Early interim 18F-FDG PET in Hodgkin’s lymphoma: evaluation on 304 patients

Purpose

The use of early (interim) PET restaging during first-line therapy of Hodgkin??s lymphoma (HL) in clinical practice has considerably increased because of its ability to provide early recognition of treatment failure allowing patients to be transferred to more intensive treatment regimens.

Methods

Between June 1997 and June 2009, 304 patients with newly diagnosed HL (147 early stage and 157 advanced stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent PET staging and restaging at baseline, after two cycles of therapy and at the end of the treatment.

Results

Of the 304 patients, 53 showed a positive interim PET scan and of these only 13 (24.5%) achieved continuous complete remission (CCR), whereas 251 patients showed a negative PET scan and of these 231 (92%) achieved CCR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival and 9-year overall survival, with a median follow-up of 31?months. Among the early-stage patients, 19 had a positive interim PET scan and only 4 (21%) achieved CCR; among the 128 patients with a negative interim PET scan, 122 (97.6%) achieved CCR. Among the advanced-stage patients, 34 showed a persistently positive PET scan with only 9 (26.4%) achieving CCR, whereas 123 showed a negative interim PET scan with 109 (88.6%) achieving CCR.

Conclusion

Our results demonstrate the role of an early PET scan as a significant step forward in the management of patients with early-stage or advanced-stage HL.     

Early therapy monitoring with FDG-PET in aggressive non-Hodgkin’s lymphoma and Hodgkin’s lymphoma

This study was designed to determine the value of 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in the early assessment of therapy response in lymphoma patients. We studied 20 patients with pathologically proven lymphoma, including 17 patients with aggressive non-Hodgkins lymphoma and three patients with Hodgkins lymphoma. All patients underwent whole-body FDG-PET imaging at baseline and after 1–2 cycles of chemotherapy. PET images were analysed visually and quantitatively by calculating the standardised uptake value (SUV). In each patient, we measured the SUV of the tumour demonstrating the highest FDG uptake at baseline study and the SUV of the same tumour after 1–2 cycles of therapy. The achievement of complete response was assessed on the basis of a combination of clinical findings and the results of conventional imaging modalities. Follow-up of progression-free survival (PFS) was obtained for the validation of PET data. Of the 20 patients, ten achieved complete remission at the completion of chemotherapy and the other ten did not respond to chemotherapy. Of the ten responders, four are still in remission (PFS 24–34 months) while the other six have relapsed (PFS 8–16 months). For the prediction of 24-month clinical outcome, visual analysis of PET after 1–2 cycles showed high sensitivity (87.5%) and accuracy (80%) but low specificity (50%). Comparison with the baseline SUVs revealed that the responders showed a significantly greater percent reduction in SUV after 1–2 cycles of therapy as compared with the non-responders (81.2%±9.5% vs 35.0%±20.2%, P<0.001). In addition, using 60% reduction as a cut-off value, the responders were clearly separated from the non-responders, with the exception of one non-responder. In conclusion, when performed early during chemotherapy, FDG-PET may be predictive of clinical outcome and allows differentiation of responders from non-responders in cases of aggressive lymphoma.     

Checkpoint inhibitors and radiation treatment in Hodgkin’s lymphoma

Background

Patients with classical Hodgkin’s lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options. A remarkable and durable response rate with a favorable toxicity profile was observed in heavily pretreated cHL patients.

Methods

Planning to perform prospective randomized clinical trials in the content of radio-immune treatment in patients with Hodgkin’s lymphoma (HL), we transferred the results of preliminary clinical studies and basic research in clinical relevant study concepts.

Results

Based on these promising early phase trial data, the German Hodgkin Study Group (GHSG) will investigate innovative treatment regimens in upcoming phase II trials.

Conclusion

The therapeutic efficacy and potential synergies of anti-PD1 antibodies in combination with chemo- or radiotherapy will be investigated in various settings of HL.

     

The impact of systemic chemotherapy on testicular FDG activity in young men with Hodgkin’s lymphoma

Purpose

Based on prior reports suggesting a positive correlation between fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/CT and total sperm count and concentration, we sought to identify changes in testicular FDG uptake over the course of chemotherapy in young men with Hodgkin’s lymphoma.

Methods

Fifty-two patients with a mean age of 24.2 years (range 15.5–44.4) at diagnosis monitored with FDG PET/CT to assess treatment response for Hodgkin’s lymphoma were selected for this retrospective analysis under an Institutional Review Board waiver. Of the patients, 26 were treated with a chemotherapy regimen known to cause prolonged and sometimes permanent azoospermia (BEACOPP—bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisolone) and 26 with a regimen known to have a much milder effect on gonadal function (ABVD—doxorubicin, bleomycin, vincristine, and dacarbazine). Each patient underwent one FDG PET/CT before treatment and at least one FDG PET/CT after start of chemotherapy. In all examinations, FDG activity was measured in the testes with different quantification metrics: maximum standardized uptake value (SUV_max), SUV_mean, functional volume (FV) and total testicular glycolysis (TTG), and blood pool activity determined (SUV_mean).

Results

Testicular FDG uptake (SUV_max) was significantly associated with blood pool activity (p?<?0.001). Furthermore, testicular FDG uptake metrics incorporating volume (e.g., FV and TTG) were associated with age. There was no significant change in SUV_max, SUV_mean, FV, and TTG from the PET/CT at baseline to the PET/CTs over the course of chemotherapy either for patients treated with BEACOPP or for patients treated with ABVD.

Conclusion

For patients undergoing chemotherapy for Hodgkin’s lymphoma, there is a significant association between testicular FDG uptake and blood pool activity, but no significant changes in FDG uptake over the course of chemotherapy. Therefore, FDG uptake may not be a feasible surrogate marker for fertility monitoring in patients with Hodgkin’s lymphoma undergoing chemotherapy.     

Evaluation of the effects of chemotherapy on brain glucose metabolism in children with Hodgkin’s lymphoma

Annals of Nuclear Medicine - Chemobrain is a recently proposed pathological entity. 18F-FDG PET/CT can show objective abnormalities to explain brain disorders caused by chemotherapy, although no...     

Analysis of <Superscript>18</Superscript>F-FDG PET diffuse bone marrow uptake and splenic uptake in staging of Hodgkin’s lymphoma: a reflection of disease infiltration or just inflammation?

Purpose  

¹⁸F-FDG PET has been successfully evaluated in the management of Hodgkin’s lymphoma (HL) and the most recent international guidelines recommended ¹⁸F-FDG PET for initial staging and final therapeutic assessment. However, ¹⁸F-FDG PET diffuse bone marrow uptake (BMU) and splenic uptake (SU) are frequently observed at the initial imaging and remain difficult to analyse. The aim of this retrospective study was to evaluate the significance of ¹⁸F-FDG diffuse BMU and SU in initial staging of HL.     

Role of F-18 FDG PET/CT in assessing bone marrow involvement in pediatric Hodgkin’s lymphoma

Objectives

The aim of the current study was to assess the utility of F-18-fluoro-2-deoxy-d-glucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) in assessing bone marrow involvement (BMI) compared to bone marrow biopsy (BMB) in initial staging of Hodgkin’s lymphoma (HL) in pediatric patients.

Methods

Data of 38 pediatric patients (mean age 9.8 years, range 3–18 years) with HL were analyzed for the involvement of bone marrow. All patients underwent non-contrast F-18 FDG PET/CT study. BMB was done in 31 patients from the bilateral iliac crests. Scans were interpreted by two nuclear medicine physicians blinded to the details of BMB.

Results

Of the 31 patients who underwent BMB, 5 patients had lymphomatous involvement on BMB. PET/CT was positive in four of these five patients. In 26 patients negative on BMB, PET was negative in 23 patients and positive in 3 patients for BMI. The sensitivity and negative predictive value of F-18 FDG PET/CT was 87.5 and 96 %, respectively, for BMI.

Conclusions

F-18 FDG PET/CT can predict BMB results with high accuracy. F-18 FDG PET/CT may be used at initial staging of pediatric Hodgkin’s lymphoma as it uncovers unsuspected BMI and BMB may be omitted in patients with PET-positive BMI.     

Role of [18F]-FDG-PET/MDCT in evaluating early response in patients with Hodgkin’s lymphoma

PURPOSE: The authors evaluated the prognostic role of 18-fluoro-fluorodeoxyglucose positron emission tomography/multidetector computed tomography ([(18)F]-FDG PET/MDCT) in treating patients with Hodgkin's lymphoma (HL). MATERIALS AND METHODS: We retrospectively evaluated 132 patients with HL studied with PET/MDCT before the start of chemotherapy (CTX) for staging purposes and again after two CTX cycles with [doxorubicin (Adriblastin), bleomycin, vinblastine, dacarbazine (ABVD_] (interim PET/MDCT), at least 30 days after the end of the last CTX cycle and/or 3 months after the end of radiotherapy, if delivered (final PET-MDCT). RESULTS: Interim PET-MDCT was negative in 104/132 patients (79%), and their final PET-MDCT showed complete remission in 102/104 (98%) of cases, with disease recurrence/persistence in two (2%). In the remaining 28 (21%) patients, interim PET-MDCT revealed an early response in 68% of cases and chemoresistance with disease progression in 32% of cases; in these 28 patients, final PET-MDCT showed a lack of response to treatment in 43% of cases (43%) and complete remission in 57% of cases. Statistical analysis of these data showed that interim PET-MDCT had a negative predictive value of 98% and a positive predictive value of 42%, with values of sensitivity, specificity and diagnostic accuracy of 85.7%, 86.4% and 86.4%, respectively. CONCLUSIONS: Interim PET-MDCT has a reliable prognostic role in diagnosis and treatment of patients with HL, as it helps predict which patients are more likely to achieve a complete response at the end of treatment. PET/MDCT may also lead to a change in treatment, with reduced treatment-related toxic effects and significantly reduced total costs.     

Value of PET/CT versus PET and CT performed as separate investigations in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma

Purpose The aim of this study was to assess the clinical benefit of combined [¹⁸F]FDG PET/CT in patients with malignant lymphoma as compared to separately performed PET and CT. Methods Overall, 100 patients with Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL) were included in this study. Co-registered PET/CT with [¹⁸F]FDG and contrast medium was performed in 50 consecutive patients with NHL (n=38) or HD (n=12) for initial staging (IS) (n=12) or re-treatment staging (RS) (n=38). Another 50 patients with NHL (n=32) or HD (n=18) underwent separate PET and CT investigations within a time frame of 10 days for IS (n=22) or RS (n=28). Lymphoma involvement was separately evaluated for seven different regions in each patient. Each patient had clinical follow-up evaluation for >6 months. PET and CT data were analysed separately as well as side-by-side or in fused mode. Results In the PET/CT group, region-based evaluation for lymphoma involvement suggested a sensitivity/specificity of 85%/91% for CT, 98%/99% for PET and 98%/99% for PET/CT. In the PET and CT group, region-based evaluation showed a sensitivity/specificity of 87%/80% for CT, 98%/99% for PET and 98%/100% for PET and CT read side by side. Conclusion PET was superior to CT alone and was improved further by side-by-side reading of both examinations. However, no significant difference was observed between PET/CT and separate PET and CT imaging in patients with lymphoma. Christian la Fougère and Walter Hundt contributed equally to this work.     

18F-FDG PET/CT bone/bone marrow findings in Hodgkin’s lymphoma may circumvent the use of bone marrow trephine biopsy at diagnosis staging

Purpose

Accurate staging of Hodgkin’s lymphoma (HL) is necessary in selecting appropriate treatment. Bone marrow trephine biopsy (BMB) is the standard procedure for depicting bone marrow involvement. BMB is invasive and explores a limited part of the bone marrow. ¹⁸F-FDG PET/CT is now widely used for assessing response to therapy in HL and a baseline study is obtained to improve accuracy. The aim of this retrospective analysis was to assess whether routine BMB remains necessary with concomitant ¹⁸F-FDG PET/CT.

Methods

Data from 83 patients (newly diagnosed HL) were reviewed. All patients had received contrast-enhanced CT, BMB and ¹⁸F-FDG PET/CT. Results of BMB were not available at the time of ¹⁸F-FDG PET/CT imaging.

Results

Seven patients had lymphomatous involvement on BMB. Four patients had bone involvement on conventional CT (two with negative BMB). All patients with bone marrow and/or bone lesions at conventional staging were also diagnosed on ¹⁸F-FDG PET/CT scan. PET/CT depicted FDG-avid bone/bone marrow foci in nine additional patients. Four of them had only one or two foci, while the other had multiple foci. However, the iliac crest, site of the BMB, was not involved on ¹⁸F-FDG PET/CT. Osteolytic/sclerotic lesions matching FDG-avid foci were visible on the CT part of PET/CT in three patients. MRI ordered in three other patients suggested bone marrow involvement. Interim and/or end-therapy ¹⁸F-FDG PET/CT documented response of FDG-avid bone/bone marrow foci to chemotherapy in every patient.

Conclusion

¹⁸F-FDG PET/CT highly improves sensitivity for diagnosis of bone/bone marrow lesions in HL compared to conventional staging.     

Quantitative evaluation of tau PET tracers <Superscript>18</Superscript>F-THK5351 and <Superscript>18</Superscript>F-AV-1451 in Alzheimer’s disease with standardized uptake value peak-alignment (SUVP) normalization

Purpose

Off-target binding in the reference region is a challenge for recent tau tracers ¹⁸F-AV-1451 and ¹⁸F-THK5351. The conventional standardized uptake value ratio (SUVR) method relies on the average uptake from an unaffected tissue sample, and therefore is susceptible to biases from off-target binding as well as variability among individuals in the reference region. We propose a new method, standardized uptake value peak-alignment (SUVP), to reduce the bias of the SUVR, and improve the quantitative assessment of tau deposition.

Methods

The SUVP normalizes uptake values by their mode and standard deviation. Instead of using a reference region, the SUVP derives the contrast from unaffected voxels over the whole brain. Using SUVP and SUVR methods, we evaluated the global and regional tau binding of ¹⁸F-THK5351 and ¹⁸F-AV-1451 on two independent cohorts (N?=?18 and 32, respectively), each with cognitively normal (NL) subjects and Alzheimer’s disease (AD) subjects.

Results

Both tracers showed significantly increased binding for AD in the targeted cortical areas. In the temporal cortex, SUVP had a higher classification success rate (CSR) than SUVR (0.96 vs 0.89 for ¹⁸F-THK5351; 0.86 vs 0.75 for ¹⁸F-AV-1451), as well as higher specificity under fixed sensitivity around 0.80 (0.70 vs 0.45 specificity for ¹⁸F-THK5351; 1.00 vs 0.78 for ¹⁸F-AV-1451). In the cerebellar cortex, an AD-NL group difference with effect size (Cohen’s d) of 0.62 was observed for AV-1451, confirming the limitation of the SUVR approach using this region as a reference. A smaller cerebellar effect size (0.09) was observed for THK5351.

Conclusion

The SUVP method reduces the bias of the reference region and improves the NL-AD classification compared to the SUVR approach.

     

A case of non-Hodgkin’s lymphoma of the ovary: Usefulness of18F-FDG PET for staging and assessment of the therapeutic response

Primary ovarian lymphoma as the initial manifestation is rare. A 27-year-old woman presented to our hospital with the symptoms of lower abdominal fullness and pollakisuria. CT scan and MRI revealed bilateral ovarian tumors, which showed heterogeneous masses. 18F-FDG PET revealed strong uptake by the abdominal masses, and the maximum standardized uptake value (SUVmax) was 12.5. Abnormal uptake was not shown by other regions. An exploratory laparotomy was performed. Histological findings revealed diffuse large B-cell lymphoma. The clinical stage was IV according to the Ann Arbor system. International prognostic index (IPI) was 3 (high-intermediate risk). Chemotherapy was administered consisting of three courses of an R-CHOP regimen, and 18F-FDG PET and CT scan revealed no signs of involvement 3 months after initiation of the chemotherapy. 18F-FDG PET was a useful method for staging and assessment of the therapeutic response in primary ovarian lymphoma.     

<Superscript>18</Superscript>F-FDG PET/CT metabolic tumor parameters and radiomics features in aggressive non-Hodgkin’s lymphoma as predictors of treatment outcome and survival

Purpose

To determine whether metabolic tumor parameters and radiomic features extracted from ¹⁸F-FDG PET/CT (PET) can predict response to therapy and outcome in patients with aggressive B-cell lymphoma.

Methods

This institutional ethics board-approved retrospective study included 82 patients undergoing PET for aggressive B-cell lymphoma staging. Whole-body metabolic tumor volume (MTV) using various thresholds and tumor radiomic features were assessed on representative tumor sites. The extracted features were correlated with treatment response, disease-free survival (DFS) and overall survival (OS).

Results

At the end of therapy, 66 patients (80.5%) had shown complete response to therapy. The parameters correlating with response to therapy were bulky disease?>?6 cm at baseline (p?=?0.026), absence of a residual mass?>?1.5 cm at the end of therapy CT (p?=?0.028) and whole-body MTV with best performance using an SUV threshold of 3 and 6 (p?=?0.015 and 0.009, respectively). None of the tumor texture features were predictive of first-line therapy response, while a few of them including GLNU correlated with disease-free survival (p?=?0.013) and kurtosis correlated with overall survival (p?=?0.035).

Conclusions

Whole-body MTV correlates with response to therapy in patient with aggressive B-cell lymphoma. Tumor texture features could not predict therapy response, although several features correlated with the presence of a residual mass at the end of therapy CT and others correlated with disease-free and overall survival. These parameters should be prospectively validated in a larger cohort to confirm clinical prognostication.

     

Assessment of alteration in liver <Superscript>18</Superscript>F–FDG uptake due to steatosis in lymphoma patients and its impact on the Deauville score

Aim

Our aim was (1) to evaluate the prevalence of steatosis in lymphoma patients and its evolution during treatment; (2) to evaluate the impact of hepatic steatosis on ¹⁸F–FDG liver uptake; and (3) to study how hepatic steatosis affects the Deauville score (DS) for discriminating between responders and non-responders.

Methods

Over a 1-year period, 358 PET scans from 227 patients [122 diffuse large B cell lymphoma (DLBCL), 57 Hodgkin lymphoma (HL) and 48 Follicular lymphoma (FL)] referred for baseline (n?=?143), interim (n?=?79) and end-of-treatment (EoT, n?=?136) PET scans were reviewed. Steatosis was diagnosed on the unenhanced CT part of PET/CT examinations using a cut-off value of 42 Hounsfield units (HU). EARL-compliant SUL_max were recorded on the liver and the tumour target lesion. DS were then computed.

Results

Prevalence of steatosis at baseline, interim and EoT PET was 15/143 (10.5%), 6/79 (7.6%) and 16/136 (11.8%), respectively (p?=?0.62).Ten out of 27 steatotic patients (37.0%) displayed a steatotic liver on all examinations. Six patients (22.2%) had a disappearance of hepatic steatosis during their time-course of treatment. Only one patient developed steatosis during his course of treatment. Liver SUL_max values were significantly lower in the steatosis versus non-steatotic groups of patients for interim (1.66?±?0.36 versus 2.15?±?0.27) and EoT (1.67?±?0.29 versus 2.17?±?0.30) PET. CT density was found to be an independent factor that correlated with liver SUL_max, while BMI, blood glucose level and the type of chemotherapy regimen were not. Using a method based on this correlation to correct liver SUL_max, all DS4 steatotic patients on interim (n?=?1) and EoT (n?=?2) PET moved to DS3.

Conclusions

Steatosis is actually a theoretical but not practical issue in most patients but should be recognised and corrected in appropriate cases, namely, for those patients scored DS4 with a percentage difference between the target lesion and the liver background lower than 30%.