Response Assessment Using Early and End-of-Treatment 18F-FLT PET Can Predict Outcome in Patients with Non-Hodgkin Lymphoma,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3679-3679
Author(s):  
Hyewon Lee ◽  
Seok-Ki Kim ◽  
Tae Sung Kim ◽  
Se Hun Kang ◽  
Weon Seo Park ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Hodgkin Lymphoma ◽  
Predictive Factor ◽  
Response Assessment ◽  
Early Response ◽  
Independent Predictive Factor ◽  
Predictive Values ◽  
Non Hodgkin Lymphoma ◽  
Flt Pet ◽  
End Of Treatment

Abstract Abstract 3679 Background Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) scan has been known as a useful modality for response assessment in malignant lymphoma. However, FDG is not tumor-specific and can be false positive in inflammatory lesions. To overcome these limitations, a new PET tracer, thymidine analog 3'-deoxy-3'-18F-fluorothymidine (FLT), was introduced recently. Preliminary data showed close correlation between FLT uptake and tumor cell proliferation in lymphoma, suggesting the possibility of noninvasive tumor grading and early response assessment. Therefore, we performed a prospective trial to evaluate the feasibility of FLT-PET in risk stratification and prediction for treatment outcome, especially in early interim analysis, in patients with non-Hodgkin lymphoma (NHL). Methods Seventy-five patients newly diagnosed with NHL were prospectively enrolled at National Cancer Center, Korea, from Oct 2005 to Oct 2008. All received standard chemotherapy for their pathologic classifications. Patients were evaluated with FLT-PET at baseline (FLT0), after 1 cycle of chemotherapy (FLT1, early), and after completion of the 1st line chemotherapy (FLTE, end-of-treatment). FLT-PET results were assessed according to the International Workshop Criteria (IWC). Maximum standardized uptake values (SUVmax) of each FLT-PET were calculated to evaluate its correlation with the clinical characteristics and treatment outcome. Treatment outcome was estimated using 3-year progression-free survival (3yr-PFS) and overall survival (3yr-OS). Results Of the 75 enrolled patients, 63 (84%) had diffuse large B-cell lymphoma. Median age at diagnosis was 57 years (range, 29–87). Twenty-eight (37.3%) presented with stage III or IV diseases and 20 (26.7%) showed more than 3 IPI scores. Median follow up duration was 4.5 years (range, 3.5–5.8). Five (6.7%) patients underwent hematopoietic stem cell transplantation at last. Three-year PFS and OS rates for all enrolled patients were 68% and 78.7%. Seventy-three (97.3%) had their FLT-PET at baseline, 69 (92%) after 1 cycle of chemotherapy, and 66 (88%) at the end of the 1st line treatment. By IWC, 50 (66.7%) patients achieved complete remission (CR) on FLT1 and 56 (74.7%) had CR on FLTE. Positive predictive values (PPV) of residual uptake on FLT1 and FLTE for relapse or disease progression were 83.3% (95%CI 57.7–95.6) and 80% (95%CI 44.2–96.5), respectively. Negative predictive values (NPV) of them were 88% (95%CI 75.0–95.0) and 82.1% (95%CI 69.2–90.7). Sensitivity and specificity were 71.4% (47.7–87.8) and 93.6% (81.4–98.3) for FLT1 and 44.4% (22.4–67.8) and 95.8% (84.6–99.3) for FLTE, respectively. Complete disappearance of uptake on FLT1 was significantly associated with better PFS compared to residual uptake on FLT1 (3yr-PFS rates, 87.5% and 12.2%, p<0.001). Three-year OS rates according to CR achievement on FLT1 were 96.0% and 27.8%, significantly lower in patients with residual disease after 1 cycle of chemotherapy (p<0.001). SUVmax of FLT0 correlated with LDH level significantly (p=0.044), but not with age (p=0.214), Ki-67 index (p=0.073), IPI score (p=0.270), and Ann Arbor stage (p=0.089). SUVmax of FLT0 were not associated with survival outcomes, however, residual SUVmax of FLT1 reflecting early response to treatment was significantly associated with poor survival outcome (PFS, HR 1.29, 95%CI 1.14–1.47; OS, HR 1.27, 95%CI 1.08–1.49). In multivariate analysis, SUVmax of FLT1 remained as an independent predictive factor for PFS (HR 1.63, 95%CI 1.25–2.13) and for OS (HR 1.89, 95%CI 1.38–2.58). Residual SUVmax of FLTE also revealed to be significantly associated with PFS (HR 1.43, 95%CI 1.05–1.94) and OS (HR 1.59, 95%CI 1.12–2.26) in the same multivariate model. Conclusion Response assessment in cooperation with FLT-PET provided accurate prediction for clinical outcome including PFS and OS in patients with NHL. Especially, early FLT-PET result after 1 cycle of chemotherapy was an independent predictive factor for survival as well as relapse or disease progression, with comparable performance with end-of-treatment FLT-PET. Disclosures: No relevant conflicts of interest to declare.

Whole body diffusion-weighted MRI to predict treatment outcome after one cycle of immunochemotherapy in aggressive non-Hodgkin lymphoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7534-7534
Author(s):  
Katja De Paepe ◽  
Frederik De Keyzer ◽  
Oliver Bechter ◽  
Ciska-Anne Van Keerberghen ◽  
Olivier Gheysens ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Treatment Outcome ◽  
Hodgkin Lymphoma ◽  
Hazard Ratio ◽  
Whole Body ◽  
Interim Pet ◽  
Non Hodgkin Lymphoma ◽  
Diffusion Weighted ◽  
End Of Treatment ◽  
Pet Ct

7534 Background: Treatment adaptation based on early identification of non-Hodgkin lymphoma (NHL) patients not responding to therapy might improve survival. The role of interim fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) after 2-4 cycles of immunochemotherapy (ICT) herein is experimental as it renders false positive results, due to a rituximab-induced inflammatory response. Whole body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) was evaluated as a radiation-free imaging technique to predict treatment outcome in NHL after one cycle ICT (2-3 weeks). Methods: 47 patients with aggressive NHL (35 DLBCL,2 primary mediastinal BCL,3 unclassifiable BCL, 2 Burkitt,2 MCL, 2 peripheral TCL and 1 extranodal NK-TCL) were enrolled. All had baseline and interim WB-DWI/MRI, and end-of-treatment PET/CT; 39/47 had interim PET/CT. International prognostic index (IPI), immunohistochemical (IHC) markers Ki-67, Bcl-6 and Bcl-2 were evaluated for their predictive value. WB-DWI/MRI was assessed quantitatively with histogram analysis (high b-value signal intensity (SI) and apparent diffusion coefficient (ADC)). Patients were categorized as non-responder when lesions had decreased ADC or insufficient SI decrease between scans. Kaplan-Meier survival analysis was performed with log rank, Cox hazard ratio calculation and multivariate analysis. Outcome measure was disease-free-survival (DFS). Results: Median follow-up time was 43 months (4-70 months). 33 patients had complete remission (CR), 5 progression and 9 recurrent disease. WB-DWI/MRI predicted DFS correctly in 45/47 (96%) [log rank p<0.001; hazard ratio (HR) 52, (CI 95% 6-401)]; end-of-treatment PET/CT was correct in 37/47 (79%) [p=0.003;HR 4.3, (1.5-12.4)], and interim PET/CT in 28/39 (72%) [p=0.016;HR 3.9, (1.2-12.5)]. IPI score and IHC parameters were not significantly predictive. Multivariate analysis showed WB-DWI/MRI as the only independent prognostic factor (p<0.001). Conclusions: WB-DWI/MRI can accurately predict treatment outcome in aggressive NHL after only one cycle of immunochemotherapy without the burden of radiation exposure. Clinical trial information: NCT01231269.

scholarly journals Ixazomib in Previously Untreated Indolent B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5326-5326
Author(s):  
Solomon A. Graf ◽  
Ryan C. Lynch ◽  
David G. Coffey ◽  
Mazyar Shadman ◽  
Sandra Kanan ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Response Assessment ◽  
Clinical Indication ◽  
Non Hodgkin Lymphoma ◽  
Tumor Reduction ◽  
Frontline Treatment ◽  
Grade 3 ◽  
Indication For Treatment

Abstract Background: Frontline treatment of indolent B-cell non-Hodgkin lymphoma (iB-NHL) typically involves intravenously administered anti-CD20 monoclonal antibodies with or without cytotoxic chemotherapy. Effective and low-toxicity therapies with improved convenience of administration are sought. We hypothesized that ixazomib (Ix) could safely and conveniently induce remissions in patients with untreated iB-NHL. Here we present the first data on frontline use of Ix in untreated iB-NHL. Methods: This single-arm, open-label phase II "window" trial for patients with untreated iB-NHL (NCT02339922) opened to enrollment in May 2016. Eligibility included histopathologically confirmed iB-NHL, measurable disease, a clinical indication for treatment based on NCCN guidelines, and no prior systemic treatment. Ix was administered at 4 mg orally once a week on consecutive 28-day cycles until disease progression or unacceptable toxicity and four doses of weekly rituximab (R) were added during the 7th cycle, after the initial window period. The primary endpoint was investigator-assessed response rate after independent radiology review. Response assessment occurred at every 2 cycles and using standard (Lugano) criteria. Tumor tissue was collected for gene expression profiling and immunohistochemical evaluation of molecular pathways associated with proteasome inhibition. Results: As of July 1, 2018, 15 patients were treated. The median age was 64 years (range, 47 to 81) and 53% were men. Disease histologies included follicular lymphoma (FL, n = 10), mantle cell lymphoma (MCL, n = 2), marginal zone lymphoma (MZL, n = 2), and small lymphocytic lymphoma (SLL, n = 1). At the start of therapy, all had stage III/IV disease and B-symptoms were present in 40%. For patients with FL, 80% had poor risk by FLIPI. Overall, the indication for treatment included symptoms due to disease (40%), steady progression of disease (33%), and cytopenia due to disease (27%). To date, 14 patients were evaluable for response and 13 experienced tumor burden reduction during the Ix-only window (Figure 1). Of patients with FL, 6 completed the Ix-only window phase and, of these, 5 achieved PR. An additional 4 patients with FL have not completed all 6 cycles of Ix monotherapy. Of these, 1 patient achieved a PR after 4 cycles and continues on treatment, 1 patient came off study with stable disease after 4 cycles, and 2 patients have experienced tumor reduction without meeting formal response criteria and continue on treatment (after 2 and 4 cycles, respectively). Of those patients with FL that received R, all achieved formal remission (3 CR, 3 PR). Median progression free survival has not been reached with a median follow up of 7.4 months. No patient with non-FL histology had yet achieved a PR during the Ix-only window or had undergone response assessment after receiving R at the time of the data cut. The most common adverse events (AEs) for all pts were grade 1-2 and included nausea (53%), diarrhea (53%), rash (40%), and fatigue (33%). Peripheral neuropathy occurred in 20% patients (grade 2 in 7%). A single grade ≥ 3 AE occurred (syncope, grade 3). Conclusions: Data from this interim analysis suggest that Ix monotherapy is well tolerated and highly active in the frontline treatment of FL with all patients demonstrating tumor reduction to date and augmented responses following the addition of R. Non-FL histologies of B-NHL appear less responsive to Ix, but numbers are small. Accrual on study continues. Correlative analyses are underway to determine if Ix or Ix-R may represent a viable frontline option for some patients with iB-NHL. Figure 1. Waterfall plot of response. Number of cycles of treatment received to date indicated for each subject. Four weekly doses of rituximab are added, per protocol, with the 7th cycle of ixazomib. Asterisk indicates treatment on study ongoing. Disclosures Graf: Acerta: Research Funding; TG Therapeutics: Research Funding; Beigene: Research Funding. Lynch:T.G. Therapeutics: Research Funding; Takeda Pharmaceuticals: Research Funding; Rhizen Pharmaceuticals S.A.: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Shadman:Genentech: Consultancy; Genentech: Research Funding; Verastem: Consultancy; AbbVie: Consultancy; Gilead Sciences: Research Funding; Beigene: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy; AstraZeneca: Consultancy; TG Therapeutics: Research Funding; Mustang Biopharma: Research Funding; Pharmacyclics: Research Funding; Acerta Pharma: Research Funding; Celgene: Research Funding. Gopal:Pfizer: Research Funding; Aptevo: Consultancy; BMS: Research Funding; Brim: Consultancy; Asana: Consultancy; Seattle Genetics: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Takeda: Research Funding; Merck: Research Funding; Janssen: Consultancy, Research Funding; Spectrum: Research Funding; Incyte: Consultancy; Teva: Research Funding.

Imaging for diagnosis, staging and response assessment of Hodgkin lymphoma and non-Hodgkin lymphoma

2019 ◽  
Vol 49 (11) ◽  
pp. 1545-1564 ◽  
Author(s):  
Kathleen M. McCarten ◽  
Helen R. Nadel ◽  
Barry L. Shulkin ◽  
Steve Y. Cho
Keyword(s):  
Hodgkin Lymphoma ◽  
Response Assessment ◽  
Non Hodgkin Lymphoma

Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study

2013 ◽  
Vol 31 (23) ◽  
pp. 2920-2926 ◽  
Author(s):  
Gilles A. Salles ◽  
Franck Morschhauser ◽  
Philippe Solal-Céligny ◽  
Catherine Thieblemont ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Group Versus ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Non Hodgkin Lymphoma ◽  
Flat Dose ◽  
End Of Treatment ◽  
Grade 3 ◽  
Anti Cd20

Purpose The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Patients and Methods Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg). Results Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory. The overall response rate at the end of treatment was 55% (95% CI, 32% to 76%) in the 1,600/800-mg group (9% complete responders) and 17% (95% CI, 4% to 41%) in the 400/400-mg group (no complete responders). Five of 10 rituximab-refractory patients had an end-of-treatment response in the 1,600/800-mg group versus one of 12 in the 400/400-mg group. Median progression-free survival was 11.9 months in the 1,600/800-mg group (range, 1.8 to 33.9+ months) and 6.0 months in the 400/400-mg group (range, 1.0 to 33.9+ months). The most common adverse events were infusion-related reactions (IRRs) seen in 73% of patients, but only two patients had grade 3 to 4 IRRs (both in the 1,600/800-mg group). No IRRs were considered serious, and no patients withdrew for IRRs. Conclusion The 1,600/800-mg dose schedule of obinutuzumab (GA101) has encouraging activity with an acceptable safety profile in relapsed/refractory indolent non-Hodgkin lymphoma.

Risk-Adapted Treatment of Advanced Hodgkin Lymphoma With PET-CT

2016 ◽  
pp. e376-e385
Author(s):  
Ryan C. Lynch ◽  
Ranjana H. Advani
Keyword(s):  
Hodgkin Lymphoma ◽  
Adaptive Design ◽  
Response Assessment ◽  
Early Response ◽  
Clinical Criteria ◽  
Interim Pet ◽  
Early Results ◽  
Pet Ct ◽  
Risk Patients ◽  
Early Response Assessment

Although patients with advanced-stage classic Hodgkin lymphoma have excellent outcomes with contemporary therapy, the outcomes of patients with refractory disease is suboptimal. Identification of these high-risk patients at diagnosis is challenging as the differences in outcomes using clinical criteria are less marked using current modern therapy. Data suggest that an interim PET-CT may be a powerful tool in risk-stratifying patients. Retrospective studies show that a negative interim PET-CT after two to four cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is predictive of favorable outcome independent of IPS score. Currently, there are several ongoing trials that aim to determine whether early-response assessment can be used to select patients who might benefit from modifications of subsequent therapy, either by intensifying or abbreviating regimens and/or omitting radiotherapy with promising early results. Longer follow-up is required to assess whether this strategy impacts overall survival (OS). Herein, we review the results of recent trials using interim PET-CT-based adaptive design in the treatment of advanced HL.

Clinicopathologic features and treatment outcome of primary intestinal non-Hodgkin lymphoma: A single center experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19523-e19523
Author(s):  
Wei-Hsun Hsu ◽  
Kun-Huei Yeh ◽  
Chung-Wu Lin ◽  
Chih-Hung Hsu ◽  
Ann-Lii Cheng ◽  
...  
Keyword(s):  
Small Intestine ◽  
Treatment Outcome ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Clinicopathologic Features ◽  
Non Hodgkin Lymphoma

e19523 Background: Primary intestinal non-Hodgkin lymphoma (NHL) is a rare but heterogeneous disease in East Asia. However, the benefit of multidisciplinary treatment is still in debate. We characterized the clinicopathologic features, and treatment outcome in a single institute database. Methods: Patients with NHL primarily involving the intestine and treated during 1992 to 2008 were selected from the Cancer Registry of National Taiwan University Hospital. The medical charts and pathology records were carefully reviewed. Results: There were 64 men and 17 women with a median age of 51.5 years. Sites involved were colon/rectum (53.2%), small intestine (30.9%), and duodenum (13%). Histopathology subclassification included diffuse large B-cell lymphoma (DLBCL) (61.7%), mucosa-associated lymphoid tissue lymphoma (11.1%), Burkitt’s lymphoma (8.6%), T cell lymphoma (6.2%), follicular lymphoma (2.5%), mantle cell lymphoma (1.2 %) and others (8.6%). Ann Arbor stage IE to IIE accounted for 61.7%, whereas lower IPI score (1-2) were 54.8%. Among them, 27 patients received surgery plus chemotherapy, 60 received chemotherapy, and 4 had radiotherapy. At average follow-up of 48.7 months, 5 year survival rate were 59%, 43% and 51% for colon/rectum, small intestine, and duodenal NHL, respectively (p=0.45). Surgery plus chemotherapy versus chemotherapy alone showed no survival benefit in lower IPI group (p=0.682) nor in higher IPI (3-5) group (p=0.939). A trend of better median overall survival (mOS) was seen in rituximab group than in non-rituximab group in DLBCL subtypes (not reach vs. 39.8mo, p=0.075). In univariate analysis, stage III/IV (p=0.008), IPI score greater than 2 (p=0.011), and T cell histology (p<0.001) were significant prognostic factors for poor OS. In multivariate analysis, T cell histology remained the independent prognostic factor for inferior OS (p<0.001, HR: 20.3, 95% CI: 5.1-80.4). Conclusions: Although B cell NHL was the majority of primary intestinal NHL in our institute, T cell histology has significant inferior survival. Chemotherapy is still the backbone of treatment for primary intestinal NHL. The benefit of rituximab to intestinal DLBCL needs further confirmation.

Correlation Of The Apparent Diffusion Coefficient Of Water Assessed By Diffusion-Weighted MR Imaging With Treatment Outcome In Refractory Non-Hodgkin Lymphoma Patients

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4323-4323
Author(s):  
Hamed Mojahed ◽  
Ahmed Sawas ◽  
Owen A. O'Connor ◽  
Fernando Arias-Mendoza
Keyword(s):  
Treatment Outcome ◽  
Lymph Nodes ◽  
Healthy Volunteers ◽  
Hodgkin Lymphoma ◽  
Mean Value ◽  
Mean Values ◽  
Non Hodgkin Lymphoma ◽  
Diffusion Weighted ◽  
Apparent Diffusion ◽  
Adc Values

Abstract Introduction The contrast of MR images can be made sensitive to the average motion of water molecules (diffusivity) in the various tissue compartments giving rise to diffusion-weighted imaging (DWI). Intensity maps of the apparent diffusion constant (ADC) of water can be generated from the DWI information and average ADC values of anatomical regions of interest can be assessed. Malignant tissues generally exhibit hypercellularity, increased nucleus-to-cytoplasm ratios, and an increased amount of macromolecular proteins, resulting in decreased water diffusivity (i.e., lower ADC). Additionally, a response-related ADC increase has been demonstrated in malignancies under therapy. We previously reported that the ADC mean value (in 10-3 mm2 s-1 [SD, n]) of tumor masses of refractory non-Hodgkin lymphoma (NHL) patients prior to start a new treatment was lower than the ADC mean value of lymph nodes of healthy volunteers (0.91 [0.23, 15] vs. 1.13 [0.14, 10], respectively). This difference was statistically significant (p< 0.01) despite of a large dispersion on the ADC data from the refractory NHL patients. Given this dispersion, we wanted to assess if refractory NHL patients with lower ADC values prior to therapy responded differently than patients with higher ADC values. Experimental Design Under ethical review board approval, refractory NHL patients underwent a pretreatment MR exam using a 1.5T Philips Achieva whole body scanner (Philips Healthcare, Best, The Netherlands), which included clinical MRI and DWI. DWI was acquired using echo-planar imaging with fat suppression and b-values of 0 and 1000 s/mm2 to obtain the ADC of water in the tumor. Treatment outcome was assessed determining the time to treatment failure (TTF) defined as the time between the end of one treatment and the start of a new one. Results DWI and TTF were obtained in 12 NHL patients refractory to previous treatments. Patients were divided into those with TTF ≤ 75 days and those with TTF > 75 days. The ADC mean value [SD, n] in refractory NHL patients with TTF ≤ 75 days was 0.73 [0.20, 5] while in patients with TTF > 75 days was 1.04 [0.20, 7]. When compared, these mean values were significantly different (p< 0.02). Furthermore, the comparison of the ADC mean value of lymph nodes of healthy volunteers with the ADC mean value of refractory NHL patients with TTF ≤ 75 days was highly significant (p< 0.0005) while the comparison of ADC mean values between healthy volunteers and patients with TTF > 75 days was not significantly different. Discussion Our results demonstrate that refractory NHL patients with tumor masses displaying abnormally low ADC values prior to the start of treatment have poorer treatment outcome than those patients with ADC tumor values that are comparable to values in normal lymph nodes. Although the appropriate biophysical interpretation of the ADC value remains controversial, the restricted diffusivity of water indicated by ADC reduction is considered secondary to increased tumor cellularity. The correlation between outcome and tumor cellularity could be possibly explained by reduced drug availability in the tumor when cellularity increases, thus explaining the substandard outcome in patients with lower ADC values. However, even though the correlation between lower ADC and poorer outcome is not yet understood, our results demonstrate an important predictive value of the ADC determination by DWI in refractory patients with NHL. This together with the fact that DWI is a noninvasive technique that requires no administration of contrast medium and its acquisition is fairly short makes the determination of ADC by DWI a technique that could become critical for the clinical examination of the patient with refractory NHL. Disclosures: No relevant conflicts of interest to declare.

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