The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas

Murawski, Niels; Held, Gerhard; Ziepert, Marita; Kempf, Barbara; Viardot, Andreas; Hänel, Mathias; Witzens-Harig, Mathias; Mahlberg, Rolf; Rübe, Christian; Fleckenstein, Jochen; Zwick, Carsten; Glaß, Bertram; Schmitz, Norbert; Zeynalova, Samira; Pfreundschuh, Michael

doi:10.1182/blood-2013-10-535021

Cited by 39 publications

(42 citation statements)

References 36 publications

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“…Little is known about specific molecular features of DLBCL of the head and neck, except that 80% are non-GCB, with frequent gain of 1q31 (containing RGS1 , 55%) and loss of 9p21.3 (containing CDKN2A , 64%) [70]. Extranodal head/neck location was associated with a better prognosis than nodal DLBCL in population-derived data, but not in clinicopathologic series [2, 14, 4, 68]. Importantly, Waldeyer’s ring is considered a primary nodal site and does not require special therapeutic considerations [71].…”

Section: Prognosis Of Extranodal Dlbcl Arising From Specific Anatomicmentioning

confidence: 99%

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Ollila

Olszewski

2018

Curr. Treat. Options in Oncol.

113

107

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Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma-risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.

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Section: Prognosis Of Extranodal Dlbcl Arising From Specific Anatomicmentioning

confidence: 99%

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Ollila

Olszewski

2018

Curr. Treat. Options in Oncol.

113

107

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“…However, there is limited evidence for this approach in patients treated with chemotherapy only, 11,12 and in diffuse large B-cell lymphoma treated with rituximab in addition to chemotherapy, no beneficial effect of intrathecal treatment has been demonstrated. 5,7,13 Similarly, the addition of etoposide to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) treatment has been associated with a lower incidence of CNS relapse, an association lost when rituximab is added. 3,5 In peripheral T-cell lymphoma (PTCL), CNS relapse has been little studied.…”

Section: Introductionmentioning

confidence: 99%

Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study

Ellin

Landström

Jerkeman

et al. 2015

Blood

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Key Points• CNS involvement at relapse/ progression in PTCL occurred at a frequency similar to what is seen in aggressive B-cell lymphomas.• Outcome after relapse is generally very poor in patients with PTCL and is not significantly altered by presence of CNS involvement at relapse.Central nervous system (CNS) relapse in non-Hodgkin lymphoma (NHL) carries a very poor prognosis. Risk factors and outcome have been studied in aggressive B-cell lymphomas, but very little is known about the risk in peripheral T-cell lymphoma (PTCL). We aimed at analyzing risk factors for CNS involvement at first relapse or progression, as well as the outcome of these patients, in a large population-based cohort of patients with PTCL. Twenty-eight out of 625 patients (4.5%) developed CNS disease over time. In multivariable analysis, disease characteristics at diagnosis independently associated with an increased risk for later CNS involvement were involvement of more than 1 extranodal site (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.07-6.29; P 5 .035) and skin (HR, 3.51; 95% CI, 1.26-9.74; P 5 .016) and gastrointestinal involvement (HR, 3.06; 95% CI, 1.30-7.18; P 5 .010). The outcome of relapsed/refractory patients was very poor, and CNS involvement was not associated with a significantly worse outcome compared with relapsed/refractory patients without CNS involvement in multivariable analysis (HR, 1.6; 95% CI, 0.96-2.6; P 5 .074). The results from the present study indicate that CNS relapse in PTCL occurs at a frequency similar to what is seen in aggressive B-cell lymphomas, but the poor outcomes in relapse are largely driven by systemic rather than CNS disease. (Blood. 2015;126(1):36-41)

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“…In contrast, in a recent analysis of 11 consecutive DSHNHL study trials, the addition of intrathecal prophylaxis with methotrexate did not affect the 2-year rate of CNS disease (4.2% compared with 2.3% in patients who did not receive intrathecal therapy, P = 0.98). 60 Therefore, the use of CNS prophylaxis remains an issue of debate and thus is administered according to institutional preference.…”

Section: Use Of Radiation For Limited Dlbclmentioning

confidence: 99%

ACR Appropriateness Criteria® Diffuse Large B-Cell Lymphoma

Dabaja

Advani

Hodgson

et al. 2015

American Journal of Clinical Oncology

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The management of diffuse large B-cell lymphoma depends on the initial diagnosis including molecular and immunophenotypic characteristics, Ann Arbor staging, and International Prognostic Index (IPI score). Treatment approaches with different chemotherapy regimens used is discussed in detail. The role of radiation as a consolidation is discussed including: (1) the prerituximab randomized trials that challenged the role of radiation, (2) recent prospective studies (UNFOLDER/RICOVER-60), and (3) retrospective studies; the last 2 showed a potential benefit of radiation both for early and advanced stage. The document also discusses the role of positron emission tomography/computed tomography for predicting outcome and potentially guiding therapy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

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The role of radiotherapy and intrathecal CNS prophylaxis in extralymphatic craniofacial aggressive B-cell lymphomas

Cited by 39 publications

References 36 publications

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence

Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study

ACR Appropriateness Criteria® Diffuse Large B-Cell Lymphoma

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