tbuckley/cabot-search huggingface dataset:
Correlation of multiparameter flow cytometric analysis of cell suspensions derived from fine needle aspiration (FNA), fresh biopsy tissue, and formalin fixed paraffin embedded (FFPE) non-small cell lung cancer tissue using the IncellPrep liquid biopsy.
Authors: Amanda Chargin, Rian Morgan, Keith Shults, Ellen Tsay, Bruce Kendrick Patterson
Journal: Journal of Clinical Oncology (2015)

e22195 Background: Cancer diagnostics including companion diagnostics can be hindered by the available sample types. IncellDx’s IncellPrep Liquid-Biopsy technology has the ability to create single cell suspensions from tissue and preserves mRNA, protein, and DNA content. Here we compare the utility of IncellPrep technology on three samples types: fine needle aspirate, punch biopsy, and formalin fixed paraffin-embedded tissue for multiparameter flow cytometry. Methods: IncellPrep is a technology that creates a single cell suspension and includes a proprietary fixative, IncellFP, that preserves protein, mRNA, and DNA for in situ analysis. Fresh lung tissue from 4 non-small cell lung cancer (NSCLC) cases were sampled by FNA and 4 mm punch biopsies. FFPE samples from each tumor were also sampled with a 4mm punch followed by deparaffinization. Fresh and FFPE punches were processed into cell suspensions using non-enzymatic homogenization (IncellPrep) in PBS. The FNA, and homogenized punch and FFPE samples were then fixed in IncellFP and stained with anti-PD-1, anti-PD-L1, and anti-CD45 antibodies as well as DAPI to measure expression of PD-1 and PD-L1, the percent inflammatory (CD45+) infiltrate, and the recovery of intact cells, respectively. Distinct cell populations were identified and expression of cellular markers identified by multiparameter flow cytometry. Results: The yield of cells from each sample type of the 4 specimens was satisfactory and averaged 6.7 x 105/mL for FNA, 4.1 x 106/mL for fresh punches, and 1.7 x 106/mL for all FFPE punches. Recovery of nucleated cells averaged 49.6% for FNA, 55% for fresh punches, and 35.2% for all FFPE punches. PD-1 and PD-L1 were detected in each specimen type and varied by tumor sample as expected. Conclusions: Here, we report a technology that creates a “universal” sample type compatible with multiparameter flow cytometry for solid tumor analysis obviating the need to use either flow cytometry and/or immunohistochemistry depending on the sample.
Prognostic factor Ki67 for breast cancer patients in each subgroup.
Authors: Naoki Niikura, Shinobu Masuda, Mizuho Terada, Mayako Terao, Nobue Kumaki, Risa Oshitanai, Toru Morioka, Banri Tuda, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yutaka Tokuda
Journal: Journal of Clinical Oncology (2012)

565 Background: Immunohistochemical (IHC) Ki67 has described it as a prognostic and predictive marker for breast cancer. The St. Gallen Consensus Meeting determined that Ki67 labeling index is chiefly important for distinguishing between “Luminal A” and “Luminal B (HER2 negative)” subtypes and is a predictive marker for chemotherapeutic efficacy. However, the high and low cutoff points remain controversial. Our objective is to compare survival in patients with low, intermediate, and high Ki67 levels in each subgroup. Methods: We retrospectively identified all the patients in the Tokai University breast cancer database for whom IHC Ki67 data were available between January 1, 2000, and December 31, 2010. Ki67 was defined as low if &lt;10% Ki67 was detected, as Intermediate if 10–20% Ki67 was detected, and as high if &gt;20% Ki67 was detected. To assess Ki67 levels and survival outcomes, survival curves were calculated using the Kaplan–Meier method and compared using the log-rank test. Results: We identified 1331 primary breast cancer patients without metastasis, of whom 686 received neoadjuvant or adjuvant chemotherapy. Patients with high Ki67 had poorer relapse-free survival (RFS) than patients with intermediate (p = 0.009) and low Ki67 (p &lt; 0.001). Patients with intermediate Ki67 had poorer RFS than patients with low Ki67 (p &lt; 0.001). In ER-positive cases (n = 1059), patients with high and intermediate Ki67 had poorer RFS than patients with low Ki67 (p &lt; 0.001 and p = 0.002, respectively). In HER2-positive and ER-negative cases (n = 103), patients with high Ki67 had poorer RFS than patients with low Ki67 (p = 0.002). In triple-negative cases (n = 164), patients with high Ki67 tended to have poorer RFS than patients with low Ki67 (p = 0.064). Conclusions: Our data demonstrated that low, intermediate, and high Ki67 levels may be used to differentiate prognosis in ER-positive cancer patients as well as HER2-positive and triple-negative cancer patients.
Additive prognostic impact of elevated De Ritis ratio and renal score in predication of survival outcomes in localized renal cell carcinoma.
Authors: Zachary Hamilton, Aaron Bloch, Charles Field, Katherine Elaine Fero, Sean Berquist, Abd−elrahma Hassan, Daniel Han, James Proudfoot, Ithaar Derweesh
Journal: Journal of Clinical Oncology (2017)

532 Background: Renal Cell Carcinoma (RCC) is a metabolically driven neoplasm. Inflammatory markers and morphometric measures have been suggested to be predictive for prognosis. We investigated the impact of a novel combination of preoperative tumor morphology (RENAL score) and a laboratory based inflammatory marker (DeRitis Ratio, AST/ALT) on survival outcomes in localized RCC. Methods: Single center, retrospective analysis of 264 patients with RCC (112 PN, 152 RN, mean follow-up 45 months) from 2003−2015. A priori, we assigned a positive marker score of “1” if RENAL &gt;8 or DeRitis &gt;1.5. Patients were stratified by increasing positive markers (“0”=RENAL ≤8 and DeRitis ≤1.5, “1”=RENAL &gt;8 or DeRitis &gt;1.5, “2”=RENAL &gt;8 and DeRitis&gt;1.5). Primary outcome was overall survival (OS). Cox models and Kaplan−Meier curves were utilized. Results: 264 patients, 61.7% male, mean age 64.5 ± 12.8 years, mean BMI 28.5 ± 5.6, mean AST/ALT 1.1 ± 0.4. With regards to tumor characteristics, mean clinical tumor size 4.7 ± 3.2cm and median RENAL score 9 (IQR 7−10). For clinical staging, 75.7% were cT1, 17.4% were cT2, and 6.9% were &gt;cT2. 32.6% had 0 positive markers, 60.2% had 1 marker, and 7.2% had 2 markers. Kaplan−Meier analysis for “0”, “1”, and “2”demonstrated significantly worsened OS (log−rank p=0.03). On Cox model for OS, RENAL &gt;8 (HR 2.13, p=0.01) or AST/ALT &gt;1.5 (HR 2.25, p=0.028) were significantly associated with worsened survival, as was combined RENAL &gt;8 and DeRitis &gt; 1.5 (HR 5.1, p&lt;0.001). Conclusions: Novel combination of a morphological score (RENAL) and an inflammatory marker (DeRitis ratio) was associated with worsened OS in localized RCC. Our findings point toward development and validation of a prognostic index to assist in risk stratification for localized RCC.
Identifying models of cancer survivorship care.
Authors: Holly Mead, Mandi Pratt-Chapman, Kan Gianattasio, Sean Cleary, Maya Gerstein
Journal: Journal of Clinical Oncology (2017)

1 Background: The growing population of cancer survivors (15.5 million in the US) face myriad health issues that require health care attention. Cancer is increasingly viewed as a chronic illness that, once treated, requires systematic and coordinated care. Little guidance, however, has been provided in terms of how programs should be organized and little research has been done to understand emerging models in the field. We aim to identify and describe the most common survivorship models of care to identify characteristics of care and provide guidance on how survivorship care should be delivered. Methods: We conducted a scan of 236 CoC-accredited cancer centers to identify characteristics that co-occur in survivorship programs and those that predict the provision of LIVESTRONG’s Essential Elements. We supplemented this approach with in-depth interviews and surveys of 32 survivorship programs to gain detailed organizational information. Results: Three models emerged from the data: The Consultative Specialized Survivorship Clinic provides a one-time onsite visit focusing on in-depth survivorship care planning and is typically led by an NP/PA. It is likely to enjoy more organizational support and to bill for services. The Longitudinal Specialized Survivorship Clinic provides ongoing care with most services delivered onsite, and is typically led by an NP/PA. It is likely to have some organizational support but less likely to bill for services. Oncology-Based Survivorship Care with Referral for Services provides ongoing survivorship care, often in tandem with treatment, but delivers most services via referral. It is typically physician-led and has no formal survivorship care planning protocol. It receives less organizational support and is less likely to bill for services. Models also differ in the numbers and types of services provided. Conclusions: These models reflect distinctive organizational and delivery system characteristics and can guide other institutions interested in providing survivorship care.
Patient Mortality During Unannounced Accreditation Surveys at US Hospitals
Authors: Michael L. Barnett, Andrew R. Olenski, Anupam B. Jena
Journal: JAMA Internal Medicine (2017)

In the United States, hospitals receive accreditation through unannounced on-site inspections (ie, surveys) by The Joint Commission (TJC), which are high-pressure periods to demonstrate compliance with best practices. No research has addressed whether the potential changes in behavior and heightened vigilance during a TJC survey are associated with changes in patient outcomes.To assess whether heightened vigilance during survey weeks is associated with improved patient outcomes compared with nonsurvey weeks, particularly in major teaching hospitals.Quasi-randomized analysis of Medicare admissions at 1984 surveyed hospitals from calendar year 2008 through 2012 in the period from 3 weeks before to 3 weeks after surveys. Outcomes between surveys and surrounding weeks were compared, adjusting for beneficiaries' sociodemographic and clinical characteristics, with subanalyses for major teaching hospitals. Data analysis was conducted from January 1 to September 1, 2016.Hospitalization during a TJC survey week vs nonsurvey weeks.The primary outcome was 30-day mortality. Secondary outcomes were rates of Clostridium difficile infections, in-hospital cardiac arrest mortality, and Patient Safety Indicators (PSI) 90 and PSI 4 measure events.The study sample included 244 787 and 1 462 339 admissions during survey and nonsurvey weeks with similar patient characteristics, reason for admission, and in-hospital procedures across both groups. There were 811 598 (55.5%) women in the nonsurvey weeks (mean [SD] age, 72.84 [14.5] years) and 135 857 (55.5%) in the survey weeks (age, 72.76 [14.5] years). Overall, there was a significant reversible decrease in 30-day mortality for admissions during survey (7.03%) vs nonsurvey weeks (7.21%) (adjusted difference, -0.12%; 95% CI, -0.22% to -0.01%). This observed decrease was larger than 99.5% of mortality changes among 1000 random permutations of hospital survey date combinations, suggesting that observed mortality changes were not attributable to chance alone. Observed mortality reductions were largest in major teaching hospitals, where mortality fell from 6.41% to 5.93% during survey weeks (adjusted difference, -0.38%; 95% CI, -0.74% to -0.03%), a 5.9% relative decrease. We observed no significant differences in admission volume, length of stay, or secondary outcomes.Patients admitted to hospitals during TJC survey weeks have significantly lower mortality than during nonsurvey weeks, particularly in major teaching hospitals. These results suggest that changes in practice occurring during periods of surveyor observation may meaningfully affect patient mortality.
An exploratory study to determine if <i>BRCA1</i> and <i>BRCA2</i> mutation carriers have higher risk of cardiac toxicity.
Authors: Roohi Ismail-Khan, Monique Sajjad, Weihong Sun, Hatem Hussein Soliman, Hyo S. Han, Susan E. Minton, Johnathan M. Lancaster, Tuya Pal
Journal: Journal of Clinical Oncology (2012)

1585 Background: Anthracycline related cardiac toxicity (CT) is a concern in treating women with breast cancer. The prevalence of heart failure (HF) affects 2% of the population, less so in women. Patients receiving anthracycline based therapy (ABT) have a dose-dependent risk of reduction in ejection fraction. Recent work by Dr. Verma suggests that BRCA-deficient mice manifest increased levels of cardiac failure. We sought to explore the risk for CT and evaluate the association between ABT and HF in female BRCA mutation carriers. Methods: An online survey was developed to collect information about breast cancer treatment (including HF) in BRCA mutation carriers through the national BRCA patient advocacy organization FORCE via their 2011 conference and their website as well as the Moffitt-based Inherited Cancer Registry (ICARE). The prevalence of CT and HF was calculated in both BRCA 1 and 2 breast cancer patients and compared to general population risks. Data from those that received ABT was compared to published HF rates from ABT. Results: Our sample included 227 BRCA1 carriers and 164 BRCA2 carriers in whom 6.4% reported cardiac toxicity (i.e., either HF and/or CT). This included similar proportions in BRCA1 vs BRCA2 carriers (i.e., 6.6% and 6.1%, respectively). These proportions are significantly higher than the published rate of 2% (all p-values &lt; 0.001). Specifically regarding ABT, 112 mutation carriers had doxorubicin (Adriamycin) for treatment of whom 8% reported HF, similar to the 11 who had Epirubicin (11 patients), of whom 9% reported HF. Conclusions: Our data suggests that BRCA mutation carriers may have an increased risk of CT compared to the general population. In particular, women with BRCA mutations treated with ABT also appear to have a higher risk of developing CT and/or HF. This exploratory study provides the basis upon which larger retrospective and prospective studies are currently being planned. The high percentage of CT observed in this study requires confirmation as they could inform recommendation for cardiac screening and review of the current standard for ABT use in this population.
PREVENTATIVE RISK FACTORS FOR OSTEOARTHRITIS IN GREAT BRITAIN'S OLYMPIANS
Authors: Dale Cooper, Mark Batt, Brigitte Scammell, Debbie Palmer-Green
Journal: British Journal of Sports Medicine (2017)

Background Relatively little is known about the risk factors associated with osteoarthritis (OA) in Olympic athletes. As the first step towards prevention, knowledge of preventative/modifiable risk factors are needed. Objective To examine injury patterns, prevalence, and risk factors for OA in Great Britain's Olympians, aged 40 years and older. Design Cross-sectional study design, with an internal nested-case control. Setting Athletes who had represented Great Britain at the Summer and/or Winter Olympic Games from 1932 to 2012. Participants Great Britain's Olympians were invited to complete and return a web-based or paper questionnaire. The response rate was 32%, with 605 returns achieved (40–97 years), between the 22nd May 2014 and the 31st January 2015. Assessment of Risk Factors Potential risk factors for OA included age, body mass index, gender, previous injury, lower limb mal-alignment, hypermobility (self-reported Beighton&gt;4/9), comorbidities, index ring finger ratio, Heberden's and Bouchard's nodes, and having competed in either impact or weight-bearing loading sports. Main Outcome Measurements The primary outcome measure was self-reported physician-diagnosed OA, whereby Great Britain's Olympians confirmed that a physician had previously diagnosed them with the condition. The most severe limb was selected as the index joint for data analysis, if bilateral. Results Knee (14%), hip (11%), and the lumbar spine (5%) are most likely affected by OA. Injury appeared the strongest modifiable risk factor for knee [aOR 4.89; 95% CI, 2.64–9.06] and hip OA [aOR 10.46; 95% CI, 3.67–29.83]. Hypermobility appeared a risk factor for knee OA only [aOR 2.26; 95% CI, 1.08–4.74]. Intra-articular injuries through participation in weight-bearing loading sports were consistently reported in those with peripheral joint OA. Conclusions As one of the few modifiable risk factors, joint injury prevention should be part of the future initiatives to reduce the risk of OA.
Autologous or allogeneic stem cell transplantation versus chemotherapy in acute myeloid leukemia and subgroups: A multicenter trial by the German AML Cooperative Group
Authors: T. Buchner, W. E. Berdel, J. Kienast, H. Kolb, P. Staib, A. Reichle, C. Schoch, T. Haferlach, M. C. Sauerland, W. Hiddemann
Journal: Journal of Clinical Oncology (2006)

6556 Background: From the data available the role of autologous and allogeneic stem cell transplantation (auto/allo SCT) versus post-remission chemotherapy appears uncertain and is readdressed in the present trial. Methods: Pts were stratified for cytogenetic groups, de-novo/secondary AML, LDH, WBC, and were up-front randomized in one step to induction by HAM-HAM vs TAD-HAM, and to G-CSF priming vs. no G-CSF. These two randomizations did not result in different outcome. Pts were also upfront randomized to auto SCT vs monthly maintenance chemotherapy. Within the two randomized arms pts with histocompatible family donors underwent priority allo SCT. Results: Since 1999 840 pts 16–60 y of age entered the trial. 14%, 62%, 21%, and 3% of pts had favorable, intermediate, unfavorable and unknown karyotype, and 19% had secondary AML. 70% of pts went into complete remission (CR). The probability of overall survival (OS) at 3 years in the auto SCT and the maintenance arm is 43% vs 41% (p=0.52), the relapse-free survival (RFS) is 40% vs 40% (p=0.78), and the ongoing remission duration (RD) is 48% vs 46% (p=0.65). Among pts alive and in CR 73% did receive auto SCT or maintenance or allo SCT, similar to previous trials (NEJM 332:217,1995, Blood 90:2978,1997, Lancet 351:700,1998, NEJM 339:1649,1998). The outcome according to therapy given in the auto SCT arm and the maintenance arm shows ongoing RD of 44% vs 50% (p=0.31), RFS of 44% vs 48% (p=0.35), and OS of 53% vs 69% (p=0.005). 128 pts underwent allo SCT. In a matched pair analysis with concordance of pairs in karyotype, de-novo/secondary AML, induction chemotherapy, and RFS at the time of SCT, RD shows a superiority of allo SCT (p&lt;0.001), while OS is similar between the two arms (p=0.65). No prognostic subgroup with a special benefit from auto or allo SCT can be identified so far. Conclusions: Among current alternative strategies only novel approaches in allo SCT reducing the high transplant related death rate may further improve the cure of pts with AML and subgroups. No significant financial relationships to disclose.
Combination of local tumor invasiveness (LTI) and International Prognostic Index (IPI) provides better predictive value in extranodal NK/T-cell lymphoma, nasal type (NTCL)
Authors: T. Kim, S. Lee, D. Kim, S. Lee, S. Im, T. Kim, C. Kim, Y. Bang, D. Heo
Journal: Journal of Clinical Oncology (2006)

17503 Background: In contrast to B-cell lymphomas, NK/T-cell lymphomas have unique clinical pattern (local invasiveness; Blood. 2005;106:3785). Prognostic factors were evaluated according to IPI as well as LTI and compared with the other prognostic model (Lee J, et al JCO 2006). Methods: 176 patients diagnosed with NTCL between 1992 and 2004 were analyzed. Overall survival (OS) and progression-free survival (PFS) were compared according to IPI, IPI combined with LTI, and the other model. LTI was briefly defined as follows: bony invasion or perforation or skin invasion (upper aerodigestive tract); serosal invasion or perforation (gastrointestinal tract); tumor more than 5cm or invasion of deep extradermal structures (skin); and neurovascular or bony invasion (muscle). Results: After a median follow-up period of 80 months, 5-year (y) OS and PFS were 33% and 25%, respectively. The IPI risk group was predictive of OS and PFS (5-y OS 52%, 23%, 10%, and 4%, respectively, P &lt; .0001; 2-y PFS 47%, 31%, 5%, and 4%, respectively, P &lt; .0001) but failed to show survival differences between the high-intermediate and high risk groups (P = .0737). However, once both IPI and LTI are combined, there were significant differences in OS and PFS between the IPI score 0–2/LTI-, IPI score 0–2/LTI+, IPI score 3–5/LTI-, and IPI score 3–5/LTI+ groups (5-y OS 60%, 14%, 7%, and 4%, respectively, P &lt; .0001; 2-y PFS 53%, 21%, 9%, and 4%, respectively, P &lt; .0001). OS and PFS were also affected by the other prognostic model but this model failed to show survival differences among the risk groups (P = .1382). Conclusions: Combination of local tumor invasiveness and International Prognostic Index provides better predictive value in extranodal NK/T-cell lymphoma, nasal type. No significant financial relationships to disclose.
Clinical efficacy and safety of regorafenib (REG) in the treatment of metastatic colorectal cancer (mCRC) in daily practice in Germany: Interim results of the prospective multicentre noninterventional RECORA study.
Authors: Holger Schulz, Jan Janssen, Uwe P. Strauss, Markus Langen, Marcel Frey, Sabine Fiala-Buskies, Carsten Bokemeyer
Journal: Journal of Clinical Oncology (2017)

769 Background: In 2013 REG was approved for mCRC based on the results achieved in the CORRECT trial. However, prospective data from daily practice use are still scarce. Methods: RECORA is investigating efficacy and safety of REG in routine clinical care in Germany. Male/female mCRC patients (pts) ≥ 18 years for whom the decision was taken to treat with REG in its approved indication were enrolled. Primary objective was overall survival (OS). Secondary objectives included progression-free survival time (PFS), time-to-progression (TTP), disease control rate (DCR), and incidence of treatment-emergent adverse events (TEAE). Results of a planned interim analysis with data cut-off 11 July 2016 are presented. Results: 480 pts were enrolled at 90 sites between 10/13 and 07/16; 458 pts were included in this interim analysis for safety, 457 for efficacy. Mean/median age was 67 years, 61% of pts were male, baseline ECOG PS was 0 in 20%, 1 in 61%, 2 in 18%, and 3 in 1% of pts, 62% had a primary colon cancer, 46% had KRAS mutated tumors at diagnosis, 23% had mets in the liver only, 9% in the lung only, and 22% in both lung and liver. Median OS was 5.6 months (mos) (95% CI 5.2-6.6) based on 277 deaths, median PFS was 3.2 mos (95% CI 2.9-3.5) based on 337 progression or death events, median TTP was 4.5 mos (95% CI 3.8-5.4) based on 195 progressions, DCR was 29.9% based on 234 tumor evaluations. There were no significant differences in OS in subgroups according to age ( &lt; 65/ ≥ 65), sex, KRAS status, number of prior treatment lines, and site of mets; whereas OS was significantly different in subgroups according to ECOG PS (ECOG 0/1 vs. 2), primary tumor site, and time from initial diagnosis ( &lt; 18/ ≥ 18 mos). Mean duration of treatment was 2.7 mos. TEAE grade ≥ 3 occurred in 23.7% of pts, in 17.3% REG related. A serious TEAE was recorded in 47.8% of pts, in 8.3% considered as REG related. Overall, 26.6% died of an AE, in 0.4% REG related. 23.8% of pts received another anti-tumor therapy after REG was stopped. Conclusions: RECORA showed clinical benefit and acceptable tolerability for REG in this interim analysis. OS was in the range of the pivotal study. Clinical trial information: NCT01959269.