Utility of FDG-PET in predicting the histology of relapsed or refractory lymphoma.

ABSTRACT: 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) is a valuable prognostic tool in modern lymphoma care. In this study, we explored the use of quantitative FDG-PET parameters in predicting the histology of suspected relapsed or refractory (R/R) lymphoma. We retrospectively analyzed 290 FDG-PET scans performed for suspected R/R lymphoma. FDG-PET parameters measured were maximum and mean standardized uptake value (SUVMax and SUVMean), total metabolic tumor volume, and total lesion glycolysis (TLG). Receiver operating characteristic curve analysis was used to obtain the optimal thresholds that best discriminate (1) benign vs R/R lymphoma, (2) indolent vs aggressive non-Hodgkin lymphoma (NHL), and (3) aggressive transformation of indolent NHL. We found that although all 4 FDG-PET parameters discriminated R/R lymphoma from benign histology, TLG was the best performing parameter (optimal cut-off ≥245, sensitivity 63%, specificity 86%, positive predictive value [PPV] 97%, negative predictive value [NPV] 30%, area under the curve [AUC] 0.798, and P < .001). SUVMax discriminated aggressive from indolent NHL with modest accuracy (optimal threshold ≥15, sensitivity 46%, specificity 79%, PPV 82%, NPV 38%, AUC 0.638, and P < .001). In patients with a prior diagnosis of indolent NHL, SUVMax was a modest predictor of transformation (optimal cut-off ≥12, sensitivity 71%, specificity 61%, PPV 50%, NPV 78%, AUC 0.676, and P .006). Additionally, SUVMax ≥25 and an increase in SUVMax (ΔSUVMax) from baseline ≥150% were highly specific (96% and 94%, respectively). These FDG-PET thresholds can aid in identification of suspected R/R lymphoma cases with higher likelihood of R/R disease and aggressive transformation of indolent NHL, guiding the necessity and urgency of biopsy.

Outcomes in grade 3B follicular lymphoma: an international study led by the Australasian Lymphoma Alliance.

Grade (G) 3B follicular lymphoma (FL) is a rare FL subtype which exists on a histological continuum between 'lowgrade' (Grade 1, 2 and 3A FL) and diffuse large B-cell lymphoma (DLBCL) appearing to share features with each. Clinical characteristics and outcomes are poorly understood due to lack of adequate representation in prospective trials and large-scale analyses. We analyzed 157 G3BFL cases from 18 international centers, and two comparator groups; G3AFL (n=302) and DLBCL (n=548). Composite histology with DLBCL or low-grade FL occurred in approximately half of the G3BFL cases. With a median of 5 years follow-up, the overall survival and progression-free survival of G3BFL patients was better than that of DLBCL patients (P<0.001 and P<0.001, respectively); however, G3BFL patients were younger (P<0.001) with better performance status (P<0.001), less extranodal disease (P<0.001) and more frequently had normal lactate dehydrogenase (P<0.001) at baseline. The overall and progression-free survival of patients with G3BFL and G3AFL were similar (P=0.83 and P=0.80, respectively). After frontline immunochemotherapy, 24% of G3BFL relapsed; relapse rates were 63% in the DLBCL cohort and 19% in the low-grade FL cohort. Eight percent of relapses occurred beyond 5 years. In this G3BFL cohort, the revised International Prognostic Index successfully delineated risk groups, but the Follicular Lymphoma International Prognostic Index did not. We conclude that patients with immunochemotherapy-treated G3BFL have similar survival outcomes to those with G3AFL, yet a favorable baseline profile and distinctly superior prognosis compared to patients with DLBCL.

Predicting primary treatment failure using interim FDG-PET scanning in diffuse large B-cell lymphoma.

Interim FDG-PET (iPET) in diffuse large B-cell lymphoma (DLBCL) is increasingly practised and used in clinical trials to adapt further therapy. However, the optimum timing and methodology of iPET remains controversial. We retrospectively analysed the iPET results and outcomes of 200 DLBCL patients where FDG-PET was routinely performed at baseline, after 2 cycles (iPET2) and at completion of chemoimmunotherapy. iPET was also performed after 4 cycles (iPET4) where at iPET2, Deauville score (DS) was ≥4. Scans were assessed by blinded expert lymphoma PET physicians for DS, maximum standard uptake value (SUVmax), total metabolic tumour volume (TMTV) and total lesion glycolysis (TLG). Treatment failure was defined as death, progression or refractory disease. 95.5% of patients received R-CHOP. No baseline PET parameter was predicted for EFS or OS independent of the NCCN-IPI. The multivariable analysis at iPET2 showed DS5 (19.5% of cases) predicted treatment failure (HR 6.29, 95% CI 3.01-13.17, P < .001), but DS4 was equivalent to DS1-3. At iPET4, ΔSUVmax < 66% predicted treatment failure (HR 5.49, 95% CI 3.03-9.99, P < .001). By multivariable analysis of all time points, high NCCN-IPI and DS5 at iPET2 were negative predictors of survival. These findings were independent of novel prognostic markers.

Outcomes of synchronous systemic and central nervous system (CNS) involvement of diffuse large B-cell lymphoma are dictated by the CNS disease: a collaborative study of the Australasian Lymphoma Alliance.

De novo diffuse large B-cell lymphoma (DLBCL) presenting with synchronous central nervous system (CNS) and systemic disease (synDLBCL) is not well described and is excluded from clinical trials. We performed a retrospective analysis of 80 synDLBCL patients treated across 10 Australian and UK centres. Of these patients, 96% had extranodal systemic disease. CNS-directed treatment with combination intravenous cytarabine and high-dose methotrexate ("CNS-intensive") (n = 38) was associated with favourable survival outcomes compared with "CNS-conservative" strategies such as intravenous high-dose methotrexate monotherapy, intrathecal therapy and/or radiotherapy (2-year progression-free survival [PFS] 50% vs. 31%, P = 0·006; 2-year overall survival [OS] 54% vs. 44%, P = 0·037). Outcomes were primarily dictated by the ability to control the CNS disease, with 2-year cumulative CNS relapse incidence of 42% and non-CNS relapse 21%. Two-year OS for CNS-relapse patients was 13% vs. 36% for non-CNS relapses (P = 0·02). Autologous stem cell transplantation as consolidation (n = 14) was not observed to improve survival in those patients who received CNS-intensive induction when matched for induction outcomes (2-year PFS 69% vs. 56%, P = 0·99; 2-year OS 66% vs. 56%, P = 0·98). Hyperfractionated or infusional systemic treatment did not improve survival compared to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (2-year OS 49% for both groups). Our study suggests that adequate control of the CNS disease is paramount and is best achieved by intensive CNS-directed induction.

The women's heart health programme: a pilot trial of sex-specific cardiovascular management.

BACKGROUND: There is increasing knowledge of sex-specific differences in cardiovascular disease and recognition of sex disparities in management. In our study, we investigated whether a cardiovascular programme tailored to the specific needs of women could lead to improved outcomes. METHODS: We randomised 100 female patients to receive cardiology follow-up with the conventional sex-neutral cardiac programme (control), or the sex-tailored Women's Heart Health Programme (intervention). The intervention group was managed by an all-women multidisciplinary team and received culture-centred health intervention workshops, designed through in-depth interviews with the participants. The primary outcome was cardiovascular risk factor improvement at 1 year. Secondary outcomes include cardiovascular event rates, quality of life scores, and self-reported improvement in knowledge, attitudes, intentions and practices. Generalised structural equation model analysis was used to determine if the intervention group had better outcomes at alpha level 0.1. RESULTS: The mean age was 67.3 ± 12.7 years, with an ethnic distribution of 70% Chinese, 18% Malays, and 12% Indians. The majority of these patients had no formal or primary level of education (63%), and were mostly unemployed (78%). Patients in intervention group had better control of diabetes mellitus (lower HbA1c of 0.63% [CI 0.21-1.04], p = 0.015) and lower body-mass-index (0.74 kg/m2 [CI 0.02-1.46], p = 0.092) at 1 year, but there was no significant difference in blood pressure or lipid control. Overall, there was a trend towards better risk factor control, 31.6% of intervention group versus 26.5% of control group achieved improvement in at least 1 CV risk factor control to target range. There was no significant difference in incidence of cardiovascular events, quality of life, or domains in knowledge, attitudes, intention and practices. CONCLUSION: This pilot study is the first of its kind evaluating a new model of care for women with heart disease. The potential to improve outcomes needs to be studied in a larger trial with longer follow up. TRIAL REGISTRATION: This trial was prospectively registered clinicaltrials.gov on 6 May 2013. Trial Number: 2013/00088. Identifier: NCT02017470.

Assessment of left atrial appendage function by transthoracic pulsed Doppler echocardiography: Comparing against transesophageal interrogation and predicting echocardiographic risk factors for stroke.

AIMS: Transesophageal echocardiographic (TEE) findings of left atrial appendage (LAA) thrombus, spontaneous echo contrast (SEC), and LAA dysfunction are established risk factors of cardioembolic stroke. The semi-invasive nature of TEE limits its utility as a routine risk stratification tool. We aim to correlate TEE and transthoracic echocardiography (TTE) pulsed Doppler measurements of LAA flow velocities and use TTE measurements to predict TEE findings. METHODS AND RESULTS: We prospectively measured pulsed Doppler LAA flow velocities in 103 consecutive patients on TEE and TTE. There was a strong correlation between TEE and TTE LAA emptying velocity (LAA E) (r = .88, P < .001) and a moderate correlation between LAA filling velocities (r = .50, P < .001). TTE LAA E predicted the presence of thrombus or SEC independent of atrial fibrillation (AF). To predict the presence of thrombus or SEC, the optimal TTE LAA E cutoff was ≤30 cm/s in all patients (75% sensitive, 90% specific) and ≤31 cm/s in AF patients (80% sensitive, 79% specific). To predict LAA dysfunction (TEE E ≤ 20 cm/s), the optimal TTE LAA E cutoff was ≤27 cm/s (100% sensitive, 89% specific in all patients and 100% sensitive, 74% specific in AF patients). CONCLUSIONS: TTE assessment of LAA function is feasible and correlates well with the more invasive TEE method. It predicts the presence of thrombus, SEC, and LAA dysfunction on TEE. TTE LAA assessment has incremental value in thromboembolic risk stratification and should be utilized more frequently.