tbuckley/cabot-search huggingface dataset:
A Galician Lung Cancer Group phase II study: Erlotinib as maintenance therapy after concurrent chemoradiotherapy in patients (p) with stage III non-small cell lung cancer (NSCLC).
Authors: S. Vazquez, J. Firvida, M. Lázaro, F. J. Barón, G. Alonso-Jaudenes Curbera, M. Amenedo, L. Santomé, F. J. Afonso, J. V. Cardona, J. Casal
Journal: Journal of Clinical Oncology (2010)

7091 Background: Combination of platinum-based chemotherapy and radiotherapy is the standard treatment for p with unresectable stage III NSCLC, but considering the high rates of recurrence, it is necessary to improve these results. Erlotinib is an EGFR TKI that prolongs survival in p with metastatic NSCLC. In this study, we aim to evaluate the role of erlotinib as maintenance therapy after a standard concurrent chemo- radiotherapy regimen in p with stage III NSCLC. Methods: P with unresectable stage IIIA/IIIB without malignant effusions NSCLC who had received a standard concurrent chemoradiotherapy regimen and had no evidence of tumor progression were enrolled in this single arm, open-label phase II study and received erlotinib 150 mg/day po for 6 months. Main elegibility criteria were: PS 0-2, adequate bone marrow, hepatic and renal function and measurable disease by RECIST criteria. Primary endpoint was the percentage of p without evidence of disease progression after 6 months of erlotinib therapy and secondary endpoints were: PFS, OS, ORR and safety profile. Results: A total of 66 p have been included in the study and data from 51 p are presented in this analysis. Baseline characteristics: median age 62 years (range 41-76); male 92.2%; caucasian 100%; smokers/never smokers (%) 94.1/3.9; ECOG PS 0/1/2 (%) 27.4/66.7/2.0; adenocarcinoma/squamous cell carcinoma/large cell carcinoma (%) 25.5/62.7/9.8; stage IIIA/IIIB (%) 25.5/72.5. Most common previous chemoradiotherapy regimen is cisplatin/docetaxel/RT (80.4%). 39 p were evaluable for tumor response: CR 17.9%; PR 20.5%; SD 56.4%; PD 5.1%. Median TTP was 9.9 months (95% CI 6.4-NR) and median OS was not reached yet. Most common adverse events related to erlotinib were rash 41,2% (2 p gr. 3) and diarrhea 27.4% (1 p gr. 3). Conclusions: Erlotinib as maintenance therapy is an active and well tolerated treatment after concurrent chemoradiotherapy in p with stage III NSCLC. In spite of the majority of patients are caucasian, males, smokers with squamous cell carcinoma, maintenance with single agent erlotinib reached a promising median TTP of 9.9 months. Data on survival will be updated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Toxicity induced by radiochemotherapy with weekly paclitaxel versus weekly cisplatin in patients with advanced head and neck cancer
Authors: D. L. Stanculeanu, A. Tache, A. Cringeanu, D. Mitulescu, R. Scheusan, M. Dragomir
Journal: Journal of Clinical Oncology (2007)

16534 Background: Head and neck cancers represent about 8 % of the total solid cancer cases. For advanced head and neck cancer (HNC) patients, the effects of disease and the side effects of aggressive treatments have the potential to severely affect quality of life. Combined chemoradiotherapy increase rates of locoregional control, but it may cause severe side effects, mainly painful mucositis. In our study we evaluated the chemoradiotherapy induced toxicities in patients treated with concomitant radiochemotherapy using weekly paclitaxel or cisplatin for advanced head and neck cancer. Methods: From April 2003 to December 2005 46 patients with locally advanced head and neck cancer were enrolled onto this study. Patients characteristics: 35 male and 11 female; mean age 62,5; performance status ECOG 0–1, carcinoma histological confirmed. All patients received external beam radiation using DT= 45 Gy, 1,8 Gy/fr, 5 fr/week in combination with chemotherapy: arm A (20 pts) - Paclitaxel 35 mg/mp days 1,8,15,22,29; arm B (26 pts)- Cisplatin 20 mg/mp days 1,8,15,22,29. Results: 40 patients have completed the planed treatment; 4 patients have interrupted treatment because of toxicity; there were 2 toxic death due to neutropenic sepsis and metabolic disorders in arm A. Toxicity grade 3–4 was hematological - neutropenia - 14, 6 % pts in arm A vs. 7, 8 % pts in arm B; gastrointestinal - nausea 6,7 % pts in arm A vs. 5,6% pts in arm B; neurological - neuropathy 5,4 % pts in arm A vs. 0 pts in arm B; dermatological - radic dermitis 4,3% in arm A vs. 4,1% in arm B; oral mucositis 33,6% in arm A vs 27,8% in arm B. All this patients received analgesics and anti-inflammatory drugs, systemic and/or topical. Other toxicities were not significantly related. Conclusions: This study confirmed that radiochemotherapy has shown to provide clinical benefit response and disease stabilization in patients with locally advanced head and neck cancer. Unfortunately, this concomitant therapy was significantly associated with hematological toxicities and oral mycosis. The most severe side effect was oral mycositis grade 3–4, especially in the paclitaxel arm. No significant financial relationships to disclose.
Adenocarcinoma of the Gallbladder in Guinea Pigs
Authors: C Hoch-Ligeti, C C Congdon, M K Deringer, H L Stewart
Journal: JNCI Journal of the National Cancer Institute (1979)

Adenocarcinoma of the gallbladder developed in 17 of 68 untreated and in 26 of 83 irradiated guinea pigs of inbred strains 2 and 13. The carcinomas spread widely by direct extension and through lymphatic and blood vessels to lymph nodes, mesenteries, omenta, abdominal wall, liver, lungs, bones, and spleen. Whole-body exposure to gamma or X-radiation increased both the number of tumors and metastases in male inbred guinea pigs but not in females. Significantly fewer (9 of 98) noninbred than inbred guinea pigs developed gallbladder carcinomas after irradiation. In 9 untreated noninbred guinea pigs gallbladder carcinomas were not found. Inasmuch as the effect of irradiation was not dose-dependent, an indirect systemic effect of irradiation was postulated. This is the first report on the occurrence of spontaneous gallbladder adenocarcinomas in guinea pigs.
Phase II randomized trial of irinotecan/docetaxel (ID) or irinotecan/gemcitabine (IG) with or without celecoxib (CBX) in 2nd-line treatment of non-small-cell lung cancer (NSCLC)
Authors: R. S. Keresztes, M. Socinski, P. Bonomi, A. Chen, L. Hart, R. Lilenbaum
Journal: Journal of Clinical Oncology (2004)

7137 Background: Current 2nd-line treatment options for pts with advanced stage NSCLC are limited. New, more effective, and less toxic agents/combinations are thus needed for treating NSCLC in the 2nd-line setting. This randomized, parallel, open-label, multicenter, phase II trial was designed to assess the efficacy/safety of the combinations ID and IG, and biomodulation with CBX, in pts with advanced NSCLC who failed 1 prior chemotherapy regimen. Methods: Men/women aged ≥18 years were randomized by 2x2 design to CBX 400 mg BID or none concurrent with chemotherapy until progressive disease, and to ID (irinotecan 60 mg/m2and docetaxel 35 mg/m2) or IG (irinotecan 100 mg/m2 and gemcitabine 1000 mg/m2) administered on days 1 and 8 every 21 days until disease progression. Results: 133 pts were enrolled, with 131 receiving ≥1 dose and evaluable for safety: median age 64 years; gender 80 men/53 women; race 107 Caucasian/14 Black/12 other; and baseline ECOG 0 = 44, and 1 = 89. All treatment arms were balanced regarding baseline demographics, disease sites, and laboratory parameters. Efficacy (n = 97)/toxicity (n = 131) are tabulated by ID vs IG and CBX vs none. One nontreatment-related sudden death due to cardiac arrest occurred on day 7. Conclusions: The results suggest that both ID and IG combination therapies are well-tolerated and efficacious 2nd-line regimens for patients with advanced NSCLC. CBX is tolerable when combined with these regimens; however, it did not enhance efficacy and may have interacted to increase hematologic toxicity. This will be formally tested when the data is mature. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly; Pfizer Eli Lilly; Pfizer Aventis; Eli Lilly; Pfizer Pharmacia
Highly sensitive quantitative detection of circulating tumor DNA in urine and plasma from advanced colorectal cancer patients in aid of early diagnosis of clinically relevant KRAS mutations.
Authors: Jason C. Poole, Cecile Rose T. Vibat, Lucie Benesova, Barbora Belsanova, Saege Hancock, Timothy Lu, Mark Erlander, Marek Minarik
Journal: Journal of Clinical Oncology (2015)

654 Background: Acquisition of point mutations in KRAS gene is causally associated with the onset of development of a resistance to anti-EGFR therapy in colorectal cancer. Newly acquired KRAS mutations can be detected in blood plasma months before radiographic detection. The objective of this study was to demonstrate feasibility of an ultrasensitive non-invasive method for detection of KRAS mutations in urine and plasma of patients with advanced colorectal cancer. Methods: Archived, matched urine and plasma samples (stored between 3-5 years prior to ctDNA extraction) from 20 treatment naïve, advanced stage cancer patients with known tumor tissue KRAS mutations determined by an accredited clinical laboratory, were used in a retrospective setting for a blinded concordance study. KRAS status in urine and plasma was compared to that in tumor tissue in order to assess clinical sensitivity of the ctDNA assay. An ultrashort-amplicon (31bp) assay for KRAS mutation enrichment and detection in highly fragmented urinary and plasma ctDNA was developed. The assay detected 1 copy of KRASG12A/C/D/R/S/V or G13D mutant allele in a background of wild-type DNA with a verified analytical sensitivity of 0.007% (7 copies per ~100,000 genome equivalents). Results: In a pilot study of 20 advanced stage colorectal cancer patients, 15 of 16 evaluable archived urine samples (94%) had KRAS mutation that was concordant with tissue biopsy. Of 20 archived plasma samples evaluated, 19 (95%) displayed the KRAS mutation concordant with tumor tissue. Of 16 paired urine and plasma samples, 15 (94%) had concordant KRAS mutation calls. Conclusions: This study demonstrates high clinical sensitivity (≥94%) of concordant KRAS mutation detection between urine, plasma and tissue specimens from advanced colorectal cancer patients. Early detection and monitoring of acquired KRAS mutations in circulating tumor DNA, and in particular urinary ctDNA, opens the possibility of a new paradigm for a truly non-invasive method of individualized care for colorectal cancer patients.
The influence of physician densities and patient characteristics on the decision to treat prostate cancer patients with varying clinical benefit.
Authors: James B. Yu, Sanjay Aneja, Danil V. Makarov, Kenneth B Roberts, Cary P. Gross
Journal: Journal of Clinical Oncology (2012)

19 Background: Our study investigates whether regional variations in physician densities or patient populations influence the decision to treat patients with prostate cancer. Methods: Data from the NCI Surveillance, Epidemiology, and End Results (SEER) database was combined with the health system factors from the Area Resource File for Health Service Areas (HSA). Patients treated from 2004-2007 with low likelihood of benefit from treatment (Gleason 6, PSA &lt;10.0, stage T1cN0M0, and age &gt;75) or high likelihood of benefit (Gleason 8-10 or PSA &gt;20.0 or stage T3N0M0, aged &lt;60) were analyzed. Health system factors analyzed were; radiation oncologist, urologist, and primary care provider densities, % unemployment, and % with at least a high school education. Patient factors analyzed included race and marital status. A logistic regression model was built to test the association between variables and attempted curative therapy (radical prostatectomy, EBRT, and/or brachytherapy). Results: For the 2630 pts with the lowest likelihood of benefit, 56.1% underwent some form of attempted curative therapy. White pts and those residing in HSAs with better-educated populations were less likely to be treated, whereas married pts (OR 0.69 [SE 0.07, p&lt;.001]) were more likely to receive treatment. For the 3207 pts with the highest likelihood of clinical benefit from treatment, 91.1% underwent curative therapy as first initial treatment. Being married was again associated with a higher odds of curative therapy (OR 1.68 [SE 0.22], p&lt;.001) whereas being black was associated with a lower odds (OR 0.43 [SE 0.16], p=.02). Both radiation oncologist density and urologist density were not found to influence receipt of treatment in either group. Conclusions: Radiation oncologist and urologist densities do not seem to influence the decision to treat prostate cancer at the regional level, whereas marital status is a significant predictor of attempted treatment. Though health system factors may influence the receipt of proper therapy, a patient’s decision-to receive treatment is potentially more influenced by his interpersonal relationships.
Cost and outcome of vascular resections during pancreaticoduodenectomy.
Authors: G. Bullock, M. J. Ott, T. Belnap, J. R. Whisenant
Journal: Journal of Clinical Oncology (2010)

6140 Background: The benefit of vascular resections (VR) as part of a pancreaticoduodenectomy (PD) in patients with pancreatic adenocarcinoma remains controversial. Most studies demonstrate equivalent long-term survival in properly selected patients undergoing PD with and without VR. The purpose of this study was to determine the efficacy of this procedure by combining cost and survival models. Methods: From 2000 through 2008, 163 patients underwent PD, of which 35 also underwent VR during the procedure. Models were generated to predict the effect of various parameters on cost of the surgical hospitalization and survival. Results: Variables that significantly increased the cost of the surgical hospitalization were: VR (p = 0.0063), length of stay (p = 0.0067), and age at diagnosis (p = 0.0086). Each of these factors independently increased overall cost with VR having the single greatest effect (an additional $11,860). The cost of hospitalization increased by $324 per year of age, such that an 80 year-old would cost $6480 more than a 60 year-old for the same stage, diagnosis, and procedure. Variables that significantly decreased overall survival were: VR (p = 0.0002), older age at diagnosis (p = 0.0008), and higher stage. Patients who received chemotherapy had increased survival rates that approached significance (p = 0.0561). The model showed that patients undergoing VR were 2.4 times more likely to die than patients undergoing a PD only. Advancing age negatively impacted survival, such that an 80 year-old was 1.8 times more likely to die than a 60 year-old. Overall survival for patients undergoing VR (1 yr = 0.443, 3 yr = 0.127, 5 yr = 0.095) and PD only (1 yr = 0.671, 3 yr = 0.179, 5 yr = 0.071) demonstrates that patients undergoing VR had a significantly worse short-term survival, but had a similar survival at 5 years. Conclusions: Patients with pancreatic adenocarcinoma undergoing PD that require VR incur significantly increased cost with significantly decreased rates of short-term survival. This coupled with the fact that older patients also incur increased costs with decreased rates of survival would suggest that VR with intent to cure as part of a PD procedure should be reserved for younger patients with apparently lower stage disease for optimal outcomes. No significant financial relationships to disclose.
Increased 14-3-3ζ Expression In The Multidrug-Resistant Leukemia Cell Line HL-60/Vcr As Compared To HL-60 Cell Line Mediates Cell Growth and Apoptosis
Authors: Rong Liang, Xiequn qun Chen, Qing xian Bai, Zhe Wang, Lan Yang, Tao Zhang, Bao xian Dong, Guang xun Gao, Hong tao Gu, Liang Zhang
Journal: Blood (2013)
Brain and tumor penetration of carbon-11–labeled lapatinib ([<sup>11</sup>C]Lap) in patients (pts) with HER2-overexpressing metastatic breast cancer (MBC).
Authors: Azeem Saleem, Graham Searle, Laura M. Kenny, Mickael Huiban, Adam Waldman, Louise Downie, Mike Lau, Philip S Murphy, Kasia Kozlowski, Yvonne Lewis, Laura Woodley, Sam Hill, Aruloly Kamalakaran, Sandra Hirschberg, Tomomi Kaneko, Eric Aboagye, Luca Marini, R. Charles Coombes
Journal: Journal of Clinical Oncology (2013)

635 Background: About a third of HER2-overexpressing (HER2+) breast cancer pts will develop brain metastases in the course of their disease. Drug access to normal brain and brain metastases is therefore key to prevention and treatment of cerebral metastases. To provide direct evidence of Lap drug access and evaluate whether therapeutic doses of Lap act as a substrate for efflux transporters, thereby increasing Lap concentrations, we performed positron emission tomography (PET) studies with [ 11 C]Lap. Methods: Pts with HER2+ MBC with an ECOG of &lt;3 were grouped into 2 cohorts: with at least one 1-cm diameter brain metastasis or without brain metastases and underwent 90-minute dynamic cranial PET-CT scans after IV administration of a microdose (&lt;1 mg) of [ 11 C]Lap before and after 8 days of oral Lap (1500 mg once daily). Arterial blood samples were performed to assess [ 11 C]Lap radioactivity contribution in blood and plasma, and the fraction of plasma [ 11 C] radioactivity corresponding to metabolites. Tissue time-radioactivity curves (TACs) were generated and [ 11 C]Lap exposure (AUC; area under TAC) derived for normal brain and brain metastases. Signal dissection of the total image activity was performed to remove the contribution of blood volume to the image and the actual tissue contribution due to [ 11 C]Lap obtained. Results: 6 pts (3 with brain metastasis) were recruited. Arterial plasma analysis revealed that [ 11 C]Lap contributed to &gt;80% of activity in plasma at 60 minutes. Tissue data revealed [ 11 C]Lap signal in normal brain was low with no appreciable uptake observed when corrected for blood volume contribution. [ 11 C]Lap uptake was higher in brain metastases compared with normal brain and appreciable, even after correction for tissue blood volume contribution. Uptake was also observed in extra-cranial normal tissue. There was no difference in [ 11 C]Lap uptake in normal brain and metastases between treatment-naïve and post-treatment scans. Conclusions: [ 11 C]Lap uptake in brain metastases was higher than in normal brain. [ 11 C]Lap drug access to brain metastases might therefore indicate possible efficacy against HER2+ brain metastases. Clinical trial information: NCT01290354.
High frequency of Gilbert's syndrome in ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL): Implications for etiology.
Authors: Y. Ravindranath, I. Brecht, J. Feldman, R. K. Severson, F. Nahhas, A. Nahar, G. Goyette
Journal: Journal of Clinical Oncology (2010)

9576 Background: Risk factors for the prevalence of the various cytogenetic subtypes in children with B precursor ALL are not fully defined. ETV6/RUNX1 (TEL/AML1) fusion, the result of a t(12;21)(p12;q22) translocation, occurs in 25% of newly diagnosed cases. This study was prompted by the serendipitous observation of Gilbert's syndrome, a mild glucuronidation defect, in two children with ETV6/RUNX1 positive BpALL. Prior epidemiology studies in childhood ALL suggested neonatal jaundice as a risk factor for childhood ALL (Podvin et al 2006). Gilbert's syndrome is a major cause of neonatal jaundice. Some environmental carcinogens (e.g. heterocyclic amines common in the diet- PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), topoisomerase I and II inhibitors (e.g. irinotecan, doxorubicin), steroids and synthetic drugs (imatinib), and flavonoids require glucuronidation for elimination. Methods: Discarded blood samples from routine blood testing were collected from 74 children with ALL followed at the Children's Hospital of Michigan under an existing IRB approved study for anonymized testing for genetic markers; in 6 cases archived diagnostic marrow samples were used. UDP-Glucuronosyltransferase (UGT)1A1 TATAA box polymorphism was tested using the FDA- approved Invader UGT1A1 Assay Kit. ETV6/RUNX1 fusion protein was tested by FISH in 74 locally and in 6 by PCR as a part of the Children's Oncology Group leukemia studies. Results: Thirty children had ETV6/RUNX1 fusion gene and 50 were negative. The overall frequency of Gilbert's syndrome (TA7/7 or 7/8 genotype) was 16.25% (13/80), slightly higher than the 12% expected frequency in the Caucasian population. Compared to ETV6/RUNX1 negative cases, there is a higher frequency of Gilbert's syndrome in ETV6/RUNX1 positive ALL (4/50 or 8 % Vs. 9/30 or 30% ; odds ratio 4.50; 95% confidence intervals 1.37, – 17.8). Conclusions: Our studies show that there is a high frequency occurrence of Gilbert's syndrome, in a common specific subtype of childhood ALL. This is a new observation and if validated suggests that chemical carcinogens that are eliminated by glucuronidation may be involved in the pathogenesis of childhood ALL. No significant financial relationships to disclose.
Pak A Proteins Are Essential for Hematopoietic Stem/Progenitor Cell (HSC/P) Engraftment Through Regulation of Signaling Pathways Controlling HSC/P Proliferation, Survival, Migration, and the Actin Cytoskeleton
Authors: Adrienne M. Dorrance, Rachelle Kosoff, Meaghan McGuinness, Chad Harris, Serena De Vita, Ronald Mathieu, Steven W. Lane, Michael D. Milsom, Jonathan Chernoff, David A. Williams
Journal: Blood (2011)
Disruptions in activities of daily living for African American prostate cancer patients compared to Whites
Authors: J. Purnell, G. R. Morrow, J. A. Roscoe, P. Jean-Pierre, J. N. Atkins, D. F. Moore, L. M. Kasper
Journal: Journal of Clinical Oncology (2008)

5163 Background: African American (AA) men continue to bear a disproportionate burden of prostate cancer relative to White (W) men, making it important to monitor their response to disease and subsequent treatment. This study compared AA and W ratings of the extent to which prostate cancer and its treatment interfered with several domains of daily living for 190 patients who participated in a group therapy intervention and reported their racial background. Methods: One-way ANOVAs were used to determine whether there were significant differences in mean scores for each group on the Impact of Illness scale at baseline and at 3- and 6-month follow-up. Results: There were significant differences (all ps < 0.05) in total scale scores at baseline (AA mean = 32.08 vs. W mean = 19.04; F = 12.83), 3 mo. (AA mean = 29.91 vs. W mean = 18.89; F = 9.77) and 6 mo. (AA mean = 28.00 vs. W mean = 18.28; F = 5.42), with AA men reporting more disruption. A similar pattern was observed for the Relationship and Personal Development and the Instrumental subscale scores, but there were no significant differences on the Intimacy subscale. At baseline 10 of 13 domains covered by the Impact of Illness scale (e.g., work, relationships, financial situation, recreation, diet) were significantly more disrupted for AA men compared to W men, and 5 of 13 domains were still worse for AA men at 6 mo. follow-up. Conclusions: Results suggest that, compared to W men, AA men are experiencing more disruption in their daily lives across multiple domains and that this disruption persists over time. Targeted efforts are required to address the particular needs of AA prostate cancer patients who face serious negative consequences of disease and treatment in addition to established disparities in incidence and mortality. No significant financial relationships to disclose.
LRF Maintains HSC Homeostasis by Preventing Lymphoid-Primed LT-HSCs From Excessive Differentiation
Authors: Sung-Uk Lee, Manami Maeda, Anne E. Wilson, Min Li, Yuichi Ishikawa, Adrian M. Judd, Nagisa Sakurai, Emma Fiorini, Freddy Radtke, Minhong Yan, Hugh Robson Macdonald, Ching-Cheng Chen, Takahiro Maeda
Journal: Blood (2011)