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ILROG Guidelines Recommend Proton Therapy to Limit Damage to OARs in Mediastinal Lymphomas

Jason Harris
Published Online:1:33 PM, Wed October 10, 2018

Bouthaina S. Dabaja, MD

Guidelines from the International Lymphoma Radiation Oncology Group (ILROG) recommend the use of proton therapy in adults with mediastinal lymphomas and for young women. Specifically, clinicians should consider proton therapy in mediastinal disease that spans below the left main stem coronary artery and is near the front of, behind, or on the left side of the heart. In young adult women, proton therapy delivers reduced breast dose, thus reducing the risk for secondary breast cancer. The ILROG also recommends proton therapy in heavily pretreated patients who are at elevated risk for radiation-related toxicity to the heart, lungs, and/or bone marrow.

Radiation oncologists have long sought to limit the damage to organs at risk (OARs) associated with radiation therapy because of the morbidity and mortality associated with ionizing radiation, especially secondary malignancies and cardiac complications. Proton therapy offers the promise of better OAR sparing and more conformal dose distribution.

These guidelines were drafted as best practice recommendations presenting the pros and cons of proton therapy. A consensus of >80% of the participating experts supported each recommendation.

The expert panel did not issue a recommendation regarding delivery technique. The magnitude of dosimetric benefit varies from patient to patient, so each case must be considered individually. Furthermore, the benefit of proton therapy should be weighed against drawbacks such as availability, particularly if a patient has to travel, out-of-pocket cost if treatment is not covered by insurance, the “potential uncertainties” associated with the therapy, and the demands placed on the medical and physics staff.
“Each proton center has different capacities and techniques, and no unified technique for proton radiotherapy for patients with lymphoma has been widely adopted,” wrote corresponding author Bouthaina S. Dabaja, MD, hematology section chief in the department of radiation oncology at the University of Texas MD Anderson Cancer Center, and colleagues. “Ultimately, key tools and concepts should be applied and a minimum requirement for competency should be acquired for those who intend to use proton therapy.”

For physicians using proton therapy, the ILROG says they must demonstrate that proton therapy is necessary despite potential long-term drawbacks such as the risk for radiogenic late effects and would provide more benefit to the patient than other forms of radiation. The physician must also understand the evolving nature of the technology, the importance of managing uncertainties, robustness optimization, and in-room volumetric imaging.

Finally, the panel encourages physicians to employ deep inspiration breath hold (DIBH) “when it further minimizes doses to the OARs.” However, the physician should understand that DIBH makes the use of proton therapy more complex.

Mitigating Uncertainties

The ILROG says that uncertainties in calculating the range of proton penetration generally arise from range errors caused by changes in tissue density, the conversion of CT number into proton linear stopping power, and change in relative biological effectiveness (RBE) of protons along the beam’s path.

Physicians can employ optimization tools that include range uncertainties, setup errors, and physiological motion to address dosimetric uncertainties caused by changes in anatomy. The panel recommended reviewing families of dose-volume histograms of clinical target volumes and OARs for scenarios such as shifts along the X, Y, and/or Z axes before delivering radiation to make sure the treatment plan is feasible.

Local dose heterogeneities can result from interference between the proton beam and the target due to movement by the patient. The panel said that spot repainting, gating, motion reduction techniques, and increasing spot size can reduce the interplay effect.

Conversion of Hounsfield units collected in CT scans to tissue-relative proton stopping powers, mistakes in range compensator fabrication, uncertainties in water measurement during beam commissioning, and beam reproducibility can lead to differences between calculated and actual proton ranges in tissue. The ILROG says each proton system will produce a unique magnitude of these types of uncertainties, but margin recipes at a given institution can help ensure target coverage.

RBE is variable and the result of several factors including dose per fraction, biological, or clinical endpoints, and linear energy transfer (LET) to the local medium among others, even though clinical practice operates from the assumption that RBE is a constant value of 1:1. Physicians must use empirical methods, such as reducing physical dose at the distal edge of the beam and use of multiple fields to dilute the effect, to spare nontarget tissues from radiation because REB-based and LET-based planning are not yet commercially available.
Dabaja BS, Hoppe BS, Plastaras JP, et al. Proton therapy for adults with mediastinal lymphomas: the international lymphoma radiation oncology group (ILROG) guidelines [published online August 14, 2018]. Blood. doi: 10.1182/blood-2018-03-837633.

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