tbuckley/cabot-search huggingface dataset:
Relationship between abiraterone exposure, prostate-specific antigen (PSA) kinetics, and overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) .
Authors: Steven Xu, Charles J. Ryan, Kim Stuyckens, Matthew R. Smith, Fred Saad, Thomas W. Griffin, Youn Choi Park, Margaret K. Yu, An Vermeulen, Italo Poggesi, Partha Nandy
Journal: Journal of Clinical Oncology (2014)

39 Background: Abiraterone, the active metabolite of abiraterone acetate (AA), is an effective androgen biosynthesis inhibitor for patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted a sequential exposure-biomarker-survival modeling analysis to explore the relationship between prostate-specific antigen (PSA) kinetics and overall survival (OS) and to establish the exposure response for PSA kinetics and OS in chemotherapy-naïve and -pretreated patients with mCRPC following AA administration. Methods: The exposure-PSA-survival modeling framework was based on two phase III studies, COU-AA-301 (chemotherapy-pretreated, N = 1184) and COU-AA-302 (chemotherapy-naïve, N = 1081), and included a mixed-effects tumor growth inhibition (TGI) model to describe PSA dynamics in response to AA and a Cox proportional hazards survival model to evaluate the relationship between relative risk of death and PSA dynamic end points. Results: The TGI model best described the longitudinal PSA dynamics following AA treatment. Abiraterone exposure significantly increased PSA decay rate (maximum effect of 2.72, p &lt; 0.0001). The estimated concentration for 50% of the maximum effect (EC 50 ) was 4.75 ng/mL. The abiraterone effect on PSA kinetics was similar in chemotherapy-naïve and -pretreated subjects, and approximately 90% of subjects had a steady-state concentration greater than the EC 50 . All model-predicted PSA metrics were strongly associated with OS in both populations; model-based post-treatment PSA doubling time showed the strongest association (hazard ratios approximately 0.9 in both populations). Simulations showed that the modeling framework could accurately predict the survival outcome for both studies. Conclusions: The analysis revealed a similar effect of abiraterone on PSA kinetics and association between PSA kinetics and OS in chemotherapy-naïve and -pretreated subjects, providing additional evidence for surrogacy of PSA kinetics and the use of PSA end points to indicate clinical benefit of abiraterone in subjects with mCRPC regardless of prior chemotherapy. Furthermore, the study confirmed that the recommended 1,000 mg/d dose of AA leads to adequate clinical exposure above the effective level. Clinical trial information: NCT00638690, NCT00887198.
Do hospitals in a large metropolitan area utilize published breast cancer care practices and guidelines?
Authors: Katherine Y. Tossas-Milligan, Christine B. Weldon, Julia Rachel Trosman, Melissa A. Simon, Betty Roggenkamp, William J. Gradishar, David Ansell, Anne Marie Murphy
Journal: Journal of Clinical Oncology (2014)

151 Background: Insufficient utilization of guideline and evidence based care practices contribute to the cancer crisis (IOM 2013). We examined utilization of published breast cancer (BC) care practices and guidelines at hospitals in a large metropolitan area. Methods: IRB approved web survey of all 35 hospitals in a large metro area that provide BC treatment. Using guidelines/recommendations (NCCN, NAPBC, ADA, IOM) and peer-reviewed literature (62 studies) we developed a survey on BC care practices. Results analyzed by simple frequencies and Fisher's exact test. Results: Response rate: 91% (32/35 sites). Care practices, included in the table, are utilized by &lt; 50% of sites. Radiation oncologist preoperative consults (53%, 8/15) and offering indicated pre-operative chemo* (67%, 10/15) are associated with 15 sites that have high volume (67+/year, Chen CS 2008) BC surgeons, compared to 17 sites without high volume BC surgeons (12%, 2/17) and (24%, 4/17) respectively, p=0.02, p=0.03. Indicated supportive services, such as a dental checkups (ADA 2008), are more likely at sites with patient-centered written treatment plans (IOM 2011) (58%, 7/12) than at sites without written treatment plans (10%, 2/20), p=0.006. Conclusions: Low utilization of published care practices and guidelines is concerning and requires attention. Other metro areas and regions should be examined as our findings indicate that patients may have limited local choices of care that is up-to-date on published guidelines and practices. [Table: see text]
Paclitaxel (P)/carboplatin (C) versus gemcitabine (G)/vinorelbine (V) in patients with adeno- or undifferentiated carcinoma of unknown primary (CUP) - A randomized prospective phase-II-trial
Authors: G. Huebner, S. Steinbach, C. H. Kohne, M. Stahl, A. Kretzschmar, A. Eimermacher, H. Link
Journal: Journal of Clinical Oncology (2005)

4089 Background: Platinum/taxane combinations are widely used in patients (pts) with CUP, yielding response rates of 30% and median overall survival (OS) of 9 months (mo) in selected patients in large phase-II-studies (Greco, et al. ProcASCO, 2004). This trial was designed to compare P + C to the non-platinum non-taxane regimen G + V in a prospective multicenter trial. Methods: 92 pts with histologically/cytologically proven CUP without prior chemotherapy were randomized to either arm A) P = 175 mg/m2 d1, C = AUC=5 d1 q d22 or to arm B) G = 1000 mg/m2 d1+8, V = 25 mg/m 2 d1+8 q d22. The primary endpoint of the study was practicability of the regimen as defined: application of >= 2 cycles of therapy (i) within 5 weeks (ii) and survival of >= 8 mo (iii). Sample size was determined to detect a practicability > 30% in each arm with 90% power (assuming a practicability of 50%). Data monitoring was done according to GCP standards. Results: Eligible pts 89, evaluable 79 (as of today); arm A: 37, arm B: 42, see table. The median OS and the median progression free survival (PFS) of pts treated in arm A was 10.7 mo and 6.4 mo with a 1-year-survival-rate (1-Y-SR) of 31%; the median OS and PFS of pts in arm B was 6.9 mo and 4.0 mo with a 1-Y-SR of 22%. The rate of practicability was 56.8% (95%-CI 39.5–72.9) in arm A and 42.9% (95%-CI 27.7–59.0) in arm B, respectively. Conclusions: In a high-risk population of pts with CUP with a high proportion of liver involvement the P/C regimen shows clinically meaningful activity in a prospective randomized trial while both regimen achieved a similar rate of partial remissions. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Lilly Oncology
Factors associated with unplanned breast cancer readmissions.
Authors: Charuta Gavankar, Cary Gross, Rogerio Lilenbaum, Anees B. Chagpar
Journal: Journal of Clinical Oncology (2013)

131 Background: Unplanned hospital readmission within 30 days (UHR) has been used as a quality metric, but data are limited for breast cancer patients. We sought to determine factors associated with UHR in these patients. Methods: The National Cancer Database is a program of the American College of Surgeons and American Cancer Society that captures 70% of newly diagnosed cancer cases in the US. Factors relating to UHR were analyzed using univariate and multivariate analyses. Results: Data from 2003-2010 were used; 28,861 patients who had UHR were compared to 1,380,433 patients who were never readmitted. Planned readmissions were excluded. Factors correlated with UHR included age, race, ethnicity, region, facility type, education, insurance status, income, urban/rural location, neoadjuvant tx, lymph node status, tumor size, Charlson/Deyo score, and margin status (all p &lt; 0 .005). On multivariate analysis, all factors but ethnicity and urban/rural remain significant (see table). Conclusions: Few breast cancer patients have UHR, but sociodemographic, clinicopathologic, and regional factors can be found that are associated with an increased risk. These may guide interventions to reduce UHR. [Table: see text]
Predictors of referral to outpatient specialty palliative care (SPC) in gynecologic cancer (GC) patients.
Authors: Rachel Ruskin, Michelle Renee Rowland, Katherine N Moore, Katrina Slaughter, Adam Walter, Lisa Michelle Landrum, Joan L. Walker, Marianne Matzo
Journal: Journal of Clinical Oncology (2015)

159 Background: Prior studies in GC patients have described predictors of inpatient palliative care (PC) consultation, but predictors of outpatient SPC consultation have not been elucidated. We sought to identify factors predictive of referral and associated care outcomes. Methods: We performed a cross-sectional study of GC patients seen in the gynecologic oncology clinic at a comprehensive cancer center over a three month period. As a part of routine care, patients completed a symptom questionnaire. Patients previously seen at the outpatient PC clinic were compared to those who had not with respect to demographics, disease characteristics, symptom scores, and provider factors using univariate statistics. A multivariate model was created to identify independent predictors of referral. Results: 913 patients completed the symptom survey. 76 patients (8%) had been seen in the outpatient PC clinic. Disease factors associated with referral included site (p &lt; 0.01), stage (p &lt; 0.01), evidence of disease (p &lt; 0.01), active treatment (p &lt; 0.01), and time point in the disease trajectory (p &lt; 0.01). Women with moderate to severe pain (p &lt; 0.01), sadness (p = 0.03), distress (p &lt; 0.01), fatigue (p &lt; 0.01), neuropathy (p = 0.03), and sexual dysfunction (p &lt; 0.01) were more likely to have seen PC. Marital status, number of symptoms, and patient provider were also predictive of referral (all p &lt; 0.01). In a multivariate model, site, stage, number of symptoms, moderate to severe sexual dysfunction, and provider were independently associated with referral. Compared to women who had not been referred, patients seen in the PC clinic were more likely to have a health care proxy documented in the electronic medical record (p &lt; 0.01). Among patients with related symptoms, patients referred to PC more often had an opioid prescribed for pain (p &lt; 0.01) and medications prescribed for depression (p &lt; 0.01), anxiety (p = 0.04), insomnia (p &lt; 0.01), and fatigue (p &lt; 0.01). Conclusions: Women with depression, anxiety, insomnia, and fatigue were more likely to receive pharmacologic treatment for these symptoms from a SPC provider. Future research should identify referral triggers for those patients most likely to benefit from outpatient SPC consultation.
Transfer of anti-breast cancer immunity induced by infusions of bispecific antibody armed T cells and boosted with ex vivo primed T cells after stem cell transplant in metastatic breast cancer patients.
Authors: Archana Thakur, Lawrence G. Lum, Ritesh Rathore, Zaid Al-Kadhimi, Elyse Tomaszewski, Dana Schalk, Qin Liu, Joseph P. Uberti, Voravit Ratanatharathorn
Journal: Journal of Clinical Oncology (2015)

3076 Background: In a recent phase I immunotherapy (IT) study in 23 women with metastatic breast cancer (MBC), 8 infusions of activated T cells (ATC) armed with anti-CD3 x anti-HER2Bi bispecific antibody (HER2Bi) given in combination with IL-2 and GM-CSF induced specific anti-SK-BR-3 breast cancer (BrCa) cytotoxicity and increased Th1 cytokines and in IL-12 in the serum. This study investigated whether specific cellular and humoral anti-BrCa immunity is induced by infusions of HER2Bi armed T cells (BATs) could be transferred after high dose chemotherapy (HDC) and stem cell transplant (SCT). Methods: BATs were cryopreserved in 8 doses for twice weekly infusions for 4 weeks along with IL-2 (3.0 x 105 IU/m2/day) and GM-CSF (250µg/m2 twice per week). Seven to 14 days after the last infusion of BATs, the patient was leukapheresed to obtain 8-20 x 109 PBMC for expansion of immune ATC. Immune ATC were harvested and cryopreserved for multiple infusions after the HDC and SCT. Results: Six of 8 MBC patients enrolled in the protocol completed the protocol were evaluable for transfer of cellular and humoral immunity. Five of 6 evaluable patients exhibited 2 to 40% CTL activity after vaccination with BATs and 2.5-45% up to 12 months post SCT. One of 6 evaluable patients showed poor immune responses and no evidence of transfer. Serum anti-SK-BR-3 IgG levels increased from 1 to 11µg/ml post IT and 1 and 8 µg/ml after SCT. In vitro antibody synthesis showed gradual increases in antibody levels after SCT. Serum cytokine profile showed changes in IL-2, IL-12, IFN-γ, MIP-1β and IP-10. No dose-limiting events for the infusions, delays in engraftment, and life-threatening infections were observed. In the one patient who rapidly progressed after SCT, CTL and IFN-γ EliSpots were absent and the serum had high levels of Th2 cytokines. Conclusions: This pilot study suggests that optimal adoptive transfer of cellular and humoral immunity, induced by BAT infusions, by immune anti-breast cancer T cells after SCT accelerates not only immune reconstitution but, more importantly, enhances reconstruction of anti-tumor cellular and humoral immunity after HDC and SCT. Clinical trial information: NCT0002780 and NCT00020722.
Preclinical Efficacy of the Investigational Orally Bioavailable Proteasome Inhibitor MLN9708 in Myeloma Bone Disease
Authors: Antonio Garcia-Gomez, Dalia Quwaider, Enrique M Ocio, Laura San-Segundo, Teresa Paíno, Juan F Blanco, Allison J Berger, Atanasio Pandiella, Jesús F San-Miguel, Mercedes Garayoa
Journal: Blood (2012)
Early salvage versus adjuvant post-prostatectomy radiation therapy: Long-term results of a large institutional experience.
Authors: Daniela Buscariollo, Michael Drumm, Rebecca Claymann, Danielle Rodin, Sigolene Galland-Girodet, Adam S. Feldman, Douglas M. Dahl, Francis J. McGovern, Aria F. Olumi, Alec Eidelman, Andrzej Niemierko, William U. Shipley, Anthony L. Zietman, Jason A. Efstathiou
Journal: Journal of Clinical Oncology (2016)

99 Background: Randomized trials and consensus statements support consideration of adjuvant radiation therapy (ART) after radical prostatectomy (RP) for adverse pathologic features (pT3, positive margins), although its use remains low. Whether early salvage radiation therapy (ESRT) is as effective as ART remains unknown. The objective of this study was to compare outcomes after ART and ESRT. Methods: We performed a retrospective institutional analysis of 719 consecutive patients receiving post-RP RT from 1992 to 2013. ESRT was defined as RT for biochemical failure (BF) with post-RP PSA ≤ 0.5 ng/ml. All included ART and ESRT patients had adverse surgical pathologic features. Outcomes examined were freedom from BF (FFBF; rising PSA ≥ 0.2 ng/ml with subsequent confirmation), freedom from subsequent androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS). ART and ESRT were compared using multivariable analyses (MVA) with propensity score (PS) matching for pre-RP PSA, age at RT, Gleason score, pT-stage, and margin status. Results: 537 patients received salvage RT, of whom 195 received ESRT; 181 patients received ART. Median follow-up from RP was 7.0 and 8.1 years in the ART and ESRT cohorts, respectively. Median time to BF after RT was 4.4 and 4.7 years in the ART and ESRT cohorts, respectively. On MVA, ART was associated with improved 10-year FFBF (74 vs 60%, HR 0.36 [95% CI: 0.23-0.58], P &lt; 0.0001) and 10-yr FFADT (91 vs 83%, HR 0.37 [95% CI: 0.18-0.76], P = 0.007). There were no significant differences in FFDM (96 vs 92%, HR 0.58 [95% CI: 0.19-1.7], P = 0.3), and OS (98 vs 95%, HR 1.24 [95% CI: 0.4-3.89], P = 0.7). After PS matching, ART (n = 169) remained significantly associated with improved FFBF (p &lt; 0.0001) and FFADT (p = 0.01), compared to ESRT (n = 176). Conclusions: Post-prostatectomy RT confers excellent long-term prostate cancer control, a finding supported by the long follow-up in this series. ART is associated with improved FFBF and FFADT compared to ESRT, although there were no statistically significant differences in FFDM and OS. Optimal timing of postoperative RT further awaits the results of ongoing randomized trials.
Surveillance for ovarian carcinoma patients after curative-intent treatment.
Authors: F. E. Johnson, K. S. Virgo, F. Gao, D. G. Mutch
Journal: Journal of Clinical Oncology (2011)

5077 Background: Surveillance following initial curative-intent treatment for ovarian cancer is commonly done. The specific surveillance modalities used currently by clinicians, and how often they are recommended, are not known. We sought to determine the current surveillance practice patterns of clinical experts who treat patients with ovarian carcinoma. Methods: We employed a survey featuring vignettes describing 4 patients with ovarian carcinoma of different clinical stages and questions based on the vignettes. These were mailed to the 943 members of the Society of Gynecologic Oncologists (SGO). Those indicating that they performed surgery for ovarian cancer and also participated in long-term surveillance were asked to indicate how often they requested 11 discrete surveillance evaluations for their patients treated for cure in the first 10 posttreatment years. These included all those mentioned in the relevant literature. Descriptive statistics (mean, standard deviation, median, and range) were calculated. Results: Of the 943 SGO members surveyed, 323 (34%) responded; 283 (30%) were evaluable. The modalities most frequently recommended for each year were clinic visit, pelvic examination, and serum CA-125 level. There was marked variability in the recommended frequency of use. For example, the number of clinic visits recommended in postoperative year 1 for a patient with stage II ovarian carcinoma ranged from 2-12. The frequency of testing decreased with increasing postoperative years for all tests commonly recommended. For example, the median number of times a serum CA-125 level was recommended for a stage II patient was 4 during the first year, decreasing to 1 by year 5. Conclusions: The details of current surveillance testing in patients treated for ovarian carcinoma have not been documented previously. There is little agreement in the literature about the most appropriate surveillance strategy. Ours are the first data on this topic, to our knowledge. Marked variability exists in the intensity of surveillance among SGO members. This is prima facie evidence of overuse and/or underuse and/or misuse of scarce medical resources. Further research should aim to identify the sources of this variability.
Patterns of radiation therapy technology use in the treatment of bone metastases.
Authors: Matthew Chan, Robert Anton Olson, Shilo Lefresne, Michael R. McKenzie
Journal: Journal of Clinical Oncology (2016)

211 Background: In recent years, there has been a transition from two-dimensional radiation therapy (2DRT) planning towards more advanced techniques such as three-dimensional conformal radiation therapy (3D-CRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT). Our study aim was to analyze these trends in the treatment of bone metastases. Methods: All patients aged 18 and older who had received palliative intent RT for bone metastases between 2009-2014 and referred to any 1 of 6 regional cancer centers in British Columbia, Canada were reviewed. Summary statistics were used to describe radiation technique patterns. Logistic regression modeling was used to assess the influence of demographic, clinical, and health services variables on receipt of types of RT. Results: We identified 8,059 patients and 15,832 courses of RT; overall, 97.9% of courses were achieved by 2DRT and 2.1% by 3D-CRT, VMAT, or SBRT. Despite the low overall use of advanced techniques, its use was significantly higher in all subsequent years compared to 2009 (p &lt; 0.05 for all years). The median age for patients treated with 2DRT was 67.0 (19-99) versus 66.0 years (19-93) for advanced techniques. There did not appear to be a statistically significant difference in age at the time of treatment start (OR 0.99; 95% CI 0.981-1.00, p &lt; 0.05). Compared to lung cancers, thyroid (OR 9.9; 95% CI 5.197-18.724, p &lt; 0.001) and kidney cancers (OR 3.9; 95% CI 2.508-5.911, p &lt; 0.001) were significantly more likely to be treated with advanced techniques, while breast (OR 0.90; 95% CI 0.621-1.306, p = 0.58) and prostate cancers (OR 0.93; 95% CI 0.613-1.410, p = 0.73) were not any more likely. Compared to the Vancouver center, all other treatment centers in the province were utilizing advanced techniques less frequently. Patients were also more likely to complete RT with 2DRT than with advanced techniques (98.3% versus 95.8%, p &lt; 0.05). Conclusions: The vast majority of treatment of bone metastases is still done by 2DRT in British Columbia. Despite these overall statistics though, a trend towards increasing use of more advanced techniques was observed.
Intergroup study in elderly patients with AML to compare complete remission rate and overall survival after intermediate-dose or low-dose AraC.
Authors: T. Lange, D. Niederwieser, V. Hoffmann, M. Pfirrmann, G. Maschmeyer, T. Fischer, M. Herold, H. G. Sayer, C. Junghanss, R. Krahl, H. K. Al-Ali, W. Pönisch, V. Vucinic, G. Doelken, M. C. Sauerland, A. Heinecke, D. Hoelzer, R. Hehlmann, W. E. Berdel, T. Buchner
Journal: Journal of Clinical Oncology (2011)

6618 Background: Until recently, elderly patients with AML were treated in protocols for younger pts or outside protocols. In order to evaluate the outcome of these pts in more detail, an intergroup study involving the AMLCG and the OSHO study groups was initiated and a 10:1 randomization in a common arm was established. Methods: The common arm consisted of AraC 100 mg/m2 c.i. over 7 days and Daunorubicin 60 mg/m2 over two hours on days 3-5. If blasts in the marrow were >5% a second induction was given. As postremission AraC 1 g/m2 was given as a three hour infusion on days 1, 3 and 5. A total of 834 eligible pts were randomized either in the common arm (n=84; 10.1%) or in the study arms (n=750; 89.9%). The median age was lower in the common arm (67, range 60 – 82 years) than in the study arms (median age: 68 and 70 years, p=0.03). Leucocytes and LDH at diagnosis, cytogenetic risk and the presence of NPM and FLT3 mutations did not differ between the common and the study arms. However, there were differences between secondary AML in the common arm (36%) compared to the study arms (42% and 27%; p=0.005). The majority of pts had intermediate risk cytogenetics in the common (65%) as well as in the study arms (65% and 61%). Results: CR was reached in 58% of pts in the common and in 62% in the study arms (p=n.s.). Of 69 pts in the common arm, 37 died (54%), as did 367 of the 591 pts (62%) in the study arms. There was no statistically significant difference between the common arm and the study arms in overall survival, which amounted to 37% at 2 years in the standard arm vs. 33% and 25% at 2 years in the study groups. Significant independent factors associated with OS were karyotype, disease characteristics, age and WBC. Relapse free survival at 2 years amounted to 40% in the common arm compared to 40% and 30% in the two study arms (p=n.s.). Significant independent risk factors associated with relapse free survival were karyotype and age, but not the allocation to the two arms. Conclusions: From this interim analysis we conclude that no significant differences were observed to date on CR between the common arm and the study arms. More follow up and patient entry is needed for OS and RFS and subgroup analysis to identify protocols with better outcome.