Erythropoietin Treatment in Advanced Multiple Myeloma Is Associated with Improved Immunological Functions: Could It Be Beneficial in Early Disease?.

Abstract Erythropoietin (Epo), the main growth regulator of erythropoiesis, is being used to treat anemias associated with renal disease and malignancies. We have previously observed prolonged survival of patients with advanced multiple myeloma (MM) who were treated with recombinant human Epo (rHuEpo) (Mittelman et al, Eur J Haematol2004:72:155). Further studies on murine MM models confirmed this observation and suggested that Epo has an anti-MM immunomodulatory effect (Mittelman et al. Proc Natl Acad Sci USA2001:98:5181; Katz et al. Acta Haematol2005:114:177). We have reported (ASH 2004) preliminary results showing that the rHuEpo-treated MM patients acquired improved immunological functions. We have since then extended the numbers of patients and the range of immunological functions tested. Here, we show that rHuEpo, prescribed for anemia in patients with advanced MM (Durie and Salmon Stage 2–3), is associated with effects on a variety of immunological parameters and functions, as presented in the table. Compared with non rHuEpo-treated MM patients, who demonstrated immunological abnormalities, rHuEpo-treated MM patients resumed normalization of the CD4:CD8 cell ratio, enhanced T-cell (both CD8 and CD4) PHA-mediated activation, improved mononuclear proliferation potential, higher expression of the co-stimulatory molecule CD28, lower values of the inhibitory CTLA-4 molecule and decreased levels of serum IL-6. The immunological parameters in the rHuEpo-treated MM patients were close to the normal healthy controls. Results are presented in the table below (mean +/− SE). We also found similar immunological abnormalities in patients at an early stage (Durie and Salmon stage 1, smoldering) MM (n=8). Our findings a) confirm and extend reports by others regarding immunological abnormalities in patients with advanced MM; b) show that patients with advanced MM treated with rHuEpo for their anemia benefit from improved immunological functions; c) show that patients with early-stage MM already manifest similar immunological abnormalities. Our data thus indicate that patients with early-stage MM might benefit from rHuEpo with improved immune functions, even prior to the development of anemia in later stages of the disease. Taken together, our study suggests rHuEpo as a potential immunomodulatory agent in the treatment of MM. Parameter Normal Healthy Controls MM Patients rHuEpo-treated Advanced MM Patients Early MM Advanced MM a. p<0.05 advanced MM compared to healthy controls. b. p<0.05 early MM compared to health controls. c. p<0.05 rHuEpo treated advanced MM compared to non-treated advanced MM patients Number of Patients N=14 N=8 N=21 N=13 CD4:CD8 2.4±0.3 1.2±0.2b 1.2±0.1a 1.9±0.3c PHA act- CD8+CD69+ (%) 60±4.4 45±4.4b 46.3±3a 63.3±3.8c PHA act-CD4+CD69+ (%) 57.1±3.8 42±4.6b 43.3±3a 59.9±3.6c Proliferation (%) 232.5±10.3 161±7.1b 146.5±15.1a 218.1±22.5c CD8+CD28+ (%) 73.2±5.2 53.7±8.2 38.8±2a 55.6±2.9c CD8+CTLA-4+ (%) 2.4±0.6 12.5±3.6 10.1±1.5a 4.6±0.9c sIL-6 (pg/ml) 2.6±0.4 5.4±1 10±2.1a 5.7±0.9c

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Elevated Normal Immunoglobulins and Stable M-Protein Levels in Multiple Myeloma Patients on Erythropoietin Treatment.

Blood ◽

10.1182/blood.v110.11.4747.4747 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4747-4747

Author(s):

Noa Gadassi ◽

Sari Prutchi Sagiv ◽

Howard S. Oster ◽

Drorit Newmann ◽

Moshe Mittelman

Keyword(s):

Multiple Myeloma ◽

Immune System ◽

M Protein ◽

Immunological Parameters ◽

Humoral Immune ◽

Protein Levels ◽

Humoral Immune Responses ◽

Human Erythropoietin ◽

Erythropoietin Treatment ◽

Cellular Immune

Abstract Recombinant human erythropoietin (rHuEPO) is a well-known treatment for anemia in multiple myeloma (MM) patients. We have previously reported that rHuEPO treatment was associated with prolonged survival of several patients suffering from advanced disease (Mittelman et al., 1997). Recently we have demonstrated that treatment of MM patients with rHuEPO is associated with significant improvements of certain immunological parameters and functions (Prutchi-Sagiv et al., 2006), mainly related to the cellular compartment. The objective of the present retrospective study was to determine whether rHuEPO treatment, in addition to its effects on the cellular immune compartment, also modulates the humoral arm of the immune system in MM patients. Medical charts of eighteen consecutive IgG and IgA MM patients were analyzed and the levels of normal immunoglobulins (Ig) and M-protein before and during rHuEPO treatment were recorded. We have found a significant increase in the levels of normal Ig (IgG, IgA and IgM) in response to rHuEPO, during the 3–9 months fromtreatment initiation. Importantly, the levels of M-protein remained stable for a period of 10–12 months from treatment initiation. These results are in line with previous studies, including our study in murine models (Katz et al., 2007), demonstrating that EPO improves humoral immune responses. The current study highlights the concept that EPO’s immunomodulatory actions on MM patients might also involve the humoral compartment of the immune system.

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An analysis of the reasons and motives of patients seeking telehealth-based second opinion for cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13621 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13621-e13621

Author(s):

Rejil Rajan ◽

Amit Kumar Jotwani ◽

Thirtha Poovaiah ◽

Rakesh Shankar Goud ◽

Rama Waghmare ◽

...

Keyword(s):

Clinical Trials ◽

Early Stage ◽

Treatment Options ◽

Locally Advanced ◽

Second Opinion ◽

Ongoing Treatment ◽

Number Of Patients ◽

Negative Perceptions ◽

Poor Outcomes ◽

Stage 1

e13621 Background: Incidence of cancer is rising with each passing year in India and a majority number of patients get diagnosed in later stages of disease that leads to poor outcomes. Studies have reported that patients and their caregivers feel the need to get more information about their treatment options making them opt for second opinions due to need for reassurance or inadequate time for communication with their treating oncologists. We sought to analyse the primary concerns and motives of patients seeking second opinion services through onco.com. Methods: A cohort of 918 eligible patients who availed online multidisciplinary tumour board opinion through Onco.com was included in the study. We analysed the primary concerns of 918 eligible patients who availed online second opinion through onco.com between January 2019 & December 2020. We looked at the specific questions they had for the multidisciplinary panel of oncologists. We also correlated the concerns with the stage of disease to understand if there was a variation for different stages of disease. Results: Of the total 918 patients, 864 had solid malignancies, out of which 16% had early (stage 1 & 2) disease, 27% had locally advanced (stage III) disease, 47% had metastatic disease & and 16% had recurrent disease. The most frequent motive for seeking a second opinion was the need for validation of ongoing treatment (72.5%) followed by enquiry for more advanced treatment options (37%), and to know any alternative treatment options (19%). Interestingly, only a minority of all patients were keen to know about clinical trials (3%). Conclusions: Our findings suggest that validation of ongoing treatment is the most frequent motive for patient driven second opinions in oncology. There was minimal interest to seek clinical trial options among patients, which could be due to general lack of awareness about clinical trials and some form of stigma associated with clinical trials due to negative perceptions and fears about adverse events. [Table: see text]

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Preliminary Exploration of the Stimulating Effect of Pomalidomide on BCMA-CART in the Treatment of Multiple Myeloma Patients

Blood ◽

10.1182/blood-2021-154489 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4846-4846

Author(s):

Yuelu Guo ◽

Kai Hu

Keyword(s):

Multiple Myeloma ◽

Cell Expansion ◽

Remission Rate ◽

Early Stage ◽

Gamma Interferon ◽

Hematopoietic Stem ◽

Soluble Cd25 ◽

Number Of Patients ◽

Tnf Α ◽

Before And After

Abstract Research Background: BCMA-CART treatment can give patients with relapsed and refractory multiple myeloma a chance of remission, but because the patient's own lymphocytes are poor in number and function, poor autologous CART cell expansion or failure to expand will affect the efficacy of CART. It is necessary to explore ways to improve the curative effect of CART so as to increase the remission rate. Research purposes The purpose of the study was to observe the changes in symptoms, signs, and vital signs of patients with pomalidomide in the early stage after BCMA-CART reinfusion, analyze the changes in cytokines and CART expansion after oral pomalidomide, and summarize the symptoms of such patients Disease remission rate and survival status. Research methods Collect the clinical characteristics of patients who took pomalidomide orally within one month after BCMA-CART cell reinfusion in our hospital from January 2019 to July 2021, and count the symptoms and signs of patients with pomalidomide before and after CART. Compare the values of cytokine and CART cell expansion before and after CART reinfusion to explore the synergistic effect of pomalidomide with CART. Research result From January 2019 to July 2021, a total of 5 patients with multiple myeloma who took pomalidomide orally within 1 month after BCMA-CART cell reinfusion were treated in our department from January 2019 to July 2021. There were 2 male patients and 3 female patients. The median age is 63 years (35-70). The median number of patients' previous treatment lines is 7 (3-18), of which 3 patients(3/5) have had previous autologous hematopoietic stem cell transplantation. The number of reinfused BCMA-CART cells in 5 patients was 8.13 (0.11-16.5)*105/kg, the median time of oral pomalidomide was 14 (8-19) days of CART reinfusion, and the dose was 1 case (1/ 5) 4 mg 1/day for patients, 2 mg 1/day for 3 patients (3/5), 1 mg 1/5 for 1 patient (1/5); 3 patients (3/5) before pomalidomide treatment ). The number of CART cell expansion in patients was 0.00%, 0.40% in 1 case (1/5), and 7.03% in 1 case (1/5). None of them had fever. 4 patients (4/5) had fever after taking pomalidomide, the median maximum body temperature was 38.95 (38.3-40.2) ℃, and the fever occurred 1.5 (1-4) days after taking pomalidomide; The amplification of CART cells of all patients can be detected by PCR method after pomalidomide, and the start time of amplification is 5 (2-8) days after taking pomalidomide; the amplification of CART cells The highest peak occurred at 9 (4-19) days after taking pomalidomide. The peak of CART cell expansion increased by 3.86 (0.06-37.8)% compared to before treatment with pomalidomide; the CRS classification after taking pomalidomide of 4 cases (4/5) were grade 2 and 1 case (1/5) was grade 3, of which 2 cases (2/5) had ICANS. Cytokines were increased in all patients after pomalidomide. Among them, IL-6 of all cases (5/5) increased after pomalidomide, and the highest value of IL-6 appeared after pomalidomide. At 9 (5-22) days after pomalidomide administration, the increase value was 20.60 (16.16-380.23) pg/mL; among the 4 patients that can be counted, TNF-α level of 4 patients (4/4) were increased after pomalidomide administration, the highest value of TNF-α appeared at 7.5 (6-8) days after pomalidomide administration, and the increase value was 21.825 (11.60-32.81) pg/mL. All 4 countable patients had higher soluble CD25 after pomalidomide administration, and the highest value of soluble CD25 appeared 11 (6-14) days after pomalidomide administration, and the value of increase was 7987 (3765-26173) pg/Ml. Gamma interferon of all 4 countable patients increased after pomalidomide administration, and the highest value of gamma interferon appeared in 9.5 (2-14) days after pomalidomide use, the increase value was 18.49 (5.3-587.8) pg/ml. The efficacy of 5 patients evaluated after 1 month after BCMA-CART was 2 cases (2/5) with stable disease, 2 cases (2/5) with partial remission, and 1 case (2/5) with disease progression. As of the deadline for submission, 5 patients are currently alive, and the median OS is 113 (42-236) days after CART reinfusion. Analysis conclusion Pomalidomide can promote the expansion and activation of CART and stimulate the release of cytokines in the early stage after BCMA-CART treatment. Whether it can enhance the anti-tumor effect of CART remains to be further studied. Disclosures No relevant conflicts of interest to declare.

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First Review of Multiple Myeloma Patients in Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates

Blood ◽

10.1182/blood-2019-128769 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5587-5587

Author(s):

Mohamed Abu Haleeqa ◽

Fatima Alkaabi ◽

Raneem Janodi ◽

Emadullah Raidullah

Keyword(s):

Multiple Myeloma ◽

United Arab Emirates ◽

Progression Free Survival ◽

The United States ◽

Abu Dhabi ◽

Cell Transplant ◽

Free Survival ◽

Number Of Patients ◽

Medical City ◽

Stage 1

First Review of Multiple Myeloma patients in Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates. Introduction Multiple Myeloma (MM) accounts for approximately 1 to 2 percent of all cancers and slightly more than 17 percent of hematologic malignancies in the United States (1). The annual incidence in the United States is approximately 4 to 5 per 100,000(2). A similar incidence has been reported in Canada, the South Thames area of the United Kingdom, and in Europe in general. Worldwide, there are approximately 160,000 cases and 106,000 deaths per year attributed to MM (3).MM occurs in all races and all geographic locations. The incidence varies by ethnicity; the incidence in African Americans and Blacks from Africa is two to three times that in Whites (4). Here we report the first study in Abu Dhabi, United Arab Emirates done on MM patients in our institution Sheikh Khalifa Medical City. Methods We did retrospective analysis of patients diagnosed with multiple myeloma from year 2016-2018 in our tertiary care institution Sheikh Khalifa Medical City in Abu Dhabi, United Arab Emirates. Total number of patients admitted with ICD 10 diagnoses containing multiple myeloma from 2016 to 2018 were 1582. Out of these we included 62 patients with confirmed multiple myeloma and excluded others. Results Total number of patients were 62 (40 males, 22 females). Median age was 43 years (range 30 to 90 years). Multiple myeloma International staging score (ISS) for our patients was stage 1 (n=3), stage 2(n=17) and stage 3(n=42). Eastern Cooperative Oncology Group Performance Score (ECOG) in MM patients was grade 0(n=3), grade 1(n=33), grade 2(n=11), grade 3(n=12) and grade 4(n=3). LDH was high in 61 patients and normal in 1 patient. 30 patients of 62 were Bone Marrow Transplant (BMT) eligible. 25 of 30 eligible transplant patients had Autologous stem cell transplant (ASCT). 41 patients till date are, 18 have died and status of 3 is unknown. 22 of 25 transplanted patients are alive till current date, 2 have died and status of 1 is unknown. Cytogenetics stratification was not possible due to lack of access to Fluorescence in situ hybridization (FISH). Discussion The male to female ratio for MM patients was approximately 2:1. In our population we noticed that majority of the patients (n=42) presented as ISS stage 3 which indicates poor prognosis. The ECOG performance score of stage 1 was for 33 which is approximately 50% for total MM patients. This indicates that most of our MM patients were in good functional status at time of diagnosis. LDH was high in 61 patients. We do not have hemopoietic stem cell transplant service in UAE hence this put pressure on patients and their physicians to push for it. BMT eligible patients were 30. 25 out of 30 patients had ASCT and 5 couldn't do it due to financial and other reasons. Of the ASCT patients (n=25), 22 are alive till date, 2 have passed away and status of 1 is unknown. The success of ASCT is almost 90% in our MM patients. We could not calculate the progression free survival of our patients as the follow up period was short. Out of our 41 alive patients till date, 22 are the ones who had ASCT. In the next phase of our study we plan to calculate 5 year progression free survival for our MM patients. Conclusion With the resources available tough cytogenetics and FISH not available easily and no HSCT service, we concluded that the MM patients in our population have higher ISS scores which indicates poor prognosis. However we believe for if we manage to do ASCT for our MM patients we would have excellent survival outcomes. This puts more incentive to open HSCT service and especially ASCT. Table Disclosures No relevant conflicts of interest to declare.

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Alterations in the number of motoneurons containing immunoreactive calcitonin gene-related peptide(CGRP)& choline acetyltransferase(ChAT) in the cervical spinal cord of the wobbler mouse during the development of the motoneuron disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141226 ◽

1995 ◽

Vol 53 ◽

pp. 970-971

Author(s):

L. Vacca-Galloway ◽

Y.Q. Zhang ◽

P. Bose ◽

S.H. Zhang

Keyword(s):

Spinal Cord ◽

Early Stage ◽

Cervical Spinal Cord ◽

Wild Type Mouse ◽

Reflex Response ◽

Mouse Strains ◽

Behavioral Tests ◽

Wobbler Mouse ◽

Stage 4 ◽

Stage 1

The Wobbler mouse (wr) has been studied as a model for inherited human motoneuron diseases (MNDs). Using behavioral tests for forelimb power, walking, climbing, and the “clasp-like reflex” response, the progress of the MND can be categorized into early (Stage 1, age 21 days) and late (Stage 4, age 3 months) stages. Age-and sex-matched normal phenotype littermates (NFR/wr) were used as controls (Stage 0), as well as mice from two related wild-type mouse strains: NFR/N and a C57BI/6N. Using behavioral tests, we also detected pre-symptomatic Wobblers at postnatal ages 7 and 14 days. The mice were anesthetized and perfusion-fixed for immunocytochemical (ICC) of CGRP and ChAT in the spinal cord (C3 to C5).Using computerized morphomety (Vidas, Zeiss), the numbers of IR-CGRP labelled motoneurons were significantly lower in 14 day old Wobbler specimens compared with the controls (Fig. 1). The same trend was observed at 21 days (Stage 1) and 3 months (Stage 4). The IR-CGRP-containing motoneurons in the Wobbler specimens declined progressively with age.

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FlowCell-enriched circulating tumor cells as a predictor of lung cancer metastasis

Human Cell ◽

10.1007/s13577-021-00500-8 ◽

2021 ◽

Author(s):

Yan Lu ◽

Yushuang Zheng ◽

Yuhong Wang ◽

Dongmei Gu ◽

Jun Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Metastasis ◽

Lung Tumor ◽

Early Stage ◽

High Rate ◽

Early Stage Lung Cancer ◽

Lung Cancer Metastasis ◽

Number Of Patients

AbstractLung cancer is the most fetal malignancy due to the high rate of metastasis and recurrence after treatment. A considerable number of patients with early-stage lung cancer relapse due to overlooked distant metastasis. Circulating tumor cells (CTCs) are tumor cells in blood circulation that originated from primary or metastatic sites, and it has been shown that CTCs are critical for metastasis and prognosis in various type of cancers. Here, we employed novel method to capture, isolate and classify CTC with FlowCell system and analyzed the CTCs from a cohort of 302 individuals. Our results illustrated that FlowCell-enriched CTCs effectively differentiated benign and malignant lung tumor and the total CTC counts increased as the tumor developed. More importantly, we showed that CTCs displayed superior sensitivity and specificity to predict lung cancer metastasis in comparison to conventional circulating biomarkers. Taken together, our data suggested CTCs can be used to assist the diagnosis of lung cancer as well as predict lung cancer metastasis. These findings provide an alternative means to screen early-stage metastasis.

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A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer

Cancers ◽

10.3390/cancers13040913 ◽

2021 ◽

Vol 13 (4) ◽

pp. 913

Author(s):

Johannes Fahrmann ◽

Ehsan Irajizad ◽

Makoto Kobayashi ◽

Jody Vykoukal ◽

Jennifer Dennison ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Stage ◽

Area Under The Curve ◽

Polyamine Metabolism ◽

Healthy Controls ◽

Test Set ◽

Exact Test ◽

Oncogenic Driver ◽

Characteristic Area ◽

Validation Set

MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasma polyamine signature may associate with ovarian cancer (OvCa) development. Using mass spectrometry, four polyamines were quantified in plasma from 116 OvCa cases and 143 controls (71 healthy controls + 72 subjects with benign pelvic masses) (Test Set). Findings were validated in an independent plasma set from 61 early-stage OvCa cases and 71 healthy controls (Validation Set). Complementarity of polyamines with CA125 was also evaluated. Receiver operating characteristic area under the curve (AUC) of individual polyamines for distinguishing cases from healthy controls ranged from 0.74–0.88. A polyamine signature consisting of diacetylspermine + N-(3-acetamidopropyl)pyrrolidin-2-one in combination with CA125 developed in the Test Set yielded improvement in sensitivity at >99% specificity relative to CA125 alone (73.7% vs 62.2%; McNemar exact test 2-sided P: 0.019) in the validation set and captured 30.4% of cases that were missed with CA125 alone. Our findings reveal a MYC-driven plasma polyamine signature associated with OvCa that complemented CA125 in detecting early-stage ovarian cancer.

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Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer

Cancers ◽

10.3390/cancers13020325 ◽

2021 ◽

Vol 13 (2) ◽

pp. 325

Author(s):

Christopher Walker ◽

Tuan-Minh Nguyen ◽

Shlomit Jessel ◽

Ayesha B. Alvero ◽

Dan-Arin Silasi ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Detection ◽

Predictive Value ◽

Early Stage ◽

Ca 125 ◽

Healthy Controls ◽

Classification Models ◽

Serum Samples ◽

Protein Biomarker ◽

Biomarker Panel

Background: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer. In this study we determine the value of combining macrophage migration inhibitory factor (MIF), osteopontin (OPN), and prolactin (PROL) with CA-125 in the detection of ovarian cancer serum samples from healthy controls. Materials and Methods: A total of 432 serum samples were included in this study. 153 samples were from ovarian cancer patients and 279 samples were from age-matched healthy controls. The four proteins were quantified using a fully automated, multi-analyte immunoassay. The serum samples were divided into training and testing datasets and analyzed using four classification models to calculate accuracy, sensitivity, specificity, PPV, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Results: The four-protein biomarker panel yielded an average accuracy of 91% compared to 85% using CA-125 alone across four classification models (p = 3.224 × 10−9). Further, in our cohort, the four-protein biomarker panel demonstrated a higher sensitivity (median of 76%), specificity (median of 98%), PPV (median of 91.5%), and NPV (median of 92%), compared to CA-125 alone. The performance of the four-protein biomarker remained better than CA-125 alone even in experiments comparing early stage (Stage I and Stage II) ovarian cancer to healthy controls. Conclusions: Combining MIF, OPN, PROL, and CA-125 can better differentiate ovarian cancer from healthy controls compared to CA-125 alone.

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Temporal changes of quantitative CT findings from 102 patients with COVID-19 in Wuhan, China: A longitudinal study

Technology and Health Care ◽

10.3233/thc-218027 ◽

2021 ◽

Vol 29 ◽

pp. 297-309

Author(s):

Xiaohui Chen ◽

Wenbo Sun ◽

Dan Xu ◽

Jiaojiao Ma ◽

Feng Xiao ◽

...

Keyword(s):

Lung Diseases ◽

Early Stage ◽

Temporal Changes ◽

Time Interval ◽

Lesion Area ◽

Quantitative Ct ◽

Diagnosis And Prognosis ◽

Ct Findings ◽

Stage 4 ◽

Stage 1

BACKGROUND: Computed tomography (CT) imaging combined with artificial intelligence is important in the diagnosis and prognosis of lung diseases. OBJECTIVE: This study aimed to investigate temporal changes of quantitative CT findings in patients with COVID-19 in three clinic types, including moderate, severe, and non-survivors, and to predict severe cases in the early stage from the results. METHODS: One hundred and two patients with confirmed COVID-19 were included in this study. Based on the time interval between onset of symptoms and the CT scan, four stages were defined in this study: Stage-1 (0 ∼7 days); Stage-2 (8 ∼ 14 days); Stage-3 (15 ∼ 21days); Stage-4 (> 21 days). Eight parameters, the infection volume and percentage of the whole lung in four different Hounsfield (HU) ranges, ((-, -750), [-750, -300), [-300, 50) and [50, +)), were calculated and compared between different groups. RESULTS: The infection volume and percentage of four HU ranges peaked in Stage-2. The highest proportion of HU [-750, 50) was found in the infected regions in non-survivors among three groups. CONCLUSIONS: The findings indicate rapid deterioration in the first week since the onset of symptoms in non-survivors. Higher proportion of HU [-750, 50) in the lesion area might be a potential bio-marker for poor prognosis in patients with COVID-19.

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DeepRePath: Identifying the Prognostic Features of Early-Stage Lung Adenocarcinoma Using Multi-Scale Pathology Images and Deep Convolutional Neural Networks

Cancers ◽

10.3390/cancers13133308 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3308

Author(s):

Won Sang Shim ◽

Kwangil Yim ◽

Tae-Jung Kim ◽

Yeoun Eun Sung ◽

Gyeongyun Lee ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Early Stage ◽

External Validation ◽

Area Under The Curve ◽

The Cancer Genome Atlas ◽

Deep Convolutional Neural Networks ◽

Prognostic Features ◽

Multi Scale ◽

Model Based ◽

Number Of Patients

The prognosis of patients with lung adenocarcinoma (LUAD), especially early-stage LUAD, is dependent on clinicopathological features. However, its predictive utility is limited. In this study, we developed and trained a DeepRePath model based on a deep convolutional neural network (CNN) using multi-scale pathology images to predict the prognosis of patients with early-stage LUAD. DeepRePath was pre-trained with 1067 hematoxylin and eosin-stained whole-slide images of LUAD from the Cancer Genome Atlas. DeepRePath was further trained and validated using two separate CNNs and multi-scale pathology images of 393 resected lung cancer specimens from patients with stage I and II LUAD. Of the 393 patients, 95 patients developed recurrence after surgical resection. The DeepRePath model showed average area under the curve (AUC) scores of 0.77 and 0.76 in cohort I and cohort II (external validation set), respectively. Owing to low performance, DeepRePath cannot be used as an automated tool in a clinical setting. When gradient-weighted class activation mapping was used, DeepRePath indicated the association between atypical nuclei, discohesive tumor cells, and tumor necrosis in pathology images showing recurrence. Despite the limitations associated with a relatively small number of patients, the DeepRePath model based on CNNs with transfer learning could predict recurrence after the curative resection of early-stage LUAD using multi-scale pathology images.

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