tbuckley/cabot-search huggingface dataset:
A multicentric phase II randomized trial of docetaxel (D) plus estramustine (E) versus docetaxel (D) as first line chemotherapy for patients (pts) with hormone-refractory advanced prostate cancer (HRPC)
Authors: O. Caffo, T. Sava, E. Comploj, A. Fariello, F. Zustovich, F. Valduga, M. Frisinghelli, R. Segati, C. Sacco, A. Perin, G. Pappagallo
Journal: Journal of Clinical Oncology (2006)

4625 Background: D is presently considered a standard treatment for HRPC pts. E has shown a synergistic activity with D in vitro, however the role of D+E combination remains to be defined in the clinical practice. We attempted to evaluate the activity, in terms of PSA decline (PSA↓), the safety and quality of life (QoL) of D ± E in HRPC pts. Methods: eligibility criteria were: HRPC diagnosis, hormone-refractory advanced disease (PSA progression after at least two hormonal therapy), ECOG PS ≤ 2, adequate renal, hepatic and hematological functions. Pts were randomized to D 70 mg/m 2 IV d1 q3w (arm A) or D 70 mg/m 2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B). The treatments were planned until best PSA response achievement or PSA progression. No anticoagulant prophylaxis was planned in ARM B pts. Qol was assessed by self-filled questionnaires during the treatment. Results: Between 04/2003 and 09/2005, 95 pts (median age 69 years, range 48–86, median PSA 80 ng/ml, range 5–2166 and measurable disease in 45) were randomized to arm A (49) or arm B (46). To date, 9 pts and 6 pts are still on treatment in arm A and B respectively. In arm A, pts received 257 cycles (median 5, range 1–14) with only 10 (3.9%) delays ≥ 7 days. In arm B, pts received 317 cycles (median 7, range 0–20) with only 15 (4.7%) delays. Median follow-up was 19.5 months. Grade 3–4 hematological toxicities consisted of neutropenia, 4% in arm A and 8% in B, anemia, 0% and 2% respectively and 1 pt with febrile neutropenia and grade 3 diarrhea (Arm B). Grade 3−4 non-hematologic toxicities were vomiting (1 pt) in arm A, stomatitis (2 pts) and vomiting (1 pt) in arm B. Two cases of stroke were reported in arm A. Responses, in terms of PSA↓ &gt;50% were: 43% in arm A and 70% in arm B with PSA normalization in 8% and 38% respectively. Progression free survival (biochemical) was 20 weeks in arm A and 31 in B. Analysis concerning QoL outcomes is planned at the treatment completion of all pts. Conclusions: D-based regimens are active in HRPC with a low toxicity profile. From this preliminary data, DE combination appears promising, in terms of activity and tolerability so, front-to-front formal comparison in a phase III trial can be recommended. No significant financial relationships to disclose.
Smoking and Mortality — Beyond Established Causes
Authors: Carla Estaquio, Hermann Nabi, Guy-Robert Auleley
Journal: New England Journal of Medicine (2015)

To the Editor: The longitudinal cohort study by Carter et al. (Feb. 12 issue)(1) provides evidence of new causes of death associated with smoking. We were surprised by the authors' statement that among the deaths that were associated with smoking, a small proportion was due to other, less plausibly causal, associations with outcomes, such as suicide and accidents. The tables in the Supplementary Appendix of the article (available at NEJM.org) show that for current smokers who were 55 years of age or older, the relative risk of death was 4.4 from suicide and 1.6 from accidents among women and 3.2. . . Language: en
Comparison of CSF Cytology and Spinal Magnetic Resonance Imaging in the Detection of Leptomeningeal Disease in Pediatric Medulloblastoma or Primitive Neuroectodermal Tumor
Authors: Maryam Fouladi, Amar Gajjar, James M. Boyett, Andrew W. Walter, Stephen J. Thompson, Thomas E. Merchant, Jesse J. Jenkins, James W. Langston, Aiyi Liu, Larry E. Kun, Richard L. Heideman
Journal: Journal of Clinical Oncology (1999)

Leptomeningeal disease (LMD) significantly affects the prognosis and treatment of pediatric patients with medulloblastoma or primitive neuroectodermal tumor (PNET). Examination of CSF for malignant cells, detection of LMD on spinal magnetic resonance imaging (MRI), or both are the methods routinely used to diagnose LMD. A recent study suggested 100% correlation between CSF and MRI findings in children with medulloblastoma. To determine the validity of this hypothesis, we compared the rate of detection of LMD between concurrent lumbar CSF cytology and spinal MRI performed at diagnosis in patients with medulloblastoma or PNET.As a part of diagnostic staging, 106 consecutive patients newly diagnosed with medulloblastoma or PNET were evaluated with concurrent lumbar CSF cytology and spinal MRI. CSF cytology was examined for the presence of malignant cells and spinal MRI was reviewed independently for the presence of LMD.Thirty-four patients (32%) were diagnosed with LMD based on CSF cytology, spinal MRI, or both. There were 21 discordant results. Nine patients (8.5%) with positive MRI had negative CSF cytology. Twelve patients (11.3%) with positive CSF cytology had negative MRIs. The exact 95% upper bounds on the proportion of patients with LMD whose disease would have gone undetected using either CSF cytology or MRI as the only diagnostic modality were calculated at 14.4% and 17.7%, respectively.With the use of either CSF cytology or spinal MRI alone, LMD would be missed in up to 14% to 18% of patients with medulloblastoma or PNET. Thus, both CSF cytology and spinal MRI should routinely be used to diagnose LMD in patients with medulloblastoma or PNET.
Suppression of Infectious Murine Leukemia Virus in Wild Mice ( Mus musculus ) by Passive Immunization: Brief Communication 2 3
Authors: Murray B. Gardner, Vaclav Klement, John D. Estes, Raymond V. Gilden, Robert Toni, Robert J. Huebner
Journal: JNCI Journal of the National Cancer Institute (1977)

Passive immunization with heterologous antivirus antiserum beginning at birth successfully suppressed infectious murine leukemia virus expression in Lake Casitas wild mice (Musmusculus) at 5-7 weeks of age.
Efficacy of carboplatin, docetaxel, and capecitabine (CTX) in the treatment of patients with advanced or metastatic upper gastrointestinal tract carcinomas. A retrospective analysis
Authors: Z. Ujmajuridze, E. Ehrnrooth, E. Lassen, H. H. Hansen
Journal: Journal of Clinical Oncology (2008)

15629 Background: The prognosis for patients with cancers of the upper gastrointestinal tract remains poor and better treatment is urgently needed. The objective of this study was to evaluate the efficacy and toxicity of carboplatin, docetaxel and capecitabine as the treatment in patients with inoperable (locally advanced) or metastatic adeno- and squamous cell carcinoma of the esophagus or stomach. Methods: The retrospective analysis included patients referred to the Finsen Center from February 2002 to August 2006. Eligibility criteria included the following: histopathologically documented carcinoma of the oesophagus, esophagogastric junction (EG) or stomach; no previous chemotherapy for upper GI cancer (except for concomitant chemo-radiotherapy); evaluable disease as evaluated according to RECIST criteria. The treatment (CTX) consisted of carboplatin AUC 5 i.v., docetaxel 75 mg/m2 i.v. and capecitabine 1000 mg/m2 twice daily for 14 days on a 4-week cycle. Results: Patient characteristics were as follows: 51 patients met the inclusion criteria; male:female, 40:11; median age 57 years (range, 34 to 77 years); adenocarcinoma:squamous cell carcinoma:carcinoma, 44:3:4; and esophagus:EG:gastric:unspecified, 9:28:13:1. The overall response rate was 29%, including 3 complete responses and 12 partial responses. The median progression-free survival was 8.8 months (95% CI = 7.8–9.8) and the overall survival 10.3 months (95% CI= 8.9–11.8) from the first day of the CTX treatment. Main dose-limiting toxicity was hematologic with neutro- and thrombocytopenia, PPE and diarrhoea. Conclusions: The CTX regimen is an effective and fairly well-tolerated treatment of advanced and metastatic upper GI carcinomas that can be given in the out-patient clinic. The median progression-free survival as well as overall survival is comparable with other types of 3-drug combinations in advanced esophageal and gastric cancer and the toxicity was manageable. The efficacy needs further confirmation in a randomized trial. No significant financial relationships to disclose.
Excellent treatment results of alternating chemoradiotherapy for nasopharyngeal cancer-A phase II study-
Authors: N. Fuwa, T. Kodaira, K. Furutani, H. Tachibana, K. Toita, N. Shikama, M. Kano, A. Yuta, N. Hayashi, H. Onishi
Journal: Journal of Clinical Oncology (2005)

5570 Background: Nasopharyngeal cancer (NPC) is characterized by a high frequency of distant metastasis and mucositis was a marked problem even when radiotherapy (RT) alone was performed. Considering these characteristics of NPC, alternating chemoradiotherapy (ALT-CRT) may be a useful method of treating NPC because sufficient amount of anti-tumor agents can be administered together with a low frequency of mucositis compared to concurrent chemoradiotherapy (CRT). Methods: The subjects consisted of 20 patients with stage II, 31 patients with stage III and 35 patients with stage IV. Using 6 MV photon, RT was performed at an exposure of 1.8Gy 5 times a week. That is, a total absorbed dose of 36 Gy was irradiated between the basal of skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 30–34Gy was additionally given thereafter. One course of chemotherapy (CT) consisted of the administration of 5-FU at a dose of 800 mg/m2/24 h for 5 days (days 1–5) and CDDP at a dose of 50 mg/m2/24 h for 2 days (days 6–7), and a total of 3 courses of CT was performed. During the ALT-CRT, CT was performed initially; and 2–3 days after completing the CT, RT was performed for 4 weeks. Thereafter, CT and RT were performed alternately. Results: The scheduled courses of ALT-CRT were completed in 69 (80%) of 86 patients. No severe adverse effects were noted in any other patients. In these 86 patients, the overall 3-year survival rate was 95%, and the progression free survival rate was 82.5% (The median follow up times was 37 months). Conclusions: This method of ALT-CRT yielded higher or at least similar survival rate and lower toxicities than concurrent CRT, and we believed that this method can be used in a controlled clinical trial in the future to compare therapeutic results with those of the Intergroup 0099 Trial. No significant financial relationships to disclose.
The ICSI procedure from past to future: a systematic review of the more controversial aspects
Authors: Patrizia Rubino, Paola Viganò, Alice Luddi, Paola Piomboni
Journal: Human Reproduction Update (2015)

ICSI is currently the most commonly used assisted reproductive technology, accounting for 70–80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment. This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation. More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure. This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
Dissecting Pulmonary Large-Cell Carcinoma by Targeted Next Generation Sequencing of Several Cancer Genes Pushes Genotypic-Phenotypic Correlations to Emerge
Authors: Giuseppe Pelosi, Alessandra Fabbri, Mauro Papotti, Giulio Rossi, Alberto Cavazza, Luisella Righi, Elena Tamborini, Federica Perrone, Giulio Settanni, Adele Busico, Maria Adele Testi, Patrick Maisonneuve, Filippo De Braud, Marina Garassino, Barbara Valeri, Angelica Sonzogni, Ugo Pastorino
Journal: Journal of Thoracic Oncology (2015)
The role of misonidazole combined with intraoperative radiation therapy in the treatment of pancreatic carcinoma.
Authors: J E Tepper, W U Shipley, A L Warshaw, G L Nardi, W C Wood, E L Orlow
Journal: Journal of Clinical Oncology (1987)

We tested the efficacy of the hypoxic cell sensitizer misonidazole in conjunction with intraoperative electron beam radiation therapy (IORT) and external beam irradiation in patients with locally advanced, nonmetastatic adenocarcinoma of the pancreas. Misonidazole was delivered intravenously (IV) at a dose of 3.5 g/m2 in conjunction with IORT of 1,500 to 2,000 cGy to the pancreas. Additional external beam radiation as administered to 4,960 cGy. The study was based on the premise that the effect of misonidazole would be maximized when a high dose of the drug was administered and, thus, high hypoxic cell sensitization could be obtained when using a high single dose of radiation where the hypoxic fraction would be expected to dominate in the survivors. In a nonrandomized study of 41 patients treated with misonidazole and 22 without, the 1-year local control was 67% and 55%, and 1-year survival was 50% and 77%, respectively. Although there was a bias towards larger tumors in the patients treated with the sensitizer, we were unable to demonstrate an advantage to misonidazole in this clinical situation.
Isolation of Antibodies Specific for Avian Viral and Cellular myc Proteins2
Authors: Jonathan H. Morgan, Takis S. Papas, J. Thomas Parsons
Journal: JNCI Journal of the National Cancer Institute (1985)

The myc gene has been implicated in the genesis of various neoplasms in birds, mice, and humans and was originally identified as the cellular homologue of the transforming gene (v-myc) of the avian myelocytomatosis virus MC29. For specific antisera to be obtained for the myc gene product, a bacterial expression vector was constructed in which the coding sequences for approximately 20 kd of MC29 p110gag-myc (amino acid residues 502 to 678) were placed between the coding sequences for the amino terminal 13 kd of Rous sarcoma virus pp60src and the coding sequences for 112 kd of beta-galactosidase. Expression of this tripartite gene was driven by a hybrid trp-lac promoter under lac repressor control. Induction of expression resulted in the production of a 145-kd hybrid protein containing src, myc, and beta-galactosidase sequences. The hybrid protein was purified and injected into rabbits to produce antisera. The resultant antisera immunoprecipitated p110gag-myc and p58myc -p60myc from MC29- and MH2-infected nonproducer quail fibroblasts, respectively. In addition, the antisera also immunoprecipitated a 58-kd protein from the bursal lymphoma cell line BK25, which was identified as chicken c (cellular)-myc gene product.
Abstract 12446: Predictors of Early Cerebrovascular Events Following Transcatheter Aortic Valve Implantation. Insights From a Large Cohort Of Patients
Authors: Luis Nombela-Franco, John G Webb, Peter de Jaegere, Stefan Toggweiler, Rutger Jan Nuis, Antonio E Dager, Ignacio J Amat-Santos, Anson Cheung, Jian Ye, Robert M van der Boon, Nicolas M Van Mieghem, Luis M Benitez, Sergio Perez, Javier Lopez, Alberto San Roman, Daniel Doyle, Robert DeLarochelliere, Jonathon Leipsic, Eric Dumont, Josep Rodes-Cabau
Journal: Circulation (2012)

Background: Transcatheter aortic valve implantation (TAVI) represents an alternative to surgical aortic valve replacement in high risk patients, but recent studies have raised major concern because of increase cerebrovascular event (CVE) rates. The aim of the study was to evaluate the timing and predictive factors of CVE following TAVI. Methods: TAVI with balloon- (64%) or self- (36%) expandable valve was performed in 1061 consecutive patients in five centers. CVE were classified as acute (≤24 hours) or subacute (1 to 30 days) according to the timing and categorized as transient ischemic attack (TIA) or stroke (major or minor), according to the VARC criteria. All clinical, echocardiographic, procedural, and follow-up data were prospectively recorded. Results: CVE occurred in 54 patients (5.1%), which 29 (54%) were acute and 25 (46%) subacute. The 30-day rate of TIA, minor and major stroke was 0.8%, 1.4% and 2.8%, respectively. Hemorrhagic stroke was recorded in 2 patients. Balloon postdilation (OR: 2.46, ...
Analysis of ERCC1 (excision repair cross complementing group 1) in squamous cell carcinoma of the head and neck (SCCHN) by quantitative immunohistochemistry (IHC) using FL297.
Authors: R. Mehra, K. Q. Cai, F. Zhu, J. Weaver, N. Nicolaou, R. B. Cohen, M. Lango, J. A. Ridge, A. K. Godwin, B. Burtness
Journal: Journal of Clinical Oncology (2010)

5539 Background: We previously found that low nuclear ERCC1 measured by AQUA with the antibody (ab) 8F1 is associated with a higher survival (75.6 months) compared to high nuclear ERCC1 (28.4 months, p=0.02) in patients (pts) with SCCHN treated with surgery and adjuvant radiation/chemoradiation (RT/CRT). We extended this analysis with FL297, a polyclonal antibody reported to be highly specific for ERCC1. Methods: Tissue microarrays were constructed with SCCHN samples from pts treated at Fox Chase Cancer Center from 1990-2002. Slides were stained by a modified indirect immunofluorescence method. Sections were incubated with ERCC1 ab (FL297, Santa Cruz Biotech) and wide-spectrum screening rabbit cytokeratin ab (Dako Z0622). Prolong Gold mounting medium (P36931; Molecular Probes) containing 4,6-Diamidino-2-phenylindole (DAPI) defined nuclei. A tumor mask (TM) image was created from the cytokeratin stain of each histospot. ERCC1 levels were measured using fluorescent IHC on the HistoRx PM-2000 image analysis platform and data analyzed using AQUA algorithms, generating quantitative measurements of protein levels within subcellular compartments. TM, nuclear (N), and cytoplasmic (C) ERCC1 expression were measured. Overall survival was analyzed using Kaplan-Meier method, with comparisons using the log-rank test. Results: 109 pts were included (70 male). Primary sites were: tongue (34), glottic (15), retromolar trigone (10), tonsil (5), pyriform sinus (3), oral cavity (36), other (6). 33 were treated with surgery. 76 received adjuvant RT or platinum based CRT. ERCC1 expression by AQUA score was defined as high versus low at the 30th percentile (2902.9 in N, 1577.1 in C, 2998.3 in TM), as in prior reports. For pts treated with surgery (p=0.33) or adjuvant RT/CRT (p=0.29), nuclear ERCC1 was not associated with survival. Conclusions: Similar to analysis with 8F1, AQUA with FL297 identifies N and C ERCC1 signal. In contrast to 8F1, ERCC1 levels with FL297 are not associated with survival differences in pts who received adjuvant therapy. Future analyses of ERCC1 expression for prediction or prognosis should use 8F1. No significant financial relationships to disclose.
The relationship of cigarette smoking to invasive fungal disease (IFD) in acute myeloid leukemia (AML) patients undergoing induction chemotherapy (IC).
Authors: M. G. Mansour, A. Z. Fu, E. A. Copelan, M. E. Kalaycio, A. S. Advani, Y. Saunthararajah, R. M. Sobecks, M. A. Sekeres
Journal: Journal of Clinical Oncology (2010)

6547 Background: Marijuana use has been linked with IFD in immunocompromised patients. Although cigarettes also contain aspergillus spores, the effect of being a cigarette smoker (CS) on developing IFD has not before been established in this population. We investigated whether being a CS increased the risk of IFD in AML patients (pts) undergoing IC. We defined IFD as proven, probable or possible using the Revised Infectious Diseases Society of America (IDSA) guidelines. Methods: We conducted a retrospective review of all AML pts treated with cytarabine-based IC at Cleveland Clinic between 1994 and 2008. Data on age, race, AML etiology, FAB or WHO classification, WBC at diagnosis (dx), cytogenetics, consolidation therapy, marijuana use, steroid use prior to AML dx, bone marrow transplant (BMT), timing of IFD, pack yrs, past smoking status, and achievement of complete remission (CR) were collected and controlled for in multivariable analyses. A logistic regression was used to assess the association between being a CS and IFD, and being a CS and overall survival (OS). Results: Mean age was 58 yrs (range, 17- 92). Of 741 pts, 45% were female, 27% had secondary AML, 24% were current CS, 18% were past CS, 3% used marijuana, and 36% developed IFD. Compared to non-smokers (NS), CS were significantly younger (53 vs. 60 yrs, p < 0.0001), more likely to be male (48% vs. 38%, p = 0.023), to have de novo AML (76% vs. 64%, p = 0.011), to use marijuana (11% vs. 0.2%, p < 0.0001), and to develop IFD (89% (proven/probable/possible = 8%/53%/28%) vs. 19%, p < 0.0001). Overall, 53% of pts achieved CR. There were no differences between groups in FAB, cytogenetics, WBC, time from admission to IC, pack yrs, chronic steroid use prior to AML dx, developing IFD post BMT, consolidation, and achieving a CR. Median OS for CS vs. NS were 0.64 vs. 0.84 yrs, p = 0.23. In multivariable analyses, smoking remained significantly associated with IFD (hazard ratio 39.4, p value < 0.0001). Conclusions: Even after adjusting for patient disease, prognostic factors, and treatment factors that could influence IFD, CS who underwent IC were significantly more likely to develop IFD, and should be considered for intensive antifungal prophylaxis. No significant financial relationships to disclose.