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RINECKER PROTON THERAPY CENTER STATUS REPORT: FOURTH MONTH OF CLINICAL OPERATIONS, JULY ´09
PROTON SCANNING IN LUNG CANCER/BRONCHIAL CARCINOMA
An optimal diagnostic investigation of lung cancer and thus bronchial carcinomas also calls for positron emission tomography (PET-CT)
A suspicion of lung cancer, known medically as bronchial carcinoma, which prompts diagnostic clarification is manifested by persistent cough, bloody sputum or pain. Smoking and passive smoking, for example due to workplace exposure, are indicative risk factors. Every possible step is taken for the diagnostic investigation: Normal x-ray images of the lungs, CT scan of the lungs, often with special analyses such as, e.g., a three-dimensional representation of the bronchial tree and the blood vessels, possibly MRI and bronchoscopy, an endoscopic survey of the bronchi, mostly to remove small tissue samples. Additional examinations may include aspirations for microscopic analysis or mediastinoscopy, in which a tissue sample is taken from a site above the sternum; this is performed under anaesthesia.
A positron emission tomography in combination with a computed tomography (PET_CT) must by all means be performed following detection of a bronchial carcinoma in order to fully analyze the stage of the disease (staging), even if compulsory health insurance still to some extent attempts to block this procedure due to cost-saving measures (see monthly report for June): “The cancer cells appear to be “glowing” areas on the PET image, and can thus be accurately distinguished from healthy cells. Even tumour cell clusters that are only a few millimetres large (> 5 mm) can still be clearly recognised”, explains Dr. Christian Berchtenbreiter (photo). “Along with early and reliable detection of even the smallest cancer foci, the exact tumor dimensions can be determined simultaneously with the method. The prognosis and the choice of treatment are crucially dependent on the extent of the disease”.
Since 50% of patients with lung cancer (bronchial carcinoma) do not die from the original tumour but rather from metastases, chemotherapy in combination with surgery as well as radiation plays a decisive role. “There is a fundamental differentiation between small-cell (SCLC) and non-small-cell (NSCLC) bronchial carcinoma”, explains Dr. med. Jochem Walther, a chemotherapy specialist who is working together with the RPTC (photo). “Small-cell bronchial carcinoma is generally diagnosed at an advanced stage. These stages are successfully treated with polychemotherapies; however, rapidly occurring relapses unfortunately remain a significant problem. The number of treatment options for non-small-cell bronchial carcinoma has increased in recent years. Different subgroups benefit from differentiated chemotherapy protocols. Today, antibodies against structures on the tumour cell surface or against the formation of tumour vessels improve the success of chemotherapy. In the future, in the case of a mutated receptor status, a tyrosine kinase inhibitor will be approved for first-line therapy so that chemotherapy-free treatment will be possible for individual patients. All in all, these are the most significant advances in the direction of individualised, customised tumour therapy“.
How helpful is surgery?
Surgical procedures with removal of the tumour, adjacent parts of the lung and also local metastases, if necessary, are possible in tumour stages I-III as a pulmonary lobe resection; in the case of proliferative cases, a resection of one of the lungs is possible. The procedures present a critical problem: Patients who develop bronchial carcinoma nearly always have damaged lungs, for example, due to many years of smoking. Conventional surgery leads not only to further functional limitation by also simultaneously removing healthy lung tissue, but also strongly disrupts respiratory mechanics over several weeks, postoperatively. The approach via an incision in the ribcage requires the ribs to be spread such that they ultimately always break in the case of elderly patients, or it is necessary to remove parts of the ribs. Both procedures are painful after surgery and limit the patient’s oxygen intake even more. But there are ways of limiting this disadvantage and thus making the surgery more competitive with radiation. The director of the Department of Minimally Invasive Surgery at our associated Surgical Hospital Dr. Rinecker, PD Dr. med. Bernd Ablaßmaier (photo), who already pioneered this field in his postdoctoral work at the Humboldt University of Berlin, states: “Thoracoscopic surgery is performed with instruments similar to those used in established laparoscopic procedures in the abdomen. These fine instruments with diameters of only 2.5 to 10 mm allow us to go in between the ribs, leave them undamaged, and thus avoid postoperatively compromising respiratory mechanics. For this reason, thoracoscopic therapy, at least in certain stages of bronchial carcinoma (lung cancer), is superior to open surgery. Unfortunately, however, this thoracoscopic resection of bronchial carcinomas is not widely performed, since these procedures require a high degree of training and respectively long education."
Issues in Radiation
“Bronchial carcinomas require relatively high radiation doses in order to cure them,” explains Prof. Dr. Manfred Herbst, Medical Director of the RPTC (photo). “Healthy lung tissue hit by the radiation, however, tolerates much less. So-called pneumonitis, a radiation-related pulmonary inflammation, forms starting at around 20 Gray. This puts patients with damaged lungs at risk not only directly during and after radiation; often, the patient develops chronic lung damage with decreased pulmonary function, overall reduced ability to perform daily tasks or even a permanent need for treatment. When choosing a method of radiation, it is critical to reduce to the greatest extent possible the amount of healthy lung tissue that receives coincidental radiation. In particular, the other lung should not be irradiated at all – something which cannot be avoided with any of even the most modern x-ray methods. Proton beam therapy for bronchial carcinomas offers crucial advantages”.
Why is proton scanning performed under general anesthesia in the case of bronchial carcinomas?
Four methods are used at the RPTC to rule out unnecessary coincidental radiation of healthy lung tissue that would be only technically necessitated during x-rays, and thus spare the patient the associated collateral damage:
- Precision targeting system. Positional control of the patients in the seconds directly prior to the start of radiation (see monthly report May 2009) allows for the greatest targeting precision. We currently use an injection needle to place a gold particle in the area of the tumour for x-ray marking, which documents the target accuracy.
- The few radiation sessions required in proton beam therapy of lung cancer are performed under general anaesthesia with brief apnoea, to eliminate movements caused by the patient’s respiration. By means of a continuous supply of oxygen, there is no oxygen deficiency (see monthly report May 2009). Our patients have found this method to be very tolerable. The target accuracy achieved in this way is better than 2 mm! By eliminating the patient’s respiratory movements, we thus avoid unnecessary expansion of the radiation zones which would destroy healthy lung tissue. A method that is less attractive, in our opinion, can also be avoided, namely waiting for pauses in respiration to perform radiation; this lengthens the radiation time and yet reduces the target accuracy and at the very least makes it impossible to even verify it.
- As three-dimensional targetable particle radiation, protons stop directly in the bronchial carcinoma, i.e. behind the side of the tumour facing away from the radiation source, no more radiation exposure occurs. In contrast to the x-ray method, this also allows the opposite lung to be completely spared. This is the crucial advantage of proton beam radiation in lung cancer.
- Proton scanning: which advantage? In older proton beam facilities, such as at Loma Linda, Harvard/Boston and others, the scattering method is used, in which the proton beam is widened by a scattering body and subsequently contained again by templates (wherein the neutron scatter radiation that is produced here still additionally reaches the patient) and then is “showered“ over the tumour. This time-consuming method allows for very good adjustment of the radiation area to the “rear” contour of the tumour, however not the anterior wall of the tumour, on the side facing the radiation source. Thus, depending on the shape of the bronchial carcinoma, regions with the highest dose are produced outside of the tumour. Only the scanning method (see also previous monthly reports) at RPTC (used partly in rudimentary form also at other newer proton beam facilities) confines the highest dose alone to the tumour field by field and thus beam direction by beam direction.
“These advantages of the RPTC method can be easily quantified”, explains Mr. Christian Skalsky (photo) from the team of medical physicists at the RPTC. “Let us calculate an example (Comparison of lung cancer treatment x-ray and scanning proton beams at the RPTC) that combines the positive effects of optimised target accuracy, the elimination of respiratory movements, and the three-dimensional particle radiation with protons and the scanning system. This shows only one case, but bronchial carcinomas located elsewhere ultimately yield similar benchmarks:
Healthy tissue exposed to radiation (over 5 Gray) in the opposite lung
X-ray 170 ml
Protons 0 ml
Radiation-damaged healthy tissue in the lung affected with cancer (over 20 Gray)
X-ray 380 ml
Protons 200 ml
Resulting loss of healthy lung tissue measured on an average lung volume of 1870 ml
X-ray 30 %
Protons 11 %
THE SECOND TREATMENT ROOM AT THE RPTC WILL SOON BE OPEN FOR SERVICE
Capacity of the first gantry. The time required to finalise the remaining radiation rooms at the RPTC, in parallel with clinical operations and additional data acquisition limit the daily clinical working time of the first treatment room available to us (the so-called gantry) to less than 5 hours per day currently. We presently treat an average of 11 patients per day.
Bringing the second treatment room into service. The second gantry has been completed in the meantime and is currently in the quality assurance phase. Final clearances of radiation facilities are always done by the certifying authorities, which is the Landesamt für Umwelt in Bavaria. The authorised engineer began the required tests on 07 July 2009. Immediately after the tests have been completed, we anticipate the expansion of the CE certificate relating to the Medical Devices Directive by the manufacturer, Varian.
RPTC ROUTINE: PROTON BEAM TREATMENT OF PROSTATE CARCINOMA
A high patient intake. The RPTC cannot presently process the many patient enquiries – at the level of 50 calls at the Call Centre every workday – with our still-limited treatment capacity. Moreover, we are burdened by the many unexpected emergency referrals from local or regional clinics of patients, including children, who would not stand much of a chance with conventional radiation methods.
Recognised proton beam indications: Prostate cancer. More than 60,000 patients worldwide have received proton-beam radiation, a large proportion of which involved treatment for prostate cancer (prostate carcinoma). The RPTC also strives to not neglect this indication, despite the burdens described. Provisions are being made for this, in that the Gemeinsame Bundesausschuss der Ärzte und Krankenkassen (GBA) now approves payment for proton prostate cancer radiation by statutory health insurance. The GBA wishes to develop a proton/x-ray comparison for further clarification by 2018 (!) in order to reproduce here in Germany the cure rates in the United States that are superior for protons. The RPTC routinely documents all case data in order to be able to enter them (anonymised of course) into these tests. The treatment of prostate cancer is certainly a concern of ours! (see standard protocol prostate cancer, monthly report for May)