tbuckley/cabot-search huggingface dataset:
Frequency and timing of thoracic tumor spread in 198 consecutive patients with advanced-stage high-grade serous ovarian cancer (HGSC).
Authors: Atul B. Shinagare, Ailbhe C O'Neill, Bhanusupriya Somarouthu, Sree Harsha Tirumani, Mizuki Nishino, Annick D. Van Den Abbeele, Nikhil H. Ramaiya
Journal: Journal of Clinical Oncology (2014)

5575 Background: HGSC is the most common type of ovarian cancer. While routinely used, the necessity of chest CT in these patients is unknown. We hypothesize that thoracic metastases in HGSC occur late, after development of abdominal disease. We aimed to describe the frequency and timing of occurrence of thoracic disease in advanced (stage III and IV) HGSC in relation to the abdominal disease. Methods: In this IRB-approved, HIPAA-compliant retrospective study, we included 198 consecutive patients with pathologically proven advanced HGSC seen from January 2012 through December 2012 (mean age 60 years, SD±9.5 years; median follow-up 40 months, IQR 25-63). Time to development of abdominal and thoracic disease and survival thereafter was recorded by review of thoracic and abdominal imaging and electronic medical records, and compared using Mann-Whitney test. Predictors of occurrence and time to development of thoracic disease were identified using multivariate analysis. Results: Abdominal disease developed in 177 patients (89%) and thoracic disease in 69 (35%). The first site of thoracic disease was visible on the abdominal CT in 51 (74%) patients (pleural effusion, n=27; epiphrenic and/or retrocrural lymph nodes, n=24), and of the remaining 18 (26%) patients with high thoracic disease (mediastinal, supraclavicular or axillary nodes, n=9; lung nodules, n=9) all except one had preexisting abdominal disease. Median time to development of thoracic disease was longer than abdominal disease (24 months, IQR 13-43 vs 13 months, IQR 7-25; p<0.0001) and survival after thoracic disease was shorter than after development of abdominal disease (13 months, IQR 6-28 vs 26 months, IQR 12-45; p=0.0002). Presence of abdominal disease was the only predictor of development of thoracic disease (p=0.0009; OR 12.08, 95%CI 2.36-221.20); time to abdominal disease predicted time to thoracic disease (p=0.003). Conclusions: Thoracic disease develops late in the course of advanced HGSC and occurs in patients with preexisting abdominal disease. Presence of abdominal disease is the only predictor of thoracic metastases. Therefore, potential exists for limiting the use of chest CT in patients with advanced HGSC.
ACOSOG Z1041 (Alliance): Cardiac events (CE) among those receiving neoadjuvant anthracyclines (A) and taxanes with trastuzumab (T) for HER2+ breast cancer.
Authors: Michael Ewer, Vera J. Suman, Aman Buzdar, Linda Mackie McCall, Funda Meric-Bernstam, A. Marilyn Leitch, Matthew James Ellis, Judy Caroline Boughey, Gary Walter Unzeitig, Melanie Royce, Kelly Hunt
Journal: Journal of Clinical Oncology (2013)

526 Background: Z1041 randomized women with HER2+ operable breast cancer to: FEC → P+T (Arm 1) or P+T → FEC+T (Arm 2). Treatment administered as 5-FU 500 mg/m 2 , epirubicin 75 mg/m 2 and cyclophosphamide 500 mg/m 2 day 1 of a 21-day cycle x 4; paclitaxel 80 mg/m 2 weekly x 12 and T 4 mg/kg once then 2 mg/kg weekly x 11. T was to continue q3 weeks post-op for 40 weeks. A secondary aim was to examine the cardiotoxicity (CE). Methods: Ejection fraction (EF) was measured at baseline (BL), between regimens (wk 12), prior to surgery (wk 24) and PRN. Eligibility: BL EF ≥ 55%. CEs included decline in EF of &gt; 15%, or &gt;10% points to a value &lt; LLN. Reversibility was adjudicated by blinded investigators as reversible (R: recovery of EF to ≤ 5% below BL), partially reversible (PR: recovery of &gt; 10% points from nadir, but ≤ 5% points below BL), indeterminate (IN: no additional EF data), or irreversible (IRR:follow-up EF studies showed no improvement). Results: Of the 280 patients (Arm 1: 138) who began treatment, 15 pts (Arm 1: 10; Arm 2: 5) did not receive T. The number of weeks of T was 13 (range: 1-18) in Arm 1 and 24 (range: 1-31) in Arm 2. Changes in EF and severe treatment related cardiac toxicities prior to surgery (sx) are tabled below. There were 271 pts (Arm 1: 131) who had post-BL EFs. Prior to sx, there were 11 CE (8.3%) in Arm 1 and 13 CE (9.2%) in Arm 2. CEs were R in 12 pts (Arm 1: 5; Arm 2: 7); PR in 6 pts (Arm 1: 4; Arm 2: 2); IN in 4 pts (Arm 1: 2; Arm 2: 3) and IRR in 1 Arm 2 pt. Conclusions: The number of CE events in arms 1 and 2 showed no significant difference; greater scatter was observed in arm 2 patients. While concern for late cardiac events makes ongoing cardiac surveillance prudent due to A, concomitant use of A and T appear to not be associated with increased cardiac risk. Clinical trial information: NCT00513292. [Table: see text]
Outpatient massage impact on symptom distress in cancer patients and caregivers.
Authors: Gabriel Lopez, Richard T. Lee, Curtiss M Beinhorn, Sat-Siri Sumler, Alejandro Chaoul, M. Kay Garcia, Kathrin Milbury, Amica D Onyemeh Sea, Amy Spelman, Qi Wei, Lorenzo Cohen
Journal: Journal of Clinical Oncology (2014)

e20651 Background: Massage as a manual therapy has shown benefit for symptomatic relief in cancer patients and their caregivers. We explored the impact of a single massage session on self-reported symptoms in an outpatient setting at a large academic cancer center. Methods: Data were reviewed from massage sessions (30 or 60 minute duration) at our Integrative Medicine Center outpatient clinic from May, 2011 through December, 2013. Participants completed a pre- and post-massage symptom assessment instrument, the Edmonton Symptom Assessment Scale (ESAS; 10 symptoms, scale from 0-10, where 10 is most severe). Global symptom distress (GSD; range 0-100) was calculated as the sum of individual symptom scores. ESAS subscales analyzed included Physical Distress (PHS; range 0-70) and Psychological Distress (PSS; range 0-30). Data were analyzed examining the pre and post scores using paired t-tests. Results: Our analysis included data collected from 1478 massage visits for 555 participants (mean 2.7 visits/person) over 32 months. During this period, our center had 2,370 massage visits (1,828 60 minute sessions and 542 30 minute sessions). Symptoms with the highest scores (score≥2; means) at baseline included: Sleep [2.9; n=1,184]; Well Being [2.88; n=1,175]; Fatigue [2.7; n=1199]; Pain [2.3; n=1,194]; and Anxiety [2.1; n=1,193]. A single massage session resulted in a significant decrease in GSD [19.2 to 11.7 (t=-23.4; p<0.0001)], PHS [12.6 to 7.6 (t=-21.5; p<0.0001)], and PSS [6.7 to 4 (t=-19.26; p<0.0001)]. Massage resulted in a statistically and clinically significant reduction (decrease in symptom score ≥1; means) in symptom expression for Fatigue [-1.23; n=784], Well Being [-1.16; n=761], and Pain [-1.13; n=783] (all p’s <0.0001). Conclusions: A single 30- or 60-minute massage session resulted in acute relief of self-reported symptoms in patients and caregivers. Further study is warranted to gain insight into the potential benefits of massage in relieving symptom distress in cancer patients and caregivers, the temporal nature of the effects, and the necessary frequency to maintain effective symptom control.
Phase III randomized, placebo-controlled clinical trial evaluating the use of adjuvant endocrine therapy +/- one year of everolimus in patients with high-risk, hormone receptor (HR) positive and HER2-negative breast cancer (BC): SWOG/NRG/Alliance S1207 (NCT01674140).
Authors: Mariana Chavez-Mac Gregor, William E. Barlow, Lajos Pusztai, Matthew P. Goetz, Priya Rastogi, Patricia A. Ganz, Eleftherios P. Mamounas, Soonmyung Paik, Hanna Bandos, Julie Gralow, Danika L Lew, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2015)

TPS637 Background: Abnormalities of the PI3kinase/AKT/mTOR signaling network are common in BC. This pathway is associated with resistance to endocrine therapies among HR+ tumors. Everolimus, an mTOR-inhibitor, increases the biological activity of endocrine therapy. S1207 evaluates the role of everolimus in combination with endocrine therapy in the adjuvant setting. Methods: Specific aims/ design: Randomized phase III double-blinded, placebo-controlled trial. Primary objective is to assess whether the addition of everolimus to standard adjuvant endocrine therapy improves invasive disease-free survival (DFS) among patients with high risk, HR+ BC. Secondary objectives include overall survival, distant recurrence-free survival, safety, adherence and QoL. Patients are randomized to receive standard adjuvant endocrine therapy in combination with one year of everolimus (10 mg PO daily) or placebo. Submission of tissue specimens/blood samples is required for translational studies Eligibility criteria: Patients wi...
A phase I study of EP-100, a luteinizing hormone releasing hormone (LHRH) ligand conjugated to a synthetic cytolytic peptide in patients with advanced refractory LHRH- receptor (R)-expressing tumors.
Authors: Ramesh K. Ramanathan, Manpreet Chadha, John Sarantopoulos, Donald W. Northfelt, Glen J. Weiss, Monica M. Mita, Kerry M. Barnhart, John Whisnant, Carola Leuschner, Hector Alila, Kelly Kevelin Curtis
Journal: Journal of Clinical Oncology (2012)

3060 Background: EP-100 is a synthetic 28 amino acid LHRH peptide conjugated to an 18 aa cytolytic peptide. Selective targeting in LHRH-R expressing cells occurs via direct binding to the extracellular membrane receptor followed by disruption of the membrane by the cytolytic peptide portion. A first in human, phase I study was performed. Methods: Eligible pts had adequate organ function and LHRH-R tumor expression, as determined by IHC. EP-100 was given IV (30-60 min) weekly x 3 for cohorts 1- 6 (n=20 at 0.6 - 5.2 mg/m 2 ) and then twice weekly x 3 for cohorts 7- 11 (n=18 at 7.8 - 40 mg/m 2 ) with a week break. The pharmacokinetic profile of EP-100 and antibody production against EP-100 was determined by a validated HPLC/MS and ELISA respectively. Potential activity of EP-100 on the pituitary gonadotropes was determined by plasma LH and FSH. Results: We screened 97 pts, archival tumor tissue obtained from 81 pts; 53 (65%) were positive for LHRH-R, of which 37 were enrolled (female 76%) and treated. The LHRH-R expression rate in breast was 81% (N=21) and in ovarian cancer 56% (n=18). Most pts had breast (n= 16, 42%) ovary (n=7,18%), colon (n=4, 11%) or uterine (n=3, 8%) cancer. Pts were treated in a 3 + 3 standard dose escalation scheme. Doses were escalated 100% in the absence of a grade 2 drug related toxicity. MTD was not reached at the highest dose level of 40 mg/m 2 . Only one DLT occurred, a grade 2 increase in ALT/AST. The only other drug-related toxicity was a self limited infusion-related skin reaction (grade 1-2) in 10 pts. EP-100 was rapidly cleared from circulation, mean half life ranged from 7.1 ± 3.8 min to 15.9 ± 3.6 min. Best response was stable disease for &gt;12 weeks in 5 pts. In 3 pts rapid, sustained decreases in LH/FSH levels were noted. Antibody production against EP-100 was absent in all pts. Conclusions: The study has completed accrual, the phase II dose is 30-40 mg/m 2 twice a week x 3 weeks.EP-100is safe, well tolerated and not antigenic/immunogenic. Preclinical studies indicated synergy with paclitaxel and doxorubicin. A phase II study of EP-100 plus paclitaxel in ovarian cancer is planned.
Time to Embrace the Digital Age in Health Care
Authors: Tarik Sammour, Andrew G. Hill
Journal: JAMA Surgery (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Preoperative concurrent chemo- and endocrine therapies for women with large operable breast cancer expressing steroid hormone receptors
Authors: S. Dellapasqua, A. Balduzzi, R. Torrisi, R. Ghisini, G. Peruzzotti, A. Rocca, A. Cardillo, A. Goldhirsch, M. Colleoni
Journal: Journal of Clinical Oncology (2007)

21153 Background: Preoperative chemotherapy and endocrine therapy yielded low pathological complete remission (pCR) rates in patients with endocrine responsive breast cancer. Methods: Patients with large operable endocrine responsive (ER ≥ 10% of the cells) breast cancer (cT2-T3, N0–2, M0) were treated in 2 consecutive studies with preoperative chemotherapy (Study I: 6 courses of either fluorouracil, leucovorin, vinorelbine (FLN), or vinorelbine, cisplatin, and continuous infusion of fluorouracil (ViFuP), chosen at the discretion of the treating physician; Study II: an oral regimen with capecitabine and vinorelbine (CAVINO). In both studies concurrent endocrine therapies (letrozole, either alone or if premenopause, with triptorelin) were given. Results: Sixty-five (58 evaluable) and fifty-five (all evaluable) patients were enrolled to Studies I and II, (ER &gt;50%, 51 and 50; Ki 67 = 20%, 42 and 39; cT2/3: 36 / 22 and 35 / 20; premenopausal 40 and 38) respectively. In Study I there were 43 objective responders (74%, 95% CI 63–85%), 4 of whom had pCR. In Study II 34 patients (62%, 95% CI 49–75%) had an objective response. Breast conserving surgery became possible for 64% and 62% of the patients in Study I and II, respectively. Conclusions: Intravenous, non anthracycline containing regimens together with tailored menopause status-adapted endocrine therapy, warrants further investigations in the preoperative setting. No significant financial relationships to disclose.
Exposing the criminal record of every blood sample: Use of SOMAmer technology and sample mapping vectors to mitigate false biomarker discoveries in lung cancer.
Authors: Rosalynn D Gill, Steve Williams, Rachel Ostroff, Ed Brody, Alex Stewart, Harvey Pass, William Rom, Joel L. Weissfeld, Jill Siegfried, Mike Mehan
Journal: Journal of Clinical Oncology (2012)

e21012 Background: Biomarker discovery studies may fail to translate to the clinic because the study population does not match the intended clinical use or because hidden preanalytic variability in the discovery samples contaminates the apparent disease specific information in the biomarkers. This can arise from differences in blood sample processing between study sites or in samples collected differently at the same study site. Methods: To better understand the effect of different blood sample processing procedures, we evaluated protein measurement bias in a large multi-center lung cancer study using the &gt;1000 protein SOMAscan™ assay. These analyses revealed that perturbations in serum collection and processing result in changes to families of proteins from known biological pathways. We subsequently developed protein biomarker signatures of cell lysis, platelet activation and complement activation and assembled these preanalytic signatures into quantitative multi-dimensional Sample Mapping Vector (SMV) scores. Results: The SMV score provides critical evaluation of the quality of every blood-based sample used in discovery and also enables the evaluation of candidate protein biomarkers for resistance to preanalytic variability. Despite uniform processing protocols for each clinic, the SMV analysis revealed unexpected case/control bias arising from collecting case and control serum from different clinics at the same academic centers, an effect that created false or bias-contaminated disease markers. We therefore used the SMV score to remove bias-susceptible analytes and to define a well-collected, unbiased training set. An improved classifier was developed, resistant to common artifacts in serum processing. Conclusions: . The performance of this classifier to detect lung cancer in a high-risk population is more likely to represent real-world diagnostic results. We believe this approach is generally applicable to clinical investigations in all fields of biomarker discovery and translational medicine.
Phase I study of everolimus (E, RAD001) and ganitumab (G, AMG 479) in patients (pts) with advanced solid tumors.
Authors: Shadia Ibrahim Jalal, Robert Matthew Strother, George Sandusky, Nagendra K Prasad, William Berry, David R Jones, Anne Younger, Jennifer M. Funke, Tammi Detty, Sandra Althouse, Susan M. Perkins, E. Gabriela Chiorean
Journal: Journal of Clinical Oncology (2013)

2529 Background: Synergism between IGF and mTOR inhibitors has been documented preclinically. We conducted a phase I study to determine the safety, recommended phase II dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), and antitumor efficacy of E with G. Methods: Eligible pts had good organ function, ECOG PS 0-1. The study had a standard “3+3” design, using E 5 or 10 mg orally daily (QD), and G 12 mg/kg IV every 2 wks (Q2W) in 28 day cycles (C); an expansion cohort was added at MTD for further efficacy analysis. E was given as single agent during C1D1-7 with PKs on C1D1 and D7, and continuously after C1D16. G was started on C1D15 with single agent PK. PKs for both drugs at steady state were performed on C3D1. PDs (blood and serial tumor biopsies) for IGF and PI3K/Akt/mTOR pathways were performed at baseline, C1D7, C3D1 and time of progression. Results: 20 ptswere enrolled to date, M/F: 8/12, median age 55 yrs (24-70); PS: 0/1= 13/7. The table summarizes dose levels and DLTs. The most common toxicities were fatigue (5), diarrhea, mucositis, dysgeusia, anemia and thrombocytopenia (4 each), and rigors (3). Grade (Gr) 3 toxicities were: mucositis (3), anemia (2), thrombocytopenia (2), and diarrhea (1). Pts received a median of 3 cycles (0-9). One pt discontinued study on C1D9 due to intracerebral bleed and 1 pt withdrew consent on C1D15. Among 18 evaluable pts, none responded and 9 pts (50%) had SD with a median duration of 20 wks (range 11-35). Prolonged clinical benefit (SD ≥ 20 wks) was noted in refractory fibrolamellar HCC, neuroendocrine, GIST and urachal cancers. PKs showed no significant interaction between E and G. Baseline IGF-1R and PTEN expression, and IGF1 levels did not affect clinical benefit. pS6 downregulation and pAkt upregulation in paired tumor biopsies occurred in all (7/7) or most (6/7) samples evaluated, and did not correlate with efficacy. IGF1 and IGFBP3 levels increased on-treatment in 80-90% of pts. Conclusions: E+G is safe and the RP2D is E 10 mg QD + G 12 mg/kg Q2W. While on target pS6 reduction occured, the IGF1-R inhibition did not affect pAkt upregulation from mTOR blockade. Clinical trial information: NCT01122199. [Table: see text]
A phase I/II study of gemcitabine (GEM) with oral S-1 in metastatic pancreatic carcinoma
Authors: K. Nakamura, T. Yamaguchi, T. Ishihara, H. Ishiguro, A. Kabayashi, H. Tadenuma, H. Saisyo
Journal: Journal of Clinical Oncology (2004)

4134 Background: Gemcitabine (GEM) alone is the standard care for advanced pancreatic cancer. And there is no combination regimen having a longer survival than GEM alone. We conducted a phase 1/2 study of GEM with S-1, oral fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate. Methods: Eligibility criteria was as follows: patients with metastatic pancreatic cancer, PS 0∼2, and normal renal, liver, and bone marrow functions. Oral S-1 was given daily from day 1 to 14, and GEM was given on days 8 and 15. This cycle was repeated every 21 days. Doses of each drug in the phase 1 part of this study were planed as follows: Level 1: S-1 60mg/m2/day GEM 800mg/m2 Level 2a: S-1 80mg/m2/day GEM 800mg/m2 Level 2b: S-1 60mg/m2/day GEM 1000mg/m2 Level 3: S-1 80mg/m2/day GEM 1000mg/m2 Phase 2 part is being conducted with doses based on the phase 1 results. Results: A total of 17 patients were entered in this trial. Most patients had liver metastasis. There were no dose limiting toxicities (DLT) observed in levels 1 and 2b. Three of 6 patients in level 2a showed DLT: one patient developed sepsis with grade 4 neutropenia, another patient developed grade 3 rash and the third patient developed grade 2 leucopenia not recovering within the specified period. Then, level 2b has been selected as recommended dose for phase 2 study and 5 patients were included in the analysis. Grade 3–4 toxicities were leucopenia (29%), neutropenia (35%), anemia (12%), thrombocytopenia (18%), anorexia (12%), nausea (6%), and rash (6%). Responses in 15 evaluable patients were: 1 complete response (7%), 6 partial responses (40%), 4 stable disease (27%), and progression in only 4 patients (27%). Conclusions: The combination chemotherapy of GEM and S-1 was well tolerated. Although most of the patients had advanced disease, we observed a promising response rate (47%) with this combination chemotherapy. Given these results it would be worthwhile to compare this therapy with GEM alone in the phase 3 studies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Japan