Node Lesions Research Articles

Clinicopathological features of in situ follicular neoplasm and relations with follicular lymphoma in Japan

This study aims to investigate the clinicopathological features of in situ follicular neoplasm (ISFN) in Japan. ISFN is a rare condition formerly considered as an early precursor of follicular lymphoma (FL). This is a first original report of ISFN from Asian country. We reviewed 19 biopsy samples of ISFN. ISFNs were categorized into two groups: (1) ISFN, consisting of ISFN with strong positivity for BCL-2 immunohistochemical staining (IHC), and obvious translocation of BCL-2; and (2) ISFN-like FL, featuring cases without obvious translocation but having morphological features and characteristic IHC findings of ISFN. As control, we adopted obvious FL. For some cases showing coexisting ISFN and FL lesions in the same lymph node, we could conduct further clonality analysis for each lesion. Nine of the 19 cases of ISFN coexisted with FL or had a history of overt B- or T-cell lymphoma including FL. Statistical comparison among ISFN-like FL and FL showed no significant differences in pathological features. Molecular analysis suggested that ISFN lesion and FL lesion in the same lymph node each have a different clonality. ISFN coexists or associates with other overt lymphomas frequently.

Comparison of Five Cytochemical Stains used for Fine Needle Aspiration Cytology of Breast and Lymph Node Lesions: A Comparative Study

Introduction: Fine Needle Aspiration Cytology (FNAC) is an established diagnostic tool aiming at an early diagnosis of mass lesions which in turn aids in planning further management of the patients. The need for minimal turnaround time with good quality of cell morphology has encouraged the development of different staining techniques. Quality Index (QI) of cytochemical stains is evaluated with a scoring system based on morphological features. Aim: To find rapid staining methods which were economical without compromising on the quality of FNAC smears. QI of five stains namely Papanicolaou stain (Pap), Haematoxylin and Eosin (H&E), May Grunwald Giemsa (MGG), Modified Ultrafast Papanicolaou (MUFP) and Rapid Economic Acetic acid Pap stain (REAP) were studied and compared. Materials and Methods: This was a prospective study conducted in the Department of Pathology, Kempegowda Institute of Medical Sciences, Bengaluru, Karnataka, India, from August 2011 to July 2013. FNAC of 80 mass lesions including 44 of breast lesions and 36 lymph nodes were included in this study. A minimum of five smears were made in each case and stained with Pap, H&E, MGG, MUFP and REAP. The QI of stain was assessed by the scores given for background of the smear, overall staining, and preservation of cell morphology, nuclear characteristics, cytoplasmic details and air drying artifacts. Statistical analysis of the data was done using chi-square test and Statistical Package for the Social Sciences (SPSS) version 15.0. Results: Pap stain showed maximum QI score followed by H&E, REAP, MGG and MUFP in case of breast lesions. In cases of lymph node highest QI was again with Pap followed by H&E, REAP, MUFP and MGG. Good cytomorphology with lesser expenditure and turnaround time was obtained by REAP and MUFP stains. Conclusion: Pap stain is still the best for cell morphology whereas MUFP and REAP are good, economical and with lesser turnaround time and can be used in routine cytopathology.

Changes in Nodal Lesions and Vocal Function after Voice Therapy for Vocal Nodules

Changes in Nodal Lesions and Vocal Function after Voice Therapy for Vocal Nodules

Lymph Node Involvement in T1a Glottic Carcinoma: Controversial Case Series

AbstractThe treatment modality of laryngeal cancer is complete resection of the primary lesion and dissection of the cervical lymph nodes that is related to their staging. Following the patient without neck dissection is the usual expectation in T1 glottic carcinomas. However, a combination of elective neck dissection with surgical treatment for clinically N0 neck in early glottic tumors may be an effective treatment modality in the prevention of missed micrometastases. In these two case reports, elective neck dissection and re-examination of the treatment were discussed accordingly. We aimed to point out the importance of evaluation, examination, and, if it is uncertain, moreover the dissection of lymph nodes in early-stage glottic carcinoma since there are rarely any studies available.

Hemosiderin deposition in lymph nodes of patients with plasma cell-type Castleman disease.

Plasma cell-type Castleman disease (PCD) is a rare idiopathic atypical lymphoproliferative disorder. It is difficult to differentiate between PCD and IgG4-related disease (IgG4-RD) based on histology alone. As PCD often presents with abundant hemosiderin deposition, lymph node lesions obtained from 22 PCD patients and 12 IgG4-RD patients were analyzed using Prussian blue staining to clarify whether hemosiderin deposition is effective in distinguishing between these two diseases. The analysis disclosed that hemosiderin was more densely deposited in PCD than in IgG4-RD. The median number of Prussian blue-positive cells ± standard deviation (SD) in PCD and IgG4-RD cases was 13 ± 36 cells/3HPFs and 4 ± 8 cells/3HPFs (P = 0.034), respectively. In addition, we analyzed the relationship between hemosiderin deposition and levels of serum interleukin (IL)-6, serum C-reactive protein (CRP), and anemia-related biomarkers. We found that hemosiderin deposition was significantly correlated with the level of serum CRP (P = 0.045); however, no significant correlation was observed between hemosiderin deposition and serum IL-6 levels (P = 0.204). A non-significant positive correlation was observed between hemosiderin deposition and serum hemoglobin levels (P=0.09). Furthermore, no significant correlation was observed between hemosiderin deposition and serum iron levels (P = 0.799). In conclusion, hemosiderin deposition characteristically observed in PCD may be related to the inflammatory aggressiveness of the disease and could be used for its differential diagnosis.

A Comparative Study of Cytomorphological Patterns of Lymph Node Aspirates in Paediatric and Adult Populations

Introduction: Lymphadenopathy is one of the most common clinical presentations of patients. Lymph node is a commonly aspirated organ for diagnostic purposes. Fine Needle Aspiration Cytology (FNAC) of lymph node has become an integral part of initial diagnosis and management. Aim: To compare the cytomorphological patterns of the lymph node lesions in the paediatric population with that of the adult population and to correlate with the available histopathological diagnosis. Materials and Methods: It was a retrospective observational study of lymph node lesions conducted at a rural tertiary care referral institute, PES Institute of Medical Sciences and Research (PESIMSR), Kuppam, Andhra Pradesh, India, from January 2017 to June 2018 for a period of 18 months. Cytology smears were retrieved, reviewed and analysed. Cytological diagnosis was compared with available histopathological diagnosis and concordance was calculated. Chi-square test was the statistical tool used to analyse the data in the study. Results: Two hundred and seventy four cases were analysed. Adult population constituted 225 cases (82.12%). Paediatric population constituted 49 cases (17.88%). Reactive lymphadenitis was the commonest pattern in both the groups. Chronic lymphoproliferative lesions {4 cases (1.7%)} constituted the least common lesion in adults and mycobacterial lymphadenitis {1 case (2.04%)} constituted the least common lesion in paediatric population. Conclusion: Distribution of cytological patterns of lymph node lesions in paediatric and adult populations are different and are found to be statistically significant. Cytological evaluation of lymph node lesions has a high diagnostic efficacy for the diagnosis of neoplastic lesions.

Histologic transformation from lung squamous cell carcinoma in primary lesion to small cell lung cancer in metastatic lymph node lesion following lobectomy and adjuvant chemotherapy: a case report

Introduction: Lung cancer is the leading cause of cancer death worldwide. Histologic transformation from lung squamous cell carcinoma to small cell lung cancer (SCLC) has become more and more, and its treatment is challenging because of unknown pathogenesis. Presentation of Case: A 62-year-old male patient presented with histologic transformation from primary lesion to metastatic recurrence lesion within 3 years following primary lobectomy and adjuvant chemotherapy. The patient had the symptom of cough at the time of initial illness and recurrence. The primary lesion at the root segment of left superior lobe was diagnosed as lung squamous cell carcinoma without gene mutation (including EGFR, ALK, BRAF V600E, etc.), and recurrence lesion at the swollen lymph nodes in mediastinum (4L group) was diagnosed as SCLC. Up to now, the patient was alive for nearly 4 years after first surgery. Discussion: Surgical resection is the main treatment for lung cancer patient in early stage. Lymph node metastasis is a big threat for the patients in early stage. Recently, the research reports focused on the mechanism and cases of histologic transformation of lung cancer have become more and more. In this case, histologic transformation from squamous cell carcinoma in primary focus to SCLC in metastatic lymph node lesion following lobectomy and adjuvant chemotherapy. However, there was no gene mutation. This is a very unusual report. Conclusion: We analyzed a lung cancer patient with histologic transformation from primary focus to lymphatic metastasis by clinical symptoms, radiologic features, laboratory tests, gene detection, histopathologic characteristics, and immunohistochemical testing. It is helpful to understand the pathogenesis of histologic transformation and metastatic progression for optimizing treatment measures to lung cancer.

P840 A surprising outcome

Abstract Introduction infective endocarditis(IE) is a high morbidity and mortality disease, and heart failure,central nervous system embolization and annular abscess account for common complications.Nevertheless,intracardiac fistula is rare and predicts higher mortality and urgency for surgery. Case 84years old male patient,with an aortic bioprosthesis valve Perimount n23 since 2015,was admitted to internal medicine ward 3months before,due to Enterococcus faecalis bacteremia.at that time,transoesophageal echocardiography(TEE) revealed moderate to severe mitral valve(MV) regurgitation(vena contracta 0.7cm) and trivial tricuspid regurgitation,but did not showed any suggestive images of endocarditis.the patient was treated with 14days of amoxicillin-clavulanate. On the current presentation,due to fadigue to mild physical activity and fever for 2weeks,he was admitted to cardiology ward for further investigation.blood cultures were positive for the previous agent,so antibiotherapy with ampicillin 12g/day and gentamicin 240mg id was started.TEE revealed thickening of aortic bioprosthesis’ leaflets with preserved systolic opening.aortic valve annulus thickening,mainly near the non-coronary cusp,was evident, without characteristic features of peri-annular abscess.on ventricular side of the prosthesis,there was a vegetation(10.7x10.8mm). a small nodule lesion,coherent with a second vegetation,was present on the MV’s posterior leaflet,without regurgitation’s worsening. a third one was observed on the septal leaflet of the tricuspid valve(7.3x6.5mm),which also caused an increasement in severity of the regurgitation,quantified as moderate. On the sixth day,the patient presented with right arm paresis,so a brain CT was performed,showing an ischemic lesion on the left middle cerebral artery.Reevaluation,5days later,owing to new neurological changes,showed multiple acute vertebrobasilar embolic strokes. As a result of poor medical response and embolic strokes,the patient was referred to surgical treatment. however, due to prohibitive surgical risk (euroscore 59%), the patient was refused. After 6weeks of blood culture driven antibiotherapy,a reevaluation TEE revealed a periprosthetic pseudoaneurysm with small aorta-to-right atrium fistula.no vegetations were found. Conclusion rate complication of cardiac fistulae is high,60%of the patients develop heart failure and mortality rate is higher than 40%.although conservative treatment was addressed,after 8months discharge,the patient remains with few heart failure symptoms(NYHA classII).

Correlation between Thyroid Imaging Reporting and Data System and Bethesda System of Reporting of Thyroid Cytopathology of Thyroid Nodule: A Single Center Experience.

Background:The incidence of thyroid cancer has been increasing worldwide. Thyroid imaging reporting and data system (TIRADS) has been proposed for risk stratification of thyroid nodules to improve categorical management. Fine needle aspiration cytology based on Bethesda system for reporting of thyroid cytopathology (BSRTC) plays a fundamental role in the evaluation of thyroid nodule microscopically. Both the systems, the TIRADS and the latest revised BSRTC 2017, are widely recommended and practiced all over the world, but the correlation between the two systems has not been established.Aims and Objectives:This study was conducted to assess the risk of malignancy (ROM) in the intermediate Bethesda categories of thyroid lesions and their correlation with the corresponding TIRADS categories.Materials and Method:It was a prospective cross-sectional study over 1 year including 69 patients aged 18 years or older having solitary thyroid nodules. All cases were triaged using both TIRADS and BSRTC 2017 and the diagnostic performances were compared with subsequent paraffin sections to evaluate ROM. Correlation between TIRADS and BSRTC systems was expressed as kappa value.Result:Good concordance was observed between TIRADS and BSRTC systems in the evaluation of benign thyroid nodule lesions (category 2-II). There was discordance in follicular lesions (category 4-IV). The kappa value generated (0.411) revealed moderate agreement between the two risk stratification systems.Conclusion:Careful application of both grading systems is essential for the proper segregation of thyroid nodules to facilitate effective clinical and surgical management. However, universally acceptable protocols need to be developed to avoid the heterogeneous approach.

Does Intravenous Contrast Improve the Diagnostic Yield of Fluorodeoxyglucose Positron-emission Tomography/Computed Tomography in Patients with Head-and-neck Malignancy.

Introduction:In the present time, iodinated contrast agents are increasingly being used in the computed tomography (CT) component of positron-emission tomography (PET) study with the assumption that contrast-enhanced CT (CECT) will provide better diagnostic yield, although the utility of this procedure is still being debated. The aim of the study was to evaluate the effect of contrast CT on the diagnostic yield of PET-CT scan in patients with head-and-neck malignancies.Materials and Methods:In a prospective study, 204 patients (140 males and 64 females) of head-and-neck malignancies underwent contrast-enhanced and nonenhanced fluorodeoxyglucose (FDG)-PET-CT for various clinical indications following informed consent. After a plain CT scan, CECT was done using iodinated contrast iopromide-370 at a dose of 1 ml/kg intravenously. After CECT acquisition, FDG-PET acquisition was done and images were reconstructed to obtain whole-body PET/CT and PET-CECT images.Results:Both the modalities could detect similar number of primary lesions (n = 127), lymph nodal lesions (n = 118), and metastatic involvement (n = 55) with no significant difference between SUVmax. However, conspicuity of primary tumors and lymph nodal architecture was significantly better delineated with CECT, leading to better interpreter confidence.Conclusion:CECT data as part of the combined PET-CT examination provide precise anatomic localization and delineation of the primary tumor in comparison to nonenhanced PET-CT. However, no significant diagnostic changes are noted in the nodal and metastatic staging.

Frequency of metastasis in sentinel lymph node and its predictors in patients with laryngeal cancer T1-2N0M0

The purpose of the work is to establish the frequency of metastatic lesions of the precricoid sentinel lymph node (SNL) in patients with laryngeal cancer T 1-2 N 0 M 0 and to determine the predictors associated with the metastatic potential of the primary cancer tumor. Materials and methods . The study involved 61 patients with T1–2N0M0 laryngeal cancer with an average age of 57.71 ± 0.93 years; among them 56 (91.1 %) persons were male patients. Confirmed diagnosis of laryngeal cancer without clinical signs of regional metastasis was the criterion for inclusion in the study. Specialized treatment was carried out according to the protocol, with the use of larynx resections of various extents with the tumor removal in the first stage of combination treatment. The metastasis of precricoid SNL was determined histomorphologically using surgical material. The relationship between metastasis and microcirculatory indices was established by calculating the association coefficient and Fisher's exact test with the creation of a 2 × 2 table. The relative risk of metastasis was calculated. Data are presented in the form of relative risk and confidence intervals of CI. Results. It has been established that in 15 patients (26.2 %) tumor extension corresponded to the T 1 N 0 M 0 criterion and in 46 (73.8 %) persons – to T 2 N 0 M 0 . The pathomorphological study of removed precricoid SNLs (n = 61) verified metastatic lesions (pN1sn) in 7 (11.4 %) patients with T 2 N 0 M 0 . Statistical analysis of the study found that there is a relationship between metastasis and the depth of invasion (association index 0.85), the degree of tumor differentiation (association index 0.66) and the bypass index (association index 0.96). It was found that when the value of the bypass index is higher than 1.63 pF units, the relative risk of metatases increases by 54 %, RR = 2.72 [1.64; 4.52] – 95 % CI, OR = 13.06 [1.39; 122.50], DI 95 %, with an invasion depth of greater than 6.28, the relative risk of metatases increases by 39 %, RR = 4.5 [1.72; 11.76], СI 95 %, OR = 8 [1.89; 33.81], СI 95 %. Conclusions. Revealed critical values of quantitative indicators of such predictors of laryngeal cancer metastasis as the extension of the process to T 2 N 0 M 0 , the depth of tumor invasion more than 6.28 ± 0.18 mm, the low degree of differentiation (G3), the prevalence of shunt blood flow over the nutritive one –shunt indicator is greater than 1.84 ± 0.05, can be used for intraoperative prediction of the presence of latent metastasis in the SNL and indicate the advisability of performing simultaneous sheath-fascial lymph node dissection of the neck on the side of the larynx lesion.

Deep neural network for automatic characterization of lesions on 68Ga-PSMA-11 PET/CT.

This study proposes an automated prostate cancer (PC) lesion characterization method based on the deep neural network to determine tumor burden on 68Ga-PSMA-11 PET/CT to potentially facilitate the optimization of PSMA-directed radionuclide therapy. We collected 68Ga-PSMA-11 PET/CT images from 193 patients with metastatic PC at three medical centers. For proof-of-concept, we focused on the detection of pelvis bone and lymph node lesions. A deep neural network (triple-combining 2.5D U-Net) was developed for the automated characterization of these lesions. The proposed method simultaneously extracts features from axial, coronal, and sagittal planes, which mimics the workflow of physicians and reduces computational and memory requirements. Among all the labeled lesions, the network achieved 99% precision, 99% recall, and an F1 score of 99% on bone lesion detection and 94%, precision 89% recall, and an F1 score of 92% on lymph node lesion detection. The segmentation accuracy is lower than the detection. The performance of the network was correlated with the amount of training data. We developed a deep neural network to characterize automatically the PC lesions on 68Ga-PSMA-11 PET/CT. The preliminary test within the pelvic area confirms the potential of deep learning methods. Increasing the amount of training data should further enhance the performance of the proposed method and may ultimately allow whole-body assessments.

Abstract B040: Is there a role for 18F-FDG PET/CT imaging in Langerhans cell histiocytosis?

Abstract Objective: Langerhans cell histiocytosis (LCH) is a rare disorder of clonal proliferation of dendritic cells usually affecting children. However, it may also appear later in life at any age. The severity of the disease varies widely, and multi-system involvement of the lungs, liver and hematopoietic system may be life threatening. This study evaluated the role of 18F-fluorodeoxyglucose positron emission tomography / computed tomography (FDG PET/CT) in patients with single system and multisystem LCHfor disease extent, restaging and response to therapy. Methods:We retrospectively evaluated the data of 37 patients (27 male, 10 female) aged 21.3 ± 18.9 years, comprising 20 children (aged 1-16 years) and 17 adults (aged 20-69 years) with pathologically confirmed LCH. All patients had undergone whole body FDG PET/CT to assess the extent of disease involvement between January 2011 and May 2019. A total of 52 scans were evaluated by two experienced nuclear medicine physicians. Increased FDG uptake with morphological changes on the corresponding CT images were interpreted as PET/CT positive and absence of FDG uptake or any structural lesion were considered PET/CT negative. The metabolic and morphological tumor status and response after chemotherapy were assessed. Out of 52 PET/CT scans, 25 scans were performed for initial work-up and the rest for restaging, follow-up or response evaluation. The results of PET/CT imaging were compared with CT or magnetic resonance imaging (MRI) reports (if available). Results: Of the 37 patients, 20 had multisystem disease (8 high risk, 12 low risk), while single system involvement was noted in 17 patients (9 unifocal, 8 multifocal). FDG PET/CT was positive in 32/37 and detected skeletal (n=28), lymph nodal (n=13), lung (n=5), liver (n=4), pituitary (n=3), ano-cutaneous (n=2) and thyroid (n=2) lesions. In the two groups, FDG PET/CT identified more lesions compared to CT or MRI in 22 patients, including bone, lymph nodal and ano-cutaneous lesions. Six patients with lung lesions had very low FDG avidity. FDG PET/CT upstaged the disease in 8 patients from single system disease to multisystem involvement (2 primary pituitary, 2 primary thyroid and 4 primary skeletal). PET positive lesions had SUVmax of 8.9 ± 3.7 (range 3.8 - 18.8). In patients with follow-up or response evaluation imaging, a complete metabolic response was noticed in the low risk group (n=7), while disease progression was noted in patients with high risk and multisystem involvement group (n=3). Conclusion:Except for lung lesions, FDG PET/CT is a better imaging modality than conventional imaging (CT/MRI) for initial staging as well as restaging and response evaluation in both single system and multisystem LCH. It also helps in management planning by upstaging the disease from single system to multisystem involvement. Citation Format: ANISH BHATTACHARYA, RAJENDER KUMAR, BHAGWANT RAI MITTAL. Is there a role for 18F-FDG PET/CT imaging in Langerhans cell histiocytosis? [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B040. doi:10.1158/1535-7163.TARG-19-B040

68Ga-prostate-specific membrane antigen PETCT-based response to androgen deprivation therapy in patients with prostate cancer.

To assess the response of castration-naïve prostate cancer to androgen deprivation therapy (ADT) in Ga-PSMA PETCT, and test the hypothesis of differential response in primary, nodal and metastatic lesions. Patients with adenocarcinoma prostate with baseline Ga-prostate-specific membrane antigen (PSMA) PETCT scan, and response scan after 3-12 months of ADT from 2014 to 2017 were analyzed. Change in radiotracer uptake in the prostate, involved regional nodes and distant metastasis was semiquantitatively assessed in paired scans using maximum standardized uptake value (SUVmax). Response was categorized into complete or partial response (CR, PR) or stable disease or progressive disease (SD, PD), and correlated with known prognostic factors. Total 86 scans of 43 patients (17 metastatic, M+) were analyzed. After median 6 months of ADT, 0% primary, 23.3% nodes and 17.6% metastases showed CR; 18.6% primary, 8.3% nodes and 35% metastases showed PD. Prostate response was not significantly associated with any prognostic factor. Nodal response was higher in M0 than in M+ disease (CR 37 vs 4%, P = 0.003). Oligometastases responded better than polymetastases (CR/PR 62.5 vs 11.1%, P = 0.05). Decline in SUVmax of primary tumor correlated with decline in serum prostate-specific antigen (PSA) (90% of partial responders showed >80% decline in serum PSA vs 50% with PD, P = 0.06). Primary prostatic tumor seems less likely to respond to ADT than nodal or metastatic lesions. Residual primary uptake may guide patient selection for local therapy in (oligo) metastatic prostate cancer.

Elevated Serum Soluble Interleukin-2 Receptor Level Is a Useful Prognostic Factor for Disease-Specific Overall Survival in Patients with Newly Diagnosed Follicular Lymphoma before Initiation of Treatment

Introduction: Serum soluble interleukin-2 receptor (sIL-2R) is recognized as a tumor-related biomarker of malignant lymphomas, including follicular lymphoma (FL). The objective of this study is to assess the prognostic significance of pretreatment serum sIL-2R level for disease-specific overall survival (DSS) in patients with FL. Methods: We retrospectively analyzed medical records of our 10 individual institutions to identify all patients (pts) ≥ 18 years old with newly diagnosed FL between 01/01/2008 and 12/31/2018. Only pts with FL grade 1-3b, confirmed at pathological review, were included. Pts with histological transformation at diagnosis were excluded. Serum sIL-2R was determined by sandwich enzyme-linked immunosorbent assay. Clinical characteristics, therapies, response, relapse patterns and follow up status were collected and analyzed in the cohort. DSS was defined from the time of initial diagnosis to death due to lymphoma or last follow up. DSS was analyzed according to Kaplan Meier method and differences between subgroups were compared with log-rank test. Multivariate cox regression analysis was used to investigate associations of sIL-2R, FL International Prognostic Index (FLIPI) and progression or relapse within 24 months after diagnosis (POD24) with DSS. Serum levels of sIL-2R was measured before initiation of treatment and the data on the nearest date of the diagnostic biopsy within six months was adopted. Results: We recorded 565 pts and 535 pts of them with pretreatment serum sIL-2R levels available were included in the analysis with median age 64 years (range: 30-90) and 305 females (57%). Clinical characteristics are summarized in Table 1. The median of the serum sIL-2R level was 896 IU/mL (range: 145 - 23800). We decided an optimal cutoff value of 1800 IU/mL by using receiver operating characteristic (ROC) analysis, which showed it was 1830 IU/mL (AUC : 0.76, 95%CI : 0.67 - 0.84). Various poor prognostic indicators, such as bulky mass, increased LDH, ≥5 nodal lesions, poor performance status (PS), bone marrow invasion, FLIPI and FLIPI-2 high-risk, decreased Hb, advanced disease, high tumor burden, increased β2MG and existence of B symptoms, were strongly associated with high serum sIL-2R level (≥1800 IU/mL), and high sIL-2R level correlated with POD24 (P<0.001, Chi-squared test). The estimated 10-year DSS rate was 87.2% with a median follow up duration of 4.4 years. In pts with POD24 (96 pts, 18%), DSS was significantly worse than those with non-POD24; 64.3% vs 93.0% (P<0.001) and rituximab maintenance did not improve DSS in both groups (P=0.85 and 0.98, respectively). In patients with sIL-2R level of ≥1800 (high sIL-2R, 378 pts, 71%), DSS was significantly worse than those with sIL-2R level of <1800 IU/mL (low sIL-2R, 157 pts, 29%); 68.2% vs 96.0% (P<0.001), respectively (Figure 1). Multivariate analyses employing sex, PS, sIL-2R, FLIPI and POD24 demonstrated that high sIL-2R was an independent prognostic factor for DSS (HR : 2.88, 95% CI : 1.15-7.21, P<0.05). Regardless of POD24 status, pts with high sIL-2R had significantly worse DSS than those with low sIL-2R; 44.6% vs 91.5% in pts with POD24 (P<0.05) and 82.6% vs 96.8% in pts without POD24 (P<0.001), respectively. Among pts treated with rituximab plus anthracycline-containing chemotherapy as the 1st line regimen (222 pts, 41%), pts with high sIL-2R had significantly worse DSS than those with low sIL-2R; 68.1% vs 97.2% (P<0.001). Among pts treated with rituximab-bendamustine as the 1st line regimen (48 pts, 9%), there was no significant difference between high and low sIL-2R populations (P=0.2), however, among pts treated with bendamustine-containing regimen at least once in their life time (180 pts, 34%), there was significant difference between them; 63.1% vs 87.8% (P<0.05). Even in pts achieving complete metabolic response after 1st line treatment (178 pts, 33%), high pretreatment sIL-2R level was a significant factor affecting poor DSS; 75.9% vs 94.3% (P<0.05). Conclusions: High sIL-2R level ( ≥1800 IU/mL) is a significant and independent adverse prognostic factor for DSS in pts with newly diagnosed FL. This study provides us useful information to predict population with worse DSS before initiation of treatment. Disclosures Nozaki: Chugai: Honoraria; Celgene: Honoraria. Kida:Eisai Co., Ltd: Honoraria. Kosugi:Novartis Pharma Co.: Honoraria; Bristol-Myers Squibb Co.: Honoraria; Eisai Co., Ltd: Honoraria; Takeda Pharmaceutical Company Limited: Honoraria; Kyowa Kirin Co., Ltd: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria; NIPPON SHINYAKU CO.,LTD.: Honoraria; Janssen Pharmaceutical K.K.: Honoraria; Celgene K.K.: Honoraria; Pfizer Inc.: Honoraria. Shibayama:Astellas, Teijin, MSD, Shionogi, Eisai, Sumitomo Dainippon, Taiho, Nippon Shinyaku: Research Funding; Celgene, Chugai, Eisai, AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Takeda, Novartis, Janssen, Chugai, Eisai, Mundi Pharma, Ono, Otsuka, Kyowa Kirin, Sumitomo Dainippon, AstraZeneca, Avvie, DaiichiSankyo, Fujimoto, Nippon Shinyaku, Sanofi, Bristol-Myers Squibb, Pfizer: Honoraria.

The Possibilities of Diffusion-Weighted Magnetic Resonance Imaging in Determining the Burden of a Tumor in Patients with Follicular Lymphoma

BACKGROUND: Follicular lymphoma (FL) is a B-cell tumor, which in most patients is characterized by slow growth and an "indolent" clinical course. In 80% of patients bone marrow is affected, which is a reflection of the pathogenesis of the tumor. The "watch and wait" tactic is a frequently used variant of patient management. For effective therapy, it is necessary to establish the stage of the disease, which requires the examination of the bone marrow (bilateral trepanobiopsy) and the identification of nodal and extranodal lesions (using PET/CT or CT of the whole body). The use of these methods is associated with high radiation exposure and the risk of complications in the intravenous radiopharmaceuticals and contrast agents. Whole body diffusion-weighted magnetic resonance imaging (WB-DWI) makes it possible to detect the burden of the tumor process without the use of contrast agents. AIM: Assess the capabilities of the WB-DWI method for determining the prevalence of a tumor and the detection of BM lesions in patients with FL. PATIENTS AND METHODS: The study was conducted during the fourth quarter of 2018 in the National Research Center for Hematology (Moscow), covered 8 patients (3 men and 5 women, with an average age of 53 years). According to the developed design of the study at the time of diagnosis of PL, all patients underwent a WB-MRI study, and then performed (with masking of participants): PET/CT, a histological examination of the bone marrow and the determination of B-cell clonality in bone marrow punctate (using PCR method). The results of the last two examinations were taken as reference (true) estimates for the detection of bone marrow lesions, and compared with the results obtained using the WB-MRI and PET/CT methods. Cohen's kappa statistical coefficient was used to assess the agreement between comparing methods. RESULTS: All 8 patients had a generalized lesion of the lymph nodes and extranodal foci (stage 4 according to An-Arbor). It was found that the measured diffusion coefficient in the lesions of the BM was 0,5‒0,9 х 10-3 mm/s. Reference tests showed that in 7 out of 8 patients, BM was affected. PET/CT gave two false-negative results, WB-DWI - one false-negative results (Tables 1‒2). Estimates of the prevalence of lesions of the lymph nodes and extranodal foci by WB-DWI and PET/CT were consistent with the accuracy of the methods. Estimates of the extent of lymph node involvement and extranodal lesions using WB-DWI and PET/CT were coincided with the accuracy of the methods errors. CONCLUSION: The results (Table 3.) of this exploratory research show that the WB-DWI method reveals a bone marrow damage not worse than the PET/CT method: kappa coefficient for WB-DWI was 0.6 and for PET/CT ‒ 0,5, respectively (due to the small sample size, strict statistical significance was not reached). WB-DWI allows you to quickly and informatively determine the affected areas and the involvement of BM, and thereby establish the stage of the disease. The results suggest an opportunity (along with the PET/CT method) to use the WB-DWI method as well. Disclosures No relevant conflicts of interest to declare.

Prognostic Value of Total Metabolic Tumor Volume and Total Lesion Glycolysis Measured By 18F-FDG PET-CT in Patients with T-Cell Lymphoblastic Lymphoma

Introduction T-cell Lymphoblastic lymphoma (T-LBL) accounts for 90% of all LBLs, a rare and aggressive precursor lymphoblast originating hematological disorder. To date, there isn't any optimal prognostic model for T-LBL, which is a barrier to identify patients at high risk for relapse. Recent studies have shown that total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) measured on18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) are useful prognostic parameters for in Hodgkin's lymphoma, diffuse large B cell lymphoma, and peripheral T cell lymphoma, etc. Here we discussed the prognostic role of these tumor burden indicators in T-LBL. Methods From January 2013 to December 2018, 37 newly diagnosed T-LBL patients with baseline PET-CT were included. The baseline maximum standardized uptake value (SUVmax) of all lesions was recorded, and the highest value was considered the SUVmax of the patient. Meanwhile, SUVmax of liver and mediastinum were obtained. The 41% SUVmax threshold method was used for MTV computation, TMTV was then obtained by summing the metabolic volumes of all local nodal and extra-nodal lesions. TLG was calculated as MTV multiply by average SUV. Progression-free survival (PFS) and overall survival (OS) were analyzed by Kaplan-Meier curves and compared by log-rank test. All statistical analyses were performed using SPSS version 25.0 software and P<0.05 was considered to be statistically significant. Results Among the 37 T-LBL patients included in the current study, the median age was 22 years with range from 12 to 75 years . 29 (78.4%) patients were male, and 32 (86.5%) of patients were in stage III and IV. 17 (45.9%) patients were given Hyper-CVAD/MA regimen, while 54.1% of these patients were treated with the modified BFM90 regimen. Detailed clinical characteristics for all patients were shown in Table 1. The optimal cut-off values for SUVmax, TMTV and TLG were 12.7, 302cm3 and 890 respectively by ROC analysis. Patients with SUVmax≥12.7 were more likely to have advanced stage of disease, while patients with TMTV≥302cm3 or TLG≥890 were more inclined to have more than 2 sites of extra-nodal involvement. With a median follow-up time of 19 months (7.5-65 months), the estimated 4-year PFS and OS of the whole cohort was 23.3% and 32.2%, respectively. With a cutoff value of 12.7, the median PFS and OS were significantly shortened for patients with high SUVmax (PFS: 10.5 vs 16.0 months, P=0.022, OS: 13.5 vs 35.0 months, P=0.004, respectively). 3-year PFS were 10.3% in patients with TMTV<302cm3 and 61.4% in patients with TMTV≥302cm3 (P=0.003), while 3-year OS were 90.9% and 26.1%, respectively (P=0.012,). Similarly high TLG also indicated inferior PFS and OS (3 years PFS: 57.3% vs 7.6%, P=0.004, OS: 90.0% vs 31.6%, P=0.003, respectively). In addition, central nervous system (CNS) involvement was also found to be associated with shortened PFS and OS in the univariable test. Multivariable survival analysis demonstrated that TMTV≥302cm3 (HR=4.746, P=0.015), and CNS involvement (HR=5.309, P=0.006) were independent risk factors for PFS, while SUVmax≥12.7 (HR=3.170, P=0.035), TLG≥890 (HR=9.253, P=0.039) and CNS involvement (HR=5.880, P=0.007) were associated with worse OS independent of Ann Arbor stage, IPI score and treatment regimen. Subsequently we integrated four independent prognostic factors SUVmax≥12.7, TMTV≥302cm3, TLG≥890 and CNS involvement to generate a risk model with each parameter ranking 1 score, which stratified the population into 3 risk groups: Group 1 (low-risk group), including patients who scored 0-1, had median PFS and OS of not reached at time of this study. Group 2 (mediate-risk group) including patients with score 2, had a median PFS of 14 months and median OS of 27 months. Group 3 (high-risk group) patients scored 3-4 with a median PFS of 7 months and OS of 13 months (Figure 2). Conclusion Baseline SUVmax , TMTV and TLG are strong predictors of outcome in T-LBL. In combination with CNS involvement, they are capable of identifying patients at high risk of early progression, which warrants further validation as a biomarker for development of first-line PET-CT adapted approaches in T-LBL. Disclosures No relevant conflicts of interest to declare.

A Phase 2 Study of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Antibody (Ab), in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL)

A Phase 2 Study of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Antibody (Ab), in Patients with Relapsed/Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (B-NHL)

Electrochemotherapy Associated with Calcium Electroporation in Metastatic Feline Cutaneous Malignant Melanoma

Background: Calcium electroporation (CaEP) is a novel therapeutic treatment that has been studied for cancer due to its selective killing cancer cells by necrosis and danger signals. Besides that, electrochemotherapy (ECT) is an effective local treatment that involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumor. The combination with ECT and CaEP has been reported in literature suggesting that additional response of immune system could have been enhanced by electroporation with calcium. This case, report on the successful treatment with CaEP combined with ECT for treatment of a regional metastasis in a feline model of malignant melanoma.Case: A 9-year-old, mixed breed cat was referred to the veterinary clinic with a 2-month history of cutaneous peripalpebral plaque lesion (0.19 cm³) and a submandibular lymph node enlargement (0.5 cm³). Incisional biopsy of the cutaneous lesion and fine-needle aspiration of submandibular lymph node confirmed a cutaneous melanoma with submandibular lymph node metastasis. Tumor staging was set in T1N1M0 according to WHO staging criteria. ECT for the primary lesion and lymph node metastasis was proposed. For the ECT, bleomycin (15,000 UI/m²) application was performed intravenous followed by electroporation (8 pulses of 100 μs at 1000 V/cm, and 1 Hz) using a needle array electrode consisted of two parallel rows with six needles in each row. At 28-day post-ECT complete remission of the primary tumor and metastatic foci was achieved. However, 120 days after ECT, recurrence was observed in submandibular and retropharyngeal lymph nodes. A second ECT approach was performed adding to bleomycin the intra lymph nodal application of calcium gluconate. The dose of calcium gluconate was diluted in an isotonic 0.9% NaCl solution resulting in a low concentration at 9 mM, injected in both metastatic lymph nodes (submandibular total volume: 1.4 ml; retropharyngeal total volume: 0.5 mL) and pulses were delivered immediately after drug administration. No systemic adverse effects were observed. Local adverse effects were considered mild as transitory edema and ulceration post procedure. One-week post-ECT+CaEP, complete remission of local metastasis occurred. However, the patient achieved five months disease free interval, and died during a surgical approach, achieving nine months of survival time.Discussion: Feline cutaneous malignant melanoma is an aggressive disease with a short survival time for the patients with mean of 4.5 months. CaEP is a novel anticancer treatment that has been study in the past years due to its selective killing cancer cells by necrosis and danger signals. The CaEP induces supraphysiological calcium influx into neoplastic cells leading to acute ATP depletion and necrosis of tumor cells. This use could be an interesting therapeutic choice for both human and veterinary medicine. In this patient, it was demonstrated a good clinical response with its use, showing temporarily tumor remission from the case presented with disease free interval of five months when compared to other report of two months. This description showed that ECT associated with CaEP improved outcome of regional melanoma lymph node metastasis in a cat. However, further investigations are needed to understand the use of CaEP in patients for local control metastasis as well as evaluate the use of both modalities to determine its synergistic effect.

18F-DCFPyL PET/CT Imaging in Patients with Biochemically Recurrent Prostate Cancer After Primary Local Therapy

Our objective was to investigate the lesion detection rate of 18F-DCFPyL PET/CT, a prostate-specific membrane antigen (PSMA)-targeted PET agent, in patients with biochemically relapsed prostate cancer after primary local therapy. Methods: This was a prospective institutional review board-approved study of 90 patients with documented biochemical recurrence (median prostate-specific antigen [PSA], 2.5 ng/mL; range, 0.21-35.5 ng/mL) and negative results on conventional imaging after primary local therapies, including radical prostatectomy (n = 38), radiation (n = 27), or a combination of the two (n = 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body 18F-DCFPyL PET/CT (299.9 ± 15.5 MBq) at 2 h after injection. The PSMA PET lesion detection rate was correlated with PSA, PSA kinetics, and original primary tumor grade. Results: Seventy patients (77.8%) showed positive PSMA PET results, with a total of 287 lesions identified: 37 prostate bed foci, 208 lesions in lymph nodes, and 42 in distant sites in bones or organs, Eleven patients had negative results, and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n = 10/21), 50% (n = 5/10), 88.9% (n = 8/9), and 94% (n = 47/50) for PSA levels of >0.2 to <0.5, 0.5 to <1.0, 1 to <2.0, and ≥2.0 ng/mL, respectively. In postsurgical patients, PSA, PSA doubling time, and PSA velocity correlated with PET results, but the same was not true for postradiation patients. These parameters also correlated with the extent of disease on PET (intrapelvic vs. extrapelvic). There was no significant difference in the rate of positive scans between patients with higher-grade and lower-grade primary tumors (Gleason score of ≥4 + 3 vs. <3 + 4). Tumor recurrence was histology-confirmed in 40% (28/70) of patients. On a per-patient basis, positive predictive value was 93.3% (95% confidence interval, 77.6%-99.2%) by histopathologic validation and 96.2% (95% confidence interval, 86.3%-99.7%) by the combination of histology and imaging/clinical follow-up. Conclusion: 18F-DCFPyL PET/CT imaging offers high detection rates in biochemically recurrent prostate cancer patients and is positive in about 50% of patients with a PSA level of less than 0.5 ng/mL, which could substantially impact clinical management. In postsurgical patients, 18F-DCFPyL PET/CT correlates with PSA, PSA doubling time, and PSA velocity, suggesting it may have prognostic value. 18F-DCFPyL PET/CT is highly promising for localizing sites of recurrent prostate cancer.