tbuckley/cabot-search huggingface dataset:
Validating the prognostic relevance of initial change in tumor size using a series of therapeutic regimens for patients with metastatic colorectal cancer (mCRC).
Authors: Ulrich Robert Mansmann, Ruediger P. Laubender, Clemens Albrecht Giessen, Ute Sartorius, Volker Heinemann
Journal: Journal of Clinical Oncology (2012)

580 Background: Piessevaux et al. (ESMO 2010, Abstr. #596P) proposed a decrease in tumor size of 20% at week 8 following 1 st -line therapy for mCRC as a predictor of clinical outcome (PFS and OS). Based on the results of a single study Suzuki et al. (Ann. Oncol. 2011) also claimed that change in tumor size at the first follow-up CT scan was strongly prognostic for PFS and OS in mCRC. It is of interest to validate these findings in different treatment regimens. Methods: Based on data from 4 randomized trials (FIRE-1, n = 479; CIOX, n = 185; OPUS, n = 337; CRYSTAL, n = 1198) a total of 6 treatment regimens were studied (mIROX/FUFIRI, CAPIRI/CAPOX + cetuximab, FOLFOX4 + cetuximab, FOLFOX4, FOLFIRI + cetuximab, FOLFIRI). A joint model was used to quantify the non-linear, J-shaped individual relationships between time and largest diameter (LD) and incorporate them into the formal risk calculation for PFS and OS. The first radiological tumor assessment was performed weeks 7-9 after the start of treatment and relative tumor shrinkage compared to baseline evaluated. Results: All 6 groups showed a consistent pattern for PFS and OS. Distinctive shrinkage week 8 (weeks 7-9) was associated with an improved individual prognosis (p&lt;0.0001 in each group). This was even more pronounced for larger sized tumors (LD &gt;100 mm) at baseline (p&lt;0.01 in each group). Distinctive individual shrinkage for a corresponding treatment was defined as shrinkage exceeding the 8 week shrinkage of its mean tumor kinetics. Distinctive shrinkage for the 3 combination chemotherapy regimens was observed with individual shrinkage above 16%, 23%, or 26%. For the 3 combination chemotherapy regimens + cetuximab distinctive shrinkage was reached if individual shrinkage was greater than 21%, 24%, and 29% respectively, independent of KRAS status. Predictivity has not yet been examined. Conclusions: Our results validate the prognostic relevance of the 20% cut-off for shrinkage at week 8. Early tumor shrinkage is a promising surrogate for PFS and OS using a variety of therapeutic regimens for mCRC. These data may serve as a basis for modifying the widely adopted RECIST criteria in favor of modified response evaluation criteria.
Risk of CKD after serial intravenous contrast exposure after nephrectomy for kidney tumors.
Authors: Chad Christian Cherington, Mark Tyson, Erik P. Castle, Thai Huu Ho
Journal: Journal of Clinical Oncology (2016)

624 Background: The risk of intravenous contrast induced nephropathy (CIN) is not well described in post-nephrectomy or metastatic kidney cancer. Patients with nephrectomies and tumors of the kidney frequently have CKD and often require serial contrast imaging placing them at risk for CIN. Methods: This is a retrospective review of 292 patients metastatic RCC and/or with partial or radical nephrectomies (PN or RN) for kidney tumors at Mayo Clinic Arizona or Florida from 2010 through 2014. Results: We found 207 patients received at least one contrast scan, of whom 99 had metastatic RCC, 104 had local RCC and 4 had oncocytoma. At baseline (pre-nephrectomy) 41% (46/113) and 15% (11/76) of RN and PN respectively had CKD stages 3-5 and with at least 3 months follow up after both nephrectomy and contrast exposure 61% (68/113) and 33% (25/76) RN and PN developed CKD stages 3-5 respectively. The median contrast exposure scans were 4 (range 1-30 scans) with a median follow up of 26 months (range 1-96 months). In all patients with at least one contrast exposure, the median change in creatinine and GFR from baseline was 0.2 mg/dL and 8 ml/min respectively. Excluding those with bilateral nephrectomy there were 8 (8/207 = 4%) CIN events, 6/113 had a radical nephrectomy and 2/76 with 1 partial nephrectomy and 1 aborted nephrectomy (P value 0.37). Of these patients 5 (5/99 = 5%) had metastatic RCC and 3 (3/104 = 3%) local RCC. The median contrast exposure scans for patients with CIN were 8 (range 3-12) and median follow up was 31 months (range 4-47 months). Three patients all with metastatic RCC developed acute kidney injury from CIN requiring dialysis and died of complications in part related to CIN during that hospital stay or soon after. Two other patients developed CKD stage III after CIN events and 3 patients (including the one with a partial nephrectomy) showed no significant change in GFR after CIN. Conclusions: In this retrospective analysis, CIN after nephrectomy or metastatic RCC contributed to acute renal failure with 3 deaths and 2 patients developing CKD stage III. Further analysis is required to determine what risk factors for CIN in this population.
Impact of use of specific Web-based “search engines” and “search strategies” on cancer information obtained by patients and the public
Authors: M. Markman, T. M. Markman
Journal: Journal of Clinical Oncology (2005)

6060 Background: As the internet has become a primary source of cancer-related information, the approach employed to Web-based data-gathering may have a substantial impact on this process. Methods: Several “search strategies” using 4 popular “search engines” (Google, Yahoo, MSN, AOL) were explored over a 3-day period (11/17–19/2004). Results: There was a 27-fold diference in the highest vs. lowest number of “cancer” sites identified by the search-engines, with considerable variation also noted in the total number of web-sites identified by the search-engines with the identical search-strategy (“breast cancer”: 200,000 vs. 7,700,000). Relatively minor changes in a specific search-strategy in an individual search-engine resulted in major changes in identified web-sites (“endometrial cancer” 300,000 vs. “endometrial adenocarcinoma” 40,000). For the more common malignancies (e.g., breast cancer) there were reassuring similarities between the initial web-sites listed by the different search-engines, but with rarer cancers there appeared to be greater variability in this initial listing. Further, within an individual search-engine, a search-strategy that identified an uncommon entity (e.g., “endometrial sarcoma”) provided a different listing from that obtained with a less specific search-strategy (e.g., “endometrial cancer”). Additional findings included: (a) the “top” listings in individual search-engines may change daily, often based on a report in the non-medical press; (b) commercial advertising strategies varied greatly between the search-engines; (c) for rarer malignancies, non-U.S. based Internet sites were more commonly identified in the “top” listings. Conclusions: There remains limited understanding of the process by which cancer patients, their families, and the public process the massive quantities of raw data available on the Internet. It is imperative that oncologists become proactive in their approach to this rapidly expanding technology, and assist patients in their “search” for web-based cancer-related information. No significant financial relationships to disclose.
Location of local recurrence after MRI-guided partial prostate brachytherapy targeting only the peripheral zone: Implications for focal therapy.
Authors: Konstantin Kovtun, Tobias Penzkofer, Neha Agrawal, Tina Kapur, Andriy Fedorov, Robert A. Cormack, Anthony Victor D'Amico, Clare M. Tempany, Paul Linh Nguyen
Journal: Journal of Clinical Oncology (2013)

149 Background: Prostate cancer local recurrences usually occur at the same site as the dominant primary tumor in patients treated with radiation therapy to the whole gland. We characterized location of local recurrences in patients who were treated with MRI Guided Partial Brachytherapy in which only the peripheral zone was targeted. Methods: We retrospectively reviewed ten patients with initial cT1c, Gleason score 3+4 or less prostate cancer who developed biopsy proven local recurrences and had available imaging after MRI Guided Partial Brachytherapy targeting the peripheral zone from 1998 to 2006. All 10 patients had 1.5T endorectal coil MRI at diagnosis, performed primarily for staging and not for tumor localization, while at recurrence 8 had 3T endorectal coil MRI and 2 had 1.5T endorectal coil MRI. Scans consisted of at least T1 and T2 sequences. Two radiologists (C.T. and T.P.) blinded to clinical data reviewed diagnosis MRI scans together and quantified likelihood of tumor on a 1 to 5 scale in each section of an eight part prostate in both pre-treatment and recurrence scans. Local recurrence was judged to be in the same location as the baseline tumor if at least 50% of the tumor location overlapped. Results: Only 3 of 10 patients had local recurrences at the same location as the baseline tumor with a mean overlap of 64%. 7 of 10 patients had local recurrences at a different location with a mean overlap of 5%. 5 of 10 patients had recurrences in the central zone of the prostate which did not definitively show tumor on review of the initial 1.5T staging scan. Conclusions: After MRI-guided brachytherapy targeting only the peripheral zone in men initially staged with 1.5T MRI, 50% of the local recurrences occurred at the non-targeted central zone, raising the possibility that focal therapy directed only at the dominant tumor will result in increased out-of-field recurrences. Whether the superior ability of modern 3T multiparametric MRI to detect and precisely localize occult prostate cancer foci will reduce this risk is the subject of current study.
Anti-miR-135b in colon cancer treatment: Results from a preclinical study.
Authors: Nicola Valeri, Chiara Braconi, Pierluigi Gasparini, Sergei Grivennikow, Jonathan R Hart, Alessio Paone, Francesca Lovat, Muller Fabbri, Roberta Gafa', Gerard Nuovo, Giovanni Lanza, Wendy Frankel, Peter K Vogt, Joanna Groden, Michael Karin, Carlo M. Croce
Journal: Journal of Clinical Oncology (2012)

457 Background: MicroRNAs (miRs) are small non coding RNAs involved in cell homeostasis. miRs are deregulated in colorectal cancer (CRC). Our study aimed at identifying miRs with a driver role in carcinogenesis altered by similar mechanisms in both human and mouse CRC. Goal of the study was to use CRC mouse models for the pre-clinical development of anti-miRs as therapeutic drugs. Methods: Azoximetane (AOM)/Dextran-Sulfate (DSS) treated mice or CDX2-CRE/APC -/- mice were used to study inflammation-associated and sporadic APC-related CRC. Human Inflammatory Bowel Disease associated (n=30), and sporadic (n=90) CRC with their matched normal tissues were collected according to Good Clinical Practice recommendation and subjected to RNA extraction using Trizol. miR and gene expression profiling was assessed by nCounter technology (Nanostring Seattle). Anti-miR-135b and scrambled probes for in vivo studies were synthesized by Girindus. Results: miRs profiling from AOM/DSS and CDX2-CRE/APC -/- CRC. revealed that miR-135b is one of the most up-regulated miRs in both models. In humans miR-135b over-expression was found in both IBD and sporadic CRC and was associated with reduced Progression Free Survival and Overall Survival in CRC patients. Molecular studies in Mouse Embryo Fibroblast and human CRC cell lines highlighted the role of two major pathways in the upstream activation of miR-135b: APC-β-Catenin and SRC-PI3K. MiR-135b up-regulation resulted in reduced apoptosis and increased invasion and metastasis due to the down-regulation of TGFRB2, DAPK1, APC and HIF1AN. Silencing of miR-135b in vivo reduced tumor multiplicity and tumor load in the AOM/DSS CRC model. Mice treated with anti-miR-135b showed well differentiated tumors and microacinar pattern while tumors in the control groups showed low differentiation and adenomatous pattern. Conclusions: Our data suggest that miR-135b is a key molecule whose activation is downstream of oncogenes and oncosuppressor genes frequently altered in CRC. Our study defines specific pathways that converge on the activation of the same microrna. The “in vivo” silencing of miR-135 shows preclinical efficacy with low toxicity and represents the first in vivo study for the use of antimiRs in CRC treatment.
Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D
Authors: Shemsi Demolli, Anuradha Doddaballapur, Kavi Devraj, Konstantin Stark, Yosif Manavski, Annekathrin Eckart, Christoph M. Zehendner, Tina Lucas, Thomas Korff, Markus Hecker, Steffen Massberg, Stefan Liebner, David Kaluza, Reinier A. Boon, Stefanie Dimmeler
Journal: Cardiovascular Research (2017)

Vessel maturation involves the recruitment of mural cells such as pericytes and smooth muscle cells. Laminar shear stress is a major trigger for vessel maturation, but the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs, which post-transcriptionally control gene expression. The aim of the present study was to unveil the mechanism by which shear stress-regulated microRNAs contribute to vessel maturation.
The effects of targeting stromal and tumor cell platelet-derived growth factor receptor (PDGFR) in non-small cell lung cancer (NSCLC).
Authors: D. E. Gerber, P. Gupta, M. T. Dellinger, J. Toombs, I. Valencia, M. Peyton, N. Loizos, R. A. Brekken
Journal: Journal of Clinical Oncology (2011)

10533 Background: Platelet-derived growth factor receptor (PDGFR) has emerged as a potential target for cancer therapy. In non-small cell lung cancer (NSCLC), PDGFR is expressed frequently by stromal cells in the tumor microenvironment and, in a subset of tumors, by cancer cells themselves. However, most recent research has focused exclusively on cancer cell PDGFR, overlooking the effect of PDGFR inhibition in the tumor stroma. Methods: To evaluate the effects of targeting stromal PDGFR, which has roles in fibroblast activation, local tissue invasion, modulation of tumor interstitial pressure, and angiogenesis, we capitalized on the xenograft model and the availability of species-specific anti-PDGFRα antibodies. In this model, IMC 3G3, a fully human anti-human PDGFRα monoclonal antibody, inhibits cancer cell PDGFRα; IMC 1E10, a fully human anti-mouse PDGFRα monoclonal antibody, inhibits stromal PDGFRα. Results: We confirmed species specificity of IMC 3G3 and IMC 1E10 via (1) patterns of immunoreactivity with human PDGFR-positive cancer cells and mouse PDGFR-positive fibroblasts, (2) inhibition of murine fibroblast PDGFRα activation by IMC 1E10 but not by IMC 3G3, and (3) in vitro inhibition of proliferation of human PDGFR-positive cancer cells by IMC 3G3 but not by IMC 1E10. As expected, only rare NSCLC featuring high-level PDGFRα expression responded to inhibition of cancer cell PDGFRα. However, in vivo, stromal PDGFRα targeting inhibited the growth of PDGFRα-negative NSCLC xenografts and enhanced the effect of chemotherapy. Conclusions: IMC 3G3 and IMC 1E10 exhibit species-specific PDGFR targeting, allowing individual evaluation of tumor- and stromal PDGFRa inhibition. Stromal PDGFR inhibition may represent a means for enhancing control of lung cancer growth in some patients, independent of tumor cell PDGFR expression. Because PDGFR is widely expressed in NSCLC stromal cells, these findings suggest that stromal PDGFR inhibition could benefit a large proportion of these patients.
Incidence of serious bleeding events (sBE) in patients (pts) with metastatic colorectal cancer (mCRC) receiving bevacizumab (BV) as part of a first-line regimen: Results from the BRiTE observational cohort study (OCS)
Authors: P. J. Flynn, M. M. Sugrue, S. Feng, D. M. Purdie, A. Grothey, D. J. Sargent, J. D. Berlin, F. F. Kabbinavar, W. Dong, M. F. Kozloff
Journal: Journal of Clinical Oncology (2008)

4104 Background: BV prolongs overall survival and progression-free survival when added to chemotherapy (CT) for 1st-line and 2nd-line treatment of pts with mCRC. Grade 3–4 BE occurred in previous controlled trials (RCTs) of BV at a rate of 3.1%-5%. Generalization of these findings is limited because pts on full dose anticoagulation (FDAC) or on doses of aspirin (ASA) > 325 mg/day were excluded from RCTs with BV. In the BRiTE OCS, the rate of serious grade 3–4 bleeding events (sBEs) was determined and the influence of underlying factors that may increase the risk of bleeding in general, including anticoagulation (AC) and antiplatelet (AP) therapies, was assessed. Methods: Pts and methods for BRiTE have been described (Kozloff, ASCO 2006; A3537). Data on sBE and use of AC (FDAC or therapeutic) or AP (including ASA) therapies were collected. Multiple logistic regression was used to identify factors significantly associated with occurrence of sBEs. Results: Of 1,953 mCRC pts treated with 1st-line BV/CT, there were 52 sBEs reported from 48 (2.5%) pts as at June 20, 2007 (median follow-up of 20.8 mo). The median time to a sBE from the first BV dose was 6 months (range, 0.1–31.7). The most common site of sBE was gastrointestinal/rectal (55.8%). Pts with primary tumor of the rectum had a higher rate of sBE than pts with primary tumor of the colon (4.0% vs 2.0%). The rate of sBE was 4.5% (17/382) in pts on chronic AP therapy, 6.0% (8/133) in pts on FDAC therapy, and 2.9% (9/309) in pts on prophylactic AC therapy. The sBE rate in pts not on AC or AP therapy was 2.2% (29/1,337). The incidence of sBE in pts on both AC and AP therapy was 7.2% (15/208). Conclusions: The overall rate of sBE was low in BRiTE and similar to previous reports of all Grade 3–4 BE in pivotal trials with BV, despite allowance of FDAC and chronic AP therapy in BRiTE. Rates of sBE were not different between pts on prophylactic AC and pts not on AC or AP tx. Rates of sBE were also low in pts on FDAC tx in BRiTE. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc., Roche, sanofi-aventis Genentech, Inc. Genentech, Inc., Roche, sanofi-aventis
Perioperative outcomes for robotic total mesorectal excision after preoperative chemoradiation for rectal cancer.
Authors: Ibrahim Nassour, Nicholas Borja, Ali El-Mokdad, Hannah Hirsch, Jeffrey John Meyer, Patricio Polanco, Glen C. Balch
Journal: Journal of Clinical Oncology (2016)

732 Background: Laparoscopic total mesorectal excision (TME) after preoperative chemoradiation therapy (P-CRT) for mid to low rectal cancer was shown to be safe and feasible by a recent randomized trial (COREAN trial). However, the safety and short-term efficacy for robotic assisted laparoscopic TME has not been demonstrated. This study is a review of the perioperative outcomes of robotic TME after P-CRT for mid to low rectal cancer at our institution. Methods: All patients that underwent robotic TME after P-CRT for rectal cancer were retrospectively reviewed in our prospectively maintained, IRB-approved surgical oncology database. All relevant demographic, clinical, operative, pathology and perioperative data were analyzed. These were compared to the COREAN trial results. Results: From 2010 to 2014, 42 patients underwent robotic TME for rectal cancer after P-CRT. Mean patient age was 60+/-13. Robotic low anterior resections (R-LAR) were performed in 69% and 31% had a robotic abdominoperineal resection (R-APR). A majority were obese patients as 74% had a BMI ≥ 25, and 50% had an ASA ≥ 3. Conversion to open rate was 9.5% (n = 4) but 3 of these were within the first 8 cases. Median estimated blood loss was 105 ml (50-400 ml). The 30-day major complication rate (Clavien III-IV) was 11.9% (n = 5) and 90-day rate was 14.2% (n = 6). One patient (2.4%) had an anastomotic leak. There were no mortalities within 90-days from operation. Median length of stay was 7 days (6-12 days). Pathological complete response was 19% while 24% had no response. The average number of lymph nodes harvested was 14.2+/-9.5. The circumferential resection margin was negative in 95.2% (n = 40) of patients. Conclusions: As compared to laparoscopic TME patients in the COREAN trial, the robotic patients in our series were more obese and had a higher ASA classification. Our conversion rate was slightly higher, but this was related to the learning curve. All other short-term outcomes were similar. It appears that robotic TME is safe and feasible after P-CRT even among a more obese and higher risk population than previously reported in large series.
Phase I trial of cremophor-free, polymeric micelle formulation of paclitaxel with carboplatin in patients with advanced epithelial ovarian cancer.
Authors: Y. Kim, S. W. Lee, S. Kim, Y. Kim, B. Kim, S. Kang
Journal: Journal of Clinical Oncology (2011)

e15533 Background: Cremorphor EL, used to enhance drug solubility, may add to paclitaxel’s toxicities such as hypersensitivity reactions or peripheral neuropathy. Genexol-PM is a Cremophor-free, polymeric micelle formulation of paclitaxel. It has been proven to have better tolerability from several clinical trials in solid tumors. The primary objective of this phase I trial is to determine the maximum tolerated dose (MTD) of Genexol-PM as a combined chemotherapy with carboplatin in patients with advanced epithelial ovarian cancer (EOC). The secondary objectives are to determine the dose limiting toxicities (DLT) and evaluate the response. Methods: Eighteen patients with stage IIIB-IV epithelial ovarian cancer were entered into the study. Genexol-PM was intravenously administered over 3 hours every 3 weeks with a constant carboplatin (AUC 5). The premedication was 100mg hydrocortisone and 45.5mg pheniramine maleate at 30 minutes before the infusion of Genexol-PM. The Genexol-PM dose was escalated from 220 mg/m2 (level 1) to 300 mg/m2 (level 3). Results: Seventeen patients were evaluable for toxicity and response. Acute hypersensitivity reaction was not observed. There were severe toxicities in 20.63% and life-threatening toxicities in 7.83%. Neutropenia, neuropathy and myalgia were the most common toxicities. Severe and life-threatening toxicities occurred in all 3-dose patients, respectively, they were mainly at 260 mg/m2 and 300 mg/m2; however they were tolerated and absolutely recovered. One DLT of myalgia was observed at 300 mg/m2, however, MTD was not reached by the level 3 (300 mg/m2). Additionally, the response rate was 94.12% (16/17) and was not different according to the dosage (p=1.00). Only one patient showed a progressive disease and there was no death related to the disease or treatment. Conclusions: Genexol-PM with carboplatin is well tolerated and effective in patients with advanced EOC and the recommended dosage for phase II trial is 260 mg/m2. Genexol-PM is considered to be superior to conventional paclitaxel because of the possibilities of delivering higher paclitaxel dose without additional toxicities.