tbuckley/cabot-search huggingface dataset:
Psychosocial outcomes among cancer survivors who receive a treatment summary or survivorship care plan.
Authors: Sarah C. Reed, Janice Bell, Robin L. Whitney, Emma Blackmon, Katherine K. Kim, Jill G. Joseph
Journal: Journal of Clinical Oncology (2016)

217 Background: Treatment summaries (TSs) and survivorship care plans (SCPs) were expected to bridge patient-provider communication challenges and better address the unique needs of cancer survivors. While interest in TSs and SCPs has been growing, acceptance and implementation has been slow and findings from studies of their effectiveness have been mixed, overall. Our study examines independent associations of receipt of TSs and SCPs with psychosocial outcomes of cancer survivors. Methods: The study sample included survivors completing the 2012 LIVESTRONG Survey for People Affected by Cancer (n = 5,156). Logistic regression was used to model three distinct psychosocial outcomes: having relationship concerns (yes/no), distress (defined as a rating of 6 or higher on the NCCN Distress Thermometer), and moderate or severe cancer-specific worry (yes/no) as functions of TS receipt, SCP receipt and important confounding variables (age, sex, race/ethnicity, marital status, employment, income, education and health insurance). Results: Among cancer survivors, only 51% received a TS and only 16% received a SCP. Survivors who received a TS or SCP had significantly lower odds of relationship concerns (TS: OR = 0.62; 95% CI 0.52, 0.75; SCP: OR = 0.73; 95% CI 0.57, 0.94); distress (TS: OR = 0.74; 95% CI 0.65, 0.85; SCP: OR = 0.81; 95% CI 0.68, 0.97); and moderate or severe cancer-specific worry (TS: OR = 0.76; 95% CI: 0.67-0.85; SCP: OR = 0.78; 95% CI: 0.67-0.92). Other covariates consistently associated with psychosocial concerns included younger age, being unemployed and income ≤ $60,000. Conclusions: Many cancer survivors do not receive a TS or SCP. Receipt of either document was associated with reporting better psychosocial outcomes, suggesting that TSs and SCPs may not be reaching cancer survivors with psychosocial health problems. Survivors with psychosocial concerns may benefit from targeted survivorship care.
A mouse model of rectal cancer that mimics the clinical disease.
Authors: H. Kishimoto, M. Momiyama, R. Aki, H. Kimura, A. Suetsugu, M. Bouvet, T. Fujiwara, R. M. Hoffman
Journal: Journal of Clinical Oncology (2011)

10604 Background: There is a need for a clinically-relevant rectal cancer mouse models. We have developed a novel technique to orthotopically transplant rectal cancer cells. Methods: This model was established by intrarectal transplantation of mouse rectal cancer cells stably expressing fluorescent protein, followed by disrupting the epithelial cell layer of the rectal mucosa by soaking with an acetic acid solution. Results: Early stage tumor was detected on the rectal mucosa from as early as 6 days after transplantation, which then became invasive into the submucosal tissue. The tumor incidence (%) on the rectal mucosa was 100% at 4 weeks after transplantation. Spontaneous lymph node metastasis and lung metastasis were also observed 4 weeks after transplantation in over 90% of mice. Conclusions: This rectal tumor model mimics the histology and natural course of rectal cancer accurately. The model will be useful for evaluation of the tumor microenvironment, metastasis as well as agents which suppress tumor growth and metastasis.
An open-label, randomized, parallel-group study of the pharmacokinetics of trifluridine as a component of TAS-102 versus FTD alone.
Authors: Weijing Sun, Lee S. Rosen, Drew W. Rasco, Kenichiro Yoshida, Jabed Seraj, Geoffrey Shapiro, James M. Cleary
Journal: Journal of Clinical Oncology (2016)

751 Background: TAS-102 is a novel oral combination therapy of FTD plus tipiracil hydrochloride (TPI) with FTD:TPI molar and weight ratios of 1:0.5 and 1:0.471, respectively. FTD is a thymidine-based nucleoside analog that has shown antitumor effects in preclinical and clinical studies. TPI stabilizes orally administered FTD by inhibiting thymidine phosphorylase and TAS-102 has shown efficacy in refractory metastatic colorectal cancer. The objective of this study was to show that TPI, administered with FTD as TAS-102, increases exposure to FTD in patients with advanced solid tumors. Methods: This is a Phase 1, randomized, open-label, pharmacokinetic study of TAS-102 in patients with advanced solid tumors. On the morning of Day 1, one group received TAS-102 35 mg/m 2 and the other group received FTD 35 mg/m 2 . Both groups received TAS-102 35 mg/m 2 on the evening of Day 1, then twice daily on Days 2-5 and 8-12 in a 28-day cycle. Blood samples were collected to evaluate FTD AUC 0-last and C max (primary endpoints). Results: Overall, 44 patients (50% male, mean age 57 years) were treated. After a single dose, the ratio of the geometric mean of FTD AUC 0-last and C max were 38- and 22-fold higher, respectively (Table) following TAS-102 vs FTD alone. After multiple doses (Day 12 in Cycles 1, 2, or 3), FTD AUC and C max were ~3- and 2-fold higher, respectively, than after a single dose of TAS-102 (Day 1). For TPI, AUC and C max were similar after single and multiple doses of TAS-102. After Cycle 1, FTD did not accumulate with successive cycles of TAS-102 treatment. The most commonly reported treatment-related adverse events were nausea (47.7%), fatigue (31.8%), and anemia (27.3%), with Grade 3-4 events at 4.5%, 2.3%, and 18.2%, respectively. Grade ≥ 3 decreases in neutrophil counts were observed in 42.9% of the TAS-102 group. Conclusions: TPI, in combination with FTD, substantially increased exposure to FTD vs FTD alone. Clinical trial information: NCT01867866. [Table: see text]
Abstract A06: Novel NF-kB reporter murine model of spontaneous, metastatic breast cancer for spatiotemporal monitoring of local and systemic therapeutic response
Authors: Mary Dockery, Megan Poorman, Stephanie Dudzinski, Whitney Barham, Vandiver Chaplin, Ryan Spears, Jiro Kusunose, Fiona Yull, Charles Caskey, William Grissom, Todd Giorgio
Journal: Cancer Research (2016)

Abstract Characterization of therapeutic response in primary and metastatic tumors is limited by endpoint studies and tissue collection. We have successfully developed a unique double-transgenic mouse model, which combines the polyoma virus middle T oncogene (PyVT), a model of human breast cancer, with a nuclear factor-kappaB (NF-kB) reporter model (NGL). PyVT mice spontaneously form primary mammary fat pad tumors, with 80% of mice developing metastatic lesions in the lungs. The reporter is luciferase, driven by NF-kB activation, to provide quantitative bioluminescent measurements of spatially-specific NF-kB activity. The resulting double transgenic (PyNGL) mice were monitored using in vivo imaging systems (IVIS) multiple times, before and after treatment, to quantitatively and spatially characterize NF-kB therapeutic response, both locally and systemically. High intensity focused ultrasound (HIFU) was guided by magnetic resonance (MR) thermometry for tumor-localized hyperthermia which was dosage-controlled by the thermal feedback MR guided HIFU (MRgHIFU) system. A single primary mammary tumor in each PyNGL was treated with sub-ablative hyperthermia of 42⁰ for up to 25 minutes. Pre-treatment IVIS measurements were collected to determine baseline NF-kB activity within each mouse, followed by IVIS imaging every twelve hours after treatment until tissue collection. Treated tumor, contralateral (untreated) tumors, and spleens were collected for immunophenotyping and cytokine analysis using flow cytometry. PyNGL mice exhibited decreased NF-kB activity, spatially correlated with HIFU treatment, as early as 12 hours. In contrast, NF-kB increased in contralateral tumors as early as 24 hours following treatment. Immunophenotyping reveals changes in tumor infiltrating leukocyte populations in HIFU-treated and contralateral tumors, including quantity and phenotype of T cells. The unique murine model developed allowed quantitative, temporal characterization of local and distant tumor response to MFgHIFU. The spontaneous, metastatic nature of PyVT tumor formation in concert with the non-destructive, spatiotemporal imaging capabilities of the NF-kB reporter transgene make the PyNGL model an unparalleled tool for research in metastatic disease. Citation Format: Mary Dockery, Megan Poorman, Stephanie Dudzinski, Whitney Barham, Vandiver Chaplin, Ryan Spears, Jiro Kusunose, Fiona Yull, Charles Caskey, William Grissom, Todd Giorgio. Novel NF-kB reporter murine model of spontaneous, metastatic breast cancer for spatiotemporal monitoring of local and systemic therapeutic response. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr A06.
AccrualNet: A novel approach to addressing clinical trial accruals through a knowledge-based, community of practice platform.
Authors: H. Massett, L. K. Parreco, R. M. Padberg, E. Richmond, D. M. Dilts
Journal: Journal of Clinical Oncology (2011)

e16621 Background: Clinicians need a good resource for accessing evidence-based strategies and practical information to support trial accrual. We present research, design and initial evaluation of a unique, web-enabled platform, AccrualNet.cancer.gov, for the development of a community of practice to address oncology accrual. Methods: NCI Office of Communications and Education conducted research with health association leaders, 5 comprehensive cancer centers, and >15 CCOP practices on accrual issues. In response to expressed need, a web-platform was conceptualized and built. 5 rounds of user testing were conducted to assure that AccrualNet is user-friendly, adaptable to local needs, populated with initial tools, and has the appropriate structure to link tools to the life cycle of a trial. AccrualNet was launched with journal articles (n=167), tools and other resources (n=127). Statistics were captured on journal sources and analyzed on use of resource by the oncology community. Results: AccrualNet has 5 levels: 3 macro-stages (pre-, active-, and post-study); 7 stages (developing a protocol, selecting a trial, preparing to open, enrolling patients, managing the trial, retaining participants, and lessons learned); multiple strategies per stage; multiple activities per strategy, and multiple tools and resources (T&R) for each activity. It is designed to foster a community of practice, allowing professionals in the field to add resources/tools and start/join conversations. The need for the platform is highlighted by literature review, showing a pronounced long tail effect for sources of T&R: 21.6% from 2 source journals (Contemp Clin Trials, 13.4%; J Clin Onc 8.2%) but 46.3% from journals with only 1. AccrualNet began with 294 unique tools and resources, and has since expanded to 486. As of 2/1/11, there were >45k page views. Conclusions: AccrualNet represents the first comprehensive-solution platform for the oncology clinical research community’s use to develop a community of practice and systematically capture knowledge for all stages of a clinical trial’s life. Using such a platform will reduce the knowing-doing gap with respect to increasing accruals to oncology clinical trials.
GCC expression in lymph nodes (LNs) as a significant determinant of recurrence in stage II colon cancer (CC) patients (pts).
Authors: D. J. Sargent, Q. Shi, B. M. Bot, M. B. Resnick, M. O. Meyers, A. Goldar-Najafi, T. E. Clancy, S. Gill, G. O. Siemons, Y. Fradet
Journal: Journal of Clinical Oncology (2011)

369 Background: A multi-center prospectively specified retrospective study Validating Indicators to Associate Recurrence (VITAR) is assessing the relationship between guanylyl cyclase C (GCC) gene expression in formalin fixed LNs and recurrence risk in stage II CC pts not treated with adjuvant chemotherapy. Here we report the preplanned initial analysis performed with 241 pts. Methods: GCC mRNA was quantified by RT-qPCR using FFPE LNs tissues from untreated stage II CC pts diagnosed from 1999-2006 with at least 10 LN examined blinded to clinical outcomes. Cox regression models examined the relationship between GCC nodal status and the prespecified primary endpoint of recurrence risk. Results: Twenty-ninepts (12%) had a disease recurrence or cancer death, median follow-up was 60 months and median LNs examined was 15. The ratio of the number of GCC+ LNs over the total number of informative LNs (LNR) significantly predicted higher recurrence risk for 84 pts classified as high risk (HR, 2.38; p=0.02). The estimated 5-yr recurrence rates were 10% and 27% for the low and high risk group, respectively. After adjusting for age, T stage, number of LNs assessed, and MMR status, the significant association remained (HR, 2.61; 95% CI, 1.17-5.83; p=0.02). In a subset of 181 pts with negative margin, T3 tumor only and ≥12 LN examined, the GCC LNR had a HR for recurrence of 5.06 (95% CI 1.61-15.91, p=0.003), translating into 5-yr recurrence rates of 4% among low risk pts and 27% for the high-risk group. Conclusions: Our results suggest that GCC expression in LNs is a significant determinant of recurrence in appropriately staged CC pts not treated with adjuvant chemotherapy. The validation component of the study is ongoing. [Table: see text] [Table: see text]
A quality improvement program within the research setting to improve cancer clinical trial recruitment, accrual, and retention.
Authors: Margo Michaels, Judith Blanchard, Kathleen Reims, Kevin Little, Gina Pokrashevsky
Journal: Journal of Clinical Oncology (2012)

124 Background: Participation in and access to cancer treatment clinical trials (CCTs) is a key measure for delivery of quality cancer care. Yet adult trial participation in the U.S. remains under 3%, with even lower participation rates among minority groups and people over 65. There is little evidence for best practices in CCT accrual. If institutions are to be evaluated by the access they provide to CCTs, it is critical to identify practical, evidence-based approaches to maximize the efficiency of CCT recruitment, accrual, and retention efforts. The National Cancer Clinical Trials Pilot Breakthrough Collaborative (NCCTBC) is the first-ever national effort to identify such best practices in a real world setting. Methods: The purpose of this pilot was to test the feasibility of applying a proven quality improvement process to CCT accrual. More than 150 evidence-based changes to processes and procedures were identified. Five community oncology practices designed, tested, and implemented changes and reported monthly on 6 core measures to gauge improvement. Teams collaborated to share challenges and were provided coaching and technical assistance by national experts. Results: Teams have tested 35 changes over a 10-month period. Outcomes from the pilot are already showing promising results in identifying those changes that can have the most impact on improving accrual. For example: Improvements in race and ethnicity data capture are helping to address disparities in patient census. Improvements in processes for trial menu selection are leading to new ways of assessing patient populations and finding trials that match them. Documentation of pre-screening and offer rates is identifying system gaps and ways to increase these rates. Conclusions: Results affirm the feasibility of applying a quality improvement framework to address persistently low accrual rates and decrease health disparities among racial and ethnic minorities and the elderly. Based on lessons learned, we are making improvements to the NCCTBC infrastructure and processes and plan to recruit 10 new teams to test further changes.
A phase I/II study of ABT-888 in combination with 5-fluorouracil (5-FU) and oxaliplatin (Ox) in patients with metastatic pancreatic cancer (MPC).
Authors: Michael J. Pishvaian, Hongkun Wang, Tingting Zhuang, Aiwu Ruth He, Jimmy J. Hwang, Amy Hankin, Lisa Ley, Keisha White, Susan Joy Littman, Louis M. Weiner, John Marshall, Jonathan Robert Brody
Journal: Journal of Clinical Oncology (2013)

147 Background: The PARP inhibitor, ABT-888 is a potent sensitizing agent for, and has been safely combined with DNA-damaging chemotherapies. The sensitizing effects of ABT-888 are magnified when cancer cells harbor underlying defects in DNA repair mechanisms, such as BRCA2 mutations. Methods: We have initiated a Phase I/II trial, and we present here the data from the Phase I portion. Patients (pts) with MPC who had any number of prior therapies were eligible. A standard 3+3 dose escalation of ABT-888 was employed, in cohorts of 40, 60, 80, 100, 150, 200, 250, and 300mg orally twice a day, days 1-7 of a 14 day cycle. Pts also received 85mg/m 2 of Ox, 400mg/m 2 of 5-FU, and 400mg/m 2 of leucovorin on Day 1, and 2400mg/m 2 of 5-FU continuous infusion Days 1-3. Restaging studies were performed every 4 cycles. The primary objective was to determine the Recommended Phase II Dose (RP2D) of ABT-888 combined with 5-FU and Ox. Secondary clinical objectives included an assessment of the pharmacokinetics (PKs) of ABT-888 metabolism, as well as response rate (RR), progression-free survival (PFS), and overall survival (OS). Results: Between 01-2011 and 09-2012, 22 pts received treatment. 55% were male; median age = 64, most with an ECOG PS of 1. 55% were previously untreated. The first 6 pts experienced persistent ≤Grade 2 myelosuppression, primarily thrombocytopenia, prompting an amendment to drop the 5-FU bolus. In the latter 16 pts, the combination of ABT-888 plus 5-FU and Ox was well tolerated, with no DLTs. The RP2D is expected to be 300mg BID of ABT-888, with the final analysis including ABT-888 PKs to be presented. For the 22 pts, the RR was 14%, and the PFS and OS were 2.9 and 5.4 months, respectively. Of the 11 previously untreated pts, the RR was 18%, and the PFS and OS were 4.3 and 7.7 months, respectively. 2 pts with deleterious mutations in BRCA2 were included: Pt 6 had a PR and remains on study after 17 months; Pt 14 had a CR and a normalization of CA 19-9, and is still on treatment after 10 months. Conclusions: The combination of ABT-888, 5-FU, and Ox is safe and well tolerated. The combination has demonstrated promising efficacy in MPC, particularly in pts with BRCA2 gene mutations. Clinical trial information: NCT01489865.
Patterns of systemic therapy in metastatic colorectal cancer (mCRC): Use of intermittent and stop-and-go strategies in a population-based setting.
Authors: Winson Y. Cheung, Howard John Lim, Daniel John Renouf
Journal: Journal of Clinical Oncology (2014)

644 Background: The concept of treatment to disease progression must be tempered by the potential for cumulative toxicities of ongoing therapy. Data suggest that treatment holidays may provide improved quality of life without significantly compromising outcomes in metastatic disease. Our aim was to characterize the frequency of intermittent and stop-and-go strategies in a population-based cohort of mCRC patients. Methods: Patients diagnosed with mCRC and who received any palliative systemic treatment at the British Columbia Cancer Agency from Jan 2008 to Dec 2010 were identified from the provincial pharmacy database. First-line (1L) and second-line (2L) therapy choices, duration on each line of therapy, and number of treatment holidays, defined as any time interval of &gt;/= 4 weeks without any therapy, were characterized. Results: In total, 946 patients were identified: median age was 64 (IQR 55-72) years, 521 (55%) were men, and 626 (66%) had colon cancer. In 1L treatment, the majority received combination systemic therapy: 474 (50%) FOLFIRI +/- bevacizumab (B), 224 (24%) FOLFOX +/- B, and 248 (26%) 5-FU/capecitabine. The median number of cycles on 1L therapy was 9 (IQR 4-13). Treatment holidays were common with 302 (32%) patients experiencing at least one break, each lasting a median of 49 (IQR 36-99) days. Compared with no B, 1L patients treated with B received more therapy (median 12 [IQR 8-20] vs 8 [IQR 4-12] cycles). However, they were also more likely to undergo a treatment holiday (34% vs 31%), but the duration of each break was shorter (median 49 [IQR 36-92] vs 56 [IQR 35-119] days). Only 312 (33%) out of the 946 patients proceeded to 2L therapy. The median interval between stopping 1L and starting 2L was 43 (IQR 20-162) days. Compared with 1L, the median number of treatment cycles was shorter in 2L (median 7 [IQR 4-12]). Treatment holidays were also less frequent with only 50 (16%) out of 312 patients experiencing at least one break, each lasting a median of 56 (IQR 38-100) days. Conclusions: The use of the stop-and-go approach was prevalent in this population-based cohort of mCRC patients. The relationship between intermittent treatment and outcomes will be presented at the meeting.
Evaluating 18F-16β-fluoro-5α-dihydrotestosterone (FDHT) and FDG PET as prognostic biomarkers for patients (pts) treated with abiraterone acetate (AA).
Authors: Jarett Lawrence Feldman, Josef J. Fox, Karen A. Autio, Somali C. Gavane, Glenn Heller, Heiko Schöder, John Humm, Danny F. Martinez, Susan F. Slovin, Howard I. Scher, Steven M. Larson, Michael J. Morris
Journal: Journal of Clinical Oncology (2014)

56 Background: There are no available imaging biomarkers that can prognosticate for clinical outcomes for patients treated with AA. FDG and FDHT PET demonstrate glucose metabolism and androgen receptor expression, respectively. This is the first study of FDG and FDHT PET as a prognostic biomarker for pts treated with AA. Methods: Pts with progressive metastatic castration resistant prostate cancer (mCRPC) starting AA underwent FDG and FDHT PET scans on an imaging clinical trial. PSA, SUV max (hottest slice of hottest lesion), and SUV maxavg (average SUVmax of 5 index lesions) were collected. An SUV value of 1 was imputed for calculating SUV maxavg in the absence of 5 index lesions. Imaging characteristics were compared to PFS, defined as time to radiographic progression, biochemical relapse or death. The Cox proportional hazards model was used to determine the association between the PET measurements and PFS. The statistics used to measure the association was the concordance probability estimate (CPE). Results: 24 scans sets were obtained. Median pt characteristics were: age 70 (48-85), Gleason score 8 (range 6-10), PSA 85 (2-459). Radiographic and PSA progression occurred in 15/24 (63%), radiographic only 4/24 (17%), and biochemical only 2/24 (9%). 1 pt died on study, 1 elected to discontinue tx, and 1 remains on AA. 16/24 (67%) and 18/24 (75%) of FDG and FDHT PET scans respectively had ≥ 5 hypermetabolic lesions. Median FDG SUV max was 8 (2-15), FDG SUV maxavg 5 (1-11), FDHT SUV max 11 (3-28) and FDHT SUV maxavg 7 (1-16). The correlation between PET measurements and PFS is described (Table). Conclusions: Preliminarily, baseline FDG SUV max and SUV maxavg appear to be prognostic for PFS in pts treated with AA. Higher SUV values prognosticate for a shorter time to progression. Further evaluations of FDG/FDHT PET in mCRPC are underway to better define the role each modality has as a prognostic and response biomarker for AA. Clinical trial information: NCT00588185. [Table: see text]
The Lack of Clinical Efficacy of Flavopiridol in Patients with Relapsed Refractory Myeloma.
Authors: Angela Dispenzieri, Keith C. Bible, Martha Q. Lacy, Tom R. Fitch, Susan M. Geyer, Robert Fenton, Rafael Fonseca, Crescent R. Getman, Steven C. Ziesmer, Charles Erlichman, Morie A. Gertz
Journal: Blood (2004)