tbuckley/cabot-search huggingface dataset:
Reversal of immature myeloid cell-mediated immunosuppression
Authors: C. Bradney, J. Dannull, Z. Su, Z. Zhang, J. Vieweg
Journal: Journal of Clinical Oncology (2005)

2563 Background Tumor-bearing animals and cancer patients exhibit defects in myelopoiesis, resulting in the accumulation of immature myeloid cells (ImC). ImC have shown to induce a profound state of immune suppression by interfering with the function of tumor-specific T cells through several mechanisms, including the production of reactive oxygen species, or increased arginine activity. Thus, there is increased interest in developing strategies that allow the elimination of ImC in cancer immunotherapy protocols. Methods In this study we sought to develop accurate and reliable methods for the isolation of ImC in the peripheral blood of RCC patients and functionally validate their immunosuppressive action in vitro. In order to reverse ImC-mediated immunosuppressive activity, we used various differentiation agents, including all-trans retinoic acid to differentiate ImC to a mature, non-suppressive phenotype. Results We show that patients with advanced RCC possess significantly elevated levels of ImC in their peripheral circulation, and that ImC can be isolated from PBMC for further phenotypic and functional characterization. Moreover, we demonstrated that ImC isolated from RCC patients dramatically suppress antigen-specific T-cell responses in vitro, and that ImC-mediated immunosuppression can be abrogated in a dose dependent fashion by incubation with the differentiation agent ATRA. Conclusions Our data suggest that ATRA-mediated ImC differentiation may represent a clinically applicable strategy capable of reversing tumor-mediated immunosuppression and enhancing the therapeutic efficacy of cancer vaccines. A pilot study exploring this novel concept is currently ongoing at our institution. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merix Biosciences
Adjuvant bi-weekly schedule of gemcitabine (G) plus carboplatin (Cb) in resected stage IA (&gt;2cm) to IIIA non-small cell lung cancer: A phase II study
Authors: M. Oda, Y. Tsunezuka, I. Matsumoto, K. Kasahara, G. Watanebe
Journal: Journal of Clinical Oncology (2008)

7598 Background: Gemcitabine (G) plus carboplatin (Ca) chemotherapy has shown to have activity against non-small cell lung cancer (NSCLC) and to be a well-tolerated treatment. Our aim was to evaluate the feasibility and clinical efficacy of adjuvant bi-weekly GCa in completely resected NSCLC. Methods: Eligibility required completely resected stage IA (>2cm) to IIIA NSCLC, no prior chemotherapy or radiotherapy, ECOG PS 0–1, age under 76 years. Patients were to receive four cycles, each at 4-week intervals, of G (1,000 mg/m2, d 1, 15) and Ca (AUC 2.5, d 1, 15). Cycles were repeated until 4 treatments. Results: Between 03/2005 and 10/2006, 54 pts were enrolled and 53 pts were eligible, 2 pts withdrawn informed consent. 51 pts (32 male and 19 female, median age 64) were evaluated. Median number of GCa treatments was 4(1–4) and median dose intensity was 94% for both G and Ca. Grade 3/4 hematologic events included leucopenia (7%), neutoropenia (7%), and anemia (4%). Grade 3/4 non-hematologic events included nausea (2%), infection (4%). 1-year disease-free survival was 90%. Conclusions: Adjuvant bi-weekly schedule of GCa was feasible with acceptable level of toxicity in completely resected stage IA (>2cm) to IIIA non-small cell lung cancer. A phase III trial is now warranted. No significant financial relationships to disclose.
Aldo-keto-reductase 1C3 expression as an independent risk factor for occurrence of castration resistant prostate cancer in high risk prostate cancer treated with neoadjuvant therapy and prostatectomy.
Authors: Yasuhiro Hashimoto, Toshikazu Tanaka, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Takuya Koie, Chikara Ohyama
Journal: Journal of Clinical Oncology (2016)

172 Background: Aldo-keto reductase family 1 member C3 (AKR1C3) is a key steroidogenic enzyme that is implicated in the development of castration-resistant prostate cancer (CRPC). In this study, we examined AKR1C3 expression in surgical specimens of high risk prostate cancer treated with neoadjuvant LHRH + EMP, and we investigate the correlation between the expression level of AKR1C3 and the occurrence of CRPC. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone ( &lt; 50 ng/dL). Along with the routine pathological assessment, AKR1C3 expression was evaluated in tissue microarray analysis (TMA) in all patients. A multivariable Cox proportional hazards model was used to evaluate the association between CRPC and clinical data. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). At a median follow-up period of 79.5 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). In TMA, overexpression of AKR1C3 was seemed in 14 patients (13.6%). 5-year CRPC free survival rate of AKR1C3(+) patients (64.2%) was significantly lower than that of AKR1C3(-) patients (97.6%). (Log-rank test: p &lt; 0.001) On multivariable analysis, AKR1C3 expression is an independent risk factor for occurrence of CRPC in this study. (p = 0.044). Conclusions: Although the present study was small and preliminary, overexpression of AKR1C3 is an independent risk factor for occurrence of CRPC in the high risk prostate cancer treated with neoadjuvant LHRH + EMP and prostatectomy. Further study is warranted to elucidate its clinical significance.
The 2008 National Comprehensive Cancer Network (NCCN) Research Benchmarking Survey (RBS): Clinical trials (CTs) operations in the academic center.
Authors: S. L. Sherman, M. B. Waldinger, E. M. Lepisto, J. M. Hinkel, K. A. Minogue, D. E. Paul
Journal: Journal of Clinical Oncology (2010)

6154 Background: The 2008 NCCN RBS focused on the operations of clinical trials offices (CTOs) at NCCN Institutions. The survey utilized clinical trials benchmarking metrics based on CTO budgets, full-time equivalents (FTEs), and patient accruals. The primary aims were benchmarking and improvement of CTO operations and processes and identification of best practices in academic cancer center clinical research. Methods: A survey instrument was developed by the NCCN Best Practices Committee based on prior 2004 and 2006 surveys, which will allow for future analysis of longitudinal data. The survey collected quantitative and descriptive data on CTO organization, research infrastructure, staffing and clinical trials management, and included questions on innovative approaches to increasing accrual to CTs. Results: 20/21 NCCN institutions participated, for a response rate of 95%. The proportion of therapeutic trials varied across sponsor (mean, range): Cooperative Group (42%, 24%-66%), Industry Sponsored (29%, 18%-38%), Institutional (19%, 8-33%), Other Peer Reviewed (10%, 2%-27%). Of the 17/20 responding centers submitting patient accrual data, over 16,000 patients were accrued to therapeutic CTs. Patients were accrued to CTs as follows: Institutional (34%), Industry Sponsored (27%), Cooperative Group (23%) and Other Peer Reviewed (16%). CT accrual rates ranged from 10% to 24%; minority accrual rates ranged from 6 to 28 %. The mean annual operating budget for 15 centers was $4.7 million. The range of sources of support for CT management was from 43% for Sponsored Industry to 5% for Sponsored Cooperatives. The mean number of therapeutic accruals per CTO FTE was 10.6. 7/20 (35%) centers demonstrated Best Practices in implementing a value stream analysis of the protocol approval process. Conclusions: Clinical Research is at the heart of NCCN center operations, as it constitutes a core mission of NCCN institutions. It also represents one of the most significant challenges with many opportunities for improvement. Development of benchmark data and Best Practices across these institutions will promote enhanced operations and patient accrual in therapeutic CTs. No significant financial relationships to disclose.
Identification of distinct phenotypes of locally advanced pancreas cancer.
Authors: MinYuen Teo, Grace Frances Crotty, Criostoir O'Suilleabhain, Derek Gerard Power, Raymond S. McDermott
Journal: Journal of Clinical Oncology (2012)

369 Background: A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease (LAPC). Optimal treatment remains controversial. There is no consensus on timing of chemotherapy and radiotherapy. We sought to analyse the clinical course of LAPC in order to identify potential distinct clinical phenotypes. Methods: Patients (pts) diagnosed with LAPC who survived &gt;2 months were identified from prospectively maintained databases from two medical oncology departments in teaching hospitals. Demographics and clinical details were collected. Sequential restaging scans were reviewed for each pts to identify date and pattern of progression. Time to progression (TTP), time from progression to death (TTD) and overall survival (OS) were defined as time from histologic diagnosis to time of radiographic progression, time from radiographic progression to death and the summation of TTP and TTD, respectively. Survival was estimated with Kaplan-Meier method and compared with log-rank test. Results: Between Mar 2005 and Apr 2011, a total of 40 pts were identified. Median age was 66yrs (range: 43 – 74) and 60%(n=24) were males. Median OS for entire cohort was 11.3mos. Of 40 pts, 20(50%) had local only progression (LP) and 16(40%) had metastatic progression (MP) at first documentation of disease progression, while 4 pts (10%) had stable disease (2 died with no evidence of progression and 2 remain on treatment). TTP was 4.0 vs 5.6mos HR 0.97 (95% CI 0.49 – 1.93, p=.94) for LP and MP, respectively. Three of the pts with LP (15%) eventually developed metastatic disease after a median of 4.2 mths (3.7 – 9.6). For MP pts, five had concurrent local progression. Sites of disease were lungs(8), peritoneum(5), liver(3) and bone(1). TTD for LP and MP was 5.6 vs 1.4mos HR 0.62 (95% CI 0.28 – 1.39, p=.24), and OS was 13.2 vs 8.0mos, HR 0.59 (95% CI 0.28 – 1.25, p=.17) respectively. Conclusions: We identified two subgroups of LAPC with clinically distinctive behaviour, one local-dominant progression with low predilection for distant metastases, and another with rapid metastatic development and worse survival. Early recognition of these phenotypes might allow a more tailored treatment approach to improve outcome.
The use of IT to improve practice quality within a radiation oncology program.
Authors: James Varghese, Julia Giovinazzo, Tessa Larsen, Gaylene Medlam, Natasha Moran, Julie Murphy, Dennis VergelDedios, Yizhen Wang
Journal: Journal of Clinical Oncology (2014)

170 Background: Our centre has used ARIA as its oncology information system since 2005. Anecdotally, since 2008, dosimetrists have identified a high rate of replanned treatment plans. In 2010, a 2% replan rate was estimated however, it was felt that the results did not capture the true rework impact. A definition for replan was created to distinguish it from plan revisions and an attempt to standardize replan naming conventions was initiated. The replan workload was again raised as an issue in 2013 and an interdisciplinary review workgroup was formed with the objective to develop a process to capture workload more accurately. Methods: Rework was further categorized into replan, rework and revision. The nomenclature for the ARIA plan name data field was standardized to identify replans and plan revisions. In addition, rework task activities were created to identify the discipline initiating the rework. Embedding these changes into our process allowed for efficient and accurate workload data extraction. Results of monthly data analysis are shared with the dosimetrists and actionable items are sent to department heads for program engagement. Results: In March 2014, we achieved 100% compliance to the plan naming convention. Data showed 6% replan and 6.5% revision rates. Table 1 shows the rework numbers initiated by discipline. Conclusions: A paperless environment lends itself well to an organization’s ability to capture data. Our experience shows that if processes are designed to support and be supported by the information system, the input of data points can be embedded seamlessly and practically in the clinician’s workflow. This results in improved data capture where data becomes more meaningful, and can then be used for continuous quality improvement, operational decision-making and research projects, all of which can lead to practice improvements. [Table: see text]
Measuring long-term disease control in patients with atopic dermatitis: A validation study of well-controlled weeks
Authors: Sinéad M. Langan, Beth Stuart, Lucy Bradshaw, Jochen Schmitt, Hywel C. Williams, Kim S. Thomas
Journal: Journal of Allergy and Clinical Immunology (2017)

Because atopic dermatitis (AD) is a relapsing remitting disease, assessing long-term control is important. Well-controlled weeks (WCWs) have been used to assess asthma long-term control but have never been validated for AD.We sought to assess the feasibility, validity, and interpretability of WCWs in patients with AD.Three studies of patients with moderate-to-severe AD, including 4 to 6 months of daily/weekly symptom and treatment use data, were evaluated (study A, n = 336; study B, n = 60; and study C, n = 224). WCWs were defined by worsening symptoms and increased medication use. Feasibility, construct validity, and interpretability of WCWs were determined by assessing missing data, association with validated AD outcomes, and floor and ceiling effects. Analysis used linear and logistic regression.WCWs were feasible to collect: 95.2% (study A) and 94.7% (study B) contributed data for at least half of the weekly data points, and 93.2% and 88.7% contributed to all data points up to 4 months. WCWs were significantly associated with validated AD severity instruments, including patient-orientated outcome measures and objective signs (Eczema Area and Severity Index, Three Item Severity Score, and Six Signs, Six Areas Atopic Dermatitis Scale). The odds of experiencing a WCW if AD severity was clear/mild was 5.8 (95% CI, 3.5-9.7), 1.9 (95% CI, 0.8-4.4), and 8.1 (95% CI, 4.5-14.6) in studies A, B, and C, respectively. WCWs were associated with ceiling effects: 31.6% (study A) and 37.5% (study B) of participants had no WCWs more than 90% of the time.WCWs are valid and feasible for measuring long-term control in AD trials. However, ceiling effects and burden of data collection can limit use.
Effect of raloxifene on invasive breast cancer incidence in postmenopausal women stratified by age (&lt; 65 and ≥ 65 years)
Authors: S. Martino, D. Disch, S. Dowsett, J. Mershon
Journal: Journal of Clinical Oncology (2005)

1009 Background: Raloxifene (RLX) is approved for osteoporosis prevention and treatment in postmenopausal women (PMW) and is being studied for breast cancer (BC) risk reduction. The Continuing Outcomes Relevant to Evista (CORE) trial is a double-blind, placebo-controlled, 4-yr follow-up to the 4-yr Multiple Outcomes of Raloxifene Evaluation (MORE) trial. The primary endpoint of CORE was time to first invasive BC; RLX was associated with a 59% reduction in invasive BC incidence versus placebo. The effect of age on invasive breast cancer incidence was a pre-specified secondary analysis. The aim of this analysis was to determine RLX’s effect versus placebo on invasive BC incidence over 8 years in PMW with osteoporosis stratified by age group (< 65, ≥ 65 years). Methods: Of the 7705 PMW enrolled in MORE, 4011 continued in CORE. Those randomized to RLX 60 or 120 mg/d in MORE were assigned to RLX 60mg/d in CORE; those randomized to placebo (PLC) in MORE received placebo in CORE. Time to first invasive BC was analyzed using Cox proportional hazard models. Results: In the PLC group, there was a 77% increase in invasive BC risk in women ≥ 65 years versus those < 65 years (hazard ratio 1.77, 95% CI 1.01, 3.12). The invasive BC rates were 29.6 and 51.0 per 10,000 women-years in the age categories < 65 and ≥ 65 years, respectively. The effect of RLX versus PLC on invasive BC risk by age category is shown in the Table. Therapy by Age Group interaction was not significant (p=0.43). Conclusion: Invasive BC risk increased with age. RLX significantly reduced the incidence of invasive BC in PMW with osteoporosis, both in those < 65 and ≥ 65 years. RLX’s effect was not dependent upon age group. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly Eli Lilly
First-line everolimus followed by second-line sunitinib versus the opposite treatment sequence in patients with metastatic renal cell carcinoma (mRCC).
Authors: J. J. Knox, A. C. Kay, E. Schiff, N. Hollaender, N. Rouyrre, A. Ravaud, R. J. Motzer
Journal: Journal of Clinical Oncology (2010)

TPS232 Background: Targeted therapies for advanced renal cell carcinoma (RCC) have changed treatment paradigms. Currently, sequential monotherapy with targeted agents is the standard of care. Sunitinib is a multikinase inhibitor approved for first-line use in advanced RCC; everolimus, an oral inhibitor of mTOR, is approved for use following sunitinib. Currently, these 2 agents have level 1 recommendations for use in the first and second line settings, respectively. However, the most appropriate sequence for everolimus and sunitinib has not been established in a prospective clinical trial. The RECORD-3 (Renal Cell Cancer Treatment with Oral RAD001 Given Daily) trial will assess progression-free survival (PFS) for everolimus- sunitinib versus sunitinib-everolimus in treatment naïve patients with mRCC. RECORD-3 is the first trial to evaluate everolimus as second-line therapy after treatment solely with sunitinib. Methods: RECORD-3 is a randomized, open-label, multicenter phase II trial currently recruiting participants. Up to 390 patients with mRCC (clear-cell or non≂̃-clear-cell), with or without nephrectomy, ≥1 measurable baseline lesion (per RECIST criteria), Karnofsky performance status ≥70%, adequate liver, renal, and bone marrow function, and left ventricular ejection fraction ≥ lower limit of normal will be enrolled. The primary objective is to determine whether everolimus is noninferior to sunitinib, as assessed by PFS, for first-line treatment of mRCC. Patients are randomized 1:1 to receive everolimus 10 mg/d PO once daily or sunitinib 50 mg/d PO for 4 wk followed by 2 wk off therapy until disease progression; upon progression, patients will cross over to second-line treatment with the opposite drug until the second occurrence of progression. The primary endpoint will assess PFS after first-line treatment. Overall efficacy of the 2 sequences will be compared based on the time from start of the sequence to progression after second-line therapy, or death. Overall survival, objective response rate, patient-reported outcomes, and safety also will be assessed. The first patient visit was October 22, 2009; 11 patients have entered the study to date. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis AVEO, Bayer, GlaxoSmithKline, Novartis, Pfizer, Roche, Wyeth Novartis Novartis, Pfizer, Roche, Wyeth Bayer, GlaxoSmithKline, Novartis, Pfizer, Roche
Impact of selected tumor and patient characteristics on outcome of lymph node-positive breast cancer patients.
Authors: Ahmed Aly Nagy, Hager Ibrahim, Lamiaa Eid, Fatma Sayed, Mohamed Reda Kelany, Mona kamal Jomaa
Journal: Journal of Clinical Oncology (2015)

66 Background: Axillary lymph node (ALN) involvement remains the most significant factor affecting long term survival in breast cancer (BC) patients, and the risk of treatment failure is increased with the higher the number of ALN involvement, The aim of this study was to determine the impact of tumor characteristics; tumor size and number of positive lymph nodes and, ER and HER-2, as well as patient characteristics on DFS of patients with Lymph node positive Breast Cancer Patients who received Adjuvant Treatment. Methods: We retrospectively reviewed data of 704 patients with BC and ALN involvement who received adjuvant treatment in the period between 2010 and 2012. DFS outcomes were estimated with the Kaplan-Meier method and compared using the log rank test to determine. The effect of prognostic factors on BC outcomes. Results: Median age was 50 years (SD±12.024, Range 21-88). About 83.7% of the tumors were IDC,. About 30.4%of the tumors were grade III. Median tumor size was 5 cm (SD± 1.3745, Range 1-7).Median number of positive axillary LN was 4 (SD± 4.987, Range 1-37). Regarding receptor expression; 21.2% were HER-2 +ve, 58.7% were ER +ve and about 30.4 were triple negative. Median DFS was 20 months (SD± 14.511, Range 1-60). Cox regression showed that age, positive ER status and more than 3 ALN involvement had a statistically significant impact on DFS ( p&lt;0.001 for all ), however, Tumor size, HER-2 overexpression, patient menstrual status had no significant effect. ER positive age &gt;50 years was associated with prolonged DFS of 23 months (95%CI=20.641-25.359) versus 19 months (95% CI=17.598-20.402) for age≤50 years (p&lt;0.001). ER positive status was associated with prolonged DFS of 22 months (95%CI=20.290-23.710) versus 17 months (95% CI=14.049-19.951) for ER negative (p&lt;0.001).The group of patients with ≤3 positive dissected LN was associated with statistically significant prolonged DFS of 25 months (95%CI=22.286-27.714) versus 15 months (95%CI = 12.353-17.647) for patients with&gt;3 positive dissected LN (p&lt;0.001). Conclusions: These study indicate that the age, ER status and more than 3 ALN involvement have impact on DFS in Lymph node positive Breast Cancer Patients.