations demonstrate the importance of HT in the treatment of particular situations of thoracic neoplasms.

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