Impact of Consolidation Radiotherapy in Bulky Diffuse Large B Cell Lymphoma By PET Based Response Assessment

The prognostic significance of bulky disease at baseline and the role of routine consolidation radiotherapy (RT) in such cases of diffuse large B cell lymphoma(DLBCL) in Positron Emission Tomography ( PET) era is not very clear. In the landmark MabThera International Trial(MInT trial), RT was administered to all patients with initial bulky disease. The 3 year event free survival(EFS) and overall survival(OS) were inferior in the group with bulk compared to no bulk ( EFS 52 % versus 78 % , OS 81% versus 92%). However the response assessment in this study was not PET-based. A retrospective study from the British Columbia Cancer Agency reported that patients with initial bulky disease , if able to achieve PET negativity at the end of treatment(EOT), had outcomes similar to those without bulk, despite omission of RT .

To date there is no published data comparing role of consolidation RT versus omission of RT if a patient with bulky disease achieves EOT PET-complete response (CR) . Since the data is not very clear, the practice of consolidation RT varies largely across different centres. Hence this study aims to assess if there is survival difference between groups with and without consolidation RT in patients with bulky disease who attain EOT PET-CR.

A retrospective multicentric study was conducted by collecting data from eleven-member centers of Hematology Cancer Consortium (www.hemecancer.org) using an electronic database. Patients with DLBCL ≥ 18 years treated with curative intent between 2019-2022 were included. Bulk was defined as ≥ 7.5 cm nodal/extranodal lesions. In addition to demographics, details on Eastern Co-operative Oncology Group Performance status(ECOG PS), stage, extranodal involvement, B symptoms, treatment regimen, radiation details, response rates, and survival were collected.

A total of 1455 patients had received curative intent treatment. Median age was 52 years( IQR 41-61), and 888 (61 %) were males. ECOG PS was < 2 in 89 %( 1140/1274). Any form of co-morbidities was noted in 41 % (600) patients. Advanced stage ( stage III/IV) was noted in 62 % (855/1374) . Extranodal involvement was noted in 53 % (777), B symptoms in 43% (621) and high LDH in 68% (804/1175) patients. The most common treatment administered was R CHOP in 1200 ( 83%) . A complete remission(CR) was attained in 786 ( 77%). Details on bulk disease status at diagnosis was available in 1326 patients . Five hundred and thirty four ( 40 %) had bulky disease. The following baseline characteristics at diagnosis namely ECOG PS ≥2 ( 34 % Vs 26 %), extranodal involvement( 60 % Vs 52%), high LDH( 82% Vs 62%), B symptoms( 47 % Vs 40 %), advanced stage ( 72 % Vs 57 %) and failure to achieve CR (28 % Vs 20 %) were all significantly higher in those with bulky disease. Among the bulky cases 192 cases attained CR by EOT PET based assessment of which 94 had received consolidation RT and 98 didn’t. There was no significant difference in disease related characteristics between RT and non-RT groups except for high LDH in the former (85 % Vs 68 %, p=0.01).

With a median follow up of 22 months, progression free survival (PFS) and overall survival (OS) for the entire cohort at 2-years were 77 % and 84 % respectively. Estimated 2-year PFS was inferior in patients with bulky disease versus non-bulky ( 73 % Vs 79 % , p= 0.02) , but OS was similar ( 82 % Vs 85 %, p= 0.16). Among patients attaining EOT PET CR , consolidation RT did not result in any improvement in PFS ( 93 % Vs 91 %, p= 0.84) or OS (96 % Vs 95 %,p=0.75) compared to non-RT group.

Presence of bulky disease at baseline is associated with inferior PFS. If bulky disease patients are able to attain CR assessed by EOT PET CT , omission of RT did not result in inferior PFS. These findings have to be confirmed by large prospective trials.