Extranodal Involvement In Patients Research Articles

Whole-body diffusion-weighted imaging with background body signal suppression and quantitative apparent diffusion coefficient in the detection, staging, and grading of non-Hodgkin lymphoma.

Assess reproducibility of detection, staging, and grading of non-Hodgkin lymphoma (NHL) using whole-body diffusion-weighted imaging with background body signal suppression (WB-DWIBS). Thirty NHL patients underwent WB-DWIBS, divided into 2 groups according to staging and grading. Image analysis and apparent diffusion coefficient (ADC) measurement of the largest lymph node in each group were performed by 2 observers. Inter-observer agreement was performed. Overall inter-observer agreement for detection of NHL was excellent (k = 0.843; 92.05%) with excellent inter-observer agreement of nodal disease (cervical, thoracic and abdominal) (k = 0.783, 0.769, and 0.856; 96.67%, 90.0%, and 93.3% respectively), extra-nodal disease (k = 1; 100%), and splenic involvement (k = 0.67; 83.3%). The overall inter-observer agreement of DWIBS in staging of NHL was excellent (k = 0.90; 94.9%) with excellent inter-observer agreement for stage I (k = 0.93; 96.4%), stage II (k = 0.90; 94.8%), stage III (k = 0.89; 94.6%), and stage IV (k = 0.88; 94.0%). There was significant difference between ADC in stage I, II (0.77 ± 0.13, 0.85 ± 0.09 × 10-3 mm2/s), and stage III, IV (0.63 ± 0.08, 0.64 ± 0.11 × 10-3 mm2/s, p < 0.002, < 0.001). Interclass correlation showed almost perfect agreement for ADC measurement in staging and grading groups (r = 0.96 and r = 0.85, respectively, p < 0.001). There was significant difference between ADC in aggressive lymphoma (0.65 ± 0.1, 0.67 ± 0.13 × 10-3 mm2/s) and indolent lymphoma (0.76 ± 0.14, 0.84 ± 0.09 × 10-3 mm2/s, p < 0.028, < 0.001). DWIBS is reproducible for detection and staging of nodal and extra-nodal involvement in patients with NHL. ADC can quantitatively participate in the staging and grading of NHL.

PET-CT Imaging of Extranodal Involvement In Non Hodgkin Lymphoma

Abstract Background Lymphoid neoplasms are broadly divided into Hodgkin disease (HD) and non-Hodgkin’s lymphoma (NHL). Non-Hodgkin lymphoma accounts for about 5% of all cases of cancer with greater predilection to disseminate to extra-nodal sites. Extranodal lymphoma describes that there is neoplastic proliferation at sites other than the expected native lymph nodes or lymphoid tissue. Lymphomas that initially appear to have the bulk of the disease at extranodal sites are described as primary extranodal lymphoma and categorized as Stage I or II. In secondary extranodal lymphoma, there is secondary involvement of the extranodal sites from primary nodal disease, which is categorized as Stage III or IV. Aim and Objectives To assess the added value of hybrid Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of extranodal involvement in patients with non-Hodgkin lymphoma in comparison to contrast-enhanced CT (CECT). Patients and Methods All patients had Non-Hodgkin lymphoma, proved by histopathological and immunophenotyping examinations. They underwent CECT and F-18 FDG PET–CT studies. Results This study included 76 patients with pathologically confirmed lymphoma who underwent PET/CT study. The patients' ages ranged between 20 and 78 years old (mean age 51 ± 14.7 years). This study included 51 males and 21 females. Diffuse large B-cell lymphoma subtype had the highest prevalence 53% (40/76), whereas mucosa-associated lymphoid tissue lymphoma was the least prevalent 4%. The Spleen was the most common site as it was involved in 20 patients followed by bone and bone marrow 15 patients, lung 13, Liver 9, Nasopharynx 4, Muscular and Cutaneous Nodules 4 patients each, CNS, Adrenal, Renal and Pleural Affection 3 patients each, Tonsillar, stomach, Pancreas and Prostate 2 patients each, and finally only one patient had salivary gland, thyroid, breast, and testicular involvement. The overall sensitivity, specificity, PPV, NPV, and accuracy of PET/CT and CECT are 97%, 20%, 94.5%, 33.3%, 91, 6 % and 87.3%, 60 %, 93.9%, 10% and 87.5%, respectively. Conclusion Combined PET/CT using 18F-FDG is the best oncologic imaging modality at present time with indispensable role and valuable application in monitoring and management of the extranodal lymphoma. It can detect metabolically active lesions without CT structural changes and identify a viable tumor in normal size lymph nodes. PET/CT is more effective than CECT in evaluating extranodal Lymphomatous infiltration, especially in spleen, bone, and bone marrow.

PB1789 EXTRA‐NODAL INVOLVEMENT IN DIFFUSE LARGE B‐CELL LYMPHOMA: PROGNOSTIC IMPACT IN RITUXIMAB TREATED PATIENTS

Background:Extra‐nodal (EN) involvement in diffuse large B‐cell lymphoma (DLBCL) is associated with a worse outcome and involvement of two or more EN sites is an independent risk factor in the R‐IPI score. The R‐IPI does not however consider the prognostic significance of individual sites of EN involvement. The enhanced IPI (NCCN‐IPI) includes bone marrow, central nervous system (CNS), liver, gastrointestinal (GI) tract and lung as unfavourable factors. However, controversies remain regarding the prognostic value of distinct EN sites.Aims:The purpose of our study was to investigate the prognostic significance of individual sites of EN involvement in patients with DLBCL treated with rituximab.Methods:Patients diagnosed with DLBCL between January 2007 and December 2018 were retrospectively identified. Exclusion criteria were primary CNS lymphoma and patients with missing staging information. EN involvement was evaluated using histology reports and PET‐CT, MRI and CT data performed at baseline assessment. The prognostic impact of individual EN sites on overall survival (OS) was assessed.Results:Three hundred and thirteen patients were included in the study with a median age of 66 years (range 18–97 years). EN involvement by DLBCL was present in 235 (75.1%) patients: one site in 141 (45.0%), two sites in 54 (17.3%), three sites in 24 (7.7%) and 4 or more sites in 15 (4.8%) patients. The EN sites involved were as follows: CNS in 8 (2.6%) patients; bone marrow in 32 (13.7%); skeletal in 60 (19.6%) for the entire cohort and in 48/169 (28.4%) patients staged with PET‐CT; naso/oro‐pharynx (including salivary glands and tongue) in 34 (11.0%); orbit in 3 (1.0%); breast in 12 (7.5% of females); kidneys in 27 (8.8%); adrenals in 20 (6.5%); GI tract in 57 (18.6%); liver in 32 (10.4%); pancreas in 17 (5.5%); lung in 45 (14.7%); muscle and soft tissue in 16 (5.2%); bladder in 6 (2.0%); thyroid in 5 (1.6%); testes in 10 (6.9% of males); ovary in 6 (3.7% of females); uterus in 9 (5.6% of females); skin in 13 (4.2%).Patients with EN disease were more likely to have a non‐germinal centre phenotype (P = 0.02), higher ECOG performance scores (P = 0.01), higher CRP levels (P = 0.01) and lower albumin levels (P &lt; 0.001). There was no significant difference in OS between patients with one EN site and patients with only nodal disease (5‐year OS 59% vs 65%, P = 0.37). However, patients with involvement of two or more EN sites had significantly worse outcome (5‐year OS 38.5%, P &lt; 0.001). On univariate analysis involvement of CNS (P = 0.03), bone marrow (P = 0.01), kidneys (P = 0.03), lungs (P = 0.02) and skin (P = 0.003) were significantly associated with worse OS. On multivariate analysis involvement of CNS (P = 0.004), bone marrow (P = 0.03) and skin (P = 0.04) remained independently associated with worse OS. The prognostic significance of these EN sites was then assessed as a group: patients with any one of the sites involved had a significantly worse OS compared to patients with none (5‐year OS 68% vs 46%, P &lt; 0.001). On multivariate analysis this remained an independent prognostic variable when adjusting for the R‐IPI risk factors (HR: 1.86; 95% CI 1.07–3.24, P = 0.03).Summary/Conclusion:Patients with DLBCL and more than one EN area involved have a worse prognosis compared to patients with one EN area or isolated nodal disease. Among patients with EN disease, the site involved is also associated with outcome. In our study involvement of CNS, bone marrow and skin were associated with a worse OS, whereas involvement of lung, GI tract and liver were not predictive of poor outcomes.

F-18 FDG PET-CT Versus Contrast Enhanced CT in Detection of Extra Nodal Involvement in Patients with Lymphoma.

Aim and Objectives:The aim of this study is to assess the added value of hybrid fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in the evaluation of extranodal involvement in patients with lymphoma in comparison to contrast-enhanced CT (CECT).Patients and Methods:All patients had lymphoma, proved by histopathological and immunophenotyping examinations. They underwent CECT and F-18 FDG PET–CT studies. Both CECT and PET/CT studies were done within 30 days.Results:The study included 144 patients 92 (63.9%) males and 52 (36.1%) females with mean age 49.3 years (range 18–80 years). A total of 102 (70.8%) patients had non-Hodgkin lymphoma and 42 patients (18.1%) had Hodgkin disease, diffuse large B-cell lymphoma subtype had the highest prevalence 52.8% (76/144), whereas lymphocytic predominance was the least prevalent 1.4% (2/144) followed by mucosa-associated lymphoid tissue lymphoma 2.8% (4/144) and small lymphocytic type 4.2% (6/144), mixed cellularity (MC), T-cell, and follicular type were equally distributed 6.9% (10/144 each). The lung was the most common site as it was involved in 34 patients followed by bone and bone marrow 32 patients, spleen 18, liver 16, nasopharynx 8, stomach 6, cutaneous and subcutaneous tissue 6, peritoneum, cecum, small intestine, brain, and intramuscular four patients each. However, the parotid and pancreas were the least common sites two patients each. The overall sensitivity, specificity PPV, NPV, and accuracy of PET/CT and CECT are 97%, 20% 94.2%, 33.3% and 91.7% and 89.6%, 60%, 96.8%, 30% and 87.5%, respectively.Conclusion:F-18 FDG-PET/CT can accurately monitor the extranodal lymphoma, it can detect metabolically-active lesions without CT structural changes and identify viable tumor in normal size lymph nodes. FDG-PET/CT is more effective than CECT in evaluating extra nodal lymphomatous infiltration, especially in the spleen, bone, and bone marrow.

Standardized uptake value for 18F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma

The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). Material and methods77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. ResultsPET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0–1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4–5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. ConclusionFDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL.

Fluorine-18 fluorodeoxyglucose PET-CT for extranodal staging of non-Hodgkin and Hodgkin lymphoma

We aimed to evaluate the role of fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) involving care-dose unenhanced CT to detect extranodal involvement in patients with non-Hodgkin and Hodgkin lymphoma. Lymphoma patients (35 Hodgkin lymphoma, 75 non-Hodgkin lymphoma) who were referred for 18F-FDG PET-CT imaging, following a diagnostic contrast-enhanced CT (CE-CT) performed within the last month, were included in our study. A total of 129 PET-CT images, and all radiologic, clinical, and pathological records of these patients were retrospectively reviewed. In total, 137 hypermetabolic extranodal infiltration sites were detected by 18F-FDG PET-CT in 62 of 110 patients. There were no positive findings by CE-CT that reflected organ involvement in 40 of 137 18F-FDG-positive sites. The κ statistics revealed fair agreement between PET-CT and CE-CT for the detection of extranodal involvement (κ=0.60). The organs showing a disagreement between the two modalities were the spleen, bone marrow, bone, and thyroid and prostate glands. In all lesions that were negative at CE-CT, there was a diffuse 18F-FDG uptake pattern in the PET-CT images. The frequency of extranodal involvement was 51% and 58% in Hodgkin and non-Hodgkin lymphoma patients, respectively. There was a high positive correlation between the maximum standardized uptake values of the highest 18F-FDG-accumulating lymph nodes and extranodal sites (r=0.67) in patients with nodal and extranodal involvement. 18F-FDG PET-CT is a more effective technique than CE-CT for the evaluation of extranodal involvement in Hodgkin and non-Hodgkin lymphoma patients. PET-CT has a significant advantage for the diagnosis of diffusely infiltrating organs without mass lesions or contrast enhancement compared to CE-CT.

Standardized uptake value for 18F-fluorodeoxyglucose is correlated with a high International Prognostic Index and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma

The aim of this study was to evaluate whether the maximum standardized uptake value (SUVmax) of (18)F-fluorodeoxyglucose (FDG) correlates with the International Prognostic Index (IPI) and the presence of extranodal involvement in patients with Diffuse Large B-Cell Lymphoma (DLBCL). 77 patients (age: 57.2±18.5, 40F, 37M) with DLBCL who underwent FDG PET/CT for initial staging were included. SUVmax of the predominant lesions were compared to Ann Arbor stage, IPI scores, the presence of extranodal involvement and the number extranodal sites. PET/CT detected nodal (n:25) and extranodal involvement (n:52) in all the patients. In 27 patients, extranodal disease could only be detected by PET. SUVmax of the predominant lesion in patients with extranodal disease was significantly higher than that of the patients who had only nodal disease (25±12 vs. 15.3±10 respectively, p=0.001). SUVmax significantly correlated with IPI scores; the average SUVmax was significantly correlated with the IPI: Mean SUVmax of the predominant lesion was 13.9±9.5 in patients with low risk (IPI=0-1), 14.2±8.8 in low-intermediate risk group (IPI=2) whereas 26.6±9.5 in high-intermediate risk group (IPI=3) and 25±13.6 in high risk group patients (IPI=4-5) (p=0.002). SUVmax was not correlated with clinical stage, the number of extranodal sites and serum LDH levels. FDG uptake correlates with IPI and the presence of extranodal involvement in DLBCL. PET is a powerful method to detect extranodal disease in DLBCL. The correlation of SUVmax with these prognostic factors may highlight the importance of pretreatment FDG uptake as a metabolic marker of poor prognosis for patients with DLBCL.

Clinical Features and Outcome in Newly Diagnosed Hodgkin Lymphoma Patients Presenting with PET/CT-Ascertained Focal Skeletal Lesions.

AbstractAbstract 2637 BackgroundHodgkin lymphoma (HL) has traditionally been regarded as a disease primarily affecting the lymphatic organs. The introduction of dual modality [18]F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may challenge this statement as PET/CT reveals more sites of extranodal disease than CT alone. The aim of this study was to characterize the clinico-pathological and prognostic features of newly diagnosed HL patients with PET/CT-ascertained skeletal involvement. Patients and MethodsWe performed a retrospective analysis of the pre-therapeutic PET/CT results from newly diagnosed HL patients at four Danish university hospitals. Criteria for inclusion in the study were (a) histologically verified HL, (b) age ≥15 years, and (c) PET/CT-based staging. Clinical information was obtained from the Danish Lymphoma Registry (LYFO) supplemented by review of medical records. Imaging reports were reviewed for extent of disease. Patients were divided into three groups according to their pattern of PET/CT-positivity: HL confined to lymphatic organs (lymph nodes, spleen, thymus, Waldeyer’s ring) (group 1); HL with focal skeletal PET/CT lesions as the only extranodal involvement (group 2); HL with any extranodal involvement, including skeletal lesions if other extranodal sites were concurrently involved (group 3). ResultsA total of 454 patients with newly diagnosed HL were included and the median follow-up time was 34 months (range 1–113). Focal skeletal PET/CT lesions were identified in 82 patients (18%). HL was confined to nodal areas in 336 (74%) patients (group 1). Among the 118 (26%) patients with extranodal disease, 39 had focal skeletal PET/CT lesions as their only extranodal manifestation (group 2), while 79 had involvement of other extranodal sites with or without co-existing skeletal lesions (groups 3). Group 1 patients exhibited the most favorable combination of clinico-pathological features, group 3 patients displayed most adverse combination of clinico-pathological features, whereas group 2 was intermediate (Table). In a 1:1 comparison between group 1 and 2 patients, the latter had significantly lower hemoglobin (Hgb) levels, higher erythrocyte sedimentation rates (ESR) and higher occurrence of B-symptoms.The PFS for group 2 patients was similar to that of group 3 patients (p=0.85), but significantly shorter than that of group 1 patients (p<0.001) (Figure). After adjusting for other risk factors in a multivariate Cox model, the presence of focal skeletal PET/CT lesions remained independently associated with shorter PFS (p=0.009). ConclusionsPET/CT-based identification of focal skeletal lesions as the only extranodal involvement in patients with newly diagnosed HL is not uncommon. This group of patients frequently presents with systemic symptoms and elevated ESR. In addition, their PFS is inferior to that of patients with nodal HL, but similar to that of HL patients with other types of extranodal disease. Although rarely histologically verified, these focal skeletal lesions are thus likely to represent extranodal manifestations of HL.Group 1 (n=336)Group 2 (n=39)Group 3 (n=79)p-valueμMedian age, years3746500.002ECOG Performance, %....0776940 <0.001.1202346.2336.3055.4003Male:female ratio1.211.791.550.4Histological subtype, %.... Nodular sclerosis5659600.09. Mixed cellularity212115. Lymphocyte rich533. Lymphocyte depleted103. Classical Hodgkin, unspecified101519. Nodular lymphocytic predominant720Hemoglobin, g/dL13.212.411.60.0001*Total leukocytes, 109/L8.79.39.60.06Thrombocytes, 109/L3083633540.02Lymphocytes, 109/L1.601.701.340.01Erythrocyte sedimentation rate, mm/h2646630.0001*Serum albumin, g/l4240350.0001Serum LDH, IU/L1862092240.005B-symptoms, %385678<0.001*μFisher's exact test for categorical variables; Kruskal-Wallis test for continuous values.*Group 2 differs significantly from group 1 (Wilcoxon rank-sum test). [Display omitted] Disclosures:Hutchings:Takeda/Millennium: Consultancy.

Prognostic impact for different sites of extranodal involvement in patients with diffuse large B-cell lymphoma in the rituximab era.

e18505 Background: Extranodal involvement is considered poor prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL); however, the prognostic impact of each involvement site has not yet been fully elucidated. Methods: We retrospectively analyzed data for 1,221 patients with DLBCL uniformly treated by R-CHOP therapy between 2003 and 2006. Patients with distinct forms of DLBCL, such as intravascular lymphoma, primary effusion lymphoma, and pyothorax-associated lymphoma, were excluded from the study. Primary CNS lymphoma and intraocular lymphoma were also excluded. We evaluated 26 extranodal involvement sites (orbita, nasal cavity, paranasal sinus, Waldeyer ring, salivary gland, thyroid gland, breast, thymus, lungs, pleura, stomach, small intestine, colon, peritoneum, liver, pancreas, kidney, spleen, adrenal gland, testes, ovary/uterus, bones, bone marrow, peripheral blood, skin, and subcutaneous tissue) with respect to prognostic impact. Results: The median age was 64 years (range, 15–91 years). Nine hundred and ten patients (74.6%) were treated with 6-8 cycles of therapy. Local irradiation was added in 297 patients (24.4%). Univariate analysis revealed that the patients with certain extranodal involvement had significantly worse overall survival (OS) than did the patients without the extranodal involvement; these sites included nasal cavity, paranasal sinus, lungs, pleura, small intestine, peritoneum, liver, pancreas, stomach, spleen, adrenal gland, testes, bones, bone marrow, peripheral blood, skin, and subcutaneous tissue. Patients with Waldeyer ring involvement had significantly better OS. Multivariate analysis revealed that patients with involvement of pleura (P < 0.001), small intestine (P = 0.015), peritoneum (P = 0.002), adrenal gland (P < 0.001), testes (P = 0.005), bone marrow (P < 0.001), and peripheral blood (P = 0.002) had significantly worse, but Waldeyer ring had significantly better OS (P = 0.038). Conclusions: Extranodal involvement affects the prognosis of patients undergoing R-CHOP therapy for DLBCL. Waldeyer ring involvement may be a better prognosis factor.

Prognostic implications of extranodal involvement in patients with diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone

The addition of rituximab (R) to standard CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy has altered the significance of previously recognized prognostic factors. We sought to re-examine the prognostic utility of (1) the number of extranodal sites of disease involvement, and (2) a primary extranodal presentation in patients with DLBCL treated with immunochemotherapy. We retrospectively analyzed all patients with DLBCL diagnosed between January 1979 and May 2006 who were treated with an anthracycline-based therapy with curative intent. In all, 1781 patients were identified, of whom 513 (29%) received R-CHOP. In the R-CHOP group, extranodal involvement as defined by the International Prognostic Index (≥2 sites) was not prognostic on multivariate analysis, but the presence of any extranodal involvement (≥1 site) was associated with decreased progression-free survival (HR 1.6, 95% CI 1.1–2.4, p = 0.024) and overall survival (HR 1.8, 95% CI 1.1–2.7, p = 0.011). A total of 133 (26%) R-CHOP treated patients presented with primary extranodal DLBCL. There was no difference in outcome between patients with primary extranodal and nodal DLBCL, and no primary site of involvement was associated with an inferior outcome. In patients with DLBCL treated with R-CHOP, the presence of extranodal disease remains prognostic, whereas a primary extranodal presentation did not affect outcome.