tbuckley/cabot-search huggingface dataset:
Physician needs and preferences for information about long-term follow-up and care of survivors of childhood cancer.
Authors: Melanie Keats, Kelsey Shea, Louise Parker, Samuel A. Stewart, Annette Flanders, Mark L. Bernstein
Journal: Journal of Clinical Oncology (2016)

66 Background: The treatments that childhood cancer survivors (CCS) undergo can lead to an increased risk of other health problems later in life, and risk-based follow-up care is necessary throughout their lifetime. Regrettably, family physicians caring for CCS often report having no record of their patients’ past disease, treatment history, or need for follow-up. As the large majority of CCS will transition from specialized pediatric oncology care to generalized adult care in the community, detailed treatment summaries and Survivorship Care Plans (SCP) are needed to ensure that both the survivor and their care providers are adequately informed of the survivors diagnosis, treatment(s), potential risk for late effects, and long-term surveillance and healthcare needs. This qualitative study sought to explore the needs, preferences, and the perceived utility of SCP for family physicians (FP) caring for CCS. Methods: Using publically available Children’s Oncology Group guidelines, a de-identified sample SCP indicating the diagnosis, treatment(s) received, and follow-up recommendations for a common childhood cancer diagnosis was automatically generated using a newly developed algorithm and patient data from the Cancer in Young People – Canada registry. Semi-structured telephone interviews with six FP that have a known CCS in their practice were then used to gain insight into the FP perceived role in the long-term management and care of CCS, their cancer information needs, concerns with communication, their perceived utility of the SCP, and preferred format(s) for receiving the SCP. The constant comparative method was used for thematic analysis. Results: The key themes emerging from the six completed interviews include a lack of confidence among FP in their ability to care for CCS and a need for additional knowledge and resources. FP also identified psychological barriers to cancer care discussions with CCS and identified a patient need for greater psychological support. Overall, SCP were viewed as helpful. Conclusions: SCP are perceived to be of benefit to FP of CCS as they serve to increase their knowledge of patient diagnosis, treatments received, and suggested risk-based follow-up.
Phospholipid ether analogs for the detection of colorectal cancers.
Authors: Dustin A. Deming, Molly Maher, Alyssa A. Leystra, Joe Grudzinski, Linda Clipson, Dawn Albrecht, Mary Kay Washington, Kristina Matkowskyj, Christopher J. Pazoles, Lance T. Hall, Sam Joseph Lubner, Jamey Weichert, Richard B. Halberg
Journal: Journal of Clinical Oncology (2014)

486 Background: The treatment of pts with localized colorectal cancer (CRC) depends on the resection of the primary tumor with adequate margins and sufficient lymph node sampling. A novel imaging agent that accumulates in CRCs and regional lymph nodes is needed. Novelos, Inc. has developed a new phospholipid ether analog therapeutic and diagnostic platform. Molecules from this platform have shown to preferentially accumulate in multiple cancer types. CLR1502 is a near-infrared fluorescent labeled phospholipid ether analog, whereas 124/131 I-CLR1404 is under clinical investigation as a PET tracer or a therapeutic agent imaged by SPECT. We investigated the use of CLR1502 for the detection of intestinal cancers in a murine model and 131 I-CLR1404 in human metastatic CRC. Methods: Mice with loss of APC and a constitutively active PI3K in the distal small intestine and colon develop multiple intestinal tumors ranging from benign adenomas to locally advanced adenocarcinomas. These mice were injected intravenously with CLR1502. At necropsy 96 hours after injection, the intestine was removed and tumors were analyzed using a Spectrum IVIS Caliper Life Science Imager and Fluobeam Handheld Imager. The intensity of the fluorescent signal was correlated with the histological characteristics for each individual intestinal tumor. In addition, SPECT imaging with 131 I-CLR404 was performed as part of a clinical trial in patients with advanced solid tumors. Results: Colon adenocarcinomas demonstrated increased accumulation of CLR1502 compared to non-invasive lesions (total radiant efficiency: 1.76E+10 vs 3.27E+9 respectively, p=0.027). Metastatic spread to the mesentery and mesenteric lymph nodes was detected with near-infrared fluorescent imaging. Similarly, 131 I-CLR1404 was shown to accumulate in metastatic tumors in a patient with colorectal adenocarcinoma. Conclusions: CLR1502 and 124/131 I-CLR1404 hold great promise for enhancing our ability to treat CRC. CLR1502 may enhance our ability to properly resect CRCs through better localization of the primary tumor and improve staging through the identification of involved lymph nodes. 124/131 I-CLR1404 has the advantage of detecting distant disease.
BT062, an Antibody-Drug Conjugate Directed Against CD138, Given Weekly for 3 Weeks in Each 4 Week Cycle: Safety and Further Evidence of Clinical Activity
Authors: Leonard T Heffner, Sundar Jagannath, Todd M Zimmerman, Kelvin P Lee, Jacalyn Rosenblatt, Sagar Lonial, Robert J. Lutz, Niklas Czeloth, Frank Osterroth, Markus Ruehle, Michelle A. Beelitz, Andrea Wartenberg-Demand, Thomas Haeder, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Blood (2012)
Analysis of fiducials implanted during endoscopic ultrasound (EUS) for locally advanced rectal cancer patients receiving high-dose rate endorectal brachytherapy (Endo-HDR).
Authors: Shalini Moningi, Ashkan Malayeri, Susan Gearhart, Jonathan Efron, Elizabeth C. Wick, Nilofer Saba Azad, Luis A. Diaz, Elwood Armour, Yi Le, Eun Ji Shin, Joseph M. Herman
Journal: Journal of Clinical Oncology (2014)

655 Background: Rectal cancer affects over 40,000 patients in the US per year. The current standard of care for patients with localized rectal cancer is neoadjuvant radiation therapy with concurrent chemotherapy (NCRT) followed by surgery; however, it has shown no proven survival benefit for locally advanced rectal cancer patients. Preliminary results show that a short course of radiation therapy, using high-dose rate endorectal brachytherapy (Endo-HDR), may be as effective with less toxicity and delay to time of surgery. This requires the placement of fiducial markers, using an endoscopic ultrasound guided method (EUS), into the tumor for accurate source placement and treatment. Our aim is to compare three different types of fiducials in terms of visibility and migration. Methods: 12 patients with locally advanced rectal cancer that received Endo-HDR and EUS guided fiducial placement were retrospectively evaluated at JHH. Results: 12 patients underwent EUS guided placement of 42 fiducials. For 11 of our 12 patients, the mean number of fiducials placed per patient was 3.63 (SD 1.03) using a 19-gauge needle. One patient received 2 fiducials using a 22- gauge needle. Of the 12 patients that received fiducials, 3 received traditional fiducials (TF), 8 received segmented fiducials (SF) and 1 received foldable fiducials. All fiducials were clearly visible. The mean number of fiducials that detached from implanted site before surgery for patients with TFs was 0.667, and for patients with SFs was 0.875 (p=0.744). The median migration distance, as measured by interfiduciary distance, for segmented fiducials was significantly larger when compared to traditional fiducials (0.45 cm for SF compared to 0.1 cm for TF; p=0.049) Conclusions: SFs appear to be less stable, with regards to migration, in the rectum when compared to traditional fiducials in our patient population. These differences could be due to placement difficulty or operator dependent differences. Improvement in fiducial structure is required in order to help decrease migration and detachment and maximize visualization, which will lead to more accurate administration of Endo-HDR.
Identification of a Human Natural Regulatory T Cell Micro-RNA Signature and Demonstration of the Major Role Played by miR31 in the Control of Foxp3 Expression
Authors: Redouane Rouas, Hussein Fayyad Kazan, Nabil El Zein, Philippe Lewalle, Françoise Rothé, Haidar Akl, Arsène Burny, Pedro Romero, Philippe Martiat, Bassam Badran
Journal: Blood (2008)
Does atypical ductal hyperplasia require 6 months of postoperative surveillance?
Authors: Jennifer Kay Plichta, Natalia Rumas, Constantine V. Godellas, Claudia Beth Perez
Journal: Journal of Clinical Oncology (2012)

60 Background: Standard follow-up imaging for women with a history of breast cancer is well defined, but the appropriate screening guidelines for other high risk breast lesions, such as atypical ductal hyperplasia (ADH), remain unclear. Current practices often parallel those of cancer patients and include a 6 month interval mammogram prior to resuming annual screening, which may be unnecessary. As such, it is critical to evaluate the utility of the current standard practice of additional screening beyond a routine annual mammogram. Methods: Our pathology database was queried for the phrase "atypical ductal hyperplasia" from 2008 to 2010, and patients who underwent surgical excision were identified. Those who did not have subsequent follow up at our institution were excluded. Results: There were 44 patients who underwent excisional biopsies that were diagnosed with ADH and proceeded with follow up. In addition to a routine clinical exam, a short-term follow up diagnostic mammogram was performed in 24 patients. The median age was 56.5 years, and the median breast cancer risk assessment scores were 2.8% at 5 years and 13.4% lifetime. Of the 24 interval mammograms, 21 yielded benign findings on initial imaging (BIRADS 2), while 3 patients (12.5%) required additional imaging that ultimately resulted in benign findings. There were only 4 patients with a lifetime risk ≥25%, and all of these patients had benign findings on their initial imaging and resumed routine follow up. To date, 22 patients have received at least one additional mammogram, and all subsequent findings have been benign. No additional biopsies or surgeries have been performed. Conclusions: In sum, a clinical exam is still recommended at 6 months following surgical excision for a diagnosis of ADH. In the post-surgical breast, imaging may be misleading and result in psychological distress for patients and possibly unnecessary procedures. Based on our findings, a 6-month follow up mammogram is not recommended and patients should resume annual surveillance.
High false-negative rate of HER2 qRT-PCR of the Oncotype DX test: An independent quality assurance study.
Authors: D. J. Dabbs, M. Klein, S. Mohsin, R. R. Tubbs, R. Bhargava
Journal: Journal of Clinical Oncology (2011)

603 Background: HER2 (ERBB2) status is an important prognostic and predictive marker in breast carcinoma. In recent years, Genomic Health, Inc. (GHI), purveyors of the Oncotype DX test, have been separately reporting HER2 by reverse transcription polymerase chain reaction (RT-PCR) to oncologists. Due to lack of independent evaluation, this quality assurance study was undertaken to define the concordance rate between immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) and GHI RT-PCR HER2 assay. Methods: All cases at three participating laboratories (MWH-Magee-Womens Hospital, CC-Cleveland Clinic, RMH-Riverside Methodist Hospital) with available HER2 RT-PCR results from GHI were included in this study. All IHC positive and equivocal cases were further evaluated and classified by FISH at respective laboratories. Results: Of the total 507 MWH cases, 236 CC cases, and 100 RMH cases; 99% (464/468) of MWH, 99.5% (221/222) of CC, and 100% (94/94) of RMH negative cases were also negative by GHI RT-PCR assay. However, all MWH (n=13), CC (n=8) and RMH (n=2) equivocal cases were reported as negative by GHI. Of the 26 MWH positive cases, 8 were positive and 18 were either negative or equivocal by GHI (concordance of 31%). Concordance for positive cases was 17% (1 of 6) at CC and 25% (1 of 4) at RMH. Conclusions: There is an unacceptable false-negative rate for HER2 status via Oncotype DX in this independent study. This can create confusion in decision making process for targeted treatment, and can potentially lead to mismanagement of breast cancer patients if only GHI HER2 information is used. The Oncotype DX assay for Her2 has a flawed, inconsistent methodology that is not robust, and this raises serious concern about the validity of the Oncotype DX test.
The negative impact of prior reprimand on radiation therapists’ and dosimetrists’ comfort in reporting errors: Results from a national survey of more than 500 respondents.
Authors: Jessica A. Church, Robert D. Adams, Laura H. Hendrix, Jordan A. Holmes, Lawrence B. Marks, Ronald C. Chen
Journal: Journal of Clinical Oncology (2012)

204 Background: The presence of a "just culture" is often noted to be critical in optimizing safety, since workers need to feel comfortable reporting errors. We performed a national survey of radiation therapists and medical dosimetrists to assess their comfort in reporting errors. We herein quantify the impact of workers’ perceptions of their workplace culture (based on prior experiences in reporting errors) on their comfort in reporting safety concerns. Methods: In 2011, a survey was mailed to 1,500 therapists and 528 dosimetrists assessing their comfort in reporting errors. The metric used to assess their perceptions of their workplace culture was if they had, or knew of staff who had been, reprimanded in the past for reporting errors. Comfort in reporting new errors among workers who have (vs. have not) experienced prior reprimand were compared using Fisher’s exact test. Results: Overall, 356 therapists from 47 states (24% response rate) and 190 dosimetrists from 35 States (36% response rate) responded to the survey. 16% of therapists and 5% of dosimetrists reported that they have been personally reprimanded for reporting an error. The proportion of workers comfortable reporting errors was lower among those with prior personal reprimand vs. those without such reprimand (47% vs. 90%, p&lt;.0001). Similarly, 29% of therapists and 8% of dosimetrists reported that other staff members have been reprimanded for reporting, and these reprimands had a similar deterrent effect on reporting errors. On multivariate analysis, previous personal reprimand for reporting errors (OR 4.13, p=.001) and reprimand of other therapists/dosimetrists (OR 2.55, p=.03) were significantly associated with discomfort in error reporting. Conclusions: A sizable proportion of respondents in our study has been personally reprimanded or knows of staff in their facility reprimanded for reporting errors. Prior reprimand has a dramatic detrimental impact on workers’ comfort to report future concerns regarding safety. A potential opportunity for future improvement in radiation oncology treatment facilities is to encourage a culture that allows error reporting without fear of reprimand.
Effect of pazopanib on myeloid-derived suppressor cells and T-cell function in patients with metastatic renal cell carcinoma.
Authors: Kiranpreet K. Khurana, Pat A. Rayman, Paul Elson, Brian I. Rini, James Finke
Journal: Journal of Clinical Oncology (2013)

455 Background: Tyrosine kinase inhibitors have been shown to have an effect on T cell function. Sunitinib decreases immunosuppression in patients with metastatic renal cell carcinoma (mRCC) as seen by a reduction in myeloid derived suppressor cells (MDSC) that inhibit T cell function. The effect of pazopanib on immune function is unknown. Methods: Peripheral blood mononuclear cells from 21 patients with mRCC treated with pazopanib were thawed for cycle 1 day 1, cycle 1 day 28, cycle 2 day 28, and cycle 4 day 28. Total MDSC and neutrophilic, monocytic, and lineage-negative MDSC subsets were measured by flow cytometry. T cell response was measured by interferon-gamma production after in vitro stimulation by anti-CD3/anti-CD28 beads. Pre-treatment cycle 1 day 1 levels were compared to cycle 4 day 28. Results: In mRCC patients, MDSCs comprise 4.7 % (median, range 1.7-32.9 %) of the peripheral blood mononuclear cells pre-treatment. Neutrophilic MDSC subset is the most prevalent at 2.0 % (median, range 0.3-30.4 %). Monocytic MDSCs comprise 1.5 % (median, range 0.4-5.3 %), and lineage-negative MDSCs comprise only 0.15 % (median, range 0.01-1.03 %). We found that pazopanib does not significantly decrease the percentage of MDSCs (total or subpopulations) over time with the exception of a modest decrease in the lineage-negative MDSC subset (p = 0.08). In terms of T cell function, pre-treatment level of CD3+ interferon-gamma was found to be 10.6 % (median, range 1.3-22.3 %). In contrast, pazopanib significantly increased CD3+ interferon-gamma level over time to 18.1 % (median, range 3.0-25.0 %), p = 0.03. Conclusions: Our study shows that pazopanib does not significantly reduce MDSC levels in patients with mRCC. However, pazopanib improves T cell function over time, as seen by a significant increase in CD3+ interferon-gamma production.
Prognostic, predictive, and surrogate value of HER2 extracellular domain (ECD) for progression-free survival (PFS) in advanced breast cancer treated with lapatinib (lap): A meta-analysis.
Authors: Chee Lee, Lucy Davies, Ian Marschner, Val Gebski, Sally Lord, Angelo Di Leo, Stephen R. D. Johnston, Charles E. Geyer, David A. Cameron, Michael F. Press, Catherine Elizabeth Ellis, Sherene Loi, John Simes, Paul De Souza
Journal: Journal of Clinical Oncology (2014)

630^ Background: We performed a meta-analysis to determine the clinical utility of HER2 ECD in advanced breast cancer patients undergoing lap therapy. Methods: Data from Phase 3 clinical trials (EGF30001, EGF30008, EGF100151) of patients randomized to receive lap-containing or control treatments were analyzed. Baseline HER2 ECD (bECD) and tissue HER2 status were examined for associations with PFS. We also performed a landmark analysis to quantify the association between ECD change, as measured at 10 weeks post-randomization, with PFS, and assessed the extent ECD change predicted lap benefit. Results: Levels of bECD were higher in HER2+ (n=378) than HER2- (n=1060) patients (61.59 vs 14.25ng/ml, p<0.0001). The effectiveness of lap was significantly associated with bECD (joint treatment-biomarker interactions P=0.001[bECD], P=0.02[HER2 tissue status]). At 10 weeks post-randomization, there was a mean 4.23ng/ml reduction in ECD with no significant difference between treatment arms (lap: 4.33ng/ml, control: 4.12ng/ml; P=0.92). In the control arms, change in ECD was prognostic for PFS (P<0.0001). The median PFS from landmark (mPFS) were 9.8 and 2.9 months for those with low ECD (≤15ng/ml) and high ECD (>15ng/ml), respectively. mPFS were 3.3 and 5.7 months for patients with ECD increase to >15ng/ml and ECD decrease to ≤15ng/ml, respectively. Similar finding was observed in the experimental arm (P<0.0001). In both treatment arms, there was 4% increase in risk of disease progression for every 10 unit ECD increment after adjustment of bECD and other factors (P<0.0001). Lap improved PFS over control (HR 0.83, P=0.002). Adjustment for ECD change yielded a similar result (HR 0.80, P<0.001), indicating that change in ECD did not explain the treatment effect of lap. Conclusions: Baseline HER2 ECD was predictive of lap benefit. ECD increase during lap and non-lap therapies was associated with a shorter PFS. Change in ECD had additional prognostic information in addition to baseline ECD, but was not a valid surrogate marker for lapatinib benefit as the treatment effect of lap was largely independent of ECD change. Clinical trial information: NCT00075270, NCT00073528, and NCT00078572.
Correlation between Immunoglobulin Gene Rearrangements and Chromosomal Abnormalities in Multiple Myeloma.
Authors: Giovanna Piras, Maria Monne, Antonella Uras, Laura Pilo, Luciana Arca, Maurizio Cucca, Angelo D. Palmas, Anna Calvisi, Annalisa Noli, Marco Murineddu, Attilio Gabbas
Journal: Blood (2007)
Acquired drug resistance in gynecologic cancer detected by drug response marker testing.
Authors: I. Benjamin, H. J. Dalton, B. J. Monk
Journal: Journal of Clinical Oncology (2011)

5068 Background: To compare in vitro drug response profiles in metachronous tumors (specimens from the same patient before and after chemotherapy) in an unselected population of gynecologic cancers. Methods: Redacted data from Precision Therapeutics, Pittsburgh, PA was provided to the authors for metachronous cases of unselected gynecologic malignancies in which ChemoFx in vitro drug response assay results were available. For each specimen a surgical pathology report, tumor test requisition form containing specimen site and primary tumor type (site and histology) were reviewed. The ChemoFx Assay Patient Report provided in vitro chemotherapy response data for single drug and/or doublets as ordered by the oncologist. Tumors were categorized as responsive (R), intermediately responsive (IR), or non-responsive (NR) to chemotherapies. For analysis, response was coded as R = 3, IR = 2 and NR =1. Statistical analysis was performed using SAS JMP 8.0.2. Results: From 2006-2009, 569 drug response assays were performed on 30 metachronous specimens (89% ovarian/peritoneal; 20% uterine) obtained before and after chemotherapy. Twenty different drug combinations (single agent and doublet) were tested. The mean time between the first and second tumor tested was 10 months (range 3-21). The average chemoresponse score for all drugs tested was 1.85 in primary tumors and 1.50 in recurrent tumors (p=<.0001). For the individual matched cases, there was a significant shift towards non-responsiveness from the primary to the recurrent tumor for carboplatin (1.64 vs 1.32; p=.03) and paclitaxel (1.59 vs. 1.22; p=.007), but not for topotecan (1.52 vs 1.30; p=0.17), doxorubicin (1.35 vs 1.25; p=.16) or gemcitabine (1.29 vs 1.19; p=.16). Conclusions: A shift toward acquired resistance following chemotherapy in metachronous gynecologic tumors was detected by the ChemoFx in vitro drug response assay. Given the inability of other drug resistance assays to detect acquired chemoresistance, future studies should define the role of these assays in individualized treatment planning.