tbuckley/cabot-search huggingface dataset:
MicroRNA expression patterns in lobular neoplasia.
Authors: L. A. Stead, A. Ramnauth, S. Fineberg, O. Loudig
Journal: Journal of Clinical Oncology (2011)

10551 Background: Lobular carcinoma in situ (LCIS) is a marker of increased risk for subsequent development of invasive breast cancer. Molecular studies have identified a clonal relationship between LCIS and concurrent invasive lobular carcinoma (ILC), suggesting that LCIS may be a precursor lesion of ILC. We hypothesized that differences in miRNA expression patterns might exist in LCIS lesions with concurrent ILC compared with LCIS lesions found alone. Methods: RNA was collected from matched frozen and archival formalin fixed paraffin embedded (FFPE) breast tissue using TRIZOL extractions. MiRNA expression profiling was performed using the Illumina miRNA DASL assay, in duplicate experiments, allowing simultaneous profiling of 735 miRNAs. MiRNAs of interest were further validated and analyzed by quantitative RT-PCR (qrt-PCR) in triplicate. To verify our data by localizing specific miRNA sequences of interest, in situ hybridization was performed on FFPE sections using a one-day protocol with locked nucleic acid (LNA) detection probes for miR-375 and miR-182, the U6 small nuclear RNA probe as a positive control and a scrambled miRNA probe as a negative control. Results: qrt-PCR analysis of the miR-183/182/96 cluster and miR-375 was performed using normal breast tissue, LCIS alone, and matched synchronous LCIS and ILC. A trend of increasing miRNA expression correlating with a model of histological progression toward invasive disease was observed. Results of in-situ hybridization confirmed this trend, showing the weakest signal intensity for both miR-375 and miR-182 in normal breast tissue, a stronger signal in LCIS alone, and the strongest signal in LCIS associated with synchronous ILC. Localization of signal to the nucleus was observed in normal breast tissue and LCIS alone, while a more diffuse cytoplasmic localization pattern was observed in LCIS associated with ILC, possibly suggesting nucleocytoplasmic transport for further processing of these miRNAs during progression to a more invasive phenotype. Conclusions: Upregulation of miR-375 and the miR-183/182/96 cluster in LCIS may correlate with risk for progression to ILC. These novel biomarkers may also be potential targets for treatment.
Treatment patterns and clinical outcomes of patients with metastatic gastroenteropancreatic neuroendocrine tumors (mGEP-NETs).
Authors: Xiaolong Jiao, Sonia J. Pulgar, Marley Boyd, Fadi S. Braiteh, Susan Pitman Lowenthal, David Cox, Patricia S. Fox, Andrew Scott Paulson
Journal: Journal of Clinical Oncology (2016)

331 Background: mGEP-NETs are rare and heterogeneous tumors. Limited data has been published on real world clinical management of these tumors. This study was conducted to understand the treatment patterns and clinical outcomes of patients with mGEP-NETs treated in the community oncology setting. Methods: A retrospective study was conducted using US Oncology’s (USON) iKnowMed electronic health record (EHR) database with supplemental chart review. The first diagnostic record of mGEP-NET in the EHR system was defined as the date of diagnosis of mGEP-NET. Inclusion criteria: ≥ 18 years of age at diagnosis; diagnosis of mGEP-NET between 1/1/2008 to 12/31/2012. Patients in clinical trials or with poorly differentiated tumors were excluded. Results: 229 patients were included with a median age of 64.0 years. Primary tumor site included small bowel (47.6%), pancreas (31.4%), and other (21.0%). Tumor grade was available for 134/229 (58.5%) patients, and the majority was reported as well-differentiated (52.8%). Chromogranin A (CgA) and urinary 5-HIAA were reported for 34.9%, and 32.8% of patients respectively. 37 (16.2%) of patients were under observation only. For those receiving systemic treatment, median time to first systemic treatment after diagnosis was 2.7 weeks, with 75% of patients starting therapy by 9.4 weeks. 120 (52.4%) patients received only somatostatin analogs (SSAs) during the study period, and 72 (31.4%) patients received chemotherapy, and/or targeted therapy. In the 1st line setting (n = 192), 148 (77%) patients received SSAs, 23 (12%) chemotherapy, and 21 (10.9%) targeted therapy. The most common AEs for SSAs were diarrhea (18.2%), abdominal pain (16.9%), and fatigue (13.5%). The median OS from diagnosis was 84.2 months [95%CI 70.9, 108.0 months] for the overall cohort. OS was longer in small bowel NETs than in pancreatic or other NETs (median OS 108.0 vs 69.9 vs 84.2 months, p = 0.017). Conclusions: Most of the patients with mGEP-NETs received systemic treatment soon after diagnosis and referral to USON. The OS and AEs were consistent with other studies. Low reporting of CgA, 5-HIAA, and tumor grade reflected variability of clinical practice in the community setting.
Evaluation of inpatient cancer pain management at an academic medical center.
Authors: Michael Mearis, Joseph Shega, Randall Knoebel
Journal: Journal of Clinical Oncology (2012)

128 Background: The National Comprehensive Cancer Network (NCCN) guidelines on cancer pain management were developed to direct pain assessment and management. The purpose of this study was to assess whether adherence to guidelines was associated with improved outcomes. Methods: One-hundred and nine patients admitted to the inpatient hematology oncology service that received at least one dose of morphine, oxycodone, or hydromorphone were evaluated and allocated into groups based on adherence to the NCCN guidelines. Safety and achievement of analgesia (pain score ≤ 4) at 24-hours after opioid initiation were compared between the two groups. A multivariate analysis was performed to identify predictors of opioid regimens non-adherent to guidelines. Results: Sixty-four percent of patients were initiated on regimens adherent to the NCCN guidelines. 63% of patients initiated on regimens adherent to NCCN guidelines reached the endpoint of analgesia at 24 hours compared to 41% of those who were not (p = 0.028). Adverse events were infrequent (p &gt; 0.5). Opioid tolerance was the variable most predictive of being initiated on regimens non-adherent to guideline recommendations (OR 3.1, 95% confidence interval 1.24-7.82). Conclusions: A significant number of patients presenting with cancer pain are initiated on regimens non-adherent to NCCN guidelines, leading to reduced attainment of adequate analgesia. Opioid tolerant patients are at an increased risk of inadequate analgesia, and should be identified and initiated on proper pain regimens taking home opioid usage into consideration.
Tumor subtype and race in male breast cancer: A population-based cohort study.
Authors: Fatih Aydogan, Yasuaki Sagara, Melissa Anne Mallory, Mustafa Tukenmez, Mehra Golshan
Journal: Journal of Clinical Oncology (2015)

149 Background: Subtypes of female breast cancer have been shown to vary by race, however data on the significance of molecular profiling and the distribution of subtype according to race/ethnicity for male breast cancer is lacking and warrants research. We sought to investigate the differences in male breast cancer according to tumor subtypes and racial/ethnic profiles using the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: We used the SEER database (SEER 18 registries) to identify all cases of male breast cancer diagnosed between 2010 and 2012. The cases were classified based on estrogen receptor (ER), progesterone receptor (PR) and HER2 status as follows: ER and/or PR positive and HER2−; ER and/or PR and HER2 +; ER−, PR−, and HER2 +; and triple negative (ER−, PR−, and HER2−). We sought the association between the subtype and race, which is categorized as non-Hispanic (NH) white, NH black, NH Asian Pacific Islander (API) and Hispanic men. Results: We identified 1515 cases of male breast cancer diagnosed during the study period; 188 were excluded because of unknown race or subtype, and the remaining 1327 were included in our final cohort. 96.8% of cases were ER positive and less than 3.2% of cases were ER negative. 1145 patients (86.1%) were HR+/HER2-, 139 patients (10.0%) were HR+/HER2+, 12 patients (0.7%) were HR-,HER2+, and 31 patients (2.3%) were triple negative (Table 1).Tumor subtype did not vary by race/ethnicity (p = 0.08). Conclusions: Our results indicate that unlike female breast cancer that male breast cancer subtype does not vary by race/ethnicity. Further research is warranted to determine how these findings may impact the treatment and prognosis of male breast cancer. [Table: see text]
Adjuvant treatment for resected rectal cancer: Effect of postoperative oxaliplatin added to 5-FU in the neoadjuvant era.
Authors: Benjamin Garlipp, Patrick Stuebs, Hans Lippert, Karsten Ridwelski, Henry Ptok, Ingo Gastinger, Ronny Otto, Christiane J. Bruns
Journal: Journal of Clinical Oncology (2015)

672 Background: Oxaliplatin (Ox) added to postoperative 5-fluorouracil (5FU) based adjuvant treatment has shown a survival benefit in colon cancer. For rectal cancer, the impact of Ox on survival has almost exclusively been tested in studies using 5FU +/- Ox both as a component of preoperative chemoradiotherapy (CRT) and as adjuvant treatment. Only one study (NCT00807911) investigated adjuvant 5FU +/- Ox in patients undergoing preop 5FU based CRT without Ox. Thus, the evidence for the benefit of adding Ox to adjuvant 5FU in patients treated with preop 5FU based CRT is limited. Methods: Data from the prospective German multicenter Quality Assurance in Rectal Cancer observational trial involving more than 300 hospitals of all levels of care throughout Germany were retrospectively analyzed. Patients undergoing R0 total mesorectal excision (TME) for rectal cancer following neoadjuvant 5FU based treatment without oxaliplatin between 01/01/2008 and 12/31/2010 were included. Disease-free survival (DFS) in patients receiving adjuvant treatment with or without Ox was compared using the Kaplan Meier method. The impact of adjuvant treatment with 5FU with or without Ox on DFS was investigated in a Cox regression analysis including open vs. laparoscopic approach, pT stage, pN stage, tumor grading, TME quality grade, and presence of anastomotic leakage as potential confounding factors. Results: The entire data set included 1,861 patients. Data for all variables investigated were available for 599 patients of whom 512 (85%) and 89 (15%) received 5FU based adjuvant treatment without and with Ox, respectively. Mean DFS was not different in patients receiving 5FU only vs. 5FU with Ox (p=0.103). Cox regression analysis revealed no significant impact of adding Ox to adjuvant 5FU on DFS. Of all factors analyzed, only pN2 (vs. pN0) status had an independent adverse effect on DFS (Hazard ratio 4.22, p&lt;0.001). Conclusions: These data indicate that adjuvant Ox added to 5FU does not provide a DFS benefit in rectal cancer patients treated with preoperative 5FU based CRT under routine care conditions. Rectal cancer patients may be different from patients with colon cancer with respect to benefit from adjuvant Ox.
Simultaneous cone beam CT scanning during prostate radiotherapy to produce clinically useful images.
Authors: Ananya Choudhury, Peter Dickinson, Julia Stratford, David Ryder, Richard C. Walshaw, Sam Mayes, John P. Logue, James Wylie, Catherine Coyle, Jacqueline E. Livsey, Anna Tran, Nooreen Sarah Alam, Tony Elliot, Carl Rowbottom, Corinne Faivre-Finn, Christopher Boylan
Journal: Journal of Clinical Oncology (2014)

220 Background: Cone beam CT (CBCT) images can be acquired during delivery of rotational radiotherapy. We assessed the quality of simultaneous CBCTs captured during prostate radiotherapy and studied the effects of arc delivery time on image quality. Methods: Fifty patients with localised prostate cancer were treated with radical rotational radiotherapy. Treatment was delivered using a single eight or 10 MV arc on an Elekta Synergy linear accelerator. Standard (stCBCT) and simultaneous CBCTs (siCBCT) were captured on fractions 1, 6, 11, and 16. The siCBCT image was reconstructed and optimised using in-house software. The image quality was assessed by four observers using a validated scoring tool. The scoring clinician was blinded to whether the scan was stCBCT or siCBCT. Results: Seventy-four siCBCT scans were performed with a mean arc delivery time of 120 seconds during which 688 CBCT frames were acquired. Following a software upgrade the subsequent 122 siCBCTs were obtained with a mean arc delivery time of 83 seconds during which 502 CBCT frames were acquired. There was moderate agreement between the four observers regarding the quality of the CBCTs (Fleiss’ kappa statistic 0.51). StCBCTs were of good quality and the four observers agreed that 98 to 100% of these scans were of sufficient quality to be used to make a clinical decision. The four observers assessed that 35 to 79% of siCBCTs were of sufficient quality to be used to make clinical decisions. Before the software upgrade 65 to 93% of siCBCTs were judged to be of sufficient quality to make a clinical decision ("slow" simultaneous CBCT). Following the software upgrade this proportion fell to 16 to 69% ("fast" simultaneous CBCT). Conclusions: SiCBCT can produce images which are clinically useful. Image quality is affected by bowel gas, patient habitus and scatter from the MV beam. Reducing arc delivery time and the number of CBCT frames acquired by approximately one-third reduces the quality of siCBCTs. Further development and refinement of siCBCT scanning is warranted. Future reductions in arc delivery times may have to be limited if the use of siCBCT scanning becomes standard practice.
A phase I and pharmacokinetic (PK) study of docetaxel (DOC) and oxaliplatin (OX)
Authors: J. J. Hwang, S. Malik, D. J. Moore, J. McGreivy, S. Park, W. C. Zamboni, J. L. Marshall
Journal: Journal of Clinical Oncology (2005)

2105 Background: Combinations of taxanes and platinums have become widely used in many malignancies and represent a standard of care in ovarian and lung cancer. DOC and OX have demonstrated broad antitumor activity, including in patients (pts) who are refractory to earlier generation platinums and taxanes. Agelaki et al performed a phase I study combining OX and DOC q 21 d (ASCO 2004 #443). The dose limiting toxicity (DLT) was neutropenia, and OX 70 mg/m2 and DOC 75 mg/m2 was recommended for further study. Weekly DOC induces myelosuppression than DOC administered every 3 weeks, with similar antitumor activity. Thus, we are performing a phase I study of the combination of OX and weekly DOC, with PK. Methods: Pts had advanced solid malignancies without available standard therapy, and no prior DOC or OX. Eligibility criteria were typical for phase I studies. Pts are enrolled in cohorts of 3. 5 dose levels (DL) have been studied. DOC 35 mg/m2D#1,8 and OX (75, 90, 105, 120, 130 mg/m2) D#1 q 21 d were given. PK for both DOC and OX will be performed. DLT is defined in cycle 1 only, as grade (gr) 4 neutropenia for 7 d or complicated by fever or infection, gr 4 thrombocytopenia or anemia, gr 3–4 nonhematologic toxicity, or any delay of therapy for 3+ weeks. Results: Through 12/1/2004, 17 pts were enrolled on 5 DL. Tumor types: pancreatic (5), esophageal (4), biliary (3), others (5). Pts with pancreatic cancer and basal cell carcinoma had improvement in non-measurable disease, and 2 pt with esophageal cancer had stable disease. 1 DLT (diarrhea) occurred at DOC 35/OX 130 resulting in expansion of the DL. Gr 3 neutropenia occurred in 3 pts, and gr 3 anemia in 1. Other toxicities include nausea/vomiting (12), fatigue (11), neuropathy (11, all gr 1), flu-like symptoms (10), dyspnea (10), diarrhea (8), anemia (7), dizziness (6), constipation (6). Conclusions: By modifiying the schedule of administration of DOC from every 3 weeks to D#1,8 every 21 d, we have been able to maintain a potentially effective systemic dose of DOC, and escalte the dose of OX from 70 to at least 120 mg/m2, with enrollment and dose escalation continuing. The study will be completed, and PK studies will be available and presented in May 2005. Supported in part by Sanofi Synthelabo and Aventis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis, Sanofi, Sanofi-Synthelabo Aventis, Sanofi, Sanofi-Synthelabo Aventis, Sanofi, Sanofi-Synthelabo
Characteristics and Outcomes of 38 Patients with Acute Myeloid Leukemia Evolving from Previous Well Characterized Myeloproliferative Disorder.
Authors: Constantine S. Tam, Francis Giles, Jorge Cortes, Guillermo Garcia-Manero, Elihu Estey, Hagop Kantarjian, Srdan Verstovsek
Journal: Blood (2006)
Chitosan degradation products facilitate peripheral nerve regeneration by improving macrophage-constructed microenvironments
Authors: Yahong Zhao, Yongjun Wang, Jiahuan Gong, Liu Yang, Changmei Niu, Xuejun Ni, Yaling Wang, Su Peng, Xiaosong Gu, Cheng Sun, Yumin Yang
Journal: Biomaterials (2017)
Phase I study of irinotecan and amrubicin in patients with advanced non-small-cell lung cancer
Authors: K. Kiura, K. Hotta, N. Takigawa, A. Bessho, S. Harita, S. Umemura, A. Ogino, M. Tabata, H. Ueoka, M. Tanimoto
Journal: Journal of Clinical Oncology (2005)

7317 Background: Combination chemotherapy of irinotecan and amrubicin for advanced non-small-cell lung cancer (NSCLC) has not been fully evaluated. To determine the maximum-tolerated dose (MTD), a Phase I study in patients with advanced NSCLC was conducted. Methods: Patients with stage IIIB/IV NSCLC were enrolled in this study. Both patients with and without prior chemotherapy were also eligible. Drugs were administered on days 1 and 8, every 3 weeks. The starting doses of irinotecan and amrubicin were 60 and 35 mg/m2, respectively. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (Ver2.0). Results: Patients with advanced NSCLC (n = 19) were enrolled between 2003 and 2004. A total of 53 courses were conducted, with a median number of 2 courses (range: 1 to 8). All patients and courses were assessable for safety and efficacy. Grade 4 neutropenia was observed in 23% of courses, whereas anemia and thrombocytopenia were generally mild. Grade 3 febrile neutropenia occurred in 5 courses. Other grade 3 or greater non-hematological toxicities were observed in only 4 of 52 courses (grade 3 infection in 3 courses and hyponatremia in 1). No patient developed cardiotoxicity. In the first course, DLT was observed in 1 of 3 patients at dose level 2 (grade 3 infection), in 2 of 6 at dose level 4 (grade 3 febrile neutropenia and grade 3 infection) and in 3 of 4 at dose level 5 (persistence of grade 4 neutropenia and grade 4 leukopenia, persistence of grade 4 neutropenia and grade 3 febrile neutropenia). Thus, MTDs of irinotecan and amrubicin were determined to be 100 and 45 mg/m2, respectively (level 5). Objective response was obtained in 2 patients (10.5%) who had received prior chemotherapy. Conclusions: This combination was well tolerated but produced only a modest anti-tumor effect for advanced NSCLC. Further investigation for the role of this regimen as a salvage chemotherapy may be warranted in relapsed patients. No significant financial relationships to disclose.
Phase Ib/II trial of gemcitabine, cisplatin, plus lenalidomide as first-line therapy for patients with metastatic urothelial carcinoma.
Authors: Che-Kai Tsao, Neeraj Agarwal, Andrea Borghese Apolo, Karen M Lee, James H. Godbold, William K. Oh, Matt D. Galsky
Journal: Journal of Clinical Oncology (2014)

321 Background: Cisplatin-based chemotherapy is standard in patients (pts) with metastatic urothelial carcinoma (MUC), though outcomes remain poor and novel approaches are needed. Lenalidomide, a potent thalidomide analog with antiangiogenic and immunomodulatory properties, has been shown to enhance the antiproliferative properties of standard chemotherapy in nonclinical studies of urothelial cancer (Apolo, ASCO 2011). In this phase Ib/II clinical trial we aimed to determine the safety and efficacy of gemcitabine, cisplatin, plus lenalidomide (GCL) in pts with MUC. Methods: Pts with chemotherapy-naïve MUC received gemcitabine 1000mg/m2 days 1 and 8 and cisplatin 70mg/m2 day 1, of a 21-day cycle. In the phase Ib portion, the dose of lenalidomide was to be dose escalated in successive cohorts starting at 10 mg PO daily, on days 1-14, using standard “3+3” dose escalation rules. The primary objective of the phase II portion was to determine the progression-free survival at one year. Results: A total of 7 pts received GCL (lenalidomide 10 mg dose level) in the phase 1b portion. A single pt experienced a dose limiting toxicity (DLT), grade 4 neutropenia. A decision was made to not dose escalate lenalidomide further due to the frequent need for dose delays and reductions of GC due to cytopenias. An additional 2 pts were enrolled in the phase II portion but the study was terminated due to frequent dose delays/reductions and slow accrual. Among the 9 pts enrolled, 5 required dose reductions of G (4 requiring &gt;1), 4 required dose reductions of C (1 requiring &gt;1), and 6 required at least one dose delay. The most frequent grade ≥ 3 adverse events were: neutropenia (n=7), anemia (n=3), thrombocytopenia (n=3), and diarrhea (n=2). Tumor responses included: partial response (n=3), stable disease (n=3), progressive disease (n=2), and unevaluable (n=1). Conclusions: Chronic administration of the combination of GCL was compromised by overlapping myelosuppression and the need for frequent dose reductions/delays of GC due to cytopenias. Despite promising nonclinical data, combining cytotoxic chemotherapy with “targeted” small molecules faces practical challenges. Clinical trial information: NCT01342172.
The use of a palliative care tool in a community private practice.
Authors: Tallat Mahmood, Helen Shock, Jane Severson, Douglas W. Blayney
Journal: Journal of Clinical Oncology (2012)

95 Background: Although symptom assessment is a routine part of oncology care, data from the Michigan Oncology Quality Consortium (MOQC) showed variation in individual practice (Health Affairs 31:718, 2012). As part of the MOQC Palliative Care Demonstration Project, we implemented the Edmonton Symptom Assessment System(ESAS) in a private oncology clinic. ESAS is a valid and reliable assessment tool that evaluates nine common symptoms experienced by cancer patients. Our target population was patients with active cancer undergoing chemotherapy. Methods: Initial implementation focused on patients of only one of the practice’s physicians. Symptoms rated &gt;3 were considered symptomatic and were addressed by the physician. To monitor overall performance, a practice profile was compiled from the individual ESAS results. For symptoms with the greatest severity and incidence, targeted resources were developed and integrated in new electronic medical record templates and educational sessions with patients. Results: Managing change incrementally with weekly reassessment of implementation problems was effective. Use of the ESAS tool allowed for a focused discussion of the patient symptomatology and lead to better efficiency for the physician. Understanding the symptom burden of the patient population and implementing practice wide interventions helped to reduce the symptom burden at an individual patient level. Conclusions: The ease of use of the ESAS tool makes it highly successful in the private oncology practice setting. Profiling the symptom burden at a practice level facilitates targeted improvements and monitoring of performance over time. [Table: see text]