tbuckley/cabot-search huggingface dataset:
Maintenance intervention to improve survival in patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment: A prospective multicenter randomized controlled clinical study.
Authors: Ying Lu, Haixin Huang, Hui Yang, Xiaohua Hu, Xianbing Feng, Changjie Huang
Journal: Journal of Clinical Oncology (2021)

6035 Background: The role of drug maintenance intervention in improving survival outcomes remains controversial.To investigate the safety and effect of Tegafur(S1) maintenance intervention in patients with metastatic nasopharyngeal carcinoma who benefit from the first-line treatment in a multicenter randomized controlled study, and to identify the related biological prognostic factors and guide the individualized treatment choice. Methods: Patients with metastatic nasopharyngeal carcinoma in the Fourth Affiliated Hospital of Guangxi Medical University and other cancer centers who met the inclusion criteria were randomly divided into maintenance therapy group: S1 maintenance therapy until disease progression or intolerance; Observation group: follow-up to disease progression. PFS, overall survival (OS) and adverse reactions of S1 maintenance therapy were compared between the two groups. The correlation between EBV-DNA, human serum amyloid A (SAA) and prognosis was evaluated. Results: Follow-up was conducted to May 2020, with a median follow-up of 19.8 months (6.1-51.3 months), 183 cases were evaluable (88 cases in S1 maintenance treatment group, 95 cases in observation group). Compared with the observation group, the S1 maintenance treatment group significantly increased patients' median PFS (16.2 months vs. 8.7 months, P &lt; 0.001) and median OS (32.1 months vs. 18.2 months, P &lt; 0.001). Reduced the risk of poor prognosis for PFS and OS (PFS: HR 0.305, 95%CI 0.211-0.441, &lt; 0.001; OS: HR 0.363, 95%CI 0.238-0.553, P &lt; 0.001). In the maintenance treatment group, the median S1 treatment lasted for 14 courses (4-58 courses), and the main adverse reactions were grade 1 skin pigmentation, oral mucositis, hand-foot syndrome, nausea, etc. No grade 4 toxic reaction occurred, and it was well tolerated. Compared with observation patients with negative EBV-DNA, observation patients with positive EBV-DNA had a higher risk of poor prognosis for PFS (HR 1.764, 95%CI 1.078-2.887, P = 0.024). The risk of poor prognosis in patients with positive EBV-NDA was significantly reduced by 61.1% ( &lt; 0.001) for PFS and 65.5% (P = 0.001) for OS (P = 0.001). Compared with the observation group with stable SAA expression, S1 maintenance therapy significantly improved the prognosis of patients. Patients with continuous decline in SAA had a 61.9% lower risk of poor prognosis in PFS (P &lt; 0.001) and a 60.2% lower risk of poor prognosis in OS (P = 0.007). Conclusions: For patients with metastatic nasopharyngeal carcinoma who benefit from first-line treatment, maintenance therapy of S1 can significantly improve the survival prognosis and is well tolerated. Patients with positive EBV-DNA and continuous decline in SAA may benefit more from maintenance intervention. Clinical trial information: ChiCTR-IOR-16007939.
Cancer environmental immunotherapy: starving tumor cell to death by targeting TGFB on immune cell
Authors: Xing Huang, Gang Zhang, Tingbo Liang
Journal: Journal for ImmunoTherapy of Cancer (2021)

The blockage of intersectional communication between tumor and its metabolic and immune microenvironment is now considered a promising solution in treating cancer. Tumors have been identified as a special type of “wounds” that do not heal. Recent studies demonstrate that the lack of the transforming growth factor beta (TGFB) signaling pathway in CD4 + helper T cells induces the remodeling of the intratumoral vascular tissue, like healing “wounds” in damaged tissues caused by tumor overgrowth, which consequently prevents tumor cells from receiving the required nutrients in their microenvironment. TGFB blockade thereby promotes damaged tissue healing, causing tumor cell death as a result of starvation, ultimately obtaining an effective anticancer immunotherapy immune response. Here, we comment on the TGFB-mediated crosstalk between immune system and nutritional supply, highlighting cancer immunotherapeutic strategies targeting environmental immune-metabolism interplay. Cancer environmental immunotherapy targeting TGFB might therefore become one of the most promising treatment strategies for patients with cancer.
Outcomes with KTE-X19 in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in ZUMA-2 who had progression of disease within 24 months of diagnosis (POD24).
Authors: Michael Wang, Javier Munoz, Andre Goy, Frederick Lundry Locke, Caron A. Jacobson, Brian T. Hill, John Timmerman, Houston Holmes, Samantha Jaglowski, Ian Flinn, Peter A. McSweeney, David Bernard Miklos, Marie José Kersten, Krimo Bouabdallah, Max S. Topp, Rhine Shen, Ioana Kloos, Weimin Peng, Xiang Fang, Patrick M. Reagan
Journal: Journal of Clinical Oncology (2021)

7547 Background: KTE-X19 is an autologous anti-CD19 CAR T-cell therapy approved in the US and EU for the treatment of R/R MCL. In the ZUMA-2 study of KTE-X19 in R/R MCL, the objective response rate (ORR) at a median 17.5-mo follow-up was 92% (67% complete responses [CR]; Wang et al. ASH 2020 #1120). Here, we report results in pts with or w/o POD24, an indicator of poor outcomes (Visco et al. Br J Haematol 2019). Methods: Eligible pts with R/R MCL underwent leukapheresis and conditioning chemotherapy followed by a single infusion of KTE-X19. Efficacy results are reported for the 60 treated pts with ≥1 y of follow-up (median 17.5 mo); safety results are presented for all 68 treated pts. Results: High-risk disease characteristics were common in pts with (n=33) and w/o POD24 (n=35), although pts with POD24 had higher tumor burden and lactate dehydrogenase (LDH) levels, and more had blastoid type MCL (Table). ORR in pts with (n=28) and w/o POD24 (n=32) was 93% and 91%, with CR rates of 61% and 72%. In pts with and w/o POD24, median progression-free survival (PFS) was 11.3 mo (range, 0.9–30.3) and 29.3 mo (range, 0–35.9). Medians for duration of response (DOR) and overall survival (OS) were not reached in either group. Most common Grade ≥3 adverse events (AEs) in pts with vs w/o POD24 were neutropenia (91% vs 80%), thrombocytopenia (61% vs 46%), and anemia (55% vs 51%); Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in 9% vs 20% and 27% vs 34%, respectively. There were no cases of Grade 5 CRS, KTE-X19–related secondary cancers, or replication-competent retrovirus in either group. In pts with vs w/o POD24, median peak CAR T-cell levels and median area under the curve were 53.4 cells/µL (range, 0.2–2566) and 583.4 cells/µL (range, 1.8–27,743.6) vs 112.4 cells/µL (range, 0.2–2589) and 1588.3 cells/µL (range, 3.8–27,238.7); by 12 mo, B cells were detectable in 8/11 (73%) vs 7/15 pts (47%) in ongoing response. Conclusions: KTE-X19 provided a high CR rate across all pts, with median DOR and OS not reached. Pts with POD24 had more aggressive high-risk disease characteristics (tumor burden, LDH levels, and blastoid MCL) and generally lower CAR T-cell expansion and PFS vs pts w/o POD24. Earlier intervention with CD19-directed CAR T-cell therapy may benefit pts with MCL with known high-risk factors. Clinical trial information: NCT02601313. [Table: see text]
An explorary analysis of a COVID-truncated REPLATINUM phase 3 trial in SCLC.
Authors: Alberto Chiappori, Mary J. Fidler, Muhammad A. Salamat, Tony R. Reid, Xiaoning Guo, Xiaohui Wang, Nacer D. Abrouk, Scott Caroen, Erica Burbano, Mary Flanagan Quinn, Jeannie Williams, Ralph J. Hauke
Journal: Journal of Clinical Oncology (2021)

e20594 Background: RRx-001 is a small molecule immunotherapeutic in Phase 3 for the treatment of SCLC that is associated with M2-M1 tumor associated macrophage (TAM) repolarization with CD47 downregulation, vascular normalization and reversal of chemoresistance. In a controlled, multicenter clinical trial called REPLATINUM that was prematurely halted due to COVID-19, data from 17 patients with third line or beyond SCLC was analyzed. Moving forward, REPLATINUM (restarted) has added SARS-CoV-2 exclusion criteria. Our aim was to explore the efficacy of RRx-001 in REPLATINUM and to assess the statistical assumptions of the REPLATINUM (restarted) trial in order to inform future clinical development in SCLC. Methods: Patients in REPLATINUM were randomized to receive 1 of 2 arms: 1) carboplatin AUC 5 IV on day 1 or cisplatin 60 mg/m 2 IV on day 1 plus etoposide 100 mg/m 2 IV on days 1 through 3 every 21 days for up to 4 cycles or 2) 4 mg of RRx-001 administered sequentially with 4 cycles of a platinum doublet (cisplatin or carboplatin plus etoposide as outlined above). Progression Free Survival (PFS) was the primary efficacy endpoint based on a blinded independent central review (BICR). Results: The trial was suspended prematurely after 17 patients had been enrolled due to widespread COVID-19 exposure with the plan to restart the trial. The decision to restart the trial has provided an opportunity to examine the data for preliminary evidence of treatment efficacy. At the time that the REPLATINUM trial was halted, there were 11 patients enrolled on the control arm and 6 on the investigational arm. The BICR assessed median PFS was approximately 7.1 months for RRx-001 + platinum doublet and 3.5 months for the platinum doublet alone based on the truncated database. The BICR assessed PFS hazard ratio was approximately 0.5. OS medians were approximately 8.2 and 6.3 months for RRx-001 + platinum doublet and platinum doublet alone, respectively. Additionally, patients on the RRx-001 + platinum doublet-treated experimental arm experienced less toxicity than patients on the platinum doublet-treated control arm. Conclusions: Despite the small sample size, preliminary results from REPLATINUM suggest a trend toward a favorable primary outcome and improved safety in RRx-001-treated patients and support the validity of the statistical assumptions that underlie the REPLATINUM (restarted) trial. Pivotal evidence will emerge from REPLATINUM (restarted) , which is imminently recommencing. Clinical trial information: NCT03699956.
Dynamic 18F-FDG Total body PET Imaging as a predictive marker of induction chemo-immunotherapy response in locally advanced non-small cell lung cancer.
Authors: Hui Liu, Bo Qiu, DaQuan Wang, Xu Zhang, Hui Liu, Yin Zhou, QiWen Li, Chu Chu, FangJie Liu, NaiBin Chen, Nan Hu, XinLei Ai, JinYu Guo, Wei Fan
Journal: Journal of Clinical Oncology (2021)

e20551 Background: The purpose of this study was to evaluate the efficacy of dynamic 18F-FDG total body PET imaging as a predictive maker of induction chemo-immunotherapy response in locally advanced non-small cell lung cancer(NSCLC) by a prospective study. Methods: Stage IIIA-IIIC NSCLC patients were prospectively enrolled in a prospective total body PETCT study ( NCT04654234, GASTO-1067) and a randomized phase II clinical trial ( NCT04085250) between September 2020 and December 2020. All patients underwent a dynamic total-body 18F-FDG PET/CT scan before any treatment and after 2 cycles of induction chemo-immunotherapy (docetaxel+cisplatin+nivolumab). The primary lung tumor, metastatic regional lymph node and inflammatory lymph node before and after treatment were manually delineated by a nuclear medicine physician and a radiation oncologist. Total Body PET was acquired between 0 – 60 mins after the injection of FDG from the subject’s feet. Patients was separated into high dynamic FDG metabolic (H-DFM) group and low DFM(L-DFM) group by the scatter plot of SUV-mean and Ki-mean of primary lung tumor. We compared lesion heterogeneity and different image-derived PET metrics including the metabolic tumor volume(MTV), SUV total lesion glycolysis(SUV-TLG), Patlak-derived influx rate constant (Ki) TLG (Ki-TLG). Results: Fifteen patients were analyzed, 8 patients was in H-DFM group and 7 in L-DFM group. Patients in H-DFM group had significant decreased levels of MTV(p &lt; 0.001), SUV-TLG(p &lt; 0.001) and Ki-TLG(p &lt; 0.001) both in primary lung tumor and metastatic lymph node by the induction chemo-immuotherapy. However, patients in L-DFM group only had a significant reduction of MTV in primary lung tumor(p &lt; 0.05). There was no significant difference in the MTV of metastatic lymph node(p &gt; 0.5), the SUV-TLG(p &gt; 0.5) and Ki-TLG(p &gt; 0.5) of primary lung tumor and metastatic lymph node, before and after induction chemo-radiotherapy. Conclusions: Patients in H-DFM group had the better treatment response of induction chemo-immunotherapy with significant decreased levels of MTV, SUV-TLG and Ki-TLG. Dynamic 18F-FDG Total body PET Imaging could be regard as a potential predictive marker of induction chemo-immunotherapy response in the setting of LA-NSCLC.
Inhibition of translation initiation factor eIF4a inactivates heat shock factor 1 (HSF1) and exerts anti-leukemia activity in AML
Authors: Yuki Nishida, Ran Zhao, Lauren E. Heese, Hiroki Akiyama, Shreya Patel, Alex M. Jaeger, Rodrigo O. Jacamo, Kensuke Kojima, Man Chun John Ma, Vivian R. Ruvolo, Dhruv Chachad, William Devine, Susan Lindquist, R. Eric Davis, John A. Porco, Luke Whitesell, Michael Andreeff, Jo Ishizawa
Journal: Leukemia (2021)
Accuracy of an urine-based liquid biopsy genetic test in detecting renal pelvic cancer.
Authors: Yansheng Xu, Min Shi, Yiming Liang, Hongzhao Li, Xin Ma, Xu Zhang, Dongxue Che, Weihua Guo
Journal: Journal of Clinical Oncology (2021)

e16500 Background: Renal pelvis cancer is accounting for about two-thirds of upper tract urinary carcinoma. Lesions in renal pelvis often lead to a differential diagnosis that requires ureteroscopic biopsy. Besides causing discomfort and pain, ureteroscopy prior to surgery increases risk of tumor implantation and recurrence. Although urine cytology and FISH were applied, more effective non-invasive diagnostic method is imperative for diagnosis of renal pelvic cancer. Methods: A total of 141 patients with one or more lesions in renal pelvis detected by ultrasound were enrolled. 50-ml first-void urine sample was collection before ureteroscopic biopsy and was analysis by Genetron uro-18 genes panel, by which mutations in 17 genes and methylation status of ONECUT2 were analysis using high-throughput sequencing. If mutations and/or ONECUT2 methylation were detected in urine sediment DNA, the patients were considered as high risk of renal pelvis cancer. The results of the urine-based liquid biopsy genetic test were compared with pathology report and urine FISH results of urinary cells. Results: According to pathological analysis with ureteroscopic biopsy, 42 out of 141 patients (29.7%) were diagnosis with renal pelvic cancer: 13 low-grade, 24 high-grade, 5 equivocal. For 33 renal pelvic cancer patients with FISH testing result of urinary cells, only 54.5% (18/33) samples were positive. By Genetron uro-18 genes test, 95 patients (67.4%) were classified as high risk and 46 (32.6%) patients were low risk. The overall specificity was 88.0% (88/95) and overall sensitivity was 92.9% (39/42), which is significant higher than FISH test of urinary cells. Conclusions: With high specificity and sensitivity, Genetron uro-18 genes test could be incorporated in renal pelvic cancer diagnosis, especially for patients with a ultrasound detectable lesions. Ureteroscopy prior to surgery could be reduced, which may lead to decrease risk of tumor implantation and recurrence.
Abstract 233: The Relationship of Maximum Troponin Values Post Out-of-hospital Cardiac Arrest with Electrocardiographic Findings, Cardiac Procedures and Survival to Discharge; A Sub-study of ROC PRIMED
Authors: Laurie J Morrison, Sean M Devlin, Michael C Kontos, Sheldon Cheskes, Andrew J Thomas, Ian G Stiell, Joseph P Ornato, Jim Christenson, Valeria E Rac, Tom P Aufderheide, Jane G Wigginton, Paul Dorian
Journal: Circulation (2013)

Objective: To describe the relationship between maximum Troponin (Tn) levels recorded within 48 hours post arrest and clinical outcomes in out-of-hospital cardiac arrest (OHCA) patients enrolled in the Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation using an IMpedance valve and Early versus Delayed analysis (PRIMED) trial. Methods: A prospective observational cohort study of all treated non-traumatic OHCAs enrolled in ROC PRIMED. Patients were classified based on first presenting in-hospital ECG as ST elevation myocardial infarction (STEMI) or not a STEMI (including NSTEMI). Peak Tn levels, evaluated on a logarithmic scale, were compared across patient and treatment characteristics using a t-test or ANOVA. The association between categories of Tn levels (&lt;0.1, 0.1-2, &gt;2) and survival to discharge was evaluated using logistic regression adjusted for Utstein predictors of survival and ROC site. Results: Of the 15617 enrolled patients, 3661 (23%) survived at least 48 hours, 17% (693) were STEMI and 78% (3188) were not a STEMI with 5% unknown and 83% (3460) with at least one Tn level measured. The mean (SD) age was 64.6 (15.9). The STEMI group had more men (74.5% STEMI, 62% not a STEMI) and was more likely to have an initial shockable rhythm (73% STEMI, 39% not a STEMI). In-hospital survival was higher with STEMI (OR 1.93, 95% CI 1.63-2.3, p&lt;0.001). The logarithm of Tn values was higher in STEMI patients (p &lt;0.001). Adjusted in-hospital survival for STEMI patients was significantly better in those patients with higher Tn values (p=0.01). Adjusted in-hospital survival was significantly worse with higher Tn levels in the not a STEMI group (p&lt;0.001). When treated with reperfusion, adjusted survival in the not a STEMI group was significantly better than the survival rate without reperfusion (OR 3.6, 95% CI 2.4-5.4 for trop&gt;0.1, p&lt;0.001). Conclusion: High Tn levels were associated with increased rates of reperfusion and better in-hospital survival in post-arrest patients with STEMI on first ECG. High Tn levels in not a STEMI patients post arrest were associated with decreased survival. Survival in not a STEMI patients was significantly higher when treated with reperfusion.
Association of baseline neutrophil-to-eosinophil ratio (NER) and neutrophil-to-lymphocyte ratio (NLR) with response to combination immunotherapy (IO) with ipilimumab plus nivolumab (ipi/nivo) in patients with metastatic renal cell carcinoma (mRCC).
Authors: Matthew D. Tucker, Landon Carter Brown, Chester Kao, Nathan Hirshman, Emily Noelle Kinsey, Yu-Wei Chen, Kristin Kathleen Ancell, Katy Beckermann, Nancy B. Davis, Renee McAlister, Kerry Schaffer, Andrew J. Armstrong, Michael Roger Harrison, Daniel J. George, Wendy Kimryn Rathmell, Brian I. Rini, Tian Zhang
Journal: Journal of Clinical Oncology (2021)

4563 Background: Previous reports have shown that the baseline neutrophil-to-lymphocyte ratio (NLR) is associated with prognosis in patients with mRCC. However, NLR has not been shown to reliably predict for response to IO. Retrospective analyses in metastatic melanoma and mRCC have shown an association of eosinophilia with improved outcomes to single agent immunotherapy. We sought to evaluate and compare the baseline NLR and NER with response to ipi/nivo in patients with mRCC. Methods: A retrospective review of patients with mRCC treated at the Vanderbilt-Ingram Cancer Center or Duke Cancer Institute with ipi/nivo was performed. Patients with clear cell histology and a baseline complete blood count with differential were included. Patients previously treated with IO were excluded. Patients were separated into groups (above and below the median) based on baseline median NER and baseline median NLR. Analyses of progression free survival (PFS) and overall survival (OS) were conducted using the log rank test. The odds ratio (OR) for objective response rate (ORR) was analyzed using Fisher’s exact test. Results: 111 patients met inclusion criteria. The median age was 60, 77% of patients were male, 68% had prior nephrectomy, 74% were naïve to systemic therapy, and 84% were IMDC intermediate/poor risk. The median NER was 25.0 and median NLR was 3.4. Patients with &lt; median baseline NER had significant improvement in PFS, OS, and ORR (see table). Patients with &lt; median baseline NLR had significant improvement in OS but not in PFS or ORR. Conclusions: Baseline NER was associated with improved outcomes with ipi/nivo. While both NER and NLR were associated with improved OS, only NER was additionally associated with both improved PFS and ORR. With multiple first-line treatment options for mRCC, baseline NER may serve as an early non-invasive predictor for response to ipi/nivo.[Table: see text]
Targeting the tumor microenvironment with amphiphilic near-infrared cyanine nanoparticles for potentiated photothermal immunotherapy
Authors: Ilkoo Noh, Youngju Son, Wonsik Jung, Munsik Kim, Dohyeon Kim, Hocheol Shin, Yeu-Chun Kim, Sangyong Jon
Journal: Biomaterials (2021)
Model-based analysis to support dose selection of pevonedistat (PEV) combined with azacitidine (AZA) in patients (pts) with higher-risk myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML).
Authors: Xiaofei Zhou, Diane R. Mould, Dan Zhao, Mikkael A. Sekeres, Lionel Adès, Ronan T. Swords, Hiroshi Handa, Robert J. Fram, Douglas V. Faller, Olga Tsukurov, Neeraj Gupta
Journal: Journal of Clinical Oncology (2021)

7042 Background: PEV+AZA has been studied in higher-risk MDS/CMML and AML, with encouraging efficacy and an acceptable safety profile without added myelosuppression. This pooled analysis was performed to evaluate the impact of PEV exposure on safety and efficacy. Methods: Data from three studies (NCT01814826, NCT02782468 and NCT02610777) were used in the PEV exposure–safety analyses, including ≥ grade 3 neutropenia (NEU3), febrile neutropenia (FN), ≥ grade 3 thrombocytopenia, ≥ grade 3 alanine aminotransferase elevation, ≥ grade 3 aspartate aminotransferase elevation and ≥ grade 3 treatment-emergent adverse event (TEAE3), in pts with higher-risk MDS/CMML and AML who received PEV+AZA. Data from NCT02610777 were used for exposure–efficacy analyses, including overall survival (OS), event-free survival (EFS), complete response (CR) and CR+partial response (PR), in pts with higher-risk MDS/CMML who received PEV+AZA. The exposure metrics for individual pts were derived from a previously developed population pharmacokinetic model with pooled data from eight phase 1/2 studies. PEV exposure–safety relationships for the toxicity endpoints, exposure–CR and exposure–CR+PR, were estimated by logistic regression. Age, sex, race, baseline Eastern Cooperate Oncology Group (ECOG) Performance Status score and disease type were evaluated as covariates. Cox proportional-hazards models were used to evaluate the PEV exposure–survival for higher-risk MDS/CMML, with age, sex, baseline ECOG PS score, Revised International Prognostic Scoring System score (IPSS-R) and disease type as potential covariates. Results: In total, 135 pts (median age, 74 years; male, 64%; Caucasian, 82%) and 41 pts (median age, 74 years; male, 76%; Caucasian, 90%; median IPSS-R, 5.5) were included in PEV exposure–safety and exposure–efficacy analyses, respectively. PEV exposure was significantly related to the incidence of NEU3 ( p = 0.003), FN ( p = 0.02) and TEAE3 ( p = 0.02), supporting PEV dose reductions for pts with treatment-related toxicities. Relationships between PEV exposures and CR, CR+PR, EFS or OS indicated consistent clinical benefit across ranges of PEV exposure following a starting dose of 20 mg/m 2 . Conclusions: The association between exposure and safety supports PEV dose reductions for pts with treatment-related toxicities. The exposure–efficacy analyses indicated consistent clinical benefit across ranges of PEV exposure following a starting dose of 20 mg/m 2 . These results support a favorable benefit–risk profile of the 20 mg/m 2 PEV dose on days 1, 3 and 5 in combination with AZA 75 mg/m 2 for 7 days in 28-day cycles. Clinical trial information: NCT01814826 , NCT02782468 , NCT02610777.