tbuckley/cabot-search huggingface dataset:
Risk factor of thrombosis and impact on prognosis in patients with pancreatic cancer receiving chemotherapy.
Authors: Kazunaga Ishigaki, Yousuke Nakai, Hiroyuki Isayama, Tsuyoshi Hamada, Naminatsu Takahara, Suguru Mizuno, Dai Mohri, Hirofumi Kogure, Saburo Matsubara, Natsuyo Yamamoto, Minoru Tada, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2016)

218 Background: Thromboembolism (TE) is common in cancer patients, and pancreatic cancer is reported to be highly associated with TE. The aim of this analysis is to clarify risk factors for TE and its clinical impact in pancreatic cancer patients. Methods: Data on consecutive pancreatic cancer patients receiving systemic chemotherapy between August 1999 and July 2015 were retrospectively studied. The diagnosis of TE was made on CT scan either performed for suspicious symptoms of TE or for evaluation of chemotherapy response, and TE was classified into two groups: arterial events including coronary artery disease (CAD), cerebrovascular disease and other artery thrombosis, and venous events including deep vein thrombosis/pulmonary embolism (DVT/PE), portal vein thrombosis (PVT) and IVC thrombosis. Overall survival and time to TE (TTE) were calculated by Kaplan-Meier analysis. Risk factors for TE development were analyzed using a Cox proportional hazards model. To evaluate the impact of TE on survival, multivariate analyses were performed using a time-dependent covariate multiple Cox model. Results: A total of 475 patients (195 female, a median age of 67 years) were analyzed. TE was identified in 57 patients (12%). Venous TE were 45 (79%) including DVT/PE 24(42%), IVC thrombosis 2 (4%), PVT 19 (33%). Arterial TE were 12 (21%) including cerebrovascular infarction 9 (16%), CAD 2 (4%) respectively. The median TTE was 169 days (95% CI, 75-203). Liver metastasis was the only significant risk factor for TE in the multivariate analysis (OR 2.01, 95%CI 1.12-3.47, P = 0.012). The median survival from TE development was 57 days (95% CI, 37-65) and TE was significantly associated with poor prognosis (HR 3.31, 95%CI 2.72-5.27, P&lt; 0.01) in the time-dependent covariate analysis. Conclusions: TE was not uncommon in pancreatic cancer patients receiving chemotherapy and was associated with poor prognosis. Whether the prophylaxis for TE can improve survival should be further investigated, especially in high risk patients such as patients with liver metastasis.
Active targeting nanoparticle for breast cancer diagnosis and treatment.
Authors: Nobutaka Iwakuma, Uhi Toh, Stephen R. Grobmyer, Keiko Koura, Miki Takenaka, Hiroko Otsuka, Ryuji Takahashi, Kazuo Shirouzu
Journal: Journal of Clinical Oncology (2012)

163 Background: Breast cancer remains a major ongoing public health problem among women. Nanotechnology is the exciting field focused on man-made materials in the size range of 1-100 nanometers (nm). Nanoparticles (NPs) are on the scale of many cellular-level processes and hence are attractive for targeting breast cancer. Emerging nanotechnologies promise new approaches to early detection and treatment of breast cancer. Our group has reported Gold Speckled Silica NPs (GSS) as multimodal contrast agents for fluorescence, magnetic resonance and photoacoustic tomographic (PAT) imaging. The near infrared (NIR) optical absorption property of these particles makes them potentially useful for therapeutic applications such as thermal ablation of tumors. Fulfilling the promise of nanotechnologies for patients with metastatic breast cancer, necessitates delivery of nanomaterials to sites of breast cancer. Now we have focused on the cancer metabolism, we have recently developed active targeting NPs with surface functionalizing agent such as glucose conjugated NPs. We hypothesize that active targeting NPs is more incorporated into cancer cells compared to normal NPs. Methods: Human breast cancer cells, BT474, were incubated with active targeting NPs or normal NPs (as control). The tumor cell uptake was assessed using flow cytometry and fluorescence microscopy experiments. Results: Uptake of active targeting NPs was significantly higher than uptake of normal NPs. Conclusions: Active targeting NPs can be used as suitable targeting NPs for development of imaging agents for early diagnosis of breast cancer. Evolving bio-nanotechnologies such as active targeting NPs promise to enhance the early detection and non-invasive treatment of breast cancer.
MRI prior to systematic lymphadenectomy in patients with locally advanced cervical cancer.
Authors: M. Gold, Z. Zhang, H. Marques, J. Gorelick, L. M. Landrum, R. S. Mannel, L. T. Chuang, J. Q. Yu, C. K. McCourt, M. Harisinghani, A. Sohaib, D. Koh, S. Raman, M. S. Gee, H. Choi, M. Atri
Journal: Journal of Clinical Oncology (2011)

5042 Background: Surgical evaluation of lymph node (LN) metastases has served as the gold standard for comparison of imaging modalities in locally advanced cervical cancers. It has been suggested that contemporary techniques such as MRI be relied upon for treatment planning and, specifically, extended-field radiation (EFRT) without pathologic confirmation. Methods: As part of a prospective, multicenter clinical trial conducted by ACRIN/GOG, patients (pts) with histologically confirmed, stage IB2, IIA≥4 cm, or IIB-IVA) cervical carcinoma underwent MRI prior to systematic pelvic (PLN) and abdominal (PALN) lymphadenectomy. LNs ≤ 1 cm were bisected while those > 1 cm were serially sectioned into 5 mm sections and a slide was made from each section. For positive & negative predictive values (PPV & NPV) of PALN on MRI, patients were grouped into those with MRI reports of both (+) PLN & PALN (G1), (+) PLN but (-)PALN (G2), and those with both (-) PLN & PALN (G3). Results: 33 pts are included in this analysis. Stage distribution was 12 1B2, 3 2A, 15 2B, 3 3B. 29 were squamous, 3 adeno, and 1 rhabdomyosarcoma. 94 (+) and 659 (-) LNs were removed. (+) LNs were found in the PALN in 12 (36%) and in the PLN in 22 (67%) pts. Two pts had PALN but not PLN metastases. The mean size of the long axis of the largest (+) (N=60) and (-) (N=209) LNs removed did not differ (18.7±9.3 vs. 18.7±11.6 mm; p=0.47). The size of the largest focus of metastasis within a LN ranged from 2-50 mm and was statistically larger in PLN compared to PALN (18 vs. 14 mm; p=0.02). The mean number of LNs counted by pathology was greater than the number reported on MRI (p <0.0001). For the above defined groups, the PPV for PALN in G1 was 0.61 (95% CI 0.48-0.73), the NPV for PALN in G2 was 0.66 (95% CI 0.55-0.75), and the NPV for PALNs in G3 was 0.86 (95% CI 0.76-0.92). Conclusions: PALN metastases are common in locally advanced cervical cancer. The NPV of MRI for PALN among pts reported to have negative PLN & PA LN on MRI is high enough that surgical evaluation and EFRT is not necessary. For all others, the PPV & NPV of MRI is too low to determine the need for EFRT without first performing surgical evaluation. This study was supported by NCI funding to the GOG (grants CA 27469 and CA 37517) and to ACRIN (grants U01 CA079778 and U01 CA080098).
Impact of advance directive (AD) completion among patients with metastatic cancer treated at an academic medical center.
Authors: Nirav S. Kapadia, Jennifer Snide, Daniel J Gelb, Evelyn Schlosser
Journal: Journal of Clinical Oncology (2014)

114 Background: Between February and September 2013, AD documentation for oncology patients across Dartmouth-Hitchcock’s Norris Cotton Cancer Center (NCCC) increased from 36% to 48%. However, it remains unclear whether AD completion itself is associated with other indicators of quality care. Methods: Using the tumor registry and National Death Index patient data, we examined a cohort of deceased NCCC patients diagnosed with metastatic disease between April 1, 2011 and October 31, 2013. To account for unmeasured care provided outside of NCCC, only patients with at least two NCCC visits, one of which occurred within the last six months of life, were included. Individual patient electronic medical record data were then linked to the registry data and multivariable regression was performed to determine the effect of AD completion on end-of-life quality metrics. Results: The cohort consisted of 225 patients, 182 (81%) of whom had an advance directive on file and 43 (19%) who did not. There were no significant differences in the age, gender or cancer diagnosis between the two groups. Patients with an AD had shorter commutes to the medical center (mean 42 vs 58 minutes, p&lt;0.01) and more visits with cancer center providers (median 11.5 vs. 4.0, p=0.03). Palliative Care consulted with 73% of patients with an AD, versus 28% of patients without an AD (p&lt;0.01). Completion of an AD did not decrease the likelihood of hospital death (OR 0.90, 95% CI 0.33-2.49), intensive care unit (ICU) death (OR 0.83, 0.19-3.66), hospital admission in the last 30 days of life (OR 0.94, 0.40-2.21), or ICU admission in the last 30 days of life (OR 1.30, 0.37-4.55). Patients with an AD were twice as likely to receive hospice referrals (OR 2.04, 0.73-5.68) and 70% less likely to visit the emergency department in the last 30 days of life compared with patients without an AD on file (OR 0.28, 0.06-1.40), although these trends were not statistically significant. Conclusions: For patients with metastatic cancer, an advance directive was associated with increased use of palliative care, though not with other measures of quality care. In an attempt to improve the cancer care provided at the end of life, we must expand our strategies beyond the use of an AD.
Increasing genetics referrals: The National Cancer Institute Community Cancer Centers Program (NCCCP) network performance improvement project.
Authors: Jeffrey Cohn, Angela Carrigan, Selvi Palaniappan, Silvana Rivero, Kathleen M. Castro
Journal: Journal of Clinical Oncology (2012)

111 Background: A NCCCP goal is to improve quality of care through increasing guideline adherence at participating community cancer centers. 14 NCCCP sites participated in a performance improvement project to (1) increase genetics referral and counseling services by 10% in accordance with established guidelines for breast or colorectal cancer. The project hypothesized that data collection and feedback improves referral rates by better targeting eligible populations for improvement interventions. Methods: Sites recorded the source and outcome of each breast/colon referral using a tool developed by the NCCCP. Aggregate data were shared on monthly project calls where site staff shared best practices/issues with peers and received feedback. Results: Data were collected Jul 2011-Apr 2012 and analyzed at 2-week intervals. The number of colorectal and breast patients referred for genetics counseling remained stable through the 9-month period. Despite no change in the rates of referrals the data were hypotheses generating. Colorectal cases of all ages were being correctly referred in accordance with established guidelines; project calls demonstrated sites’ efforts to improve referral processes, such as including genetics counselors in the multidisciplinary team discussions, implementing universal screening for Lynch syndrome, and developing new linkages with referring staff. Conclusions: The project was a successful proof of concept study showing the feasibility of pooling genetic counseling data across diverse community cancer centers. Robust data collection is inadequate to drive sustainable improvement; specific process changes are also required. Future NCCCP collaborative initiatives are needed to ensure all eligible patients have access to genetic counseling referral services as there remain a significant group of patients eligible for genetic counseling who are not being seen. Funded by HHSN261200800001E.
Concurrent weekly cisplatinum versus gemcitabine with radiation in advanced carcinoma cervix: A study on 120 patients.
Authors: D. R. Samanta, S. N. Senapati, L. Pattanayak, A. Mohanty, S. K. Giri
Journal: Journal of Clinical Oncology (2010)

5067 Background: Cervical cancer is one of the leading causes of death among women in developing countries. With radiation the 5 years overall survival ranges from 30% to 35%. Various trials proved that the concurrent cisplatinum with radiation improves the loco regional control as well as survival. Two radio-sensitizing drugs that have shown promising result are gemcitabine and cisplatinum. Methods: 120 patients of squamous cell carcinoma cervix of stage IIB to IIIB who satisfied the eligibility criteria were enrolled during Oct 2000 to Aug 2004 and were randomized to evaluate the response, toxicity, compliance as well as overall survival.68 patients received inj. cisplatinum 40 mg /m2 weekly on monday with proper premedication and hydration, concurrently with radiation. 52 patients received inj. gemcitabine 200 mg weekly on monday with proper premedication. All patients were treated with concurrent external beam radiotherapy of 50 Gy in 25# over 5 weeks followed by intracavitary brachytherapy 25 Gy to point A with LDR or 7 Gy/sitting X 3 sittings by HDR. Results: After 12 weeks of completion of study 72.05% patients in cisplatinum arm achieved complete response (CR),where as in gemcitabine it was 80.39%. 27.05% patients in cisplatinum arm had partial response (PR) while it was 19.61% in gemcitabine. Acute lower gastrointestinal toxicity (gr 2/3) was 58.82% in cisplatinum and 73.07% in the gemcitabine arm. Urinary toxicity (gr 2/3) was 19.11% in the cisplatinum and 21.15% in the gemcitabine arm. 17.30% patients in gemcitabine arm had thrombocytopenia while 22.05% patients in cisplatinum had anemia. Incidence of proctitis was higher in gemcitabine arm. 60.29% of patients in cisplatinum arm and 42.30% in gemcitabine arm completed the external beam RT within 5 wks as per schedule. With a median follow up of 33 mo and 34 mo for cisplatinum vs. gemcitabine the 3-years overall survival in cisplatinum arm was 67.76% and in gemcitabine arm was 61.53%. Conclusions: In Indian context, concurrent chemo-radiation using cisplatinum was more acceptable than gemcitabine in advanced carcinoma cervix as there was better compliance with cisplatinum and no difference in overall survival. No significant financial relationships to disclose.
The expression profiles of miRNAs in the progression of prostate cancer from high-grade prostatic intraepithelial neoplasia to metastatic diseases.
Authors: Okyaz Eminaga, Jochen Fries, Fabian Woetzel, Susanne Neiss, Ute Warnecke-Eberz, Michaela Heitmann, Axel Heidenreich
Journal: Journal of Clinical Oncology (2016)

221 Background: The epigenetic regulation by miRNA plays an important role in tumor progression of prostate cancer (PCa). Methods: The expression data of 1054 miRNAs from TCGA were applied to identify relevant miRNAs associated with tumor progression (i.e. miR-210, miR-375, miR-378, miR-345, miR-143 miR-183 and miR-98). miRNA were isolated by miRNeasy FFPE kit (Qiagen, Hilden, Germany) from paraffin-embedded tissues of prostate specimens with PCa, HGPIN and normal tissues. Early-stage PCa was defined as PCa with pT2 tumor stage, Gleason score &lt; = 7a (3+4) and PSA level &lt; 10 ng/ml. PCa with pT3/4 or Gleason &gt; 7a was defined as advanced PCa. PCa with pN1 were considered as metastatic diseases. Additionally, 3 cases with castration-resistant prostate cancer (CRPC) were considered. Quantitative miRNA expression data were acquired and analyzed using a real-time TaqMan-based PCR. ANOVA analyses were performed to evaluate the expression of miRNAs between HGPIN, Normal and PCa tissues. The small nuclear U6 RNA was used as an endogenous control Results: ANOVA analysis revealed a significant variation in expression of all miRNAs among groups. The expression level of miR-183 and miR-375 increased with the tumor progression. miR-143, miR-375-3p were inversely correlated with the tumor progression. miR-210 and miR-183 were significantly overexpressed in metastatic diseases compared to non-metastatic diseases (FDR &lt; 0.01), whereas the expression level of miR-378-3p was lower in metastatic diseases than in organ-confined PCa. The expression of miR-98 was lower in PCa compared to normal tissues. In silico analysis, the down-regulation of miR-98 and miR-345-5p seems to activate the HIF-1 signaling pathway initiating the up-regulation of miR-210 that interact with genes related to cell cycle, RNA transcription, homologous recombination and non-homologous end-joining. Conclusions: Our data reveal epigenetic regulations of miRNA, which are associated with transition from normal tissues to HGIPN, from HGPIN to early-stage PCa, and early-stage PCa to advanced PCa. Advanced PCa represents the first stage of metastatic diseases.
Efficacy and safety of zoledronic acid in patients with moderate to severe pain induced by bone metastasis associated with solid tumor or multiple myeloma: A randomized, double-blind, multicenter phase III clinical trial
Authors: M. Dong, F. F. Yi
Journal: Journal of Clinical Oncology (2008)

14679 Background: Zoledronic acid is a new-generation bisphosphonate that has demonstrated greater potency compared with pamidronate in clinical testing. This randomized trial was conducted as a registration trial in China to determine the efficacy of zoledronic acid on moderate to severe bone pain and bone resorption markers in Chinese patients with bone metastasis and to evaluate the safety of zoledronic acid. Methods: A randomized, double-bland, and multi-center phase III clinical trail was conducted with pamidronate as control. Patients with moderate to severe bone pain (VAS>50mm) induced by solid tumor or multiple myeloma were randomized to receive zoledronic acid 4mg or pamidronate 90mg one time. The primary endpoint is the change of VAS and the secondary endpoind is the change of urinary NTX/Cr and CTX/Cr. Results: From Jul. 2005 to Sep. 2006, 228 pts from 15 cancer center with bone metastatic bone pain were randomize into 2 groups: 116 patients in zoledronic acid group and 112 patients in pamidronate group. The VAS value was decreased gradually after treatment in these two groups. There were significant improve in zoledronic acid group and control groups compare with baseline in 8days (-11.77% vs -10.87%), 15 days (-24.60% vs -21.06%) and 28 days (-32.37% vs -31.26%) after treatment (p<0.001), but no significant difference existed between two groups (P=0.6587) (Fig.1). The urine NTX/Cr level was decreased rapidly after treatment in both two groups, the nadir were at 8th day, the median decreased percentage at 28 day were -36.9% vs - 32.1% (p=0.7922) compare with baseline (Fig.2). The urine CTX/Cr level was decreased rapidly after treatment in both two groups, the nadir were at 8th day, the median decreased percentage at 28 day were -63.2% vs -47.9% (p=0.834) compare with baseline (Fig. 3). The frequently reported adverse events were pyrexia (19.0% vs 31.3%), and hypocalcemia (5.2% vs 3.6%) in two groups. Conclusions: 4mg of Zoledronic acid significantly reduced bone pain and bone resorption marker in Chinese population with bone metastases, the efficacy was comparable with pamidronate. Zoledronic acid was well tolerated. No significant financial relationships to disclose.
Pegylated liposomal doxorubicin (PLD)-carboplatin (C) (C-D) vs paclitaxel-carboplatin (C-P) in relapsing sensitive ovarian cancer (OC): A 500-patient interim safety analysis of the CALYPSO GCIG Intergroup phase III study
Authors: E. Åvall-Lundqvist, P. Wimberger, L. Gladieff, V. Gebski, J. B. Huober, A. Floquet, B. Fitzharris, A. G. Zeimet, M. Heywood, B. Schmalfeldt
Journal: Journal of Clinical Oncology (2008)

5565 Background: The preliminary results from the phase III study of carboplatin - PLD (C-D) vs Paclitaxel-Carboplatin (C-P) in patients (pts) with OC in late relapse is presented. While the primary endpoint of the study is PFS, the specific toxicity observed from these 2 regimens is critically important. Methods: From 4/05 to 10/07, 974 pts were recruited. Pts were randomized to either (C-P) ([C] AUC 5 iv d1 + [P] 175 mg/m2 iv d1, q3 wks) or (C-D) ([C] + PLD [D] 30 mg/m2 iv d1 q4 wks) for at least 6 cycles. Results: The data from the first 500 pts (C-D, n=251; C-P, n=249) were analyzed (Table). Median number of cycles received was 6 (1- 14) in two arms. Haematological toxicity contributed to more cycle delays in the CD (21%) than in the CP (14%) arm. Neutropenia & infection rates were similar in both arms. G-CSF was administered more frequently to pts in C-D arm (21%) than in C-P arm (15%). Grade (G) > 2 non-haematological toxicity was more frequent in the C-P arm. There were 104 (76 related) severe adverse events (SAE) in the C-P arm vs. 81 (44 related) in the C-D arm. Conclusions: This planned interim safety analysis on the first 500 patients confirmed different toxicity profiles in the two arms, with less drug-related SAE and less early therapy termination in the C-D arm. TOXICITY % Pts in C-D arm % Pts in C-P arm Anaemia G3–4 13 7 Thrombocytopenia G3–4 18 4 Alopecia G>2 9 85 Neuropathy G>2 3 29 Allergic reactions G>2 6 19 Arthralgia /myalgia G>2 4 20 Hand-foot syndrome G>2 13 2 Mucositis G>2 15 7 Early treatment termination (toxicity related) 6 14 No significant financial relationships to disclose.
Pathologic complete response (pCR) to preoperative sequential doxorubicin/cyclophosphamide (AC) and taxane (AC-T) or AC followed by paclitaxel and trastuzumab (AC-TH) in stage II-III HER2-positive breast cancer
Authors: S. Chumsri, S. C. Jeter, L. K. Jacobs, J. R. Lange, N. E. Davidson, L. A. Emens, J. H. Fetting, E. Gabrielson, Z. Zhang, V. Stearns
Journal: Journal of Clinical Oncology (2008)

11521 Background: The addition of trastuzumab to adjuvant chemotherapy has markedly improved survival outcomes of women with HER2+ breast cancer. We hypothesized that the addition of trastuzumab to the taxane portion of preoperative AC-T chemotherapy will be associated with a significantly improved pCR, a surrogate marker for long-term survival. Methods: We conducted a retrospective review of treatment outcomes of women with stage II or III HER2+ breast cancer treated with preoperative sequential AC-T or AC-TH. We compared patient characteristics and pCR of the treatment groups using Fisher’s exact tests. Results: We identified 37 women who received preoperative therapy for HER2+ breast cancer from May 2002 to January 2007. Of those, 14 women received AC-T and 17 received AC-TH (Table). Six women who did not receive sequential anthracycline and taxane based therapy were not included in the analysis. pCR was observed in 3 (21%) women in the AC-T group and in 11 (65%) AC-TH treated women (P=0.029). Trastuzumab-based treatment was well tolerated. We observed neither absolute declines in ejection fraction >10% from baseline nor cardiac symptoms. Conclusions: Preoperative AC-TH results in a significantly higher pCR rate compared to AC-T in patients with HER2+ breast cancer, comparable to other trastuzumab-based preoperative regimens. These results suggest that trastuzumab should be incorporated in the treatment of women considered for preoperative therapy. The optimal duration of trastuzumab in patients who achieve pCR after neoadjuvant trastuzumab-containing therapy should be further investigated. Patient Characteristics (%) AC-T (N=14) AC-TH (N=17) P Median age (range) 46 (35 –59) 51 (33 –68) 0.495 Stage III 64 76 0.698 ER+ 43 41 0.279 pCR 21 65 0.029 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech Amgen, Genentech