tbuckley/cabot-search huggingface dataset:
Assessment of EGFR mutations in patients diagnosed of squamous non-small cell lung cancer (NSCLC).
Authors: Francisco Lobo, Manuel Domine, Federico Rojo, Yann Izarzugaza, Ana Leon, Victoria Casado, Maria Jesus Fernandez-Acenero, Gustavo Rubio, Jose Ignacio Martin-Valades, Juan Luis Arranz, Gloria Serrano, Cristina Carames, Sharon Cordova, Juan Madoz, Sandra Zazo, Raul Rincon, Carmen Canadas, Nuria Perez-Gonzalez, Angel Campos, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

e18106 Background: Mutations in the Epidermal Growth Factor Receptor (EGFR) predict a better outcome to EGFR tyrosine kinase inhibitors than platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Previous studies with Caucasian patients have shown a prevalence of EGFR mutation of 10-15%. The aim of this study is to analyze the prevalence of EGFR mutations in squamous-cell NSCLC patients from an area of influence of 500,000 habitants. Methods: Prospective mutation testing in NSCLC patients included in our institution since October 2010 to January 2012 was performed on DNA obtained from available tumor tissue and cytologic samples, using ARMS-scorpion TheraScreen EGFR 29 Mutation Test Kit (Qiagen). Results: From 218 consecutive NSCLC diagnoses, 18 (8.25%) patients showed EGFR mutations: 6 (33.3%) exon 19 deletion, 9 (50%) exon 21 mutations (7 L858R and 2 L861Q) and 3 (16.6%) cases exon 20 insertion. In the EGFR mutated population, 16 (88.88%) patients were diagnosed as adenocarcinoma and 2 (11.11%) as squamous cell carcinoma. The characteristics of these squamous cell cancer patients were: 2 male; 1 non-smoker, 1 former-smoker; 1 stage IV and 1 stage IB at diagnosis; one case exon 20 insertion and one exon 21 mutation (L858R). Conclusions: The EGFR mutation rate in squamous-cell NSCLC patients in our referral area is superior (11.17%) than previously reported, reinforcing the importance of including EGFR mutation testing in squamous-cell NSCLC population for selecting optimal therapy for these patients.
Changing pattern for HER2 positivity due to updated ASCO/CAP guidelines for HER2 testing and its impact.
Authors: Mithun Vinod Shah, Anne E. Wiktor, Reid G. Meyer, Kathleen S. Tenner, Karla V. Ballman, Rhett P. Ketterling, Edith A. Perez, Robert B. Jenkins
Journal: Journal of Clinical Oncology (2014)

523 Background: ASCO/CAP guidelines for HER2 testing in breast cancer were published in 2007 and updated in 2013. HER2-directed therapies (HDT) should be recommended in patients who are deemed HER2 positive, while they are not recommended in HER2 negative patients. If HER2 testing is equivocal, the guideline suggests that HDT be considered. It is not known how implementation of updated guidelines will change clinical practice. Methods: After the implementation of the 2013 guidelines, 321 breast tumor samples were received by the Mayo Clinic Cytogenetics laboratory for FISH analysis of HER2 status. The prevalence of HER2 alterations in this cohort was analyzed using both 2007 and 2013 guidelines. We also retrospectively analyzed HER2 data from N9831 (Alliance), a prospective multicenter randomized trial that evaluated the use of trastuzumab in the adjuvant setting. The trial included 3,505 women with histologically confirmed node-positive/high-risk node-negative HER2 positive invasive breast cancer. US FDA criteria were used to define HER2 positivity in N9831. Results: Using 2007 guidelines, 44 (14%) of the Mayo clinical practice cases were HER2 positive, 262 (82%) negative, and 11 (3.5%) equivocal. Using 2013 guidelines, 80 (25%) were positive, 225 (70%) negative, and 12 (4%) equivocal. The interpretation changed in 48 (15%) cases (p< 0.0001). In N9831 using 2007 guidelines, 2,878 cases were HER2 positive (80.7%), 607 negative (17%), and 80 (2.2%) equivocal. Using 2013 guidelines, 2,937 (82.4%) were positive, 538 (15.1%) negative, and 90 (2.5%) equivocal. The increase in the prevalence of positive cases was significant (p<0.0001). Preliminary analysis suggests no disease-free survival benefit in women who had change in classification when stratified by whether they received HDT or not. Conclusions: There is a significant increase in the proportion of HER2 positive cases when breast cancer specimens are assessed using the 2013 ASCO/CAP guidelines. The updated guidelines also result in more equivocal cases requiring reflex testing. Interpreting HER2 status using updated guidelines will result in an increase in the number of breast cancer patients eligible for HDT. Clinical trial information: NCT00005970.
Degarelix as neoadjuvant hormone therapy in patients with prostate cancer: Results from a phase IIIb randomized, comparative trial versus goserelin plus bicalutamide.
Authors: Malcom Mason, Christopher P Steidle, Charalambos Deliveliotis, Stephane Guerif, Xavier Maldonado, Vincent Khoo, Thomas Wiegel, Egbert van der Meulen, Peter Bergqvist
Journal: Journal of Clinical Oncology (2012)

e15199^ Background: The current approach in patients with high-risk localised or locally advanced PCa is ADT prior to radiotherapy, which improves disease-specific and overall survival vs radiotherapy alone. Whether degarelix, a GnRH antagonist performs comparably with the use of GnRH agonist under flare protection in neoadjuvant settings has not yet been investigated. Methods: Patients with intermediate to high risk PCa were randomised (3:1) to receive either degarelix or goserelin plus bicalutamide (G+B) for 12 wks. The primary endpoint was the percentage reduction from baseline in prostate volume at wk 12 as measured by TRUS. The non-inferiority margin was -10%. Other endpoints included changes in the IPSS, testosterone and PSA. Results: 177 in the degarelix and 62 patients in the G+B arm have completed the trial. 62% and 38% of the patients had localised and locally advanced PCa, respectively. The primary endpoint was successfully met establishing noninferiority between the two treatments in terms of prostate volume reduction at wk 12 (Table). Conclusions: Degarelix was equally effective as prostate shrinking neoadjuvant hormone therapy in patients with intermediate to high risk PCa, but elicited more pronounced LUTS relief compared with G+B after 12 wks of treatment. Possible explanations may involve more pronounced effects on the tumour per se or differences in the action of these drugs on peripheral GnRH receptors expressed in the prostate and the urinary bladder. [Table: see text]
Importance of tumor grade in stage III mucinous appendiceal carcinoma: An analysis of the SEER Database.
Authors: Olivia Fukui, Kendall W. Carpenter, Yimei Han, Matthew Salvino, Jonathan C. Salo, Edward S. Kim, Joshua S. Hill
Journal: Journal of Clinical Oncology (2015)

4112 Background: Appendiceal cancers are rare tumors with prognostic heterogeneity and treatment-responses dependent upon histologic characteristics. In the 7th edition AJCC manual, mucinous tumors were separated from non-mucinous. Histologic grade was used to distinguish stage IVa from IVb in mucinous tumors. We examined SEER data to investigate the impact of cancer grade on all stages of appendiceal cancer. Methods: We identified patients (pts) with primary appendiceal cancer from the SEER data. Disease-specific survival (DSS) was analyzed based on histologic subtype, stage, and grade. Hazards ratios were calculated using Cox models. Tumor grades were grouped according to AJCC criteria (Grade 1 vs. Grade 2 and above). Results: From 1988-2011 a total of 4491 appendiceal adenocarcinomas were identified in the SEER database; 2026 (45%) pts had mucinous histology and 1578 (35%) had non-mucinous histology. Tumor grade had no impact on DSS in stage I and II tumors. However, in Stage III and IV mucinous tumors higher tumor grade was significantly correlated with worse survival. In pts with Stage III mucinous disease, those with grade 1 tumors had significantly longer DSS than those with tumors ≥ grade 2, with 5-year survival of 75% vs. 44%, respectively (p = 0.02, HR 3.15, 95% CI 1.11 - 8.96). Survival for mucinous stage III grade 1 tumors was similar to stage II tumors. Conclusions: Tumor grade is a strong prognostic indicator in pts with stage III mucinous appendiceal carcinoma. We propose that tumor grade should be included in AJCC staging for stage III mucinous appendiceal cancers, and should not be limited to Stage IV disease as in the AJCC 7th staging manual. Continued investigation into the clinical implications of the observed difference in survival in patients with Stage III appendiceal mucinous adenocarcinoma is warranted, and may potentially alter adjuvant treatment recommendations in selected pts.
Estrogen levels in premenopausal (prem) patients (pts) with hormone-receptor positive (HR+) early breast cancer (BC) receiving adjuvant triptorelin (Trip) plus exemestane (E) or tamoxifen (T) in the SOFT trial: SOFT-EST substudy.
Authors: Meritxell Bellet, Kathryn P. Gray, Prudence A. Francis, Istvan Lang, Eva Ciruelos, Ana Lluch, Miguel Angel Climent, Gustavo Catalan, Roser Ferrer Costa, Roberto Catalan, Agnita Rajasekaran, Josefa Morales, Josep Vazquez, Gini F. Fleming, Karen N. Price, Meredith M. Regan
Journal: Journal of Clinical Oncology (2014)

585 Background: Optimal endocrine therapy for prem pts with early HR+ BC may depend on complete estrogen suppression with GnRH-A, and is crucial for those receiving concurrent aromatase inhibitors (AI). SOFT-EST is a prospective substudy of the phase III SOFT trial. Aims of SOFT-EST are to describe estradiol (E2), estrone (E1) and estrone sulphate (E1S) during monthly Trip + E or T and to assess if there is a group in E+Trip with suboptimal estrogen suppression (SES). Methods: All pts enrolled in SOFT from selected centers who consented, selected Trip as ovarian function suppression method and were randomized to E+Trip or T+Trip were enrolled in SOFT-EST until reaching the accrual goal (E=90;T=30 pts). Prem status for SOFT was based on local E2. Blood sampling timepoints (tp) were: 0, 3, 6, 12, 18, 24, 36 & 48 months (m). Serum estrogens were measured by GC/MSMS due to high specificity/sensitivity and no E cross-reactivity. SES for E+Trip for this first pre-planned (12 m) analysis was defined as E2 levels >2.72 pg/mL (10 pmol/L). Results: 116 pts (E/T=86/30) who started Trip and had ≥ 1 sample drawn constituted the analytic cohort. In E+Trip, median reductions from baseline in E2, E1 & E1S levels were >95% at all tp, and significantly lower than in T+Trip. 27 of 79 E+Trip pts with ≥1 post-baseline sample had E2 levels >2.72 pg/mL at least once (25%, 24% & 17% at 3, 6 & 12m, respectively); 2 had vaginal bleeding >3 m beyond start of E+Trip, 1 with SES. Baseline factors related to SES in E+Trip were no prior chemo (p=0.06), high BMI (p=0.05), low FSH & LH (p<0.01 for both), but not age (p=0.8). Conclusions: Most pts on E+Trip reached E2 below the defined threshold, consistent with postmenopausal pts on an AI, but some may be suboptimally suppressed. The clinical relevance will be further explored with the full 4-yrs of estrogen results and outcome data. Clinical trial information: NCT00066703/NCT00066690. Baseline factors all pts: N=116 Age (median, range) 44 (25, 53) BMI (median, range) 24 (16, 44) Prior chemo 55% Prior T 31% Amenorrhea 36% Estrogen (pg/mL) (median, range) E2 51 (0.6, 766) E1 42 (1.6, 486) E1S 894 (7.2, 8770) FSH/LH (IU/L) FSH 16 (1.7, 123) LH 14 (0.5, 72)
Assessment of the incidence of medical events reported following Y90 treatment.
Authors: Petra Prins, Simone Wahnschafft, Kiara Rivera Guevara, Ahsum Khan, Anna Fishbein, Keith Robert Unger
Journal: Journal of Clinical Oncology (2017)

491 Background: Radioembolization (Y90) is a minimally invasive procedure combining embolization and radiation therapy to treat primary and metastatic liver tumors. During radioembolization, resin beads loaded with the radioactive isotope, yttrium Y-90, are administered through the hepatic arterial vasculature. Although the safety profile of Y90 is well described, the number of dosage errors associated with treatment delivery is unknown. The purpose of this study is to assess incidence of medical events reported following Y90 treatment. Methods: A search was conducted of the US Nuclear Regulatory Commission events notification database for reported medical events between January 2000 and July 2016 using the following search terms: Y90, SIRS spheres, and TheraSpheres. Results: We recorded 96 reported medical events related to Y90 treatment: 26% were related to human error, 20% to equipment malfunction, 14% to catheter blockage, 2% were caused by catheter movement, 5% were the result of improper microsphere migration, and 33% had undetermined cause. The human error-related events consisted of application of an incorrect dose (82%), administration to the incorrect liver lobe (7%), or targeting of the wrong organ (11%). For the events involving incorrect dose administration, the total dosage exceeded the prescribed dose by greater than 20% in 5 events, while the total dosage was less than the prescribed dose by &gt; 20% in 86 events. In 12 cases, dose inaccuracies were indicated but final dose administered was not reported. Conclusions: Although the incidence of medical events was relatively small, equipment failure and human errors were frequent. Under dosages occurred more often than over dosages. Stopcock malfunction and catheter blockage were common causes and equipment redesign should be considered. Human errors involving administration of the incorrect dose are potentially avoidable with procedural modifications.
A phase I/II study combining dasatinib (D) and erlotinib (E) in non-small cell lung cancer.
Authors: Faye M. Johnson, XiMing Tang, Hai T. Tran, Chelsey Mc Intyre, Justina Price, J. Jack Lee, Nusrat Harun, Ignacio Ivan Wistuba, Kathryn A. Gold
Journal: Journal of Clinical Oncology (2013)

8102 Background: In preclinical models, combining EGFR and Src inhibition has been shown to have at least additive and possibly synergistic effects. In this phase I/II (phI/II) trial, we combined EGFR inhibitor E with D, a multi-targeted tyrosine kinase inhibitor with activity against Src. Primary endpoint of PhI was to determine maximum tolerated dose (MTD) of the combination of E and D; primary endpoint of PhII was progression free survival (PFS) at 12 weeks. Methods: In preclinical models, combining EGFR and Src inhibition has been shown to have at least additive and possibly synergistic effects. In this phase I/II (phI/II) trial, we combined EGFR inhibitor E with D, a multi-targeted tyrosine kinase inhibitor with activity against Src. Primary endpoint of PhI was to determine maximum tolerated dose (MTD) of the combination of E and D; primary endpoint of PhII was progression free survival (PFS) at 12 weeks. Results: 53 pts were enrolled between 2/09 and 4/12. 6 were not eligible. Of the 47 eligible pts (12 in PhI, 35 in PhII): median (range) age was 62 yrs (44-88), 26 pts (45%) were female. 6 pts in PhI and all 35 pts in PhII had NSCLC: adeno 25 pts, squamous 11, NSCLC NOS 5. Other tumor types enrolled in PhI: head and neck cancer (2), adenoid cystic carcinoma (1), mesothelioma (2), small cell lung cancer (1). 47% of pts were chemo-naïve. 8 pts had activating EGFR mutations (6 exon 19 deletions, 2 L858R mutations). The PhI starting dose E150/D100 was not well tolerated as 2 of 3 pts experienced grade 3 hypophosphatemia as a dose limiting toxicity. MTD was found to be E150/D70. 11% achieved PR and 44% SD. All observed responders had EGFR mutations. 9 pts (19%) stopped treatment early and were unevaluable. Median time on treatment was 43 days (range 1-262). Median time on treatment for the 8 pts with activating EGFR mutations was 144 days. Conclusions: Combination of E and D is safe and feasible in NSCLC, with MTD E 150 mg PO daily and D 70 mg PO daily. Rate of PR and SD were 11%,and 44%, respectively. Biomarker and pharmacokinetic studies will be reported. Clinical trial information: NCT00826449.
Vascular occlusive events (VOE) and mortality among elderly patients (pts) with chronic myeloid leukemia (CML): A retrospective analysis of linked SEER-Medicare data.
Authors: Kathleen Lang, Lisa McGarry, Huan Huang, David J. Dorer, Elise Kaufman, Kevin B. Knopf
Journal: Journal of Clinical Oncology (2015)

e17709 Background: Tyrosine-kinase inhibitors (TKI) used in CML may be associated with VOE; however, expected VOE rates in CML pts are unknown. This study used real-world data to examine event rates and mortality among elderly CML and non-cancer pts using US national data. Methods: Linked Surveillance, Epidemiology, and End Results (SEER) cancer registry and Medicare claims data from 2003-2010 were used to identify pts aged 66+ years with an incident (index) diagnosis of CML during 2004-2009. A comparison cohort without cancer was created from the SEER 5% Medicare sample and matched 1:1 to the CML cohort based on age, sex, race and region. All pts were required to have continuous enrollment and were followed from 12 months before index through death or the end of data availability. Mortality and rate of stroke, myocardial infarction (MI) and pulmonary embolism (PE) were analyzed. Kaplan-Meier (KM) survival analysis was conducted for overall survival. Results: 1,466 pts with CML were identified and matched 1:1 to a cohort without cancer. Mean age was 78 years for both cohorts, with average follow-up durations of 25 and 42 months for CML and comparison pts, respectively. Among 15% of CML pts with a Medicare Part D claim for TKI therapy, 97% received imatinib. 63% of CML pts died during follow-up compared with 23% of non-cancer pts (median survival: 23 months vs. > 84 months, p < 0.01). Among those who died, mean time to death was shorter for CML pts (15 vs. 26 months, p < 0.01). During follow-up, compared with non-cancer pts, CML pts were more likely to have MI (11% vs. 7%; with rates of 54 vs. 20 per 1,000 person-years [PYs]), stroke (25% vs. 21%; rate: 138 vs. 69 per 1,000 PYs), or PE (4% vs. 1%; rate: 20 vs. 4 per 1,000 PYs), all p < 0.03. Event rates were not elevated for the subset of CML pts with evidence of TKI compared with overall CML pts (TKI pts: MI: 39 per 1,000 PYs; stroke: 97; PE: 11). Conclusions: Elderly CML pts had shorter survival and higher rates of MI, stroke and PE than matched non-cancer pts. Event rates were not elevated among pts with evidence of TKI (primarily imatinib) use, suggesting the excess risk in CML pts may be driven primarily by underlying risk factors associated with CML.
Primary debulking surgery (PDS) for stage IIIc ovarian cancer: <i>Quo vadis</i>?
Authors: Leslie A. Garrett, Whitfield Board Growdon, David M. Boruta, Marcela G del Carmen, Anna M. Priebe, Annekathryn Goodman, Leslie Bradford, Rachel Marie Clark, John O. Schorge
Journal: Journal of Clinical Oncology (2012)

e15568 Background: The efficacy of PDS for advanced ovarian cancer has recently been challenged by data suggesting equivalent clinical outcomes for neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS). The strongest known predictor of prolonged survival in either group is the ability to achieve complete resection (CR) to no residual disease. PDS that results in a CR is associated with the longest overall survival of any sequence of treatment. The aim of this study was to determine what type of surgical approach is required to successfully perform PDS. Methods: All women with newly diagnosed stage IIIC epithelial ovarian carcinoma treated at our institution from 2000 to 2010 were identified. Pathology was prospectively reviewed by a faculty gynecologic pathologist. Treatment planning was discussed and documented at our weekly multidisciplinary tumor board conference. Data was retrospectively extracted from computerized medical records. Results: 344 (86%) of 401 women underwent PDS. Optimal debulking was achieved in 278 patients (81%): 35% had CR while 46% had 0.1-1.0 cm residual disease. 56 stage IIIC pts (19%) had a suboptimal surgical outcome with ≥ 1.0 cm. Compared to those having a CR, patients with 0.1-1.0 cm residual were more likely to require splenectomy (17 v 5%; P = 0.002) and transverse colectomy (19 v 10%; P = 0.042), with comparable rates of rectosigmoid resection (41 v 39%; P = 0.712) and en bloc pelvic resection including total peritonectomy (26 v 30%; P = 0.050). Patients undergoing CR were more likely to have diaphragmatic surgery (31 v 20; P = 0.068) and lymphadenectomy (67 v 33%; P &lt; 0.001). Conclusions: PDS is the preferred treatment of stage IIIC epithelial ovarian cancer at high-volume centers demonstrating &gt;75% rates of optimal cytoreduction. Tumor biology may lead to the need for more aggressive upper abdominal procedures in patients with 0.1-1.0 residual. Diaphragm resection, stripping or ablation is more often required in order to achieve CR. Since subclinical macroscopic nodal metastases are often present, lymphadenectomy is also frequently performed to ensure that all possible disease has been resected.
Cost-effectiveness of adjuvant radiotherapy for older women with early hormone-receptor positive breast cancer.
Authors: Katherine Elizabeth Reeder-Hayes, Stephanie B. Wheeler, Andrea K Biddle
Journal: Journal of Clinical Oncology (2012)

6096 Background: Radiation therapy (XRT) following breast conserving surgery decreases local recurrence at the expense of additional morbidity and treatment costs. However, its utility in elderly women at low risk of recurrence has been questioned. This study assessed the cost-effectiveness of adding XRT to hormonal therapy (HT) in women over 70 with stage I, hormone-receptor positive (HR+) breast cancer after breast conserving surgery. Methods: A decision tree model was used to assess the costs and benefits of XRT + HT versus HT alone in 10,000 women age 70+ with stage I HR+ breast cancer. Using a societal perspective, we considered medical costs and quality of life effects of initial treatment, recurrences, and metastatic disease as well as long-term XRT-associated complications including breast fibrosis, chronic pneumonitis and cardiac disease. Probabilities of recurrence and death were modeled on recent clinical trial results, while toxicity probabilities were taken from literature review. The primary health outcome was incremental quality-adjusted life years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the sensitivity of model results and conclusions to various parameter estimates. Results: In the base-case scenario, the incremental cost-effectiveness ratio (ICER) for the addition of XRT was $923,017/QALY. The ICER was highly sensitive to variations in utility weights, particularly those reflecting patient preferences for initial treatment with or without XRT and those reflecting the decrement in quality of life resulting from breast fibrosis. In PSA, XRT was associated with lower quality-adjusted life expectancy at higher cost in 58% of simulations. Conclusions: In women over 70 with stage I HR+ breast cancer, the addition of XRT to HT is not cost-effective at a willingness-to-pay threshold of $100,000/QALY, and is associated with little or no improvement in quality-adjusted life expectancy. Providers should be aware that the cost-effectiveness of XRT in this population is strongly influenced by patient preferences surrounding recurrence and toxicity risks, and should weigh these factors when making shared decisions with patients.
Adding Defibrillation Therapy to Cardiac Resynchronization on the Basis of the Myocardial Substrate
Authors: Sérgio Barra, Serge Boveda, Rui Providência, Nicolas Sadoul, Rudolf Duehmke, Christian Reitan, Rasmus Borgquist, Kumar Narayanan, Françoise Hidden-Lucet, Didier Klug, Pascal Defaye, Daniel Gras, Frédéric Anselme, Christophe Leclercq, Jean-Sébastien Hermida, Jean-Claude Deharo, Khang-Li Looi, Anthony W. Chow, Munmohan Virdee, Simon Fynn, Jean-Yves Le Heuzey, Eloi Marijon, Sharad Agarwal
Journal: Journal of the American College of Cardiology (2017)