tbuckley/cabot-search huggingface dataset:
A randomized phase III study to determine the efficacy of capecitabine in addition to a taxane and bevacizumab as first-line therapy in patients with metastatic breast cancer.
Authors: Hans-Joachim Lueck, Kristina Luebbe, Joachim Bischoff, Nicolai Maass, Gabriele Feisel, Oliver Tome, Wolfgang Janni, Mustafa Aydogdu, Tanja Neuhoeffer, Angelika Ober, Bahriye Aktas, Tjoung-Won Park-Simon, Claudia Schumacher, Heinz-Gert Hoeffkes, Thomas Illmer, Harald Wagner, Keyur Mehta, Valentina Nekljudova, Sibylle Loibl, Gunter Von Minckwitz
Journal: Journal of Clinical Oncology (2013)

1082 Background: Conventional chemotherapy combined with novel molecular targeted agents has been proven effective and tolerable in metastatic breast cancer (MBC). Taxanes (T) plus bevacizumab (B) and T plus capecitabine (X) showed a benefit in progression free survival (PFS) compared to T alone. Life-threatening or highly symptomatic situations require poly-chemotherapies in MBC patients; therefore a combination of all 3 drugs appears reasonable. Methods: TABEA (NCT01200212) is a prospective, randomized, open label, phase III trial comparing T plus B +/- X as 1 st -line therapy in MBC. Patients with histologically confirmed HER2- locally advanced or MBC were included. All patients received T (paclitaxel 80 mg/m2 i.v. d1,8,15 q22 or docetaxel 75 mg/m2 i.v. d1 q22) and B (15 mg/kg i.v. d1 q22) (TB) and were randomized to X (1800 mg/m² daily d1-14 q22) in addition and concurrently to TB (TBX) or TB alone. Randomization was stratified by receptor status, planned taxane, and disease free interval (≤ or &gt;12 months). Primary objective was PFS. Secondary objectives were response rate and duration, clinical benefit rate (CR, PR, stable disease ≥ 24 weeks), 3yr overall survival, PFS in patients ≥ 65 years, toxicity, and compliance. Sample size calculation assumed a PFS of 10 and 13.3 months for TB and TBX, respectively (HR=0.75) requiring 432 patients and 386 events with 2-sided α=0.05 and β=0.2. Interim analysis was planned after 25% of required events (n=96). Results: Planned interim futility and safety analyses after 100 documented events in 202 patients have shown no efficacy benefit and higher toxicity in the TBX arm. For PFS, HR=1.061, 95% CI (0.715, 1.576) was observed, futility boundary was crossed. Overall grade 3-4 adverse events (e.g., thrombopenia, diarrhea, hand-foot-syndrome) (72.3 vs. 57.4%, p=0.039)and serious adverse events (40.6 vs. 24.8%, p=0.016) rates were higher for TBX after 16.3 months median follow up. There were 6 deaths in the TBX vs. 1 in the TB arm. Recruitment and therapy were stopped on 5 th Oct 2012 following the advice from the IDMC. Conclusions: TABEA failed to show an improvement using the 3 drug regimen TBX in high-risk MBC patients. Clinical trial information: NCT 01200212.
NCI experience using yeast-brachyury vaccine (GI-6301) in patients (pts) with advanced chordoma.
Authors: Christopher Ryan Heery, Harpreet Singh, Jennifer L. Marte, Ravi Amrit Madan, Geraldine Helen O'Sullivan Coyne, Benedetto Farsaci, Timothy C. Rodell, Claudia Palena, Jeffrey Schlom, James L. Gulley
Journal: Journal of Clinical Oncology (2014)

3081 Background: Saccharomyces cerevisiae has been genetically modified to express Brachyury (Br) protein and developed under a CRADA with GlobeImmune/NCI as a heat-killed immune-stimulating therapeutic cancer vaccine (GI-6301). Br is a member of the T-box family of transcription factors and is a key factor in embryonic (mesoderm) development. Chordoma, a rare tumor of the notochord (derived from mesoderm) is known to overexpress Br while expression in normal adult tissue is minimal or not present. Preclinical work has demonstrated Br specific T cells can lyse human Chordoma cells expressing Br in an MHC restricted fashion. Methods: We enrolled a cohort of 7 pts with advanced Chordoma on an expansion cohort of a phase I study (NCT01519817) and evaluated their clinical and immunologic outcomes. All pts had undergone previous radiation (median 470 days since radiation: range 111-1883). All received 40 yeast units of vaccine every 2 weeks x 7 with first restaging at day 85. If stable, pts went on to monthly dosing with restaging scans every 2 months. The primary endpoint was safety, but clinical outcomes were followed as well. Br-specific T cell responses were also analyzed by flow-cytometry intracellular staining (ICS) of CD4 and CD8 T lymphocytes for the cytokines IFN-g, TNF, and IL-2. Results: All 7 pts had undergone extensive previous treatment. Median age was 59 (41-66). Two pts had relatively stable disease for 6 and 12 months, respectively, coming on the study, and both remain stable at day 141 and 197 restaging, respectively. The remaining 5 had progressive disease at enrollment. Of those 5, 1 had a decrease in index lesions >30% at day 141 with a confirmed PR on repeat scan 4 weeks later. 1 has stable disease through day 141 restaging. The other 3 progressed at day 141 restaging. Adverse events were minimal with injection site reaction being the most common (13 events in 63 doses (21%), 6 of 7 pts (86%)). Two of 7 pts had a Br-specific T cell response by ICS. Conclusions: This cohort of pts with advanced Chordoma in the phase I study with GI-6301 vaccine demonstrated safety and enhanced immune response with a confirmed PR. These findings are encouraging and warrant further study using this vaccine in pts with Chordoma. Clinical trial information: NCT01519817.
Survival outcomes for de novo versus primary progressive metastatic prostate cancer.
Authors: Kanika Gupta, Antoine Nafez Finianos, Brandon Clark, Samuel J. Simmens, Jeanny B. Aragon-Ching
Journal: Journal of Clinical Oncology (2017)

258 Background: We reported initial findings on the phenotypic differences between de novo versus primary progressive metastatic prostate cancer (Finianos et al., ASCO GU; abstr 285). We sought to determine the differences in the phenotypic characteristics of these 2 cohorts of patients and update the data with overall survival and patterns of response to androgen deprivation therapy (ADT) in patients presenting with de novo versus primary progressive prostate cancer. Methods: A retrospective chart review in a single-institution center for a period of 2 years was undertaken. Phenotypic characteristics included age at diagnosis, race, overall survival, treatment patterns, and response to ADT. Analysis was by t-test, Mann-Whitney U test, and Fisher’s Exact test. Results: A total of 90 patients were included in this cohort with de novo, dn (n = 38) and primary progressive, pp (n = 52) patients. There were no significant differences between the 2 cohorts with regard to the median age at diagnosis (dn = 66, pp = 61, p = 0.11), alkaline phosphatase level (dn = 135.5, pp = 86, p = 0.27), BMI (dn = 28.47, pp = 27, p = 0.78), creatinine (dn = 1.02, pp = 0.99, p = 0.34), LDH (dn = 188, pp = 166, p = 0.34), and testosterone on metastasis (dn = 276, pp = 31, p = 0.16). However, de novo cancers were diagnosed with higher mean gleason scores (dn = 8.36, pp = 7.7, p = 0.004), had higher median PSA upon diagnosis (dn = 63.1, pp = 8.8, p &lt; .0001) and higher PSA on metastasis (dn = 61.7, pp = 12.5, p = .0002), and had a statistically significant decreased duration of hormone sensitivity (dn = 642 days, pp = 1783 days, p = &lt; .0001). Patients with d e novo cancers also had a shorter median survival than primary progressive cancers (dn = 2257 days, pp = 4217 days, p = 0.02). Conclusions: Patients who present with de novo metastatic prostate cancer appear to develop early castration resistance and have worse overall survival than those who present with primary progressive disease. We are exploring the molecular differences in terms of androgen receptor expression as a potential etiology for development of early castration resistance.
Treatment (T) of metastatic colorectal cancer (mCRC) patients (pts) ≥75 years (y) old in clinical practice: A multicenter analysis.
Authors: Roberta Grande, Carlo Garufi, Ida Pavese, Fabrizio Ciancola, Donatello Gemma, Arianna Pellegrino, Luigi Di Lauro, Domenico C. Corsi, Diego Signorelli, Isabella Sperduti, Giada Cortese, Emanuela Risi, Federica Morano, Domenico Sergi, Carlo Signorelli, Clara Natoli, Enzo Ruggeri, Germano Zampa, Marco Russano, Teresa Gamucci
Journal: Journal of Clinical Oncology (2014)

e14514 Background: CRC pts have a median age of incidence > 65y although they are largely under-represented in phase III trials. This large population contains pts unfit for T, those suitable for monotherapy or for doublets and the impact of chemotherapy (CHT) outside clinical trial is unclear. Aim of the study was to retrospectively analyse T of elderly mCRC pts. Methods: Kaplan-Meir method was used for OS, the log-rank or Tarone-Ware test for differences between subgroups, Cox’s proportional hazard model to assess the impact of known prognostic factors and T. Results: 751 pts with mCRC observed from January 2000 to January 2013 were collected. Median age was 79y (75-93);<80y 58.1%, 80-84y 32.1%, ≥84y 9.2%; M/F 61/39%, ECOG PS:0-1/2-3 85/15%, colon/rectum 74/26%; multiple metastatic sites 34%, only liver 41% of pts. KRAS status was studied in 35% of pts with 44% mutated (M); 20,5% of pts were untreated including surgery (33% of pts ≥80y). Comorbidities: cardiovascular 34%, diabetes 14%, hypertension 50%. Primary tumor was resected in 80.6%; surgery(S) of liver metastasis in 19% of pts (2.3% of pts ≥80y). 78 % of pts underwent CHT (target therapy for 25% of pts). Median follow up was 12 months (m) (range 1-124). Median OS was 17 m (CI 95%15-19); mOS in no-treated pts was 5 m (4-6); mOS of pts with at least one T was 20 m (18-22). In KRAS M group mOS was 19 m (15-23) while in KRAS wild type pts mOS was 25m (20-30). At multivariate analysis sex (female), age (<80y), PS (0-1), CHT, S of metastasis, S of primary tumor, and Site of metastasis (liver) were prognostic factors for OS. Conclusions: These data show that in clinical practice treatment has a positive effect on elderly pts OS, confirmed at multivariate analysis. KRAS analyses deserve further evaluation. Update results will be presented. Variables HR (CI95%) P value Sex 1.21(1.01-1.46) 0.04 Age 1.75(1.45-2.12) <0.0001 ECOG PS 2.51(1.94-3.25) <0.0001 CT 2.14(1.68-2.73) <0.0001 S of metastasis 2.48(1.88-3.29) <0.0001 S of primary tumor 1.66(1.31-2.11) <0.0001 Site of metastasis 1.33(1.09-1.63) 0.006
False-negative interferon-gamma release assay results in active tuberculosis: a TBNET study
Authors: Veerle de Visser, Viovanni Sotgiu, Christoph Lange, Martine G. Aabye, Marleen Bakker, Filippo Bartalesi, Kristián Brat, Cynthia B.E. Chee, Keertan Dheda, Jose Dominguez, Fusun Eyuboglu, Maha Ghanem, Delia Goletti, AsliGorek Dilektasli, Lorenzo Guglielmetti, Won-Jung Koh, Irene Latorre, Monica Losi, Monica Polanova, Pernile Ravn, Felix C. Ringshausen, Rudolf Rumetshofer, Maria Luiza de Souza-Galvao, Steven Thijsen, Graham Bothamley, Aik Bossink
Journal: European Respiratory Journal (2015)

Tuberculosis is one of the leading causes of morbidity and
mortality worldwide [1]. Rapid identification of contagious
tuberculosis patients and effective treatment are necessary to
prevent the spread of Mycobacterium tuberculosis, the causative
bacterium of the disease. Although interferon-gamma release
assays (IGRAs) have been developed for the diagnosis of latent
infection with M. tuberculosis, these assays are sometimes used
as adjunctive tests in the diagnostic workup for active
tuberculosis, despite poor specificity.
A comparative analysis of 3DCRT, IMRT, and VMAT in the palliative treatment of spinal metastases.
Authors: Haresh Kunhiparambath, M. A Laviraj, Subhash Gupta, Dayanand Sharma, Rajendran M, Pramod Kumar Julka, Goura Kishor Rath
Journal: Journal of Clinical Oncology (2013)

e20679 Background: Radiotherapy is very important in the palliation of spinal metastases. Traditionally, a simple two-dimensional single direct posterior spinal field giving unnecessary exit dose to the normal structures is used. The studies evaluating the recent advances like 3DCRT, IMRT, VMAT for spinal metastases are rare. Present study evaluates these three modalities for the treatment of spinal mets. Methods: Ten patients with metastases to the body of lumbar spine were included. Planning CT was done with the patient supine on Philips wide bore CT (for 3 mm). The CT images were transferred online to the Pinnacle TPS V.8.0M. Tumor and the critical structures like spinal cord, kidneys, liver and bowels were contoured on pinnacle. 3DCRT was planned on pinnacle with seven equidistant beams. The CT images with the contoured structures were sent to Monaco TPS V.3.10.02. IMRT (seven equidistant fields) and VMAT (a single 360 degree arc in 25 degree increments) were planned on Monaco. Dose: 30 Gy in 10 fractions. PTV indices analyzed: D mean, D2 (dose received by the hottest 2 percent volume), D98 (dose received by 98 percent), homogeneity index HI [(D2-D98)/D50)], and conformity index CI (PTV volume/volume of PTV covered by 95 percent isodose). Dmax and D2 (dose received by hottest 2cc) for the spine, V12, V18 and V28 (percent volume receiving the respective dose) for the kidneys, D50 (dose received by the 50 percent volume) of liver, V15 (percentage volume of bowel receiving 15 Gy) were evaluated. The average were calculated and compared. Statistical analysis was done by SPSS Version 14. Results: The Table shows that there is no much significant difference between the three plans for the PTV indices. But for the normal structures, VMAT provides the least dose followed by IMRT. Conclusions: VMAT is superior to IMRT and both are better than 3DCRT for normal tissue sparing in the palliative RT for spinal metastases. [Table: see text]
Three-Year Follow-Up of an Alectinib Phase I/II Study in <i>ALK</i>-Positive Non–Small-Cell Lung Cancer: AF-001JP
Authors: Tomohide Tamura, Katsuyuki Kiura, Takashi Seto, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Haruyasu Murakami, Hiroshi Kuriki, Tadashi Shimada, Tomohiro Tanaka, Kengo Takeuchi, Makoto Nishio
Journal: Journal of Clinical Oncology (2017)

Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.
Frequency and clinical significance of extramammary findings on breast magnetic resonance imaging.
Authors: Catherine Elizabeth Moore, Limin Yang, Sneha Deepak Phadke, Mary C. Schroeder, Chang Xia, Alexandra Thomas
Journal: Journal of Clinical Oncology (2014)

1588 Background: Breast magnetic resonance imaging (MRI), often obtained for management of newly diagnosed breast cancer, or other indications, uncovers extra-mammary findings (EMF) with some frequency. These results often prompt further work-up and cause pt concern. Methods: We retrospectively reviewed 1322 breast MRI reports performed at the University of Iowa between 2007 and 2012. We completed a chart review of the radiology reports, patient characteristics, and breast cancer characteristics. We then focused specifically on the EMFs that were detected on breast MRI. The EMFs in the field of breast MRI include lesions in the chest (lung, heart, mediastinum, and chest wall), liver, bone, spleen, lymph nodes, blood vessels, and bones. Results: A total of 1,322 MRI reports were reviewed. EMFs were reported in 130 (9.8%). An EMF was more likely to occur in postmenopausal pts (p = 0.021) or if the MRI indication was for breast cancer (p <0.001). EMFs were more frequent in pts with hormone receptor (HR) positive disease. HER2 status did not impact rate of EMFs. Most EMFs occurred in liver and bone. Of the 130 EMFs, 5 (3.8%) resulted in pts with active breast cancer being upstaged to stage IV disease. Of these 5 lesions, 3 were sternal and 2 were hepatic. One pt had an MRI for a high-risk indication and a sternal lesion was found which represented recurrence of previously treated breast cancer. These 6 studies represented 0.5% of all breast MRIs in this series. There were 2 additional cases where both the MRI and staging studies obtained the same day showed metastatic disease. Conclusions: Unexpected EMFs occurred with some frequency on breast MRI. Postmenopausal state, a diagnosis of breast cancer and HR positive disease, were associated with a higher EMF rate. These findings very rarely represented distant breast cancer. EM finding No EM finding P value Number 130 1192 Median age 51 50 0.0375 Menopausal status (%) Premenopause 8.5 91.5 Menopause 12.3 87.7 0.027 Indication for MRI (%) Breast cancer 16.0 84.0 High risk 6.6 93.4 Clinical significance 5.5 94.5 Other 0.0 100.0 <0.001 HR status (%)* Negative 8.4 91.6 Positive 20.1 79.9 0.001 HER2 status (%)* Negative 16.3 83.7 Positive 16.3 83.8 0.998 * For those with active breast cancer.
A phase I clinical trial of MVA expressing 5T4 and high-dose interleukin-2 (IL-2) for metastatic renal cell carcinoma
Authors: H. L. Kaufman, G. Deraffele, J. Mitcham, D. Moroziewicz, S. Kim-Schulze, C. A. Petrulio, R. Harrop, S. Naylor
Journal: Journal of Clinical Oncology (2006)

12500 Background: Metastatic renal cell carcinoma (RCC) is an immune responsive tumor. 5T4 is a tumor antigen expressed on the cell surface of clear cell and papillary RCC. We sought to evaluate the safety and immunologic effects of vaccination with modified vaccinia virus Ankara (MVA) expressing 5T4 followed by IL-2 in patients with advanced RCC. Methods: A single dose Phase I clinical trial was conducted in patients with metastatic RCC and who were eligible for high-dose IL-2. Vaccination was given every three weeks by intramuscular injection and was followed immediately by standard high-dose bolus IL-2 (600,000 IU/kg) after the second and third vaccinations. The regimen could be repeated if there was no evidence of disease progression. Peripheral blood and serum was collected before treatment and every three weeks for analysis. Routine blood counts, chemistry, and pituitary functions were monitored. Anti-5T4 antibody titers were determined by ELISA assay and 5T4-specific T cell responses were monitored by interferon-γ ELISPOT assay using overlapping peptides. Results: 25 patients with RCC are being sequentially enrolled. There have been no serious vaccine-related adverse events although typical Grade 3 IL-2 related toxicity has been seen in all patients. To date, all patients tested have developed an increase in 5T4-specific antibody titers following three initial vaccinations. T cell assays are currently in progress. Seven patients have completed the trial through at least one course of treatment (mean age 62.3 years). Of these 7, one patient who presented with a primary tumor in place and synchronous metastatic disease had an objective complete response of all metastatic disease and underwent a post-treatment nephrectomy; the primary tumor demonstrated highly necrotic tumor. Two additional patients have had stable disease and are receiving booster vaccinations every three months. Conclusions: These results demonstrate that local vaccination with an MVA virus expressing 5T4 administered in combination with high-dose IL-2 is safe and induces 5T4-specific antibodies in all patients. Additional T cell responses and clinical follow-up will be presented. The use of MVA-5T4 and IL-2 appears to be a promising approach for the treatment of advanced RCC. [Table: see text]
Randomized phase II study of dacarbazine plus gemcitabine versus DTIC alone in patients with advanced soft tissue sarcoma: A Spanish Group for Research on Sarcomas (GEIS) study
Authors: X. Garcia Del Muro, J. Fra, A. Lopez Pousa, J. Maurel, J. Martín, J. Martínez Trufero, A. Casado, J. Cruz, M. A. Gómez España, J. Lavernia
Journal: Journal of Clinical Oncology (2009)

10529 Background: Dacarbazine (D) and gemcitabine (G) are active as single agents in the treatment of patients (pts) with advanced soft tissue sarcoma (STS) resistant to standard chemotherapy. The purpose of this study was to assess if the combination of D and G (Buesa et al. Cancer. 2004;101:2261) improved clinical outcome compared with standard D. Methods: Pts with advanced STS progressing after doxorubicin and ifosfamide, PS 0–2, no prior G or D, measurable disease and adequate organ function, were randomized to receive G 1,800 mg/m2 as a fixed dose infusion rate (10 mg/m2/min) and D 500 mg/m2 every 2 weeks, or D 1,200 mg/m2 alone every 3 weeks. Pts were stratified by PS and interval since the initial diagnosis. The primary endpoint was progression-free rate (PFR) at 3 months, based on EORTC reference values. A one-sample binomial design was used. To detect an increase in PFR at 3 months from 40% to 60% with a power of 80% and a two-sided alpha of 0.05, 49 pts had to be accrued per arm (an additional 10% was permitted, to allow for pts who could not be evaluated). Results: From November 2005 to September 2008, 113 pts from 18 centers were randomized. 3 pts were ineligible. Baseline characteristics were well-balanced between both arms. The median number of cycles administered of D+G and D were 6 (2–13) and 2 (1–10), respectively. PR and SD &gt;12 weeks rates were 9% and 38% (D+G) vs. 4% and 19% (D) respectively (p=.01). PFR at 3 months was 59% (D+G) vs. 35% (D) (p=.001). 29 pts were free of progression at 3 months among the first 49 pts in the D+G arm (26 required to be the study positive). Median progression-free survival was 4.4 (D+G) vs. 1.9 (D) months (p=.002). Median overall survival was 17.1 (D+G) vs. 9.9 (D) months (p=.007). Asthenia, emesis and stomatitis were the most common nonhematologic effects. Severe anemia and thrombocytopenia were more frequent with D and granulocytopenia with D+G. Conclusions: The combination of D plus G is active and well-tolerated in pts with pretreated STS, yielding significant improvement in survival. No significant financial relationships to disclose.