tbuckley/cabot-search huggingface dataset:
Ultra-high-quality sequencing assay for comprehensive genetic panel analysis of tumor-derived circulating cell-free DNA in colorectal cancer patients.
Authors: Jeeyun Lee, Stefanie Mortimer, Gangwu Mei, Dragan Sebisanovic, LaiMun Siew, Helmy Eltoukhy, AmirAli Talasaz
Journal: Journal of Clinical Oncology (2014)

504 Background: Current approaches based on invasive biopsy genetic analysis can fail to capture an accurate picture of the real-time cancer profile due to limited spatial window of biopsy into residual disease throughout the body. Moreover, tumor rebiopsy has significant challenges to be widely used in practice for serial monitoring of disease progression or acquired resistance. Analysis of circulating tumor nucleic acids (ctDNA), on the other hand, presents a new tool for the monitoring and treatment of cancer. However, due to high-quality false positives in current NGS assays, the majority of studies on ctDNA have been limited to hotspot analyses, and typically only involve patients where ctDNA fractions are high (&gt;1-5%). Methods: We have developed a differentiated sequencing assay, Digital Sequencing Technology (DST) that enables detection of rare genomic abnormalities with ultra high-specificity and sensitivity. Our assay is able to eliminate the error and distortion created by sample-prep and sequencing processes in standard NGS workflows and produce near-perfect representations of all rare variants. Results: We have shown that in sequencing a comprehensive cancer panel of 80kbp in 0.1% cancer cell line titration samples, standard Illumina SBS generates many high-quality false positive variant calls in the range of 0.05-5%, while our assay resulted in highly sensitive and completely error-free variant calls across the entire panel. We then profiled ctDNA and matched primary tumor samples in more than 50 plasma samples collected from metastatic colorectal cancer patients. We found mutations in ctDNA with allele frequencies in the range of 0.05-40%. We established the concordance of ctDNA mutations with different clones within primary tumors. We further investigated the potential clinical usefulness of discordant mutants based on the treatment history of each patient. Conclusions: This work indicates the remarkable potential of using our assay in deep analysis of ctDNA, thereby allowing researchers and clinicians to comprehensively and non-invasively monitor the genetic dimension of cancer throughout the body.
Docetaxel, cisplatin, and capecitabine (DCX) as perioperative chemotherapy in gastroesophageal adenocarcinoma: A phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
Authors: P. C. Thuss-Patience, M. Kneba, R. Hofheinz, D. Arnold, A. Florschütz, S. Daum, A. Kretzschmar, L. Mantovani-Löffler, D. Bichev, G. Schumacher
Journal: Journal of Clinical Oncology (2010)

4116 Background: Perioperative chemotherapy with ECF or ECX is the standard approach in Europe for resectable gastroesophageal cancer. Docetaxel significantly improves efficacy if added to cisplatin and 5-FU as palliative treatment. To translate this efficacy into the curative approach this study investigates docetaxel (D), cisplatin (C) and capecitabine (X) in the perioperative setting. Methods: Pts with curatively resectable adenocarcinoma of the distal esophagus, gastroesophageal junction (GEJ) or stomach were treated with 3 preop and 3 postop cycles of chemotherapy: D 75 mg/m2 d1, C 60 mg/m2 d1 and × 1875 mg/m2/d d1-14, q3w. G-CSF was not routinely administered. Results: Accrual is completed with 50 pts included. Here we report on the protocol specified interim safety analysis of the preop chemo and surgery after 15 patients: male/female:15/0; med. age 65 yrs (45-73); esophagus/GEJ/stomach: 2/12/1 pts; ECOG PS 0/1/2: 7/8/0 pts; reduction of preop chemo was necessary in 7/15 pts; chemo toxicity, see Table. Resection ypR0: 14/15 pts. Surgical complications: 3/15 pts: anastomotic leakage with septic shock (1 pt), pneumonia and thrombosis (1 pt); urinary tract infection (1 pt); mortality: 0/50. Conclusions: DCX seems well tolerated and can safely be administered as preoperative chemotherapy as part of a perioperative regimen. Updated results will be presented. Toxicity of preop chemotherapy (worst grade per pt) (n;%) CTC 1 CTC 2 CTC 3 CTC 4 Nausea 9 (60%) 3 (20%) 1 (7%) - Vomiting 3 (20%) 2 (13%) - - Loss of appetite 4 (27%) 4 (27%) 1 (7%) - Diarrhea 3 (20%) 5 (33%) 1 (7%) 1 (7%) Asthenia 7 (47%) 7 (47%) 1 (7%) - Stomatitis 6 (40%) 5 (33%) - - Alopecia 4 (27%) 11 (73%) - - Neutrop. fever - - 3 (20%) - Hand-foot syndrome 8 (53%) 3 (20%) - - Nail changes 5 (33%) - - - Taste changes 10 (67%) 3 (20%) - - Paresthesia 9 (60%) 1 (7%) - - Central neurotoxicity 1 (7%) 1 (7%) - - Visual disturbances 1 (7%) 2 (13%) - - Hearing impairment 2 (13%) - - - Dizziness 7 (47%) 2 (13%) - - Leukopenia 3 (20%) 4 (27%) 7 (47%) 1 (7%) Neutropenia 2 (13%) - 2 (13%) 11 (73%) thrombocytes 5 (33%) 3 (20%) - - Anemia 4 (27%) 2 (13%) - 1 (7%) Other 6 (40%) 4 (27%) 2 (13%)* - * GI-bleed., sigma-perf. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Roche, sanofi-aventis Roche, sanofi-aventis
A proof-of-principle trial of bexarotene in patients (pts) with resectable non-small cell lung cancer (NSCLC)
Authors: J. R. Rigas, K. H. Dragnev, W. J. Petty, W. C. Nugent, V. A. Memoli, C. C. Black, L. D. Lewis, G. Loewen, A. Negro-Vilar, E. Dmitrovsky
Journal: Journal of Clinical Oncology (2005)

7136 Background: Bexarotene (Targretin) is a selective retinoid X receptor (RXR) agonist that appears to prolong survival in pts with NSCLC. To determine mechanisms of action, preclinical studies and a short-term, proof-of-principle clinical trial were performed. Methods: BEAS-2B immortalized human bronchial epithelial cells were treated with bexarotene and effects on EGFR and cell cycle regulatory proteins were determined by Western analyses. To evaluate bexarotene tissue pharmacokinetic (PK) and pharmacodynamic effects, 12 pts with pathologically confirmed stage I and II NSCLC were enrolled. Subjects were given 300 mg/m2/day of bexarotene orally for 7 to 9 days prior to surgical resection. Resected tumor tissue was evaluated for biomarker expression and tumor tissue bexarotene concentrations. Plasma bexarotene concentrations were measured at the time of resection. Biomarker changes were assessed immunohistochemically comparing pre- and post-treatment tissues by pathologists blinded to the tissue origin and PK measures. Results: In vitro studies revealed that bexarotene induced concentration-dependent repression of cyclin D1, cyclin D3, total EGFR, and phospho-EGFR. In the clinical trial, 6 pts had paired pre- and post-treatment tissues that were evaluable for changes in biomarker expression. Of these 6, 1 demonstrated repression of cyclin D1 as well as a reduction of proliferation rate measured by Ki-67. One case demonstrated repression of cyclin D3 without a substantial reduction in Ki-67. These 2 pts exhibited considerably higher tumor tissue bexarotene concentrations (range 107 - 159 ng/g) than did cases demonstrating no appreciable change in these biomarkers (range 3.7–74 ng/g). Conclusions: Bexarotene induces concentration-dependent repression of cyclin D1 and cyclin D3 in vitro. Repression of these proteins also occurs in certain clinical NSCLC cases treated with this agent. Our data are compatible with a non-linear relationship between tumor tissue bexarotene concentrations and the tumor biomaker pharmacodynamics. Support for this study was provided in part by Samuel Waxman Cancer Research Foundation, CA23108, and Ligand. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Ligand Ligand Ligand Bristol-Myers Squibb, Ligand
Randomized phase II study of IV topotecan versus CRLX101 in the second-line treatment of recurrent extensive-stage small cell lung cancer (ES-SCLC).
Authors: Thomas A. Hensing, Theodore Karrison, Edward Graeme Garmey, Meliessa G. Hennessy, Ravi Salgia
Journal: Journal of Clinical Oncology (2013)

TPS7610 Background: SCLC remains an area of high unmet medical need with an aggressive clinical course and &lt; 10% 5-year overall survival. In the U.S., topotecan (Hycamtin, GlaxoSmithKline) is the reference standard for treatment of chemotherapy (C)-sensitive (S) relapsed disease but its use remains compromised by toxicity. There currently exists no standard therapy for patients (pts) with C-resistant (R) disease (relapse occurring &lt; 60 days from last C). CRLX101 is a novel cyclodextrin-containing polymer conjugate of camptothecin (CPT) that self-assembles into nanoparticles and delivers sustained levels of active CPT into cancer cells while substantially reducing systemic exposure. In vitro and in vivo data suggest superior activity of CRLX101 compared to approved agents in multiple animal tumor models including SCLC. A monotherapy recommended phase 2 dose of 15 mg/m2 IV every 2 weeks has now been administered to over 150 cancer pts across five ongoing phase 2 clinical trials. Methods: This ongoing, randomized phase 2 clinical trial compares the effect on progression free survival (PFS) of 2nd-line treatment with IV CRLX101 (15 mg/m2 on days 1 and 15 every 28 days) to IV topotecan (1.5 mg/m2 on days 1-5 every 21 days) in pts with CS relapsed ES-SCLC. In parallel, the effect of 2nd-line CRLX101 on 3-mo. PFS rate of pts with CR relapsed ES-SCLC will be evaluated. Secondary objectives in both cohorts include evaluation of objective response rates (by RECIST v1.1), overall survival, and safety. In the randomized cohort, 112 pts (56/arm) will be enrolled in order to achieve 90% power to detect an improvement in median PFS from 3 to 5 mos. (HR=0.60). An interim analysis will be performed after 1/2 of expected PFS events have occurred. Pts with CR disease will all receive CRLX101 and the trial will employ a 2-stage design: 14 pts will be enrolled in stage 1 and the study will be terminated if ≤ 3 pts remain progression free at 3 mos. Otherwise, an additional 30 pts will be enrolled and if ³ 15/44 (34%) pts remain progression free at 3 mos., the drug will be considered worthy of further investigation. The first patient on this clinical trial was enrolled on January 30, 2013. Clinical trial information: NCT# is pending.
More space, less toxicity: Toxicity report of the first patients with prostate cancer treated in Heidelberg within the SpaceOAR hydrogel study.
Authors: M. Uhl, G. Habl, F. Sterzing, K. Schubert, J. Debus, K. Herfarth
Journal: Journal of Clinical Oncology (2011)

e15052 Background: Delivering high radiation dose to prostate while sparing adjacent OARs like the rectum and bladder is challenging. We evaluated acute and late genitourinary (GU) and gastrointestinal (GI) toxicities in prostate cancer patients within the SpaceOAR Hydrogel study. Methods: Overall, 20 patients with localized prostate cancer recieved definitive radiotherapy by tomotherapy from Oct. 2009 through Jan. 2011. Patients were treated within the SpaceOAR Hydrogelstudy, a prospective, multi-center, open-label trial. Before treatment planning the spacer gel, an absorbable polyethylene glycol (PEG) hydrogel spacer, which extends the space between anterior rectum wall and prostate, was perennially injected between rectum and prostate. Absorption time of the gel is about 6 months. The prescribed dose for the PTV (= [prostate+2/3 seminal vesicle] +margin of 5mm in all directions) was 78 Gy in 39 fractions. During the treatment and at 3, 6 and 12 months after treatment GI and GU toxicity was evaluated utilizing the grading developed by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC). Late rectal toxicity was also detected by using proctoscopy 12 months after the completion of irradiation and scored by using the Vienna rectoscopy score (VRS-Score). Results: The space between rectum and prostate could be increased an average of 10.48mm at base, 9.61mm at mid gland and 9.35mm at the apex. So far, 13 patients have finished irradiation. The incidences of acute Grade 1 GI or GU toxicities at the end of treatment were 7% and 46% in these patients. One patient showed Grade 2 GU toxicity (n=13). After 3 months follow up 27% had Grade 1 GU toxicity but no patient showed GI toxicity (n=11). After 6 month fu Grade 1 GU toxicity decrease to 25% (n=8). After one year (n=4) no patient showed late GI toxicities and 2 patients had Grade I GU toxicity No patient showed any problems of the rectal mucosa in the rectoscopy after 12 months (100% VRS score 0). Conclusions: Use of SpaceOAR Hydrogelis an easy and safe way to reduce toxicity to the rectum. Further evaluations with dose escalation to the prostate or application in other regions are possible.
A phase II trial of letrozole and trastuzumab for ER and/or PgR and HER2 positive metastatic breast cancer: Final results
Authors: P. K. Marcom, C. Isaacs, L. Harris, M. Bryant, A. Kommareddy, Y. Tao, G. Mann, M. J. Ellis
Journal: Journal of Clinical Oncology (2005)

596 Background: About 50% of HER2+ breast cancers exhibit ER coexpression and HER2 signaling may impair responses to endocrine treatment. A Phase II trial was therefore conducted to examine trastuzumab (TRAS) with letrozole (LET) in patients with ER and HER2 positive advanced disease. Methods: Postmenopausal women with ER and/or PR+, HER2 IHC 2–3+ or FISH+, measurable (WHO) metastatic breast cancer, ECOG 0–2 and LVEF greater than 50%. Loading dose TRAS within 28 days of initiating aromatase inhibitor (AI). Patients who had been started on other AI were switched to LET. The exclusion criteria were prior AI > 28 days, prior TRAS, cumulative anthracycline > 360 mg/m2, brain metastases, visceral crisis, prior radiation to only evaluable lesion, severe comorbidity or other malignancies and > 1 prior chemotherapy for metastatic disease. All responses at 3 months were confirmed with a second CT scan at six months. Results: 32 patients were accrued. The majority had visceral metastases (72%). Twenty tumors were either HER2 3+ and/or FISH+, the rest were either 2+ to 3+ or 2+. 30 were ER+ and 2 ER-, PgR+. Twenty-six had received prior tamoxifen the remaining six were endocrine-therapy naïve. Of 27 patients evaluable for response at the time of this report, there were 2 CR, 5 PR, 7 SD (at 24 weeks) and 13 PD giving an objective RR of 25% and clinical benefit rate (response or stable disease) of 52%. Median duration of response was 73 weeks (range 47 to 180+). The median overall TTP was 32 weeks (range 6 to 180+ weeks). Of the remaining 5 patients, 2 have been followed for less than 24 weeks, 1 came off study early for toxicity and 2 withdrew consent before response could be assessed. 7 patients are still on therapy. The toxicities were mainly grade 1 to 2. The only serious complication was cardiomyopathy in a patient with prior doxorubicin and left chest wall irradiation. Conclusions: TRAS with LET was well-tolerated and active with durable responses in about 1 in 4 patients. However, despite dual targeting, early progression occurred in 1 in 2 patients suggesting TRAS and AI have common resistance pathways. A final update and a central HER2 FISH analysis will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Genentech, Novartis Genentech, Novartis
External validation of current nomograms in invasive bladder cancer.
Authors: G. Gakis, T. Todenhoefer, M. Renninger, C. Schwentner, A. Stenzl
Journal: Journal of Clinical Oncology (2011)

e15184 Background: To externally validate whether published bladder cancer nomograms, i.e. The Bladder Cancer Research Consortium (BCRC) and the International Bladder Cancer Nomogram Consortium (IBCNC) are superior to the Tumor-Node-Metastasis based AJCC Staging System for predicting bladder cancer recurrence and are therefore feasible for routine use. This is more important since, as although these nomograms had a high accuracy by internal validation, they derive mainly from high-volume U.S. centers and have not been sufficiently externally validated so far and, thus, their general applicability remains unproven. Methods: This analysis was based on a consecutive series of 275 patients treated with radical cystectomy with pelvic lymphadenectomy for invasive bladder cancer between 1999-2010. The median follow-up for patients alive at last CT-scan was 27 months (6-95). Patients were excluded from analysis if CT-scan was not performed on a regular basis during follow-up period. The expected recurrence rates according to the nomograms and AJCC system were calculated. The independent prognostic value of each nomogram was assessed using Cox-regression analysis. The predictive accuracy of the models was calculated by the concordance index. Results: The median age at radical cystectomy was 66 years (range: 40-86). The BCRC (c-index: 0.863) and IBCNC nomograms (c-index: 0.847) showed an overall improvement in the predictive accuracy of disease recurrence of 3.4% and 1.8%, respectively, as compared to TNM stage-based predictions (c-index: 0.829). The BCRC nomogram performed significantly better than the IBCNC nomogram and TNM classification (p=0.02). Conclusions: The BCRC and IBCNC nomograms provide improved predictions for disease recurrence in invasive bladder cancer as compared to the TNM based AJCC predictions when applied to an external cohort of patients from a European center. Therefore, the routine use of both nomograms in invasive bladder cancer can be supported on a sound basis. However, in this series, the consideration of selective prognostic clinical and pathological parameters, as defined in the BCRC nomogram, predicted the risk of recurrence more accurately.
Impact of pulmonary vascular volume on mortality in IPF: is it time to reconsider the role of vasculature in disease pathogenesis and progression?
Authors: Ermanno Puxeddu, Francesco Cavalli, Gabriella Pezzuto, Elisa Teodori, Paola Rogliani
Journal: European Respiratory Journal (2017)

The article by Jacob et al . [1], reporting a computer-based computed tomography (CT) approach able to provide a precise quantification of disease extension in idiopathic publmonary fibrosis (IPF) patients by means of specific computer algorithm, CALIPER, is very interesting. Vascular disarrangement as a possible central event in disease progression in idiopathic pulmonary fibrosis (IPF) <http://ow.ly/hln3307TyBk>
Topical application of hangeshashinto (TJ-14) in the management of chemotherapy-induced oral mucositis: A preliminary study.
Authors: T. Kono, M. Satomi, Y. Ebisawa, N. Chisato, M. Suno, T. Asama, K. Matsubara, H. Furukawa
Journal: Journal of Clinical Oncology (2011)

603 Background: Oral mucositis is a common toxicity associated with cytotoxic chemotherapy used for cancer treatment and results in severe discomfort and impairs patients' ability to eat, swallow, and talk. The treatment of chemotherapy-induced oral mucositis is not well established. The cyclooxygenase pathway mediates tissue injury and pain through upregulation of pro-inflammatory prostaglandins. Recent study showed that one of the Japanese traditional medicines (kampo), hangeshashinto (TI-14), may be useful for periodontal disease via downregulation of pro-inflammatory prostaglandins in human. The aim of this study was to evaluate the effect of TJ-14 on chemotherapy- induced oral mucositis. Methods: Fourteen patients with chemotherapy-induced oral mucositis during mFOLFOX6 or FOLFIRI treatment for requiring to the metastasis of advanced colorectal cancer were received topical application of TJ-14. Topical TJ-14 was applied to the oral mucositis three times a day. Patients were asked to make 50 mL of TJ-14 solution (2.5 g) with a tap water and were advised to rinse the TJ-14 solution on the oral mucosa for 10 seconds and then to spill it. Additionally, TJ-14 was topically applied with a cotton pellet on the oral mucositis. The above treatment was advised throughout the course of chemotherapy. Patients were evaluated for the oral mucositis using the Common Terminology Criteria for Adverse Events (CTCAE) version 4 before and after 2-weeks TJ-14 treatment. Results: Thirteen of the fourteen patients (92.8 %) responded to the TJ-14 therapy. There was significant reduction in the grade 3/4 mucositis from 3.2 to 1.8 (p=0.02) as well as in the grade 1/2 mucositis from 1.6 to 0.6 (p=0.034). There is no patient showed worse than before. The compliance of TJ-14-treatment was good. Conclusions: Topical application of TJ-14 may have therapeutic effects on chemotherapy-induced oral mucositis via downregulation of pro-inflammatory prostaglandins. No significant financial relationships to disclose.
Identification of Immunodominant Alloreactive T-Cell Epitopes on the Jka Red Blood Cell Protein Inducing Either Th1 or Th2 Cytokine Expression: Role of DRB1*01 Molecules in Jka Peptide Presentation.
Authors: Helene Ansart-Pirenne, Dominique Zeliszewski, Ketty Lee, Stephanie Martin-Blanc, Philippe Rouger, France Noizat-Pirenne
Journal: Blood (2004)
Stereotactic body radiosurgery versus intensity modulated radiotherapy for prostate cancer: Comparison of toxicity.
Authors: James B. Yu, Laura D. Cramer, Jeph Herrin, Pamela R. Soulos, Arnold L. Potosky, Cary Gross
Journal: Journal of Clinical Oncology (2014)

89 Background: Stereotactic body radiosurgery (SBRT) is a recent innovation in the treatment of prostate cancer that has begun to disseminate into national practice. Comparative studies have yet to be performed and little is known about the cost to Medicare or difference in toxicity between SBRT and intensity modulated radiation therapy (IMRT). Methods: We performed a retrospective study using a national sample of all Medicare beneficiaries age 66 or older who received SBRT or IMRT as primary treatment for prostate cancer during 2008 through 2011. Each SBRT patient was matched to two IMRT patients with similar follow-up (6, 12, or 24 months) and clinical and demographic characteristics. Cost of treatment was calculated for matched patients with six months of follow-up. We assessed toxicity by searching Medicare claims for procedure or diagnosis codes indicative of treatment related toxicity. We used a random effects model to compare the likelihood of genitourinary (GU), gastrointestinal (GI), and other toxicity from 0 to 6, 0 to 12, and 0 to 24 months after the initiation of SBRT or IMRT treatment. Results: The study sample consisted of 1,335 SBRT patients matched to 2,670 IMRT patients. The mean cost of SBRT was $11,668 compared to $15,838 for IMRT. At all follow-up points, SBRT patients were significantly more likely to experience GU toxicity. In the first six months after treatment initiation, 15.6% of SBRT versus 12.6% of IMRT patients had claim indicative of a GU complication (p=.009). In the first 12 months, 27.1% of SBRT versus 23.2% of IMRT had a GU complication (p=.014). Finally, from 0-24 months, 43.9% of SBRT versus 36.3% of IMRT had a GU complication (p=.001). The higher rate of GU toxicity after SBRT was largely due to an increase in urethral strictures and bladder outlet obstructions and urinary incontinence or obstruction. Conclusions: In this retrospective observational study, while SBRT was associated with lower costs, there was a greater rate of urinary obstructive toxicity for patients undergoing SBRT compared to IMRT at all time points studied. Whether this increased rate of complication is offset by a higher cure rate or lower cost should be the subject of further study.