tbuckley/cabot-search huggingface dataset:
Chemotherapy treatment patterns and survival outcomes in patients with visceral metastatic upper tract urothelial cell carcinoma.
Authors: Elena Sevillano, Lillian Werner, Guillermo de Velasco, Stephanie A. Mullane, Josefa Terrasa, Aranzazu Gonzalez del Alba, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2016)

415 Background: Upper tract carcinoma (UTUC) is a poorly studied location amongst urothelial tumors. Treatment strategies are often extrapolated from bladder cancer and are not well defined. We aimed to retrospectively evaluate the chemotherapy (CT) treatment patterns and prognostic factors associated with outcome in patients (pts) with visceral metastatic UTUC. Methods: We collected clinical data on 102 UTUC pts treated at Dana-Farber Cancer Institute between Jan 2001 and Dec 2014. We focused our analysis on pts who recurred with visceral metastasis after radical nephroureterectomy and were subsequently treated with CT. Patients with lymph node only recurrence were excluded. Of 102 pts, 74 developed visceral metastasis from which 45 were treated. Overall survival (OS) was defined from date of first line CT for metastatic disease to date of death or censored at last follow up. Kaplan Meier method was used to estimate median OS. Cox regression model was used to summarize the association of OS and potential prognostic factors. Results: Overall, 45 pts received CT. The most common sites of metastases were lung (60%, n = 27), liver (49%, n = 22) and bone (36%, n = 16). 36 % of the pts (n = 16) received first line CT with cisplatin-based combinations. With a median follow up of 29.8 mo the median OS was 14.7 mo, with 32 pts having died at the time of analysis. PS, Hb ≤ 11 and other described known factors were analyzed as well as the impact on OS of the type of CT given cisplatin vs non cisplatin. 81% of the pts (n = 37) had PS &lt; 2. PS 0-1 vs &gt; 1 was included as an exploratory analysis being the number of pts small for grouping. Lower Hb was associated with shorter OS (p = 0.04). Cisplatin vs non cisplatin regimens had a trend on survival benefit in the analysis done in 11 pts (19,3 vs 13,2 mo). Further analysis is ongoing. Conclusions: Although only one third of patients were eligible, this study supports the use of cisplatin regimen to optimize survival in patients with UTUC and visceral metastasis. A significant correlation between Hb ≤11 and OS were observed. The exploratory analysis of PS 0-1 vs &gt; 1 did not have an impact on survival. [Table: see text]
Effect of a novel II-key hybrid HER2/neu peptide (AE37) vaccine with GM-CSF as compared to GM-CSF alone on levels of regulatory T-cell (Treg) populations.
Authors: G. T. Clifton, K. S. Clive, R. Patil, J. P. Holmes, L. C. Benavides, J. D. Gates, J. Tyler, E. A. Mittendorf, S. Ponniah, G. E. Peoples
Journal: Journal of Clinical Oncology (2010)

2565 Background: Regulatory T cells (Treg) inhibit effector T-cell function and prevent autoimmunity; they are recognized as obstacles to cancer immunotherapy. Tregs are predominantly CD4+, suggesting that MHC class II peptide vaccines may stimulate Tregs, decreasing vaccine efficacy. Additionally, results from recent trials have suggested that GM-CSF immunoadjuvant may decrease the efficacy of cancer vaccines or even be harmful. We addressed these issues in an ongoing phase II clinical trial in breast cancer (BCa) patients receiving the novel Ii-key MHC class II HER2/neu peptide vaccine (AE37). Methods: Disease-free, high-risk BCa patients enrolled after standard therapy and were randomized to 6 monthly inoculations of AE37+GM-CSF (peptide group; PA) or GM-CSF alone (adjuvant group; AA). Peripheral blood is drawn before, during, immediately after and 6 months after vaccination (R0, R3, R6, and RC6 respectively). Tregs were detected with CD4, CD25, CD127 and FoxP3 antibodies and flow cytometry. Patients are monitored for recurrence of BCa. Results: Of 150 post-vaccination patients, paired data are available in 57 (28 AA, 29 PA). CD4+ and CD8+ lymphocyte levels are similar in both groups and do not significantly change with vaccination. Treg (CD4+CD25hi) populations do not change in the AA (R0: 5.1±.3%; R3: 4.8±.3%; R6: 5.0±.3%; RC6: 5.2±.2%, p=NS) but decrease in the PA (R0: 5.1±.3%; R3: 4.5±.2%, p=0.004; R6: 4.7±.3%, p=NS; RC6: 4.3±.6%, p=0.01) with vaccination. Tregs as quantified by CD4+CD25hiCD127- cells also do not change in the AA but decrease in the PA (R0: 4.3±.3%; R3: 3.8±.2%, p=0.01; R6: 3.8±.3, p=NS; RC6: 3.8%±.7, p=0.04) with vaccination. Populations of CD4+FoxP3+ and CD25hiFoxP3+ cells do not significantly differ between groups or change with vaccination. At a median follow up of 13 mo., there have been 7.2% (6/83) recurrences in the AA and 2.9% (2/67) in the PA (p=0.30). Conclusions: The AE37 + GM-CSF vaccine decreases Tregs during and after completion of vaccination while GM-CSF alone does not alter Treg levels. This suggests that AE37 may allow the immune system to more effectively fight cancer and correlates with an observed decrease in recurrences. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Antigen Express
Achieving the triple aim in cancer care through a tri-part research collaboration.
Authors: Manali I. Patel, David Ramirez, Andrew Nguyen, Caroline Hagan, Steven M Asch, Hilda H. Agajanian, Richy Agajanian, Arnold Milstein, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2016)

52 Background: Curbing rising cancer care costs require models that safely lower expenditures and improve experience and outcomes. We developed a care delivery model integrating lay health workers to address early goals of care and symptoms (JOP 2015). We then created a research-collaboration with a health plan (which paid for care and processed claims), a contracted oncology group (which implemented the model), and a university research center (which designed the intervention and conducted the evaluation) to test effects on patient satisfaction, utilization, and costs. Methods: All patients newly diagnosed with cancer, referred to the contracted oncology group, and who were beneficiaries of the health plan from 11/17/13 through 9/30/15 were enrolled. We analyzed descriptive statistics and pre-intervention and 5-month post-intervention surveys to assess satisfaction with care and decision-making. Results: There were a total of 412 patients with cancer enrolled over the study period. The mean age of enrollees was 76 years; 53% were women. The mean risk adjustment score was 2.5 (www.CMS.gov). Gastrointestinal malignancies were the highest proportion of cancer diagnoses (26%) followed by breast (23%) and genitourinary cancers (13%). Thirty-one percent of patients were diagnosed with stage IV disease; 22% with stage I; 18% with stages II and III; and 10% with unknown stage. Twenty-two percent of patients died during the study period. In comparison to pre-intervention surveys, there were statistically significant improvements in overall mental and emotional health (p &lt; 0.05) and improvements in satisfaction with care and decision-making (p &lt; 0.05). Conclusions: Research collaborations can help to rapidly implement and test novel strategies of care delivery. These collaborations are needed to align stakeholder priorities to improve cancer care and reduce healthcare spending. Our collaboration demonstrates the feasibility of an all-stakeholder approach to designing and implementing innovative high-value cancer care delivery strategies. Our early findings demonstrate improvements in patient emotional and mental health and satisfaction with care and decision-making.
Carboplatin-based sequential chemotherapy for advanced bladder cancer patient with impaired renal function.
Authors: Takahiro Yoneyama, Jotaro Mikami, Naoki Fujita, Tendo Sato, Yuta Kojima, Hiromichi Iwamura, Atsushi Imai, Shingo Hatakeyama, Yasuhiro Hashimoto, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

401 Background: We retrospectively evaluated the feasibility and effectiveness of a caboplatin-based sequential chemotherapy for the patients with advanced bladder cancer whose creatinine clearance (Ccr) was 60 ml/min or below. Methods: We treated 68 patients with advanced bladder cancer at our clinic between August 2004 and December 2014. 48 patients with advanced bladder cancer (33 men and 15 women) whose Ccr were 60 ml/min or below were enrolled. Their average age was 72.5 years old (43–83), average Ccr of 43.3 ml/min (14.5–57.0), and an average follow-up period of 24.5 months (5–92). The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. GCarbo consisted of 800mg/m 2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD, which consisted of 800mg/m 2 gemcitabine on days 1 and 8, 70mg/m 2 docetaxel on day 1, and carboplatin (AUC 3) on day 2. Results: Of the 48 subjects who had undergone the GCarbo therapy, the response rate was 35.4% (CR+PR) with 3 and 14 subjects exhibiting complete response (CR) and apartial response (PR), respectively; the average response duration was 10.8 months (2–90). The response rates of 9 instances of GCardoD was 33.3%; the overall median survival was 18.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 30 of those who had undergone the GCarbo therapy (62.5%). Conclusions: Although the present study is small and preliminary, the present carboplatin-based sequential chemotherapy is safe and active for advanced bladder cancer with impaired renal function. GCarbo regimen achieved acceptable response rate (35.4%) in advanced bladder cancer. The median overall survival of 18.0 months is acceptable when average Ccr of 43.3 ml/min for the subjects is took into consideration.
Genomic analysis of circulating tumor cells (CTCs) from men with metastatic castration resistant prostate cancer (mCRPC) in the context of enzalutamide therapy.
Authors: Andrew J. Armstrong, Jing Li, Joshua Beaver, Rhonda Lynn Bitting, Simon Gregory
Journal: Journal of Clinical Oncology (2014)

65 Background: Given the evolving treatments available in metastatic castration resistant prostate cancer (mCRPC), predictive biomarkers are desirable that maximize benefit and minimize harms and costs.The goal of this study was to determine the feasibility of DNA copy number and whole exome sequencing (WES) analysis of circulating tumor cells (CTCs) from men with mCRPC receiving enzalutamide. Methods: We collected CTCs from men with mCRPC in the context of enzalutamide therapy. CTCs were isolated from EDTA blood through red cell lysis, CD45 depletion, and flow sorting on EpCAM/CD45 expression. Whole genomic amplification and array based comparative genomic hybridization (CGH) was performed using Qiagen Repli-Gene Single Cell kit, multiple displacement amplification, and Agilent microarray analysis. CTC copy number changes were compared with patient leukocyte DNA and reference metastatic PC datasets. CTC AR amplification and PTEN loss was confirmed with FISH. WES on REPLI-g amplified CTC and leukocyte DNA was performed using GeneWiz and TruSeq Exome Capture Kit, and sequenced with Illumina HiSeq 2000 (20x). Results: A novel method for CTC array CGH was developed that reproducibly identified genomic lesions previously reported in metastatic CRPC including: AR amplification or focal deletions, deletions of CHD1, Rb, PHLLP, FGFR2, FOXA1, and NCOA2, and amplifications of EZH2 and MYC. AR amplification was noted in a man with mCRPC who subsequently responded to enzalutamide, with loss of AR amplification and gain of MYCN and c-MET amplification noted at progression. CGH analysis was feasible down to 10 to 20 cells using spiked cell lines. Interpatient tumor specific genomic heterogeneity was observed. FISH confirmed AR changes and PTEN loss heterogeneity. WES demonstrated acquired PTEN, MAGI1, SMAD4, and RB1 mutations in a patient who progressed through enzalutamide therapy, in addition to AR region deletion detected by CGH. Conclusions: Whole genome DNA copy number and exome sequencing analysis from CTCs in men with mCRPC is feasible in men with high CTCs and identified previously validated and novel genomic lesions and suggest the potential to identify predictive biomarkers of enzalutamide efficacy and resistance in the clinic.
Diverse clinical outcome and predictors for clinical outcome in patients with HCC treated with TACE.
Authors: Prarthna Bhardwaj, Petra Prins, Alexander Y. Kim, Rheena Jha, Hongkun Wang, David Sullivan, Salha Taher, Tiger Zhang, J Zhu, John Marshall, Aiwu Ruth He
Journal: Journal of Clinical Oncology (2016)

442 Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer, and the second leading cause of cancer-related death, worldwide. This reflects the challenges facing HCC treatment. Methods: Patients (pts) with HCC receiving TACE treatment (n = 96) were examined retrospectively for clinical outcome and its possible predictors. The number of TACE treatments and the time elapsed between each treatment were assessed and correlated with overall survival (OS) using the log rank test of Kaplan Meier curves. T-stage, level of differentiation, vascular invasion, and Child Pugh score at the time of HCC diagnosis were compared among pts who received different numbers of TACE treatments (Kaplan-Meier survival analysis, ANOVA and student T test). Results: TACE treated pts had a median OS of 46 month (mo) and progression free survival of 12 mo (difference in time between the date of first progression and the date of diagnosis). Pts received 1-2 (n = 52), 3-4 (n = 28), or 5-6 (n = 16) TACE treatments. We found that pts who had only 1-2 TACE treatments had significantly shorter median OS (38 mo) than those who received 3-4 or 5-6 treatments (48 and 83 mo; p &lt; 0.05). Of the 96 pts studied 22, 33, 37, and 3 pts had T1, T2- T3 and T4-stage HCC, respectively. Only 39 pt tumors underwent pathological analysis, and 13 were well-differentiated (WD), while 24 were moderately- or poorly- differentiated (MPD) (p &gt; 0.05). Tumor T-stage and differentiation were correlated with the number of TACE treatments received. Thus, 30% of pts (n = 10) with T2-stage disease compared with 10% (n = 4) with T3-stage disease received 5-6 TACE treatments (p &lt; 0.001). Similarly, 30% of WD cases (n = 4) compared with only 8% of MPD cases (n = 2) received 5-6 TACE treatments (p &lt; 0.001). The duration between the second and third TACE treatments ( &lt; 4 mo, 5-8 mo or &gt; 8 mo) seemed to correlate with outcome (p &lt; 0.05). Conclusions: Pt survival time following TACE treatment is diverse and correlates with the number of TACE treatments. Pts with T3-stage, or MPD HCC tended to receive fewer TACE treatments than those with T2-stage or WD HCC, and have worse outcomes. Other therapies should certainly be considered for pts with T3-stage and/or MPD tumors.
Gleason score upgrade among 10,282 men who underwent surgery as initial treatment in 2010: A population-based study.
Authors: Hong Zhang, Edward M. Messing, Hamza Ahmed, Yuhchyau Chen
Journal: Journal of Clinical Oncology (2014)

72 Background: Active surveillance is now accepted initial management for men who have localized prostate cancer with low risk of disease progression. Many criteria have been used for patient identification, including Gleason score (GS) obtained from prostate biopsy. Because of concerns of sampling error, some have recommended repeated biopsy before committing to active surveillance. However, there is limited information about the risk of missing high grade disease using the current standard biopsy approach. This study seeks to compare GS difference from biopsy and surgery to provide an estimated rate of GS upgrade. Methods: The Surveillance, Epidemiology, and End Results (SEER) program was used to identify men with American Joint Committee on Cancer stage T1-2cN0M0 prostate cancer diagnosed between January 2010 and December 2010. Patients who underwent prostatectomy were selected for further analysis. Based on prostate-specific antigen (PSA) levels and GS, cases were divided into low (PSA &lt;=10 and GS &lt;=6) and intermediate (10&lt;PSA&lt;=20 or GS=7) risk groups. The rates of GS upgrade were reported for each group. Chi-square tests were used to assess differences in categorical variables (e.g. age and race) between groups of GS upgrade and no change/downgrade. Results: A total of 10,282 men were evaluated, with 9.2% (n=942) having low-risk disease, and 90.8% (n=9340) having intermediate-risk disease. Among men with low-risk prostate cancer, 22.3% (n=210) had GS upgrade and 0.8% (n=8) had GS 8 disease. Among men with intermediate risk disease, 26.2% (n=2446) had GS upgrade and 2.3% (n=214) had GS 8 disease. There was no statistically significant difference in either age or race distribution among men who had GS upgrade versus no change or downgrade at the time of surgery. Conclusions: A substantial number of low- and intermediate-risk prostate cancer patients had GS upgrade at the time of surgery, but few had upgraded to GS 8 high risk disease. These observations suggest that repeat biopsy prior to active surveillance may not be necessary.
Correlation of matrilysin levels and IGF-1/IGFBP-3 ratio with acquired chemo-resistance in advanced colorectal cancer (ACRC)
Authors: R. Gallego, X. Garcia-Albeniz, J. Codony-Servat, C. Nadal, E. Carcereny, R. Longaron, J. Augé, P. Gascón, J. Maurel
Journal: Journal of Clinical Oncology (2008)

15023 Background: High serum concentrations of insulin-like growth factor-1 (IGF-1) are associated with chemo-resistance in colorectal cancer, whereas IGF binding protein-3 (IGFBP-3) seems to exert a pro-apoptotic effect. Additionally metalloproteinase-7 (MMP-7), an enzyme with in vitro ability to degrade IGFBP-3 (Nakamura et al Biochem Biophys. Res. Communications, 333 (2005), has shown poor prognosis in advanced colorectal cancer. We studied whether chemotherapy treatment for ACRC modulates IGF-1, IGFBP-3 and MMP-7 serum levels. Methods: In 41 patients undergoing first-line therapy for ACRC, IGFR-1, IGFBP-3 and MMP-7 levels were measured with immunoassays basally and every 3 months until progressive disease or a maximum of 5 determinations, during chemotherapy regimen of either FOLFOX or FOLFIRI. Associations were assessed using paired samples t-test or Wilcoxon ranks test for paired samples depending on normality of the variable, verified with Shapiro-Wilk test. Results: A median of 4 extractions (range 3 to 5) were done for a total of 157 determinations. Mean pre-treatment values of IGF-1, IGFBP-3, IGF-1/IGFBP-3 ratio and median MMP-7 were 82 (95% CI, 73–92) ng/ml, 2372 (95% CI,2120–2623) ng/ml, 0.037 (95% CI,0.03–0.041) and 6.9 (median 3.4–55.8) ng/ml, respectively. No significant changes in IGF-1 but a significant increment of IGFBP-3, was observed during or after chemotherapy treatment without progressive disease, compared with basal levels (p<0.001). A significant decrease of IGFBP-3 to 1983 (1675–2291) ng/ml and a significant increase of IGF-1/IGFBP-3 ratio to 0.047 (0.026–0.067) ng/ml as well as MMP-7 levels to 6.9 (2.9–78) ng/ml were observed at progressive disease compared to basal and treatment levels (p<0.001). Conclusion: This study supports the hypothesis that MMP-7 could play a role in the acquired resistance, and by degrading IGFBP-3, may contributes to ligand-dependent IGFR-1 activation. No significant financial relationships to disclose.
Sexual functioning in young women with breast cancer.
Authors: Shoshana Rosenberg, Rulla M. Tamimi, Shari I. Gelber, Kathryn Jean Ruddy, Sandra Kereakoglow, Virginia F. Borges, Steven E. Come, Lidia Schapira, Eric Winer, Ann H. Partridge
Journal: Journal of Clinical Oncology (2012)

9100 Background: Sexual dysfunction is a known complication of adjuvant therapy for breast cancer and an important determinant of quality of life. Little is known about the frequency and magnitude of this problem among very young women with breast cancer during the year following diagnosis. Methods: 298 sexually-active women enrolled in an ongoing multi-center cohort study with Stage 0-III breast cancer at or before age 40 were included in this analysis. Treatment data was self-reported on a survey mailed to participants at enrollment. Sexual functioning was assessed using the sexual interest and dysfunction subscales from the Cancer Rehabilitation Evaluation System (CARES). Scores range from 0-4, with higher scores indicative of poorer function. The survey included a measure of anxiety and depression (Hospital Anxiety and Depression Scale), of body image (CARES) and of physical and menopausal symptoms (Breast Cancer Prevention Trial Symptom Checklist). Mean differences in CARES scores between treatment groups (chemotherapy vs. none; hormone therapy vs. none; lumpectomy vs. mastectomy vs. mastectomy + reconstruction vs. no surgery; radiation vs. none) were compared using T-tests and ANOVA. Multiple regression models were fit to assess symptoms thought to be mediators of the treatment-sexual functioning association. Results: Mean age at diagnosis was 36 (range: 22-40) years and mean time from diagnosis to survey completion was 5 months (range: 1-16). Mean CARES sexual interest and dysfunction scores were higher in women who received chemotherapy compared to those who did not (p&lt;0.0001). In the multivariate analysis, chemotherapy was no longer associated with decreased sexual interest or function. Anxiety, depression, musculoskeletal pain, and poorer body image were predictive of both decreased sexual interest and function. Vaginal pain symptoms were associated with greater dysfunction, while unhappiness with appearance was associated with decreased interest. Conclusions: Young women who receive chemotherapy are at risk for problems related to sexual functioning early in the survivorship period. This effect appears to be mediated through several physiologic and psychologic mechanisms, underscoring the need for interventions that target both.