When is 4 Gy enough? Defining dose sufficiency and durable control in indolent B-cell lymphoma

Ultra-low-dose radiotherapy, most commonly delivered as 4 Gy in two fractions (2 Gy × 2), is an established low-burden approach for radiosensitive indolent B-cell lymphoma. Its use as stand-alone definitive local therapy is constrained by a persistent gap between early tumor regression and durable local control. This review examines when 4 Gy should be considered sufficient by integrating clinical intent, lesion biology, response assessment, immune context, and emerging biomarkers. We distinguish its use as stand-alone local treatment, palliation, response-adapted de-escalation, and immune-integrated strategies. Across these settings, early response indicates radiosensitivity but does not prove lesion sterilization or equivalence to standard-dose radiotherapy. Dose sufficiency depends on durable in-field control, tumor burden, anatomical definition, reassessment reliability, feasibility of salvage, and the consequences of local failure. Immune and cellular combinations may extend the value of 4 Gy beyond local cytoreduction, but the contribution of irradiation should be tested separately from systemic or intratumoral partners. PET response, MRD, ctDNA, and immune correlates may help distinguish transient cytoreduction from durable clearance and local response from patient-level disease control. At present, these biomarkers are better suited to trial design and mechanistic validation than to routine dose selection. Future studies should move beyond response rates and define decision rules that link early response, immune modulation, biomarker dynamics, lesion-level durability, salvageability, and cumulative treatment burden.