Cancer-related Fatigue and the Additive Effect of Treatment in the Context of Lymphoma: An Analysis of the Lymphoma Coalition's 2022 Global Patient Survey.

Cancer-related fatigue (CRF) continues to be a challenging phenomenon that is often under-reported and poorly understood. With etiologies in both disease and treatment manifesting as a symptom and a side effect respectively, CRF is highly incident and presents a significant clinical problem that impacts survivorship. We conducted a survey to ascertain the patient reported incidence of symptoms and side effects for people with lymphoma or chronic lymphocytic leukemia. We found that CRF was enhanced in those who received more intense therapies that coincided with more aggressive lymphoma subtypes. These data illuminate an unmet need among patients with lymphoma and provides an opportunity to further refine treatment regimens to reduce the burden of CRF in this vulnerable population. SIGNIFICANCE: CRF is a highly incident phenomenon in lymphoma that can be ascribed to a combination of causes. We have demonstrated substantial variability across various subtypes of lymphoma and have estimated that nearly half of the reported fatigue comes from treatment. Increased screening for and monitoring of fatigue will yield favorable health-related quality of life that will benefit health technology assessment activities and yield improved outcomes for patients.

Prognostic Value of CSF IL-10 at Early Assessment of Induction Chemotherapy in Primary CNS Lymphomas: A LOC Network Study.

OBJECTIVES: Despite a high response rate at the first evaluation during induction chemotherapy, the risk of early relapse remains high and unpredictable in primary CNS lymphomas (PCSNLs). We aimed to assess the prognostic value of early IL-10 levels in CSF (e-IL-10) after 2 months of induction chemotherapy. METHODS: We retrospectively selected from the LOC (Lymphomes Oculo-Cérébraux) network database patients with PCSNLs who had complete or partial response at the 2-month evaluation of a high-dose methotrexate-based first-line chemotherapy for whom e-IL-10 was available. RESULTS: Thirty patients (median age: 62 years, brain involvement in 30/30, CSF involvement in 10/30, median baseline CSF IL-10: 27.5 pg/mL) met the selection criteria. e-IL-10 was undetectable in 22 patients and detectable in 8 patients. At the end of induction treatment, 7 of 8 and 4 of 22 of the patients with detectable and undetectable e-IL-10 had experienced progressive disease, respectively (p = 0.001, OR: 26.8, 95% CI 2-1,478). The median progression-free survival times were 5.8 months (95% CI 2.8-8.8) and 28.7 months (95% CI 13.4-43.9) in the groups with detectable and undetectable e-IL-10, respectively (p < 0.001). DISCUSSION: Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.

Long-term survival for lymphoid neoplasms and national health expenditure (EUROCARE-6): a retrospective, population-based study.

BACKGROUND: Management of lymphoid malignancies requires substantial health system resources. Total national health expenditure might influence population-based lymphoid malignancy survival. We studied the long-term survival of patients with 12 lymphoid malignancy types and examined whether different levels of national health expenditure might explain differences in lymphoid malignancy prognosis between European countries and regions. METHODS: For this observational, retrospective, population-based study, we analysed the EUROCARE-6 dataset of patients aged 15 or older diagnosed between 2001 and 2013 with one of 12 lymphoid malignancies defined according to International Classification of Disease for Oncology (third edition) and WHO classification, and followed up to 2014 (Jan 1, 2001-Dec 31, 2014). Countries were classified according to their mean total national health expenditure quartile in 2001-13. For each lymphoid malignancy, 5-year and 10-year age-standardised relative survival (ASRS) was calculated using the period approach. Generalised linear models indicated the effects of age at diagnosis, gender, and total national health expenditure on the relative excess risk of death (RER). FINDINGS: 82 cancer registries (61 regional and 21 national) from 27 European countries provided data eligible for 10-year survival estimates comprising 890 730 lymphoid malignancy cases diagnosed in 2001-13. Median follow-up time was 13 years (IQR 13-14). Of the 12 lymphoid malignancies, the 10-year ASRS in Europe was highest for hairy cell leukaemia (82·6% [95% CI 78·9-86·5) and Hodgkin lymphoma (79·3% [78·6-79·9]) and lowest for plasma cell neoplasms (29·5% [28·9-30·0]). RER increased with age at diagnosis, particularly from 55-64 years to 75 years or older, for all lymphoid malignancies. Women had higher ASRS than men for all lymphoid malignancies, except for precursor B, T, or natural killer cell, or not-otherwise specified lymphoblastic lymphoma or leukaemia. 10-year ASRS for each lymphoid malignancy was higher (and the RER lower) in countries in the highest national health expenditure quartile than in countries in the lowest quartile, with a decreasing pattern through quartiles for many lymphoid malignancies. 10-year ASRS for non-Hodgkin lymphoma, the most representative class for lymphoid malignancies based on the number of incident cases, was 59·3% (95% CI 58·7-60·0) in the first quartile, 57·6% (55·2-58·7) in the second quartile, 55·4% (54·3-56·5) in the third quartile, and 44·7% (43·6-45·8) in the fourth quartile; with reference to the European mean, the RER was 0·80 (95% CI 0·79-0·82) in the first, 0·91 (0·90-0·93) in the second, 0·94 (0·92-0·96) in the third, and 1·45 (1·42-1·48) in the fourth quartiles. INTERPRETATION: Total national health expenditure is associated with geographical inequalities in lymphoid malignancy prognosis. Policy decisions on allocating economic resources and implementing evidence-based models of care are needed to reduce these differences. FUNDING: Italian Ministry of Health, European Commission, Estonian Research Council.

Sociodemographic factors and Child Opportunity Index disparities associated with missed care opportunities in pediatric patients with lymphoma and leukemia referred for FDG-PET/CT.

BACKGROUND: Little data exists on the association of missed care opportunities (MCOs) in children referred for nuclear medicine/nuclear oncology imaging examinations and socioeconomic disparities. OBJECTIVE: To determine the prevalence of MCOs in children with lymphoma/leukemia scheduled for fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and the impact of sociodemographic factors and Child Opportunity Index (COI). MATERIALS AND METHODS: Retrospective analysis of MCOs in children with lymphoma/leukemia scheduled for FDG-PET/CT (2012 to 2022) was performed. In univariate analysis, patient, neighborhood, and appointment data were assessed across MCOs and completed appointments. Logistic regression evaluated independent effects of patient-, neighborhood-, and appointment-level factors with MCOs. Two-sided P-value < .05 was considered statistically significant. RESULTS: In 643 FDG-PET/CT appointments (n = 293 patients; median age 15 years (IQR 11.0-17.0 years); 37.9% female), there were 20 MCOs (3.1%) involving 16 patients. Only 8.2% appointments involved Black/African American non-Hispanic/Latino patients, yet they made up a quarter of total MCOs. Patients living in neighborhoods with very low or low COI experienced significantly higher MCOs versus zip codes with very high COI (6.9% vs. 0.8%; P = 0.02). Logistic regression revealed significantly increased likelihood of MCOs for patients aged 18 to 21 [odds ratio (OR) 4.50; 95% CI 1.53-13.27; P = 0.007], Black/African American non-Hispanic/Latino (OR 3.20; 95% CI 1.08-9.49; P = 0.04), zip codes with very low or low COI (OR 9.60; 95% CI 1.24-74.30; P = 0.03), and unknown insurance status. CONCLUSION: Children with lymphoma/leukemia, living in zip codes with very low or low COI, and who identified as Black/African American non-Hispanic/Latino experienced more MCOs. Our study supports the need to address intersecting sociodemographic, neighborhood, and health system factors that will improve equitable access to necessary healthcare imaging for children.

Assessment of left and right ventricular systolic function in dogs with multicentric lymphoma.

OBJECTIVE: Myocardial dysfunction in cardio-oncology is generally thought to be related to the cardiotoxicity of chemotherapy treatment. However, it is known that some tumors have direct effects on myocardial function. These effects have already been studied in man, but there are no publications of these of the effects in dogs. Novel advanced echocardiographic techniques may allow early detection of myocardial dysfunction when compared to conventional echocardiographic techniques. This study aims to assess myocardial systolic function in dogs with multicentric lymphoma prior to initiation of chemotherapy. ANIMALS: Fifteen dogs with multicentric lymphoma and nineteen healthy dogs. METHODS: Case-control study. Dogs with multicentric lymphoma and healthy control dogs underwent physical examination, electrocardiography, systolic blood pressure measurement, standard and speckle tracking echocardiography to assess biventricular systolic function. RESULTS: There were no differences between groups in terms of ejection fraction, fractional shortening, left ventricular systolic and diastolic diameter, tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and fractional area change of the right ventricle (RV). However, there was a reduction in the values of global circumferential strain (p = 0.0003), RV strain (p = 0.01) and RV tissue motion annular displacement (p < 0.05) in the dogs with lymphoma when compared to the control group. CONCLUSIONS: Speckle tracking techniques appear to demonstrate early systolic dysfunction, primarily affecting the RV, in dogs with lymphoma prior to chemotherapy treatment.

Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold: a retrospective assessment of plan robustness.

PURPOSE/BACKGROUND: The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment.  Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated. RESULTS: The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs. CONCLUSION: PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.

Assessment of Y chromosome copy number alterations in non-neoplastic and neoplastic leukocytes of male dogs.

The loss of the Y chromosome (ChrY), also known as LOY, is a common genetic alteration observed in men. It occurs in non-neoplastic cells as an age-related change as well as in neoplastic cells of various cancer types. While well-documented in humans, LOY has not been extensively studied in non-human mammals. In this study, we developed simple digital PCR-based assays to assess the copy number of ChrY relative to the X chromosome (ChrX) and chromosome 8 (Chr8) to evaluate ChrY numerical alterations in male canine DNA specimens. Using these assays, we analyzed non-neoplastic leukocytes from 162 male dogs without hematopoietic neoplasia to investigate the occurrence of age-related LOY in non-neoplastic leukocytes. Additionally, we examined 101 tumor DNA specimens obtained from male dogs diagnosed with various types of lymphoma and leukemia to determine whether copy number alterations of the ChrY occur in canine hematopoietic cancers. Analysis of the 162 non-neoplastic leukocyte DNA specimens from male dogs of varying ages revealed a consistent ∼1:1 ChrY:ChrX ratio. This suggests that age-related LOY in non-neoplastic leukocytes is rare or absent in dogs. Conversely, a decreased or increased ChrY:ChrX ratio was detected in canine neoplastic leukocytes at varying frequencies across different canine hematopoietic malignancies (P = 0.01, Fisher's exact test). Notably, a higher incidence of LOY was observed in more aggressive cancer types. To determine if this relative LOY to ChrX was caused by changes in ChrY or ChrX, we further analyzed their relative copy numbers using Chr8 as a reference. Loss of ChrX relative to Chr8 was found in 21% (9/41) of B-cell lymphomas and 6% (1/18) of non-T-zone/high-grade T-cell lymphomas. In contrast, a subset (29%, 4/14) of T-cell chronic lymphocytic leukemia showed gain of ChrX relative to Chr8. Notably, no relative LOY to Chr8 was detected indolent hematopoietic cancers such as T-zone lymphoma (0/9) and chronic lymphocytic leukemia of B-cell (0/11) and T-cell origins (0/14). However, relative LOY to Chr8 was present in more aggressive canine hematopoietic cancers, with incidences of 24% (10/41) in B-cell lymphoma, 44% (8/18) in non-T-zone/high-grade T-cell lymphoma, and 75% (6/8) in acute leukemia. This study highlights both similarities and differences in LOY between human and canine non-neoplastic and neoplastic leukocytes. It underscores the need for further research into the role of ChrY in canine health and disease, as well as the significance of LOY across various species.

Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy.

BACKGROUND: Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities. AIMS: To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation. METHODS AND RESULTS: The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m2 /day). CONCLUSION: Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.

Assessment of the three-test genetic toxicology battery for groundwater metabolites.

The two-test in vitro battery for genotoxicity testing (Ames and micronucleus) has in the majority of cases replaced the three-test battery (as two-test plus mammalian cell gene mutation assay) for the routine testing of chemicals, pharmaceuticals, cosmetics, and agrochemical metabolites originating from food and feed as well as from water treatment. The guidance for testing agrochemical groundwater metabolites, however, still relies on the three-test battery. Data collated in this study from 18 plant protection and related materials highlights the disparity between the often negative Ames and in vitro chromosome aberration data and frequently positive in vitro mammalian cell gene mutation assays. Sixteen of the 18 collated materials with complete datasets were Ames negative, and overall had negative outcomes in in vitro chromosome damage tests (weight of evidence from multiple tests). Mammalian cell gene mutation assays (HPRT and/or mouse lymphoma assay (MLA)) were positive in at least one test for every material with this data. Where both MLA and HPRT tests were performed on the same material, the HPRT seemed to give fewer positive responses. In vivo follow-up tests included combinations of comet assays, unscheduled DNA synthesis, and transgenic rodent gene mutation assays, all gave negative outcomes. The inclusion of mammalian cell gene mutation assays in a three-test battery for groundwater metabolites is therefore not justified and leads to unnecessary in vivo follow-up testing.

Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Assessment of Bcl-xL, TAX, and HBZ Gene Expression in Adult T cell Leukemia/Lymphoma Patients.

Adult T cell leukemia/lymphoma is a malignancy with a poor prognosis caused by human T lymphocyte virus type 1 (HTLV-1) infection. Tax and HBZ are two major viral proteins that may be involved in oncogenesis by disrupting apoptosis. Because Bcl-xL plays an integral role in the anti-apoptotic pathway, this study examines the interaction between host apoptosis and oncoproteins. We investigated 37 HTLV-1-infected individuals, including 18 asymptomatic and 19 adult T cell leukemia/lymphoma (ATLL) subjects. mRNA was extracted and converted to cDNA from peripheral blood mononuclear cells, and then gene expression was determined using TaqMan q-PCR. Moreover, the HTLV-1 proviral load (PVL) was also measured using a commercial absolute quantification kit (Novin Gene, Iran). Data analysis revealed that the mean of TAX, HBZ, and PVL was significantly higher among the study groups (ATLL and carrier groups p = .003, p = .000, and p = .002 respectively). There was no statistical difference in Bcl-xL gene expression between the study groups (p = .323). It is proposed that this anti-apoptotic pathway may not be directly involved in the development of ATLL lymphoma. Bcl-xL, TAX, HBZ gene expression, and PVL can be utilized as prognostic markers.

The global burden of lymphoma: estimates from the Global Burden of Disease 2019 study.

OBJECTIVES: The aim of this study was to describe the global trends in the burden of lymphoma from 1990 to 2019. STUDY DESIGN: The data used in this study were from the Global Burden of Disease 2019 study. METHODS: This study described the age-standardised rates of incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs) of lymphoma (non-Hodgkin and Hodgkin's lymphoma, NHL and HL, respectively) annually from 1990 to 2019, stratified by sociodemographic index (SDI) and 21 world regions. The estimated annual percentage changes in these indexes were calculated. RESULTS: In 2019, the age-standardised rates of HL per 100,000 population were lower than those of NHL in terms of incidence (1.1 vs 6.7 per 100,000 person-years, respectively) and prevalence (0.3 vs 5.7 per 100,000 person-years, respectively) but not mortality (21.6 vs 3.2 per 100,000 person-years, respectively). From 1999 to 2019, the global incidence of HL decreased and the incidence of NHL increased, and the prevalence of both HL and NHL increased, but the mortality rates decreased. When stratified by SDI, the incidence of HL decreased in all but middle-SDI regions, the mortality rate of HL decreased in all regions, and both the incidence and mortality rate of NHL increased in all but high-SDI regions. The prevalence of HL and NHL increased in all SDI regions, especially in middle-SDI regions. YLLs and DALYs of HL in all SDI regions and those of NHL in high-SDI regions decreased. YLDs slightly increased in middle- to high-SDI regions. CONCLUSIONS: Lymphoma remains a major public health issue, and better prevention, precise identification, and promising treatments are vitally important.

Improved early outcome prediction by MRI-based 3D tumor volume assessment in patients with CNS lymphomas.

BACKGROUND: Central nervous system lymphomas (CNSL) display remarkable clinical heterogeneity, yet accurate prediction of outcomes remains challenging. The IPCG criteria are widely used in routine practice for the assessment of treatment response. However, the value of the IPCG criteria for ultimate outcome prediction is largely unclear, mainly due to the uncertainty in delineating complete from partial responses during and after treatment. METHODS: We explored various MRI features including semi-automated 3D tumor volume measurements at different disease milestones and their association with survival in 93 CNSL patients undergoing curative-intent treatment. RESULTS: At diagnosis, patients with more than 3 lymphoma lesions, periventricular involvement, and high 3D tumor volumes showed significantly unfavorable PFS and OS. At first interim MRI during treatment, the IPCG criteria failed to discriminate outcomes in responding patients. Therefore, we randomized these patients into training and validation cohorts to investigate whether 3D tumor volumetry could improve outcome prediction. We identified a 3D tumor volume reduction of ≥97% as the optimal threshold for risk stratification (=3D early response, 3D_ER). Applied to the validation cohort, patients achieving 3D_ER had significantly superior outcomes. In multivariate analyses, 3D_ER was independently prognostic of PFS and OS. Finally, we leveraged prognostic information from 3D MRI features and circulating biomarkers to build a composite metric that further improved outcome prediction in CNSL. CONCLUSIONS: We developed semi-automated 3D tumor volume measurements as strong and independent early predictors of clinical outcomes in CNSL patients. These radiologic features could help improve risk stratification and help guide future treatment approaches.

Subcutaneous panniculitis-like T-cell lymphoma: Morphological, immunophenotypical and clonality assessment in six cats.

BACKGROUND: Primary cutaneous lymphoma represents 0.2%-3% of all feline lymphomas, with nonepitheliotropic lymphomas being the most common. In humans and dogs, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a primary nonepitheliotropic lymphoma with a T-cell phenotype developing in the subcutis and often mimicking inflammation. OBJECTIVE: The aim of this report is to describe pathological, phenotypical and clonal features of SPTCL in cats. ANIMALS: Six cats with SPTCL were included in this study. MATERIALS AND METHODS: Skin biopsies were formalin-fixed, routinely processed and stained. Histological and immunohistochemical investigation for anti-CD18, CD204, CD79a, CD20, CD3, FeLVp27and FeLVgp70 and clonality assessment were performed. RESULTS: Four male and two female domestic shorthair cats, mean age 11.2 years, developed SPTCL in the abdominal (three), inguinal (two) and thoracic (one) regions. Variably pleomorphic neoplastic lymphoid cells were present in the panniculus in percentages, expanding the septa (six of six) and extending into fat lobules in one of six cats. Tumours were associated with elevated numbers of neutrophils (five of six), lesser macrophages (six of six) and variable necrosis (six of six). Neoplastic cells expressed CD3+ (six of six), with clonal T-cell receptor rearrangement detected in five of six cats. CONCLUSIONS AND CLINICAL RELEVANCE: This is the first description of SPTCL in cats. Lesions can be confused with panniculitis, leading to delay in diagnosis and therapy. Awareness of this neoplastic disease is relevant to avoid misdiagnoses and to gain greater knowledge about the disease in cats.

qRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes-An improved method for assessment of tumor stage and prognosis.

One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.

The diagnostic value of dual-layer CT in the assessment of lymph nodes in lymphoma patients with PET/CT as a reference standard.

This study aimed to evaluate the diagnostic performances of dual-layer CT (DLCT) for the identification of positive lymph nodes (LNs) in patients with lymphoma and retrospectively included 1165 LNs obtained by biopsy from 78 patients with histologically proven lymphoma, who underwent both pretreatment DLCT and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). According to 18F-FDG PET/CT findings as a reference standard, cases were categorized into the LN-negative and LN-positive groups. LNs were then randomly divided at a ratio of 7:3 into the training (n = 809) and validation (n = 356) cohorts. The patients' clinical characteristics and quantitative parameters including spectral curve slope (λHU), iodine concentration (IC) on arterial phase (AP) and venous phase (VP) images were compared between the LN-negative and LN-positive groups using Chi-square test, t-test or Mann-Whitney U test for categorical variables or quantitative parameters. Multivariate logistic regression analysis with tenfold cross-validation was performed to establish the most efficient predictive model in the training cohort. The area under the curve (AUC) was used to evaluate the diagnostic value of the predictive model, and differences in AUC were determined by the DeLong test. Moreover, the predictive model was validated in the validation cohort. Repeatability analysis was performed for LNs using intraclass correlation coefficients (ICCs). In the training cohort, long diameter (LD) had the highest AUC as an independent factors compared to other parameter in differentiating LN positivity from LN negativity (p = 0.006 to p < 0.001), and the AUC of predictive model jointly involving LD and λHU-AP was significantly elevated (AUC of 0.816, p < 0.001). While the AUC of predictive model in the validation cohort was 0.786. Good to excellent repeatability was observed for all parameters (ICC > 0.75). The combination of DLCT with morphological and functional parameters may represent a potential imaging biomarker for detecting LN positivity in lymphoma.