Abstract
Simple SummaryHodgkin lymphoma (HL) is a highly curable disease; in this context, the limitation of late adverse events is of prime importance for the patient. Proton therapy for mediastinal HL irradiation theoretically limits secondary cancer excess risk and should reduce late toxicities compared with classical radiation therapy techniques. However, due to the limited clinical experience, strong evidence is still lacking to support proton therapy in HL management despite excellent tolerance. In addition, randomized controlled trials are probably unrealistic in this context. National and international registries may be useful to strengthen support for HL proton therapy.Consolidative radiation therapy (RT) is of prime importance for early-stage Hodgkin lymphoma (HL) management since it significantly increases progression-free survival (PFS). Nevertheless, first-generation techniques, relying on large irradiation fields, delivered significant radiation doses to critical organs-at-risk (OARs, such as the heart, to the lung or the breasts) when treating mediastinal HL; consequently, secondary cancers, and cardiac and lung toxicity were substantially increased. Fortunately, HL RT has drastically evolved and, nowadays, state-of-the-art RT techniques efficiently spare critical organs-at-risks without altering local control or overall survival. Recently, proton therapy has been evaluated for mediastinal HL treatment, due to its possibility to significantly reduce integral dose to OARs, which is expected to limit second neoplasm risk and reduce late toxicity. Nevertheless, clinical experience for this recent technique is still limited worldwide. Based on current literature, this critical review aims to examine the current practice of proton therapy for mediastinal HL irradiation.
Highlights
Hodgkin lymphoma (HL) is a rare hematologic malignancy with an estimated incidence of 2.7–2.8 cases per 100,000 person-year [1] and is characterized by a high curative rate, evaluated between 80% and 90% [2]
Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models for radiation pneumonitis were derived from a thymoma cohort by Moiseenko et al [29] and from breast, lymphoma, and non-small cell lung cancer (NSCLC) cohorts by Seppenwoolde et al [30]
radiation therapy (RT) was the first evaluated curative treatment of early-stage HL, the off-target radiation exposure resulted in potentially fatal RT-related toxicities, such as cardiovascular events or second primary malignancies that substantially increased with follow-up, after 10 years [4]
Summary
Hodgkin lymphoma (HL) is a rare hematologic malignancy with an estimated incidence of 2.7–2.8 cases per 100,000 person-year [1] and is characterized by a high curative rate, evaluated between 80% and 90% [2]. Drastic technical progress was made to spare organs-at-risks (OAR) without altering local tumor control or patient survival. Such evolutions included generalization of intensity-modulated radiation therapy (IMRT) and democratization of respiratory control such as gating or deep-inspiration breath-hold (DIBH) [6]. Newer IMRT techniques for HL management, such as volumetric modulated arctherapy (VMAT) or helical tomotherapy sensibly increase low-dose exposure to OARs which had been debatably suspected to potentially increase secondary malignancies, based on low-dose radiation data from A bomb survivors [8]; other biological models failed to demonstrate any risk increase of second cancers for low-dose exposure [9] and this issue is still controversial. The purpose of this review is to provide a contextualized analysis of the expectations and of the current clinical evidence for mediastinal HL management with proton therapy
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