Recommendations for research
The guideline committee has made the following recommendations for research.
In people with diffuse large B‑cell lymphoma stage II or above, does a baseline FDG‑PET‑CT scan have any advantages over a baseline CT scan in the correct interpretation of the end‑of‑treatment FDG‑PET‑CT scan?
A number of consensus‑based guidelines and a body of clinical opinion advocate baseline FDG‑PET‑CT imaging as being important for interpreting end‑of‑treatment response using FDG‑PET‑CT, although there is little published evidence for this. Baseline FDG‑PET‑CT is also considered to have an important contribution 'over and above' that of contrast‑enhanced diagnostic CT in assigning the International Prognostic Index (IPI), in terms of identifying disease stage and number of extranodal sites involved (influencing the decision to offer central nervous system prophylaxis). A prospective trial is needed to determine whether baseline FDG‑PET‑CT is needed to interpret end‑of‑treatment FDG‑PET‑CT and its role in assigning IPI. People with newly histologically diagnosed diffuse large B‑cell lymphoma would have baseline contrast‑enhanced CT, baseline FDG‑PET‑CT and end‑of‑treatment FDG‑PET‑CT imaging. Readers would need to be trained in both imaging techniques and be experienced members of lymphoma multidisciplinary teams. The reference standard would be histological confirmation of any positive or equivocal end‑of‑treatment FDG‑PET‑CT findings, or follow‑up if there is a negative end‑of‑treatment scan.
In people with high‑grade transformation of follicular lymphoma, which biological and clinical factors predict good outcomes with immunochemotherapy alone?
Before rituximab, it was accepted that high‑grade transformation of follicular lymphoma to diffuse large B‑cell lymphoma portended a poor prognosis. Recent data suggest that although transformation remains an important clinical event, outcomes have improved. It is unclear which people are likely to do well with conventional treatment (such as R‑CHOP) and which people may benefit from intensive treatment with, for example, high‑dose therapy and autologous stem cell transplantation. Many factors are likely to influence outcome, including clinical factors (such as age, stage at transformation and extranodal involvement at transformation), radiological findings (such as early improvement of disease identified using an interim FDG‑PET‑CT scan) and molecular factors (such as certain driver mutations present at transformation, the presence of MYC translocation and response of circulating tumour DNA to treatment). A better understanding of which factors are associated with high‑risk or low‑risk disease would enable therapy to be tailored to the person's needs, reducing unnecessary toxicity for people at low risk and reserving intensive therapy for people at high risk. Outcomes of interest include progression‑free survival and overall survival in subgroups defined by clinical factors, radiological findings and molecular analyses.
In people presenting with diffuse large B‑cell lymphoma and sites of bulky disease, are outcomes improved by radiotherapy to those sites following a full course of chemotherapy?
The role of radiotherapy to sites of original bulky disease in treating diffuse large B‑cell lymphoma is uncertain. Some clinical teams will consider radiotherapy in this setting while others will not because of concerns about morbidity and late effects of treatment. In a recent randomised trial of chemotherapy in people over 60 years old with diffuse large B‑cell lymphoma, people having radiotherapy were identified and compared with a cohort having no radiotherapy. Significant improvements in event‑free, progression‑free and overall survival were seen in the group having radiotherapy. These results have encouraged some teams to reconsider radiotherapy for bulky diffuse large B‑cell lymphoma. A definitive randomised trial is needed to address this question. Outcomes of interest include overall survival, disease‑free survival, progression‑free survival, treatment‑related mortality, treatment‑related morbidity, health‑related quality of life, patient satisfaction, patient preference and overall response rate (complete or partial remission).