tbuckley/cabot-search huggingface dataset:
INTRAHEPATIC CD25+CD122-TCR gamma delta T CELLS IN PATIENTS WITH AUTOIMMUNE HEPATITIS PRODUCE MORE IL-17 THAN IFN-gamma
Authors: Pengyun Wang, Maria Serena Longhi, Munther Hussain, Roshni Vara, Tassos Grammatikopoulos, Pushpa Subramaniam, Giorgina Mieli-Vergani, Diego Vergani, Yun Ma
Journal: Hepatology (2009)
Durable remissions from fludarabine followed by the iodine I-131 tositumomab Bexxar therapeutic regimen for patients with previously untreated follicular non-Hodgkin's lymphoma (NHL)
Authors: J. P. Leonard, M. Coleman, L. Kostakoglu, A. Chadburn, J. M. Fiore, R. R. Furman, M. W. Schuster, S. M. Kroll, S. J. Goldsmith
Journal: Journal of Clinical Oncology (2004)

6518 Background: The sequential combination of chemotherapy and radioimmunotherapy offers a novel strategy for the initial management of NHL. Tositumomab and iodine I 131 tositumomab (Bexxar) have been demonstrated to have substantial clinical activity in both untreated and relapsed/refractory low-grade NHL. Fludarabine synergizes in vitro with unlabeled and radiolabeled antibodies and can be employed as a “debulking” agent prior to radioimmunotherapy. Methods: Patients with previously untreated, advanced low-grade NHL were treated with IV fludarabine 25 mg/m2/day for 5 days, every 5 wks for 3 cycles followed in 6 to 8 wks by Bexxar therapy. Results: Between August 1998 and June 1999, 38 pts (51% follicular mixed, 49% follicular small cleaved) were enrolled and 97% had stage III/IV disease. Thirty-five subjects received both fludarabine and Bexxar therapy. Three patients came off study before or during fludarabine therapy (one due to cytopenias, 2 unrelated to toxicity or lymphoma progression). Response to fludarabine (n=35) was 89% (3 CR, 28 PR). Following Bexxar therapy, 35 of 35 subjects (100%) had a response including 83% CR. With a median follow-up of 4.4 years, median progression-free survival has not been reached, and 72% of pts achieving a CR remain in CR. Among 35 evaluable pts, grade 4 neutropenia, thrombocytopenia, and anemia were noted in 34%, 29%, and 3% of pts, respectively. Sixteen (46%) pts received growth factor or transfusion support. There were no serious infections. Four (12%) pts developed elevated TSH and 2 (6%) pts developed HAMA. No pts have developed MDS/AML. Conclusions: Fludarabine followed by Bexxar therapy appears to be a highly effective and well tolerated regimen for the initial therapy of advanced follicular NHL, producing long-term durable complete remissions in the majority of patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Corixa Corp. Corixa Corp. Corixa Corp. Corixa Corp. Corixa Corp.
Implications of smoking for quality of life and illness perceptions of lung cancer patients.
Authors: Sarah Danson, Christine Rowland, Christine Eiser, Richard Rowe, Sue Ellis, Carol Crabtree, Janet M Horsman, Jonathan Wadsley, Matthew Hatton, Penella Woll
Journal: Journal of Clinical Oncology (2012)

6113 Background: Adverse publicity about smoking may lead to feelings of guilt among lung cancer patients or pessimism about their future, potentially compromising health-related quality of life (QoL) and adherence with medical advice. QoL is an important outcome in clinical trials, particularly where survival rates are low. We aim to compare QoL and illness perceptions of lung cancer patients depending on smoking history. Methods: Clinical data, measures of QoL (EORTC-QLQ-C30+LC13) and illness perceptions (Brief IPQ – includes items to assess perceived severity, causality, timeline, understanding, emotional impact, and control over illness) were completed by 190 newly diagnosed lung cancer patients (Non-small cell: 75%; Mean age: 68 years, range: 48-85 years; 58% males). Of these, 24% were current smokers, 69% former smokers, and 7% never smoked. Results: Although overall QoL was similar between the three smoker groups, there was a significant effect of smoking status on QoL subscale emotional function (EF)(F(2,168)=4.08,p=.019). Those who never smoked had significantly higher EF than current smokers (p=.03). There was also a significant effect of smoking history on cough (F(2,166);=5.40 ,p=.005) with smokers reporting significantly greater levels than former smokers (p=.004). Smokers were more likely than former smokers (p=.015) to attribute their lung cancer to smoking (F(2,161)=16.49,p&lt;.000). Furthermore, there was a significant effect of smoking on the perceived timeline of illness (F(2,144)=3.33,p=.039), with smokers being more pessimistic about this than former smokers (p=.043). Conclusions: These findings have implications for planning the care of lung cancer patients. In addition to the different treatment needs of smokers and former smokers, smokers may need greater support to cope with the emotional effects of their illness. Our findings suggest that smokers blame their illness on their own behaviour, and have a more pessimistic view of likely survival time, so they may need more encouragement to accept life-prolonging treatments. These results may also inform tailored smoking-cessation advice.
Discrepancies in treatment of osteosarcoma according to insurance coverage: A review of the National Cancer Data Base.
Authors: Mimi Longo, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2014)

10072 Background: Osteosarcoma is the most common primary bone malignancy in children and adolescents. It is an aggressive tumor with a tendency to metastasize to the lungs. It is believed that at the time of diagnosis, all patients have micrometastases. Therefore, neoadjuvant and adjuvant chemotherapy in addition to surgical removal of the tumors became the gold standard of care in the 1990s. The authors sought to learn if patients in the National Cancer Database from 2000-2011 received surgery and chemotherapy as their first course treatment. Methods: The National Cancer Data Base contains cases of cancer diagnoses from 1,404 American College of Surgeons-Accredited hospitals. There are 5,501 cases of osteosarcoma from 2000-2011 in the database, and these cases were used for analysis. Results: The authors found that 46.6% of patients with no insurance received surgery and chemotherapy, but 63.8% of patients with private/managed insurance received surgery and chemotherapy as their first course treatment (p-value <0.01). Only 21.20% of patients who had Medicare got surgery and chemotherapy as their first course treatment. Furthermore, a significant number of patients with no insurance received no therapy (14.8%) as compared to 3.7% of patients who had private/managed insurance (p<0.001). Conclusions: Patients with no insurance were less likely to receive chemotherapy and surgery for their disease, and they were much more likely to receive no treatment. Lack of insurance prevented patients from receiving life-saving treatments. Thirty-four percent of patients with no insurance were under age 20. Although only 21.20% of patients who had Medicare got surgery and chemotherapy as their first course treatment, 79% of the patients who had Medicare and got osteosarcoma were age 60 and older, so they may have had comorbidities that prevented them from getting surgery and chemotherapy. This is the largest review of osteosarcoma treatments according to insurance status to date.
Multicenter, Open-Label Phase I Clinical Study of Oral Rigosertib in Japanese Patients with Recurrent/Relapsed or Refractory Myelodysplastic Syndromes: Tolerability, Efficacy, and Pharmacokinetic Profiles
Authors: Kenichi Ishizawa, Kensuke Usuki, Kiyoshi Ando, Yasunori Ueda, Toru Kiguchi, Naokuni Uike, Yasushi Onishi, Hiroatsu Iida
Journal: Blood (2016)
Nationwide Survey on the Use of Eltrombopag in Patients with Severe Aplastic Anemia: Report on Behalf of the French Reference Center for Aplastic Anemia
Authors: Etienne Lengline, Bernard Drenou, Pierre Peterlin, Olivier Tournilhac, Julie Abraham, Ana Berceanu, Brigitte Dupriez, Gaelle Guillerm, Emmanuel Raffoux, Flore Sicre de Fontbrune, Lionel Ades, Marie Balsat, Driss Chaoui, Paul Coppo, Selim Corm, Thierry Leblanc, Natacha Maillard, Louis Terriou, Gerard Socie, Regis Peffault de Latour
Journal: Blood (2016)
Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration
Authors: Michiko Mandai, Akira Watanabe, Yasuo Kurimoto, Yasuhiko Hirami, Chikako Morinaga, Takashi Daimon, Masashi Fujihara, Hiroshi Akimaru, Noriko Sakai, Yumiko Shibata, Motoki Terada, Yui Nomiya, Shigeki Tanishima, Masahiro Nakamura, Hiroyuki Kamao, Sunao Sugita, Akishi Onishi, Tomoko Ito, Kanako Fujita, Shin Kawamata, Masahiro J. Go, Chikara Shinohara, Ken-ichiro Hata, Masanori Sawada, Midori Yamamoto, Sachiko Ohta, Yasuo Ohara, Kenichi Yoshida, Junko Kuwahara, Yuko Kitano, Naoki Amano, Masafumi Umekage, Fumiyo Kitaoka, Azusa Tanaka, Chihiro Okada, Naoko Takasu, Seishi Ogawa, Shinya Yamanaka, Masayo Takahashi
Journal: New England Journal of Medicine (2017)

We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).
Impact of duodenal invasion on outcomes in patients with pancreatic cancer treated with stereotactic body radiotherapy.
Authors: Gilbert Murimwa, Eric Albert Mellon, Jessica M. Frakes, Will Jin, Pamela Joy Hodul, Jose Mario Pimiento, Richard D. Kim, Heloisa P. Soares, Mokenge Peter Malafa, Sarah E. Hoffe
Journal: Journal of Clinical Oncology (2017)

408 Background: Clinical trials for pancreatic adenocarcinoma patients treated with a uniform SBRT tumor dose prescription exclude tumors invading the duodenum due to potential for increased GI mucosal complications. We analyzed our non-trial patients to determine the impact of SBRT in the setting of known duodenal invasion. Methods: An IRB-approved institutional database was queried identifying all 220 localized borderline resectable or locally advanced pancreatic cancer patients treated with SBRT from 2009 to 2015. Eligibility included patients with head tumors, a minimum of 6 months of follow up, and duodenal invasion on pretreatment endoscopic ultrasound (EUS). Dose painted SBRT delivered 25-30 Gy to tumor abutting the duodenum and up to 50 Gy to focal tumor/vessel abutment. Analysis evaluated whether patients with duodenal invasion had increased incidence of grade ≥ 3 (G3+) toxicity, GI ulceration or bleeding, or worsened overall survival (OS). Fisher’s Exact Test (2-tailed) compared patient characteristics and binary outcomes. Survival estimates by Kaplan-Meier were compared using log-rank test. Results: The study population included 126 patients (median F/U 14.1 months). Of 23 patients with duodenal invasion, 14 (61%) underwent resection, 3 (13%) developed G3+ toxicity and 1 (4%) had acute pre-op G3 GI bleeding that was controlled endoscopically prior to surgery. Of 103 without duodenal invasion, 48 (47%) underwent resection, 9 (9%) suffered G3+ toxicity and 7 (7%) had any GI bleed or ulceration. None of the 7 patients with GI bleeding or ulceration underwent pancreatectomy, and 3 had bleeding from tumor progression into the duodenum. There was no association between duodenal invasion and the incidence of G3+ toxicity (p = 0.76) or GI ulceration/bleeding (p = 1.0). There was no worsened OS (p = 0.17) or G3+ toxicity (p = 0.22) for patients with duodenal invasion on EUS. Patients with a GI bleeding or ulceration event had decreased OS (p = .014). Conclusions: Duodenal invasion on EUS prior to SBRT did not worsen GI bleeding risk or survival. Our data suggests that excluding pancreatic adenocarcinoma patients with duodenal invasion from SBRT when using a dose-painted approach is unnecessary.
Novel imaging detailing the origins of a pneumothorax
Authors: Kozo Nakanishi, Hidenori Goto, Tomokazu Ito, Yasuhito Nagata, Shinichi Hayashi, Toshihiro Ishihara
Journal: Thorax (2017)

This is a prospective clinical study aimed at introducing a method to visualise the location of an air leak and to identify the bulla responsible on three-dimensional (3-D) cine CT. In 10 patients with spontaneous pneumothorax, dynamic 320-detector row CT was performed with injection of 0.9% saline into the affected pleural cavity via a preplaced chest tube. In eight cases, 3-D cine CT thoracography revealed the location of the air leak and the bulla responsible (7 cases: air stream sign; 1 case: repeated collapse and expansion of a bulla with the patient's breathing).
Moderate Hypofractionation in High-Risk, Organ-Confined Prostate Cancer: Final Results of a Phase III Randomized Trial
Authors: Giorgio Arcangeli, Biancamaria Saracino, Stefano Arcangeli, Sara Gomellini, Maria Grazia Petrongari, Giuseppe Sanguineti, Lidia Strigari
Journal: Journal of Clinical Oncology (2017)

Purpose To report the final results on treatment outcomes of a randomized trial comparing conventional and hypofractionated radiotherapy in high-risk, organ-confined prostate cancer (PCa). Patients and Methods This single-institution, randomized clinical trial, conducted from January 2003 to December 2007, enrolled 168 patients with high-risk PCa who were randomly assigned in a 1:1 ratio to conventional (80 Gy in 40 fractions in 8 weeks) or hypofractionated radiotherapy (62 Gy in 20 fractions in 5 weeks) to prostate and seminal vesicles. The primary outcome measure was late toxicity. Additional outcomes were freedom from biochemical failure (FFBF), prostate cancer–specific survival (PCaSS), and overall survival (OS), evaluated on an intention-to-treat basis. Results A total of 85 patients were assigned to conventional and 83 to hypofractionated radiotherapy. At a median follow-up of 9 years (interquartile range, 7.5 to 10.1 years), no differences was observed in physician-assessed late gastro intestinal and genitourinary toxicity greater than or equal to grade 2 ( P = .68 and .57, respectively) were found between the two arms. The 10-year FFBF rate was 72% in the hypofractionation group and 65% in the conventional fractionation group ( P = .148). Ten-year OS rates were 75% in the hypofractionation group and 64% in the conventional group, respectively ( P = .22). The same features for 10-year PCaSS were 95% and 88%, respectively ( P = .066). Hypofractionation, pretreatment prostate-specific antigen level, Gleason score, and clinical tumor stage for FFBF, and hypofractionation and Gleason score for PCaSS were significant prognostic variables on the multivariate analysis. Conclusion Long-term findings showed that hypofractionated radiotherapy failed the intent of either reducing physician-assessed late toxicity or maintaining the same efficacy. A postrandomization analysis, however, revealed that hypofractionation was a significant prognostic factor for FFBF and PCaSS, when adjusted for clinical prognostic variables.
Understanding at-risk subgroups for lung function impairment in life-long nonsmokers with α<sub>1</sub>-antitrypsin deficiency
Authors: Victor E. Ortega, Matteo Pecchiari
Journal: European Respiratory Journal (2017)

The association of α1-antitrypsin deficiency with emphysema and chronic obstructive pulmonary disease (COPD) was first described in 1964 [1]. However, it was not until 1976 that uncommon coding variants in the gene encoding α1-antitrypsin ( SERPINA1 ) were identified as the cause, specifically variants at amino-acid positions 288 (Glu288Val or protease inhibitor (PI) type S) and 366 (Glu366Lys or PI type Z) [2, 3]. Over the past 40 years, the role of SERPINA1 genetic variation and α1-antitrypsin deficiency as a risk factor for emphysema and COPD has become well established for individuals with a history of tobacco smoke exposure who are homozygotes with two copies of these variants (PI ZZ and SS) and compound heterozygotes with PI types Z, S (PI ZS) or other pathogenic PI types [4–6]. However, it is unclear whether α1-antitrypsin deficiency determines the risk for lung function impairment in individuals without a critical gene by environment interaction with tobacco smoke exposure. Small airways function is a potential marker for lung function impairment in α1-antitrypsin deficiency <http://ow.ly/qZ5x309idJz>
Results of a pilot trial of OSI-461 in patients with chronic lymphocytic leukemia
Authors: C. H. Reynolds, R. N. Raju, S. J. Vukelja, R. J. Belt, W. J. Hyman, K. A. Boehm, L. Asmar
Journal: Journal of Clinical Oncology (2004)

6676 Background: OSI-461 is a selective apoptotic antineoplastic drug (SAAND), a novel class of drugs that induce apoptosis by inhibiting cGMP phosphodiesterases. OSI-461 has about 100x more affinity for cGMP PDE than does exisulind, the first generation of this drug class. OSI-461 has been shown to inhibit the growth of a variety of human tumor cell lines as well as lymphocytes from CLL patients (pts). Phase-I clinical studies have also demonstrated that OSI-461 administration is well-tolerated. In this multicenter pilot study, we sought to assess the safety and activity of OSI-461 in previously untreated CLL pts. Methods: Between June 2001 and February 2002, 23 pts with progressing CLL were registered; 1 was ineligible (prior chemotherapy). Fifteen pts received OSI-461 400 mg (Group 1) and 7 received 800 mg (Group 2) PO as a split dose (200 mg [Group1] or 400 mg [Group 2]) twice daily every 28-day cycle. Patients continued to receive treatment in the absence of intolerable toxicity or disease progression. At baseline, 91% were white, 59% were male, median age was 65.8 years (range, 49–84), and the ECOG performance status was 0–1. Results: Responses were 1 PR (4.6%), 18 SD (81.8%, 12 Group 1 vs. 6 Group 2) and 3 PD (13.6%, 2 Group 1 vs. 1 Group 2). The median cumulative dose per cycle was 11200 mg in Group 1 (range, 1000–14500) and 22400 mg in Group 2 (range, 3600–24800). Patients received a median of 4.5 cycles of treatment (range, 2–27). NCI Grade 3 drug-related toxicities included neutropenia, reflux, and headache in Group 1 with anemia, cough, and increased bilirubin reported in Group 2. As of August 2003, 91% of pts were off-study due to: progression (10), physician's decision (4), toxicities (2), lab abnormalities (2), withdrawal of consent (1), and protocol deviation (1). One pt in Group 1 died of progression 121 days after receiving last dose of treatment. Conclusion: OSI-461 has minimal toxicity at the doses administered and shows modest activity in previously untreated CLL. Supported by OSI Pharmaceuticals, Inc., Boulder, CO, USA Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI Cell Pathways (now taken over by OSI Pharm.)
MUC4 expression in non-small cell lung cancer.
Authors: Apar Kishor Ganti, Sukhwinder Kaur, William W West, Prabin Dhangada Majhi, Imayavarambam Lakshmanan, Lynette Smith, Cleo E Rolle, George Carey, Poonam Sharma, Ravi Salgia, Surinder Batra
Journal: Journal of Clinical Oncology (2012)

e17549 Background: MUC4 has been shown to play a key role in breast and pancreatic cancer. MUC4 expression is seen in the normal bronchial epithelium, but its role in non-small cell lung cancer (NSCLC) is unclear. Here we study the association between MUC4 overexpression and clinical features of NSCLC. Methods: The diagnosis of lung cancer was confirmed in H&amp;E sections. MUC4 level was semi-quantified by immunohistochemistry. Each sample was given a composite score based on intensity and extent of staining. The intensity was graded on a 4 point scale: – (0), + (1), ++ (2), and +++ (3). The extent of staining too was graded on a 4 point scale: 1 (1-25%), 2 (26-50%), 3 (51-75%), and 4 (76-100%). The composite score was obtained by multiplying the two values, with possible scores of 0-12. Poisson mixed effects models were used to compare the score between groups. Kaplan-Meier method was used to estimate survival distributions and the log-rank test was used to compare them. Wilcoxon sign rank test was used to compare the difference in score between lung tissue and corresponding lymph node. P value &lt;0.05 was considered to be statistically significant. Results: 167 samples from 54 non-metastatic NSCLC patients were analyzed. Of these, 13 (25%) patients had stage I, 33 (63%) had stage II and 6 (12%) patients had stage III disease. Distribution of the composite score differed significantly by stage (p=0.0043). A higher proportion of patients with stage I NSCLC had a score of 12 (77%) compared to stage II (18%) and stage III (57%) (p=0.0001). When patients who had data for both the primary tumor and corresponding metastatic lymph node were analyzed, MUC4 expression was higher in the primary tumor compared to the metastasis (p=0.05). The effect of MUC4 expression on survival was analyzed in 29 patients with survival data. Of these, 16 had a composite score of 12, while 13 had a score &lt;12. Patients with a score &lt;12 had significantly worse survival than those with a score of 12 (p&lt;0.045). Conclusions: MUC4 expression is more common in early stage NSCLC and appears to be associated with a better outcome in patients with non-metastatic NSCLC. The therapeutic implications of this finding need to be investigated further.
Meta-analysis of aprepitant combination regimens (ACR) for prevention of chemotherapy-induced nausea and vomiting (CINV) in adults.
Authors: Neha Gupta, Hassan Hatoum, Omar Al Ustwani, Pongwut Danchaivijitr, Katy Wang, Roberto Pili
Journal: Journal of Clinical Oncology (2014)

e20622 Background: Various randomized controlled trials (RCTs) have shown improved outcomes with addition of aprepitant to standard antiemetic treatment (SAT) in preventing CINV. We conducted a meta-analysis to study the overall impact of ACR in CINV prevention in adults. Methods: We searched Pubmed and Ovid databases, and American Society of Clinical Oncology meetings abstracts for RCTs using ACR with SAT for CINV prevention in adult cancer patients (pts). Major study end points were complete response to treatment (CR; defined as no emesis and no use of rescue medications) in overall phase (OP; 0-120 hours of chemotherapy), acute phase (AP; 0-24 hours) and delayed phase (DP; 24-120 hours). Additionally, we assessed the control of nausea and toxicity profile (TP). Stouffer's Z-score method was used to calculate the overall effect. Results: 16 RCTs (5,547 pts) were included. 11 trials (3,314 pts) involved highly emetogenic chemotherapy (HEC) and 5 trials (2,233 pts) involved moderately emetogenic chemotherapy (MEC). ACR increased CR in OP from 47% to 63% (OR=0.52, CI=0.46 to 0.58; p<0.001), in AP from 73% to 81% (p<0.01), and in DP from 51% to 66% (p<0.001). Significant increase in nausea control was seen in DP (p=0.03) but not in OP or AP. Incidence of various toxicities was statistically similar in both groups except slightly higher rate of fatigue (p=0.02) and hiccups (p<0.001), and lower rate of neutropenia (p=0.02) in ACR. Conclusions: ACR is effective in CINV due to both HEC and MEC in adult cancer pts. ACR improves the control of emesis in all phases, and nausea in delayed phase only. With the exception of causing more fatigue & hiccups, and lesser neutropenia, overall TP of ACR is similar to SAT.