tbuckley/cabot-search huggingface dataset:
Testosterone levels in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Christoph A. J. von Klot, Alena Boeker, Thomas R. W. Herrmann, Mario W. Kramer, Markus A. Kuczyk, Axel S. Merseburger
Journal: Journal of Clinical Oncology (2015)

191 Background: It is common practice to continue anti-androgen therapy in terms of androgendeprivation when performing chemotherapy or androgendeprivation with new second generation therapeutic agents such as enzalutamide or abiraterone acetate. Clinical Studies aiming at the question whether continuation of conventional ADT is necessary in this setting are currently recruiting. In this study we analyzed androgen deprivation in patients with mCRPC under chemotherapy and second generation androgen suppression. Methods: Out of 620 screened patients a total of 36 patients with continuous testosterone monitoring and mCRPC underwent therapy with docetaxel, abiraterone acetate, enzalutamide, carboplatin, carbozantinib or cabazitaxel and were evaluated. Data were gathered from our center over a median follow up period of 27.8 (0.6 - 65.1) month. A cutoff of 0.5 ng/dL was used to discriminate patients according to testosterone castration levels. Statistical evaluation was performed applying Kaplan Meier survival estimates, Cox regression and log rank test. Results: Median follow up was 26.2 month (range 1.4 - 64.8 month). Mean patient age was 70.9 years (range 51 - 86 years). The mean testosterone concentration in our cohort was 0.5 ng/dL. Serum testosterone levels varied greatly: ranging from 0 to 16 ng/dL. A total of 18 patients died during follow up. Median survival over all patients according to Kaplan-Meier survival estimation was 38.7 month (95% CI: 31 - NA month). Median survival for patients with testosterone levels below and above 0.5 ng/dL were 48.67 and 18.13 month respectively (log rank test: p = 0.0029). In Cox regression analysis, the hazard ratio for risk of death for patients with testosterone concentrations &gt; 0.5ng/dL was 6.03 (95% CI: 1.5 - 25, p - 0.0132). For the covariates PSA velocity, patient age and primary Gleason score there was no significant effect on risk of death (p = 0.0597, 0.5006, 0.7354). Conclusions: In patients with mCRPC i.e rising PSA or progression under androgen deprivation, conventional suppression of testosterone levels still represents a vital factor for overall survival even at the mCRPC stage and under therapy with second line anti hormonal therapeutic medication and chemotherapy.
Living with ‘melanoma’ … for a day: a phenomenological analysis of medical students’ simulated experiences
Authors: M. Corr, G. Roulston, N. King, T. Dornan, C. Blease, G.J. Gormley
Journal: British Journal of Dermatology (2017)

Despite the rising incidence of melanoma, medical students have progressively fewer opportunities to encounter patients with this important condition. Curricula tend to attach the greatest value to intellectual forms of learning. However, compared with intellectual learning, experiential learning affords students deep insights about a condition. Doctors who experience ill health are more empathic towards patients. However, opportunities to learn about cancer experientially are limited. Temporary transfer tattoos can simulate the ill health associated with melanoma. We reasoned that if doctors who have been sick are more empathic temporarily 'having' melanoma might have a similar effect.To explore the impact of wearing a melanoma tattoo on medical students' understanding of patienthood and attitudes towards patients with melanoma.Ten fourth-year medical students were recruited to a simulation. They wore a melanoma tattoo for 24 h and listened to a patient's account of receiving their diagnosis. Data were captured using audio diaries and face-to-face interviews, transcribed and analysed phenomenologically using the template analysis method.There were four themes: (i) melanoma simulation: opening up new experiences; (ii) drawing upon past experiences; (iii) a transformative introduction to patienthood; (iv) doctors in the making: seeing cancer patients in a new light.By means of a novel simulation, medical students were introduced to lived experiences of having a melanoma. Such an inexpensive simulation can prompt students to reflect critically on the empathetic care of such patients in the future.
AORTIC ROOT REMODELING AFTER TRANSCATHETER AORTIC VALVE IMPANTATION: EVALUATION BY COMPUTED TOMOGRAPHY
Authors: Stephan Achenbach, Martin Arnold, Josef Ludwig, Richard Feyrer, Annika Schuhbaeck, Michael Weyand, Holger Nef, Christian Schneider, Jonathan Leipsic, James Min, Christian Hamm, Werner Daniel, Mohamed Marwan
Journal: Journal of the American College of Cardiology (2012)
Respiratory pathophysiologic responses
Authors: Beth L. Laube, Alan M. Edwards, Richard N. Dalby, Peter S. Creticos, Philip S. Norman
Journal: Journal of Allergy and Clinical Immunology (1998)

Approximately one third of patients with allergy-induced asthma who are treated with aerosolized cromolyn sodium (CS) fail to achieve a full therapeutic effect. This lack of effectiveness could involve nonhomogeneous distribution of drug in the lung as a result of high inspiratory flow rates.We sought to determine the efficacy of slow versus faster inhalation of CS in protecting against allergen challenge in patients with asthma.Eight patients with asthma underwent two allergen challenges 30 minutes after pretreatment with CS that was inhaled from a large holding chamber at approximately 30 L/min or approximately 70 L/min. Percent decreases in FEV1 at a common dose of allergen on the two challenge days were compared. Values of skew (an indicator of aerosol distribution homogeneity) obtained from gamma camera lung images after slow and faster inhalation of radiolabeled CS were also compared.Mean (+/- SD) allergen-induced decrease in FEV1 was 5.4% +/- 4.2% after slow inspiration of CS, which was significantly less than the allergen-induced decrease in FEV1 after faster inhalation of CS with 12.6% +/- 11% (p < 0.05). Mean skew values were also significantly decreased after slow inspiration of CS, and differences in decreases in allergen FEV1 and skew values for the two breathing maneuvers were significantly correlated.These data indicate that protection against allergen-induced asthma can be optimized by slowly inspiring CS from a large holding chamber compared with faster inhalation of the drug. These results appear to be related to enhanced distribution homogeneity of CS within the lungs.
Impact of prior radiation treatment (tx) on sipuleucel-T (sip-T) product parameters in PROCEED patients (pts).
Authors: Steven E. Finkelstein, Luke T. Nordquist, Shaker R. Dakhil, Nathan B. Green, Elisabeth I. Heath, Ronald Tutrone, Nicholas J. Vogelzang, Andrew J. Armstrong, Matthew R. Cooperberg, Robert Claude Tyler, Robert Brownell Sims, James Boyd Whitmore, Celestia S. Higano
Journal: Journal of Clinical Oncology (2014)

183 Background: Sipuleucel-T (sip-T) is an autologous cellular immunotherapy indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. Approval of sip-T was based primarily on the randomized, controlled, phase 3 study (IMPACT) that demonstrated a 22% reduction in the risk of death. Since radiation tx could suppress bone marrow function and therefore immune function, IMPACT excluded patients (pts) who received radiation more than or equal to 28 days prior to registration. PROCEED is an ongoing phase 4 registry enrolling pts tx with commercial sip-T in the real-world setting. Palliative radiation (PR) tx for bone pain prior to sip-T is not restricted in PROCEED, so the effects of prior radiation on sip-T manufacturing parameters can be evaluated. Methods: Pts treated with sip-T at or before six months were eligible. Baseline pt demographics and disease characteristics were collected. Sip-T product parameters that were assessed included: total nucleated cell (TNC) count, antigen presenting cell (APC) count (large CD54 + cells), and APC activation (upregulation of CD54; a measure of product potency). Results: Data were available for 1,244 pts enrolled by May 2013, who completed tx; of those, 112 (9.0%) pts received PR to bone metastases prior to sip-T and 517 (41.6%) pts had no prior radiation of any kind (NRT). To ensure that groups (grp) were homogeneous and to limit the comparison of NRT pts with those who had PR only for bone metastases, pts with radical prostatectomy were isolated from each grp for further study, resulting in 44 pts in the PR grp and 159 pts in the NRT grp. Median cumulative APC counts were similar between grp, however TNC counts (PR: 9.89 vs. NRT: 12.09 x 10 9 ; P=0.002) and APC activation (PR: 34.2 vs. NRT: 38.5; P=0.048) were lower in the PR grp. However, the percentage of pts receiving all three infusions in each group was comparable (PR: 93.2% vs NRT: 95.0%; P=0.71). Conclusions: In the real-world setting, there is no evidence that prior radiation inhibits successful production of sip-T. Although TNC counts and APC activation were lower, APC counts were comparable in radiation treated pts. Effects on in vivo post treatment immune measures are being collected prospectively in a companion trial called PRIME. Clinical trial information: NCT01306890.
Model-based prediction of patient-specific residual disease levels for imatinib-treated chronic myeloid leukemia.
Authors: M. Loeffler, M. Horn, I. Glauche, M. C. Müller, A. Hochhaus, I. Roeder
Journal: Journal of Clinical Oncology (2011)

6604 Background: Molecular response to imatinib (IM) therapy in chronic myeloid leukemia (CML) patients is associated with a biphasic decline of BCR-ABL transcript levels exhibiting a substantial heterogeneity. It is of clinical interest to predict the time courses over several years to decide about treatment discontinuation. Methods: We here present a mathematical model of hematopoietic and leukemic stem cell organization, which can explain CML dynamics and the biphasic decline in response to IM treatment accounting for inter-patient heterogeneity. Model parameters are estimated using 7-year follow-up data from a prospective randomized clinical trial (German IRIS cohort). Results: Based on data on the initial decline of BCR-ABL transcript levels, our model predicts individual long-term response to IM treatment. Furthermore, the model provides estimates on the remaining number of residual leukemic stem cells (LSCs), which is important to decide about treatment termination. In order to test the validity of the model, we provide predictions for an independent data set (German CML IV trial). Whereas we find that the majority of patients (66%) will require IM therapy for more than 30 years to achieve a complete eradication of all LSCs, a subset of patients (10%) is predicted to achieve the complete LSC eradication within less than 15 years of continuous IM administration. Conclusions: We conclude that our mathematical model is able to provide individual long-term predictions on IM-treated CML. Although developed and validated for IM treatment, the proposed model will be applicable to forthcoming molecular response data from first-line second-generation tyrosine kinase inhibitor therapy.
Overall survival with adjuvant zoledronic acid in patients with premenopausal breast cancer with complete endocrine blockade: Long-term results from ABCSG-12.
Authors: M. Gnant, B. Mlineritsch, H. Stoeger, G. Luschin-Ebengreuth, S. Poestlberger, P. C. Dubsky, R. Jakesz, C. F. Singer, H. Eidtmann, R. Greil
Journal: Journal of Clinical Oncology (2011)

520 Background: Adjuvant zoledronic acid (ZOL) significantly improved disease-free survival (DFS) in premenopausal patients (pts) with endocrine-responsive early breast cancer in ABCSG-12 (Gnant et al. NEJM 2009). The ZOL anticancer effect was confirmed in other prospective trials, such as ZO-FAST and the postmenopausal (> 5 yrs) cohort of AZURE. Long-term follow-up of ABCSG-12 (> 6 yr) now allows pre-planned subgroup analyses that more precisely identify the ZOL benefit, and interactions with pt and tumor characteristics. Methods: Premenopausal pts with early breast cancer (N = 1,803) were randomized to ovarian function suppression with goserelin (3.6 mg q28d) and tamoxifen (TAM; 20 mg/d) or anastrozole (ANA; 1 mg/d) ± ZOL (4 mg q6mo) for 3 yr. Endpoints included DFS and overall survival (OS), both analyzed using log-rank test and Cox models. Preplanned subgroup analyses included subpopulation treatment effect pattern plot (STEPP). Results: At 68 mo median follow-up, ZOL significantly reduced the risk of DFS events by 32% vs no ZOL (HR = 0.68; P = .009); in addition, there was a strong trend toward reduced risk of death (HR = 0.66; P = .08) with ZOL vs no ZOL. Multivariate analyses showed no interaction between ZOL benefit and ANA/TAM or any classic tumor parameter (eg, T, N, grade, ER). However, a strong interaction between ZOL and pt age was demonstrated. Pts > 40 yr of age (n = 1,390) derived significant DFS benefits from ZOL (HR = 0.58; 0.40-0.83; P = .003), whereas there was no apparent benefit in pts < 40 yr of age. ZOL reduced the risk of death by 42% in pts > 40 yr of age (P = .05), with presumed complete ovarian blockade. In several age subgroups > 40 yr, HRs < 0.5 were observed for both DFS and OS. Conclusions: ABCSG-12 long-term follow-up at 68 mo suggests that anticancer benefits of adjuvant ZOL mainly occur in pts with a low-estrogen environment. As in the postmenopausal (> 5 yrs) cohort of AZURE, ZOL leads to highly significant DFS and OS benefits. This suggests that both estrogen deprivation and reduction of bone-turnover–derived growth factors in the bone marrow microenvironment are needed for sufficient suppression of dormant micrometastases.
Bridging to survivorship in breast cancer: Learning how treatment impacts mental health among early-stage breast cancer survivors.
Authors: Debra A. Patt, Janet L. Espirito, Brian Turnwald, Robyn K. Harrell, Debajyoti Bhowmik, J. Russell Hoverman, Barry Don Brooks, Neelima Denduluri, Roy A. Beveridge
Journal: Journal of Clinical Oncology (2013)

9604 Background: Depression (D) and anxiety (A) complicate survivorship in breast cancer (BC) patients (pts). The prevalence of D and A after BC treatment (Tx) in the community and concordance with BC Tx type is poorly described, but vitally important to characterize risks of Tx and optimize support for BC pts and goals for survivorship care planning. Methods: We queried the electronic health record (EHR), iKnowMed, from a a large network of community oncology practices for pts treated with stage I-III breast cancer from 2007-2010 with at least 5 visits and follow up through 2012 for our retrospective study. We excluded pts who developed metastatic disease or died. We stratified pts by chemotherapy (CT) utilization (yes/no),hormone receptor (HR) status, age, and documented body mass index (BMI) at diagnosis, and post diagnosis development of D (y/n), A (y/n) or utilization of venlafaxine (E) like antidepressants (Ads), non-E like Ads or anti-A medications within the study period. Time to onset of A or D was analyzed using Cox proportional hazard methodology. Results: We identified 8,506 patients with a documented BMI at 1, 2, and 3 years (yrs) post diagnosis. 4369(51%) of patients received adjuvant CT and 4137 (49%) did not. Baseline characteristics were similar between tx groups, and active D or A was low at the time of dx, but as a whole rose to 41% during the study period. Pts with pre-existing D or A at the time of diagnosis were excluded. CT increases the risk of D or A (HR: 1.23, CI: 1.15-1.33). HR+ status also increases the risk of D or A (HR: 1.21, CI:1.11-1.32). Age conveyed a small diminished risk of D or A (HR: 0.98, CI: 0.98-0.99) while baseline BMI conveyed a small increased risk (HR: 1.02, CI 1.01-1.3). When excluding E like compounds that are often used to treat hot flashes in BC pts, CT was still found to have an increased risk of D or A (HR: 1.28, CI: 1.18-1.39), and HR+ was still associated with higher risk of D or A as well (HR: 1.11, CI: 1.01-1.22). Conclusions: Mental health disorders such as D and A are common among BC survivors, and more prevalent among BC survivors who received CT and have HR+ disease. This warrants further investigation on how to evaluate and support the mental health needs of BC survivors.
A systematic approach to companion diagnostic development: A case study for omacetaxine (OM) for the treatment of chronic myelogenous leukemia (CML).
Authors: Carol L. Preisig
Journal: Journal of Clinical Oncology (2012)

100 Background: In the age of genomically informed medicine, therapeutic development carries with it the imperative to employ genomics in patient selection. Physicians expect genomics-based methods to identify treatments likely to be effective, and identify anomalies likely to cause adverse response for a given patient. Companion diagnostics should support such rule-in and rule-out decisions. We demonstrate a systematic approach to companion diagnostics that leverages new methods in translational bioinformatics and clinical economics. CML therapies have been at the forefront of genomically informed medicine. Early TKI inhibitors targeting the BCR-ABL fusion protein are highly effective. With time, however, they induce resistance-creating mutations in many patients. Omacetixine, a translation inhibitor, was expected to help this CML patient subpopulation which has few therapeutic alternatives. We use this well-characterized drug and publicly available data to demonstrate a prospective approach to companion diagnostics. Methods: We used translational bioinformatics, incorporating pathway, cell line, and patient data to identify biologically plausible biomarkers from which alternative companion diagnostic paths were constructed. These alternatives were analyzed using a modified version of the MIT Stratified Medicine Model to assess the clinical economics of each path. Results: From a systematic look at the biology of the disease, the unique mechanism of action of OM and the clinical need, we identified 3 alternative companion diagnostics for OM. Economic analyses quantified the trade-offs of targeting different subpopulations for the indication, clarifying the impact of biomarker selection based on clinical need or biology. Other analyses have shown that eNPV can be halved or doubled based on strategy choice. Conclusions: Combining applied translational bioinformatics and stratified medicine economics provides an effective approach to companion diagnostic selection. This approach can reduce drug-development cost and clinical risk while providing physicians with better genomics-based methods for clinical decision-making.
Incidence of hyponatremia in a cohort of patients with colorectal cancer.
Authors: Jorge J. Castillo, Ilya Glezerman, Susan Boklage, Joseph Chiodo, Kathy L. Schulman
Journal: Journal of Clinical Oncology (2015)

545 Background: Hyponatremia (HN), a common electrolyte disturbance in hospitalized patients, is a prognostic factor in some cancers. The incidence of HN in patients diagnosed with colorectal cancer (CRC) is unknown and is investigated here. Methods: This retrospective cohort analysis combined electronic medical record and tumor registry data from an integrated delivery network. Patients included were adults diagnosed with incident invasive CRC between 2005 and 2011 with ≥1 administration of radiation or chemotherapy within 6 months of diagnosis who met continuous clinical activity criteria. Exclusions included unknown index cancer stage or ≥1 post-index hypovolemic HN episode. Patients were followed until study end, death, clinical trial entry, new primary cancer onset, or end of continuous clinical activity. HN incidence (serum sodium ≤135 mEq/L) was measured per 1,000 person years (PY) of observation (95% confidence intervals [CI]) and classified as mild (131–135), moderate (125–130) or severe (&lt;125) based on the lowest observed value. Results: In all, 132 CRC patients were included (52% male; mean [SD] age 64±13.1 years, 99% Caucasian). Mean (SD) follow-up was 3±2.6 years. Thirty-six percent of patients had metastatic disease at diagnosis and 80% received chemotherapy, 39% radiation therapy and 83% surgical resection. Patients with HN post-CRC diagnosis had significantly greater incidence of metastatic disease during follow-up (p=0.033) and exposure to anti-metabolites (p=0.023) or platinum based agents (p=0.017). Episodes of HN (n=262) occurred in 81 patients (61%) at a rate of 598 per 1,000 PY (95% CI, 523–680). Mean (SD) episodes per patient were 1.8±2.6. Overall, 84% of episodes were mild, 14% moderate and 2% severe; 52% were classified as syndrome of inappropriate antidiuretic hormone secretion. Mean (SD) time to first hyponatremia episode was 139±296 days, with a median duration of 12 days; 84% of patients had a first episode within the first 6 months. Conclusions: The incidence of HN after diagnosis with CRC was about 61% and episodes occurred primarily within 6 months of diagnosis. Based on these results, along with emergent evidence from other studies, clinicians should anticipate HN in newly-diagnosed CRC patients.
Global, multicenter, open-label, randomized phase II trial comparing gemcitabine (G) with. G plus AGS-1C4D4 (A) in patients (pts) with metastatic pancreatic cancer (mPC).
Authors: B. M. Wolpin, E. M. O'Reilly, Y. Ko, L. S. Blaszkowsky, M. U. Rarick, C. M. S. Rocha Lima, P. S. Ritch, E. Chan, J. L. Spratlin, T. Macarulla, E. McWhirter, D. Pezet, M. Lichinitser, L. D. Roman, A. Hartford, L. Jackson, M. Vincent, L. M. Reyno, M. Hidalgo
Journal: Journal of Clinical Oncology (2011)

4031 Background: A is a fully human monoclonal antibody directed against prostate stem cell antigen (PSCA), a cell surface protein expressed on pancreatic cancer cells. Methods: Previously untreated pts with pathologically- confirmed mPC and ECOG performance status (PS) of 0-1 were randomized 1:2 to G (1000 mg/m2 IV over 30 minutes weekly x7, 1 week rest, then weekly x3 q4weeks) or G plus A (48 mg/kg loading dose, then 24 mg/kg q3weeks over 60 minutes IV), stratified by region (North America vs. Europe/Russia). Primary endpoint was 6-month (mo) overall survival (OS) in the intention-to-treat population. With a planned sample size of 185 pts, the study was designed to detect an improvement in 6-mo OS from 45% to 65% with 90% power and one-sided α=0.10. Tumor samples were collected for pre-planned secondary analyses by PSCA expression. Results: 196 pts (63 in G arm, 133 in G+A arm) were enrolled from 04/09-05/10 at 55 centers in U.S., Canada, Spain, France, and Russia. For G/G+A arms: median age 63/62 years, male 40/56%, PS 1 83/73%, deaths to date 73/67%. Grade 3/4 adverse events (G/G+A; %): any 63/78%, neutropenia 14/26%, thrombocytopenia 2/9%, and pulmonary embolism 2/6%. Tumor tissue was available from 118 pts (60%) for immunohistochemistry (IHC): 64 pts strong/moderate (pos) and 54 weak/no staining (neg) for PSCA. Efficacy data for 6-mo OS are shown in the table. Disease control rates (PR+SD) and 95% CI were 49% (36, 62) for G arm and 50% (41, 58) for G+A arm in the full population, and 57% (34, 78) for G arm and 70% (54, 83) for G+A arm in the PSCA pos population. Conclusions: The addition of A to G is well-tolerated and resulted in a trend toward improved 6-mo OS, primarily in patients with moderate or strong tumor PSCA expression. Follow-up is ongoing for secondary endpoints. Population 6-mo OS (%) (95% CI) Difference (95% CI) P value* G G+A (G+A) - A Full 44 (32, 58) 56 (47, 64) 11 (-4, 26) 0.07 PSCA pos 57 (34, 78) 74 (59, 87) 17 (-10, 42) 0.08 PSCA neg 32 (13, 57) 34 (19, 52) 3 (-25, 30) 0.42 PSCA not available 44 (23, 66) 55 (41, 68) 11 (-13, 35) 0.19 *One-sided Cochran-Mantel-Haenszel test.