tbuckley/cabot-search huggingface dataset:
Bereavement practices of Canadian cancer physicians
Authors: N. Chau, C. Zimmermann, C. Ma, N. Taback, M. K. Krzyzanowska
Journal: Journal of Clinical Oncology (2008)

9550 Background: Bereavement follow-up is essential to quality end-of-life care, yet little is known about physician-family interaction after a patient dies. Our objectives were to determine current bereavement practices among medical oncologists (MO), radiation oncologists (RO) and palliative care specialists (PC); and to identify barriers and strategies to facilitate bereavement care. Methods: We surveyed all Canadian MO, RO and PC via their respective national organizations between 03–05/2007 using an anonymous electronic and post mail survey. Frequencies of bereavement practices were assessed using a five-point Likert scale; results were described using summary statistics and Fisher’s exact test. Logistic regression was used to determine predictors of bereavement practices. Results: Response rate was 71% (550/771). Median age of the respondents was 48 years, 40% were female, 55% worked in an academic setting, 75% spent over half of their time in patient care. Median number of patient deaths per month was 3 MO, 2 RO, 8 PC. Table 1 shows frequency of bereavement practices. Only 9% (95%CI 6.6–11.5%; 48/528) of respondents felt that physicians had a responsibility to send a condolence card. Stepwise regression showed that: lack of time (OR=1.77, p=0.02) and lack of responsibility (OR=3.79, p=0.03) rather than anxiety or guilt are significant barriers; and being female (OR=2.27, p=0.0009), palliative care specialty (OR=8.33, p<0.0001), access to a bereavement care program (OR=1.95, p=0.008) and working in an academic setting (OR=1.77, p=0.02) were significant predictors of more frequent bereavement practices. Conclusions: Physicians do not routinely provide bereavement follow-up due to lack of time and perceived responsibility. Interdisciplinary bereavement programs and defining physician role may facilitate bereavement follow-up. Further research is needed to determine the relationship between physician bereavement practice and caregiver grief reactions or physician burnout. Frequency of bereavement practices according to specialty Bereavement practice MO% (95% CI); n RO% (95% CI); n PC% (95% CI); n p-value Always/usually send condolence card 18.2 (12.7–23.7); 34/187 7.1 (3.4–10.9); 13/182 29.5 (22.3–36.7); 46/156 <0.0001 Always/usually telephone family 21.3 (15.4–27.1); 40/188 9.3 (5.1–13.5); 17/183 34.8 (27.4–42.2); 55/158 <0.0001 Always/usually initiate family meeting 6.4 (2.9–9.9); 12/187 3.3 (0.7–5.9); 6/181 13.4 (8.1–18.7); 21/157 0.002 Always/usually attend funeral service 0.5 (−0.5–1.6); 1/187 1.1 (−0.4–2.6); 2/183 3.8 (0.8–6.8); 6/158 0.08 Always/usually refer family to bereavement support program 6.5 (2.9–9.9); 12/186 3.9 (1.1- 6.7); 7/180 19.1 (13.0–25.3); 30/157 <0.0001 No significant financial relationships to disclose.
Urinary dysfunction appears to be the primary determinant of castration versus observation for prostate cancer patients with PSA failure
Authors: J. A. Zagory, C. Chang, S. Knight, E. A. Lyons, C. L. Bennett
Journal: Journal of Clinical Oncology (2006)

14621 Background: After undergoing definitive treatment for a primary localized disease, prostate cancer patients may experience a rise in their prostate specific antigen (PSA) levels. Treating PSA failure with hormonal treatment has many health related quality of life (HRQOL) implications, including urinary, bowel, sexual, and male hormonal problems. Predictors of choice between hormonal treatment versus watchful waiting have not been investigated. Methods: Patients were approached after consecutive rises in PSA levels (n = 31). Patients completed HRQOL and decision satisfaction questionnaires, and a literacy assessment. Results: Patients were between 56 and 85 years old; 55% were African American. 71% of African Americans and 50% of whites had low functional literacy. 58% of patients chose hormonal therapy to treat their PSA rise; 81% of patients reported urinary problems. All patients reported decision satisfaction (see Table). Factors associated with castration versus watchful waiting were primarily related to poor urologic function, and were not specifically prostate cancer related (dysuria, nocturia, urination frequency). Conclusions: Primary treatment of urinary dysfunction, rather than castration, should be evaluated as initial therapy for prostate cancer patients with PSA failure. [Table: see text] No significant financial relationships to disclose.
MicroRNA expression profiling of human metastatic cancers
Authors: R. Baffa, B. O'Hara, M. Fassan, C. Liu, S. Volinia, J. P. Palazzo, C. M. Croce, A. L. Rosenberg
Journal: Journal of Clinical Oncology (2008)

1059 Small non-coding microRNAs (miRNAs) contribute to cancer development and progression and are differentially expressed in normal tissues and cancers. To test the hypothesis that a specific miRNA expression signature characterizes the metastatic phenotype of solid tumors, we performed miRNA micro-array analysis on 43 paired primary tumors and lymphnode metastasis. Specimens were collected at the Department of Pathology, Thomas Jefferson University from 43 patients consisting in 13 breast carcinomas, 10 lung cancers, 10 bladder urothelial cell carcinomas and 10 colon cancers. 5 μg of total RNA from each sample were used. Hybridization of biotin-labeled complementary DNA was performed on a two new miRNA microarray chip (OSU_CCC version 3.0 and 4.0), which contains ∼1,100 miRNA probes (326 human and 249 mouse miRNA genes, spotted in duplicates). We identified a common metastatic cancer miRNA signature mainly composed by over-expressed miRNAs. Some of these miRNAs (miR-10b, miR-20a, miR-21) have a well characterized association with cancer progression. In particular, in metastatic breast cancers there was an up-regulation of miR-450a, miR-148a and a down-regulation of miR- 205, miR-130b. In metastatic lung cancer there was an up-regulation of miR-369–3p and a down-regulation of miR-138–1. In metastatic bladder cancer there was an up-regulation of miR-29a, miR-10b, miR-126 and a down-regulation of miR-145, miR-143, and in metastatic colon cancer there was an up-regulation of miR-138, miR-21 and a down-regulation of miR-20a and miR-204. Moreover, in the metastatic samples we found that miRNAs associated to inflammation and immune response were over-expressed due to the partial contamination of our samples by the lymphocytes. The over-expression of most miRNAs that we found over-expressed in the primary tumors had been previously reported in published signatures of the corresponding normal tissues, thus confirming that miRNA signatures are a potent tool in classifying tissues of different origin.Our results indicate that specific miRNAs may be directly involved in cancer metastasis and that they may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets. No significant financial relationships to disclose.
Cancer incidence and mortality in the Caribbean
Authors: A. A. Phillips, J. S. Jacobson, C. Magai, N. Consedine, N. C. Horowicz-Mehler, A. I. Neugut
Journal: Journal of Clinical Oncology (2007)

21110 Background: Nearly 10% of immigrants to the United States come from the Caribbean region. In this paper, we analyzed incidence and mortality rates of the major cancers in the Bahamas, Barbados, Cuba, the Dominican Republic, Haiti, Jamaica, Puerto Rico, and Trinidad and Tobago, and compared them with US patterns. Methods: We obtained age-standardized, sex-specific cancer incidence and mortality rates for cancers of the bladder, breast, cervix, esophagus, large bowel, liver, lung, pancreas, prostate, and stomach for eight Caribbean countries and the US from the GLOBOCAN program of the International Agency for Research in Cancer (IARC) and for the US population from the Surveillance, Epidemiology, and End Results (SEER) Program of the NCI. Results: GLOBOCAN incidence and mortality rates for the overall US were lower than but correlated with overall SEER rates. Based on GLOBOCAN data, the incidence and mortality rates of cancers of the breast, prostate, large bowel, and lung, and, among males, bladder cancer were lower in the Caribbean countries than the US. Caribbean countries had higher rates of cancers of the cervix, esophagus, liver, and stomach. Haiti had the highest incidence and mortality rates of cervix and liver cancers. Jamaica and Haiti had the highest rates of stomach cancer. Conclusions: Cancer incidence and mortality in the Caribbean generally follow known patterns of association with economic development, infectious agents, and racial/ethnic origin. Studying these patterns and how immigration changes them may yield clues to cancer etiology. A better understanding of cancer incidence and mortality rates may help health policymakers to implement state-of-the-art treatment and preventive services for people of Caribbean descent both in their native countries and in immigrant communities in the US. [Table: see text] No significant financial relationships to disclose.
Comparison of adjuvant chemotherapy and radiation in patients with cervical adenocarcinoma after radical surgery: SGSG/TGCU Intergroup Surveillance
Authors: M. Shimada, J. Kigawa, R. Nishimura, M. Hatae, M. Hiura, K. Takehara, T. Tase, A. Sato, H. Kurachi, T. Sugiyama
Journal: Journal of Clinical Oncology (2008)

5559 Background: Patients with cervical adenocarcinoma have worse prognosis compared with those with SCC. Several authors reported lower sensitivity to radiation for adenocarcinoma, although radiotherapy including concurrent chemoradiotherapy (CCRT) is commonly used as adjuvant treatment for cervical cancer. We conducted the present surveillance to know whether adjuvant chemotherapy is useful for cervical adenocarcinoma with risk factor for recurrence. Methods: A total of 324 patients with FIGO stage Ib-IIb cervical adenocarcinoma, who underwent type III radical hysterectomy in 13 institutes of SGSG/ TGCU Intergroup between April 1997 and March 2003, were enrolled in this study. There were 264 adenocarcinoma and 60 adenosquamous cell carcinoma. There were 212 patients in stage Ib1, 46 in stage Ib2, 13 in stage IIa, and 53 in stage IIb. Mean age of patients was 46.2 yrs (range: 18 - 84 yrs). The indication for adjuvant treatment is as follows: pelvic lymphnode involvement, parametrial extension, deep stromal invasion, vessel permeation, and compromised surgical margin. Results: Of 324 patients, 154 patients received adjuvant treatment (radiotherapy including CCRT; 71, platinum-based chemotherapy; 65, both radiotherapy and chemotherapy; 18). There were 71 patients in stage Ib1, 33 in stage Ib2, 8 in stage IIa, and 42 in stage IIb. The 5-year overall survival rate (OS) for patients with and without adjuvant treatment was 86.5% and 95.6% in stage Ib1, 78.6% and 66.7% in stage Ib2, 42.9% and 75.0% in stage IIa, and 57.3% and 64.8% in stage IIb. Chemotherapy showed an advantage to improve the prognosis for high-risk cervical adenocarcinoma compared with radiotherapy (5-year PFS; 69.8% vs. 47.0%, 5-year OS; 80.5% vs. 65.2%). Recurrent sites did not differ between chemoptherapy and radiation. Conclusions: Adjuvant chemotherapy may be more useful for high-risk cervical adenocarcinoma after radical surgery. No significant financial relationships to disclose.
The use of daclizumab for treatment of steroid refractory acute GVHD. A City of Hope experience
Authors: J. M. Zain, E. Smith, J. Palmer, P. Parker, D. Snyder, R. Rodriguez, R. Nakamura, V. Pullarkat, Z. Al-Kadhimi, J. Rosenthal, D. Smith
Journal: Journal of Clinical Oncology (2005)

6672
Preliminary treatment patterns and safety outcomes for non-small cell lung cancer (NSCLC) from ARIES, a bevacizumab treatment observational cohort study (OCS)
Authors: T. J. Lynch, J. Brahmer, N. Fischbach, J. Garst, P. Kumar, D. R. Spigel, S. Teng, R. Vidaver, L. Wang, W. Navarro
Journal: Journal of Clinical Oncology (2008)

8077 Background: Bevacizumab (BV), an anti-VEGF monoclonal antibody, provides benefit in advanced NSCLC, prolonging both progression-free and overall survival. OCSs such as ARIES provide valuable safety and effectiveness data for a broader patient (pt) population than controlled trials such as ECOG 4599. ARIES objectives are to further delineate clinical outcomes associated with BV use in a real-world setting. Methods: Pts with locally advanced/metastatic non-squamous NSCLC whose 1st therapy includes BV may enroll. There are no protocol- specified treatments or assessments. Data are collected at baseline (BL), then quarterly, including targeted safety events, until death, consent withdrawal, loss to follow-up (F/U), or study closure. ARIES is conducted at 248 US sites. Planned NSCLC accrual is 2,000 pts. Results: As of 9/5/07, 621 NSCLC pts have been enrolled. Median F/U is 4.7 months; 72% of pts have ≥1 quarterly update. Key demographics are shown in the table. Targeted serious adverse events (SAEs) to date: Grade 3/4 bleeding, venous thromboembolic event (TE), arterial TE, other, 1% each; GI perforation, RPLS, pulmonary hemorrhage, <1% each; hypertension, wound complication: none. Most common chemotherapy regimens are: carboplatin (Cb)+ paclitaxel: 61%; Cb + docetaxel: 12%; non-platin-based: 13%. Conclusions: Low rates of targeted SAEs were preliminarily observed despite inclusion of pts underrepresented in E4599 such as ECOG PS2, brain metastasis, therapeutic anticoagulation at BL, and older age. Updated safety data, treatment patterns (with BV dose, duration), and demographics will be provided at the meeting based on >800 pts. BL Demographics ARIES (n=621) E4599 CbP + BV group (n=434) % % Women 44 50 Age ≥ 65 50 43 ECOG ≥ 2 10 0 Brain Mets Present 7 0 Therapeutic Anticoag. 9 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology AstraZeneca Oncology, Boehringer Ingelheim, Genentech™ BioOncology, Lilly Oncology, OSI Oncology, sanofi-aventis, Xelixis Genentech™ BioOncology Amgen, Aventis, Bristol-Myers Squibb, Genentech™ BioOncology, GlaxoSmithKline, Lilly Oncology, Ortho Biotech Genentech™ BioOncology Genentech™ BioOncology
A randomised trial of carboplatin versus carboplatin and thalidomide in ovarian cancer, with evaluation of potential surrogate markers of angiogenesis
Authors: S. R. Muthuramalingam, J. Braybrooke, S. Madhusudan, A. Blann, S. Wilner, A. Jenkins, C. Han, T. Perren, T. S. Ganesan
Journal: Journal of Clinical Oncology (2004)

5024 Background: Thalidomide has anti-angiogenic activity and as a single agent induces responses in several tumour types. However, the activity and safety of thalidomide in combination with chemotherapy has not been assessed. In this study, we wished to evaluate if there was synergy with carboplatin in ovarian cancer. Methods: Patients with stage IC–IV ovarian cancers were randomised to receive either carboplatin (C) (AUC 7) alone every 4 weeks (6 cycles) or carboplatin and thalidomide (CT) 100 mg daily for 6 months, between 1997–2002. Ca125 and surrogate markers of angiogenesis, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), von Willebrands factor (vWF), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were measured in the serum pre- treatment and after each cycle of chemotherapy. Sensory nerve action potentials (SNAP) were performed every 2 months in all patients. Results: 40 patients (Median age: 67.2yrs, range 39 to 83) were entered in the study [20 (C) and 20 (CT)] and 15 were alive at last follow up. There was no significant difference in clinical characteristics between the two groups. Overall response rate (CR+PR) was 90% in C group and 75% in CT group. There was no neurotoxicity (> Grade 1) in any patient due to thalidomide. No significant difference in toxicities or QoL (EORTC QLQ-C 30) was observed between the two groups. There was a significant fall in serum E-selectin and VCAM with treatment in both groups (p <0.02), similar to Ca 125. However, none of the surrogate markers differed significantly between the two groups in evaluable patients. Conclusions: Low dose oral thalidomide can be safely administered in combination with carboplatin chemotherapy. Chemotherapy alone with carboplatin can affect markers of angiogenesis, and this is due to tumour response. The addition of thalidomide did not significantly alter the markers (in comparison to carboplatin alone) which were evaluated. No significant financial relationships to disclose.
Evaluation of brain natriuretic peptide (BNP), troponin levels, and left ventricular ejection fraction (LVEF) in older adults with diffuse large B cell lymphoma (DLBCL)
Authors: M. A. Rodriguez, W. Wei, X. Huang, M. Fisch, J. B. Durand
Journal: Journal of Clinical Oncology (2009)

e19506 Background: Troponin and BNP are markers that rise acutely during myocardial injury and cardiac dysfunction, respectively. Doxorubicin (Dox) is an effective drug for treatment of DLBCL, in the regimen RCHOP (Coiffier, et.al. NEJM, 2002). Dox has risk of myocardial toxicity, which is higher in older patients (pts). Pegylated liposomal doxorubicin (D) has greater cardiac safety yet similar efficacy to Dox in breast cancer. D replaced Dox in RCHOP (DRCOP) in a phase II study in patients &gt;60 yrs of age, with troponin and BNP levels pre and post-treatment to see if they would predict a fall in LVEF secondary to DRCOP. Methods: DRCOP is: Rituximab 375 mg/m2 IV day (d) 1; D 40 mg/m2 IV d 1; cyclophosphamide 750 mg/m2 IV d 1; vincristine 2 mg IV d 1 total dose; prednisone 100 mg/d p.o. d 1–5. Eligibility criteria: &gt; 60 years; untreated DLBCL; Ann Arbor stage II-IV; baseline LVEF ≥ 50%. Consult at baseline by Cardiologist required, and at follow-up as indicated. The Wilcoxon rank sign test was used to compare baseline BNP with subsequent BNP. A linear mixed model was used to assess the effect of time on troponin at baseline, midpoint and endpoint. All tests were two-sided and p-values of 0.05 or less were considered statistically significant.. Statistical analysis was carried out using SAS version 9 (SAS Institute, Cary, NC). Results: 60 patients are enrolled; only one patient has developed systolic dysfunction, (LVEF to &lt;50%). Conclusions: DLBLC older patients Older adults with DLBCL treated with DRCOP maintain preserved LVEF and troponin levels, suggesting less cardiotoxicity. There is a significant rise in BNP without clinical cardiac dysfunction. This is a new observation that merits further study. [Table: see text] No significant financial relationships to disclose.
AR splice variant 7 (AR-V7) and response to taxanes in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Emmanuel S. Antonarakis, Changxue Lu, Yan Chen, Brandon Luber, Hao Wang, Mary Nakazawa, Angelo M. De Marzo, William B. Isaacs, Rosa Nadal, Channing Judith Paller, Samuel R. Denmeade, Michael Anthony Carducci, Mario A. Eisenberger, Jun Luo
Journal: Journal of Clinical Oncology (2015)

138 Background: AR-V7 is a truncated form of AR that lacks the ligand-binding domain but remains constitutively active. We previously showed that detection of AR-V7 from circulating tumor cells (CTCs) in men with mCRPC was associated with primary resistance to enzalutamide and abiraterone. Here, we hypothesized that AR-V7[+] patients would retain sensitivity to taxane chemotherapy. Methods: We used a qRT-PCR assay to interrogate CTCs for AR-V7 mRNA in prospectively enrolled patients with mCRPC starting docetaxel or cabazitaxel. We sought associations between AR-V7 status and PSA response rates (the primary endpoint), PSA progression-free survival (PSA-PFS), and clinical/radiographic progression-free survival (PFS). Multivariable regressions were performed to determine the independent effect of AR-V7 status on clinical outcomes. 36 taxane-treated men were required to produce a 2-sided 95% CI for the difference in PSA response rates (between AR-V7[+] and AR-V7[–] men) with an upper bound of 60%, assuming that 30% of men would be AR-V7[+]. Results: 37 taxane-treated patients were enrolled, and 17 (45.9%) had detectable AR-V7 in CTCs. PSA responses were achieved in both AR-V7[+] and AR-V7[–] men (41% vs 65%, P=0.19). Median PSA-PFS was comparable in AR-V7[+] and AR-V7[–] men (4.5 vs 6.2 mo, HR 1.72, P=0.32). Likewise, median PFS was comparable in AR-V7[+] and AR-V7[–] men (5.1 vs 6.9 mo, HR 2.65, P=0.11). After incorporating data from our prior study in 62 abi/enza-treated patients, it was observed that clinical outcomes in AR-V7[+] men were superior with taxanes than with abi/enza, while outcomes did not differ by treatment type in AR-V7[–] men. For example, in AR-V7[+] men, PSA responses were higher in taxane-treated versus abi/enza-treated men (41% vs 0%, P&lt;0.001), and median PSA-PFS and PFS were longer in taxane-treated men (HR for PSA-PFS = 0.19, P=0.001; HR for PFS = 0.21, P=0.003). Conclusions: Detection of AR-V7 in CTCs from men with mCRPC is not associated with primary resistance to taxane chemotherapy, and such patients may retain sensitivity to taxanes. Further, in AR-V7[+] men, taxanes appear to be more efficacious than abi/enza. AR-V7 may represent a treatment-selection marker in mCRPC.
Phase I trial of vorinostat plus bortezomib (bort) in relapsed/refractory multiple myeloma (mm) patients (pts)
Authors: A. Z. Badros, S. Philip, R. Niesvizk, O. Goloubeva, C. Harris, J. Zweibel, J. J. Wright, A. Burger, M. R. Baer, M. J. Egorin, S. Grant
Journal: Journal of Clinical Oncology (2008)

8548 Vorinostat, a histone deacetylase inhibitor, affects cell growth by modifying the transcription of cellular proteins (histones, transcription factors, ubiqutin E3 ligases and stress response proteins). In vitro, vorinostat showed synergistic cytotoxicity with proteasome inhibitors in MM cells by disruption of aggresome function and induction of ER stress (Pei, 2004). The study aims were to determine the MTD, pharmacokinetics (PK) and pharmacodynamics (PD) of vorinostat plus Bort in MM pts. Twenty-three pts were treated. Median age was 54 yrs (range 39–78). Median time from MM diagnosis to study entry was 5.3 yrs (range 1.5–9). Isotypes were IgG (n=11), IgA (n=4), light chain (n=8). Fourteen pts had complex karyotypes. Median number of prior regimens was 7 (range 3–13), including autologous transplant (n=20), thalidomide (n=23) and lenalidomide (n=17). Nineteen pts had a median of 2 (range: 1–5) Bort-based prior regimens (table below). Median time from last therapy to study was 20 days (range 15–39). Pts recieved Bort 1.3 mg/ m2 IV days 1, 4, 8 and 11 and vorinostat 100–400 mg days 4–11. Five 3- pt cohorts were evaluated at each level. Two pts in the 500 mg level had DLTs: prolonged QT and fatigue. Additional 8 pts were treated at MTD. Grade 3–4 toxicities included myelosuppression requiring transfusion (n= 13) and growth factors (n=6), fatigue (n=11), diarrhea (n=5), atrial fibrillation (n=1), shingles (n=1) and pneumonia (n=2). In 21 pts evaluable for response after cycle 2, there were 2 VGPR and 7 PR (ORR of 42%), 10 pts had SD and 2 had PD. The PK of vorinostat after a single oral dose were linear from 100–500 mg with mean AUC of 0.7 + 0.45 to 4.4+ 0.07 mM/h, Cmax 0.3 + 0.14 to 1.2 + 0.06 mM and Tmax 1.3 + 0.4 to 2.3 + 2.5 /h. Ten pts had CD138+ cells isolated from bone marrow on day 1 and on day 11 of cycle 1; PD studies showed reduction of NF-KB, Bcl-2, bcl-xl, p21, XIAP in responders compared to pts with SD/PD. MTD is Bort 1.3 mg/ m2 d 1, 4, 8, 11 and vorinostat 400 mg days 4–11. The regimen is well tolerated and has promising activity in MM. Prior Bortezomib No of Pts Response VGPR PR SD PD NE Naïve 4 1 2 1 Prior treatment 10 1 2 5 1 1 Refractory 9 3 4 1 1 PR, partial response; VGPR very good PR; SD, stable disease; PD progressive disease; NE not evaluable; prior treatment indicate initial response followed by progression; refractory indicate pts who never responsed to Bort. No significant financial relationships to disclose.