non-Hodgkin Lymphoma Response Research Articles

Tumor Size Measurements for Predicting Hodgkin's and Non-Hodgkin's Lymphoma Response to Treatment.

The purpose of this study was to investigate the value of tumor size measurements as prognostic indicators of treatment outcome of Hodgkin’s and Non-Hodgkin’s lymphomas. 18F-FDG PET/CT exams before and after treatment were analyzed and metabolic and anatomic parameters—tumor maximum diameter, tumor maximum area, tumor volume, and maximum standardized uptake value (SUVmax)—were determined manually by an expert and automatically by a computer algorithm on PET and CT images. Results showed that the computer algorithm measurements did not correlate well with the expert’s standard maximum tumor diameter measurements but yielded better three dimensional metrics that could have clinical value. SUVmax was the strongest prognostic indicator of the clinical outcome after treatment, followed by the automated metabolic tumor volume measurements and the expert’s metabolic maximum diameter measurements. Anatomic tumor measurements had poor prognostic value. Metabolic volume measurements, although promising, did not significantly surpass current standard of practice, but automated measurements offered a significant advantage in terms of time and effort and minimized biases and variances in the PET measurements. Overall, considering the limited value of tumor size in predicting response to treatment, a paradigm shift seems necessary in order to identify robust prognostic markers in PET/CT; radiomics, namely combinations of anatomy, metabolism, and imaging, may be an option.

Utility of PET/CT for therapy response assessment in non-Hodgkin's lymphoma

Abstract Aim of the study to evaluate the role of PET/CT in initial diagnosis and staging of lymphoma, and to determine the predictive value of 18F-FDG PET by monitoring the early response and final response after completion of chemotherapy in patients with non-Hodgkin's lymphoma. Patient and Methods our prospective study included 25 patients with pathologically confirmed nonHodgkin Lymphoma diffuse large B cell lymphoma selected from Department of Radiology at Ain Shams University Hospital from January 2019 to March 2020. The patients included in this study performed the followings: Initial PET/CT for staging, interim PET/CT and end of the treatment PET/CT. We performed low dose non enhanced CT scan first, then a whole body PET study followed by diagnostic enhanced whole body CT scan. The whole study took approximately 20-30 minutes. Results PET/CT has greater sensitivity 100% and specificity 68.8% than CT alone for detecting sites of nodal and extra-nodal involvement and for assessment of therapeutic response in non-Hodgkin lymphoma. Conclusion PET / CT is an accurate method for evaluating tumor viability in the post-therapy setting of Non-Hodgkin lymphomas. PET / CT has a significant advantage for the diagnosis of diffusely infiltrating organs without mass lesions or contrast enhancement compared to contrast enhanced CT.

Activating the Antitumor Immune Response in Non-Hodgkin Lymphoma Using Immune Checkpoint Inhibitors.

Non-Hodgkin lymphomas comprise a heterogenous group of disorders which differ in biology. Although response rates are high in some groups, relapsed disease can be difficult to treat, and newer approaches are needed for this patient population. It is increasingly apparent that the immune system plays a significant role in the propagation and survival of malignant cells. Immune checkpoint blocking agents augment cytotoxic activity of the adaptive and innate immune systems and enhance tumor cell killing. Anti-PD-1 and anti-CTLA-4 antibodies have been tested as both single agents and combination therapy. Although success rates with anti-PD-1 antibodies are high in patients with Hodgkin lymphoma, the results are yet to be replicated in those with non-Hodgkin lymphomas. Some lymphoma histologies, such as primary mediastinal B cell lymphoma (PMBL), central nervous system, and testicular lymphomas and gray zone lymphoma, respond favorably to PD-1 blockade, but the response rates in most lymphoma subtypes are low. Other agents including those targeting the adaptive immune system such as TIM-3, TIGIT, and BTLA and innate immune system such as CD47 and KIR are therefore in trials to test alternative ways to activate the immune system. Patient selection based on tumor biology is likely to be a determining factor in treatment response in patients, and further research exploring optimal patient populations, newer targets, and combination therapy as well as identifying biomarkers is needed.

The Role of Positron Emission Tomography/Computed Tomography (PET/CT) in Assessment of Therapeutic Response in Non-Hodgkin Lymphoma

AbstractBackground: Lymphoma is the most common primary hematopoietic malignancy, make up a heterogeneous group of neoplastic diseases of lymphocytes origin broadly divided into Hodgkin Disease (HD) and Non-Hodgkin's Lymphoma (NHL) In the past decade, functional imaging with 18F-FDG PET has been the fastest growing diagnostic modality in oncology, the addition of PET to CT adds sensitivity and specificity in tumor imaging. Thus, PET/CT is a more accurate test than either of its individual components.Aim of Study: This study was undertaken to evaluate the role the PET/CT in assessment of response to chemotherapy and or radio therapy, follow-up and assessment of remissions and relapses in patients with lymphoma.Patients and Methods: Retrospective diagnostic interven-tional study in Ain Shams University Hospitals. Study popu-lation: Non Hodgkin lymphoma patients receiving therapy-presenting to Ain Shams University Hospitals since Jan. 2018- Apr. 2019. Patients included will perform one or more of the following: Initial PET/CT for staging and follow-up PET/CT exams. All exams will be done on the PET/CT scanner. intravenous glucose Fluorodeoxyglucose (FDG) dose depend-ing on the protocol of department. After 60min of 18F-FDG injection MCDT diagnostic nonionic contrast examination for anatomical localization followed by PET images. The whole study took approximately 20-30 minutes.Results: This study included 20 patients with pathologi-cally confirmed non Hodgkin lymphoma (diffuse large B cell) who underwent PET/CT study after they had finished their treatment protocol. The PET/CT exam of each patient was interpreted for the assessment of treatment response after end of treatment. About 65% of patients received 6 cycles of chemotherapy, however only 35% received 8 cycles of chem-otherapy.In our study, 12 patients (60%) had extra-nodal involve-ment and were as follow: 7 patients (55%) had only one extra nodal affection site and 5patients (45%) had more than one extranodal affection site. It had high sensitivity (100%) and specificity (75%) for the evaluation of therapeutic response than contrast enhanced CT and fair agreement (Kappa 0.610) according to the Deauville criteria. We assess therapeutic response in our study using IHP and correlated with visual assessment using (Deauville Criteria-five-point scale).Conclusion: Combined PET/CT using 18F-FDG is the best oncologic imaging modality at present time with indis-pensable role and valuable application in management of lymphoma. According to the Deauville criteria in end of treatment response assessment. We recommend in reporting of PET-CT for response assessment using the Deauville criteria.

Assessment of chemotherapy response in non-Hodgkin lymphoma involving the neck utilizing diffusion kurtosis imaging: a preliminary study.

We aimed to examine the utility of non-Gaussian diffusion kurtosis imaging (DKI) for assessment of chemotherapy response in patients with cervical (neck) non-Hodgkin lymphoma (NHL). Patients with cervical NHL underwent 3.0 T magnetic resonance imaging with maximal b value of 2000 s/mm2 at baseline and seven days after chemotherapy onset. Apparent diffusion coefficient (ADC) value and diffusion kurtosis imaging maps for diffusion coefficient (D) and kurtosis (K) were calculated. Based on clinical examination, laboratory screening, and PET/CTs, patients were classified as responders or nonresponders. Twenty-six patients were enrolled. Among them, 24 patients were classified as responders and two as nonresponders. For responders, mean follow-up ADC and D increased significantly compared with baseline (ADC: 0.92±0.11 ×10-3 mm2/s vs. 0.68±0.11 ×10-3 mm2/s; D: 1.47±0.32 ×10-3 mm2/s vs. 0.98±0.21 ×10-3 mm2/s, P < 0.001 for both). Mean follow-up K decreased significantly compared with baseline (1.14±0.10 vs. 1.47±0.19, P < 0.001) for responders. Dratio showed significant positive correlation and high agreement with ADCratio (r = 0.776, P < 0.001). Likewise, Kratio showed significant negative correlation and high agreement with ADCratio (r = -0.658, P < 0.001). The new DKI model may serve as a new biomarker for the evaluation of early chemotherapy response in NHL.

132P - Using diffusion-weighted MRI derived apparent diffusion coefficient as a predictive biomarker of tumor response in non-Hodgkin lymphoma

132P - Using diffusion-weighted MRI derived apparent diffusion coefficient as a predictive biomarker of tumor response in non-Hodgkin lymphoma

Abstract B31: EZH2 suppresses the interferon-stimulated gene response in non-Hodgkin lymphoma

Abstract Pharmacological inhibition of the histone lysine methyltransferase EZH2 has emerged as a therapeutic strategy for the treatment of non-Hodgkin Lymphoma (NHL), in particular for cases with mono-allelic mutations in the EZH2 catalytic domain. Potent, selective EZH2 small molecule inhibitors have achieved tumor regression in mutant EZH2-containing preclinical lymphoma models and several of these inhibitors are currently engaged in cancer-focused clinical trials. Here, we show that the presence of EZH2 mutations do not always confer EZH2 inhibitor sensitivity. We discovered that EZH2 is usurped by lymphoma cells to attenuate JAK/STAT signaling and to repress pro-apoptotic interferon response genes. EZH2 inhibition results in the broad induction of interferon-stimulated genes (ISGs) in several phenotypically sensitive NHL cell models. In mutant EZH2-containing insensitive models, EZH2 inhibitors synergize specifically with type I interferons (IFNs) in vitro and in vivo to induce ISGs and apoptosis. The profound combinatorial activity of EZH2 inhibitors and type I IFNs is not restricted to NHL models with mutant EZH2 and, is preferentially observed in models that are not affected by either single agent. Molecular consequences of EZH2 inhibitor and type I IFN combinatorial treatment include STAT1 activation, binding of STAT transcription factor complexes to ISGs, reduction of H3K27me3 levels and increase of H3K4me3 levels at ISG transcriptional start sites, and ISG transcriptional activation. The molecular and anti-proliferative effects of the combination can be suppressed by inactivation of the JAK/STAT signaling pathway, by using the JAK inhibitor ruxolitinib. We suggest that EZH2 inhibitors can be therapeutically combined with type I IFNs for the treatment of NHL. Citation Format: William D. Bradley, Chih-Chi Yuan, Feng Zhao, Christina Lee, Kaylyn E. Williamson, Shilpi Arora, Charlie Hatton, Barbara M. Bryant, Patrick Trojer. EZH2 suppresses the interferon-stimulated gene response in non-Hodgkin lymphoma. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr B31.

Whole-body diffusion-weighted magnetic resonance imaging at 3 Tesla for early assessment of treatment response in non-Hodgkin lymphoma: a pilot study

Objective: To evaluate 3 Tesla (T) whole-body diffusion-weighted magnetic resonance imaging (WB DWI) for early treatment assessment in aggressive non-Hodgkin lymphoma (NHL). Methods: Fourteen patients with NHL treated with standard chemotherapy underwent 3-T WB DWI before and 2 and 4 weeks during treatment, using b-values of 0–1000 s/mm2 from which the apparent diffusion coefficient (ADC) was calculated. Patient follow-up (average 20.3 months, range 15–23 months) was the reference standard. Volume and ADC changes between baseline and 2 weeks (Vratio2w, ADCratio2w) and 4 weeks (Vratio4w, ADCratio4w) of responding and non-responding lesions (lymph node and organ lesions) were compared using Mann–Whitney U tests. The per patient values of VratioN and ADCratioN to predict progression-free survival were determined with a log-rank test. Results: Eight patients showed complete remission and 6 showed tumour progression. The ADCratio2w and ADCratio4w differed significantly in lesions showing tumour progression versus complete remission (ADCratio2w = 4 ± 21% versus 119 ± 68%; ADCratio4w = 18 ± 61% versus 155 ± 78%; both P < 0.0001); the Vratio2w and Vratio4w did not (P > 0.05). Per body region, the ADCratio2w showed a negative predictive value of 100% and positive predictive value of 86%. Per patient, the ADCratio2w and ADCratio4w correlated significantly with progression-free survival (P < 0.05). Conclusion: 3-T WB DWI with ADC quantification may enable early treatment assessment of aggressive NHL.

FDG-PET Lymphoma Demonstration Project Invitational Workshop

The proceedings of a workshop focusing on a project to evaluate the use of fluorodeoxyglucose-positron emission tomography (FDG-PET) as a tool to measure treatment response in non-Hodgkin lymphoma (NHL) are described. Sponsored by the Leukemia & Lymphoma Society, the Foundation of the National Institutes of Health, and the National Cancer Institute, and attended by representatives of the Food and Drug Administration, the Centers for Medicare and Medicaid Services, and scientists and clinical researchers from academia and the pharmaceutical and medical imaging industries, the workshop reviewed the etiology and current standards of care for NHL and proposed the development of a clinical trial to validate FDG-PET imaging techniques as a predictive biomarker for cancer therapy response. As organized under the auspices of the Oncology Biomarker Qualification Initiative, the three federal health agencies and their private sector and nonprofit/advocacy group partners believe that FDG-PET not only demonstrates the potential to be used for the diagnosis and staging of many cancers but in particular can provide an early indication of therapeutic response that is well correlated with clinical outcomes for chemotherapy for this common form of lymphoma. The development of standardized criteria for FDG-PET imaging and establishment of procedures for transmission, storage, quality assurance, and analysis of PET images afforded by this demonstration project could streamline clinical trials of new treatments for more intractable forms of lymphoma and other cancers and, hence, accelerate new drug approvals.