tbuckley/cabot-search huggingface dataset:
Association between body mass index and pathologic complete response in different breast cancer molecular subtypes.
Authors: Bryan Vaca-Cartagena, Andrea Becerril Gaitan, Ana Sofia Ferrigno, Alejandro Aranda-Gutierrez, Fabio A. Gonzalez-Mondellini, Mariana Roman-Zamudio, Marcos A Acosta-Sandoval, Ma. Inés Torres-Leal, Héctor Marcelino Díaz-Pérez, Servando Cardona-Huerta, Cynthia Villarreal-Garza
Journal: Journal of Clinical Oncology (2021)

e12624 Background: Obesity (BMI ≥30 kg/m 2 ) and breast cancer (BC) are two major public health concerns worldwide. Obesity has been linked with aggressive clinicopathological features and inferior survival rates in patients with BC, regardless of molecular subtype. In addition, obesity has been associated with decreased pathological complete response (pCR) rates in some BC cohorts. However, the impact of obesity on pCR rates in different BC molecular subtypes is still a subject of debate. This study aims to explore the impact of obesity on pCR rates in women with different BC subtypes in a public health-care center. Methods: Medical records of women diagnosed with primary BC between 2009 and 2020 in a center in Monterrey, Mexico were reviewed. Patients with stage II or III at diagnosis treated with neoadjuvant chemotherapy (NAC) were considered eligible. Associations between variables were examined using Fisher's exact test of independence, employing logistic regression to calculate odds ratios (OR) when appropriate. Results: A total of 559 patients with a median age at diagnosis of 48 years (range 25-85) were included. Patients were diagnosed with stages II (37%) and III (63%). The most common molecular subtype was HR+/HER2- (49%), followed by TNBC (25%), HR-/HER2+ (15%), and HR+/HER2+ (11%). Regarding BMI, a significant proportion of patients was either overweight (34%) or obese (47%). In this cohort, a total of 134 (24%) patients achieved pCR following NAC with anthracycline- and/or taxane-containing regimens. pCR rates by subtype were as follows: HR-/HER2+ (41%), TNBC (34%), HR+/HER2+ (31%), and HR+/HER2- (13%). A significant association between pCR rates and molecular subtype was found (p&lt;0.001). Overall, obesity was not significantly associated with pCR rates. However, on a stratified analysis, obese patients with HR+/HER2+ tumors had significantly decreased pCR rates compared to their non-obese counterparts (OR=0.21; 95%CI 0.05-0.93; p=0.040). pCR rates according to molecular subtype and obesity status are shown in the table below. Conclusions: Obesity has an adverse influence on pCR rates in patients with HR+/HER2+ tumors. Given the endemic nature of obesity in several low- and middle-income countries, effective programs that focus on prevention, weight reduction strategies, and health promotion are warranted. Furthermore, women should be encouraged to improve their diet and engage in regular physical activity. Efforts to elucidate potential factors that underlie lower pCR rates in obese patients with certain BC subtypes are required. [Table: see text]
Central nervous system involvement in blastic plasmacytoid dendritic cell neoplasm
Authors: Naveen Pemmaraju, Nathaniel R. Wilson, Joseph D. Khoury, Nitin Jain, Naval Daver, Sherry Pierce, Elias Jabbour, Tapan Kadia, Courtney DiNardo, Guillermo Garcia-Manero, Muzaffar Qazilbash, Marina Konopleva, Hagop Kantarjian
Journal: Blood (2021)
Radical surgery in malignnant pleural mesothelioma (MPM): An analysis of SEER database.
Authors: Qian Wang, Yaning Zhang, Meng Ru, Changchuan Jiang, Jessica Tran, Juan P. Wisnivesky, Rajwanth Veluswamy
Journal: Journal of Clinical Oncology (2021)

8554 Background: MPM is an aggressive malignnancy with poor overall prognosis. A combined treatment approach involving radical surgery (RS), radiation (RT) and chemotherapy (CT) provide improved survival compared to systemic treatment alone. Selecting patients who may benefit from RS is challenging. The NCCN guidelines recommend that up to T3N1M0 (Stage IIIA) epithelioid or biphasic MPM should be considered for multimodality therapy incorporating RS. However, the impact of clinical and pathologic features within each histologic subtype of MPM on RS outcomes is unknown. Methods: MPM patients from the SEER 18 program from 2004-2015 were identified. Cox proportional hazard regression models were used to examine the independent contribution of several clinical and pathologic features on overall survival (OS) in patients who received RS vs those that did not. Results: A total of 5,498 MPM patients were identified, of which 531 underwent RS. Overall, RS was associated with improved OS in the multivariate model adjusting for important clinical and pathological characteristics (Table). When stratifying according to histology, epithelioid subtype was linked to improved OS with RS despite of the presence male gender, age &gt; 60 years old, T3, T4 or N2 or above disease; and the OS improved among those who also underwent CT ± RT with RS. Patients with sarcomatoid histology also had OS benefit from RS (HR=0.59, 95%CI: 0.37-0.93), even those that were &gt; 60 years old, but not among those with more advanced disease (T3/4, N2/3). Sarcomatoid patients who received CT ± RT (HR = 0.52, 95%CI: 0.30-0.90) also experienced OS benefit. Among biphasic histology, no OS benefit was found overall (P = 0.11) or within other high-risk clinical features except for those who were treated CT ± RT (HR = 0.64, 95%CI: 0.45-0.90). Conclusions: Our findings demonstrate that the presence of high-risk clinical and pathologic features does not impact OS benefit of RS in epithelioid MPM, however should be considered when deciding on RS in sarcomatoid and biphasic histologies. Poor prognostic histology especially sarcomatoid subtype may experience improved survival with RS if in conjunction with other treatment modalities.[Table: see text]
Persistent Somatic Mutation at Remission Is Associated with Poor Survival and Higher Risk of Relapse in Patients with Acute Myeloid Leukemia
Authors: Kiyomi Morita, Feng Wang, Keyur Patel, Carlos Bueso-Ramos, Ghayas C. Issa, Xingzhi Song, Jianhua Zhang, Samantha Tippen, Rebecca Thornton, Marcus Coyle, Latasha Little, Curtis Gumbs, Farhad Ravandi, Tapan Kadia, Naval Daver, Marina Konopleva, Michael Andreeff, Jorge E. Cortes, Guillermo Garcia-Manero, Elias J. Jabbour, Andrew Futreal, Hagop M. Kantarjian, Koichi Takahashi
Journal: Blood (2017)
Abstract 15467: Variations in T1 Mapping and LV Functional Parameters in a Multi-Center Study: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Patricia B Rizzi, Marcelo S Nacif, Erin P Ricketts, Chia-Ying Liu, Antoinette S Gomes, Gregory Hundley, Martin R Prince, James Carr, Robyn McClelland, Kiang Liu, John Eng, Craig Johnson, Raimond L Winslow, David A Bluemke, Joao A Lima
Journal: Circulation (2012)

Introduction: T1 mapping techniques may be useful as an index of myocardial fibrosis, but have not previously been assessed in a multi-center study. We sought to assess site variation/reproducibili...
H101 treatment of hepatic metastasis of colorectal cancer with recombinant human adenovirus 5 injection: A phase I clinical trial-TROJAN 021.
Authors: Yang He, Jianhua Chen, Zhongzheng Zhu, Song Gao, Hui Wang, Wei Mao, Hong Qian, Weixing Liu, Xianling Guo, Huanlong Qing, Qing Xu
Journal: Journal of Clinical Oncology (2021)

3605 Background: Recombinant human adenovirus serotype 5 injection (H101), obtained through genetic engineering to delete the E1B domain and part of the E3 domain and then selectively replicated in tumor cells, has been approved in 2005 for the local treatment of nasopharyngeal carcinoma and head and neck cancers. This trial aimed to evaluate the safety and the preliminary treatment efficacy of H101 combined with standard treatments in patients with liver metastases from colorectal cancer. Methods: In this phase 1, dose-escalation trial (ChiCTR1900027922), 17-75 years old colorectal cancer patients with unresectable liver metastases that failed to first-line therapy were included at The Tenth People's Hospital Affiliated to Tongji University between 2018.9 and 2020.12. All patients received H101 combined with standard therapy (bevacizumab + mFOLFOX6/FOLFIRI). Ultrasound-guided injection of H101 into the liver metastases was performed for all patients, with one of the following doses: 5×10 11 vp/injection for the low, 1×10 12 vp/injection for the moderate, 2×10 12 vp/injection for the moderate-high, and 3×10 12 vp/injection for the high dose groups. Intravenous infusion of bevacizumab (5 mg/kg) and administration of standard-dose mFOLFOX6 or FOLFIRI within 48 h after the intratumor injection was performed. The primary endpoint of the trial was the maximum tolerated dose (MTD). The secondary endpoints included safety, tumor responses, and tumor marker CEA. The adverse events (AEs) were monitored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) and evaluated within 1 week after injection. Imaging examinations were performed for all patients to evaluate the tumor responses, according to the irRECIST. Results: Finally, 8 patients were included; the numbers of patients in the 4 groups were 1, 3, 3, and 1, respectively. MTD was not observed in this study. No grade &gt;4 AEs were observed. The major AE included fatigue (5/8), fever (4/8), shiver (3/8), abdominal pain (3/8), and night sweat (3/8). The tumor responses included partial response in one patient (moderate dose group), stable disease in 6 patients (1, 1, 3, and 1 in the low, moderate, moderate-high, and high dose groups, respectively), and progressive disease in 1 patient (moderate group). No dose-effect response was found. The tumor marker CEA was reduced in 6 of the 8 patients, including 1 (1/1), 3 (3/3), 2 (2/3), and 0 patients in the low, moderate, moderate-high, and high-dose groups, respectively. Conclusions: The safety of H101 combined with standard therapy for liver metastases from colorectal cancer is acceptable, which also shows certain preliminary efficacy. The phase 2 trial is now ongoing. Clinical trial information: ChiCTR1900027922. [Table: see text]
Clinical and economic burden among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) receiving first-line (1L) chemoimmunotherapy (CIT) by risk status: A chart-linked claims analysis.
Authors: Lori A. Leslie, Nilesh Gangan, Hiangkiat Tan, Qing Huang
Journal: Journal of Clinical Oncology (2021)

e19505 Background: In patients with CLL/SLL, high risk genetic abnormalities are associated with inferior responses to CIT, and the economic burden of this remains uncertain. This study aimed to compare real world clinical and economic outcomes in high risk and perceived non-high risk patients initiating 1L CIT. Methods: This retrospective cohort study identified patients with CLL/SLL from the HealthCore Integrated Research Database representing a national managed care population with over 58 million members. Medical records were obtained for eligible patients who initiated 1L CIT between 1/1/2007 and 7/31/2019 and underwent prognostic testing to classify them as high risk (HR: del17p, TP53 mutation, del11q or unmutated IGHV) or as non-high risk by FISH only (NHR: non-del17p and non-del11q). The first CIT claim date was the index date. Patients were required to have ≥12 months of pre-index and ≥30 days of post-index eligibility. Study outcomes included testing rate, time to next treatment (NT) or death, time to treatment failure (TF; defined as time to change of therapy, non-chemotherapy intervention, hospice care or death), and total plan paid costs (medical + pharmacy) per patient per month (PPPM) in the 1L period. Cox proportional hazard models and generalized linear models were used to calculate adjusted hazard ratio or rate ratio. Results: Among the 1,808 patients with CLL/SLL, 612 were FISH or IGHV tested and the rate of testing increased from 2007 to 2019 (30% to 44%), especially after adding ibrutinib for 1L CLL with del17p in NCCN guidelines v4.2014. Risk status was available for 253 patients (HR: 119; NHR: 134), with 80% of patients initiating 1L BR/FCR-based therapy in both cohorts. Median follow up was 26.4 vs. 25.8 months (HR vs NHR). HR patients had 65% higher risk of NT/death (median time: 2.4 vs 3.7 years), and 65% higher risk of TF (median time: 3.0 vs 4.9 years) compared to NHR patients (Table). The total costs PPPM were also significantly higher for HR patients in the 1L period ($12,194 vs $9,055, p=0.027; Rate Ratio=1.33, p&lt;0.001). Conclusions: Initiating 1L CIT among HR patients with CLL/SLL was associated with increased risks of NT/death, TF, and higher costs compared to NHR patients identified by FISH only. Assessment of cytogenetic/molecular risk status for appropriate treatment is vital to optimize clinical and economic outcomes, especially in the novel agent era. Recent testing practices to assess genetic risk in CLL remains suboptimal.[Table: see text]
Phase III study of NUC-1031 + cisplatin versus gemcitabine + cisplatin for first-line treatment of patients with advanced biliary tract cancer (NuTide:121).
Authors: Jennifer J. Knox, Mairead Geraldine McNamara, Lipika Goyal, David Cosgrove, Christoph Springfeld, Katrin Marie Sjoquist, Joon Oh Park, Helena Verdaguer, Chiara Braconi, Paul J. Ross, Do-Youn Oh, Aimery De Gramont, John Raymond Zalcberg, Daniel H. Palmer, Juan W. Valle
Journal: Journal of Clinical Oncology (2021)

TPS4164 Background: Biliary tract cancer (BTC) is an aggressive disease with a poor prognosis. Gemcitabine + cisplatin (GemCis) is the accepted global standard of care (SoC), however key cancer resistance mechanisms associated with the transport, activation and breakdown of gemcitabine are known to limit its clinical activity across a range of tumor types, including BTC. NUC-1031 is a phosphoramidate transformation of gemcitabine designed to overcome these key resistance mechanisms and generate much higher levels of the active anti-cancer metabolite, dFdCTP, in cells. Promising efficacy has been observed with single-agent NUC-1031 in a phase I study in advanced solid tumors and in the phase Ib ABC-08 study of NUC-1031 + cisplatin for first-line treatment of advanced BTC. Of 21 patients enrolled in 2 dose cohorts (NUC-1031 625 mg/m 2 or 725 mg/m 2 + cisplatin 25 mg/m 2 on Days 1 and 8 of 21-day cycle), 16 were considered to be efficacy evaluable. In this population, 1 patient had a CR and 6 patients had PRs, resulting in an ORR of 44% (7/16). This compares favorably to the 26% ORR reported for the SoC regimen. In addition, 6 patients had SD, resulting in a DCR of 81% (13/16). The combination was well tolerated with no unexpected AEs or DLTs. The recommended dose of NUC-1031 with cisplatin was 725 mg/m 2 . The tolerability profile, together with encouraging efficacy led to initiation of a global registrational study. Methods: NuTide:121 is a phase III, open-label, randomized study of NUC-1031 + cisplatin vs GemCis for first-line treatment of advanced BTC. Patients ≥18 years with histologically- or cytologically-confirmed BTC (including cholangiocarcinoma, gallbladder, or ampullary cancer), who have had no prior systemic chemotherapy for locally advanced/metastatic disease, are eligible. A total of 828 patients are being randomized (1:1) to either 725 mg/m 2 NUC-1031 or 1000 mg/m 2 gemcitabine, both with 25 mg/m 2 cisplatin, administered on Days 1 and 8 of 21-day cycles. Primary endpoints are OS and ORR. Secondary endpoints include PFS, safety, PK and patient-reported quality of life. In addition to the final analysis, three interim analyses are planned. The study has passed an initial safety analysis, with no protocol changes required. NuTide:121 is being conducted at approximately 130 sites across North America, Europe and Asia Pacific. Clinical trial information: NCT04163900.
Evaluation of different <i>MET</i> genotypes as biomarkers for immunotherapy outcomes in NSCLC patients.
Authors: Xuanzong Li, Linlin Wang
Journal: Journal of Clinical Oncology (2021)

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.
Risk factors for <scp>CKD</scp> stage <scp>II</scp> onset in a prospective cohort of homozygous sickle cell adults
Authors: Camille Roger, Francois Lionnet, Sarah Mattioni, Marine Livrozet, Olivier Steichen, Emmanuel Letavernier, Nadjib Hammoudi, Virginie Avellino, Jean‐Philippe Haymann
Journal: American Journal of Hematology (2021)

Prevalence of renal impairment is increasing with aging in sickle cell anemia (SCA) patients, and is responsible for a high morbidity and mortality. However, sickle cell nephropathy's natural course remains mostly unknown. We conducted a prospective observational cohort study aimed to identify risk factors for CKD stage II in a cohort of SCA patients. Baseline clinical and biological parameters were collected. Renal parameters were updated at each visit. Risk factors were analyzed using the Cox model. Five-hundred and thirty-five SCA patients were included with a median follow-up of 5.33 (IQR:2.10-8.13) years. Median age was 22 (IQR:19-30) years old. Glomerular hyperfiltration was detected in 299 (55.9%) patients, microalbuminuria and macroalbuminuria in 180 (34%) and 67 (12.7%) patients respectively. During follow up, CKD stage II onset was detected in 39 patients (7.3%). Risk factors for CKD stage II after adjustment on baseline eGFR and age were macroalbuminuria HR: 3.89 [95% CI: 1.61;9.43], diastolic blood pressure (DBP) above 70 mm Hg HR: 2.02 [1.02-3.971], LDH (for 100 IU/L increase) HR: 1.28 [1.12;1.48] and tricuspid regurgitation velocity >2.5 m/sec HR: 2.89 [1.20-6.99]. Multivariate analysis also found age as a strong independent risk factor with HR: (per year increase) 1.13 [1.09;1.16] and a 13.3-fold increase above 30 years (p < 0.001). Our results show a high incidence of CKD stage II with aging, with a strong significant risk increase after 30-years-old, and pinpoint baseline DBP, macroalbuminuria and increased LDH as independent risk factors raising the issue of optimal blood pressure targets for SCA patients.
Phase I study of adoptive immunotherapy for advanced MUC1* positive breast cancer with autologous T cells engineered to express a chimeric antigen receptor, huMNC2-CAR44 specific for a cleaved form of MUC1 (MUC1*).
Authors: Jennifer M. Specht, David G. Maloney, Cecilia Yeung, Vicky Wu, Cynthia Bamdad
Journal: Journal of Clinical Oncology (2021)

TPS2663 Background: Chimeric antigen receptor (CAR) T cell therapy targeting CD19 results in marked tumor regression for patients with CD19+ malignancies. It would be ideal to extend the success of CAR-T cell therapy to epithelial cancers. MUC1* is a post-translationally modified/cleaved form of mucin 1 (MUC1) that is frequently expressed on breast tumors, functions as a growth factor receptor, and a promising antigen for CAR-T cell therapy. Minerva Biotechnologies developed a CAR (huMNC2-CAR44) which recognizes MUC1* and does not bind to full-length or MUC1* negative cells. huMNC2-CAR44 product consists of autologous T cells transduced with a lentiviral vector encoding humanized MNC2-scFv (MUC1* targeting head), sequences from CD8 𝛼 leader, hinge and transmembrane domains, 4-1BB and CD3ζ domains. Methods: NCT04020575 is a phase I study evaluating the safety of adoptively transferred autologous T cells genetically modified to express huMNC2-CAR44 in patients with metastatic MUC1* positive breast cancer. After screening, leukapheresis is performed, CD8+ and CD4+ T cells are selected, transduced with huMNC2-CAR44, expanded, and antigen stimulated in vitro. Lymphodepletion with cyclophosphamide and fludarabine is followed by infusion of huMNC2-CAR44 CAR-T cells in escalating doses (3.3 x 10 5 CAR+ T cells/kg – 1 x 10 7 CAR+ T cells/kg). Key inclusion criteria include metastatic breast cancer of known ER, PR and HER2 status, MUC1* membrane expression &gt; or = 30% with 2+ staining by IHC, measurable or evaluable disease, receipt of standard systemic therapies known to confer benefit, age &gt; 18, informed consent, adequate organ function, and KPS &gt; or = 60%. Patients with active autoimmune disease, uncontrolled infection, anticipated survival &lt; 3 months, and/or untreated CNS metastases are not eligible. The primary objective is to identify the maximum tolerated (MTD) dose of huMNC2-CAR44 T cells by CTCAE v5 and Lee criteria. Secondary objectives include persistence and phenotype of adoptively transferred huMNC2-CAR44 T cells and preliminary antitumor activity. Exploratory objectives include trafficking of huMNC2-CAR44 T cells to tumor sites, effector function of huMNC2-CAR44 T cells in vivo, association between tumor MUC1* expression and huMNC2-CAR44 T cell persistence and response, change in tumor immune microenvironment by multiplex IHC in pre- and post-treatment tumor biopsies. Dose escalation is completed using a "3+3" design. Once the MTD has been determined, up to 15 more patients will be enrolled in each of 3 expansion cohorts (Luminal, HER2 positive, and TNBC) to inform future huMNC2-CAR44 T cell trials. Study is open to screening and enrollment in dose escalation. Up to 69 patients may be enrolled in dose escalation and expansion phases. Clinical trial information: NCT04020575.