As with Hodgkin lymphoma, early-stage (I-II) diffuse large B-cell lymphoma is often managed with a combination of systemic therapy and radiation therapy. This typically consists of three to six cycles of immunochemotherapy, most commonly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), followed by consolidation radiation therapy. The Eastern Cooperative Oncology Group study 1484 demonstrated that consolidation radiation therapy after eight cycles of CHOP was associated with reduced rates of local failure (4 % vs. 16 %, p = 0.06) and improved 6-year disease-free survival (73 % vs. 56 %, p = 0.05), the primary endpoint of the study (Horning et al. 2004). A dose of 30 Gy is typically utilized after a complete response to immunochemotherapy is achieved. Higher doses (≥40 Gy) may be necessary in the setting of a partial response or with refractory disease.

Patients with advanced disease (III-IV) are generally treated with immunochemotherapy alone. Radiation therapy is utilized in select patients. Indications for radiation therapy include bulky disease (Held et al. 2014), partial response to systemic therapy (Dorth et al. 2011; Sehn et al. 2013), and limited skeletal involvement (Held et al. 2013). Select patients with technically advanced disease but limited presentations may also benefit from consolidation radiation therapy. In advanced stages, as more chemotherapy cycles are generally used with more widespread disease (and thus larger field sizes), lower doses such as 20 Gy seem reasonable (Dorth et al. 2012).

About a third of patients with diffuse large B-cell lymphoma will suffer a relapse. First-line treatment at relapse for appropriate candidates is non-cross-reactive chemotherapy followed by high-dose chemotherapy and autologous hematopoietic cell transplantation. Further radiation therapy must be tailored to the individual circumstances. Factors that must be considered include the prior dose of radiation utilized, field treated, interval between initial treatment and relapse, extent of relapse, response to salvage chemotherapy, etc.

Total body irradiation may be utilized, in select circumstances, in the relapsed setting as part of the conditioning regimen (Fig. 3). As doses of 12–14 Gy are required for transplant, this is usually feasible without significant risk. A second course of localized radiation therapy in the salvage setting may also be feasible depending on the circumstances. Finally, in those patients who are nonresponders to high-dose chemotherapy, fail transplant, or have a poor performance status, palliative radiation therapy can be considered. Radiation can be used in this setting to relieve symptomatic areas. As in Hodgkin lymphoma, re-treatment is generally possible due to the lower consolidation radiation doses needed for lymphoma. Response rates have been reported to be as high as 50–80 % with doses as low as 4 Gy (Murthy et al. 2008; Haas et al. 2005). Such doses can be utilized in almost all patients. If this is unsuccessful, more conventional palliative doses can be pursued (20–24 Gy).

Approximately 20 % of patients with follicular lymphoma present with localized (stage I or contiguous stage II) disease. The optimal treatment for these patients is controversial as no randomized studies have compared radiation therapy alone (the traditional standard) with more modern approaches such as immunochemotherapy, with or without radiation therapy (Friedberg et al. 2012), or observation. Large database studies suggest that radiation therapy improves survival in this setting (Vargo et al. 2015; Pugh et al. 2010). With radiation therapy alone, approximately 50 % of patients have long-term disease control. When the disease does relapse, the predominant pattern of failure is distant (i.e., originally uninvolved lymph node sites).

The majority of patients with follicular lymphoma present with advanced (stage III–IV) disease. Systemic therapy, consisting of both immunotherapy (e.g., rituximab) and chemotherapy, is the foundation of follicular lymphoma management. Radiation therapy can be beneficial in a number of circumstances. For example, in settings where there is localized disease progression or poor response to systemic therapy, especially if symptoms are present that require palliation, radiation therapy may be appropriately employed. Depending upon the clinical circumstances, it is often prudent to treat with a low-dose approach (2 Gy × 2). A total dose of 4 Gy is almost always well tolerated, and response rates exceed 80–90 % (Haas et al. 2003; Russo et al. 2013).

Local control with conventional doses of radiation therapy is very high (24–30 Gy). The most common re-irradiation scenario is in patients receiving 2 Gy × 2 for palliation who either fail to respond or subsequently relapse in field. In this circumstance, it is almost always feasible to give a more protracted regimen (20–30 Gy) which invariably leads to the desired response (Fig. 4) or, in the instance of relapsing patients, to give another 4 Gy.

The most common subtype of marginal zone lymphoma encountered by radiation oncologists is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). These lymphomas most commonly arise within the stomach, orbital adnexa, parotid gland, skin, thyroid gland, and lung. The majority of patients present with localized disease. While an initial trial of antibiotics is appropriate for localized Helicobacter pylori-positive gastric MALT lymphoma, definitive radiation therapy is the preferred treatment for most other presentations. Complete responses to low-dose radiation therapy (24–30 Gy) are the norm (>95 %). Local failure is extraordinarily rare. In a recent large series from the Princess Margaret and Memorial Sloan Kettering Hospitals, failure within the radiation field occurred in 3–5 % of patients (Goda et al. 2010; Teckie et al. 2015). The dominant pattern of failure is at distant sites, typically in areas that are commonly involved by MALT. Thus, the need for radiation therapy for a previously irradiated area is unusual. In such circumstances, low-dose (2 Gy × 2) radiation could be used for palliative purposes (Russo et al. 2013). In select circumstances, depending upon initial dose and location, it may be possible to pursue a second definitive (~24–30 Gy) course of therapy. The more common circumstance is treating a new area for a localized distant relapse (Fig. 5).

The most common plasma cell neoplasms that radiation oncologists encounter are solitary plasmacytomas and multiple myeloma. Only 5 % of plasma cell neoplasms are solitary lesions, which can develop at either osseous sites or in extramedullary locations, the latter most commonly in the head and neck region. For both, the preferred treatment is definitive radiation therapy to a dose of 40–45 Gy. Local control is largely determined by size of the primary tumor with larger tumors having a higher risk of local recurrence (Ozsahin et al. 2006; Tsang et al. 2001). The dominant pattern of failure is systemic progression to multiple myeloma. For osseous and extramedullary plasmacytomas, the 10-year risk of developing multiple myeloma is approximately 70 % and 35 %, respectively (Ozsahin et al. 2006). The majority of patients diagnosed with a plasma cell neoplasm have multiple myeloma. Painful lytic lesions are a common complication which a short course of radiation therapy can palliate. In general, doses of 8–24 Gy are recommended.

It is unusual for a solitary plasmacytoma to fail locally without evidence of systemic progression. In such cases, a second course of radiation therapy could be considered. There have been anecdotal reports of long-term disease control in such circumstances (Mendenhall et al. 1980). The location of the original disease and ability to avoid critical normal regional structures would dictate whether re-irradiation is feasible. Similarly, it is typically unnecessary to repeat a course of radiation therapy for myeloma. However, in circumstances where pain recurs and there is obvious radiographic or pathologic evidence of persistent disease, a second course of radiation is almost always feasible given the relatively low doses that are sufficient to palliate pain (Fig. 6).

Primary central nervous system (CNS) lymphoma is a relatively rare subtype of non-Hodgkin lymphoma. The most important treatment component is high-dose methotrexate, typically given in conjunction with other systemic agents including rituximab (Morris and Abrey 2009). The role of consolidation radiation therapy is controversial, primarily due to the risk of neurotoxicity in older adults after systemic high-dose methotrexate (Abrey et al. 1998). In the presence of a complete response, low-dose (23.4 Gy) whole brain radiation therapy is often utilized and seems to be associated with favorable clinical outcomes, including a low risk of subsequent failure in the brain and a low risk of neurotoxicity (Morris et al. 2013).

Secondary CNS lymphoma occurs when systemic disease secondarily involves the CNS. Current regimens in fit patients utilize a similar approach as primary CNS lymphoma, often in conjunction with high-dose chemotherapy and autologous stem cell transplant. The role of radiation therapy in secondary CNS lymphoma is not established.

Generally, repeat whole brain radiation therapy is not recommended in primary or secondary CNS lymphoma. Stereotactic radiosurgery, in which a tumor is treated with a single, high-dose conformal treatment, has been employed in the setting of limited intracranial progression after whole brain radiation therapy for CNS lymphomas (Kumar et al. 2015; Matsumoto et al. 2007; Kenai et al. 2006) (Fig. 7). Doses of 12–18 Gy have been utilized with overall response rates of ~85 %. Median survival, in heterogeneous populations of patients, is reported to be 10–17 months. As expected, radiosurgery is well tolerated without significant complications. However, distant brain failures are common after stereotactic radiosurgery (Matsumoto et al. 2007), presumably given the multifocality of intracranial disease.

Cutaneous lymphomas consist of both T-cell and B-cell histologies. The most common T-cell histologies are mycosis fungoides and CD30-positive lymphoproliferative disorders, which include lymphomatoid papulosis and primary cutaneous anaplastic large cell lymphoma. The B-cell histologies include primary cutaneous follicle center lymphoma, marginal zone lymphoma, and diffuse large B-cell lymphoma, leg type.