Radiotherapy has several indications in the treatment of diffuse large B-cell lymphoma (DLBCL). Depending on the clinical scenario, it can be used as palliative, consolidation, peritransplant, or salvage therapy.

Here we present recommendations for palliative radiotherapy in DLBCL as suggested by Wright and colleagues in Clinical Lymphoma, Myeloma and Leukemia, separated by sections of the body in which it can be used.

Gastric

Radiotherapy can be used for palliation of symptoms in advanced-stage or relapsed gastric DLBCL. Recommended doses for palliation range from 8 Gy in 1 fraction to 30 Gy in 10 fractions. Other schemes (eg, 6 to 8 Gy in 2 fractions) may be considered but require close follow-up.

In palliative radiotherapy, the gross tumor volume (GTV) or clinical target volume (CTV) should include gross disease. In contrast to curative intent radiotherapy, there is no need to include the entire stomach in the GTV/CTV.

Daily target delineation for palliative radiotherapy may be influenced by variabilities in stomach positioning during the respiratory cycle and stomach filling. Hence, if possible, the internal target volume should be determined. If it can not be estimated, an additional margin of at least 1-2 cm should be added to the planning target volume (PTV). Moreover, Wright et al recommend that patients are nil per os for at least 4 hours prior to simulation and daily treatments.

They also recommend daily image guidance with cone-beam computed tomography.

Breast

Radiotherapy may be considered for palliation in advanced-stage curable-intent DLBCL with recommended doses similar to other extranodal sites.

Usually, whole breast radiotherapy using tangent fields or a prone technique is recommended, albeit partial breast irradiation may be considered in some cases to reduce morbidity. Elective nodal coverage of uninvolved lymph nodes is not recommended.

Strategies to reduce dose to the heart and its substructures include the use of intensity-modulated radiotherapy (IMRT) and respiratory motion management or deep inspiratory breath hold.

Head and Neck

Radiotherapy should be directed to sites of initial or suspected involvement. Prophylactic nodal irradiation is not recommended in palliation. Target volume delineation and treatment planning might benefit from magnetic resonance imaging (MRI) evaluation in some cases.

Recommended doses for palliation range from 20 Gy in 5 fractions to higher doses in standard fractionation. Lower doses may be applied in specific cases, considering prognosis, performance status, and affected structures.

Strategies to optimize the therapy include immobilization with a 3- or 5-point thermoplastic mask for smaller PTV expansions, the use of IMRT in nonemergent situations to decrease the dose to organs at risk (OARs), and a careful delineation of the salivary glands, orbital structures, and the oral cavity to minimize dose to these regions.

Bone

Recommended doses for radiation in bone DLBCL vary from a lower dose (8 Gy in 1 fraction) for uncomplicated bone metastases to higher doses (20 Gy in 5 fractions or 30 Gy in 10 fractions) for patients with pathologic fractures, lesions in weight-bearing bone, or lesions along the neuroaxis.

The volumes for bone DLBCL should include the GTV or CTV when treating for pain or impending fracture. PTV margins of 0.5-1 cm are possible if using image-guided radiotherapy, but most commonly 1.5-2 cm are recommended depending on site, immobilization, and image guidance.

Cord Compression

Wright and colleagues recommend the use of hypofractionated radiotherapy to palliate DLBCL-related epidural spinal cord compression, with regimens varying from lower doses (8 Gy in 1 fraction) for patients with a poor performance status or life expectancy of less than 3 months to higher doses (20 Gy in 5 fractions or 30 Gy in 10 fractions) for those with a more favorable prognosis.

If palliation is required prior to initiating chemotherapy, radiotherapy can be used upfront with abbreviated regimens of 7.5 Gy in 3 fractions or 6 Gy in 2 fractions.

The study team also favors the use of anterior-posterior/posterior-anterior fields with field borders, including 1 vertebral body above and below the involved vertebral levels.

The timing for radiotherapy is crucial. For instance, it should start at least 1 week postinfusion with intrathecal methotrexate or intravenous doxorubicin, whereas concurrent treatment with intrathecal cytarabine is advisable.

Central Nervous System

Whole brain radiotherapy is an effective palliative approach for relapsed/refractory central nervous system (CNS) lymphoma. A median palliative RT dose of 36-40 Gy may be considered to provide durable control or cure the disease in patients with good performance status.

Lower doses (23.4-30.6 Gy) may be used in elderly patients (>60 years) or in situations in which neurotoxicity given past chemotherapy is a concern—these cases may benefit from a sequential or integrated boost to 39.6-45 Gy to gross disease. Craniospinal irradiation may be considered in cases of CNS-only relapse and limited systemic options.

A short course of 20 Gy in 5 fractions or 30 Gy in 10 fractions to the whole brain may be considered for patients with limited prognosis. Moreover, partial-brain radiotherapy is an option for elderly patients or those with neurocognitive deficits of concern.

Despite the improvements in neurologic symptoms provided by whole brain radiotherapy, the impact on patients’ survival is limited.

Orbit

Radiotherapy has been applied to both primary and secondary DLBCL of the orbit with doses varying from 24-54 Gy. However, retinopathy has been reported with retinal doses as low as 30 Gy, with considerable risk increase with doses greater than 45 Gy. Hence, Wright et al recommend a dose of 30-36 Gy, with an eventual boost to 40 Gy or above for gross disease. In this case, particular attention should be given to retina and lacrimal gland dose.

Patients with diffuse extraorbital metastases may benefit from a more abbreviated regimen (20-24 Gy in 10-12 fractions), though lower doses of 4-8 Gy in 2 fractions may be considered with close interval follow-up.

The decision to treat the entire or partial orbit should be carefully balanced. In cases of DLBCL, the entire orbital canal is treated except when prognosis is limited. Additional techniques can be used to spare OARs, such as the contralateral orbit.

Radiotherapy might also be used to treat intraocular lymphomas.

“When treating ocular lymphoma in the absence of CNS disease with radiotherapy, a total dose of 36 Gy to the bilateral orbits is recommended for gross disease using an opposed lateral technique,” Wright et al wrote. “Following a [complete response] with CNS-directed chemotherapy, a lower consolidation dose of 23.4 to 30.6 Gy may be appropriate.”

Reference

Wright CM, Koroulakis AI, Baron JA, et al. Palliative radiotherapy for diffuse large B-cell lymphoma. Clin Lymphoma Myeloma Leuk. 2021;21(10):650-658. doi:10.1016/j.clml.2021.05.007

Walburn T, Grover NS, Shen CJ, et al. Consolidative or palliative whole brain radiation for secondary CNS diffuse large B-Cell lymphoma. Leuk Lymphoma. 2021;62(1):68-75. doi:10.1080/10428194.2020.1821014