Scanning proton beam radiotherapy under functional apnea

Reporter: J. Taylor Whaley, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 14, 2011

Presenter: Eckermann M, Hillbrand M, Herbst M, Rinecker H
Presenter's Affiliation: Rinecker Proton Therapy Center, Munich, Germany


  • Proton therapy potentially has numerous advantages to conventional radiation therapy when treating cancer in locations that remains relatively motionless; however, many tumors are found in the thoracic and abdominal cavities, which have been documented to move substantially throughout the respiratory cycle.
  • Tumors located in the areas present a particular challenge to treat with protons due to the mobile nature of the targets during respiration.
  • Intrafraction motion can dramatically affect the proton dose distribution, and reliable target localization is critical due to the sharp distal margin of the proton beam.
  • One method that has been postulated as means of stabilizing target volumes is daily treatment under anesthesia with treatment occurring during a particular respiratory phase.
  • The technique of anesthesia known as functional apnea, apneic oxygenation, and diffusion respiration, although new to the field of radiation oncology, is well established and is currently used during some thoracic surgeries.
  • Because oxygen diffuses more readily than carbon dioxide in the lungs, even without respirations, it produces a gradient that forces gas into the alveoli of the lungs. Using a constant oxygen flow and pressure, patients can remain oxygenated without respirations.
  • Although carbon dioxide levels are known to increase 2-4 mmHg/min without respirations, this has been shown to have no negative impacts if apneic episodes remain short.
  • The purpose of the study was to evaluate the feasibility of daily anesthesia using the functional apnea technique to demonstrate stability of tumor positions by eliminating respiratory movements, which is turn, improves localization of proton therapy to intra-thoracic and intra-abdominal tumors.

Materials and Methods

  • 61 patients were treated under general anesthesia by proton pencil beam scanning in a total of 673 fractions (range 1-30 treatments per patient) at the Rinecker Proton Therapy Center.
  • General anesthesia was performed with intravenous infusion and oral intubation.
  • Functional apnea was achieved by muscle relaxation, stopping mechanical ventilation, and continuous oxygen-flow under standard monitoring, including EKG, blood pressure, arterial oxygen levels, and carbon dioxide levels.
  • Functional apnea was used in the initial treatment planning simulation to obtain treatment planning CT images.
  • CT images were again obtained later in the course of treatment to demonstrate reproducibility.
  • Patients remained apneic while proton therapy was delivered from individual gantry positions. During gantry movements, the patient was ventilated to remove carbon dioxide.
  • Tumor position was correlated with relative position to the spinal cord and diaphragm.
  • For individual treatment, in room X-ray based position verification was performed daily to verify placement and investigate intrafraction deviations of the treatment fields.


  • Overall, 3025 periods of induced apnea occurred during the 673 fractions. Average duration of apneic periods was 2.3 minutes (Range- 1-9 minutes).
  • Age range was 28 to 88 years old.
  • ASA physical status classifications, which assesses the fitness of patients prior to procedures, ranged from 1 (healthy patients) to 4 (very ill patients).
  • No episodes of hypoxia (SpO2 <97%) occurred. Maximum CO2 concentration was 61 mmHg, which occurred during 9 minutes of apnea.
  • No treatments were terminated prematurely.
  • Time of anesthesia ranged from 28 to 133 minutes with an average of 57 minutes. Time on the proton treatment table averaged 30 minutes.
  • Recovery ranged from 45 minutes to 3 hours. Average recovery time was 90 minutes.
  • No adverse events occurred.
  • Only mild side effects were noted. Specifically, laryngeal irritation (<1%), dysphagia (<1%), hypotension (<1%), nausea (<1%), and drowsiness (<3%).
  • In total, 73 verification CTs were performed to evaluate reproducibility. The average target motion during apneic periods was 2 mm (range 0-4 mm).

Authors' Conclusions

  • Due to the mobile nature of intra-thoracic and intra-abdominal organs secondary to respirations, functional apnea during irradiation appears to be a safe, well-tolerated, and reproducible method to fix tumor position for scanning proton beam therapy.

Clinical Implications

  • As proton beam therapy is employed for mobile tumors within the abdominal and thoracic cavity, it is critical to evaluate methods to minimize tumor motion.
  • Due to the physical characteristics of protons, accurate prediction of inter- and intrafraction organ motion is paramount during delivery of proton therapy.
  • The authors report their successful experience with functional apnea as a method of anesthesia. The treatment appeared to be effective, safe, and reproducible.
  • The applicability of this technique could be challenging in other cancer centers due to its complexity.
  • The results of this study will surely contribute to the growing body of literature demonstrating the implementation of proton therapy to more complex tumor locations.

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