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

Abstract

Purpose: Proton radiotherapy (PRT) is potentially associated with a lower risk for secondary malignancies due to a decreased integral dose to the surrounding organs at risk (OARs). Prospective trials confirming this are lacking due to the need for long-term follow-up and the ethical complexities of randomizing patients between modalities. The objective of the current study is to calculate the risk for secondary malignancies following PRT and photon-based intensity-modulated radiotherapy (IMRT). Materials and Methods: Twenty-three patients (16 female and seven male), previously treated with active scanning PRT for malignant mediastinal lymphoma at Heidelberg Ion Beam Therapy Center, were retrospectively re-planned using helical photon IMRT. The risk for radiation-induced secondary malignancies was estimated and evaluated using two distinct prediction models (1-4). Results: According to the Dasu model, the median absolute total risk for tumor induction following IMRT was 4.4% (range, 3.3-5.8%), 9.9% (range, 2.0-27.6%), and 1.0% (range, 0.5-1.5%) for lung, breast, and esophageal cancer, respectively. For PRT, it was significantly lower for the aforementioned organs at 1.6% (range, 0.7-2.1%), 4.5% (range, 0.0-15.5), and 0.8% (range, 0.0-1.6%), respectively (p ≤ 0.01). The mortality risk from secondary malignancies was also significantly reduced for PRT relative to IMRT at 1.1 vs. 3.1% (p ≤ 0.001), 0.9 vs. 1.9% (p ≤ 0.001), and 0.7 vs. 1.0% (p ≤0.001) for lung, breast, and esophageal tumors, respectively. Using the Schneider model, a significant risk reduction of 54.4% (range, 32.2-84.0%), 56.4% (range, 16.0-99.4%), and 24.4% (range, 0.0-99.0%) was seen for secondary lung, breast, and esophageal malignancies, favoring PRT vs. X-ray-based IMRT (p ≤ 0.01). König et al. Secondary Malignancy Risk After Radiotherapy Conclusion: Based on the two prediction models, PRT for malignant mediastinal lymphoma is expected to reduce the risk for radiation-induced secondary malignancies compared with the X-ray-based IMRT. The young age and the long natural history of patients diagnosed with mediastinal lymphoma predisposes them to a high risk of secondary malignancies following curative radiotherapy treatment and, as a consequence, potentially reducing this risk by utilizing advanced radiation therapy techniques such as PRT should be considered.

Radiation-induced gliomas represent H3-/IDH-wild type pediatric gliomas with recurrent PDGFRA amplification and loss of CDKN2A/B

“…Our findings unfortunately suggest that no conclusions can currently be drawn regarding predictive features in the patient or primary tumor for assessing the probability of subsequent RIG formation. An important question to address in future will be the precise role of radiotherapy protocols (craniospinal vs local boost, fractionation schema, photons/protons/heavy ions) in determining the risk of secondary malignancy [46][47][48][49][50] .…”

Development and Implementation of Proton Therapy for Hodgkin Lymphoma: Challenges and Perspectives

“…Oinam et al [28] demonstrated that different NTCP calculation models, such as LKB or Niemerko model, could lead to significantly different toxicity predictions. Finally, most NTCP models disregard patient clinical characteristics; however, Köthe et al [29] demonstrated for ocular toxicity of proton therapy that considering additional clinical variables such as age, tumor involvement, HTA, or sex, could substantially increase the performance of the NTCP models. This is particularly important for HL proton therapy since the expected benefit of proton therapy depends on the clinical features of the patient: to exemplify, patients with multiple cardiovascular risk factors are expected to benefit the most from heart sparing.…”

Current Situation of Proton Therapy for Hodgkin Lymphoma: From Expectations to Evidence

“…Based on the Schneider model and taking as a reference the anterior-posterior threedimensional (3D) RT (3D-RT) planning, Cella et al [14] found that HL proton therapy was associated with a significantly reduced relative risk (RR) of secondary breast cancers (RR = 0.3-0.7) compared with 3D-RT; while a benefit for secondary lung cancers was also observed (RR = 0.6-0.7), this was not the case for thyroid cancers. Taking the "butterfly" IMRT technique [15] as a reference, König et al [16] similarly demonstrated that secondary breast, lung, and esophageal cancers could be reduced by 56.4%, 54.4% and 24.4% respectively. Scorsetti et al [17] evidenced that proton therapy could also reduce thyroid cancers compared with VMAT; however, this benefit is expected to be limited to an EAR reduction of 0.2 for 10,000 person-years.…”