Lymphoma: advances in imaging and radiotherapy – introductory editorial

Lymphomas are highly radiosensitive and radiation remains the most active single modality for achieving local control in most types of lymphoma. The early successes of extended field radiotherapy in the treatment of localised lymphomas, in particular Hodgkin lymphoma, were subsequently tempered by the realisation of the serious late effects in the large volumes of irradiated normal tissues that were seen in long-term survivors. This led to doubts about the use of radiotherapy, and with the advent of systemic therapies, numerous attempts were made to reduce or avoid radiation therapy in the treatment of lymphomas.

Modern, highly advanced imaging and radiation therapy planning and delivery have revolutionised the field of radiotherapy. Imaging with CT-, PET-, and MR-scans allows accurate target and normal tissue definition, and intensity-modulated photon or proton therapy with motion management, on board imaging, and adaptive therapy allow very precise delivery of the prescribed radiation dose to the defined target with minimal radiation to normal tissues. In solid tumours, these techniques are used to achieve better target coverage and increased doses to the tumours. In the treatment of lymphomas, relatively low doses of radiation are needed, and the goal of using the new advanced techniques is primarily to reduce doses to normal tissues. Massive reductions in the irradiated volume have now led to significant reductions of acute toxicity of lymphoma radiotherapy, making it tolerable even for older and frail patients, and to massive reductions in late effects. The International Lymphoma Radiation Oncology Group (ILROG) has been very active in disseminating the modern principles of lymphoma radiotherapy worldwide, publishing research and detailed guidelines on the modern treatment principles in order to ensure that lymphoma patients worldwide will gain the full benefit from modern radiotherapy.

In this BJR special feature dedicated to lymphomas, the present state-of-the-art imaging and radiation therapy of lymphomas are reviewed by lymphoma experts. Moreover, future prospects and opportunities are presented.

There are four review articles on different aspects of imaging. Wijetunga et al¹ review the history of imaging in lymphomas, from 2D to 3D and the introduction of functional imaging with PET. Future research in image analysis and radiomics are likely to enable further improvements in personalised treatment. Meignan et al² review the promising work on the total metabolic tumour volume as a surrogate marker for the total tumour burden, a well-known strong prognostic factor. Hopefully the total metabolic tumour volume can be evaluated using automated or semi-automated techniques that will allow the general clinical use as a tool to stratify patients before treatment into risk groups with different outcomes. Philips et al³ provide a perspective on PET response evaluation for individualised management of patients with Hodgkin lymphoma and diffuse large B-cell lymphoma. Milgrom et al⁴ describe the use of PET–CT-scans in lymphoma with a focus on their role in staging, response assessment, prognostication, and radiation therapy planning.

Three review papers address different advanced techniques for optimal radiation therapy of lymphomas. Aznar et al⁵ review the issue of motion management in highly conformal radiation therapy. In particular, they focus on methods to minimise uncertainties from breathing motions by respiratory gating and breath control in patients with mediastinal lymphomas. Petersen et al⁶ review the techniques and the application of motion management and online treatment verification, the emerging techniques of adaptive radiotherapy in MR- and CT-based treatment systems, and the implementation of proton therapy. The variety of techniques that are available are challenging for the clinician, and new systems calculating risks with specific treatment plans, integrating clinical factors and risk factors, will be needed. Modiri et al⁷ review the complexity of optimising radiation therapy plans for lymphoma patients, considering not just radiation doses but the chance of tumour control and the risks of different adverse events. The principles of quantitative outcome-based multi objective optimisation of treatment plans for lymphomas are described. As the many different events in this optimisation process are incommensurable, the use of pareto-optimisation is proposed.

Two clinical reviews concern the use of radiation therapy in patients with disease progression after primary treatment, a situation where radiotherapy has not hitherto had a major role. Pinnix et al⁸ examine the treatment of primary refractory and relapsed diffuse large B-cell lymphoma, and the possible role of salvage radiotherapy to increase the likelihood of cure in these patients. De Selm et al⁹ give an overview of radiation therapy and its potential to modulate the immune system. Specifically, they discuss the possibility to use radiation to improve the outcome of patients treated with CAR-T-cells.

Finally, in a commentary, Phillips and Illidge¹⁰ discuss the challenges and opportunities of image guided personalised risk-adaptation of the management of lymphomas, which is now routinely used in some lymphoma types and clinical situations.

We Guest Editors of this BJR special feature, Lena, Tim, Achy, and George, wish to thank all contributors for sharing their insights and experience. We hope that this collection will inspire the readers to participate in the continued development and implementation of the best possible treatment for our lymphoma patients.