Early-stage pulmonary adenocarcinoma (T1N0M0): a clinical, radiological, surgical, and pathological correlation of 104 cases. The MD Anderson Cancer Center Experience

227 Background: The association between the GH/IGF-1 axis and HCC was reported in patients (pt) with underlying cirrhosis. However, there is limited information among HCC pt without (w/o) cirrhosis. We herein investigated the role of GH as a circulating biomarker for HCC diagnosis and prognosis in pt w/o cirrhosis. Methods: Under IRB approval, we prospectively enrolled 1267 newly-diagnosed HCC pt in a case control study at the MD Anderson Cancer Center (2000-2015). Controls were healthy individuals (n = 1104). Plasma GH and AFP were measured 274 HCC pt w/o cirrhosis 200 healthy controls. IGF-1 was measured in 133 and 82 pt, respectively. We classified HCC pt into higher and lower GH values (cutoff for women, 3.7 µg/L; men, > 0.9 µg/L). Results: Most pt (74%) were male, with advanced BCLC staging (C-D, 74%) and 61% were older than 60y. Baseline GH was higher in HCC w/o cirrhosis (mean 3.3 µg/L) than controls (mean 0.4 µg/) (p < .001). ROC curve was plotted to assess diagnostic role. The AUC for AFP was 82.9 (p < .001); for GH 78.2 (p < .001). When only non-cirrhotic HCC pt with early stage (CLIP 0-2) and AFP < 20 ng/m were compared to controls, the GH/IGF-1 ratio had high prediction of early stage HCC - AUC 83 (95% CI 78-89%) (p < .0001). At a specificity of 90%, sensitivity of GH/IGF ratio was 67%. In addition, among HCC w/o cirrhosis, higher GH levels correlated with presence of vascular invasion (p < .001) and thrombosis (p = .004), tumor involvement of > 50% liver (p = .003), and more advanced BCLC (p < .001) and TNM staging (p < .001). Median overall survival (months) of HCC pt w/o cirrhosis with high GH levels was 13.1 (10.8-15.4) compared to 37.4 (19.8-55.1) of pt with lower plasma GH (p < .001). Multivariate cox-regression analysis identified high GH as an independent risk factor for mortality (HR = 1.8; 95% CI, 1.3-2.4; p < .001). Conclusions: Our study demonstrates the diagnostic and prognostic role of plasma GH in non-cirrhotic HCC and identifies the GH/IGF-1 ratio as a promising diagnostic marker for early stage HCC w/o cirrhosis and low AFP; this analysis excludes the confounding effect hepatocyte impaired function by presence of cirrhosis. Further studies are warranted to assess the causes of the observed differences.

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High Levels of Common Cold Coronavirus Antibodies in Convalescent Plasma Are Associated With Improved Survival in COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.675679 ◽

2021 ◽

Vol 12 ◽

Author(s):

Uri Greenbaum ◽

Kimberly Klein ◽

Fernando Martinez ◽

Juhee Song ◽

Peter F. Thall ◽

...

Keyword(s):

Survival Time ◽

Common Cold ◽

Early Stage ◽

Cancer Center ◽

Specific Antibodies ◽

Promising Therapeutic Target ◽

Younger Age ◽

Common Domain ◽

Md Anderson ◽

Antibody Levels

BackgroundCOVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.Patients and MethodsPatients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.ResultsCCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.ConclusionsCommon cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

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Thoracic Cancer: 2021 ASCO Annual Meeting Highlights for the Advanced Practitioner

Journal of the Advanced Practitioner in Oncology ◽

10.6004/jadpro.2021.12.6.4 ◽

2021 ◽

Vol 12 (6) ◽

Author(s):

Elizabeth S. Waxman, RN, MSN, AOCN, ANP-BC

Keyword(s):

Annual Meeting ◽

Early Stage ◽

Cancer Center ◽

Important Research ◽

Early Stage Lung Cancer ◽

Advanced Practitioner ◽

Thoracic Cancer ◽

Md Anderson ◽

Doublet Chemotherapy ◽

Stage Lung Cancer

Elizabeth S. Waxman, RN, MSN, AOCN®, ANP-BC, of MD Anderson Cancer Center, reviews important research in thoracic cancers presented at the 2021 ASCO Annual Meeting, including atezolizumab in early-stage lung cancer, the addition of doublet chemotherapy to doublet immunotherapy in advanced-stage NSCLC, the first-in-class KRAS G12C inhibitor sotorasib, and the combination of amivantamab and lazertinib. Coverage provided by The ASCO Post.

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Investigating the Natural History and Prognostic Nature of NTRK Gene Fusions in Solid Tumors

10.21203/rs.3.rs-573656/v1 ◽

2021 ◽

Author(s):

Limin Zhu ◽

Brian Hobbs ◽

Jason Roszik ◽

Vijaykumar Holla ◽

David S. Hong

Keyword(s):

Natural History ◽

Solid Tumors ◽

Gene Fusion ◽

Early Stage ◽

The Cancer Genome Atlas ◽

Cancer Center ◽

Gene Fusions ◽

Risk Of Progression ◽

Md Anderson ◽

Trk Inhibitors

Abstract BackgroundSeveral TRK inhibitors have demonstrated clinical efficacy in patients with solid tumors harboring NTRK gene fusions. However, the natural history and prognostic implications of NTRK fusions in solid tumors remain unknown.MethodsA cohort of 77 MD Anderson Cancer Center patients (MDACC) with NTRK gene fusions was identified and retrospectively compared to a second cohort from the Cancer Genome Atlas (TCGA) database. Due to paucity of events in early stage cancers and lack of TCGA data in rare tumors, 25 randomly selected MDACC patients were matched to 122 TCGA patients without NTRK gene fusion. Next we assessed the associations between NTRK gene fusion and overall (OS) and progression-free survivals (PFS).ResultsAmong the 77 MDACC patients with NTRK gene fusions, 18 NTRK fusion partners were identified. There were insufficient OS events for analysis in the matched cohort. PFS was not significantly different (p=0.49) between the NTRK-fusion positive MDACC patients (median PFS 786 weeks, 95% CI 317-NE) and the NTRK-fusion negative TCGA patients (median PFS NE). The adjusted hazard ratio comparing TCGA patients to MDACC patients was HR=0.72 (95% CI: 0.23-2.33), which trended towards a reduced rate of progression or death experienced by TCGA patients.ConclusionsThis study did not identify statistically significant associations between NTRK fusion and PFS. Nonsignificant trends estimated increases in the risk of progression or death events for patients with NTRK fusions when compared to matched controls. Our findings help illuminate the influence of NTRK fusions on the natural history of a variety of solid tumors.

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Cytomegalovirus seropositivity is significantly associated with mycosis fungoides and Sézary syndrome

Blood ◽

10.1182/blood-2002-07-2247 ◽

2003 ◽

Vol 101 (6) ◽

pp. 2132-2135 ◽

Cited By ~ 59

Author(s):

Kelly L. Herne ◽

Rakhshandra Talpur ◽

Joan Breuer-McHam ◽

Richard Champlin ◽

Madeleine Duvic

Keyword(s):

Bone Marrow ◽

Mycosis Fungoides ◽

Late Stage ◽

Viral Infections ◽

Early Stage ◽

Cancer Center ◽

Seropositivity Rate ◽

Persistent Antigen ◽

Md Anderson ◽

Hiv 1

Although mycosis fungoides (MF) may arise through persistent antigen stimulation, cytomegalovirus (CMV) is not a known risk factor. To study the incidence of seropositivity to viral infections, we compared MF and Sézary Syndrome (SS) patients to healthy bone marrow donors and other historical control groups. Baseline screening serologies at baseline were performed on 116 biopsy-proven MF/SS patients at MD Anderson Cancer Center from 1992 to 2001 and on healthy bone marrow donors evaluated by the transplant service from 1988 to 2001. Antibodies to HTLV-I/II, HIV-1, EBV, and CMV were measured using standard enzyme-linked immunosorbent (ELISA) and membrane enzyme immunoassay (MEIA) assays. One hundred thirteen (97.4%) of all MF/SS patients had positive CMV IgG serologies at initial presentation. Early- and late-stage patients' seropositivity rates were significantly higher than healthy bone marrow donor controls (χ2.05(df=1) = 71.79). By stage, 98.1% of early-stage MF patients (IA, IB, IIA; 52/53) and 96.8% of late-stage MF and SS patients (IIB-IVB; 61/63) were seropositive compared with healthy bone marrow donors whose seropositivity rate was 57.3% (757/1322). Because the rate of CMV seropositivity increases with age, a subset of cutaneous T-cell lymphoma (CTCL) patients 55 years or younger were compared to age-matched healthy donor controls; their seropositivity rate for CMV was also significantly higher (χ2.05 05(df=1) = 20.4). EBV titers were positive by serology in 13 patients who were examined prospectively. CMV seropositivity is highly associated with MF and SS, even in the earliest stages of the disease, and is significantly higher than that of healthy and immunocompromised controls.

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High levels of common cold coronavirus antibodies in convalescent plasma are associated with improved survival in COVID-19 patients

10.1101/2021.03.08.21252775 ◽

2021 ◽

Author(s):

Uri Greenbaum ◽

Kimberly Klein ◽

Fernando Martinez ◽

Juhee Song ◽

Peter F. Thall ◽

...

Keyword(s):

Survival Time ◽

Common Cold ◽

Early Stage ◽

Cancer Center ◽

Specific Antibodies ◽

Promising Therapeutic Target ◽

Younger Age ◽

Common Domain ◽

Md Anderson ◽

Antibody Levels

AbstractBackgroundCOVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP.Patients and MethodsPatients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed.ResultsCCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex.ConclusionsCommon cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

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657 Interleukin-6 receptor blockade for management of immune checkpoint inhibitor related adverse events in patients with melanoma

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0657 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A694-A694

Author(s):

Chantal Saberian ◽

Faisal Fa’ak ◽

Jean Tayar ◽

Maryam Buni ◽

Sang Kim ◽

...

Keyword(s):

Adverse Events ◽

Disease Activity ◽

Median Time ◽

Interleukin 6 ◽

Immune Checkpoint ◽

Activity Index ◽

Critical Role ◽

Cancer Center ◽

Interleukin 6 Receptor ◽

Md Anderson

BackgroundManagement of certain immune mediated adverse events (irAEs) can be challenging and may require prolonged/chronic immune suppression with corticosteroids or other immunosuppressant which could compromise and even reverse the efficacy of immune checkpoint inhibitors (ICI). While the exact immunobiology of irAEs is not fully understood there is enough evidence that IL-6 induced Th-17 that may play critical role in the pathogenesis. Herein, we describe our clinical experience using interleukin-6 receptor (IL-6R) blockade in management of irAEs in melanoma patients.MethodsWe searched MD Anderson databases to identify cancer patients who had received ICIs between January 2004 and March 2020. Of 11,391 ICI-treated patients, 21 patients with melanoma who received IL-6R blockade after ICI infusion were identified and their medical records were reviewed.ResultsMedian age was 61 years (41–82), 52% were females, 90% received anti-programmed cell death-1 antibodies. Fourteen patients (67%) had de novo onset irAEs (11 had arthritis, and 1 each with polymyalgia rheumatica, oral mucositis, and CNS vasculitis), and 7 patients (33%) had flare of their pre-existing autoimmune diseases (5 had had rheumatoid arthritis, and 1 each with myasthenia gravis and Crohn’s disease). Median time from ICI initiation to irAEs was 91 days (range, 1–496) and to initiation of IL-6R blockade was 6.6 months (range, 0.6–24.3). Median number of IL-6R blockade was 12 (range, 1–35), and 16 patients (76%) were concomitantly receiving corticosteroids of median dose of 10 mg (range, 5–20 mg). Of the 21 patients, irAEs improved in 14 (67%) (95% CI: 46%-87%). Of 13 evaluable patients with arthritis, 11 (85%) achieved remission or minimal disease activity as defined by the clinical disease activity index. Median time from initiation of IL-6R blockade till improvement of irAEs was 2.9 months (range, 1.5–36.9). Nineteen patients tolerated well IL-6R blockade, while two patients stopped treatment due to abdominal pain and sinus tachycardia. The median CRP levels at irAEs was 84 mg/L (0.6–187) and decreased to 1.9 mg/L (0.56–12) at 10 weeks after initiation of IL-6R blockade (P=0.02). Of the 17 evaluable patients, the overall tumor response rate by RECIST-1.1 criteria was similar before and after IL-6R blockade initiation (41% vs. 53%).ConclusionsOur data demonstrated that IL-6R blockade could be an effective therapy for irAEs management without dampening the efficacy of ICIs. Prospective clinical trials with longitudinal blood, tumor, and inflamed tissue biopsies are planned to accurately validate these findings and better study the immunobiology of irAEs.Ethics ApprovalThe study was approved by The University of Texas MD Anderson Cancer Center intuition’s Ethics Board, approval number PA19-0089

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321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0321 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A347-A347

Author(s):

Shipra Gandhi ◽

Mateusz Opyrchal ◽

Cayla Ford ◽

Victoria Fitzpatrick ◽

Melissa Grimm ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Phase I ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Standard Dose ◽

Surrogate Marker ◽

Comprehensive Cancer Center ◽

Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

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Recurrence of venous thromboembolism among adults acute leukemia patients treated at the University of Texas MD Anderson Cancer Center: Incidence and risk factors

Thrombosis Research ◽

10.1016/j.thromres.2017.05.019 ◽

2017 ◽

Vol 156 ◽

pp. 14-19 ◽

Cited By ~ 4

Author(s):

Nhiem V. Luong ◽

Michael H. Kroll ◽

Khanh Vu

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Acute Leukemia ◽

Cancer Center ◽

University Of Texas ◽

Md Anderson ◽

The University

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236 Predictors of ICI renal toxicity: a pathological approach

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2021-sitc2021.236 ◽

2021 ◽

Vol 9 (Suppl 3) ◽

pp. A252-A252

Author(s):

Ala Abudayyeh ◽

Liye Suo ◽

Heather Lin ◽

Omar Mamlouk ◽

Cassian Yee ◽

...

Keyword(s):

Overall Survival ◽

Renal Toxicity ◽

Checkpoint Inhibitors ◽

Interstitial Fibrosis ◽

Transplant Rejection ◽

Categorical Variables ◽

Rank Test ◽

Cancer Center ◽

Renal Response ◽

Md Anderson

BackgroundInflammatory response in unintended tissues and organs associated with the use of immune checkpoint inhibitors also known as immune related adverse events (irAEs) is a management challenge, and renal irAEs are associated with increased patient morbidity and mortality. The most common renal toxicity is acute interstitial nephritis (AIN), characterized by infiltration of renal tissue with immune cells, and may be analogous to kidney transplant rejection. Using both clinical variables and tissue findings we evaluated a large cohort of ICI cases to determine predictors of renal response and overall survival.MethodsWe retrospectively reviewed all patients treated with ICI (August 2007 to August 2020) at MD Anderson Cancer Center. A total of 38 patients with biopsy confirmed AIN and available tissue were identified. All slides were reviewed by two board certified renal pathologists and the severity of inflammation and chronicity was graded using transplant rejection BANFF criteria. Patients were categorized as renal responders if creatinine improved or returned to baseline after treatment and non-responders if it did not. Fisher’s exact tests for categorical variables and t-test/ANOVA or the counterparts of the non-parametric approaches (Wilcoxon rank-sum or Kruskal-Wallis) for continuous variables were used to compare patient‘s characteristics between groups. The distribution of overall survival (OS) was estimated by the Kaplan-Meier method. Log-rank test was performed to test the difference in survival between groups.ResultsBased on the detailed pathological findings, patients with increased interstitial fibrosis were less likely to have renal response with treatment compared to patients with less fibrosis, (p < 0.05). Inflammation, tubulitis, number of eosinophils and neutrophils had no impact on renal response. Patients with response within 3 months of AKI treatment had a superior OS in comparison to patients who responded late (12-month OS rate: 77% vs 27%, p < 0.05). Notably, patients who received concurrent ICI and achieved renal response within 3 months had the best OS while those who did not receive concurrent ICI nor achieved renal response had worst OS (12-month OS rate: 100% (renal response and concurrent ICI) vs 72% ( renal response with no concurrent ICI), vs 27% ( no renal response and nonconcurrent ICI) (p < 0.05).ConclusionsThis is the first analysis of ICI induced nephritis where a detailed pathological and clinical evaluation was performed to predict renal response. Our findings highlight the importance of early diagnosis and treatment of ICI-AIN while continuing concurrent ICI therapy.Ethics ApprovalThis retrospective study was approved by the institutional review board at The University of Texas MD Anderson Cancer Center, and the procedures followed were in accordance with the principles of the Declaration of Helsinki.

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