tbuckley/cabot-search huggingface dataset:
Phosphorylated Akt expression as a favorable prognostic factor for patients undergoing curative resection and adjuvant chemoradiotherapy for proximal extrahepatic bile duct cancer.
Authors: Kyubo Kim, Hye Sook Min, Eui Kyu Chie, Jin-Young Jang, Sun-Whe Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Sung W. Ha
Journal: Journal of Clinical Oncology (2013)

182 Background: To evaluate the prognostic significance of phosphorylated Akt (p-Akt), phosphorylated mammalian target of rapamycin (p-mTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression in patients undergoing adjuvant chemoradiotherapy for proximal extrahepatic bile duct (EHBD) cancer. Methods: Sixty-three patients with proximal EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled into this study. Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to a median of 40 Gy (range; 40-54). Fifty-nine patients also received fluoropyrimidine chemotherapy as a radiosensitizer. p-Akt, p-mTOR, and PTEN expression were assessed with immunohistochemical staining on the tissue microarray. Results: p-Akt, p-mTOR, and PTEN were expressed in 23 (36.5%), 17 (27.0%) and 25 patients (39.7%), respectively. p-Akt expression was associated with distant metastasis and overall survival, but not with loco-regional recurrence. The 5-yr distant metastasis-free and overall survival rates were 25.8% vs. 58.2% (p = 0.007), and 27.5% vs. 50.2% (p = 0.0167) in patients with negative and positive expression, respectively. On multivariate analysis, nodal involvement was the only significant prognosticator predicting inferior distant metastasis-free survival (p = 0.0105), while p-Akt expression had a borderline significance (p = 0.0541). As for overall survival, p-Akt expression was a marginally significant prognosticator (p= 0.0635), whereas other risk factors lost the statistical significance. Conclusions: p-Akt expression was a favorable prognostic factor for patients undergoing curative resection followed by adjuvant chemoradiotherapy for proximal EHBD cancer.
CpG island hypermethylation of corticotropin-releasing hormone-binding protein in kidney cancer and association with clinicopathological parameters.
Authors: Hossein Tezval, Faranaz Atschekzei, Natalia Dubrowinskaja, Axel S. Merseburger, Inga Peters, Jan Becker, Jens Bedke, Stephan Kruck, Arnulf Stenzl, Markus A. Kuczyk, Juergen Serth
Journal: Journal of Clinical Oncology (2013)

414 Background: Significance of Urocortin (Ucn or UcnI), Ucn2, Ucn3, and their receptors, Corticotropin Releasing Factor Receptor 1 and 2 (CRFR1 and CRFR2), and the binding protein, Corticotropin-Releasing Hormone-Binding Protein (CRHBP) in oncology is growing rapidly. Recently we found that the UCN system may also be a relevant structure in renal cell cancer. Here we investigate whether CRHBP CGI methylation occurs in cc-RCC and whether its methylation is associated with clinicopathological parameters of patients. Methods: Tumoral tissues of 109 patients with renal cell cancer and their corresponding normal tissues have been used. Combined bisulfite restriction analysis (COBRA) for detection of relative degree of CpG island (CGI) methylation and pyrosequencing have been performed. Results: We found an approximately five-fold increase in mean methylation of the CRHBP CGI for tumor tissues (p &lt; 0.00005). Higher DNA methylation of the CRHBP CGI showed a positive correlation with advanced disease as well (p = 0.024). Conclusions: To our knowledge we report for the first time the CGI methylation of CRHBP in clear cell renal cell carcinoma indicating a contribution of epigenetic alteration of CRHBP to RCC tumorigenesis. Moreover, our results suggest CRHBP as a potential molecular marker for assessment of progression and aggressiveness of tumors.
Phase II clinical trial of weekly oxaliplatin concurrent with capecitabine plus preoperative radiotherapy in locally advanced resectable rectal cancer
Authors: M. Majem, M. Navarro, F. Losa, V. Alonso, M. Gallen, M. Benavides, F. Rivera, P. Escudero, B. Massuti, E. Aranda
Journal: Journal of Clinical Oncology (2008)

15013 Background: The aim of the study was to evaluate the efficacy of preoperative treatment with weekly Oxaliplatin and Capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable rectal cancer in terms of pathological complete response. Methods: from 6/05 to 11/05 forty-five patients (pt) with resectable T3-T4, N-/+ rectal cancer were treated with Oxaliplatin (50mg/m2 day 1 weekly), Capecitabine (825 mg/m2, twice daily for 5 days/week) and concurrent RT (45 Gy,1.8 Gy/fraction, 5 fraction/week during 5 weeks). Patients underwent surgery after 6–8 weeks. The primary end point was to determine the rate of pathologic complete response. Secondary end points were to assess the toxicity profile of the combination and rate of complete resection. Results: 45 pt (35 male, 10 female; median age 62.4 [59.8–69.4]) have been included. TNM Stage: 43 pt T3, 2 pt T4; 27 pt N+. 93% pt completed the planned RT and 87% pt completed QT. No grade 4 toxicity was observed. Grade 3 toxicity included limfopenia (13%), diarrhoea (9%), emesis (4%), asthenia (7%), anorexia (2%) and hepatic toxicity (2%). Grade 1 neurotoxicity was observed in 35% of pt and 2% of pt experienced grade 2 neurotoxicity. Grade 1 palmoplantar eritrodysesthesia was observed in 2% of pt. All patients underwent surgery, 98% with complete resection. Sphincter-saving operation was performed in 67% of pt and total mesorectal excision was performed in 67% of pt. The overall clinical response rate was 83%, with a pathologic complete response rate of 12%. Conclusions: Preoperative chemoradiation with Oxaliplatin, Capecitabine and RT seems to be effective in locally advanced resectable rectal cancer, with a favourable safety profile. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche, sanofi-aventis
Cladribine plus rituximab for the initial treatment of mantle cell lymphoma.
Authors: T. Pindyck, S. E. Spurgeon, C. Y. Okada, E. E. Epner
Journal: Journal of Clinical Oncology (2010)

8099 Background: Mantle cell lymphoma (MCL) is incurable with standard immuno-chemotherapy and the best initial treatment regimen remains unclear. The North Central Cancer Group published their experience with the combination of rituximab and cladribine (R-cladribine) in 29 newly diagnosed MCL patients which showed an overall response rate (ORR) of 66% (CR rate of 52%) with 80% of patients remaining in CR at a median follow up of 21.5 months.(Inwards D et al. Cancer. 113:108). To further define the role of R-cladribine in the treatment of newly diagnosed MCL, we performed a retrospective chart review of patients with newly diagnosed MCL treated with R-cladribine. Methods: We reviewed the charts of 24 patients with newly diagnosed MCL seen in a University and VA setting treated with R-cladribine. One patient had been previously treated with 2 cycles of R-CHOP followed by R-cladribine, but all other patients were untreated. All patients had measurable disease at diagnosis and follow up imaging at the completion of therapy. Chemotherapy consisted of cladribine 5 mg/m2 given over two hours on days 1-5 of each cycle and rituximab on days 1, 8, 15, and 22 with the first cycle and then on day 1 with subsequent cycles. Each cycle was 28 days for up to a total of 6 cycles. The majority of patients with an initial response received maintenance rituximab. Results: The median age of our cohort was 67 years. All patients had advanced stage disease (stage ≥ 3) and the majority of patients had poor risk disease. The ORR was 91% with 14 of 24 (58%) patients achieving a complete remission (CR/CRu). At a median follow up of 25 months (2-87 months), only 1 of the 14 (7%) CR patients has relapsed (at 33 months). All patients who attained a PR have progressed. No significant trends were seen regarding response rate and pre-treatment disease defining parameters including Ki67, beta-2 microglobulin, FLIPI, or MIPI. There was one treatment related death from neutropenic sepsis. One patient had persistent neutropenia and thrombocytopenia post therapy. Conclusions: R-Cladribine appears to be a highly effective initial therapy for MCL with a long duration of response. It offers an attractive therapeutic backbone for combination with novel agents. Prospective trials have been initiated. No significant financial relationships to disclose.
Adenovirus-Mediated Gene Transfer to Mesenchymal Stem Cells: Comparison of the Cytomegalovirus- and Rous Sarcoma Virus-Promoter.
Authors: Weiwen Deng, Troy A. Giambernardi, Rick V. Hay, Daniel W. Pietryga, Aly S. Abdel-Mageed
Journal: Blood (2007)
Phase I trial of irinotecan and epirubicin in patients with advanced solid tumors
Authors: P. J. Gold, S. Refice, H. West
Journal: Journal of Clinical Oncology (2005)

2120 Background: Irinotecan (I) and Epirubicin (E) have broad anti-tumor activity and different mechanisms of action. A Phase I clinical trial was initiated to define the maximum tolerated dose (MTD) of this combination. Methods: Patients who had received at least 1 prior chemotherapy regimen for advanced solid tumors were eligible. Patients in the first cohort received I 250 mg/m2 IV and E 50 mg/m2IV every 21 days. No hematopoetic growth factor support was permitted. Due to dose-limiting neutropenia in cohort 1, the doses were de-escalated to I 200 mg/m2 IV and E 35 mg/m2IV every 21 days. Results: 11 patients were enrolled, 6m/5f. The median age was 62 years (range 34–82). There was 1 each of breast, colon, endometrial, gastric, lung, ovarian, and unknown primary cancers. There were 2 each of melanoma and pancreatic cancer. The patients were heavily pre-treated, with a median of 3 (range 2–9) prior chemotherapy regimens. Three patients in the first cohort had dose-limiting neutropenia, which prevented escalation. A subsequent 6 patients were treated at dose-level -2, and three patients had dose-limiting neutropenia as well. One patient with lung cancer had a partial response of 3.5 months duration. Another patient with colon cancer had stable disease for 5 months. Conclusions: In this heavily pre-treated population, it was not possible to determine the MTD. Clinical activity was noted in lung and colon cancer. Future studies should focus on less heavily pre-treated patients and should consider cytokine support. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer
Documentation of pharmacist-provided patient education for oral chemotherapy.
Authors: Anderson Jennifer, Neeta K. Venepalli, Patrick Joseph Fleming, Christina Haaf, Adam Bursua, Little Irene Park, Sandra Cuellar
Journal: Journal of Clinical Oncology (2016)

237 Background: Pharmacist-provided patient education for oral chemotherapy is poorly documented in patient electronic medical records (EMR) at UIC Oncology Pharmacy. At baseline, 41% of patients who started new therapy with selected oral chemotherapies had a patient education note documented by a pharmacist in their EMR. Our aim is to provide and document patient education for at least 90% of patients who start new oral chemotherapy and fill their prescriptions at UIC Oncology Pharmacy over three months. The importance of patient counseling and documentation is recognized by the Quality Oncology Practice Initiative (QOPI) group. Approximately 25% of patients undergoing chemotherapy are on oral chemotherapy. (Deutsch S, Koerner P, Miller RT, Craft Z, Fancher K. Utilization patterns for oral oncology medications in a specialty pharmacy cycle management program. J Oncol Pharm Pract. 2014;0:1-8.) Methods: A multi-disciplinary team performed an affinity sort and created a process map to identify areas of intervention. The first intervention was labelling prescription bags to identify them as oral chemotherapy prescriptions that require counseling by a pharmacist. Data was collected after two weeks. Results: At the completion of the first PDSA cycle, 40% of patients who started new oral chemotherapy had a documented patient education note written by a pharmacist in their EMR. Documentation of education was performed on the day of pick-up in 89% of cases. Table 1 shows the percentage of notes that included the elements recognized by QOPI standards: documentation of start date, adherence, and adverse effects. Conclusions: Documentation of patient education for oral chemotherapy should be a well-integrated component of ambulatory pharmacy practice. A second PDSA cycle is planned to increase rates of documentation by utilizing the pharmacy resident to perform patient counseling and documentation. Future interventions will be aimed at improving the quality of the data included in the documented notes. [Table: see text]
Effect of primary tumor resection on survival in patients with metastatic colorectal cancer in the post-2000 era: A California Cancer Registry analysis.
Authors: Ana Milena Rodriguez Fahrni, I-Yeh Gong, Yingjia Chen, Rosemary Cress, Thomas John Semrad, Vijay P. Khatri
Journal: Journal of Clinical Oncology (2013)

504 Background: Resection of primary tumors in the setting of metastatic colorectal cancer (MCRC) is controversial. Fewer primary tumor resections are being performed due to the improved tumor response and disease control rates associated with modern systemic therapy. Recent studies suggest a survival benefit for patients with MCRC who had primary tumors resection prior to systemic therapy. This analysis evaluates the independent prognostic impact of primary tumor resection on overall survival (OS) for patients with MCRC using the California Cancer Registry (CCR). Methods: We queried the CCR for all patients with MCRC diagnosed between 2003 and 2010. Patients were categorized by whether or not they had primary tumor resection at time of diagnosis. Covariates included gender, age, race/ethnicity, socioeconomic status (SES), and rural-urban commuting area (RUCA) score of patients. Univariate comparisons were made using the Kaplan Meier method. Multivariate comparisons were performed using the Cox proportional hazards regression method. Results: 19,836 patients met the criteria for analysis of whom 11,566 (58%) had primary tumor resection. Primary tumor resection rates declined over this time period (63% in 2003 v. 52.8% in 2010, p&lt;0.0001), varied by SES (55% v. 62%: lowest versus highest, p&lt;0.001) and residence (63% in rural versus 58% for urban, P=0.0160). On multivariate analysis, overall survival was significantly better for patients that had primary tumor resection (HR: 0.467 [95% CI: 0.467-0.482]; p&lt;0.0001). Survival was statistically longer in younger patients (HR: 1.385 for age 65-75, HR: 2.217 if greater than age 75), highest SES (HR: 0.869, p&lt;0.0001), Hispanics (HR: 0.884, p&lt;0001), and Asian/Pacific Islanders (HR:0.892, p&lt;0.0001). Overall survival was worse for African Americans (HR:1.105, P=0.0001). Conclusions: Our study demonstrates the independent prognostic value on survival of primary tumor resection in patients with MCRC. There is significant variability of resection rates by SES and rural-urban residence. As analysis of CCR data cannot eliminate the influence of patient and provider biases, a prospective randomized trial is warranted.
Role of routine adjuvant chemotherapy after neoadjuvant chemoradiotherapy and resection in low-risk patients with rectal cancer.
Authors: R. P. Kiran, P. J. Nisar, R. J. Pelley, V. W. Fazio, I. C. Lavery
Journal: Journal of Clinical Oncology (2011)

e14032 Background: The current standard of care is the routine administration of adjuvant chemotherapy after neoadjuvant chemoradiation and surgery for locally advanced rectal cancer. The aim of this study is to identify specific groups where adjuvant chemotherapy may reasonably be avoided. Methods: Patients > 65 years age undergoing rectal resection after neoadjuvant chemoradiation for primary rectal cancer from 1998-2004 were identified from SEER-Medicare data. Patients were grouped according to whether or not they received adjuvant chemotherapy in the 12 months after surgery. Overall survival (OS) was adjusted for the presence or absence of involved lymph nodes in the resection specimen. Results: 1,363 patients met inclusion criteria and were extracted from the SEER-Medicare registry. 798 (58.5%) received adjuvant chemotherapy (+chemo group) while 565 (41.5%) did not (-chemo group). The median follow up time was 53 months. Treatment with adjuvant chemotherapy was associated with improved survival for patients with lymph nodal involvement on pathological staging and stratified as AJCC stages II and III. Conclusions: The findings of this study suggest that the decision whether to perform adjuvant chemotherapy after chemoradiation and resection for rectal cancer patients can be stratified based on lymph node status and AJCC stage. Adjuvant chemotherapy may reasonably be avoided, without adversely affecting survival, in selected low risk patients. Overall survival (%) for patients receiving adjuvant versus no adjuvant chemotherapy following surgery for rectal cancer with preoperative chemoradiotherapy. Included patients Adjuvant chemo N 12 months 36 months 60 months P value All patients No 565 86 69 56 0.10 Yes 798 96 73 58 AJCC stage I No 180 94 84 75 0.63 Yes 152 98 86 72 AJCC stage II No 215 88 70 55 0.016 Yes 261 97 82 64 AJCC stage III No 88 73 47 35 0.0002 Yes 262 94 63 52 AJCC stage IV No 34 56 32 16 0.084 Yes 59 93 41 19 LN+ No 81 98 40 27 <0.0001 Yes 262 94 59 46 LN- No 323 90 77 63 0.058 Yes 358 97 85 71
Effects of complementary and alternative medicine use on hopelessness in ovarian cancer patients
Authors: A. H. Gross, J. Cromwell, A. B. Kornblith, H. Lee, H. Li, L. Pereira, R. T. Penson, U. A. Matulonis
Journal: Journal of Clinical Oncology (2008)

9598 Background: Hopelessness is a significant factor affecting the quality of life (QOL) of cancer patients (pts). Despite the millions of dollars spent annually on Complementary and Alternative Medicine use (CAM) there is little research demonstrating any beneficial effect of CAM on QOL and hope despite the fact that these are reasons patients cite for using CAM. Methods: A secondary dataset (n=130 pts) was concatenated from subsets of 2 QOL studies of ovarian cancer pts. A recursive path model was estimated to quantify the hypothesized direct and indirect effects of recurrence and age (>55 yrs) on spirituality (FACT Spirituality Scale), # of CAM use (special diet, psychotherapy, movement, physical therapies, mind/body, spiritual practices, vitamins, herbs) and on feelings of hopelessness (Beck’s Hopelessness Scale). Age and recurrence were also hypothesized to affect hopelessness indirectly through spirituality, which in turn should raise CAM use and reduce hopelessness. Results: Pt median age was 55, range 34–87 years. 73 had recurrent disease (RD). 57 were survivors > 3 years from diagnosis without RD. 97% of all pts reported use of CAM however CAM had only a minimal positive, insignificant effect on hopelessness controlling for other factors. RD directly increased hopelessness (path coefficient [PC] 0.32, p<0.001) which was significantly offset due to heightened spirituality by some RD pts (PC 0.24, p<0.01) that reduced hopelessness (PC −0.56, p<0.001). Older pts were likely to use fewer CAMs (PC −0.26, p<0.01) but were not more spiritual or more hopeful, controlling for RD. A continuous age variable was positively correlated with RD implying another path of age to hopelessness. Conclusions: A significant causal relationship between CAM use and hopelessness was not established. Feelings of hopelessness, natural in pts with RD, were significantly offset through their spirituality. Increasing spirituality, especially among RD pts may significantly improve feelings of hopefulness. Future research should explore direct effects of specific CAM therapies, excluding spiritual practices, on QOL and hope, the interactive relationship between spirituality and hopefulness and continuous effects of age on both recurrence and hope. No significant financial relationships to disclose.
Establishment and Characterization of a Novel Human Myeloid Leukemia Cell Line, AMU-AML1, Carrying t(12;22)(p13;q11) with No Fusion of MN1-TEL
Authors: Mayuko Goto, Ichiro Hanamura, Motohiro Wakabayashi, Hisao Nagoshi, Tomohiko Taki, Norikazu Imai, Mineo Goto, Shohei Mizuno, Miyuki Takahashi, Kazuto Suganuma, Akihito Hiramatsu, Hidesuke Yamamoto, Masaya Watarai, Masato Shikami, Akira Imamura, Hidetsugu Mihara, Masafumi Taniwaki, Hiroshi Miwa, Masakazu Nitta
Journal: Blood (2010)
Patterns of care and survival trends in elderly metastatic colorectal cancer patients: A SEER-Medicare analysis.
Authors: V. Shankaran, S. J. Beck, D. K. Blough, Y. Yim, E. Yu, S. D. Ramsey
Journal: Journal of Clinical Oncology (2011)

520 Background: Over the last decade, the treatment of metastatic colorectal cancer (mCRC) has changed dramatically as new drugs and hepatic resection have been incorporated into practice. The goal of this study is to examine treatment patterns and survival trends for older patients (pts) with mCRC. Methods: Pts ≥ age 65 with mCRC diagnosed (dx) 2001-2005 were identified from the SEER-Medicare database. Pts were excluded for lack of Medicare parts A and B in the year prior to dx, second malignancy, or non- adenocarcinoma histology. First-line (1L) chemotherapy (CTx) use was identified by claims within 3 months of dx. Metastatectomy was identified by various claims for liver resection. Comorbidity was assessed by Klabunde index. A Cox proportional hazards regression model was used to assess the effect of demographic and treatment factors on survival. Results: A total of 5,725 pts (median age 77) met inclusion criteria. 274 pts (5%) underwent hepatic resection and 2,647 (46%) received CTx. From 2001-2003, 43% of pts received 1L CTx (34% and 1% with regimens containing irinotecan (Iri) and oxaliplatin (Ox) and 49% with 5-FU/cap alone). From 2004-2005, 51% of pts received 1L CTx (25%, 14%, and 37% with regimens containing bevacizumab (Bv), Iri, and Ox and 40% with 5-FU/cap alone). In the multivariate analysis using the Cox proportional hazards model, survival was significantly improved in pts receiving CTx or hepatic resection and in pts dx 2004-2005 (Table). Conclusions: In an older mCRC population, hepatic resection, CTx use, and mCRC dx in 2004-2005 are associated with improved survival. Improved survival of pts dx in 2004-2005 coincides with the 2004 approval dates and uptake of Bv and Ox, and may be associated with the use of these therapies. Further analysis will examine the associations between specific Ctx regimens, Bv, and survival and will include pts dx through 2007. [Table: see text] [Table: see text]