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Currently, at our clinic, patients with a limited stage mediastinal lymphoma are either being treated with a photon technique in breath-hold (BH) or a proton technique in free-breathing (FB).  To date, most of our patients are being treated with a BH photon technique as these plans result in the lowest mean heart dose (MHD). Combining BH and proton therapy may result in a further reduction of the MHD.  With this study we aim to quantify the dosimetric advantages and the expected effect on the risk of cardiac toxicity of BH proton therapy for mediastinal lymphomas. Moreover, we assessed if our current BH method results in sufficiently stable breath holds.

BH CT scans of 10 patients with a mediastinal Hodgkin’s lymphoma who were previously treated with a VMAT photon technique (5mm PTV margin) were used to generate 10 proton plans for the same target volume and prescription dose. A robustness margin of 5 was used for proton planning. Per patient the MHD of the proton plan was compared with the MHD of the existing photon plan. For each patient a ΔNTCP for the life time risk of ≥ grade 4 acute coronary events was calculated using an existing and validated model (LIPP borstkanker, NVRO, 2020). Moreover, mean lung dose (MLD) and V5Gy of the bilateral lungs were compared per patient.

During the CT and photon fractions, the above-described patients received visual BH coaching using a C-Rad Sentinel (during CT) and Catalyst (during treatment) system with a gating window of 3 mm. BH stability of these 10 patients during photon treatment was evaluated using pre- and post-fraction (BH) CBCT images and intra-fraction surface tracking data of the thoracic wall collected using C-Rad (Figure 1).

For all patients, proton planning resulted in a reduction of the MHD (Table 1). The median reduction was 2.2 Gy (IQR 1.5 Gy). As a consequence, using proton therapy, the risk of ≥ grade 4 acute coronary events would be reduced in all patients with a median ΔNTCP of 2.6% (IQR 2.5%). In 7 out of 10 patients the ΔNTCP was ≥ 2%, the clinical threshold to qualify for proton therapy, while in FB only 1 out of 10 patients qualified. Proton planning resulted in a reduction of the MLD (median 2.5 Gy, IQR 1.6 Gy) and lung-V5Gy (median 18.7%, IQR 12.8%) in all patients.

CBCT analyses showed a CTV intra-fraction movement of <4.5 mm in 90% of fractions. Surface tracking data showed an average intra-BH variation of 1.5 mm and an average maximal inter-BH variation of 3.2 mm.

Our BH technique results in sufficiently stable breath-holds for proton therapy. The BH proton technique resulted in a lower MHD than the BH photon technique in all patients. In the current cohort, BH proton therapy would have resulted in a clinically significant reduction of ≥ 2% in the life time risk of ≥ grade 4 acute coronary events in the majority of patients.