tbuckley/cabot-search huggingface dataset:
Feasibility of using memantine in smoking cessation among cancer survivors.
Authors: John Spangler, Kathryn E Weaver, Doug Case, Glenn Lesser, Gary Von Burton, Irene Ang Dy, Carrie Dul, Pavan Reddy, James Lloyd Wade, Benjamin Esparaz, Edward G. Shaw
Journal: Journal of Clinical Oncology (2015)

1559 Background: Memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist, has been proposed for smoking cessation by virtue of opposing the effects of glutamate in the CNS “addiction center,” the nucleus accumbens. This study evaluated Memantine’s feasibility and preliminary efficacy for quitting smoking among cancer survivors. Methods: A prospective randomized feasibility trial was conducted by the Wake Forest CCOP Research Base. Feasibility outcomes included accrual, retention, adherence, and toxicity. Clinical outcomes included smoking cessation at 12 weeks (defined as no smoking in the past week). 130 patients were accrued between 9/12 and 11/13, 65 on Memantine (M) and 65 on Control (C). Ages ranged from 29 to 84 with a median of 57; 85% were female and 85% were Non-Hispanic White. 75% had breast cancer, 12% colorectal cancer, 11% lung cancer, and 2% prostate cancer. On average, patients started smoking at 16, had smoked for 40 years, and smoked a pack a day. Characteristics were similar in the two arms. Results: Over 20 CCOP sites participated; accrual was approximately 10 patients per month. Retention at 12 weeks was poor (54% M, 68% C). Self-reported adherence was good while patients were on study (86% M, 93% C). Four serious adverse events were noted (3 M, 1 C), none related to treatment. Toxicities were similar in the two arms. Only two patients reported being smoke-free at 12 weeks, both in the Control arm. The number of cigarettes smoked at 12 weeks was similar in the two arms. Conclusions: While accrual was robust and patients reported good adherence, 40% dropped out by 12 weeks and very few patients could remain smoke-free for one week prior to the 12 week evaluation following randomization. Other options for smoking cessation need to be assessed. (Funding for this study was provided by NCI to the Wake Forest CCOP Research Base, grant number U10CA081851). Clinical trial information: NCT01535040.
Relationship between Onco<i>type</i> DX testing and the use of chemotherapy in high-risk patients (pts).
Authors: Winston Wong, Joseph Cooper, Steve Richardson, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2012)

6098 Background: CareFirst BlueCross BlueShield (CFBCBS) insurance network partnered with Cardinal Health Specialty Solutions (CHSS) to develop a cancer care pathway for network physicians in 2008. The program included a recommendation for molecular diagnostic testing with the Oncotype DX assay for pts with early-stage estrogen receptor-positive breast cancer. Based on NCCN guidelines, the pathway suggested adjuvant chemotherapy for all pts with Oncotype DX Recurrence Scores (RS) in the high-risk category. We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using data from CFBCBS, CHSS proprietary claims software, and Genomic Health, we retrospectively identified a cohort of women with breast cancer who were treated on the CFBCBS clinical care pathways program from 8/2008 to 6/2011 and received Oncotype DX testing. We determined the number of pts with a RS value in the low- (RS &lt;18), intermediate- (RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received chemotherapy in each category. Results: Of 1174 women who received Oncotype DX testing, 53% of pts were in the low-, 35% in intermediate-, and 12% in the high-risk groups. Five percent of low-, 41% of intermediate-, and 74% percent of pts in the high-risk category were treated with chemotherapy. Twenty-six percent of pts in the high-risk group did not receive chemotherapy. Conclusions: The proportionate use of chemotherapy in the low and intermediate risk groups was as expected based on adjuvant chemotherapy guidelines; however, the underuse of chemotherapy in 26% of high-risk pts was an unexpected finding. Further study is needed to determine: (1) why physicians avoided chemotherapy in 26% of high-risk pts; (2) the overall number of appropriate pts who underwent Oncotype DX testing; and, (3) the tumor characteristics that may have driven the underutilization of chemotherapy in the high-risk population.
Cost-effectiveness of alternative adjuvant bisphosphonate regimens in postmenopausal women with early breast cancer.
Authors: Katherine Elizabeth Reeder-Hayes, Shellie D. Ellis, Stacie Dusetzina, Stephanie B. Wheeler
Journal: Journal of Clinical Oncology (2014)

6565 Background: The benefit of bisphosphonate drugs in adjuvant breast cancer care has been a topic of clinical debate. A recently presented meta-analysis of clinical trials by Coleman et al (2013) suggested recurrence and survival gains from adding bisphosphonates to the adjuvant treatment of post-menopausal women, but the most efficacious bisphosphonate dose and schedule has not been defined. Our study assessed the cost-effectiveness of bisphosphonate regimens available in the United States based on available clinical trials and meta-analysis data. Methods: We used a decision tree model to assess costs and benefits of the following regimens: no treatment, alendronate (A) 70 mg/week, low dose ibandronate (I) 150 mg/month, high dose I 50 mg/day, low dose zoledronic acid (Z) 4 mg/6 months, or high dose Z (six doses in the first 6 months, eight doses in the next 24 months and five doses in the final 30 months). All regimens except high dose Z were continued for three years. The model followed a simulated cohort of 100,000 post-menopausal women with non-metastatic breast cancer over ten years. Using a payer perspective, we considered direct medical costs and quality of life effects of initial treatment, distant recurrence, and complications of bisphosphonate therapy. The primary outcome was cost per quality-adjusted life year (QALY). We performed one-way and probabilistic sensitivity analyses to assess the robustness of results to variations in parameter estimates. Results: In the base-case model, A and low dose I were cost-saving compared to no therapy, while low dose Z was cost-effective with an incremental cost-effectiveness ratio (ICER) of $10,317/QALY gained. More intensive regimens including high dose I and high dose Z were not cost-effective at a willingness-to-pay threshold of $50,000/QALY gained. Conclusions: The cost-effectiveness of adjuvant bisphosphonate therapy in this patient population varies considerably depending on the choice of regimen. Until further evidence is available regarding the comparative benefit of differing regimens used in clinical trials, clinicians seeking to integrate bisphosphonates into adjuvant breast cancer care should consider lower dose regimens.
Differences in outcome due to bevacizumab (BEV) discontinuation versus BEV failure in adults with glioblastoma.
Authors: Mark Daniel Anderson, Vinay K. Puduvalli, Mohamed Ali Hamza, Mark R. Gilbert, W. K. Alfred Yung
Journal: Journal of Clinical Oncology (2012)

2030 Background: BEV is approved for use in recurrent glioblastoma. Patients (pts) who benefit from BEV therapy are often treated until tumor progression but fail to respond to salvage therapy suggesting that BEV may alter tumor biology. In a subset of pts who benefit from BEV, treatment is discontinued for reasons other than disease progression; the characteristics and outcomes of this subset are poorly defined. Methods: In this IRB approved retrospective study, our neuro-oncology longitudinal database was screened for pts treated with BEV for ≥ 6 months (mo) between 2005-2010 and 18 pts were identified in whom BEV was discontinued for reasons other than disease progression (BEV-D group). A cohort of 72 pts who received BEV until treatment failure due to progression was used as comparator (BEV-F group). Results: In the BEV-D group, 5 pts completed a planned treatment course and 13 stopped BEV due to toxicity; in this group, progression free survival at 12 mo (PFS12) was 83.3% (95% CI, 56.8-94.3) and median time to progression (TTP) 27.6 mo. Median TTP after BEV discontinuation was 7.0 mo. In contrast, in the BEV-F group, PFS12 was 24.6% (95% CI, 13.9-36.2) and median PFS 9.7 mo. Length of BEV therapy was not significantly different between the groups with a median time to discontinuation of 10.2 and 12 mo. In 12/18 pts in the BEV-D group who subsequently had tumor recurrence a predominantly local pattern of progression was seen unlike those in the BEV-F group who had more infiltrative or distant failures. Salvage therapy yielded a PFS-6 of 28.6% (95% CI, 4.1-61.2) with a median PFS of 17.1 wk compared with 6.8% (95% CI, 1.2-19.8) and 9 wk in the comparator group. Conclusions: Among pts who benefit from BEV therapy, the BEV-D group did not experience an immediate progression suggesting continued benefit after BEV cessation. This cohort also had a less invasive pattern of recurrence and a possibly improved response to salvage therapy compared with BEV-F group. Our results suggest that planned cessation of BEV therapy could potentially change patterns of progression and response to subsequent therapy. This strategy warrants further evaluation in prospective studies given the absence of effective salvage therapy after BEV failure.
Complementary and alternative medicine (CAM) use among patients with cancer undergoing palliative care: A pilot study of a single institution in Poland.
Authors: Janusz Wojtacki, Leszek Pawlowski, Iga Pawlowska, Monika LichodziejewskaNiemierko
Journal: Journal of Clinical Oncology (2017)

178 Background: Real life observations suggest CAM is frequently used by cancer patients. The profound knowledge of CAM use details is crucial for both efficacy and safety of anticancer and supportive therapy. Methods: Semi-structured pilot questionnaire about details of CAM use was presented to all 202 consecutive patients of Palliative Care Outpatient Clinic, E. Dutkiewicz SAC Hospice, Gdańsk, Poland (April-22 and September-30/2016). After excluding 112 patients (no-responders group = N-RES) due to low performance status (N = 64), lack of written agreement (n = 10), diagnosis of non-malignant disease (N = 26), others (N = 12), the final analysis included 90 patients (female: 72,0%, median age: 63,5, range: 24-94 yrs) with advanced cancer (responders = RES). Demographic and clinical data were collected at the same time, then statistically related to CAM use details. Results: RES patients were significantly younger (p = 0,0045) and in better performance status (p &lt; 0,05) as compared to N-RES group (no difference with regard to gender, education level, primary cancer location, duration of malignant disease, marital status). Since the primary cancer diagnosis, CAM was used by 56 (62,2%) RES patients and mostly included vitamin/mineral formulations (36,7%), herbs (32,2%), alternative nutrition (24,4%), music therapy (11,1%) and Chinese medicine (5,6%). The main reasons for CAM use were: to enhance the effects of anticancer therapy (48,9%), to treat its side-effects (15,6%) or the lack of conventional therapy possibilities (5,6%). CAM was used more frequently by patients who experienced weight loss since diagnosis of cancer (p = 0,0028) or those who used CAM methods to control symptoms not related to cancer (p = 0,0109); age, gender, education level, marital status, religious practices frequency were not significantly related to CAM use. Conclusions: 1) CAM use is common among patients with advanced cancer under palliative care; 2) some factors might be in relation to higher CAM use (weight loss, CAM use to control symptoms not related to cancer); 3) further research is required to investigate better different aspects of CAM use such as safety, efficacy and outcomes in this population.
Clinical prognostic factors associated with survival after definitive chemoradiotherapy in advanced squamous cell carcinoma of esophagus.
Authors: Hyun-Jeong Shim, Won-young Choi, Dae-Eun Kim, Jun-Eul Hwang, Woo Kyun Bae, Sang-Hee Cho, Ik-Joo Chung
Journal: Journal of Clinical Oncology (2013)

e15121 Background: Definitive chemoradiotherapy (dCRT) has been used as a standard care for treating and palliating of symptoms in advanced esophageal cancer patients even if they have metastatic disease. The purpose of this study is to identify the treatment outcomes and prognostic factors for survival in squamous cell type of esophagus. Methods: We retrospectively studied the patients who treated with dCRT using 5-FU and cisplatin, and histologically proven squamous cell esophageal carcinoma of stage III and IV between January 2004 and December 2010. Results: In total 110 patients were enrolled in analysis of whom 64 patients were stage III and Iva (localized advanced) and 46 patients were stage IVb. The ratio of male/female was 109/1 and the median age was 65 years. T-stage was cT2=8%, cT3=75, cT4=17% and N-stage was cN0=5%, cN1=95%. The most common metastatic site was distant LN (60%). The median dose of radiation was 5400 cGy (range, 4400-6600). The median OS for locally advanced and metastatic disease group was 19.0 and 12.8 months, respectively (p=0.032). The median PFS for these groups was 8.3 and 6.9 months, respectively (p=0.208). The most common pattern of failure was locoregional area. In univariate analysis, cell type (poorly differentiation), dysphagia score, PS (ECOG 1-2 vs. 0), PFS (&lt;5months) and CRP were significantly associated with OS and cell type, PS, PFS were shown significantly poor prognostic factors for OS in multivariate analysis. Among the patients who had locally advanced disease, maintenance chemotherapy after dCRT did not influence the OS. However, “good risk” patients who had less than 2 risk factors receiving maintenance chemotherapy showed better OS than those with no maintenance chemotherapy (40.9 vs. 12.3 months; p=0.011). Conclusions: dCRT has a major role in improving survival and palliation of dysphagia in inoperable advanced esophageal cancer even in metastatic stage. Cell type and PS have been still important prognostic factors in survival. In addition, maintenance chemotherapy after dCRT may be helpful for prolongation survival in good risk patients.
Adaptive immune resistance in gastro-esophageal cancer: Correlating tumoral/stromal PDL1 expression with CD8<sup>+</sup> cell count.
Authors: Ronan Joseph Kelly, Elizabeth Thompson, Marianna Zahurak, Toby Cornish, Nathan Cuka, Eihab Abdelfatah, Janis M. Taube, Stephen Yang, Mark Duncan, Nita Ahuja, Adrian Murphy, Robert A Anders
Journal: Journal of Clinical Oncology (2015)

4031 Background: In adaptive resistance, tumors use PDL1 induction as a protective mechanism against an antitumor immune response implying underlying immuno-surveillance. By upregulating the expression of ligands for inhibitory receptors on tumor specific lymphocytes in the tumor microenvironment a growing malignancy can avoid immune elimination. Here we report the interaction between PDL1 status and the density of CD8+ at the tumor stromal interface in gastric and gastroesophageal junction adenocarcinomas (G/GEJ). Methods: 34 invasive G/GEJ were stained for PDL1 using the 5H1 clone both at the tumor cell and associated tumor infiltrating lymphocyte/macrophages (TILs/TAMs). Tumors with greater than 5% membranous staining were considered PDL1 positive. TILs/TAMs were scored as no significant staining (0), less than 50% (focal) or greater than 50% (high). CD8+ density was determined using image analysis. Survival was evaluated according to PDL1 and CD8+ status. Results: 4/34 tumors (12%) showed membranous PDL1 expression. 45% of G/GEJ demonstrated PDL1 expression among TILs with 27% showing focal interface expression and 18% high expression. Patients whose tumors were defined as stroma high (CD8+ > 500 cells/m2) had a worse PFS, HR = 3.91 (95% CI: 1.32, 11.59) p = 0.01, and OS, HR = 3.46 (95% CI: 1.09, 10.96) p = 0.03, compared to stroma low (CD8+< 500 cells/mm2). Interestingly in the stroma, 8/9 tumors (89%, CI: 51.8%, 99.7%) with high CD8+ were also positive for PDL1 while only 7/24 (29%, CI: 12.6%, 51.1%) with low CD8+ were PDL1 positive (p = 0.004). PDL1 stromal expression was identified in 33.3% stage I, 53.9% stage II, 37.5% stage III, and 66.7% of stage IV tumors (p = 0.51). Stromal PDL1 expression occurred in 60% of intestinal and 38.5% of diffuse tumors (p = 0.45). Conclusions: PDL1 is expressed on both tumor cells and TILs across all stages and histologies of G/GEJ. Patients with higher CD8+ levels have higher PDL1 expression indicating adaptive resistance is occurring in the tumor microenvironment. Phase II and Phase III clinical trials investigating the efficacy of PD1/PDL1 inhibitors either alone or in combination with CTLA-4 inhibitors are currently ongoing in patients with advanced G/GEJ.
Clonal Dynamics of Refractory Aplastic Anemia in Patients Treated with Eltrombopag
Authors: Bhumika Patel, Bartlomiej P Przychodzen, Michael J. Clemente, Cassandra M. Hirsch, Caner Saygin, Marissa Versalle, Swapna Thota, Aziz Nazha, Roy Souaid, Valeria Visconte, Taha Bat, Suresh Kumar Balasubramanian, Tomas Radivoyevitch, Hetty E. Carraway, Mikkael A. Sekeres, Jaroslaw P Maciejewski
Journal: Blood (2016)
Lenalidomide and bortezomib induce osteoclast cytotoxicity and decrease BAFF secretion in osteoclasts in human multiple myeloma: Clinical implications
Authors: I. Breitkreutz, Y. Tai, X. Li, R. Coffey, M. S. Raab, W. Song, T. Hideshima, D. Chauhan, N. Munshi, K. C. Anderson
Journal: Journal of Clinical Oncology (2006)

7606 Background: Myeloma bone disease is caused by an enhanced osteoclast (OCL) activation, leading to osteolytic bone lesions. OCL have recently been reported to produce abundant B-cell activating factor (BAFF) in the bone marrow microenvironment that is important for myeloma cell growth and survival (Blood 106, 1021–30, 2005; ASH2005, #627). The proteasome inhibitor bortezomib (PS341, Velcade) has potent anti-myeloma activity with impressive clinical responses. A recent study indicated that bortezomib has inhibitory effects on OCL (ASH 2005, #2488). Lenalidomide (CC-5013, Revlimid) is an immunomodulatory derivative of thalidomide that has shown promising anti-myeloma effects in patients with relapsed or refractory multiple myeloma (MM) (ASH 2005, #6 &amp; #1565). However, the effect of lenalidomide on human OCL lineage is unknown. Therefore, the aim of this study is to investigate the effect of lenalidomide and bortezomib on human OCL. Methods: OCL formation from healthy donors and MM patients were stimulated with RANKL (50ng/ml) and GM-CSF (10ng/ml) in 20% FBS/RPMI. Cells were incubated with lenalidomide 2μM or bortezomib 2nM, alone and in combination, for two weeks followed by [3H]thymidine uptake assay to measure growth inhibition of OCL. Similar experiments were also performed in cocultures of CD138-purified cells from MM patients with OCL, in the presence or absence of lenalidomide and bortezomib. In addition, ELISA was performed to measure cytokine release of BAFF produced by OCL in these cultures. Results: OCL growth was decreased by lenalidomide (n=6) (median 49.2%, range 20–62.5%; coculture: 53% and 35%) as well as bortezomib (96 and 49%; coculture 63 and 59%) and by the combination of both drugs (95 and 55%; coculture 42 and 44%). BAFF secretion was dramatically decreased in cultures treated with lenalidomide 2μM (n=3) (median 72%, range 61–75.9%). Conclusions: These results indicate that lenalidomide and bortezomib inhibit OCL growth and survival. Importantly, lenalidomide and bortezomib also block growth and survival of MM cells cocultured with OCL, suggesting that lenalidomide may inhibit OCL growth and survival through inhibition of BAFF and may prevent development of osteolytic lesions in MM. No significant financial relationships to disclose.
Azacitidine in older patients with acute myeloid leukemia (AML). Results from the ALMA study according to the MRC risk index score.
Authors: Jose F Falantes, Violeta Martinez Robles, Joan Bargay, Guillermo Deben, Ana Garrido, Javier Casano, Olga Salamero, Juan M Bergua, Enrique Colado, Regina Garcia, Carmen Pedro, Santiago Redondo, Mar Tormo, Santiago Bonanad, Maria Diez-Campelo, Manuel Perez-Encinas, Adolfo de la Fuente, Blanca Xicoy, Pau Montesinos, Fernando Ramos
Journal: Journal of Clinical Oncology (2015)

7061 Background: Treatment of patients (pts) >60y with AML remains challenging. The MRC and LRF validated a 1y survival risk index score in 2843 older AML pts treated with intensive (IC) and non-intensive (NI) chemotherapy, identifying 3 groups with different risk estimates1. Azacitidine (AZA) prolonged OS in older AML pts vs. conventional care (AZA-AML-001 trial)2. Nevertheless, comparison between AZA and IC was jeopardized by the low number of subjects randomized to AZA or IC. Aim: To assess the impact of AZA in a retrospective cohort of older AML pts, unfit for IC, stratified by the MRC/LRF risk score. Methods: The ALMA cohort accrued 110 unfit AML pts who received compassionate front-line AZA before 2011 in 22 Spanish sites (Ramos F et al, Leuk Res. 2014). Cytogenetic, age, white blood count (WBC), PS and AML type categorized pts as good, standard and poor-risk, as stated by Wheatley’s score. Results: Characteristics of the ALMA cohort and distribution across MRC/LRF risk categories are shown in Table 1. After accounting for the above 5 parameters, the ALMA cohort included more poor-risk pts than the MRC/LRF series (63% vs. 31%/37% in the AML11/AML14 trials, respectively). After 28 months median follow-up, 1y survival of ALMA cohort was 66%, 40% and 31%, respectively, for the good, standard and poor-risk groups. Comparison of these estimates with those of MRC/LRF trials are also shown in Table 1. Potentially relevant clinical differences are apparent in the poor-risk group when comparing AZA to either approach. Conclusions: Although retrospective and non-matched, AML pts unfit for IC seemed to benefit from AZA to a similar extent to IC. Moreover, in the poor-risk subset (n=70), 1y survival with AZA was equivalent and likely superior to previous AML/MRC strategies. ALMA cohort. Parameter N (%) Age (median) 75 (56-89) PS 0-1: 77 2: 27 >2: 6 WCB (<109/L) 79 (72) Therapy-related AML & AHD 16 (14%) & 27 (24.5%) MRC cytogenetics Fav: 1 (0.9) Inter: 64 (58.2) Adv: 30 (27.3) NA: 15 (13.6) Risk categories (AML11 risk) Good: 7 (6.4) Standard: 33 (30) Poor: 70 (63.6) 1y survival estimates (%) MRC/LRF Risk group AML11 AML14I AML14NI AML14NIA AML14 (all) ALMA Good 53 60 25 36 59 66 Standard 43 48 33 42 45 40 Poor 16 30 10 14 24 31