tbuckley/cabot-search huggingface dataset:
Association of Nestin with aggressive histologic features and poor endometrial cancer patient outcome.
Authors: Erica Ray Hope, Paulette Mhawech-Fauceglia, Thomas P Conrads, George Larry Maxwell, Chad Hamilton, Kathleen M. Darcy, Viqar Syed
Journal: Journal of Clinical Oncology (2015)

e16521 Background: Nestin, an intermediate filament protein, appears to be associated with poor outcome in a number of cancers but has not yet been examine in uterine cancers. Cancers of the uterine corpus represent a significant health problem globally with an annual incidence and mortality exceeding 319,000 and 76,000, respectively. The purpose of this study was to evaluate the clinical relevance of nestin in a cohort of well-annotated endometrial cancer patients. Methods: Tumor expression of nestin was assessed by immunohistochemistry in four tissue microarrays (TMAs) representing archival primary tumor from patients with a diagnosis of endometrioid, serous or clear cell endometrial cancer, or carcinosarcoma of the uterine corpus, and was categorized as high expression when > 10% of tumor cells exhibited brown staining. Results: Of the 345 eligible cases, 67 (19%) displayed high nestin expression, 164 (48%) were 65+ years at diagnosis, 116 (34%) had advanced stage disease, and 129 (37%) exhibited type II disease. High nestin expression was more common in advanced vs. early stage disease (28% vs. 15%, p = 0.004), type II cancers or uterine carcinosarcoma vs. type I cancers (30% or 61% vs. 9%, p < 0.0001), grade 3 disease yes vs. no (34% vs. 9%, p < 0.0001), and lymphovascular space invasion yes vs. no (30% vs. 14%, p = 0.001), respectively. Women with high vs. low nestin expression had worse progression-free (logrank p < 0.0001, hazard ratio [HR] = 2.7, 95% confidence interval [CI] = 1.8-4.1, p < 0.0001), cancer-specific (logrank p = 0.002, HR = 2.3, 95% CI = 1.3-4.0, p = 0.003) and overall survival (logrank p = 0.014, HR = 1.8, 1.1-2.9, p = 0.016), respectively. Conclusions: High tumor expression of nestin, a crucial cytoskeletal protein, was not only associated with aggressive histologic features but also with poor progression free, cancer-specific and overall survival in endometrial cancer patients, and may represent an attractive candidate for targeted therapeutic intervention in endometrial cancer.
A meta-analysis of smoking status on clinical outcomes of non-small cell lung cancer patients harboring activating epidermal growth factor receptor (EGFR) mutations receiving first-line EGFR tyrosine kinase inhibitor.
Authors: Yoshikazu Hasegawa, Masahiko Ando, Makoto Maemondo, Satomi Yamamoto, Shun-ichi Isa, Hideo Saka, Akihito Kubo, Tomoya Kawaguchi, Minoru Takada, Takayasu Kurata, Sai-Hong Ignatius Ou
Journal: Journal of Clinical Oncology (2014)

8101 Background: In several univariate analyses from randomized phase 3 trials, ever-smokers with advanced EGFR mutated (m) NSCLC did not seem to benefit from improved progression-free survival (PFS) even when EGFR TKIs were is used compared to doublet chemotherapy as first-line treatment. Methods: We performedpooled analysis of PFS outcome of six published randomized phase 3 trials comparing EGFR TKI to doublet chemotherapy in EGFRm NSCLC patients (WJTOG3405, NEJ002, EURTAC, OPTIMAL, LUX Lung-3, LUX Lung-6). Hazard ratio (HR) and corresponding 95% confidence interval (CI) were collected from each study published in the literature and pooled. We computed a pooled HR and its 95% CI using random-effect model. Results: 1,432 EGFRm NSCLC patient data were analyzed, 1,163 (81.2%) were Asians and 430 (30.0%) were ever-smokers. A total of 592 patients, including 178 ever-smokers (30.1%), received doublet chemotherapy and 840, including 252 (30.0%) ever-smokers, received EGFR TKI. The pooled HR for never-smokers was 0.29 (95%CI: 0.21-0.39) while the pooled HR for ever-smokers was 0.54 (95%CI: 0.38-0.76). The p-value comparing HR for never-smokers and ever-smokers by meta-regression analysis was 0.007. The pooled HR for exon 19 was 0.26 (95%CI: 0.19-0.36) while it is 0.45 for exon 21 substitution (95%CI: 0.32-0.64) with a significant difference (p = 0.019) between the two pooled HRs. The pooled HR was 0.33 (95%CI: 0.24-0.46) for Asians and 0.48 (95%CI: 0.27-0.85) for non-Asians. Asians did not derive significantly more PFS benefit than non-Asians (p = 0.256). The pooled HR for erlotinib was 0.25 (95%CI: 0.16-0.41), 0.38 (95%CI: 0.24-0.59) for gefitinib, and 0.41 (95%CI: 0.24-0.68) for afatinib. No significant differential PFS benefit was noted in any one specific EGFR TKI. Conclusions: In this meta-analysis analysis EGFRm NSCLC patients derived significant PFS benefit from TKI over chemotherapy regardless of smoking status but the PFS benefit from EGFR TKIs over chemotherapy is significantly higher in never-smokers than ever-smokers by meta-regression analysis.
Randomized phase 2 trial of plinabulin (NPI-2358) plus docetaxel in patients with advanced non-small cell lung cancer (NSCLC).
Authors: Rebecca Suk Heist, Osvaldo Rudy Aren, Alain C. Mita, Jonathan Polikoff, Lyudmila Bazhenova, G Kenneth Lloyd, William Mikrut, Steven D. Reich, Matthew A. Spear, Lan Huang
Journal: Journal of Clinical Oncology (2014)

8054 Background: Plinabulin (N) inhibits tumor growth by targeting both angiogenesis and tumor vasculature as well as directly by inducing apoptosis via the Ras-JNK pathway. This trial compared the combination of N and docetaxel (DN) to docetaxel alone (D). Methods: Patients (pts) with advanced NSCLC previously treated with standard chemotherapy (ChRx) were randomized between D (75 mg/m2 IV) on Day 1 plus N 30 mg/m2 IV on Days 1 and 8 in 21-day cycles (DN) vs D (75 mg/m2 ) (30 Cohort). Pts with Stage IIIB/IV NSCLC and 1 or 2 prior ChRx were eligible. Prior D or vascular disrupting agent (VDA) were not allowed. A 2nd dose cohort (DN 20 mg/m2) of pts with 1 prior ChRx (20 Cohort) was enrolled. The primary end point was overall survival (OS). Results: 172 pts were randomized into 2 dosing cohorts with 163 treated: 30 Cohort (50 DN; 55 D) and 20 Cohort (40 DN; 18 D). For 30 Cohort, OS (months (M)), 90% confidence interval [90% CI]) was 8.7 (6.6, 12.6) for DN and 7.5 (6.3, 10.5) for D; response rate was 14.0% for DN and 14.5% for D; and duration of response (M, 90% CI) for DN was 12.7 (4.0, 13.9) and 1.5 (1.1, 3.1) for D (p=0.049). Results appeared better for the DN 30 Cohort vs 20 Cohort. Post hoc subset analysis identified pts with large, lung tumors (>3 cm) and 1 prior ChRx as having better survival with DN. OS (M, 95% CI) for this subset was 11.5 (7.1, 15.1) DN vs 7.8 (4.1, 17.4) D. The most common adverse events were nausea, fatigue, diarrhea, constipation, and anorexia. There were fewer dose reductions of D among DN pts (10%) vs D pts (18.2%). There was a lower incidence of neutropenia in patients in the DN 30 Cohort compared to D (8.0% vs 36.4%, p<0.001) and the DN 20 Cohort compared with its companion D (7.5% vs 22.2%). A post hoc analysis showed that the DN 30 Cohort (n=50) had a significantly lower incidence of ≥ Grade 3 neutropenia vs the pooled D (n=73) at 8.0% vs 27.4%, respectively (p=0.010). Conclusions: Pts with large, lung tumors (>3 cm) and 1 prior ChRx may be more likely to have an increased survival with DN as compared to D. This finding is consistent with the mechanism of action of a VDA with anti-angiogenesis and apoptotic properties. A Phase 3 trial in pts with large, lung tumors is planned. Clinical trial information: NCT00630110.
A randomized, phase II, multicenter, double-blind, placebo-controlled study evaluating onartuzumab (MetMAb) in combination with mFOLFOX6 plus bevacizumab in patients with metastatic colorectal cancer.
Authors: Johanna C. Bendell, Thomas J. Ervin, David H. Gallinson, Jaswinder Singh, James Alfred Wallace, Mansoor N. Saleh, Marcy Vallone, Stephen Paul Hack
Journal: Journal of Clinical Oncology (2012)

TPS3640 Background: Dysregulation of the HGF/Met (Met) pathway has been linked with poor prognosis in colorectal cancer. Crosstalk between the Met and vascular endothelial growth factor (VEGF) pathways may be important during tumorigenesis. Aberrant activation of the HGF/Met pathway may promote angiogenesis via tumor cell secretion of angiogenic factors or directly activating endothelial cells. Onartuzumab (MetMAb) is a monovalent, monoclonal antibody that specifically binds to the Met receptor. The combination of onartuzumab and VEGF inhibition in preclinical models resulted in enhanced antitumor activity over either treatment alone. Preclinical efficacy data support the combination of onartuzumab with platinum agents. In phase I studies, onartuzumab has been generally well tolerated alone and in combination with bevacizumab. Adverse events most commonly associated with onartuzumab are peripheral edema and fatigue. Methods: This is a randomized, two-arm, phase II study in patients with previously untreated metastatic colorectal cancer. Patients (n=188) will be randomized (1:1) to either mFOLFOX6/bevacizumab/placebo or mFOLFOX6/bevacizumab/onartuzumab. Oxaliplatin will be discontinued after 8 cycles with remaining drugs continued until progression. The primary endpoint of this study is PFS in all patients. PFS by Met IHC diagnostic status (Met positive vs Met negative) will also be analyzed. Secondary endpoints include OS, ORR, safety, and biomarker analyses. Primary and secondary analyses will include all randomized patients and will be conducted according to assigned treatment arm. Kaplan–Meier methodology will be used to estimate median PFS for each treatment arm. An estimate of HR with 95% CI will be determined using a Cox regression model. Safety will be assessed in all patients receiving at least one dose of any treatment. This study is open for accrual; further details can be found on ClinicalTrials.gov (NCT01418222).
Thromboembolic events (TE) among patients with metastatic pancreatic ductal adenocarcinoma (mPDA) after chemotherapy (Chemo).
Authors: Gary H. Lyman, Vernon F Schabert, Philip Agop Philip, Michael Stokes, Sharvari Bhurke, Nicole M Kuderer, Ammar Qadan, Alok A. Khorana
Journal: Journal of Clinical Oncology (2017)

280 Background: Clinical trials suggest that patients with mPDA are at high risk of TE from both disease and treatment. TE rates and anticoagulant use among mPDA patients after first line chemo were investigated. Methods: Medicare beneficiaries enrolled in parts A, B, and D; diagnosed with mPDA; aged ≥ 65 years; and starting chemo between 1/1/2007 and 12/31/2012 were obtained from Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Eligible patients were enrolled from 12 months before chemo and followed until death, post-chemo disenrollment, or 12/31/2012. Arterial (ICD-9 410-411, 433-434), venous (ICD-9 415.1x, 453.4x, 453.8x, 453.9), and total TE were defined as ≥ 2 outpatient diagnoses ≥ 30 days apart, one inpatient diagnosis, or one outpatient diagnosis followed by outpatient anticoagulants within 90 days. Post-chemo TE incidence was calculated as the number of first events per 100 person-years (PY) for patients with and without TE 12 months before chemo. Time from chemo to first TE was estimated using the Kaplan-Meier (KM) method. Results: Among 1,308 eligible patients, mean age was 74 years [range 65-93]; 56% were female; 85% had no prior TE. Overall, 419 (32%) had a TE after chemo including 121 (9%) arterial and 363 (28%) venous TE. The table shows incidence, and time to TE for those with and without prior TE. Outpatient anticoagulants were prescribed for 276 (25%) patients with no prior TE and 110 (57%) patients with prior TE. Table. TE incidence and time to TE among mPDA patients after chemo Conclusions: mPDA patients face a substantial risk of TE after chemo, with nearly one-third of patients without prior TE and one-half of patients with prior TE experiencing events during treatment. These high rates of TE indicate the importance of conducting risk assessments for preventive measures early during a patients’ care.[Table: see text]
Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal malignancy patients.
Authors: Mariko Kamiya, Toru Aoyama, Nobuhiro Sugano, Tsutomu Sato, Naoto Yamamoto, Masataka Taguri, Takeharu Yamanaka, Takashi Oshima, Norio Yukawa, Yasushi Rino, Munetaka Masuda
Journal: Journal of Clinical Oncology (2017)

115 Background: Delirium is one of the common postoperative complications. When postoperative delirium occurred, the patient management becomes much more difficult, leading to functional recovery delay, and is also associated with postoperative mortality and morbidity. Although many attempts to prevent and treat delirium have been developed, a higher level of evidence is needed. In the present study, we evaluated the efficacy and safety of TJ-54 (Yokukansan; one of the traditional Japanese medicines, Kampo) for the prevention and/or treatment of postoperative delirium in a randomized phase III trial for the patients receiving surgery for gastrointestinal malignancy. Methods: Patients 70 years of age or older, who were received surgery for gastrointestinal malignancy were eligible in this study. The 167 eligible patients were randomly assigned on a 1:1 ratio to receive TJ-54 or control during their perioperative care (between day 7 before surgery and day 4 after surgery). The signs and symptoms of delirium were assessed with using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV by the investigator during perioperative period. Results: We analyzed 167 eligible gastrointestinal malignancy patients (TJ-54; 83, control; 84). There were no disparities between the two PPS randomized groups. The incidence of delirium was 7.2% (6 patients) in the TJ-54 group and 10.7% (9 patients) in the control group with no significant difference (p=0.431), also no significant difference was observed in duration of delirium between the two groups (p=0.477). The ratio of patients who needed some kind of the medication which including treatment of delirium were significantly less in the TJ-54 group than in the control group (p=0.037). Conclusions: In this study, TJ-54 did not demonstrate the contribution to prevention of occurring delirium in the patients receiving surgery for gastrointestinal malignancy. However, TJ-54 might be effective in reducing the medication for treating delirium after surgery for gastrointestinal malignancy. Clinical trial information: 000005423.
A phase II study of 5-FU/l-LV/oxaliplatin (mFOLFOX6) in patients with metastatic or unresectable small bowel adenocarcinoma.
Authors: Norisuke Nakayama, Takahiro Horimatsu, Seiichi Takagi, Toshikazu Moriwaki, Yoshinori Hirashima, Mikio Fujita, Masako Asayama, Ichiro Moriyama, Koji Nakashima, Eishi Baba, Hiroshi Kitamura, Takao Tamura, Ayumu Hosokawa, Manabu Muto
Journal: Journal of Clinical Oncology (2014)

3646 Background: Several prospective and retrospective studies have suggested that chemotherapy prolongs survival in patients with metastatic or recurrent small bowel adenocarcinoma (SBA). However, there is no standard chemotherapyregimen for this disease. The aim of this study was to evaluate the efficacy and safety of mFOLFOX6 as a first-line therapy in patients with SBA. Methods: This study was designed as a multi-center, single-arm, open-label phase II study. Eligibility criteria included a histologically proved diagnosis of adenocarcinoma, age 20–80 years, and an Eastern Cooperative Oncology Group performance status (PS) of 0–2. The mFOLFOX6 treatment comprised oxaliplatin (85 mg/m2) and l-leucovorin (200 mg/m2) administered intravenously over a two hour period on day one, followed by a bolus of 5-FU bolus (400 mg/m2) and a 46 hour infusion of 5-FU (2400 mg/m2) every two weeks. The primary endpoint was one year progression-free survival (PFS). The secondary endpoints included overall response rate (ORR), overall survival (OS), PFS, and safety. Results: Between April 2010 and November 2012, 24 patients were enrolled from 12 institutions. Median age: 63 years (range, 31–79); male/female ratio: 18/6; PS 0: 17 (71%); PS 1: 7 (29%); locally advanced/metastatic disease: 2/22; primary tumor site: duodenum (58%) and jejunum (42%). The median follow-up time was 14.7 months (3.7-40.3). The one-year PFS was 23.3%. The ORR was 45% (9/20). The median PFS and OS were 5.9 months (95% CI, 3.0–10.2) and 17.3 months (95% CI, 11.7–19.0), respectively. The common grade 3 or 4 toxicities were neutropenia (38%), anemia/peripheral neuropathy (25%), stricture (17%), fatigue/anorexia/bilirubin increase (8%), and diarrhea (4%). There were no treatment-related deaths. Conclusions: This phase II study showed a good efficacy with an acceptable safety profile. The mFOLFOX6 regimen is moderately active and well tolerated as a first-line treatment for SBA. Clinical trial information: UMIN000002797.
Effects of dose reduction on gemcitabine-based neoadjuvant chemoradiotherapy for localized pancreatic cancer.
Authors: Joseph J. Shatzel, Rebecca Wang, Kabir Mody, Spencer L. James, Parambir S. Dulai, Thomas Anthony Colacchio, Richard J. Barth, Bassem I. Zaki, Michael J. Tsapakos, Arief A. Suriawinata, John E. Sutton, Stuart R. Gordon, Kerrington D. Smith, Gregory H. Ripple, Timothy B. Gardner, Kathryn Cunningham Hourdequin, Gregory J. Tsongalis, Elizabeth Boutin McGrath, J. Marc Pipas
Journal: Journal of Clinical Oncology (2014)

e15262 Background: Patients receiving gemcitabine-based neoadjuvant chemoradiotherapy for non-metastatic pancreatic cancer often have difficulty tolerating full treatment courses. Providers are thus faced with the difficult decision of holding or reducing chemotherapy. As the effects of chemotherapy dose reduction are not well understood, we evaluated the impact of dose reduction on survival and other outcomes. Methods: We performed a single center retrospective review of patients receiving two gemcitabine-based neoadjuvant chemoradiation protocols for localized pancreatic cancer over a 9 year period. For inclusion, patients were required to have completed at least 95% of their prescribed radiation dose. The dose intensity of completed chemotherapy was stratified into three tiers of 90%-100%, 75%-89%, and <75% of total protocol dose. Our primary outcome was the effect of dose reduction on overall and progression-free survival. Secondary outcomes included completion of surgery, radiologic down staging, R0 resection rate, and nodal status. Results: A total of 113 patients (mean age 62 yr) were included, of which 28 (25%) had resectable disease, 51 (45%) had borderline resectable disease, and 34 (30%) had locally advanced disease. Forty-seven patients (41.6%) received 90-100% of the total protocol dose (dose level I), 36 patients (31.9%) received 75-89% (dose level II), and 30 patients (26.5%) received <75% (dose level III). The most common reasons for dose reduction were thrombocytopenia, neutropenia, or obstruction of the biliary tract. Overall survival and progression free survival at 1, 2, and 5 years were 69.3%, 37.1% and 19.6%, and 43.1%, 26.4%, and 19.5%, respectively. Five year survival in the resectable, borderline and unresectable groups was 39.9%, 22.5% and 3.1%, respectively. Multivariate analysis showed no statistically significant effect of dose reduction at any dose level, on overall survival, progression-free survival, or any secondary outcomes. Conclusions: Mild to moderate dose reduction has no significant impact on outcomes. Providers should feel reassured when reducing gemcitabine doses for patients experiencing treatment side effects.
Impact of donor source on allogeneic stem cell transplantation for Philadelphia chromosome-negative acute lymphoblastic leukemia.
Authors: Satoshi Nishiwaki, Koichi Miyamura, Kazuteru Ohashi, Mineo Kurokawa, Shuichi Taniguchi, Takahiro Fukuda, Kazuhiro Ikegame, Hisashi Sakamaki, Yasuo Morishima, Koji Kato, Ritsuro Suzuki, Junji Tanaka
Journal: Journal of Clinical Oncology (2012)

6533 Background: Although allogeneic stem cell transplantation (allo-SCT) could improve the outcome of adult Philadelphia chromosome-negative acute lymphoblastic leukemia [Ph(-) ALL], the impact of the donor source, particularly the position of cord blood (CB) transplantation, is still uncertain. Methods: We retrospectively analyzed 1726 adult Ph(-) ALL patients transplanted at the first time between 1998 and 2009 with myeloablative preparative regimens who were registered in the Japan Society for Hematopoietic Cell Transplantation database. Two hundred and thirty-three received CB transplantation [first complete remission (CR1): 95, subsequent CR: 53, non-CR: 85], 809 received allo-SCT from unrelated donor (URD) (CR1: 434, subsequent CR: 158, non-CR: 217), and 684 received allo-SCT from related donor (RD) (CR1: 388, subsequent CR: 89, non-CR: 207). Results: Overall survival (OS) in patients after CB transplantation in CR1 was comparable with that after allo-SCT from URD or RD [57% in CB, 64% in URD, and 65% in RD at 4 years, respectively, P=0.11]. Donor source was not a significant risk factor for OS in multivariate analysis. Although URD was a favorable factor for relapse and an unfavorable factor for non-relapse mortality (NRM), CB was not a significant factor for them [Relapse: 22% in CB, 17% in URD, and 24% in RD at 3 years, respectively (P=0.02); NRM: 27% in CB, 23% in URD, and 13% in RD at 3 years, respectively (P=0.0001)]. Among CB recipients in CR1, age at allo-SCT (45 years or older) was solely a significant adverse prognostic factor in multivariate analysis. Among patients younger than 45 years who received allo-SCT in CR1, OS after CB transplantation was significantly better than that after allo-SCT from mismatched URD (4-year OS: 68% vs. 49%, P=0.04). Similarly, OS was not different by donor source in subsequent CR or non-CR [Subsequent CR: 48% in CB, 39% in URD and 48% in RD, P=0.33; non-CR: 18% in CB, 21% in URD, and 15% in RD, P=0.20 at 4 years, respectively]. Conclusions: Allo-SCT using CB led to similar outcomes as either RD or URD in any disease status. CB transplantation is a good alternative for adult Ph(-) ALL patients without a suitable RD or URD.
Safety and Histological Effect of Liquid Nitrogen Metered Spray Cryotherapy in the Lung
Authors: Dirk-Jan Slebos, David Breen, James Coad, Karin Klooster, Jorine Hartman, Robert Browning, Pallav L. Shah, William H. McNulty, Mohammed al-Abdul Mohsin, Kashif Irshad
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Addition of Bortezomib to High Dose Melphalan As Conditioning Regimen for Autologous Stem Cell Transplantation Improves the Response Rate in Newly Diagnosed Multiple Myeloma Patients
Authors: Benedetta Dalla Palma, Lucia Prezioso, Fabrizio Accardi, Stefano Bisbano, Federica De Luca, Franco Aversa, Nicola Giuliani
Journal: Blood (2016)