The "Radiation and the Modern Management of Lymphoma" issue (May 1, 2015) of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO), is focused on the integral role of radiation therapy in current lymphoma treatment. May 2015 marks 50 years since the first multidisciplinary lymphoma conference, "La Radiotherapie de la Maladie de Hodgkin," was held in Paris in 1965, which led to a more comprehensive understanding of the cancer's pathology, staging and treatment.
In the first half of the 20th century, radiation therapy was primarily used to palliate patients' symptoms because of technical limitations, and it was generally believed that the disease was incurable. During the 1965 Paris conference, the work of individuals such as M. Vera Peters, MD, Henry Kaplan, MD, and Maurice Tubiana, MD, PhD, demonstrated that cure was indeed possible using radiation therapy. A classification system was agreed upon using observations about the patterns of spread and new forms of imaging such as the lymphangiogram. This system distinguished between those with localized disease who could be managed by radiation therapy to the affected nodes and the neighboring nodal regions where the disease may also be hiding, and the more advanced disease that would ultimately need chemotherapy for cure. In the early 1960s, chemotherapy regimens, such as MOPP (mechlorethamine, vincristine, procarbazine and prednisone), were used for curative intent in patients with more advanced stage disease. During the next several decades, the integration of radiation therapy with novel chemotherapy was progressively evaluated in a series of trials.
Twenty-six studies and articles are included in this issue of the Red Journal, and they detail the complex role of radiation therapy, including treatment design and delivery, combination therapies and modern imaging, which have led to improved outcomes for patients with Hodgkin lymphoma and patients with non-Hodgkin lymphoma.
Two guidelines from the International Lymphoma Radiation Oncology Group (ILROG) analyze field and dose guidelines. Joachim Yahalom, MD, FASTRO, et al, address the technical challenges of simulation, volume definition and treatment planning for commonly involved organs in patients with extra-nodal lymphomas, which account for approximately one-third of all non-Hodgkin lymphomas. Lena Specht, MD, PhD, et al, outline recommendations on the delivery of radiation therapy in the treatment of primary cutaneous lymphomas, which require a modified approach compared to treatment for nodal or systemic lymphomas.
Two studies focus on the use of rituximab, which is used in diseases with an excessive amount of B cells including lymphoma. Susan M. Hiniker, MD, et al, explore the use of post-treatment surveillance studies for patients with limited-stage diffuse large B-cell lymphoma who were treated with chemotherapy with or without rituximab, radiation therapy or combined modality therapy. The authors found that the use of PET scans for post-treatment surveillance was not associated with a survival advantage and suggest limited use of post-treatment surveillance in this patient population.
A study by Naresh Jegadeesh, MD, et al, identifies predictors of local recurrence to determine which patients with stage III and stage IV diffuse large B-cell lymphoma treated with rituximab alone may benefit from the addition of consolidative radiation therapy. The authors conclude that patients with stage III disease or with disease ≥5 cm, and patients with <5 cm disease and SUV-max ≥15 have a higher risk of local recurrence and may benefit from consolidative radiation therapy following chemoimmunotherapy.
In another study, Jeanny Kwon, MD, et al, explore the role of involved-lesion radiation therapy after R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) for patients with limited stage diffuse large B-cell lymphoma. Involved-lesion radiation therapy may reduce toxicity through the use of smaller radiation therapy fields than involved-field radiation therapy. The authors analyzed the rates of progression-free survival and overall survival in patients treated with R-CHOP therapy alone compared to patients treated with R-CHOP followed by involved-lesion radiation therapy. The study's results suggest that adding involved-lesion radiation therapy after R-CHOP therapy improves both progression-free and overall survival.
Chelsea C. Pinnix, MD, PhD, et al, evaluate predictors of radiation pneumonitis (radiation-induced lung disease) in patients with Hodgkin and non-Hodgkin lymphoma, who are treated with intensity modulated radiation therapy (IMRT) to the thoracic region. The results demonstrate that patients who received salvage chemotherapy for relapsed or refractory disease in addition to IMRT had the highest risk of radiation pneumonitis. Low doses of radiation to large lung volumes was also a predictor of radiation pneumonitis.
Additional studies and editorials included in this Red Journal issue are:
• Richard T. Hoppe, MD, FASTRO, and Saul Rosenberg, MD - Editorial: "The Paris Conference, "La Radiothérapie de la Maladie de Hodgkin" A first step in the cure of Hodgkin's disease"
• Joan Reinhardt-Reiss, MS, and Sarah S. Donaldson, MD, FASTRO - Editorial: "Homage to M. Vera Peters, MD"
• Stephanie Terezakis, MD - Editorial: "Dorothy Reed: Expressions of a Pioneer in Hodgkin's Disease"
• Bradford S. Hoppe, MD, MPH, and Richard T. Hoppe, MD, FASTRO - "Expert Radiation Oncologist Interpretations of Involved-Site Radiotherapy Guidelines in the Management of Lymphoma"
• Jan Kriz, MD, et al - "Relapse analysis of irradiated patients within the HD15 trial of the German Hodgkin Study Group"
• Jordan A. Torok, MD, et al - "Low-Dose Consolidation Radiation Therapy for Early-Stage Unfavorable Hodgkin Lymphoma"
• Kavita V. Dharmarajan, MD, MSc, et al - "Patterns of Relapse From a Phase III Study of Response-Based Therapy for Intermediate-Risk Hodgkin Lymphoma (AHOD0031): A Report From the Children's Oncology Group"
• Martin King, MD, PhD, et al - "Management of Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) in the Modern Era"
• Naamit K. Gerber, MD, et al - "Characteristics and Outcomes of Patients with Nodular Lymphocyte-Predominant Hodgkin Lymphoma vs. Classical Hodgkin Lymphoma: A Population-Based Analysis"
• Francisco Mestre, MD, et al - "Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma"
• Chelsea C. Pinnix, MD, PhD, et al - "Single Institutional Experience in the Treatment of Primary Mediastinal B Cell Lymphoma Treated with Immunochemotherapy in the Setting of Response Assessment by 18Fluorodeoxyglucose Positron Emission Tomography"
• Randa Tao, MD, et al - "Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-cell Lymphoma"
• Sewit Teckie, MD, et al - "Long-Term Outcomes and Patterns of Relapse of Early-Stage Extra-nodal Marginal Zone Lymphoma Treated with Radiotherapy with Curative Intent"
• Maria R. Kamstrup, PhD, et al - "Low-Dose (10 Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis"
• Maja Maraldo, MD, PhD, et al - "Radiation Therapy Planning for Early-Stage Hodgkin Lymphoma: Experience of the International Lymphoma Radiation Oncology Group"
• Frederika A. Nimwegen, MSc, et al - "A simple method to estimate mean heart dose from Hodgkin lymphoma radiotherapy based on simulation X-rays"
• Andrea Riccardo Filippi, MD, et al - "Optimized Volumetric Modulated Arc Therapy vs. 3D-CRT for Early Stage Mediastinal Hodgkin Lymphoma without Axillary Involvement: a Comparison of Second Cancers and Heart Disease Risk"
• M.C. Aznar, PhD, et al - "Minimizing Late Effects for Patients With Mediastinal Hodgkin Lymphoma: Deep Inspiration Breath-Hold, IMRT, or Both?"
• Thatcher R. Heumann, BA, et al - "Total Skin Electron Therapy for Cutaneous T-Cell Lymphoma Using a Modern Dual-Field Rotational Technique"
"Few malignancies have been examined with the same history and rigor as the lymphomas," said Anthony L. Zietman, MD, FASTRO, editor-in-chief of the Red Journal and professor of radiation oncology at Massachusetts General Hospital in Boston. "Meticulous study in a series of well designed trials by radiation oncologists and medical oncologists working together and separately has led us to where we are today. The exceptional studies in this Red Journal issue capture the spirit of investigation that has yielded really meaningful advances for contemporary lymphoma management."