tbuckley/cabot-search huggingface dataset:
Factors influencing the switch from Tamoxifen (TAM) to Aromatase Inhibitors (AIs) as adjuvant therapy in early breast cancer (EBC) patients (pts). Results from the NORA study
Authors: P. Pronzato, M. E. Cazzaniga, G. Mustacchi, A. De Matteis, F. Di Costanzo, C. Verusio, N. Marzano, E. Rulli, I. Floriani
Journal: Journal of Clinical Oncology (2006)

10633 Background: Results from recent trials indicate that AIs as adjuvant treatment, either as up-front therapy or sequencing after TAM, can improve the clinical outcome of EBC pts. It is therefore important to assess the prevalence of the AI use in adjuvant setting and the reasons associated to the choice of this treatment. PATIENTS AND Methods: The NORA trial is an observational study, aimed at investigating adjuvant treatment modalities, that consecutively enrolled 3515 EBC pts, according to the following criteria: 10 pts each year starting from 2000 (retrospective cohort) and 20 pts starting from the beginning of 2003 or the date of ethical approval, if subsequent (prospective cohort). Using data from NORA, we focused on the subgroup of pts who switched from TAM to AIs in order to determine which factors are more likely to be associated with the probability of switching. Multivariate analysis was conducted using the Cox’s regression model. Results: Out of 2075 pts who started TAM, 329 (15.9%) switched to AIs. They had a median age of 63.1 yrs, 147 (45.9%) were N+, 190 (57.8%) received chemotherapy, 179 (54.6%) were T1, 248 (77.5%) were ER+/PgR+. Switch from TAM to AIs was influenced by N+ status, previous chemotherapy and age, whereas no effect was observed for T size or HR status. Previous chemotherapy increases the probability of switching by 27% (95% CI -4% to +70%, p = 0.10), each age decade increase by 35% (95% CI +21% to +52%, p &lt; 0.0001), N+ status by 16% (95% CI +1% to 34%, p = 0.03). Conclusion: As expected, high risk N+ pts have higher probabilities to be switched in comparison to other groups, probably due to the encouraging results of AIs trials. In previously treated or older age pts, TAM side effects could have determined the switch. No significant financial relationships to disclose.
Role of viral infections in exacerbations of asthma
Authors: R. Neville, G. Hoskins, B. Smith, R. Clark
Journal: BMJ (1995)

problem of stratification and selection for admission to those units.Finally, it is worth emphasising that not all investigations are of unproved value and that effective strategies for managing high risk patients do exist.We can avoid surgery altogether, and, indeed, quantification of risk may be particularly important in those operations, such as carotid endarterectomy, in which the benefit of surgery disappears at a given (and low) rate of perioperative complications.'As we stated in our last paragraph, further studies are urgently needed; these should not only assess methods of stratifying risk but also evaluate their effectiveness in reducing morbidity.Until such evidence is forthcoming, our article sum- marises the best methods available.
Second-line therapy in patients with malignant pleural mesothelioma. French retrospective study 2005-2006
Authors: Jacques Margery, Pierre Ruffie, Frédéric Riviere, David Planchard, Hervé Le Floch, Wanda Gaspard, Benjamin Besse, Fabien Vaylet
Journal: European Respiratory Journal (2011)

Background: The role of second-line chemotherapy (SLC) is not yet established in malignant pleural mesothelioma (MPM) but SLC is being used increasingly in our experience because many patients are still fit at the time of disease progression.

Methods: In this retrospective study, we reviewed our experience of SLC in pemetrexed-pretreated patients with MPM at two French thoracic oncology units (Institut Gustave Roussy, Villejuif; Hopital Percy, Clamart).

Results: Between January 2005 and December 2006, 84 consecutive patients with MPM who progressed after pemetrexed-chemotherapy were enrolled. Forty-four patients (52,3%) received a SLC. There were 30 men and 14 women. The median age was 58 years (range, 34-76). Most patients had a PS ≤ 1 (82%) and an epithelial histologic subtype (91%). The median time to progression (TTP) after first-line chemotherapy was 6,1 months. The SLC was a pemetrexed therapy in 21 patients (with a relapse more than 3 months), and a new regime in 20 patients (gemcitabine alone or with oxaliplatin). The other 3 patients were enrolled in a phase I study. According to RECIST criteria, a partial response was observed in 7 patients and 9 patients had stable disease after SLC. The median TTP after SLC was 3,8 months. The median survival was 12,2 months (range: 2 to 72 months). Four of these 44 patients then received third-line (4,8%) and two received fourth-line therapy (2,4%).

Conclusions: Our experience suggests the feasibility of giving SLC to patients with MPM who are healthy at the time of disease progression. The optimal treatment has not been defined to date and prospective trials are needed in this setting.
Interstitial lung disease (ILD) during gefitinib treatment in Japanese patients with non-small cell lung cancer (NSCLC): Okayama Lung Cancer Study Group
Authors: K. Hotta, S. Harita, A. Bessho, T. Yonei, K. Gemba, K. Aoe, M. Tabata, K. Kiura, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2004)

7063 Background: Risk factors of ILD during gefitinib treatment in patients with NSCLC are undetermined. The objective of this study was to elucidate the risk factors of ILD by analyzing the characteristics of patients with ILD. Methods: We retrospectively reviewed the clinical records of 325 patients with NSCLC who had received gefitinib in 12 hospitals between November 2000 and October 2003. Correlations between the various factors and the frequency of ILD following gefitinib treatment were investigated. Results: Patients characteristics were as follows; male/female: 68%/32%, Ad/others: 74%/26%, median age: 67 (range; 29–88), and ECOG PS 0–1/2–4: 66%/34%. An objective response rate by gefitinib treatment was 20% (62/307 patients). The median survival time after the initiation of gefitinib treatment was 6.7 months, with a median follow-up time of 10.8 months. Toxicities (grade 3 or more by the National Cancer Institute-Common Toxicity Criteria) included hepatic toxicity (5.0%), skin rash (2.2%), diarrhea (0.6%), and nausea/vomiting (0.3%). Twenty-two patients (6.8%) developed ILD after gefitinib treatment. The median toxicity grade of ILD was 3 (range; 2–4), and 10 (3.1%) patients have died. The median time to ILD after initiation of gefitinib treatment was 18 days (range; 3–123). Half of the patients developing ILD manifested the acute onset of dyspnea. Radiographic findings of the ILD were characterized mainly by diffuse ground-glass opacity. Statistically significant factors affecting the occurrence of ILD by multivariate analysis were presence of pulmonary fibrosis before gefitinib treatment and poor PS. Conclusions: The results of this study indicate that ILD during gefitinib treatment is considerably frequent. Physicians should carefully decide the indication of gefitinib treatment, especially for patients with lung comorbidities or poor PS. No significant financial relationships to disclose.
Targeting phosphatidylserine synergizes with immune checkpoint blockade by inducing de novo tumor specific immunity
Authors: Xianming Huang, Jian Gong, Dan Ye, Van Nguyen, Michael Gray, Steven King, Jeff Hutchins, Rolf Brekken, Bruce Freimark
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Extensive studies have demonstrated that the inside-out membrane phospholipid phosphatidylserine (PS) actively drives global immunosuppression in the tumor microenvironment and is a major contributor to tumor resistance to immune checkpoint blockade. We have shown that PS
Imaging metabolic heterogeneity in cancer
Authors: Debanti Sengupta, Guillem Pratx
Journal: Molecular Cancer (2016)

As our knowledge of cancer metabolism has increased, it has become apparent that cancer metabolic processes are extremely heterogeneous. The reasons behind this heterogeneity include genetic diversity, the existence of multiple and redundant metabolic pathways, altered microenvironmental conditions, and so on. As a result, methods in the clinic and beyond have been developed in order to image and study tumor metabolism in the in vivo and in vitro regimes. Both regimes provide unique advantages and challenges, and may be used to provide a picture of tumor metabolic heterogeneity that is spatially and temporally comprehensive. Taken together, these methods may hold the key to appropriate cancer diagnoses and treatments in the future.
Genetic counseling for pancreatic cancer in a high-risk clinic setting
Authors: M. Hall, O. Olopade
Journal: Journal of Clinical Oncology (2004)

9640 Background: Syndromes predisposing to pancreatic cancer (PC) include hereditary pancreatitis, familial multiple mole melanoma, hereditary breast/ovarian cancer (HBOC), HNPCC, FAP, and Li-Fraumemi syndrome. In view of BRCA2's identification as a major PC susceptibility gene, we performed pedigree analysis on persons presenting to our Cancer (CA) Risk Clinic reporting a relative with PC. Our goal was to examine PC occurrence in a high-risk clinic and to identify families (fams) who may benefit from screening and/or genetic testing to quantify risk. Methods: We identified all PC in 1300 fams over 10 years. PC pedigrees were analyzed for all CA, mutation status, relation to incident PC, age at PC diagnosis, and grouped by CA syndrome criteria. Results: Among 1300 fams, we found 110 PC in 77 kindreds. While 7 probands presented for family history of PC, 29 met familial PC criteria (≥2 1stdeg PC; PC<50), and 6 had ≥3 1stdeg PC. Majority PC (61%) were in fams meeting HBOC criteria, 22 with genetic testing complete (8 BRCA1+, 5 BRCA2+, 9 neg). 4 fams met Amsterdam criteria, one with MSH2+; one FAP fam was APC+. Mean diagnosis age was similar among syndromes (61.2 y HBOC, 61.2 y HNPCC, 61.4 y sporadic). Mean diagnosis age of non-syndrome fams with ≥2 1stdeg PC (57.4 y) was less than syndrome fams (66.7 y, p=0.025). 23 HBOC fams had mean age onset breast CA < 50 y (2.6 cases/fam, u=42 y), and 15/22 early (≤60 y) PC occurred in the same fams (u=48.6 y, p=0.013 Chi2). Of ovarian CA, 12/18 were multiple/< 50 y, 8 in fams with early PC (p=0.110). Conclusions: The population presenting by self/physician referral to a CA risk clinic is heterogeneous. Incident PC are often found in close proband relatives. With improved benefits of multi-modality screening/early diagnosis, efforts should be directed to identify persons at risk for PC. PC's association with HBOC and recent BRCA2 data show a proportion of persons in HBOC kindreds are at risk for PC and vice versa–persons in PC fams are at risk for breast/ovarian CA, underscoring a need to develop testing/screening protocals as part of a comprehensive PC risk assessment so at-risk fams may be advised to consider surveillance/genetic testing to avoid the bleak outcomes of PC and ovarian CA. No significant financial relationships to disclose.
Does hormone receptor (HR) positivity affect the prognosis in breast cancers with human epidermal growth factor receptor 2 (HER2) overexpression?
Authors: Y. Lee, J. Sohn, B. Park, H. Chung, C. Suh, S. Kim, J. Koo, J. Kim, H. Choi, Y. Kim
Journal: Journal of Clinical Oncology (2009)

e22091 Background: Biologically, there is an unclear issue about the role of HR positivity in HER2 positive breast cancer. These HER2(+)/ HR(+) pts were grouped into luminal B type apart from HER2(+)/ HR(-) pts in molecular profiling. However, from the clinical point of view, these pts have been categorized and been treated as either the only HER2(+) disease regardless of HR status or vice versa. Thus, we investigated the impact of HR status on clinical outcomes in HER2-overexpressed breast cancers. Methods: We retrospectively reviewed medical charts of HER2-positive breast cancer pts who underwent curative surgical resection from 1996 to 2001 in the Severance hospital, Korea. Demographic comparisons were performed by Chi-square tests. Tumor size, nodal stage, TNM stage, HR status, and adjuvant tamoxifen use were included in the Cox proportional hazards model. Results: Among the total 174 HER2-positive pts, HR (n=93) was positive in 53.5% (n = 93) and HR-positive tumors were more likely to be premenopausal (73% v 52%; P=0.01) and well- differentiated (grade 1or 2; 77% v 62%; P=0.04). There were no significant differences according to HR status in terms of tumor size, nodal stage, TNM stage, operation methods, and chemotherapy regimen. In these HER2-positive pts, the 5-year disease free survival (DFS) was longer in HR(+) pts than in HR(-) pts (DFS; 82.9% v 61.5%; P= 0.01). In a subset analysis, the 5-year DFS of HER2(+)/ER(+) pts without adjuvant tamoxifen (n=26) was not different from that of HER2(+)/ ER(-) pts (DFS; 57.7% v 61.5%; P= 0.32). However, the 5-year DFS of HER2(+)/ ER(+) pts with adjuvant tamoxifen was significantly prolonged compared with that of HER2(+)/ ER(-) pts (DFS; 91.5% v 61.5%; P&lt; 0.001). In a multivariate analysis of DFS, tumor size and adjuvant tamoxifen use significantly affected DFS with an adjusted hazard ratio of 2.56 (95% CI, 1.2–4.9; P= 0.01) and 6.58 (95% CI, 2.8–20.3; P&lt; 0.001), respectively. Conclusions: In an analysis of HER2-overexpressed breast cancer, the presence of HR itself did not affect the prognosis. However, most of the survival benefit seems to be driven from adjuvant tamoxifen therapy not the HR status itself. No significant financial relationships to disclose.
Weight gain in breast cancer patients: Tamoxifen versus anastrazole
Authors: P. McGowan, M. C. Perry, J. E. Hewett, B. Ge, K. Sanfilippo
Journal: Journal of Clinical Oncology (2006)

10544 Background: Weight gain is a common complaint among breast cancer patients, especially those taking tamoxifen. Aromatase inhibitors have been increasingly used in postmenopausal breast cancer patients, and are generally thought to have a more tolerable side-effect profile than selective estrogen receptor modulators (SERM’s). This study specifically addresses weight gain in patients on the SERM, tamoxifen, compared to patients on the aromatase inhibitor, anastrazole. Methods: Ninety-six outpatients with primary breast cancer of any stage received standard doses of adjuvant hormonal therapy. Seventy received tamoxifen (Group T) and 26 anastrazole (Group A). The nursing staff in the clinic weighed all patients at the time of diagnosis, at start of chemotherapy (if received), at start of hormone therapy, and at 3 month intervals for 12 months after starting hormone therapy. Data were gathered in a retrospective manner. Results: Demographic variables were compared between the two groups. In all patients, it was noted that increasing age was correlated with greater weight gain at 3 months after starting hormone therapy (p = 0.0257), but not at any other intervals. No other variables were significantly correlated with weight gain. In Group T, mean weight gain was clinically (&gt;1.8 kgs) and statistically significant at 9 and 12 months (p = 0.0137, p = 0.0003). In Group A, mean weight gain was not clinically significant at any point. Using the Wilcoxon two-sample tests to compare groups T and A, it was shown that there was no statistically significant difference in weight gain between the two groups at any interval (see table). Conclusions: These results are consistent with previous studies that show significant weight gain in breast cancer patients on tamoxifen. This study failed to show a statistically significant difference in weight gain between patients on tamoxifen and patients on anastrazole. Group A did not have statistically significant weight gain at any interval after starting hormone therapy. [Table: see text] No significant financial relationships to disclose.
Predicting survival and metastasis in soft tissue sarcoma: A gene microarray study using RNA derived from archival paraffin-embedded tumours
Authors: K. M. Linton, Y. Hey, M. Jeziorska, C. L. Wilson, C. Miller, E. Saunders, S. Pepper, A. Freemont, J. A. Radford
Journal: Journal of Clinical Oncology (2006)

10074 Background: The genetic determinants of survival and metastasis in soft tissue sarcoma (STS) are poorly understood and progress in this field has been limited by the rare nature of STS and the need for fresh/frozen tissue (FT) for gene microarray analyses. Our objective was to determine whether valid gene microarray data can be obtained from archival formalin-fixed paraffin-embedded tumours (FFPET) in order to retrospectively identify prognostic STS gene signatures and potential molecular targets from patients with known clinical outcome data. Methods: Total RNA was extracted from macrodissected viable tumour tissue for 34 FFPET (14 liposarcomas, 11 leiomyosarcomas and 9 synovial sarcomas) and two paired FFPET and FT primary leiomyosarcomas (modified Optimum kit, Ambion, for FFPET RNA extraction and Trizol, Invitrogen, for FT RNA extraction). One-cycle labelled cRNA was hybridised to Affymetrix U133 Plus 2 microarrays, and strict QC protocols used to identify 19 arrays for further analysis using R and BioConductor. Log rank regression and Kaplan-Meier plots of disease-specific survival were performed to identify genes predictive of survival and/or metastasis. Results: Similar fold changes in gene expression were obtained for paired cRNA samples, although the number of genes called present was lower for cRNA from FFPET. Five hundred genes (selected from FFPET cRNA arrays) were discriminatory for survival (p=0.0006 to 0.0088) across all STS subtypes and correctly assigned 17/19 cases by leave-one-out cross validation. Many are known tumour prognostic genes, significant for survival, metastasis, invasion, angiogenesis and apoptosis. Twenty-five novel and known candidate genes (with 3–10 fold differential expression) were selected for validation on 19 test and 60 independent cases by RT-PCR for relative gene expression and immunohistochemistry for protein detection. Conclusions: We have shown that prognostic information can be derived from archival FFPET, permitting the identification of candidate prognostic genes and therapeutic targets in STS, and opening the way for studies in other tumours where FT is unavailable. No significant financial relationships to disclose.
Late toxicities, long-term follow-up, less intensive treatment: leading issues in the therapy of testis cancer.
Authors: P W Kantoff, M B Garnick
Journal: Journal of Clinical Oncology (1988)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1988.6.8.1216 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2842462 Late toxicities, long-term follow-up, less intensive treatment: leading issues in the therapy of testis cancer. P W KantoffxP W KantoffSearch for articles by this author , M B GarnickxM B GarnickSearch for articles by this author Show More Dana-Farber Cancer Institute, Harvard Medical School, Boston. https://doi.org/10.1200/JCO.1988.6.8.1216 First Page PDF © 1988 by American Society of Clinical Oncology
Use of endothelin-A-receptor expression to predict poor response to primary chemotherapy in locally advanced breast cancer
Authors: P. Wulfing, J. Tio, C. Kersting, B. Sonntag, H. Buerger, C. Wulfing, U. Euler, W. Boecker, A. H. Tulusan, L. Kiesel
Journal: Journal of Clinical Oncology (2004)

576 Background: Endothelin-1 (ET-1) and its receptors (ETAR and ETBR), referred to as the ET-axis, are overexpressed in breast carcinomas and seem to influence tumorigenesis and tumor-progression. Failure of breast carcinomas to respond to treatment is still a major impediment to successful cytotoxic therapy and to date no tumor biological factor is available for clinical use predicting chemotherapy response in breast cancer. The aim of our study was to determine the predictive value of ET-axis protein expression in breast carcinomas for chemotherapy response. Methods: 44 patients with locally advanced breast cancer who took part in a prospective phase III study evaluating a high-dose primary chemotherapy of epirubicin and cyclophosphamide were included. Expression of ET-1, ETAR and ETBR was determined by semiquantitative immunohistochemical (IH) analysis of paraffin-embedded breast cancer tissue from the prechemotherapy tru-cut biopsies. Results: IH staining was positive for ET-1 in 61.5%, for ETAR in 35% and for ETBR in 35.9% of breast carcinomas. The overall clinical response rate was 58.1%, the overall pathological response rate was 72.7%. Pathological response to primary chemotherapy was significantly decreased in ETAR-positive patients (p=0.002). Pathological "no change" was obtained in 50% of ETAR-positive as compared to 7.7% of ETAR-negative patients. Logistic regression confirmed ETAR as an independent predictive marker for pathological response (p=0.009). Also, ETBR expression correlated with pathological non-response (42.9%), although statistical significance was not reached (p=0.065). Clinical response to chemotherapy was reduced in ETAR-positive patients as compared to ETAR-negative patients (46.2% vs. 73.1%, respectively; p=0.098). Conclusions: Our findings suggest that expression of ET receptors and especially of ETAR in breast cancer is associated with chemotherapy resistance. Thus, determination of ETAR status may serve as a predictive marker for identifying patients with a poor chance of response to chemotherapy and, therefore, potential candidates for more individualized treatments. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories
Phase I study of ON-01910.Na, a novel cell cycle inhibitor in adult patients with solid tumors
Authors: R. C. Donehower, A. Jimeno, J. Li PhD, K. Galvin, F. Anthony, R. Reddy, P. Reddy, W. Messersmith, D. Laheru, S. D. Baker
Journal: Journal of Clinical Oncology (2006)

13026 Background: ON-1910.Na is a new chemical entity, novel cell cycle inhibitor which arrests cells in G 2 /M, affects phosphorylation of several regulatory kinases and lacks cross resistance to other standard chemotherapy agents. This is a first-in-man Phase I dose escalation study to determine the dose limiting toxicities, recommended Phase II dose, and pharmacokinetic (PK) profile, and to document any antitumor activity of ON-01910.Na. Methods: Patients had histologically confirmed solid tumors refractory to standard therapy. ON-1910.Na, formulated as a solution in PEG400, was administered as a 2-hour infusion on days 1, 4, 8, 11, 15, and 18 followed by a 10 day observation period for a total of 28 days per cycle. The initial dose was 80 mg and was escalated using an accelerated titration schedule; one patient was treated per cohort until grade 2 toxicity was documented. A dose confirmation cohort of up to 12 patients will be treated at the maximun tolerated dose (MTD). A comprehensive PK study was performed on days 1 and 15 of the first cycle, plus trough samples were collected. Results: Thirteen patients (7F, 6M; ages 46–73) have received 20 cycles. Dose levels of 80, 160, 320, 480, 800, 1280, 2080, and 3120 mg were evaluated in 8 patients, and a further dose of 4370 mg has been evaluated in 5 patients. Toxicities have been anemia (2 G1, 1 G2), leucopenia (1 G1, 1 G2), hyperglycemia (2 G1), elevated AST/ALT (1 G1, 1 G2), nausea (3 G1), diarrhea (3 G1), skeletal pain (5 G1, 1 G2), abdominal pain (2 G1), tumor pain (1 G2), and fatigue (3 G1, 1 G2), and have clustered at the latter 3 dose levels. PK analysis shows increasing ON-1910.Na exposure with increasing doses. ON-1910.Na has a low clearance (13 L/h), long half-life (20 h), distribution in excess of blood volume (58 L) and PK parameters are similar on days 1 and 15. Approximately 3-fold and 5-fold inter-subject variation in ON-1910.Na clearance was observed on days 1 and 15, respectively. No antitumor activity has been documented by standard criteria. Conclusions: Dose escalation is continuing. [Table: see text]