Times Not to Forget Radiotherapy When Treating Patients With Lymphoma

Charles A. Enke, MD


J Oncol Pract. 2019;15(4):167-172. 

In This Article

Extranodal NK/T-cell Lymphoma, Nasal Type

Extranodal NK/T-cell lymphomas, nasal type, are common in Asia, but are relatively rare in Western countries. In China, NK/T-cell lymphoma accounts for 12% to 17% of all lymphomas.[19] NK/T-cell lymphoma most commonly involves the nasal cavity and/or paranasal sinuses. Waldeyer's ring is also at risk with upper aerodigestive tract presentations. Whereas lymph node involvement is uncommon with disease limited to the nasal cavity, involvement of Waldeyer's ring is associated with an increased risk for regional lymph node involvement. Presentations within the nasal cavity frequently are limited to stages I and II. Although there has been a significant evolution in the role of systemic therapy for this disease entity, inclusion of radiation therapy in the treatment plan is critical for disease control. In the absence of a clinical trial, the sequencing of radiation therapy and systemic therapy is dependent on the chemotherapy regimen that is selected. The radiation dose that is recommended is also dependent on the systemic regimen used. Concurrent chemoradiotherapy with radiation therapy doses of 50 Gy combined with three courses of DeVIC (dexamethasone, etoposide, ifosfamide, and carboplatin) is one approach. Another option would include initial radiation therapy with doses of 40 to 52.8 Gy combined with cisplatin followed by three cycles of VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone). A third option is on the basis of a modified-SMILE (steroid=dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) regimen for patients with stage I or II disease. The chemotherapy is given for two to four cycles followed by radiation therapy to doses of 45 to 50.4 Gy. This was based on a clinical trial performed at Memorial Sloan Kettering Cancer Center.[20] In this case, the radiation therapy does follow chemotherapy; however, it should be noted that this is an asparaginase-containing regimen. There is a sandwich approach involving two cycles of P–GEMOX (pegaspargase plus gemcitabine, oxaliplatin) followed by radiation therapy to a dose of 56 Gy followed by an additional two to four cycles of P–GEMOX. In those patients who are not fit for systemic therapy, radiation therapy as monotherapy is still a reasonable option, although it does seem that a dose of 50 Gy or higher is important. Treatment of patients with NK/T-cell lymphoma involving the nasal cavity and/or paranasal sinuses requires an integrated multimodality approach. There must be communication among the otolaryngologist, radiologist, and radiation oncologist to understand the macroscopic extent of disease. For nasal cavity presentations, there must be clear understanding of whether there is involvement of one or both sides of the nasal cavity as well as evidence of extension into the paranasal sinuses, including ipsilateral versus bilateral maxillary sinus involvement. Imaging is useful to assess for involvement of the ethmoid sinuses. A guidelines paper published by the International Lymphoma Radiation Oncology Group describes the details for radiation therapy volumes and treatment dose.[6] The radiation technique has evolved over time, and there seems to be evidence of benefit to the use of IMRT, including volumetric modulated arc therapy techniques. While ISRT is a common technique used for combined modality lymphoma therapy, the radiation volumes that are required for NK/T-cell lymphoma generally increase with staging procedures as the result of inclusion of additional adjacent areas after imaging and communication with the diagnostic team. The sequencing of radiation therapy in the combined modality setting seems to be important and is dependent on which systemic regimen is used. In nonasparaginase regimens, the radiation therapy should be initiated upfront or in combination with systemic therapy, including sandwich regimens. Delaying radiation therapy until all systemic therapy is completed may result in higher local failure rates when using nonasparaginase-containing regimens.[21]