tbuckley/cabot-search huggingface dataset:
Diagnosis of bone metastasis in patients with lung cancer using urinary and serum collagen type I telopeptide (NTx).
Authors: H. Okada, M. Tamiya, S. Tokunaga, H. Daga, K. Taira, S. Kobayashi, A. Tanaka, N. Miyamoto, M. Hattori, M. Kobayashi, N. Okamoto, S. Sasada, H. Suzuki, N. Morishita, Y. Matsuura, T. Hirashima, K. Takeda
Journal: Journal of Clinical Oncology (2011)

e18044 Background: Many cancers metastasize to bone. Bone metastasis may cause an increase in bone resorption due to direct effects of the tumor itself or osteoclastic activation. This study evaluates the bone resorption biomarkers urinary NTx (uNTx) and serum NTx (sNTx) for the diagnosis of bone metastasis in patients with lung cancer. Methods: uNTx and sNTx were measured in 100 patients with lung cancer and 50 control patients with benign respiratory diseases using the uNTx:OSTEOMARKTM and sNTx:OSTEOMARKTM serum NTx assays (Inverness Medical Japan). Bone metastasis was characterized by scintigraphy. The extent of disease (EOD) was determined by the number of sites of bone metastasis. Area under the curve (AUC) for receiver operating characteristic (ROC) analysis was used to evaluate the detection of bone metastasis. Sensitivity and specificity of uNTx and sNTx to detect bone metastasis were calculated using cutpoints of 64 nM BCE/mM Cr for uNTx and 22 nM BCE/mM Cr for sNTx. All patients were required to provide written informed consent. Results: Patients with bone metastasis had significantly higher levels of both uNTx and sNTx (uNTx; 93.2 +/- 105.1 nM BCE/mM Cr., sNTx; 24.0 +/- 14.6 nM BCE/L) vs. lung cancers without bone metastasis (uNTx; 51.6 +/- 26.8 nM BCE/mM Cr., sNTx;17.2 +/- 4.1 nM BCE/L), or benign respiratory diseases (uNTx; 42.8 +/- 21.8 nM BCE/mM Cr., sNTx; 16.8 +/- 7.9 nM BCE/mM Cr.). There was good correlation between uNTx and sNTx (R = 0.807). ROC AUC for the detection of bone metastasis was 0.743 for uNTx and 0.712 for sNTx. The sensitivity and specificity for the diagnosis of bone metastasis using uNTx was 48.0% and 86.0%, and using sNTx was 40.0% and 87.0%, respectively. Levels of uNTx and sNTx were increased in patients classified as EOD grade 1 compared to controls and in patients classified as EOD grade 2 or greater, compared to patients classified as EOD grade 1. Conclusions: Both biomarkers may have value as an aid in the diagnosis of bone metastasis in patients with lung cancer.
Systematic reviews of resection of metastases in metastatic colorectal cancer.
Authors: M. Edwards, Z. Zhao, S. Chadda, B. Barber
Journal: Journal of Clinical Oncology (2011)

e16530 Background: The objective of these systematic reviews of literature was to assess initial resectability, resection rates after conversion therapy, and post-conversion therapy resection survival in patients with metastatic colorectal cancer (mCRC). Methods: Three separate systematic searches were performed, one for each of the review questions: rates of initial resectability; resection rates after conversion therapy for initially unresectable metastases (conversion therapy is treatments, mainly systemic therapies, which are used to achieve sufficient shrinkage of tumors to allow resection in patients who were previously considered unresectable); and survival following post-conversion therapy resection. Publications were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library, and through manual searches of the reference lists of relevant articles. The MEDLINE and EMBASE searches were limited to articles published in English, whereas the Cochrane library search had no language restrictions. Results: A total of 792 citations/abstracts were identified for data on initially resectable metastases; of these, 61 underwent full-paper review. Sixteen studies reported definitions of resectability and resection rates ranging from 4% to 55%. Of 789 citations/abstracts were identified for data on resection rates after conversion therapy for initially unresectable metastases, 74 clinical studies reported a wide variation in overall resection rates ranging from 1% to 75%, and in complete resection (R0) rates ranging from 0% to 39%. Of 1,589 citations/abstracts were identified for data on post-conversion therapy resection survival data, 29 studies reported median overall survival ranging from 20 to 63 months and median progression-free survival ranging from 13 to 20 months. Conclusions: The findings from these systematic literature reviews suggest that the interpretation and comparison of resection data from different studies should be made cautiously due to differences in definitions of resectability, study designs, patient populations, year when study was conducted, and country/centre where patients were treated across different studies.
Twenty-year results of alternating radiotherapy and chemotherapy in nonmetastatic inflammatory breast cancer.
Authors: E. Lima Pessoa, A. Dunant, S. Heymann, S. Delaloge, M. Spielmann, C. Uzan, M. Mathieu, R. Arriagada, H. Marsiglia, C. Bourgier
Journal: Journal of Clinical Oncology (2010)

638 Background: IBC is the most aggressive form of locally advanced breast cancer with a poor clinical outcome. The locoregional treatment is crucial because local relapses are commonly associated with distant metastases. At IGR, we conducted a monocentric clinical trial combining primary chemotherapy (CT) with an alternating split course scheme of CT and radiotherapy (RT*CT) (Thomas F. et al. Cancer 1995 ; 76 : 2286-90) to improve local relapse-free survival (LRFS), metastases-free survival (MFS) and overall survival (OS). We present here the long-term results (median follow-up of 20 years). Methods: From September 1983 to December 1989, 124 women with IBC (T4dM0) were treated as follows (Thomas F. et al. Cancer 1995 ; 76 : 2286-90.): 3 primary cycles of A (doxorubicin) V (vincristine)-CMF and then alternating RT*CT scheme RT1*FEC*RT2*FEC*RT3 (RT1-2 = 25 Gy/ 10 fractions/17 days to the breast and ipsilateral lymph nodes; RT3 = 15-25 Gy, 2.5 Gy/fraction to tumor bed) followed by 3 cycles of FEC. The IBC was considered locally controlled if a complete or a partial response (> 50%) was achieved, assessed by clinical examination and mammography at treatment completion. Hormonal treatment was systematically given: ovarian irradiation (12 Gy/4fractions) or tamoxifen 20 mg/d. Results: Mean age: 51.9 years (30-69). Histological characteristics: breast adenocarcinoma.Positive axillary nodes (79%); histologic grade 1/2/3 unknown (7%; 36%; 33% and 21%). Local control was achieved in 82% of patients. The 5-, 10- and 20-year LRFS rates were 48%; 29% and 18%, respectively. The 5-, 10- and 20-year MFS rates were 45%, 30% and 20%, respectively. The 5-, 10- and 20-year OS rates were 50%, 39% and 19%, respectively. Grade 1 and 2 cardiac toxicity was observed in 3% and 2%, respectively. Conclusions: This regimen allowed a good long-term local control despite the absence of surgery. Long-term MPFS and OS rates were similar to those described in the literature after primary chemotherapy, total mastectomy and adjuvant radiotherapy. Since IBC remains an entity with dismal prognosis, this approach safely combining radiation therapy and systemic treatments should be re-assessed at the time of the availability of many suitable targeted agents. No significant financial relationships to disclose.
Supportive Oncology Collaborative: Initial impact of supportive oncology screening and care.
Authors: Shelly S. Lo, Lauren Allison Wiebe, Catherine Deamant, Amy Scheu, Betty Roggenkamp, Urjeet Patel, Pam Khosla, Patricia A. Robinson, Frank J. Penedo, James Gerhart, William Dale, Oana Cristina Danciu, Rosa Berardi, Christine B. Weldon, Julia Rachel Trosman
Journal: Journal of Clinical Oncology (2016)

180 Background: The Institute of Medicine (IOM) 2013 report recommends supportive oncology care from diagnosis through survivorship, to end of life. The Coleman Supportive Oncology Collaborative (CSOC) developed a city-wide plan to improve supportive oncology. Metrics derived from the Commission on Cancer (CoC), ASCO Quality Oncology Practice Initiative (ASCO-QOPI) and National Quality Forum (NQF) were used to assess the CSOC impact. Methods: Medical records of consecutive cancer patients from 6 practice improvement cancer centers in Chicago (3 academic, 2 safety-net, 1 public) were reviewed for 2 periods: 2014 (n = 843) and Q1 of 2015 (n = 313). Descriptive statistics assessed differences in quality metrics. Results: Significant improvement was achieved in 6 of 8 core supportive oncology metrics (see table). Conclusions: Consolidated metrics are feasible to assess supportive oncology quality. Early data indicate improvement and effectiveness of the collaborative approach. [Table: see text]
Disease-free survival of women 70 years or older with stage I-II BC treated with BCS and RT.
Authors: Mounika Gopi, Steven Jeffrey Hager, Beth Kimball, Jedidiah Mercer Monson
Journal: Journal of Clinical Oncology (2016)

e268 Background: Breast RT is the standard of care for women undergoing BCS. Recent trends suggest omitting RT for women &gt; 70 years of age. Our retrospective study evaluated the DFS and failure pattern of women &gt; 70 treated with BCS and RT compared with their younger cohorts. Methods: Between 2009-2011, 101 women with Stage I-II BC were treated with BCS and RT at a physician-owned, community-based cancer center. Clinical, pathologic and treatment characteristics were extracted from patients’ medical records. Results: Of the 101 patients, 71 comprised the &lt; 70 cohort and 30 comprised the &gt; 70 cohort. Patients in the older cohort were more likely to have Stage I tumors (80% vs 64%), but the cohorts were otherwise balanced in terms of T-size, grade, ER/PR and Her2 status. RT was typically delivered in a first course of 50.4 Gy to the whole breast followed by a 10 Gy boost. Median DFS for the older cohort was 36 months (range, 1-66) and 41 months for the younger cohort (range, 1-74). There was only one event in the older cohort, a patient who developed DM at 40 months. In the younger cohort one patient developed LR at 54 months, and 4 developed DM at 18, 33, 51 and 54 months. Conclusions: In our community-based study, women &gt; 70 who received BCS and RT experienced excellent DFS and local control. The three-year median DFS observed in the older women in our study suggests that a long-term view should be taken when treating older patients and that biological age rather than chronological age is a better determinant of when cancer therapies should be withheld.
Patient and physician factors associated with overuse and underuse of cancer screening: A factorial, cluster-randomized trial.
Authors: James Austin Talcott, Kelly A Cassano, Roy Cohen, Jessica Herzstein, Floyd Jackson Fowler, Aparna Balakrishnan, Michael P. Osborne
Journal: Journal of Clinical Oncology (2014)

206 Background: Cancer screening, like other interventions, requires close patient-provider collaboration. By patient recall, key elements are often omitted from informed consent discussions. Most screening guideline compliance efforts focus on reducing underuse, but overuse is also harmful and may be influenced by distinct factors. Therefore, we are performing a prospective randomized trial of educational interventions to improve screening compliance for breast, cervical, colorectal, lung and prostate cancer at an urban academic medical center. Our hypothesis is that gender, age, prior screening experience, provider recommendations, anticipated benefit and distress, communication and informational support will affect compliance. Our primary data collection will be complete before the Symposium. Methods: We will enroll an age- and sex-stratified sample of 216 patients aged 40 to 89 years, 18 each treated by 12 primary care physicians at two affiliated hospitals, undergoing an annual physical examination in a cluster-randomized prospective trial of educational supports for screening. Screening guideline format (color-coding) and academic detailing will be randomly assigned independently. Patients and providers are surveyed immediately after the encounter to record their recollections of screening discussions and recommendations and their plans. Follow-up surveys at 3, 6 and 12 months assess concordance between expressed screening intentions and behaviors. Results: Pilot results indicate patient gender, age, anticipated screening-related distress and benefit, and prior screening experience affect screening recommendations and intentions. These factors vary by cancer. Patients recall less discussion than providers. Reasons not to screen are infrequently discussed. Conclusions: Cancer screening decisions are complex and vary by screening modality, patient and provider factors and communication. Improving underuse and overuse compliance may require distinct strategies. Screening overuse may be a “lower-stakes” environment to develop strategies to reduce overuse of cancer interventions of marginal or negative benefit, including treatment.
Polymorphisms in Exons 2 and 7 of the Human Organic Cation Transporter (hOCT1) (Solute Carrier Family 22, SLC22A1): Correlation with Imatinib Levels and Clinical Course in Chronic Myeloid Leukemia Patients,
Authors: Jacob Vine, Sara Bar Cohen, Rosa Ruchlemer, Neta Goldschmidt, Moshe Levin, Diana Libster, Alexander Gural, Moshe E. Gatt, David Lavie, Dina Ben-Yehuda, Deborah Rund
Journal: Blood (2011)
Neuroendocrine tumors (NET) of the gastrointestinal tract: Patterns of management and experience at Winship Cancer Institute of Emory University.
Authors: Syed Farhan Zafar, Dattatraya Hari Patil, John S. Kauh, Volkan Adsay, Edith Brutcher, Shishir K. Maithel, Zhibo Wang, Zhengjia Chen, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2013)

326 Background: NET are a group of diverse malignancies observed commonly in the gastrointestinal tract. Pancreatic neuroendocrine tumors (PanNET) have been reported to have worse outcomes as compared to neuroendocrine tumors of the gastrointestinal tract (GNET). Our objective was to compare the clinical characteristics, patterns of treatment and survival in PanNET and GNET. Methods: After IRB approval, we identified 379 patients (pts) from 1996-2011 in the Winship registry. A chart review was done. Patients were categorized in mutually exclusive groups of PanNET and GNET. Results: Demographic information and basic characteristics are listed in the table. Treatment modalities for PanNET included surgery (91%), chemotherapy (14%), biologics (sunitinib or everolimus)(6%) and somatostatin analogues (11%). Liver directed therapies were employed in 30 pts with PanNET. Most common modality was radiofrequency ablation (23 pts) followed by Yttrium-90 embolization (5 pts) and chemoembolization (2 pt).Treatment for GNET included surgery (78%), chemotherapy (11%) and somatostatin analogues (17%). Median survival for GNET (all stage) was 11.6 years and PanNET (all stage) was 10.5 years (p=0.063). Using multivariate analysis, only age at diagnosis (p&lt;0.001 for age cohort of &lt;55 yrs) and clinical stage (p=0.002, for local disease) were found to be significant factors. Conclusions: Pts with NET have good prognosis. In our series, both PanNET and GNET, had comparable survival outcomes even in advanced stage. [Table: see text]
Simultaneous protection against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR-signaling blockade by oncogenic RAS.
Authors: M. H. Schuler, F. Breitenbuecher, T. Trarbach, S. Brandau, K. W. Schmid, S. Kasper
Journal: Journal of Clinical Oncology (2011)

440 Background: Monoclonal antibodies against the epidermal growth factor receptor (EGFR) have improved treatment options for colorectal cancer (CRC), but tumors harboring RAS mutations are resistant. Full molecular understanding of RAS-mediated protection is key to the development of sensitization strategies. Methods: We have used cell culture and murine CRC transplant models to study whether RAS solely imposes resistance by compensating EGFR signaling blockade, or additionally interferes with antibody-dependent cellular cytotoxicity (ADCC). Results: Both clinically approved anti-EGFR antibodies, cetuximab and panitumumab, were equally cytotoxic in CRC cells in vitro. Interestingly, cetuximab, a chimeric IgG 1 antibody capable of triggering ADCC, was more effective than panitumumab (human IgG 2 ) in murine CRC transplant models in vivo. The advantage of cetuximab in vivo was completely abolished by leukocyte depletion following total body irradiation. Moreover, oncogenic RAS neutralized the in vivo therapeutic activity of cetuximab and panitumumab to the same extent. Mechanistically, RAS conferred antibody resistance by upregulation of BCL-XL, which was overcome by cotreatment with a BH3 mimetic. In support, RAS-mutant primary human CRCs exhibited increased BCL-XL expression as detected by immunohistochemistry. Conclusions: RAS-mutant CRCs escape anti-EGFR antibody-mediated receptor blockade as well as ADCC in vivo. Pharmacologic modulation of RAS downstream effectors, such as BCL-XL, can restore sensitivity to antibody effector mechanisms. [Table: see text]
Significance of incidentally detected oval, circumscribed enhancing lesions on preoperative breast MRI.
Authors: Jong Yoon Lee, Mi Jung Jang, Sun Mi Kim, Bo La Yun, Ja Yoon Jang
Journal: Journal of Clinical Oncology (2015)

12 Background: To evaluate the characteristics and malignancy rate of oval, circumscribed enhancing lesions seen on preoperative breast MRI in patients with breast cancer. Methods: From January 2010 through May 2013, a total number of 502 oval, circumscribed mass was incidentally found in 326 patients with breast cancer who had undergone preoperative breast MRI. Seventy-eight lesions were excluded due to the lack of follow-up imaging or total mastectomy. Biopsy was performed when suspicious enhancing kinetics or interval change were detected on MRI. Otherwise, MRI or ultrasound follow up for correlated lesion were performed at least 2 years. Clinical and imaging features were recorded for analysis. Results: Of the 424 oval, circumscribed enhancing lesions detected on MRI, twelve (2.8%) were malignant and 412 (97.2%) were benign. There was no significant difference in size between malignant (0.72±0.26 cm) and benign (0.71±0.34 cm) lesions (p = 0.932). Among 424 lesions, 43 lesions (10.1%) were pathologically confirmed and twelve were malignant. Positive predictive value (PPV) of malignancy for the biopsy was 27.9%. Among 12 malignant lesions, 7 (58.3%) were invasive ductal carcinoma, 4 (33.3%) were ductal carcinoma in situ, and 1 (8.3%) was tubular carcinoma. Of the pathologically confirmed benign lesions, 8 (25.8%) were fibroadenoma, 7 (22.6%) were intraductal papilloma. Interestingly, there were significantly frequent MRI features with early fast enhancement and delayed washout pattern in malignant (11/12) compared to benign (29/412) lesions (p &lt; 0.001). PPV of malignancy for early fast enhancement and delayed washout pattern in MRI was 27.5%. Conclusions: Cancer yield in patients with oval, circumscribed enhancing lesion on preoperative breast MRI was 12 (2.8%) of 424. MRI features with early fast enhancement and delayed washout pattern strongly suggested malignancy.
Mechanisms of apoptosis induction by flavokawain B in a uterine leiomyosarcoma cell line.
Authors: R. Eskander, T. Sakai, Y. Guo, X. Zi, B. H. Hoang, L. M. Randall-Whitis
Journal: Journal of Clinical Oncology (2011)

e13021 Background: Leiomyosarcomas are aggressive tumors associated with a poor prognosis. Recurrence rates range from 53-71% even when early diagnosis is made. Furthermore, adjuvant chemotherapy with Doxorubicin or Docetaxel/Gemcitabine has shown response rates of 27-36%. Thus, there is a strong need for novel agents in the treatment of leiomyosarcoma. Methods: SK-LMS1 and ECC-1 cell lines were cultured in RPMI 1640 and MEM Alpha medium with 10% FBS (fetal bovine serum). Pure Flavokawain B (FKB) was obtained from LKT laboratories (St. Paul, MN). Cell lines were grown to confluence and treated with 8.8, 4.4, 2.2, and 1.1 µM of FKB. The IC50 was determined for each cell line using XTT assay. Fluorescence-activated cell sorting (FACS) analysis of apoptosis and cell cycle analysis were performed for FKB treated cell lines. Lastly, real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot analysis were performed to evaluate differences in the expression of apoptotic markers in treated and non-treated cell lines. Statistical analysis was performed using student’s t test. Results: Both SK-LMS-1 and ECC-1 were sensitive to FKB treatment, while control endometrial fibroblasts were resistant. FKB treatment resulted in an increase in both early and late apoptosis in SK-LMS1 and ECC-1 cell lines relative to control (35.4 ± 3.1%; 29.1 ± 1.3%; p<0.01). Cell cycle assays illustrated an increase in the G2-M fraction in treated SK-LMS1 and ECC-1 cell lines relative to control (34.3 ± 4.9%; 22.1 ± 3.5%; p<0.01). RT-PCR showed a dose dependent up-regulation of death-receptor 5 (DR5), Bim and Bax, and down regulation of Bcl-xL and survivin consistent with the pro-apoptotic effects of FKB, confirmed by western blot. Conclusions: FKB appears to induce apoptosis in SK-LMS-1 and ECC-1 cell lines via increased expression of DR5, Bim and Bax, leading to activation of the death receptor pathway, and down regulation of Bcl-xL and survivin. FKB may be a novel, naturally occurring compound effective in the treatment of uterine leiomyosarcoma.
G17DT+gemcitabine [Gem] versus placebo+Gem in untreated subjects with locally advanced, recurrent, or metastatic adenocarcinoma of the pancreas: Results of a randomized, double-blind, multinational, multicenter study
Authors: J. Shapiro, J. Marshall, P. Karasek, A. Figer, H. Oettle, F. Couture, K. Jeziorski, P. Broome, R. Hawkins
Journal: Journal of Clinical Oncology (2005)

LBA4012 Background: G17DT is a novel immunotherapeutic targeted at the gastrin-17 tumor growth factor. It was shown to be effective as monotherapy in advanced pancreatic cancer [APC] (Gilliam et al, ASCO 2004 Abstract 2511) and has also shown encouraging efficacy in Phase 2 trials in combination with chemotherapy in gastric (Michaeli et al, ASCO 2004 Abstract 4048) and colorectal cancer (Rocha Lima et al, ASCO 2004 Abstract 3573). In this study, the combination of G17DT+Gem was investigated in patients with APC. Methods: This was a randomized, double-blind study in subjects with intact organ function, KPS≥70, and evaluable or measurable disease. Subjects were randomized 1:1 to G17DT+Gem or identical matching placebo+Gem in two strata (disease stage II+III vs IV). G17DT/placebo was administered im at wk 0, 4, 8 and 24; Gem (1 g/m2 according to the package insert) was administered to subjects in both arms. 180 deaths per arm would provide 80% power to detect a hazard ratio of 0.744 with α = 0.048. Results: 394 subjects were randomized, with 369 deaths included in this analysis. Data analysis is taking place in January - February 2005. Results of the analyses of the primary endpoint, survival, and of secondary endpoints (tumor response, time to disease progression, and relationship between anti-G17 antibody responder status and efficacy endpoints), as well as of safety analyses, will be presented. Conclusions: TBD Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aphton Aphton Aphton