tbuckley/cabot-search huggingface dataset:
A randomized phase II study of bicalutamide (BIC) followed by placebo or gamma secretase inhibitor RO4929097 (RO492) in men with rising PSA.
Authors: Mark N. Stein, Robert S. DiPaola, Tina M. Mayer, Chandrika Jeyamohan, Dorinda Metzger, Monica Anand, S. Percy Ivy
Journal: Journal of Clinical Oncology (2012)

219 Background: Notch signaling is a key determinant of cell fate. RO492 is a selective γ-secretase inhibitor blocking cleavage of Notch. We hypothesize that anti-androgen therapy will lead to an enriched population of basal prostate cancer stem cells. Targeting Notch following anti-androgen treatment will lead to delay in re-growth of mature luminal PC cells. We are using a novel double blind, placebo controlled randomized discontinuation design to treat men with rising PSA. A non-castrating anti-androgen (BIC) was used to induce initial tumor regression Methods: Pts with rising PSA after primary therapy for PC, and no radiographic evidence of disease were enrolled in this ongoing study. All pts received BIC 50mg/day for 16 weeks (induction phase). Pts achieving a &gt;50% (modified from 80% decrease after the first 8 pts) decrease in PSA were randomized to placebo or RO492 20mg orally 3 days on/ 4 days off per week (randomization phase). Primary endpoint is PSA progression (increase in PSA by 50% over nadir with minimum PSA rise of 2ng/mL) during randomization phase. Pts meeting primary endpoint could receive 12 months of RO492 and BIC (combination phase). Serum is collected for evaluation of soluble markers of gamma secretase inhibition. 29 pts/arm in randomization phase gives 90% power to detect a decrease in1 yr PFS from 80% to 45% with 5% alpha. Results: We report on the first 16 patients that have enrolled. Median pretreatment PSA was 6.3ng/ml (0.35 to 34). 9 of 16 pts on the induction phase came off study due to PSA progression, although 5 of 9 pts would have been randomized using the 50% PSA response criteria. 6 pts have been randomized to RO492 or placebo (1 pt not yet randomized) and 2 pts have proceeded to combination phase. Median PSA decrease during induction phase in 6 pts who went on to randomization was 86% (69–97). Overall decline in PSA in induction phase was 67% (7.3-99%). Placebo/RO492 has been well tolerated with 1 pt experiencing g1 fatigue, and 1 pt experiencing g1 nausea in the combination phase. 8/16 pts had g1 breast tenderness with BIC. Conclusions: In this ongoing randomized phase II trial, BIC decreased PSA by &gt;50% in 12/16 pts. Placebo/RO492 is well tolerated. Enrollment continues with analysis of plasma correlates to be compared to clinical results.
Increasing Efficacy of Autologous Haematopoetic Cell Transplantation in Acute Myeloblastic Leukaemia; a Single Centre Experience in 141 Patients.
Authors: Jerzy Holowiecki Prof, Tomasz Czerw, Jerzy Wojnar, Malgorzata Krawczyk-Kulis, Sebastian Grosicki, Beata Stella-Holowiecka, Slawomira Kyrcz-Krzemien Prof, Maria Sadus-Wojciechowska, Sebastian Giebel, Lucja Kachel, Krzysztof Wozniczka, Aleksandra Holowiecka-Goral
Journal: Blood (2007)
A phase II study of recombinant adeno-viral human p53 gene combined with radiotherapy in treatment of patients with locally advanced cervical carcinoma.
Authors: J. Pan
Journal: Journal of Clinical Oncology (2011)

5097 Background: The study objective was to evaluate the efficacy and safety of recombinant adeno-viral human p53 gene (rAd-p53) conbined with radiotherapy (RT) in treatment of advanced cervical carcinoma. Methods: Patients aged ≥18 years, with stage IIB--IVA cervical carcinoma, expecting to live more than 3 months, without any anti-tumor treatment in 2 weeks, with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 were randomly assigned in two groups: experimental group (EG) receiving weekly intratumoral injection of 1-4×1012 rAd-p53 viral particles (VP) for 6 weeks conbined with 1.8-2Gy/f of external beam therapy in Point B (total dose of 45-50Gy) and 7Gy/f of high dose rate (HDR) brachytherapy in Point A (total dose of 70 Gy) in 6 week; control group (CG) receiving the same dose of RT. The response rate, long-term effecacy and adverse effects were evaluated. Results: Thirty-nine eligible patients, 21 in EG and 18 in CG, were enrolled between 2008 and 2009. In EG, 11 patients (52.4%) achieved a complete response (CR), 10 (47.6%) had a partial response (PR), and the overall response rate (RR) was 100%, In CG, there was 8 (44.4%) CR, 5 (27.8%) PR, 3 (16.7%) stable diseases (SD) and 2 (11.1%) progressive diseases (PD), and the RR was 72.2%. The RR difference is statistically significant (Fisher's Exact Test: p=0.0149). In EG, 15 (71.4%) patients has self-limited fever and 8 (38.1%) had a grade 1 or 2 myelosuppression. In CG, 9 patients (50%) had a grade 1 or 2 myelosuppression. The result of long-term effecacy is not available at this time. Conclusions: Intratumoral rAd-p53 injection combined with radiotherapy significantly increases overall response rate. The main adverse effect of rAd-p53 is fever.
Comparative analysis of second and subsequent chemotherapy lines on short- and long-term survival of elderly Medicare metastatic colon cancer patients.
Authors: Nader Hanna, Ebere Onukwugha, Kaloyan A Bikov, Zhiyuan Zheng, Brian S. Seal, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2013)

455 Background: Metastatic colon cancer (mCC) patients often receive multiple lines of chemotherapy as treatment (TX) to improve survival or quality of life, yet the “real world” benefits and risks of multiple TX lines have not been fully examined. Methods: Elderly (65+) SEER-Medicare patients diagnosed with mCC in 2003-2007 were followed until death or 12/31/09 to examine the survival benefits for different chemotherapy lines. The median time between diagnosis date and the starting date of 2 nd line was 352 days. Therefore, we restricted comparative analysis of 2 nd and subsequent chemotherapy TX lines to patients who survived at least 1 year after mCC diagnosis date. We used Cox regression framework and adjusted for patients’ TX and censoring histories by using inverse probability weighting method. Separate analyses were conducted for short (2 years) and long-term (5 years) survival to examine different benefits of 2 nd and subsequent chemotherapy lines. Results: Of 2,600 elderly Medicare mCC patients diagnosed between 2003-2007 and who survived at least 1 year, 2,530 were dead by the end of 2009. Significant factors associated with long-term survival were 1 st line therapy(HR = 0.76; p &lt; 0.01), 2 nd line therapy (HR = 0.83; p &lt; 0.01) , and subsequent chemotherapy line therapy(HR = 0.85; p = 0.04), as compared to no therapy, age groups 95 + (HR = 3.07; p &lt; 0.01), 85-94 (HR = 1.33; p &lt; 0.01), and 75-84 (HR = 1.10; p = 0.04) as compared to 65 + -74, Asian vs. White (HR = 0.71; p &lt; 0.01), and zip code level household median income (HR = 0.98; p = 0.01). For short-term survival, the benefits of 2 nd and subsequent chemotherapy lines were maintained until month 29. Patients with poor performance status were less likely to proceed to 2nd line therapy. No statistically significant variables predicting receipt of subsequent chemotherapy lines were identified. Conclusions: Among elderly Medicare mCC patients who survived at least 1 year after diagnosis, 1 st line therapy improved both short and long-term survival. 2 nd and subsequent chemotherapy line therapy reduced short-term mortality (2 years); however, they didn’t add any additional long term survival benefit (5 years) as compared to 1 st line therapy.
Our experience with postoperative adjuvant abdomino-pelvic radiotherapy after surgery and chemotherapy for advanced ovarian cancer.
Authors: A. Rodica Maricela, L. Gales, A. Tarlea, X. Bacinschi, I. Isacu
Journal: Journal of Clinical Oncology (2011)

e15561 Background: In ovarian cancer the most frequent recurrences occur into the peritoneum. In this study we assessed the efficacy and tolerability of abdomino-pelvic radiotherapy as consolidation therapy after surgery and chemotherapy in advanced ovarian cancer. Methods: Between January 2005 and December 2008, 32 patients with stage III G2-3 epithelial ovarian cancer were included. The patients received 6 cycles of paclitaxel + carboplatin chemotherapy after optimum surgical resection. At the end of chemotherapy the patients had no residual disease. They received conformal whole abdominal radiation therapy. The target volume was whole peritoneal cavity and pelvic and para-aortic lymph nodes. The total dose was 30 Gy for abdomen, 45 Gy for pelvis, 25 Gy for liver and 15 Gy for kidney. Results: The treatment was well tolerated with no grade 4 toxicities. Grade 3 acute toxicities were leucopenia in 4 patients, thrombocytopenia in 2 patients and diarrhea in 5 patients. 4 patients experienced late toxicity consisting in bowel obstruction, requiring surgery. Median follow-up was 26 months (range 12-53). The 1-year disease free survival was 90.6% and overall survival was 100%. Two-year disease survival rate was 65.6% and overall survival was 75%. Disease recurred in 3 patients in the first year and in 8 patients in the second year. There were 7 local recurrences and 4 distant metastases. Conclusions: Whole abdominal radiation therapy is a safe adjuvant therapy after surgery and chemotherapy in advanced ovarian cancer. Disease free survival and overall survival rates justified radiation therapy in selected high-risk patients.
Nipple-sparing subcutaneous mastectomy (NSSM) as dual-plane prosthetic reconstruction using the modified Wise pattern mastectomy, fasciocutaneous flap, and titan-polypropylen-mesh-interponation in women with macromastia.
Authors: Stefan Paepke, Evelyn Klein, Johannes Ettl, Markus Niemeyer, Holger Bronger, Daniela Paepke, Marion Kiechle
Journal: Journal of Clinical Oncology (2012)

156 Background: Ablative surgery of voluminous, ptotic breasts poses the problem of implant cover of the lower and lateral two thirds that are not coverd by the liftet pectoral muscle. Based on reduction mammaplasty techniques we applied a method that utilizes the excess mammary skin in terms of vertical, lateral, and medial de-epithelialized fascio-cutaneous tissue columns that serve together with a mesh (TiLoop bra) as cover for the subpectoral implant. Methods: Between 06/2009 and 01/2012 we performed 16 nipple and skin sparing mastectomies with marked tissue reduction (defined as difference in weight between implant and resected tissue of more than 300 g) in 7 patients. Indications comprise primary and secondary prophylactic as well as 4 nipple sparing mastectomies after neoadjuvant chemotherapy. Results: Mastectomy weights ranged between 325 and 1100 g; implant volumes ranged between 295 and 800 cm 3 . There occured five partial necrosis of the nipple-areolar complex (NAC) and three partial skin necrosis at the margin of the vertical incision. Two patients had to be operated on a second time for cosmetic reasons. The overall complication rate was low. Conclusions: The method described herein using the de-epithelialized excess mammary skin and the advantages of the titanized polypropylene mesh archieves stable reconstructions and a safe vascularization of the NAC.
Utilizing electronic technologies to measure patient-reported outcomes (PRO) assessment completion time.
Authors: Norman Brito-Dellan, Tony Lam, Marsha N. Richardson, Ellen F. Manzullo, Michael Kallen, DerShung Yang, Niina Mari Haas, Carmelita P. Escalante
Journal: Journal of Clinical Oncology (2016)

69 Background: Patient-reported outcomes (PROs) contribute to the assessment and treatment of cancer-related fatigue (CRF). Paper-based symptom assessments are cumbersome and time-consuming. Electronic assessments are an efficient alternative. This study describes CRF Clinic patients at a major cancer Institution, the time they required to complete self-reported CRF symptom assessments via a tablet computer (iPad), and the factors influencing PRO assessment completion time. Methods: From 1/1/2011 to 8/21/2012, 190 newly-referred CRF Clinic patients utilized an iPad to complete standardized CRF symptom assessments for: fatigue, pain, depression, anxiety, stress, sleepiness, and apathy. A web-based assessment module (BrightOutcome) was employed, which recorded assessment start and completion times. Non-Parametric test statistics were utilized for analysis. Results: Of the initial 190 patients, 3 were excluded due to non-cancer diagnoses and 1 was excluded due to an erroneous completion time of 8,903 minutes. Sample size is 186 patients; mean age was 55.49 years (range: 31-89); 69.4% (n = 119) were female. Patient mean fatigue score (Brief Fatigue Inventory) was 6.4. Mean assessment completion time was 16.73 minutes (range: 4-47). Assessments took longer to complete for patients ≥ 65 years (mean: 21.53 minutes; range: 9-43), males (mean of 18.3 vs. 16 minutes for females), patients with severe fatigue (7-10) (mean 18.31 minutes; range: 4-47), greatest apathy (38-72) (mean: 19.5 minutes; range 8-47), those with active cancer (mean: 18.02 minutes vs. 15.15 minutes in cancer survivors), and those with 2 or more comorbidities (mean: 18.41 minutes vs. 15.86 minutes in those with less than 2 comorbidities). Pain severity and interference, anxiety, depression, stress, and sleepiness did not statistically significantly impact assessment completion time. Conclusions: Patients who are older, male, fatigued, apathetic, with active cancer or with 2 or more comorbidities may require longer in-clinic time to complete standard symptom assessments. Further studies exploring these and other patient characteristics potentially impacting the integration of new technologies into patient care and research are warranted.
Procoagulant Profile of Platelets from Immune Thrombocytopenia Patients
Authors: María Teresa Álvarez Román, Raul Justo Sanz, Elena Monzon Manzano, Monica Martín Salces, Ihosvany Fernandez Bello, Sergio Rivas Muñoz, María Isabel Rivas Pollmar, Miguel Canales, Victor Jiménez Yuste, Nora Butta
Journal: Blood (2016)
Effect of simultaneous blockade of androgen and estrogen receptors on prostate cancer: In vivo study.
Authors: Rafael Nunez-Nateras, Erin N. Ferrigni, Naomi M. Gades, Erik P. Castle
Journal: Journal of Clinical Oncology (2013)

214 Background: In our preliminary in vitro studies, we have demonstrated evidence of enhanced apoptosis and inhibition of cellular proliferation in both hormone sensitive and castrate resistant prostate cancer (PCa) cell lines using a combination of an antiandrogen (Bicalutamide) and a selective estrogen receptor modulator (Raloxifene). The aim of this study was to study the effect of the administration of these two drugs in in vivo models of castrate resistant PCa. Methods: In vivo model consisted on NCr Nude: Mice bearing s.c. human prostate (PC3 cell line) xenografts. Based on the treatment received, mice were divided into 5 groups as follows: Group 1: No drugs (control); Group 2: Bicalutamide 50mg; Group 3: Raloxifene 60 mg; Group 4: Combined administration of Bicalutamide 50 mg and Raloxifene 60 mg; Group 5 Combined administration of Bicalutamide 150 mg and Raloxifene 120 mg. A total of 10 mice where included in each group. All drugs dosages were converted to their equivalent in the mice. Drugs were administered by gavage technique to the mice once per day for a total of 14 days. Results: As expected, Bicalutamide administered alone causes minimal inhibition without reaching statistical significance (Group 2: 0.34 g Vs Group 1: 0.40 g; p=0.073). Although Raloxifene causes some marked growth inhibition, its effect is not statistically significant (Group 3: 0.31 Vs Group 1: 0.40 g; p=0.062). Bicalutamide and Raloxifene, when administered in combination, induced prominent growth inhibition in PC3 tumors when compared to the control group (Group 4: 0.26 g Vs Group 1: 0.40 g; p=0.038). Growth inhibition is significantly more evident when the drugs dosages are increased (Group 5: 0.17 g Vs Group 1: 0.40 g; p=0.024). Conclusions: The simultaneous administration of Bicalutamide and Raloxifene appears to have a synergistic effect on tumor growth inhibition in PC3 xenografts. The pathway(s) responsible for this observation may be independent of the androgen receptor as PC3 cells are AR negative and still affected by the combination over the drugs administered alone. Research is warranted to identify these potential pathways.
A comparison of QOPI metrics in solid tumor oncology clinic with or without concomitant supportive oncology consultation.
Authors: Ran Huo, Bethann Scarborough, Nathan Goldstein, Cardinale B. Smith
Journal: Journal of Clinical Oncology (2015)

173 Background: The Quality Oncology Practice Initiative (QOPI) is a voluntary quality measurement and improvement program designed to assess practice performance for a series of consensus based and evidenced based measures. Several measures within QOPI pertain to the use of supportive care in the treatment of cancer patients. We hypothesized that patients receiving integrated oncology and palliative care (intervention group) may meet a higher number of quality metrics as compared to patients receiving oncologic care alone (control group). Methods: We conducted a retrospective chart review of patients treated between June of 2013 to June of 2015 from our intervention group and matched these to similar patients within the control group based on tumor type and date of initial visit to oncologic care. We performed bivariate analysis comparing differences in supportive care QOPI measures among the intervention and control group. Results: We identified a total of 200 patients. Patients in the intervention group were younger (p = 0.27) and female (p = 0.21). Among the QOPI metrics, pain was significantly better addressed (p &lt; 0.001) among the intervention group. No significant difference was detected in other QOPI metrics. Of note, the intervention groups had significantly higher rates of enrollment in hospice (p &lt; 0.001) and significantly lower rates of death within the hospital and/or the ICU (p = 0.04). Conclusions: Integrating outpatient palliative care consultation along with standard oncologic care did improve pain being adequately addressed, improved hospice utilization and decreased death within the hospital and ICU. Many of the supportive oncology QOPI metrics can be satisfied by a prompt from the EMR, however adequately addressing pain requires specialized skills. These data support the need for increased primary palliative education regarding pain management for oncologists.
Longitudinal analysis of circulating tumor cell (CTC) counts in prostate cancer patients: assessment of treatment efficacy
Authors: O. B. Goodman, L. M. Fink, J. T. Symanowski, B. Y. Wong, D. A. Pomerantz, Y. Ma, B. Grobaski, D. Broome, D. C. Ward, N. J. Vogelzang
Journal: Journal of Clinical Oncology (2008)

5169 Background: Recent data suggest that CTC count correlates with other known tumor markers in prostate cancer (PC). We are conducting a longitudinal analysis of CTC counts in patients being treated to assess the prognostic significance of this biomarker in PC. Methods: Peripheral blood was analyzed by the Veridex Cell Search Methodology to obtain serial CTC measurements in 44 patients undergoing treatment for prostate cancer. Circulating tumor cell counts were then correlated with clinical response and outcome using PSA and radiographic criteria. Disease extent at the beginning of each treatment interval was classified radiographically by serial computed tomography or bone scintigraphy, and correlated with changes in CTC. Results: 44 evaluable patients were treated over 71 treatment intervals with a median length of 70 days (range 15 - 295 days). Eighteen percent (13/71) had localized or radiographically undetectable disease, 5.6 % (4/71) had metastatic hormone-sensitive disease, and 76% (54/71) had metastatic, castrate-resistant disease. The treatment segments involved the following therapeutic modalities: 9.9 % with active surveillance (7/71), 21% with novel agents on phase one or two clinical trials (15/71), 17% with hormonal therapy (12/71), 44% with chemotherapy (34/77), and 4.2% with definitive surgery or radiation therapy (3/71). Serial measurements were then analyzed for each segment and correlated with PSA response, and when possible, for radiographic response. Change in CTC was strongly correlated (r=0.61) with PSA velocity (p<0.01) over the treatment interval. Using ANOVA there was a trend towards decreased CTC in the chemotherapy and hormone modalities. In the patients treated with definitive therapy, there was the greatest discordance between the PSA and CTC changes, suggesting a role for CTC monitoring during definitive therapy. There was no correlation observed between CTC, PSA, and radiographic changes. Conclusions: The data support the use of serial CTC counts as a marker of therapeutic response in conjunction with serial PSAs and radiographic studies. Larger numbers of patients are needed to increase the statistical power and prognostic significance of CTC changes as a potential marker of therapeutic response. No significant financial relationships to disclose.
Effect of adjuvant (AD) radiotherapy (RT) on outcomes following pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PDA): A margin-stratified analysis.
Authors: Lee Mayer Ocuin, Jennifer Lee Miller, Mazen S Zenati, Jennifer Steve, Aatur D. Singhi, Steven A. Burton, Nathan Bahary, David L Bartlett, Melissa Ellen Hogg, Herbert J. Zeh, Amer H. Zureikat
Journal: Journal of Clinical Oncology (2016)

311 Background: The role of RT following PD for PDA remains controversial due to ambiguity in the definition of R0/R1 margin status in existing clinical trials. Recent data suggest that increased margin clearance (MC) is associated with improved survival after PD for PDA, however the role of adjuvant radiotherapy (ADRT) in patients with known MC is undefined. We sought to analyze the influence of ADRT on outcomes of PD for PDA based on MC data. Methods: We retrospectively identified 326 patients with MC data (in mm) who underwent PD between 2002-2014. Recurrence-free (RFS) and overall survival (OS) was determined by Kaplan-Meier analysis. Hazard ratios (HR) were calculated by Cox multivariate regression analysis on significant variables. Results: Mean age was 68 yrs and 55% were male. Median follow-up was 21 mos (IQR 12-34 mos). ADRT was administered to 87 patients (27%). Median RFS and OS for the entire cohort was 14 mos and 25 mos. On univariate analysis, ADRT was not associated with improved median RFS (13 vs. 14 mos; p = NS) or OS (23 vs. 27 mos; p = NS), but increasing MC was associated with prolonged median RFS [10 (0mm) vs. 13 (0-1mm) vs. 23 mos ( &gt; 1mm); p &lt; 0.02 for all pairs] and OS [16 (0mm) vs. 23 (0-1mm) vs. 40 mos ( &gt; 1mm); p &lt; 0.01 for all pairs]. After controlling for sex, BMI, neoadjuvant therapy, LVI, PNI, lymph node ratio &gt; 0.2, tumor size &gt; 2.5cm, and adjuvant chemotherapy, increasing MC was independently associated with improved OS [HR 0.680; p = 0.034 (0-1mm); HR 0.451; p &lt; 0.001 ( &gt; 1mm), compared to 0mm]. Patients were subsequently stratified into 3 groups based on MC [0mm (n = 73); 0-1mm (n = 118); &gt; 1mm (n = 135)]. ADRT was administered less frequently to patients with greater MC [0mm (n = 29; 41%); 0-1mm (n = 36; 31%); &gt; 1mm (n = 22; 16%); p &lt; 0.001]. Even when stratified by MC, ADRT was not associated with improved RFS [10 vs. 9 mos (0mm); 13 vs. 12 mos (0-1mm); 21 vs. 23 mos ( &gt; 1mm); p = NS for all pairs] or OS [16 vs. 18 mos (0mm); 24 vs. 23 mos (0-1mm); 33 vs. 42 mos ( &gt; 1mm); p = NS for all pairs]. Conclusions: ADRT is not associated with improved RFS or OS following PD for PDA regardless of MC. The use of RT following PD for PDA should be re-examined.