The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma: An international multicenter study of 1532 patients treated with chemoimmunotherapy.

PURPOSE: Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. METHODS: We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. RESULTS: Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2-21.2%) compared with 2.6% (95% CI 1.7-3.5) among those with ≤2 sites (P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. CONCLUSIONS: Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.

Uterine, but not ovarian, female reproductive organ involvement at presentation by diffuse large B-cell lymphoma is associated with poor outcomes and a high frequency of secondary CNS involvement.

Involvement of the internal female reproductive organs by diffuse large B-cell lymphoma (DLBCL) is uncommon, and there are sparse data describing the outcomes of such cases. In total, 678 female patients with DLBCL staged with positron emission tomography/computed tomography and treated with rituximab-containing chemotherapy were identified from databases in Denmark, Great Britain, Australia, and Canada. Overall, 27/678 (4%) had internal reproductive organ involvement: uterus (n = 14), ovaries (n = 10) or both (n = 3). In multivariate analysis, women with uterine DLBCL experienced inferior progression-free survival and overall survival compared to those without reproductive organ involvement, whereas ovarian DLBCL was not predictive of outcome. Secondary central nervous system (CNS) involvement (SCNS) occurred in 7/17 (41%) women with uterine DLBCL (two patients with concomitant ovarian DLBCL) and 0/10 women with ovarian DLBCL without concomitant uterine involvement. In multivariate analysis adjusted for other risk factors for SCNS, uterine involvement by DLBCL remained strongly associated with SCNS (Hazard ratio 14·13, 95% confidence interval 5·09-39·25, P < 0·001). Because involvement of the uterus by DLBCL appears to be associated with a high risk of SCNS, those patients should be considered for CNS staging and prophylaxis. However, more studies are needed to determine whether the increased risk of secondary CNS involvement also applies to women with localized reproductive organ DLBCL.

No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish-Swedish population-based observational study.

The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population-based study, we examined the post-remission survival of Danish and Swedish HL patients for whom follow-up practices were different. Follow-up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow-up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18-65 years, diagnosed in the period 2007-2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1-7) for patients with stage I-II disease vs. 12% (95% CI 6-18) for patients with stage III-IV disease. An imaging-based follow-up practice was not associated with a better post-remission survival in general (P = 0·2) or in stage-specific subgroups (P = 0·5 for I-II and P = 0·4 for III-IV). Age ≥45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post-remission survival. The present study supports clinical follow-up without routine imaging, as encouraged by the recent Lugano classification.

A population-based study of prognosis in advanced stage follicular lymphoma managed by watch and wait.

Watch and wait (WAW) is a common approach for asymptomatic, advanced stage follicular lymphoma (FL), but single-agent rituximab is an alternative for these patients. In this nationwide study we describe the outcome of patients selected for WAW. A cohort of 286 out of 849 (34%) stage III-IVA FL patients seen between 2000 and 2011, were managed expectantly and included. The 5-year progression-free survival (PFS) was 35% [95% confidence interval (CI) 29-42]. The 10-year overall survival (OS) was 65% (95%CI 54-78), and the cumulative risk of dying from lymphoma within 10 years of diagnosis was 13% (95%CI 7-20). Elevated lactate dehydrogenase and > four nodal regions involved were associated with a higher risk of lymphoma treatment and death from lymphoma. The WAW patients and a matched background population had similar OS during the first 50 months after diagnosis (P = 0·7), but WAW patients had increased risk of death after 50 months (P < 0·001). The estimated loss of residual life after 10 years was 6·8 months. The 10-year cumulative risk of histological transformation was 22% (95%CI 15-29) and the 3-year OS after transformation was 71% (95%CI 58-87%). In conclusion, advanced stage FL managed by WAW had a favourable outcome and abandoning this strategy could lead to overtreatment in some patients.

Prognostic impact of clinician-based interpretation of 18F-fluorodeoxyglucose positron emission tomography/computed tomography reports obtained in patients with newly diagnosed diffuse large B-cell lymphoma.

The aim of this study was to evaluate the prognostic value of clinician interpretation of positron emission tomography/computed tomography (PET/CT) reports at mid-therapy, interim PET (I-PET) and after the end of first-line therapy (E-PET) in patients with diffuse large B-cell lymphoma (DLBCL). Four hundred and thirty patients were enrolled in this study comprising a total of 617 PET reports. Each report was evaluated by three expert hematologists randomly selected from a panel of nine. Reports were labeled positive or negative if all three interpreters agreed. All others were considered indeterminate. Indeterminate reports accounted for 59% of I-PET and 49% of E-PET reports. Two-year overall survival (OS) for patients with a positive, indeterminate and negative I-PET was 58%, 87% and 89% (p < 0.001), respectively. Two-year OS for patients with E-PET was 41%, 89% and 97% (p < 0.001) for positive, indeterminate and negative interpretation of PET/CT reports. Progression-free survival and OS did not differ significantly in patients with a negative and an indeterminate I-PET report. The use of well-defined reporting criteria, e.g. the Deauville five-point scale, is likely to reduce the number of scans perceived as indeterminate.