Lymphoma Patients Undergoing Mediastinal Radiotherapy in the Era of Modern Chemoradiation

Malignant anterior mediastinal tumors essentially include lymphomas and thymomas. The location of mediastinum is anatomically close to several critical organs such as heart, lung, and breasts, which might be affected meaningfully when the mediastinal region is irradiated. There have been quite a few studies investigating long-term toxicities concerning the above critical organs and risks of secondary malignancies related to treatment regimens combining chemotherapy and mediastinal radiotherapy. With the advancement of modern radiotherapy, highly conformal and intensity modulated radiotherapy have become a radiotherapeutic standard in recent years. However, most previous studies analyzed patients treated in the era of 2D techniques rather than conformal 3D plans. Almost inevitably, a large volume of the heart and lung was irradiated via the 2D technique with which substantial dose levels might be given to these organs unavoidably. Certainly long-term radiotherapy related toxicities are significantly associated with the dose and volume irradiating the normal organs at risk. Relying on the techniques of modern conformal radiotherapy and the contemporary strategy of multimodality therapy, the dose and volume irradiating the heart and lung were considerably reduced. Therefore, objective tools including heart echocardiography and lung function test will be utilized in this prospective study to evaluate and monitor mainly the patients diagnosed as malignant lymphoma who are recommended to receive mediastinal radiotherapy in the era of modern treatment strategy and techniques.

The participants potentially included in the current study are mainly lymphoma patients with mediastinal malignant lymphoma or patients whose radiation therapy field essentially encompasses anterior mediastinum. Patients are prospectively enrolled in this study after physicians' clinical judgement. After signing the consent form, the recruited patient will receive comprehensive pre-radiotherapy evaluations, including cardiac echocardiography, laboratory tests (BNP, and NT-pro BNP), and lung function tests. Participants who are particularly female patients under the age of 45 will receive pre-radiotherapy breast echocardiography. Radiotherapy treatment planning of both photon and proton respectively will be simulated on Eclipse® treatment planning system. Subsequently participants will receive mediastinal RT within one month after being enrolled in the study. Eligible patients should receive standard multidisciplinary treatment as the tumor board at our institute has suggested. Modern radiotherapy techniques comprise all available modalities in our hospital, including photon or proton beams, intensity-modulated radiotherapy, volumetric modulated arc therapy, image-guidance, and breathing control system. The prescription of treatment field designing and dose scheme will comply with our institutional protocols and updated cancer treatment guidelines. Participants will receive longitudinal follow-up examinations at 3, 6, 9, 12, 18, 24, 36 months after the start of RT course. Standardized examinations include the above mentioned cardiac echocardiography and relevant tests.

It is anticipated that long-term mediastinal RT-related late effects are prospectively and longitudinally surveyed through consistent heart examinations and lung function tests. Long-term effects are expected to be lower with using maturely and widely adopted modern RT techniques. Therapeutic and survival outcomes are expected to be satisfactory, achieving the international level in this prospective observational study focusing on mainly lymphoma patients with mediastinal involvement who are suggested and scheduled to receive mediastinal RT as part of the combined modality treatment.

This study aims to standardize the application of clinical examinations including cardiac echocardiography, lung function tests, and relevant laboratory tests as part of objective tools for monitoring patients' cardiac and pulmonary functions after receiving mediastinal RT. Therefore, it is expected that the risk factors of predisposing patients to develop cardiac toxicities after chemoradiation particularly including mediastinal RT will be explored and identified. In addition objectivity of BNP (or NT-pro BNP) will also be verified in combination with the objective measurement and findings obtained from cardiac echocardiography. It is anticipated that our study would be an important and leading one that integrates radiation oncology, hematology, cardiology, and pulmonology into prospective and longitudinal cardiopulmonary surveillance carried out for mainly malignant lymphoma patients undergoing mediastinal RT in this era of modern chemoradiation.