Radiation therapy research holds significant promise for improving outcomes in non-Hodgkin’s lymphoma (NHL), a diverse group of blood cancers originating in lymphocytes. NHL is characterized by abnormal growth of lymphocytes, which form tumors in lymph nodes and other organs. Because NHL cells are generally sensitive to radiation, advances in radiation therapy techniques and combinations with other treatments are actively being explored to enhance effectiveness, reduce relapse, and improve survival rates.
One of the key areas of research involves **radioimmunotherapy (RIT)**, which combines radiation with targeted antibodies that specifically bind to lymphoma cells. NHL cells often express surface markers such as CD20, CD19, and CD45, making them ideal targets for antibody-based therapies. By attaching radioactive isotopes like yttrium-90 or iodine-131 to anti-CD20 antibodies, RIT delivers radiation directly to cancer cells while sparing most healthy tissue. This targeted approach has already improved response rates and remission durations in NHL patients, especially those with relapsed or refractory disease.
Recent studies have focused on **escalating the dose of CD20-targeted RIT** combined with autologous stem cell transplantation (ASCT). This strategy has shown promising results, with response rates exceeding 90% in heavily pretreated patients and improved progression-free survival. However, current RIT methods still deliver only about twice the radiation dose to tumor sites compared to non-target organs, indicating room for improvement in targeting precision and dose escalation to further reduce relapse rates.
Another important development is **pretargeted radioimmunotherapy (PRIT)**, which separates the targeting antibody and the radioactive payload into two steps. First, a fusion protein or antibody fragment binds to the tumor antigen, and then a radioactive molecule is administered that binds to the pretargeted antibody. This two-step process can increase the radiation dose delivered to tumors while minimizing exposure to healthy tissues, potentially improving efficacy and reducing side effects.
In addition to RIT, **involved-site radiation therapy (ISRT)** is a refined technique used for localized NHL, especially in early-stage disease. ISRT precisely targets the lymph nodes or regions involved with lymphoma, sparing surrounding normal tissues. This approach is often combined with chemotherapy or immunotherapy to maximize treatment effectiveness. For example, in clinical stage I or contiguous stage II NHL, ISRT following immunotherapy or chemotherapy has become a preferred treatment option.
Radiation therapy also plays a crucial role in treating NHL involving the central nervous system (CNS), where chemotherapy alone is often insufficient. CNS lymphomas are challenging due to the blood-brain barrier limiting drug delivery, so radiation is used either alone or alongside chemotherapy to improve control of the disease in this sanctuary site.
Beyond direct radiation approaches, research is exploring **synergistic combinations of radiation with novel targeted agents**. For instance, combining radiation with drugs like venetoclax, which promotes cancer cell death, has shown enhanced therapeutic effects in B-cell lymphomas. Such combinations may allow lower radiation doses while maintaining or improving efficacy, reducing toxicity.
Immunotherapy advances, including monoclonal antibodies and CAR T-cell therapies, are also being integrated with radiation strategies. Radiation can modulate the tumor microenvironment and enhance immune recognition of lymphoma cells, potentially boosting the effectiveness of immunotherapies. Ongoing clinical trials are investigating these combinations to find optimal sequencing and dosing.
Despite these advances, challenges remain. NHL is a heterogeneous disease with many subtypes, each responding differently to radiation and systemic therapies. Relapses are common, and some lymphoma cells may be resistant to radiation. Therefore, personalized approaches based on tumor biology, radiation sensitivity, and patient factors are critical. Research into biomarkers that predict response to radiation and combined treatments is underway to tailor therapies better.
Radiation therapy research is also focused on minimizing side effects. Techniques such as intensity-modulated radiation therapy (IMRT) and proton therapy allow more precise delivery of radiation, reducing damage to health
