tbuckley/cabot-search huggingface dataset:
Clinical and morphological criteria of an initial ovarian cancer
Authors: E. V. Bakhidze, O. P. H. Chepic, S. Y. Maximov
Journal: Journal of Clinical Oncology (2004)

5125 Background: The cultivation of initial ovarian cancer's criteria determines possibility of improvement of the fertility reserved treatment's technology. The estimation of the clinical and morphological prognostic factors of ovarian cancer stage I gives the opportunity to pick out the fundamental initial ovarian cancer's criteria. Methods: A retrospective analysis was performed on 182 cases of stages I ovarian cancer diagnosed since 1980 to 1995. The morphological research included an estimation of proliferate activity of a tumour (mitotic regimen, performance of pathological mitosises and secretory function of tumoural cells). 47 indications were studied and the most informative criteria were chosen on the basis of the multifactor analysis. It allowed judging the prognosis of current of malignant ovarian tumours stages I. Results: It was fixed, that recurrence-free survival rate of the patients, which had made on the average 82,9 %, was in direct relation to mitotic activity of a tumour and availability of pathological mitosises. The most appreciable influence on a survival rate of the patients rendered such form of a pathological mitosis, as dispersion of chromosomes in a metaphase (5-year's survival rate had made 60,0 %), and also combination of the diverse forms of pathological mitosises (5-year's survival rate had made 66,7%). Recurrence-free survival rate did not depend on methods of treatment (radical or savings). Conclusions: Initial ovarian cancer can be identified in those cases when there are G1, serous, mucinous or endometrioid tumours, Ia and Ib of stages, low mitotic activity of epithelial cells (amount of mitosises up to 5 on 10 fields of vision, lack of pathological mitosises) and dominance a cell-like component by comparison with stromal one. In these cases fertility reserved operations are admissible without risk of deterioration of the prognosis. No significant financial relationships to disclose.
A phase II trial of lapatinib in hormone refractory prostate cancer
Authors: Y. E. Whang, C. N. Moore, A. J. Armstrong, W. K. Rathmell, P. A. Godley, J. M. Crane, G. I. Grigson, K. Morris, C. P. Watkins, D. J. George
Journal: Journal of Clinical Oncology (2008)

16037 Background: Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) tyrosine kinases represent potential targets in prostate cancer. HER2 promotes progression of prostate cancer to the hormone refractory stage and ligand-independent activation of androgen receptor in preclinical models. Inactivation of HER2 leads to inhibition of androgen receptor transcriptional activity and decreased synthesis of prostate specific antigen (PSA). Lapatinib (GW57206) is a tyrosine kinase inhibitor of EGFR and HER2. Methods: In this multicenter, open-label trial, patients with rising PSA on androgen deprivation therapy who completed antiandrogen withdrawal, if previously on antiandrogen, and have not received chemotherapy were eligible. They were treated with lapatinib at an oral dose of 1500 mg daily. The primary endpoints were to determine PSA response rates and time to PSA progression. Results: Twenty-nine patients enrolled on the study had a median age of 72.5 years (range 58–91 y) and a baseline PSA of 21.6 (4.5–196.5). Six patients had no radiologic evidence of metastatic disease while the remaining patients had bone or measurable disease or both. The most frequent adverse events were diarrhea (76%), fatigue (72%), rash (41 %) and anemia (38%). Dyspepsia, anorexia, and nausea were less frequently noted. Grade 3 treatment-related toxicities were diarrhea (17%) and rash (3%) that led to discontinuation in one patient for rash and dose interruption/reduction for diarrhea. One of 21 evaluable patients had >50% reduction in PSA (197 to 49), while another patient had 47% reduction in PSA (12.9 to 6.9), with a duration of response of >15 months. The median time to PSA progression was 29 days. Two patients had nonprogressive disease lasting >15 and >5 months. Conclusions: Lapatinib was well tolerated. Lapatinib showed single agent activity in a small subset of unselected patients with hormone refractory prostate cancer, as measured by PSA. Future trials should incorporate predictive biomarkers and a combination with other agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline
Predictors of Hypersensitivity Reactions (Hsrs) in Patients Receiving Carboplatin-Based Chemotherapy for Ovarian Cancer
Authors: K.J. Jerzak, S.D. Manshadi, P. Ng, M. Maganti, J.M. McCuaig, A.M. Oza, H. Mackay
Journal: Annals of Oncology (2014)
Vaginal progesterone in the treatment of cervical dysplasia grade I: A phase II trial
Authors: L. A. Hefler, C. Grimm, L. Six, G. Sliutz, A. Reinthaller
Journal: Journal of Clinical Oncology (2005)

5174 Background: Cervical intraepithelial neoplasia (CIN) grade I is a frequent HPV associated disease. The development of CIN was linked to a decrease of apoptosis and Langerhans’ cell (LC) count in the cervical epithelium, as well as to an increase in the expression of various adhesion molecules. Preliminary studies show that vaginally administered progesterone locally increases apoptosis and the number of LCs, and decreases the expression of various adhesion molecules. We hypothesized that vaginal progesterone increases the regression rate of CIN I. Methods: We are performing a prospective, non-randomized, open phase II trial with vaginal progesterone as treatment of CIN I. As of 12/5/2004, 18 patients are receiving vaginal micronized progesterone 400mg 1x daily for 10 days/month from menstrual cycle day 16–25 for 6 months. After 3 and 6 months patients are examined for possible regression, persistence, or progression of disease and treated accordingly. A total of 40 patients will be included in the study. Regression rates are compared with 40 controls managed expectantly. Results: Of the 40 controls, 14 lesions regressed within a mean observation time of 194 days. HPV status at inclusion (p=0.01), but not age, number of sexual partners, parity, smoking habits, use of contraceptive devices, and social status were associated with the regression rate. During the study period, 23 women were screened and asked to participate. Of those, only 5 refused to participate. Of the 18 progesterone treated women, already 6 had their 3-month examination. Regression was ascertained in 2 women during a mean follow-up of 103 (SD=11.1) days. Patients’ compliance is excellent, no side effects were noted. As of 12/05/04, we did not ascertain any statistical difference between women with and without progesterone treatment due to the low number of women enrolled in the active treatment arm to date. Conclusions: Vaginal progesterone is a well-established treatment option in gynecology. In women with CIN I, the participation rate and compliance is high and no side effects of the applied treatment were reproted. We expect to present more comprehensive data on the efficacy of vaginal progesterone with respect to CIN I regression rates in a few months. No significant financial relationships to disclose.
Abstract 5317: Evidence for intracellular calcium-regulated secretion in gastrointestinal stromal tumor.
Authors: Erik Berglund, David Berglund, Pinar Akcakaya, Mehran Ghaderi, Elisabetta Dare, Per-Olof Berggren, Craig A. Aspinwall, Weng-Onn Lui, Jan Zedenius, Catharina Larsson, Robert Bränström
Journal: Cancer Research (2013)

Abstract Gastrointestinal stromal tumors (GISTs) are considered to originate from the electrically active pacemaker cells of the gut. Despite the presence of synaptic like vesicles and proteins involved in exocytosis and secretory response in other cell types, it still remains unclear if GIST cells have a regulated secretion. A GIST tumor cell line (GIST882) was used as a model cell system, and stimulus-secretion coupling was investigated performing measurements of intracellular Ca2+, confocal microscopy, flow cytometry and an ATP-based assay to measure secretory response. We demonstrate that GIST cells have an intracellular signaling pathway downstream regulating cell secretion observed as an ATP release. Cell membrane integrity was preserved showing that ATP is released and not related to cell membrane rupture or cell death. The stimulus-secretion signal transduction is, at least partly, dependent on Ca2+ influx, since exclusion of extracellular Ca2+ diminishes the secretory response. We conclude that measurements of the secretory response in GIST by using ATP as a marker may be a useful tool in dissecting the signal transduction pathway, identification of secretory substances and in the development of drugs. Citation Format: Erik Berglund, David Berglund, Pinar Akcakaya, Mehran Ghaderi, Elisabetta Dare, Per-Olof Berggren, Craig A. Aspinwall, Weng-Onn Lui, Jan Zedenius, Catharina Larsson, Robert Bränström. Evidence for intracellular calcium-regulated secretion in gastrointestinal stromal tumor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5317. doi:10.1158/1538-7445.AM2013-5317 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Metabolic syndrome in long-term testicular cancer survivors
Authors: H. Sagstuen, N. Aass, S. D. Fosså, O. Dahl, O. Klepp, E. Wist, J. Svartberg, T. Wilsgaard, R. M. Bremnes
Journal: Journal of Clinical Oncology (2005)

4576 Background: The purpose of this study was to investigate if treatment for testicular cancer (TC) increases the risk of metabolic syndrome (MetS) in long-term survivors of TC. Methods: 1264 patients, treated for unilateral TC during 1980–1994, were included in this study (1998–2002), including measurements of systolic (SBP) and diastolic (DBP) blood pressure, body mass index (BMI), blood tests and a questionnaire providing information about medical history. For the present analyses we excluded patients > 60 years at follow-up, leaving 1135 patients eligible. Patients were categorized in four treatment groups: Surgery (n=225), radiotherapy (RT, n=446), and two chemotherapy groups: Cumulative cisplatin dose ≤850 mg (n=376) and cumulative cisplatin dose >850 mg (cis>850, n=88). A healthy control group consisted of males from the Tromsø Population Study (n=1150). MetS was present if ≥ 2 of the following four components were present: Hypertension (SBP≥140 mmHg and/or DBP≥90 mmHg and/or use of antihypertensive medication); obesity (BMI≥30); hypercholesterolemia (total cholesterol ≥5.2 mmol/l and/or use of statins); diabetes mellitus. Results: Median observation time was 11.1 years (range 4–22). Median age at follow-up was 43 years (range 23–60). Age-adjusted logistic regression analyses were performed to compare the prevalence of MetS between treatment groups, using the surgery group as reference. The RT group did not differ from the surgery group, while both chemotherapy groups had significantly increased odds of MetS, highest for the cis>850 group (OR 2.8, 95% CI 1.6–4.7). When MetS was classified as ≥ 3 components present, only the cis>850 group differed from the surgery group (OR 2.6, 95% CI 1.1–6.0). The prevalence of MetS for the total patient group did not differ from that of healthy controls. Subgroup analysis showed that the cis>850 group had significantly increased odds of having MetS (OR 2.1, 95% CI 1.3–3.4), while the other treatment groups did not differ from healthy controls. Conclusion: Long-term TC survivors treated with cisplatin-based chemotherapy have a significantly increased risk of developing metabolic syndrome, compared to patients treated with other modalities or to healthy controls. No significant financial relationships to disclose.
Cognitive function and fatigue in colorectal cancer (CRC) patients: Baseline assessments prior to chemotherapy
Authors: J. L. Vardy, H. Dhillon, W. Xu, A. Dodd, A. Park, S. B. Rourke, S. J. Clarke, J. Ringash, R. Burkes, I. F. Tannock
Journal: Journal of Clinical Oncology (2009)

9557 Background: A subset of women with breast cancer have cognitive impairment &amp;/or fatigue before and after chemotherapy (CTh). We evaluated these symptoms and potential mechanisms prior to CTh in patients with CRC. Methods: Chemo-naïve patients with stage I-III CRC (Group 1) and pts with limited stage IV CRC prior to 1 st line metastatic CTh (Group 2) were evaluated. Neuropsychological (NP) performance was assessed by classical and computerized (CANTAB) test batteries, with cognitive impairment defined using a global deficit score approach, and concurrent questionnaires for fatigue &amp; quality of life (FACT-F), anxiety/depression (GHQ), and perceived cognitive function (FACT-COG). Group 1 had blood tests to evaluate 10 cytokines, clotting factors, sex hormones, CEA and apoE genotype. Primary endpoints were cognitive function (classical tests) and fatigue in group 1. Associations between test results, demographic and disease-related factors were sought. Results: We assessed 326 patients: Group 1, 253 (post-surgery [median 56 days] 174; pre-surgery 79); Group 2, 73. Median age was 59 (23–75); 61% were male. In group 1, 36% had cognitive impairment on classical tests &amp; 29% on CANTAB; 32% and 30% in group 2. No differences were seen by disease stage or surgery status. Men had more cognitive impairment than women on classical tests (p=.001). Self-reported cognitive symptoms was 10%; higher in women (p=.08). Fatigue, QOL, anxiety/depression &amp; self-reported cognitive symptoms were strongly associated with each other (r=.45-.76, p&lt;.0001), but not with NP test performance. Fatigue was 52% in Group 1 vs 66% in Group 2 (p=.03); and greater in women (p=.002). All cytokines were elevated compared to healthy volunteers (p&lt;.001). Cognitive function and fatigue prior to CTh were not associated with cytokines, sex hormones, clotting factors, CEA or apoE genotype. Symptoms of anxiety/depression were reported by 13% of group 1 pts vs 25% in group 2 (p=.02). Conclusions: Cognitive impairment was present in 36% of CRC patients prior to adjuvant CTh, with 10% self-reporting impairment and 52% reporting fatigue. Cytokine levels were elevated but were not associated with cognitive function or fatigue. The etiology of cognitive impairment prior to cancer treatment remains unknown. No significant financial relationships to disclose.
Characterization of bone mineral density (BMD) at the time of diagnosis in postmenopausal patients with operable breast cancer: Association with clinical-pathological findings
Authors: K. Altundag, E. Kim, K. Broglio, A. U. Buzdar, G. N. Hortobagyi, B. Arun
Journal: Journal of Clinical Oncology (2005)

9611 Background: Estrogen is involved in the pathogenesis of breast cancer. Because bone contains estrogen receptors and is, therefore, highly sensitive to levels of circulating estrogen, bone mineral density (BMD) may be a surrogate marker of a woman’s long-term exposure to endogenous estrogen. Some studies suggest that women, especially postmenopausal women with high BMD, have an increased risk for breast cancer. Methods: In this study we evaluate the association of BMD at the time of diagnosis with clinical-pathologic findings (history of hormone replacement therapy, existence of in situ component, estrogen and progesterone receptor concentrations, tumor size, nodal status, stage, grade, existence of lympho-vascular invasion, and histology) in patients with operable postmenopausal breast cancer. 117 patients were identified as having undergone BMD measurement at the time of their breast cancer diagnosis. Lumbar spinal, total hip BMD were measured by dual-energy X-ray absorptiometry. Patients were divided into two groups based on the median BMD. The median spinal BMD was 0.93 (0.56 - 1.48) gr/cm2 and the median total hip BMD was 0.85 (0.54 - 1.23)gr/cm2 Results: Median age at diagnosis was 62 (range 49 - 83). Sixty-two patients had stage I disease and 55 had stage II disease. Patients with higher BMD were found to have low grade disease, (P=0.01 for lumbar spine BMD and P=0.09 for total hip BMD), no lymphovascular invasion (P=0.02 for lumbar spine BMD and P=0.03 for total hip BMD) and progesterone receptor-positive tumors (P=0.05 for lumbar spine BMD). Patients with low Ki-67 level also tended to have high BMD P=0.06 for lumbar spine BMD). Conclusions: In our study cohort, high BMD at the time of their breast cancer diagnosis was associated with several favorable prognostic factors. High BMD might be related to higher circulating estrogen levels in these women. Further studies with a larger patient population are needed to determine whether high endogenous estrogen levels and high BMD is also associated with favorable prognostic features and outcome in breast cancer. No significant financial relationships to disclose.
Factors impacting survival of patients with post-surgical disease recurrence in non-small cell lung cancer (NSCLC)
Authors: S. Banerji, Z. Nugent, A. Demers, S. Navaratnam
Journal: Journal of Clinical Oncology (2006)

7223 Background: There are no standard recommendations for follow-up of NSCLC patients post surgery. To be of value, follow-up should detect disease recurrence early enough to allow timely initiation of effective treatment leading to clinical benefit. Methods: Patients diagnosed with NSCLC in Manitoba, Canada, who underwent a surgical procedure at the two teaching hospitals between January 1996 and December 2001, were identified using the Cancer Registry. We included 435 patients who underwent complete surgical resection of pathologic Stage IA to IIB disease. To date, a detailed retrospective chart review has been completed on 249 of these patients. Median follow-up of this population was 3.45 years. Results: The median age was 66.4 years and 51% were male. 68% had Stage I disease. Lobectomy (73%) was more commonly performed over wedge resection (14%) and pneumonectomy (13%). The most frequent histological diagnosis was adenocarcinoma (52%) followed by squamous cell (29%) and bronchoalveolar carcinoma (13%). Disease recurred in 68% of patients. Recurrence was detected in 52 patients by routine imaging during follow-up. 117 had symptoms suggestive of disease recurrence prompting additional investigation. Median time to recurrence was 1.2 and 1.5 years (NS) respectively for the symptomatic and asymptomatic group. The median overall survival of the asymptomatic patients (4.19 years) was significantly (p = 0.007) greater than the symptomatic patients (2.66 years). Similarly, the median survival from the time of recurrence was greater for the asymptomatic patients (1.6 vs. 0.7 years, p = 0.004). A multivariate analysis identified symptoms (p = 0.02) at the time of recurrence and stage (p = 0.01) of the disease at the initial presentation as significant independent factors impacting overall survival. Only the absence of symptoms had a significant association (p = 0.006) with improved survival after diagnosis of recurrent disease. Conclusions: The diagnosis of recurrence while patients are asymptomatic resulted in better survival. This may suggest that routine post-surgical follow-up of patients with early NSCLC is justified. No significant financial relationships to disclose.
Benefits, limitations and pitfalls of sentinel lymph node (SLN) mapping (M) for colorectal carcinoma (CRCa): A multicenter trial
Authors: S. Saha, R. Sehgal, M. Patel, D. Wiese, A. Bilchik, T. Beutler, D. Iddings, M. Espinosa, C. Yee, M. Ghanem
Journal: Journal of Clinical Oncology (2006)

3621 Background: Clinical application of SLNM in CRCa patients (pts) is controversial due to the variable results in the literature for its success, skip metastases (mets) and accuracy. Hence prospective data from 5 institutions were analyzed to identify the factors associated with failure and skip mets in CRCa pts undergoing SLNM. Methods: SLNM was performed by peri-tumoral injections of 1–3 ml of 1% lymphazurin subserosally. First 1–4 blue nodes marked as SLNs were examined by 4 sections with H &amp; E and 1 for cytokeratin. Rate of failure and skip mets rate along with age, sex, tumor site, size, grade, T &amp; N stages were analyzed. Results: 549 consecutive CRCa pts underwent SLNM; 453 colon (C) and 96 rectal (R) pts. M: F ratio was 48%: 52% and median age of 72 years. The average no. of LNs was 14.5. SLNM failed in 1% of C and 8% of R pts ( Table ). Of the 8 R failures, 7 had neoadjuvant therapy. No correlation was found between failure, size or T-stage. Overall nodal positivity (+ve) rate was 48%. Of the 466 invasive CRCa pts with successful SLNM, rate of skip mets was 7% in C and 4% in R. Age, sex, grade and neoadjuvant therapy had no correlation with skip mets. Of 28 skip mets pts, 79% had tumors &gt;3cm and 93% had advanced (T3, T4) tumors. Higher skip mets also was found in the transverse colon tumor. The success, accuracy, and sensitivity rates were 98%, 95%, and 88% respectively. Of node +ve pts, 47% had mets found only in the SLNs. SLNM upstaged 35% of C and 36% of R pts with micromets. Conclusions: In CRCa, SLNM is highly successful and accurate in predicting the presence or absence of nodal mets. Submucosal fibrosis of the lymphatics due to neoadjuvant therapy may result in higher failure rates for R pts. Skip mets are higher in transverse C tumors and increase in frequency as the T-stage increases. Pts upstaged by SLNM may benefit from adjuvant chemotherapy. [Table: see text] No significant financial relationships to disclose.
Polymorphisms of the TGF-β pathway and breast cancer risk: A case control study
Authors: V. G. Kaklamani, Y. Bian, J. Liu, C. Bradley, A. Rademaker, H. Ahsan, K. Offit, B. Pasche
Journal: Journal of Clinical Oncology (2004)

9548 Background: Recent studies indicate that variants coding for ligand and receptor within the Transforming Growth Factor Beta (TGF-β) signaling pathway may modify breast cancer risk. A common genotype that increases circulating TGF-β levels, TGFB1*CC, is associated with decreased breast cancer risk. Conversely, a common variant that results in decreased TGF-β mediated growth inhibition, TGFBR1*6A, is associated with increased breast cancer risk. Objective: To examine breast cancer risk associated with TGF-β signaling pathway as assessed by two common and functionally relevant variants. Methods: Peripheral blood DNA from 660 consecutive breast cancer cases from Memorial Sloan-Kettering Cancer Center and 880 healthy females from New York. Estrogen receptor (ER), progesterone receptor (PR) status as well as disease stage were available for 152 patients. Main Outcome Measures: Breast cancer risk as assessed by combined TGFB1 and TGFBR1 genotyping. Breast cancer risk for TGFB1*CC carriers. Breast cancer risk for TGFBR1*6A carriers. Results: The O.R. for individuals with the lowest expected TGF-β signaling level (TGFB1*CT or TGFB1*TT and TGFBR1*6A) was 1.69 (1.08–2.66) when compared with individuals with the highest expected TGF-signaling levels (TGFB1*CC and TGFBR1/TGFBR1). TGFBR1*6A was associated with a significantly increased risk for breast cancer O.R. 1.46 (1.04–2.06) but TGFB1*CC was not associated with any modified breast cancer risk O.R. 0.89 (0.63–1.21). TGFBR1*6A effect was most pronounced among women diagnosed after the age of 50: O.R. 2.20 (1.25–3.87). Conclusions: Our findings suggest that common variants of the TGF-β signaling pathway are potent modulators of breast cancer risk. No significant financial relationships to disclose.