tbuckley/cabot-search huggingface dataset:
Up-regulation of thymidine phosphorylase (TP) by radiotherapy (RT): a phase I study of capecitabine (CAP) with concurrent RT for pts with locally advanced (LA) pancreatic cancer (Pan Ca)
Authors: M. W. Saif, M. Eloubeidi, J. Thornton, J. Johns, R. Diasio, M. R. Johnson, C. F. Moisa, S. Russo
Journal: Journal of Clinical Oncology (2004)

4104 Introduction: Concurrent 5-FU-RT is the standard Rx for LA Pan Ca. CAP is metabolized by TP to its metabolite, 5-FU. Preclinical studies suggest that RT prior to CAP leads to synergistic cytotoxicity and better antitumor effects than 5-FU-RT due to up-regulation of TP. Objective: This is a hypothesis-driven phase I study which examines the effect of RT on TP and TNF-alpha expression, defines MTD of CAP with RT and determines if there is a correlation between pt response and intra-tumor TP/DPD ratio. Patients and Methods: During Part A (CAP-RT) pts received concurrent RT (50.4 Gy) with escalating doses of CAP (600mg/m2 PO BID; 800mg/m2 PO BID; 1000mg/m2 PO BID) on days 1–5, 8–12, 15–19, 22–26, 29–33, and 36–40 in consecutive cohorts of 3–6 pts till MTD is achieved. After finishing Part A, pts were assessed for tumor response and resectability. During Part B (CAP), stable, responding and resected pts were treated with CAP 1000mg/m2 PO BID for 14d q 3 wks until disease progression. Re-staging asessment was performed q 3 cycles. Tumor specimens procured by EUS pre- and post-therapy (wk 2) were evaluated for TP, TNF-alpha and DPD mRNA levels by RT-Q-PCR. Results: From April to Dec 2003, 11 pts (4M/ 7F; Median age: 63 yrs; PS ECOG: 0–2) were enrolled. Toxicities are summarized in Table 1. DLT [Grade 3 diarrhea] was observed at 1000mg/m2 BID, and a total of 6 pts will be enrolled at this level to define MTD and DLT. No occurrence of Hand-Foot syndrome (HFS) was seen during Part A, and Grade 2 HFS was observed in 2 pts during Part B. With 5 pts still on study, 24 cycles have been administered, with a median of 3. Three pts responded to Rx (2 PR: 54% and 43%; 1 SD; 1 PD; 3 off-study due to delay > 2 wks). Intra-tumor expression of TP, TNF-alpha, and DPD are pending and will be available at the meeting. Conclusions: CAP-RT appears to be well tolerated and active in LA Pan Ca. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche; Sanofi Roche Pharmaceuticals
Phase II study of gemcitabine, capecitabine and cisplatin in patients with advanced pancreatic cancer
Authors: H. M. Chang, T. W. Kim, J. H. Ahn, M. H. Ryu, J. S. Lee, W. K. Kim, Y.-K. Kang
Journal: Journal of Clinical Oncology (2004)

4219 Background: In advanced pancreatic cancer (APC), gemcitabine (G) monotherapy is considered as a standard chemotherapy. However, the benefit of this treatment is needed to be improved. In previous studies, gemcitabine plus capecitabine (X) or cisplatin (P) showed promising activity although there was no statistically significant survival benefit compared to gemcitabine alone. We conducted phase II study with the combination of G, X and P (GXP) in pts with APC. Methods: Pts who were chemotherapy-naive with histologically confirmed, measurable APC were enrolled. Starting doses were G (800 mg/m2, IV over 80 min, D1, 8), X (1,300 mg/m2/day, po, D1–14) and P (60 mg/m2, IV, D1) per every 3 weeks (wks). After 4 pts were treated with this dose level, toxicities were mild and the dose of G was elevated to 1,000 mg/m2 (infused over 100 min). Results: Between Jun 2001 and Jul 2003, 40 pts were enrolled. Median age was 53 years (range, 35–66) with 32 males. Pts with metastatic lesions were 28 and locally advanced diseases (LA) 12. Thirty eight pts were assessable for activity and 40 were assessable for toxicity. A total of 185 cycles were administered (median, 4.5; range, 1–12). Twelve pts achieved partial response giving an overall response rate of 30.0% in intention-to-treat population (95% confidence interval (CI), 15.8–44.2%) and 14 pts (35.0%) had stable disease. The median time to progression (TTP) of all patients was 5.1 months (mo) (95% CI, 3.8–6.3). In pts with LA and metastatic lesions, the median TTP was 8.1 mo and 4.4 mo, respectively. The median overall survival (OS) of all patients was 7.5 mo (95% CI, 6.7–8.3). In pts with LA and metastatic lesions, the median OS was 11.8 mo and 7.0 mo, respectively. Median duration of response in 12 responders was 3.3 mo (range, 0.7–11.0). Grade 3/4 neutropenia and thrombocytopenia were noted in 47.5% and 10.0% of the pts, respectively. Grade 2/3 non-hematologic toxicities were asthenia (45.0 % of pts), diarrhea (12.5%), stomatitis (12.5%) and hand-foot syndrome (7.5%). There was no treatment-related death. Conclusions: The combination of gemcitabine, capecitabine and cisplatin is an active and tolerable regimen in pts with APC. No significant financial relationships to disclose.
Metformin Use in Prediabetes Among U.S. Adults, 2005–2012
Authors: Eva Tseng, Hsin-Chieh Yeh, Nisa M. Maruthur
Journal: Diabetes Care (2017)

To determine the prevalence of and characteristics associated with metformin use among U.S. adults with prediabetes using the National Health and Nutrition Examination Survey (NHANES) 2005-2012.The American Diabetes Association's guidelines for metformin use in prediabetes have evolved, with 2017 recommendations suggesting metformin be considered in patients with prediabetes and additional risk factors (BMI ≥35 kg/m2, age <60 years, or prior gestational diabetes mellitus) or rising hemoglobin A1c (HbA1c). We estimated the age-adjusted prevalence of metformin use among individuals with prediabetes (defined by HbA1c 5.7-6.4%, fasting glucose 100-125 mg/dL, 2-h poststimulated glucose 140-199 mg/dL, or self-report) and used multivariate logistic regression to evaluate characteristics associated with metformin use.Of 22,174 adults, 7,652 had prediabetes. The age-adjusted prevalence of metformin use among those with prediabetes was 0.7%. Metformin use was associated with higher mean BMI (35.1 kg/m2 vs. 29.6 kg/m2, P < 0.01) and higher glucose (fasting glucose 114 mg/dL vs. 105 mg/dL, P = 0.03; 2-h poststimulated glucose 155 mg/dL vs. 128 mg/dL, P = 0.003; and HbA1c 6.0% [42 mmol/mmol] vs. 5.6% [38 mmol/mmol], P < 0.01). Metformin use was low even among those with BMI ≥35 kg/m2, a group for whom metformin use is recommended. Metformin use did not vary by race, poverty-to-income ratio, or education.Metformin use was <1% among U.S. adults with prediabetes and only slightly more common among those with additional risk factors for diabetes.
Preventing Respiratory Syncytial Virus Infection to Prevent Asthma: The Missing Link
Authors: Tebeb Gebretsadik, Pingsheng Wu, Kecia Carroll, William Dupont, Tina Hartert
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

result of our adjustment for confounders.Moreover, the data in Ayubi and Safiri's Table 1 were not the same as ours.The numbers for non-asthma-chronic obstructive pulmonary disease overlap syndrome (unaffected) cases were 174 and 218 instead of 8 and 10.These numbers can be estimated from Table E1 in the online supplement of our article.We encourage other authors with similar data to consider applying Firth logistic regression or penalized logistic regression with data augmentation to reduce sparse data bias.
The patient experience: Patient characteristic differences in response.
Authors: Stephen Flaherty, Constance Barysauskas, Paul J. Catalano
Journal: Journal of Clinical Oncology (2017)

144 Background: Understanding and addressing patient experience (PX) is an integral part of oncology care. The Press Ganey Outpatient Oncology instrument is used to better understand PX and performance differences at a large ambulatory oncology center. We investigated select patient characteristics of response among all eligible patients, the surveyed sample, and survey respondents. Methods: Over a six month period at a large ambulatory oncology center, 26,660 patients were eligible to report their PX. 11% of patients were identified following the center’s sampling criteria, of which Press Ganey applied their sampling strategy. Thus, 2,857 patients were randomly selected and sent the survey instrument, of which 828 patients responded. Patient characteristics of the three cohorts were compared across the center and by disease center. Results: Surveyed patients were a representative sample of eligible patients, as surveyed patients were of similar age (NS), gender (NS), education level (NS), and primary insurer (NS). In some dimensions, responders were not a representative sample of eligible/surveyed patients. Respondents were slightly older (p &lt; 0.001), more often male (NS), more college educated (NS), and more frequently had a primary insurance of Medicare (p &lt; 0.001). Similar population differences continued among eligible, surveyed and responders, in further comparisons by disease center. Conclusions: Population based sampling allowed the opportunity to investigate accuracy of the sampling strategy and the ability to identify a representative sample of patients across the oncology center. A comparison across the oncology center and disease centers revealed we cannot assume respondents are similar to the eligible and surveyed populations, thus we caution all assumptions made with unadjusted PX comparisons. Further research allows the opportunity to continuously update/improve the sampling strategy and administer electronic surveys to identify a more representative sample better positioned for future quality improvement opportunities. [Table: see text]
Docetaxel, carboplatin, trastuzumab, and bevacizumab (TCH+B) for early-stage HER2/neu(+) breast cancer and bone marrow micrometastases.
Authors: Joseph Baar, Paula Silverman, G. Thomas Budd, Laura Gibson, Howard Meyerson, Pingfu Fu, Dawn Diorio
Journal: Journal of Clinical Oncology (2012)

TPS655 Background: Bone marrow (BM) micrometastases confer a poor prognosis to early-stage breast cancer (BC) and HER-2/neu(+) BC is a high-risk phenotype. We have shown that BM-associated stromal cells support the survival of metastatic BC in microenvironmental niches and this activity is dependent on VEGF and CXCL-12. Therefore, the growth of nascent tumor cell clusters in BM might be impeded by disrupting stromal cells or their activating ligands, such as VEGF. There is also a positive association between HER-2/neu and VEGF expression in BC, thereby implicating VEGF in the aggressive phenotype of HER-2/neu overexpression. These observations support the use of combination therapies directed against both HER-2/neu and VEGF for the treatment of HER-2/neu(+) BC. We therefore hypothesize that an anti-VEGF agent (bevacizumab) given with docetaxel, carboplatin and trastuzumab (TCH) will eradicate the BM of HER-2/neu(+) BC micrometastases by disrupting stromal cell support within the micrometastatic BM niche. Methods: Subjects with AJCC Stage I-III HER2/neu(+) BC will undergo a single iliac-crest BM aspirate and biopsy. If the BM is positive for CK+ micrometastases, up to 17 patients will receive TCH+B therapy (docetaxel at 75 mg/m 2 IV and carboplatin at AUC 6 IV given every 3 weeks for 6 cycles; trastuzumab at 4 mg/kg IV loading dose, then 2mg/kg IV every week; bevacizumab at 15 mg/kg IV every 3 weeks). Four weeks after the 6 th cycle of therapy, a repeat BM aspiration and biopsy will be performed to score for response of BC micrometastases to therapy. Patients with a complete clinical response in BM will continue with trastuzumab every 3 weeks at 6 mg/kg to a total of 1 year. Patients with persistent micrometastases will receive both trastuzumab and bevacizumab every 3 weeks to a total of 1 year of therapy. These patients will then have a repeat BM aspirate and biopsy at the end of the 1 year to score for final response. The primary objective of this clinical trial is to determine clinical response against BC micrometastases in BM. The second objective is to investigate the specific contribution of VEGF and CXCL-12 signaling to BM support of micrometastatic BC cells.
Multicenter phase II study of the combination of carboplatin and paclitaxel as first line treatment in elderly patients with advanced non small cell lung cancer (NSCLC)
Authors: I. Okamoto, E. Moriyama, H. Kishi, M. Nomura, F. Imamura, H. Iwagoe, S. Miyajima, T. Mori, K. Setoguchi, M. Matsumoto
Journal: Journal of Clinical Oncology (2004)

7239 Purpose: Thirty percent of NSCLC arise in patients over 70 years. The purpose of this phase II trial is to evaluate the efficacy and the safety of the combination of carboplatin and paclitaxel for advanced NSCLC in elderly patients aged 70 years or older. Patients and Method: Eligibility criteria included: chemotherapy-naive advanced NSCLC, age>=70; measurable lesion; ECOG PS 0–1; adequate organ functions and signed informed consent. Patients received carboplatin at an AUC of 5 mg/mL.min and paclitaxel 180 mg/m2 on day 1 every 3 weeks. Results: Between January 2001 and July 2003, 25 elderly patients with NSCLC (median: 76y, range: 70–83y) were enrolled to this study. There were 4 stage IIIB, 17 stage IV and 4 other medically inoperable patients. The median number of treatment cycles was 3 (range 1–4). There were 1 complete response and 6 partial response for an objective response rate (ORR) of 25% (95%CI: 12–40%). The median survival was 11.3 months and the 1-year survival rates were 37%. Hematological toxicities with grade 3/4 were as follows; 32%/8% for leukopenia, 28%/40% for neutropenia, 4% for anemia. Non-hematological toxicities with grade 3 were: arthralgia/myalgia 16% of patients, neuropathy 12% and infections 20%. Efficacy and toxicity analyses were also conducted on patients over age 75 years (n=15). ORR for patients > 75 years were 26% and no evidence of excessive toxicity were observed when compared with patients < 75 years. Conclusion: This carboplatin/paclitaxel combination chemotherapy is an active first-line treatment option with a favorable toxic profile for elderly patients with advanced/metastatic NSCLC. No significant financial relationships to disclose.
Presurgical axitinib and androgen deprivation therapy (ADT) in prostate cancer (PCa) patients (pts) presenting with lymph node (LN) metastasis.
Authors: Amado J. Zurita, Lance C. Pagliaro, Patricia Troncoso, John W. Davis
Journal: Journal of Clinical Oncology (2014)

TPS5109 Background: Strategies that integrate systemic therapy and curative-intent surgery/radiation are being considered for men presenting with PCa with regional spread. In our previous phase II study of pre-surgical chemotherapy and ADT followed by radical prostatectomy (RP) in LN metastatic pts (Pagliaro et al., ASCO 2011), we found no apparently better pathologic or survival outcomes than might be seen with ADT alone and surgery. To improve effectiveness of the pre-surgical therapy and characterize tumor changes associated with potent anti-angiogenic treatment response, we designed a trial testing the combination of the VEGF receptor inhibitor axitinib and ADT before consideration of consolidative RP. Methods: In this randomized phase II clinical trial, eligible pts either have biopsy-proven PCa and evidence of LN metastasis (TxN1M0 or TxNxM1a) on imaging (LN size ≥2 cm) or pathology (nodal biopsy or resection), or suspected LN extension based on the presence of any of the following: stage T3 (and Gleason score [GS] ≥7), stage T4 (any GS), or serum PSA concentration ≥25 ng/mL (and GS ≥8). Pts with bone or visceral involvement are excluded. After 2 months of ADT, pts are randomized to receive 4 more months of ADT in combination with open label axitinib (5 mg PO bid daily) vs. continuation of ADT until surgery in a 2:1 fashion (2 ADT + Axitinib to 1 ADT alone), for a total duration of pre-surgical therapy of 6 months. At that time, clinically responding pts are offered RP and extended pelvic LN dissection. Systemic therapy is discontinued postoperative and PSA measured every 3 months until 1 year. Pts are stratified based on LN metastatic status (present vs. suspected). The primary objective is to define the proportion of pts progression-free 12 months after surgery, defined as PSA ≤1.0 ng/mL and no radiation or ADT. Fifty-four pts are being accrued. This sample size ensures that, if the trial continues to completion, we will have an 80% power to detect a 35% difference in the proportions of pts progression-free between the two treatment arms. Early stopping rules for lack of efficacy and toxicity are included. Status: 35 pts have so far consented for participation, and accrual is ongoing. Clinical trial information: NCT01409200.
Indium-111 pentetreotide therapy in somatostatin receptor expressing neoplasms: Results from clinical practice
Authors: L. Le, L. Linares, S. Andrews, L. Anthony
Journal: Journal of Clinical Oncology (2004)

4269 Background: Therapeutic In-111 pentetreotide effectively controls symptoms in two-thirds of pts with hormonally active neuroendocrine neoplasms that overexpress the somatostatin receptor subtype 2. Auger electrons that are internalized into the nucleus provide cell-specific cytotoxicity. Renal excretion is the major route of elimination for In-111 pentetreotide. We hypothesized that In-111 pentetreotide therapy in community practice would not only offer an unmet medical need but provide an opportunity to further establish safety and efficacy of this particular form of radiolabeled somatostatin analog therapy. Methods: Between September 1999 and July 2003, pts undergoing therapeutic In-lll pentetreotide at Memorial Medical Center New Orleans, LA were included into this study. Clinical data including age, gender, diagnosis, date of diagnosis, prior treatment(s), hepatic and renal function were recorded. Serial data were collected for those pts receiving 2 or more In-111 pentetreotide therapies. Complete blood counts and differentials were reviewed. Creatinine clearance and survival were calculated as end measures of safety and efficacy, respectively. Results: 85 pts (46 females) were treated with an average dose of 487.9 mCi of In-111 pentetreotide during this 4-year period. The median age was 54.9 yrs. The majority of pts had a well-differentiated neuroendocrine tumor such as carcinoid or pancreatic islet cell carcinoma. 142 treatments were delivered with 41 pts receiving 2 or more treatments (28 pts were treated twice; 10 pts received 3 doses and 3 pts received 4 doses). The baseline creatinine clearance was 93 ml/min. For the 41 subjects treated on more than one occasion, subsequent creatinine clearances were 82.8, 95.2 and 81.9 ml/min following cumulative doses 493, 986 and 1,483 mCi, respectively. Treatment-related myelosuppression or myelodysplasia were not observed. The median survival was 22.1 mos from the time of the first In-111 pentetreotide treatment and 84.3 mos from the time of diagnosis. Conclusions: In-111 pentetreotide therapy can be safely administered in a community hospital setting. No significant financial relationships to disclose.
A phase III randomized trial of two cisplatin-based concurrent chemoradiation (CCRT) regimens for locally advanced head and neck squamous cell carcinoma (LAHNSCC).
Authors: Cristina P. Rodriguez, David J. Adelstein, Lisa A. Rybicki, Panayiotis Savvides, Jerrold P. Saxton, Shlomo A. Koyfman, John Greskovich, Min Yao, Joseph Scharpf, Pierre Lavertu, Benjamin J. Wood, Brian Burkey, Robert Lorenz, Rod Rezaee, Chad Zender, Denise I. Ives
Journal: Journal of Clinical Oncology (2013)

6035 Background: Excellent outcomes have been reported using both single and multiagent CCRT in LAHNSCC. This trial compares a 5FU/cisplatin regimen to single agent cisplatin CCRT. Methods: Patients (pts) with previously untreated stage III-IV, M0, LAHNSCC of the larynx, oropharynx (OP), oral cavity or hypopharynx received definitive once or twice daily radiation (70-74.4 Gy) and were randomized between concurrent chemotherapy with either Arm A: cisplatin 100mg/m2 on days 1, 22 and 43 or Arm B: cisplatin (20mg/m2/day) and 5-FU (1000mg/m2/day) as continuous 96 hour infusions weeks 1 and 4. ECOG performance status ≤ 1, and adequate renal, liver and marrow function were required for entry. The primary endpoint was recurrence free survival (RFS). Results: Between 2/2008 and 10/2011, 69 pts were enrolled. An accrual of 126 pts was planned in order to demonstrate an improvement in 2-year RFS from 55% to 75%. The study was closed prematurely when a scheduled interim analysis confirmed markedly better outcomes in both arms and the futility of further comparison. Pt and tumor characteristics were well balanced in both arms. OP cancer was diagnosed in 83% of pts; 86% of the OP cancers were HPV/p16+. With a median follow up of 29.4 months, 2 yr Kaplan-Meier outcome estimates were similar between arms (Table). Pts on Arm A experienced more nephrotoxicity (26% vs. 3%; p=0.007) and ototoxicity (11% vs. 0%; p=0.042), but less Grade ≥2 radiation dermatitis (43% vs. 68%; p=0.038), neutropenia &lt;1000/mm3 (34% vs. 65%; p=0.012), and unplanned hospitalization (43% vs. 68% p=0.038). Treatment outcomes were inferior and feeding tube requirements greater in the HPV/p16 negative and actively smoking pts. Conclusions: Although these CCRT regimens produced similar outcomes, their toxicity profiles proved different and may serve to inform individual pt treatment. Tobacco use and HPV status had far greater impact on treatment outcomes than did the CCRT regimen. Clinical trial information: NCT00608205. [Table: see text]
Relationship of progestin receptor to estrogen receptor and the relevance of the progestin receptor in predicting survival in breast cancer.
Authors: Hari Singhal, Geoffrey Greene
Journal: Journal of Clinical Oncology (2015)

e11514 Background: While estrogen receptor alpha (ER) and progestin receptor (PR) are commonly used biomarkers in breast cancer prognosis, the clinical value of PR is controversial and whether or how PR modulates estrogen signaling and breast carcinogenesis or progression is poorly understood. These gaps in knowledge impede the optimization of breast cancer biomarkers and receptor targeted therapies. Methods: Using ChIP-seq and RNA-seq we determine ER and PR genomic binding and ER- and PR-mediated gene expression in ER+/PR+ T47D, ZR75 and MCF7 cells treated with estrogen (E2), progestin (R5020) or joint E2+R5020. We combine the binding and expression profiling data to map ER and PR transcriptional networks and study them to investigate how PR reprograms ER binding and activity. Subsequently, we investigate the clinical impact of our findings in METABRIC, TCGA and NKI patient tumor cohorts. Results: We found that PR is both necessary as well as sufficient to abrogate and override estrogen signaling. Progestin-activated PR forms complexes with ER to expand and reprogram ER genomic recruitment towards PR transcriptional networks and genes highly expressed in luminal-like cancers and lowly expressed in basal cancers. These gained ER binding events have a 90% overlap with PR binding and they occur at genomic loci enriched in response elements for PR and its cofactors. Our data further demonstrate that genomic agonism between PR and ER correlates with improved survival of patients with ER+/PR+ tumors. Also, PR-regulated genes can diagnostically differentiate breast cancer subtypes and patient survival. Furthermore, tumor’s PR status and PR-mediated reprogramming of estrogen signaling is essential to predict survival. Conclusions: The study underscores the clinical value of PR in breast cancer prognosis and as a therapeutic target in breast cancer. Tumor’s PR status and PR-mediated reprogramming of estrogen signaling predicts patient survival, which impacts prognosis assessment. Furthermore, global non-competitive ER and PR interactions also provide a rationale for the development of anti-PR drugs and testing joint ER- and PR-targeted therapies in breast cancer treatment.