Role of Bone Marrow Biopsy in the Staging of Diffuse Large B-Cell Lymphoma in the PET/CT Era
Bibliographic record
Abstract
Abstract Background Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) and bone marrow involvement by lymphoma is seen in up to one third of cases, as assessed by iliac crest bone marrow biopsy (BMB) at the time of diagnosis. Traditionally, BMB has been the gold standard test to detect bone marrow infiltration by lymphoma. 18-Fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT), has become standard in the initial staging of DLBCL. Prior studies have suggested that PET/CT staging may obviate the need for staging BMB in patients with Hodgkin lymphoma. However, because of limited evidence, this approach has not been adopted in patients with DLBCL. We investigated whether BMB adds useful information to PET/CT staging in patients with an initial diagnosis of DLBCL. Patients and Methods Patients with a new diagnosis of DLBCL who underwent both staging PET/CT and BMB were retrospectively identified across three institutions: British Columbia Cancer Agency (n=149, 2011-2013), Aalborg University Hospital (n=179, 2007-2013), and Copenhagen University Hospital (n=202, 2009-2012). We reviewed the reports of PET/CT scans and BMBs from each academic institution performed at the time of diagnosis prior to treatment of DLBCL. Ann Arbor stage was determined including PET/CT with and without the contribution of BMB, and the proportion of stage IV cases by each method was calculated. Results 530 patients were identified: median age 65 years (range 16-90), 294 (56%) male, 137 (26%) largest mass >10cm, 263 (50%) elevated LDH, 105 (20%) performance status >2, and 149 (28%) with more than one extranodal site. International Prognostic Index score was 0-1 in 159 (30%), 2 in 145 (27%), 3 in 119 (23%), and 4-5 in 107 (20%) patients. 520 (98%) received rituximab-containing chemotherapy, 130 (25%) radiotherapy, and 3 (<1%) consolidative autologous stem cell transplantation. A total of 181 (34%) patients had bone marrow involvement established by either PET/CT (n=146, 28%), BMB (n=87, 16%), or both (n=52, 10%). Focal skeletal lesions on PET/CT were unifocal (n=42), bifocal (n=15), multifocal/diffuse (n=89). 52 of the 146 patients (36%) with positive PET/CT had a positive BMB (39 DLBCL, 13 iNHL), while 35 of the 384 patients (9%) with negative PET/CT had a positive BMB (12 DLBCL, 23 iNHL). Table 1 shows the distribution of Ann Arbor staging as defined by PET/CT alone and with inclusion of BMB results. BMB upstaged 12/209 (6%) stage I/II patients to stage IV, including 3 patients with DLBCL and 9 patients with iNHL in the bone marrow. Focal skeletal lesions on PET/CT identified bone marrow involvement by lymphoma (DLBCL or iNHL) with sensitivity 60%, specificity 79%, positive predictive value 36%, and negative predictive value 91%. In a subgroup analysis excluding the 36 patients with iNHL in the bone marrow, focal skeletal lesions on PET/CT identified bone marrow involvement by DLBCL with sensitivity 78%, specificity 79%, positive predictive value 29%, and negative predictive value 97%. Conclusions In patients with DLBCL, staging PET/CT does not identify all cases with bone marrow involvement. BMB upstaged 6% of patients with stage I/II who had a PET/CT negative for any skeletal involvement. However, the majority had indolent histologies in the bone marrow, and only 1% were upstaged due to involvement of the bone marrow with DLBCL. Although PET/CT has a high negative predictive value for ruling out bone marrow involvement by high grade lymphoma, BMB remains a necessary component in the evaluation of patients with a new diagnosis of DLBCL mainly because of its ability to detect iNHL that was missed by PET/CT which may have implications in the post-treatment surveillance setting. Table 1. Clinical staging by PET/CT alone and with inclusion of bone marrow biopsy results. Clinical Stage Staging Modality Patients upstaged to stage IV by bone marrow biopsy PET/CT alone PET/CT and bone marrow biopsy N (%) N (%) N I 121 (23) 114 (21) 7 (2 DLBCL, 5 iNHL) II 88 (17) 83 (16) 5 (1 DLBCL, 4 iNHL) III 92 (17) 77 (15) 15 (5 DLBCL, 10 iNHL) IV 229 (43) 256 (48) Not applicable Disclosures No relevant conflicts of interest to declare.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".