Until the 1990s, most patients with early-stage Hodgkin lymphoma were treated with full-dose (35–40 Gy) subtotal nodal irradiation, treating both involved nodal sites and adjacent uninvolved areas. The addition of chemotherapy to radiotherapy was shown to decrease the risk of relapse (Ferme et al. 2007; Specht et al. 1998). Further randomized studies demonstrated that in the setting of systemic therapy, smaller radiation doses and fields were adequate (Bonadonna et al. 2004; Engert et al. 2003, 2010). Currently, the most effective treatment is chemotherapy, typically ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by low-dose, conformal radiotherapy to originally involved areas (Aviles and Delgado 1998; Laskar et al. 2004; Meyer et al. 2012; Noordijk et al. 2005; Pavlovsky et al. 1988; Picardi et al. 2007; Wolden et al. 2012; Herbst et al. 2010). Most randomized studies that have evaluated RT in the context of a combined modality treatment program have utilized the involved field concept (Fig. 13.2).

The principles of volumetric treatment planning discussed above can be used to define consolidation RT target volumes in early stage Hodgkin lymphoma. The volume of the CTV should be defined with careful consideration of the factors listed in Fig. 13.1. In general, the superior and inferior extent of the CTV should include the pre-chemotherapy extent of disease with 2 cm margin regardless of treatment response. The post-chemotherapy width, particularly in the mediastinum and retroperitoneum, is utilized to define the CTV. In cases where there is concern for residual disease, a shrinking field boost technique may be considered.

The treatment fields utilized in Hodgkin lymphoma are presently in flux. Three treatment options are shown in Fig. 13.3 for a patient with early stage, favorable Hodgkin lymphoma involving the left supraclavicular and axillary lymph nodes receiving consolidation RT after two cycles of ABVD. Treatment of an anatomically defined target volume, IFRT, is shown in panel a (see Table 13.1). ISRT and INRT are shown in panels b and c, respectively. Compared to IFRT, the ISRT field includes the axial extent of the involved lymph node stations with smaller superior-inferior margins and no prophylactic irradiation of uninvolved adjacent regions. In this case, the more generous IFRT was used as indicated by the recently published German HD10 study (Engert et al. 2010). In this study, only two cycles of ABVD were administered, and radiation therapy was given to an involved field. Whether involved site or involved-node radiotherapy is adequate in patients receiving only two cycles of ABVD is not clear.

Though infrequent, full-dose STNI is still employed in the contemporary management of Hodgkin lymphoma. A recent trial showed no difference in progression-free or overall survival in patients with favorable disease treated with either ABVD or STNI (Meyer et al. 2012). However, a combined modality approach is still generally pursued given the known late effects of STNI. More commonly, STNI is pursued when a patient has localized (stage I-II) disease that is refractory to multiple chemotherapy regimens.

The initial treatment fields are anatomically defined (Table 13.1) and include the lymph nodes in the bilateral cervical, supraclavicular, axillary, mediastinal, and hilar regions (mantle field). A dose of ~30 Gy to this area is followed by a ~10 Gy boost to sites of gross disease. Prophylactic treatment of para-aortic lymph nodes and the spleen typically follows after a 2-week break. Figure 13.4 shows a standard STNI field setup. Strategies to optimize accurate matching of supra- and infradiaphragmatic fields are needed. In the presented case (Fig. 13.4), a complete response was achieved after STNI, and the patient was then considered for a stem cell transplant.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an unusual subtype of Hodgkin lymphoma, consisting of ~5 % of cases. It has a distinct immunophenotype (CD15 and CD30 negative, CD20 and CD45 positive), presentation, and natural history. While overall relapse rates are similar between classical Hodgkin lymphoma and NLPHL, patients with the latter tend to relapse later and survive relapses better (Nogova et al. 2008; Diehl et al. 1999). The optimal treatment is not clear, and given the rarity of this disease, randomized trials will be difficult to perform. For patients with localized disease, RT alone is generally recommended (Nogova et al. 2005; Chen et al. 2010). However, at least one study has suggested that the addition of chemotherapy may be associated with better outcomes (Savage et al. 2011).

The same principles of volumetric treatment planning should be applied to NLPHL. In cases where systemic therapy is not used, a more generous CTV is recommended. On the other hand, following a good clinical response to systemic therapy, more conformal CTV volumes may be more appropriate.

For instance, Fig. 13.5 shows two clinical target volumes for a patient with NLPHL involving a single left inguinal lymph node. In the presented case, no systemic therapy was utilized, and the larger clinical target volume was treated (panel a) with a boost to the smaller clinical target volume (panel b), as RT was utilized to eradicate both clinical and subclinical disease. Theoretically, however, if systemic therapy had been given, it may have been more appropriate to irradiate the smaller CTV (panel b). For treatment of the inguinal region, the patient should be positioned frog-legged in order to separate the leg from the external genitalia and minimize skin folds. When possible the genitalia should be positioned out of the field, and the testicles should be shielded in men.

Historically, RT was the preferred treatment for localized diffuse large B-cell lymphoma (DLBCL). Single-institution studies demonstrated that long-term disease control was achieved in ~40–45 % of patients (Vaughan Hudson et al. 1994; van der Maazen et al. 1998; Kaminski et al. 1986). Subsequent randomized trials demonstrated that the addition of chemotherapy to RT significantly decreased the risk of disease recurrence (Landberg et al. 1979; Monfardini et al. 1980; Nissen et al. 1983). Currently, the majority of patients are treated initially with immunochemotherapy, mostly commonly R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Most (Horning et al. 2004; Martinelli et al. 2009; Miller et al. 2001), but not all (Bonnet et al. 2007), studies have shown that consolidation RT decreases the risk of recurrence after chemotherapy, and a combined modality approach has become a standard of care in localized DLBCL.

The principles of target volume delineation and treatment are similar to that of Hodgkin lymphoma for nodal DLBCL. DLBCL involves extranodal sites more commonly than Hodgkin lymphoma. When treating extranodal sites, clinical judgment is necessary to determine how much of the structure should be included in the clinical target volume. This will depend on the site treated as well as quality of diagnostic imaging. Figure 13.6 depicts the treatment plan for a patient with stage IIA DLBCL involving the left tonsil and ipsilateral level 2 neck. An ISRT CTV was delineated using the pre-chemotherapy PET/CT to include the entire tonsil and ipsilateral neck. Due to the proximity of the CTV to critical normal structures, namely, the parotid gland and oral cavity, IMRT was utilized to improve conformality. The prescription isodose contour is shown in cyan with simultaneous coverage of the CTV (red contour) and avoidance of the left parotid (yellow contour) and oral cavity (pink contour). IMRT is often advantageous for irradiation of targets in the head and neck due to proximity of many dose-limiting normal structures.

Figure 13.7 shows the opposed lateral treatment fields utilized in the consolidative irradiation of a patient with ocular DLBCL. In this case, the retina and vitreous were the targets for irradiation. The isocenter of treatment was placed at the anterior edge of the globe in order to minimize tangential irradiation of the cornea. Tissue-compensating wedges were used to improve dose homogeneity.

Follicular lymphoma is the second most common subtype of non-Hodgkin lymphoma. Most present with advanced disease and are primarily managed with systemic immunochemotherapy. Low-dose RT can complement systemic therapy by providing very effective palliation of symptomatic areas (4 Gy in 1–2 fractions). For the minority of patients with localized disease, most published guidelines recommend RT alone (24–30 Gy). This recommendation is based on multiple studies with long follow-up showing 10-year failure-free survival of ~50 % (Vaughan Hudson et al. 1994; Campbell et al. 2010; Guadagnolo et al. 2006; Mac Manus and Hoppe 1996), with few relapses occurring thereafter. A study using data from the Surveillance, Epidemiology, and End Results (SEER) program demonstrating superior survival in patients who receive RT for stage I follicular lymphoma supports this approach (Pugh et al. 2010).

Diagnostic imaging, preferably contrast-enhanced PET/CT, should be used to delineate the GTV. In most cases, localized follicular lymphoma will be treated with RT alone. Thus, RT is relied upon to eradicate clinically apparent and microscopic disease in the immediate region. Hence, IFRT is preferred over INRT. Most patients with stage I follicular lymphoma present with disease in the inguinal region, axilla, or neck. Treatment of these sites, compared to those more centrally located, is associated with a low risk of morbidity. Figure 13.8 depicts the GTV (red contour) and CTV (green contour) for a patient with stage IA FL of the left axilla treated with RT alone. The medial axillary lymph nodes are located where the axillary vessels cross the lateral aspect of the pectoralis minor. Since no systemic therapy was given, the medial lymph nodes are included as well as the lymph nodes in the supraclavicular fossa. Full humeral head blocking should be avoided when treating the axilla.

Marginal zone lymphoma is the third most common non-Hodgkin lymphoma and consists of three entities – extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), splenic marginal zone lymphoma, and nodal marginal zone lymphoma. The latter two entities are fairly rare and will not be discussed further. Most patients with MALT lymphoma present with localized disease. The most commonly involved sites include the stomach, orbital adnexa, salivary glands, thyroid, skin, and lungs (Goda et al. 2010). Though patients with localized MALT lymphoma are often treated with RT alone, the simulation and treatment planning approach vary widely. The most common sites of involvement receive additional attention below.

The microorganism Helicobacter pylori is the causative agent of gastric MALT lymphoma for many patients. Eradication of the bacterium results in lymphoma regression and long-term disease-free survival in ~50 % of patients (Wundisch et al. 2005; Schechter et al. 1998). RT is used in those patients without an apparent H. pylori infection or who have refractory or progressive disease despite antibiotics. RT results in lymphoma eradication and long-term disease control in >90 % of patients.