tbuckley/cabot-search huggingface dataset:
The onset of skeletal complications in hormone refractory prostate cancer patients is not influenced by the duration of androgen deprivation therapy
Authors: M. Tucci, A. Berruti, A. Mosca, G. La Manna, F. Vana, C. Terrone, M. Tampellini, R. Tarabuzzi, G. Gorzegno, L. Dogliotti
Journal: Journal of Clinical Oncology (2004)

4700 Background: Skeletal complications frequently complicate the natural history of prostate cancer with metastatic bone disease. Androgen deprivation therapy (ADT), the mainstay of therapy for advanced prostate cancer, induces osteoporosis and may cause adverse skeletal related events (SRE) irrespective of disease progression in bone. SRE, however, are relatively uncommon until the tumor is responsive to ADT but they are more frequent when the tumor become hormone refractory. The relative contribution of ADT in predisposing SRE in hormone refractory stage is totally unknown. Methods: From July 1990 to September 2003, 205 prostate cancer patients with hormone refractory disease were treated and followed in our Institution. Eighty-three of them (41.0%) underwent SRE defined as vertebra collapses (20.0%), bone fractures (12.7%), spinal cord compression (8.0%). SRE occurred before hormone refractoriness in 8 patients (3.9%). Results: Hormone refractory patients destined to undergo SRE had at baseline conditions greater bone pain (p=0.002), greater values of serum bone alkaline phosphatase (p<0.01), and urinary N-telopeptide (p=0.02) than their counterpart. There was no difference in serum calcium levels and serum PSA between the 2 groups. The distribution of SRE did not differ in patients with blastic bone lesions (40.5%) as opposed to those with lytic/mixed bone lesions (53.7%). Stratifyfing patients according to disease extent in bone, the distribution of SRE was 31.7% in patients with ≤ 3 bone lesions, 40.5% in patients with 3–6 bone lesions and 53.6% in patients with > 6 bone lesions (p=0.01). Median duration of ADT (range) was 22.9 months (1.1–138.) in hormone refractory patients destined to undergo SRE and 25.9 months (1.0–211) in hormone refractory patients who did not develop SRE (p=n.s.). Conclusions: the occurence of SRE in hormone refractory prostate cancer with metastatic bone disease is significantly influenced by tumor load in bone, levels of bone turnover markers, but not by the duration of androgen deprivation therapy. No significant financial relationships to disclose.
Abstract P376: Risk Factors for the Progression and Incidence of Aortic Calcification in an International Multi-ethnic Cohort of Men Aged 40-49 Years: ERA JUMP Study
Authors: Siyi Shangguan, Jingchuan Guo, Hemant Mahajan, Kamal Masaki, Bradly J Willcox, Katsuyuki Miura, Hirotsugu Ueshima, Akira Fujiyoshi, Takashi Hisamatsu, Lewis H Kuller, Emma J Barinas-Mitchell, Daniel Edmundowicz, Akira Sekikawa
Journal: Circulation (2017)

Background: Aortic calcification (AC) is independently related to cardiovascular (CV) disease mortality. No previous study has examined associations of risk factors with the progression of calcification in the entire aorta. Methods: 1033 men aged 40-49 years without overt CV diseases from the ERA-JUMP cohort were examined for AC, CV risk and other factors in 2002-07 with rigid standardization with a median follow-up of 5.9 years. AC was assessed by electron-beam CT and was quantified using the Agatston’s method. We defined annual AC progression as the absolute difference of Agatston score divided by follow-up time in years, which was further dichotomized at the 80th percentile: ≥100/year vs. &lt;100/year. In participants free of detectable AC at baseline, AC incidence was calculated. Logistic regressions were performed to analyze the association of risk factors with both annual AC progression and AC incidence. AC progression was adjusted for baseline AC and AC incidence was adjusted for follow-up time. Results: After excluding missing data (n=287) and extreme outliers (n=10), our sample included: 234 Caucasian, 53 African American, 207 Japanese American and 242 Japanese in Japan. AC was present in 55.3% (407 out of 736) at baseline. Baseline mean (SD) of age, pack-years of smoking, systolic blood pressure (SBP), BMI, LDL-C and AC Agatston score were 45.3 (2.9) years, 9.1 (14.0) pack-year, 124.5 (13.4) mmHg, 26.6 (4.6) Kg/m2, 129.7 (33.9) mg/dl and 103.0 (336.8), respectively. Overall analysis showed that baseline BMI, smoking, SBP and diabetes were significant or marginally significant determinants of AC progression (table 1). Incidence analysis showed that baseline smoking, SBP and LDL-C were significant or marginally significant determinants of AC incidence. Japanese in Japan displayed significantly lower incidence as well as progression. Conclusion: Both AC progression and incidence were closely related to multiple traditional CV risk factors, most significant for pack-years of smoking and blood pressure.
The effects of global and targeted advance care planning efforts at a national comprehensive cancer center.
Authors: Finly Zachariah, Lindsay Emanuel, Gayle Ito-Hammerling, Judy Wong-Toh, Denise Morse, Linda Klein, Matthew J. Loscalzo, Nellie Garcia, Sorin Buga, Michael Lew, David Horak, Chandana Banerjee, Stefanie Mooney, Joseph C. Alvarnas
Journal: Journal of Clinical Oncology (2017)

79 Background: Advance Care Planning is a central component of patient centered care and helps assure treatment aligns with a patient’s goals, values, and priorities. Various studies demonstrate advance care planning decreases stress and anxiety, increases satisfaction, improves awareness and implementation of a patient’s end of life wishes, and reduces costs in select populations. At City of Hope (COH) National Medical Center, we made concerted efforts over the last four years to improve the overall number of advance directives(ADs), and have additionally focused on improving AD capture rates in clinically relevant populations (patients undergoing surgery, those with metastatic disease, and those undergoing hematologic transplant). Methods: The Department of Supportive Care Medicine with executive team endorsement and in collaboration with medical oncology, hematology, anesthesia, surgery, nursing, marketing, and informatics created a patient-centric advance care planning program. We developed disease specific workflows, created multi-lingual AD workshops in the Sheri &amp; Les Biller Patient and Family Resource Center, changed policy to provide complimentary patient/caregiver and staff notarizations for ADs, leveraged the electronic medical record (assured providers were able to document discussions, know when ADs were absent, and easily retrieve ADs when present), deploy AD specific screening questions, and most recently created a culturally sensitive branding campaign coined “Plan Today for Tomorrow.” Results: The rate of advance directive capture for all patients new to COH has continuously improved from 12% in 2012 to 22% in 2016. In transplant patients, AD capture rate increased to 63%. In a pilot for bladder cancer patients undergoing cystectomy, ADs were increased to 68%, and in the pre-anesthesia testing clinic, ADs were increased to 35%. Conclusions: We have made significant strides in the capture of advance directives at City of Hope with markedly higher capture rates in selectively targeted, clinically relevant populations. We anticipate improved patient centric care as a result, with the unintended consequence of cost savings and decreased resource utilization.
Characterization of heart failure patients with mid‐range left ventricular ejection fraction—a report from the <scp>CHART</scp>‐2 Study
Authors: Kanako Tsuji, Yasuhiko Sakata, Kotaro Nochioka, Masanobu Miura, Takeshi Yamauchi, Takeo Onose, Ruri Abe, Takuya Oikawa, Shintaro Kasahara, Masayuki Sato, Takashi Shiroto, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
Journal: European Journal of Heart Failure (2017)
A phase I/II study of azacitidine in combination with temozolomide in patients with unresectable or metastatic soft tissue sarcoma or malignant mesothelioma.
Authors: Gleneara Elizabeth Bates, Robert N. Taub, Igor Matushansky, Thomas S. Uldrick, Maya Khandker, Yaakov Bressler, Yi Wang
Journal: Journal of Clinical Oncology (2014)

10560 Background: Soft tissue sarcomas are rare tumors, for which complete surgical resection offers the best chance of survival. However, two thirds of diagnosed tumors are unresectable and/or metastatic, with a median survival of 12 months, and chemotherapy is the only treatment option. Temozolomide has been used in soft tissue sarcomas and has shown the most activity in leiomyosarcomas; response rates ranged from 5-15%. Azacitidine has not previously been used in the treatment of soft tissue sarcomas. Because of known effects of hypomethylating agents on caspase-8 genes, and the DNA repair gene MGMT involved in the action of temozolomide, we hypothesized that incorporating azacitidine into the treatment of soft tissue tumors with temozolomide could enhance its efficacy. Methods: Between June 2008 and July 2012, 28 patients with soft tissue sarcomas were enrolled. Among the 25 patients who completed the treatment, median age was 61 (range 41-83), 13 male and 12 female; 4 liposarcoma, 2 myxoid liposarcoma, 1 synovial sarcoma, 1 granular cell sarcoma, 1 epithelioid mesothelioma, 1 Ewing's sarcoma, 1 hemangioepithelioma, 7 leiomyosarcoma, 1 spindle cell sarcoma and 6 unspecified sarcoma. Treatment consisted of 10-11 cycles of azacitidine and temozolomide. Dosing: Azacitidine: dose level 1: 25mg/m2 SQ qd; dose level 2: 50mg/m2 SQ qd; dose level 3: 75 mg/m2 SQ qd; combined with temozolomide: 200 mg/m2PO qd x 5; both on days 1-5 of a 28-day cycle. Toxicity was graded by CTCAE IV. Results: Median number of cycles administered: 2 (range 1-6). There were nine drug-related adverse events experienced by 3 or more patients, none of which were dose-limiting. The maximum tolerated dose was 200mg/m2 temozolomide and 75 mg/m2 azacitidine. 15 patients died from their disease 2-59 months after enrollment; 10 patients are alive with stable disease. The median overall survival was 22 (95% CI:9-59) months, with a 1-year survival of 64% (95% CI:42-79%). Conclusions: We have not yet determined the antitumor effectiveness of this combination. These encouraging data show that temozolomide combined with azacitidine can be administered in their full doses with no dose-limiting toxicities. Clinical trial information: NCT00629343.
Multiplexed IHC analysis to enable Hodgkin lymphoma differential diagnosis on a single slide.
Authors: Lawrence Weiss, Alexander Bordwell, Alex Corwin, Dave Henderson, Denise Hollman- Hewgley, Kevin Kenny, Michael Lazare, Colin McCulloch, Antti Seppo
Journal: Journal of Clinical Oncology (2013)

e19536 Background: Routine diagnosis of classical Hodgkin lymphoma is performed with a panel of immunohistochemistry markers to evaluate the biomarker expression profile of the relatively rare Hodgkin cells. One of the key challenges of this technique is that serial immunostains are used and hence it can be difficult or impossible to locate the same Hodgkin cell on adjacent slides. Given the rarity of the Hodgkin cells coupled with the number of markers that are needed for a definitive diagnosis, we developed a new technique in which a single patient slide is multiplexed with nine different antibodies . Methods: One FFPE tissue section from 11 cases was probed for the following nine biomarkers: CD30, CD15, CD45, Pax5, CD20, CD79a, OCT2, Bob1, and CD3. An initial 10x whole slide fluorescent image of CD30 was acquired and presented to the pathologist who based on this staining selected regions of interest for higher magnification (40x) imaging of the CD30 and the other antibodies. The fluorescent images acquired were processed for interpretation using an in-house developed viewing tool. The pathologist was able to view each biomarker as a standard grayscale, monochromatic image, an overlay of two or more biomarkers, or as a virtually created molecular DAB image. Results: A correct diagnosis of classical Hodgkin lymphoma vs. other was able to be made using the MultiOmyx platform in all cases. Subjectively, the pathologist noted that the novel methodology allowed for a significantly more confident assessment of marker expression on the Hodgkin cells in the seven cases of classical Hodgkin lymphoma, eliminating many issues of staining ambiguity and allowing recognition of subtle nuances of staining intensity in the Hodgkin cells. The CD30+ cells in the four other cases, three cases of B-cell lymphoma and one case of lymphocyte predominance Hodgkin lymphoma, showed a B-cell profile that was distinguishable from the classical Hodgkin cell phenotype. Conclusions: This new method of fluorescent multiplexing on a single tissue section allows more accurate interpretation of the biomarker expression profile on the same Hodgkin cell. It is likely that this paradigm can be expanded to a greater range of challenging cases in hematopathology.
Future Surveillance of Mental Disorders in the United States
Authors: Kathleen R. Merikangas, Evelyn J. Bromet, Benjamin G. Druss
Journal: JAMA Psychiatry (2017)

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Clinical presentation of hepatotoxicity-associated crizotinib in ALK-positive (ALK+) advanced non-small cell lung cancer (NSCLC).
Authors: Patrick Schnell, Allan Zachary Safferman, Cynthia Huang Bartlett, Yiyun Tang, Keith D. Wilner
Journal: Journal of Clinical Oncology (2012)

7598 Background: Severe hepatotoxicity has been observed with most receptor tyrosine kinase inhibitors. Crizotinib, a first-in-class oral inhibitor of ALK, was recently FDA approved for the treatment (tx) of advanced (ALK+) NSCLC. We provide a review of hepatotoxicity in the crizotinib clinical development program. Methods: Relevant tx-emergent adverse event (AE) reports from 2 pooled single-arm trials in patients (pts) with ALK+ NSCLC who received crizotinib 250 mg BID (n=588) up to Jun 2011 were reviewed. Five reports of severe hepatotoxicity received through Dec 13, 2011 were also evaluated. Results: Incidence of elevation in ALT and AST lab values by CTCAE grade are shown in the table. Additionally, 16 all-grade (7 grade 3 or 4) cases of pertinent hepatic events have been reported. Transaminase elevations generally occurred in the first 2 months of tx and were usually reversible. Pts usually resumed tx at a lower dose without recurrence; however, 4 (&lt;1%) required permanent discontinuation from tx. Five (&lt;1%) cases of severe, potentially drug-related hepatotoxicity (2 fatal) were reported through Dec 13, 2011, with an estimated exposure of 1400 pts. Pts presented with fatigue, nausea, anorexia, weakness, and abdominal pain. Time from starting crizotinib to onset of hepatotoxicity was &lt;6 weeks in 4 cases, while significant transaminase elevation was observed after 6 months in the fifth case. Significant hepatic metastases and abnormal enzymes at baseline were present in 1 (fatal) case, while baseline transaminases were normal in 3 cases, or just above the upper limit of normal in 1 case. Conclusions: Crizotinib is uncommonly associated with severe hepatotoxicity and was reported in &lt;1% of pts. Nausea, malaise, decreased appetite, vomiting, and abdominal pain may indicate hepatic toxicity. ALT and total bilirubin should be monitored monthly and as clinically indicated. Discontinuation of crizotinib is recommended when severe drug-induced hepatic toxicity is suspected or diagnosed. [Table: see text]
A phase II study to assess the efficacy of combined preoperative irinotecan (I)/cisplatin (C) chemotherapy and conformal radiotherapy (RT) followed by surgery for potentially resectable esophageal cancer
Authors: J. J. Knox, G. Darling, M. Guindi, S. Keshavjee, E. X. Chen, J. Hornby, R. Wong
Journal: Journal of Clinical Oncology (2004)

4063 Background: Five-year survival for locally advanced esophageal cancer is < 20%. Whereas primary surgery is generally recommended, preoperative chemotherapy-RT (CRT) has shown potential to impact on survival. In combination with RT, I and C appear well tolerated. Efficacy is assessed in this phase II trial. Methods: Eligible patients with squamous cell (SCC) or adenocarcinoma of the thoracic esophagus or gastroesophageal junction, technically resectable, without distant metastases, were treated with induction CRT and a RT boost. I (65 mg/m2) plus C (30 mg/m2) were given weeks 1, 2, 4, 5, 7 and 8 with concurrent RT (40 Gy/20) during weeks 4–8. The RT boost was either conformal (10 Gy) or brachytherapy (5 Gy). After a 4–8 week interval and re-staging, the patients underwent resection. Quality of life (QOL) was evaluated using the FACT-E scale. Results: Twenty-one of a planned 30 patients have been entered, 16 have completed CRT and 14 have had their surgery so far. There were 15 men and 6 women, mean age of 58 ±10 yrs, 16 adenocarcinoma and 5 SCC. Twelve out of 14 patients (80%) with baseline severe dysphagia reported resolution after the first 2 weeks of chemotherapy eliminating the need for feeding tube support. There have been no treatment-related deaths. Grade 3 neutropenia was seen in 31% but no patients experienced febrile neutropenia. There was no grade 3/4 GI toxicity. Operative mortality was 0 % and 13/14 patients had R0 resections. Postoperative complications included anastomotic leak (3/14), atrial fibrillation and pneumonia (2/14). Clinical RRs: 1 CR, 5 PR, 8 SD and no PD by RECIST criteria. Pathological responses (histological evaluation of entire tumor site) include 3 pCRs and 10 PRs, 2 of which were minimal residual disease. Conclusions: Induction therapy with concurrent irinotecan / cisplatin and RT was well tolerated and did not appear to prevent resection, or increase operative morbidity and mortality. The overall pathological RR of 92% is encouraging and updated clinical, pathological and QOL data will be presented. Generously supported by Pfizer No significant financial relationships to disclose.
What makes the chemo drug work better? Development of an expression cloning method for genes that affect spindle poison sensitivity in mammalian cells
Authors: Hiroshi Y. Yamada, Gary J. Gorbsky
Journal: Cancer Research (2005)

4412  (a: Introduction) Chemotherapy is standard procedure for cancer treatment to eradicate small group of cancer cells that escaped surgical removal, or to control tumor growth. In contrast to radiation therapy and surgery, which treat localized tumors, chemotherapy drugs treat whole body. Since normal cells will be exposed to the drug as well, side effect is major problem of chemotherapy. Patients on chemotherapy commonly experience nausea, vomiting and hair loss. Large dose of drug may leave damage on normal cells, which may result in secondary tumor years later. Clinical studies have demonstrated that treatment of malignant germ cell tumor with topoisomerase poisons such as etoposide increases the rate of secondary leukemia. By developing a method that enhances the effect of chemotherapy, we would require less drug dose and it may help to reduce chemotherapy side effects. (b: experimental procedures) A class of chemotherapy drugs, spindle poisons (e.g. taxol, vinblastine), inhibits mitotic spindle function, activates the mitotic spindle checkpoint, arrests cells in mitosis, and then causes cell death by mechanisms that are poorly understood. To investigate the signal transduction pathways involved in modulating these processes and to isolate factors that serve to sensitize cells to spindle poisons, we developed a cDNA library expression cloning method that identifies genes whose expression increases the substrate attachment of cells arrested in M phase with spindle poisons, due to mitotic exit and/or mitotic apoptosis. (c: summary of results) Here we identify and validate seven cDNA’s from the screen that induce spindle poison sensitivity. We then characterize HeLa cell lines that stably express two of the cDNA’s. pSC3 encodes a fragment of human S8/p45/TRIP1/Sug1, a component of the 19S proteasome regulatory complex. Stable expression of pSC3 decreased the proteasome activity and increased the levels of apoptosis in cells treated with spindle poisons or proteasome inhibitors. Cells stably transfected with pSC3 exhibited decreased expression of BubR1, a kinase required for activation of the mitotic checkpoint in response to treatment with spindle poisons. pSC29 encodes the bromodomain from thyroid hormone receptor coactivator isoform 2. Cells stably transfected with pSC29 also exhibited significantly decreased expression of BubR1. Thus these cDNA fragments both appear to affect stability of a spindle checkpoint component. (d: conclusions) The screening method described provides a general approach for revealing genes and gene fragments whose expression modulates cellular responses to spindle poisons. These genes may be a target for development of drug used in combination with spindle poisons.
Phase III randomized sequential open-label study to evaluate efficacy and safety of sorafenib (SO) followed by sunitinib (SU) versus sunitinib followed by sorafenib in patients with advanced/metastatic renal cell carcinoma without prior systemic therapy (SWITCH Study): Safety interim analysis results.
Authors: Maurice Stephan Michel, Walter Vervenne, Peter J. Goebell, Ludwig Fischer Von Weikersthal, Werner Freier, Maria De Santis, Uwe Zimmermann, Monique M.E.M. Bos, Lutz Trojan, Christian A. Lerchenmuller, Marcus Schenk, Michael D. Staehler, Anne Flörcken, Sascha Pahernik, Maartje Los, Cornelis Van Arkel, Silke Schirrmacher-Memmel, Christian Eichelberg
Journal: Journal of Clinical Oncology (2012)

4539 Background: Several retrospective studies have investigated the sequential use of SO and SU. Some smaller trials support the use of SO followed by SU forming the rationale for this study. Methods: Pts with metastatic RCC unsuitable for cytokines without prior systemic therapy, ECOG PS 0/1, MSKCC score low or intermediate, and ≥1 measurable lesion (CT/MRI every 12 weeks) were randomized to SO-&gt;SU or SU-&gt;SO in standard dosage (primary endpoint total PFS from randomization to event during 2 nd line therapy). Treatment continues until progression or intolerability. Monitoring includes echocardiography and NT pro-BNP. Results: Baseline characteristics of 361 randomized pts (116 completed) are balanced between arms. Safety data of 333 pts are evaluable. AE occurring in &gt;10% of pts are listed in tab. 1. Left-ventricular ejection fraction (LVEF) at screening, switch of treatment, and end of study are given in tab. 1. AE occurred in 93.4% and 92.8%; grade 3/4 AE in 59.9% and 50%; and SAE in 46.7% and 42.2% in the SO-&gt;SU and SU-&gt;SO arm, respectively. Updated results will be presented. Conclusions: AE frequencies are higher in 1 st than in 2 nd line treatments. Typical AE profiles for SO and SU are observed. LVEF values are in a similar range. [Table: see text]