tbuckley/cabot-search huggingface dataset:
Prostate cancer–specific mortality after definitive radiation therapy: Who dies of disease?
Authors: M. M. Kim, K. E. Hoffman, L. B. Levy, S. J. Frank, S. Choi, Q. N. Nguyen, T. Pugh, S. E. McGuire, A. Lee, D. A. Kuban
Journal: Journal of Clinical Oncology (2011)

181 Background: A competing risks analysis was undertaken to identify patient subgroups at greatest risk of dying from prostate cancer (CAP) after treatment with definitive external beam radiation therapy (RT) +/− androgen deprivation therapy (ADT) in the PSA era, and to determine which factors predict for survival from disease. Methods: A total of 2,675 men with localized CAP treated with RT +/− ADT at M. D. Anderson Cancer Center from 1987-2007 were evaluated. Prostate cancer-specific mortality (PCSM) and other cause mortality rates were calculated after stratifying patients according to NCCN risk group, RT dose, use of ADT, and age at treatment. In total, 21% had low-risk, 40% had intermediate-risk, and 39% had high-risk disease. Multivariate analysis (MVA) was performed using Cox regression modeling. Results: Median age was 68.5 years and median follow-up was 6.4 years. For patients with low-risk disease, only 0.2% died of CAP 10 years after treatment. None of the low-risk patients &lt;70 years old who received ≥72 Gy died of CAP. The majority of deaths in the intermediate-risk group were also due to other causes; men ≥70 years old who received &lt;72 Gy had the highest 10-year PCSM (5%). High-risk patients &lt;70 years old who received &lt;72 Gy without ADT had similar 10-year rates of CAP (15.2%) and non-CAP (18.5%) mortality. Men with high-risk disease &lt;70 years old treated with higher doses &gt;72 Gy were twice as likely to die from non-CAP causes (15.9%) than die from CAP (8.6%). In older men ≥70 years old with high risk disease, dose-escalation with ADT reduced 10-year PCSM from 14% to 4%, and most deaths were due to other causes (41% and 20%). On MVA, dose (p=0.002), ADT (p=0.007), PSA (p&lt;0.0001) and Gleason score (p&lt;0.0001) were predictive of PCSM in the high-risk group. Conclusions: Men with low- and intermediate-risk CAP treated with definitive RT are unlikely to die of disease. PCSM is higher in men with high-risk disease but can be reduced with dose escalation and ADT, although patients are still twice as likely to die of other causes. No significant financial relationships to disclose.
Preclinical Analysis of the Combined Activity of SGN-40, Anti-CD40 Monoclonal Antibody, with Rituximab in Non-Hodgkin Lymphoma.
Authors: Timothy S. Lewis, Renee S. McCormick, Julie A. McEarchern, Kim Kissler, Ivan J. Stone, Hans-Peter Gerber, Jonathan G. Drachman, Iqbal Grewal, Che-Leung Law
Journal: Blood (2008)
Author’s reply to Dangoor and colleagues
Authors: Peter H Wise
Journal: BMJ (2016)

Dangoor and colleagues make some good points.1 2 My sources are indeed from different health systems— The BMJ is an international journal. I took care to validate all relevant material without prejudice, but I am happy to debate the validity of data from other sources.

Conflicts of interest are ethically important—above all in human, but also in …
Under- and upgrading of prostate cancer after radical prostatectomy in a screening setting.
Authors: X. Zhu, M. Bul, P. J. van Leeuwen, M. J. Roobol, F. H. Schröder
Journal: Journal of Clinical Oncology (2011)

105 Background: It has been well established that there is an upward drift in assigned Gleason score (GS) to prostate cancer (PC) biopsies. However, few studies have examined the concordance between biopsy GS and pathological GS after radical prostatectomy (RP) in a screening setting over time. We assessed the proportion of under and upgrading of PC after RP by comparing the prevalence screen with the incidence screens from the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. Methods: From 1993 to 1999, a total of 42.376 men identified from population registries in the Rotterdam region (55-74 yrs) were randomized into a screening or control arm. Men with PSA ≥3.0 ng/ml were recommended for sextant prostate biopsy, which were lateralized since 1996. The screening interval was 4 yrs. Men with screen-detected PC, who underwent RP within 1 yr, were eligible for this study. Results: In all, biopsy and pathological GS were known for 639 men who underwent RP. Of these RPs, 405 were performed between 1994 and 2000 (prevalence screen) whereas 235 cases were performed between 1998 and 2008 (incidence screens). In the prevalence screen, 49.8% of the biopsy GS matched the pathological GS ( Table ). This percentage improved to 58.3% in the incidence screens (p=0.045). The proportion of undergrading after RP was 23.0% in the prevalence screen, which declined to 16.2% in the incidence screens (p=0.049). Upgrading occurred in 27.2% of the cases in the prevalence and 25.5% in the incidence screens (p=0.71). Conclusions: We have demonstrated an improved concordance between biopsy and pathological GS over time by comparing cancers detected in the prevalence screen with those detected in the incidence screens, which is in line with the upward shift of GS classification over time. In addition, significant less undergrading occurred in the incidence screens. However, one should keep in mind that within this screening program still a quarter of the biopsy GS were upgraded after RP in the incidence screens. [Table: see text] [Table: see text]
Accelerated partial breast irradiation using brachytherapy (APBIb) for breast cancer (bca): Predictors of use and guideline concordance.
Authors: J. A. Hattangadi, N. Taback, B. A. Neville, J. R. Harris, R. S. Punglia
Journal: Journal of Clinical Oncology (2011)

84 Background: APBIb is a novel alternative to whole breast irradiation (WBI). The American Society for Radiation Oncology Guidelines (ASTRO-G) established appropriateness for APBIb use off protocol. Methods: 138,815 bca patients from the Surveillance, Epidemiology, and End Results database underwent WBI or APBIb after lumpectomy from 2000 to 2007. Patients were classified as suitable, cautionary, or unsuitable for APBIb according to ASTRO-G. Logistic regression was applied to study APBIb use overall and within each guideline category. Results: Overall, 2.6% received APBIb and use varied by ASTRO-G: 5% in suitable, 3.4% in cautionary, and 1.6% in unsuitable patients (p&lt;0.0001). APBIb use increased with time (2000: 0.3%, 2007: 7%) and varied widely with region (0% Alaska; 7% Atlanta, Georgia). Independent predictors of APBIb among suitable patients included white (OR 2.0, p&lt;0.001) race, region (OR 2.6-8.6, p&lt;0.0001), later year (2006-7 v 2000-2 OR 20.3, p&lt;0.0001), and lower grade (OR 1.3, p=0.01). Among cautionary patients, white race (OR 1.8, p&lt;0.001), non-Hispanic ethnicity (OR 1.3, p&lt;0.04), region (OR 3.1-10.2, p&lt;0.0001), metropolitan location (OR 1.9, p=0.01), later year (2006-2007 OR 17.6, p&lt;0.0001), and lower grade (OR 1.4, p&lt;0.0001) predicted for APBIb. Among unsuitable patients, race (p&lt;0.0001), region (OR 3.3-21.6, p&lt;0.0001), later year (2006-7 OR 12.7, p&lt;0.0001), estrogen receptor-positive status (OR 1.3, p=0.002), lower grade (OR 1.3, p&lt;0.01), and negative lymph nodes (OR 2.0, p&lt;0.0001) predicted for use. In several regions, odds of APBIb increased as appropriateness decreased (see Table). Conclusions: APBIb has been rapidly adopted in the US. Its use varied by race, ethnicity, and region, especially among patients who may not be suitable candidates for this technique. [Table: see text]
Long-Term Outcome of Therapy-Related Myelodysplastic Syndromes and Acute Myeloid Leukemias Arising in Patients Treated for Lymphoma or Solid Tumors.
Authors: Raffaella Milani, Salvatore Palmieri, Manuela Zanni, Filiberto Pollio, Anna Dodero, Francesco Spina, Adele Testi, Corrado Tarella, Massimo Bernardi, Andrea Gallamini, Giuseppe Bandini, Fabio Benedetti, Felicetto Ferrara, Paolo Corradini
Journal: Blood (2007)
Phase II study of XL184 in a cohort of patients (pts) with castration-resistant prostate cancer (CRPC) and measurable soft tissue disease.
Authors: D. C. Smith, M. R. Smith, E. J. Small, C. Sweeney, R. Kurzrock, M. S. Gordon, N. J. Vogelzang, C. Scheffold, M. D. Ballinger, M. Hussain
Journal: Journal of Clinical Oncology (2011)

127 Background: XL184 is an oral, potent inhibitor of MET and VEGFR2. MET pathway activation promotes tumor growth, invasion and metastasis. Overexpression of MET and/or its ligand HGF are associated with prostate cancer metastasis. In preclinical studies, androgen ablation upregulates MET signaling. Preliminary data from the open label Lead-in Stage of an ongoing adaptive design phase II randomized discontinuation trial are presented. Methods: Eligible pts had CRPC, measurable disease with or without bone metastasis, and disease progression on ≤1 prior non-hormonal systemic treatment. XL184 was administered orally for 12 weeks (wks). Tumor (RECIST) and bone scan response (complete or partial resolution) were assessed every 6 wks. Primary endpoint is objective response rate at wk 12. Pts with SD at wk 12 will enter a placebo-controlled randomized phase. Results: As of 10/4/10, 72 pts have been enrolled. Median time on study was 50 days (range, 6+-350+ days). Median age was 69 yrs; 45% of pts were docetaxel-pretreated. All pts had measurable disease, including 69% with visceral metastases. To date, there are 24 response evaluable pts, defined as enrolled ≥12 wks prior to data cutoff. 5/24 (21%) pts had a partial response (≥30% reduction) in measurable disease with 3 responses confirmed at 12 wks and 2 unconfirmed responses ongoing. 6/24 (25%) had PSA declines of ≥50%. 13 of 15 (87%) pts with known bone metastases had either complete or partial resolution of lesions on bone scan. Bone scan responses were associated with investigator-reported improvement in bone pain in 11/15 (73%) with pain at baseline. Effects on osteoclast and osteoblast activity were observed: plasma C-telopeptide declined ≥50% in 8/12 (66%) pts and serum total alkaline phosphatase (tALP) declined ≥50% in 5/8 (63%) pts with bone metastases and baseline elevated tALP. The most common AEs ≥Grade 3 severity (related) were fatigue (10%), diarrhea (3%) and elevated AST (3%). Conclusions: XL184 results in tumor responses, partial or complete resolution of lesions on bone scan, and symptom relief in pts with metastatic CRPC, including those pretreated with docetaxel. XL184 also decreased biomarkers of both osteoblast and osteoclast activity. [Table: see text]
PAWS-GIST national initiative: A joint patient/carer/professionals initiative in the United Kingdom for pediatric/adolescent/wild-type/syndromic gastrointestinal stromal tumors.
Authors: V. R. Bulusu
Journal: Journal of Clinical Oncology (2011)

e20523 Background: Gastrointestinal stromal tumours (GISTS) are the most common mesenchymal tumours of the gastrointestinal tract. Over 90% of the GISTS have either KIT or PDGFRA mutations. The pediatric/adolescent/wild-type/syndromic (PAWS) GISTS are a heterogeneous group of patients with a different biology and natural history compared with the adult sporadic GISTS. Standard therapeutic approaches using tyrosine kinase inhibitors like imatinib or sunitinib have been less successful in PAWS-GIST patients. Better understanding of the biology and newer therapeutic strategies are needed to make any advances in the treatment of these extremely rare cancers. Methods: A joint collaborative group comprising of GIST specialists (Oncologists, pathologists, surgeons, radiologists, paediatricians, specialist nurses) and patients/carers was established in October 2010 to form the PAWS-GIST Focus group in UK. The first meeting took place in London in November 2010. The aims of the group are the following: (a) clinically gather UK-wide information on the number of patients, natural history, treatment, etc; (b) act as a facilitator between various specialist groups treating these patients; (c) provide information and support to patients and carers and opportunities for fundraising activities; and (d) encourage collaborative research work leading to better understanding of the biology, exploring newer small molecules/kinase inhibitors and explore establishing GIST cell lines. Results: As of January 2011, we have been able to identify 13 paediatric/adolescent GIST patients in United Kingdom. Work is in progress as part of the UK national GIST registry to prospectively identify all PAWS-GIST patients in the UK. Conclusions: PAWS-GIST initiative is the first of its kind in UK and is fully supported by the UK GIST professional and patient groups. Future plans include establishing national clinics based on the NIH USA model. Fund raising activities are ongoing.
Osimertinib for the Treatment of Metastatic EGFR T790M Mutation–Positive Non–Small Cell Lung Cancer
Authors: Sean Khozin, Chana Weinstock, Gideon M. Blumenthal, Joyce Cheng, Kun He, Luning Zhuang, Hong Zhao, Rosane Charlab, Ingrid Fan, Patricia Keegan, Richard Pazdur
Journal: Clinical Cancer Research (2016)

On November 13, 2015, the FDA granted accelerated approval to osimertinib (TAGRISSO; AstraZeneca), a breakthrough therapy-designated drug for the treatment of patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer, as detected by an FDA-approved test, with progression on or after EGFR tyrosine kinase inhibitor therapy. Approval was based on durable tumor response rates in two single-arm, multicenter trials: the dose extension cohort of a first-in-human trial (FIH; AURA extension; n = 201) and a fixed-dose, activity-estimating trial (AURA2; n = 210). Osimertinib was administered at 80 mg orally once daily. The objective response rates (ORR) per blinded independent committee review were 57% [95% confidence interval (CI), 50-64) in AURA extension and 61% (95% CI, 54-68) in AURA2. Median duration of response (DOR) could not be estimated. Supportive efficacy data from 63 patients in the dose-finding part of the FIH trial demonstrated an ORR of 51% (95% CI, 38-64), with a median DOR of 12.4 months. Common adverse events (AE) evaluated in 411 patients included diarrhea (42%), rash (41%), dry skin (31%), and nail toxicity (25%). Grade 3 to 4 AEs occurred in 28% of patients, and 5.6% discontinued treatment due to AEs. Clin Cancer Res; 23(9); 2131-5. ©2016 AACR.
A randomized, double-blind phase III study (VEG105192) of pazopanib (paz) versus placebo (pbo) in patients with advanced/metastatic renal cell carcinoma (mRCC): Updated safety results.
Authors: C. N. Sternberg, R. E. Hawkins, C. Szczylik, I. D. Davis, J. Wagstaff, L. McCann, M. Chen, S. D. Rubin
Journal: Journal of Clinical Oncology (2011)

313 Background: This study evaluated the efficacy and safety of paz in 435 pts with mRCC. The primary endpoint of PFS with paz vs pbo was met with a median PFS of 9.2 vs. 4.2 mo (HR 0.46; p&lt;0.0001) respectively. Final OS was 22.9 mos in paz arm vs. 20.5 mos in pbo (HR 0.91; p=0.224); however, OS was confounded by extensive crossover of pbo pts to paz and other therapies. Two independent analyses to adjust for crossover, IPCW (Inverse Probability of Censoring Weighted) and RPSFT (Rank Preserving Structural Failure Time) suggest an OS benefit with paz;HR 0.504; p=0.002 by IPCW and HR 0.43; p=0.172 by RPFST. At the final OS analysis, pts on the paz arm had a 30% increase or in absolute terms 70 yrs (303.7 yrs from 233.5 yrs) in cumulative exposure since analysis 2 yrs ago (Sternberg; JCO 2010). Updated safety data is reported. Methods: Pts with clear cell mRCC and measurable disease with no prior treatment or 1 prior cytokine-based trt were randomized (2:1) to paz 800 mg QD or pbo and treated until progression (PD), death, or unacceptable toxicity. Upon PD, pts on the pbo arm could receive paz through a parallel open-label study. Results: Median exposure duration was nearly doubled in the paz arm vs. pbo (7.4 mo vs. 3.8 mo). In the paz arm, 32% of subjects remained on treatment &gt; than 12 mos, 15% for &gt; 24 mos and 8% for &gt; 36 mos. The mean daily dose of paz was 679 mg. ALT elevations &gt;3xULN occurred in 54 pts; upon interruption of paz, or with continuation (adaptation), 85% of pts had documented recovery, 9% no recovery data and 6% not recovered. Further details regarding these and less frequent class effect AEs such as hand-foot syndrome (6%), myocardial dysfunction (&lt;1%) will be reported. Conclusions: This safety update reflects a 30% increase in the cumulative exposure to paz since the previous clinical cutoff. There are no significant changes to the type, frequency or severity of AEs and no differences in grade 3, 4, or 5 AEs. No new safety signals have been detected. [Table: see text] [Table: see text]
Phase II Study of Denileukin Diftitox (Ontak) for Relapsed/Refractory T-Cell Non-Hodgkin’s Lymphoma.
Authors: Nam H. Dang, Barbara Pro, Fredrick Hagemeister, Felipe Samaniego, Dan Jones, Maria Rodriguez, Andre Goy, Jorge Romaguera, Pamela L. Walker, Anas Younes, Sattva Neelapu, Larry Kwak, Luis Fayad
Journal: Blood (2005)
Prospective Study Evaluating Use of Traditional Chinese Medicine to Treat Refractory Cytopenia(s) In Chronic Hematological Disorders - Safety, Efficacy and Impact on Quality of Life
Authors: Lay-Cheng Lim, Jia-Hui Lu, Yeh-Ching Linn, Hui-Li Sun, Jue Sun, Yong-Ming Zhou
Journal: Blood (2010)
Salvage treatment for metastatic penile cancer after first-line chemotherapy with paclitaxel, ifosfamide, and cisplatin: Analysis of response and survival outcomes.
Authors: Jennifer Wang, Curtis A. Pettaway, Lance C. Pagliaro
Journal: Journal of Clinical Oncology (2012)

340 Background: There are few effective salvage treatment options for men with advanced metastatic penile cancer. Patients who remain disease-free for 2 years after surgical removal of regional lymph node metastases are likely cured of the disease, but the survival is short for those who recur. Our objective was to estimate the efficacy of salvage treatments for metastatic penile cancer after neoadjuvant paclitaxel, ifosfamide, and cisplatin. Methods: Patients are from a 30-patient cohort who we saw between April 2000 and September 2008 presenting with stage TxN2-3M0 squamous cell carcinoma of the penis. All were treated with 1 to 4 courses of neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy prior to planned lymphadenectomy. For the patients who had progression or recurrence of disease, we retrospectively evaluated the salvage therapies given, response data, and survival times from the date of first progression. Results: Nineteen of the 30 patients (63.3%) had tumor progression and 17 received one or more salvage therapies. Median age at diagnosis was 57 years (range 24-72 years). The median survival from time of first progression was 5.8 months (range 3.7 to 30.9 months). Two of five patients (40%) who had received bleomycin, methotrexate, and cisplatin experienced an objective response (1 complete and 1 partial), and one (20%) developed pneumonitis. Two patients had received gemcitabine combinations without response. Two patients had received epidermal growth factor receptor-targeted therapy with gefitinib or cetuximab and cisplatin, both without response. Three patients had received chemo-radiotherapy, one with stable disease for 13.5 months and 2 with no apparent benefit. Five patients underwent salvage surgery, and they all progressed within 2 months with one case of fatal hemorrhage. Conclusions: Men with metastatic penile cancer that progresses through or recurs after front-line neoadjuvant chemotherapy have poor responses to the described salvage treatments, and median overall survival is less than 6 months. Emphasis should be placed on clinical trials for development of effective therapy in this setting.
Feasibility of Routine Frailty Screening Assessment for Patients in a Hematologic Oncology Clinic: Results from a Pilot Study
Authors: Gregory A. Abel, Tammy T. Hshieh, Nolan B. Condron, Caron A. Jacobson, David P. Steensma, Jacob P. Laubach, Richard M. Stone, Jane A. Driver
Journal: Blood (2015)
Prognostic implications of phosphatidylinositol 3-kinase (PI3K) pathway alterations in metastatic triple-negative breast cancer (mTNBC).
Authors: M. Oliveira, L. De Mattos-Arruda, G. Sánchez-Ollé, B. Graña, J. Cortes, J. M. Perez-Garcia, E. Muñoz-Consuelo, M. Vidal, M. Bellet, S. Di Cosimo, P. Gomez Pardo, J. Rodon Ahnert, J. Hernandez-Losa, A. Vivancos, L. Prudkin, C. Aura, V. Serra, J. Baselga, J. Tabernero, C. Saura
Journal: Journal of Clinical Oncology (2011)

1081 Background: PI3K pathway alterations (receptor tyrosine kinase amplification, activating mutations of PIK3CA or PTEN loss) are frequent in breast cancer (BC). In hormone receptor (HR) + / HER2- BC, they are associated with a better outcome, but their prognostic implications in TNBC is not clear. Our aim was to characterize the clinical outcome of mTNBC patients (pts) according to their PI3K pathway status. Methods: mTNBC pts treated in our hospital in 1 year were identified. Written informed consent was obtained for PI3K pathway somatic determinations. DNA was extracted from paraffin embedded tumor tissue (EZ1 DNA Tissue Kit) and was analyzed with DxS PI3K Mutation Test Kit or Sequenom MALDI-TOF MassARRAY technology. PTEN status was determined by immunohistochemistry. PTEN loss was defined as Hscore≤50. Clinical data were collected from medical records. DFS and OS were calculated from the diagnosis until progression or death, respectively. SPSS software was used for the statistical analysis. Results: 32 pts identified, median age 47; premenopausal 15 (47%). PIK3CA status could be determined in 21 and 8 (38%) had a mutation: H1047R n=6, Q536K n=2. PTEN status could be determined in 26 and 10 (38%) had PTEN loss. 2 pts had both PIK3CA mutation and PTEN loss. Overall, 67% of the pts for whom either determination was done had an alteration of the pathway. Median number of chemotherapy lines was 3 (range 1-10). 3 pts (9%) received a PI3K inhibitor. The table shows median DFS and OS for the whole cohort and according to PIK3CA and PTEN status. Conclusions: In this sample set, the prevalence of PI3K pathway alterations in mTNBC pts was higher than it has previously been reported. Although not statistically significant, probably due to a small cohort, it seems to be a trend to a worse OS in mTNBC pts with PIK3CA mutations, the opposite that is commonly observed in HR+ pts. These findings must be prospectively validated because of their potential therapeutic implications. PTEN loss PIK3CA mutation Time (months) Overall Yes No P Yes No P Median DFS (95%CI) 28 (17-38) 19 (0-69) 28 (16-39) 0.37 28 (9-35) 39 (0-58) 0.52 Median OS (95%CI) 128 (60-196) 88 (9-167) 87 (55-119) 0.80 51 (39-63) 128 (45-211) 0.23
Erratum: Corrigendum: Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET
Authors: Héctor Peinado, Maša Alecˇković, Simon Lavotshkin, Irina Matei, Bruno Costa-Silva, Gema Moreno-Bueno, Marta Hergueta-Redondo, Caitlin Williams, Guillermo García-Santos, Cyrus M Ghajar, Ayuko Nitadori-Hoshino, Caitlin Hoffman, Karen Badal, Benjamin A Garcia, Margaret K Callahan, Jianda Yuan, Vilma R Martins, Johan Skog, Rosandra N Kaplan, Mary S Brady, Jedd D Wolchok, Paul B Chapman, Yibin Kang, Jacqueline Bromberg, David Lyden
Journal: Nature Medicine (2016)
Prospective Evaluation of Prognostic Parameters in Early Stage Chronic Lymphocytic Leukemia (CLL): Results of the CLL1-Protocol of the German CLL Study Group (GCLLSG).
Authors: Manuela A. Bergmann, Barbara F. Eichhorst, Raymonde Busch, Dagmar Adorf, Stephan Stilgenbauer, Michael J. Eckart, Clemens-Martin Wendtner, Michael Hallek
Journal: Blood (2007)
A Phase I Trial of Adoptively Transferred Ex-Vivo Expanded Autologous Natural Killer (NK) Cells Following Treatment with Bortezomib to Sensitize Tumors to NK Cell Cytotoxicity
Authors: Robert N Reger, Maria Berg, Andreas Lundqvist, Theresa Donohue, Mattias Carlsten, Dawn M Betters, Lisa Cook, Catalina Ramos, Sophia Grasmeder, Su Su, David Stroncek, Jeremy Pantin, Keyvan Keyvanfar, Cristian A. Carvallo, Hahn Khuu, Richard Childs
Journal: Blood (2011)