tbuckley/cabot-search huggingface dataset:
Phase II randomized, placebo-controlled, double-blind study of IM862 plus a short course of androgen ablation for patients with androgen-dependent prostate cancer who failed local therapies: A platform for new drug screening
Authors: S. Mao, D. Daliani, X. Wang, K.-A. Do, P. F. Thall, C. A. Perez, M. A. Brown, C. J. Logothetis, J. Kim
Journal: Journal of Clinical Oncology (2005)

4684 Background: Androgen ablation has been the cornerstone of treatment for patients (pts) with androgen-dependent prostate cancer (ADPC) who relapsed after initial local therapies. IM862, a naturally occurring dipeptide (L-glu-L-trp) with immunomodulatory and anti-angiogenic properties, has produced significant anti-cancer activity in Kaposi’s sarcoma. The goal of this study was to explore novel agent that can inhibit prostate cancer progression synergistically with androgen ablation. Methods: Eighty-four pts with ADPC who had PSA relapse after initial local therapies were enrolled. All pts underwent three month combined androgen ablation (CAA). Pts were randomized to either IM862 or placebo arm at day 60. The study drugs were given intranasally twice a day until day 180. The primary endpoints were to evaluate the time to PSA recurrence (PSA ≥1) and safety of IM862. The Wilcoxon rank-sum test was performed to compare the difference in PSA values at day 90 or 180 between IM862 and placebo arms. The time to PSA recurrence was estimated using the Kaplan and Meier method and compared using the log-rank test. Results: Baseline pt characteristics: median age 68.4 (range 51.3–82.2), median PSA at initiation 5.3 (range 0.7–44.4), and initial local therapies [prostatectomy (34), radiation (26), and both (24)]. Seventy-five pts were evaluable. The testosterone levels of both arms were sufficiently suppressed by day 90, but values recovered by day 180. The median PSA at day 90 was 0 (range 0–3) for IM862 arm and 0 (range 0–2.2) for placebo arm (p = 0.78); at day 180, 0.9 (range 0–32.3) for IM862 arm and 2.5 (range 0–14.7) for placebo arm (p = 0.08). The time to PSA recurrence was 107.6 ± 8.8 (mean ± SE) days for IM862 arm and 97.3 ± 9.8 days for placebo arm (p = 0.45). No toxicities greater than grade 2 were observed in either arm. Conclusions: IM862 does not have major toxicities, but combination with CAA does not prolong time to PSA recurrence compared to CAA alone in pts with ADPC. However, the study model, i.e., combination of the intermittent CAA with a new drug, can be a useful platform for screening novel agents for ADPC. No significant financial relationships to disclose.
Global Methylation Array Analysis of Multiple Myeloma Samples Indicate An Alteration of Epigenetics During the Transition From MGUS to Myeloma and An Increased Frequency of Gene Methylation in t(4;14) Myeloma.
Authors: Brian A Walker, Emma M Smith, Nicholas J Dickens, Fiona M Ross, Faith E Davies, Gareth J Morgan
Journal: Blood (2009)
Can response of dysphagia to neoadjuvant docetaxel, cisplatin, and 5-flourouracil (DCF) for locally advanced esophagogastric adenocarcinoma predict disease recurrence?
Authors: A. Andalib, T. Alcindor, P. Guevremont, M. Rousseau, M. P. Thirlwell, S. Ades, L. Ferri
Journal: Journal of Clinical Oncology (2011)

e16631 Background: Improvement of dysphagia in pts with esophagogastric adenocarcinoma (EGC) is a crude sign of local tumor response to chemotherapy, however its impact on survival is unknown. We sought to determine if response of dysphagia to neoadjuvant chemotherapy predicted disease free survival in patients with locally advanced EGC undergoing curative intent treatment. Methods: Patients undergoing neoadjuvant DCF (docetaxel 75 mg/m2 IV day 1, cisplatin 75 mg/m2 IV day 1, 5-FU 750 mg/m2 CIV for 120 hrs, Q3wks) for EGC (at least T3 or N1), were identified from a prospective database. All were monitored with serial dysphagia scores (DS: 0 best – 4 worst) and disease status after resection was documented with CT and endoscopy (Q3mos). Pts in whom DS did not improve by at least 2 points (Non-RESP) after 3 cycles of DCF were compared to those who did improve (RESP) in terms of their mean disease free survival using student’s t test. Data is presented as median(range). Cox proportional hazard regression was used to estimate crude and adjusted hazard ratios (HR) for recurrence. 95% CI are reported. Results: From 5/07 to 10/10, 34 pts with severe dysphagia (DS of 2-4) due to locally advanced EGC completed 3 cycles DCF and underwent complete curative intent resection (R0). None required a stent or feeding tube. We followed 29/34 pts for at least one year (21 [12-43] mos) and these are included in the analysis. DS improved in 26/29 (89.7%), and in 11 of these disease recurred (13.5 [5-36] mos). The 3 Non-RESP pts all recurred (7 [5-8] mos). The mean disease free survival was lower in Non-RESP (P=0.03). The crude HR for the recurrence based on response of dysphagia was 0.1 (0.02, 0.46) 95% CI. After adjustments were made for tumor location and histologic grade, age and pathologic TNM stage, the HR was again estimated to be 0.1 (0.01, 0.73) 95% CI. Conclusions: Neoadjuvant chemotherapy with a highly effective regimen rapidly improves dysphagia in EGC in the majority of pts and likely obviating the need for invasive tube feeding. Non-response of dysphagia to DCF is a major predictor for poor outcome, questioning the value of curative intent surgery in these pts.
Recovery after surgery and care coordination pathway at City of Hope: Length of stay, readmissions, and complications.
Authors: Steven V. Kardos, Kevin G. Chan, Bertram E. Yuh, Jonathan Yamzon, Nora Ruel, Finly Zachariah, Clayton S. Lau, Laura E. Crocitto
Journal: Journal of Clinical Oncology (2016)

410 Background: Bladder cancer is the second most common urologic malignancy with over 73,350 new cases diagnosed annually of which the incidence is increasing in the elderly. Radical cystectomy (RC), the gold standard for muscle invasive disease, carries a particularly high risk of morbidity and mortality, as well as a protracted length of stay (LOS) and increased readmission rates when compared with other major urologic procedures. Furthermore, in 2013, the Institute of Medicine (IOM) declared cancer care in the US a national crisis with a priority to improve quality of care through care coordination (CC). Simultaneously, enhanced recovery after surgery (ERAS) protocols have surfaced as coordinated, evidence-based models designed to standardize medical care, improve outcomes, and lower healthcare costs. At City of Hope (COH), we evaluated our ERAS and CC pathway. Methods: In April of 2014, an ERAS and CC pathway for bladder cancer was launched at COH with an emphasis on the perioperative care of patients (pts) from a multi-disciplinary team perspective. Preoperatively, pts undergo orientation on stoma education, goals of care, and treatment expectations. The pathway clinically focuses on avoidance of bowel preparation, early feeding, minimizing narcotics, and u-opioid antagonists. On discharge, pts are closely monitored via scheduled phone calls as well as clinic visits. Quality metrics including LOS, complications, and readmissions are reported as median and interquartile range along with descriptive statistics including chi-square and Wilcoxon rank-sum tests. Results: Since implementation, the median LOS was statistically significant between cohorts with 6 days for pts on pathway compared to 8 days for those preceding the pathway (p = 0.0007). Furthermore, the complication and readmission rates have decreased from 67.5% to 50% and from 35% to 30%, respectively. Dehydration and urinary tract infection (UTI) accounted for 17.9% and 21.4% of readmissions for those prior to the pathway, while UTI occurred in 5% of pts readmitted after adhering to the pathway. Conclusions: Our ERAS and CC pathway has reduced LOS without an increase in complication nor readmission rates.
X-TRAP: Phase I/II study of capecitabine (X) plus ziv-aflibercept (TRAP) in metastatic colorectal cancer (mCRC).
Authors: John H. Strickler, Fatima A. Rangwala, Christel Rushing, Donna Niedzwiecki, Ivy Altomare, Hope Elizabeth Uronis, Shiaowen David Hsu, Yousuf Zafar, Michael Morse, David Z. Chang, James Leroy Wells, Kimberly L. Blackwell, P. Kelly Marcom, Anna Renee Webb, Evan Dropkin, Christy Arrowood, Herbert Hurwitz
Journal: Journal of Clinical Oncology (2016)

687 Background: Patients (pts) with chemotherapy refractory mCRC have a poor prognosis, with a median survival of approximately 6 months (mos). Ziv-aflibercept is FDA-approved in combination with FOLFIRI for the 2 nd line treatment of mCRC, but its tolerability and activity in pts with chemotherapy refractory disease is unknown. We designed a phase I/II study of X+TRAP to define the recommended phase II dose (RPTD), and assess the safety, tolerability, and clinical activity for the combination. Methods: Eligible pts with refractory, advanced solid tumors were enrolled in a 3+3 dose escalation cohort (ESC) to identify the RPTD. Cycle length was 21 days. Radiographic assessment occurred every 3 cycles. X was administered po bid on days 1-14. The dose of X was 850 mg/m 2 bid in ESC cohort 1 and 1,000 mg/m 2 bid in ESC cohort 2. TRAP was administered on day 1 of each cycle (6 mg/kg IV). Pts with mCRC that had progressed on all standard therapies were then enrolled in a single-arm, phase II expansion cohort (EXP) and treated at the RPTD. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate (RR) and overall survival (OS). Results: As of 6/19/2015, 55 pts were evaluable for toxicity (13 ESC; 42 EXP) and 47 pts were evaluable efficacy (12 ESC; 35 EXP). In the phase I ESC cohorts, 3 DLTs occurred (1/6 cohort 1; 2/6 cohort 2): GI perforation (1), oral mucositis (1), and fatigue (1). The RPTD was X (850 mg/m 2 po bid, days 1-14) and TRAP (6 mg/kg IV, day 1). In the ESC and EXP cohorts, there were no treatment related grade 4/5 adverse events (AEs). The most frequently reported treatment related AEs (grades 2+3; grade 3) were palmar-plantar erythrodysesthesia (36%; 5%), hypertension (29%; 20%), and oral mucositis (18%; 4%). Median follow up in the phase II EXP cohort was 9.3 mos (95% C.I., 6.5–11.1). Median PFS was 4.1 mos (95% C.I., 2.3-4.8). Response assessment in 35 pts (n; %): partial response (PR) (2; 6%); stable disease (SD) (12; 34%); SD &gt; 6 mos (2; 6%). Median OS was 9.3 mos (95% C.I., 6.2–n/a). Conclusions: The combination of X+TRAP demonstrated an acceptable safety profile, with encouraging clinical activity at the RPTD. Recruitment for the phase II EXP cohort is now complete. Clinical trial information: NCT01661972.
FLT3 Mutations Determine the Clinical Outcome in Children with De Novo Acute Myelogenous Leukemia (AML) and Normal Karyotype: Pediatric Oncology Group (POG) Study # 9421.
Authors: Norman J. Lacayo, Soheil Meshinchi, Susana C. Raimondi, Dennis J. Kuo, Ron Yu, Myron N. Chang, Cheryl L. Willman, Robert Tibshirani, Yaddanapudi Ravindranath, Branimir I. Sikic, Howard Weinstein, Gary V. Dahl
Journal: Blood (2004)
Effect of geographic variability for pancreatectomy rates on outcomes in patients with stage I and II pancreatic adenocarcinoma.
Authors: Bradley D. McDowell, James R. Howe, Elizabeth A. Chrischilles, James J. Mezhir
Journal: Journal of Clinical Oncology (2013)

240 Background: Low usage of pancreatectomy for stage I/II pancreatic cancer in the US has been reported, yet it is not clear to what extent this reflects underutilization of resection versus appropriate selection of operative candidates. To address this, we examined the geographic variation in pancreatectomy. Methods: We queried the US Surveillance, Epidemiology, and End Results (SEER) data for stage I/II pancreatic head cancer diagnosed from 2004-2009. Factors included in multivariate analyses (MVA) were age, gender, race, stage, and geographic region and primary endpoints were rate of pancreatectomy and median survival. Results: 10,520 patients with stage I (n=2,068) and stage II (n=8,452) pancreatic head cancer were analyzed. Pancreatectomy was performed in 528 patients (25.5%) with stage I disease and in 4,295 patients (50.8%) with stage II disease (overall resection rate=45.9%). Rates of resection significantly varied across the 18 SEER regions after controlling for age, gender, race, and stage in MVA (p&lt;0.0001). For the analysis, SEER regions were divided into groups of high/medium/low rates of resection (56.3%, 46.6%, and 41.1%, respectively). Median survival in the high resection regions was 12 months, which was significantly longer than in low and medium resection regions (both=10 months, p&lt;0.0001). MVA confirmed that regions with high resection rates have improved survival while controlling for age, gender, and race (Table). Conclusions: Pancreatectomy rates vary highly across geographic regions, and areas with higher rates of resection are associated with better outcome. These data may reflect poor adherence to treatment guidelines, which possibly reflects a lack of confidence in the effectiveness of pancreatectomy or expertise in performing the procedure. Studies that control for patient selection factors are underway to further elucidate these important findings. [Table: see text]
Preparedness for surgery as a quality indicator.
Authors: Deirdre Kiely, Kristin D. Pego, Freya Ruth Schnabel
Journal: Journal of Clinical Oncology (2016)

80 Background: There has been growing attention to the informational priorities of patients in a shared decision making model of care. Patients report adequate information provision as an unmet need throughout their cancer experience. This is especially of concern when faced with complex decision making based on an understanding of medical information in an unfamiliar learning environment. This project is designed to identify informational priorities of patients related to diagnosis and treatment decisions. Methods: Patients’ perceived preparedness for surgery was measured to determine whether information needs were addressed and illustrate overall satisfaction with the surgical experience. A self-administered questionnaire was used to measure satisfaction with information related to diagnosis, treatment and recovery. Results: An active role in decision making that considers patients’ information needs increases satisfaction with treatment choices, preparedness for surgery and outcomes. Methods of providing information are often limited to written and verbal with written generally non-specific and not tailored to patients’ informational needs. Providers are also unable to control for access to other information sources such as the internet. Conclusions: A treatment plan developed through a shared decision making model should be evidence based including an assessment of the patient’s informational priorities. A combination of written and verbal information may be optimal with the written building on the verbal and not introducing new information. Encouraging recording of meetings may be helpful when stress becomes a barrier to comprehending and retaining the information. The patient should also be provided with reliable websites to supplement this information. This results in greater patient satisfaction with the interaction and overall surgical experience.
A phase II trial of weekly cisplatin and docetaxel in advanced non-small cell lung cancer (NSCLC)—Final report
Authors: M. A. Sovak, L. Guensch, P. Joyce, S. G. Lutzker, S. Schwartz, W. J. Shih, L. Zheng, J. Aisner
Journal: Journal of Clinical Oncology (2008)

19105 Background: Every 3-week cisplatin doublets used to treat advanced NSCLC carry a significant risk of renal and other toxicities and can be difficult for patients with co-morbidities. To reduce these toxicities, we conducted a phase II study to evaluate the efficacy and toxicity of weekly cisplatin and docetaxel in patients with advanced NSCLC. Methods: Eligibility included patients with advanced/recurrent NSCLC, ECOG PS=0–1, no prior chemotherapy for metastatic disease. This Cancer Institute of New Jersey network, single stage phase II clinical trial was designed to give 3 weekly doses of cisplatin at 25 mg/m2 and docetaxel at 35 mg/m2 every 28 days, for a total of 6 cycles. Toxicity was monitored weekly, and disease evaluation performed every 2 cycles. The primary endpoint was response rate (RR); secondary endpoints included time to progression (TTP), median and 1-year survival. Results: From 12/03 to 12/07, 47 patients were enrolled. The median age of patients is 63 (range 34–83), the majority is white (n=40) with an ECOG PS=1, 35 have stage IV disease, and 21 are women. Histologic subtypes are: adenocarcinoma (n=29), NSCLC NOS (n=11), squamous (n=7). Fourteen patients received ≥ 4 cycles of therapy; median number of cycles delivered is 2.5. Reasons for treatment discontinuation include completion of therapy (n=7), progression of disease (n=19), adverse events (n=9), and patient preference (n=6). Four patients continue on therapy at this time. No complete responses were observed; 10 patients (21%) achieved a partial response, 11 had stable disease, 12 progressed, and 9 came off study before first disease evaluation. Median TTP was 3.8 months (mo) (95% CI 2.3,5.8), median survival is 9.1 mo (95% CI 5.8,14.9) and 1-year survival is 38% (95% CI 22%,54%). Most related toxicities were mild but also included neutropenia (grade 3, n=4; grade 4, n=2), neutropenic fever (n=1), renal toxicity (grade 3, n=2), nausea/vomiting (grade 3, n=2), fatigue (grade 3, n=3), diarrhea (grade 3, n=7) and metabolic abnormalities (grade 3, n=4). This trial is closed to accrual and final data are being collected. Conclusion: Weekly cisplatin and docetaxel is well tolerated with a low incidence of toxicity and demonstrates activity similar to every 3-week treatment in patients with advanced NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis
Psychological distress in cancer patient during chemotherapy: A cross-sectional study.
Authors: Harminder Singh, Raja Banipal
Journal: Journal of Clinical Oncology (2016)

231 Background: The State of Punjab is experiencing a rising burden of cancer. The objective of this study was to analyze and compare depression, anxiety and stress levels and their impacting factors in heterogenous surviving cancer patients. Methods: this is a cross sectional study, data collection was performed by Depression, anxiety, stress scale 21-DASS 21. Results: study population include 300 cancer patients and 300 matched controls. The mean age of the cases and controls were 50.58 years ± 13. 64 and 46.1 years ± 11.78 (M ± SD). A Statistical significant difference was observed in mean scoring of depression, anxiety and stress in cancer patients when compared to control groups. Anxiety mean score significantly affected by chemotherapy cycles and duration of disease. Conclusions: Holistic approach in cancer management is a need of time as the present study revealed, the range of depression, anxiety and stress was 90%, 56% and 28% respectively. [Table: see text]
Magnetic resonance image-guided radiation therapy (MR-IGRT) for the treatment of prostate cancer: Initial clinical experience and patient selection.
Authors: Benjamin Walker Fischer-Valuck, Jeff M. Michalski
Journal: Journal of Clinical Oncology (2016)

156 Background: Magnetic resonance image-guided radiation therapy (MR-IGRT) has been implemented at our institution since 2014. We report on the initial clinical experience and patient selection in treating prostate cancer utilizing the first commercially-implemented MR-IGRT system. Methods: A total of 13 patients with prostate cancer have been treated with intensity-modulated radiation therapy (IMRT) using an MR-IGRT system. Of those treated, 6 patients received definitive radiation therapy (RT) for low, intermediate or high risk prostate cancer, 5 patients were treated with salvage RT after biochemical failure following surgery, and 1 patient was treated for the boost portion of definitive RT. Results: Patients were selected for MR-IGRT based on various clinical decisions. Four patients had co-morbidities requiring anticoagulation for which fiducial marker placement was contraindicated and soft tissue visualization via MR imaging was thought to be beneficial for daily set-up. Three patients were referred from outside institutions with concerns of radiation dose to the small bowel, and daily MR monitoring of bowel anatomy could be performed with plans for treatment adaptation if anatomy changed. One patient had received prior RT for rectal cancer and dose to organs at risk was of concern. The remainder of patients were post-operative salvage cases selected based on physician concern of accurate and reproducible daily localization with fiducial markers alone. Daily volumetric MR was monitored with the ability for treatment adaptation should small bowel dose increase, and no treatment changes were required. For all cases, onboard sagittal cine MR was visually monitored for bladder and target motion, and qualitative evaluation demonstrated no significant intra-fraction motion. Conclusions: MR-IGRT provides unique advantages when fiducial markers are contraindicated or when daily visualization of dose to the small bowel or other organs at risk is required to monitor and potentially prevent normal tissue toxicity. Clinical trials are in development to formally evaluate MR-IGRT for the treatment of intact and salvage prostate cancer.
First-line sunitinib versus pazopanib in metastatic renal cell carcinoma (mRCC): Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Jose Manuel Ruiz Morales, J Connor Wells, Frede Donskov, Georg A. Bjarnason, Jae-Lyun Lee, Jennifer J. Knox, Benoit Beuselinck, Ulka N. Vaishampayan, James Brugarolas, Reuben James Broom, Aristotelis Bamias, Takeshi Yuasa, Sandhya Srinivas, D. Scott Ernst, Carmel Jo Pezaro, Lori Wood, Christian K. Kollmannsberger, Brian I. Rini, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2016)

544 Background: Sunitinib (SU) and Pazopanib (PZ) have been compared head-to-head in the first-line phase III COMPARZ study in metastatic renal cell carcinoma (mRCC). We compared SU versus PZ, to confirm outcomes and subsequent second-line therapy efficacy in a population-based setting. Methods: We used the IMDC to assess overall survival (OS), progression-free survival (PFS), response rate (RR) and performed proportional hazard regression adjusting for IMDC prognostic groups. Second-line OS2 and PFS2 were also evaluated. Results: We obtained data from 3,606 patients with mRCC treated with either first line SU (n=3226) or PZ (n=380) with an overall median follow-up of 43.5 months (m) (CI95% 41.4 – 46.4). IMDC risk group distribution for favorable prognosis was 440 (17.3%) for SU vs 72 (25%) for PZ, intermediate prognosis 1414 (55.6%) for SU vs 153 (53%) for PZ, poor prognosis 689 (27.1%) for SU vs 62 (22%) for PZ, p= 0.0027. We found no difference between SU vs. PZ for OS (20.1 [CI95% 18.76-21.42] vs. 23.68 m [CI95% 19.54 - 28.81] p=0.19), PFS (7.22 [CI95% 6.76 - 7.78] vs. 6.83 m [CI95% 5.58 - 8.27] p=0.49). The RR was similar in both groups (Table 1). Adjusted HR for OS and PFS were 0.952 (CI95% 0.788 – 1.150 p=0.61) and 1.052 (CI95% 0.908 – 1.220 p = 0.49), respectively. We also found no difference in any second-line treatment between either post-SU vs. post-PZ groups for OS2 (12.88 [CI95% 11.89 – 14.19] vs. 12.91 m [CI95% 10.3 – 19.1] p=0.47) and PFS2 (3.67 [CI95% 3.38 – 3.87] vs. 4.53 m [CI95% 3.08 – 5.35] p=0.4). There was no statistical difference in OS2 and PFS2 if everolimus was used after SU or PZ (p = 0.33 and p = 0.41, respectively) or if axitinib was used after SU or PZ (p = 0.73 and p = 0.72, respectively). Conclusions: We confirmed in real world practice, that SU and PZ have similar efficacy in the first-line setting for mRCC and do not affect outcomes with subsequent second-line treatment. [Table: see text]