tbuckley/cabot-search huggingface dataset:
A feasibility study of gene expression analysis from enriched circulating tumor cells (CTC) in metastatic breast cancer (MBC).
Authors: A. M. Drucker, D. Pinto, E. Teh, J. Williams, D. Rayson, S. Douglas
Journal: Journal of Clinical Oncology (2011)

e21156 Background: The most common methods for CTC isolation from peripheral blood depend on positive selection based on tumor cells’ surface EpCAM expression. However, EpCAM expression may vary between CTCs and may be downregulated in cells undergoing epithelial-to-mesenchymal transition, potentially resulting in the failure to capture CTC subsets having a critical role as intermediates in cancer progression. Methods: We previously reported on a feasibility study using an unbiased approach with three different enrichment methods, involving both positive and negative selection, and obtained consistently high recovery of small numbers of MDA-MB-231 cancer cells spiked into donor human peripheral blood using the RosetteSep Human Circulating Epithelial Tumor Cell Enrichment Cocktail (Stem Cell Technologies, Vancouver, BC Canada). Cytospins prepared from recovered cells were used for identification and enumeration by immunocytochemistry using fluorescently laballed anti-CD45 and anti-CK19 antibodies. We optimized RNA amplification from the equivalent of one MDA-MB-231 cell (~10 pg) and used the resulting amplified RNA in microarray experiments. Peripheral blood from MBC patients was enriched for CTC, RNA was isolated and amplified, and microarray and qPCR analysis was used to investigate global and gene-specific transcription changes, respectively. Results: Numbers of CTC enriched from eight MBC patients ranged from 1 to 125 per 5 mL blood. EpCAM, CK19, vimentin, and CD45 expression by CTC was determined by qPCR. Preliminary results from microarray analysis of enriched CTC from four of six initial patients showed ~ 130 common genes upregulated more than twofold, including genes involved in tumorigenesis. Two of six patients had insufficiently amplified RNA. Gene enrichment analysis showed an abundance of genes involved in translation. Conclusions: Although preliminary, these methods may lead to a more thorough characterization of micrometastases in advanced breast cancer and potentially early stage disease. Further microarray analysis and optimization methods are ongoing in MBC patients.
Buspirone treatment of dyspnea in outpatients receiving chemotherapy: A University of Rochester Cancer Center Community Clinical Oncology Program (URCC CCOP) study.
Authors: P. W. Bushunow, J. A. Roscoe, D. J. Dudgeon, J. J. Kirshner, C. E. Heckler, G. R. Morrow, S. R. Dakhil, T. S. Collins, D. A. Churchill
Journal: Journal of Clinical Oncology (2011)

9023 Background: Dyspnea is a commonly reported symptom in patients with cancer, not just at end-of-life, but at presentation and during treatment, and it is not limited to patients with lung cancer diagnosis, pleural effusions or other specifically identifiable causes. A prior study by our group found that one third of 1715 patients receiving chemotherapy for cancer in community practice settings reported dyspnea. Buspirone is a non-benzodiazepene anxiolytic which does not suppress respiration and has been reported to relieve the sensation of dyspnea in patients with COPD and other conditions. Methods: We recruited 433 chemotherapy patients with grade 2 or higher dyspnea, assessed on the Modified Medical Research Council Dyspnea Scale (MMRCDS), being treated at 16 participating CCOP sites. Patients were randomized to buspirone 10mg po daily for 3 days then 20mg po daily for a total of 28 days or to matching placebo. Dyspnea, depression, anxiety, fatigue, and quality of life were assessed with validated scales prior to and at the end of the intervention. The primary assessment instrument was an Oxygen Cost Diagram, a simple scale for quantifying a patient's evaluation of tolerance for exertion, which can range from a low of 2 (even sleep requires exertion) to 14 (unable to walk briskly uphill). Results: The buspirone and placebo groups were balanced in terms of sex (52% female) prior chemotherapy (82% had received prior chemotherapy) prior diagnosis of COPD (37%) cancer diagnoses and stage. 62% of patients had lung cancer diagnosis. We found a trend to improvement of dyspnea for the overall group of patients. However, Buspirone was associated with a 0.57 decrease in oxygen cost, P=0.029. Hence, patients treated with buspirone reported more dyspnea than those treated with placebo. We found no influence of age, gender, disease, stage, QOL, presence of COPD, metastases, smoking history, baseline fatigue or anxiety on the effect of buspirone. Conclusions: Dyspnea is a common symptom in ambulatory cancer patients who are being treated with chemotherapy. Buspirone treatment had no benefit for these patients.
Comparison of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by radiation versus concurrent chemoradiotherapy with TPF in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)
Authors: H. Katori, M. Tsukuda, J. Ishitoya, M. Kimura, S. Hirose, M. Takahashi, Y. Sakuma, K. Yamamoto, N. Satoh
Journal: Journal of Clinical Oncology (2005)

5580 Background: The aim of this study was to compare the effectiveness of induction chemotherapy with docetaxel, cisplatin, and 5-Fluorouracil (TPF) followed by radiation to that of concurrent chemoradiotherapy with TPF in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods: In group of induction chemotherapy followed by radiation, they received 2 cycles of chemotherapy with docetaxel 60 mg/m2, cisplatin 70 mg/m2 and 5-day 5-FU 750 mg/m2/day. Radiotherapy was begun on 21 days after completion of chemotherapy. In the group of concurrent chemoradiotherapy, they received 2 cycles of chemotherapy with docetaxel 50 mg/m2, cisplatin 60 mg/m2, and 5-day 5-FU 600 mg/m2/day. Radiation was begun on the first day of chemotherapy. The total radiation dose was between 63.0 and 74.0 Gy. Results: Overall response rate (PR+CR) (both 100%) and CR rate (87% and 84%) were similar, but in 3-year survival rate (64% and 83%), concurrent chemoradiotherapy with TPF was better than induction chemotherapy with TPF followed by radiation (p=0.029). Grade 3≤ mucositis (40% and 79%) and anemia (0% and 16%) were more frequent in the group of concurrent chemoradiotherapy, but concurrent chemoradiotherapy with TPF improved overall survival. Conclusions: In the present study, we compared induction chemotherapy with TPF followed by radiation and concurrent chemoradiotherapy with TPF in patients with locally advanced SCCHN. Both regimens were generally well tolerated and resulted in a high overall response rate and CR rate. Concurrent chemoradiotherapy with TPF required more supportive care and experience to deliver, with more frequent mucositis and hematological toxicity. Given these reservations, it achieved improved disease control better than induction chemotherapy with TPF followed by radiation. While overall response rate and CR rate were similar, in 3-year survival rate, concurrent chemoradiotherapy with TPF was better than induction chemotherapy with TPF followed by radiation. No significant financial relationships to disclose.
Lentiviral Vector-Mediated Transfer of the Gamma-Globin Gene Into Normal and Beta-Thalassemic Human CD34+ Cells Results in Potentially Therapeutic Levels of Fetal Hemoglobin in Erythroid Progeny.
Authors: Andrew Wilber, Phillip W. Hargrove, Yoon-Sang Kim, Arthur W. Nienhuis, Derek A. Persons
Journal: Blood (2009)
Effectiveness of an Internet-Delivered Exercise and Pain-Coping Skills Training Intervention for Persons With Chronic Knee Pain
Authors: Kim L. Bennell, Rachel Nelligan, Fiona Dobson, Christine Rini, Francis Keefe, Jessica Kasza, Simon French, Christina Bryant, Andrew Dalwood, J. Haxby Abbott, Rana S. Hinman
Journal: Annals of Internal Medicine (2017)

Background: Effective, accessible biopsychosocial treatments are needed to manage chronic knee pain on a population level. Objective: To evaluate the effectiveness of Internet-delivered, physiotherapist-prescribed home exercise and pain-coping skills training (PCST). Design: Pragmatic parallel-group randomized, controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12614000243617) Setting: Community (Australia). Patients: 148 persons aged 50 years or older with chronic knee pain. Intervention: The intervention was delivered via the Internet and included educational material, 7 videoconferencing (Skype [Microsoft]) sessions with a physiotherapist for home exercise, and a PCST program over 3 months. The control was Internet-based educational material. Measurements: Primary outcomes were pain during walking (11-point numerical rating scale) and physical function (Western Ontario and McMaster Universities Osteoarthritis Index) at 3 months. Secondary outcomes were knee pain, quality of life, global change (overall, pain, and functional status), arthritis self-efficacy, coping, and pain catastrophizing. Outcomes were also measured at 9 months. Results: Of participants enrolled, 139 (94%) completed primary outcome measures at 3 months and 133 (90%) completed secondary outcome measures at 9 months; multiple imputation was used for missing data. The intervention group reported significantly more improvement in pain (mean difference, 1.6 units [95% CI, 0.9 to 2.3 units]) and physical function (mean difference, 9.3 units [CI, 5.9 to 12.7 units]) than the control group at 3 months, and improvements were sustained at 9 months (mean differences, 1.1 units [CI, 0.4 to 1.8 units] and 7.0 units [CI, 3.4 to 10.5 units], respectively). Intervention participants showed significantly more improvement in most secondary outcomes than control participants. At both time points, significantly more intervention participants reported global improvements. Limitation: Participants were unblinded. Conclusion: For persons with chronic knee pain, Internet-delivered, physiotherapist-prescribed exercise and PCST provide clinically meaningful improvements in pain and function that are sustained for at least 6 months. Primary Funding Source: National Health and Medical Research Council.
Effect of race and comorbidities on patterns of bevacizumab toxicity: A single-institution experience.
Authors: M. Raza, S. Raza, Z. Latif, J. C. Sachdev
Journal: Journal of Clinical Oncology (2010)

6132 Background: Bevacizumab (Bev) is associated with unique adverse effects (AE) like hypertension (HTN), proteinuria, arterial thromboembolism (ATE), venous thromboembolism (VTE), and hemorrhage. We evaluated the pattern of bevacizumab AE by race (African American: AA or Caucasian: CA) and the association between specific comorbidities and AE. Methods: Retrospective chart review of patients treated with Bev between 2004 and 2009 in our practice. Toxicities were graded according to NCI CTCAE 3.0. HTN AE was defined as either new onset or worsening HTN (increase by ≥ 1 grade above baseline HTN). Chi-square test was used to test for association between race and AE. Logistic regression models were fitted for comorbidities and AE. Results: N= 302. Table: Patient characteristics, AE frequency, and distribution by race. There was a significant association between race and any AE (AA: 60% vs. CA: 31% p < 0.001) and HTN AE but not proteinuria or VTE (Table). There was a trend for an association between HTN AE and proteinuria (p 0.05). Baseline co-morbidities of HTN, diabetes mellitus (DM) or the combination were not significantly associated with proteinuria (p 0.32 for HTN or DM, p 0.64 for HTN + DM). Among patients who had baseline HTN + DM, race was not significantly associated with proteinuria. No other significant associations of baseline co-morbidities and specific AE were identified. Conclusions: In our cohort, AA patients were more likely to experience Bev-related AE, particularly HTN. Despite frequent comorbidities, the frequency of severe life-threatening AE including hemorrhage and ATE was low. Further research to identify predictive factors for Bev AE is needed. % % % p value Age, yrs Median 60 (18-95) Race AA 49 CA 50 Other 1 Baseline comorbidities Overall AA CA HTN 48 51 47 0.48 DM 13 17 11 0.12 HTN + DM 13 17 9 0.04 CAD 8 ATE 1 CHF 2 Tumor type Colorectal 57 Lung 22 Breast 13 RCC 3 Other 8 Adverse events (%) HTN 27 38 18 < 0.01 New onset 24 8 < 0.01 Worsening 44 18 < 0.01 Proteinuria 18 23 16 0.12 VTE 4 6 3 0.38 ATE 0.6 Hemorrhage 4 Any grade 4/5 AE 2 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech
Emerging trends in radiation therapy use among women older than age 70 with stage I breast cancer from 2000-2007: A population-based analysis.
Authors: X. Shen, A. P. Wojcieszynski, M. V. Mishra, P. R. Anne, T. N. Showalter
Journal: Journal of Clinical Oncology (2011)

6094 Background: The use of radiation therapy (RT) after lumpectomy is the standard of care in breast conserving therapy (BCT). A randomized trial published in 2004 suggested that women age ≥70 years with stage I, estrogen receptor (ER) positive breast cancer may not require RT after lumpetomy. We performed a population-based analysis to evaluate changes in patterns of RT usage among women age ≥70 from 2000-2007. Methods: We used the Surveillance, Epidemiology and End Results (SEER) database to identify women diagnosed with stage I invasive ductal breast cancer from 2000 – 2007 who were treated with lumpectomy. We extracted information on patient demographics, tumor characteristics, initial treatment course, and survival. Patients were classified by modality of RT: beam radiation, radioactive implant, other, or none. We used chi-square test for differences in proportion of RT modality usage and linear regression to test for trends in usage. Results: We identified 18,789 women age ≥ 70 (median age 77, range 70-108) diagnosed with stage I breast cancer from 2000 – 2007 and treated with lumpectomy. Overall, 62.8% of these women received external beam RT, 3.2% implant RT, 5.5% other RT, and 28.5% omitted RT. From 2000 to 2007, there has been a decrease in the use of external beam RT from 68.5% to 55.9% (p<0.001) and a simultaneous rise in the use of radioactive implants from 0.5% to 7.7% (p<0.001). Large geographic variations in utilization exist across SEER regions, such as in the percentage of older women who omit RT, from 15.1% (Seattle) to 42.3% (Los Angeles). For patients with known ER status, those with ER positive tumors were more likely to omit RT than those with ER negative tumors (26.9% vs 23.8% p = 0.02). Since 2000, the percentage of older women with ER positive tumors who receive no RT has increased from 24.4% to 29.5% (p=0.02). In contrast, the percentage of older women with ER negative cancers who received no RT did not significantly change. Conclusions: Patterns of RT usage in BCT for women ≥ 70 years with stage I breast cancer are changing with increasing use of radioactive implants and more patients with ER positive tumors omitting RT. Further follow-up is required to determine the effect on survival.
Age as a prognostic factor for prostate cancer patients treated with brachytherapy
Authors: A. Nagavi, R. Shirazi, N. Dunlap, W. Barrett
Journal: Journal of Clinical Oncology (2005)

4731 Background: PSA level and Gleason score are well-established prognostic factors for patients with prostate cancer. The purpose of this retrospective study was to investigate the prognostic importance of age in prostate cancer patients treated with I-125 seed implantation. Methods: 162 consecutive patients with stage T1a, T1b, T1c, T2a, T2b, and T2c prostate cancers underwent Iodine-125 seed implantation at our institution between 1996 and 2001. 7 patients received neo-adjuvant hormone ablation therapy, and 5 patients received adjuvant external beam radiation therapy. All underwent an initial workup consisting of pretreatment PSA level and multiple biopsies with determination of Gleason score. Patients were stratified into a group of patients consisting of individuals aged 60 years or less at the time of brachytherapy (Group A, n=35), and another group of patients aged 61 and over at the time of brachytherapy (Group B, n=127). The mean follow up for patients in both groups was 4.0 years, and all patients were followed for a minimum of 2 years. Biochemical outcome was determined by the ASTRO definition of biochemical failure and also by patients achieving and maintaining PSA nadirs of ≤1.0, ≤0.5, and ≤0.2 ng/ml. Results: Pretreatment disease characteristics and post-treatment results for both groups are presented in the table below. Conclusions: Patients who were younger than 61 years of age when treated for prostate cancer with brachytherapy had a similar incidence of biochemical control by the ASTRO definition, but had a lower likelihood of achieving PSA nadirs of ≤.5 ng/ml and ≤.2 ng/ml. The younger patient group had a lower mean PSA level and Gleason score, yet had a higher likelihood of achieving PSA nadirs above .5 ng/ml and .2 ng/ml, which may support a more aggressive disease in younger patients. No significant financial relationships to disclose.
Use of gene expression of specific marker genes in intraperitoneal lavage samples to predict peritoneal dissemination in gastric carcinoma.
Authors: A. Serizawa, H. Kuramochi, G. Nakajima, K. Hayashi, S. Takeichi, Y. Kitamura, H. Kamikozuru, R. Okuyama, M. Yamamoto
Journal: Journal of Clinical Oncology (2010)

e14553 Background: Since peritoneal dissemination is the most important prognostic factor for patients with gastric cancer, high sensitivity and specificity is required for a diagnosis of dissemination. Peritoneal lavage cytology is widely used in Japan in order to assess a risk of peritoneal dissemination, but it requires great skill and its sensitivity is very limited. Methods: Peritoneal lavage samples were collected from 34 gastric cancer patients (M/F 24/10, median age 66.5) either during surgical operation or through intraperitoneal catheter which was inserted when recurrence was suspected. Lavage samples were centrifuged and floating intraperitoneal cells were collected. Total RNA were extracted and converted to cDNA. Real-time RT-PCR was performed for quantification of targeted 9 genes (CDH, TERT, CEA, KRT20, DDC, FABP1, BIRC5, TACSTD1, TFF1). GAPDH was used as a reference gene. Conventional peritoneal cytology was also assessed with using same samples. Results: Among all 34 samples, conventional cytology diagnosed 13 samples as positive, which meant existence of cancer cells, and 21 samples as negative. Gene expression levels of 9 genes were compared between cytology-positive and negative samples and 6 genes (CEA, TERT, KRT20, FABP1, DDC, TFF1) showed significantly higher median expression levels in cytology-positive samples than negative (CEA: p < 0.0001, TERT: p = 0.05, KRT20: p = 0.01, FABP: p < 0.0001, DDC: p = 0.007, TFF1: p = 0.001, Mann-Whitney's U test). All 13 cytology-positive samples showed at least one gene expression (100% sensitivity) while 14 out of 21 cytology-negative samples did not show any of these 6 gene expressions. In 7 samples which showed at least one gene expression and cytology-negative, 5 samples were given a diagnosis of peritoneal dissemination during surgical operation. In these 5 samples, conventional cytology was seemed to show false-negative, while this PCR-based method diagnosed correctly. Conclusions: These data suggest that this PCR-based method may have a potential of higher sensitivity for a diagnosis of peritoneal dissemination compared with conventional lavage cytology. No significant financial relationships to disclose.
Highly Phosphorylated FOXO3A Is An Adverse Prognostic Factor in Acute Myeloid Leukemia.
Authors: Steven M. Kornblau, Neera Singh, YiHua Qiu, Wenjing Chen, Stefan Faderl, Gautam Borthakur, Marina Konopleva, Nianxiang Zhang, Coombes Kevin
Journal: Blood (2009)
A multicenter phase II study of “adjuvant” bi-weekly Irinotecan, infusional 5-fluorouracil (5FU) and leucovorin (LV) with oral tegafur/uracil (UFT) following resection of colorectal hepatic metastases
Authors: T. Kono, Y. Ebisawa, N. Chisato, T. Asama, I. Tomita, Y. Yamamoto, N. Ohe, T. Ayabe, T. Ashida, S. Kasai
Journal: Journal of Clinical Oncology (2005)

3658 Irinotecan combined with continuous infusional 5FU has shown to be an effective and tolerable regimen in MCRC.UFT enhanced plasma 5FU concentration and anti-tumor effects during 5FU infusion.Bi-weekly four-drugs combination chemotherapy of irinotecan 30 mg/m2 (day1, i.v.1hr), leucovorin (LV); 200 mg/m2 (day1, 2i.v.1hr), 5-fluorouracil (5-FU); 300 mg/m2 (day1, 2c.i.v. in 22hr) bi-weekly, UFT was 400mg/day (day8–14 p.o.), has been shown to be very active and safe in metastatic colorectal cancer (ASCO2004 #3666). We planned to conduct a phase II study of bi-weekly four-drugs combination chemotherapy, allowing for its use in the adjuvant setting.The main endpoint of this study was the relapse-free survival. Results: From february 2002 to may 2004,58 patients (34m/24f; median age = 65, range 39–80; ECOG 0–2; 1–4 liver lesions) underwent hepatectomy and were treated with “adjuvant” four-drugs chemotherapy for 12 planned cycles. The 58 patients received a total of 634 cycles of therapy with a median of 11 (range 4 to 12) cycles. The major toxicity was not recognized. Grade1/2 nausea was common. No treatment related death was recorded(NCI-CTC). At a median follow-up of 625(range 81–1613) days, 2 patients (3%) have died. The median time from liver resection to relapse was 417 (range 70–1517) days. Recurrence occurred in: lung (45%), liver (33%) and abdominal nodes (14%). 1 year relapse-free survival (RFS) is 64% (95%CI, 515–702days). 18 month RFS is 50%. 2year RFS is 41%. Conclusions: This bi-weekly four-drugs combination was safe in patients with colorectal carcinoma, possibly allowing for its use also in the adjuvant setting. The tolerability of this regimen after major liver resection supports further evaluation of four-drugs combination “adjuvant” chemotherapy in this group of patients. The latest data will be reported at the meeting. No significant financial relationships to disclose.