tbuckley/cabot-search huggingface dataset:
Tumor CD47 expression and a high M2/M1 ratio of tumor-associated macrophages as an adverse prognostic factor in resected stage Ⅲa non-small cell lung cancer.
Authors: Yan Xu, Bing Tong, Minjiang Chen, Wei Zhong, Jing Zhao, Changting Liu, Haihua Fu, Mengzhao Wang
Journal: Journal of Clinical Oncology (2018)

e20531 Background: Immunotherapy is one of the most promising advances in the field of oncology. However, limited information exists regarding characterization of the tumor associated macrophages (TAMs) related immune microenvironment in patients with non-small cell lung cancer (NSCLC), by which it may possible to predict the efficacy of novel immunotherapies. Methods: 191 resected NSCLC specimens were retrospectively studied for the expression of CD47 expression was examined using immunohistochemistry (IHC). The infiltration of TAMs (M2-macrophages & M1-macrophages) and PD-L1 expression& CD8+T-lymphocytes were evaluated using dual-IF staining, respectively. 47 cases of pulmonary infectious diseases served as the control group. Finally, the prognostic role of these immune features was assessed in stage IIIa NSCLC. Results: CD47-positive staining was observed in 53.4% (102/191) of NSCLC and 78.7% (37/47) of pulmonary infectious samples, respectively (P = 0.002). CD47 expression was more frequently detected in adenocarcinoma, female, never-smoking, stage Ⅲa, and high-differentiation NSCLCs (P < 0.001, P = 0.002, 0.008, 0.035 and 0.001, respectively). 65.3% (62/95) of Stage Ⅲa cases detected M2-macrophage infiltration in tumor area, significantly higher compared to 32.3% (31/96) of Stage Ⅰ (P < 0.001) . A high M2 / M1 ratio was more common in NSCLC compared with the control group (71.7% vs 46.8%, P = 0.001), especially in stage Ⅲa NSCLC (stage Ⅰ vs stage Ⅲa: 60.4% vs 84.2%, P < 0.001). Patients expressing CD47 or with concurrence of CD47+ and high M2/M1 ratio tended to show poor DFS (22.03 ms vs 34.77 ms, P = 0.021; 19.97ms vs 34.77ms, P = 0.005), and multivariate analysis identified the latter one as negative predictor for DFS (P = 0.016). Conclusions: Tumor CD47 expression and a high M2/M1 ratio of tumor-associated macrophages is an adverse prognostic factor in resected stage Ⅲa NSCLC. Anti-CD47 treatment might be a novel adjuvant treatment option for resected stage Ⅲa NSCLC.
Outcomes with inotuzumab ozogamicin (InO) in patients with Philadelphia chromosome–positive (Ph+) relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL).
Authors: Wendy Stock, Giovanni Martinelli, Matthias Stelljes, Daniel J. DeAngelo, Nicola Gökbuget, Anjali S. Advani, Susan Mary O'Brien, Michaela Liedtke, Akil Abid Merchant, Ryan Daniel Cassaday, Tao Wang, Erik Vandendries, David I. Marks, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2018)

7030 Background: InO, a CD22-directed antibody-drug conjugate, is approved to treat adults with R/R ALL. Historically, patients (pts) with Ph+ ALL (~20–30%) have had poor prognoses compared with Ph− pts. Methods: Pts with R/R ALL received InO in a phase 1 dose-finding/phase 2 study (1010; DeAngelo et al, Blood Adv 2017) and a phase 3 trial (1022; Kantarjian et al, NEJM 2016) comparing InO vs standard chemotherapy (SC). We analyzed outcomes in Ph+ pts (Ph chromosome or BCR-ABL gene by FISH) treated with InO (InO-1010 or InO-1022) or SC based on final data from each study. Results: In 1010 and 1022, respectively, 16 and 22 Ph+ pts received InO; 27 Ph+ pts were randomized to SC in 1022 (22 received SC). Pts in 1010 were heavily pretreated. Among Ph+ pts in 1022, 19 (86%) InO pts and 26 (96%) SC pts had previous tyrosine kinase inhibitors (TKIs). Prior stem cell transplants (SCT) were 8 (50%) for InO-1010, 7 (32%) for InO-1022, and 9 (33%) for SC. Also, 15 (94%), 10 (45%), and 15 (56%) pts were treated in ≥2nd salvage for InO-1010, InO-1022, and SC, respectively. Efficacy outcomes are shown (Table). A total of 3 (19%) InO-1010 pts, 9 (41%) InO-1022 pts, and 5 (19%) SC pts proceeded to SCT after treatment. The most common nonhematologic grade 3-4 adverse events with InO in Ph+ pts were gastrointestinal disorders (31%) in 1010 and multi-organ laboratory abnormalities (41%) in 1022; 2 Ph+ pts in each InO study had veno-occlusive liver disease. Among SC pts, infections (55%) were the most common grade 3-4 nonhematologic events. Clinical trial information: NCT01363297. Conclusions: In Ph+ pts with R/R ALL who failed prior TKIs +/- SCT, InO-treated pts had higher rates of CR/CRi, MRD negativity, and subsequent SCT. However, overall outcomes in 1022 InO vs SC were still inferior to those reported in Ph– pts; thus additional treatment combinations should be explored. Efficacy Endpoints InO-1010 (n = 16) InO-1022 (n = 22) SC (1022) (n = 27) Complete remission (CR/CRi), n (%) 9 (56) 16 (73) 15 (56) Minimal residual disease (MRD) negativity, n (%) 10 (63) 14 (64) 5 (19) Overall survival (mos), median (95% CI) 7.4 (4.3–11.3) 8.7 (3.6–14.1) 8.4 (5.0–14.3) Progression-free survival (mos), median (95% CI) 4.4 (1.8–5.9) 3.9 (2.1–9.2) 3.1 (1.1–6.2)
Fosaprepitant as a risk factor for ifosfamide induced encephalopathy: A single institution experience.
Authors: Ridhi Gupta, Rebekah Hartwell, Rashmi Khanal, Jinayo Chen, Genevieve Luehrs Hayes, Andy Perez, John M. Wrangle
Journal: Journal of Clinical Oncology (2016)

e14104 Background: Ifosfamide is a moderate to highly emetogenic agent used in multiple chemotherapy regimens. Ifosfamide (Ifo) induced encephalopathy (IIE) is a neurotoxic adverse event with a reported incidence ranging from 10 to 40%. Aprepitant has been associated with an increased risk for inducing IIE. There are no published data evaluating fosaprepitant (fosA), prodrug for aprepitant, as a risk factor for IIE. The objective of our study is to examine the relationship between the use of fosaprepitant and development of IIE Methods: A retrospective chart review was performed of all patients (n = 81) receiving Ifo at the Medical University of South Carolina (MUSC) between July 2013 and June 2015. Data was collected for previously described risk factors of IIE and other clinical parameters including age, gender, albumin level, presence of pelvic disease, ECOG performance status (PS), serum creatinine (S.Cr), type of cancer, drug interactions (CYB2B6 and CYP3A4 inhibitors), rate of infusion, and concomitant use of fosA. Fisher's exact test with two-tailed p-value was used for analysis between groups Results: Of 81 patients (1 lost to follow up) that were analyzed, 8.7% (7/80) experienced IIE. Of patients experiencing IIE 3 had sarcoma, 3 had lymphoma, and 1 had a germ cell tumor. Patients with IIE had lower albumin, poorer performance status (ECOG PS ≥ 2), more pelvic disease, and higher baseline serum creatinine when compared to patients without IIE (Table 1). The rate of neurotoxicity appears to be similar in patients receiving fosA: IIE developed in 3 out of 45 (6.6%) patient who received fosA vs. 4 out of 31 (11.1%) patients who did not receive fosA (p = 0.69) Conclusions: In the MUSC experience, IIE does not appear to be associated with the use of fosA, but does appear to be associated with previously described risk factors including hypoalbuminemia, presence of pelvic disease, poor PS, and higher baseline S. creatinine. Risk factors associated with IIE. Risk factor IIE n = 7 (%) No IIE n = 73 (%) S. Albumin ( < 3.5 gm/dL) 7 (100) 35 (47.9) p = 0.012 Presence of Pelvic disease 6 (85.7) 29 (39.7) p = 0.039 ECOG PS ≥ 2 4 (57.1) 8 (10.9) p = 0.008 Baseline S.Cr ( > 1.2 mg/dl) 3 (42.2) 7 (9.6) p = 0.038 Fosaprepitant Use 3 (42.2) 42 (57.3) p = 0.69
EORTC 1559-HNCG: A pilot study of personalized biomarker-based treatment strategy or immunotherapy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN)—"UPSTREAM".
Authors: Rachel Galot, Lisa F. Licitra, Christophe Le Tourneau, Joel Guigay, Inge Tinhofer, Anthony Hee Kong, Carmela Aves Caballero, Catherine Fortpied, Anne-Sophie Govaerts, Dominiek Staelens, Tiana Raveloarivahy, Jean-Francois Laes, Jean-Luc Re Canon, Stéphanie Henry, Esma Saada-Bouzid, Jean-Pascal H. Machiels
Journal: Journal of Clinical Oncology (2018)

TPS6095 Background: The treatment of R/M SCCHN includes platinum-based chemotherapy, cetuximab, and anti-PD-1 compounds. Some genetic alterations have been identified, making SCCHN attractive for molecular targeted therapies. However, when these agents are given to unselected SCCHN patients (pts), only limited activity is observed. EORTC 1559 is a biomarker-driven umbrella trial for R/M SCCHN that investigates the activity of immunotherapy or targeted agents in tumors harboring pre-defined biomarker(s). Methods: Pts with R/M SCCHN progressing after platinum-based chemotherapy are enrolled. Inclusion criteria are: ECOG 0-1 and measurable disease by RECISTv1.1. Previous treatment with anti-PD(L)1 is allowed. Before inclusion, a fresh tumor biopsy is taken and analyzed in a certified central laboratory (OncoDNA, Belgium). We designed a custom theranostic test that includes IHC, NGS and gene fusions. Based on a pre-defined algorithm, pts are allocated to different treatment cohorts: afatinib (one cohort for p16- cases with either EGFR or HER2 mutation/amplification or PTEN H-score > 150 and another cohort for p16- cetuximab naïve pts), palbociclib (p16- and cyclin D1 amplification), niraparib (one cohort for p16+ oropharyngeal cancer and another cohort for p16- platinum sensitive disease) and entrectinib (NTRK1/NTRK3 or ROS1 fusions). Pts not eligible for the biomarker-driven cohorts are included in 1 of the immunotherapy cohorts (monalizumab monotherapy or monalizumab + durvalumab). Each cohort is designed as a phase II trial with its own statistical hypothesis. The 10 endpoint is either PFS or ORR depending on the investigated drug, cohort sizes range from 32 to 76 pts. The study is designed to allow the addition of new treatment cohorts based on new biomarker hypotheses. We are currently working on adding FGFR inhibitors cohorts. The EORTC HN1559 Upstream trial is the 1st international umbrella trial with a personalized treatment strategy or immunotherapy for pts with SCCHN. The study is open since November 2017 in Belgium and France with 12 first patients enrolled. We plan to open Italy, UK and Germany. Clinical trial information: NCT03088059.
Ulceration of primary cutaneous melanoma and the development of brain metastases: A retrospective chart review.
Authors: Veronica Rutt, Rachel Kinney, Arsha Nambiar Sreedhar, Dhwani Pandya, Shannon McVey Wiedersum, Jennifer Macfarlan, April Pearson, Susan Mothersele, Jeremy Agostinho, Suresh Nair
Journal: Journal of Clinical Oncology (2016)

e21036 Background: Malignant melanoma is the third most common tumor to metastasize to the brain, with a reported incidence of 10-40%. Patients who develop brain metastases have a median survival of less than six months and often develop devastating neurologic consequences. Tumor ulceration is a poor prognostic indicator and it has been reported that the presence of ulceration is associated with the development of brain metastases. Methods: We performed a retrospective analysis of 1129 patients diagnosed with melanoma to identify an association between ulceration of primary melanomas and the development of brain metastases. After reviewing the primary biopsy pathology reports, we identified Breslow depth, the presence or absence of ulceration, and tumor stage according to the 7th edition of the American Joint Committee on Cancer. Further review of the charts identified those patients who went on to develop brain metastases. We included all patients diagnosed or treated with malignant melanoma from January 2001 to December 2012 at Lehigh Valley Health Network (LVHN) who had a completed pathology report of their primary melanoma. Association was determined using the Chi-Square Test of Independence and Fisher’s Exact Test. Results: Of 1129 total patients, 15% (n = 169) had primary melanomas that were ulcerated, and 4.25% (n = 48) developed brain metastases. Of this patient subset, 62.5% (n = 30) also had ulceration. The presence of ulceration of primary melanoma was significantly associated with the development of brain metastases (p < 0.0001). When broken down by stage, the same association was statistically significant only for stage III (p < 0.0003), in which 84.2% (n = 16) developed brain metastases and also had ulceration.The median Breslow depth of our cohort was 0.890mm. Conclusions: The results of this study further confirm the previously reported strong association between presence of ulceration and development of brain metastases. Future prospective studies should be aimed at patients with ulceration of primary tumors to determine if active surveillance for brain metastases is associated with improved clinical outcomes.
Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: Results of a pivotal international study.
Authors: Robert J. Kreitman, Claire Dearden, Pier Luigi Zinzani, Julio Delgado, Tadeusz Robak, Phillipp D. Le Coutre, Bjorn T. Gjertsen, Xavier Troussard, Guiseppe Saglio, Gail J. Roboz, Lionel Karlin, Douglas Edward Gladstone, Kemal Balic, Nathan Standifer, Peng He, Shannon Marshall, Wyndham Hopkins Wilson, Ira Pastan, Nai-Shun Yao, Francis J. Giles
Journal: Journal of Clinical Oncology (2018)

7004 Background: A pivotal multicenter, single-arm study evaluated moxetumomab pasudotox, a first-in-class recombinant immunotoxin, in patients (pts) with relapsed/refractory hairy cell leukemia (HCL). Methods: Eligible pts (≥2 prior systemic therapies, including ≥1 purine nucleoside analog) received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 of 28-d cycles, up to 6 cycles. Disease response and immunohistochemistry (IHC) minimal residual disease (MRD) status were determined by blinded independent central review. Primary end point was durable complete response (CR), defined as CR with hematologic remission (blood count normalization, HR) for > 180 d. Results: Eighty pts (63 male; median age 60 y) received moxetumomab pasudotox. Median number of prior systemic therapies was 3 (2–11); 39 pts (49%) had > 3 prior lines of therapy and 60 (75%) had prior rituximab. At 16.7 months median follow-up, objective response (OR) rate was 75% (60/80), HR rate 80% (64/80), CR rate 41% (33/80), and durable CR rate 30% (24/80). Of 33 pts achieving CR, 27 (82%) had IHC MRD negative status. Median time to HR was 1 mo. Median duration of OR and median PFS were not reached. Most frequent treatment-related adverse events (AEs) were nausea (28%), peripheral edema (26%), headache (21%), and pyrexia (20%); 8% had infections and 3% had neutropenia deemed treatment related. Three deaths occurred; none were treatment related. Treatment-related AEs leading to discontinuation were hemolytic uremic syndrome (HUS; 4 [5%]), capillary leak syndrome (CLS; 2 [3%]), and increased blood creatinine (2 [3%]). Seven pts (9%) had CLS (grade 2: n = 5; grade 4: n = 2), 7 (9%) had HUS (grade 2: n = 2; grade 3: n = 3; grade 4: n = 2), and 4 (5%) had both. CLS and HUS were manageable and reversible (no plasma exchange in HUS). Median immunoglobulin levels remained unchanged after treatment. Median CD4 cell counts were stable or improved after the first week of treatment. Conclusions: Moxetumomab pasudotox achieved a high rate of independently assessed durable CR, with the ability to eradicate MRD in heavily pretreated HCL patients, and showed a favorable safety profile without immuno/myelosuppression. Clinical trial information: 01829711.
Association between glycemic control, age, and outcomes among intensively treated patients with acute myeloid leukemia (AML).
Authors: Patrick Kuhlman, Scott Isom, Timothy S. Pardee, Cynthia Burns, Bernard Tawfik, Zanetta S. Lamar, Bayard L. Powell, Heidi D. Klepin
Journal: Journal of Clinical Oncology (2017)

10043 Background: Hyperglycemia and increased glycemic variability are associated with infection and increased mortality. We evaluated the relationship between glycemic control during AML induction and outcomes by age. Methods: We retrospectively evaluated outcomes in 262 consecutive patients (pts) with newly diagnosed AML hospitalized for intensive induction at Wake Forest Baptist Hospital (2002-2009). Data on mean blood glucose (BG) (mg/dL) during hospitalization and standard deviation (SD) of BG (measure of glycemic variability, GV), complete remission ± incomplete count recovery (CR+CRi), and overall survival (OS) were collected. Modified Charlson Comorbidity Index (CCI), diabetes, age, gender, race, cytogenetics, hemoglobin, WBC, LDH, body mass index, and insurance were used in uni- and multi-variate models. We used logistic regression to evaluate CR+CRi, and Cox proportional hazard models for OS, stratified by age ( &lt; 60 vs ≥60 yrs). Results: 124 pts were &lt; 60 (median age 47, median OS 23.1 months), 138 were ≥60 yrs (median age 70, median OS 7.9 months). Older pts had higher baseline comorbidity (CCI &gt; 1 60.1% vs 25.8%) and a higher prevalence of diabetes (20.3% vs 7.3%). The mean ±SD number of BG values obtained per patient during hospitalization was 61±71. The mean ±SD of each individuals mean BG during hospitalization was 111.6±16.4 in younger versus 121.7±25.9 older pts. The mean SD of BG values [GV] was 26.8±18.6 in younger versus 33±22.8 in older pts. In multivariable analysis higher mean BG was associated with lower odds of CR+CRi in younger (odds ratio (OR) 0.67, 95% CI 0.48-0.93) and older pts (OR 0.78, 95% CI 0.65-0.93) per 10 mg/dL BG increase. Higher mean BG was associated with shorter OS in older adults (HR 1.12, 95% CI 1.04-1.21). Higher GV was associated with lower odds of CR+CRi in younger (OR 0.73, 95% CI 0.56-0.96) and older (OR 0.71, 95% CI 0.57-0.88), as well as shorter OS in older pts (HR 1.17, 95% CI 1.08-1.26) for each 10 mg/dL SD increase in GV. Conclusions: Hyperglycemia and GV during intensive induction are associated with lower CR+CRi rates (all ages) and shorter OS among older adults.Glycemic control during induction may be a modifiable factor to improve AML outcomes.
Clinical outcomes after fractional flow reserve-guided treatment of oncology patients.
Authors: Teodora Donisan, Tariq Dayah, Dinu Valentin Balanescu, Kaveh Karimzad, David L Boone, Juan Lopez-Mattei, Peter Y Kim, Jean-Bernard Durand, Eric H Yang, Joerg Herrmann, Konstantinos Marmagkiolis, Nils P Johnson, Cezar Iliescu
Journal: Journal of Clinical Oncology (2018)

e22106 Background: Unique considerations apply regarding percutaneous coronary intervention (PCI) in cancer patients. Evidence supports lesion assessment using fractional flow reserve (FFR), but its application to oncology patients has not been specifically reported. We describe FFR-guided care and outcomes in a population of cancer patients with coronary artery disease. Methods: All cancer patients at our center who underwent FFR assessment between August 2008 and September 2016 were included. Baseline demographics, all-cause mortality, cardiovascular (CV) mortality, and nonfatal myocardial infarction were noted by chart review. Each coronary lesion was evaluated by quantitative coronary angiography. Patients with lesions showing an FFR > 0.75 received medical therapy alone and those with an FFR≤0.75 underwent revascularization. Univariate Cox proportional hazards regression was used to identify factors significantly associated with risk of death. Results: 57 patients fulfilled inclusion criteria (Table 1). FFR of 57 lesions was technically successful in all cases. Patients that received a stent had a decreased risk of death (HR: 0.365, 95% confidence interval [CI] 0.148-0.898, p = 0.0281). No peri-procedural complications were noted. At 1 year, there was a 22.8% mortality, all cancer related (disease progression or cancer therapy related complications). During a median of 43 months (95%, CI 31-53 months) of follow-up, 22 (38.6%) deaths occurred, out of which 1 (1.8%) due to a CV cause. Conclusions: Our study demonstrates that within 1 year, there was a survival benefit from the revascularization of angiographic obstructive lesions ( > 70% stenosis) that were hemodynamically significant based on FFR (≤0.75). Performing PCI in lesions with FFR ≤0.75 significantly reduces mortality compared to deferring PCI. Table 1. Descriptive Statistics for Entire Group Variable Mean ± SD or Count (%) Age (years) 64.8 ± 9.92 Gender Female 16 (28.1%) Male 41 (71.9%) Lesions LAD 39 (68.4%) LCX 3 (5.3%) LM 4 (7%) RCA 10 (17.5%) Ramus 1 (1.8%) Stenosis severity (%) 65.88 ± 9.92 Stenosis severity group < 70% 25 (43.9%) ≥70% 32 (56.1%) FFR 0.77 ± 0.12 Stent No 26 (45.6%) Yes 31 (54.4%) Death within 12 months No 44 (77.2%) Yes 13 (22.8%)
Natural history of delp53 multiple myeloma.
Authors: Arjun Lakshman, Utkarsh Painuly, S. Vincent Rajkumar, Angela Dispenzieri, Morie A Gertz, Francis Buadi, Martha Lacy, David Dingli, Suzanne R. Hayman, Taxiarchis Kourelis, Rahma M. Warsame, Wilson I. Gonsalves, Prashant Kapoor, Nelson Leung, Ronald S. Go, John Anthony Lust, Stephen J. Russell, Steven R. Zeldenrust, Robert A. Kyle, Shaji Kumar
Journal: Journal of Clinical Oncology (2018)

e20017 Background: We examined patients (pts) with delp53 MM diagnosed between 2004 and 2016 to define their outcomes and identify predictors of acquiring delp53 during treatment. Methods: We identified 310 pts with MM and de novo-delp53 (detected within 6 months from diagnosis by FISH) and 620 age and period-matched controls without delp53 [divided into high-risk translocation (HRT; n = 79) and standard risk (SR; n = 541) groups]. Their progression free survival (PFS) and overall survival (OS) were compared. Eighty patients with acquired delp53 (negative by FISH initially and delp53 detected on follow-up) were compared with 160 controls for the above outcomes and putative baseline predictors. Results: In the de novo-delp53 group, median age at diagnosis was 64 yrs (range, 34-91), 39% of pts being female. 26%, 36%% and 38% patients belonged to ISS I, II and III stages respectively. 24% pts had elevated LDH. 24% pts had coexistent high-risk translocations and 50% had trisomies. Median follow up period was 60 (95% CI: 55-94) months (mo). In the de novo delp53, HRT and SR groups, 39%, 24% and 19% received proteasome inhibitor+ immunomodulatory drug-based induction and 76%, 87% and 84% pts respectively attained ≥PR as best response to induction. Median PFS in the three groups were 21 (CI, 19-24), 25 (CI, 17-27) and 31 (CI, 28-33) mo respectively and OS were 45 (CI, 40-55), 76 (CI, 53-NR) and 105 (CI, 84-113) mo respectively (P < 0.01). Age ≥65 yrs (HR: 1.5), ISS III stage (HR: 2) and presence of high-risk translocations (HR: 1.7) predicted shorter OS in de novo-delp53 MM pts. Median time to acquisition of delp53 was 36 (range, 5-116) mo. Median PFS in the acquired delp53 and control groups were, 23 (CI, 20-26) and 30 (CI, 27-34) mo and OS were 68 (CI, 50-75) and 106 (CI, 102-119) mo respectively (P < 0.05). Elevated LDH at baseline [OR- 4.9 (CI, 1.6-15.3)] predicted acquisition of delp53 while presence of high risk translocations at diagnosis showed borderline significance [OR- 2.0 (CI, 0.89-4.48)]. Age ≥65 yrs, ISS III vs. I/II stage, t(11;14), hyperdiploidy, del 13q/monosomy 13, bone marrow plasma cell percentage, initial therapy and prior stem cell therapy were not predictive. Conclusions: OS in pts with de novo delp53 is worse than those with HRT alone, and those who acquire delp53 during treatment.