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3.
Cancer Med ; 9(2): 663-670, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31808316

RESUMEN

Marginal zone lymphoma of the central nervous system (CNS MZL) is rare. The clinical features, treatment, and prognosis are not well characterized. We performed a multicenter retrospective study of CNS MZL. Twenty-six patients were identified: half with primary and half with secondary CNS involvement. The median age was 59 years (range 26-78), 62% female and 79% with ECOG performance status ≤ 1. The most common disease site was the dura (50%). Treatment was determined by the treating physician and varied substantially. After a median follow up of 1.9 years, the estimated 2-year progression-free (PFS) and overall survival (OS) rates were 59% and 80%, respectively. Secondary CNS MZL was associated with 2-year OS of 58%. CNS MZL is rare, but relative to other forms of CNS lymphoma, outcomes appear favorable, particularly among the subset of patients with dural presentation and primary CNS presentation.

6.
J Cardiovasc Imaging ; 27(4): 268-279, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31614398

RESUMEN

BACKGROUND: Radiation exposure increases the risk of coronary artery disease (CAD). We explored the association of CAD with coronary artery dose-volume parameters in patients treated with 3D-planned radiation therapy (RT). METHODS: Patients who received thoracic RT and were evaluated by cardiac computed tomography ≥ 1 year later were included. Demographic data and cardiac risk factors were retrospectively collected. Dosimetric data (mean heart dose, dmax, dmean, V50 - V5) were collected for the whole heart and for each coronary artery. A coronary artery calcium (CAC) Agatston score was calculated on a per-coronary basis and as a total score. Multivariable generalized linear mixed models were generated. The predicted probabilities were used for receiver operating characteristic analyses. RESULTS: Twenty patients with a median age of 53 years at the time of RT were included. Nine patients (45%) had ≥ 3/6 conventional cardiac risk factors. Patients received RT for breast cancer (10, 50%), lung cancer (6, 30%), or lymphoma/myeloma (4, 20%) with a median dose of 60 Gy. CAC scans were performed a median of 32 months after RT. CAC score was significantly associated with radiation dose and presence of diabetes. In a multivariable model adjusted for diabetes, segmental coronary artery dosimetric parameters (dmax, dmean, V50, V40 V30, V20, V10, and V5) were significantly associated with CAC score > 0. V50 had the highest area under the ROC curve (0.89, 95% confidence interval, 0.80-0.97). CONCLUSIONS: Coronary artery radiation exposure is strongly correlated with subsequent segmental CAC score. Coronary calcification may occur soon after RT and in individuals with conventional cardiac risk factors.

7.
Blood Adv ; 3(13): 2035-2039, 2019 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-31289030

RESUMEN

Mantle cell lymphoma (MCL) generally exhibits an aggressive disease course with poor outcomes. Despite inherent radiosensitivity, radiation therapy (RT) is not commonly used for MCL. This study assesses the role of low-dose RT (LDRT) with concurrent chemotherapy in relapsed, multiply refractory MCL. From 2014 through 2018, 19 patients with relapsed, refractory MCL had 98 sites treated with 4 Gy. Median follow-up from initial LDRT was 15.4 months. Patients had received a median 7 courses of chemotherapy since diagnosis, and 58% were ibrutinib-refractory. Of the 98 sites, 76% were refractory to ongoing chemotherapy, and LDRT was delivered with concurrent chemotherapy for 76%. The complete response (CR) rate was 81% at a median 2.7 months post-LDRT. There were no differences in CR despite ibrutinib-refractory disease, prior chemotherapy courses (>5), or tumor size (>3 cm). There were no RT-related toxicities. Overall survival at 1 year following initial LDRT was 90%, and 1-year progression-free survival following last course was 55%. In summary, LDRT is effective for relapsed, multiply refractory MCL, and may be safely delivered with chemotherapy, to multiple sites, and repeatedly without issue. By treating active sites of disease, LDRT can provide durable local control, help achieve remission, and potentially bridge patients to subsequent novel therapies.

8.
Leuk Lymphoma ; 60(13): 3258-3265, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31234671

RESUMEN

Patients with early-stage nodal follicular lymphoma (FL) may be rendered free of detectable disease by a diagnostic excisional biopsy. We reviewed the management and outcomes of 48 patients with FL, diagnosed from 2003-2013, treated at a single institution. The primary endpoints were local control (LC) and progression-free survival (PFS).Median age at diagnosis was 54.5 years (range 15-74 years). Forty-seven patients were stage I (97.9%); 15 patients (31.3%) had grade 3 disease. Initial management consisted of observation (12 patients; 25.0%), radiation therapy (RT) alone (12 patients; 25.0%), systemic therapy alone (9 cases; 18.8%), or both (15 patients; 31.3%). Median follow-up was 4.92 years (range 0.5-13.83 years). 4-year PFS and OS were 80.9% and 97.1%, respectively. Patients treated with additional therapy experienced significantly better 4-year LC (100% vs. 81.8%; p = .012) and 4-year PFS (86.7% vs. 63.6%; p = .006).Patients with completely resected limited-stage FL would benefit from therapy beyond excisional biopsy alone.

9.
Blood Adv ; 3(9): 1356-1367, 2019 05 14.
Artículo en Inglés | MEDLINE | ID: mdl-31036721

RESUMEN

Radiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

10.
Clin Lymphoma Myeloma Leuk ; 19(8): e465-e469, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31133526

RESUMEN

PURPOSE: To characterize local relapse after surgical fixation and postoperative radiotherapy (RT) for multiple myeloma (MM) with cortical involvement of long bones. PATIENTS AND METHODS: We retrospectively identified patients with MM involving cortical long bones treated with surgical fixation followed by postoperative RT at our institution. Local failures, defined as radiographic recurrence along the surgical hardware, were documented, and potential associations of independent variables (RT dose, fractionation, and extent of hardware coverage) with local failure were assessed by univariate Cox regression. RESULTS: We identified 33 patients with 40 treated sites with a median follow-up of 25.7 months; 68% of treatments were for pathologic fracture, and 32% were for impending fracture. The most common dose and fractionation were 20 to 25 Gy in 8 to 12 fractions. On average, 76% of the surgical hardware was covered by the postoperative RT field (median, 80%; range, 28%-100%). Local failure was observed in 5 cases (12.5%), 2 within the RT field and 3 out of field. None of the relapses resulted in hardware failure, and 2 were retreated with RT. The extent of hardware coverage predicted disease relapse along the hardware (hazard ratio = 6.44; 95% confidence interval, 1.09-37.97; P = .04); however, total RT dose, biologically effective dose, and number of fractions did not. CONCLUSION: After internal fixation of long bones with MM, full hardware coverage with the RT field could reduce the risk, though small, of disease developing in the future in the proximate hardware. Postoperative RT doses of 20 to 25 Gy in 8 to 10 fractions can achieve excellent local control.

12.
Clin Lymphoma Myeloma Leuk ; 19(6): 381-389, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30935940

RESUMEN

INTRODUCTION: Extranodal follicular lymphoma (E-FL) is a rare entity that has distinct characteristics and outcomes compared with nodal follicular lymphoma. PATIENTS AND METHODS: This cohort comprised 37 patients with stages I/II E-FL, diagnosed from 2003 to 2013. Outcomes included progression-free survival (PFS), and overall survival (OS). Survival outcomes were calculated using Kaplan-Meier methods. RESULTS: Median age was 60 years (range, 37-84 years). Disease was stage I in 29 (78.4%). The Follicular Lymphoma International Prognostic Index score was 0 to 1 in 31 (83.8%), 2 in 2 (5.4%), 3 in 1 (2.7%), and missing in 3 (8.1%). Sites of involvement included the gastrointestinal (GI) tract in 22 (59.5%), and non-GI sites in 15 (40.5%). Initial management consisted of chemotherapy (CHT) alone in 21 (56.8%), radiation therapy (RT) alone in 2 patients (5.4%), RT and rituximab in 1 (2.7%), CHT and RT in 7 (18.9%), and observation in 6 (16.2%). RT was to a median dose of 30.6 Gy (range, 23.4-44.0 Gy). At a median follow-up of 69 months (range, 8-157 months), 5-year PFS and OS were 70.4% and 94.4%, respectively. Although the 5-year PFS of those observed was worse than for those who received therapy (33.3% vs. 77.6%; P = .011), that did not translate into an OS difference. Patients who received RT as part of upfront management had a 100% local control (LC) rate and a trend toward improved 5-year PFS (90% vs. 62.2%; P = .067). CONCLUSION: Early stage E-FL is an indolent disease and is associated with excellent OS. Treatment strategies should be individualized with RT prioritized when LC is a significant goal.

13.
Leuk Lymphoma ; 60(10): 2432-2440, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30942648

RESUMEN

Controversy exists regarding the optimal management of limited stage grade 3 follicular lymphoma (FL3). We assessed the treatment outcomes of 190 consecutive patients with stage I-II FL. Fifty two patients had FL3 disease, in whom the median age was 55 years. At a median follow-up of 65 months, 5-year progression-free survival (PFS) and overall survival (OS) rates were 76.6% and 87.6%, respectively. Patients receiving systemic therapy followed by radiation therapy (RT) had a significantly better PFS (p=.003) than those treated with RT alone, but similar OS (p = .476). Patients treated with RT had 100% local control. Compared to 132 patients with grade 1-2 FL, those with FL3 had similar PFS (p = .493) and OS (p = .330). Patients with FL3 can experience favorable outcomes when treated with a combination of systemic therapy and RT, comparable to low grade FL.

14.
Int J Radiat Oncol Biol Phys ; 104(3): 522-529, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-30858143

RESUMEN

PURPOSE: We previously reported that ∼30% of patients with localized follicular lymphoma (FL) staged by 18F-fluorodeoxyglucose positron emission tomography-computed tomography receiving primary radiation therapy (RT) will relapse within 5 years. We sought to report outcomes for those who relapsed. METHODS AND MATERIALS: We conducted a multicenter, retrospective study of patients aged ≥18 years who received RT ≥ 24 Gy for stage I to II, grade 1 to 3A FL, staged with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography. Observation was defined as >6 months without treatment from relapse. Overall survival (OS) and freedom from progression (FFP) were estimated with Kaplan-Meier analysis and univariable and multivariable analyses with Cox regression. RESULTS: Of 512 patients with median follow-up of 52 months, 149 (29.1%) developed recurrent lymphoma at a median of 23 months (range, 1-143) after primary RT. Median follow-up was 33 months after relapse. Three-year OS was 91.4% after recurrence. OS was significantly worse for those with relapse ≤12 months from date of diagnosis versus all others-88.7% versus 97.6%, respectively (P = .01)-and remained significantly worse on multivariable analyses (follicular lymphoma international prognostic index-adjusted hazard ratio, 3.61; P = .009). Histology at relapse included 93 indolent (grade 1-3A), 3 FL grade 3B/not otherwise specified, and 18 diffuse large B-cell lymphoma; 35 patients did not undergo biopsy. Of those with follow-up ≥3 months who underwent biopsy (n = 74) or had presumed (n = 23) indolent recurrence, 58 patients (59.8%) were observed, 19 (19.6%) had systemic therapy, 16 (16.5%) had RT, and 4 (4.1%) had systemic therapy + RT. For patients with indolent recurrences that were observed, 3-year FFP or freedom from treatment was 56.6% (median, 48 months). For all patients with biopsied/presumed indolent recurrence receiving salvage treatment (n = 59, including 20 initially observed) 3-year FFP was 73.9%. CONCLUSIONS: Prognosis for patients with relapsed FL after primary radiation therapy is excellent, supporting the role of primary radiation in the management of early stage disease. Patients with localized FL treated with primary RT who experience early relapse (<12 months) have inferior survival compared with those with longer disease-free interval.


Asunto(s)
Linfoma Folicular/mortalidad , Linfoma Folicular/radioterapia , Terapia Recuperativa , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Fluorodesoxiglucosa F18 , Humanos , Estimación de Kaplan-Meier , Linfoma Folicular/diagnóstico por imagen , Linfoma Folicular/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/administración & dosificación , Supervivencia sin Progresión , Radiofármacos , Recurrencia , Estudios Retrospectivos , Rituximab/uso terapéutico , Factores de Tiempo , Vincristina/administración & dosificación , Espera Vigilante , Adulto Joven
16.
Int J Radiat Oncol Biol Phys ; 104(2): 447-455, 2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30769175

RESUMEN

PURPOSE: In patients with gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma, the standard radiation therapy (RT) dose is ≥30 Gy. We report the outcome of patients treated with reduced dose 24 Gy compared with those treated with ≥30 Gy. METHODS AND MATERIALS: We reviewed results from 32 patients who received a diagnosis of gastric MALT lymphoma between 2007 and 2017 who were treated with involved site RT using intensity modulated radiation therapy (IMRT). Response to therapy was based on post-RT endoscopic biopsy. Freedom from local treatment failure (FFLTF), freedom from treatment failure (FFTF), and overall survival (OS) outcomes were determined. RESULTS: The median age of patients at diagnosis was 58 years. Therapy for MALT was given prior to RT in 14 patients with residual biopsy proven disease documented in all cases (anti-microbial, n=11; rituximab, n=2; rituximab, cyclophosphamide, doxorubicin, vincristine, n=1). One patient received RT (36 Gy) and concurrent rituximab. The median RT dose was 30 Gy; it was 30 to 36 Gy in 66% of patients (n = 21) and 24 Gy in 34% of patients (n = 11). Post-RT biopsy documented a complete response in all patients. Failures occurred in the stomach and duodenum, respectively, at 3.6 and 4.5 years, after 30 Gy. At a median follow-up of 55.2 months (73.8 for ≥30 Gy compared with 28.7 for 24 Gy; P < .001), the 2-year FFLTF, FFTF, and OS were 100%, 100%, and 97%, respectively. No association was found between the lower (24-Gy) dose and FFLTF (P = .819), FFTF (P = .819), or OS (P = .469). CONCLUSIONS: Contemporary RT with involved site targeting using IMRT is associated with high complete response rates for patients with gastric MALT lymphoma, even using reduced doses of 24 Gy. Additional follow-up and increased patient numbers are required to confirm equivalent disease control.


Asunto(s)
Mucosa Gástrica , Linfoma de Células B de la Zona Marginal/radioterapia , Radioterapia de Intensidad Modulada/métodos , Neoplasias Gástricas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/mortalidad , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Dosificación Radioterapéutica , Estudios Retrospectivos , Rituximab/administración & dosificación , Neoplasias Gástricas/mortalidad , Resultado del Tratamiento , Vincristina/administración & dosificación
17.
Radiother Oncol ; 131: 88-92, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30773193

RESUMEN

BACKGROUND AND PURPOSE: A lower proportion of CD8+ tumor infiltrating lymphocytes in mycosis fungoides (MF) patients is associated with worse survival. However, it is not known whether circulating CD4:CD8 ratio is a prognosticator of response to total skin electron beam therapy (TSEBT). METHODS AND MATERIALS: We identified 126 MF patients treated with TSEBT from 2001 to 20014 at two high-volume academic centers. Circulating CD4:CD8 ratio was obtained within 1 week before TSEBT. TSEBT was delivered with 6-9mEV electrons with low (12 Gy) or conventional (≥12 Gy) doses. Treatment response was assessed with the modified Severity Weighted Assessment Tool (mSWAT). Post-treatment mSWAT decrease of ≥75% was classified as near complete response (CR) while mSWAT decrease of <75% was considered partial response (PR). Receiver operating characteristic analysis determined an optimal CD4:CD8 threshold value to predict TSEBT response in the derivation cohort and was applied to an external validation cohort. RESULTS: 71.4% and 28.6% of patients achieved CR and PR after TSEBT. Higher CD4:CD8 ratio predicted poorer response: median CD4:CD8 in patients with PR vs. CR was 4.84 vs. 1.97 (p = 0.002). A threshold CD4:CD8 of 4.42 optimally discriminated in the discovery cohort patients with PR vs. XR (sensitivity 90%, specificity 59%, area under curve (AUC) = 0.71; p = 0.002). Within an independent test cohort (n = 32), 73.9% of patients with CD4:CD8 <4.42 achieved CR vs. 33.3% of those with CD4:CD8 ≥4.42 (p = 0.033). Among all patients with CD4:CD8 <4.42 (n = 73), 74% achieved CR with low-dose TSEBT vs. 93% with conventional dose TSEBT (p = 0.02). On multivariable logistic regression, CD4:CD8 remained a significant independent predictor of TSEBT response in all patients (OR = 0.107, 95% CI 0.395-0.290, p < 0.001). CONCLUSION: Peripheral blood CD4:CD8 ratio was a significant independent predictor of TSEBT response of MF patients as validated in an independent cohort at separate academic center. The potential for CD4:CD8 ratio as a biomarker to inform radiation treatment dosing warrants further investigation.


Asunto(s)
Relación CD4-CD8 , Electrones/uso terapéutico , Micosis Fungoide/radioterapia , Neoplasias Cutáneas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis Fungoide/sangre , Micosis Fungoide/inmunología , Pronóstico , Inducción de Remisión , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/inmunología , Adulto Joven
19.
Sci Rep ; 9(1): 1322, 2019 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-30718585

RESUMEN

First-order radiomic features, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), are associated with disease progression in early-stage classical Hodgkin lymphoma (HL). We hypothesized that a model incorporating first- and second-order radiomic features would more accurately predict outcome than MTV or TLG alone. We assessed whether radiomic features extracted from baseline PET scans predicted relapsed or refractory disease status in a cohort of 251 patients with stage I-II HL who were managed at a tertiary cancer center. Models were developed and tested using a machine-learning algorithm. Features extracted from mediastinal sites were highly predictive of primary refractory disease. A model incorporating 5 of the most predictive features had an area under the curve (AUC) of 95.2% and total error rate of 1.8%. By comparison, the AUC was 78% for both MTV and TLG and was 65% for maximum standardize uptake value (SUVmax). Furthermore, among the patients with refractory mediastinal disease, our model distinguished those who were successfully salvaged from those who ultimately died of HL. We conclude that our PET radiomic model may improve upfront stratification of early-stage HL patients with mediastinal disease and thus contribute to risk-adapted, individualized management.

20.
Clin Lymphoma Myeloma Leuk ; 19(4): 244-250, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30686775

RESUMEN

INTRODUCTION: We report our experience in treating patients with primary breast extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) to better elucidate the natural history and optimal treatment approach for these patients. PATIENTS AND METHODS: Patients with localized primary breast MALT lymphoma treated between 1995 and 2016 were included. Disease-related endpoints including progression-free survival (PFS) were analyzed. RESULTS: Eleven patients met inclusion criteria; all patients were women with a median age of 62 years (range, 42-75 years). Most (73%) patients presented with stage I disease, and most (73%) patients were treated initially treated with radiation therapy (RT). Local control following RT was 100%; all patients with progression following RT experienced distant relapse. Additionally, none of the 3 patients treated with ultra-low-dose RT (4 Gy) experienced subsequent progression (local or distant). Six (55%) patients progressed after initial therapy, of whom 5 received initial RT; the 5-year PFS after initial therapy was 60%. Salvage systemic therapy was utilized in all patients with progression, with 5 of 6 patients receiving single-agent rituximab. Of the patients treated with salvage therapy, only 1 experienced second relapse, with a 5-year PFS of 100% after salvage systemic therapy. With a median follow-up of 8 years, there were no deaths in the cohort. CONCLUSIONS: Patients with primary breast MALT lymphoma achieve excellent outcomes. Initial RT affords local control, and although subsequent distant progression is common, salvage rituximab yields high rates of PFS.

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