tbuckley/cabot-search huggingface dataset:
Prophylactic growth factor (GF) support with adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) for node-negative breast cancer (BC): An interim safety analysis of the GEICAM 9805 study
Authors: M. Martin, A. Lluch, M. A. Seguí, A. Antón, A. Ruiz, M. Ramos, A. Rodríguez-Lescure, E. Adrover
Journal: Journal of Clinical Oncology (2004)

620 Background: For patients (pts) with node-positive BC, TAC confers signficant disease-free and overall survival benefits vs FAC (5-fluorouracil, doxorubicin, cyclophosphamide), but with a higher rate of febrile neutropenia (Martin, SABCS 2003 ab 43). In our study of TAC vs FAC for node-negative BC, we performed an interim safety analysis to assess the impact of GF support on the incidence of TAC-related adverse events. Methods: Following surgery, patients (pts) with operable, high-risk (St Gallen, 1998), node-negative BC, 18–70 yr old, KPS ≥ 80%, and adequate hematologic and organ function were randomized to FAC (F 500 mg/m2, A 50 mg/m2, C 500 mg/m2) or TAC (T 75 mg/m2, A 50 mg/m2, C 500 mg/m2) day 1 every 3 wk for 6 cycles. After enrollment of 224 pts, the study was amended to require prophylactic G-CSF for pts subsequently treated with TAC, but not FAC. The present analysis assessed the impact of G-CSF on the incidence of febrile neutropenia (FN; fever ≥ grade 2 with gr 4 neutropenia) and other gr 3/4 toxicities in pts treated with TAC. Results: At the cut-off date for this analysis, 448 pts had been enrolled: 124 received FAC (111 prior to amendment) and 124 TAC (109 without mandatory G-CSF [TAC-G]; 115 with G-CSF [TAC+G]). For pts receiving FAC, the incidence of FN (% pts) was 1.3% (0.9% pre-, 1.7% post-amendment); other gr 3/4 adverse events were observed in 26.7% (27% pre-, 26.5% post-amendment). Among pts treated with TAC, the rates of FN were 23.8% for TAC-G (95% CI: 15.9–31.9%) and 3.5% for TAC+G (1.0–8.7%); the rates of other gr 3/4 toxicities were 50.4% for TAC-G (41.1–59.8%) and 20% for TAC+G (12.7–27.3%). The relative dose intensities for TAC-G vs TAC+G, respectively, were T: 92% vs 96%, A: 93% vs 97%, C: 93% vs 97%. Conclusion: Within the limitations of a non-randomized comparison, the use of G-CSF beginning with the first cycle of TAC substantially reduces the incidence of FN and other gr 3/4 toxicities and enables maintenance of chemotherapy dose intensity for women with early stage breast cancer. The adverse event rate with TAC+G is similar to that of FAC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis
Tumor angiogenesis as a predictor of recurrence in gastric carcinoma.
Authors: K Maeda, Y S Chung, S Takatsuka, Y Ogawa, T Sawada, Y Yamashita, N Onoda, Y Kato, A Nitta, Y Arimoto
Journal: Journal of Clinical Oncology (1995)

PURPOSE We investigated the correlation between tumor angiogenic activity and progression of gastric carcinoma using immunohistochemical staining with antifactor VIII-related antigen (F-VIII RAg) antibody. MATERIALS AND METHODS One hundred twenty-four specimens resected from patients with gastric carcinoma were investigated by staining with a monoclonal antibody against F-VIII RAg. Correlations between the microvessel count (the mean number of microvessels in the five areas of highest vascular density at 200 times magnification), various clinicopathologic factors, and prognosis were studied. RESULTS The microvessel count increased with histologic stage. The microvessel count was significantly higher in patients with lymph node metastases than in those without such metastases. Moreover, in patients with a high microvessel count (&gt; or = 16), prognosis was significantly poorer than in those with low count (&lt; 16). Multivariate analysis indicated that the microvessel count is an independent prognostic factor in patients with gastric cancer. According to the mode of recurrence, the frequency of hepatic metastases was significantly increased in patients with a high count. CONCLUSION Microvessel count may be a good prognostic indicator and may be useful as a predictor for the mode of recurrence in patients with gastric carcinoma.
Full seven day NHS service is unachievable in near future, conference hears
Authors: Matthew Limb
Journal: BMJ (2015)

Providing full seven day services for every kind of service offered in the NHS looks “unachievable” in the near future, a leading NHS policy expert has said.

Saffron Cordery, director of policy and strategy for NHS Providers, the membership organisation for NHS service providers, said that the government had to be clearer about what it meant by its seven day service provision and questioned its affordability.

She also warned that patients could be misled by the policy and that their expectations would have to be managed well or the NHS risked “setting ourselves up to fail.” She queried whether the plans could be …
Malignant gastrointestinal stromal tumors treated with imatinib in France: Results in unselected patients
Authors: A. Mathieu-Boue, O. Bouché, A. Cioffi, M. Rios, F. Duffaud, L. Chaigneau, I. Ray-Coquard, J. Blay, A. Le Cesne, C. Deschaseaux
Journal: Journal of Clinical Oncology (2009)

e22177 Background: GISTs are rare tumors of the GI tract. In France, their incidence is estimated to be 9- 12/10 6 inhabitants/year. Imatinib (IM) has been approved to treat unresectable and/or metastatic Kit-positive GISTs since 2002 but information on routine use, safety and efficacy in unselected “real life” setting is lacking. An observational cohort (EPIGIST) in France was designed to provide data on survival, safety and treatment patterns and quality of life. Methods: EPIGIST is a nationwide multi-center, observational study on GIST patients (pts) treated with IM for the first time between the availability on the French Market and the end of the 2008. Centers were randomly selected in national files of oncologists, gastrointestinal surgeons and gastrointestinal specialists. The planned follow-up duration was three years. A case report form (CRF) had to be completed at inclusion and during each follow-up visits. Quality of life was assessed using QLQ-C30 and SF36 questionnaires. Results: 29 on 51 selected centers enrolled at least one pt and 127 pts were included (as of 12/2008), The median age of disease onset was 59 years (range 29 - 85) with 48% pts&gt;50 years. 63% were symptomatic at diagnosis; 69% were fully active (grade 0 on the ECOG index). Primary tumors were most often gastric (34%), or from jejunum/ileum (24%). At diagnosis 84% of pts had a tumor size over 5cm. 64% of patients had surgery of the primary tumor before starting IM. For 86% of the pts, IM was given at an in initial dosage of 400 mg, 8% at 300 mg and 6% at 800mg. Compliance was superior to 90% for all pts. With a median follow-up of 1.72 years (CI95%: [1.08;1.95]), two-years overall survival from first treatment with IM was 88.1% (CI95%: [65.3%-96.3%]). Conclusions: EPIGIST is still an ongoing survey. Current results confirm previous published data on survival in GIST treated with IM in an unselected cohort of patients outside of a clinical trial. [Table: see text]
Respiratory symptoms and change of workplace in the general population of Telemark, Norway
Authors: Anne Kristin M. Fell, Regine Abrahamsen, Martin Veel Svendsen, Paul K. Henneberger, Oscar Espeland, Kjell Torén, Johny S. Kongerud
Journal: European Respiratory Journal (2014)

INTRODUCTION: Respiratory symptoms at work are common and may lead to change of workplace. So far no data has been available regarding the change of workplace due to respiratory symptoms in Norway. The county of Telemark is of particular interest because it is one of the most industrialized onshore parts of Norway.

METHOD: A self-administered respiratory and work exposurequestionnaire was mailed to a random sample of 50.000 inhabitants aged 16 to 50 years living in Telemark County, Norway. The response rate was 33%. Prevalence of asthma was 12% both in responders and in non-responders (contacted by telephone, n=183), suggesting the sample is representative.

RESULTS: Fifteen percent of the sample reported exposure to vapor, gas, dust and fumesat work on a daily basis. Twenty-six percent reported asthma symptoms (wheezing, chest tightness or dyspnoea) during the past 12 months, and 1.5% had ever changed their work due to respiratory symptoms. The most frequently reported exposures, based on an asthma-specific job-exposure matrix (the Nordic JEM), leading to change of work were irritative-agents (62%), low-molecular weight-agents (25%) and high-molecular weight-agents (15%). The most prevalent reported single exposures associated with workplace change due to respiratory symptoms were: low temperatures 52% and odds ratio (OR) 2.0 (95% CI 1.4, 2.8), welding fumes 40% and OR 3.7 (2.6, 5.3), paint 40% and OR 3.7 (2.6, 5.3), and metal dust 39% and OR 3.6 (2.5, 5.1).

CONCLUSION: Exposures to low temperatures, welding fumes, paints and metal dust were associated with increased risk of change of workplace due to respiratory symptoms in this sample from the general population of Norway.
The ACTS intervention effect on adherence to recomended chemotherapy among black women with breast cancer
Authors: M. Rosenzweig, S. Sereika, A. M. Brufsky, J. Simon, S. Underwood
Journal: Journal of Clinical Oncology (2008)

20524 Background: Improving poor adherence rates noted locally (64%) and nationally (50%) to recommended primary systemic breast cancer treatment among black US women may be an important factor in equalizing breast cancer survival disparity. The ACTS Intervention, a 30 minute tailored intervention addressing common attitudes toward chemotherapy (CT), communication coaching, treatment explanation and emotional support was developed to improve adherence to chemotherapy among black women. The purpose of this study was to evaluate the ACTS Intervention vs. Usual Care (UC) among black women recommended to receive CT in the treatment of breast cancer on adherence trends (days from CT recommendation to first CT, overall adherence to recommended CT). Feasibility of intervention testing (eligible participant recruitment and retention) was also evaluated. Methods: Design was pilot, randomized, 2 group design, with one time intervention in urban cancer clinics. Participants (n=20) were randomized to UC or ACTS Intervention upon CT recommendation. ACT Intervention was provided by a black breast cancer survivor in addition to standard CT education. UC was standard CT education. Results: Enrollment (3/07 through 12/07) is complete with 20/22 (90%) of eligible subjects recruited with 19/20 (95%) subjects retained. Follow up is complete on 14 subjects. Mean age was 51.6±8.1(range 39 to 59) for ACTS and 51.0 ±11.2 (range 28 to 61) UC. Religiosity was noted to be “extremely important” for 100% of participants. Adherence Results: Mean days from CT recommendation to start of CT were 20.0 days (SD10.4) for ACTS Intervention and 27.3 days (SD 12.3) for UC subjects. Adherence to subsequent recommended CT was 10/10 (100%) for ACTS Intervention and 8/10 (80%) for UC, with one subject refusing to begin recommended CT, and one subject discontinuing after 2/4 treatments. Conclusions: Recruitment and retention were excellent within a minority population. These pilot data suggest that women who receive the ACTS intervention had a shorter time to the reception of first CT (20 vs. 27.3 days) and improved adherence (100% vs. 80%) to recommended CT compared to women who received UC. Testing within a larger sample is needed. No significant financial relationships to disclose.
Surgeon fails in attempt to get patients’ inquest verdict changed
Authors: Clare Dyer
Journal: BMJ (2015)

A consultant heart surgeon under investigation by the UK General Medical Council over allegations that he misrecorded data to make his surgical outcomes look better has failed in a High Court attempt to quash part of the verdict of an inquest into the deaths of three patients.

Ian Wilson was a consultant cardiothoracic surgeon at Queen Elizabeth Hospital in Birmingham until he was sacked in October 2013 after an internal review found misrecording of bypass and other data.1

In August 2012 the hospital’s internal recording …
Modulatory Effects of Aspergillus Colonization and Abpa on Blood and Sputum Granulocytes in CF
Authors: Yael Gernez, Jeffrey Waters, Colleen E. Dunn, Zoe Davies, Cassie Everson, Rabindra Tirouvanziam, Leonore Herzenberg, Richard B. Moss
Journal: Journal of Allergy and Clinical Immunology (2016)
Dose analysis of ASSURE (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma, an ECOG-ACRIN-led, NCTN phase 3 trial.
Authors: Naomi B. Haas, Judith Manola, Keith Flaherty, Robert G. Uzzo, Michael B. Atkins, Janice P. Dutcher, Christopher G. Wood, Christopher J. Kane, Michael A. S. Jewett, Bob Coomes, Surena F. Matin, Timothy Kuzel, Wade Jeffers Sexton, Yu-Ning Wong, Toni K. Choueiri, Roberto Pili, Igor Puzanov, Manish Kohli, Walter Michael Stadler, Robert S. DiPaola
Journal: Journal of Clinical Oncology (2015)

4508 Background: E2805 is a phase III trial of sunitinib (SU), sorafenib (SOR) or placebo (PB) in patients (pts) with completely resected locally advanced renal cell carcinoma (RCC). There was no difference in DFS between the arms. Midway through the trial, starting doses were reduced. We analyzed the effect of this approach on drug dosing, toxicity and outcome. Methods: 1,943 pts stratified by risk, histology, ECOG PS, and nephrectomy type, were randomized to SU daily (4 of 6 wk cycle), SOR daily, or PB, for ≤ 1 yr. The primary endpoint was disease-free survival (DFS). After 1322 pts, starting doses of SU and SOR were reduced from 50 to 37.5 mg (25%) and from 800 to 400mg (50%), respectively, to mitigate the impact of pt discontinuation (DISC). Escalation to full dose after the first 2 cycles was mandatory when tolerated. Total dose of each agent over the entire yr, relative dose (actual/intended x 100), and number (no.) of cycles were related to DFS. Results: The redesign reduced the 3-month DISC rate from adverse events or refusal from 25%/30% in pts starting at full dose to 17%/11% in pts starting at reduced dose on SU/SOR (Gray's p = 0.01/0.0001). Total dose did not differ between groups on either SOR (p = 0.41) or SUN (p = 0.83). Most common grade ≥ 3 adverse events were hypertension, hand-foot reaction, rash and fatigue. There was no relationship between no. of cycles received or dose intensity and DFS. Conclusions: Dose titration reduced the DISC rate but not the total dose, with no impact on overall DFS by arm. Decreased DFS with reduced-dose SOR raises concern about the differential effects of multi-kinase inhibitors across a range of doses. Clinical trial information: NCT00326898. SU SOR PB Randomized 647 649 647 Treated 629 630 632 DFS Events 265 272 270 Median DFS (yrs) 5.8 5.8 6.0 Hazard Ratio 1.01 0.98 (ref) 97.5% CI 0.83 – 1.23 0.81 – 1.20 Starting Dose Grp Pts Full 438 Red 191 Full 441 Red 189 Full 443 Red 189 SOR/PB, rel dose, % (sd) 85 (22) 91 (18) 84 (42) 91 (22) 92 (14) 93 (14) SU/PB, rel dose, % (sd) 90 (18) 93 (16) 87 (42) 93 (18) 95 (13) 95 (13) Cycles, median[range] 8 [1 –9] 9 [1 –9] 7 [1 –9] 9 [1 –9] 9 [1 –9] 9 [1 –9] 5-yr DFS (%) 55.1 56.0 56.6 29.2 55.0 55.8 97.5% CI 49.7 – 61.2 46.7 – 67.1 51.2 – 62.6 15.0 – 56.7 49.7 – 61.0 45.5 – 68.3 Hazard Ratio 0.92 1.13 0.86 1.44 ref ref
Significance of a partial or slow response to front-line chemotherapy in the management of intermediate-grade or high-grade non-Hodgkin's lymphoma: a literature review.
Authors: R Haw, C A Sawka, E Franssen, N L Berinstein
Journal: Journal of Clinical Oncology (1994)

PURPOSE The purpose of this review was to assess the outcome of patients with non-Hodgkin's lymphoma (NHL) who achieve an incomplete or slow response to front-line chemotherapy and to determine whether salvage treatment with intensive combination chemotherapy with or without autologous bone marrow transplantation (ABMT) is successful in such patients. METHODS A comprehensive literature search of studies using combination chemotherapy for the front-line therapy of advanced-stage intermediate- and high-grade NHL and for salvage therapy of patients with a partial response (PR) was reviewed. RESULTS The median survival duration of patients with a PR ranged between 5 to 14 months, while the median survival duration of patients with a complete response (CR) was not reached in many studies. For patients in CR, the probability of survival at 24 months ranged between 0.79 to 1, while for patients in PR it ranged from 0 to 0.31. The rapidity of a response to front-line therapy was often found to be of prognostic importance. Patients who relapsed after a PR to front-line therapy had similar outcomes to intensive salvage therapy as those who relapsed after a CR. ABMT performed immediately after a PR to induction therapy, before progressive disease occurred, resulted in high CR rates in nonrandomized studies. CONCLUSION Patients with aggressive NHL who experience a PR or who respond slowly to front-line chemotherapy have a poor prognosis. Early introduction of dose-intensive salvage therapy before the development of progressive disease may benefit patients with a PR and requires testing in randomized clinical trials.
American Cancer Society (ACS) clinical trial matching service (CTMS)
Authors: T. Gansler, K. Sharpe, C. Demler, H. Eyre
Journal: Journal of Clinical Oncology (2006)

18501 Background: The low prevalence of clinical trial participation limits progress in clinical research and practice. ACS assists individuals in finding trials appropriate to their medical and personal situation. Methods: The ACS call center and website provide access to a comprehensive cancer clinical trial database and matching software platform licensed from EmergingMed. This report outlines characteristics and outcomes of constituents who met initial eligibility criteria and requested further information for at least one trial after entering data on their diagnosis and prior treatment. Results: Among 4525 CTMS constituents during 2004–5, 58% were patients, 40% were their relatives and 2% were friends. 62% entered data via the call center, the rest used www.cancer.org (although for quality assurance reasons, all must speak with a call center specialist before receiving trial site contact information). They requested protocols for a median of 6 trials (range 1 to 75); most often requesting information on trials for lung cancer (16.4%), breast cancer (11.4%), colorectal cancer (7.3%), prostate cancer (7.0%), and melanoma (5.2%). Likelihood of trial enrollment varied by cancer type (χ 2 , p &lt; 0.0001) and was highest with kidney cancer (10.7%), melanoma (7.8%), multiple myeloma (4.4%), head &amp; neck cancer (4.4%), and leukemia (3.8%). We studied several common cancer types in greater detail. For example, in analysis of data from 2004, non-small cell lung cancer patients requesting trial information had more advanced disease than typical patients in the National Cancer Database (χ 2 , p &lt; 0.001). Enrollment rates for patients with stage I-IIIA and IIIB-IV were 0% and 3.7% (NS), respectively; rates for those with ECOG performance 0–1 and &gt;1 were 4.8% and 0.0% (χ 2 , p &lt; 0.05). Conclusions: The ACS CTMS can substantially augment participation in clinical trials among patients not recruited into trials by their oncologists. No significant financial relationships to disclose.
Agonist anti-GITR monoclonal antibody and stereotactic radiation induce immune-mediated survival advantage in murine intracranial glioma
Authors: Mira A. Patel, Jennifer E. Kim, Debebe Theodros, Ada Tam, Esteban Velarde, Christina M. Kochel, Brian Francica, Thomas R. Nirschl, Ali Ghasemzadeh, Dimitrios Mathios, Sarah Harris-Bookman, Christopher C. Jackson, Christina Jackson, Xiaobu Ye, Phuoc T. Tran, Betty Tyler, Vladimir Coric, Mark Selby, Henry Brem, Charles G. Drake, Drew M. Pardoll, Michael Lim
Journal: Journal for ImmunoTherapy of Cancer (2016)

Glioblastoma (GBM) is a poorly immunogenic neoplasm treated with focused radiation. Immunotherapy has demonstrated synergistic survival effects with stereotactic radiosurgery (SRS) in murine GBM. GITR is a co-stimulatory molecule expressed constitutively on regulatory T-cells and by effector T-cells upon activation. We tested the hypothesis that anti-GITR monoclonal antibody (mAb) and SRS together would confer an immune-mediated survival benefit in glioma using the orthotopic GL261 glioma model.Mice received SRS and anti-GITR 10 days after implantation. The anti-GITR mAbs tested were formatted as mouse IgG1 D265A (anti-GITR (1)) and IgG2a (anti-GITR (2a)) isotypes. Mice were randomized to four treatment groups: (1) control; (2) SRS; (3) anti-GITR; (4) anti-GITR/SRS. SRS was delivered to the tumor in one fraction, and mice were treated with mAb thrice. Mice were euthanized on day 21 to analyze the immunologic profile of tumor, spleen, and tumor draining lymph nodes.Anti-GITR (1)/SRS significantly improved survival over either treatment alone (p < .0001) with a cure rate of 24 % versus 0 % in a T-lymphocyte-dependent manner. There was elevated intratumoral CD4+ effector cell infiltration relative to Treg infiltration in mice treated with anti-GITR (1)/SRS, as well as significantly elevated IFNγ and IL-2 production by CD4+ T-cells and elevated IFNγ and TNFα production by CD8+ T-cells. There was increased mRNA expression of M1 markers and decreased expression of M2 markers in tumor infiltrating mononuclear cells. The anti-GITR (2a)/SRS combination did not improve survival, induce tumor regression, or result in Treg depletion.These findings provide preclinical evidence for the use of anti-GITR (1) non-depleting antibodies in combination with SRS in GBM.
Understanding potential communication gaps between oncologists and patients with advanced breast cancer: A survey of oncologists.
Authors: Adam Brufsky, Marc L. Citron, Deana Percassi
Journal: Journal of Clinical Oncology (2014)

124 Background: About 232,670 cases of breast cancer will be diagnosed in the US in 2014, of which 86,088 (37%) will be metastatic advanced breast cancer (ABC). The 2013 Global Count Us, Know Us, Join Us survey found that 53% of US women with ABC wanted more time to discuss their needs during clinic visits, and 60% believe their cancer treatment options are limited. To better understand unmet patient needs and potential communication gaps with physicians, surveys were developed for women with ABC, their caregivers, and oncologists. The oncologists’ survey results are presented. Methods: The Make Your Dialogue Count survey for oncologists has 32 items. Responses are single or multiple response numeric text or rated on a 4-point Likert scale. Harris Poll conducted this online survey from June through July 2014 among randomly selected, licensed US medical oncologists who treat ≥ 5 women with ABC per month. Responses for geographic region and number of years in practice by sex were weighted to match actual proportions in the population. Results: By July 15, 2014, 228 oncologists responded. At initial diagnosis, showing care and compassion was very important to 79% of oncologists; helping patients cope with diagnosis (62%) and manage cancer symptoms (56%) and discussing expected treatment response (57%) and side effects (51%) were also very important. Most oncologists (88%) revealed that treating women with ABC has a negative emotional toll. Although 81% of oncologists believe it to be unprofessional to let their emotion affect treatment recommendations, 26% reported that their emotions kept them from providing some information. Notably, 31% of oncologists reported that in certain situations, they have not discussed with patients that ABC is incurable. Conclusions: Caring for terminally ill patients has an emotional impact on oncologists. For some, their emotions have influenced what treatments they recommend and what information they impart. Our findings show that oncologists are compassionate and share disease- and treatment-related information and highlight the need to develop communication strategies that facilitate exchange between oncologists and their patients with ABC.