tbuckley/cabot-search huggingface dataset:
Clinical impact of high-throughput sequencing in patients with advanced cancer: Lessons learned from the Michigan Oncology Sequencing Center.
Authors: Erin Frances Cobain, Dan R. Robinson, Yi-Mi Wu, Francis P. Worden, David C. Smith, Scott Schuetze, Rashmi Chugh, Nithya Ramnath, Anne F. Schott, Daniel F. Hayes, Arul M. Chinnaiyan, Moshe Talpaz
Journal: Journal of Clinical Oncology (2015)

11057 Background: The molecular aberrations that drive cancer are diverse and multiple defects are often present. Next generation sequencing permits detection of numerous aberrations within a tumor, which may identify targets for therapy. Methods: From 5/2011-12/2014, 452 patients (pts) underwent comprehensive next generation sequencing (Illumina) of a primary or metastatic tumor at the University of Michigan under an IRB approved protocol. Somatic and germline mutations, copy number alterations, gene fusions, and gene expression findings were reviewed at an institutional tumor board. Clinically actionable alterations were categorized as follows: rationale for use of an investigational targeted agent, rationale for off-label use of therapy approved in another condition, information predictive of treatment efficacy and germline mutations known to confer increased cancer risk. We report subsequent treatment information for the first 200 patients enrolled. Results: Sequencing was successful in 183 samples (92%). Somatic alterations of biological relevance were identified in 176 cases (96%). 100 pts (55%) had potentially actionable results. 79 pts (43%) had alterations providing rationale for use of an investigational targeted therapy and 7 enrolled in a trial informed by results. Somatic alterations provided rationale for off-label use of a drug in 13 cases (7%) and 5 pts received off-label therapy. 22 pts (12%) had alterations predictive of treatment efficacy, prompting treatment change in 3 pts. 5 pts (3%) were found to have germline mutations conferring increased cancer risk. 48 pts (26%) died within 5 months of enrollment. Conclusions: These data demonstrate that comprehensive tumor genome analysis can identify potentially actionable somatic aberrations, indicating this approach is useful as a screening tool for clinical trial participation. Early in the course of the study, many pts died shortly after enrollment. This experience led us to employ this strategy earlier in the therapeutic algorithm.
Imatinib and Leptomycin B Are Effective in Overcoming Imatinib-Resistance Due to Bcr-Abl Amplification or Clonal Evolution but Not Due to Bcr-Abl Kinase Domain Mutation.
Authors: Rama K. Kancha, Cornelius Miething, Nikolas V. Bubnoff, Katharina Gotze, Christian Peschel, Justus Duyster
Journal: Blood (2005)
Biochemical failure after treatment for localized prostate cancer: Does original therapeutic modality affect long-term survival?
Authors: Chad A. Reichard, Evan Kovac, Jay P. Ciezki, Rahul D. Tendulkar, Eric A. Klein, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2015)

65 Background: Mortality among men with biochemical failure (BF) after treatment is variable. We examined the long-term survival of men with BF to determine if differences exist, depending on original treatment modality. Methods: Between 1995 and 2008, 6,084 patients underwent treatment for clinically localized prostate cancer at our institution (4,276 underwent radical prostatectomy (RP); 1,808 underwent EBRT). Clinical information and follow up data was obtained from prospectively maintained databases. Survival was assessed using log rank test. Results: 526 (12%) patients had BF defined by PSA &gt; 0.4 after RP. 326 (18%) patients had BF after EBRT, defined as PSA nadir +2. 197 (60%) of EBRT patients received ADT as neoadjuvant/concurrent/adjuvant therapy. Median overall survival was 154 months (95%CI 148-157) versus 129 months (95%CI 123-135) for RP and EBRT respectively (p&lt;.0001). Median prostate cancer specific survival was 125 months (95%CI 93-148) versus 107 months (95%CI 92-123) for RP and EBRT respectively (p=0.17). There was no difference in prostate cancer specific survival between treatments among patients in D’Amico intermediate and high risk groups. Conclusions: In patients with biochemical recurrence after definitive treatment, patients treated with RP have improved overall survival compared to patients treated with EBRT. However, there is no difference among treatment groups in prostate cancer specific survival.
Incidence of cytogenetic (CG) abnormalities in acute myeloid leukemia (AML) in African American (AA) population.
Authors: R. Khillan, A. S. Braverman, C. A. Axiotis, R. Khillan, R. Latif, G. S. Sidhu
Journal: Journal of Clinical Oncology (2011)

6622 Background: CG characteristics play a critical role in outcome and therapy of AML. The incidence of normal CG in general population is estimated at 40%. The incidence of abnormal CG in AA population is not known. CG abnormalities help define the pathogenesis of AML subtypes and are prognostically significant; they occur in 40% of all AML cases, but their incidence in African Americans is not known. Methods: Records of adult patients with acute leukemia at Kings County Hospital and Downstate Medical Center from 2004 through 2010 were reviewed. The CG data were stratified into three prognostic groups: good; inv (16), t (8:21) and t (15:17); intermediate: normal CG, +8, t (9:11); poor: ≥ 3 CG abnormalities, including: -5, 5q-, -7, 7q-, inv (3), t (6:9), t (9:22). Results: Of the 52 patients with acute leukemia, 46 had AML; 29 were male and 17 female. Forty-three (93%) of these patients were AA. Ages ranged from 20-82 years (median 53), 15 (33%) having been over 65. Seven (15%) patients had a prior hematological malignancy (HM). CD34 was over-expressed in 23 of 46 (48%) patients with AML. CG data was available in 41 patients, 26 men and 15 women; and was normal in 13 (31%) and abnormal in 28 (69%). Of patients with de-novo AML and known CG; 21 (62%) were abnormal; and 13 (38%) were normal. The distribution of patients in risk stratified groups were: good: 8 (20%); intermediate: 19 (46%); and poor: 14 (34%). In patients with prior HM five (71%) had abnormal CG. The median age of patients with good, intermediate and poor risk CG was 57, 53 and 57 years respectively. Intermediate or poor risk AML occurred in 22 of 26 men (85%) and 11 of 15 women (73%). Conclusions: Our data suggest that CG in AA AML patients are more often abnormal, and of intermediate or poor risk than in the general population.
Analysis of characteristics in patients (pts) with metastatic renal cell cancer (MRCC) who achieved a prolonged benefit from sunitinib or sorafenib
Authors: S. Négrier, M. Gross-Goupil, D. Pérol, J. Gautier, J. Balcaceres, C. Massard, C. Celier, A. Ravaud, S. Oudard, B. J. Escudier
Journal: Journal of Clinical Oncology (2008)

16022 Background: Anti-tyrosine kinases (TKI) arenow the standard of care in pts with MRCC; some pts benefit from these treatments (ttt) for long periods of time. However, the prognostic factors for achieving a sustained activity over time are not known. We undertook this analysis to identify such prognostic factors. Methods: Pts with MRCC of clear cell origin who received sunitinib or sorafenib throughout compassionate programs in 4 French centres were taken into account. We analyzed the characteristics of patients who were maintained under TKI over the median time of progression already reported according to the line of treatment and the type of drug. Age, gender, PS, time from diagnosis to metastases, number of metastatic sites, different metastatic organs, number of ttt lines, type of TKI, Fürhman grade, haemoglobin level, neutrophil count, LDH, corrected calcium level and best response status according to the RECIST criteria were tested for correlation with PFS by univariate and multivariate analyses. Results: 105 patients were concernedover an 8 month period of time; the median time of follow up (Fup) was 22 months, median PFS was 15 months (95% CI: 12–18) and median overall survival (OS) was 48 months (95% CI: 26–70). 46 pts (43.8%) previously received cytokines (5 unknown), 68 pts received sorafenib and 35 sunitinib. 2 parameters were significantly correlated with PFS: elevated LDH level (P: 0.02) and ttt by sunitinib (P: 0.02) after the univariate analysis. The analysis was then focused on the 44 first line pts; median Fup time was 21.5 months, median PFS was 14 months (95% CI: 11-17) and median OS was not reached. Hepatic metastases (P: 0.002) and elevated LDH (P: 0.03) were significantly correlated with PFS while type of treatment was in favor of sunitinib (P: 0.09). After multivariate analysis, hepatic metastases only remained significant (P: 0.003). Conclusions: LDH and hepatic metastases that were previously identified as independent prognostic factors in MRCC pts seem to be still relevant in pts treated by TKI. In addition these results confirm the more prolonged effect of sunitinib over sorafenib. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Bayer, Pfizer Bayer, Pfizer
Role of innate immune responses in the effectiveness of oncolytic adenovirus as an anticancer agent
Authors: Elaine Y Leung, Melanie Weigert, Josephine B Walton, Darren P Ennis, Dimitris Athineos, Suzanne Dowson, Chris Hansell, Karen Blyth, Gerard Graham, Iain A McNeish
Journal: The Lancet (2017)
Novel data sharing between a comprehensive cancer center and a private payer to better understand care at the end of life.
Authors: Sherri Oliver Stuver, Belen Fraile, Caitlin C. Donohue, Oreofe Olukemi Odejide, Gregory Alan Abel, Anton Dodek, John A. Fallon, Joseph O. Jacobson
Journal: Journal of Clinical Oncology (2014)

1 Background: Assessment of care at the end of life (EOL) is critical to improving the quality of care for oncology patients. EOL measures based on guidelines from the National Quality Forum (NQF) and ASCO have been examined in older cancer patients using Medicare claims. We performed a project to evaluate the use of private payer claims data to enumerate EOL measures in patients of all ages at a comprehensive cancer center. Methods: Claims data were obtained for Dana-Farber Cancer Institute (DFCI) adult patients who died between July 1, 2010, and December 31, 2012, and were insured by Blue Cross Blue Shield of Massachusetts (BCBSMA). We assessed NQF-based measures related to hospitalizations, emergency department visits, and intensive care unit admissions in the last 30 days of life, chemotherapy in the last 14 days, hospice stay, and death in a hospital. In addition, we examined red blood cell and platelet transfusions, radiation therapy, and surgery in the last 30 days of life, as well as death in the ICU. Results: Of a total of 674 patients, 580 had solid tumors and 82 had hematologic malignancies; their median age was 59 years (range, 18-92). The Table provides results for the EOL measures examined. Up to 50% of the measured events did not occur at a DFCI-affiliated hospital. Conclusions: Using private insurance claims data in conjunction with medical records, we were able to successfully capture a broad range of EOL quality measures. Access to the claims data provided information not readily available in hospital medical records and for care not occurring at DFCI. Data sharing between private payers and cancer centers may provide a unique method of comprehensively examining quality of EOL care for oncology patients. [Table: see text]
Individualizing the benefit of repeated screening with low-dose helical CT for lung cancer: Update of Anti-Lung Cancer Association project
Authors: N. Seki, K. Eguchi, M. Kaneko, H. Ohmatsu, R. Kakinuma, E. Matsui, M. Kusumoto, T. Tsuchida, H. Nishiyama, N. Moriyama
Journal: Journal of Clinical Oncology (2008)

1549
Methylation profiling of locally advanced rectal cancer (LARC): Exploration of potential predictive markers for neoadjuvant chemoradiation (NACR).
Authors: Songchuan Guo, Jonathan Melamed, Ogechukwu Eze, Christopher Bowman, Sunjida Ahmed, Harvey G. Moore, Cynthia Loomis, Adriana Heguy, Rachel Brody, Debra J. Morrison, Jonathan Serrano, Kevin Lee Du, Jennifer J. Wu, Theresa Ryan, Deirdre Jill Cohen, Ping Gu, Judith D Goldberg, Matija Snuderl, Lawrence P. Leichman, Cynthia G. Leichman
Journal: Journal of Clinical Oncology (2016)

614 Background: NACR followed by total mesorectal excision (TME) is standard of care for LARC. However, only 10-20% of patients achieve complete pathologic response with associated optimal clinical outcome. No predictive biomarker is currently available. Aberrant DNA methylation is well known for its key role in the pathogenesis of colorectal cancer. Previous rectal cancer methylation studies were conducted in patients without NACR or inconclusive. We hypothesized a correlation between methylation status and pathologic outcome following NACR. Methods: This is an IRB approved, retrospective, translational study of patients with LARC who received identical NACR before TME at New York University hospitals. Ten micron sections from FFPE tissue blocks underwent laser capture microdissection (LCM) followed by genome DNA isolation. Illumina Infinium 450k methylation array was used to assess 485,000 methylation sites. Methylation profiles and copy number changes were analyzed using in-house bioinformatics. Histone H3K27me, a global methylation marker, was assessed using immunohistochemistry (IHC) and expression quantified in carcinoma cells, normal epithelium, inflammatory cells, stromal cells and endothelial cells. Results: Tumor specimens from 52 patients were collected. Analyzed specimens of stromal and cancer cells showed distinct methylation profiles pre- and post- therapy. The histone H3K27me3 mark was markedly increased in carcinoma compared to normal epithelium and strong trimethyl mark expression persisted in invasive carcinoma after the therapy including single cells. We obtained adequate DNA to demonstrate differences between pre- and post- NACR specimens and tissue sites. Full data set, including the known clinical and pathologic results, is to be presented. Conclusions: This is the first study to combine LCM and high throughput quantitative methylation profiling in rectal cancer to correlate with NACR outcome. Histone H3K27me3 IHC can be used to identify high-grade and invasive carcinoma with high specificity. Data from our annotated clinical cohort and correlative molecular results can inform a future prospective trial.
Development and implementation of a longitudinal quality assessment for community outreach programs.
Authors: Yolanda Martins, Elizabeth Gonzalez-Suarez, Luis de Zengotita, Magnolia Contreras, Anne L Levine
Journal: Journal of Clinical Oncology (2014)

235 Background: Part of Dana-Farber Cancer Institute’s mission is to educate the community and raise awareness about the importance of cancer prevention, outreach, screening, early detection, clinical trials and survivorship. Development of a logic model and evaluation plan enables us to assess program quality and identify areas for improvement and future outreach. Methods: A forward logic, iterative approach was used to develop logic models for our community outreach programs. Models were reviewed by key stakeholders including program staff and management. These were used as the basis for a comprehensive logic model encompassing the common elements across all programs. Results: Seven logic models were developed to capture work in tobacco, sun safety, breast health, obesity prevention, community education programs, as well as comprehensive community benefits program model. We designed a developmental evaluation to allow for an assessment that could be adapted in a dynamic, ever-changing environment. This approach is also responsive to program growth and changes. It measures demographic information about our community participants, satisfaction with our programs, and strength of our community partnerships and compares these to internal benchmarks and state information. We can re-contact participants for on-going assessments and provide cross-sectional and longitudinal reports. RedCap freeware was used to create online versions of all tracking measures. Since (date) we have captured information from 119 community participants, most of whom are Black and Latino/a, and are representative of traditionally underserved minorities. Conclusions: Logic models and evaluation plans are integral components of community outreach programming. They ensure that effective, high-quality community outreach programming is being delivered, allow for the assessment of impact and assessment against program benchmarks. More importantly, they provide continuous information about areas for program growth and improvement.
Multicenter observational study on adherence and acceptance of lapatinib treatment in patients with HER2+ metastatic breast cancer.
Authors: R. Addeo, B. Vincenzi, F. Riccardi, A. Febbraro, L. Maiorino, P. Incoronato, R. Mabilia, M. Bianco, E. Russo, A. Pisano, S. Del Prete
Journal: Journal of Clinical Oncology (2011)

e11102 Background: Lapatinib, an oral tyrosine kinase inhibitor, is active in combination with capecitabine in women with HER2-positive metastatic breast cancer that has progressed after trastuzumab-based therapy. Patient sharing and adherence are critical in evaluating the effectiveness of an oral therapy. We investigated the level of therapy approvement, the rates and predictors of nonadherence to anti-HER2 oral therapy in patients enrolled. Methods: Between January 2010 and November 2010, patients with HER2+ metastatic breast cancer eligible for treatment with lapatinib were enrolled. The level of acceptance was evaluated using a questionnaire with sixteen questions administered every 3 months thereafter during the treatment. Patients scored each item on a 5-point ordinal scale range ranging from 0 to 4 during the previous 7 days. Medication adherence was estimated monthly from three sources of data: patient-completed medication diaries, self-report during the physician interview, and the pharmacy control of the drug box. Results: Overall, 69 patients were enrolled. Median age was 57 years (range, 34 to 71 years), 34 received a previous oral therapy, and 20 had at least one comorbidity. Forty women were married, 29 had high school qualification, 21 patients were homemakers. In total, 441 cycles of therapy were administered, with a median of 6.4. Overall acceptance of therapy did not change during the treatment. Adherence was 82% across all cycles, and adherence did not vary by cycle. Dosing violations occurred in 45 of the patients (65%). Adherence was not related to age, tumor stage, or performance status. On the other hand the marital status and the educational qualification influence the adherence. Conclusions: Our results suggest that despite the advanced disease, most women accept the therapy with lapatinib without any difficulties. Patients with metastatic breast cancer were adherent to oral target therapy. The level of adherence depend on cultural, familiar and social factors.
Using the 21-gene recurrence score and the recently developed Recurrence Score-Clinical-Pathologic to assess recurrence risk in patients with node-negative, ER-positive early-stage breast cancer receiving aromatase inhibitor treatment alone.
Authors: M. Crager, G. Tang, S. Shak
Journal: Journal of Clinical Oncology (2011)

592 Background: The 21-gene Oncotype DX recurrence score (RS) is widely used for assessment of distant recurrence risk and prediction of chemotherapy benefit in patients with early stage ER-positive breast cancer. The Recurrence Score-Clinical-Pathologic (RSPC) risk assessment tool assesses distant recurrence risk when tamoxifen (TAM) therapy is used without chemotherapy, integrating RS with tumor grade, tumor size, and patient age (Tang et al., J Clin Oncol 28:15_suppl, 2010 [suppl; abstr 509]). Neither RS nor RSPC risk assessment have significant treatment interaction with TAM versus aromatase inhibitor (AI) use. Individualized risk assessment when AI therapy is planned would be desirable. Methods: A recent meta-analysis (Dowsett et al, JCO 2010) compares the relative efficacy of AIs and TAM in reducing the risk of distant recurrence. The AI:TAM hazard ratio from the meta-analysis was combined with 10-year risk of distant recurrence as assessed by RS or RSPC for individual N0, ER+ patients to assess the patient’s distant recurrence risk with planned AI therapy. Results: From log rank statistics reported in the AI meta-analysis, we derived a treatment hazard ratio estimate of 0.82 (AI:TAM). Assessments of recurrence risk with AI depend, as expected, on the distant recurrence risk with TAM alone as assessed by RS or RSPC. Confidence interval widths for the AI-alone and TAM-alone risk assessments did not differ greatly. The estimated absolute benefit of AI relative to TAM for 10-year distant recurrence risk in individual patients ranges from about 1% to about 5%. Conclusions: The AI:TAM meta-analysis hazard ratio estimate can be combined with individual patient’s RS and RSPC distant recurrence risk assessment to assess the patient’s distant recurrence risk with planned treatment with AI alone.
A comparative analysis of single objective dose volume histogram (SDVHO)–based inverse planning optimization versus volume-based geometric optimization in real-time prostate brachytherapy planning with Oncentra Prostate.
Authors: H. Kunhiparambath, M. A. Laviraj, G. K. Rath, R. Prabhakar, D. Sharma, P. K. Julka
Journal: Journal of Clinical Oncology (2011)

e15109 Background: Ultrasound-based real time HDR brachytherapy planning is a recent advance in prostate brachytherapy. There are a number of optimization methods in Oncentra Prostate (previously SWIFT). We have compared two most important optimization methods: single objective dose volume histogram-based inverse planning optimization (SDVHO-IP) versus volume-based geometric optimization (VBGO). Methods: Five patients of localized prostate cancer were chosen for this planning study. They underwent a planning transrectal ultrasound scan on the Oncentra Prostate. Prostate (PTV), bladder, rectum and urethra were contoured on all slices. Two plans: one with SDVHO-IP and other with VBGO were generated for each patient. Plan comparison was done for PTV coverage and critical organ doses. For the PTV, D100 and D90 which is the dose received by 100 and 90 % of the target volume respectively are calculated. Also V100, V90 and V200 which are the volume of the prostate receiving 100, 90 and 200% of prescribed dose are also calculated. For bladder and rectum V75 which is the volume receiving 75% of the prescribed dose and for the urethra V125 which is the volume of urethra receiving 125% of the prescribed dose is calculated. COIN index was also compared. SPSS Version 14 software used p value to compare means. Results: The table shows that SDVHO-IP provides better target coverage and conformity than VBGO. But there is no difference as far as dose to the critical organs are concerned. Conclusions: Single objective dose volume histogram-based inverse planning optimization is superior to volume-based geometric optimization. Inverse planning with oncentra prostate needs to be encouraged. Parameter Inverse planning Geometric optimization (p value) PTV: D100 59.34% 51.93% (p=0.019). PTV: D90 97.71% 87.17% (p=0.01). PTV: V100 88.40% 79.02% (p=0.02). PTV: V90 94.55% 87.91% (p=0.025). PTV: V200 5.07% 2.82% (p=ns). Urethra: V125 0.58 mm3 (0.01%) 0.58 mm3 (0.01%; p=ns) Bladder: V75 0 mm3 (0%) 0 mm3 (0%; p=ns) Rectum: V75 3149.47 mm3 (29.9%) 3038.87 mm3 (28.85%; p=ns) COIN index 0.66 0.54 (p=0.02).