tbuckley/cabot-search huggingface dataset:
A randomized controlled trial of ibandronate for the prevention of bone loss following allogeneic stem cell transplantation.
Authors: Xerxes Pundole, Richard E. Champlin, Uday R. Popat, Carmelita P. Escalante, William A Murphy, Robert F. Gagel, Huifang Lu
Journal: Journal of Clinical Oncology (2015)

7029 Background: Bone mineral density (BMD) loss occurs rapidly within the first year following allogeneic hematopoietic stem cell transplantation (alloHCT), which can lead to fractures. Nonpharmacologic prophylaxis measures are inadequate in preventing bone loss following alloHCT and the effect of ibandronate has not been evaluated. Methods: We performed a phase 3 single-center open-label randomized controlled trial of intravenous ibandronate to prevent BMD loss in adult recipients of alloHCT at The University of Texas MD Anderson Cancer Center. The treatment group received 3 mg of intravenous ibandronate over 15–30 seconds starting within 45 days of alloHCT and at 3, 6, and 9 months after alloHCT. All patients received daily calcium (500 mg) and daily vitamin D (400 IU) oral supplements twice daily for 12 months. We compared changes in BMD in the lumbar spine, femoral neck, and total hip at 6 and 12 months following alloHCT relative to baseline between treatment and control groups. Results: Of 414 patients screened, 78 were enrolled in the trial, 39 randomized to the ibandronate group and 39 to the control group. Baseline age, sex, race, underlying disease, donor type, stem cell origin, hormonal status, and baseline BMD did not differ significantly between the 2 groups. The treatment group had less BMD loss in the lumbar spine at 6 and 12 months than the control group (P ≤ 0.03). Both groups lost more BMD in the femoral neck and total hip than in the lumbar spine at 6 and 12 months, and changes in BMD in the femoral neck and total hip at 6 months (P = 0.33 & P = 0.10 respectively) and 12 months (P = 0.81 & P = 0.44 respectively) did not differ significantly between groups. Both glucocorticoids and tacrolimus reduced BMD in the lumbar spine, but ibandronate had a significant protective effect and prevented this loss. Conclusions: Ibandronate prevents bone loss in the lumbar spine in patients who undergo alloHCT, particularly those who received high doses of glucocorticoids or tacrolimus. However, ibandronate does not completely prevent bone loss at the femoral neck and total hip. Pharmacologic agents with different mechanisms of action should be evaluated in this population for better prevention of bone loss. Clinical trial information: NCT00824993.
Kim Harmon #SayNoToSuddenCardiacDeath #SuperEverything
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2017)

My fondest memories are the people I’ve worked with over the years. At the University of Washington (UW), Jon Drezner, John O’Kane, Ashwin Rao and Hank Pelto are terrific and drive me to be better. They make work fun and interesting and they push me to be better. It has been awesome to teach residents and fellows. I’ve appreciated the work I’ve been able to do in the athletic department—I never quite got over being part of a team as an athlete—and it is gratifying to be able to continue that, although in a different way. The American Medical Society for Sports Medicine (AMSSM) has been the single most important factor in career growth by giving me the opportunity to network and get involved. So, I guess my fondest career memory is the people I’ve met and the friends I’ve made.

Total chaos. Four boys (my sons) need to get lunches made, get off to different schools, find everything they need for the day, and my husband and I try to get to work on time.

Persistence. Much of the time …
Contents, Vol. 2, 1954
Authors: L Annell, Uppsala Betlheim, Zagreb Brachfeld, Mérida Brenman, T Stockbridge, Paris Brosse, Kobenhavn Brüel, J Zürich, Havana Bustamante, Wien Caruso, Milano Cazzullo, Anvers Dellaert, Athen Dracoulides, Paris Ey, Kreuzlingen Fierz, Lisboa Fontes, London Foulkes, Wien Frankl, Th French, Anvers Günzburg, Wien Hoff, Aires Buenos, Tübingen Kretschmer, Casablanca Laforgue, Groot Lampl-De, A Amsterdam, Zürich Maeder, Jyväskylä Maki, Basel Meng, Heidelberg Mitscherlich, Düsseldorf Mohr, Zürich Moor, Calcutta De, Roma Perrotti, Ishak Prokop1dis, Cairo Ramzy, Marseille Schächter, Berlin Schultz, Anibal Lima, Säo Silveira, Brasil Paulo, Lindau Speer, York New, Wien Stransky, Boulogne Stern, E Seine, London Strauss, Wien Strotzka, Istanbul Sükrü Aksel, F Villinger, Budapest Völgyesi, Wien Wanecek, Amsterdam Waterink, Pa Weiss, Montreal Wittkower, Tel-Aviv Woolf, F Alexander, . Boss, Zürich Dlnbar, New York, N Hanselmann, Ascona Van Der Horst, Amsterdam Mulder, Leiden Redactores, E Carp, Leiden Stokvis
Journal: Psychotherapy and Psychosomatics (1954)
Retrospective study to evaluate variables predicting no-show international patients.
Authors: Renato Lenzi, Martha Coleman, Lianchun Xiao, Reham Abdel-Wahab, Manal Hassan
Journal: Journal of Clinical Oncology (2014)

e17528 Background: Patients not appearing for scheduled medical appointments (no shows) has negative effects on a number of parameters including medical outcomes, quality of patient care and economic consequences. The proportion of no-shows among International Patients referred to large US cancer centers may depend on many factors. Data available regarding the no-show rate of International Patients in the United States are limited. Moreover, little is known regarding the reasons for International Patients’ failure to show for their scheduled medical appointments. Methods: Referral records from the population of patients evaluated in 2010 and 2011 for their initial visit at the International Cancer Assessment Center at M.D. Anderson Cancer Center were reviewed. A total of 760 International Patients with different types of cancer requested to be seen, and of those 558 (73.4%) were given an appointment. Univariate analysis was done using the c2or Fisher’s exact test for categorical variables and the Kruskal-Wallis test for continuous variables. Results: A total of 355 International Patients (63.8%) kept their appointment and 201 (36.2%) failed to show. The majority were from the Middle East, followed by South America and Asia. While the area of origin had no impact on failure to show up rate, we found a significant impact of the payment method. Self-pay was more common among those who failed to show up: 68.7% (138/201), as compared to 49% (174/355) among those who showed up. Thus self-pay patients were at two-fold higher risk of missing their appointment as compared to those with medical expenses covered by their government or by personal medical insurance, OR (95% CI)= 2.3 (1.6-3.3). We found no impact of the cancer type and disease site on failure to show for the scheduled medical appointments. Conclusions: This study suggests that approximately one third of the International Patients who are given an appointment at a large cancer center may not show up for their visit, with the highest rate of not showing being observed among self-pay patients.
Secondary efficacy subanalysis by histology from the phase III BRIGHT study: First-line bendamustine-rituximab (BR) compared with standard R-CHOP/R-CVP for patients with advanced indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL).
Authors: Ian Flinn, Richard H. C. Van Der Jagt, Brad S. Kahl, Peter Wood, Tim E. Hawkins, David MacDonald, Mark Hertzberg, Yiu-Lam Kwan, David Simpson, Michael Craig, Kathryn S. Kolibaba, Samar Issa, Regina Clementi, Doreen M. Hallman, Mihaela C. Munteanu, Ling Chen, John M. Burke
Journal: Journal of Clinical Oncology (2013)

8537 Background: BR was previously reported to be statistically noninferior to R-CVP/R-CHOP for complete response rate in the treatment of patients with indolent NHL or MCL. Evaluation of time-to-event outcomes is immature. This subanalysis reports response by histology. Methods: Indolent NHL or MCL was histologically confirmed &lt;6 months before study enrollment in patients who were therapy-naïve. Patients were stratified according to predetermined standard treatment (R-CHOP or RECVP) and lymphoma type, then assigned to receive BR (28-day cycles: bendamustine 90 mg/m 2 on days 1 and 2, rituximab 375 mg/m 2 on day 1) or standard treatment (21-day cycles at standard doses) for 6-8 cycles. Responses were assessed by a blinded independent review committee. The primary efficacy measure was noninferiority of BR complete response (CR) rate for evaluable patients with ≥1 postbaseline efficacy assessment. If the noninferiority threshold was met, superiority was assessed. Secondary measures included tolerability. Results: Of 447 patients enrolled in the study, 213 receiving BR and 206 receiving R-CHOP/R-CVP were evaluable with postbaseline data (Table). BR achieved a statistically noninferior CR rate compared with R-CHOP/R-CVP in patients with indolent NHL and MCL. Conclusions: In patients with treatment-naïve indolent NHL and MCL, BR achieved the primary endpoint of noninferior CR rate. Most CR rates were numerically, but not significantly, higher with BR. Small subgroup results should be interpreted with caution. Support: Teva BPP R&amp;D, Inc. Clinical trial information: NCT00877006. [Table: see text]
Relationship between BRCA1 promoter methylation and sensitivity of breast cancer cell lines to cisplatin and paclitaxel
Authors: C. Collins, D. Huo, J. Xu, W. K. Bleibel, M. E. Dolan, O. I. Olopade, R. Nanda
Journal: Journal of Clinical Oncology (2007)

21083 Background: While BRCA1 germline mutations are uncommon, and contribute to fewer than 5% of breast cancer cases, epigenetic alterations in BRCA1 occur more frequently. BRCA1 promoter methylation has been detected in 10–30% of breast tumors. Given the role of BRCA1 in DNA repair and cell cycle regulation, we hypothesize that cells with decreased expression of BRCA1 secondary to promoter methylation will be sensitive to DNA damaging agents and resistant to microtubule inhibitors, as has previously been shown for cells deficient in BRCA1 secondary to mutation. Methods: BRCA1 methylation was determined using methylation specific PCR (MSP) as previously described (Wei et al, Cancer Research 2005). The relative sensitivities of BRCA1 methylated, mutated and competent cells to cisplatin and paclitaxel were determined in five representative breast cancer cell lines using the AlamarBlue cytotoxicity assay. Exponentially growing cells were treated with increasing concentrations of cisplatin and paclitaxel for 96 hours. IC 50 values and 95% confidence intervals (CI) were calculated from sigmoidal dose response curves fitted with SAS 9.1 Proc NLIN. Western blot analysis for BRCA1 was performed on each cell line. Results: Conclusions: Only one of the two BRCA1 methylated cell lines studied (UACC3199) was sensitive to cisplatin and resistant to paclitaxel, as hypothesized. While both cell lines are methylated, western blot analysis revealed that both express BRCA1, but to a lesser degree than unmethylated cells. BRCA1 methylation, as assessed by non-quantitative MSP, does not correlate with sensitivity to cisplatin and resistance to paclitaxel. Quantification of BRCA1 promoter methylation may better predict chemosensitivity. Identification of the degree of BRCA1 methylation which does correlates with sensitivity to cisplatin and resistance to paclitaxel could improve treatment selection for patients with breast cancer. This work was supported by the US Army Grant W81XWH-04–1-0545. [Table: see text] No significant financial relationships to disclose.
Risk factors for metastatic prostate cancer: A sentinel event case series.
Authors: Channing Judith Paller, Alexander Cole, Alan W. Partin, Michael Anthony Carducci, Norma Kanerak
Journal: Journal of Clinical Oncology (2017)

235 Background: After 25 years of declines in late stage prostate cancer (PCa), evidence is mounting that an increasing fraction of men may present with metastatic disease, well after they might have been treated with local therapy. Identification of modifiable risk factors may allow for systems-level interventions to reduce delayed diagnoses. Methods: We performed an in-depth case series analysis of 15 patients who presented with metastatic disease at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center using root cause analysis, a tool commonly employed to understand the root cause of dangerous adverse events. Results: Key factors in late diagnosis include lack of insurance, lack of routine PSA testing, comorbidities, reluctance of patients to follow up actionable PSA as well as aggressive disease. Three patients had aggressive disease that would likely not have been discovered at an early stage regardless screening. However, analysis of the remaining 12 patients illuminated how health system factors led to missing important diagnostic information might have led to diagnosis of PCa at an earlier stage. Conclusions: These cases emphasize the need for systems-based approaches to early diagnosis of prostate cancer, which may prevent men from missing the opportunity to cure prostate cancer at an early stage. These results show how one might target PCa screening recommendations to more fully reflect key risk factors such as race and family history.
Do patients with small cell lung cancer (SCLC) who have chemotherapy initiated during a hospital admission benefit from therapy?
Authors: David Dawe, Gregory Russell Pond, Peter Michael Ellis
Journal: Journal of Clinical Oncology (2014)

e17661 Background: Lung cancer patients (pts) admitted to hospital in Canada generally have a poor performance status (ECOG 3 or 4). This often precludes treatment for pts with NSCLC, although many oncologists will offer chemotherapy (CT) to hospitalized SCLC pts due to rapid and frequent responses. However, this practice is based on little published data. This study investigates the proportion of SCLC pts with CT initiated in hospital and their outcomes. Methods: We conducted a retrospective cohort study of all Ontario pts diagnosed with SCLC (ICD-9 codes 162.2-162.9) between January 1, 2000-December 31, 2010. De-identified data including demographic, staging, treatment and outcome information were extracted by the Institute for Clinical Evaluative Sciences. The outcomes of this sub-study were the proportion of patients initiating CT while hospitalized versus outpatient based CT initiation and their overall survival. Initiation of CT while admitted to hospital was defined as the first instance of billing for CT dated between a hospital admission and discharge. Results: Among 9021 pts diagnosed with SCLC, 6,568 (73.8%) received chemotherapy, of which 1631 (24.8%) initiated CT while admitted to hospital. The proportion of pts treated in hospital decreased over time. More pts initiating CT in hospital had late stage disease at diagnosis compared to those treated as outpatients, although staging information was not routinely recorded prior to 2007. Median overall survival (OS) for SCLC pts initiating CT in hospital was 6.9 months versus 11.7 months for those treated as outpatients and 1.4 months for patients receiving no CT. One year survival rates were 24.8%, 48.7%, and 10.4%, respectively. All differences have a p-value <0.001. Conclusions: This study shows that a substantial proportion of pts initiate CT while admitted to hospital. These pts likely have a poor performance status. While treatment of this group is associated with poorer median OS than patients initiating CT as an outpatient, CT appears to prolong life in comparison to no treatment. These data provide supportive evidence for the use of CT in poor functioning pts with SCLC.
Relationship of Src activity and prior oxaliplatin on outcomes after hepatectomy for metastatic colorectal cancer.
Authors: Van Karlyle Morris, Nila Parikh, Michael J. Overman, Zhi-Qin Jiang, Dipen M Maru, Paul Elvin, Scott Kopetz, Gary E. Gallick
Journal: Journal of Clinical Oncology (2012)

3561 Background: The nonreceptor tyrosine kinase Src regulates pathways critical to tumor proliferation, chemoresistance, and epithelial-to-mesenchymal transition. In vitro, Src is activated after acute oxaliplatin exposure and in acquired oxaliplatin resistance, but not after 5-FU alone. Activation of Src and its substrate FAK in metastatic colorectal cancer treated with oxaliplatin has not been studied in human specimens. Methods: Samples from 170 hepatic resections from two cohorts of patients with metastatic colorectal cancer were examined by IHC for expression of activated Src (pSrc) and FAK (total and pFAK). In the first cohort (n=50), tissue was collected at consecutive hepatic resections before and after oxaliplatin. Patients in the second cohort (n=120) were compared based on whether or not oxaliplatin was administered after resection. IHC was graded semi-quantitatively, 0 to 4 based on intensity (first cohort), and by automated image analysis (second cohort). Results: In the first cohort, pFAK expression increased after oxaliplatin exposure (mean IHC score 2.04 vs. 1.18, p&lt;0.01). In the second cohort, Src activation was correlated with pFAK expression (p&lt;0.01). Patients pretreated with oxaliplatin demonstrated increased expression of activated FAK (p=0.02) compared to 5-FU alone or irinotecan regimens. There was a weak association between total Src expression and the number of oxaliplatin cycles (p=0.06). Among patients in the second cohort, five-year relapse-free survival was inversely related to levels of pFAK (21.1%, 16.5%, and 7.4% for low, medium, and high levels of pFAK, respectively; p=0.02) and of pSrc (19.6%, 13.6%, and 8.2% for low, medium, and high levels of pSrc, respectively; p= 0.01). Conclusions: Patients treated with neoadjuvant oxaliplatin demonstrated increased Src signaling in liver metastases, a finding associated with worse relapse-free survival. These results are consistent with prior in vitro studies correlating oxaliplatin exposure with Src pathway activation and support the idea that inhibition of Src, when used in combination with platinum chemotherapy, warrants further investigation in patients with metastatic colorectal cancer.
Clinical outcome prediction in esophageal adenocarcinoma based on tumor and germ-line single nucleotide polymorphisms (SNP) in DNA-repair pathways
Authors: H. Yoon, K. M. Murphy, M. K. Gibson
Journal: Journal of Clinical Oncology (2007)

15144 Background: Germ-line SNPs in DNA repair enzymes are studied as predictive factors in various cancers. More rarely studied, however, is the presence of SNPs in tumor cells and how they relate to both germ-line SNPs as well as outcome. We explored the presence of and relationship between germ-line and tumor SNPs in esophageal adenocarcinoma using two systems: (1) Cell lines, to determine whether loss of heterozygosity (LOH) occurs near DNA repair genes, and for genotyping; (2) Patient samples, to determine whether SNPs differ between normal and tumor mucosa. Methods: (1) For LOH analysis, we examined three short tandem repeat (STR) loci on 19q13.2- 13.3 (near DNA-repair genes XPD, ERCC1, and XRCC1) in four esophageal adenocarcinoma cell lines. (The STR markers have a false positive rate of &lt;10 -3 for LOH when all three demonstrate homozygosity.) Then, using a real-time PCR allelic discrimination TaqMan assay (AB), we analyzed two SNPs of interest in these cell lines. (2) We performed SNP analysis on tumor and adjacent normal mucosa from paraffin-embedded esophageal specimens taken at resection in patients with T 3 N 0–1 esophageal adenocarcinoma who received preoperative cisplatin, paclitaxel, gefitinib and radiotherapy followed by transhiatal resection. Results: (1) Cell lines: SEG1 and BiC1 were consistent with LOH, showing a single-allele pattern at XPD 751 (C allele) and XPD 312 (G allele). TE7 and SKGT4 did not have LOH. (2) Tumor and normal tissue: We obtained data on two patients for XPD 751. Genotypes in normal mucosa were heterozygous for one patient and homozygous at the minor allele (Q/Q) for the second patient. Genotypes in tumor were identical to those in normal tissue. Conclusions: Our cell line data shows that LOH occurs in esophageal tumor cells at DNA-repair genes of interest. Our data in two patients with esophageal adenocarcinoma did not demonstrate a difference at XPD 751 between tumor and normal tissue. Given the technical success and encouraging data from this work, we plan to evaluate tissue from ∼90 patients who underwent preoperative cisplatin-based chemoradiotherapy followed by surgery (as part of completed ECOG trial E1201). [Table: see text]
Programmed cell death 1 (PD-1) and its ligand (PD-L1) expression in thymic epithelial tumors (TETs): Impact on the treatment efficacy and alteration in expression after chemotherapy (C).
Authors: Yuki Katsuya, Hidehito Horinouchi, Tetsuhiko Asao, Shinsuke Kitahara, Kuniko Sunami, Yoshitaka Seki, Yasushi Goto, Shintaro Kanda, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Koji Tsuta, Shun-ichi Watanabe, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2015)

7515 Background: Recent studies have demonstrated the efficacy of anti-PD-1/L1 antibodies. To understand the clinical impact of PD-1/L1 expression in TETs, we evaluated the frequency of PD-1/L1 expression in pre- and post-C (Pre/Post) specimens and the correlation between PD-1/L1 expression and the treatment efficacy. Methods: The expression of PD-1/L1 was evaluated by immunohistochemistry in patients (pts) with thymoma (TM) or thymic carcinoma (TC) treated by chemotherapy between 2000 and 2014 at the National Cancer Center Hospital. Using formalin-fixed paraffin-embedded tissue samples and a validated PD-L1 antibody (E1L3N), the PD-L1 expression in TET cells was reported in terms of the H-score (0-300), with a score ≥ 1 being defined as positive. PD-1 expression in the tumor-infiltrating lymphocytes was evaluated based on the intensity (0–3) of staining using a PD-1 antibody (NAT105). The objective response rate (ORR), progression-free survival (PFS) and the difference in PD-1/L1 expression between the Pre/Post TM specimens were evaluated. Results: A total of 29 pts was included; TM/TC, 12/17; male/female, 14/15; median age 57; WHO histology (B1/B2/B3/Squamous/others), 1/7/3/12/6. Pre/Post serial specimens were available for 6 TMs. All pts received platinum-based C, and the ORR was 42% in TMs and 18% in TCs. Expression of PD-L1 was positive in 9 (75%) of the TMs and 8 (47%) of the TCs. In the PD-L1 positive population, ORR was 56% (5/9) in TMs and 13% (1/8) in TCs. In the PD-L1 negative population, ORR was 0% (0/3) in TMs and 22% (2/9) in TCs. There were no statistically significant differences in the PFS according to the PD-L1 expression status. Increase of the PD-L1 score and PD-1 staining intensity were observed after C in serial specimens of TM; mean Pre/Post PD-L1 score, 41.6/92.5 (p = 0.058); median Pre/Post PD-1 intensity, 0/2.5 (p = 0.055). Conclusions: Although there was no obvious correlation between PD-L1 expression and the efficacy of C in pts with TETs, increased expression of PD-1/L1 after C was observed in the TMs. Further efforts to develop novel therapies, including anti PD-1/L1 antibodies, are warranted.