tbuckley/cabot-search huggingface dataset:
Breast pain and subsequent breast cancer diagnosis
Authors: G. L. Giron, J. Fey, P. I. Borgen, L. L. Montgomery
Journal: Journal of Clinical Oncology (2004)

866 Background: Physicians rarely consider complaints of breast pain to be indicative of an underlying malignancy. We examine the incidence of self-reported breast pain as the sole breast complaint and subsequent cancer diagnosis. Methods: Between 5/01and 5/03, 6047 patients completed a National Comprehensive Cancer Network (NCCN) survey, of whom 186 (3%) subjectively reported breast pain as the sole reason for their visit. A retrospective review was conducted of the medical records with respect to physical exam (PE), diagnostic intervention, and subsequent breast cancer diagnosis. Results: The mean patient age was 53.7 years (median=52). Sixty percent (25/42) of the cancers found in patients with abnormal PE and 24% (8/33) of the cancers found in patients with normal PE were associated with the subjective painful area (P=0.0026). Conclusion: Self-reported breast pain was the sole presenting complaint in a small proportion of patients subsequently diagnosed with breast cancer in the surveyed population. The presence or absence of pain should not alter the usual management of patients with breast complaints—through clinical breast exam and appropriate diagnostic imaging. No significant financial relationships to disclose.
Polymorphisms in IL-8 and the GSTP1 are associated with survival of metastatic colorectal cancer patients treated with CPT-11
Authors: N. Mallik, W. Zhang, D. Y. Yang, S. Iqbal, J. Yun, O. Press, M. Gordon, H.-J. Lenz
Journal: Journal of Clinical Oncology (2004)

3606 Background Irinotecan (CPT-11), an analogue of Camptothecins, demonstrates a broad spectrum of antitumor activity. Currently, there are no prognostic molecular markers for CPT-11 efficacy. Therefore, we investigated associations between polymorphisms in genes involved in CPT-11 metabolism (UGT1A1), chemoresistance (GSTP1), DNA repair (XPD, ERCC1, XRCC1, Werner 1074, and Werner 1367), and angiogenesis (IL-8 and COX-2) and survival of patients with metastatic colorectal cancer receiving CPT-11 based chemotherapy. In vivo studies show GSTP1 to detoxify chemotherapeutic agents by glutathione conjugation. In vivo and in vitro studies show IL-8 to possess angiogenic properties and its overexpression is associated with metastasis potential in colorectal cancer. Positional cloning studies identified Werner as the gene responsible for Werner Syndrome (WS), and cells from these patients have been shown to be particularly sensitive to Camptothecin. Methods The gene polymorphisms were tested using PCR-RFLP method on genomic DNA extracted from peripheral blood from metastatic colorectal cancer patients treated with CPT-11. Results 55 patients were collected; 31 males and 24 females; median age 55 (range 34–77) years. The response to CPT-11 was 40% (18/45, 1 pt was inevaluable, and 9 pts are still receiving treatment and were too early to be evaluated), with median survival of 22.9 (95% CI: 18.4, 29.3) months. The median time of follow-up and range was 15.4 (4.7–26.1) months. Individually, IL-8 and GSTP1 showed trends for overall survival (log rank p=0.07 and p=0.077, respectively). A combined analysis of these two genes showed patients carrying two favorable genotypes (homozygous Ile for GSTP1 and T allele for IL-8) had longer survival when compared with those patients carrying no favorable genotypes or only 1 favorable genotype (p=0.005). The Werner Loci polymorphisms also showed a trend for overall survival. Conclusion These data suggest that IL-8, GSTP1, and the Werner Loci polymorphisms may be potential prognostic molecular markers for clinical outcome of metastatic colorectal cancer patients treated with a CPT-11 regimen. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron NCI; NIH; Roche; Lilly; Pharmacia; Bayer; Bristol-Myers Squibb; Chiron; Aventis; Genentech; ImClone; Cellpathway; Newbiotics; Sanofi
Heart Failure and Sleep-Disordered Breathing — The Plot Thickens
Authors: Ulysses J. Magalang, Allan I. Pack
Journal: New England Journal of Medicine (2015)

Central sleep apnea occurring within the cyclic breathing pattern of Cheyne–Stokes respiration has been reported to be common in patients with heart failure.1 During sleep, episodes of hyperventilation followed by a complete cessation (apnea) or decrease (hypopnea) in breathing are associated with oxyhemoglobin desaturations, arousals, and sympathetic nervous system activation that could be deleterious to the failing heart. Thus, suppression of central sleep apneas and hypopneas seemed to be a reasonable target in the treatment of patients with heart failure.Cowie et al.2 now describe in the Journal the results of the SERVE-HF (Treatment of Sleep-Disordered Breathing with Predominant Central . . .
Pharmacokinetics (PK) and tolerability of GW786034, a VEGFR tyrosine kinase inhibitor, after daily oral administration to patients with solid tumors
Authors: A. B. Suttle, H. Hurwitz, A. Dowlati, N. Fernando, S. Savage, K. Coviello, M. Dar, P. Ertel, B. Whitehead, L. Pandite
Journal: Journal of Clinical Oncology (2004)

3054 Background: GW786034 is a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor with anti-tumor and anti-angiogenic activity in vitro and in vivo. Preclinical models suggest that plasma GW786034 concentrations above ∼18μg/mL throughout the dosing interval were associated with optimal activity. Methods: Patients (pts) with solid tumors were enrolled into an ongoing Phase I, dose-escalation study. Dose escalation occurred in cohorts of 3–6 pts based on dose-limiting toxicity. Serial plasma GW786034 concentrations and circulating VEGF, d-dimer, VCAM-1, E-selectin, thrombin, and Factor VIII were evaluated . Wound healing assays and dynamic MRI's were obtained before and during GW786034 dosing. Results: Twenty-eight patients were enrolled at dose levels up to 400mg daily. Selected mean PK results are: Drug-related adverse events by grade (G) included: hypertension (n=2; G1, G3); GI hemorrhage (n=2; G1, G4); emesis (n=2; G1); diarrhea (n=2; G1); myoclonus (n=1; G3); ecchymoses (n=1; G1); increased alkaline phosphatase (n=1; G1), SGPT (n=1; G1), SGOT (n=1; G1), and bilirubin (n=1, G1). Six patients have remained on study for greater than 3 months. Dose escalation is continuing. Conclusions: Daily oral doses of GW786034 can achieve plasma concentrations similar to those that show anti-tumor and anti-angiogenic activity in preclinical models. Doses of up to 400mg daily were well tolerated. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline; Merck GlaxoSmithKline; Merck GlaxoSmithKline
Pre-treatment plasma Epstein Barr virus –DNA (pEBV DNA) level and association with magnetic resonance imaging (MRI)-delineated tumor volume and positron-emission tomography (PET) FDG-uptake in undifferentiated nasopharyngeal carcinoma (NPC)
Authors: B. Ma, A. King, B. Zee, S. F. Leung, E. P. Hui, M. Lai, D. Y. M. Lo, A. Ahuja, W. H. Kwan, A. T. C. Chan
Journal: Journal of Clinical Oncology (2004)

5526 Background: As post-treatment pEBV DNA level reflects post-radiotherapy (RT) residual tumor load in NPC (JNCI 2002:94(21);1416–29), we examine any correlation between pEBV DNA level, MRI-delineated volume and FDG-PET uptake of primary tumor (T) and regional nodes (N) in patients (pts) with NPC before undergoing chemoradiation (chemo-RT). Methods: Pts enrolled in an ongoing clinical trial involving chemo-RT at an institution entered this parallel study. Eligible pts had non-metastatic UICC stage III-IV NPC based on “conventional” staging: nasopharyngoscopy, physical examination, computered tomography (CT) of nasopharynx (NP), chest X-ray, bone scan, abdominal ultrasound. Consented pts underwent pre-treatment PET-CT (whole body excluding brain), MRI (NP- neck), pEBV DNA (copies/ml) analysis using real-time polymerase chain reaction. Net volume (cm3) of T (MRI-Tv), N (MRI-Nv), total tumor volume (TTv = Tv + Nv) were quantified on axial MR images. FDG-PET uptake expressed as maximum standard uptake value (SUVmax) for T (SUVmaxT) and N (SUVmaxN) were anatomically matched with CT images of the PET-CT scan. Lesions with SUVmax≥ 2.0 were considered malignant. Results: 28 pts were enrolled (21 males/ mean age 48 yrs/ UICC stage (conventional staging): No. of pts: III=15, IVa=6, IVb=7). PET showed no metastatic disease. Mean pEBV DNA level = 7190 copies/ml (range 0–92840), mean SUVmaxT=10 (range 4.2–21), mean SUVmaxN= 27 (range 2–77); mean MRI-Tv = 3325cm3, mean MRI-Nv = 3795 cm3. pEBV DNA level correlated with MRI-Tv (p<0.01, Spearman correlation, r = 0.50, 95%CI=0.15–0.74), MRI-TTv (p< 0.01, r = 0.51, 95% CI= 0.17–0.74), but not MRI-Nv (p=0.10). pEBV DNA did not correlate with SUVmaxT or SUVmaxN. Conclusions: Pre-treatment pEBV DNA level may quantitatively reflect tumor burden at primary NP. Sample size expansion is warranted and accrual continues. Post-treatment PET-CT will be obtained to examine the significance of elevated pEBV DNA following chemo-RT. No significant financial relationships to disclose.
Breast involvement in patients with HTLV-1-associated adult T-cell leukemia/lymphoma (ATL)
Authors: K. Sharma, J. E. Janik, C. A. Torres-Cabala, C. C. Lee, D. O’Mahony, J. C. Morris
Journal: Journal of Clinical Oncology (2008)

14009 Background: Adult T cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder with a poor prognosis caused by human T cell lymphotrophic virus type 1 (HTLV-1). The aggressive subtypes of ATL are associated with high circulating peripheral leukemic cell counts or rapidly progressing lymphadenopathy, acute hepatosplenomegaly, hypercalcemia, rising serum LDH and infiltration of the skin, bones, lungs, eyes, G.I. tract, heart and CNS with malignant T cells. Clinical involvement of the breast has been reported only on one previous occasion in a male patient. We report four female patients that presented with or developed clinical breast involvement with ATL. Methods: Medical records and imaging study reports on female patients registered on NCI-IRB approved protocols for the treatment of HTLV-1-associated ATL including 96-C-0147 (yttrium-90 labeled daclizumab), 00-C-0030 (high-dose unlabeled daclizumab), and 03-C-0194 (alemtuzumab) accrued between 1996 and 2007 were reviewed with specific reference to diagnoses and information related to the presence of breast abnormalities, breast lymphoma, mammography, computerized tomography (CT) and breast biopsies. Mammograms and CT-scans were reviewed. Available pathology was reviewed. To meet the case definition, a subject demonstrated a palpable breast mass or abnormality, demonstrated lesion on mammography and/or CT scan that was positive for ATL on biopsy. Results: Four women, ages 37, 46, 55 and 56 years were identified that met these criteria. Three were of Jamaican origin and one was from Trinidad. Conclusions: A review of the literature found a single case of malignant gynecomastia occurring in a male with HTLV-1-associated ATL. The breast masses in two of our patients resolved with systemic treatment of their ATL. ATL may involve the female breast and is often seen in the setting of progressive diease. Lymphomatous involvement should be considered in the setting of a breast mass in patients with ATL. Patient Demographics Characteristic Patient No. Total Patients 4 Age Median (range years) 50.5 (37-56) Sex Male Female 0 4 Ethnicity Afro-Carribean 4 ATL Subtype Chronic Acute Leukemia Lymphomatous Smoldering 0 0 4 0 arnofsky Performance Status Median (range %) 90 (80-100) Prior Treatment Chemotherapy Monoclonal Antibody Therapy Radioimmunotherapy 3 3 2 1 No significant financial relationships to disclose.
Cetuximab + capecitabine + irinotecan (CCI) versus cetuximab + capecitabine + oxaliplatin (CCO) as first line therapy for patients with metastatic colorectal cancer (CRC): Preliminary results of a randomized phase II trial of the AIO CRC Study Group
Authors: V. Heinemann, L. Fischer Von Weikersthal, N. Moosmann, U. Vehling-Kaiser, M. Stauch, D. Oruzio, M. Schulze, J. Walther, J. Weiss, H. Dietzfelbinger
Journal: Journal of Clinical Oncology (2006)

3550 Background: Combinations of infusional 5-FU/FA with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) have become standards of care in the treatment of metastatic colorectal cancer. In this trial, 5-FU/FA was replaced by capecitabine, an oral fluoropyrimidine. In addition, cetuximab, an antibody directed against the EGF-receptor was added to further improve treatment efficacy. Methods: Patients (pts) with metastatic CRC (age 18 to 75 years) and measurable disease were randomized to 3-week cycles of therapy. In the CCI-arm, pts received cetuximab (400 mg/m 2 iv on day 1 of cycle 1 and 250 mg/m 2 iv subsequently), capecitabine (2 × 800 mg/m 2 po on days 1 to 14), and irinotecan (200 mg/m 2 iv on day 1). In patients &gt;65 years doses of irinotecan and capecitabine were reduced by 20%. In the CCO arm, cetuximab (as described above) was combined with capecitabine (2 × 1000 mg/m 2 po on days 1 to 14) and oxaliplatin (130 mg/m 2 iv on day 1). Both treatment arms were planned separately according to the optimal design described by Simon (p 0 = 0.3, p 1 = 0.5, α = 0.1, β = 0.1) with objective response rate (ORR) according to RECIST) as the primary endpoint. Results: The recruitment goal of 92 patients has been achieved. Among evaluable patients, median age in the CCI arm was 63 yrs (range 38–72) and 58 yrs (range 38–74) in the CCO arm. Median Karnofsky performance status was 90% (range 70–100) and 100% (range 70–100), the EGFR-status was positive in 64% and 69% of pts, respectively. The ORR in the CCI arm was 41% (11/27) (95%-CI: 22% to 61%), while in the CCO arm an ORR of 71% (15/21) (95%-CI: 48% to 89%) was documented. Toxicity data were available for 25 pts in each arm. The most common grade 3–4 CTC- toxicities observed in the CCI and the CCO-arm respectively were skin toxicity (4 vs 5 pts), allergic reactions (0 vs 5 pts), diarrhea (5 vs 3pts), neurotoxicity (1 vs 3 pts), and leucopenia (4 vs 5 pts). Conclusion: The preliminary evaluation of this randomized phase II trial suggests the feasibility of both treatment arms. Updated results regarding response rate and progression-free survival will be presented at the meeting. [Table: see text]
Down Syndrome Developmental Brain Transcriptome Reveals Defective Oligodendrocyte Differentiation and Myelination
Authors: Jose Luis Olmos-Serrano, Hyo Jung Kang, William A. Tyler, John C. Silbereis, Feng Cheng, Ying Zhu, Mihovil Pletikos, Lucija Jankovic-Rapan, Nathan P. Cramer, Zygmunt Galdzicki, Joseph Goodliffe, Alan Peters, Claire Sethares, Ivana Delalle, Jeffrey A. Golden, Tarik F. Haydar, Nenad Sestan
Journal: Neuron (2016)
Crizotinib and Testing for ALK
Authors: Alice T. Shaw, Benjamin Solomon, Mari Mino Kenudson
Journal: Journal of the National Comprehensive Cancer Network (2011)

Crizotinib was recently approved by the US FDA for the treatment of advanced non–small cell lung cancer (NSCLC) harboring the ALK (anaplastic lymphoma kinase) gene rearrangement. To ensure identification of patients most likely to benefit, the FDA approved crizotinib concurrently with a companion diagnostic test—the Vysis ALK Break Apart FISH Probe Kit. This kit was used in 1 of the 2 pivotal trials leading to the FDA approval of crizotinib and has become the gold standard for detecting ALK rearrangement in NSCLC. Although ALK FISH is clinically validated, the assay can be technically challenging and costly. Therefore, other diagnostic modalities are being explored, including immunohistochemistry (IHC) and reverse transcriptase–polymerase chain reaction. This article provides an overview of the diagnostic assays available for detecting ALK rearrangement. Each assay, including ALK FISH, has its strengths and weaknesses. Recent work with commercially available ALK antibodies suggests that IHC-based tests may represent a reliable and cost-effective screening strategy; however, large multicenter studies comparing IHC with FISH are needed to validate ALK IHC. While ALK FISH remains the current standard for diagnosing ALK positivity, large-scale screening of patients with newly diagnosed advanced NSCLC, as recommended by NCCN, may require development and validation of alternative screening strategies, such as combination IHC and FISH.
Association of Rosacea With Risk for Glioma in a Danish Nationwide Cohort Study
Authors: Alexander Egeberg, Peter R. Hansen, Gunnar H. Gislason, Jacob P. Thyssen
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> Rosacea, a common facial skin disorder, has a poorly understood pathogenesis in which increased matrix metalloproteinase activity might play an important role. Glioma accounts for 80% of all primary malignant tumors in the central nervous system, and these tumors also show upregulation of certain matrix metalloproteinases. <h3>Objective</h3> To investigate the association between rosacea and the risk for glioma. <h3>Design, Setting, and Participants</h3> Nationwide cohort study of the Danish population from individual-level linkage of administrative registers. All Danish citizens 18 years or older from January 1, 1997, to December 31, 2011, were eligible for inclusion. A total of 5 484 910 individuals were eligible for analysis; of these, 68 372 had rosacea and 5 416 538 constituted the reference population. Data were analyzed from July 14 to August 10, 2015. <h3>Main Outcomes and Measures</h3> The outcome of interest was a diagnosis of glioma. Incidence rates per 10 000 person-years were calculated, and incidence rate ratios adjusted for age, sex, and socioeconomic status were estimated by Poisson regression distribution models. <h3>Results</h3> Of the 5 484 910 individuals in the study population, 21 118 individuals developed glioma during the study period, including 20 934 of the 5 416 538 individuals in the reference population (50.4% women; mean [SD] age, 40.8 [19.7] years) and 184 of the 68 372 patients with rosacea (67.3% women; mean [SD] age, 42.2 [16.5] years). The incidence rate (95% CI) of glioma was 3.34 (3.30-3.39) in the reference population and 4.99 (4.32-5.76) in patients with rosacea. The adjusted incidence rate ratio (95% CI) of glioma in patients with rosacea was 1.36 (1.18-1.58) in our primary analysis. When analyses were limited to patients with a primary diagnosis of rosacea by a hospital dermatologist (n = 5964), the adjusted incidence rate ratio was 1.82 (1.16-2.86). <h3>Conclusions and Relevance</h3> Rosacea was associated with a significantly increased risk for glioma in a nationwide cohort. This association may be mediated, in part, by mechanisms dependent on matrix metalloproteinases. Increased focus on neurologic symptoms in patients with rosacea may be warranted.
<i>Science Translational Medicine</i> Podcast: 30 September 2015
Authors: Blythe D. Sather, Guillermo S. Romano Ibarra, Andrew M. Scharenberg, David J. Rawlings, Annalisa M. VanHook
Journal: Science Translational Medicine (2015)

Blythe Sather, Guillermo Romano Ibarra, Andy Scharenberg, and David Rawlings describe their new efficient method for repairing or replacing human genes using homologous recombination.
Gemcitabine/platinum alone or in combination with cetuximab as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: C. A. Butts, D. Bodkin, E. L. Middleman, C. W. Englund, D. Ellison, Y. Z. Alam, V. Pautret, M. Weber, H. Kreisman, F. A. Shepherd
Journal: Journal of Clinical Oncology (2007)

7539 Background: This randomized phase II study was conducted to evaluate the benefit of adding cetuximab, an IgG1 monoclonal antibody targeting the EGF receptor, to gemcitabine/platinum chemotherapy in patients with recurrent or metastatic NSCLC. Methods: Patients with previously untreated stage IIIB (malignant pleural effusion) or stage IV NSCLC irrespective of their EGF receptor status were eligible for this study. Patients on arm A received cetuximab (400 mg/m 2 IV on day 1 followed by 250 mg/m 2 weekly) combined with either cisplatin (75 mg/m 2 IV q3 weeks) and gemcitabine (1,250 mg/m 2 IV days 1 and 8) or carboplatin (AUC 5 IV q3 weeks) and gemcitabine (1,000 mg/m 2 IV days 1 and 8). Patients on Arm B received the same chemotherapy regimen without cetuximab. The primary endpoint was tumor response rate with progression-free (PFS) and overall survival (OS) as secondary endpoints. Results: 73 women and 58 men, median age 66 years (35–88) were randomized to arm A (n=65) or arm B (n=66). Partial responses occurred in 18 (27.7%, 95% CI: 17.3–40.2) patients in arm A and 12 (18.2%, 95% CI 9.8–29.6) in arm B. Median PFS was 5.09 months for arm A (95% CI: 4.17–5.98) and 4.21 months (95% CI: 3.81–5.49) in arm B; median OS was 11.99 (95% CI: 8.80–15.20) and 9.26 months (95% CI: 7.43–11.79) respectively. The incidence of drug related infusion reactions (any grade) in arm A was 15.6% and 1.5% in arm B. Three patients in arm A had grade 3–4 cetuximab related infusion reactions. Severe acneform rash was observed in 14.1% of patients in arm A and none in arm B. Other toxicities were similar and only 18.5% of patients in arm A and 10.6% patients in arm B discontinued treatment for toxicity. Conclusions: These data confirm the previously observed benefit for the combination of cetuximab with a platinum based doublet chemotherapy regimen patients with metastatic NSCLC. The difference of 2.7 months in median OS between treatment arms seems to suggest a more substantial clinical benefit. Fully powered phase III studies addressing this question are on- going and results will become available in 2007. [Table: see text]
Gene Expression Changes in Bone Marrow of MDS Patients with Del(5q) During Lenalidomide Treatment.
Authors: Esther Natalie Oliva, Maria Cuzzola, Roberto Latagliata, Francesca Ronco, D'Errigo Maria Grazia, Morabito Fortunato, Galimberti Sara, Enrico Balleari, Giorgina Specchia, Agostino Cortelezzi, Antonella Poloni, Carlo Finelli, Giuliana Alimena, Pasquale Iacopino, Carmelo Laganà, Francesco Mendicino, Filippo Rodà, Francesco Nobile
Journal: Blood (2009)
Haploidentical Allogeneic Transplantation As Salvage in Relapsed Multiple Myeloma
Authors: Phyllis McKiernan, David H. Vesole, David S. Siegel, Scott D Rowley, Melissa F Baker, Brenda Diaz, Themba Nyirenda, Joshua R. Richter, Pamela Sutherland, Michele L. Donato
Journal: Blood (2014)