tbuckley/cabot-search huggingface dataset:
Immunohistochemistry to initiate a complex screening cascade in the detection of Lynch syndrome.
Authors: Grainne O'Kane, Terri Patricia McVeigh, Denise Keegan, Delia Flannery, Katrina O'Connor, Michael P. Farrell, Conor Shields, Brian Meighan, Paul McCormick, Des C Winter, Niall Mulligan, C. Muldoon, Robert Geraghty, Andrew J. Green, Michael John Kennedy, Kieran Sheahan, David J. Gallagher
Journal: Journal of Clinical Oncology (2015)

3571 Background: Lynch Syndrome (LS) accounts for 2-4% of all colorectal cancers (CRC) and is caused by germline mutations in DNA mismatch repair (MMR) genes. Increasing literature supports routine screening for LS using immunohistochemistry (IHC) to detect loss of MMR protein expression on tumour samples. We reviewed practices at 3 Irish cancer centres. The number of MMR deficient (dMMR) tumours detected was evaluated, and the subsequent number of genetic referrals and LS diagnoses determined. Methods: Colorectal databases at 3 Irish academic centres were reviewed from January 2005 - 2013. Centre 1 performs IHC upon physician request, centre 2 implemented reflex IHC (rIHC) in November 2008, and centre 3 has been performing rIHC since 2005. All new diagnoses of colorectal adenocarcinoma with available histology were included. Pathology reports were reviewed and genetic referrals analysed. Results: A total of 4,021 new CRC were diagnosed in 3,929 patients across 3 centres. The results are presented in the table below. The implementation of universal screening using rIHC in cancer centre 3 detected an increased number of dMMR tumours (11%, p<0.01), however this did not result in a similar increase in cancer genetics referrals or lynch syndrome diagnoses. A high proportion of patients underwent germline testing once referred. Conclusions: Increased IHC testing for MMR proteins results in more Lynch syndrome diagnoses. Adherence to protocols for cascade testing and appropriate clinical referral is required to realise the benefit of universal screening. Centre 1 (IHC when requested) Centre 2 (rIHC since Nov 2008) Centre 3 (rIHC since 2005) Total new CRC with available histology 964 1246 1811 Total patient number 949 1220 1760 Median age yrs (range) 70 (17-97) 70 (16-97) 69 (27-96) No. (%) patients with IHC 153 (16%) 536(44%) 1760 (100%) p<0.01 No. (%) patients with dMMR 32 (3%) 56 (5%) 202 (11%) p<0.01 No. (% ) dMMR pts. with BRAF testing 3 (9%) 4(7%) 56 (28%) No. dMMR pts. referred to genetics* 14 17 37 No. (%) referrals who underwent germline testing 12(86%) 14 (82%) 33 (89%) No. (%) LS pts (of total pts) 7 (0.7%) 7 (0.6%**) 19 (1.1%***) * Numbers do not account for BRAF+ve patients who may not have been referred ** 2 results pending *** 7 results are pending
ICE (Ifosfamide, carboplatin, and etoposide) Was the Best Salvage Regimen in Patients with Relapsed or Refractory Malignant Lymphoma
Authors: Yoshiharu Kusano, Yasuhito Terui, Noriko Nishimura, Kyoko Ueda, Gunji Tadahiro, Hideaki Nitta, Yuko Mishima, Masahiro Yokoyama, Naoko Tsuyama, Kengo Takeuchi, Kiyohiko Hatake
Journal: Blood (2014)
Plerixafor (P) plus G-CSF (G) in previous peripheral blood progenitor cell (HPC) mobilization failures (MF)
Authors: F. Van Rhee, S. Panozzo, E. Anaissie, M. Pineda-Roman, S. Waheed, Y. Alsayed, B. Nair, M. Cottler-Fox, B. Barlogie
Journal: Journal of Clinical Oncology (2009)

7095 Background: Successful autologous stem cell transplantation (AT) requires harvesting sufficient HPC to ensure reliable engraftment, which cannot be accomplished in ∼10% of previously treated patients. Methods: MF was defined as the inability to collect at least 2 x10 6 CD34+ cells/kg with growth factor alone (GF) (n=38) or in combination with chemotherapy (GF-CT) (n=27). Of 65 patients reported here, 45 were enrolled in a compassionate use program and 20 were part of a clinical trial (AMD3100–2102); 55 had MM, 9 had lymphoma and 1 had primary amyloidosis. All patients had been treated previously and included prior AT in 26 patients, 15 of whom had 2 AT and 2 had ≥3 AT. The P+G regimen started with G (10 μg/kg) for 4 days, P (240 μg/kg) was added on the evening of day 4; both P and G were continued until completion of collection. In the case of MM, all collected products were analyzed for tumor contamination by DNA/cIg flow cytometry. Results: Of all 65 patients, 63 initiated apheresis which yielded a median 3.6x10 6 CD34/ kg (range, 0.3–17.8) during a median of 5 days (d) of collection (range, 2–7), with successive median daily CD34 yields of 1.1, 0.9, 0.6, 0.5, 0.3, 0.4 and 0.5 x10 6 /kg. MM cells were mobilized in only 2/55 patients. Additional collection was undertaken in 25 patients, using GF or GF-CT in 19 (median, 3.2x10 6 CD34 cells; range, 0–8.5), further P+G in 5 (median, 1.7x10 6 CD34 cells/kg; range, 0.9–3.5), and 1 patient received P+G on a third occasion (2.2x10 6 CD34 cells /kg). Of 63 patients, 51 (81%) and 24 (38%), respectively, collected ≥2.0 and ≥5.0x10 6 CD34 /kg. AT was supported with P+G derived products in 43 patients including 7 who received 2 AT. With median infused CD34+cells of 3.6x10 6 / kg (range, 1.0–7.7), the median times to neutrophils &gt; 500/μl and platelets &gt;20,000/ μl were 14 d (range, 11–35) and 15 d (range, 9–253). Conclusions: P+G ensures collection of an adequate HPC product after MF in 81% that affords durable engraftment even though 40% had prior AT. [Table: see text]
Abstract P092: Patient Ethnicity Predicts Poor Health Access and Gaps in Perception of Personal Cardiovascular Risk Factors
Authors: Yeunjung Kim, Gail D’Onofrio, Basmah Safdar
Journal: Circulation (2017)

Background: Focus of health literacy campaigns has centered around raising awareness. It is unknown whether awareness of cardiovascular risk factors accurately reflects personalization of one’s own cardiovascular risk especially in different ethnic groups. Methods: A cross-sectional survey was performed in consecutive patients presenting with chest pain and admitted to a large, urban Chest Pain Center at Yale-New Haven Hospital. A 32-item multiple item questionnaire was administered in English or Spanish to examine knowledge of CHD risk factors. Separately, the personalization of coronary risk factors was determined by having patients list [write in] their individual risk factors for having a heart attack. Multivariate logistic regression model and odds ratios were used to evaluate predictors of misperception, defined as gap between knowledge and personalization of risk. Primary outcome was the evaluation of ethnic disparities in awareness of cardiovascular risk factors and the patient’s misperceptions on personal risk factors. Secondary outcome was the assessment of access to information in the same population by gender and ethnicity. Results: Between Oct 2006-April 2008, 1584 consecutive patients admitted to the Chest Pain Center were screened for eligibility, and 1051 patients were enrolled. Between Hispanic, White, and African American patients, Hispanic patients were least aware of major CHD risk factors. In addition, misperception about personal risk was significantly higher in nonwhite compared to the white participants. This disparity persisted for the major modifiable coronary risk factors including hyperlipidemia and diabetes even when controlled for age, gender, employment, marital status, prior history of CAD and sources of health information. Conclusion: Knowledge of CHD risk factors vary by ethnicity. In addition, there are major gaps between awareness and personalization of risk in major modifiable CHD risk factors in different ethnic groups.
Evaluation of a cell viability assay based on cultures of CTICs to identify treatment options in third-line pancreatic cancer.
Authors: Mark Ricigliano, William H. Isacoff, Allyson J. Ocean, Brandon Cooper, Mary Welkie, Andrew Bartlett, Kenneth H. Yu
Journal: Journal of Clinical Oncology (2017)

338 Background: Standard of care treatment for pancreatic adenocarcinoma (PDAC) includes FOLFIRINOX or gemcitabine with nab-paclitaxel used in either the front-line or 2 nd line treatment setting. There is no consensus for 3 rd line treatment for this cohort of poor prognosis patients with clinical trials being the only viable option. We evaluated a cell viability assay using cultures of circulating tumor and invasive cells (CTICs) to identify effective 3 rd line PDAC treatment options. Methods: CTICs were isolated from peripheral blood samples of 17 PDAC patients who previously had received one of the two standard of care regimens using an immunomagnetic separation for EPCAM epitope Ber-EP4 and cultured in enriched DMEM-F12 medium. After 14 days, seven chemotherapeutics (gemcitabine (G), oxaliplatin (O), fluorouracil (F), irinotecan (I), mitomycin C (M), cisplatin (C) and paclitaxel (P)) were added to the cultures and response to treatment was measured 48 hr. after treatment by immunofluorescence using a live-cell resazurin assay. Response to treatment was determined by a reduction of fluorescence in the treated cultures compared to control and the mean florescence (Fm) was calculated for each chemotherapeutic. A one-sample t-test was used to measure the variance between Fm control and treated samples. (p-value &lt;0.005). Sensitivity to treatment was determined using linear regression based on Fm values and the sensitivity of each chemotherapeutic was interpolated from a standard curve (range 1.0-5.0, sensitive &lt;2, intermediate 2-3, resistant &gt;3). Results: m (Fm=1.6) demonstrated the most effective treatment option with marked resistance to treatment for G, I, P and O. (Fm=3.4, 3.7, 3.4 and 3.7). Intermediate response was observed for F and C (Fm=2.8 and 2.8). Patient treatment response to m will be described. Conclusions: CTICs can be routinely isolated and cultured for cell viability assays. m based regimens with C and F should be considered for 3 rd line PDAC patients.
Functional Connectivity of the Subcallosal Cingulate Cortex And Differential Outcomes to Treatment With Cognitive-Behavioral Therapy or Antidepressant Medication for Major Depressive Disorder
Authors: Boadie W. Dunlop, Justin K. Rajendra, W. Edward Craighead, Mary E. Kelley, Callie L. McGrath, Ki Sueng Choi, Becky Kinkead, Charles B. Nemeroff, Helen S. Mayberg
Journal: American Journal of Psychiatry (2017)

Objective: The purpose of this article was to inform the first-line treatment choice between cognitive-behavioral therapy (CBT) or an antidepressant medication for treatment-naive adults with major depressive disorder by defining a neuroimaging biomarker that differentially identifies the outcomes of remission and treatment failure to these interventions. Method: Functional MRI resting-state functional connectivity analyses using a bilateral subcallosal cingulate cortex (SCC) seed was applied to 122 patients from the Prediction of Remission to Individual and Combined Treatments (PReDICT) study who completed 12 weeks of randomized treatment with CBT or antidepressant medication. Of the 122 participants, 58 achieved remission (Hamilton Depression Rating Scale [HAM-D] score ≤7 at weeks 10 and 12), and 24 had treatment failure (<30% decrease from baseline in HAM-D score). A 2×2 analysis of variance using voxel-wise subsampling permutation tests compared the interaction of treatment and outcome. Receiver operating characteristic curves constructed using brain connectivity measures were used to determine possible classification rates for differential treatment outcomes. Results: The resting-state functional connectivity of the following three regions with the SCC was differentially associated with outcomes of remission and treatment failure to CBT and antidepressant medication and survived application of the subsample permutation tests: the left anterior ventrolateral prefrontal cortex/insula, the dorsal midbrain, and the left ventromedial prefrontal cortex. Using the summed SCC functional connectivity scores for these three regions, overall classification rates of 72%−78% for remission and 75%−89% for treatment failure was demonstrated. Positive summed functional connectivity was associated with remission with CBT and treatment failure with medication, whereas negative summed functional connectivity scores were associated with remission to medication and treatment failure with CBT. Conclusions: Imaging-based depression subtypes defined using resting-state functional connectivity differentially identified an individual’s probability of remission or treatment failure with first-line treatment options for major depression. This biomarker should be explored in future research through prospective testing and as a component of multivariate treatment prediction models.
PDE10 inhibitors suppress lung tumor growth in mice.
Authors: Suzanne M. Russo, Veronica Ramirez-Alcantara, Michele Schuler, Bing Zhu, Nan Li, Joshua Canzoneri, Adam Keeton, William E. Grizzle, Xi Chen, Gary Piazza
Journal: Journal of Clinical Oncology (2014)

e22187 Background: Phosphodiesterase 10 has been studied in the brain as a therapeutic target for psychiatric and neurological conditions, but has not been associated with tumorigenesis. Low levels of PDE10 exist in adult peripheral tissues and we found that 68% of lung tumors (n=19) displayed more than 2-fold increase compared with normal lung, and 26% showed greater than a 10-fold difference. High levels of PDE10 mRNA and protein were also found in human NSCLC cells compared with normal airway epithelium. PDE10 knockdown by siRNA suppressed lung tumor cell growth, as did PDE10 selective inhibitors, papaverine, PQ-10 and Pf-2545920. A novel PDE10 inhibitor, MCI-020 was developed from the indene scaffold of the NSAID, sulindac and was found to potently and selectively inhibit the growth of human NSCLC cells. These observations suggest that PDE10 is essential for lung tumor cell growth and represents a novel therapeutic target for lung cancer. We evaluated pharmacokinetics, tissue distribution and antitumor efficacy of MCI-020 in mice. Methods: MCI-020 suspension was administrated orally to C57BL/6 female mice. Free levels of MCI-020 were quantified in plasma and tissues by reverse-phase chromatography with tandem mass spectrometry detection. Athymic nude-Foxn1nu female mice were treated with MCI-020 (150 mg/kg bid) for 5 days before inoculation with 1x106A549 cells/mouse into the left lung. After inoculation, MCI-020 treatment continued for 4 weeks. Anti-tumor efficacy was evaluated by gross and histological grading of the lungs. Results: With attractive pharmacokinetic properties, MCI-020 was found to achieve high concentrations in lung tissue compared with other tissues and plasma. MCI-020 was well tolerated and strongly inhibited tumor formation in an orthotopic model of lung cancer at a dose of 150 mg/kg bid. Compared with the vehicle group in which 85% of the mice formed lung tumors, only 25% of the mice in the treatment group developed tumors. Histological grading of the extent of tumor formation revealed a score of 0.83 ± 0.3 (low) in treated mice, compared with 2.6 ± 0.4 (high) (vehicle). Conclusions: These observations support a role of PDE10 in lung tumor growth and suggest that inhibitors such as MCI-020 may be useful for prevention or treatment of lung cancer.
A randomized, multicenter phase III clinical trial comparing gemcitabine and cisplatin with 5-fluorouracil and cisplatin in the treatment of recurrent or metastatic nasopharyngeal carcinoma.
Authors: Li Zhang, Yan Huang, Xuan Wu, Wenhua Liang, Wenfeng Fang, Zhihuang Hu, Tao Qin
Journal: Journal of Clinical Oncology (2014)

TPS6098 Background: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy and chemotherapy. Nowadays, the regimen of 5-Fluorouracil plus cisplatin (FP) is widely used in recurrent or metastatic (R/M) NPC patients, but the response period is usually short and the adverse reaction is frequent and badly tolerant. Several small phase II trials suggest gemcitabine plus cisplatin (GP) has promising efficacy and better tolerability. Unfortunately, there is no head to head comparison study to evaluate these two regiments in this setting. This phase III trial will evaluate the efficacy and safety of GP versus FP as first-line therapy in patients with R/M NPC. Methods: The population consists of R/M NPC patients that failed the radical radiotherapy or chemotherapy-naïve advanced NPC (stage IV). Eligible patients will be randomized in a 1:1 ratio to receive either GP (gemcitabine 1,000 mg/m2 on days 1, 8, cisplatin 80 mg/m2 on day 1, every 3 weeks) or FP regimens (5-Fluorouracil 4,000 mg/m2 CIV over 96 hours, cisplatin 80 mg/m2 on day 1, every 3 weeks) for 4 to 6 cycles. The primary endpoint is progression free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), safety and quality of life. According to previously reported, it was assumed that the median PFS would be 4 months in the FP group and 6 months in the GP group. To detect a hazard ratio of 0.67, and a two-sided significance level of 5%, with a power of 80%, accommodating for a maximum drop-out rate of 5%, the necessary sample size was calculated to be 198 patients per group. Therefore, the trial plans to enroll 362 patients at 21 sites in China. Thus far, 203 patients have been enrolled. Clinical trial information: NCT01528618.
Is the proportion of patients with synchronous stage IV breast cancer surviving &gt; 2 years increasing over time?
Authors: Shaheenah S. Dawood, Benjamin Haaland, Constance T. Albarracin, Ana M. Gonzalez-Angulo, Sudeep Gupta, Javier Cortes, Yoon Sim Yap, Rebecca Dent
Journal: Journal of Clinical Oncology (2013)

524 Background: Studies have shown a moderate increase in survival over time among pts with stageIV breast cancer. Median survival is approximately 2 yrs. The aim of this study was to evaluate trends over time of pts with synchronous stage IV disease who survive &gt;2 yrs. Methods: Using the SEER registry we identified female pts with synchronous stage IV breast cancer diagnosed between 1990-2007. Pts were divided into 3 groups according to year of diagnosis(1990-1995, 1996-2000, 2001-2007). Probability of surviving more than &gt;2 yrs was computed within each group. A multivariable logistic regression model was then fitted to determine the association between year of diagnosis and the probability of surviving &gt;2 yrs after adjusting for other prognostic factors. Results: 22,492 pts were identified of whom 9,388 (41.7%) had a survival of &gt;2 yrs. The probability of surviving &gt;2 yrs was 36.2%, 40.1%, and 44.2% among pts diagnosed in periods 1990-1995, 1996-2000, and 2001-2007 respectively (p-value &lt; 0.0001). The probability of surviving &gt;2 yrs was 55.3% and 29.3% among pts with ER+ and ER- disease respectively (p-value &lt;0.0001) and was 32.9% and 43.5% among pts of black and white race respectively (p-value &lt;0.0001). In the multivariable model the probability of surviving &gt;2 yrs increased with increasing year of diagnosis (OR 1.04, 95% CI 1.03-1.05, p &lt;0.0001). Other factors significantly associated with an increased probability of surviving &gt;2 yrs included radiation therapy, lower grade, younger age, hormone receptor (HR) positive disease and non-inflammatory disease. Interaction term between race and year of diagnosis was marginally significant, such that black pts had a more slowly increasing probability of surviving &gt;2 yrs compared to whites (OR 0.97, 95% CI 0.96-1.00, p = 0.037). Interaction term between HR status and year of diagnosis was not significant. Conclusions: Our results indicate that among pts with synchronous stage IV breast cancer the probability of surviving &gt;2 yrs has increased over time reflecting the introduction and FDA approval of multiple efficacious chemotherapeutic and endocrine therapeutic options. Of concern, the probability of surviving &gt;2 yrs has increased more slowly among pts of black race.
Partners of young breast cancer survivors: A cross-sectional evaluation of psychosocial issues and mental health.
Authors: Nancy Borstelmann, Shoshana M. Rosenberg, Shari I. Gelber, Meghan E Meyer, Kathryn Jean Ruddy, Lidia Schapira, Steven E. Come, Virginia F. Borges, Tamara Cadet, Peter Maramaldi, Ann H. Partridge
Journal: Journal of Clinical Oncology (2017)

184 Background: While evidence of the challenges of cancer caregiving has been growing, scant research addresses the experience of partners of young adults with cancer. These individuals and their relationships may be particularly vulnerable to stress, especially when managing the complexity of cancer care and survivorship with their partner. We sought to evaluate psychosocial concerns and mental health in the partners of young survivors of early stage breast cancer (BC). Methods: We invited partners of young women w/BC diagnosed at age ≤ 40 yrs enrolled in a prospective cohort study to participate in a one-time survey evaluating psychosocial concerns including quality of life, coping, social support, financial insecurity, partnership concerns, parenting concerns, anxiety and depression. Logistic regression was used to explore predictors of anxiety (score &gt; 8 on Hospital Anxiety and Depression Scale (HADS)). Results: Most respondents (284/289) were male, with median age 43 yrs (range 27-65). The median time of survey completion was 62 months (range 16 -114) after their partner’s dx. Respondents were mostly white (93%), working full time (94%), and college educated (78%); 29% reported some financial stress, 74% were parenting children &lt; 18 yrs, and 32% reported at least a fair amount of relationship concern. 42% (106/250) had anxiety (39/289 respondents (13%) had incomplete/missing HADS). In univariable analyses, lower education, working full time, parenting concerns, insufficient social support and maladaptive coping were associated (p &lt; .05) with anxiety. In the multivariable model, only maladaptive coping remained significantly associated with anxiety (p &lt; .01, OR = 2.32 (95% CI: 1.22, 4.39)). Conclusions: Partners of young BC survivors who used less constructive/more maladaptive coping strategies experience negative mental health outcomes after tx has ended. Caregivers’ anxiety may have implications for both their own and survivors’ health and QOL. Future interventions might focus on the development of constructive coping strategies to enhance adjustment and role effectiveness in dealing with the impact of cancer.