tbuckley/cabot-search huggingface dataset:
Automatic inpatient palliative care consultation (PCC): Too little, too late to impact quality of life for advanced cancer patients?
Authors: Gabrielle Betty Rocque, Toby Christopher Campbell, Anne Elizabeth Barnett, Renae M Quale, Jens C. Eickhoff, Howard Harry Bailey, Mark E. Burkard, James F. Cleary
Journal: Journal of Clinical Oncology (2013)

e20565 Background: Patients with advanced cancer who are hospitalized have high symptom burden and a short life expectancy, which may warrant PCC. Methods: Using sequential cohorts, we prospectively assessed implementation of automatic PCC for hospitalized cancer patients. The primary outcome was hospice utilization. Secondary outcomes included evaluation of changes in quality of life (FACIT-PAL), symptoms (ESAS), satisfaction (FAMCARE), and anxiety and depression (HADS). Surveys were administered at baseline, 2 weeks and 3 months post-hospitalization. Chart abstraction was utilized to assess demographics, resource use, and survival information. Results: Patients were evaluated consecutively (65 in the control group, 70 in the intervention). At admission, 91% reported uncontrolled symptoms: 52% pain; 15% dyspnea. 60% of intervention patients received PCC during their first admission. 54 patients completed surveys (29 control group, 25 PCC group), 64 patients declined or were unable to complete surveys, 16 patients were excluded due to language barriers, physician preference, or not receiving surveys. Using an intent-to-treat analysis, there was no difference between patients in the control and the intervention group in FACIT-PAL (119 ± 29 vs 123 ± 30, p = 0.68 ), ESAS (28 ± 14 vs 26 ± 15, p = 0.74) HADS (13 ± 6.6 vs. 12.± 4.7, p = 0.58), or FAMCARE (58 ± 9.1 vs 59 ± 8.6, p = 0.61). In both groups, patients had modest worsening of symptoms and quality of life over the course of the study. Survival and Health Services data analysis, including hospice referral, is proceeding. Conclusions: Automatic PPC had little impact on patient-reported symptoms and quality of life. Limitations included: small patient population; high rate of incomplete surveys, likely due to illness burden; penetration of the PCC was limited to 60% by patient or provider preference and consultant availability. Our primary outcome analysis (hospice utilization) is forthcoming, as are data on survival and Health Services outcomes.
Extracting predictor variables for late effects of childhood cancer treatments from clinical notes.
Authors: Robert M Johnson, Shruti Rao, Varun Singh, Priya Kasturirangan, Aziza T. Shad, Kenneth Tercyak, Michael A. Harris, Subha Madhavan
Journal: Journal of Clinical Oncology (2014)

10085 Background: Today almost 80% of children and adolescents diagnosed with cancer will be long term survivors. As a result of their treatment/cancer, research studies on childhood cancer survivors from the 1970s-1990s show that 75% of the survivors have at least one chronic health condition thirty years after diagnosis. Our goal was to develop a model that predicts late effects of cancer treatment given a set of drugs and diagnoses, which were extracted from clinical notes. Such late effects data could inform current treatments to minimize the incidence of late effects, and help clinicians monitor potential health outcomes for follow up care. Methods: We processed 27,533 clinical notes from 245 patients using cTAKES to extract disease/disorder, sign/symptom, and medication mentions. Patients were automatically diagnosed from clinical notes by filtering these extractions to a list of 26 known pediatric cancer diagnoses. Explicitly extracting drug mentions in text was not always reliable. Sometimes only protocols were mentioned (e.g.
PIK3CA mutations in breast cancer: A potential predictive marker
Authors: M. Santarpia, G. Altavilla, M. Margeli, M. Mesiti, V. Cavallari, B. Cirauqui, N. Reguart, A. Barnadas, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2006)

639 Background: Somatic mutations in phosphoinositide-3-kinase catalytic alpha (PIK3CA) activates Akt, attenuates apoptosis and promotes tumor invasion. The common mutations E545K and H1047R confer resistance to paclitaxel in immortalized breast cancer cell lines. We screened primary breast cancers for PIK3CA mutations in the helical and catalytic domains. Methods: Tumor samples from 61 stage I-III breast cancer patients treated with adjuvant chemo- and/or hormone therapy were examined for PIK3CA mutations E542K, E545K and H1047R by the 5-nuclease assay (TaqMan) using the ABI Prism 7900HT Sequence Detection System. Results: Mutations were found in 17 patients (27.9%): 6 E542K; 5 E545K; 6 H1047R. PIK3CA mutations were not associated with expression of estrogen or progesterone receptors, lymph node metastases, or ERBB2 overexpression. (See table ) Conclusions: PIK3CA mutations occur frequently in breast cancer and could be a novel predictive marker of chemoresistance and an appealing target for therapeutic inhibition, independent of hormone receptors and ERBB2 status. [Table: see text] No significant financial relationships to disclose.
Pathologic complete response rates observed in women with locally advanced and inflammatory breast cancer receiving neoadjuvant carboplatin and paclitaxel.
Authors: Arvind Manohar Shinde, John H Yim, Laura Kruper, Courtney Vito, Steven L. Chen, Isaac Benjamin Paz, Thehang H. Luu, Tomoko Tagawa, Kim Wai Yu, Sharon Wilczynski, Sally Shaw, Lalit Vora, Jinha Mark Park, George Somlo
Journal: Journal of Clinical Oncology (2012)

1035 Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NCT) is predictive of outcome in patients with locally advanced breast cancer (LABC). A non-anthracycline containing NCT regimen (Sikov et al. JCO 10/09) may reduce the risk of associated secondary hematologic malignancies and cardiac toxicity while yielding comparable pCR rates. Methods: A retrospective review of all LABC and inflammatory breast cancer (IBC) cases treated from 4/09 to 12/11 with a NCT regimen of carboplatin (AUC of 6, administered on day 1) and paclitaxel 80 mg/m 2 (given weekly on a 21-28 day cycle) was conducted at the City of Hope Cancer Center (COHCC). Pts with HER2+ (HER+) tumors received trastuzumab during the NCT treatment. All pCRs (pCR of primary only – "pCR1°"; pCR of primary and lymph nodes – "pCR-All") were determined by a COHCC pathologist based on final surgical specimens. Results: 38 pts were identified, with 39 breast primaries; 18% had IBC, 62% of LABCs/IBCs were hormone receptor positive (HR+), 46% of tumors were HER2+, and 26% were triple negative. Median age was 51 [27-63]. All pts completed the planned number of cycles. Four pts required carboplatin dose reductions, 4 pts required dose reductions in paclitaxel, 3 pts had paclitaxel changed to nab-paclitaxel, and 17 pts required G-CSF to complete their planned treatment. One pt receiving trastuzumab experienced asymptomatic LVEF decline below normal limits. Conclusions: A non-anthracycline-containing NCT regimen of carboplatin/paclitaxel was well tolerated and resulted in high pCRs when given to triple negative (HER2-/HR-) pts, and HER2+ pts, especially with HER2+HR- subtypes. The findings warrant further studies of this regimen in a prospective randomized setting. [Table: see text]
Tailored vinorelbine-capecitabine treatment in elderly metastatic breast cancer patients. A SICOG phase II study
Authors: I. Carreca, G. Iodice, G. D’Aiuto, R. Thomas, R. Costanzo, M. Licenziato, A. Petrillo, L. Maiorino, G. Frasci, G. Comella
Journal: Journal of Clinical Oncology (2006)

10556 Purpose: To determine the antitumor activity of vinorelbine (VNR) and capecitabine (Xeloda) when given together, as first-line treatment, in elderly metastatic breast cancer (MBC) patients. Patients and Methods: MBC patients, aged &gt;65 years, with no prior chemotherapy for metastatic disease, received capecitabine 1,000–1,250 mg/m 2 d 1→14 and VNR 20–25 mg/m 2 d 1–8, q3wk for a maximum of 6 cycles. Doses of VNR and Xeloda were alternately escalated in each patient (VNR 20→25 on 2 nd cycle, Xeloda 1,000→1,250 on 3 rd cycle), in absence or relevant hematologic/nonhematologic toxicity. Results: Forty-seven MBC pts., median age 72 (range: 66–82) were enrolled. Metastatic sites: visceral/other = 30/17. Adjuvant chemotherapy: Yes/no = 21/27. The doses were escalated as planned in 24/47 pts. To date, 41/47 pts. are evaluable for response. Three CRs and 25 PRs have been recorded, giving a 68% ORR (Visceral/other = 59%/85%). At a median follow-up of 15.3 months, 19 pts. have progressed, and 18 died, median PFS and OS being 14.1, and 20.3 months, respectively. Toxicity has been in general mild or moderate. Grade 3–4 neutropenia has occurred in 29% of pts., with only 2 episodes of neutropenic sepsis. Severe gastrointestinal side effects have been observed in only 2 pts., while severe mucositis and hand-foot syndrome have never occurred. Conclusions: VNR-Xeloda combination is highly active in elderly MBC patients. The adoption of an intrapatient dose escalation permits to minimize the risk of severe toxicity, without compromising efficacy. The accrual still continues until the planned sample size (60 pts.). No significant financial relationships to disclose.
Treatment of Alopecia Areata With Tofacitinib
Authors: Omer Ibrahim, Cheryl B. Bayart, Sara Hogan, Melissa Piliang, Wilma F. Bergfeld
Journal: JAMA Dermatology (2017)

Treatment of Alopecia Areata With Tofacitinib2][3] In this study, investigators searched the medical records of the Cleveland Clinic for any patients with confirmed AA who were treated with oral tofacitinib (Xeljanz; Pfizer) using a standardized, systematic treatment regimen.
Plasma EBV DNA and cell-free GAPDH DNA as prognostic factors of locally advanced nasopharyngeal carcinoma
Authors: J. Chen, L. Ting, J. Ko, P. Lou, C. Wang, T. Yang, R. Hong
Journal: Journal of Clinical Oncology (2007)

6053 Background: Plasma cell-free nucleic acids have been investigated to be potential prognostic and predictive markers of treatment response, residual disease, and survival of cancer patients. However, these nucleic acids will be confounded by normal cell death, which might be caused by cancer-related inflammation, infection, or chemotherapy. Nasopharyngeal carcinoma is endemic in Taiwan, highly related to EBV infection. Plasma EBV DNA level has been suggested to be predictive of disease status and outcomes. We try to find out whether plasma EBV and cell-free glyceraldehydes-3-phosphate dehydrogenase DNA before definite treatment of locally advanced NPC predict tumor outcomes better. Methods: 144 stage IV (AJCC version 6) NPC patients received induction chemotherapy followed by concurrent chemoradiotherapy in National Taiwan University Hospital from 1998 to 1999. Pre-treatment blood samples were colleted for real-time quantitative polymerase chain reactions of EBV and GAPDH DNA. The results will be analyzed by SPSS version 13 to see if correlated with tumor extent, locoregional/distant failure, and overall survival. Results: Our patients were mainly composed of T4(97%) and N2(56%) patients. 23 % were in N3 stage. Plasma EBV and cell-free GAPDH DNA levels were not correlated with T stage. Plasma EBV DNA level was significantly correlated with N3 status(Mann-Whitney test p=0.021). After Cox regression model, only age (p=0.024) was a significant predictor of recurrence-free survival; N3 status(p=0.007) and positive plasma EBV DNA (p=0.002) predicted shorter metastasis-free survival. N3 status (p=0.031) and positive plasma EBV DNA (p=0.002) were significantly related to poor survival by log-rank test; whereas T4 lesions (p=0.524) and plasma cell-free GAPDH DNA level (p=0.182) were not. After multivariate Cox regression, positive plasma EBV DNA (hazard ratio 4.936 p=0.006) was the only significant predictor of poor survival. Conclusions: To use circulating DNA as prognostic marker, a specific one, such as EBV DNA, might be better than a non-specific one, like GAPDH DNA. This is important in the development of tumor markers for other solid tumors. No significant financial relationships to disclose.
Health care worker attitudes about clinical trials at a comprehensive cancer center.
Authors: Erica Leigh Campagnaro, Seunghee Margevicius, Barbara J. Daly, Jennifer Rachel Eads, Tyler G. Kinzy, Tasnuva Munir Liu, Sharon Manne, Dawn M. Miller, Mark D. Schluchter, Neal J. Meropol
Journal: Journal of Clinical Oncology (2013)

e20633 Background: Cancer patient (pt) participation in clinical trials (CT) is low. Little is known about the beliefs and attitudes of health care workers (HCW) and how they impact intention to discuss CT with pts. The overall goal of this project was to develop a conceptual model to guide future interventions to enhance communication about CT between HCW and cancer pts. Methods: Two email surveys of non-physician HCW at an NCI-designated comprehensive cancer center were conducted. The first was sent to a random sample of 150 HCW. The second was sent to 80 who completed the first survey. Based on our prior work (Eads et al. ASCO 2011) and Ajzen’s Theory of Planned Behavior, domains of the first included CT knowledge (19 items, agree/disagree) and attitudes (27 items, 5-point Likert); the second included normative beliefs about institutional attitudes toward CT (6 items, 5-point Likert), self-efficacy about engaging in discussion about CT (14 items, 5-point Likert), and intention to discuss CT with pts (4 items, 7-point Likert). Results: 41 HCW completed both anonymous surveys; 27 could be matched by demographics. Median age of matched respondents was 44.3 yrs (range 24-63), 26 female, 22 caucasian, 9 nurses. Overall, CT knowledge was high (median 17/19 items correct). There were strong associations between attitudes and self-efficacy (Spearman r=-0.425, p=0.03), as well as perceived normative beliefs and self-efficacy (r=0.651, p=0.0002). These associations were strong amongst nurses (r=-0.818, p=0.007 and r=0.656, p=0.05, respectively), with a particularly strong correlation between self-efficacy and intention to discuss clinical trials with pts (r=0.891, p=0.001). Conclusions: In spite of a small sample size, these pilot data strongly support a behavioral framework to understand and address the impact of HCW attitudes and beliefs about CT on discussions of CT with pts. Insofar as HCW (especially nurses) have substantial pt contact, and serve as a resource for pts regarding treatment decisions, educational interventions to address HCW barriers to discussing CT with pts (i.e. attitudes, beliefs, and self-efficacy) could positively impact pt attitudes and improve decision making.
Neoadjuvant epirubicin, gemcitabine, and docetaxel for primary breast cancer: Survival and prognostic factors in two consecutive neoadjuvant phase I/II trials.
Authors: Frederik Marme, Justo Lorenzo Bermejo, Hans-Peter Sinn, Peter Lichter, Florian Schuetz, Joachim Rom, Julia Aigner, Christof Sohn, Andreas Schneeweiss
Journal: Journal of Clinical Oncology (2012)

1096 Background: We previously reported primary end points of two consecutive phase I/II trials which evaluated two different schedules of neoadjuvant gemcitabine (G), epirubicin (E) and docetaxel (Doc) for primary breast cancer. Here we report mature survival data and evaluate prognostic factors for disease-free (DFS) and overall survival (OS). Methods: 151 patients were treated in two phase I/II trials of G, E and Doc as neoadjuvant chemotherapy (NAC) for T2-4 N0-2 M0 PBC between Feb. ’02 and Dec. ’04. Patients were treated with six cycles of GEDoc (G 800mg/m 2 day (d) 1+8, E 60-90mg/m 2 d 1, Doc 60-75mg/m 2 d 1 every three weeks) or five cycles of G 1250mg/m 2 plus E 90-100mg/m 2 every two weeks followed sequentially by four cycles of Doc 80-100mg/m 2 every two weeks (GEsDoc). Pathologic complete response (pCR), clinical/pathological factors were correlated with DFS and OS. Results: There was no significant difference in DFS or OS between patients in the GEDoc and GEsDoc trial (DFS: Hazard ratio (HR) 1.13, p=0.67; OS: HR 1.06, p=0.88) with a 5-year DFS and OS of 72 vs 74% and 85 vs 86%, respectively. In an univariate analysis pCR unexpectedly was associated with a worse OS (HR 3.11; p= 0.007). HR for DFS showed a similar but non-significant trend (HR 1.78; p=0.1). Molecular subtypes (OS: HR [lum B] 3.17; [triple negative] 5.81; [HER2] 11.5; p=0.002), negative estrogen receptor (ER) status (OS: HR 3.14; p=0.002) and Ki-67 &gt;20% (OS: HR 5.41; p=0.001) were all significantly associated with DFS and OS. The recently published CPS-EG score (Mittendorf 2011) was also significantly correlated with OS (p=0.006) and DFS (p=0.0006). In a multivariate analysis high Ki-67 was the only significant predictor of OS (HR 10.4; p=0.0026) whereas molecular subtype (p=0.05) and Ki-67 (p=0.04) were significantly associated with DFS. Conclusions: These results raise caution on the reliability of pCR as a single surrogate marker for survival in trials with small sample sizes. Our results emphazise the role of additional factors, esp. Ki-67 and subtypes. Integrative scores based on clinical and pathologic stage as well as tumor biology, might be more reliable predictors of survival.
Doxorubicin-induced vascular toxicity: Targeting potential pathways to reduce procoagulant activity.
Authors: Hadas Bar-Joseph, Irit Ben-Aharon, Moran Tzabari, Naftaly Savion, Ruth Shalgi, Salomon M. Stemmer
Journal: Journal of Clinical Oncology (2012)

e13080 Background: In a former study in mice using the gonads as an end-organ prototype, we have characterized by real-time intravital imaging an acute deleterious effect of doxorubicin (DXR) on the gonadal vasculature, manifested by a reduction in blood flow and disintegration of the vessel wall. We hypothesized this pattern may represent the formation of microthrombi. We aimed to further characterize the effect of DXR on platelets’ function and to use potentially protectants to reduce DXR acute effect on the blood flow. Methods: 100 µg/mouse 24 hours and 1 hour prior to DXR treatment (8 mg/kg), or with eptifibatide (integrilin,75µg/mouse) 90min prior to DXR treatment. Testicular arterial blood flow was examined in real-time by pulse wave Doppler ultrasound. Platelet adhesion to confluent endothelial cells (EC) was evaluated following exposure of EC to DXR (100 µM) for 4h followed by exposure to whole blood under defined shear rates. Fixed platelets were immunostained by anti- CD41a antibody. DXR effect on platelet adhesion was determined by pre-incubation of platelet rich plasma for 15min with increasing concentrations of DXR and induction of aggregation by ADP. For in vivo study, mice were injected with either LMWH (Enoxaparin; Clexane). Results: There was a significant 3.6-fold increase in platelet adhesion to DXR-exposed EC (p&lt;0.002) reflecting the toxic effect of DXR on EC. Yet, significant DXR- dose dependent decrease in platelet aggregation was observed reaching up to 40% inhibition at 100 µM (p&lt;0.001). Testicular arterial blood flow was preserved as a result of pre-treatment with LMWH or eptifibatide prior to DXR (P&lt;0.01). Conclusions: DXR-induced acute vascular toxicity may trigger the coagulation pathway while enhancing platelet adhesion yet inhibiting massive aggregation, which result in compromised blood flow due to microthrombi formation. Anti-platelet/anti-coagulant agents appear to be effective in reducing the detrimental effect of DXR on the vasculature.
<i>KRAS </i>and <i>EGFR </i>mutations to distinguish adenocarcinomas and squamous cell carcinomas of the cervix.
Authors: Alexi A. Wright, Michelle S. Hirsch, Nikhil Wagle, Brooke E Howitt, Emanuele Palescandolo, Laura E. MacConaill, Paul Van Hummelen, Melina Shoni, William C Hahn, Ursula A Matulonis
Journal: Journal of Clinical Oncology (2012)

5011 Background: Cervical adenocarcinomas (AC) have higher rates of recurrence and distant metastasis, compared with squamous cell carcinomas (SCC), and decreased survival in advanced disease. Yet, tailored treatments for cervical cancers have not emerged. The aim of this study was to compare the frequency and type of somatic mutations in cervical AC and SCC to identify novel therapeutic targets for both subtypes. Methods: Tumors from 61 patients with cervical cancer (36 AC, 25 SCC) underwent genomic profiling by OncoMap, a multiplexed mass spectrometric genotyping technology that interrogates more than 400 known mutations in 33 cancer genes. Results: Overall, 31/61 (50.8%) tumors harbored candidate mutations, and 6/61 (9.8%) had ≥2 mutations. PIK3CA mutations were present in 21/64 (34.4%) of cervical cancers, with a trend towards higher rates in SCC compared with ACC (21/25 or 48.0% vs. 9/27 or 33.3%, p=0.10). KRAS mutations were present in 6/31 (16.7%) of AC, but none of the SCC (0%; 0/25). EGFR mutations were present in 9/25 (36.0%) of SCC, including G719S, but none of AC (0%; 0/31). Conclusions: The identification of distinct genomic alterations in SCC and AC of the cervix suggest different therapeutic rationales for each subtype. EGFR amplification in cervical SCC has been previously reported, but this is the first identification, to our knowledge, of activating EGFR mutations in cervical SCC. Together, this suggests that EGFR-inhibitors might be useful in selected patients with cervical SCC. Similarly, activating mutations in KRAS and PIK3CA in AC suggest that inhibition of the MAPK pathway (MEK inhibitors) and/or PI3K pathway may be beneficial in this subtype. Future studies should include more comprehensive genomic profiling strategies, such as targeted massively parallel sequencing, to detect multiple types of genomic alterations.
Long-term quality of life comparison after endoscopic submucosal dissection versus surgery in early gastric cancer patients.
Authors: Young-Il Kim, Young Ae Kim, Chan Gyoo Kim, Keun Won Ryu, Young Woo Kim, Jin Ah Sim, Young Ho Yun, Il Ju Choi
Journal: Journal of Clinical Oncology (2017)

24 Background: The aim of this study was to compare the serial changes of health-related quality of life (HRQOL) after Endoscopic submucosal dissection (ESD) with those after surgery in patients with early gastric cancer (EGC). Methods: Gastric cancer patients were prospectively enrolled from 2004 through 2007. HRQOLs of 161 EGC patients were prospectively assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC-QLQ-C30) and the stomach cancer-specific module EORTC-QLQ-STO22 at the baseline, 1, 6, 12, 18 and 24 months after treatments. Analysis was done using the generalized linear model and paired- ttests. Results: Of 161 patients, 48 (29.8%) underwent ESD (ESD group) and 113 (70.2%) underwent surgery (surgery group). The median age of stomach cancer patients was 57 years. Surgery group had poorer scores compared with those of ESD group in the most HRQOL factors one month after treatments ( P&lt; 0.05), except for emotional and cognitive functioning, financial problems, anxiety, and hair loss. However, most of the functional and symptom scales after surgery subsequently improved and became insignificant until 24 months of follow up. Only 3 parameters including physical functioning, diarrhea and body image in ESD group still remained better until 24 months after treatment ( P&lt; 0.05). Conclusions: Because poorer HRQOLs after surgery in the early post-treatment periods become insignificant during long-term follow-up, surgical treatment should not be discouraged in EGC treatment solely based on the QOL aspects.