Radiation-induced liver disease mimicking liver metastasis after low-dose hepatic irradiation during radiotherapy for gastric mucosa-assisted lymphoid tissue lymphoma: A case report.

RATIONALE: Radiation-induced liver disease (RILD) is an established complication of hepatic irradiation that is typically reported in patients receiving high-dose radiotherapy for hepatocellular carcinoma or liver metastases. However, RILD can also occur after unintentional low-dose liver exposure during radiotherapy for other gastrointestinal malignancies when careful precautions are not taken. PATIENT CONCERNS: We report the case of a 44-year-old woman with gastric mucosa-associated lymphoid tissue lymphoma who underwent salvage radiotherapy administered to the entire stomach. One month after completing this radiotherapy, computed tomography and magnetic resonance imaging of the patient's abdomen revealed a 4 cm lesion in the left lateral liver segment, suggestive of metastasis. DIAGNOSES: An ultrasound-guided biopsy was performed, and the histopathological findings were consistent with those of RILD. INTERVENTIONS: Conservative management was pursued with close monitoring of liver function tests. OUTCOMES: The patient's imaging findings and liver enzyme levels normalized approximately 3 months after the initial diagnosis. LESSONS: This case highlights the importance of considering RILD in the differential diagnosis of new hepatic lesions detected after radiotherapy, even in patients with low-dose liver exposure within generally acceptable limits. Careful correlation with the radiotherapy plan is crucial to avoid misdiagnosing RILD as metastatic disease and to guide appropriate management.

Orbital Richter Transformation With Subsequent Orbital MALT-type Lymphoma in a Patient With Chronic Lymphocytic Leukemia.

A 74-year-old man with a history of chronic lymphocytic leukemia (CLL) presented with large salmon-colored patch lesions along the inferior fornix and superotemporal conjunctiva of the OS. The patient underwent an incisional biopsy of the lesions, which showed a CLL with areas of large B-cell lymphoma, consistent with Richter transformation. Following medical and radiation-based therapy of these lesions, the patient returned 3 months later with inferomedial preseptal swelling in the contralateral eye, which biopsy proved to be recurrent/resistant low-grade CLL with a posttreatment extranodal marginal zone B-cell lymphoma pattern. This case exemplifies a rare presentation of CLL with Richter transformation and a recurrent/resistant posttreatment orbital CLL with a marginal zone B-cell lymphoma-like pattern.

Evaluation of PTV margin in CBCT-based online adaptive radiation therapy for gastric mucosa-associated lymphoid tissue lymphoma.

The aim of this study was to investigate planning target volume (PTV) margin in online adaptive radiation therapy (oART) for gastric mucosa-associated lymphoid tissue (MALT) lymphomas. Four consecutive patients with gastric MALT lymphoma who received oART (30 Gy in 15 fractions) on the oART system were included in this study. One hundred and twenty cone-beam computed tomography (CBCT) scans acquired pre- and post-treatment of 60 fractions for all patients were used to evaluate intra- and interfractional motions. Patients were instructed on breath-holding at exhalation during image acquisition. To assess the intrafraction gastric motion, different PTVs were created by isotropically extending the CTV contoured on a pre-CBCT image (CTVpre) at1 mm intervals. Intrafraction motion was defined as the amount of expansion covering the contoured CTV on post-CBCT images (CTVpost). Interfractional motion was defined as the amount of reference CTV expansion that could cover each CTVpre, as well as the evaluation of the intrafractional motion. PTV margins were estimated from the cumulative proportion of fraction covering the intra- and interfractional motions. The extent of expansion covering the CTVs in 90% of fractions was adopted as the PTV margin. The PTV margin for intrafractional gastric motion using the oART system with breath-holding was 14 mm. In contrast, the PTV margin for interfractional gastric organ motion without the oART system was 25 mm. These results indicated that the oART system can reduce the PTV margin by >10 mm. Our results could be valuable data for oART cases.

Response-adapted ultra-low-dose 4 Gy radiation as definitive therapy of gastric MALT lymphoma: a single-centre, pilot trial.

BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.

Spontaneous regression and rare relapse after excisional biopsy in long-term observation of 31 patients with primary conjunctival lymphoma.

To elucidate long-term outcome in primary conjunctival lymphoma, a review was conducted of 31 consecutive patients: 21 men and 10 women with an age range of 28 to 85 (median, 61) years at presentation and follow-up periods ranging from 1 to 19 (median, 7) years. Conjunctival lymphoma was on the right side in 10 patients, on the left side in 12, and on both sides in 9. Upper, lower, or both fornix lesions in 28 patients were all diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), while thick nasal bulbar conjunctival lesions in 3 patients were differently diagnosed as MALT lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma, respectively. Seven patients underwent local radiation (30 Gy): as initial treatment in 5 patients and treatment for relapse in 2 patients. The remaining 24 patients were observed without additional treatment after excisional biopsy: 5 of these 24 patients showed relapse 0.5 to 6 years later and underwent excisional biopsy again that revealed MALT lymphoma. Of the 5 patients with relapse, only one with second-time relapse underwent radiation. Fluorodeoxyglucose positron emission tomography was performed in 18 patients and showed no systemic lesions: high uptake was noted in the residual conjunctival lesions of 4 patients and in the relapsed conjunctival lesions of 3 patients. One patient died of rectal cancer while no patients died of lymphoma. Observation is an option in patients with primary conjunctival lymphoma after excisional biopsy. Radiation is a treatment option in the case of relapse.

Low-grade malt lymphoma of the nasopharynx in young adults: Successful treatment of a rare diagnosis at a rare site by radiotherapy.

INTRODUCTION: Mucosa Associated Lymphoid Tissue (MALT) lymphoma is the third most common subgroup of Non-Hodgkin's lymphoma and is the most common type of primary extranodal lymphoma. They are rarely found in the nasopharyngeal region and their mean age at presentation is the sixth decade of life. MATERIALS AND METHODS: We present the clinical, pathological, treatment and 5-year follow-up data of 5 cases of nasopharyngeal MALT lymphoma treated with definitive radiotherapy at our hospital, between 2009 and 2011. RESULTS: The average age of diagnosis was 27 years which is more than a decade earlier than what has been reported previously. Clinical symptoms included nasal obstruction, tinnitus and hearing loss. All five patients had locoregional disease. They were treated by definitive radiotherapy to a dose between 30 to 40 Gy. At 5 years of follow-up, 4 patients were in complete remission while one had disease relapse. CONCLUSION: The younger age of presentation compared to older reports in this rare subsite was an interesting finding in our study. The authors speculate that rising levels of particulate air pollution may have played a part in the etiology in this younger population. Our series shows that despite the younger age, the disease displays an indolent course and responds well to radiotherapy alone as the primary treatment. Recurrence or disseminated disease is also highly treatable with systemic chemotherapy.

Influence of Respiratory Motion on Dose Distribution in Gastric Mucosa-associated Lymphoid Tissue Lymphoma Radiotherapy.

BACKGROUND/AIM: The present study investigated the effect of respiratory motion on planned radiotherapy (RT) dose for gastric mucosa-associated lymphoid tissue (MALT) lymphoma using four-dimensional dose (4D-dose) accumulation. PATIENTS AND METHODS: 4D-computed tomography (4D-CT) images of 10 patients with gastric MALT lymphomas were divided into 10 respiratory phases. Further, the 3D-dose was calculated using 3D conformal RT (3D-CRT) and volumetric modulated arc therapy (VMAT) plans based on the average intensity projection (AIP) images. Then, both plans were recalculated according to each phase image. Moreover, the dose distributions in each phase were transferred to the AIP images using deformable image registration. The 4D-dose distribution was calculated by summing the doses of each phase, and it was compared with the dosimetric parameters of the 3D-dose distribution. RESULTS: For 3D-CRT, the D95 and D99 of the 4D-dose in the planning target volume (PTV) were significantly lower than those of the 3D-dose, with mean differences of 0.2 (p=0.009) and 0.1 Gy (p=0.021), respectively. There were no significant differences in the other PTV and organ-at-risk dosimetric parameters of 3D-CRT or in any dosimetric parameters of VMAT between the 3D- and 4D-dose distributions. CONCLUSION: The effect of respiratory motion on the planned 3D-CRT and VMAT dose distributions for gastric MALT lymphoma is minimal and clinically negligible.

Clinicopathologic features of conjunctival MALT lymphomas refractory to radiation therapy.

OBJECTIVE: Clinicopathologic features of patients with limited-stage mucosa-associated lymphoid tissue (MALT) lymphoma refractory to radiotherapy have not been fully elucidated. This study aimed to elucidate clinicopathologic features of localized conjunctival MALT lymphoma concerning radiosensitivity by analyzing cell proliferation and expression of mismatch repair proteins. METHODS: We enrolled 26 patients with localized conjunctival MALT lymphoma treated with radiotherapy from November 2007 to March 2020. Monoclonal immunoglobulin H gene rearrangement was tested in addition to histopathologic evaluation. Thirty-six specimens were immunostained with antibodies to Ki-67 and MutL protein homologue 1 (MLH1), MutS protein homologue 2 (MSH2), and MutS protein homologue 6 (MSH6). Positive rates under a high-power field at a hot spot were counted manually. RESULTS: After radiotherapy, 21 patients showed clinical disappearance of the tumour without recurrence (effective group). Three patients showed temporary disappearance of the tumour, which later recurred (relapse group). Two patients did not show disappearance of the tumour (ineffective group). The 2 ineffective patients were young, had bilateral lesions, and received x-ray beam therapy. The mean positive rates of Ki-67, MLH1, MSH2, and MSH6 were higher in tumours with complete remission (CR) than in those without CR (23.4% ± 4.0% and 18.7% ± 4.7%, 14.7% ± 2.3% and 7.1% ± 3.7%, 23.9% ± 4.7% and 14.4% ± 5.2%, and 11.5% ± 3.2% and 5.4% ± 2.2%; p > 0.05 for each, respectively). CONCLUSIONS: A few patients could not achieve CR following radiotherapy, whereas there were no significant differences in proliferation activity and mismatch repair proteins between tumours with and without CR.

Very low-dose radiotherapy for extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue.

Extranodal marginal zone lymphoma of bronchus-associated lymphoid tissue (BALT) is a rare cancer for which optimal treatment strategies are undefined. Retrospective analyses suggest excellent outcomes with surgical resection for localized BALT lymphoma; however, the role of radiotherapy remains underexplored. We report the largest-to-date single-center analysis of 13 primary BALT lymphoma patients treated with radiotherapy. Of 15 treated lesions, we report a 100% response rate with complete response (CR) achieved in 67% of lesions. Among 10 lesions treated with very low-dose radiotherapy (VLDRT; 4 Gray [Gy]), 6 (60%) achieved a CR; among 5 lesions treated with full-dose radiotherapy (24-36 Gy), 4 (80%) achieved a CR. There were no local recurrences. Only one patient, treated with 30 Gy, developed an acute grade 3/4 toxic effect. There were no events of radiation-induced secondary malignancies. Our institutional experience indicates that radiotherapy, including VLDRT, is a safe and effective treatment for primary BALT lymphoma.

Outcome of Hypofractionated Radiotherapy for Localized Gastric Mucosa-associated Lymphoid Tissue Lymphoma.

BACKGROUND/AIM: With the prevalence of COVID-19, the importance of short-course radiotherapy (RT) in many cancers has been discussed. The aim of this study was to evaluate the results of hypofractionated schedule RT for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma. PATIENTS AND METHODS: We assessed 45 patients with localized gastric MALT lymphoma who underwent RT between 2005 and 2019. The total RT dose ranged from 24-36 Gy in 10-18 fractions (median of 28 Gy/14 fractions). Patients were divided into three groups according to the dose fractionation: Group A, 30-36 Gy in 15-18 fractions; Group B, 26-28 Gy in 13-14 fractions; and Group C, 24-25 Gy in 10 fractions. RESULTS: All the patients achieved complete remission without local recurrence. The 5-year overall, cause-specific, and progression-free survival rates were 97.5%, 100%, and 97.5%, respectively, with a median follow-up period of 82 months. Among the dose fractionation groups, there were no statistically significant differences in local control or incidence of grade 2 or worse adverse events. CONCLUSION: Results of RT for localized gastric MALT lymphoma showed excellent local control and survival with no serious adverse events, regardless of dose fractionation. In situations where short-term RT is required, a hypofractionated RT schedule of 24-25 Gy in 10 fractions could be an option for RT schedules.

Long-term Outcomes of Early-stage Non-stomach Gastrointestinal Mucosa-associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy.

BACKGROUND/AIM: Non-stomach gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma is rare, and there are only a few reports regarding radiation therapy (RT) for non-stomach gastrointestinal MALT lymphoma. There has been no established cure and no reports on RT use with long-term follow-up. Herein, we report a retrospective long-term investigation of early-stage non-stomach gastrointestinal MALT lymphoma. Our aim was to evaluate whether RT is a valid treatment option for this disease. PATIENTS AND METHODS: We retrospectively analyzed 6 patients who were diagnosed with early-stage non-stomach gastrointestinal MALT lymphoma and received RT. The median age was 66 years (range=38-89 years). The primary tumor originated from the duodenum in 2 patients and from the rectum in 4 patients. The RT dose was 30-34 Gy in 15-20 fractions to the involved site or field, depending on the case. RESULTS: The median follow-up time was 89.5 months (range=6-170). All patients had complete remission within 3 months after RT. The 5-year overall survival and progression-free survival rates were 83.3% and 100%, respectively. During the observation period, no patient had a confirmed recurrence. One patient died of causes unrelated to cancer or treatment. There were no late toxicities by RT. CONCLUSION: Our results show good long-term local control and no late toxicities requiring treatment. Moderate-dose RT was appropriate and well tolerated for early-stage non-stomach gastrointestinal MALT lymphoma.

Primary Duodenal Mucosa-associated Lymphoid Tissue Lymphoma Treated with Radiation Therapy Alone.

Primary mucosa-associated with a lymphoid tissue (MALT) lymphoma is a rare distinct subtype of non-Hodgkin's lymphoma that occurs in approximately 8% of all non-Hodgkin lymphomas. Primary gastrointestinal MALT lymphoma usually occurs in the stomach, but duodenal involvement is extremely rare. Therefore, the clinical manifestations, treatment, and prognosis of primary duodenal MALT lymphoma have not yet been validated because of its rarity. This paper reports a case of a 40-year-old male with primary duodenal MALT lymphoma who was treated successfully with radiation therapy alone. A 40-year-old male visited for a medical check-up. Esophagogastroduodenoscopy revealed whitish multi-nodular mucosal lesions in the second and third portions of the duodenum. Biopsy specimens from mucosal lesions in the duodenum were reported to be suspicious for MALT lymphoma of the duodenum. He received a total dose of 3,000 cGy in 15 fractions with external beam radiation therapy for three weeks. Three months after radiation therapy, an endoscopic examination revealed complete resolution of the duodenal lesions. The follow-up 12 months after radiation therapy showed no evidence of tumor recurrence.

Risk factors analysis and establishment of predictive nomogram of extranodal B-cell lymphoma of mucosal-associated lymphoid tissue.

PURPOSE: 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 AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Surgical resection and orbital iodine-125 brachytherapy for orbital malignancy: a novel treatment for orbital lymphoma.

OBJECTIVES: Orbital lymphoma is one of the most common adult orbital malignancies, accounting for approximately 10% of all orbital tumors. This study aimed to analyze the effects of surgical resection and orbital iodine-125 brachytherapy implantation for orbital lymphoma. PATIENTS AND METHODS: This was a retrospective study. Clinical data of 10 patients were collected from October 2016 to November 2018 and followed up to March 2022. Patients underwent the primary surgery for maximal safe removal of the tumor. After a pathologic diagnosis of a primary orbital lymphoma was established, iodine-125 seed tubes were designed based on the tumor size and invasion range, and direct vision was placed into the nasolacrimal canal or/and under the orbital periosteum around the resection cavity during the secondary surgery. Then, follow-up data, including the general situation, ocular condition, and tumor recurrence, were recorded. RESULTS: Of the 10 patients, the pathologic diagnoses included extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (6 cases), small lymphocytic lymphoma (1 case), mantle cell lymphoma (2 cases), and diffuse large B-cell lymphoma (1 case). The number of seeds implanted ranged from 16 to 40. The follow-up period ranged between 40 and 65 months. All patients in this study were alive and well had tumors that were completely controlled. No tumor recurrences or metastases occurred. Three patients had dry eye syndrome and two patients had abnormal facial sensation. No patient had radiodermatitis involving the skin around the eye, and no patient had radiation-related ophthalmopathy. CONCLUSIONS: Based on preliminary observations, iodine-125 brachytherapy implantation appeared to be a reasonable alternative to external irradiation for orbital lymphoma.

Primary urinary bladder marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue.

Primary urinary bladder marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) is an extremely rare disease. Here, we have reported a case of MALT lymphoma that was successfully treated with transurethral resection of the bladder tumor (TUR-BT) and radiotherapy. A 65-year-old woman presented with macroscopic hematuria. She had a history of chronic cystitis. Cystoscopy of the bladder revealed a submucosal tumor measuring 4 cm in the trigone of the bladder floor. Magnetic resonance imaging showed that the lesion had intermediate intensity on T2-weighted images. TUR-BT was performed, and the lesion was diagnosed with marginal zone B-cell lymphoma of MALT histopathologically. Positron emission tomography (PET) showed a slightly higher fluorine-18-deoxyglucose (FDG) accumulation, with a maximum standardized uptake value of 17.3, than the physiological accumulation in the tumor resection area of the bladder, with no obvious abnormal accumulation outside the bladder. The patient underwent field radiotherapy at a dose of 30 Gy in 15 fractions, administered in 5 fractions per week. She developed grade 2 cystitis as an acute radiation-related adverse event, without any hematological adverse events. On PET at 5 months after radiotherapy, FDG accumulation in the posterior wall of the bladder was obscured and remained regressed after 2 years.

Influence of age on long-term net survival benefit for early-stage MALT lymphomas treated with radiotherapy: A SEER database analysis (2000-2015).

BACKGROUND: Given the lower incidence of lymphoma-related death but higher background mortality in patients with early-stage mucosa-associated lymphoid tissue (MALT) lymphoma, it is critically important to examine how age affects a treatment's survival benefit. METHODS: 9,467 patients with early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000-2015 were extracted and analyzed. Primary therapy was classified as radiotherapy (n = 3,407), chemotherapy (n = 1,294), and other/unknown treatments including observation (n = 4,766). Inverse probability of treatment weighting (IPTW) was conducted to balance baseline characteristics between groups. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were conducted to compare survival differences between treatment modalities by controlling for the background mortality. Radiotherapy-age interaction was examined. RESULTS: Across age-groups, early-stage MALT lymphoma patients were at lower risk of lymphoma-related death than death due to other causes. The 10-year overall survival (OS, 73.8 %) and RS (96.6 %) rates were significantly higher, and the SMR (1.14) significantly lower, with radiotherapy than with chemotherapy (OS, 61.7 %; RS, 86.4 %; SMR, 1.54; P < 0.001) or other/unknown treatments (OS, 61.1 %; RS, 87.2 %; SMR, 1.41; P < 0.001). By multivariable analysis and IPTW, radiotherapy remained an independent predictor of better RS (HR 0.81, 95 %CI, 0.73-0.89; P < 0.001). A significant interaction between age and radiotherapy was identified for both RS (Pinteraction = 0.016) and OS (Pinteraction = 0.024), indicating greater benefit in young adults. CONCLUSION: Radiotherapy was associated with significantly better survival in early-stage MALT lymphoma, especially in young adults.

Real World Long-term Follow-up Experience with Yttrium-90 ibritumomab tiuxetan in Previously Untreated Patients with Low-Grade Follicular Lymphoma and Marginal Zone Lymphoma.

INTRODUCTION: Yttrium-90 ibritumomab tiuxetan [(90)Y-IT] is a CD20-targeted radio-immuno conjugate. Clinical trials of (90)Y-IT as a first-line stand-alone treatment in follicular lymphoma (FL) and/or marginal zone lymphoma (MZL) showed high efficacy. However, long-term survival outcomes and toxicities are not well-defined. METHODS: We report a retrospective single-institution, multi-center study of (90)Y-IT in previously untreated low grade (LG)-FL and MZL at Mayo Clinic Cancer Center between January 2000 and October 2019. We selected patients with LG-FL and MZL who received standard-dose (90)Y-IT as a single agent in the first line setting. RESULTS: The cohort (n = 51) consists of previously untreated LG-FL (n = 41) or MZL (n = 10). Median follow-up was 5.3 years (95% CI; 4.2, 6.2). Overall response rate (ORR) was 100% with complete response rate (CR) of 94%. Continuous CR was observed in 59% patients who had more than 2 years of follow-up. Long-term CR (>7 years) was seen in 25% of patients. Median progression free survival (mPFS) for the whole cohort was not reached (NR) (95% CI; 4.9, NR). Bulky disease was associated with shorter median PFS of 3.5 years (CI 95%; 0.8, 4.9) compared to non-bulky disease NR (CI 95%; 5.8, NR), P = .02. The incidence of grade 3 or higher thrombocytopenia, neutropenia and anemia were 47%, 37%, and 4% respectively. No therapy-related myelodysplasia or acute myeloid leukemia were observed. CONCLUSION: Long real-life follow-up showed that single-agent (90)Y-IT is highly efficacious with durable long-term survival in previously untreated LG-FL and MZL without significant risk for secondary malignancies.