Node Lesions Research Articles

Cytomorphological study of lymph node lesions

Lymph nodes are important components of peripheral or secondary lymphoid organs which play a huge role in immune response. To study cytomorphological features and incidence of various lymph node lesions in patients ≤18 years. The data has taken from 100 patients of ≤18 years having lymph node lesion presented at central clinical laboratory for Fine Needle Aspiration cytology examination. FNAC was done in all cases & correlated with their clinical data. Interpretation of their cytology examination is showing that in our tertiary care centre most common lymph node lesion in patient ≤18 year is granulomatous lymphadenitis(44%) followed by reactive lymphadenitis (37%), Acute inflammation(06%), Abscess formation (05%), Cystic lesion (03%), and Leukemic infiltration (02%). Most affected age is 6 to 10 years. Granulomatous & Reactive lymphadenitis are common causes of lymphadenitisin ≤18 years age group. Among this study 6-10 years are more affected age group. These result can be obtain by Fine Needle Aspiration cytology examination.

Cytomorphological study of head and neck lymph node lesions

The head and neck area is a complex anatomical structure which includes various non-neoplastic and neoplastic lesions of lymph node, salivary gland, thyroid gland and soft tissue. Fine needle aspiration cytology of head and neck lymph nodes proved useful in separating inflammatory lesions, which do not require surgical excision from cystic and neoplastic lesions with good certainty. Fine needle aspiration cytology (FNAC) is a simple, feasible, cost effective and minimally invasive procedure. But histopathological examination is more valuable for confirmatory diagnosis in suspected lesions. To assess the utility of FNAC in diagnosis of head and neck lymph node lesions and to establish the diagnostic accuracy of cytology by comparing with the histopathological diagnosis, wherever possible. Materials and Methods: A 6 months retrospective study was done from March 2020 to August 2020 at Khaja Bandanawaz institute of medical sciences on 50 patients presenting with head and neck lymph node enlargement. 50 cases were evaluated by FNAC. In this study out of 34 benign cases, 14 cases were of Reactive lymphadenitis, 17 cases of Granulomatous/Tuberculous lymphadenitis and 3 cases were of Acute suppurative lymphadenitis. Out of 16 malignant cases, 5 cases were of Non Hodgkins lymphoma, 2 cases were of hodgkins lymphoma and 9 cases were of metastatic carcinoma. FNAC has been found to be a satisfactory tool in the diagnosis of tubercular and malignant lymphadenopathy in our study. The lucidity and rapidity of the procedure makes it most appropriate for use on outpatient basis even in peripheral hospitals and dispensaries.

The Value of 18 Fluorine-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Imaging in Breast Cancer Staging

BACKGROUND: Accurate staging is important for management decisions in patients with newly diagnosed breast cancer.
 AIM: This study was conducted to evaluate the value of 18 fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) imaging in breast cancer staging..
 METHODS: A prospective study of 80 patients (1 male and 79 female) mean age 51.13 years with histologically confirmed breast cancer. The staging procedures included history, physical examination, mammography, and CT of neck, chest, abdomen, and pelvis; then, PET/CT was performed in a time interval <30 days. The findings of PET/CT were compared with those of the other conventional methods.
 RESULTS: The agreement between conventional methods (mammography, breast ultrasound, contrast-enhanced CT of the neck, chest, abdomen, and pelvis) and 18F FDG-PET/CT was 0.6 for assessing the T stage, 0.39 for N stage, and 0.75 for M stage. There was moderate agreement between CT and 18F FDG-PET/CT in the detection of nodal lesions (K=0.6) and pulmonary lesions (K=0.51), while a perfect agreement was noted for detecting osseous (K=0.82) and liver lesions (K=0.81). In total, 50 patients (62.5%) were concordantly staged between the conventional imaging and 18F-FDG PET/CT, while 30 patients (37.5%) showed a different tumor, node, and metastasis stage. The changes were driven by the detection of additional findings (n=26) or exclusion of findings (n=4), mainly at the lymph nodes (LNs) and/or distant sites. Regarding N status, 18F FDG-PET/CT revealed previously unknown regional lymphatic spread in supraclavicular (n=4; 5%), infraclavicular (n=11; 13.7%), and internal mammary (n=12; 15%) lymph node groups. 18F-FDG PET/CT changed M status in a total of four patients (5%); three of them were upstaged by detecting distant metastases, while osseous deposits were excluded in one patient leading to downstaging.
 CONCLUSION: 18F-FDG-PET/CT is considered a valuable imaging tool in the initial staging of breast cancer, which significantly impacts the overall American Joint Committee on Cancer staging in 37.5% of our study population.

The effect of preoperative 18F-FDG PET on the surgical decision in early breast cancer: 5-Year follow-up.

The diagnosis, treatment, and management of the breast cancer (BC) require a multidisciplinary approach. In newly diagnosed BC, fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) can detect extra-axillary regional nodal and distant lesions. Between 2010 and 2015, this study included 101 patients with early-stage BC who were examined with 18F-FDG PET before surgery. Patients were divided into two groups: Group 1 consisted of patients with suspected 18F-FDG uptake and Group 2 with the remaining 18F-FDG-negative patients. Differences between these groups were tested using the Pearson chi-square test, Fisher's exact test, Mann Whitney-U test, independent t-test and ROC analysis. They could be followed-up after 2015 for 5 years. All patients were then rediscussed either neoadjuvant therapy or surgery in the oncology board in 2020 with changing neoadjuvant criteria and oncoplastic surgery techniques. Fluorine-18-FDG PET was found to have a sensitivity of 77.8% and a specificity of 90.8% in detecting axillary lymph node metastasis. During the minimum 5-year follow-up, one patient had bone metastasis, 2 patients had a local recurrence, and 3 patients had metastatic lymph nodes in the axilla. In the re-evaluation of the same patients over 5 years, the decrease in mastectomy decision was remarkable (P-value 0.01). We observed that we could not achieve a significant difference in 5-year metastasis/recurrence between the groups. Moreover, due to 18F-FDG-PET high false positivity, it significantly extended the time to surgery (P-value 0.01). In early-stage BC, 18F-FDG PET demonstrated better performance in axillary lymph nodes metastases detection in comparison with other diagnostic imaging methods, even if SLNB remains the gold standard technique.

Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year.

Vaccination has been proposed as a supplementary tool for the control of tuberculosis in livestock. The long-term immunogenicity elicited by bacillus Calmette–Guerin (BCG) and the efficacy of revaccination were investigated in thirty goat kids distributed into three groups: unvaccinated controls, BCG (vaccinated at week 0) and BCG-BCG (vaccinated at weeks 0 and 56). Sixty-four weeks after the first vaccination, all animals were challenged with Mycobacterium caprae and examined post-mortem (pathology and bacterial load) at week 73. Antigen-specific interferon-gamma (IFN-γ) release was measured throughout the experiment. At week 59, peripheral blood mononuclear cells were stained for CD4, CD45RO and IFN-γ to determine the presence of antigen-specific cells secreting IFN-γ. The BCG-BCG group showed reductions in rectal temperatures, M. caprae DNA load in pulmonary lymph nodes (LN), the volume of lesions in pulmonary LN, mineralization in lungs, and higher weight gains compared to unvaccinated controls. IFN-γ responses were undetectable from 32 weeks after primary vaccination until revaccination, when the BCG-BCG group showed detectable IFN-γ production and a greater percentage of antigen-specific CD4+CD45RO+IFNγ+ and CD4−CD45RO+IFNγ+ cells compared to the BCG and control groups, which may be an indicator of the mechanisms of protection. Thus, re-vaccination of goats with BCG appears to prolong protection against infection with M. caprae.

Stereotactic Ablative Radiation Therapy to All Lesions in Patients With Oligometastatic Cancers: A Phase 1 Dose-Escalation Trial

Increasing evidence suggests that patients with a limited number of metastases benefit from SABR to all lesions. However, the optimal dose and fractionation remain unknown. This is particularly true for bone and lymph node metastases. Therefore, a prospective, single-center, dose-escalation trial was initiated. Dose-Escalation trial of STereotactic ablative body RadiOtherapY for non-spine bone and lymph node metastases (DESTROY) was an open-label phase 1 trial evaluating SABR to nonspine bone and lymph node lesions in patients with up to 3 metastases. Patients with European Cooperative Oncology Group performance status ≤1, an estimated life expectancy of at least 6 months, and histologically confirmed nonhematological malignancy were eligible. Three SABR fractionation regimens, ie, 5 fractions of 7.0 Gy versus 3 fractions of 10.0 Gy versus a single fraction of 20.0 Gy, were applied in 3 consecutive patient cohorts. The rate of ≥grade 3 toxicity, scored according to the Common Toxicity Criteria for Adverse Events v. 4.03, up to 6 months after SABR, was the primary endpoint. The trial was registered on clinicaltrials.gov (NCT03486431). Between July 2017 and December 2018, 90 patients were enrolled. In total 101 metastases were treated. No ≥grade 3 toxicity was observed in any of the enrolled patients (95% CI 0.0%-12.3% for the first cohort with 28 analyzable patients; 95% CI 0.0%-11.6% for the second and third cohort with 30 analyzable patients each). Treatment-related grade 2 toxicities occurred in 4 out of 30 versus 2 out of 30 versus 2 out of 30 patients for the 5, 3 and 1 fraction schedule, respectively. Actuarial local control rate at 12 months was 94.5%. All 3 treatment schedules were feasible and effective with remarkably low toxicity rates and high local control rates. From a patient and resource point of view, the single-fraction schedule is undoubtedly most convenient.

Is there a requirement for a staging CT thorax in T1N0 and T2N0 oral squamous cell carcinomas?

Introduction: At the time of diagnosis 1 in 10 patients with oral squamous cell carcinoma has a secondary cancerous lesion or metastasis in the local lymph nodes. The incidence of occult metastasis in patients with T1 and T2 tumours has been 7–33% and 28–53% respectively. The 2016 NICE recommendation was that all people with cancer of the upper aero digestive tract should be offered systemic staging except those with T1N0 or T2N0 disease. In this study we review the staging scans for our T1N0 and T2N0 patients.

An Angiomyomatous Hamartoma With Features of Vascular Transformation of Sinuses in the Mediastinal Lymph Node of a Beagle Dog.

Two similar benign, nonneoplastic vascular lesions have been described in the lymph nodes of humans and animals: angiomyomatous hamartoma (AMH), which is characterized by the replacement of lymphoid tissue by blood vessels, smooth muscle, and fibrous tissue, and vascular transformation of sinuses (VTS), which is considered a reactive transformation of lymph node sinuses into capillary-like vascular channels. We hereby report a lesion with features common to both lesions in the mediastinal lymph nodes of a 1-year-old beagle dog in a 1-month toxicity study. Grossly, enlargement and red discoloration were observed, while microscopically, the lesion was characterized by effacement of the lymph node parenchyma with replacement by mature blood vessels, smooth muscle, and fibrous tissue, associated with lymphoid atrophy, which is consistent with AMH. However, multifocal areas of anastomosing or plexiform capillary-like channels lined by normal to slightly plump endothelium, similar to those described for VTS, were also present. Immunohistochemistry analysis revealed abundant positive staining for smooth muscle actin and endothelial cells (von Willebrand factor/factor VIII) and the absence of proliferation (Ki67). In conclusion, these lesions most likely represent a mixture of both AMH and VTS.

Expression level and prognostic value of PD-L1 in microsatellite instability-high gastric cancer

Objective: To study the clinicopathological features and PD-L1 expression of microsatellite instability-high (MSI-H) gastric cancer. Methods: The clinicopathological data of the 2 472 patients who had undergone radical surgical resection and been performed immunohistochemical staining of four major mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) from March 2014 to December 2018 at Peking University Cancer Hospital were collected. One hundred and seventy-one patients showed mismatch repair-deficient (dMMR), and microsatellite instability of these patients were detected with polymerase chain reaction (PCR). Then, taken PCR results as the standard, PD-L1 was assessed using immunohistochemistry (IHC) in the MSI-H gastric cancers. Results: MSI-H (vs. MSI-L) in gastric cancers was associated with female gender, advanced age, gastric-antrum location, intestinal type, lesion diameter exceeding 5 cm, absence of lymph node metastasis and positive PD-L1 expression (P<0.05, respectively). Combined positive score (CPS) was an independent risk factor (P=0.026, HR=8.385, 95%CI=1.293-54.367). Although no relationship between PD-L1 expression pattern and prognosis was observed,"diffuse-pattern" of the PD-L1 expression was related to lymphatic-vascular invasion (P=0.007) and infiltration depth (P=0.04). Among the patients with MSI-H and PD-L1 positive gastric cancer, the patients who experienced recurrence or died all had the pattern of "diffuse" PD-L1 expression. Also, regarding the expression level and staining pattern of PD-L1, the metastasis lesion of lymph node had a high coincidence with primary site (P=0.45). Conclusions: MSI-H gastric cancer shows distinctive clinicopathological characteristics. The CPS can be used as a prognostic indicator in MSI-H gastric cancers, while the "diffuse-pattern" of PD-L1 expression could possibly be used as a prognostic indicator. The patients with advanced gastric cancer could obtain the expression level and staining pattern of PD-L1 using the biopsy material of metastatic lesions.

Clinical Exome Sequencing in B-Cell Ph-Negative ALL Patient Demonstrates Clonal Changes at Different Stages of the Disease

CONTEXT:A substantial number of patients with acute lymphoblastic leukemia (ALL) die from progressive disease after relapse that is frequently associated with clonal evolution. Clinical exome sequencing (CES) is a useful tool for mutation investigation, particularly in leukemic subclones during relapse. OBJECTIVE:The objective of this pilot study was to determine the specific genetic abnormalities associated with primary tumor comparing with normal hematopoietic tissue and to define clonal evolution patterns at relapse. DESIGN:CES (TruSightTM One Sequencing Panel) was performed on samples obtained from the patient with B-cell Ph-negative ALL at diagnosis, remission and relapse. SETTING:DNA was extracted from bone marrow samples according to modified salting out method. Libraries were pooled together and underwent two rounds of hybridization and capture, and additional quantification and size assessment. Between 21 and 26 million reads for each sample were obtained with a MiSeq (Illumina, USA), with a coverage of at least 20x for 97% of all sequences. More than 99% of reads passed quality and length control and were used in the analysis. De-multiplexing of indexed reads and the generation of FASTQ files were performed by the MiSeq system on-instrument software. The sequencing data, composed of 150 bp paired-end reads, were processed for MiSeq Reporter (Illumina), which is endowed with Burrows-Wheeler Aligner (BWA) for alignment on a reference sequence of hg19 and Genome Analysis Toolkit (GATK) for variant calling. Then, the Variant Call format (VCF) file was processed for analyzing on VariantStudio (Illumina) and wANNOVAR (Yang H. et al, 2015), which contain annotation databases, such as the ClinVar database, OMIM, the dbSNP database), the Polymorphism Phenotyping v2 database (Polyphen-2), and the Sorting Intolerant from Tolerant database (SIFT) and some others. PATIENTS OR OTHER PARTICIPANTS :A 27-year-old woman, who was admitted to the National Research Center for Hematology (Moscow, Russia) on March, 2017, presented with a three-month history of paleness and ossalgia. Common B-ALL (BII) ALL with complex karyotype and extramedullary lesions in ovaries, kidneys, intra-abdominal and peripheral lymph nodes has been diagnosed. Patient achieved complete remission (CR) after first induction therapy according to ALL-2016 protocol (ClinicalTrials.gov NCT03462095). After 16 months of CR during maintenance therapy (July, 2019) was diagnosed a relapse, which was refractory to multiple chemotherapy approaches and the patient died from the disease (January, 2020). RESULTS:Primary dataset analysis included more than 9000 gene variations for each of the three samples. Only clonal variations (at diagnosis) that are pathogenic either by the type of mutations (insertions (frameshift) and splice site mutations) or by prediction databases (PolyPhen-2, SIFT) were selected. As a result, about 70 variations were identified for each of the samples. Table 1 shows all clonal somatic mutations by which tumor tissue differs from normal hematopoietic tissue. At the time of diagnosis, a clone with monosomy of chromosome 3 was identified, that disappeared at CR and reappeared as a minor clone at relapse. Taking in consideration that the loss of one allele was caused by monosomy, we searched for pathogenic variations in genes localized on the chromosome 3 in order to identify genes inactivated according to Knudson's "Two-Hit" Theory of cancer causation (Knudson A., 1971). Out of 500 genes variations on chromosome 3, mutations in 5 genes according to prediction databases (PolyPhen-2, SIFT) were defined as pathogenic. All mutations were germinal. Moreover, four out of five mutations were homozygous. Table 2 shows the dynamics of pathogenic variations in genes localized on the chromosome 3 at different stages of the disease. The missense mutation ofCOL7A1gene (c.2791C&amp;gt; T), which was found in a small percentage (8%), was localized on the disappeared copy of chromosome 3, and its detection in this case was possible due to the presence of normal cells. CONCLUSIONS:There is an evident change in tumor clones at relapse: a major clone diagnosed inde novoB-cell ALL patient became minor at relapse. The data obtained from this analysis suggest that at the time of diagnosis, several clones are present in the tumor, and that most of the diagnosed pathogenic variations are not associated with oncogenesis and are germinal. Disclosures No relevant conflicts of interest to declare.

A Phase 2 Study of Odronextamab (REGN1979), a CD20 x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

A Phase 2 Study of Odronextamab (REGN1979), a CD20 x CD3 Bispecific Antibody, in Patients with Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma

Totality of Scientific Evidence in the Development of ABP 798, a Biosimilar to Rituximab

Background: ABP 798 is a proposed biosimilar to rituximab reference product (RP). Regulatory approval of biosimilars is based on a totality of evidence (TOE) approach which includes similarity in analytical characteristics (structural and functional), in mechanism of action (MoA) -clinical pharmacology, pharmacokinetics (PK), pharmacodynamics (PD), and in comparative clinical studies. Evidence from analytical, functional, clinical PK/PD, and efficacy and safety evaluations indicate that ABP 798 is similar to rituximab RP. Similarity of efficacy and safety in patients with non-Hodgkin lymphoma (NHL) was demonstrated in a randomized, double-blind, comparative clinical study in which the primary analysis was based on data from central, independent, and blinded assessments of disease and the sensitivity analysis was based on data using investigator assessments of disease. Here we present in vitro chemo synergy, preclinical in-vivo tumor efficacy data and show how the results of the sensitivity analysis using investigator assessments of the response rate from the NHL clinical study further add to the TOE supporting similarity of ABP 798 with the RP. Methods: In vitro synergy with chemotherapeutic agents was investigated by assessing the effect of docetaxel, gemcitabine, or doxorubicin with ABP 798 and rituximab RP in SU-DHL-6 cell lines and measured using the ATP-based cell viability endpoint (ATPLite). In vivo efficacy was assessed by evaluating the anti-tumor activity of ABP 798 and rituximab RP in NHL xenograft models in NOD/SCID mice using CD20-expressing RL and Raji cell lines. A sensitivity analysis was conducted to assess the robustness of the results of the primary efficacy endpoint of the proportion of patients with the best overall response of complete response, partial response, or unconfirmed complete response (ORR) in the NHL comparative clinical study using the investigator's assessment of disease on the full analysis set. Waterfall plots of the maximum percent reduction in the sum of the products of the greatest diameters (SPD) for index nodal lesions based on both the central, independent, blinded assessment of disease and the investigator's assessment of disease were used. Results: In vitro study results demonstrated synergistic activity of the combination of docetaxel and ABP 798 or the RP (synergy score = 6.35±0.69 [with ABP 798]; 6.79±0.12 [with RP]). In contrast, combinations with gemcitabine (synergy score = 2.68±0.20 [with ABP 798] and 2.54±0.29 [with RP]) or doxorubicin (synergy score = 1.95±0.56 [with ABP 79]) and 3.23±0.53 [with RP]) were additive. In RL cell lines, ABP 798 inhibited tumor growth similarly to rituximab RP, with no statistical difference between dose groups at 3 and 30 mg/kg (p = 0.951 and p = 0.996, respectively). In Raji cells, ABP 798 and rituximab RP significantly and similarly inhibited tumor growth when compared to an IgG1 isotype control (p &amp;lt; 0.001 for 3 and 30 µg/kg doses). ABP 798, at both dose levels, inhibited tumor growth similarly to rituximab RP by 27-41%, with no statistical difference. In the NHL comparative clinical study, risk difference (RD) of ORR with 1-sided 95% lower and upper confidence limits from the adjusted linear model was 7.7% (-3.2%, 18.6%) using central, blinded, independent assessments of the modified full analysis set based on randomized treatment assignment. The sensitivity analysis using investigator assessments of disease of the full analysis set of all randomized subjects based on the randomized treatment assignment received was RD = 0.5% (-7.8%, 8.8%). Waterfall plots of the maximum percent reduction in the SPD for index nodal lesions further demonstrate similarity of efficacy with central or local assessments of disease. Conclusions: In vitro and in vivo preclinical studies demonstrated chemo synergy and in vivo tumor efficacy. The sensitivity analysis of ORR using local assessments in the NHL comparative clinical study was consistent with results from the primary efficacy analysis; the maximum percent reduction in index nodal lesions was similar for central and local assessments of disease. These results further support that ABP 798 is similar to the RP across a range of efficacy evaluations as well as primary and secondary mechanisms of action and add additional supporting data to the TOE. Disclosures Niederwieser: Novartis: Speakers Bureau; Cellectis: Membership on an entity's Board of Directors or advisory committees; Daiichi: Research Funding; Amgen: Speakers Bureau. Hamm:Amgen: Consultancy. Cobb:Amgen: Consultancy. Thway:Amgen: Current Employment, Current equity holder in publicly-traded company. Forsyth:Amgen: Consultancy; Janssen Pharmaceuticals Australia: Honoraria, Membership on an entity's Board of Directors or advisory committees. Tucci:Amgen: Consultancy. Delwail:Amgen: Consultancy. Hajek:Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria; PharmaMar: Consultancy, Honoraria; Oncopeptides: Consultancy. Hanes:Amgen: Current Employment, Current equity holder in publicly-traded company.

Abstract PO-25: CLR 131 demonstrates 100% overall response rate in relapsed or refractory lymphoplasmacytic lymphoma (LPL)/Waldenstrom's macroglobulinemia (WM): initial results from ongoing phase 2 trial, CLOVER-1 study

Abstract Introduction: CLR 131 (I-131-CLR1404) is a novel targeted radiotherapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Based on preclinical and clinical experience and the radiosensitivity of MM, CLR 131 is being examined in relapsed or refractory B-cell malignancies through an open-label, phase 2 trial, CLOVER-1 (NCT02952508); initial results in pts with LPL/WM are reported here. Procedures: The primary objective of this study is to determine the efficacy and safety of CLR 131 in select B-cell malignancies. Eligibility criteria include adult pts with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Wadenstrom's macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), or diffuse large B-cell lymphoma (DLBCL). Pts with LPL/WM must have received at least two prior treatment regimens unless ineligible to receive standard agents and have measurable disease: either a nodal lesion &amp;gt; 15 mm, an extranodal lesion &amp;gt; 10 mm, or measurable IgM. Prior external beam radiation therapy is allowed (&amp;lt; 20% of total marrow irradiated). CLR 131 is administered intravenously up to 30 minutes at total body doses (TBD) of &amp;lt;50 mCi, ~50 mCi, and ~75 mCi. Adverse events (AEs) are graded by NCI-CTCAE v4.03; responses are assessed by the 2012 WM Criteria for Response Assessment. Results: Four pts with LPL/WM have been enrolled in the study with data presented as of 1 Mar 2020. The median age was 70 (range 54-81) and included 2 females and 2 males who had a median of two prior regimens (range 1-5). The overall response rate was 100%, including one pt with a complete response, one pt with a partial response, and one pt with a minimal response; one pt remains under evaluation. The primary treatment-emergent AEs across all doses in pts with LPL/WM included neutropenia, thrombocytopenia, nausea, fatigue, anemia, and decreased white blood cell count, in line with experience to date with CLR 131 in other B-cell malignancies. Median time to resolution of cytopenias was 21 days. One pt received two cycles of CLR 131 with a TBD of ~100 mCi. The pt was determined to be a partial response 43 days post initial dose and a complete response at approximately 200 days; this was confirmed radiologically 406 days post initial dose. The duration of response for this pt is currently at 25 months and is ongoing. One pt received ~ 50 mCi CLR 131 and saw an 89% decrease in IgM at 64 days post infusion. One pt received ~ 75 mCi CLR 131 and had a 45% decrease in IgM at 64 days post infusion. One pt received two cycles of CLR 131 with a TBD of ~150 mCi, experiencing a 48% reduction in IgM to date and has not yet completed the evaluation period. Conclusions: CLR 131 is a unique, first-in-class targeted radiotherapeutic in development for multiple B-cell hematologic malignancies. The observed positive signals of efficacy and safety from this preliminary data in relapsed or refractory LPL/WM pts is encouraging and will be further explored. Citation Format: Sikander Ailawadhi, Jarrod Longcor, Kate Oliver, Igor D. Grachev. CLR 131 demonstrates 100% overall response rate in relapsed or refractory lymphoplasmacytic lymphoma (LPL)/Waldenstrom's macroglobulinemia (WM): initial results from ongoing phase 2 trial, CLOVER-1 study [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-25.

Heterogeneity of CEACAM5 in breast cancer.

CEACAM5 is overexpressed in many primary breast carcinomas. However, the exact role of CEACAM5 in breast cancer tumorigenesis remains unresolved. Here, we examined a repository of 110 cryopreserved primary breast carcinomas by immunohistochemistry to assess the distribution of CEACAM5 in tumor subtypes. The majority of estrogen receptor-positive and HER2-overexpressing tumors were CEACAM5-positive, whereas most of Triple-negative tumors were negative. Assessing sample sets of paired primary breast cancers and corresponding lymph node lesions from a total of 59 patients revealed a high correlation between primary tumor and lymph node with regard to CEACAM5-status. However, a notable subset of sample sets demonstrated intratumoral heterogeneity in the primary tumor, the metastatic lesion or both, suggesting that both CEACAM5-positive and –negative cells can play a role in tumor dissemination. When examining the consequence of expression of CEACAM5 in breast cancer cell lines in culture assays we found that CEACAM5-expressing cells were less invasive. In survival analysis, using cohort studies of breast cancer, expression of CEACAM5 predicted different clinical outcomes depending on molecular subtypes. Altogether, our analysis suggests that CEACAM5 plays a context-dependent role in breast cancer that warrants further investigation.

PET/CT and contrast-enhanced CT: making a difference in assessment and staging of patients with lymphoma

BackgroundThe aim of this study is to evaluate the diagnostic performance of contrast-enhanced computed tomography (CECT) and 2-[Fluorine-18] fluoro-2-deoxy-d-glucose positron emission tomography combined to computed tomography (18 F-FDG PET/CT) in assessment of lymphoma.MethodsHundred patients, pathologically proven as lymphoma, were evaluated by CECT and 18F-FDG PET/CT for initial assessment and staging of the disease. The number of lesions and the disease stage detected by each modality was calculated and further analyzed to be compared.Results18F-FDG PET/CT diagnosed a total number of 545 lymphoma involved regions with sensitivity 96.6%, specificity 98.8%, and accuracy 99% that was higher than CECT which diagnosed a total number of 439 lymphomatous regions with sensitivity 87.5%, specificity 85.7%, and accuracy 88%. Discordant staging by both modalities was found in 23% of the patients. Lymphoma was upstaged by PET/CT in 17% of the patients; with major changes in 12% of them and downstaged in 6% of the patients.Conclusion18F-FDG PET/CT scan has a better diagnostic performance, represented by sensitivity, specificity, and accuracy, than CECT scan in the initial assessment of lymphoma regarding its nodal and extra-nodal lesions that could lead to alteration of disease staging which in turn markedly affecting the decision of treatment regimens.

Fine Needle Aspiration Cytology (FNAC) for Chinese Patients With Acral and Cutaneous Melanoma: Accuracy and Safety Analysis From a Single Institution.

This study aimed to investigate the accuracy and safety of fine-needle aspiration cytology (FNAC) in Chinese patients with acral and cutaneous melanoma, and also to evaluate the influencing factors and their impact on prognosis. Data of 128 patients with stage 0–III acral and cutaneous melanoma treated in Fudan University Shanghai Cancer Center from 2009 to 2016 were collected from a prospective database. Further, 128 patients who did not undergo FNAC but had similar parameters were recruited as the matched group. Clinical features, FNAC status, and recurrence or metastasis status of patients were analyzed for overall survival (OS), melanoma-specific survival (MSS), recurrence-free survival (RFS), and metastasis-free survival (MFS). Of the 128 patients with FNAC, 5.5% (7/128) had a negative cytological diagnosis, 12.2% (5/41) had primary lesions, and 2.3% (2/87) had lesions in lymph nodes. Tumor thickness, status of ulceration, and subtype were not associated with accuracy for both primary and lymph node FNAC. With a median follow-up of 40 months in all patients, 55 had melanoma-specific death; the median OS and MSS were 95 months and 104 months, respectively. Patients with FNAC had significantly worse OS. Tumor progression occurred in 130 patients. The survival analysis revealed differences in OS and disease-free survival between the two groups. FNAC impacted patients' RFS and MFS; the difference in survival curves of RFS and MFS was also statistically significant. FNAC on primary or superficial lymphatic lesions was a good diagnostic tool for Chinese patients with acral and cutaneous melanoma, but it adversely impacted prognosis.

Artificial intelligence-based detection of lymph node metastases by PET/CT predicts prostate cancer-specific survival.

Lymph node metastases are a key prognostic factor in prostate cancer (PCa), but detecting lymph node lesions from PET/CT images is a subjective process resulting in inter-reader variability. Artificial intelligence (AI)-based methods can provide an objective image analysis. We aimed at developing and validating an AI-based tool for detection of lymph node lesions. A group of 399 patients with biopsy-proven PCa who had undergone 18 F-choline PET/CT for staging prior to treatment were used to train (n=319) and test (n=80) the AI-based tool. The tool consisted of convolutional neural networks using complete PET/CT scans as inputs. In the test set, the AI-based lymph node detections were compared to those of two independent readers. The association with PCa-specific survival was investigated. The AI-based tool detected more lymph node lesions than Reader B (98 vs. 87/117; p=.045) using Reader A as reference. AI-based tool and Reader A showed similar performance (90 vs. 87/111; p=.63) using Reader B as reference. The number of lymph node lesions detected by the AI-based tool, PSA, and curative treatment was significantly associated with PCa-specific survival. This study shows the feasibility of using an AI-based tool for automated and objective interpretation of PET/CT images that can provide assessments of lymph node lesions comparable with that of experienced readers and prognostic information in PCa patients.

Rectal clear cell sarcoma-a case report

Gastrointestinal clear cell sarcomas (GICCSs) are malignant mesenchymal tumour that occur in the wall of gastrointestinal tract, mostly in the ileum and rarely in the rectum. These tumours are highly invasive, and often have metastasized via the lymphatic system or bloodstream by the time of diagnosis. In this case, the patient was admitted for gastric fundus mass, who was subsequently found and confirmed by biopsy as clear cell sarcoma of rectum. Computed tomography (CT) and magnetic resonance imaging (MRI) showed multiple metastatic lesions in lymph node, lung, liver and bone. Furthermore, energy spectrum CT was used to confirm that the nature of gastric fundus mass and rectal lesion were consistent. So, this case may be multiple clear cell sarcomas in the rectum and stomach or clear cell sarcoma in the rectum with gastric fundus metastasis. Unfortunately, after several days of immunotherapy, the patient died due to abnormal liver function. At present, GICCS mainly relies on surgical resection, and the effect of radiotherapy and chemotherapy is not good. Therefore, how to find lesions as earlier as possible and make accurate diagnosis is particularly important. CT and MRI are essential examinations in the diagnosis of tumors. Whether they are helpful for the diagnosis of GICCS is the focus of our attention.

Clinic analysis of cervical lymph node lesions in children

Objective:Explore the clinical features of cervical lymph node lesions in children with different pathological types, and provide help for the early diagnosis of the disease. Method:The data of 73 children with cervical lymph node disease diagnosed by lymph node biopsy were collected, and the gender composition, age distribution, lymph node characteristics and clinical manifestations of children with different pathological types were analyzed. Result:Among the 73 children with cervical lymph node disease, the incidence of male patients in the benign disease group was less than that of female ones, and the incidence of male patients in the malignant disease group was greater than that of female ones, the difference in gender composition between the two groups was statistically significant（P<0.05）. The benign disease group had the largest proportion in the school-age period（27.4%）, and the malignant disease group had a larger proportion in the preschool period（21.9%） and school-age period（20.5%）, both groups had a relatively smaller proportion in the infant and adolescent period, the difference in age distribution within the group was statistically significant（P<0.01）. Among the various pathological types, the proportion of 73 children with lymph node inflammatory reactive hyperplasia was the largest, 35.6%（26/73）, and was mainly at school age; the second was Hodgkin's lymphoma, accounting for 20.5%（15/73）, mainly in the preschool and school age. The average maximum transverse diameter of lymph nodes in the malignant disease group was greater than that in the benign disease group（P<0.05）. The lymph nodes in the benign disease group were mainly distributed in areas Ⅰ, Ⅱ, and Ⅲ, and the lymph nodes in the malignant disease group were mainly distributed in areas Ⅱ, Ⅲ, Ⅳ, and Ⅴ, there was a statistically significant difference in the distribution of enlarged lymph nodes between the two groups（P<0.01）. Conclusion:Different pathological types of cervical lymph node lesions in children are different in gender composition, age distribution, lymph node size and distribution, and cervical lymph node lesions in children have their own characteristics.

A novel CAD system to automatically detect cancerous lung nodules using wavelet transform and SVM

A novel cancerous nodules detection algorithm for computed tomography images (CT-images) is presented in this paper. CT-images are large size images with high resolution. In some cases, number of cancerous lung nodule lesions may missed by the radiologist due to fatigue. A CAD system that is proposed in this paper can help the radiologist in detecting cancerous nodules in CT- images. The proposed algorithm is divided to four stages. In the first stage, an enhancement algorithm is implement to highlight the suspicious regions. Then in the second stage, the region of interest will be detected. The adaptive SVM and wavelet transform techniques are used to reduce the detected false positive regions. This algorithm is evaluated using 60 cases (normal and cancerous cases), and it shows a high sensitivity in detecting the cancerous lung nodules with TP ration 94.5% and with FP ratio 7 cluster/image.