tbuckley/cabot-search huggingface dataset:
A phase II trial of neoadjuvant chemotherapy (NCT), organ-sparing surgery, and radiation in squamous cell head and neck cancer (SCHNC): Results of neoadjuvant chemotherapy
Authors: S. Shibata, B. Paz, J. Ellenhorn, N. Vora, G. Somlo, M. Koczywas, D. Lim, P. Frankel, L. Wagman, J. Doroshow
Journal: Journal of Clinical Oncology (2004)

5617 Background: NCT with radiation has facilitated organ-sparing treatment in locally advanced SCHNC. We conducted a phase II study of patients (pts) with SCHNC to evaluate a combination of NCT, radiation, and surgery to evaluate response to NCT as well as evaluate overall survival and recurrence patterns. Methods: Pts had resectable untreated stage III, IV SCHNC of the oral cavity, oropharynx, hyopharynx, or larynryx, and stage II cancer of the base of tongue, hypopharynx, and larynx. An ANC ≥ 1500/μl, platelet ≥ 100K/μl, serum creatinine ≤ 1.5mg/dl, bilirubin ≤ 1.5 mg/dl, liver function tests < 2.5 ULN, Karnofsky Performance Status (KPS) ≥ 60%, and signed informed consent were required. NCT consisted of docetaxel 60 mg/m2, then a 96-hour infusion of cisplatin 25mg/m2/d, 5-fluorouracil 700 mg/m2/d, and leucovorin 500 mg/m2/d. After 2 courses (C), those with at least a partial response received a third C. Pts with clinical complete response (CCR) or tumors < T1 were received radiation or chemoradiation and, as needed, surgery including modified lymph node dissection. Results: A total of 31 pts (1 with tonsillar lymphoepithelioma) were enrolled with response data for NCT in the first 25 pts presented. Pts had stage III (9), IVa (13), IVb (2), and stage II (1) disease. Median age was 63 yrs and 84% had a KPS ≥ 80%. After 2 Cs, 23/25 pts were in response, 6 in clinical complete response (CCR) in both neck and primary site. After a third cycle, 11/22 were in CCR with 16/22 in CCR at the primary site. Biopsies and/or surgical resection were performed in 18 of these pts; 11 pathologic complete responses (PCR) were seen. PCR was seen in 15/18 primary sites, and no pt required laryngectomy or base of tongue resection. Hemiglossectomy was performed in 2 pts and tonsillectomy in 3 pts (with 2/3 in PCR). C 2 dose reductions were needed in 12/24 pts and most required growth factor support. C 3 included 7/23 pts without dose reductions. Conclusions: NCT using a multi-agent regimen induces promising response rates allowing organ-sparing surgery in a high percentage of pts with SCHNC. Supported in part by grants from Aventis and CA 33572. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
An epidemiologic study of carcinoma gall bladder.
Authors: D. Panda, A. Sharma, N. K. Shukla, S. N. Dwivedi, V. Raina
Journal: Journal of Clinical Oncology (2010)

e14677 Background: Most gall bladder cancer (GBC) patients present in advanced/unresectable stage with poor response to therapy. Prevention or early detection is the best way to prevent death which requires identification of susceptible sub-group. Keeping this in mind this study was done to study the association between selected demographic, lifestyle and dietary factors and GBC. Methods: A hospital based case-control study was done in All India Institute of Medical Sciences, New Delhi, India. Cases were defined as newly registered primary GBC patients. Controls were defined as healthy relatives of patients other than GBC. Data were collected from February 2008 to October 2009 using a semi-structured interview schedule from both cases and controls. Food frequency questionnaire was used for dietary variables. Analysis was done using SPSS version 15 and Epi-Info version 6. For categorical variables chi-square test and chi square for trend were used. For continuous variables t-test was done. P value < 0.05 was considered as significant. Factors found significant in bi-variate analysis were entered in a multivariate logistics regression analysis. Results: A total of 122 cases and 122 controls were included in the study. There was no significant difference in age (p = 0.06) and gender (p = 0.66) between cases and controls. In bivariate analysis factors found significantly associated with GBC were illiteracy (odds ratio [OR]: 8.00, 95% confidence interval [CI] :3.47- 18.62; p 0.000), lower socioeconomic status (OR 2.45: 95% CI 2.45-9.10, p - 0.000), parity > 3 (OR 9.06, CI 4.10-20.35, p - 0.000), age at first pregnancy <20 yrs (OR 2.034, 95% CI 1.27-3.36, p - 0.018), non-liquefied petroleum gas (LPG) cooking fuel (OR 4.17, 95% CI 1.88-9.40, p - 0.000). Higher vitamin C intake had protective effect (OR 0.33, 95% CI 0.15-0.76, p - 0.004). In multivariate analysis education, intake of vitamin C, parity and type of fuel used were significant factors. Conclusions: The risk factors for carcinoma gallbladder that have been identified in the present study delineate a high-risk population group that can be targeted for preventive measures including improvement in socioeconomic status, education and life style and dietary intervention. No significant financial relationships to disclose.
Multicenter, Randomized, Double-Blind Phase Ii Study of Sorafenib Compared to Placebo with Best Supportive Care After Failure of Docetaxel in Metastatic Castration-Resistant Prostate Cancer
Authors: G. Kramer, A. Maj-Hes, A. Hobisch, S.F. Shariat, W. Loidl
Journal: Annals of Oncology (2014)
One-stop breast unit: Acceptable levels of anxiety and good retention of information
Authors: S. Dauchy, F. Zenasni, C. Balleyguier, C. Bourgier, V. Suciu, C. Uzan, S. Gouy, F. André, P. Vielh, S. Delaloge
Journal: Journal of Clinical Oncology (2008)

20624 Background: One-stop diagnosis for breast lesions might have potential deleterious consequences on affective functioning. As well, the level of retention of information after this single-day deserves exploration. We therefore prospectively explored emotional and cognitive states and functions of a consecutive series of patients (pts) seen at the One Stop Breast Unit of a single Institution. Patients and Methods: Pts with sub-clinical breast abnormalities addressed to the One-Stop Breast Unit during a 6 month (mo) period, were proposed to participate to this study. Emotional states and anxiety were self-evaluated at day -2, on day 1 before and immediately after diagnosis, at day 3 and at 3 months using Self Assessment Manikin, State-Trait Anxiety Inventory, Distress Thermometer questionnaires. Retention of information was evaluated on day 3 with specific questionnaires allowing to distinguish correct and incorrect recall. At 3 mo we used the revised Impact of Event Scale to evaluate the traumatic impact of diagnosis. Results: 279 pts filled the first form. 247 (88%) agreed to be evaluated on day 1, 61.5% answered the day 3 and 33% answered the 3 mo questionnaire. At day -2, 32% of pts were anxious of which 10% had severe anxiety. On day 1, only 10% of pts did not dominate their emotional states. After diagnosis, 24% pts reported high levels of distress, 20% emotional difficulties both significantly related to diagnosis (all p< .00001). At day 3, emotional scores appeared globally stable and 70–80% of information was correctly recalled, whatever the diagnosis and treatment proposed. Anxiety at day 3 significantly impaired information recall, but did not increase incorrect recall. At 3 mo, 28 % of the pts reported post-traumatic stress (35% of cancer pts), which was significantly correlated with emotional states and anxiety at day 3. Conclusions: While most pts have very acceptable emotional states before, during and after one stop breast assessment, 10% have severe anxiety before, and 10% do not dominate their emotional state during the day. Results are reassuring regarding the retention of correct information. Efforts have to be made to identify those pts who need early psychological care. No significant financial relationships to disclose.
RARα1/RARα2-PML mRNA Expression in Acute Promyelocytic Leukemia Cells: A Molecular and Laboratory-Clinical Correlative Study
Authors: Yun-Ping Li, Janet Andersen, Arthur Zelent, Sreenivas Rao, Elisabeth Paietta, Martin S. Tallman, Peter H. Wiernik, Robert E. Gallagher
Journal: Blood (1997)
Increased epithelial production of LPLUNC1 in cystic fibrosis lung disease
Authors: Colin Bingle, Kirsty Wilson, Marcus Mall, Doris Rassl, Lynne Bingle
Journal: European Respiratory Journal (2011)

Members of the PLUNC family of secreted proteins have been implicated in innate defence of the upper airways and nasopharynx. Although array data suggest that they are differentially expressed in some lung diseases validation has not been forthcoming. We previously showed that SPLUNC1 is increased in severe cystic fibrosis (CF). In the present study we have investigated the expression of LPLUNC1 in severe CF and studied both proteins in mouse models of CF lung disease. There was marked epithelial staining of LPLUNC1 in diseased small airways and submucosal glands. in CF, similar to our previous data with SPLUNC1. The two proteins are not co-expressed in the CF lung as LPLUNC1 is co-localised with MUC5A/C in goblet cells, whereas SPLUNC1 is present in a non-ciliated, non-goblet cell population. Expression of both proteins was unchanged (and very limited), in CFTR knockout mice. However, in CCSP-betaENaC transgenic mice, a model for CF lung disease, there was very strong staining of both proteins in the airways and in the luminal contents. This was most marked for lplunc1 and was noted within 2 weeks of birth. As in CF, the two proteins are present in distinct cells within the epithelium. Lplunc1 was absent from the lavage fluid of non-transgenics, in keeping with the lack of goblet cells, but was readily detected in transgenics. Our results suggest that alterations in expression of these putative innate immune molecules is associated with CF lung disease in both humans and mice. It remains unclear if this elevation of protein production, which results from phenotypic alteration of the cells within the diseased epithelium, plays a role in the pathogenesis of the disease.
The relation between hormone receptor status and disease-free survival in adjuvant breast cancer: A multivariate analysis
Authors: H. A. Azim, R. A. Malek, I. Elattar, D. Elkheshen, H. Azim
Journal: Journal of Clinical Oncology (2008)

11527 Background: Hormone receptor positive breast cancers carry lower risk of relapse compared to hormone receptor negative tumors. Among hormone receptor positive tumors, it is not clear whether the variation in the ER/PR status could affect disease-free survival (DFS). We tested the correlation between ER/PR status and DFS in patients with adjuvant breast cancer. Methods: Retrospective analysis was done for patients with breast cancer treated with adjuvant systemic therapy at our center from 1997–2005. The survival functions were estimated by the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis was performed using the Cox proportional hazard model. Results: Of 1,116 patients, 811 were eligible for DFS analysis. ER -ve and PR -ve tumors were independently associated with shorter DFS compared to ER +ve and PR +ve tumors (p<0.001 and p=0.002 respectively). On multivariate analysis, T3–4 (HR: 2.10; 95% CI 1.39–3.18; p<0.001), lymph node positivity (HR: 2.13; 95% CI 1.47–3.10; p<0.001) and ER -ve tumors (HR: 1.56; 95% CI 1.12–2.18; p=0.009) were independent predictors of poor DFS, after comparing the effect of other factors. No difference in outcome was observed between ER+ve, PR-ve and ER+ve, PR+ve (HR: 0.94; 95% CI 0.57–1.54; p=0.799) or between ER-ve, PR+ve/ER+ve, PR+ve (HR: 0.25; 95% CI 0.03–1.80; p=0.168). Patients with both ER and PR negativity had a worse DFS as compared to those who overexpressed both receptors (HR: 1.71; 95% CI 1.21–2.42; p=0.002). Conclusions: In patients with early-stage breast cancer treated adjuvantly, ER and not PR status independently affected DFS. Among hormone receptor positive tumors, variation in ER/PR status was not associated with significant differences on DFS. No significant financial relationships to disclose.
Multiagent concurrent chemoradiotherapy (MACCRT) and gefitinib in locoregionally advanced head and neck squamous cell cancer (HNSCC)
Authors: C. P. Rodriguez, D. J. Adelstein, J. P. Saxton, L. A. Rybicki, R. R. Lorenz, B. G. Wood, J. Scharpf, W. T. Lee, D. I. Ives
Journal: Journal of Clinical Oncology (2009)

6037 Background: In patients (pts) with stage III-IV HNSCC, MACCRT has led to excellent locoregional control. Distant metastases (DM) are now the most common cause of treatment failure. This phase II study tested whether the oral EGFR inhibitor gefitinib (G) added to our Cleveland Clinic MACCRT regimen would decrease DM and improve survival. Methods: Between 4/03 and 9/07, 60 previously untreated pts with stage III-IV (M0) HNSCC, and a performance status of &lt;1 were enrolled on this study. Pts received hyperfractionated radiation (72–74.4 Gy at 120cGy bid) and concurrent chemotherapy with cisplatin (20 mg/m2/day) and fluorouracil (1,000 mg/m2/day), both given as 96-hour continuous IV infusions during weeks 1 and 4. G 250 mg daily was begun on day 1 of the radiation and continued for 2 years. The results were retrospectively compared to our previous study of 44 pts treated with the same MACCRT regimen without G between 1/96 and 9/00. Results: The study population included a preponderance of Caucasian (97%) males (88%) with stage IV (80%) oropharynx tumors (68%), and with a median age of 58 (range 24–75) years. Patient and tumor characteristics were similar to the non-G treated historical cohort. When comparing the G vs. non-G treated pts, acute toxicities including transient renal dysfunction (28% v. 5% p = 0.002) and all-cause re-hospitalization (83% v. 64%, p = 0.022) were worse. Myelosuppression was similar. G-specific toxicity included &gt; grade 1 rash in 60% and diarrhea in 35%. There were 5 deaths during treatment in the G group v. one in the non-G group (p = 0.19). Only a projected 44% of pts will complete the 2-year course of G. With a median follow-up in this trial of 37 (range 13–64) months, 3-year Kaplan-Meier outcome estimates do not differ between the study and the historical cohorts. Local control without surgery is 80% v. 88% (p = 0.21), DM control is 86% v. 76% (p = 0.19), freedom from recurrence is 72% v. 71% (p = 0.79), and overall survival is 67% v. 68% (p = 0.63) respectively. Conclusions: The addition of G to our MACCRT regimen was difficult for pts to complete. It did not improve any measured outcome and was associated with increased toxicity when compared to historical controls. [Table: see text]
Impact of vaginal dehydroepiandosterone (DHEA) on vaginal symptoms in female cancer survivors: Trial N10C1 (Alliance).
Authors: Debra L. Barton, Jeff A. Sloan, Lynne T Shuster, Paula Gill, James D. Bearden, David B Johnson, Philip J. Stella, Shelby A. Terstriep, Fauzia N. Rana, Daniel M. Anderson, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2014)

9507 Background: Impaired sexual satisfaction is a prevalent and distressing issue for female cancer survivors. The aim of this study was to evaluate the impact of vaginal DHEA on vaginal atrophy symptoms and sexual function. Methods: A controlled, randomized trial evaluating 3.25 versus 6.5 mg of DHEA vaginally was conducted. Postmenopausal women with previous breast or gynecologic cancer were eligible if they reported ≥ moderate vaginal dryness or pain. DHEA was compounded in a bioadhesive vaginal moisturizer. Women inserted the bioadhesive moisturizer with or without DHEA using a pre-filled syringe daily x 12 weeks before going to sleep, after any sexual activity. The most bothersome vaginal symptom (dryness or pain) was evaluated with a single item Likert scale, and sexual function with the Female Sexual Function Index (FSFI). Side effects were graded by providers using the Common Terminology Criteria for Adverse Events (CTCAE) and self-report. Laboratory tests to assess systemic absorption were done. Analysis of change from baseline to 12 weeks (primary endpoint) included independent t-tests, comparing each DHEA treatment arm with plain moisturizer. Results: 441 women from 82 institutions were randomized, 147 in each arm. Women in all 3 arms reported significant improvement in their most bothersome symptom. Cohen’s d effect size for severity decrease was 1.4, 1.6 for DHEA 3.25, 6.5 mg respectively and 1.3 without DHEA. Compared with no DHEA, women receiving DHEA 6.5 mg reported statistically significant improvements in sexual function at 12 weeks, based on the FSFI full scale score as well as all sexual domain scores except orgasm (p-values <.0001 to 0.03.). Effect sizes ranged from 0.3 to 0.6. There were no significant differences in grade 2/3 toxicities. Two self-reported side effects, voice changes and headaches, were worse for DHEA arms compared to no DHEA. Lab data demonstrated no evidence of clinically important systemic estrogenic activity. Conclusions: These data support use of a daily vaginal moisturizer to improve vaginal atrophy symptoms. Vaginal DHEA significantly improves sexual desire, arousal, pain and overall sexual function, compared to this bioadhesive moisturizer alone. Clinical trial information: NCT01376349.
Incidence of subdural hematoma in patients with pulmonary arterial hypertension (PAH) in two randomized controlled clinical trials
Authors: Gerald Simonneau, Lie-Ju Hwang, Simon Teal, Nazzareno Galie
Journal: European Respiratory Journal (2012)

Background: Recent reports have emerged of increased incidence of subdural haematoma in patients with PAH, a serious adverse event with high mortality and morbidity. We evaluate the event rate in two randomized controlled trials, SUPER-1/2 and PACES-1/2.

Methods: In SUPER-1, 277 patients (IPAH, CTD-, CHD-PAH, WHO FC II-IV, mean baseline PVR 952.0 dyne.s/cm*5) naive to targeted therapy received placebo or sildenafil 20/40/80mg TID for 12 weeks. In the open-label extension (OLE) phase patients were up-titrated (as tolerated) to 80mg TID. In PACES-1, 267 patients (IPAH, CTD-PAH, WHO FC I-IV, mean baseline PVR 810.5 dyne.s/cm*5) stable on IV epoprostenol received placebo or sildenafil (up-titrated to 80mg TID, as tolerated) for 16 weeks. Patients in both OLE trials received sildenafil for ≥3 years. Treatment with conventional agents (anticoagulants, diuretics, digoxin, oxygen, calcium-channel blockers) was permitted. We determined the annual event rate of subdural haematoma by treatment exposure in person-years. Patient days on therapy does not include days on placebo.

Results: 2 patients experienced subdural haematoma, both during OLE; one received placebo in PACES-1, one sildenafil 40mg TID in SUPER-1. Patients were female, aged 58 and 62 years, diagnosed with IPAH, WHO FC III, mean PVR 557 (PACES-1) and 1073 dyne.s/cm*5 (SUPER-1) at baseline. Both patients received oral anticoagulants. In SUPER-1 and PACES-1, 73 and 82% of patients were on anticoagulants, respectively. Incidence of subdural haematoma in these 2 studies was 0.0015 events/ patient-year.

Conclusion: Subdural haematoma is a rare event in PAH patients in these 2 randomized controlled trials.
THU0228 Reduction of Inflammation Drives Lipid Changes in Ankylosing Spondylitis
Authors: S.C. Heslinga, M. Peters, M. Ter Wee, A. Van Sijl, Y. Smulders, I. van der Horst-Bruinsma, M. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Cancer is becoming a chronic disease. Oncology patients have a higher risk of suffering medication related problems (MRPs) due to patient characteristics (ageing populations, polypharmacy and comorbidities) and the toxicity of cancer therapies. The presence of a clinical pharmacist in an oncology ward may be an effective intervention to reduce this risk, and may contribute to the optimisation of therapy and quality of services provided to patients. <h3>Purpose</h3> The aim of the study was to characterise pharmacist interventions (PIs) and report acceptance rates by physicians in order to reduce MRPs. <h3>Material and methods</h3> A satellite unit pharmacy was established in an oncology ward (27 beds) of a large teaching hospital. Clinical pharmacy services including systematic medication reviews and medication reconciliation were provided daily by the clinical pharmacist. All PIs and their acceptance rate, and MRPs were recorded during the 12 month study period (2015) according to a validated classification system (Act IP). <h3>Results</h3> Medication reviews were performed in 2080 patients and 7020 therapy forms were analysed. Detection of MRPs led to 505 PIs that were subdivided into safety PIs (60%) and medication optimisation PIs (40%). The most frequent causes of MRPs in the safety group were: excessive dosage (44%), untreated indications (17%), interactions, especially concerning cytotoxic drugs (12%), and suboptimal dosage (11%). Most common PIs in the safety group were dose modification (41%) and drug discontinuation (23%). The drug classes with more interventions were antiemetic drugs, antithrombotic agents and analgesic drugs. The most frequent cause of MRPs in the optimisation group was inadequate choice of drug related to drug formulary (40%). Medication reconciliation was performed on 210 selected high risk patients and led to 30 PIs. The most repeated medication error was omission (57%). The overall physician acceptance rate was 81% for medication reviews and conciliation processes. <h3>Conclusion</h3> Detection and resolution of potential MRPs, as well as high rates of PIs acceptance by physicians, confirm the clinical pharmacist's role in improved patient safety in a multidisciplinary healthcare oncology team. An interesting challenge in the future will be to explore the real clinical impact of PIs. <h3>References and/or acknowledgements</h3> Thanks to all clinical pharmacists in our hospital. No conflict of interest
An open-label phase II study of the Hsp90 inhibitor ganetespib (STA-9090) as monotherapy in patients with advanced non-small cell lung cancer (NSCLC).
Authors: K. Wong, M. Koczywas, J. W. Goldman, E. H. Paschold, L. Horn, J. M. Lufkin, R. K. Blackman, F. Teofilovici, G. Shapiro, M. A. Socinski
Journal: Journal of Clinical Oncology (2011)

7500 Background: Ganetespib is a potent, next-generation Hsp90 inhibitor that is structurally unrelated to the first-generation ansamycin class of Hsp90 inhibitors and has shown superior activity to these agents in preclinical studies. Ganetespib has been well tolerated and has shown promising antitumor activity in early trials in multiple cancers. Methods: Patients (pts) with advanced NSCLC who failed prior treatments received 200 mg/m2 ganetespib as a 1-hr infusion once weekly for 3 of a 4-wk cycle in a Simon two-stage study design assessing primary endpoint of PFS rate at 16 wks. Initial cohorts were defined by mutation status: A) EGFR B) KRAS C) EGFR and KRAS wild type (WT). If ≥2/14 pts in A, B or C were progression-free at 16 wks, enrollment increased to 23 pts for that cohort. Tumor response was assessed every 8 wks. Cohort D was added to include 35 additional EGFR and KRAS WT pts with adenocarcinoma histology. Additional mutational analysis of BRAF, PIK3CA, ERBB2 and MET, as well as FISH analysis for ALK translocation, were performed for Cohorts C and D. Results: 73 pts (31 M, 42 F; median age 62 yrs, range 28-82; ECOG 0-1; prior therapies range 1-10) received a median of 2 cycles (range 1-12) of ganetespib in cohorts A (14), B (17), and C+D (42). AEs reported in ≥20% of pts included diarrhea, fatigue, nausea, anorexia, constipation, and dyspnea and were generally grade 1-2. Expansion criteria were achieved for cohort C, including a durable partial response (PR) and seven pts with prolonged stable disease (≥16 wks). Cohort D continues recruitment. Mutational analyses of Cohort C and D samples will be presented. Conclusions: Ganetespib administered as a single-agent is well-tolerated in pts with NSCLC at 200 mg/m2 once weekly without severe liver, ocular, cardiovascular or renal toxicity. Clinical activity has been observed in pts with advanced NSCLC tumors harboring wild-type EGFR and KRAS.