The breath-hold technique has been used for a long time in radiotherapy of breast cancer to prevent heart damage. For the same reason, this technique is increasingly used in the irradiation of mediastinal lymphomas and, more recently, gastric lymphomas as well.1,2 Within Maastro, radiotherapist-oncologist BDP (Bastiaan) Ta has built up experience with this for the irradiation of mediastinal lymphomas. Radiotherapist-oncologist Dr Francisca Ong (Medical Spectrum Twente) recently presented the results of the implementation of this technique in gastric lymphomas during ESTRO 2022.3
With the breath-hold technique, the patient holds his breath several times until the complete irradiation fraction has been performed. This ensures that the heart is moved relative to the target area to be irradiated, so that less radiation reaches the heart.
Preventing late effects
Mediastinal lymphomas usually involve young patients with a good prognosis. “Most are between the ages of 20 and 40,” Ta says. “They have a very high chance of complete remission, so it is extremely important to avoid late effects. In the case of the heart, this mainly concerns acute coronary disorders, such as myocardial infarction or heart valve disease. Patients who received irradiation decades ago have an increased risk of serious cardiac complications for life compared to their peers. The dose-effect relationship between the mean number of grays entering the heart and the increased risk of cardiac complications appears to be linear and occurring earlier than previously suspected.”4
Advanced techniques
Secondary tumor induction due to radiation also plays a role in mediastinal lymphomas: patients have an increased risk of, among other things, breast cancer and lung carcinoma, depending on the dose in these healthy organs. Young smokers or people who have recently stopped smoking have a statistically higher risk of lung cancer in the area that has been irradiated.
“To qualify, today’s patients receive a lower total dose and are treated with advanced radiotherapy techniques,” says Ta, “including techniques with highly-conformal dose distributions, protons and radiation combined with breath-hold, reducing current doses in heart, lungs and breasts. be much lower.” In that sense, it makes sense to make a trial plan when in doubt as to whether a patient can undergo radiation. The chance that radiotherapy cannot be applied is lower than before.
Long Survival
In gastric lymphomas, the age distribution among patients is larger than in mediastinal lymphomas. “They are usually a bit older,” says Ong. “But they are still young enough to want to prevent heart damage. In most cases these are marginal zone (MALT) lymphomas, so you really go for curation. Survival is decades.”
Also in gastric lymphomas, radiation in deep inhalation has the advantage that the heart moves further away from the stomach, so that the dose to the heart can be reduced.5,6 The technique is already being used internationally in several institutes and has now also been introduced in Medisch Spectrum Twente. “During the introduction phase, all steps were checked extra and this was presented at the ESTRO. Only when we were sure that the quality was guaranteed did we adopt this technique as standard,” explains Ong. “Prior to each irradiation, a cone beam CT scan is made in deep inhalation. Usually in two breaths, because otherwise the patient will not last. We first had to make sure that the quality of this was sufficient to see the upper abdominal organs.” The daily cone beam CT scan then checks whether the stomach is properly positioned in the radiation field. Only if this is the case, radiation will be started.
Careful implementation
Ta estimates that half of the radiotherapy departments in our country apply a breath-hold technique for the irradiation of mediastinal lymphomas. “Such innovations have a long roll-out time,” he says. “It requires extensive preparatory work to technically guarantee that it can be carried out safely and can be properly monitored. The patient must also be able to hold their breath long enough, but fortunately this appears to be applicable for almost all patients, even if they are in a moderate condition.”
The patient is put on VR glasses that allow him to see the target area in which he needs to breathe. If he is outside this area, the system will immediately switch off the radiation. In addition to the breath-hold technique, monitoring a patient can be done in various ways. “We use the C-RAD system surface scanning, whereby during the CT scan – which is made for the radiation plan – a three-dimensional reference image of the patient contours is developed with several cameras. During irradiation, the patient contour is compared live with the reference image. As soon as this deviates too much, for example due to an exhalation, the radiation stops immediately.”
The point is that the approach takes more time. The net irradiation time is approximately three to ten minutes. “The total appointment time can be as much as 15 to 30 minutes or more as it involves a lot of preparation – connecting the devices, more extensive position verification with cone beam CTs, and more interruptions due to the breaths”, says Ta. “It also requires expertise from radiotherapeutic technicians with specific training.”
Video screen
Ong: “In our system, cameras register the movement of a block that is placed on the patient’s abdomen. We use a video screen instead of VR glasses. This is placed at eye level above the patient, so that the patients can check for themselves whether they have inhaled deeply enough. Patients experience it as very pleasant that they are so actively involved in their treatment. Of course, also with us, the irradiation device stops automatically when breathing goes outside the predetermined range.”
The application of the breath-hold technique for gastric lymphomas is still relatively new. But Ong states that the results of her research are sufficiently positive to introduce it as a standard for this patient category. “The doctor is present during the first irradiation and also checks halfway through the process whether this is going properly, as an extra safety guarantee,” she says. “But of course we work with a permanent team of radiotherapeutic technicians who have been specially trained for this.”
Follow-up research
In gastric lymphomas, large margins around the target area are needed, because changes in shape and volume of the stomach must be taken into account. A next step that Ong would like to take is to investigate whether the irradiation margin can be reduced. “I’m thinking of using adaptive radiation on our Ethos accelerator,” she says. “On the cone beam CT scan that is made prior to radiation, the organs imaged can be automatically drawn in by artificial intelligence in the software and adjusted manually if necessary. A new radiation plan is then calculated within a few minutes, taking into account the position of the organs at that time. A stomach that has changed significantly in shape or size is therefore always properly irradiated. In February 2020, we were the first hospital in the world to treat patients with prostate cancer in this way. The time required on the device is only 15 minutes. Patients with bladder carcinoma and cervical carcinoma are now also irradiated in this way and the indications are being expanded further. I think that great gains can also be made for gastric lymphomas, with a further reduction of the dose to the surrounding organs.”
Also for proton therapy?
Meanwhile, for mediastinal lymphomas, Ta has become interested in the possibility of translating the gain of the breath-hold technique in photon therapy to proton therapy. “We currently still do irradiation with protons while breathing freely,” he says. A small planning comparison study of ten patients from Maastro showed that doses in the critical organs were reduced even further with protons in breath-hold versus photons in breath-hold.
Ta: “My colleagues are now working on implementing this breath-hold technique on the proton device. This is an innovation working group, consisting of clinical physicists, radiotherapeutic technicians and radiotherapists, who will introduce the technique clinically for all thoracic malignancies, such as lung carcinoma, thymoma, lymphoma and breast cancer. Of course, the point remains that proton therapy may only be used if a certain minimum dose reduction can be achieved in healthy tissue. Patients will therefore still receive a plan comparison of the best photon technique versus the best proton technique. The proton plan currently provides the best dose reduction, but our breath-hold photon plan may approach this in some patients.”
In the treatment of gastric lymphomas, Ong does not immediately see room for further research in this area. “Our hospital has a collaboration agreement with the proton center of the UMC Groningen for the application of proton therapy,” she says. “But by applying the breath-hold technique in patients with gastric lymphoma, we hope to achieve such a high reduction in damage to the surrounding healthy tissue that a plan comparison shows insufficient benefit for protons and we can save the patient the trip to Groningen. The cardiac dose is reduced by 50% using the breath-hold technique and may be further reduced with adaptive irradiation. So I think we already achieve a sufficiently significant benefit for the patients with that.”
References:
- Aznar M, Maraldo M, Schut D, et al. Minimizing late effects for patients with mediastinal Hodgkin lymphoma: deep inspiration breath-hold, IMRT, or both? Int J Radiat Oncol Biol Phys. 2015;1:169-74.
- Aznar M, Ntentas G, Enmark M, et al. The role of motion management and position verification in lymphoma radiotherapy. Br J Radiol. 2021;94:0618.
- Ong F, Bouwhuis-Scholten S, Oude Hesselink C, et al. Deep inspiration breath hold and online CBCT verification in gastric lymphoma patients. Radiother Oncol. 2022;170, suppl 1:S269-70. ESTRO2022-DIBHmaaglymfoom-abstr.pdf.
- Van Nimwegen F, Schaapveld M, Cutter D, et al. Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma. J Clin Oncol. 2016;34:235-43.
- Christopherson K, Gunther J, Fang P, et al. Decreased heart dose with deep inspiration breath hold for the treatment of gastric lymphoma with IMRT. Clin Transl Radiat Oncol. 2020;24:79-82.
- Choi S, Park S, Lee J, et al. Combining deep inspiration breath hold and intensity-modulated radiotherapy for gastric mucosa-associated lymphoid tissue lymphoma: dosimetric evaluation using comprehensive plan quality indices. Radiat Oncol. 2019;14:59.
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