This study demonstrated that HFOV controlled respiration during heavy iron radiation therapy was safety with stable hemodynamics and gas exchange. In addition, HFOV could significantly decreased the diaphragm movement, which was ideal for tumor location during radiation therapy. This is the first study to show the safety and efficacy of HFOV during heavy iron therapy.
The heavy ion therapy has two major advantages compared to traditional photon therapy. One is the advantage of the Bragg peak physics, and the other is the relative radiation biological effect. The Bragg peak's occurrence in the depth of the biological body is highly sensitive to the entry of carbon ions, meaning that once a certain amount of carbon ion energy enters the body, the location where the Bragg peak occurs remains fixed at a specific depth. Therefore, when the tumor's position shifts due to respiratory movement, it can cause an accumulation of radiation dose from carbon ions at the wrong location, leading to a dual loss in treatment - where the treatment fails to reach the intended area while causing harmful radiation to unintended areas.
Respiratory motion is a major factor affecting the positioning of thoracoabdominal tumors during radiation therapy. The relationship between tumor motion and respiratory motion is closely intertwined, with their cycles and amplitudes being fundamentally synchronized. Therefore, in the absence of other interfering factors, tumor motion can be attributed mainly to respiratory motion [8]. Due to the influence of motion on the diaphragm during respiration, tumors located in the lower lung and upper abdomen are more prone to moving "off-target", which suggests that tumors can move up to 50 mm off target [9]. Such off-target movement can result in underdosing of the target area and overdosing of normal tissues, significantly impacting treatment efficacy and prognosis.
Previous studies have shown that the displacement of the geometric center of the target area due to respiratory motion in the left-right, anterior-posterior, and cranio-caudal directions is 0.34 ± 0.21, 0.21 ± 0.27, and 0.84 ± 0.42 cm, respectively [10, 11]. These studies collectively highlight the significance of organ movement caused by respiratory motion, especially of thoracoabdominal tumors. The impact of respiratory motion during tumor radiotherapy cannot be underestimated, and precise radiation therapy can only be achieved by minimizing the effects of respiratory motion.
Therefore, numerous researchers have explored methods to mitigate the impact of tumor movement due to respiratory motion. The methods for reducing the influence of respiratory motion can be broadly categorized into five groups: motion-encompassing techniques, breath-holding techniques, forced shallow breathing techniques, respiratory gating techniques, and real-time motion tracking techniques, each with its own advantages and disadvantages.
To control respiratory motion during heavy ion therapy, we introduced HFOV technology for heavy ion therapy. Analysis of the data from 30 patients showed vital signs were stable. Respiratory motion under HFOV was 1.33 ± 0.39 mm, which was significantly less than that during spontaneous breathing and there was no "off-target" movement during radiation therapy. Therefore, when the target area is set, ITV can be ignored, and the positioning error of patients is reduced to 1-3mm due to respiratory control, and PTV only needs to be expanded by 1-3mm on the basis of GTV. When there is no breathing control, GTV expands outward by 8-10mm to form ITV, and the positioning error of ITV expands outward by 5-8mm to form PTV[12]. Therefore, heavy ion therapy under the control of high-frequency oscillatory breathing can reduce the unnecessary external emission boundary of PTV, control and narrow the target area, reduce the irradiation dose of normal tissues within the target area, and reduce the damage to normal healthy tissues.
In the course of treatment, the incidence of adverse reactions was low and mild. Radiation pneumonia occurred in 1 of the 30 patients, which was significantly lower than that reported previously (15%-40% ) [13, 14]. All these further indicated that the HFOV breathing control technology significantly reduced the damage of healthy lung tissues and was relatively safer. It was related to precise tumor targeting by minimizing irradiation on normal tissues with HFOV controlled respiration movement during heavy ion therapy, Moreover, it allowed for simultaneous irradiation of multiple lesions in a single session, thereby reducing the patients’ hospitalization duration and economic burden. Hence, the use of HFOV for respiration control in carbon ion therapy can achieve the requirement for high precision, efficiency, and dose accumulation at the tumor site.
There were several limitations in this study. First of all, this is a retrospective study, and the inherent limitation of the retrospective study would affect the conclusion. Secondly, the current study has only involved 30 cases, which presents a limited sample size. The third, there were no comparisons with other ventilation modes. Therefore, a well designed RCT is needed to confirm the discoveries.
In summary, the use of HFOV controlled chest movement in thoracic and abdominal tumor heavy ion therapy could ensure high safety. This technology enables patients to receive precise heavy ion treatment with accurate positioning, high tumor radiation dosage, and minimal exposure to normal tissues. More studies are needed in future treatments.