Purpose
Burkitt’s lymphoma (BL) is an aggressive lymphoma subtype with high 18F-FDG avidity at 18F-FDG-PET/CT, but no validated criteria for PET/CT in treatment evaluation or prediction of outcome in ...BL are available. The aim of our study was to investigate whether the metabolic baseline PET/CT parameters can predict treatment response and prognosis in BL.
Materials and methods
We retrospectively enrolled 65 patients who underwent baseline 18F-FDG-PET/CT, interim and end of treatment PET/CT. The PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), the maximum standardized uptake value lean body mass (SUVlbm), the maximum standardized uptake value body surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R), lesion to blood-pool SUVmax ratio (L-BP SUV R), total metabolic tumor volume (tMTV) and total lesion glycolysis (TLG). Survival curves were plotted according to the Kaplan–Meier method.
Results
At a median follow-up of 40 months, the median PFS and OS were 34 and 39 months. MTV and TLG were significantly higher in patients with partial response compared to complete response group at end of treatment, while no significant differences were found at interim. Other metabolic PET/CT parameters were not related to treatment response. MTV and TLG were demonstrated to be independent prognostic factors for both PFS and OS; instead SUVbw, SUVlbm, SUVbsa, L-L SUV R and L-BP SUV R were not related to outcome survival.
Conclusions
Metabolic tumour features (MTV and TLG) were significantly correlated with response to treatment and long-term outcome.
Objective
Mantle cell lymphoma (MCL) is an aggressive lymphoma sub-type with poor prognosis and high 18F-FDG avidity at PET/CT; nowadays, no validated criteria for PET/CT in treatment response ...evaluation and prediction of outcome are present. The aim of study was to investigate whether the metabolic PET/CT features may predict treatment evaluation and prognosis in MCL.
Methods
We retrospectively enrolled 87 patients who underwent baseline 18F-FDG PET/CT and 85 end-of-treatment (eot) PET/CT. The baseline PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), lesion-to-liver SUVmax ratio (L-L SUV R), lesion-to-blood pool SUVmax ratio (L-BP SUV R), metabolic tumor volume (MTV) and total lesion glycolysis (TLG). EotPET/CT was visually interpreted according to the criteria of the Deauville 5-point scale (DC). Survival curves were plotted according to the Kaplan–Meier method.
Results
At a median follow-up of 40 months, relapse/progression occurred in 47 and death in 23 patients. Median PFS and OS were 30 and 41 months. Baseline MTV and TLG were significantly higher in patients with progressive metabolic response compared to complete/partial response group. EotPET/CT results using DC significantly correlated with PFS, not with OS. MTV and TLG were demonstrated to be independent prognostic factors for PFS; instead the other metabolic parameters were not related to outcome survival. Considering OS, no variable was significantly associated.
Conclusions
EotPET/CT results (using DC), MTV and TLG were significantly correlated with response to treatment and PFS.
Summary
The prognostic role of TP53 disruption has been established in diffuse large B‐cell lymphoma (DLBCL). Aim of this analysis was to correlate TP53 mutations by Sanger sequencing, cell of origin ...(COO) profile by Lymph2Cx panel on the NanoString platform and MYC, BCL2 and BCL6 overexpression or re‐arrangements by immunohistochemistry (IHC) and fluorescent in‐situ hybridization (FISH), with outcome in DLBCL patients enrolled into the FIL‐DLCL04 trial (NCT00499018). One hundred and twenty‐five DLBCL patients with tumour block available were analyzed. TP53 was mutated in 11/125 (9%) cases; 60/125 patients received high‐dose chemoimmunotherapy up‐front, as for the randomization arm; COO was reported in 88 patients: 48 germinal centre B‐cell like, 25 activated B‐cell like and 17 unclassified; 26 patients were double expressors in IHC and 11 double hit in FISH. After a median follow‐up of 72 months, five‐year failure‐free survival (FFS) for TP53 mutated versus wild‐type was 24% and 72%, and five‐year overall survival (OS) was 34% and 83%, respectively. Adjusted hazard ratio (HR) was 2·28 95% confidence interval (CI) 0·89–5·86, p = 0·086 and 4·05 (95% CI 1·37–11·97, p = 0·011) for FFS and OS, respectively. In this series of young DLBCL patients, TP53 gene mutation identified a poor prognosis subgroup, regardless of treatment and other biological markers.
The aim of this retrospective study was to investigate the longitudinal body changes in terms of muscle and adipose areas and their prognostic role in elderly (>65 years) patients affected by Hodgkin ...lymphoma (HL). Skeletal muscle area (SMA), skeletal muscle index (SMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intramuscular adipose tissue (IMAT), and total dispose tissue (TAT) were measured using the computed tomography (CT) of fluorine-18-fluorodeoxyglucose positron emission tomography/CT (18FFDG PET/CT) in 88 patients who undertook baseline, interim (after two cycles of chemotherapy), and end-of-treatment (after 6 cycles of chemotherapy) PET/CT scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured at pre-treatment PET/CT. Metabolic response applying Deauville score was evaluated at interim and end-of-treatment PET/CT. Survival curves, such as progression free survival (PFS) and overall survival (OS), were calculated for the whole population. Fifty-eight (66%) patients had sarcopenia at baseline and sarcopenia rate increased at interim scan with 68 (77%) cases and at end-of-treatment scan with 73 (83%) cases. Muscular areas (SMA and SMI) declined significantly during the treatment (p < 0.001), decreasing from baseline by 5% and 7% at interim and end-of-treatment evaluation, respectively. Instead, VAT, SAT, IMAT, and TAT increased significantly over this time (p < 0.001). Sarcopenia was significantly related with comprehensive geriatric assessment. PET/CT response at interim and end-of-treatment, MTV, TLG, and baseline sarcopenia were independent prognostic factors for PFS. Instead, metabolic response at interim and end-of-treatment PET, baseline sarcopenia, ΔSMI at interim, and ΔSMI at end-of-treatment for OS were independent prognostic factors.
translocations, a hallmark of Burkitt lymphoma, occur in 5-15% of diffuse large B-cell lymphoma, and have a negative prognostic impact. Numerical aberrations of
have also been detected in these ...patients, but their incidence and prognostic role are still controversial. We analyzed the clinical impact of
increased copy number on 385 patients with diffuse large B-cell lymphoma screened at diagnosis for
,
, and
rearrangements. We enumerated the number of
copies, defining as amplified those cases with an uncountable number of extra-copies. The prevalence of
translocation, increased copy number and amplification was 8.8%, 15%, and 1%, respectively. Patients with 3 or 4 gene copies, accounting for more than 60% of patients with
copy number changes, had a more favorable outcome compared to patients with >4 copies or translocation of MYC, and were not influenced by the type of treatment received as first-line. Stratification according to the number of
extra-copies showed a negative correlation between an increasing number of copies and survival. Patients with >7 copies or the amplification of
had the poorest prognosis. Patients with >4 copies of MYC showed a similar, trending towards worse prognosis compared to patients with
translocation. The survival of patients with >4 copies, translocation or amplification of
seemed to be superior if intensive treatments were used. Our study underlines the importance of fluorescence
hybridization testing at diagnosis of diffuse large B-cell lymphoma to detect the rather frequent and clinically significant numerical aberrations of
.
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, including one-third of cases overexpressing MYC and BCL2 proteins (double expressor lymphoma, DEL) and 5-10% of patients with ...chromosomal rearrangements of MYC, BCL2 and/or BCL-6 (double/triple-hit lymphomas, DH/TH). TP53 mutations are detected in 20- 25% of DEL. We report the efficacy of dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in a series of 122 consecutive patients, including DEL (n=81, 66%), DEL-MYC (n=9, 7%), DEL-BCL2 (n=13, 11%), or high-grade lymphomas (DH/TH) (n=19, 16%). Central nervous system (CNS) prophylaxis included intravenous methotrexate (n=66), intrathecal chemotherapy (IT) (n=40) or no prophylaxis (n=16). Sixty-seven patients (55%) had highintermediate or high International Prognostic Index (IPI) and 30 (25%) had high CNS-IPI. The 2-year progression-free survival (PFS) and overall survival (OS) for the entire study population were 74% and 84%, respectively. There was a trend for inferior OS for DH/TH (2-year OS: 66%, P=0.058) as compared to all the others. The outcome was significantly better for the IPI 0-2 versus IPI 3-5 (OS: 98% vs. 72%, P=0.002). DA-EPOCH-R did not overcome the negative prognostic value of TP53 mutations: 2-year OS of 62% versus 88% (P=0.036) were observed for mutated as compared to wild-type cases, respectively. Systemic CNS prophylaxis conferred a better 2-year OS (94%) as compared to IT or no prophylaxis (76% and 65%, respectively; P=0.008). DA-EPOCH-R treatment resulted in a favorable outcome in patients with DEL and DEL with single rearrangement, whereas those with multiple genetic alterations such as DEL-DH/TH and TP53 mutated cases still have an inferior outcome.
Background
Elderly classical Hodgkin lymphoma (cHL) (ecHL) is a rare disease with dismal prognosis and no standard treatment. Fitness‐based approaches may help design appropriate treatments. ...Sarcopenia has been associated with an increased risk of treatment‐related toxicities and worse survival in various solid tumours, but its impact in ecHL is unknown. The aim of this retrospective multicentre study was to investigate the prognostic role of sarcopenia in ecHL.
Methods
We included newly diagnosed >64 years old cHL patients who performed a baseline comprehensive geriatric assessment and high‐dose computed tomography (CT) or 18fluorine‐fluorodeoxyglucose positron emission tomography/CT before any treatment. Sarcopenia was measured as skeletal muscle index (SMI, cm2/m2) by the analysis of high‐dose CT or low‐dose positron emission tomography/CT images at the L3 level. The specific cut‐offs for the SMI were determined by receiver operator curve analysis and compared with those proposed in literature and studied in diffuse large B‐cell lymphoma. Survival functions progression‐free survival PFS and overall survival (OS) were calculated for the whole population and for different subgroups defined as per different sarcopenia cut‐off levels.
Results
We included 154 patients (median age 71 years old, 76 female). The median L3‐SMI was 42 cm2/m2. The specific cut‐off derived in our male population was 45 cm2/m2; using this cut‐off, 27 male patients (35%) were defined as sarcopenic. After a median follow‐up of 5.9 years, the overall 5‐year PFS and OS rates were 53% and 65%, respectively, and were significantly shorter in sarcopenic male patients compared with non‐sarcopenic (PFS 31% vs. 61%, P = 0.008; OS 51% vs. 74%, P = 0.042). Applying diffuse large B‐cell lymphoma‐derived sarcopenic thresholds, there were no significant differences between sarcopenic and non‐sarcopenic patients for both PFS and OS, with a sole exception of a significant reduced PFS in sarcopenic male patients using Namakura cut‐off. The comprehensive geriatric assessment‐determined frail functional status was an independent adverse prognostic factor for both female and male patients.
Conclusions
Baseline evaluation of sarcopenia through radiological examinations performed for ecHL staging may help define a proportion of male patients with unfavourable outcome with current treatment strategies. Also the functional status evaluation could allow to identify a frail subgroup of patients with worse outcome.
Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. ...Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians LO) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.
Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) fingerprinting has recently become an effective instrument for rapid microbiological diagnostics and in ...particular for identification of micro-organisms directly in a positive blood culture. The aim of the study was to evaluate a collection of 82 stored yeast isolates from bloodstream infection, by MALDI-TOF MS; 21 isolates were identified also directly from positive blood cultures and in the presence of other co-infecting micro-organisms. Of the 82 isolates grown on plates, 64 (76%) were correctly identified by the Vitek II system and 82 (100%) by MALDI-TOF MS; when the two methods gave different results, the isolate was identified by PCR. MALDI-TOF MS was unreliable in identifying two isolates (Candida glabrata and Candida parapsilosis) directly from blood culture; however, direct analysis from positive blood culture samples was fast and effective for the identification of yeast, which is of great importance for early and adequate treatment.
•MALDI-TOF mass spectrometry was applied to rapid fungal diagnosis.•Direct identification from positive blood cultures was the aim of the study.•Direct analysis is of great importance for early and adequate antifungal treatment.