Long-term outcomes of patients with limited-stage ocular adnexal DLBCL treated with combined modality therapy in the rituximab era.
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ABSTRACT:
SUBMITTER: Qualls D
PROVIDER: S-EPMC10407681 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
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Long-term outcomes of patients with limited-stage ocular adnexal DLBCL treated with combined modality therapy in the rituximab era.
Qualls David D Imber Brandon S BS Okwali Michelle M Hamlin Paul A PA Kumar Anita A Lahoud Oscar B OB Matasar Matthew J MJ Noy Ariela A Owens Colette C Zelenetz Andrew D AD North Victoria S VS Schöder Heiko H Dogan Ahmet A Salles Gilles G Yahalom Joachim J Falchi Lorenzo L
British journal of haematology 20221209 4
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Project description:BackgroundApproximately 50% of limited-stage ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) patients with adverse prognostic factors relapse after radiotherapy. Chemoimmunotherapy has been proposed as an alternative frontline therapy. However, only a few studies have reported its long-term treatment outcome.MethodsIn 2011, we commenced a phase 2 trial to investigate the efficacy of rituximab, cyclophosphamide, doxorubicin, and prednisolone (R-CVP) in bilateral and non-conjunctival limited-stage OAML patients. Results of the clinical trial showed a response rate of 100% and a 4-year progression-free survival of 90.3% without significant toxicity. We extended the study period to December 2020 to determine the long-term efficacy of R-CVP chemoimmunotherapy.ResultsAt a median observation period of 66.0 months, eight of 33 study patients had relapsed. The cumulative incidence of relapse was 18.9% at 5 years and 44.7% at 8 years. The majority of relapses developed more than 4 years after treatment. Local relapse was more prevalent than distant relapse. The relapse risk of orbital and lacrimal diseases was likely to be higher than that of conjunctival and eyelid diseases (HR: 2.5, 95% CI: 0.498-12.500, p = 0.25).ConclusionAlthough the response rate was remarkable for chemoimmunotherapy, the risk of late relapse was considerable. Based on our findings, clinical trials for limited-stage OAML patients should have a long-term observation period. To minimize radiation toxicity and reduce the risk of delayed relapse (local relapse and distant relapse), a future study with sequential or combination treatment of local low-dose radiation and systemic chemoimmunotherapy can be considered.
| S-EPMC9302339 | biostudies-literature
Project description:ImportanceCombined-modality therapy with chemotherapy and radiation therapy plays a crucial role in the upfront treatment of patients with limited-stage small cell lung cancer (SCLC), but there may be barriers to utilization in the United States.ObjectiveTo estimate utilization rates and factors associated with chemotherapy and radiation therapy delivery for limited-stage SCLC using the National Cancer Database.Design, setting, and participantsAnalysis of initial management of all limited-stage SCLC cases from 2004 through 2013 in the National Cancer Database.Main outcomes and measuresUtilization rates of chemotherapy and radiation therapy at time of initial treatment. Multivariable analysis identified independent clinical and socioeconomic factors associated with utilization and overall survival.ResultsA total of 70 247 cases met inclusion criteria (55.3% female; median age, 68 y [range, 19-90 y]). Initial treatment was 55.5% chemotherapy and radiation therapy, 20.5% chemotherapy alone, 3.5% radiation therapy alone, and 20.0% neither (0.5% not reported). Median survival was 18.2 (95% CI, 17.9-18.4), 10.5 (95% CI, 10.3-10.7), 8.3 (95% CI, 7.7-8.8), and 3.7 (95% CI, 3.5-3.8) months, respectively. Being uninsured was associated with a lower likelihood of both chemotherapy (odds ratio [OR], 0.65; 95% CI, 0.56-0.75; P < .001) and radiation therapy (OR, 0.75; 95% CI, 0.67-0.85; P < .001) administration on multivariable analysis. Medicare/Medicaid insurance had no impact on chemotherapy use, whereas Medicaid (OR, 0.79; 95% CI, 0.72-0.87; P < .001) and Medicare (OR, 0.86; 95% CI, 0.82-0.91; P < .001) were independently associated with a lower likelihood of radiation therapy delivery. Lack of health insurance (HR, 1.19; 95% CI, 1.13-1.26; P < .001), Medicaid (HR, 1.27; 95% CI, 1.21-1.32; P < .001), and Medicare (HR, 1.12; 95% CI, 1.09-1.15; P < .001) coverage were independently associated with shorter survival on adjusted analysis, while chemotherapy (HR, 0.55; 95% CI, 0.54-0.57; P < .001) and radiation therapy (HR, 0.62; 95% CI, 0.60-0.63; P < .001) were associated with a survival benefit.Conclusions and relevanceSubstantial proportions of patients documented in a major US cancer registry did not receive radiation therapy or chemotherapy as part of initial treatment for limited-stage SCLC, which, in turn, was associated with poor survival. Lack of radiation therapy delivery was uniquely associated with government insurance coverage, suggesting a need for targeted access improvement in this population. Additional work will be necessary to conclusively define exact population patterns, specific treatment deficiencies, and causative factors leading to heterogeneous care delivery.
| S-EPMC5885163 | biostudies-literature
Project description:Radiotherapy is a commonly used treatment for limited-stage ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) but showed a substantial relapse risk if the disease involves beyond-conjunctiva or bilateral conjunctivae. Systemic chemoimmunotherapy may be an alternative frontline therapy for the limited disease with those adverse prognostic factors.We designed a multicenter, phase II study of the chemoimmunotherapy, rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) for the treatment of patients with limited-stage OAML with bilateral or beyond-conjunctival involvement. Thirty-three patients with Ann Arbor stage I OAML with the adverse factors were enrolled. Patients received six cycles of R-CVP followed by two cycles of rituximab therapy.At the end of treatment, all the enrolled patients had responded. The cumulative complete response achievement was 93.9% at 2 years. At a median follow-up of 50.6 months, three patients had progressed. Progression-free survival and overall survival at 4 years was 90.3±5.3% and 100%, respectively.This phase II study demonstrated durable efficacy of R-CVP chemoimmunotherapy, which has promise as an alternative frontline therapy for the limited-stage OAML patients with adverse prognostic factors.NCT01427114.
| S-EPMC5620279 | biostudies-literature
Project description:Rituximab-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant (ASCT) in chemosensitive patients remains the standard of care for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL). However, its role in those patients achieving less than a complete response to first-line therapy (primary refractory disease) in the rituximab era is not well defined. We reviewed the outcomes of 82 transplant-eligible patients with primary refractory DLBCL who underwent salvage therapy with the intent of administering high-dose therapy and ASCT to patients achieving chemosensitive remission. The estimated 3-year overall and progression-free survival for all patients was 38% and 29%, respectively, and 65% and 60% respectively for patients proceeding to stem cell transplant. Long-term remission was achieved in 45% of patients achieving a partial response (PR) to initial induction therapy and <20% of patients with stable or progression of disease following initial therapy. These results suggest that salvage chemotherapy with the intent of subsequent high-dose therapy and ASCT remains a feasible strategy in certain patients with primary refractory DLBCL, particularly for those achieving a PR to frontline therapy. The primary barrier to curative therapy in patients with primary refractory disease is resistance to salvage therapy, and future studies should be aimed towards increasing the response rate in this population.
| S-EPMC5556376 | biostudies-other
Project description:The CORAL study highlighted the need to develop novel salvage regimens in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Carfilzomib (CFZ) can overcome rituximab chemotherapy resistance in lymphoma preclinical models by targeting the ubiquitin-proteasome system. We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698). In the dose-escalation phase, 18 patients were enrolled at 6 dose levels with no dose-limiting toxicities noted. CFZ 45 mg/m2 was selected as the recommended dose for expansion. Eleven additional patients were enrolled in the dose-expansion phase. Overall response rate (ORR) was 66% (48% CR; 17% PR); 52% patients underwent HDC-ASCT. An ORR of 85% was observed in patients with nongerminal center B-cell-like (non-GCB) DLBCL compared with only 13% in those with GCB DLBCL. Median progression-free survival (PFS) was 15.2 months (5.1 months, not reached [NR]), and median overall survival (OS) was 22.6 months (6.8 months, NR). Patients with non-GCB subtype had a significantly longer PFS (NR vs 6.6 months; P = .0001) and OS (NR vs 6.6 months; P = .001) than those with GCB subtype. C-R-ICE is well tolerated in patients with R/R DLBCL with toxicities comparable to rituximab, ifosfamide, carboplatin, and etoposide therapy. Our data show that patients with non-GCB DLBCL benefit significantly from incorporating CFZ into second-line therapy and HDC-ASCT.
| S-EPMC10111346 | biostudies-literature
Project description:BackgroundThe choice of a primary treatment for ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) depends on the extent of tumor spread. However, radiotherapy is commonly used as a first-line therapy despite ophthalmic complications, because most OAMLs are in a limited stage of progression. However, the initial therapeutic modality, including chemotherapy and treatment of the advanced stage, has not been fully established for OAML. Therefore, we evaluated the optimal therapeutic options and survival outcome-related parameters for patients with primary OAML.MethodsWe evaluated 208 consecutive patients with primary OAML who were diagnosed at the Catholic University Lymphoma Group between January 2004 and April 2015.FindingsDuring a median follow-up of 70.0 months (range, 3.2-182.0 months) in 208 patients with primary OAML, most patients were female and the median age was 46 years old. Overall survival (OS) and progression-free survival (PFS) at 13 years were excellent (92.7% and 69.7%, respectively). Of the 117 patients who received the first-line radiotherapy, 92% achieved complete remission (CR), usually by being treated with less than 30 Gy. Radiation-related ophthalmic complications including dry eye syndrome (59%) and cataract (22%) caused a decline in the quality of life (QoL). Chemotherapy alone was used to treat 86 OAML patients, with 84.9% achieving CR and 12.8% achieving partial remission with tolerable toxicities. There were no differences in survival outcomes between patients treated with radiotherapy versus those treated with rituximab-containing chemotherapy, although the latter group had more advanced stages of OAML (OS, p = 0.057; PFS, p = 0.075).InterpretationOAML patients were predominantly female and relatively young, and radiotherapy as a primary therapeutic option was more likely to lead to radiation-related complications, resulting in lower QoL. On the other hand, frontline chemotherapy showed consistent therapeutic outcomes with tolerable toxicities compared to radiotherapy, and there were no long-term or delayed adverse events. Therefore, when considering therapeutic efficacy and therapy-related QoL, chemotherapy is recommended for younger patients, and radiotherapy is recommended for older and chemotherapy-ineligible patients.FundingA National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. NRF-2016R1A2B4007282).
| S-EPMC6537565 | biostudies-literature
Project description:PurposeTo characterize demographic, clinical, and histopathologic features of ocular adnexal lymphoma (OAL) at a single institution.MethodsRetrospective review of all patients with pathologic diagnosis of OAL between 2015 and 2020.ResultsThere were 133 patients with OAL, with a median age of 65 years (range 23-97) and a slight female predominance (male: female = 1:1.46), (n = 79, 59%). The majority of tumors were non-Hodgkin B-cell lymphomas (n = 131, 99%), most frequently Extranodal Marginal Zone B-Cell Lymphoma (EMZL, n = 93, 70%), followed by follicular lymphoma (n = 21, 16%), chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 7, 5%), diffuse large B-cell lymphoma (n = 5, 4%), and mantle cell lymphoma (n = 5, 4%). The most frequently involved sites included the orbit (n = 85, 64%) and conjunctiva (n = 43, 32%). Information was available on oncologic staging in 78 (59%), treatment in 82 (62%), and follow-up in 75 (56%) patients. By the Ann-Arbor classification system, patients were classified as IE (54/78, 69%), IIE (9/78, 12%), IIIE (6/78, 8%), and IVE (9/78, 12%). The most common treatments included external beam radiotherapy (standard and ultra-low-dose) (48/82, 59%), biologics (22/82, 27%), and surgical excision with cryotherapy (14/82, 17%) (some patients had >1 therapy). Median follow-up time was 24 months (range 0-221 months). Recurrence was observed in 13% (10/75) with a median time to recurrence of 60 months (95% confidence interval 47-73 months). Excision with cryotherapy as a sole treatment modality was associated with earlier recurrence (P = 0.003).ConclusionIn this largest single-center study of OAL, we found that most OAL were Ann-Arbor Stage IE EMZL, occurring in older patients with a female predominance. Early recurrence was noted in tumors treated with excision and cryotherapy alone.
| S-EPMC9116088 | biostudies-literature
Project description:PurposeMantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger.Patients and methodsWe retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed.ResultsData were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2).ConclusionIn this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.
| S-EPMC7554677 | biostudies-literature
Project description:RationaleDiffuse large B-cell lymphoma (DLBCL) is a common subtype of non-Hodgkin's lymphoma characterized by high malignancy, rapid onset and aggressive clinical behavior. The disease exhibits considerable heterogeneity, which influences clinical and immunophenotypic characteristics, which in turn affect treatment outcomes and prognosis. Recently, targeted therapies have been introduced, offering improved therapeutic efficacy but with risks such as immunosuppression and opportunistic infections.Patient concernsWe report a case of a patient diagnosed with DLBCL who experienced immunosuppression as a result of treatment with rituximab and a Bruton's tyrosine kinase inhibitor, which subsequently led to Strongyloides stercoralis infection.DiagnosesThe patient was diagnosed with S. stercoralis infection, confirmed by appropriate diagnostic tests after the onset of clinical symptoms suggestive of parasitic infection.InterventionsThe patient was treated with a combination of rituximab and a Bruton's tyrosine kinase inhibitor as part of her DLBCL therapy. Antiparasitic treatment was started after diagnosis of S. stercoralis infection.OutcomesThe patient's infection was successfully managed with antiparasitic therapy, although the case highlights the need for vigilant monitoring of immunosuppressive therapy in patients with DLBCL due to the risk of opportunistic infections.LessonsThis case highlights the potential complications of targeted therapies in DLBCL, particularly the risk of opportunistic infections such as S. stercoralis. It highlights the importance of careful patient monitoring and prompt intervention to effectively manage such infections.
| S-EPMC11856888 | biostudies-literature
Project description:Stage III NSCLC comprises of a heterogeneous group of patients with regard to stage, extent of disease and prognosis. Disease presentation can often be complex in clinical practice, and the challenges are not well-defined in clinical trials or practice guidelines. In order to improve the therapeutic ratio of treatment, one needs to either increase the benefit of treatment or reduce toxicities, or both. Priorities in radiation therapy include dose escalation, imaging advances, improved target delineation, reduced planning target volume margin, intensity-modulated radiotherapy, image-guided radiotherapy, motion management and the use of cytoprotectants. Priorities in systemic therapy include the incorporation of molecularly targeted and immune-modulatory agents.
| S-EPMC6310316 | biostudies-literature