tbuckley/cabot-search huggingface dataset:
Race, Oncotype DX, and other characteristics in a highly screened population.
Authors: Jennifer Chun, Freya Ruth Schnabel, Shira Schwartz, Jessica Billig, Elizabeth Kern, Karen Hiotis, Deborah M. Axelrod, Amber Guth
Journal: Journal of Clinical Oncology (2014)

32 Background: Oncotype DX breast cancer 21 gene assay recurrence score (RS) is used to predict disease recurrence and response to chemotherapy in order to offer patients the highest treatment benefit to risk ratio. There is a dearth of literature on the relationship of Oncotype RS and race in women with hormone receptor positive and node negative/positive disease. The purpose of this study was to investigate the relationship of race and clinical characteristics (including Oncotype RS) in an insured population of highly screened women with newly diagnosed breast cancer. Methods: The Breast Cancer Database of our institution was queried for patients who were newly diagnosed with breast cancer. We looked at demographics, risk factors, tumor characteristics, and Oncotype RS. Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: A total of 1,767 women were diagnosed with breast cancer from 1/2010 to 4/2014. The median age was 59 years. There was a total of 1327 (75%) Whites, 162 (9%) Blacks, 163 (9%) Asians, and 108 (6%) Hispanics. Majority of patients had a college-level education (83%), had annual/biannual screening mammography (78%), and clinical breast exams (89%). Majority of patients had invasive ductal carcinoma (61%), early stage (0, I, II) tumors (94%), ER+ (85%), PR+ (72%), Her2-negative (86%), and node-negative disease (80%). Compared to Whites, there was a significantly higher proportion of later stage disease among Blacks (p = 0.001) and Asians (p = 0.003), more triple negative breast cancers among Blacks (p &lt; 0.0001) and higher Ki-67 scores among Blacks (p &lt; 0.001) and Asians (p &lt; 0.001). Oncotype RS was not significantly different among the race categories and a majority of patients had a low Oncotype RS (57%). These results did not change after stratifying for nodal status. Conclusions: In a population of women who had health insurance and were highly screened, we found clinical differences among races with respect to tumor histology. However, we did not find a statistically significant difference among race and Oncotype RS, even after stratifying for nodal status. Further studies are warranted to determine which tumor proliferation markers are contributing to ethnic differences in breast cancer mortality.
Cost-effectiveness analysis (CEA) of third-line erlotinib therapy compared to best supportive care for advanced non-small cell lung cancer (NSCLC) in British Columbia (BC)
Authors: K. van der Hoek, S. C. Taylor, S. Peacock, K. Johnston, B. L. Melosky
Journal: Journal of Clinical Oncology (2007)

7678 Background: Erlotinib was approved for funding as a systemic therapy treatment for 3rd line management of advanced NSCLC by the BC Cancer Agency (BCCA) in April 2004. BCCA patient outcome and cost data are routinely collected to verify the therapeutic effectiveness and cost-effectiveness of systemic treatment policies. Methods: This was a pragmatic retrospective analysis of all patients who received 3rd line erlotinib compared to a historical group treated with 2nd-line docetaxel then no further active treatment, both according to BCCA protocol. The primary end-point was cost-effectiveness, measured in terms of cost per-life-year-gained. Secondary end-points included: median overall survival (MOS); overall survival (OS) at 1 year; and comparison to phase III efficacy results. Data was retrieved from the Cancer Agency Information System (CAIS) and Systemic Therapy Data Warehouse. Life-years- gained were calculated from the area under the survival function curve. CEA took the BCCA perspective and costs included all direct drug costs for treatment of advanced disease. Sensitivity analyses included varying life expectancy across its 95% CI, cost to the extremes of ranges, and start date for length of survival: method 1. progression after 2nd line therapy or 3 weeks post last dose of chemotherapy for control group and start date of erlotinib for treatment group; method 2. last date of 2nd line therapy for both groups Results: 75 control and 70 erlotinib patients were included in the analysis. Results are presented in the table . The Incremental Cost-Effectiveness Ratio (ICER) was $28,516 per life-year-gained under method 1, and $17,632 under method 2. The erlotinib group had similar 1-year OS compared to literature (36 vs. 31%). Conclusions: Erlotinib appears to be cost-effective in terms of life-expectancy under a range of assumptions. No significant financial relationships to disclose. [Table: see text]
Paclitaxel, carboplatin and gemcitabine (PCG) as neoadjuvant therapy in patients with locally advanced transitional cell carcinoma (TCC) of the bladder
Authors: D. C. Smith, M. Bhandari, M. Hussain, J. E. Montie, D. P. Wood, C. T. Lee, D. P. Petrylak, U. N. Vaishampayan
Journal: Journal of Clinical Oncology (2004)

4541 Background: PCG has substantial activity in the treatment of TCC with lower rates of severe toxicity than MVAC. Recent studies have shown a survival benefit for chemotherapy in the neoadjuvant setting. This study is designed to assess the activity of neoadjuvant PCG in patients with locally advanced TCC of the bladder. Methods: Patients with clinically staged T3, N0, M0 TCC or T2 disease with hydronephrosis (Arm I) receive 3 cycles of PCG (paclitaxel 200 mg/m2, IV over 3 hours day 1, carboplatin target AUC=5 IV day 1, and gemcitabine 800 mg/m2; IV day 1 & 8 every 21 days) and then proceed to cystectomy with an endpoint of pathologic complete response (pCR). Patients with T4 or node positive (Tany, N1–3, M0) disease (Arm II) receive 6 cycles of PCG with an endpoint of conversion to resectability as assessed by the urologist. Results: 49 patients have been entered (26 arm I, 23 arm II). Median age was 65 years in arm I and 56 years in arm II. 23 patients in arm I have completed therapy and 5 (22%) have a pCR. 16/23 patients on arm II have been resected. A total of 187 cycles of therapy have been delivered (65 in arm I, 112 in arm II) and 55% of patients had grade 3/4 hematologic toxicity. Three patients died during therapy, due to previously unrecognized heart disease (1), bowel obstruction (1), and post-cystectomy in a patient with Crohn's disease. Conclusions: Patients treated with PCG achieved a high rate of resectability in locally advanced TCC and a substantial number had pathologic complete response at resection. Hematologic toxicity was acceptable with this regimen with most patients received all cycles of planned therapy. Enrollment to this study is ongoing. Support from Bristol-Myers Squibb, Eli Lilly, and 2P30 CA 46592–14 from the National Cancer Institute Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Bristol-Myers Squibb; Eli Lilly
Prognostic value of biomarkers in tissue microarrays (TMAs) of squamous cell carcinomas of the oral tongue (SCCOT).
Authors: W. N. William, M. Nunez, X. Gu, R. W. Jacobs, A. M. Litvak, C. R. Pickering, J. Lee, A. K. El-Naggar, B. S. Glisson, J. Myers
Journal: Journal of Clinical Oncology (2010)

5548 Background: We studied associations between recurrence-free survival (RFS) and expression levels of hypoxia-inducible factor-1 alpha (HIF-1a) and its activated (phosphorylated) upstream molecules mammalian target of rapamycin (mTOR), epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) in SCCOT of patients treated homogeneously with surgery ± radiotherapy. Methods: TMAs of 113 resected SCCOT were immunohistochemically stained with antibodies against pEGFR, pIGF-1R, p mTOR and HIF-1a. Scoring equaled intensity of staining (0–3) in each cellular compartment (membrane, cytoplasm and nucleus) times the percentage of stained cells (0%–100%). Marker associations were analyzed via the Spearmen correlation coefficient (SC). Impact of clinical variables or biomarkers on RFS was assessed in the Cox proportional hazards model. Results: Univariate analysis showed that T and N stage, depth of muscle invasion, extracapsular lymph node spread, and perineural invasion were associated with decreased RFS (p<0.05). There was no correlation between pEGFR and p mTOR, pIGF-1R and p mTOR, pEGFR and HIF-1a, pIGF-1R and HIF-1a, or p mTOR and HIF-1a (p>0.05). We found a statistically significant correlation between membrane pEGFR and cytoplasmic pIGF-1R (SC=0.24, p=0.04). There were no statistically significant associations between any marker and RFS (p>0.05). Conclusions: We found no association between HIF-1a and upstream, phosphorylated EGFR, IGF-1R, or mTOR. The positive correlation between pEGFR and pIGF-1R may signify cross-phosphorylation between these receptors, as previously found in other tumor types in vitro. No marker correlated with RFS. Although needing validation in prospectively collected specimens for phospho-protein studies, our preliminary data suggest that multiple pathways (rather than any single marker alone) activate key signaling molecules leading to recurrence. Thus, we continue to assess additional markers in the TMAs to characterize the potentially relevant pathways more comprehensively. Supported by The ASCO Cancer Foundation (YIA)/Head and Neck SPORE P50CA097007. No significant financial relationships to disclose.
Efficacy and safety of long-term, once-daily morphine sulfate extended-release capsules in cancer patients with chronic, moderate-to-severe pain
Authors: E. S. Groves, S. M. Shelby, L. Schlosser
Journal: Journal of Clinical Oncology (2004)

8075 Background: This subset analysis evaluated the long-term efficacy and safety of once-daily morphine sulfate extended-release capsules (Avinza®, Ligand Pharmaceuticals [LMSER]) in cancer patients (pts) with chronic moderate-to-severe pain. Once-daily LMSER provides sustained morphine plasma levels with minimal peak-to-trough fluctuation over a 24-hr dosing interval. Methods: Pts completing a prior study with LMSER were eligible for a 1-year, multicenter, open-label trial, of which this subset analysis includes all pts with malignancies. Analgesic efficacy was assessed monthly using the Brief Pain Inventory (BPI, scale of 0 to 10); daily LMSER dose; number (#) of doses of rescue drugs; and the SF36 Survey. Safety was assessed by recording treatment-emergent side effects (TESE) and changes in lab values or physical exam. Results: The LMSER open-label study enrolled 284 pts, of which 31 (15 male; median age 61 years, range 42–78) were in this cancer pt subset; 13 completed >6 months of the trial. The median once-daily LMSER dose was 120 mg at baseline (range 60–390 mg) and 90 mg at endpoint (range 60–180 mg). During the one-year course of pain therapy, pts experienced median BPI scores for 24-hr average pain of moderate to low intensity. Pts who completed > 6 mo of the trial had a median # of rescue doses per day ranging from 1 to 2. Twenty-nine percent of pts required no rescue drugs during the trial. The once-daily LMSER dose did not correlate with the # of rescue doses required (Spearman's correlation = .36). As assessed by the SF36, changes in social function were minimal. The most common TESE were mild to moderate asthenia (35.5%) and nausea (29%). There were 11 deaths from underlying malignancy. Conclusion: Once-daily LMSER provided effective pain control despite disease progression through this 1-year study; BPI remained stable, as did the # of rescue doses required. TESE were of acceptable severity. Breakthrough pain in pts receiving higher LMSER doses was no more difficult to manage than that of pts who were on lower doses of LMSER, as reflected in the same requirement for numbers of rescue medication doses. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Pharmaceuticals Ligand Pharmaceuticals Ligand Pharmaceuticals
CeCil: A randomized, noncomparative phase II clinical trial of the effect of radiation therapy (RT) plus temozolomide (TMZ) combined with cilengitide or cetuximab on the 1-year overall survival of patients with newly diagnosed MGMT-promoter unmethylated glioblastoma.
Authors: V. Verschaeve, L. A. D'Hondt, L. M. J. Verbeke, F. Van Fraeyenhove, S. Du Four, J. Duerinck, B. Neyns
Journal: Journal of Clinical Oncology (2011)

TPS134 Background: The overall survival (OS) of newly diagnosed glioblastoma (GB) patients (pts) treated with RT and TMZ is correlated with the methylation status of the MGMT-promoter. Pts with an unmethylated MGMT-promoter in particular have a poor prognosis and are in need of new active treatment options. Cilengitide, a selective αvβ3/5 integrin inhibitor, and cetuximab, a monoclonal EGFR-targeted antibody, have demonstrated anti-tumor activity against GB and can be safely combined with RT and TMZ. Methods: CeCil is an academia sponsored, multi-center, randomized phase II clinical trial of postoperative RT with daily concomitant TMZ (75 mg/m²/day) followed by 6 adjuvant cycles of TMZ (75-100 mg/m²/d x21d q 28d). Pts are randomized (1:1) to additional treatment with either cilengitide 2000 mg 2x weekly i.v., or cetuximab 1x weekly i.v. (400 mg/m² for the 1st administration and 250mg/m² for subsequent administrations). Cilengitide and cetuximab administration is started 1 week prior to RT/TMZ and is continued for up to 52 consecutive weeks in non-progressive pts. The 1-year OS-rate is the primary endpoint. Secondary endpoints include the PFS, and safety. Eligibility criteria include histologically confirmed, newly diagnosed GB without a methylated MGMT promoter (pts with an “unmethylated” or “invalid” test result are eligible), age ≥ 18 year, performance status of 0-1, and prior tumor resection or open biopsy. Recruitment is a 2-step process: after informed consent, histopathological diagnosis of glioblastoma and MGMT–promoter methylation status are centrally determined; GB-confirmed patients with an “unmethylated” or “invalid” test result are randomized (stratification by RPA classes: III vs. IV-V) between the two treatment arms. According to a one-stage Fleming design (a: 0.05; b: 0.05), with P0=60% and P1=80%, 54 pts will be recruited per study-arm. At least 39 pts must be alive at 12 months to validate the predefined hypothesis of activity. Accrual is ongoing in 7 medical centers in Belgium. ClinicalTrials.gov identifier: NCT01044225.
Effect of hormone receptor status and local treatment on overall survival for early-stage breast cancer.
Authors: Catherine Parker, Heather Y. Lin, Yu Shen, Liang Li, Meeghan Ann Lautner, Henry Mark Kuerer, Simona Flora Shaitelman, Gildy Babiera, Isabelle Bedrosian
Journal: Journal of Clinical Oncology (2014)

60 Background: Mastectomy and breast conserving therapy (BCT) have been established as interventions with equivalent survival for early stage breast cancer. However, trials comparing these approaches pre-date the understanding of breast cancer heterogeneity. We hypothesized that if heterogeneity is considered, the surgical approach may impact survival. Methods: Using the National Cancer Database (NCDB) from 2004 to 2005, we evaluated the overall survival (OS) of women with Stage I breast cancer who underwent mastectomy, BCT (surgery with radiation), or breast conserving surgery (BCS, surgery without radiation). Since only ER and PR data were available, we categorized tumors as ER and/or PR positive (HR+) or ER and PR negative (HR-). We performed propensity score-matched analysis using the covariates associated with the choice of surgical therapy. We used the Cox proportional hazards model for analyses of OS in pre-matched and matched cohorts. Double robust estimation under the Cox model was used in the analyses of the matched cohort. Results: A total of 16,646 female patients met study criteria: 1,845 (11%) received BCS, 11,214 (67%) received BCT, and 3,587 (22%) underwent mastectomy. Patients undergoing BCT had superior survival outcomes compared to those undergoing mastectomy or BCS (5-year OS was 96% vs 90% vs 87% respectively, p&lt;0.001). After adjusting for other risk factors, BCT remained significantly associated with OS (HR 0.57 [95% CI 0.50, 0.66] for BCT vs BCS; HR 0.67 [95% CI 0.6, 0.76] for BCT vs mastectomy). In the matched cohort (1706 patients in each treatment group), comparison of OS in multivariate analysis confirmed the survival benefit associated with BCT over mastectomy (HR 0.73 [95% CI, 0.59, 0.89]) in the HR+ subset but not in the HR- subset (HR 0.91 [95%CI 0.62, 1.34]) of patients. BCT showed better OS than BCS in both HR+ and HR- subsets (HR 0.63 [95% CI, 0.52, 0.77], HR 0.67 [95%CI 0.46, 0.98] respectively). No differences were seen in OS between mastectomy and BCS in either HR+ or HR- cohorts (HR 0.87 [95%CI. 0.73, 1.03]), HR 0.73 [95%CI 0.51, 1.06] respectively). Conclusions: When tumor heterogeneity is considered, type of local therapy appears to impact the survival of women with Stage I breast cancer.
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Inhibitory Effect of Interferon on Multiplication of Friend Leukemia Cells In Vivo&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: G B Rossi, M Marchegiani, G P Matarese, I Gresser
Journal: JNCI Journal of the National Cancer Institute (1975)

The multiplication of Friend leukemia cells in the spleens of irradiated or nonirradiated histocompatible DBA/2 mice was determined by the uptake of 125-5-iodo-2'-deoxyuridine. The multiplication was inhibited by daily treatment with mouse interferon preparations or the interferon inducer, Newcastle disease virus. Since, under the experimental conditions used, the proliferation of the Friend leukemia cells was independent of the replication of the Friend virus, the inhibitory effect of interferon might not be mediated by an antiviral effect but by some other mechanism.
Elucidating distinct tumorigenic pathways in nodular versus superficial spreading melanoma.
Authors: Joshua Andrew Farhadian, Kathryn E. O'Reilly, Eleazar Vega-Saenz de Miera, Fei Ye, Jiri Zavadil, Jack Taunton, David Y. Zhang, Iman Osman
Journal: Journal of Clinical Oncology (2012)

8544 Background: Superficial spreading melanoma (SSM) and nodular melanoma (NM), which account for 70% and 20% of all melanoma diagnoses respectively, are believed to represent sequential phases of linear progression from radial to vertical growth. Recent evidence from several groups including ours challenges this linear progression model and suggests that SSM and NM are biologically distinct. In this study, we focused on identifying tumorigenic pathways that are differentially activated in melanoma subtypes and that can be therapeutically exploited. Methods: We performed Protein Pathway Array on SSM/radial growth phase (RGP) and NM/vertical growth phase (VGP) primary melanoma cell lines to determine expression levels of 141 tumorigenic proteins/phospho-proteins. Differential protein expression was determined using the Pavlidis Template Matching algorithm in TIGR Multi Experiment Viewer. Differentially expressed proteins were validated in an expanded panel of RGP, VGP, and metastatic melanoma cell lines using western blot. Constitutively active, overexpressed proteins in VGP melanoma were down-regulated in cell lines using several small molecule inhibitors and the effects on proliferation and migration were assessed. Results: 17 (12%) proteins/phospho-proteins are significantly overexpressed in VGP versus RGP melanoma (p&lt;0.05). Western blot confirmed the results of 5 proteins/phospho-proteins. Each of those 5 was equally overexpressed in VGP and metastatic melanoma cell lines. Phospho-p90 ribosomal s6 kinase (RSK) was prioritized for functional studies based on its role in both the MAPK and AKT signaling cascades, two tumorigenic pathways often dysregulated in melanoma. Constitutive phosphorylation of p90 RSK in VGP, but not RGP melanoma was observed in response to serum starvation. Small molecule inhibition of phospho-p90 RSK attenuated proliferation and migration (p&lt;0.05) in VGP melanoma. Conclusions: Data demonstrate discrete tumorigenic pathways are activated in nodular versus superficial spreading melanoma and suggest that phospho-p90 RSK might be a viable target against nodular melanoma.
Efficacy and safety of intravenous ibandronic acid 6 mg infused over 15 minutes: Results from a 2-year study of colorectal cancer patients with metastatic bone disease
Authors: P. Heras, A. Hatzopoulos, K. Kritikos, S. Karagiannis
Journal: Journal of Clinical Oncology (2008)

9572 Background: Metastatic bone disease is associated with various skeletal-related events (SREs), including pathological fracture, spinal cord compression, and radiotherapy or surgery to bone. Ibandronate is a single-nitrogen, non-cyclic bisphosphonate with proven efficacy for decreasing the incidence of SREs. In this study, a randomized, placebo-controlled trial was performed to evaluate the efficacy and safety of ibandronate infused over 15 minutes in a cohort of colorectal cancer patients with metastatic bone disease. Methods: Patients received intravenous ibandronate 6mg or placebo via a 15-minute infusion every 4 weeks for 24 months. Study endpoints included the proportion of patients who developed SREs and time to first event. Results: In a group of 150 patients with colorectal cancer and bone metastases, intravenous ibandronate significantly reduced the proportion of patients who experienced an SRE compared with placebo (39% versus 50%; p=0.029). Time to first SRE was also delayed significantly (median 469 versus 307 days; p=0.009). In a multiple-event analysis, ibandronate reduced the risk of developing an SRE by 33% (hazard ratio= 0.69; 95% confidence interval 0.42 0.79; p=0.003). In general, ibandronate was well tolerated, with a renal adverse event profile comparable to placebo and no clinically-relevant changes in serum creatinine levels. Conclusions: These data demonstrate the efficacy and safety of 15-minute infusions of ibandronate. Compared with placebo, ibandronate reduced the proportion of patients who experienced an SRE, and decreased the median time to first SRE and the SRE risk. There was no evidence of renal toxicity. Ibandronate is a safe and effective treatment for preventing the complications of metastatic bone disease in colorectal cancer patients. No significant financial relationships to disclose.