tbuckley/cabot-search huggingface dataset:
Long-term followup analysis of a randomized prospective study comparing intravesical electromotive mitomycin-C, passive diffusion mitomycin-C and bacillus Calmette-Guerin in patients with carcinoma in situ of the bladder
Authors: G. Zampa, S. M. Di Stasi, L. Storti, A. Giurioli, M. Sciarra, G. Capelli
Journal: Journal of Clinical Oncology (2008)

5078 Background: This randomized trial was designed to assess the long-term efficacy of intravesical passive diffusion mitomycin-C (PD/MMC), electromotive/mitomycin-C (EMDA/MMC) and bacillus Calmette-Guerin (BCG) in carcinoma in situ (Tis) of the urinary bladder. Methods: 108 patients with Tis of the bladder were randomly assigned to: 40 mg PD/MMC for 60 min (n=36); 40 mg EMDA/MMC with 20 mA electric current for 30 min (n=36); or 81 mg BCG for 120 min (n=36). All patients were scheduled for 6 weekly treatments. Non-responders received another 6 weekly treatments while responders received 10 monthly treatments. Analyses were done by intention to treat. Results: The complete response rates at 3 months for the PD/MMC, EMDA/MMC and BCG groups were 28%, 53% and 56%, respectively (p=0.0361). At 6 months the corresponding rates rose to 31%, 58% and 64% (p=0.0123). After a median follow-up of 82.5 months (range 17.8–148.8) 32/108 patients (29.6%) were disease-free. They included 7 (19.4%) in the PD/MMC group, 12 (33.3%) in the EMDA/MMC group and 13 (36.1%) in the BCG group (p<0.0001). Median time to first recurrence was 9.1 months in the PD/MMC group, 15.0 months in the EMDA/MMC group and 17.8 months in the BCG group (p<0.0001). Progression to muscle invasive disease was reported in 37/108 patients (34.2%), who included 16 (44.4%) in the PD/MMC group, 11 (30.6%) in the EMDA/MMC group and 10 (27.8%) in the BCG group (p=0.0612). Median time to progression was 21.5 months in the PD/MMC group, 26.9 months in the EMDA/MMC group and 27.8 months in the BCG group (p=0.0612). The overall mortality rate was 50.9% (55/108). Death occurred in 19 patients (52.7%) in the PD/MMC group, 17 (47.2%) in the EMDA/MMC group and 19 (52.7%) in the BCG group (p=0.4964). 27 deaths (25%) were due to bladder cancer with 11 patients (30.5%) dying in the PD/MMC group, 8 (22.2%) in the EMDA/MMC group and 8 (22.2%) in the BCG group (p=0.4941). Conclusions: Intravesical EMDA/MMC provides a better response rate and disease-free interval than passive MMC transport. However, after all approaches, the complete response rates and times to recurrence are unreliable predictors of outcome in these high risk patients. No significant financial relationships to disclose.
Use of serum biomarkers to differentiate benign breast lesions from invasive breast cancer in women with a BI-RADS 3 or 4.
Authors: Meredith C. Henderson, Michael Silver, Susan Yeh, Christa Corn, Sherri Borman, David Emery Reese
Journal: Journal of Clinical Oncology (2014)

20 Background: The Provista Biomarker Assay (PBA) combines multiple serum biomarkers, measured at high sensitivity, in order to determine the likelihood of an invasive breast tumor at the time of testing. PBA, when paired with traditional breast imaging technologies, provides a biochemical tool that can help guide additional imaging or biopsy decisions. As part of our ongoing efforts to characterize clinical performance, we conducted a proof-of-concept study wherein PBA assay performance was tested in prospectively enrolled BI-RADS 3 and 4 patients. Methods: To maximize performance and sensitivity, we utilized the Meso Scale Discovery ELISA-based system to analyze a randomized cohort of 350 prebiopsy serum samples from women under the age of 50. Enrollment in the trial required a BI-RADS 3 or 4 radiologic assessment utilizing multiple imaging modalities. Serum proteins and autoantibodies were measured for each patient and applied to a proprietary statistical algorithm. Results: We were able to obtain statistically significant differentiation using the Provista Biomarker Assay in women under age 50 who were characterized as BI-RADS 3 or 4. The majority of patients in the study were diagnosed with a benign breast lesion, consistent with prior studies. However, the data indicate that PBA, when used in combination with imaging techniques, more accurately informs clinical decision-making. Conclusions: The Provista Biomarker Assay provides a powerful tool for physicians to more accurately assess patients with a BI-RADS 3 or 4 classification. With more clinical evidence, the assay may translate into changes in clinical treatment decisions for women under the age of 50 with a BI-RADS 3 or 4 classification. Clinical trial information: NCT01839045.
Therapy-related acute promyelocytic leukemia (t-APL): Observations on APL pathogenesis.
Authors: M. A. Elliott, L. Letendre, A. Tefferi, W. J. Hogan, C. C. Hook, R. Pruthi, S. H. Kaufmann, A. D. Pardanani, K. Begna, A. Ashrani, A. P. Wolanskyj, A. Al-Kali, M. R. Litzow
Journal: Journal of Clinical Oncology (2011)

6567 Background: Therapy-related acute promyelocytic leukemia (t-APL) is a well-recognized form of APL for which the underlying pathogenesis has been well defined. Most cases arise as de novo APL (dn-APL) for which epidemiologic studies have identified increased body mass index (BMI) and ethnicity as possible risk factors. We analyzed demographics, clinical features and treatment responses in a contemporary series of patients (pts) treated with ATRA and anthracycline-based induction and consolidation to assess for differences in these 2 etiologically distinct pt groups. Methods: Retrospective analysis of 64 consecutive APL pts treated from 2003 to 2010 Results: Eleven (17.2%) had t-APL due to chemotherapy and or radiation for carcinoma (n=8) or autoimmune disease (n=3). Cytogenetic analysis in these t-APL pts showed the typical t(15;17)(q22;q12) alone. Compared to pts with t-APL, those with dn-APL had a greater median BMI of 31.33 vs 28.48 and 60.4% vs 27.3% were obese (p =0.04). More dn-APL pts (45.3% vs 18.2%) had hyperlipidemia (p=0.01). Incidence of M3v at 0.9% vs 11.3% and median WBC at 0.9 vs 1.6 x 109/ L (p-0.03), was lower in t-APL while age (61 vs 56 yrs) was not statistically significantly different. Complete remission was achieved in fewer t-APL than dn-APL pts (63.6% vs 92.5%), reflecting a greater induction death (ID) rate (36.4% vs 7.5%). The incidence of DS was similar at 27.3% and 22.6%, respectively. No cases of leukemic resistance were seen in either group. Median follow up of surviving patients (n=48) is 49 m (2.5-200).The OS was lower in t-APL (45.5% vs 79.2%) primarily secondary to the higher ID rate. Relapse occurred in 16.1% overall, with none in the t-APL cohort. Conclusions: Patients with dn-APL had a significantly greater incidence of obesity and hyperlipidemia, a higher presenting WBC and more had M3v disease than those with t-APL, for whom pathogenesis is well-defined. These observations suggest that abnormalities in lipid metabolism may be of etiologic and phenotypic significance in dn-APL. The lower OS of the t-APL cohort cannot be attributed to leukemic resistance or relapse because ID mortality was the main cause of failure.
Final results of a French multicentric prospective study of dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of antiangiogenic treatments in 537 patients.
Authors: N. Lassau, S. Koscielny, J. Lacroix, M. Cuinet, R. Aziza, S. Taieb, V. Vilgrain, A. Sarran, C. Labbe, F. Journeau, J. Bonastre, J. Soria
Journal: Journal of Clinical Oncology (2011)

e13500 Background: A prospective evaluation of dynamic contrast-enhanced ultrasound (DCE-US) with quantification to evaluate antiangiogenic treatments was launched in 2007 in 19 French comprehensive anticancer centers with 65 radiologists, and was supported by the French National Cancer Institute. The objectives were to disseminate the standardized method and to identify the perfusion parameters predicting tumor response to different antiangiogenic treatments. Methods: All patients had an examination just before the start of the antiangiogenic treatment (D-1) and at D7, D14, D30 and D60. Each examination included a bolus injection of Sonovue (Bracco) and raw linear data were recorded over 3 minutes with an Aplio (Toshiba). The raw linear data were analyzed with a mathematical model (patent PCT/IB2006/003742) to evaluate 7 parameters characterizing the tumor perfusion curve. The quantification of DCE-US raw data was done blinded to clinical data. Response to treatment was evaluated every 2 months with RECIST criteria with scanographic evaluations and blind double reading Complete or partial responses and stabilization were classified as successes and progression as treatment failure. Results: Since October 2007, 537 patients have been included (mainly with renal cell carcinomas [157] and hepatocellular carcinoma [107]). 1823 DCE-US examinations and 1296 scanographic evaluations have been performed. After a median follow-up of 12 months, we confirm that 5 parameters exhibit a significant difference (P<0.05) in their variation between D-1 and D30 according to DFS. Conclusions: Our results confirm the validity of this tool for monitoring antiangiogenic treatments. Decision rules will be proposed to classify patients according to their risk of relapse.
Analysis of stage of melanoma diagnosis in relation to insurance type and income as indicator of early/late diagnosis.
Authors: Peter Makram Lamie
Journal: Journal of Clinical Oncology (2013)

9099 Background: This study compares the average stage of diagnosis for melanoma by insurance status and household income. This is the largest such study for melanoma to date. Methods: Using the National Cancer Database we examined 299K patients with melanoma between 2000 and 2009 at 1,408 hospitals. The relationship of average stage of diagnosis is compared across insurance types and by income for 293K patients. Results: The VA patients had the lowest average stage of diagnosis 0.8 with the Medicaid population exhibiting the highest 1.8. The VA was lower than Tricare which had an average diagnosis of 1.1, private insurance 1.2, Medicare 1.3, and uninsured 1.7. The lowest rate of stage IV was private insurance 3.3%, Tricare 3.6%, VAH 4.4%, Medicare 5.7%, uninsured 10%, and the highest rate was among Medicaid 14.3%. The highest income category ≥$49K had the lowest average stage at diagnosis of 1.1 compared to $39K to $48K 1.2, $33K to $38K 1.3, $28K to $32K 1.4, and &lt;$28K had the highest average stage of diagnosis 1.4. Stage IV rate increased from the highest income 3.6%, $39K to $48K 4.6%, $33K to $38K 5.1%, $28K to $32K 5.8%, and &lt;$28K 6.9%. Data available. Conclusions: VA, higher income and private insurance had earlier stage of melanoma compared to uninsured and Medicaid who had higher frequency of stage IV disease. [Table: see text]
The prognostic significance of MET overexpression in Chinese patients with gastric adenocarcinoma.
Authors: Jin Li, Chenchen Wang, Qin Su, Yanong Wang, Yingqiang Shi, Menghong Sun, Lian Liu, Zuojun Sun, Xin Liu, Wenhua Li, Xiaoying Zhao, Dongmei Ji, Wei Peng, Hui Yu, Zhe Zhang, Xiaowei Zhang, Yongzhe Piao, Wanling Hsu, Sally Yan Bai, Xiyuan Wang
Journal: Journal of Clinical Oncology (2014)

53 Background: MET, receptor for hepatocyte growth factor (HGF), has been proposed as a therapeutic target in gastroesophageal cancer (GEC). The purpose of this study was to evaluate MET expression in Chinese patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma and to correlate expression with clinicopathologic parameters and prognosis. Methods: MET protein expression was assessed by immunohistochemistry (IHC) in paraffin-embedded tissues from resected tumor specimens. MET IHC was conducted using the CONFIRM SP44 anti-MET monoclonal antibody (Ventana Medical Systems Inc., Tucson, AZ). Four MET IHC scores were defined: 3+ (≥50% of tumor cells staining with strong intensity); 2+ (≥50% of tumor cells with moderate or higher staining, but &lt;50% with strong intensity); 1+ (≥50% of tumor cells with weak or higher staining, but &lt;50% with moderate or higher intensity); or 0 (no staining, or &lt;50% of tumor cells with any intensity) (Spigel et al, J Clin Oncol 2011;29:Suppl, Abst 7505). Kaplan-Meier was used to estimate OS and differences between MET subgroups were compared using the log-rank test. Univariate survival analysis was performed using the stratified Cox model. Results: 442 resected gastric adenocarcinoma samples were collected from patients who underwent surgery between Sept 2007 and Feb 2010. After excluding patients with missing survival, MET, tumor location, differentiation status and stage data, 362 samples were analyzed. Stage II and III accounted for 23% and 59%, respectively. MET prevalence by IHC was: 3+, 5.5%; 2+, 19.6%; 1+, 37.0%; 0, 37.9%. At the OS cut-off, 15 Apr 2012, median follow-up was 35.3 months (range 5.9–49.8 months). The group with MET IHC scores of 2+ or 3+ had significantly shorter OS compared to those with scores of 0 or 1+. The 2-year survival rate was 64% in the 2+/3+ group and 73% in the 0/1+ group (p=0.047). The HR for MET 2+/3+ versus 0/1+ was 1.65 (95% CI: 1.13–2.39, p=0.009), stratified by stage, tumor location and differentiation status. Conclusions: MET expression in resected tissue from Chinese patients with GEC was correlated with poor prognosis. This finding further supports the development of anti-MET agents in this patient population.
Locoregional control in locally advanced breast cancer using neoadjuvant chemotherapy followed by breast conservation
Authors: M. O. Meyers, N. Klauber-Demore, D. W. Ollila, E. C. Dees, B. F. Calvo, D. T. Moore, W. G. Cance, C. I. Sartor, L. A. Carey
Journal: Journal of Clinical Oncology (2008)

539 Background: Neoadjuvant chemotherapy is commonly employed in the treatment of locally advanced breast cancer. However, the difference in local-regional recurrence (LRR) rates between those undergoing BCT and those with mastectomy is not well defined. The purpose of this study was to examine the incidence of LRR in these two groups after neoadjuvant chemotherapy at a single institution. Methods: Under IRB approval, a prospective database was utilized to identify all patients with locally advanced Stage II and III breast cancer undergoing neoadjuvant chemotherapy from 1991 to 2005. Patients presenting with stage IV disease or T4d primary breast cancer were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy by log-rank test and Cox regression analysis was utilized to evaluate individual variables associated with LRR. Results: 236 patients were included, 94 (40%) underwent BCT and 142 (60%) mastectomy. 93/94 (99%) of the BCT and 115/142 (81%) of the mastectomy patients received postoperative radiation. Pathologic complete response (CR) was seen in 60 patients, of which 34 underwent BCT. Those achieving BCT were more likely to have T2 or smaller tumors before treatment (p=0.0053) and smaller tumors post-treatment (p<0.0001) and were more likely to have a pathologic CR (p=0.0035) than those with mastectomy. At a median f/u of 58 months, the rate of LRR was 5% (5/94) in the BCT group and 9% (13/142) in the mastectomy group (p=0.32). Univariate Cox modeling showed ER status (p=0.01), number of positive axillary nodes (p=0.039), post-treatment T stage (p=0.02), tumor size post-treatment (p=0.04) and pathologic stage (p=0.008) were independent predictors of LRR. Pre-treatment T and N stage were not associated with LRR. Five-year overall survival was 90% in the BCT group and 69% in the mastectomy group (p=0.01). Conclusions: In this series of locally advanced breast cancer patients undergoing neoadjuvant chemotherapy, the rate of LRR was very low and was not significantly different between those undergoing BCT as compared to mastectomy. However, overall survival was improved in those achieving BCT, suggesting this may be a surrogate for prognosis. No significant financial relationships to disclose.
Determinants of anemia in screen-detected colorectal cancer.
Authors: David Mansouri, Donald McMillan, Emilia M. Crighton, Paul G. Horgan
Journal: Journal of Clinical Oncology (2014)

430 Background: Anaemia is an important clinical feature in colorectal cancer, since it may result in blood transfusion that may in turn compromise long term survival. The aim of the present study was to examine the relationship between tumour and host features, and anaemia in patients undergoing surgery for screen detected colorectal cancer. Methods: A prospectively maintained database of patients with cancer detected through a population based faecal occult blood test (FOBt) screening programme was analysed. Preoperative anaemia was defined as Hb&lt;115 g/l in females and Hb&lt;130 g/l in males. The amount of blood in the stool was classified on the degree of positivity of the FOBt (strong/weak) and the SIR was measured by the preoperative neutrophil to lymphocyte ratio (NLR&gt;5/NLR&lt;5). Results: A total of 263 patients were included: 174 (66%) males, 49 (19%) rectal, 177 (67%) node negative. Preoperative anaemia was present in 61 (23%) patients. The presence of anaemia was associated with more advanced T-stage (5% T1 vs. 42% T4, p&lt;0.001), advanced N-stage (18% N0 vs. 45% N2, p=0.001), and the presence of a right-sided tumour (44% vs. 14%, p&lt;0.001). In addition, anaemia was more likely to be present in patients with a strongly positive FOBt (30% strong vs. 19% weak, p=0.034), and in patients with an elevated SIR (44% vs 22%, p=0.045). Right-sided tumours were more likely to be strongly positive on FOBt compared to left-sided tumours (43% vs. 34%, p=0.053). Furthermore, strong FOBt positivity was associated with advanced T-stage (p=0.015), however was not associated with the presence of an elevated SIR (p=0.604). When T-stage, FOBt positivity and the SIR were examined in binary logistic regression analysis, only advanced T-stage (O.R. 2.82, 95% C.I. 1.32 – 6.02, p=0.008) remained significant in predicting those more likely to be anaemic. Conclusions: In this predominantly early stage cohort of screen-detected colorectal cancer, anaemia was uncommon. Its presence was related to both a greater amount of enteric blood loss and an elevated SIR, however these appear to be driven by the stage of the tumour itself. Further work, exploring in more detail the mechanism by which anaemia develops in early stage colorectal cancer is required.
Safety of cisplatin in patients with urothelial carcinoma (UC) and renal dysfunction.
Authors: Parminder Singh, Andrea Necchi, Patrizia Giannatempo, Guenter Niegisch, Giuseppe di Lorenzo, Chiu-Hsieh Hsu, Guru Sonpavde
Journal: Journal of Clinical Oncology (2015)

321 Background: Patients (pts) with UC and creatinine clearance (CrCl) &lt; 60 ml/min are considered cisplatin-ineligible. Since the safety of cisplatin use in patients with CrCl &lt; 60 has not been comprehensively studied, we conducted a retrospective study in this population. Methods: Data were requested and retrospectively collected from 5 collaborating institutions. All patients had stage 2 or higher UC and CrCl &lt; 60. Patient characteristics including age, sex, indication for chemotherapy (neoadjuvant, adjuvant or metastatic disease), schedule, total dose of cisplatin, adverse effects, renal function, blood cell counts and radiologic tumor response were collected. Descriptive statistics were employed with no baseline assumptions. Results: 104 patients were evaluable with a mean age of 63.7+ 8.1 yrs (range 41-77yrs) and 63.5% (n=66) were men. Mean CrCl by Cockroft-Gault formula was 50.8 + 8.0 ml/min (range 26-59 ml/min). Baseline ECOG performance status was 0 in 71.8% (n=74); 1 in 20.3% (n=21) and 2 in 7.8% (n=8) of patients. 40.4% (n=42) received chemotherapy for metastatic disease and the rest received perioperative chemotherapy. Of the patients with metastatic disease, 7.1% patient had complete response (CR), 40.5 % patients had partial response. Mean total dose of cisplatin used in all patients was 414.32±198.01 mg, with 81.7% (n=85) patients receiving ≥70mg/m 2 dose per cycle. Percentage of patients with any toxicity with baseline CrCl &lt;45 and &gt;45 were 43.5% and 39.5%, respectively (p=0.81). Neutropenic infection occurred in 16.3% and thrombocytopenic bleed in 8.6%. Grade 3 renal toxicity was seen in only one patient (0.96%) and no toxic deaths were reported. Conclusions: This retrospective clinical experience in pts with UC with CrCl &lt;60 ml/min and mostly ECOG-PS 0-1 suggests that cisplatin-based chemotherapy is feasible and warrants exploration given CRs induced in metastatic disease. Incorporation of prophylactic growth factors and modified schedules may mitigate myelosuppression.
Gene-pair classifier in circulating tumor and invasive cells to predict pharmacological response.
Authors: Vineet Sangar, John C Earls, Kenneth H. Yu
Journal: Journal of Clinical Oncology (2015)

279 Background: Improved diagnostic tools for predicting treatment response and prognosis are needed in pancreatic adenocarcinoma (PDAC), the fourth leading cause of cancer mortality in the U.S. In this study, we explored the diagnostic potential of gene expression signatures from circulating tumorigenic and invasive cells (CTICs). Methods: We recruited 50 PDAC patients to participate in our IRB-approved study. 35 patients were evaluable for response to chemotherapy treatment. 10 mL of peripheral blood was collected from patients with unresectable PDAC prior to initiating chemotherapy and again at disease progression. Clinical data was prospectively collected. Blood was processed for isolation of circulating TP cells (Vita-Cap, Vitatex Inc.), total RNA was extracted and gene-expression analysis was performed (Affymetrix GeneChipHuman Genome U133 Plus 2.0 array). Using time to progression (TTP) as a threshold, twenty-five patients with TTP&gt;120 days were labeled as responders and ten patients with TTP&lt;=120 days were labeled as non-responders. Results: Network analysis of expression profiles revealed that the PTC1 and CDC25 pathways were significantly different in responders and non-responders. Both pathways contribute towards tumorigenesis, and enhance tumor resistance to therapeutic intervention in PDAC. Further investigation into these pathways revealed that the relative expression of ATM and XPO1 was the most accurate classifier (76% accuracy, Specificity = 80% and Sensitivity = 72%). Additionally, 18 out of 20 patients of the patients with ATM &lt; XPO1expression pattern responded to treatment. Mechanistically, this observation suggests that ATM may be counteracting DNA damage inflicted by chemotherapy during G2/M transition of the cell cycle. Conclusions: Computational analysis of gene expression data from CTICs can reliably predict pharmacological response. Pathway analysis identifies gene interaction networks relevant to tumorigenesis and drug response. Data will be updated with longitudinal analysis of treatment response in both responders and non-responders to the treatment.