Influence of differing radiotherapy strategies on treatment results in diffuse large-cell lymphoma: a review

In the absence of evidence from randomised trials, radiation treatment of diffuse large-cell lymphoma of B-cell type represents an area of controversy with considerable differences in patterns of practice. The present literature survey aims at clarification of the role of radiotherapy in combined modality settings by identification of dose-response relationships, predictive factors for local control, and potential pitfalls in the interpretation of retrospective studies. Radiotherapy might increase local control in initially involved areas and is usually delivered to these sites (involved-field treatment). Combined modality treatment is currently recommended for patients in stage I or II if they are not treated in the context of prospective studies. Whether involved-field consolidation radiotherapy after systemic treatment in patients with bulky, stage III-IV lymphomas should be routinely recommended is presently unclear. Definition of bulky disease is arbitrary and varied between 6 and 10cm, reflecting a considerable difference in the number of clonogenic tumour cells. Several retrospective and one prospective randomised study suggest improved disease-free and overall survival by radiotherapy in advanced stages. The 5-year local control by radiotherapy was 93-98%. Currently, we recommend the following minimum doses for involved-field radiotherapy derived from this literature survey. Lymphomas with initial size <3.5 cm (possibly <6 cm) can be treated with 30 or 30.6Gy when a complete remission (CR) has been achieved by chemotherapy. The next group might be sufficiently controlled by 36Gy, but it remains unclear whether the cut-off should be 6cm or higher. Forty Gy appears to control tumours in the range of 7-10cm. Most likely, 45Gy does not have to be exceeded for larger lesions. Data on those with less than CR are contradictory. Judging the amount of viable tumour in these patients is problematic, but crucial to determine the intensity of further treatment. The value of positron emission tomography is still under investigation. Because the difference between doses of 30 and 40Gy might actually make a difference for the long-term toxicity of radiotherapy in some of the normal tissues and organs at risk (salivary glands, orbital structures, lung, heart, etc.), it appears prudent to resolve the open questions in prospective trials with careful documentation of side effects.