tbuckley/cabot-search huggingface dataset:
Referral patterns among patients with metastatic breast cancer in an integrated palliative care program.
Authors: Rebecca Small, Jeffrey Belkora, Melanie Catherine Majure, Amy Jo Chien, Michelle E. Melisko, Hope S. Rugo, Michael W. Rabow
Journal: Journal of Clinical Oncology (2016)

163 Background: ASCO recommends palliative care (PC) concurrently with oncologic treatment for patients with metastatic disease and there is emerging data about the benefits of early PC. However, little is known about referral patterns to specialty PC among patients who die of metastatic breast cancer. Methods: After years of offering a stand-alone outpatient PC consult service in our comprehensive cancer center, we established an integrated PC program in breast oncology (the “Advanced Breast Cancer (ABC) Program”) with a care coordinator, PC physician, and co-location with oncology. Among patients who died, we analyzed referral patterns, program participation, and end-of-life quality outcomes from October 2014 through May 2015. Results: 38 of 108 patients (35.2%) referred to and seen in ABC died, with an average of 2.9 PC visits (range 1-17) and 7 months (range 0-20) between referral and death. Reasons for referral among ABC patients who died included: symptom management (15 patients, 39.5%); goals of care discussions (12, 31.6%); psychosocial support (5, 13.2%); discharge referral from the inpatient PC team (4, 10.5%); and new diagnosis of metastatic disease (3, 7.9%). At the time of referral, average time since metastatic diagnosis was 23.6 months (range: 0-106); 10 patients (26.3%) had received &gt; 3 lines of treatment. 15 referred patients (13.9%) died but were not seen by ABC: of those, 6 initiated hospice before they could be seen; 5 initially declined or deferred the referral but then were too sick to be seen in clinic by the time they agreed; and 4 were unwilling to accept extra appointments or did not follow-up to repeated outreach. 24 ABC patients who died (63.2%) were seen early (&gt; 90 days before death), whereas in the year prior to the ABC clinic, among patients who died, only 11 of 44 (25%) who had received PC consultation received it early. 19 of 33 (57.6%) ABC patients for whom data was available utilized hospice, with only 2 (5.3%) using hospice &lt; 3 days. Conclusions: Embedding and integrating a PC practice in breast oncology resulted in patients being seen earlier. Future efforts should be directed at further increases in earlier referrals by oncologists and in facilitating patient acceptance of early referrals.
Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas.
Authors: K. Oda, K. Shoji, S. Nakagawa, T. Kashiyama, Y. Ikeda, Y. Miyamoto, M. Tanikawa, H. Kuramoto, M. Nishida, O. Hiraike-Wada, T. Yano, S. Kozuma, Y. Taketani
Journal: Journal of Clinical Oncology (2011)

5110 Background: PI3K (phosphatidylinositol-3-kinase) /mTOR (mammalian target of rapamycin) pathway is frequently activated in endometrial cancer through various PI3K/AKT activating genetic alterations, including mutations in PTEN, PIK3CA, and K-Ras. We evaluated the activity of a dual PI3K/mTOR.inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial cancer cell lines. Methods: We examined anti-tumor effect of RAD001 and NVP-BEZ235 in 13 endometrial cancer cell lines, all of which possess one or more alterations in PTEN, PIK3CA and K-Ras. We also combined these compounds with a MAPK pathway inhibitor in cell lines with K-Rasalterations (mutations or amplification). Results: PTEN mutant cell lines without K-Rasalterations (n=9) were more sensitive to both RAD001 and NVP-BEZ235 than the other cell lines with K-Rasalterations (n=4). NVP-BEZ235 showed lower IC50 values than RAD001 in eight of the nine sensitive cell lines, and G1 arrest was more effectively induced by NVP-BEZ235 than RAD001. We observed in vivo anti-tumor activity of both RAD001 and NVP-BEZ235 at a tolerated dose in nude mice. Combination of NVP-BEZ235 with a MEK inhibitor PD98059 and UO126 synergistically suppressed the proliferation in cells with K-Rasalterations. Conclusions: Robust growth suppression by NVP-BEZ235 suggests that a dual PI3K/mTOR inhibitor, such as NVP-BEZ235, is a promising therapeutics in endometrial carcinomas. Our data suggest that presence of PTEN mutations without K-Ras alterations may be a good predictive biomarker to NVP-BEZ235 in certain endometrial carcinomas. Combination of a PI3K/mTOR inhibitor with a MEK inhibitor PD98059 and UO126 might be effective to the tumors with K-Ras alterations.
The senses of interns worked in hospice center
Authors: S.-J. Koh, K. S. Lee, Y. S. Hong, J.-H. Kang, I. S. Woo, M. A. Lee, S. O. Choe
Journal: Journal of Clinical Oncology (2005)

8162 Background: As the education on palliative & end-of-life care for physicians and the opportunity of clinical practice to treat terminally ill cancer patients is very insufficient. Methods: From January to October, 2004, questionnaire was performed to interns worked in Kangnam St. Mary’s hospital hospice center and in general ward except hospice center of the same hospital. Results: Demographics 20 interns worked in hospice center and 28 interns in general ward only. It was found that interns worked in hospice center participating in the treatment of advance cancer patients more than those worked in general ward only(66% vs 13%, p=0.0012). Collaboration with Supportive/Palliative care team Interns worked in hospice center maintained constant relation with palliative care medical specialist (p=0.0058), palliative care nurse specialist (p=0.0015), inpatient hospice (p=0.0147) and social worker (p=0.0329), thereby performing cooperative diagnosis and treatment. Direct participation in Supportive and Palliative care of patients with Advanced Cancer The experience of managing patients in hospice center was able to actively control the physical and psychological symptom usually seen from advance cancer patients. Furthermore, the interns worked in hospice center execute discussing end-of-life care preference with patients and directly administer end-of-life care to dying cancer patients in higher frequency. Attitude Interns worked in hospice center showing positive senses on palliative care. Especially, they are highly interested in searching knowledge (p=0.0178) or the study on palliative care (p=0.1539). Conclusion: The experience of interns of directly taking care of patients in hospice center motivated them to actively participate in the treatment of terminally ill cancer patient, facilitating cooperative diagnosis with palliative care team. Especially, it was observed that there was conspicuous difference in the quest of knowledge related to palliative care. No significant financial relationships to disclose.
Clinical observation in nasopharyngeal carcinoma (NPC) treated with the anti-EGFR monoclonal antibody followed by helical tomotherapy.
Authors: L. Feng, H. Jun, B. CAI, N. LU, L. DU, L. MA, S. Xu, X. Zhang, C. Xie
Journal: Journal of Clinical Oncology (2011)

e16010 Background: To evaluate the clinical outcome and the acute toxicity in nasopharyngeal carcinoma (NPC) treated with Tomotherapy followed by the anti-EGFR monoclonal antibodies. Methods: Between March 2008 and November 2009, 34 newly diagnosed NPC patients were treated with Helical Tomotherapy combined with Nimotuzumab (N) or Cetuximab (C). All the patients accepted Tomotherapy at the dose of 70Gy/33F for the gross tumor volume (pGTVnx) and positive lymphnodes (GTVnd), and 60Gy/33F for the high risk clinical target volume (CTV1), and 56Gy/33F for the low risk clinical target volume (CTV2), respectively. 17 patients in group N were given weekly injection of 200 mg/m2 for 6-7 weeks and 17 patients in group C were given intravenously an initial dose of 400mg/m2 in the first week followed weekly injection of 250 mg/m2 for 6-7 weeks. Acute lesions were evaluated with the RTOG/EORTC criteria. Results: The median follow-up time was 22 months. The effective rates (CR+PR) in 3, 6 and 12 months were 82.4% (14/17), 70.6% (12/17), 70.6% (12/17) in group N and 88.2% (15/17), 82.4% (14/17), 82.4% (14/17) in group C. The one year survival rate was 88.2% (15/17) in group N and 100% (17/17) in group C. Nimotuzumab has less acute mucositis reaction (u=2.245, P<0.05), weight loss (t,=2.563, P=0.0153) and rash (u=4.362, P<0.01) than Cetuximab. Conclusions: Helical Tomotherapy combined with Nimotuzumab or Cetuximab was effective and no difference in the short-term efficacy and one year survival rate for the patients with NPC. Nimotuzumab has less acute reaction than Cetuximab. More studies should be done to prove long-term effects.
Safety Profile of Venetoclax Monotherapy in Patients with Chronic Lymphocytic Leukemia
Authors: John F Seymour, Matthew S. Davids, Andrew W. Roberts, Michael Hallek, William G. Wierda, Peter Hillmen, John F. Gerecitano, Elisa Cerri, Jalaja Potluri, Su Young Kim, Todd Busman, Maria Verdugo, Rod A. Humerickhouse, Andrea Best, Monali Desai, Stephan Stilgenbauer
Journal: Blood (2016)
A multiplex immunoassay for the non-invasive detection of bladder cancer.
Authors: Charles Joel Rosser, Yoshiko Shimizu, Hideki Furuya, Peter Bryant-Greenwood, Owen Chan, Yunfeng Dai, Mark Thornquist, Steve Goodison
Journal: Journal of Clinical Oncology (2016)

471 Background: Urine based assays that can non-invasively detect bladder cancer (BCa) have the potential to reduce unnecessary and invasive procedures. The purpose of this study was to develop a multiplex immunoassay that can accurately and simultaneously monitor 10 diagnostic urinary protein biomarkers for application as a non-invasive test for BCa detection Methods: A custom electrochemiluminescent (ECL) multiplex assay was constructed (Meso Scale Diagnostics, LLC, Rockville, MD) to detect the following urinary proteins; IL8, MMP9, MMP10, ANG, APOE, SDC1, A1AT, PAI1, CA9 and VEGFA. Voided urine samples from two cohorts (cohort #1 n = 62 and cohort #2 n = 200) were collected prior to cystoscopy and samples were analyzed blinded to the clinical status of the participants. Means (±SD) and receiver operating characteristic (ROC) curve analysis were used to compare assay performance and to assess the diagnostic accuracy of the diagnostic signature. Results: Comparative diagnostic performance analyses revealed an AUROC value of 0.9258 for the multiplex assay and 0.9467 for the combination of the single-target ELISA assays (p = 0.625), so there was no loss of diagnostic utility for the MSD multiplex assay. Analysis of the independent 200-sample cohort using the multiplex assay achieved an overall diagnostic sensitivity of 0.85, specificity of 0.81, positive predictive value 0.82 and negative predictive value 0.84. Conclusions: It is technically feasible to simultaneously monitor complex urinary diagnostic signatures in a single assay without loss of performance. The described protein-based assay has the potential to be developed for the non-invasive detection of BCa.
Using the decline in CA19-9 after the start of chemotherapy to predict survival in patients with inoperable bile duct cancer.
Authors: Mie Grunnet, Lene Baeksgaard, Inga Laursen, Ulrik Niels Lassen, Morten Sorensen
Journal: Journal of Clinical Oncology (2012)

287 Background: CA 19-9 has been approved by the FDA as a tumour marker in pancreatic cancer. The prognostic value of CA19-9 in cholangiocarcinoma is unclear.The aim of the study was to determine if an early CA 19-9 response after the first cycle of chemotherapy is predictive of survival in patients with inoperable bile duct cancer. Methods: CA 19-9 response was defined as a 20% decline in CA 19-9 compared to baseline after four weeks of chemotherapy, in patients with a baseline CA 19-9 level above 1.5 times the upper limit of normal (ULN). Patients were identified retrospectively database at a single institution. Chemotherapy used was gemcitabine day 1 and 15 (1g/m 2 ), oxaliplatin day 1 and 15 (60 mg/m 2 ) and capecitabine (1g/m2 BID) days 1 to 7 and days 15-21 for six cycles. Patients with a baseline CA 19-9 above 1.5 the ULN and at least one CA 19-9 value measured four weeks after the start of chemotherapy were included in the study. Survival in CA 19-9 responders was compared to non-responders by use of the log rank test. A Cox regression analysis was performed using performance status, gender, disease extent and location, need for endoluminal stenting, baseline CA 19-9, and CA 19-9 response as co-variables. Results: 212 patients were registered from Feb 2004 until Nov 2010. Among these, 170 were treated with chemotherapy for cholangiocarcinoma and 131 had a baseline CA 19-9 value and at least one follow-up CA 19-9. Patients with baseline CA 19-9 less than 1.5 times the ULN (n=45) or inconclusive measurements (n=7) were excluded leaving 79 patients in the study. Fifty per cent of patients had a CA 19-9 response to chemotherapy. The median survival in the CA 19-9 response group was 11.7 months (95%CI: 7.5 – 16.0) vs. 8.2 months (95% CI: 6.4 – 9.8) in the non-response group. CA 19-9 response (HR: 0.535 (95%CI; 0.331-0.866), p=0.01) and disease extent (metastasis vs. no metastasis) (HR: 0.604 (95%CI; 0.369-0.99) p=0.046) were independent predictors of survival in a Cox model. Conclusions: CA19-9 response is useful as predictor of survival in patients with inoperable cholangiocarcinoma undergoing chemotherapy.
Cancer survivorship in Germany: Education of GPS—Why and how?
Authors: Georgia Schilling, Wilhelm Niebling, Angelika Mack-Hennes, Dirk Arnold
Journal: Journal of Clinical Oncology (2016)

97 Background: General Practitioners (GP) play a pivotal role in caring for patients with malignant diseases in screening and detection, additional supporting care whilst treatment, and (long-term) follow-up. They often do not feel to be qualified enough for this task, and as well claim to lack support by specialists. This is a well-known problem, already addressed by the Institute of Medicine a few years ago. As an increasing number of patients will be diagnosed with cancer – and will survive for many years, following curatively intended treatment or with a chronic cancer disease, Cancer Survivorship was identified as the area of utmost importance. The relevance of this field was underlined by the disappointing results of the simple question we asked GPs: “When and how often should the tumor markers CEA, CA 15.3, and PSA be assessed during standardized follow-up of patients with early breast cancer, colorectal cancer or prostate cancer?”. Only one out of 30 answered it correctly. Together with the State Chamber of Medicine of Südbaden, we started an education program for GPs to improve this critical interface. Methods: During a full day training, we provided an educational program covering the most relevant topics in Cancer Survivorship: physical long-term sequelae and late complications after multimodal therapy strategies, their prevention and treatment; fatigue and self management, reasonable complementary and alternative medicine; management of chronic pain syndromes, recommendations for tertiary prevention, physical activities, nutrition and a guideline conform follow-up. Training was completed by a knowledge test and an overall evaluation. Results: All participants welcomed this newly implemented training program and considered it as very useful for their daily practice. Further support was urgently requested by the GPs, preferably in the format of (defined) Survivorship Care plans and follow-up schedules. Conclusions: GPs need more support and information in Cancer Survivorship. Widespread trainings programs should be developed and offered, in close collaboration with the respective State Chambers of Medicine and cancer specialists, and GPs, and further improve the outpatient care of cancer survivors.
Unanticipated hospital admissions in patients undergoing radiotherapy with or without concurrent chemotherapy: Incidence and predictive factors.
Authors: Nabeel H. Arastu, Ronald C. Chen, Marianne Jackson, Rebecca L. Green, Bahjat F. Qaqish, Jayne Camporeale, Zijie S. Xu, Frances A. Collichio, Lawrence Bruce Marks
Journal: Journal of Clinical Oncology (2012)

6093 Background: Unanticipated admissions are burdensome for patients and the healthcare system. An improved understanding of their frequency and predictive factors can inform initiatives to prevent such admissions and mitigate their associated human and financial costs. Methods: Electronic medical records of 500 patients undergoing external beam radiotherapy (RT) at our center in 2010 were reviewed. Unanticipated admission within 90 days of initiating RT, and associated clinical factors, were recorded. Chi-squared and uni- and multivariate logistic regression was used to examine factors associated with admission. Results: Unanticipated admissions occurred in 20% (101/500) of patients, mean length of stay was 4 days (range 1-16), and the mean interval between the start of RT and admission was 32 days (0-86 days). The most common indications for admissions were pain (19% of admissions), respiratory distress (15%), and neurologic symptoms (13%). On univariable analysis, 33% of patients treated for palliative intent were admitted (vs. 16% of curative intent patients, p&lt;0.001), as were 26% of patients receiving concurrent chemotherapy (vs. 17% receiving RT alone, p=0.02). Multivariable analysis showed treatment intent, chemotherapy, and marital status to be associated with unplanned admissions (Table). A highly variable rate of unanticipated admission per diagnosis was observed (e.g. 4% for breast, 19% for GI/GU/GYN/ENT, and 37% for metastatic sites). Conclusions: Rates of unanticipated admissions are ≈20% in patients undergoing RT. Approximately 1/3 of patients receiving palliative RT, and more than 1/4 receiving concurrent chemoradiation, experienced an unplanned admission. Prophylactic measures should be studied in these high-risk patients to reduce admission rates, as unplanned admission may be an important quality of care indicator in oncology. [Table: see text]
Prevalence of putative breast cancer stem cells (BCSC) in lymph node occult metastases (LNOM) of patients with node-negative (LN-) breast cancer (BC)
Authors: D. Hawes, M. Patel, K. K. Hunt, A. E. Giuliano, R. J. Cote
Journal: Journal of Clinical Oncology (2008)

1069 Background: Cancer stem cells are a subpopulation of tumor cells that have the properties of self-renewal and differentiation and are thought to drive tumorigenisis. The putative BCSC phenotype is CD44+/CD24-/low and in primary BC represents a minority population (<10%). We have found BCSC constitute about 70% of tumor cells found in the bone marrow (BM) of patients with primary BC. We sought to determine the proportion of BCSC in LNOM of patients with LN- BC. Methods: Fifty sentinel LN positive for OM from the American College of Surgeons Oncology Group (ACOSOG) Z0010 clinical trial were assessed using immunohistochemistry double marker analysis for the presence of CD44/CD24. Slides were examined by spectral imaging using the Nuance FLEX Imaging System (CRI, Woburn, WA). Tumor cells present in the sentinel LN were simultaneously assessed for the presence of CD44 and CD24. Results: Sufficient tumor cells were identified by CD44/CD24 double staining on 43 of the 50 cases. Of these 43 cases 22 (51%) had no BCSC (CD24>CD44, 12 cases; CD44-/CD24+, 2 cases; CD44=CD24, 7 cases; CD44-/CD24-, 1 case). In eleven (26%) cases 100% of tumor cells showing the putative BCSC phenotype and 10 cases (23%) had a subpopulation of stem cells with the BCSC phenotype (0–25% 2 cases, 26–50% 4 cases, 51–75% 1 case, 76–99% 3 cases). Conclusions: The majority of tumor cells identified in the sentinel nodes of patients with LNOM do not show the BCSC phenotype, with 51% showing no BCSC. Four different negative phenotypes were identified. In those cases in which the LNOM showed BCSC, the majority of the tumor cells had the BCSC phenotype. These results are in contrast to OM in BM, where the majority of tumor cells were BCSC. These results may have implications for risk for disease progression based on the proportion of BCSC in the LNOM tumor cell population, an idea that will be pursued as the outcomes for the Z0010 trial are evaluated. No significant financial relationships to disclose.
Effect of nab-rapamycin versus rapamycin in colorectal cancer cell lines and associations with KRAS and PI3K mutations.
Authors: H. F. Kennecke, M. Rahman, S. Yip, R. Woods, D. Schaeffer, I. Tai
Journal: Journal of Clinical Oncology (2011)

e13532 Background: The value of mTOR inhibitor therapy in metastatic colorectal cancer (mCRC) has not been established. Activation of the PI3K-AKT-mTOR pathway may be influenced by KRAS and PI3K mutations and may point to therapeutic subgroups for mTOR therapy. The effect of rapamycin and nab-rapamycin, nanoparticle albumin-bound rapamycin, was evaluated in colorectal cancer cell lines for which mutational status was determined. Methods: KRAS (codon 12,13) and PI3K (exon 9,20-1,20-2) mutation status was determined on cell lines (MIP101, RKO, HCT116 and SPARC-overexpressing MIP101 (MIP/SP) and on a tissue microarray (TMA) cohort of 96 patients with mCRC. Immunohistochemical staining was done on the TMA for mTOR, PTEN and pAKT. Univariate analyses were done to estimate association between KRAS, PI3K and protein expression. Cell viability assays were conducted with rapamycin and nab-rapamycin (0, 10, 50 and 100 nM) on CRC cell lines. Results: Among 96 cases included on the TMA, 35% were KRAS mutant and 6% were PI3K mutant. Four of the 5 PI3K mutations occurred in KRAS mutant tumors. There was no association between KRAS status and mTOR expression, or PI3K status and mTOR,pAKT or PTEN. Increasing expression of mTOR (0-3+) was modestly associated with increasing pAKT expression (rho = 0.37, p <0.001). In mutational testing of cell lines, 100% had a PI3K mutation and 100% had either a KRAS or BRAF mutation. Nab-rapamycin and unbound rapamycin were both effective in reducing cell viability in RKO, HCT116 and MIP/SP cells, whereas only nab-rapamycin significantly reduced cell viability in MIP101 cells (p<0.039). In MIP101 cells, nab-rapamycin, but not unbound rapamycin, resulted in a significant decrease levels of phosphorylated p70 S6 kinase. Conclusions: In this study, associations between PI3K, KRAS and IHC expression in the PI3K-AKT-mTOR pathway could not be established. CRC cell lines had a high rate of PI3K and KRAS/BRAF mutations not seen in human tumors. Nab-rapamycin reduces CRC cell viability and decreases downstream signaling.