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Editorials
Towards individualized radiation therapy in multiple myeloma
Felix Momm,1 Christine Greil2 and Henning Schäfer3
1Department of Radiation Oncology, Ortenau Klinikum Offenburg-Kehl, Teaching Hospital of Albert-Ludwigs University Freiburg, Offenburg; 2Department of Hematology, Oncology and Stem Cell Transplantation, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg and 3Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, German Cancer Consortium (DKTK) Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, Germany
E-mail: FELIX MOMM - felix.momm@ortenau-klinikum.de doi:10.3324/haematol.2019.243451
Fortunately, recent progress in systemic treatment has prolonged the median overall survival of myeloma
1,2
patients. However, this leads to increasing numbers
of radiation cycles being administered for supportive rea- sons (e.g. pain, stability). Although radiation can result in hematopoietic insufficiency in a dose-dependent manner, leading to ineligibility for systemic treatment, the best radiation regimen providing optimal local control and minimized bone marrow toxicity is still under investiga- tion. The current guidelines for radiotherapy in patients diagnosed with multiple myeloma were summarized in a critical review by the International Lymphoma Radiation Oncology Group in 2018.3 In their letter published in this issue of Haematologica, Elhammali et al. contribute the large and high-value experience of the MD Andersson Cancer Center to this ongoing discussion.4 After analysis of treatment, toxicities and tumor control in 772 myelo- ma patients with 1,513 irradiated lesions and a median follow-up of 65.6 months the authors claim that radiation doses as low as 20-25 Gy were sufficient to avoid reirra- diation in more than 97% of all cases. However, in uni- variate analysis, a biologically effective dose assuming an α/β ratio of 10 Gy (BED10) of <28 Gy was associated with an increased risk of reirradiation. As the authors state themselves, the study is limited by the well-known bias of retrospective data with a long observation period.4 From our perspective, the most important problems seem to be the comparatively weak endpoint of reirradiation and the selection bias of how dose was determined in the individual patient.4 Our own clinical experience shows that lower doses are preferentially given to elderly or frail patients, in order to save treatment time and reduce acute
toxicity, or in cases of small lesions with low tumor bur- den. In fragile patients reirradiation is often not per- formed as these patients may die prior to local tumor recurrence because of systemic disease progression or rel- evant comorbidities and the reirradiation is therefore underestimated. In patients with small lesions, a lower irradiation dose may probably be sufficient to achieve local tumor control. Despite the reported data, we would therefore still recommend higher doses of 30-40 Gy to large lesions as stated by the International Lymphoma Radiation Oncology Group.3 Especially when treating critical lesions of the spine or the skull base as well as lesions particularly prone to fractures, it is essential to reach stable local tumor control. In this context we sug- gest that toxicity should be avoided by shrinking the irra- diation field rather than by reducing dose. Targeted dosage to bone lesions or extramedullary tumors will not compromise bone marrow function relevantly.
Nevertheless, the reported routine clinical records of a reference center with a high number of cases4 still con- tribute valid arguments to the ongoing discussion: The authors could show that in this selected cohort compara- tively low doses were sufficient for a high rate of tumor control, emphasizing that selected plasmacytoma sites with low tumor burden might definitely be effectively irradiated with doses as low as 20-25 Gy, and that in advanced disease stage, lower doses and therefore shorter time of treatment are still sufficient for local control.4
The best approach is probably to apply high doses pre- cisely to sites with large tumor burden and to reduce doses in sites with less or disseminated tumor and if func- tional bone marrow may be affected. With modern inten-
AB
Figure 1. Planning computed tomography scanning of a myeloma lesion in the right ischium. The dose distribution is depicted by a color wash from red (= high dose) to dark blue (= low dose). (A) Conventional technique: 50 Gy in 20 fractions of 2.5 Gy to complete target volume. Black arrow: areas of high dose out of target volume (red line/white arrow). (B) Volume modulated arc therapy (VMAT) technique. Red line/white arrow: main target volume 40 Gy in 20 fractions of 2.0 Gy; orange line/red arrow: integrated boost target volume 50 Gy in 20 fractions of 2.5 Gy. The complete dose of each fraction is delivered simultaneously integrated to both tar- get volumes.
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