1. Figure 3 Risk-adapted and response-adapted
strategies, staging, response assessment and surveillance
Figure 3 | Risk-adapted and response-adapted strategies, staging, response assessment and surveillance. a | Pathway diagram summarizing current practice in assigning patients to receive conventional chemotherapies. b | A template for future practice in assigning patients to receive novel agents/long-term therapies. The yellow boxes highlight some of the key questions that are best answered using clinical trials involving novel agents. Q1. Combined-modality imaging using contrast-enhanced CT, diffusion-weighted (DW)–MRI and/or PET–CT, depending on lymphoma subtype, might facilitate the more-accurate measurement of tumour volume and provide data that enables radiogenomic approaches. Genetic profiling of diagnostic biopsy samples and analysis of circulating tumour DNA (ctDNA) could define a genetic signature that enables non-invasive disease monitoring in the majority of patients. An integrated Specialist Integrated Haematological Malignancy Diagnostic Services (SIHMDS)/ Specialist Integrated Haematological Malignancy Imaging Reporting (SIHMIR) document should ideally contain the diagnosis, stage, risk category and genetic profile for tailoring treatment, recommended imaging modality and genetic signature for ctDNA monitoring. Q2. This is perhaps the most challenging aspect of patient management with novel therapies, and is likely to depend on tumour type and therapy used. Clinical response and treatment tolerability, rather than imaging findings, are more likely to guide the initial approach to therapy for treatments associated with 'tumour flare'. Clinical trials should attempt to define the critical time points for assessing refractoriness to individual agents using imaging and/or based on the emergence of resistance mutations. The latter is likely to be more informative in terms of selection of the next line of therapy. Q3. Two cohorts of patients requiring surveillance exist: those 'with' and those 'without' measurable residual disease, whether or not they continue on therapy. The former cohort should be monitored more frequently compared with the latter, with the intervals defined based on lymphoma histology and therapy. Surveillance with ctDNA is preferable to avoid exposure to radiation, with scans repeated if clinically indicated by evidence of progression according to ctDNA or disappearance of ctDNA (to confirm lymphoma clearance). Patients with 'low risk, curable' lymphomas who have completed treatment could receive only clinical surveillance. Q4. Clinical trials should be conducted to evaluate the possibility of discontinuation of therapy in patients with undetectable MRD. Randomized trials should also be undertaken to evaluate the role of consolidation or maintenance strategies in the setting of undetectable MRD, particularly in patients with high-risk disease.
Cunningham, J. et al. (2017) Evolution of lymphoma staging and response evaluation: current limitations and future directions
Nat. Rev. Clin. Oncol. doi: /nrclinonc