tbuckley/cabot-search huggingface dataset:
Education practices in prostate cancer: A comparison of patient and caregiver experiences.
Authors: John Clayton Allen, Liping Du, Ivy A Ahmed, Alicia Katherine Morgans
Journal: Journal of Clinical Oncology (2016)

88 Background: Evidence suggests that greater knowledge of an illness is associated with better health outcomes, and interventions that enhance disease-specific knowledge can improve these outcomes. Information needs among prostate cancer survivors and their caregivers are incompletely described. We assessed information needs and practices among men with prostate cancer and prostate cancer caregivers at the time of diagnosis. Methods: Using the online “Prostate Cancer Education Survey” performed by prostate cancer non-profit ZERO completed 2013-2014, we evaluated 824 patients with prostate cancer and 168 prostate cancer caregivers to determine information needs regarding prostate cancer. We used Pearson chi-squared tests and multivariable logistic regression models to determine educational needs and experiences among patients and caregivers, and their association with clinical and sociodemographic factors. Results: Among 824 patients and 168 caregivers describing information received at diagnosis, statistically significantly fewer caregivers reported receiving information as compared with patients (79% of patients vs 71% of caregivers; p = 0.002). Among 543 patients and 98 caregivers who reported receiving information, patients were more likely to report that the information was more useful, and caregivers were more likely to report that the information was less useful on a five-point usefulness scale (p = 0.05). Only time since diagnosis was significantly associated with report of receipt of educational material at diagnosis for both patients and caregivers (p &lt; .001) in multivariable regressions. Conclusions: Although most patients and caregivers report receiving prostate cancer information when diagnosed, caregivers report this less frequently, and more frequently report that it was not useful. Efforts to address this disparity should further investigate the information needs of prostate cancer caregivers to provide them with more consistent and useful information.
Randomized phase II trial comparing two strategies in high-risk rectal cancer (RC): Chemoradiation (CRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy (CT) or induction CT followed by CRT and TME— Preliminary results of the multicenter GCR-3 study
Authors: C. Fernandez-Martos, C. Pericay, A. Salud, V. Alonso, B. Massuti, M. Safont, R. Vera, P. Escudero, J. Maurel, J. Aparicio
Journal: Journal of Clinical Oncology (2008)

4087 Background: Preoperative CRT followed by TME and CT is a standard strategy in locally advanced rectal cancer. Systemic disease is a major problem in this setting and for several reasons at least 50% of patients (P) can not receive the planned post-op CT. Induction CT prior to CRT and TME may be associated with better compliance and downstaging can improve CRT efficacy. Methods: Eligible P had medium or distal RC with high risk criteria defined by MRI and/or US: Tumors within 2mm of mesorectal fascia, distal T3 at/below levators, resectable T4 and T3N+ tumors. P, stratified by center, were randomized assigned to receive either Arm A : Cap 825 mg/m2 po BID 5 d/w throughout RT, Ox 50 mg/m2 IV weekly x 5 and concomitant RT: 50.4 Gy in 28 fractions. TME was planned 5–6 w after CRT. Post-op four cycles of Cap 1,000 mg/m2 bid on days 1 to 14; Ox 130 mg/m2 on day 1 were administrated or Arm B: Induction CapOx followed by CRT and TME. Primary end point: pCR. Standardized pathology examination was performed using the Quirke protocol. Trial design: 2 parallel, Simon 2-stage designs; requires 2- 6 pCR in 24 evaluable pts for 2nd stage; 54 p/arm. A randomized phase II selection design was used to identify the strategy most likely to be superior. Results: 108 P enrolled at 14 sites were randomized between 5/06–11/07. In this planned interim analysis 48 p (arm A/B 24/24) are evaluable for toxicity; 40 (19/21) for p response. Overall Grade ¾ toxicity (%pts A/B) 48/39. Diarrhoea: 17%/17%; Fatigue 13%/9%; sensory neuropathy 4%/0%, neutropenia 4%/0%, hand-foot syndrome 0%/4%.Two deaths (1/1) occurred during the postop period due to surgical complications. pCR rate 10% (95%CI; 1.3% to 33.1%)/19% (95%CI; 5.5% to 41.9%). Additionally good-moderate tumor regression grade in 90%/63%. Median Dose intensity of adjuvant/induction was 0.75/1.0 (p=0.001) for Cap and 0.62/1.0 (p=0.003) for Ox. (Wilcoxon Two-Sample Test). Conclusions: Both strategies seem active and safe in this high risk population. Induction CT seem associated with better compliance to treatment plan. This trial is supported by sanofi- aventis No significant financial relationships to disclose.
The estimated hospital-wide financial impact of a comprehensive inpatient palliative care (PC) program.
Authors: Sarina Isenberg, Chunhua Lu, John P McQuade, A. Rab Razzak, Natasha Gill, Michael A Cardamone, Deirdre Torto, Terry Langbaum, David R Holtgrave, Thomas J. Smith
Journal: Journal of Clinical Oncology (2016)

173 Background: Inpatient PC improves quality of care, patient and family satisfaction, and lowers costs. PC consultation during a cancer hospital stay led to a 14 (if by day 6) to 24% (by day 2) reduction in direct cost, and especially when people had comorbidities. (May, JCO 2015; Health Affairs 2016). We attempted to discern the financial impact of both a PC inpatient unit (PCU) and PC consultations on patients in other inpatient units for a large academic medical center, the Johns Hopkins Hospital (JHH), as we prepared to expand the PCU from 6 to11 beds and increased inpatient PC consultation capacity. Methods: We estimated the savings for an 11 bed PCU based on cost per day from FY 2015 with a 6 bed unit ($444 lower costs per PCU day compared to inpatient stay prior to transfer to the PCU). We then calculated the cost savings for an 11 bed unit operating at 80% occupancy. We estimated the direct cost savings of consultations by adjusting the $/discharge saved (Morrison, Arch Int Med 2008) to 2014 $ (by multiplying the $/discharge saved by 1.4 to adjust for medical inflation). Results: The PCU inpatient stays resulted in projected lower costs of $6.7M over 5 years ($444/day x 3009 days/year, or $~1.3M yearly). IP revenue and margins were small (data not shown). For PC consults of 785 alive discharges ($2197/case) and 97 decedent discharges ($6357/case), total estimated savings in direct costs per case are $2,530,000/year. The PCU allows for additional benefits not calculated in this analysis, including inpatient backfill opportunities, more appropriate ICU bed use, savings from increased referral to hospice (hospice referrals increased 340% in 3 years), and reduced readmission rates from increased PC and hospice use. Conclusions: In addition to improving quality of care and patient satisfaction, the combined IP and consult PC programs contribute to substantially lower charges and costs per day. Backfill revenue, the opportunity for increased revenue from improved patient satisfaction (HCAHPS) scores, and reduced readmission rates will increase this financial impact. [Table: see text]
Dissecting the therapeutic effects of anti-CTLA-4 and ADT in a murine hormone-sensitive prostate cancer.
Authors: Sumit Kumar Subudhi, Welby Montalvo-Ortiz, Howard I. Scher, James Patrick Allison
Journal: Journal of Clinical Oncology (2013)

61 Background: Immune checkpoint blockade with anti-CTLA-4 has emerged as a successful, novel form of cancer immunotherapy that acts directly on activated T cells instead of on cancer cells. CTLA-4 blockade can result in durable, long-term responses, but only a subset of patients treated benefit from this approach. Androgen deprivation therapy (ADT) is the first-line treatment for advanced prostate cancer, and it produces some of the most dramatic responses in clinical oncology. Clinically, the combination of ADT and anti-CTLA-4 was found to be more effective than ADT alone. To optimize the development of combination regimens, we examined the kinetics of the immune effects of ADT ± anti-CTLA-4 in a murine model of hormone-sensitive prostate cancer. Methods: Mice with established Myc-CaP prostate tumors were divided into 4 treatment groups: 1) untreated, 2) degarelix, 3) anti-CTLA-4, or 4) degarelix plus anti-CTLA-4. Tumor growth was measured biweekly. Tumor-infiltrating lymphocytes and T cell cytokine production was determined by flow cytometric analysis and serum IFN-gamma levels were assessed by ELISA. Results: We found that degarelix rapidly induces castrate levels of testosterone within 24 hours in mice and maintains these levels for at least 35 days. The combination of degarelix and anti-CTLA-4 improved median overall survival compared to degarelix alone (P&lt;0.030, Mantel-Cox log-rank test). Tumor regression was associated with the production of the Th1-cytokines, IFN-gamma and TNF-alpha by tumor-infiltrating CD4+ and CD8+ T cells within 1 week of treatment initiation. This response peaked at 2 weeks after treatment initiation and was associated with elevated levels of serum IFN-gamma levels. In this model, anti-CTLA-4 monotherapy had no effect on tumor growth rates or intratumoral/sera cytokine levels. Conclusions: The combination of immune checkpoint blockade with anti-CTLA-4 and medical castration with degarelix is therapeutically effective in a murine model of hormone-sensitive prostate cancer, likely through an IFN-gamma-dependent manner. This model can be used to better identify potential post-treatment biomarkers that can be studied for associations with clinical outcomes.
Epoetin beta in patients with metastatic breast cancer receiving chemotherapy: Results from the Breast Cancer - Anemia and the Value of Erythropoietin (BRAVE) study
Authors: M. Marangolo, N. Malamos, J. L. Pedrini, M. Rotarski, I. Láng, C. Beato, R. Colomer, L. Ukarma
Journal: Journal of Clinical Oncology (2005)

8141 Background: Many patients with metastatic breast cancer are treated with anthracycline and/or taxane-based chemotherapy; such therapies produce a high incidence of anemia. The aim of the BRAVE study was to evaluate the impact on survival, efficacy, safety and quality of life (QoL) of once-weekly epoetin beta 30 000 IU (NeoRecormon) in patients with metastatic breast cancer receiving anthracycline and/or taxane-based chemotherapy. Methods: Adult patients with metastatic breast cancer, scheduled to receive anthracycline and/or taxane-based chemotherapy and with hemoglobin (Hb) <12.9 g/dl at screening were entered into this open-label, randomized, multicenter, two-arm study. Patients were randomized to receive epoetin beta 30 000 IU once weekly or standard care (red blood cell transfusion as required) for 24 weeks. The primary endpoint was overall survival, which will be available 18 months after the last patient last treatment visit. Results: Recruitment for the study was completed in June 2004 and 463 patients were enrolled. Baseline data of 462 patients are shown in the table. In those patients completing the 24-week study period and analyzed to date (n=347), median Hb levels increased during epoetin beta treatment to 13.4 g/dl (interquartile range [IQR] 12.5–14.5) at the end of week 24. In contrast, median Hb levels remained unchanged in the control group at 11.4 g/dl (IQR 10.5–12.5) at the end of week 24. Conclusions: Once weekly epoetin beta 30 000 IU corrects anemia in patients with metastatic breast cancer receiving anthracycline and/or taxane-based chemotherapy. Full patients' and treatment safety data will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Ltd. Hoffmann-La Roche Ltd.
BCR-ABL Levels Continue To Decrease up to 42 Months after Commencement of Standard Dose Imatinib in Patients with Newly Diagnosed Chronic Phase CML Who Achieve a Major Molecular Response.
Authors: Susan Branford, Z. Rudzki, A. Grigg, J. F. Seymour, K. Taylor, P. Browett, A. Schwarer, K. Bradstock, C. Arthur, S. Durrant, D. Ma, D. Joske, K. Lynch, T. Hughes
Journal: Blood (2004)
Extrapulmonary neuroendocrine tumors: An institutional experience of 337 patients at the National Cancer Center Hospital in Japan.
Authors: T. Terashima, C. Morizane, H. Ueno, M. Ikeda, Y. Saito, Y. Shimada, R. Kushima, N. Hiraoka, Y. Kanai, T. Okusaka
Journal: Journal of Clinical Oncology (2011)

293 Background: Extrapulmonary neuroendocrine tumors (EPNET) are a rare and heterogeneous disease entity, and little information regarding these tumors is available. The aim of the present study was to clarify the clinical behavior, treatment strategy, and outcome of EPNET arising from various primary sites. Methods: We retrospectively reviewed the medical records of 337 patients with pathologically confirmed NET arising from extrapulmonary site between January 2000 and December 2008 at the National Cancer Center Hospital of Japan. Results: The major primary tumor site was the rectum followed by the pancreas and stomach. Among the gastrointestinal tract tumors, 113 patients had NET from the foregut, 92 patients from the hindgut, and only 4 patients from the midgut. The median patient age was 60 years, and 57% of the patients were male. The histologic grade was as follows: 39% were well-differentiated neuroendocrine tumors (WDNET); 20% were well-differentiated neuroendcrine carcinomas (WDNEC); 33% were poorly differentiated neuroendocrine carcinomas (PDNEC); and 8% were mixed exocrine-endocrine tumors (Mixed). Most NETs from the rectum or duodenum are WDNET, whereas the ratio of PDNEC was high among NET from the genital organs or esophagus. The treatment strategy was associated with the clinical stage or the primary organ; in particular, 94% of the localized rectal NET were resected endoscopically. The 2-year survival rate for all the patients were 70%. A multivariate analysis demonstrated that distant disease of clinical stage and PDNEC of histological grade had a stronger impact on a poor outcome than the primary tumor site. The 2-year survival rate among the patients with WDNET, WDNEC and PDNEC were 97%, 80% and 36%, respectively, and 94%, 72%, and 32% of the patients had localized, regional, and distant disease, respectively. Conclusions: Japanese patients with EPNET have different clinicopathological features such as the primary organ or treatment procedure compared with previous reports in Western countries. Identifying the precise clinical stage and histological grade of patients with NET is essential because these factors influence the patient outcome. No significant financial relationships to disclose.
Regulation of Oct4 signaling on tumorigenesis and modulation of wnt/β-catenin and TGF-β signal pathways in hepatocellular carcinoma cells.
Authors: A. R. Bassiouny
Journal: Journal of Clinical Oncology (2011)

e13551 Background: Hepatocellular carcinoma (HCC) is a dreadful cancer, and is the third leading cause of cancer related death worldwide. Standard therapy is ineffective partly because HCC is intrinsically resistant to conventional chemotherapy. The cancer stem cell (CSC) hypothesis proposes that CSCs are responsible for chemo-resistance, recurrence, and metastasis. Its poor prognosis and limited treatment options make it critical to develop novel and selective chemotherapeutic agents. Since Oct4 is essential in stem cell and in embryo regulation, we sought to evaluate the role of Oct4 in HCC and the relationship among Oct4 and Wnt/β-catenin and TGF-β signal pathways, and evaluate the therapeutic efficacy of curcumin, a known Wnt/β-catenin pathway inhibitor. Methods: We analyzed the functional implications of Oct4 in HCC and the relationship among Oct4 and Wnt/β-catenin and TGF-β signal pathways, in tumor specimens from HCC patients. Results: We demonstrated that Oct4 is highly expressed in a subgroup of human HCC tissues compared to paired adjacent non-tumor tissues with other genes including STAT3, Wnt-1, β-catenin, Smad3 and Smad4. Treatment with curcumin led to a dose-dependent decrease in the expression of Oct4 and Wnt-1 in HCC cell line from tumor specimens. Silencing of Oct4 in human HCC cell line revealed that there were complicated relationships among Oct4, Wnt/β-catenin family and TGF-β family genes. Apoptosis was also observed in human HCC cells after treatment with curcumin. Conclusions: Our results suggest that the blockade of Oct4-mediated signaling with curcumin may offer an attractive new therapeutic strategy for the treatment of patients with HCC.
The predictive values of carcinoembryonic antigen (CEA) in patients with metastatic non-small cell lung cancer (NSCLC) treated with gefitinib
Authors: L. D. Bharwani, G. Lopes, E. H. Lim, W. Hsieh, A. Y. Chang, L. Shen
Journal: Journal of Clinical Oncology (2008)

22145 Background: Gefitinib inhibits the signaling of the EGFR tyrosine kinase and has shown activity in the treatment of advanced NSCLC, especially in Asian patients. Mutation in EGFR exon 19 and 21 have been shown to be the strongest predictor of response to gefitinib. Other clinical factors which also predict for response include female gender, adenocarcinoma, never smoker and Asian ethnicity. Recently, CEA was reported as a predictive factor of the efficacy of gefitinib and its level was associated with the frequency of EGFR mutation. Methods: We retrospectively reviewed records of 125 patients with metastatic NSCLC who received gefitinib as the only treatment and identified 24 cases that had at least one CEA serum level determined before starting gefitinib and response could be evaluated. 9 cases had serial serum CEA determined during the gefitinib therapy. Response was evaluated every 2 months by CT scans and using the RECIST criteria. Pre-treatment CEA>5 ug/L was defined as abnormal. Results: See Table. 7/9 patients with serial CEA measurements had abnormal pre-treatment CEA. The fall and rise of CEA in these 7 patients coincided with the response and progression respectively to gefitinib 100% of the time. Conclusions: Female gender, never smoking, and adenocarcinoma remain the significant factors to predict response to gefitinib. Pre-treatment CEA level did not predict for response to gefitinib. However, serial measurements of CEA in patients with abnormal CEA may be worthwhile as an indicator of disease status. Clinical Factors N Response to Gefitinib P value CR+PR SD PD Never smokers 17 12 4 1 0.033 Ex- or current smoker 7 2 1 4 Female 17 14 1 2 0.0003 Male 7 0 4 3 Adenocarcinoma 19 13 4 2 0.042 Non-adenoca 5 1 1 3 Pre-treatment CEA 0.671 Abnormal 16 9 4 3 Normal 8 5 1 2 No significant financial relationships to disclose.
Sequential azacitidine and lenalidomide in elderly acute myeloid leukemia: completed results of the phase I study.
Authors: D. A. Pollyea, H. E. Kohrt, L. Gallegos, B. Zhang, M. Figueroa, A. Melnick, C. Berube, S. E. Coutre, J. R. Gotlib, J. L. Zehnder, M. Liedtke, B. S. Mitchell, B. C. Medeiros
Journal: Journal of Clinical Oncology (2011)

6505 Background: Most AML patients (pts) are elderly with poor outcomes, correlating with tumor suppressor gene (TSG) hypermethylation. Azacitidine (AZA) demethylates TSGs; lenalidomide (LEN) has anti-leukemia activity. We hypothesize this combination hypomethylates/activates TSGs and is a tolerated maintenance regimen for pts without curative options. Methods: We enrolled pts ≥ 60 with untreated AML. Cohort 1 received 75 mg/m2 AZA SC/IV (d 1-7), 21 days off, then a cycle of AZA (d 1-7) followed by LEN 5 mg PO (d 8-28), and 14 days off (d 29-42). Cohorts 2, 3 and 4 got the same dose/schedule of AZA with LEN 10, 25 and 50 mg, respectively. Pts received 12 cycles if a complete response (CR), CR with incomplete recovery (CRi) or partial response (PR) was achieved without toxicity. A genome wide assay of DNA methylation was performed. Results: Eighteen pts enrolled. Median age was 72 (64-86). Ten of 18 (56%) had AML with MDS, 7 had AML NOS (39%) and 1 had t-AML. Three of 18 (17%) had adverse cytogenetics; 15/18 (83%) were intermediate. Maximum tolerated dose (MTD) was not reached. Pts received a median of 3 cycles (0-10). Common AEs were fatigue (94%), injection reaction (72%), constipation (61%), nausea (61%). Eleven pts had 17 serious AEs; none were regimen related. Ninety day mortality was 22% from progression (n=3) or hemorrhage (n=1). No treatment related deaths occurred. With follow up of 246 d (21-482), 10/18 (56%) are alive. In cohort 1, 2 did not complete a full cycle and were replaced; 0/3 evaluable pts responded. In cohorts 2, 3 and 4, 2/3, 2/4 and 5/6 responded, respectively. The overall response rate (CR+CRi+PR) was 56% (10/18). Seven evaluable pts had a CR/CRi (44%), and 3 had a PR (19%). All 6 non-responders died of progression. Median response duration was 199 d (42-403); median OS was 246 d (21-482). The HELP assay showed treatment resulted in demethylation. A trend toward differential methylation was observed between pts who did and did not achieve a CR. Conclusions: Sequential AZA and LEN was well tolerated. The MTD was not reached; the Phase II dose/schedule is AZA 75 mg/m2 d 1-7 and LEN 50 mg d 8-28 q 6 weeks. The 56% ORR and high CR/CRi rate support further study of AZA and LEN as maintenance therapy for elderly AML.
Phase II study of gefitinib adaptive dose escalation to skin toxicity in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
Authors: C. A. Perez, H. Song, L. E. Raez, M. Agulnik, T. A. Grushko, A. Dekker, K. Stenson, E. A. Blair, O. I. Olopade, T. Y. Seiwert, E. E. Vokes, E. E. Cohen
Journal: Journal of Clinical Oncology (2011)

5517 Background: Gefitinib (G) has shown activity as a single agent in patients (pts) with advanced SSCHN, and a dose-response relationship has been observed. Skin toxicity has been postulated to be a predictor of response and improved outcome. The purpose of this study is to evaluate the activity of G when administered as single agent at a dose that produces grade 2 skin toxicity in pts with recurrent and/or metastatic SCCHN. Methods: Pts were started on 250 mg/day of G. If skin toxicity was less than grade 2, the dose was escalated to the next level of dose, 500 mg/day then 750 mg/day if necessary. Tumor response was assessed by RECIST 1.0. EGFR gene copy number was analyzed by FISH. Results: From 05/2005 to 04/2008, 44 pts were enrolled, including 35 males(79.5%). 40 (90.9%) pts received prior radiation therapy and 39 (88.6%) prior chemotherapy. Twenty three (54.8%) experienced skin rash of grade 2 or more, 17 of them with G 750 mg/day; 10 patients did not get G escalated to 750 mg/day; 6 because of early progressive disease (PD). Of 44 pts, 8 were not evaluable for response. Partial responses (PR) were noted in 3 (7%), stable disease (SD) in 8 (18%) and PD in 33 pts (75%). The disease control rate (PR+SD) in the 36 evaluable pts was of 31%. 2/3 PR and 6/8 SD had skin rash of grade 2 or more. Median progression-free survival (PFS) was 1.9 months (95% CI 1.6 to 2.2 months) and median overall survival (OS) was 5.1 (95% CI 2.4 to 7.8) months. Grade of skin rash was not associated with the response rate (p=0.169, OR 0.583, 95% CI 0.049~6.977) nor tumor control rate (p=0.284, OR 0.352, 95% CI 0.078~1.579). Of the 11 tissue samples analyzed for EGFR gene copy by FISH, 7 were EGFR FISH positive (EGFR/CEP7 ratio >2), but this was not associated with improved tumor control, PFS or OS. Diarrhea and rash were the most common toxicities, seen in 73% and 63% of the pts. Conclusions: Gefitinib has clinical activity as monotherapy in SCCHN. EGFR FISH was not associated with clinical outcome in the small subset analyzed; dose escalation of gefitinib to increase skin toxicity grade did not improve respose rate in this study.