tbuckley/cabot-search huggingface dataset:
Status of health insurance predicts time from symptom onset to cancer diagnosis (T<sub>Dx</sub>) in young adults
Authors: A. Bleyer, C. Ulrich, S. Martin, M. F. Munsell, G. O. Lange, S. H. Taylor
Journal: Journal of Clinical Oncology (2005)

6079 Background: Young adults and older adolescents diagnosed to have cancer have had less progress in survival improvement than either younger or older patients (Proc. ASCO 21:389a, 2002). Because young adult Americans have the lowest rates of health insurance, delays in diagnosis may be one explanation for the cancer survival deficit. Accordingly, we compared health insurance status with the time from 1st cancer symptom onset to the day of diagnosis (TDx) in 15- to 29-year-olds. Methods: From June 2001 to May 2003, MDACC registered 270 newly-diagnosed 15–29 year-olds with acute lymphoblastic or myelogous leukemia (ALL, AML), Hodgkin disease (HD), non-Hodgkin lymphoma (NHL), sarcomas, brain tumors and thyroid cancer (TCa). 235 had complete data on TDx, cancer type, age, sex, race/ethnicity, marital status, and health insurance. Results: In multivariate analysis, only the type of cancer and health insurance status were significantly correlated with TDx (p < 0.05). The log mean TDx in patients with public or no health insurance was 6.3 weeks longer than in patients with private insurance and 13.1 weeks longer than in self-pay patients (p < 0.001) (Table). In 6 of 7 evaluable histologies [ALL, AML, diffuse large-cell NHL, gliomas, osteosarcoma (OS), follicular TCa], the log mean TDx was longer, by an average of 10.6 wks, in patients with public vs. those with private insurance (p < 0.05 in 5 histologies). In all 4 histologies evaluable for stage [diffuse large-cell NHL, HD, OS, follicular TCa], the mean TDx was longer, by an average of 17.5 wks, in patients with advanced stage than in those with localized disease (p > 0.05). Conclusions: Older adolescents and young adults with cancer are likely to have a delay in diagnosis due to a lack of adequate health insurance, and thus a more advanced stage of disease at diagnosis. As a cause for the survival improvement deficit in young adults, lack of health insurance in this age group is a problem that the United States can and should solve. No significant financial relationships to disclose.
ACOSOG Z1031: A randomized phase II trial comparing exemestane, letrozole, and anastrozole in postmenopausal women with clinical stage II/III estrogen receptor-positive breast cancer.
Authors: M. J. Ellis, G. Babiera, G. W. Unzeitig, P. K. Marcom, J. M. Guenther, F. K. Deshryver, D. C. Allred, V. Suman, K. Hunt, J. A. Olson
Journal: Journal of Clinical Oncology (2010)

LBA513 Background: Neoadjuvant aromatase inhibitor (AI) therapy is a rational and effective approach to improving the breast conservation surgery (BCS) rate for postmenopausal patients with large, estrogen receptor (ER) rich breast cancers. Barriers to adopting this strategy include lack of experience in this management approach in the US and uncertainty regarding the comparative effectiveness of the three approved aromatase inhibitors for this indication. Methods: ACOSOG Z1031 is a multicenter, open-label, neoadjuvant phase III screening study that randomized postmenopausal women with clinical stage II/III ER rich (Allred score 6-8) breast cancer to 16 weeks of either exemestane (EXE) 25 mg daily, letrozole (LET) 2.5 mg daily, or anastrozole (ANA) 1 mg daily. At baseline study participants were either marginal for BCS (MBCS), candidates for mastectomy only (MO), or inoperable (IO). Planned enrolment was 125 patients per arm in order that the likelihood of the treatment with the “best” 16-week clinical response rate (based on caliper measurements) by WHO criteria (cRR) was included among the subset of treatments with “similar” cRR (90% power). Secondary endpoints included: extent of surgery, radiologic and pathologic response rates. Results: From 4/1/2006 to 10/1/2009, 377 postmenopausal women with clinical stage II or III ER rich breast cancer were enrolled. 374 women began treatment and were included in an intent-to-treat analysis. Median age was 66 yrs (range: 43-90 yrs), Median tumor size was 4.0 cm (range: 2-13 cm). The 16-week cRR was 60.5% (95%CI: 51.3-69.1%) for EXE; 70.9% (95% CI: 62.2-78.6%) for LET, and 66.7% (95% CI: 57.6-74.9%) for ANA. Seventeen patients did not have surgery due to refusal (12 pts), progression (3 pts) or other medical conditions (2 pts). The BCS rate was 78% (163/207) in MBCS group; 42% (77/163) in MO group; and 75% in IO group (3/4). Surgeons made the decisions regarding procedure choice 75% of the time in both the MBCS and the MO categories. Conclusions: This large multicenter screening trial selected non-steroidal AIs for further development due to their higher observed cRR. The study demonstrates that high response and breast conservation rates and low rates of disease progression can be achieved through patient selection based on high ER expression. We are currently refining our approach for early detection of poor response to AIs through an assessment of the tumor Ki67 proliferation index at 2 to 4 weeks (Z1031 Cohort B). [Table: see text]
Characterization of 14 NUP214-ABL1 Fusions in T-Cell Acute Lymphoblastic Leukaemia (T-ALL) Exhibits a Genomic Heterogeneity.
Authors: Carlos Graux, Marina Lafage, Nicole Dastugue, Francine Mugneret, Roland Berger, Stéphanie Struski, Marie-José Gregoire, Nathalie Nadal, Eric Lippert, Marian Stevens-Kroef, Jan Cools, Anne Hagemeijer, Hélène A. Poirel
Journal: Blood (2006)
Outbreak of adenovirus 14 respiratory illness - Prince of Wales Island, Alaska, 2008.
Authors: J. McLaughlin, D. Fearey, S. A. Jenkerson, K. Martinek, C. Panozzo, E. Schneider, J. Tate, C. L. Robbins, D. Esposito, T. J. Gardner
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
A 10-year history of lung cancer practice guideline development: Process, productivity and impact
Authors: W. K. Evans, C. A. Smith, Y. Ung
Journal: Journal of Clinical Oncology (2007)

17044 Background: CCO's Program in Evidence-based Care at McMaster University, has developed and disseminated clinical guidance documents through provincial DSGs for 10 years. The 37 member Lung DSG includes medical oncologists (17), radiation oncologists (11), thoracic surgeons (4), nurses (2), and a research coordinator. Pathologists (3), community/patient representatives (2), a medical resident and medical sociologist have previously been members. Methods: The LDSG has used the practice guideline (PG) development cycle described by Browman GP et al (JCO 1998; 16(3):1226–31). Results: 31 reports have been published in peer-reviewed journals, including 25 guidelines; all PGs are posted on the CCO website. Topics were initially selected on the basis of known practice variability (chemotherapy for Stage IV NSCLC) or clinical controversy (combined modality therapy for Stage III NSCLC); PGs for single chemotherapy drugs (6) or chemotherapy usage in specific situations (7) have dominated DSG activity; 5 PGs on radiotherapy alone and 3 on RT as part of CMT have been completed; recent PGs have been written for rare tumours (mesothelioma, thymoma) and diagnostic imaging (PET). Initially, PGs were based solely on published RCT evidence. Evidence from publicly accessible abstracts/meeting presentations, and Phase II trials (in the absence of higher quality evidence) is now considered. For rare tumours (thymoma), the DSG has used a Delphi consensus methodology. Knowledge transfer occurs through the DSG meeting process (twice yearly face-to-face; 2–4 teleconferences), practitioner feedback (PF), publications, presentations and web posting. PF using a standardized feedback questionnaire is generally high (59.9%) but varies by PG and discipline; PF is incorporated into final guideline documents. Guideline recommendations for the use of vinorelbine, gemcitabine, taxanes and erlotinib in NSCLC have been successful in securing government funding. No significant financial relationships to disclose.
Cremophor EL-free formulation of paclitaxel: A randomized, multicenter, safety, and efficacy study of nanosomal paclitaxel lipid suspension (NPLS) versus paclitaxel in women with metastatic breast cancer (MBC).
Authors: Ateeq Ahmad, Saifuddin Sheikh, Ajay O. Mehta, Rajnish Vasant Nagarkar, Krishnan Srinivasan, Anup Majumdar, Kalyan Kusum Mukherjee, Jitendra K Singh, SP Shrivastav, C T. Satheesh, Tanveer Maksud, Suraj Pawar, Satish Ramkrishna Sonawane, Satish V Kamat, Manish Sharma, R. C. Rane, Imran Ahmad
Journal: Journal of Clinical Oncology (2014)

573 Background: The primary reason for the development of Lipid Based formulation of Paclitaxel is to improve the drug's safety profile by eliminating Cremophor EL (CrEL) and ethanol from Paclitaxel.The use of CrEL, a surfactant, has been associated with severe anaphylactoid hypersensitivity reactions, hyperlipidaemia, abnormal lipoprotein patterns, aggregation of erythrocytes and peripheral neuropathy in patients treated with Taxol. Methods: 120 MBC patients were enrolled in the study and the racial make-up was 100% Asian. They were administered NPLS (Arm A) or Paclitaxel (Arm C) at a dose of 175 mg/m2 tri-weekly or NPLS (Arm B) at dose 80 mg/m2weekly as per randomization schedule, by IV infusion at a ratio of 48 patients on Arm A: 45 patients on Arm B: 27 patients on Arm C. No pre-medication was given to the patients in NPLS groups. Safety and efficacy was determined for all treated patients. The efficacy was measured by Objective Response Rate (ORR = CR + PR) and Disease Control Rate ( DCR = CR + PR + SD). Results: (A) Efficacy - An independent radiologic review demonstrated clinically superior efficacy in terms of ORR, in MBC patients receiving the NPLS (175mg/m2) or (80mg/m2) versus the standard dose of Paclitaxel(175mg/m2). The ORR was 36.4% (95% CI, 22.1 – 50.6%) for NPLS arm A, 46.5% (95% CI, 31.6 – 61.4%) for NPLS arm B and 20.8% (95% CI, 4.6 – 37.1%) for Paclitaxel arm C. The DCR was 86.4% for NPLS Arm A, 88.4% for NPLS Arm B and 80% for Paclitaxel Arm C. (B) Safety - A total of 450 adverse events (AEs) reported to 97 patients during the course of the trial. 157 AEs occurred to patients under NPLS Arm A, 239 AEs occurred to patients under NPLS Arm B and 54 AEs occurred to patients under Paclitaxel Arm C. Conclusions: In both Arm A and B, patients treated with NPLS showed higher ORR and DCR than patients receiving Paclitaxel (Arm C). The NPLS was well tolerated by patients. Majority of the post-dose AEs were resolved without any sequelae. The patients in NPLS treatment arms were not pre-medicated. Taken together, NPLS tri-weekly or weekly demonstrates clinical benefit versus Taxol for MBC patients. Clinical trial information: CTRI/2010/091/001344.
Phase II trial of R-CHOP plus maintenance rituximab for previously untreated intermediate or high grade non-Hodgkin’s lymphoma (IHGNHL) with filgrastim support for older patients greater than 60 years
Authors: C. Desch, D. Case, L. Kalman, P. Vongkovit, J. Liebmann, M. Fridman, B. Allen
Journal: Journal of Clinical Oncology (2005)

6623 Introduction: R-CHOP is considered standard treatment (tx) for IHGNHL. Administering full doses of R-CHOP is crucial to maximize response. Older patients (pts) may experience a higher incidence of therapy-related myelosuppression impairing efficacy. In a phase 3 study of pts >60 years (yrs), not allowing for prophylactic growth factor use, the incidence of febrile neutropenia (FN) was 41% over all cycles and 20% in cycle 1 (ECOG 4494; Blood 2004, abstract 3309). The purpose of this similarly designed study was to determine if adding Filgrastim to R-CHOP in older pts would result in decreased incidence of FN, and allow full doses to be delivered. Methods: This multi-center community-based study enrolled 101 chemotherapy (CT)-naïve pts with IHGNHL at 21 sites. Tx consisted of Rituximab followed by standard-dose CHOP CT for 6–8 cycles. Filgrastim was administered at 5 ug/kg/d until ANC≥10,000 with every cycle starting with cycle 1 for pts>60 years (yrs) old. FN was defined as fever (≥38.2°C) with ANC<500. Responding pts after 6 cycles received maintenance Rituximab. We report overall and age group response rates (RR), toxicity, and delivered dose. 2-sided p-values for age group comparisons were derived from Fisher’s Exact and 2-sample t tests. Results: Of 101 pts enrolled, 59(58%) were >60 yrs old. Response was evaluable in 90(89%) pts. The overall RR was 93%. RR in pts>60 and <60 yrs were similar; 91% v. 97% (p=0.40). For pts>60 yrs the FN rate was 12% in cycle 1 and 22% over all cycles. Relative dose intensity was 94% in pts>60 yrs, which compared favorably with 95% for younger pts(p=0.58). No pt deaths were attributed either to sepsis or neutropenia. Conclusion: Pts>60 yrs receiving R-CHOP with Filgrastim achieved a RR that was similar to younger pts, with a 50% reduction in FN compared to a previously reported phase 3 study (p=0.005) without Filgrastim in 1st cycle. Additionally, delivered dose was similar in pts>60 and <60 yrs. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen Agmen Amgen
The NOTCH1 Driven Long Non-Coding RNA Repertoire in T-Cell Acute Lymphoblastic Leukemia
Authors: Annelynn Wallaert, Kaat Durinck, Pieter Rondou, Inge van de Walle, Wouter Vanloocke, Pieter-Jan Volders, Suzanne Vanhauwaert, Ellen Geerdens, Maté Ongenaert, Nadine Van Roy, Bruce Graham Poppe, Yves Benoit, Jan Cools, Jo Vandesompele, Jean Soulier, Pieter Van Vlierberghe, Tom Taghon, Frank Speleman
Journal: Blood (2014)
A phase Ib dose-escalation study of TRC105 (anti-endoglin antibody) in combination with axitinib in patients with metastatic renal cell carcinoma.
Authors: Toni K. Choueiri, M Dror Michaelson, Edwin M. Posadas, Guru Sonpavde, David F. McDermott, Meghara K. Walsh, Kevin C. Wall, Ben K. Seon, Manoj A. Jivani, Bonne J. Adams, Charles P. Theuer
Journal: Journal of Clinical Oncology (2015)

426 Background: Resistance to VEGF-targeted therapy is a major challenge in contemporary treatment of metastatic renal cell carcinoma (mRCC), and endoglin (CD105) activation may be an important mechanism leading to resistance. Endoglin is an essential angiogenic receptor expressed on proliferating tumor vessels and mRCC cancer stem cells that is upregulated following VEGF inhibition. TRC105 is an anti-endoglin monoclonal antibody that potentiates bevacizumab (Bev) and VEGF receptor tyrosine kinase inhibitors (VEGFR TKI) in preclinical models. Methods: Heavily-pretreated mRCC pts with ECOG PS 0-1, and acceptable organ function were treated with TRC105 weekly (8 mg/kg and then 10 mg/kg) in combination with axitinib (initially at 5 mg PO BID and then escalated per patient tolerance to a maximum of 10 mg PO BID). Results: Eighteen mRCC pts (median age=61.5; M:F 16:2; median number of prior therapies=3, including &gt;1 VEGFR TKI, clear cell=13, prior axitinib allowed) were treated. TRC105 dose escalation proceeded from 8 mg/kg (n=3) to 10 mg/kg (n=15) without dose limiting toxicity. Low grade AEs characteristic of each drug were not increased in frequency or severity at the recommended phase 2 doses of the two drugs. Three pts (18%) were PR by RECIST and 8 of 17 pts (47%) exhibited &gt;10% tumor reduction. Median PFS is not mature and is at least 5.8 months in the overall population and at least 5.9 months in ccRCC pts. The single patient who progressed on axitinib immediately prior to study entry remains progression free at month 5 with minor tumor regression. Conclusions: TRC105 at 8 and 10 mg/kg was well tolerated with axitinib in mRCC pts with signs of activity. A multicenter randomized phase II trial of axitinib +/- TRC105 is accruing at this time. Clinical trial information: NCT01806064.
Male breast cancer: a 13-year review of 89 patients.
Authors: C Erlichman, K C Murphy, T Elhakim
Journal: Journal of Clinical Oncology (1984)

A retrospective chart review was conducted of men with the diagnosis of carcinoma of the breast seen at this institution between January 1967 and March 1981. Eighty-nine patients were available for analysis. These cases were evaluated to determine whether the natural history of this disease was similar to that of women with carcinoma of the breast and to identify prognostic variables in carcinoma of the male breast. The results of this review would suggest that many similarities exist between breast cancer in women and in men. The most common presenting symptom is a lump, the patterns of recurrence are similar for both men and women, and survival is determined by initial T stage and the presence or absence of nodes. Local postoperative radiotherapy does not influence overall survival in male breast cancer but does decrease the incidence of chest wall recurrence. Survival after recurrence is short and is similar to that observed for women with recurrent carcinoma of the breast. The differences observed in the present series were that the median age at presentation of 63.6 years is somewhat greater than that usually observed in women; no cases of lobular carcinoma were observed; and in the 44 patients who developed recurrences to date, none had evidence of liver metastases as the initial site of recurrence. In most respects the natural history of male breast cancer is similar to that of carcinoma of the breast in women. Since carcinoma of the male breast is a relatively rare malignancy. it is reasonable to recommend management of this disease be based on the greater base of knowledge available for carcinoma of the female breast.
Phase II trial of decitabine in myelofibrosis with myeloid metaplasia
Authors: O. Odenike, J. E. Godwin, K. van Besien, D. Huo, P. J. Stiff, J. L. Wade, E. Lester, N. Klekowski, R. A. Larson, W. Stock
Journal: Journal of Clinical Oncology (2007)

7088 Background: DNA hypermethylation of promoter-specific CpG islands has been implicated in the pathogenesis and progression of disease in MMM. We are evaluating Decitabine, a DNA methyltransferase inhibitor in patients (pts) with MMM. Methods: This is a single stage Phase II trial: planned accrual of 20 pts. Pts had to have MMM with anemia and/or splenomegaly. Decitabine is given subcutaneously (SQ) at a dose of 0.3 mg/kg/d on days 1–5, and days 8–12; cycles are repeated every 6 weeks, in the absence of dose limiting toxicities. Response is determined every 12 weeks as an improvement in cytopenias and/or splenomegaly. CD34+ cells are measured by flow cytometry in peripheral blood at baseline, and at days 5 and 12 of therapy; elevated levels are associated with advanced stage and evolution to blast phase in MMM. Results: Pt characteristics: M/F: 6/4, median age 67 (range 42–89), median absolute CD34+ cell count 116 × 10 6 /L (11–4,959), Dupriez score of 2, 1 and 0 in 50%, 30% and 20% respectively. Median number of cycles administered: 3 (range 1- 9). Median WBC and platelet (plt) count: 5.2 K/uL (1.5–29), and 171 K/uL (47–465 K/uL); 5 pts were red cell transfusion dependent. Grade 4 neutropenia (ANC) occurred in all pts, and grade 3/4 plts in 6 pts. 7 pts have developed febrile neutropenia. Grade 3–4 non-hematologic toxicities include a variceal bleed in a patient with baseline portal hypertension and a splenic infarct occurring in another pt. 7 pts are evaluable for response: 3 pts have responded including 1 pt with a CR (normalization of blood counts and transfusion independence), and 1 pt with a PR (Hb increase of &gt; 2 g/dL). A third pt in the blast phase of the disease had a hematological improvement as evidenced by a normalization in plts (from 62 K/uL to 219 K/uL) associated with a significant decrease (from 2.58 K/uL to 0.03 K/uL) in circulating blasts. The other 4 pts have had stable disease. There was a reduction in CD34+ levels: mean decrease of approximately 75% at day 12 of therapy (p&lt;0.0001). Conclusions: Low dose SQ decitabine is feasible in MMM and is associated with a significant decrease in CD34+ cells. There is preliminary evidence of clinical activity. Myelosupression is significant, though reversible and requires close monitoring. These findings must be validated in a larger group of pts. Sponsored by NCI grant NO1-CM-62201 No significant financial relationships to disclose.
Abstract 15151: Novel Tiplaxtinin Eluting Stent Inhibits the Migration of Vascular Smooth Muscle Cells but not Endothelial Cells
Authors: Mayank K Mittal, Tammy Strawn, Fay P William
Journal: Circulation (2012)

Introduction: Plasminogen activator inhibitor-1 (PAI-1), a key regulator of the plasminogen activator system and fibrinolysis, also regulates vascular remodeling. Elevated levels of PAI-1 are assoc...
Molecular markers of metastases in advanced stage adenocarcinoma of the prostate
Authors: A. Potti, G. Chen, N. Shukeir, S. A. Rabbani, I. Sehgal
Journal: Journal of Clinical Oncology (2005)

9672 The receptor for urinary plasminogen activator (uPAR), Wnt-1, and beta-catenin are being increasingly recognized in preclinical studies to play an important role in the pathogenesis of genitourinary malignancies. We investigated the predictive role of uPAR, Wnt-1 and beta-catenin as pathologic makers for metastatic hormone refractory prostate cancer. 67 patients with metastatic prostate cancer who had adequate tissue (primary and metastatic sites) for analysis were identified. Pathologic specimens evaluated included tissues from primary prostatic adenocarcinoma, lymph node metastases, and skeletal metastases. Immunohistochemical analysis was performed to investigate the expression of Wnt-1 and beta-catenin in the archival, paraffin-embedded sections. For uPAR expression, the malignant tissues and ’control’ normal prostatic tissue were immunoblotted and probed with a monoclonal uPAR antibody recognizing the native uPAR protein (R&D Systems). Tissue expression status for uPAR, Wnt-1 and beta-catenin was compared to Gleason score, androgen receptor (AR) status, serum PSA, and the presence of lymph node and/or skeletal metastases. In the 67 samples of primary malignant prostatic tissue, Wnt-1 and cytoplasm/nuclear beta-catenin expression was observed in 52% and 34%, respectively, where as uPAR expression was detected in only 35% of the samples. However, high levels of expression of Wnt-1 and beta-catenin were seen in 77% of lymph node metastases and in 85% of skeletal metastases, and uPAR overexpression was seen in 90% of these metastatic sites. Interestingly, maximum tissue expression of Wnt-1, beta-catenin, and uPAR was observed in skeletal metastases. Furthermore, overexpression of Wnt-1, beta-catenin, and uPAR correlated with AR status, worsening Gleason score, and rising PSA levels. In summary, Wnt-1, uPAR, and beta-catenin expression are associated with advanced stage, hormone-refractory prostate carcinoma, in which they can serve as markers of disease progression, especially skeletal metastasis. Strategies aimed at regulating Wnt-1, uPAR and beta-catenin must be aggressively explored as therapeutic modalities, as they are likely to benefit patients with metastatic prostate cancer. No significant financial relationships to disclose.