R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma

Lamy, Thierry; Damaj, Gandhi; Soubeyran, Pierre; Gyan, Emmanuel; Cartron, Guillaume; Bouabdallah, Krimo; Gressin, Rémy; Cornillon, Jérôme; Banos, Anne; Dû, Katell Le; Benchalal, M.; Moles, Marie‐Pierre; Gouill, Steven Le; Fleury, J; Godmer, Pascal; Maisonneuve, Hervé; Deconinck, Eric; Houot, Roch; Laribi, Kamel; Marolleau, Jean Pierre; Tournilhac, Olivier; Branger, B.; Devillers, Anne; Vuillez, J.-P.; Fest, Thierry; Colombat, Philippe; Costes, Valérie; Szablewski, Vanessa; Béné, Marie C.; Delwail, Vincent

doi:10.1182/blood-2017-07-793984

Cited by 141 publications

(124 citation statements)

References 31 publications

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“…This finding is in line with the abovementioned assumption that immunochemotherapy alone is insufficient to achieve optimal local tumor control, and suggests a complementary benefit between rituximab and RT in the management of PB‐DLBCL. However, our finding seems to be at odds with results of a recently published phase III study that reported no significant difference in event‐free survival and OS between limited‐stage DLBCL patients treated with R‐CHOP with and without RT . This discrepancy could be explained by the different patterns of relapse between PB‐DLBCL and DLBCL in general.…”

Section: Discussioncontrasting

confidence: 99%

“…The incorporation of rituximab into CT has led to a paradigm shift in the treatment of DLBCL, with a number of phase III studies reporting significant survival benefit of R‐CHOP vs CHOP as first‐line therapy of DLBCL patients . This benefit from rituximab has also challenged the value of consolidative RT in the treatment of limited‐stage DLBCL, as results from one randomized controlled trial have shown that consolidative RT could not offer additional benefit for early stage DLBCL patients treated in the rituximab era . However, in the case of PB‐DLBCL, only a few studies have evaluated the role of rituximab, and most of them did not show an advantage in PFS or OS .…”

Section: Introductionmentioning

confidence: 99%

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Primary breast diffuse large B‐cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure

Song

Sun

et al. 2018

Cancer Science

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Primary breast diffuse large B‐cell lymphoma (PB‐DLBCL) is a rare subtype of DLBCL with limited data on patterns of failure. This multicenter study aimed to define the optimum treatment strategy and patterns of failure for PB‐DLBCL patients. We retrospectively reviewed data on 108 PB‐DLBCL patients from 21 Chinese medical centers. Only patients with localized disease (involvement of breast and localized lymph nodes) were included. After a median follow‐up of 3.2 years, 32% of patients developed progression or relapse. A continuous pattern of relapse was observed, characterized by frequent late relapses in the contralateral breast and central nervous system (CNS). Although rituximab significantly reduced the overall cumulative risk of progression or relapse (5‐year cumulative risk 57% vs 24%, P = .029), it had limited effect on the reduction of breast relapse (P = .46). Consolidative radiotherapy significantly decreased the risk of breast relapse, even in the subgroup of patients treated with rituximab (5‐year cumulative risk 21.2% vs 0%, P = .012). A continuous risk of CNS progression or relapse up to 8.2 years from diagnosis was observed (10‐year cumulative risk 28.3%), with a median time to CNS relapse of 3.1 years. Neither rituximab nor prophylactic intrathecal chemotherapy significantly decreased the risk of CNS relapse. In summary, our study indicates that PB‐DLBCL has a continuous pattern of relapse, especially with frequent late relapses in the CNS and contralateral breast. Rituximab and RT confer complementary benefit in the reduction of relapse. However, neither the addition of rituximab nor prophylactic intrathecal chemotherapy could effectively prevent CNS relapse for PB‐DLBCL patients.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Primary breast diffuse large B‐cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure

Song

Sun

et al. 2018

Cancer Science

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“…Historical series have suggested better outcomes after consolidative RT [75], but data from the R-CHOP era are lacking. Patients with thyroid DLBCL have received immunochemotherapy alone on contemporary clinical trials [8]. …”

Section: Prognosis Of Extranodal Dlbcl Arising From Specific Anatomicmentioning

confidence: 99%

“…Primary extranodal DLBCL is thus more often recognized at early stage (IE/IIE), except when it originates from organs that define stage IV disease. The distinction between primary and secondary involvement makes many studies difficult to interpret, particularly because clinical trials usually report only the number of involved extranodal sites, rather than individual sites of origin [5–8]. The recognition that occurrence of DLBCL in specific organs may be associated with distinct clinical or molecular features, as well as consistent patterns of recurrence, raised interest in examining both extranodal origin and secondary involvement as prognostic factors [3, 2, 4, 9, 10].…”

Section: Introductionmentioning

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.

115

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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“…Considering the serious long‐term adverse effects of radiotherapy, this is an important issue to resolve in order to avoid unnecessary toxicity. Factors that have been suggested as indications to radiotherapy are primary bulky disease, residual tumor mass after immunochemotherapy and extranodal tumor locality …”

Section: Introductionmentioning

confidence: 99%

Significance of bulky mass and residual tumor—Treated with or without consolidative radiotherapy—To the risk of relapse in DLBCL patients

et al. 2020

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Bulky and residual tumor are considered to increase the risk of relapse in diffuse large B‐cell lymphoma (DLBCL) patients. Radiotherapy is conventionally used to reduce the risk, but the evidence is controversial. We performed a retrospective analysis to evaluate the significance of bulky and residual tumor treated with or without radiotherapy in DLBCL patients. We analyzed 312 DLBCL patients treated from 2010‐2017 in Oulu University Hospital. A bulky tumor was detected in 123 patients and 55 of these patients (44.3%) received consolidative radiation therapy (RT) to the bulky tumor. Residual tumor meeting the required criteria was found in 138 (39.3%) patients, and 65 (45.5%) of these patients received consolidative RT to the site of residual tumor. iPET‐CT scans were performed in 102 patients. In multivariate analyses, bulky was an independent risk factor in limited stage patients in progression free survival (HR 6.43 [95%CI 1.609‐25.710]; P = .008) not related to International prognostic index (HR 1.35 [95% CI 0.256‐7.124]; P = .724) or age (HR 1.62 [95% CI 0.468‐5.638]; P = .445). This was not seen in advanced stage patients or in patients with residual tumor. Radiotherapy to the bulky or residual tumor was not able to improve the long‐term PFS of patients. In this study, it appears that performing iPET is the most convincing method in improving evaluation and in finding patients with increased risk of relapse. Evidently, patients with negative iPET will not benefit from including RT in the treatment after metabolic complete response (CR), and patients with primary refractory disease are most likely in the group of positive iPET.

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R-CHOP 14 with or without radiotherapy in nonbulky limited-stage diffuse large B-cell lymphoma

Cited by 141 publications

References 31 publications

Primary breast diffuse large B‐cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure

Primary breast diffuse large B‐cell lymphoma in the rituximab era: Therapeutic strategies and patterns of failure

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

Significance of bulky mass and residual tumor—Treated with or without consolidative radiotherapy—To the risk of relapse in DLBCL patients

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