The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer

We evaluated the prognostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS-SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUV_max), and sum of metabolic tumor volume (MTV_sum) and total lesion glycolysis (TLG_sum). The relationship between the highest SUV_max and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox''s proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan–Meier method.The SUV_max of the highest metabolic lesion had a significant positive correlation with MTV_sum and TLG_sum (P < 0.001). Upon multivariate analysis, the highest SUV_max was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTV_sum was a significant prognostic factor of PFS (10-cm³ increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUV_max was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUV_max (≥11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUV_max.The highest SUV_max is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUV_max might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter.     

A retrospective analysis of primary gastric diffuse large B-cell lymphoma with or without concomitant mucosa-associated lymphoid tissue (MALT) lymphoma components

Primary gastric diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity that includes patients with (DLBCL/MALT) and without detectable mucosa-associated lymphoid tissue (MALT) lymphoma components (de novo DLBCL). We sought to evaluate the clinical characteristics and outcome of this disease in a large number of cases. Patients with primary gastric DLBCL (n?=?162) seen on 2001–2011 at the Tianjin Medical University Cancer Institute and Hospital and the First affiliated Hospital of Chinese PLA General Hospital were retrospectively reviewed. The distribution of sex, age, Lugano staging, and other main clinical characteristics was similar between the de novo DLBCL and DLBCL/MALT groups (p?>?0.05). However, the proportion of patients with a stage-modified international prognostic index (m-IPI)?≥?2 was higher in the de novo DLBCL (34 %) than the DLBCL/MALT group (17 %) (p?=?0.026). In addition, the Helicobacter pylori infection rates were higher in the DLBCL/MALT (75 %) than the de novo DLBCL group (36 %) (p?<?0.001). Five-year progression-free survival (PFS) and overall survival (OS) estimates were similar for patients in the de novo DLBCL (p?=?0.705) and DLBCL/MALT groups (p?=?0.846). Surgical treatment did not offer survival benefits when compared with chemotherapy for 5-year PFS (p?=?0.607) and OS estimates (p?=?0.554). There were no significant differences in 5-year PFS and OS estimates for patients treated with rituximab–chemotherapy (p?=?0.261) or conventional chemotherapy (p?=?0.227). Non-GCB subtype and m-IPI?≥?2 were independently associated with shorter OS, and advanced stages of lymphoma were independently associated with shorter PFS.     

The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma

The choice of a rituximab-based regimen and the prognostic significance of interim 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in primary mediastinal large B cell lymphoma (PMBCL) are debatable. We evaluated the clinical features and outcomes of 95 consecutive patients with PMBCL who were treated between 1985 and 2009. Forty-three patients received rituximab-based chemotherapy, R-VACOP-B (N?=?30) or R-CHOP21 (N?=?13), whereas 52 patients were treated with VACOP-B (N?=?47) or CHOP21 (N?=?5). Radiotherapy was not given. Patients who received rituximab had a 5-year progression-free survival (PFS) of 79 % and overall survival (OS) of 97 % compared with 58 % (p?=?0.06) and 88 % (p?=?0.2), respectively, without rituximab. Five-year PFS in patients treated with R-VACOP-B, R-CHOP21, VACOP-B, and CHOP21 were 83, 69, 62, and 20 %, respectively (p?=?0.039). However, direct comparison showed that the difference between PFS rates in patients receiving R-VACOP-B compared to R-CHOP21 was not statistically significant (p?=?0.3). None of the standard clinical risk factors predicted for PFS and OS in patients receiving rituximab (R)-chemotherapy. Mid-interim FDG-PET/CT scans were performed in 30/43 patients who received R-chemotherapy. The negative predictive values of mid-PET activity were high (100 % for R-VACOP-B and 86 % for R-CHOP21) while the positive predictive values (PPV) were relatively low (30 and 75 %, respectively). Despite the low PPV, the 5-year PFS for mid-PET-negative patients (N?=?16) was significantly higher (94 %) than that for mid-PET-positive (N?=?14) patients (57 %, p?=?0.015). This retrospective analysis demonstrates that the superiority of VACOP-B over CHOP21 for treatment of PMBCL disappeared once rituximab was added. The potential benefit of using interim PET activity as a guide for continuing therapy in patients with PMBCL remains unclear due to the relatively low PPV.     

Diminishing prognostic role of preexisting diabetes mellitus for patients with diffuse large B-cell lymphoma in the rituximab era

Rituximab reforms the treatment of diffuse large B-cell lymphoma (DLBCL) and the prognostic significance of baseline patient features should be reevaluated. Few population-based studies have investigated the association of diabetes mellitus (DM) and outcomes of lymphoma; however, the results remain inconclusive. From January 1, 2000 to December 31, 2009, a total of 468 consecutive newly diagnosed DLBCL patients receiving first-line chemotherapy with cyclophosphamide, vincristine, doxorubicin, and prednisolone (CHOP) or rituximab plus CHOP (R-CHOP) were enrolled. Pre-existing DM was defined according to medical history, use of antidiabetic medications, or any record of an abnormal hemoglobin A1c test. Progression-free survival (PFS) and overall survival (OS) were estimated and compared using the Kaplan–Meier method with a log-rank test. CHOP was administered in 194 patients, and 274 patients received R-CHOP. DM was identified in 16.2 % (76/468) of patients. Diabetic patients were older and more performance restricted, compared to the non-DM patients in both the CHOP and R-CHOP groups. In the CHOP group, 5-year PFS and OS were inferior in DM patients (PFS, 32.4 vs. 50.0 % (P?=?0.039); OS, 38.2 vs. 62.5 % (P?=?0.002)). However, outcomes were similar for both DM and non-DM patients in the context of R-CHOP treatment (PFS, 69.0 vs. 57.3 % (P?=?0.179); OS, 76.2 vs. 69.8 % (P?=?0.586)). The response rate of chemotherapy in DM patients was also improved to a level similar to non-DM patients with rituximab use. In conclusion, the prognostic significance of preexisting DM in DLBCL patients is changing in the rituximab era. The potentially additional benefit of rituximab in DM patients merits further investigation.     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Survival of patients with transformed lymphoma in the rituximab era

In the pre-rituximab era, transformation of indolent B-cell lymphoma to diffuse large B-cell lymphoma (DLBCL) was associated with an extremely poor outcome and a median post-transformation survival ranging from 1 to 2 years. We evaluated the impact of rituximab-cyclophosphamide, adriamycin, vincristine, prednisone (R-CHOP) on the survival outcomes of transformed lymphoma compared with de novo DLBCL. Between 2002 and 2010, 317 DLBCL patients who were consecutively diagnosed and treated with R-CHOP were identified at our institution. Patients with transformed lymphoma were included if they had not previously received R-CHOP. Patient characteristics, treatment, and outcome data were retrospectively collected. Sixty patients (19 %) had transformed lymphoma of which 37 (62 %) had transformed from follicular lymphoma, 50 (83 %) were chemotherapy naïve, and 58 (96 %) were rituximab naïve at the time of treatment. With a median follow-up of 31.4 months, 231 patients achieved either complete response or complete response unconfirmed (73 %) with no significant difference between de novo DLBCL (n?=?192, 75 %) and the transformed group (n?=?39, 65 %) (P?=?0.25). Six patients (15 %) relapsed in the transformed group at a median time to relapse of 29.3 months. The 2-year and 5-year overall survivals for all patients were 82 and 72 %, respectively. The overall and progression-free survivals for transformed lymphoma and de novo DLBCL were not statistically different (P?=?0.45 and P?=?0.38, respectively). With R-CHOP chemotherapy, the prognosis of transformed lymphoma in patients with minimal chemotherapy exposure for indolent disease is similar to that of de novo DLBCL.     

Clinico-biological characteristics and outcome of hepatitis C virus-positive patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Diffuse large B cell lymphoma (DLBCL) patients carrying hepatitis C virus (HCV) have higher risk of treatment toxicity and complications. The aim of this study was to assess the impact of HCV in a series of DLBCL patients treated with immunochemotherapy. 321 patients (161 M/160F; median age, 66 years) diagnosed with de novo DLBCL in a single center between 2002 and 2013 were included. Immunodeficiency-related lymphomas were excluded. HCV+ cases were defined by the presence of IgG anti-HCV. Main clinico-biological characteristics and outcome were analyzed according to the viral status. Two hundred ninety patients were HCV? and 31 HCV+. HCV+ patients were older (median age 71 vs. 64 years, P = 0.03), had more often B symptoms (P = 0.013), spleen (P = 0.003), and liver (P = 0.011) involvement, higher rate of early death (<4 months, P = .001), and shorter overall survival (OS). Eleven HCV+ patients had cirrhosis criteria. HCV+ patients with impaired liver function before or during treatment showed inferior OS. Elevated pre-treatment bilirubin correlated also with higher liver toxicity. In a multivariate analysis that included R-IPI score, serum beta2-microglobulin (β2m), HCV status, and presence of cirrhosis, only R-IPI, β2m, and cirrhosis showed independent prognostic impact on OS. The presence of HCV in DLBCL patients entails higher number of complications and early deaths; however, liver impairment and not the hepatitis viral status was the key feature in the outcome of the patients.     

Cold-induced activity of brown adipose tissue in young lean men of South-Asian and European origin

Aims/hypothesis

South Asians have a disproportionately high risk of developing abdominal obesity, insulin resistance and type 2 diabetes. Brown adipose tissue (BAT) has been identified as a possible target to fight obesity and protect against metabolic disturbance. We explored whether lower BAT activity in South Asians compared with Europids may contribute to the high risk of metabolic disturbance.

Methods

We studied 20 healthy men (ten Europids/ten South Asians, BMI 19–25 kg/m², age 18–32 years). Following 2 h of cold exposure (16–18°C) after an overnight fast, ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography-computed tomography (CT) and ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) single-photon emission computed tomography-CT were performed to visualise metabolic BAT activity and sympathetic stimulation of BAT. Metabolic BAT activity was defined as maximal standardised uptake value (SUV_max) of ¹⁸F-FDG, and sympathetic stimulation of BAT as semiquantitative uptake value (SQUV) of ¹²³I-MIBG. We performed hyperinsulinaemic–euglycaemic clamps to assess insulin sensitivity. Spearman’s correlations for SUV_max of ¹⁸F-FDG and both SQUV of ¹²³I-MIBG and insulin sensitivity were determined.

Results

The median (interquartile range) SUV_max of ¹⁸F-FDG in South Asians (7.5 [2.2–10.6] g/ml) was not different from the median SUV_max obtained in Europids (4.5 [2.2–8.4] g/ml; p?=?0.59). There was no correlation between BAT activity and insulin sensitivity. Correlations between SQUV of ¹²³I-MIBG and SUV_max of ¹⁸F-FDG were positive, both in the total population (ρ?=?0.80, p?<?0.001) and after stratification by ethnicity (Europids, ρ?=?0.65, p?=?0.04; South Asians, ρ?=?0.83, p?=?0.01).

Conclusions/interpretation

This is the first study to prospectively investigate ethnic differences in metabolic BAT activity during cold exposure. We did not find differences in BAT activity between South Asians and Europids. Therefore, it seems unlikely that BAT plays an important role in the development of unfavourable metabolic profiles in South Asians.     

Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores

After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively. The secondary International Prognostic Index (IPI2) scores after R-CHOP were low (0–1) in 68.2% and high (2–3) in 31.8% of the patients. The Deauville scores from 18-fluorodeoxyglucose positron emission tomography after R-CHOP showed low (2–3) in 58.0% and high (4) in 42.0% of the patients. High IPI2 and high Deauville scores were associated with worse PFS2 (P < 0.001 and P = 0.009) and OS2 (P = 0.013 and P = 0.067). The high-risk group defined by the IPI2 and Deauville scores, whose scores were both high, showed significantly lower 3-year PFS2 (P < 0.001) and OS2 (P = 0.006) rates compared with those of the other groups. In multivariate analyses, the IPI score of ≥?3 at diagnosis and bone marrow involvement at diagnosis were independent prognostic factors. In addition, high IPI2-Deauville score after R-CHOP was significantly associated with poor PFS2 (P = 0.009) and demonstrated a trend toward inferior OS2. In conclusion, DLBCL patients who partially responded to R-CHOP are still a heterogeneous group, for which IPI2 and Deauville scores should be evaluated for prediction of prognosis.     

The role of 18F-fluorodeoxyglucose positron emission tomography at response assessment after autologous stem cell transplantation in T-cell non-Hodgkin’s lymphoma patients

Although a few studies have evaluated the utility of ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) in treatment-naive T-cell non-Hodgkin’s lymphomas (T-NHLs), a few studies had been conducted to evaluate the role of FDG-PET in patients after treatment. A total of 41 patients with T-NHLs were included who underwent post-autologous stem cell transplantation (ASCT) PET for response assessment in addition to contrast-enhanced CT. The impact of post-ASCT PET on response assessment and predicting prognosis was retrospectively evaluated. Of the 41 patients, 11 (26.8 %) patients showed discordant response between two image modalities (Cohen’s κ?=?0.465). The additional PET study actually guides changing the post-ASCT response in six (54.5 %) of these 11 patients. Moreover, positive post-ASCT PET was associated with worse prognosis in event-free survival and overall survival than negative post-ASCT PET (P?=?0.003 and P?=?0.044, respectively). Excluding four patients in whom further confirmation was not available due to early mortality, in 22 lesions showing discrepancy between two image modalities, 12 lesions were true positive (N?=?4) or true negative (N?=?8) for PET and ten lesions were false positive (N?=?7) or false negative (N?=?3). The accuracy for the discrepant lesions was 54.5 % (12 of 22), the overall accuracy for the detected lesions was 76.7 % (33 of 43), and the overall accuracy for patients was 89.2 % (33 of 37). Post-ASCT PET was useful in response assessment after ASCT, and the positive post-ASCT PET result was associated with worse prognosis than the negative post-ASCT PET in patients with T-NHLs.     

The Enhanced International Prognostic Index for Diffuse Large B-cell Lymphoma

Objective

To explore the prognostic value of the enhanced International Prognostic Index (NCCN-IPI) for Asian patients with diffuse large B-cell lymphoma (DLBCL) treated in the rituximab era.

Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4–8) and advanced stage (III–IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P?<?0.001) and OS (P?<?0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR?=?1.90, 95% CI: 1.15–3.16 for PFS, P?=?0.013; HR?=?2.65, 95% CI: 1.46–4.79 for OS, P?=?0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P?=?0.0194 for PFS, P?=?0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.     

Standardised uptake value of 18F‐FDG on staging PET/CT in newly diagnosed patients with different subtypes of non‐Hodgkin’s lymphoma

Objectives: Positron emission tomography using 2‐[fluorine‐18]‐fluoro‐2‐deoxy‐d ‐glucose (¹⁸F‐FDG) is considered to be the most beneficial imaging method for staging patients with non‐Hodgkin’s lymphoma (NHL). The intensity of ¹⁸F‐FDG accumulation may be determined by calculating the so‐called standardised uptake value (SUV). The study aimed at assessing the benefit of SUV_max determination in staging ¹⁸F‐FDG PET/CT in untreated patients with NHL. Methods: One hundred and forty‐nine initial staging ¹⁸F‐FDG PET/CT scans performed in patients with NHL between January 2007 and August 2009 were assessed, and the SUV_max was determined. Results: The highest mean and median values of SUV_max were observed in patients with diffuse large B‐cell lymphoma (DLBCL), the lowest mean and median values were found in small lymphocytic lymphoma. The overlap in SUV_max < 10 between DLBCL and the other subgroups of NHL was very significant. Statistically, no correlation was found between the lactate dehydrogenase and SUV_max values. On the other hand, a correlation of the Ki‐67 proliferative index of tumour cells and SUV_max was revealed (r = 0.409, P < 0.001). The geometric mean of SUV_max in patients with Ki‐67 ≤ 60 and those with Ki‐67 > 60 was 8.8 and 14.3, respectively (P < 0.001). Conclusions: The results confirm that SUV_max is not beneficial for making a more precise diagnosis in most patients with NHL. Correlation of SUV_max with the Ki‐67 values suggests that SUV_max might have a prognostic values in NHL.     

Clinical impact of bulky mass in the patient with primary extranodal diffuse large B cell lymphoma treated with R-CHOP therapy

Although numerous studies about primary extranodal diffuse large B cell lymphoma (DLBCL) were reported sporadically, the literature of clinical value of immunophenotype and bulky diameter in rituximab era is limited. Ninety-six patients with primary extranodal DLBCL receiving R-CHOP therapy were analyzed to evaluate whether immunophenotype and size of bulky disease are significantly important. The International Prognostic Index was still an important prognostic factor for progression-free survival (PFS) and overall survival (OS; p?=?0.003, p?=?0.027). Difference of survival between germinal center (GC) type and non-GC type was not different (PFS: p?=?0.192; OS: p?=?0.197). In two separated groups according to extranodal maximum tumor diameter (EN-MTD) 7.5 cm as cutoff value for survival, the group of EN-MTD ≥7.5 cm had lower PFS and OS than <7.5 cm (PFS: p?=?0.001; OS: p?=?0.008). In four divided subgroups according to EN-MTD combined with immunophenotype, the subgroup of non-GC type with EN-MTD ≥ 7.5 cm had lower PFS and OS compared with the other subgroups (PFS: p?<?0.001; OS: p?=?0.008). Multivariate analysis revealed that non-GC with EN-MTD ≥ 7.5 cm was an independent prognostic parameter (PFS: HR?=?5.407, 95%CI?=?2.378–12.294, p?<?0.001; OS: HR?=?4.136, 95%CI?=?1.721–9.941, p?=?0.002). Bulky primary extranodal DLBCL would be associated with unfavorable outcome especially in non-GC type.     

Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma

Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m² (n?=?2) or 120 mg/m² (n?=?57) on days 1 and 2 and rituximab at 375 mg/m² on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile.     

Positron Emission Tomography in the Evaluation of Pulmonary Nodules Among Patients Living in a Coccidioidal Endemic Region

Background

Within a coccidioidal endemic region, pulmonary nodules due to coccidioidomycosis are common. Uptake of ¹⁸fluorodeoxyglucose (¹⁸FDG) by positron emission tomography with computed axial tomography (PET/CT) has been used to assess whether pulmonary nodules are malignant but inflammatory lesions can be positive. The purpose of this study was to compare by PET/CT the ¹⁸FDG uptake in pulmonary nodules likely due to coccidioidomycosis to that of nodules shown to be malignant among patients living in a coccidioidal endemic region.

Methods

We retrospectively reviewed patients who underwent a PET/CT at the Southern Arizona Veterans Affairs Health Care System between January 2008 and March 2012 who were subsequently found on biopsy to have pulmonary nodules that were coccidioidal or granulomatous or were due to malignancy.

Results

Among 245 diagnostic biopsies where the subject had a previous PET/CT, 15 (6.1 %) were either coccidioidal (n = 12) or granulomatous without an identified organism (n = 3). The median maximum standard unit of uptake (SUV_max) on PET/CT of coccidioidal or granulomatous lesions was 2.0 compared to 9.8 for malignant lesions (P < 0.001). The maximum diameter of the coccidioidal or granulomatous nodules was 2.1 cm compared to 3.0 cm for the malignant lesions (P = 0.009). On multivariable analysis, an elevated SUV_max was the only distinguishing feature between the malignant and the granulomatous lesions (OR 1.28, 95 % CI 1.05–1.55; P = 0.013).

Conclusions

Coccidioidal pulmonary nodules take up significantly less ¹⁸FDG than those due to malignancies, but there is considerable overlap between granulomatous and malignant lesions at lower SUV_max.     

Prognostic value of SUVmax in breast cancer and comparative analyses of molecular subtypes: A systematic review and meta-analysis

Background:To assess the prognostic capability of the maximum standardized uptake values (SUV_max) measured in the primary tumor and axillary lymph nodes (ALNs) by pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography and analyze outcomes according to the molecular breast cancer subtypes.Methods:The databases were systematically searched using keywords for breast cancer, positron emission tomography/computed tomography, and SUV_max; the extracted studies reported at least 1 form of survival data, event-free survival (EFS) and overall survival. Comparative analyses of the pooled hazard ratios (HRs) for EFS and overall survival were performed to assess their correlations with SUV_max. The pooled HR was estimated using random-effects model according to the results of heterogeneity.Results:Thirteen eligible studies comprising 3040 patients with breast cancer were included. The pooled HRs of high SUV_max in the primary tumor and ALN were 3.01 (95% CI 1.83–4.97, P < .00001; I2 = 82%) and 3.72 (95% CI 1.15–12.01; I2 = 92%; P = .03), respectively. Patients with higher SUV_max demonstrated a poorer survival prognosis. Furthermore, comparative analyses according to the molecular subtypes demonstrated that the SUV_max in the primary tumor or ALN can be a predictive parameter in patients with the luminal subtype disease. Subtype analysis results indicated a significant association of the luminal group, with a HR of 2.65 (95% CI 1.31–5.37; I2 = 27%; P = .007).Conclusions:SUV_max from pretreatment is a significant prognostic factor for EFS in patients with breast cancer. Despite several limitations, correlation with molecular subtype (luminal type) was demonstrated. Further large-scale studies are required to investigate the precise prognostic capability of SUV_max.     

Is 18F-fluorodeoxyglucose positron emission tomography meaningful for estimating the efficacy of corticosteroid therapy in patients with autoimmune pancreatitis?

Background

Autoimmune pancreatitis (AIP) is often misdiagnosed as pancreatic cancer (PC). Both conditions accumulate ¹⁸F-fluorodeoxyglucose (FDG), so FDG positron emission tomography (FDG-PET) is not discriminatory. This study aimed to evaluate the pattern of FDG accumulation, and the change in FDG uptake after steroid treatment in AIP and PC.

Methods

We compared FDG-PET patterns between 18 patients with AIP and 20 patients with PC, and also evaluated the short-term changes in FDG uptake after steroid therapy.

Results

FDG uptake was observed in 88.9% in AIP and 90.0% in PC. FDG uptake in extra-abdominal lymph nodes was seen more frequently in AIP, and uptake in salivary glands, eyes and biliary ducts was seen only in AIP. Follow-up PET was performed in 6 AIP patients and in 3 PC patients. Changes in SUV_max after steroid therapy were estimated within 1 week in 5 AIP patients and in all 3 PC patients, retrospectively. In 4 AIP patients, the change in SUV_max was more than 10%. On the other hand, in PC, SUV_max increased or remained almost unchanged (within 10%).

Conclusions

FDG-PET pattern at baseline, and a decrease in FDG uptake after a short steroid trial can be useful for discriminating AIP from PC.     

Clinical outcome of HCV-positive patients with diffuse large B-cell lymphoma treated with rituximab-based chemotherapy

The influence of rituximab therapy on prognosis and hepatic toxicity (HT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is unclear. Thus, we assessed HT and clinical outcome in patients with DLBCL and HCV infection who received rituximab-containing immunochemotherapy. We carried out a prospective analysis on a total of 280 HCV-positive patients with DLBCL, 200 of whom received chemotherapy plus rituximab (R-CHT), 80 received chemotherapy (CHT)-only. Survival outcomes and HT were compared according to rituximab administration. The median follow-up was 41 months. Addition of rituximab did not significantly affect prognosis (median progression-free survival, 40 vs 35 months, P?=?0.26; median overall survival, 51 vs 43 months P?=?0.09). Of 200 patients who received rituximab, 53 (26.5 %) had severe HT (grade 3–4), compared with 11 of 80 (13.75 %) patients who received rituximab-free regimens (P?=?0.033). Among patients treated with rituximab, 50 patients (25 %) did not complete planned course of therapy, 14 patients because of hepatic toxicity and 36 patients because of progressive disease. Pretreatment liver function impairment was predictive of severe HT. These results raise concerns regarding the routine use of rituximab with chemotherapy in individuals with HCV-positive DLBCL. However, more studies are warranted before a definitive conclusion can be made.     

Alemtuzumab in chronic lymphocytic leukemia: final results of a large observational multicenter study in mostly pretreated patients

This retrospective study evaluated the benefit of alemtuzumab monotherapy in unselected patients with advanced B-cell chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (B-PLL) to definitely describe the impact of this antibody in clinical routine use. Data were collected from 208 consecutive, mainly pretreated, patients with CLL (n?=?202), and B-PLL (n?=?6) who had received alemtuzumab. Response, progression-free survival (PFS), and overall survival (OS) in various settings were assessed, and toxicities were documented. In these routine patients, a comparably low cumulative dose of alemtuzumab (median, 403 mg) was applied. In CLL, overall response rate was 32 %, and various pre-therapeutic parameters were predictive for inferior response, among them, the prior administration of ≥3 therapy lines (P?<?0.001), refractoriness to fludarabine (P?=?0.002), and bulky lymphadenopathy (P?=?0.003). PFS and OS after start of alemtuzumab were 6.2 and 21.0 months, respectively. Bulky lymphadenopathy was the prominent risk factor for both inferior PFS (P?<?0.001) and OS (P?=?0.002). In B-PLL, four patients experienced a fatal outcome, whereas two patients had some benefit with alemtuzumab. The main adverse effects were CMV reactivation (20 %) and a broad spectrum of infections, which together were the main reasons for treatment interruption and/or premature termination. In conclusion, alemtuzumab administered even at low dose levels was effective but overall considerably toxic in routine CLL patients. We emphasize that alemtuzumab remains an important therapeutic option in subsets of CLL patients.