<p>Proton Therapy For Lymphomas: Current State Of The Art</p>

Abstract

The combination of brief chemo-radiotherapy provides high cure rates and represents the first line of treatment for many lymphoma patients. As a result, a high proportion of long-term survivors may experience treatment-related toxic events many years later. Excess and unintended radiation dose to organs at risk (particularly heart, lungs and breasts) may translate in an increased risk of cardiovascular events and second cancers after a few decades. Minimizing dose to organs at risk is thus pivotal to restrain the risk of long-term complications. Proton therapy, with its peculiar physic properties, may help to better spare organs at risk and consequently to reduce toxicities especially in patients receiving mediastinal radiotherapy. Herein, we review the physical basis of proton therapy and the rationale for its implementation in lymphoma patients, with a detailed description of the clinical data. We also discuss the potential disadvantages and uncertainties of protons that may limit their application and critically review the dosimetric studies comparing the risk of late complications between proton and photon radiotherapy.

Proton Therapy in Supradiaphragmatic Lymphoma: Predicting Treatment-Related Mortality to Help Optimize Patient Selection

“…The mean OAR doses for the PBT plans in our patients were comparable with those of previous studies, 11 , 28 , 30 but our photon RT doses were lower than in other studies. For example, the average MHD, MLD, and MBD for photon RT in our study was 9.5 Gy, 7.9 Gy, and 2.5 Gy, respectively, but a recent review of 16 studies in patients with mediastinal HL reported an average MHD, MLD, and MBD of 11.4 Gy, 9.4 Gy, and 4.4 Gy, respectively.…”

“…This is particularly beneficial for patients with relapsed disease who have already received RT as it may lower the risk of acute cord and bone marrow toxicities as well as risk of radiation pneumonitis. 29 The mean OAR doses for the PBT plans in our patients were comparable to previous studies 11,28,30 , but our photon-RT doses were lower than in other studies. For example, the average MHD, MLD, and MBD for photon-RT in our study was 9.5 Gy, 7.9 Gy and 2.5 Gy respectively whilst a recent review of 16 studies in patients with mediastinal HL reported average MHD, MLD and MBD of 11.4 Gy, 9.4 Gy and 4.4 Gy respectively.…”

“…These doses are shown in Table 2. Further details are given in Supplemental texts B and C. 30 for the 80 patients in this study. AMR 30 includes background mortality risk (grey bar), absolute excess risk after chemotherapy (CT) (black bar), absolute excess risk after photon RT (Photons) (yellow bar) and proton beam therapy (PBT) (blue bar).…”

Secondary Malignancy Risk Following Proton vs. X-ray Treatment of Mediastinal Malignant Lymphoma: A Comparative Modeling Study of Thoracic Organ-Specific Cancer Risk

“…Nevertheless, the potential benefit is variable and dependent on many factors including age, gender, tumor location, and patient-specific comorbidities. This specific radiation modality should be discussed on a "case-by-case" basis and, if found to be warranted, patients should be treated at PT facilities with sufficient expertise (41). At our facility, all lymphoma patients treated with PT are placed on a prospective registry study with long follow-up to investigate long-term toxicities like cardiac events or SM.…”

On the Importance of Individualized, Non-Coplanar Beam Configurations in Mediastinal Lymphoma Radiotherapy, Optimized With Automated Planning

“…Voong et al (21) observed a reduction in heart dose (but not in breast dose) by using five to seven IMRT beams (butterfly) with eventually one non-coplanar beam, relative to 3D-CRT in patients without bilateral axillary involvement. Proton therapy has also been proposed for further reductions of late toxicity in selected lymphoma patients (17,(22)(23)(24)(25).…”