Primary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)

doi:10.1016/j.ijrobp.2009.04.018

International Journal of Radiation OncologyBiologyPhysics

Volume 77, Issue 1, 1 May 2010, Pages 86-91

https://doi.org/10.1016/j.ijrobp.2009.04.018 Get rights and content

Purpose

To evaluate the outcomes of patients with localized orbital marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) who were treated with radiotherapy (RT).

Methods and Materials

We retrospectively reviewed the records of 46 patients who were treated with RT for pathologically confirmed localized stage IE marginal zone B-cell lymphoma of MALT. The radiation dose ranged from 21.6 to 45 Gy (median, 30.6 Gy) at 1.8–2.0 Gy per fraction. Median follow-up duration was 32.3 months (range, 3.1–113.6 months).

Results

Forty-three patients (93%) achieved complete remission (CR), and three patients (7%) achieved partial remission (PR). Five-year relapse-free survival, cause-specific survival, and overall survival were 93%, 100%, and 100%, respectively. Among the patients with CR, two had recurrence at three sites. One patient relapsed locally and was successfully salvaged with reirradiation. The other patient relapsed in a distant site and was successfully treated with six cycles of CHOP chemotherapy. Late complications were noted in four patients. Two patients developed cataracts at 26 and 37 months after completion of RT. The other two patients developed nasolacrimal duct obstructions at 4 and 11 months after completion of RT.

Conclusion

Our study showed that a modest dose of RT is an excellent treatment modality with low complication and recurrence rates. We suggest that a dose of 30.6 Gy is tolerable and sufficient for treating orbital MALT lymphoma. Even following recurrence, successful salvage is possible with RT or chemotherapy.

Introduction

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) was first described in 1983 by Isaacson and Wright (1). This tumor has generally been considered to have an indolent natural history and a favorable prognosis, and it usually responds well to local radiotherapy (RT) alone 2, 3, 4, 5, 6, 7. However, the data on the clinical behavior of orbital MALT lymphoma is limited, inconsistent, and still unclear because the literature includes variable histologies from benign to malignant entities.

The use of immunophenotypic analysis, in addition to hematoxylin/eosin-stained microscopic examination, could make possible a more exact diagnosis of orbital MALT lymphoma. These procedures can distinguish MALT lymphoma from the other types of Non-Hodgkin's lymphoma (NHL), such as small lymphocytic lymphoma, mantle cell lymphoma, and reactive lymphoid infiltration.

Several groups have recently published valuable treatment results for this tumor 2, 3, 4, 5, 6, and these studies included patients with orbital MALT lymphoma confirmed by immunophenotypic studies. Their data could be compared with each other, and the characteristics of MALT lymphoma arising in the orbit are now better understood.

In this study, we retrospectively reviewed the results of primary RT in 46 patients with localized orbital MALT lymphoma and evaluated the clinical features and treatment outcomes.

Section snippets

Patient characteristics

Between May 1999 and July 2008, 46 patients with pathologically confirmed localized orbital MALT lymphoma were treated with primary RT at Kangnam St. Mary's Hospital and St. Mary's Hospital, which are affiliated hospitals of a single institution.

All the patients were diagnosed according to the World Health Organization histologic diagnostic criteria. In addition to a hematoxylin/eosin-stained microscopic examination, immunohistochemical staining for CD20, CD3, CD5, and cyclinD1 was performed to

Local control, RFS, and OS

The 5-year local control, RFS, and OS rates were 93%, 93%, and 100%, respectively (Fig. 2). Among the 46 patients, 43 (93%) achieved CR, of whom 18 had residual or suspicious lesions at their initial response evaluation. However, their lesions gradually regressed 3–13 months after the completion of RT. The median duration for achieving CR was 2 months (range, 0.1–25 months). Three patients (7%) who achieved PR had lymphoma lesions of the retro-orbit arising in the rectus muscles and optic

Discussion

MALT lymphoma was initially described by Isaacson and Wright (1), and it is known to be a rare disease. However, its incidence in Korea is relatively high, comprising 17.3% of all NHL cases in Korea (8). Diffuse large B-cell lymphoma (DLBL) is usually the most common pathologic NHL subtype. However, MALT lymphoma constitutes 76%–100% of orbital NHL cases in Far Eastern countries, including Korea and Japan 3, 4, 8, 9.

Many studies in the literature have shown that excellent local control can be

References (18)

C.O. Suh et al.
Orbital marginal zone B-cell lymphoma of MALT: Radiotherapy results and clinical behavior
Int J Radiat Oncol Biol Phys
(2006)
Q.T. Le et al.
Primary radiotherapy for localized orbital MALT lymphoma
Int J Radiat Oncol Biol Phys
(2002)
Y. Ejima et al.
Ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiotherapy
Radiother Oncol
(2006)
J. Suzuki et al.
Clinicopathologic and immunogenetic analysis of mucosa-associated lymphoid tissue lymphomas arising in conjunctiva
Jpn J Ophthalmol
(1999)
C.Y. Fung et al.
Ocular adnexal lymphoma: Clinical behavior of distinct World Health Organization classification subtypes
Int J Radiat Oncol Biol Phys
(2003)
P. Zhou et al.
Radiation therapy for orbital lymphoma
Int J Radiat Oncol Biol Phys
(2005)
M.R. Pfeffer et al.
Orbital lymphoma: Is it necessary to treat the entire orbit?
Int J Radiat Oncol Biol Phys
(2004)
S. Hitchcock et al.
Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin's lymphoma
Int J Radiat Oncol Biol Phys
(2002)
H.J. Deeg et al.
Cataracts after total body irradiation and marrow transplantation: A sparing effect of dose fractionation
Int J Radiat Oncol Biol Phys
(1984)

There are more references available in the full text version of this article.

Cited by (57)

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue
2023, Cancer/Radiotherapie
The role of radiation therapy in mucosa-associated lymphoid tissue (MALT) lymphoma is poorly defined. The objective of this study was to explore the factors associated with the performance of radiotherapy and to assess its prognostic impact in patients with MALT lymphoma.
Patients with MALT lymphoma diagnosed between 1992 and 2017 were identified in the US Surveillance, Epidemiology, and End Results database (SEER). Factors associated with the delivery of radiotherapy were assessed by chi-square test. Overall survival (OS) and lymphoma-specific survival (LSS) were compared between patients with and without radiotherapy, using Cox proportional hazard regression models, in patients with early stage as well as those with advanced stage.
Of the 10,344 patients identified with a diagnosis of MALT lymphoma, 33.6% had received radiotherapy; this rate was 38.9% for stage I/II patients and 12.0% for stage III/IV patients, respectively. Older patients and those who already received primary surgery or chemotherapy had a significantly lower rate of receiving radiotherapy, regardless of lymphoma stage. After univariate and multivariate analysis, radiotherapy was associated with improved OS and LSS in patients with stage I/II (HR = 0.71 [0.65–0.78]) and (HR = 0.66 [0.59–0.74]), respectively, but not in patients with stage III/IV (HR = 1.01 [0.80–1.26]) and (HR = 0.93 [0.67–1.29]). The nomogram built from the significant prognostic factors associated with overall survival of stage I/II patients had a good concordance (C-index = 0.749 ± 0.002).
This cohort study shows that radiotherapy is significantly associated with a better prognosis in patients with early but not advanced MALT lymphoma. Prospective studies are needed to confirm the prognostic impact of radiotherapy in patients with MALT lymphoma.
Le rôle de la radiothérapie dans les lymphomes du tissu lymphoïde associé aux muqueuses (MALT) est mal défini. L’objectif de cette étude était d’explorer les facteurs associés à la réalisation d’une radiothérapie et d’évaluer son impact pronostique chez les patients atteints de lymphome de type MALT.
Les patients atteints d’un lymphome de type MALT, diagnostiqué entre 1992 et 2017, ont été identifiés dans la base de données américaine SEER (Surveillance, Epidemiology, and End Results) Les facteurs associés à la réalisation d’une radiothérapie ont été évalués par le test du Chi-2. La survie globale et la survie spécifique ont été comparées entre les patients avec et sans radiothérapie, à l’aide de modèles de régression du risque proportionnel de Cox, chez les patients atteints d’un lymphome de stade précoce ainsi que ceux atteints d’un lymphome de stade avancé.
Sur les 10 344 patients identifiés avec un diagnostic de lymphome de type MALT, 33,6 % avaient reçu une radiothérapie, ce taux était respectivement de 38,9 % pour les patients atteints d’un lymphome de stade I/II et de 12,0 % pour ceux atteints d’un lymphome de stade III/IV. L’âge des patients, la réalisation d’une chirurgie ou bien d’une chimiothérapie, étaient significativement associés à ne pas recevoir une radiothérapie, quel que soit le stade du lymphome. Après analyse unifactorielle et multifactorielle, la radiothérapie était associée à un allongement respectivement de la survie globale et de la survie spécifique chez les patients atteints d’un lymphome de stade I/II (HR [Hazard Ratio] = 0,71 [0,65–0,78]) et (HR = 0,66 [0,59–0,74]) mais pas chez les patients aatteints d’un lymphoma de stade III/IV (HR = 1,01 [0,80–1,26]) et (HR = 0,93 [0,67–1,29]). Le nomogramme construit à partir des facteurs pronostiques significatifs associés à la survie globale des patients atteints d’un lymphoma de stade I/II avait une bonne concordance (C-index = 0,749 ± 0,002).
Cette étude de cohorte montre que la radiothérapie est significativement associée à un pronostic plus favorable chez les patients atteints d’un lymphome de type MALT de stade précoce, mais pas de stade avancé. Des études prospectives sont nécessaires afin de confirmer l’impact pronostique de la radiothérapie chez les patients atteints de lymphome de type MALT.
Long-Term Clinical Outcomes and Sequelae of Therapy in Early-Stage Orbital Mucosa-Associated Lymphoid Tissue Lymphoma
2022, Clinical Lymphoma, Myeloma and Leukemia
Orbital mucosa-associated lymphoid tissue (MALT) lymphoma, which are rare and indolent, often present at an early stage. We report the efficacy and safety outcomes of treatment in these patients.
We analyzed adult patients with stage IE or IIE orbital MALT lymphoma between 1999 and 2017 treated at our institute. We assessed local control (LC) rates, overall survival (OS), relapse-free survival (RFS) using Kaplan Meier method and the incidence of late toxicities.
Seventy patients were analyzed for clinical outcomes. The median age at diagnosis was 52 years (IQR-45-62 years). Radiotherapy was offered to 97% of patients and the dose ranged from 36 to 45 Gy. Chemotherapy was administered in 5(7.1%) patients. Relapse occurred in 8 patients (local: 2, distant: 6). At a median follow-up of 101 months (IQR-47-146 months), the median OS and RFS was not reached. 8-year OS, RFS and LC rates were 96.5%, 88.5%, 96.7% respectively. Univariate analysis showed age ≤60 years and lacrimal involvement significantly correlated with better OS (P = .01 and .04, respectively). Cataract was the most common sequelae observed in 31 patients (44.3%).
Moderate doses of radiotherapy are curative in early-stage orbital MALT lymphoma with favorable clinical outcomes. Lower doses of radiation can reduce the toxicity further, without compromising efficacy.
Dosimetric parameters predictive of nasolacrimal duct obstruction after carbon-ion radiotherapy for head and neck carcinoma
2019, Radiotherapy and Oncology
Little information is available on the risk factors for nasolacrimal duct obstruction after radiotherapy for head and neck tumors. We investigated the incidence and predictive dosimetric parameters for nasolacrimal duct obstruction following carbon-ion radiotherapy for head and neck tumors.
Twenty-eight patients with head and neck non-squamous cell carcinoma were analyzed in this single-institution prospective study. More than half of the tumors were located in the nasal cavity and maxillary sinus. Carbon-ion radiotherapy consisting of 57.6 or 64.0 Gy(relative biological effectiveness; RBE) in 16 fractions was administered. Nasolacrimal duct obstruction was recorded according to Common Terminology Criteria for Adverse Events version 4.0. Cutoff values were determined using receiver operating characteristic (ROC) curve analysis. VX indicates the volume irradiated with X Gy(RBE).
The median follow-up period was 60.3 months. Incidences of Grade 1 and 2 nasolacrimal duct obstructions were 46% (13/28) and 7% (2/28), respectively; no Grade 3 or greater toxicities were recorded. Throughout the dose range, the volumes of the irradiated nasolacrimal ducts were significantly higher in the obstruction-positive patients than in the obstruction-negative patients (p < 0.001 for V10, V20, V30, V40, V50, and V60). Cutoff values determined by the ROC curve analysis classified the obstruction-positive patients with an accuracy of >96% over the entire range of V10–V60.
The incidence and predictive dosimetric parameters for nasolacrimal duct obstruction after carbon-ion radiotherapy were demonstrated in a prospective cohort. These data should help optimize carbon-ion radiotherapy treatments for patients with head and neck tumors.
Treatments for Ocular Adnexal Lymphoma: A Report by the American Academy of Ophthalmology
2018, Ophthalmology
Citation Excerpt :
Two studies reported results of using oral doxycycline as the primary treatment method. The clinical outcomes and complications of the included studies are presented in Table 2.1,3,7,12,13,18–39 The outcomes reported from studies involving radiotherapy for MALT lymphomas universally are very good, both for radiotherapy used as a stand-alone treatment or in combination with chemotherapy.
To review the literature to determine the efficacy of available treatments for ocular adnexal lymphoma (OAL) and to evaluate the outcomes and complications of treatments in patients older than 13 years.
A literature search was conducted last in March 2017 in the PubMed and Cochrane Library databases for English-language original research investigations that evaluated treatment outcomes for OAL. The searches identified 307 unique citations, and 27 studies were selected according to the criteria outlined for this assessment.
The 27 studies reviewed comprised 2009 patients. Seventy-five percent of the cases reported were extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). Twenty-five studies reported results using radiotherapy with or without chemotherapy or surgery. The local control rate of MALT lymphomas with treatments involving radiotherapy averaged 95.9%. Distant and local relapses can occur, and in studies reporting only on MALT lymphomas (884 patients), the 5-year and 10-year disease-free survival rates were reported to be 86.4% and 78.7%, respectively. However, overall survival in patients receiving radiotherapy remained very good, with the 5-year and 10-year survival rates reported to be 93.8% and 84.9%, respectively. Studies that included data on multiple histologic subtypes of lymphoma or non-MALT lymphomas (988 patients) reported local control rates to be 93.1%; 5-year and 10-year disease-free survival rates to be 75.7% and 71.0%, respectively; and 5-year and 10-year overall survival rates to be 78.9% and 73.5%, respectively. Studies on the use of doxycycline for MALT lymphomas (137 patients) reported complete responses of between 4.4% and 13%. Complete and partial responses combined were between 26.7% and 65%. Disease-free survival was not reported for these 2 studies, although progression-free survival was reported to be between 55% and 60.9%. The most frequently reported complications of treatment were cataracts (12.1%) and dry eye (8.5%).
For MALT lymphomas, local control, disease-free survival, and overall survival are good with radiation treatment. The results of treatment of non-MALT lymphomas using radiotherapy also were good, but they were not as favorable as the treatment results of MALT lymphomas.
Local Disease Control in Ocular Adnexal Lymphoproliferative Disorders: Comparative Outcomes of MALT Versus Non-MALT Histologies
2017, Clinical Lymphoma, Myeloma and Leukemia
Ocular adnexal lymphoproliferative disorders (OALDs) are almost exclusively of B-cell origin, with the majority being extra-nodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). The comparative efficacy of involved field radiation therapy (IFRT) in MALT vs. non-MALT OALDs is not known.
We present a single-center, large cohort, retrospective study of the efficacy of IFRT in OALDs. Failure-free survival (FFS), complete remission, and local, regional, and distant failure were determined for 112 patients with MALT OALDs (n = 71) and non-MALT OALDs (n = 41) cohorts.
Fifty-six patients with MALT OALD and 26 patients with non-MALT OALD received IFRT only (without any planned concurrent or sequential systemic chemothereapy or chemo-immunotherapies). Among the OALD cohorts treated with only IFRT, complete remission was achieved in 49 (87.5%) patients in the MALT cohort and 23 (88.4%) in the non-MALT cohort (P = .99). Clinically, resolution of symptoms occurred in 83.3% and 93.3% of the patients in the MALT and non-MALT cohorts, respectively. Local failure occurred in 4 (7.1%) patients in the MALT cohort, compared with 4 (15.3%) patients in the non-MALT cohort (P = .24). Regional failure (or extra-orbital failure) occurred in 5 (8.9%) patients in the MALT cohort and in 3 (11.5%) patients in the non-MALT cohort (P = .71). Distant failure was reported in 1 (1.7%) and 2 patients (7.6%) in the MALT and non-MALT cohorts, respectively (P = .18). The median follow-up of survivors was 5.1 years (range, 0.1-22.5 years) in the MALT cohort and 3.9 years (range, 0.1-22.9 years) in the non-MALT cohort. The 5-year and 10-year FFS was 95% (95% confidence interval [CI], 88%-100%) and 83% (95% CI, 70%-98%) for the ocular MALT and 67% (95% CI, 48%-94%) and 56% (95% CI, 34%-91%) for the non-MALT cohorts, respectively (log rank for P = .025). On multivariate analyses, age (hazard ratio [HR], 1.06; 95% CI, 1.10-1.12; P = .03), presence of non-MALT histology (HR, 13.9; 95% CI, 2.05-94.4; P = .007), and radiation dose < 30.6 Gy (HR, 5.27; 95% CI, 1.14-24.3; P = .03) were associated with worse FFS. The 5-year and 10-year overall survival was 92% (95%, CI 83%-100%) and 80% (95% CI, 66%-96%) for the MALT and 78% (95% CI, 61%-100%) and 62% (95% CI, 38%-100%) for the non-MALT cohorts, respectively (P = .80).
Our results reveal that IFRT provided excellent disease control with superior FFS in the MALT cohort when compared with the non-MALT group.
Long-term course of patients with primary ocular adnexal MALT lymphoma: A large single-institution cohort study
2017, Blood
Citation Excerpt :
Only 1 of our patients received treatment with doxycycline with no response. RT was reported to achieve an excellent local control (86% to 100%) in all previous studies of patients with Ann Arbor stage I POAML.14,25,34,43,44 Similarly, RT achieved local control in 97% of our Ann Arbor stage I POAML patients.
While primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common orbital tumor, there are large gaps in knowledge of its natural history. We conducted a retrospective analysis of the largest reported cohort, consisting of 182 patients with POAML, diagnosed or treated at our institution to analyze long-term outcome, response to treatment, and incidence and localization of relapse and transformation. The majority of patients (80%) presented with stage I disease. Overall, 84% of treated patients achieved a complete response after first-line therapy. In patients with stage I disease treated with radiation therapy (RT), doses ≥30.6 Gy were associated with a significantly better complete response rate (P = .04) and progression-free survival (PFS) at 5 and 10 years (P < .0001). Median overall survival and PFS for all patients were 250 months (95% confidence interval [CI], 222 [upper limit not reached]) and 134 months (95% CI, 87-198), respectively. Kaplan-Meier estimates for the PFS at 1, 5, and 10 years were 91.5% (95% CI, 86.1% to 94.9%), 68.5% (95% CI, 60.4% to 75.6%), and 50.9% (95% CI, 40.5% to 61.6%), respectively. In univariate analysis, age >60 years, radiation dose, bilateral ocular involvement at presentation, and advanced stage were significantly correlated with shorter PFS (P = .006, P = .0001, P = .002, and P = .0001, respectively). Multivariate analysis showed that age >60 years (hazard ratio [HR] 2.44) and RT<30.6Gy (HR=4.17) were the only factors correlated with shorter PFS (P = .01 and P = .0003, respectively). We demonstrate that POAMLs harbor a persistent and ongoing risk of relapse, including in the central nervous system, and transformation to aggressive lymphoma (4%), requiring long-term follow-up.

View all citing articles on Scopus

: Conflict of interest: none.

¹: S. H. Son and B. O. Choi contributed equally to this work.

View full text

Clinical InvestigationPrimary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)

Purpose

Methods and Materials

Results

Conclusion

Introduction

Section snippets

Patient characteristics

Local control, RFS, and OS

Discussion

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Radiother Oncol

Jpn J Ophthalmol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Clinical Investigation
Primary Radiation Therapy in Patients With Localized Orbital Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue (MALT Lymphoma)