tbuckley/cabot-search huggingface dataset:
IMAGE, a randomized phase Ib/II study of elisidepsin (E) as a single agent in pretreated advanced gastroesophageal (GE) cancer.
Authors: Ramon Salazar, Jean Philippe Metges, David Alan Anthoney, Gianluca Laus, Maria Alsina Maqueda, Anthony Goncalves, Clara Montagut, Jennifer Brown, Katharina Gunzer, Sergio A. Szyldergemajn, Russell D. Petty
Journal: Journal of Clinical Oncology (2013)

92 Background: E is a new marine compound with broad in vitro/in vivo antitumor activity. Low μM concentrations lead to cell-death through membrane permeabilization. E has shown evidence of activity in pre-treated GE patients (pts) in phase I trials. Methods: The primary objective was to determine the tolerability and efficacy of E in pts with GE cancer after 1-2 prior chemotherapy (CT) lines. Initially, dose was optimized (Phase Ib) in two different schedules: a fixed flat dose (FD) of intravenous (i.v) E (8 and 10 mg), in 24h, biweekly (Arm A) and i.v E (3.0 and 3.75mg), in 3h, weekly (Arm B). After dose optimization patients were included and stratified by histology to each optimal dose (Phase II) to determine the rate of progression-free survival at week 16 ± 1 (PFS4) in an intention to treat analysis. If at least two out of 15 pts reached PFS4, recruitment would continue to a maximum of 40 pts per arm. Results: A total of 45 pts were recruited, 12 pts into Phase Ib (Arm A/B: 6/6 pts) and 33 pts into Phase II (Arm A/B: 15/18 pts). Median age was 60 years (35–81 years), 39 were males and ECOG PS was 1 in 75% of pts. Tumour sites were gastric (32% pts), esophageal (39% pts) and esophago-gastric junction (30% pts). Ninety percent of pts had metastatic disease, 31.8% of which had liver metastasis; 55% of pts had two prior lines of CT . No DLTs occurred during the first cycle in the Phase Ib. The optimal dose for Arm A was 10 mg FD, 24h, biweekly; the optimal dose for Arm B was 3.75mg FD, 3h, weekly. Two patients reached PFS4 in Phase Ib (Arm A). Only one patient reached PFS4 in Phase II (Arm A). No objective responses were observed. Therefore, protocol criteria for further recruitment were not met. The safety profile showed grade 1-2 toxicity pruritus (29.5%), nausea (15.9%), vomiting (6.8%) and fatigue (25%). Grade 3-4 toxicity consisted of asymptomatic reversible liver enzyme increases in 20.5% of patients. Conclusions: E is a very tolerable drug with a unique mechanism of action. In the current setting of non-stratified advanced GE patients, E has insufficient antitumor activity to warrant further investigation. Clinical trial information: 2010-020325-40.
Pathologic indicators of chemotherapy response in colorectal liver metastases: A comparative study.
Authors: J. Maresch, S. Stremitzer, D. Tamandl, F. Wrba, T. Gruenberger
Journal: Journal of Clinical Oncology (2011)

e14159 Background: Improvement in the treatment of colorectal liver metastases (CLM) demands histopathological indicators of chemotherapy response and predictors of clinical outcome. Currently, decisive factors are the percentage of viable tumor cells and chemotherapy-related tissue changes like tumor necrosis and fibrosis. The goal of this study was to compare the tumor regression grade (TRG) scheme with a newer method, which focuses on the tumor thickness at the tumor-normal-interface (TNI). Methods: A retrospective analysis was performed in 79 patients who underwent neoadjuvant chemotherapy for 3 months (fluoropyrimidine, oxaliplatin and bevacizumab), followed by resection. Both, the TRG modified by Rubbia-Brandt and the TNI by Maru were assessed according to the described protocols. Spearman correlation analyses were performed to identify comparability. The 5 TRG scores were subsumed in major (MjHR), partial (PHR) and no histological response (NHR). Using the method suggested by Maru, the response rates were classified as complete (0% tumor cells), major (<50%) and minor response (≥50%). The mean TNI was categorized in groups of <0,5, 0,5-4,9 and ≥5 mm and correlated to recurrence-free survival (RFS) and overall survival (OS). Results: TRG: 36 (46%) patients showed a MjHR, 19 (24%) a PHR and 24 (30%) patients NHR. According to Maru, eight (10%) patients had a complete response, 52 (66%) a major and 19 (24%) a minor response; TNI: a mean TNI of 0.73 mm (range, 0-2 mm) in major responders and a mean TNI of 1,83 mm (range, 0.5-3.75 mm) in minor responders. Comparison of both methods displayed similar results with significant correlation (Spearman correlation coefficient, r=0,67, P<0,001). Patients with NHR or PHR had a higher risk of relapse (2-year RFS 28%) than patients with MjHR (2-year RFS 41%). The same applies to overall survival (NHR 70% vs. MjHR 89%). Increasing TNI (≥0.5 mm) was associated with a shorter RFS (2-year RFS 29% vs. 43%) and a poorer overall outcome (3-year OS 77% vs. 96%). Conclusions: TRG and tumor thickness at the TNI are equivalent and comparable methods for assessing the degree of pathologic response in CLM, which therefore provide important prognostic information after neoadjuvant therapy.
Evaluation of neuropathy in breast cancer patients treated with ixabepilone
Authors: J. J. Lee, J. A. Low, E. Croarkin, R. Parks, A. W. Berman, N. Mannan, S. M. Steinberg, S. M. Swain
Journal: Journal of Clinical Oncology (2005)

657 Introduction: Ixabepilone, a microtubule stabilizing agent, has activity in breast cancer and is associated with peripheral neuropathy (PN) which has not been well characterized. This analysis was performed to look for predictive factors for PN. Methods: Metastatic breast cancer patients (pts) with grade (G) 0 or 1 PN were treated with ixabepilone 6 mg/m2 daily x 5 every 21 days. Baseline functional testing included balance testing (BT), Semmes-Weinstein monofilaments (SWM), the Jebsen test of hand function (JTHF) for non-dominant (ND) and dominant (D) hands, and the grooved peg board test (GPBT) for ND and D hands. Baseline testing and factors were compared with the exact Wilcoxon rank sum test, while Fisher’s exact test compared binomial parameters, p<0.01 was considered significant. Results: 42 patients were enrolled, and 30 patients with > 2 cycles of treatment were analyzed. They received a median of 6 cycles (3 - 22 cycles). 9 patients (30%) developed PN of G2/3 (7 pts with G2 and 2 pts with G3) with a median onset of 144 days (42 - 189 days) after on-study date. 5 patients had resolution of G2/3 PN with a median duration of 9 days (6 - 29 days) after onset while 4 patients did not resolve within a median follow up of 151 days (51 - 597 days). Mean values and proportions for the baseline factors examined are shown in the table. There was no significant difference in the number of treatment cycles between patients who did and did not develop G2/3 PN (p=0.28). Conclusions: Ixabepilone-associated G2/3 neuropathy developed in 30% of patients receiving >2 cycles of treatment. Differences in baseline values of GPBT, BT and JTHF between patients who did or did not develop G2/3 PN are suggestive of trends for prediction of G2/3 PN. These functional tests merit evaluation in subsequent, larger studies. No significant financial relationships to disclose.
Results of employing a plerixafor dosing algorithm to mobilize hematopoietic stem cells in patients with multiple myeloma and lymphoma.
Authors: T. Bechtel, Y. A. Efebera, S. M. Devine, P. Elder
Journal: Journal of Clinical Oncology (2011)

6541 Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) is standard of care for some patients with multiple myeloma (MM) and non-Hodgkin’s lymphoma (NHL) and its success depends on harvesting an adequate number of CD34+ cells. Mobilization with growth factors alone or with chemotherapy has resulted in reported failure rates of 20-40% (NHL) and 10-20% (MM). Plerixafor (P) enhances the mobilization and subsequent harvesting of CD34+ cells. To ensure its appropriate and fiscally responsible use, we developed a dosing algorithm to be used in select patients thought to potentially be poor mobilizers. The inclusion criteria and dosing decision pathways were determined by a review of the evidence-based literature. Methods: The records of 64 (37M, 27F) pts with MM or NHL mobilized with P Apr 2009-Nov 2010 using our dosing algorithm were reviewed. A comparative group of 93 (58M, 35F) pts with MM and NHL mobilized Apr 2008-Mar 2009 with filgrastim alone (F) or with chemotherapy (FC) were also reviewed. Patient demographics, number of CD34+ cells harvested, number of P doses, apheresis days and number failing to mobilize at least 2x 106 CD 34+/kg cells were recorded. Results: The median ages were: P-62 yrs (22-76), F-52 yrs (20-76) & FC-52 yrs (20-68). P consisted of 31 MM and 33 NHL pts, F-67 MM and 10 NHL pts and FC-14 MM and 2 NHL pts. The median number of (P) doses and (P) apheresis days were: MM 1 (1-2) and 2 (0-3), NHL 2 (1-4) and 2 (0-4), the median number of apheresis days in F- MM 3 (0-5), NHL 2 (0-3) and FC-MM 2 (0-4), NHL 2.5 (2-3). The median number of CD34+ cells harvested was: P-MM 6.47 (0-15.0), NHL 3.53 (0-10.29), F-MM 6.3 (0-16.26), NHL 3.65 (0-8.41) and FC: MM 6.22 (0-12.34), NHL 5.72 (5.33-6.11). The number of patients failing to mobilize at least 2 x 106 CD34+/kg cells was: P-MM 2 (6.5%), NHL 4 (12%), F-MM 8 (11.9%), NHL 3 (33%) and FC-MM 3 (21.4%), NHL 0. Conclusions: The failure rates for MM and NHL pts receiving P were well below reported literature values and that of our own comparative groups. Additionally, P group required a fewer number of apheresis days than either the F or FC group leading to cost savings. These positive results justify P use in select patients
Risk factors for local-regional failure in patients with T1-T2 breast cancer after breast-conserving therapy. Indications for nodal irradiation
Authors: L. Livi, S. M. Magrini, I. Meattini, F. Paiar, S. Scoccianti, S. Bianchi, L. Cataliotti, G. Biti
Journal: Journal of Clinical Oncology (2008)

626 Background: To determine the incidence and risk factors for local-regional failure (LRR) and to evaluate the indications for nodal irradiation in patients with stage I-II breast cancer. Methods: A total of 3,960 cases of stage pT1-pT2 breast cancer were treated with breast-conserving therapy at University of Florence. The lymph nodes were pathologically involved in 29% of patients, 19.7% with one to three positive nodes (PAN) and 9.3% with more than three PAN. All patients received whole breast irradiation without nodal irradiation. Results: The 3, 5 and 10 years actuarial rates for any LRR were 2.3%, 4.3% and 7.4%, respectively. While the 3, 5 and 10 years actuarial recurrence rates for nodal relapse (NR) were 1.0%, 2.0% and 2.0%, respectively. We found that the most common site for LRR was breast (3.9%) and that NR occurred in 1.3% of patients. In the multivariate analysis for NR, angiolymphatic invasion, pT2 and more than three PAN were statistically significant. Anyhow, NR was the only site of recurrence in a very small percentage of patients with more than three PAN. Conclusions: Concerning patients with negative or one to three PAN, there is no indication for nodal irradiation. But also in case of patients with more than three PAN our data suggest that a routine node irradiation is not justified. No significant financial relationships to disclose.
Carboplatin and paclitaxel as first-line treatment of unresectable or metastatic esophageal or gastric cancer.
Authors: Gopi Kesaria Prithviraj, Kathryn Anissa Baksh, William J. Fulp, Ken Meredith, Sarah E. Hoffe, Ravi Shridhar, Khaldoun Almhanna
Journal: Journal of Clinical Oncology (2014)

140 Background: Survival in patients with metastatic esophageal and gastric cancer is dismal. No standard treatment has been established. Carboplatin/paclitaxel is active in both advanced gastric and esophageal cancer. Here we present the data of our single center retrospective analysis. Methods: Between 1998-2013, a total of 134 patients with metastatic esophageal and gastric adenocarcinoma treated with carboplatin/paclitaxel (carboplatin predominantly AUC 5 and paclitaxel predominantly 175 mg/m 2 ) every 3 weeks as first-line therapy were identified. Baseline characteristics, response to therapy, toxicities, and survival in this patient population were evaluated. Overall survival was defined as date from biopsy to death or last follow-up and progression-free survival was defined at time from cycle 1 to death, progression, or last follow-up. Kaplan-Meier curves were fit to estimate overall and progression-free survival. Results: Of the 134 patients evaluated, the median age at diagnosis was 65 years. Overall response rate (ORR) was 62.6% (complete response (CR)- 11%, partial response (PR)- 28%, stable disease (SD)-33%). Median overall survival from date of initial diagnosis was 1.29 years (95% confidence interval [CI] 1.06-1.5). Median progression-free survival from date of initiation of carboplatin and paclitaxel was 0.44 years (95% CI 0.34-0.5). Grade III toxicity occurred in 18.7% of patients. The most common grade III toxicity was neuropathy, present in 3.7% of total study population. Conclusions: In patients with metastatic or unresectable esophageal or gastric cancer, the combination of carboplatin and paclitaxel is well tolerated with comparable overall survival and progression-free survival to existing regimens in this population.
Treatment prices at the point of care: Pilot.
Authors: Nora B Henrikson, Rebecca W. Lau, Leah Tuzzio, Matthew Alan Christianson, Eric Y. Chen, Thanh-Hien Phan
Journal: Journal of Clinical Oncology (2016)

4 Background: People with cancer increasingly wish to discuss cancer care costs with clinicians. In our organization all price questions go to a central customer service line with limited capacity to address oncology-specific questions. We aimed to improve clinician access to treatment prices to assist them in responding to patient concerns about prices. Methods: We developed, launched, and evaluated a pilot tool and accompanying workflow for four oncology clinics in an integrated delivery system in WA. The online tool included a series of 50 printable worksheets for the most commonly ordered cancer treatment protocols accessible directly from the electronic health record. The worksheets included codes and prices for all drugs, supportive medications, tests, and professional services for one treatment cycle presented in patient-friendly language. We audited the accuracy of the cost information against patient bills. The worksheets did not provide patient-level cost-shares. We evaluated the resource’s launch, initial use, and acceptability through a convenience survey of initial users. Results: The project was successfully launched. Initial web traffic to price sheets exceeded the number of treatments being ordered during the launch period. A third of survey respondents (33%) reported using the cost sheets at least once a week. Reported most useful features were improved access to cost information, treatment protocol-based layout, and the service of previously unmet patient needs. Seventy percent (70%) reported that the resource had no impact on their workload. The mean value of the resource (1 lowest and 10 highest value) was 7.9 (value to patients); 7.8 (to oncology service line), 7.7 (to Group Health) and 6.5 (to own work or practice). Staff reporting of patient response was generally positive. Suggested improvements included provide patient-level cost share (63%) followed by expanding the project to include more protocols (33%). Conclusions: The pilot was feasible, built capacity to locate price data, and did not adversely impact staff workload. It addressed a clear need and demonstrated high potential overall value, especially its protocol-based format. The resource’s lack of personalized estimates of out-of-pocket charges was the biggest gap reported.
Accessibility and barriers to oncology appointments at 40 NCI-designated cancer centers.
Authors: Geoffrey Hamlyn, Kathryn Hutchins, Abby Johnston, Rishonda Thomas, James Tian, Arif Kamal
Journal: Journal of Clinical Oncology (2016)

55 Background: Newly diagnosed cancer patients face fear and uncertainty regarding their prognosis and treatment options. As a first step, these patients and their family members may reach out to top-tier, comprehensive cancer centers for evaluation and treatment; however, recent literature reveals barriers to access. To identify these barriers, we evaluated obstacles patients and caregivers face in accessing services at major cancer centers. Methods: We used a ‘mystery shopper’ format to contact 40 NCI-designated, comprehensive cancer centers. We simulated a patient’s family member calling to make an initial consultation appointment using a standardized script. Each center received four calls on separate dates – two calls presented a patient with private insurance; two with Medicaid. Call order and patient name were randomized. We evaluated quantitative and qualitative components of the call, including time to next available appointment and availability of supportive services. Descriptive statistics were calculated for each quantitative measure. Results: We placed 160 calls to 40 NCI-designated cancer centers. 117 (73%) of calls were first answered by electronic prompts or voicemail, not a live person. Mean call duration was 9.4 minutes, with a range of 1 to 31.9 minutes. On average, callers spent 7.1 minutes speaking to an attendant and spent 2.4 minutes on hold or being transferred. Only a minority of callers (19.3%) were able to obtain an actual date for a next-available appointment without first registering into the cancer center’s records system. 51.3% were given an estimated date for a next-available appointment and 29.4% were told that a date for an appointment could not be estimated unless the patient was registered. When an appointment date was given (estimated or actual), only 27% were within a week. Specifically, only 1.3% of next-available appointments were within 1-2 days, 25.7% were within 3-7 days, 57.5% were within 7-14 days, 15% were not available until &gt; 14 days. At the most extreme, the next-available appointment was not for 37 days. Conclusions: NCI-designated cancer centers often place significant roadblocks in front of patients and caregivers seeking an appointment.
Peanut Allergen Threshold Study (PATS): Novel single-dose oral food challenge study to validate eliciting doses in children with peanut allergy
Authors: Jonathan O'B. Hourihane, Katrina J. Allen, Wayne G. Shreffler, Gillian Dunngalvin, Julie A. Nordlee, Giovanni A. Zurzolo, Audrey Dunngalvin, Lyle C. Gurrin, Joseph L. Baumert, Steve L. Taylor
Journal: Journal of Allergy and Clinical Immunology (2017)
Molecular pathway profiling as a tool for personalized medicine.
Authors: O. v. Ahsen, P. S. Kim, O. Politz, T. A. T. Lee, G. Harvie, R. Barham, G. Leesman, X. Liu, K. Ziegelbauer, S. Singh, T. Krahn
Journal: Journal of Clinical Oncology (2011)

e21118 Background: Patients selected for targeted therapy based on single biomarker status often show inherent resistance or develop de novo resistance. Hence, comprehensive pathway profiling is critical for rational selection/combination of suitable targeted agents at base line and during the course of treatments. Here we report a comparative profiling of receptor tyrosine kinases (RTKs) and downstream signal proteins (HER1, HER2, HER3, cMET, IGF1R, PI3K, AKT, ERK and other pathway proteins) in 10 diverse tumor cell lines treated with a panel of therapeutic agents and show the correlation between pathway inhibition and proliferation block as well as insights for potential resistance mechanisms. Methods: The Collaborative Enzyme Enhanced Reactive-immunoassay (CEER) is a multiplexed protein microarray platform requiring co-localization of two detector enzyme-conjugated-antibodies. Channeling events between two detector enzymes in proximity provides extremely high sensitivity. In this study, cell lysates were prepared from 10 cell lines treated with 6 compounds at various concentrations, and inhibition of target proteins as well as modulations of other signaling proteins were measured on the multiplexed CEER platform. Results: Profiling of pathway proteins determined the efficacy of inhibitors for target kinase and downstream signal protein modulations. The most dramatic suppression in AKT activity was observed with PI3K and AKT inhibitors and correlated with proliferation suppression. Inhibitors of RAF and MEK strongly reduced ERK activity, also blocking cell growth. On the other hand, inhibition of single RTKs often showed ineffective suppression of AKT and ERK activity. Treatment with single agents often showed adverse profile shifts through feedback loops or pathway cross-talk. Conclusions: As CEER is a suitable technology to evaluate modulations in multiple targeted pathways and associated signalling proteins from very small samples (such as FNA or CTCs), it is now possible to test pathway activity to select the most effective targeted agents. Clinical samples should be evaluated during the course of the therapy to monitor the efficacy and treatment regimens should be adjusted according to profile shifts.
Factors affecting receipt of invasive pain management among Medicaid beneficiaries with cancer.
Authors: Michael T. Halpern, Mallorie Fiero
Journal: Journal of Clinical Oncology (2016)

7 Background: Previous studies have reported that a substantial proportion of cancer patients do not receive appropriate pain management. Inadequate pain management may be greater among Medicaid beneficiaries with cancer. However, it is unknown whether Medicaid policies or patient characteristics affect the likelihood of receiving pain management services. Methods: We used 2006-2008 Medicaid claims data for individuals diagnosed with breast or colon cancer to assess patient characteristics and state-level policy factors associated with receipt of invasive pain management (IPM). Generalized estimating equations (GEE) were used to examine factors influencing receipt of IPM, including patient age, race/ethnicity, comorbidities, Medicaid reimbursements, redetermination period for Medicaid eligibility, required patient co-payments. Separate analyses were performed for the breast and colon cancer study populations. Results: Overall, 3% of Medicaid beneficiaries in the study population with breast cancer and 6% with colon cancer received IPM. Among the breast cancer population, non-white patients were significantly less likely to receive IPM compared with white breast cancer patients (Odds Ratio (OR) = 0.88, p &lt; 0.0001). Increased comorbidity score was associated with significantly increased likelihood of IPM (OR = 1.27, p &lt; 0.0001). Among the colon cancer population, older age was associated with significantly increased likelihood of IPM (OR = 1.36 for 10 years of age, p = 0.02). Patients in states with a Medicaid eligibility re-determination period of 12 months were less likely to receive IPM compared to those in states with a period &lt; 12 months (OR = 0.60, p = 0.046). Conclusions: Patient characteristics and (for colon cancer patients) state Medicaid policies predict receipt of IPM among Medicaid beneficiaries with cancer. As many of these factors are not associated with the need for pain management, quality improvements in supportive care are needed for this underserved population.