tbuckley/cabot-search huggingface dataset:
Staging in early breast cancer: Help or hindrance?
Authors: Naera Waters, David James Porter
Journal: Journal of Clinical Oncology (2014)

6564 Background: In 2012, ASCO identified staging CT, radionuclide or PET scans for asymptomatic, low risk breast cancer pts as one of the 5 big money wasters in oncology, due to a lack of demonstrated benefit and the potential harm of a false positive diagnosis. We assessed the frequency of staging CT and bone scans in asymptomatic pts with early breast cancer, whether metastases were conclusively detected, and the impact of inconclusive results. Methods: 664 consecutive pts with breast cancer referred to the Auckland Regional Cancer and Blood Service between 1 Nov 2010 and 25 Oct 2013 were identified from a prospectively collated referral database. 273 pts were excluded for locally recurrent or metastatic disease, symptoms requiring investigation, or neoadjuvant therapy. Age, LN status, tumour type and grade, receptor and HER2 status and results of staging and follow up scans were recorded in 391 women. Results: 81/330 (25%) pts with <4 nodes involved (N0/1) had staging CT, bone scan or both. Metastatic breast cancer (MBC) was found in 2/81(2%) and staging was negative in 51%. 38(47%) pts had radiological abnormalities of uncertain importance. Follow up scans showed 2/38 of these abnormalities were MBC, and 2 lung cancer (1 early stage, 1 metastatic), (total metastatic 3/38=8%). 59/61(97%) pts with >4 nodes (N2+) had staging. MBC was identified in 2 pts (3%), 1 of whom also had early stage lung cancer. 33 (56%) pts had indeterminate radiological findings, of which 5 (15%) were later confirmed to be MBC. Staging was negative in 41%. Up to 5 follow up scans per pt and 1-24 mo were required to clarify indeterminate findings Conclusions: Staging investigations modified adjuvant treatment plans in only 4/140 (3%) pts who were found to have MBC. 11% of women with indeterminate lesions on staging were later shown to have either metastatic breast (n=7) or metastatic lung cancer (n=1) underscoring the importance of continuing adjuvant therapy where uncertainty exists. Indeterminate results were frequent, imply the possibility of incurable cancer, and required up to 24 mo and 5 extra scans before pts could be reassured. This causes great uncertainty and distress for pts and consumes limited healthcare resources. The harms and benefits of staging in early breast cancer should be carefully weighed.
Randomized phase III study of recombinant human Apo-2 ligand (Apo-2 Ligand) plus vinorelbine/cisplatin (NP) verus placebo plus NP in patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A single center report.
Authors: Lanfang Yu, Peng Shen, Sui Huang, Jing Chen, Genming Shi, Jing Deng, Xiaoting Wang
Journal: Journal of Clinical Oncology (2014)

e19153 Background: Recombinant Human Apo-2 Ligand (Apo-2 Ligand) is reported that it can induce the transformation of cells and the apoptosis of tumor cells, but have no effect on normal cells. In the early stage of studies, it have been showed the good security and anti-tumor effects. This phase III study is to investigate the effect of Apo-2 Ligand combined with chemotherapy treating local advanced or metastatic non-small cell lung cancer (NSCLC). Methods: Patients with stage IIIB/IV NSCLC primary untreated or only one option treated were randomly assigned into group A (Apo-2 Ligand 7.5mg/kg plus vinorelbine 25mg/m2 d1,d8/cisplatin 30mg/m2 d2-4 (NP),q3w) and group B (placebo plus NP) according to 2:1 ratio. 28 patients with stage IIIB/IVNSCLC in our center were enrolled, two cases withdrew, 21 patients in group A and 5 patients in group B. All patients have completed two to six cycles chemotherapy, and were evaluated every two cycles, then were followed up until death or the end of study. Results: All the people have achieved clinical remission: 11 partial remission (PR) and 10 stable disease (SD)in group A, 4 PR and 1 SD in group B. The median progress free survival (mPFS) and median overall survival (mOS) was 6.9m and 9.7m in group A compared with 4.8m and 7.7m in control group. The hematological and non hematological toxicities were similar in two groups. G3/4 toxicities included leucopenia ( 34.4% in group A vs 52.2% in group B), neutropenia (44.8% vs 56.5%), thrombocytopenia (8.3% vs 8.7%), anemia (19.8% vs 17.4%), alopecia (100% vs 100%) and vomiting (1.1% vs 0%). Conclusions: Recombinant Human Apo-2 Ligand (Apo-2 Ligand) combined with chemotherapy for treating local advanced or metastatic NSCLC was well tolerable and promising. More comprehensive and detailed data will be expected after the final analysis of the whole study. Clinical trial information: 2009L07690.
SUV max of FDG-PET/CT as a prognostic factor in ovarian clear cell adenocarcinoma.
Authors: Kazuhiro Takehara, Haruhisa Konishi, Atsumi Kojima, Shinichi Okame, Yuko Shiroyama, Takashi Yokoyama, Takayoshi Nogawa, Yoshifumi Sugawara
Journal: Journal of Clinical Oncology (2014)

e16509 Background: FDG-PET/CT is useful for diagnosing malignant tumors and has recently been used to evaluate gynecologic malignant tumors. Intracellular FDG uptake is measured as the standardized uptake value (SUV), which differs depending on tumor characteristics. Malignant tumors of various histologic types occur in the ovaries, and the pathogenesis differs according to histologic type. This study investigated differences in SUVmax according to histologic type in ovarian epithelial cancer and the relationship of SUVmax with prognosis. Methods: This study included 80 patients with ovarian epithelial cancer based on histopathologic findings at surgery, and who had undergone PET/CT before treatment, between January 2008 and December 2012. SUVmax on PET/CT of primary lesions and histopathology were compared based on histologic type. In addition, cases were categorized into two groups based on median SUVmax, and the prognosis associated with different SUVmax was evaluated. Results: Clinical tumor stage was I in 35 patients, II in 8, III in 25, and IV in 12. Histologic type was serous adenocarcinoma (AC) in 33 patients, clear cell AC in 27, endometrioid AC in 15, and mucinous AC in 5. Median SUVmax was lower in mucinous AC (2.76) and clear cell AC (4.9) than in serous AC (11.4) or endometrioid AC (11.4). Overall, median SUVmax was lower in clinical stage I (5.37) than in clinical stage ≥II (10.3). However, in both clear cell AC and endometrioid AC, when histologic evaluation was possible, no difference was seen between stage I and stage ≥II. Moreover, in clear cell AC, the 5-year survival rate was significantly higher in the low SUVmax group (100%) than in the high SUVmax group (43.0%, P=0.009). Conclusions: SUVmax on preoperative FDG-PET/CT in ovarian epithelial cancer differs according to histologic type. In clear cell AC, SUVmax may represent a prognostic factor.
mRNA expression levels of candidate genes and clinical outcome in mCRC patients treated with FOLFOXIRI plus bevacizumab (bev) or FOLFIRI plus bev in the TRIBE study.
Authors: Dongyun Yang, Fotios Loupakis, Chiara Cremolini, Carlotta Antoniotti, Marta Schirripa, Lisa Salvatore, Miriana Moran, Stephanie H. Astrow, Alfredo Falcone, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2014)

3640 Background: Phase III TRIBE trial demonstrated that first-line FOLFOXIRI plus bev improved PFS and RECIST response and, at adjusted analyses, OS as compared to FOLFIRI plus bev. Previous data suggested that higher ERCC1 expression levels could be responsible for resistance to oxaliplatin-containing chemotherapy. Limited data are available up today for the predictive effect of the expression levels of major genes involved in tumoral angiogenesis. Methods: mRNA expression levels of ERCC1, VEGF-A, -B, -C, VEGFR1, VEGFR2, ACVRL1, EGFL7 and EPHB4 were measured using RT-PCR. Biomarker-adaptive threshold design by Jiang, Freilin and Simon (JNCI 2007) was used to identify which mRNA levels may predict subsets of patients who were more likely to benefit FOLFOXIRI + bev than FOLFIRI + bev. Results: Tissue samples adequate for expression analyses were available for 228 out of 503 randomized pts (45%). Pts with the tissue available had similar baseline characteristics as the whole cohort. Pts with high intratumoral ERCC1 (>0.62) or high VEGF C (>0.211) were more likely to have longer PFS in FOLFOXIRI + bev (median=12.0 mths) than in FOLFIRI + bev (median=9.7 mths) (HR=0.46 and 0.24 for high ERCC1 and VEGF-C expression level vs. HR=1.55 and 1.20 for low ERCC1 and VEGF-C expression level; unadjusted P for interaction=0.0035 and 0.0037 for ERCC1 and VEGF-C, respectively). ERCC1 and VEGF-C expression levels also predicted similar differences in response and OS between two therapies. Applying recursive partitioning identified distinct signatures of genes predicting response (ranging from 20 to 76%, PFS (6-18 mths) and OS (18-49 mths). Conclusions: the findings suggested predictive roles for ERCC1 and VEGF-C levels in patients receiving first-line FOLFOXIRI + bev vs in FOLFIRI + bev. Gene expression signature specific for response, PFS and OS may be important new biomarkers which warrant further validation.
GP who worked as obstetrics and gynaecology locum is struck off after risky caesarean
Authors: Clare Dyer
Journal: BMJ (2019)

A GP who sought to pursue a career in obstetrics and gynaecology despite lacking the training or qualifications has been struck off after he undertook a risky caesarean section that left a patient in intensive care and with “significant and ongoing problems.”

A medical practitioners tribunal found that David Nzegbulem took on a locum post as a specialist registrar in obstetrics and gynaecology at Watford Hospital in November 2015 knowing that he lacked the experience to undertake trials of operative vaginal delivery and caesarean sections unsupervised. He had undertaken only locum sessions over a 10 month period in 2015 and worked as a senior house officer in the specialty 20 years before.

He had never been recruited into a formal training programme either in …
Is overall survival in multiple myeloma associated with a shortage in health care providers? A SEER database analysis.
Authors: Dipesh Uprety, Thomas M. Churilla
Journal: Journal of Clinical Oncology (2014)

e19588 Background: The U.S. Department of Health and Human Services designates counties as Primary Care Health Professional Shortage Areas (HPSAs) based on a population to physician ratio. If the ratio is greater than 3,500:1, an area is eligible to be designated as a primary care HPSA. The purpose of our study was to evaluate overall survival in multiple myeloma patients living in HPSA vs. non-HPSA designated areas in the United States. Methods: The design of the study was a case-control analysis. Adult patients (age≥20 years) with multiple myeloma from 2000-2010 were identified through the Surveillance, Epidemiology, and End Results (SEER) database, and counties designated as HPSAs were identified through the Health Resources and Services Administration website (Basic HPSA Reports: Primary Medical Care). Cases represented patients living in counties with HPSA designation, while controls represented patients living in counties without HPSA designation. Cases were defined by linking HPSA status to SEER data through Federal Information Processing Standard (FIPS) county codes. Overall Survival was assessed with respect to HPSA designation by Kaplan-Meier analysis and the log rank test. Statistical significance was defined as p < 0.05. Results: From 2000-2010, there were 51,769 patients with multiple myeloma identified through SEER database for analysis. Patients living in HPSA designated counties represented 51.3% of cases, while controls included 41.7% of patients residing in counties without HPSA designation. The median overall survivals for patients living in HPSA counties was 12 months, while the median overall survival for patients living in counties without HPSA designation was 13 months (p<0.001). Conclusions: Patients with multiple myeloma living in counties designated as Health Professions Shortage Areas demonstrated a modest, but significant decline in overall survival relative to patients living in counties without HPSA designation. The implications of this observation remain unclear, but likely warrant further investigation
Clonal Hematopoiesis of Indeterminate Potential
Authors: Steffen Boettcher, Benjamin L. Ebert
Journal: Journal of Clinical Oncology (2018)

Article Tools UNDERSTANDING THE PATHWAY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation. November 07, 2018 ARTICLE CITATION DOI: 10.1200/JCO.2018.79.3588 Journal of Clinical Oncology - published online before print December 27, 2018 PMID: 30589599 Clonal Hematopoiesis of Indeterminate Potential Steffen Boettcher, MD1,2xSteffen BoettcherSearch for articles by this author and Benjamin L. Ebert, MD, PhD1,2xBenjamin L. EbertSearch for articles by this author Show More 1Dana-Farber Cancer Institute, Boston, MA2Broad Institute of MIT and Harvard, Cambridge, MA https://doi.org/10.1200/JCO.2018.79.3588 First Page Full Text PDF Figures and Tables Supplements © 2018 by American Society of Clinical Oncology Companion Role of Donor Clonal Hematopoiesis in Allogeneic Hematopoietic Stem-Cell Transplantation
Abstract 14206: First-in-Human Study of an Autologous In-Body Tissue-Engineered Vascular Graft (Biotube type C) for Hemodialysis Access
Authors: Yasuhide Nakayama, Yoshiyuki Kaneko, Noriko Okumura
Journal: Circulation (2016)

Background and Purpose: An arteriovenous (AV) fistula is the current gold standard for chronic hemodialysis access. However, a substantial number of shunt will fail because of stenosis or obstructi...
Sexual problems of female cancer survivors compared to women without cancer.
Authors: Ah Reum An, Dong Wook Shin, Seung Mi Lee, Juhee Cho, Eunmi Ahn, Hyejin Lee, Ki Young Son, Ho-Chun Choi, Jin Ho Park, Belong Cho
Journal: Journal of Clinical Oncology (2014)

9586 Background: Sexual dysfunction is one of the distressing problems experienced by female cancer survivors. In this study, we aimed to investigate female sexual dysfunction of cancer survivors compared to women without cancer in South Korea across various cancer types. Methods: We performed a case-control study of 5,350 women visited the center for health promotion and optimal aging at Seoul National University Hospital between January 2010 to December 2011. Cases were defined as women who were diagnosed cancer before the health check-up and completed the female sexual function index (FSFI) questionnaires (n = 233), and controls were women without cancer before and after the health check-up and completed the FSFI questionnaires (n = 3,024). The control group was matched on age to survivors at a 1:1 ratio individually. Results: The proportion who are sexually active female cancer survivors were not different from that of controls (37.8% vs. 36.9%, P = 0.848). Among sexually active women, the mean total FSFI score were 22.3 ± 5.4 in cancer survivor group and 24.2 ± 4.4 in control group (P = 0.012). Cancer survivors scored lower than controls in domains of desire, lubrication and orgasm. Thyroid cancer survivors tended to have more difficulties having desire and reaching orgasm than their matched controls with marginal significance. Breast cancer survivors reported significantly more troubles in lubrication and more pain. Cancer survivors of other cancer types tended to have more dyspareunia compared to the controls. No difference in any aspects of sexual function was observed between gynecologic cancer survivors and the controls. Conclusions: Female cancer survivors have poorer sexual function compared to women without cancer. Sexual problems vulnerable in cancer survivors seemed different according to cancer types.
Preoperative malnutrition as criteria for tumor resection completeness and overall survival in patients with ovarian cancer: Results of a prospective study.
Authors: Paulina Skowronek, Marc Kuhberg, Rolf Richter, Frank Chen, Elena Ioana Braicu, Jalid Sehouli
Journal: Journal of Clinical Oncology (2014)

e16532 Background: The purpose of this study was to examine the impact of preoperative malnutrition on surgical outcome and overall survival in patients with ovarian and peritoneal cancer. Methods: Data from 152 patients with ovarian and peritoneal cancer were collected prospectively. Each patients nutritional status was assessed prior to cytoreductive surgery. The Nutritional Risk Score (NRS-2002) was used to determine patients at high nutritional risk (NRS≥3). The Bioelectrical Impedance Analysis (BIA) identified malnourished individuals (phase angle alpha Phα ≤ 4,5º) basing on body composition evaluation. Data to tumor resection were documented intraoperatively and together with follow-up information correlated with nutritional parameters. Results: The median age at the time of diagnosis was 56 years (range: 19-84). Overall 79 patients suffered from primary and 73 from recurrent disease. 28 (18,4%) patients were classified as at high nutritional risk (NRS≥3) and 44 (29,1%) were malnourished according to Phα. The complete tumor resection rate was significantly decreased by women with NRS≥3 compared to patients with NRS<3 (32,1% vs. 69,1%, p=0,014). By the malnourished (NRS≥3) overall survival was shorter than by the well-nourished (NRS<3) (median: 7 months, 95%CI=0-24 vs. 46 months, 95%CI not available, p=0,001). Multivariate analyses showed, that malnutrition is an independent predictor for non-complete tumor resection in patients with ovarian cancer (OR: 4,55, 95%CI=1,45-14,29, p=0,009 for NRS; OR: 5,56, 95%CI=1,75–16,67, p=0,003 for Phα). Also as measured by Phα≤ 4,5º malnutrition is an independent prognostic factor for overall survival (HR: 2,88, 95%CI=1,60–5,19, p<0,001). There is however no independent significant correlation between NRS-2002 and overall survival (p=0,051). Conclusions: In ovarian and peritoneal cancer patients malnutrition is an independent predictor of non-complete tumor resection. As measured by Phα, but not NRS-2002, it is also an independent prognostic factor for poor overall survival. Preoperative evaluation of nutritional status seems to be a valid method to predict clinical outcome in these patients.
A chimeric antibody (MV-DN30) inhibiting
Authors: Elisa Vigna, Fiorella Petronzelli, Silvia Giordano, Paolo Maria Comoglio
Journal: Journal of Clinical Oncology (2014)

e14019 Background: Clinical evidence indicates that the MET oncogene plays a role in progression of cancer toward metastasis and/or resistance to targeted therapies. While mutations are rare, the common mechanism of MET activation is overexpression, either by gene amplification (addiction) or transcriptional activation (expedience: Nature Rev Drug Discov 2008; 7: 504). In both instances ligand-independent kinase activation plays the major role in sustaining the transformed phenotype. Currently available MET antibodies are directed against the receptor binding site, behaving essentially as ligand (HGF) antagonist, and are ineffective in ligand-independent activation Methods: The monovalent chimeric MV-DN30 antibody (Metheresis Translational Research SA, Lugano), delivered as purified protein, binds the fourth IPT extracellular domain and induces proteolytic cleavage of MET, dramatically inhibiting downstream signaling pathways, in both absence or presence of ligand (J Biol Chem 2010; 285: 36149). As an inventive approach, Mv-DN30 was delivered by gene therapy driven by a implemented bidirectional lentiviral vector (Cancer Res 2008; 68 :9176) Results: In vitro, the antibody displayed a strong inhibition of ligand-independent invasive growth of MET ‘addicted’ cancer lines, and –notably- of primary cells from a MET amplified gastric ca. patient. In vivo the anti-body strongly impaired the growth of a panel of MET addicted human cancer lines, xenotransplanted in nude mice lacking HGF. In patient-derived RAS wt colorectal cancer xenografts, MET amplification was found to correlate with resistance to anti-EGFR therapy. By the gene therapy approach, direct Mv-DN30 gene transfer in nude mice, intra-tumor or systemic, was followed by a therapeutic response of MET addicted human glioblastomas and lung carcinomas Conclusions: The MV-DN30 antibody is a strong candidate for targeting tumors sustained by a ligand-independent MET oncogenic activation resulting from MET amplification or mutations, and for overcoming resistance to anti-EGFR therapies. These results also provide proof of concept for a gene transfer immunotherapy strategy and encourage clinical studies with Mv-DN30.
Initial utilization of Oncotype DX in the Medicare population between 2005 and 2007.
Authors: Michaela Ann Dinan, Xiaojuan Mi, Shelby D. Reed, Bradford Richard Hirsch, Gary H. Lyman, Lesley H Curtis
Journal: Journal of Clinical Oncology (2014)

6508 Background: In 2005 the Centers for Medicaid and Medicare Services approved reimbursement for the Oncotype DX (ODX) 21-gene assay in women with early stage ER-positive, node negative breast cancers to help guide recommendations for adjuvant chemotherapy. This analysis provides the first nationally representative examination of the adoption of ODX in Medicare beneficiaries with breast cancer. Methods: Retrospective analysis of SEER-Medicare linked data for breast cancer patients diagnosed between 2004 and 2007 was used to characterize overall utilization of ODX and identify demographic and clinical factors associated with receipt of ODX. Results: A total of 46,084 Medicare beneficiaries diagnosed with breast cancer in the SEER registries met study criteria. Utilization of ODX testing among newly diagnosed Medicare breast cancer patients increased from 1.2% to 5.2% among all stages and subtypes and from 1.9% to 7.5% among women with localized, ER positive, node negative disease from 2005 to 2007. As compared to patients who did not receive ODX testing, beneficiaries who received ODX testing were more likely to have higher baseline histologic grade, larger tumor sizes, and be ER and PR positive. Increasing age category (71-75, 76-80, 80 or older) and number of comorbidities (1, 2 or more) conditions were associated with a decreased odds of receiving ODX, whereas being married was associated with increased odds of receiving ODX testing in multivariable analysis (all P<0.001). Relative to patients with stage 1 disease, patients with stage 0, II, III, and IV disease all had decreased odds of receiving ODX (OR 0.02, 0.55, 0.04, 0.04, all P<0.001). We found no significant difference in regional ODX utilization. Conclusions: Following the approval of ODX coverage by CMS in 2005, the utilization of ODX has significantly increased. Utilization was largely limited to patients in whom testing is considered medically necessary by CMS and is supported by current guidelines, and in younger and healthier patients in whom chemotherapy would be more likely to be a clinically appropriate management option. The impact and utilization of ODX adoption on the care of breast cancer patients in the future remains an important area of health policy research.
A Phase I/Ib Study of Nivolumab for Relapsed Hematologic Malignancies after Allogeneic Hematopoietic Cell Transplantation (alloHCT)
Authors: Matthew S. Davids, Haesook T. Kim, Caitlin L. Costello, Alex F. Herrera, Frederick L. Locke, Rodrigo O. Maegawa, Alexandra Savell, Michael Mazzeo, David E. Avigan, Yi-Bin Chen, Sarah Nikiforow, Vincent T. Ho, Corey S. Cutler, Edwin P. Alyea, Pavan Bachireddy, Catherine J. Wu, Howard Streicher, Edward D Ball, Asad Bashey, Robert J. Soiffer, Philippe Armand
Journal: Blood (2018)