tbuckley/cabot-search huggingface dataset:
Activity of tivozanib (AV-951) in patients (Pts) with different histologic subtypes of renal cell carcinoma (RCC).
Authors: P. Bhargava, B. Esteves, M. Al-Adhami, D. Nosov, O. N. Lipatov, A. A. Lyulko, A. A. Anischenko, R. T. Chacko, D. Doval, W. Slichenmyer
Journal: Journal of Clinical Oncology (2011)

327 Background: This phase 2 randomized discontinuation trial evaluated tivozanib, a potent and selective vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3 kinase inhibitor. Median progression-free survival (PFS) in all pts was 11.8 mo, and the objective response rate (ORR) was 27%. Methods: Pts received 1.5 mg/d tivozanib (3 wk on, 1 wk off = 1 cycle). A retrospective analysis evaluated efficacy and safety by histologic subtype. Response was evaluated by independent radiology review using standard RECIST criteria. Results: 272 pts were enrolled: 70% were male; median age was 56 y (range, 26–79). 226 (83%) pts had clear cell (CC) RCC; 46 had non–clear cell (NCC) RCC, including 11 with papillary RCC. Of pts with CC RCC, 176 (78%) had undergone nephrectomy; of pts with NCC RCC, 23 (50%) had undergone nephrectomy. Median treatment duration was 8.5 mo (range, 0.03– 23.8) as of the data cutoff. Median PFS was 12.5 mo (range, 9.9–17.7) for pts with CC RCC, not yet reached for pts with papillary RCC, and 5.4 mo (range, 3.7–12.0) for pts with other NCC subtypes. ORR and disease control rate (DCR; ORR + stable disease), respectively, were 29% and 85% for pts with CC RCC, 18% and 100% for pts with papillary RCC, and 17% and 74% for pts with other NCC subtypes. For pts with CC RCC, median PFS, ORR, and DCR, respectively, were 14.8 mo, 32%, and 88% for those who had undergone nephrectomy and 8.9 mo, 18%, and 76% for those who had not. Among pts with NCC RCC, median PFS was 6.6 mo for pts who had undergone nephrectomy and 7.2 mo for pts without nephrectomy; ORR was 17% for both NCC subgroups, with a DCR of 78% for pts who had undergone nephrectomy and 83% for pts who had not. Common drug- related adverse events (AEs) for pts with CC and NCC RCC, respectively, included hypertension (49% and 48%), dysphonia (22% and 22%), asthenia (12% and 13%), and diarrhea (13% and 9%). The most common grade ≥3 drug-related AE was hypertension (CC, 8%; NCC, 4%). Conclusions: Disease control was observed for pts with all RCC histologic subtypes. The rate of AEs was similar among patients with CC and NCC RCC and consistent with that of a selective VEGFR inhibitor with minimal off-target toxicities. Tivozanib is currently being tested in a phase 3 trial in pts with CC RCC. [Table: see text]
Clinical Relevance of the Dose of Cytarabine In the Treatment of Primary CNS Lymphomas with Methotrexate-Cytarabine Chemotherapy Combination
Authors: Andrés JM Ferreri, Giada Licata, Marco Foppoli, Gaetano Corazzelli, Emanuele Zucca, Caterina Stelitano, Francesco Zaja, Sergio Fava, Rossella Paolini, Alberto Franzin, Letterio Politi, Maurilio Ponzoni, Michele Reni
Journal: Blood (2010)
Engraftment Rate and Kinetics Following Umbilical Cord Blood Transplantation Is Critically Affected by CD34+ Progenitor Cell Dose and CD8+ T-Cell Dose Complementary.
Authors: Seitaro Terakura, Eiichi Azuma, Makoto Murata, Tadashi Kumamoto, Masahiro Hirayama, Makoto Yazaki, Tomoki Naoe, Koji Kato
Journal: Blood (2006)
Outcomes of radical cystectomy for micropapillary urothelial carcinoma at the University of Southern California.
Authors: Adrian Stuart Fairey, Siamak Daneshmand, Anne Schuckman, Gary Leiskovsky, Hooman Djaladat, Jie Cai, Gus Miranda, Eila C. Skinner
Journal: Journal of Clinical Oncology (2012)

300 Background: The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival. Methods: A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1681 patients underwent radical cystectomy and extended pelvic lymph node dissection for primary bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized according to the WHO/ISUP 1998 classification as urothelial carcinoma (UC; n=1648) or MUC (n=33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. Results: The median follow-up duration was 10 years (range, 0 to 25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1-3: 2% versus 9%, p=0.03) and pathologic (pTanyN1-3: 23% versus 46%, p=0.01) TNM stage, multifocality (37% versus 58%, p=0.02), and high nuclear grade (84% versus 97%, p=0.04). The predicted 5-year OS (59% and 67%, Log rank p=0.79) and RFS (67% and 58%, Log rank p=0.50) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.92, 95% CI 0.56 to 1.50, p=0.73) or RFS (HR 0.92, 95% CI 0.52 to 1.63, p=0.77). Conclusions: Outcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.
Successful Experience of Treatment of Angioimmunoblastic T-Cell Lymphoma By Prolonged Therapy
Authors: Natalia G. Chernova, Yulia E. Vinogradova, Yulia V. Sidorova, Alla M. Kovrigina, Nelly G. Gabeeva, Eugene E. Zvonkov, Elena N. Parovichnikova, Valeri G. Savchenko
Journal: Blood (2015)
P0821 : Are extended durations and/or ribavirin useful for genotype 1 (G1) cirrhotic patients who receive DAAs combination? A meta-analysis of randomized controlled trials (RCTS)
Authors: V. Di Martino, C. Richou, J.-P. Cervoni, D. Weil, C. Vanlemmens, T. Thévenot
Journal: Journal of Hepatology (2015)
NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?
Authors: Tingting Huang, Yuhang Zhou, Alfred S. L. Cheng, Jun Yu, Ka Fai To, Wei Kang
Journal: Molecular Cancer (2016)

Gastric cancer (GC) ranks the most common cancer types and is one of the leading causes of cancer-related death. Due to delayed diagnosis and high metastatic frequency, 5-year survival rate of GC is rather low. It is a complex disease resulting from the interaction between environmental factors and host genetic alterations that deregulate multiple signaling pathways. The Notch signaling pathway, a highly conserved system in the regulation of the fate in several cell types, plays a pivotal role in cell differentiation, survival and proliferation. Notch is also one of the most commonly activated signaling pathways in tumors and its aberrant activation plays a key role in cancer advancement. Whether Notch cascade exerts oncogenic or tumor suppressive function in different cancer types depends on the cellular context. Mammals have four NOTCH receptors that modulate Notch pathway activity. In this review, we provide a comprehensive summary on the functional role of NOTCH receptors in gastric and other gastrointestinal cancers. Increasing knowledge of NOTCH receptors in gastrointestinal cancers will help us recognize the underlying mechanisms of Notch signaling and develop novel therapeutic strategies for GC.
Comparison of the clinical benefit of an adjuvant therapy in gastrointestinal stromal tumors (GIST) with other adjuvant cancer therapies.
Authors: Morgan Deflin, Anju Parthan, Douglas Taylor, John Coombs, Medha Sasane, Marc Paolantonio
Journal: Journal of Clinical Oncology (2012)

129 Background: Imatinib in the adjuvant setting for GIST has shown significant improvements in recurrence- free survival (RFS) vs placebo. Number needed to treat (NNT) is a useful measure to compare effectiveness across treatments (txts) from a health policy or population perspective. The objective of this study is to compare the NNT for adjuvant imatinib in GIST with other adjuvant cancer txts at both 1 and 3 yrs of follow-up using RFS. Methods: In the absence of a placebo controlled trial for 3 yr imatinib, data from ACOSOG Z9001 and SSGXVIII/AIO trials were used to indirectly estimate NNT for adjuvant imatinib in GIST. Adjuvant txts in other cancer types were identified from published literature. Studies meeting the following criteria were included in the analysis: (1) study population consisted of cancer patients (pts) who underwent surgical resection of the primary tumor and considered cancer-free, (2) a randomized clinical trial conducted in pts in the US or Europe, (3) comparators were either placebo or no txt (4) RFS was reported and showed benefit with the experimental txt. NNT is defined as the number needed to treat to prevent 1 recurrence or death. NNT was calculated as the inverse of the absolute risk reduction (difference in event rate) between the study groups in each trial. Results: 24 adjuvant txts in 8 different cancer types were identified. With longer follow-up (3 yrs vs 1 yr), 62.5% of txts showed a decreased NNT, including imatinib which decreased from 7 (1 yr) to 4 (3 yrs). The largest relative decrease in NNT over time was 91% for trastuzumab &amp; cyclophosphamide (both used for breast cancer). About 25.0% of the txts had an increase in NNT over time. NNT for imatinib was lower than all other txts at 3 yrs of follow-up and lower than all but 2 txts at 1 yr of follow-up (mitomycin + tegafur [gastric cancer, NNT = 5] and gemcitabine [pancreatic cancer, NNT = 4]). About 28.0% and 41.7% of txts had an NNT less than 10 at 1 and 3 yrs of follow up, respectively. Conclusions: Imatinib has one of the lowest NNTs among other adjuvant txts, at 1 and 3 yrs of follow-up. With longer follow-up duration, most adjuvant cancer txts show a decreased NNT.
Margaret McCartney: Vocation, vocation, vocation
Authors: Margaret McCartney
Journal: BMJ (2016)

In the end, vocation is what it’s all about. We’re tested on its presence before we enter medical school. We’re implored to hold ourselves to the highest standards. We’re judged according to these standards, even when the resources to achieve them are wilfully withheld.

Christmas and New Year should mean some respite and time for thinking about where we’ve come and what we’ve seen. But many working in the NHS will have none of this. Work will simply keep beating on.

This past year has been absurd: a fracturing of relationships between junior doctors …
Phase III study of gemcitabine/oxaliplatin (GEMOX) with or without erlotinib in unresectable, metastatic biliary tract carcinoma.
Authors: H. Y. Lim, J. Lee, H. Chang, J. S. Kim, H. J. Choi, M. A. Lee, J. Jang, H. Jeung, J. H. Kang, H. W. Lee, D. Shin, H. J. Jang, J. Sun, S. H. Park, J. O. Park, Y. Park, W. K. Kang
Journal: Journal of Clinical Oncology (2011)

LBA4032 Background: Currently, there is no standard regimen for palliative chemotherapy in metastatic, unresectable biliary tract cancer (BTC). A phase II trial of erlotinib monotherapy showed a promising anti-tumor activity in BTC with tolerable toxicity. Additionally, gemcitabine + erlotinib demonstrated superior efficacy when compared to gemcitabine alone in pancreatic cancer. Hence, we conducted a phase III trial to compare between GEMOX vs GEMOX+erlotinib (Tarceva [T]) (GEMOX/T) as first-line chemotherapy in unresectable, metastatic BTC. Methods: Eligible patients were as follows: histologically confirmed adenocarcinoma of biliary tract (CCC), ampulla of vater (AOV) or gall bladder (GB); unresectable or metastatic; ECOG performance status of 0~2; adequate marrow, hepatic, renal and cardiac functions; no prior chemotherapy. The primary endpoint was progression free survival (PFS). The study regimen was gemcitabine 1,000mg/m 2 , oxaliplatin 100mg/m 2 , erlotinib 100mg qd daily q 2 weeks. Results: From February 2009 to August 2010, 268 pts were randomized, 133 patients to GEMOX arm and 135 patients to GEMOX/T arm. Patient characteristics: median age 61 yrs (range 30-82); male (63.4%); CCC (n=180, 67.2%), GB (n=82, 30.6%), and AOV (n=6, 2.2%). With a median follow-up of 13.9 months (range, 6.7 – 25.0), median PFS was 5.8 months (95% CI, 4.6 - 7.0) in GEMOX/T arm and 4.2 months (95% CI, 2.7 - 5.7) in GEMOX arm (P=0.080). In subgroup analysis (CCC, n=180), however, median PFS was significantly longer in GEMOX/T arm (5.9 months) when compared with GEMOX arm (3.0 months, P=0.049). The overall response rate was significantly higher in the GEMOX/T arm when compared with GEMOX arm. There was no significant difference in overall survival between the two arms (GEMOX/T: 9.5 months, 95% CI, 7.6 – 11.4; GEMOX: 9.5 months, 95% CI, 7.5 – 11.5; P=0.611). The EGFR mutation testing results in correlation to responsiveness to erlotinib will be presented at the meeting. Conclusions: This phase III represents the first multicenter, randomized trial to compare GEMOX vs GEMOX/T in unresectable, metastatic BTC. Although PFS was not prolonged in GEMOX/T, there was a significant benefit in terms of PFS in GEMOX/T arm for CCC patients.
Long-term QOL outcome after proton beam monotherapy for localized prostate cancer.
Authors: J. Coen, J. J. Paly, E. A. Weyman, A. Rodrigues, W. U. Shipley, A. L. Zietman, J. A. Efstathiou, J. A. Talcott
Journal: Journal of Clinical Oncology (2011)

68 Background: High-dose conformal proton radiation for localized prostate cancer results in favorable clinical outcomes and low toxicity rates. Here, we report long-term quality of life (QOL) outcome for men treated with conformal protons. Methods: Serial QOL questionnaires were administered to men who received proton radiation. Long-term questionnaires (minimum 2 years) were completed by 72 patients. Men were stratified into functional groups from their baseline questionnaires (normal, intermediate or poor function) for each symptom domain. Symptom scores were calculated at baseline and long-term follow-up and expressed as mean values. QOL changes were assessed overall and within functional groups in a paired fashion using the Student's t-test. Results: The median age at treatment and follow-up were 66 years and 44 months, respectively. The median dose was 82 GyE (range 74-82 GyE). For all 72 patients, there were increased scores for incontinence (ID) (3.2 baseline vs. 9.9 long-term, p=&lt;0.001), obstructive/irritative voiding (OID; 20 vs. 24, p=0.028), bowel (BD; 4.4 vs. 8.0, p=0.001) and sexual dysfunction (SD; 25 vs. 48, p&lt;0.001). When stratified by functional category, more specific estimates were possible. For ID, only normal function was associated with a significant increased score (0 vs. 8.4 at baseline and long-term, p=&lt;0.001); for OID, only the group with normal baseline function showed a significant increased score (12 vs. 17, p=0.01); similarly for BD, only men with normal function had a significant increased score (0 vs. 5.4, p&lt;0.001). For SD, the score increased in men with normal (1.4 vs. 30, p&lt;0.001) and intermediate function (17 vs. 46, p&lt;0.001). Conclusions: Patient reported outcomes are sensitive indicators of treatment related sequelae and here quantitate, for the first time, the long-term consequences of proton monotherapy for prostate cancer. Analysis by baseline functional category is a useful means of predicting long-term QOL scores for an individual patient. High-dose proton radiation was associated with small increases in bowel dysfunction, obstructive/irritative voiding dysfunction and incontinence. With long term follow-up, sexual dysfunction increased more than any other symptom domain. No significant financial relationships to disclose.
A phase II neoadjuvant trial of concurrent trastuzumab and paclitaxel without anthracycline in women with HER2-positive operable breast cancer.
Authors: H. Jinno, T. Sato, M. Takahashi, T. Hayashida, M. Sakata, S. Hirose, Y. Kitagawa
Journal: Journal of Clinical Oncology (2011)

e11070 Background: Neoadjuvant paclitaxel plus trastuzumab followed by 5-fluorouracil, epirubicin, and cyclophosphamide plus trastuzumab revealed the high pathologic complete response (pCR) rate of up to 60% in patients with HER-2-positive breast cancer. However, combination of trastuzumab and anthracycline has been associated with an increased incidence of cardiac dysfunction. The objective of this study was to determine the efficacy of concurrent administration of trastuzumab and paclitaxel without anthracycline as neoadjuvant chemotherapy. Predictive factors of pCR including deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway were also investigated. Methods: Patients with HER2-positive operable breast cancer received 12 cycles of weekly paclitaxel (80 mg/m2 IV) plus weekly trastuzumab (4mg/kg loading dose followed by 2 mg/kg IV) before surgery. PTEN status was evaluated by IHC with PTEN antibody (Thermo Scientific, CA). PTEN expression level was scored semiquantitatively based on staining intensity (0; no staining , 1+; reduced staining, and 2+; equal staining as compared to the internal control). PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. pCR was defined as no residual invasive carcinoma in the breast. Results: Among 37 patients enrolled, ER and PgR were positive in 18 (48.6%) and 16 (43.2%) patients, respectively. The overall response rate was 86.5% (32/37) and the pCR rate was 48.6% (18/37). pCR rate was significantly correlated with PgR negativity (p=0.004) and higher Ki67 (p=0.01). PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that the combination of trastuzumab and paclitaxel without anthracycline is effective neoadjuvant chemotherapy with high pCR rate. PTEN loss and/or PIK3CA mutation were not useful predictors of resistance to trastuzumab.
Prognostic Value of Minimal Residual Disease (MRD) Detection in Adult Acute Lymphoblastic Leukemia (ALL) – HYPER-CVAD Protocol
Authors: Nikolaos Tsagarakis, Nektaria Kentrou, Mirsini Pergaminou, Theodore Marinakis, Stefanos I Papadhimitriou, Georgios Gortzolidis, Athanasios Galanopoulos, Evridiki Michali, Konstantinos Papadimitriou, Dimitra Skoumi, Nikolaos Anagnostopoulos, Georgios Paterakis
Journal: Blood (2008)
Determination of Imatinib Plasma Levels by High Performance Liquid Chromatography (HPLC): Evaluation of Pharmacokinetic Variability and Haematological Consequences.
Authors: Stephanie Haiat, Xavier Decleves, Benedicte Mittaine, Ollivier Legrand, Stephanie Francart, Bernard Rio, Anne Vekhoff, Francois Chast, Jean-Pierre Marie, Christophe Bardin
Journal: Blood (2006)
The neoadjuvant management of muscle-invasive bladder cancer (MIBC) in Canada: A national survey of urologists.
Authors: Srikala S. Sridhar, Kim N. Chi, Scott A. North, Peter C. Black, Lori Wood, Tina Hsu
Journal: Journal of Clinical Oncology (2012)

303 Background: There is level 1 evidence and a 5% absolute survival benefit supporting the use of cisplatin-based neoadjuvant chemotherapy (NC) for the management of MIBC. Despite this, it is well known that the majority of eligible patients undergoing cystectomy do not receive NC. We previously surveyed medical oncologists and found that the majority will offer NC to MIBC patients depending on stage, renal function, performance status (PS), and comorbidities. However, the number of MIBC patients being referred for consideration of NC by urologists remains low. The aim of this followup survey to urologists was to better understand their approach to MIBC, and referral patterns for NC. Methods: A survey consisting of 24 questions was administered to Canadian urologists belonging to the Canadian Urologic Oncology Group. Respondents completed the survey and mailed/faxed back their responses. The survey was similar to, but not identical to the previous medical oncology survey. Results: Of the 25 respondents, 21/25 (84%) were academic, &gt;90% were in full-time practice, and 72% were practising for &gt;10 yrs. Most (84%) treated over 20 bladder cancer cases annually. Overall, 22/25 (80%) will offer a NC approach if appropriate. In 2009, 9/24 (38%) sent &gt;6 referrals for NC; 2/24 (25%) sent 5-6 referrals, 6/24 (20%) sent 3-4 referrals, and 5/24 (8%) sent 1-2 referrals. NC was offered as standard of care or to downsize tumors. Initial staging included cystoscopy, CT chest/abdo/pelvis and bone scan. Key factors cited for not offering NC were: T2a disease, GFR &lt;40ml/min, age &gt;85 or PS 3 or 4. Average time from NC to cystectomy was 4-6 wks. Conclusions: The majority of academic urologists in Canada will refer MIBC patients for NC except those with T2a disease, poor renal function, age &gt;85 or poor PS. Non-academic urologists are underrepresented in this survey, and may represent the group facing the greatest challenges in offering NC, due to issues such as access to medical oncology, or lack of local expertise in managing MIBC. Targeting non-academic urologists, and encouraging consultation with a medical oncologist for all patients with MIBC, may lead to increased utilization of NC, and better outcomes in this disease.
Low-Density Lipoprotein Levels and Risk of Major Cardiovascular Events
Authors: David Rott
Journal: JAMA Internal Medicine (2016)

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Experiences with Haploidentical Allogeneic Blood STEM CELL Transplantation for High-Risk Hematologic Disease in a Colombian Reference Center
Authors: Claudia Lucia Sossa Melo, Sara Sanguino Jimenez, Angela Peña Castellanos, Luis Antonio Salazar Montaño, Sonia Osma, Miguel Angel Ayala, Nick Tarazona, Edgar David Gomez Laiton
Journal: Blood (2016)