tbuckley/cabot-search huggingface dataset:
Results of a phase II study of pemetrexed as first-line chemotherapy for advanced or metastatic breast cancer
Authors: N. J. Robert, P. R. Conkling, P. R. Kuefler, K. J. McIntyre, F. Zhan, L. Asmar, Y. Wang, O. O. Shonukan, J. O'Shaughnessy
Journal: Journal of Clinical Oncology (2008)

1073 Background: Pemetrexed, a multitargeted antifolate, inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyl transferase (GARFT), a folate-dependent enzyme involved in purine synthesis. Inhibition of these targets contributes to its cytotoxicity. As palliation is the primary goal for patients (pts) with advanced breast cancer, safe and efficacious new single-agent options are needed. Methods: The primary objective was response rate (RECIST); secondary objectives were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. Women with advanced or metastatic disease continued Tx until intolerable toxicity or PD. Treatment (Tx): pemetrexed (P) 600 mg/m2 IV on Day 1 each 14-day cycle. Std dexamethasone premed (day prior, day of, and day after) was given, unless contraindicated. Folic acid and vitamin B12 were given throughout the study. Results: 37 pts enrolled; 36 received >1 dose of P and 34 were evaluable. The median age was 61.4 yrs; ECOG 0/1 was 51%/49%; 68% were ER+ and 54% were PR+. Prior Tx included adjuvant chemotherapy (60%), or hormones/biologics (60%). Pts received a median of 6 cycles of P (range, 1 - 21). 15 pts had doses delayed (n=9) or reduced (n=6). Based on 34 evaluable pts, the overall response rate (ORR) was 26.5% (1 CR, 3% and 8 PR, 23.5% for an ORR of 26.5 % (CI 12.9, 44.4); 16 pts had SD, 47% with 3 pts, 9% having SD for >6 months for a Clinical Benefit Rate (ORR + SD >6 mos) of 35%; 9 had PD (26.5%). The median DOR was 6.5 mos (range, 1.6 - 15.1). Median PFS was 4.1 mos (range, <1 - 11.3) and 6-month PFS was 31.2%. Median OS was 18.9 mos (range, <1 - 22.6). Reasons off Tx were progression (59.5%), toxicity (13.5%), MD or pt request/WD consent (11%, each), and other (5%, 1 pt each Tx error and ineligibility after Dose 1). Grade 3–4 Tx-related toxicities were neutropenia (36%); leukopenia, fatigue (14%, each); anemia (11%); hyperglycemia, asthenia and nausea (6%, each). Mild alopecia was seen in 11% of patients. Conclusions: In this small phase II study single-agent pemetrexed showed moderate activity in the first line setting with acceptable toxicity and no significant alopecia. This research was sponsored by Eli Lilly and Company, Indianapolis, IN. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly Eli Lilly AstraZeneca Oncology, GlaxoSmithKline, Novartis Abraxis Oncology, Eli Lilly, Pfizer Oncology
Characteristics of patients with gastric cancer who had undergone curative surgery: A 15-year monoistitutional experience.
Authors: W. Evangelista, M. Satolli, R. Napoletano, A. Giacobino, A. Novarino, C. Mecca, F. Brusa, L. Pomba, M. Garino, L. Ciuffreda, G. Fronda
Journal: Journal of Clinical Oncology (2011)

e14526 Background: Gastric carcinoma remains a major health problem in many regions of the world. Incidence is extremely high in Oriental, South American and Eastern European countries, but is also significant in North America, Australia and Western Europe. Localized gastric carcinoma presents special strategic and practical challenges. An achievement of a curative (R0) resection (a potentially curative resection when the argins are free of cancer cells) and postoperative American Joint Committee on Cancer (AJCC) stage dictate the survival of patients. There is growing evidence that gastric cancer surgery should be performed in high-volume centers with experienced specialists to reduce morbidity and operative mortality and to achieve better survival results. Methods: From November 1993 to end December 2009 were admitted in the SC General Surgery 467 patients with gastric cancer who had undergone gastrectomy. 273 patients underwent subtotal gastrectomy and 194 patients total gastrectomy. Results: Of the 467 patients resected, 51 (11%) experienced major complications. Of these, 31 had undergone total gastrectomy, while the remaining 20 subtotal gastrectomy. The rate of major complications was therefore 31/194 total gastrectomy (15.9%) and 20/273 subtotal gastrectomy (7.3%), distributed as follows: 31 cases with major complications / 194 in total gastrectomy; 20 cases with major complications / 273 subtotal gastrectomy. If we consider the extension of lymphadenectomy, the incidence of major complications was 22/204 for D1 (10.8%) and 29/248 for D2 (11.7%). The peri-operative mortality of resected patients was 4.1% overall (19/467). Conclusions: Our data show that a dedicated surgery for gastric carcinoma allows to obtain good perioperative morbidity and mortality data with 5-years survival rates with surgery alone, higher than the average.
Evaluation of African American ethnicity and socioeconomic status as prognostic factors for overall survival in bladder cancer.
Authors: F. Jiang, A. Ziogas, J. A. Zell, S. I. Ou
Journal: Journal of Clinical Oncology (2010)

4571 Background: In prior analyses of prognostic factors for survival in bladder cancer, African-American race, and low socioeconomic status (SES) have been associated with poor overall survival. However, it is not known whether African-American ethnicity and SES are independent prognostic factors for overall survival in bladder cancer. Methods: Retrospective population-based analysis of all histologically-diagnosed bladder cancer during 1989-2006 from the California Cancer Registry. Univariate analyses of overall survival were conducted using the Kaplan-Meier method. Multivariate survival analyses were performed using Cox proportional hazards ratios (HRs). Results: 79,422 incident bladder cancer cases were analyzed. African-American patients presented with a greater proportion of stage IV disease (9.5% vs. 5.1%, p<0.0001), and more poorly differentiated tumors (18.6% vs. 13.4%, p<0.0001) compared to Caucasians, and had the greatest proportion (33.7%) of patients in the lowest SES quintile compared to other ethnicities. Patients in the lowest SES quintile presented with the highest proportion of stage IV disease compared to the highest SES quintile (7.6% vs. 4.7%, p<0.0001). Univariate analysis revealed that African-Americans had the poorest OS among all major ethnicities and patients in the lowest SES quintile had the poorest OS among all SES qunitiles. Multivariate analysis revealed that African American ethnicity was an independent unfavorable prognostic factor (vs. Caucasians; HR=1.155 CI: 1.096-1.217, p<.0001). Additionally, low SES was an independent unfavorable prognostic factor (ptrend<0.0001) (low vs. high SES HR= 1.404, 95% CI 1.355-1.454). Other independent unfavorable prognostic factors included advanced AJCC stage, poor tumor differentiation, overlapping lesions (tumor location), male gender, unmarried status, and recent period of diagnosis. Conclusions: African-American ethnicity and low SES are independent unfavorable prognostic factors for overall survival in bladder cancer. Factors not evaluated in this study such as health care access, comorbidities, or biologic differences may underlie these associations. No significant financial relationships to disclose.
Phase II trial of S-1 plus split cisplatin (SSP) in patients with advanced gastric cancer (HGCSG0702): Final report.
Authors: Satoshi Yuki, Yoshito Komatsu, Hiraku Fukushima, Takahide Sasaki, Yoshimitsu Kobayashi, Kazuaki Harada, Masayoshi Dazai, Susumu Sogabe, Takuto Miyagishima, Atsushi Ishiguro, Takenori Takahata, Atsushi Sato, Mineo Kudo, Sosuke Kato, Kanji Kato, Ichiro Iwanaga, Nobuyuki Ehira, Minoru Uebayashi, Yuh Sakata
Journal: Journal of Clinical Oncology (2014)

113 Background: On the basis of SPIRITS trial, S-1 plus cisplatin has been regarded as standard first-line chemotherapy for patients with advanced gastric cancer (AGC) in Japan (Koizumi W, et al. Lancet Oncol, 2008). However, conventional S-1 plus cisplatin (60mg/m 2 ) regimen requires hospitalization for hydration. Therefore, we conducted phase II trial of S-1 plus split Cisplatin (SSP) for outpatient chemotherapy. Methods: Eligibility criteria included pathologically confirmed AGC; no prior chemotherapy; Age 20 to 75, ECOG performance status (PS) of 0 to 1; adequate organ function; and written informed consent. S-1 (40 mg/m 2 ) was given orally, twice daily for 21 days, and cisplatin (30 mg/m 2 ) was given intravenously on day 1 and 15, followed by 2-week rest period, within a 5-week cycle. Primary endpoint was the response rate (RR), and secondary endpoints were progression-free survival, overall survival, safety profile, and non-hospitalized survival. Results: Between Mar 2008 and Mar 2012, 40 pts were enrolled. Patients characteristics were as follows: median age 63 years (range 41-75), Male: female 30:10, PS 0:1 33:7, diffuse: intestinal 23:17. Median number of cycles was 3. The main grade 3-4 AE were neutropenia (37.5%), anemia (30%), anorexia (30%) and fatigue (15%). These toxicities were safely managed. The median relative dose intensity of S-1 was 0.782, and cisplatin was 0.824. Response rate was 57.5% (95%CI 42.2-72.8%) and disease control rate was 90.0%. Median progression-free survival was 6.1 months (95%C.I. 3.0-9.1 months) and median survival time was 15.8 months (95%C.I. 12.7-18.8 months). Conclusions: SSP showed comparable tolerability and efficacy to SPIRITS trial. In addition, most patients underwent the treatment without hospitalization. SSP may be one of practical alternatives for AGC.
The incidence of acute kidney injury among children treated for fever and neutropenia after elimination of empiric gentamycin use.
Authors: Andras Heczey, Kathy McCarthy, Meng-Fen Wu, Curtis Kennedy, Marilyn Hockenberry
Journal: Journal of Clinical Oncology (2012)

120 Background: The mortality rate of chemotherapy-related fever and neutropenia (F&amp;N) has decreased significantly in recent years with attention shifting to antibiotic regimens with the least side effects. Multiple randomized controlled clinical trials have demonstrated that antibiotic regimens without aminoglycosides are sufficient for successful treatment of F&amp;N and the addition of aminoglycosides significantly increases the risk of acute kidney injury among adults. The institutional F&amp;N Guideline of Texas Children’s Hospital (TCH) mandated the use of gentamycin in combination vancomycin and piperacillin-tazobactam (P-T) for the treatment of hig- risk (HR) patients with F&amp;N. To decrease the incidence of nephrotoxicity while maintaining excellent survival, empiric gentamycin use was stopped. Methods: Bacterial susceptibility and characteristics of patients with positive blood cultures treated at TCH during 2009 were retrospectively analyzed (pre-intervention group). Negligible P-T resistance was confirmed among bacterial isolates and empiric use of gentamycin for HR patients with F&amp;N was stopped. After a 6 month adjustment period, data for all patients treated according to the new HR algorithm were prospectively collected (post-intervention group) for 12 months. The pre- and post-intervention groups were evaluated for differences in treatment success and incidence of nephrotoxicity. Results: Data from 69 patients from the pre-intervention group and 39 patients from the post-intervention group who had bacteremia were analyzed. No statistical difference was found between pre- and post-intervention groups for age, gender, survival, baseline creatinine level and baseline estimated creatinine clearance. However, significant difference was found for change in creatinine levels (0.12 vs. 0.04 mg/dl p=0.01), change in estimated creatinine clearance (24.8 vs. 12.1ml/min/1.73m2, p=0.01) and incidence of acute kidney injury (30.1 vs. 11.1%, p=0.04). Conclusions: Children with high risk F&amp;N episode may be treated effectively and safely with decreased incidence of acute kidney injury without the empiric use of gentamycin.
Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutations.
Authors: K. Kim, D. H. Lee, J. Lee, C. Suh, S. Kim, J. C. Lee, C. Choi, S. J. Jang, J. Choi
Journal: Journal of Clinical Oncology (2011)

7606 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) have not been fully evaluated regarding their efficacy for brain metastasis related to adenocarcinoma of the lung. Methods: This is a prospective study of patients with histologically confirmed adenocarcinoma of the lung, EGFR mutations of either exon 19 or 21, and documented brain metastatic lesions without prior therapy including radiotherapy or radiosurgery or surgical resections. Either erlotinib 150 mg or gefitinib 250 mg was administered every day. EGFR mutations were genotyped by direct sequencing. Results: A total of 23 patients were enrolled. Median age was 57 years (range 37-77). Female accounted for 61% (14/23) and ECOG PS 0-1 74% (17/23). Fourteen patients (61%) had mutations in exon 19 and 9 (39%) exon 21. Synchronous brain metastasis was documented in 15 patients (65%). Seventeen patients used EGFR TKI as second line therapy. Six patients (26%) received erlotinib and 17 gefitinib. Response rate was 70.0%. Median PFS and OS were 6.6 months (95% CI: 0.0-14.7) and 19.8 months (14.1-25.6). Drug modification related to toxicities occurred in 4 patients (17.4%). Patients with exon 19 mutations had longer PFS than those with exon 21 mutations (14.0 months vs 4.6 months; P=0.031); however, no difference in OS was seen (exon 19 15.9 months, exon 21 19.8 months; P=0.498). Patterns of treatment failure included progression of intracranial lesions (42%, 5/12), extracranial lesions (25%, 3/12) and both intra- and extracranial lesions(33%, 4/12). Following progression, 6 patients underwent gamma-knife radiosurgery and 2 patients whole brain radiation. Conclusions: EGFR TKI were effective in NSCLC patients with brain metastasis harboring either exon 19 or 21 mutations. Exon 19 mutations were associated with better disease control when compared to exon 21.
Effects of variation of sentinel lymph nodes submitted during breast cancer sugery: Analysis of practice variation and costs.
Authors: Louis H. Barr, Meiling Wu, Yai-Ping Mimi Shao, Xiang Zhu
Journal: Journal of Clinical Oncology (2014)

94 Background: Routine node evaluation involves simple bivalving the node with slides made from the resultant surfaces. SLNs are more thoroughly evaluated with 2-3 mm slices and histologic evaluation of each slice, resulting in many more slides to review. These slides would often have immunohistochemical analysis adding to the time and cost. In early studies of SLN efficacy and accuracy, the mean number of nodes was between 2 and 3 per patient though with some variation. As the number of submitted SLNs increases, the concern of benefit of the procedure comes into question. This is a retrospective examination of all SLN procedures for the year 2012 to examine the variation in the number of SLNs submitted for focused pathologic evaluation. Variation in the number of nodes submitted by surgeon is determined along with the associated costs of the pathologic evaluation. In addition, intraoperative evaluation of lymph node status may be useful to allow for immediate axillary node dissection during the initial operation. Utilization of this procedure was also examined to determine ultimate correlation with permanent pathologic evaluation. Methods: Retrospective examination of all breast cancer patients &gt;=18 yrs who underwent SLN procedures during 2012. Introperative evaluation of lymph node for metastatic disease was also examined for correlation with permanent pathologic result. Results: 259 cases among 21 surgeons had touch prep performed. True positive number: 29. True negative number: 224. False negative number: 6. Fasle negative rate (FNR): 17.14%. Cost Effectiveness Evaluation: CPT 88307 - surg path gross and micro level V. CPT 88342 - Immunohistochemistry. CPT 88333 - Touch Prep. Pathologist time: 30 minutes per case. Conclusions: There is significant variation among surgeons as to number of cases and number of nodes submitted. There is a significantly greater number of sentinel lymph nodes examined by the pathologist as compared to the number of nodes submitted by the surgeon. The frequency of outliers is infrequent, but when it occurs there is significant cost in terms of time and dollars. The false negative rate from pathological evaluation is under study for isolated tumor cells.
The use of technology to improve the delivery process of ambulatory chemotherapy at the Odette Cancer Centre (OCC).
Authors: Maureen E. Trudeau, Philomena Sousa, Kathy Beattie, Thane Fitzgerald, Michael Jung Chu Leung, Matthew C. Cheung, Simron Singh, Ben De Mendonca
Journal: Journal of Clinical Oncology (2012)

290 Background: The OCC manages over 24,000 chemotherapy patient visits/year. Over time the number of patients, complexity of treatment and staffing requirements increase. Barriers to efficient delivery of chemotherapy include: same day (as clinic visit) treatment, missing MD orders, manual appointment scheduling and poor communication between chemo nurses and pharmacists during drug preparation. These issues were addressed by (1) non-same day chemotherapy, (2) MD orders expected day prior to treatment, (3) development of two web-based tools for chemotherapy scheduling and communication. Methods: Two independent process reviews were undertaken confirming system inefficiencies. The move to non-same day chemotherapy was implemented. An electronic Chemotherapy Appointment Reservation Manager (CHARM) was developed and linked to the computerized physician order entry (CPOE) system, and reminders were sent to MDs with outstanding orders 72, 48, and 24 hours pre-chemotherapy. The tool was developed to facilitate staff communication during chemotherapy preparation. Data relating to each process improvement was collected pre- and post-implementation. Results: Over 300 of the more than 400 chemotherapy regimens were reviewed for nurse assessment, medication preparation, and in-chair infusion times, with the results used to build the algorithms for CHARM. With the move to non-same day chemotherapy over 80% of patients are treated on a non-clinic day compared with 40% pre-implementation. With CHARM the average number of patients booked/day went from 68 to 100, a 47% increase. Currently, 90% of physician orders are entered by 2pm the day before treatment. Use of the communication tool resulted in an 89% reduction in phone calls between the nurses and pharmacy. 36% of patients started treatment +/- 30 min of scheduled time in both time peroids. Conclusions: OCC introduced several innovative approaches to improving the safe delivery of chemotherapy to cancer patients. Patient volumes have increased while communication around care delivery has improved. The approach allows ongoing research and development to improve workflow and communication.
Utilization of 17-gene biopsy-based genomics scores in treatment decisions for low- to intermediate-risk patients with prostate cancer.
Authors: Aaron Katz, Megan Mulcahy, Jacquelyn Rice, Kaitlin E. Kosinski
Journal: Journal of Clinical Oncology (2016)

e627 Background: Patients with prostate cancer are faced with many different treatment options for their disease. A biopsy-based 17-gene genomic analysis is clinically validated as a predictor of favorable pathology and is used in our practice to aid men considering Active Surveillance in lieu of definitive treatment for their low- to intermediate-risk prostate cancer. We analyzed the treatment decisions made after receiving the Genomic Prostate Score (GPS) results of this test. Methods: We identified 77 patients between 2013 to 2015 from our practice who received Genomic Prostate Score results. We characterized their demographics, NCCN criteria both before and after the test, their Genomic Prostate Score (GPS), chance of favorable pathology, and treatment decision after the test. Results: Average age of the group electing surveillance after the genomic test was 61 years versus 65 in the group electing treatment (p=0.04). Average GPS in the surveillance group was 20 versus 28 in the treatment group (p=0.03). Average percent chance of favorable pathology was 80% in the surveillance group versus 63% in the treatment group (p&lt;0.001). Conclusions: Biopsy-based genomics analysis can be a helpful tool for patients and practitioners who are evaluating candidacy for an Active Surveillance regimen versus definitive treatment for low- to intermediate-risk prostate cancer. [Table: see text]
Effect of high expression of fatty acid binding protein 5 on prognosis and epithelial-mesenchymal transition in hepatocellular carcinoma.
Authors: Takanori Ohata, Hideki Yokoo, Toshiya Kamiyama, Takeshi Aiyama, Kenji Wakayama, Tatsuya Orimo, Tatsuhiko Kakisaka, Yousuke Tsuruga, Hirofumi Kamachi, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2015)

310 Background: Hepatocellular carcinoma (HCC) is one of the cancer types with poor prognosis. The high expression of Fatty Acid Binding Protein 5 (FABP5) has been reported its malignant potential in several cancers. However, the function of FABP5 in HCC remains unknown. We analyzed the correlation between the expression of FABP5 and malignant behavior of HCC using HCC tissues and human HCC cell lines. Methods: A total of 231 HCC samples were obtained through our institute and subjected to immunohistochemical analysis. In vitro, protein expression of FABP5 in HCC cell lines was assessed by Western blot analysis. To the higher FABP5 expression cell lines, we performed proliferation assay, migration assay and invasion assay with or without genetic down-regulation of FABP5 by short hairpin RNA (shRNA). Results: The intensity of immunostaining in HCC tissues was determined comparing to immunoreactivity of Kupffer cells, and the patients were divided into a strong staining group (n=127) and a weak staining group (n=104) according to the intensity of immunostaining. In the strong staining group, 5-year overall survival rate was 58.3%, compared with 90.5% in the weak staining group (p&lt;0.0001). In addition, 5-year relapse free survival rate in the strong staining group was 23.1%, compared with 46.9% in the weak staining group (p&lt;0.0001). Moreover, the strong staining of FABP5 positively correlated with early recurrence, extrahepatic metastasis, AFP, AFP-L3%, PIVKA II, tumor size, poor differentiation, and micro/macro vascular invasion (P&lt;0.05). In vitro, the knockdown of FABP5 significantly inhibited cell proliferation, migration and invasiveness. Additionally, the knockdown of FABP5 was associated with inhibition of epithelial-mesenchymal transition (EMT), including down-regulation of N-cadherin, and Snail converse to the activation of E-cadherin and ZO-1. Conclusions: FABP5 was closely related with the gain of malignant potential through the activation of EMT, and also behaved as a significant prognostic and recurrence factor. Therefore, FABP5 may serve as a new biomarker of HCC and a potential molecular target for the development of HCC therapies.