Hodgkin lymphoma is one of the most common cancers in adolescents and young adults (AYAs), a population with distinct biological, clinical, and developmental characteristics. Yet care remains fragmented between pediatric and adult systems contributing to variability in treatment exposure and survivorship outcomes. We synthesized current evidence on AYA HL epidemiology, biology, treatment strategies, supportive care needs, long-term toxicity risk, and survivorship. AYAs have access to multiple efficacious treatment options with high cure rates, but long-term survivors face significant medical, psychosocial, and financial effects with notable risks for cardiopulmonary disease, secondary malignancies, fertility impairment, and unmet psychosocial needs. Harmonized pediatric-adult treatment frameworks, AYA-focused support, and developmentally tailored survivorship care are essential to improving outcomes for AYA HL survivors.
Particle therapy represents a cutting-edge modality in radiation oncology that offers potential advantages over conventional radiation therapy; however, its cost-effectiveness has not been established. We conducted a systematic search of several electronic databases to synthesize contemporary evidence on the cost-effectiveness of particle therapy. The methodological quality of the included studies was assessed, and reported outcomes on costs, health benefits, and incremental cost-effectiveness ratios (ICERs) were extracted. We identified 57 studies, which collectively reported 134 comparisons for particle therapies. In general, studies were of good quality, although better reporting of data sources and modeling assumptions is warranted. Included studies primarily evaluated the cost-effectiveness of proton therapy, used photon therapy as the comparator, utilized a Markov Cohort model, and used the payer's perspective. Findings were inconsistent, with the reported ICERs ranging from $55 to $1,066,266 per unit of benefit gained, with discrepancies across cancer sites and treatment modalities. Particle therapy is cost-effective for specific groups but may not be universally cost-effective. More research is warranted to identify subgroups for which particle therapy is cost-effective.
In this article, we review the development of accelerator and beam delivery technology for particle therapy. The working principles of accelerators, encompassing isochronous cyclotrons, synchrocyclotrons and synchrotrons, and recent advancements in other accelerator technology, are presented. For beam delivery technology, we focus on pencil beam scanning (PBS) for intensity modulated proton therapy (IMPT). In addition, we incorporate aspects of proton arc therapy, ultrahigh-dose rate FLASH therapy, and motion management for PBS beam delivery. Last, we have discussions on imaging guidance for particle therapy treatment delivery, upright patient positioning, and online adaptive therapy.
Hypofractionated particle therapy (HPT) is an evolving treatment paradigm in radiation oncology, offering enhanced therapeutic ratios through both biological and dosimetric advantages. Proton therapy leverages the Bragg peak phenomenon to reduce the integral dose to normal tissues, a benefit amplified by delivering larger doses per fraction. Carbon ion radiotherapy (CIRT) further augments this approach through high linear energy transfer (LET) and greater relative biological effectiveness (RBE), potentially overcoming radioresistance mechanisms. This review synthesizes updated clinical evidence for HPT, including proton and CIRT across various disease sites. Clinical trial data on efficacy and toxicity are reviewed, including comparisons with photon-based radiotherapy. The clinical outcomes observed thus far highlight the safety and efficacy of biologically intensified HPT regimens, underscoring the need for continued, well-designed phase II/III trials to define optimal indications and fractionation strategies.
Proton therapy requires accurate, reliable normal tissue complication probability (NTCP) models for treatment planning and evidence-based patient selection. This review examines 2 challenges in proton therapy: developing NTCP models that accurately reflect proton-specific toxicity and managing NTCP prediction uncertainty to ensure reliable clinical decision-making. Regarding model accuracy, photon-derived NTCP models work for some endpoints but fail for others when proton therapy exhibits distinct dose-response characteristics, indicating that the need for proton-specific models is endpoint-dependent. Clinical evidence that supports updating NTCP models by incorporating variable relative biological effectiveness is statistically weak due to interpatient heterogeneity and inconsistent findings. Despite ongoing efforts in improving NTCP prediction accuracy, the impact of prediction uncertainty on patient selection decisions has received limited attention. Further study is required to establish a robust, model-uncertainty-aware NTCP-guided patient selection framework for proton therapy that addresses both model accuracy and prediction confidence.
