tbuckley/cabot-search huggingface dataset:
Analysis of predictive factors of ramucirumab plus paclitaxel for advanced gastric cancer.
Authors: Naoki Fukuda, Daisuke Takahari, Hiroki Osumi, Tomohiro Matsushima, Izuma Nakayama, Takeru Wakatsuki, Mariko Ogura, Takashi Ichimura, Masato Ozaka, Mitsukuni Suenaga, Eiji Shinozaki, Keisho Chin, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2017)

185 Background: Ramucirumab (RAM) is a novel anti-VEGF antibody approved in 2015 in Japan. Predictive factors for RAM in combination with paclitaxel (PTX) remain largely unknown. Methods: We reviewed 77 consecutive advanced gastric cancer patients who were treated with RAM plus PTX between June 2015 and June 2016 in our institution. We evaluated treatment outcome and analyzed potential predictive factors by univariate and multivariate analyses. Results: Median age was 67 years (range 35-83) and 51 % of the patients were male. The ECOG performance status (PS) was ≥ 2 in 8 patients. 89% (69/77) patients were treated as second line chemotherapy. Objective response rate (ORR) in patients who have measurable disease was 52 % (17/33). Median progression free survival (PFS) and overall survival (OS) and was 6.0 months (95% confidence interval [CI] = 4.3-7.1) and 10.4 months (95% CI 6.8-13.6), respectively. The most frequent adverse events were peripheral neuropathy (44%), G3 ≥ neutropenia (34%), hypertension (32%) and bleeding (27%). At multivariate analysis, hypertension was independent factor for OS (Hazard ratio [HR] = 0.35, 95% CI = 0.14-0.90, P = 0.03). Also, bleeding (HR = 0.23, 95% CI = 0.09-0.55, P = 0.001) was independent factor for PFS and hypertension (HR = 0.47, 95% CI = 0.22-1.02, P = 0.06) had trend toward to show better PFS. Conclusions: RAM plus PTX showed promising efficacy for advanced gastric cancer. RAM related toxicities such as hypertension and bleeding/hemorrhage were independent factors for better outcome. Further investigation is warranted to verify our analysis.
Thromboembolism (TE) in children with acute lymphoblastic leukemia (ALL) treated on Dana Farber Cancer Institute (DFCI) protocols: Effect of dose and type (prednisone versus dexamethasone) of steroids used
Authors: U. H. Athale, S. A. Siciliano, R. D. Barr, A. K. C. Chan
Journal: Journal of Clinical Oncology (2004)

8525 Background: Comparison of two multi-institutional Berlin-Frankfurt-Munster (BFM)-ALL studies showed that dexamethasone (Dex), instead of prednisone (Pred), with asparaginase (ASP) significantly reduces the risk of TE. To confirm this observation, we studied the effect of dose and type of steroids used in combination with ASP on incidence of TE in children with ALL treated at a single institution on three consecutive DFCI-ALL protocols. Methods: Data on prospectively assembled cohorts of children (≤ 18 years) was analyzed. All patients received similar induction therapy including Pred. During intensification therapy, patients received either Dex (protocol 91–01) or Pred (protocol 95–01) or were randomized to receive Pred or Dex (protocol 20–01) at 5/21 days cycles with weekly ASP. On all 3 protocols, high-risk patients received high-dose (HD) steroids (Pred 120 mg/m2/d or Dex 18 mg/m2/d) while standard-risk patients received low-dose (LD) steroids (Pred 40 mg/m2/d or Dex 6 mg/m2/d). Results: In all 129 patients were eligible for analysis. Details of steroids during intensification and frequency of TE in each group are shown in Table. On 20–01 protocol, 3 of 21 (14.3%) patients on Pred had TE compared with 3 of 16 (18.7%) on Dex (p=1.0). Conclusions: The dose, but not the type, of steroid used in combination with ASP significantly altered the risk of TE in children treated on DFCI-ALL protocols. Patients receiving HD steroids were at significantly increased risk of TE. Unlike BFM studies, Dex in combination with ASP was not associated with lower risk of TE. Randomized controlled trials with larger patient populations are recommended to confirm these results. No significant financial relationships to disclose.
Thymidylate synthase (TS) polymorphisms (Pol) in buffy coat-derived genomic DNA as a clinical outcome predictor in non-Asian stage III/IV non-small cell lung cancer (NSCLC) patients (pts) receiving pemetrexed (Pem).
Authors: Estefania Arevalo, Ines Lopez, Maria Antonia Fotuño, Eduardo Castanon, Victor Collado, Maria Rodriguez, Alicia Olarte, Maria Pilar Andueza, Jose Luis Perez Gracia, Ana Patiño-García, Ignacio Gil-Bazo
Journal: Journal of Clinical Oncology (2013)

e19112 Background: TS is the main biological target of the antifolate Pem. Some TS Pol may confer a short survival and a poor response to antifolate-treated colo-rectal cancer pts. Whether TS genotype has an independent prognostic/predictive impact on non-Asian advanced NSCLC pts treated with Pem is unknown. Methods: Twenty-five non-Asian advanced NSCLC pts treated with Pem-based regimens (1st, 2nd or 3rd line) were included. Genomic DNA was isolated from periferal blood prior to treatment. The variable number of tandem repeat (VNTR) Pol, the G&gt;C single nucleotide Pol (SNP) and the TS 6-bp insertion/deletion (6/6) in the 3' untranslated region (UTR) Pol were analyzed and correlated with response rate (RR), progression-free survival (PFS), overall-survival (OS) and toxicity (Tx). Results: Regarding the VNTR Pol, most of the pts showed 2R/2R or 3R/2R Pol (17 pts; 68%), and 8 pts (32%) showed 3R/3R or 3R/4R Pol. A SNP (G&gt;C) in VNTR was observed in 18 pts (72%). The Pol found in the 3´UTR region were +6/+6 in 12 pts (48%), +6/-6 in 11 pts (44%) and -6/-6 in 2 pts (8%). In the subgroup of T3-T4 pts, there was a higher RR among those showing 3R/3R Pol than those with 2R/2R Pol (100% vs 83.8%; p=0.029). The genotype +6/+6 predicted a higher RR among active/former smokers (A/FS) compared to +6/-6 (100% vs 37.5%; p=0.026). A 3R/3R Pol followed by 2R/2R and 2R/3R Pol predicted a superior RR in pts with EGFR mutations (p=0.018). Overall, a trend towards a better PFS in pts showing 2R/2R Pol was found (p=0.076). The cohort’s median overall survival (OS) was not reached during follow-up. The most frequent Tx was grade (G)1 anemia (28%) and nausea (20%) and G2 leucopenia (40%). G3-4 anemia (4%), leucopenia (16%), neutropenia (4%), astenia (8%) and dyspnea (4%) were uncommon but more frequent in pts with 2R/2R Pol (p=0.545). Conclusions: In this cohort of NSCLC pts 3R/3R Pol among T3-T4 pts and EGFR mutant pts and +6/-6 bp among A/FS significantly predicted a higher RR to Pem and may aid in treatment selection. Tx was not significantly correlated with a specific TS genotype. These interesting preliminary data warrant further validation in larger series.
Autonomous TNF is critical for in vivo monocyte survival in steady state and inflammation
Authors: Yochai Wolf, Anat Shemer, Michal Polonsky, Mor Gross, Alexander Mildner, Simon Yona, Eyal David, Ki-Wook Kim, Tobias Goldmann, Ido Amit, Mathias Heikenwalder, Sergei Nedospasov, Marco Prinz, Nir Friedman, Steffen Jung
Journal: The Journal of Experimental Medicine (2017)

Monocytes are circulating mononuclear phagocytes, poised to extravasate to sites of inflammation and differentiate into monocyte-derived macrophages and dendritic cells. Tumor necrosis factor (TNF) and its receptors are up-regulated during monopoiesis and expressed by circulating monocytes, as well as effector monocytes infiltrating certain sites of inflammation, such as the spinal cord, during experimental autoimmune encephalomyelitis (EAE). In this study, using competitive in vitro and in vivo assays, we show that monocytes deficient for TNF or TNF receptors are outcompeted by their wild-type counterpart. Moreover, monocyte-autonomous TNF is critical for the function of these cells, as TNF ablation in monocytes/macrophages, but not in microglia, delayed the onset of EAE in challenged animals and was associated with reduced acute spinal cord infiltration of Ly6Chi effector monocytes. Collectively, our data reveal a previously unappreciated critical cell-autonomous role of TNF on monocytes for their survival, maintenance, and function.
Regorafenib antitumor activity alone and in combination with radio or chemotherapy in preclinical models of pediatric solid tumors.
Authors: Estelle Daudigeos-Dubus, Ludivine Le Dret, Claudia Lanvers-Kaminsky, Olivia Bawa, Paule Opolon, Irene Villa, Jacques Bosq, Gilles Vassal, Dieter Zopf, Birgit Geoerger
Journal: Journal of Clinical Oncology (2014)

10049 Background: Angiogenesis plays a pivotal role in tumor growth and metastatic spread in children. High VEGF expression is correlated with invasion, metastases and risk for recurrence. In several pediatric tumors, angiogenesis is further driven by PDGFR and FGFR signaling. We evaluated the novel potent oral multikinase inhibitor regorafenib (BAY-73-4506) against pediatric cell lines and xenografts. Methods: Inhibition of cell proliferation and migration was explored in vitro against the Innovative Therapies for Children with Cancer (ITCC) cell line panel by MTS assay and against neuroblastoma cells by phase-contrast with Incucyte. In vivo, athymic mice bearing subcutaneous PDGFRA gene amplified IGRG93 glioma (derived from an adult patient) and IGRM57 medulloblastoma, and orthotopic IGR-N91-Luc neuroblastoma xenografts were treated with regorafenib at 10 or 30 mg/kg orally during at least 21 days alone or in combination with irradiation or irinotecan. Results: Regorafenib inhibited cell proliferation in vitro at GI50s of 1.85 – 31.8 µM in pediatric cell lines. It exhibited a dose-dependent effect on proliferation and migration of IMR-32-Luc and IGR-N91-Luc neuroblastoma cells with IC50s of 0.8 µM and 2.6 µM respectively. In IGR-N91-Luc neuroblastoma, IGRG93 glioma and IGRM57 medulloblastoma xenografts, regorafenib at 10 or 30 mg/kg resulted in significant tumor growth inhibition associated with decreased tumor vascularisation. In IGRG93 glioma, regorafenib resulted in significant tumor growth delay and 100% tumor regression (3/10 complete responses (CR) and 7/10 partial responses (PR) at 10 mg/kg; 5/11 CR and 6/11 PR at 30 mg/kg) when combined with irradiation which alone resulted in 3 PR in 11 tumors. Equivalent effects were observed against IGRM57 medulloblastoma when regorafenib was combined with irinotecan (5/7 CR and 2/7 PR versus 2/7 CR and 5/7 PR respectively). Inhibition of angiogenesis was associated with induction of tumor cell death, particularly in the combination strategies. Conclusions: Regorafenib exhibits significant antitumor activity alone and increased effects when combined with standard of care treatments.
A prospective evaluation of cognitive function in patients with early breast cancer receiving adjuvant chemotherapy
Authors: M. Ruzich, B. Ryan, C. Owen, A. Delahunty, R. Stuart-Harris
Journal: Journal of Clinical Oncology (2004)

549 Background: Previous retrospective studies have suggested that cognitive function (CF) may be impaired after adjuvant chemotherapy for early breast cancer. We have completed the first prospective study to assess the CF of women with early breast cancer, before, during and after adjuvant chemotherapy. Methods: Between May 2000 and November 2001, 90 female patients with early breast cancer planned to receive adjuvant chemotherapy were invited to participate and 37 agreed. The cognitive assessment was comprised of an extensive battery of neuropsychological tests and psychological inventories assessing quality of life, cognitive, physical and emotional functioning. All 37 patients were tested prior to chemotherapy, but two were excluded because of poor overall performance suggestive of early dementia. In the remaining 35 patients, CF was assessed again after three (n=31) and six months of chemotherapy (n=30) and six months following completion of chemotherapy (n=27). Twenty-seven patients completed testing on all four occasions. Thirty-one received oral CMF (6 cycles) and 6 received EC (4 cycles) followed by oral CMF (3 cycles) [EC/CMF]. Results: Prior to chemotherapy, 18 of the 35 remaining patients (51%) had impairment on two or more neuropsychological tests. Group analysis of neuropsychological test scores indicated that scores for measures of verbal memory and verbal learning were significantly lower at six months (on completion of chemotherapy) than either before chemotherapy or six months after completion of chemotherapy. Group analysis of other measures, indicated that CF either remained constant or significantly improved. Conclusions: Patients with early breast cancer may have evidence of impaired CF prior to chemotherapy. Although a transient deterioration in verbal memory and verbal learning was observed on completion of chemotherapy, on all other neuropsychological measures, CF did not decline during the administration of adjuvant chemotherapy. No significant financial relationships to disclose.
Clinical features and overall survival (OS) in patients (pts) with post-docetaxel (DTX) metastatic castration-resistant prostate cancer (mCRPC) receiving second-line (2L) therapy in the community setting.
Authors: William K. Oh, Raymond Miao, Mei Sheng Duh, Francis Vekeman, Jennifer Sung, Wendy Y Cheng, Daniel Hennessy, Marjolaine Gauthier-Loiselle, Jonathan Fortier, Ravinder Dhawan
Journal: Journal of Clinical Oncology (2015)

e16029 Background: Treatment of mCRPC has evolved in the last decade with approval of new chemotherapies and androgen receptor (AR)-targeted therapies. Despite trial data showing clinical efficacy of these drugs, clinical features and outcomes of pts receiving 2L treatments post-DTX are unclear. Our study assessed real-world data from US community oncology practices. Methods: mCRPC pts ≥ 18 years old who had ≥ 2 therapies (chemotherapy: DTX, cabazitaxel [CBZ]; AR therapy: abiraterone, enzalutamide) after DTX were identified from Altos Solutions’ electronic medical records. OS from start of 2L therapy was assessed using Kaplan–Meier and Cox regression models adjusting for site of metastasis, prostate-specific antigen (PSA), hemoglobin (Hb), alkaline phosphatase (ALP) and albumin (ALB) levels. Results: Of 629 pts who received first-line DTX, 123 received CBZ and 506 received AR therapy in 2L. Pts receiving 2L CBZ had higher mean PSA (441 v 263 ng/mL, P < .001) and ALP (201 v 183 U/L, P < .001), lower mean lactate dehydrogenase (375 v 692 U/L, P = .035) and Hb (10.7 v 11.3 g/dL, P < .001), and more pts in Halabi intermediate-/high-risk groups (59% v 44%, P = .003) (JCO 2014:32;671–7) than pts receiving 2L AR therapy. Overall crude median OS was 10.2 v 15.1 months for pts receiving CBZ who had worse prognostic features than pts receiving AR therapy, but this did not reach statistical significance (P = .155); after multivariate adjustment for differences in clinical features, there remained no statistical difference in OS with a trend in favor of CBZ (adjusted hazard ratio [HR] for CBZ v AR = 0.81, 95% CI 0.60–1.09). In the Halabi high-risk subgroup, OS was significantly longer for pts receiving CBZ v AR therapy (HR 0.35, 0.17–0.74), as well as in pts with ALB below the lower limit of normal (HR 0.45, 0.23–0.86) and Hb < 11 g/dL (HR 0.64, 0.43–0.96). Conclusions: In the community oncology setting, post-DTX pts receiving CBZ have more high-risk features than pts receiving AR therapy. For pts with a Halabi high-risk score, or low ALB or Hb, CBZ may offer greater OS benefit than AR-targeted therapy. A prospective study is warranted. Funding: Sanofi.
“Fight fat with fat”: The impact of brown adipose tissue (BAT) on breast cancer prognosis–A retrospective analysis.
Authors: Orlando Esteban Silva, Sean Michael Warsch, Alfredo Enrique Torres, Alexandra Gomez Arteaga, Gustavo Westin, Richa Dawar, Quinton Randall Sparrow, Damien Mikael Hansra, Karen Hernandez, Marta Torroella, Purvi Doshi, Aldo N. Serafini, Marc E. Lippman
Journal: Journal of Clinical Oncology (2015)

1585 Background: Two types of adipose tissue exist: white adipose tissue (WAT) and BAT. WAT is the main energy store in humans and is associated with obesity and inflammation. BAT is thought to be protective against obesity and acts as an energy dissipating organ, which may fight obesity by reducing adipokines, inflammatory cytokines, and insulin resistance. The relationship of brown fat activation and cancer prognosis is unknown. We hypothesize that BAT may be protective to breast cancer patients by shifting glucose pool away from tumors and reducing tumor activity. Methods: Through a retrospective chart review of over 900 patients treated by the Breast Cancer Group at our institution, we identified 98 patients with BAT on PET CT scans. We collected information on patient demographics, lifestyle, staging and treatments received and response, progression of disease, overall survival, labs (lipids, hemoglobin A1C, Vitamin D, CRP), metabolic syndrome, metformin use, and antidepressants. Results: Of the 98 cases identified, 26 had Stage I disease at diagnosis, 32 had Stage II, 27 had Stage III, and 13 had Stage IV. The median age at diagnosis was 46. 62% of patients were Hispanic, 30% Caucasian, and 5% African-American. The majority of cases (86%) were of ductal histology. 77% were ER positive and 24% were HER2 positive. The median BMI of our cohort was 25.1. The 5 year PFS for our cohort was 74.6% (CI 64.2-82.4). The 5 year breast cancer specific OS was 94.2% (CI 86.6-97.6), with OS by stage showing I 100%, II 92.9% (CI 74.6- 98.2), III 91.7% (CI 70.5-97.9), and IV 92.3% (CI 56.6-99.0). While the total OS is within the range of 89.2% reported by SEER, our stage III and IV patients had a markedly improved OS compared to historical controls (41-67% and 15%, respectively, per ACS). Conclusions: To date, we have compiled the largest cohort of breast cancer patients with known BAT. While knowledge and clinical applicability of brown fat is still in its infancy, we hope that our study, with its remarkable OS for advanced stage disease, will shed light on the manner in which the presence of brown fat activation affects metabolism, treatment response, tumor microenvironment, and long-term prognosis.
Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China
Authors: Yuankai Shi, Bo Jia, Wei Xu, Wenyu Li, Ting Liu, Peng Liu, Weili Zhao, Huilai Zhang, Xiuhua Sun, Haiyan Yang, Xi Zhang, Jie Jin, Zhengming Jin, Zhiming Li, Lugui Qiu, Mei Dong, Xiaobing Huang, Yi Luo, Xiaodong Wang, Xin Wang, Jianqiu Wu, Jingyan Xu, Pingyong Yi, Jianfeng Zhou, Hongming He, Lin Liu, Jianzhen Shen, Xiaoqiong Tang, Jinghua Wang, Jianmin Yang, Qingshu Zeng, Zhihui Zhang, Zhen Cai, Xiequn Chen, Kaiyang Ding, Ming Hou, Huiqiang Huang, Xiaoling Li, Rong Liang, Qifa Liu, Yuqin Song, Hang Su, Yuhuan Gao, Lihong Liu, Jianmin Luo, Liping Su, Zimin Sun, Huo Tan, Huaqing Wang, Jingwen Wang, Shuye Wang, Hongyu Zhang, Xiaohong Zhang, Daobin Zhou, Ou Bai, Gang Wu, Liling Zhang, Yizhuo Zhang
Journal: Journal of Hematology & Oncology (2017)

The efficacy and safety of chidamide, a new subtype-selective histone deacetylase (HDAC) inhibitor, have been demonstrated in a pivotal phase II clinical trial, and chidamide has been approved by the China Food and Drug Administration (CFDA) as a treatment for relapsed or refractory peripheral T cell lymphoma (PTCL). This study sought to further evaluate the real-world utilization of chidamide in 383 relapsed or refractory PTCL patients from April 2015 to February 2016 in mainland China. For patients receiving chidamide monotherapy (n = 256), the overall response rate (ORR) and disease control rate (DCR) were 39.06 and 64.45%, respectively. The ORR and DCR were 51.18 and 74.02%, respectively, for patients receiving chidamide combined with chemotherapy (n = 127). For patients receiving chidamide monotherapy and chidamide combined with chemotherapy, the median progression-free survival (PFS) was 129 (95% CI 82 to 194) days for the monotherapy group and 152 (95% CI 93 to 201) days for the combined therapy group (P = 0.3266). Most adverse events (AEs) were of grade 1 to 2. AEs of grade 3 or higher that occurred in ≥5% of patients receiving chidamide monotherapy included thrombocytopenia (10.2%) and neutropenia (6.2%). For patients receiving chidamide combined with chemotherapy, grade 3 to 4 AEs that occurred in ≥5% of patients included thrombocytopenia (18.1%), neutropenia (12.6%), anemia (7.1%), and fatigue (5.5%). This large real-world study demonstrates that chidamide has a favorable efficacy and an acceptable safety profile for refractory and relapsed PTCL patients. Chidamide combined with chemotherapy may be a new treatment choice for refractory and relapsed PTCL patients but requires further investigation.
Has the paradigm changed away from lobectomy for stage I non-small cell lung cancer (NSCLC)? Anatomic segmentectomy: Surgery’s answer to image-guided ablation/radiation therapy for the small peripheral lung lesion.
Authors: Matthew J. Schuchert, Joseph J. Wizorek, Daniel Paul Normolle, David O Wilson, Jill Siegfried, Omar Awais, Ghulam Abbas, James D. Luketich, Rodney Jerome Landreneau
Journal: Journal of Clinical Oncology (2013)

7577 Background: Lobectomy has been the “gold standard” for stage I NSCLC management. Image guided ablation/radiation therapy approaches are now being touted as alternatives to surgery despite concerns regarding diagnosis, pathologic staging, local control, and delayed toxicities. We evaluated the diagnostic utility and oncologic efficacy of lung sparing, anatomic segmentectomy for indeterminate pulmonary nodules and clinical stage I NSCLC. Methods: Retrospective review of 1,005 anatomic segmentectomies from 2002-2012 for indeterminate pulmonary nodules and clinical stage I NSCLC. Outcome variables included perioperative data, morbidity and mortality. Survival was assessed with the Kaplan-Maier method. Results: Mean age was 66.7 years. Median lesion size was 1.9 cm. VATS was employed in 62.8% of cases. Median operative time and blood loss was 112 minutes and 80 ml, respectively. Median hospital stay was 5 days. Major complications occurred in 12.7%. Thirty-day mortality was 1.0%. Of these, NSCLC was identified in 71.6%, metastases in 8.7%, and other benign conditions in 19.7%. Among patients with clinical stage I NSCLC, clinical: pathological upstaging was seen in 34.5%. Local recurrence rate was 5.2% and five-year freedom from any recurrence was 69%, equivalent to lobectomy in our experience. Conclusions: Anatomic segmentectomy is a valuable primary surgical approach today. In this era of competing image-guided ablation modalities, anatomic segmentectomy provides safety, diagnostic accuracy and adherence to oncologic surgical principles including completeness of resection with adequate surgical margins, systematic nodal staging improving pathologic accuracy, and tissue for pharmacogenomic assessment to guide individualized adjuvant therapy.
Chronic breathlessness associated with poorer physical and mental health-related quality of life (SF-12) across all adult age groups
Authors: D C Currow, E Dal Grande, D Ferreira, M J Johnson, N McCaffrey, M Ekström
Journal: Thorax (2017)

Little is known about the impact of chronic breathlessness (modified Medical Research Council (mMRC) score ≥2 for most days, at least three of the last six months) on health-related quality of life (Short Form-12 (SF-12)). 3005 adults from randomly selected households were interviewed face-to-face in South Australia. mMRC ≥2 community prevalence was 2.9%. Adjusted analyses showed clinically meaningful and statistically significant decrements of physical and mental components of SF-12 (mean SF-12 summary scores in physical (-13.0 (-16.0 to -10.2)) and mental (-10.7 (-13.7 to -7.8)) components compared with people with mMRC=0) as chronic breathlessness severity increased, across five age groupings.