tbuckley/cabot-search huggingface dataset:
The influence of a gene expression signature on the diagnosis and recommended treatment of melanocytic tumors by dermatopathologists.
Authors: Loren E Clarke, Emily Bess, Kelsey Moyes, Kathryn A Kolquist, Colleen Rock
Journal: Journal of Clinical Oncology (2014)

TPS9111 Background: Many studies have documented suboptimal accuracy and reproducibility in the diagnosis of melanocytic lesions by histopathology, even by experienced dermatopathologists. Therefore, adjunctive methods that provide objective and reliable data have been sought. Recently, a 23-gene expression signature that assesses immune signaling and cell differentiation and uses quantitative reverse-transcription polymerase chain reaction was developed using a cohort of 464 melanocytic neoplasms. (J Cutan Pathol. 2014; 41:144-275 [abstr 292263]) The assay has been clinically validated to differentiate benign nevi from malignant melanoma with a sensitivity of 90% and a specificity of 91% in a second, independent cohort of 437 melanocytic lesions representing a broad spectrum of histopathologic types. (Pending publication) This study aims to quantify the impact of this assay on diagnosis and management recommendations made by dermatopathologists. Methods: Forty-nine dermatopathologists submitted 821 representative histological sections of difficult to diagnose melanocytic lesions encountered during routine practice to a clinical laboratory for gene expression testing. Currently, 513 cases are eligible for study inclusion based upon completed pre- and post-test surveys accompanying each case. Surveys document the physician’s diagnosis, predicted biologic behavior (benign, malignant, or indeterminate), level of confidence, and recommendations for management. Study endpoints include the measured level of change in diagnosis, confidence, and treatment recommendations between the pre- and post-test surveys.
Favorable Leukemia-Free Survival (LFS) for Adults and Children Undergoing Myeloablative Umbilical Cord Blood (UCB) Transplantation with Cyclophosphamide (CY), Fludarabine (FLU) and Total Body Irradiation (TBI): A Single Center Analysis of 194 Patients.
Authors: Claudio Brunstein, Daniel Weisdorf, Todd DeFor, Jeffrey S. Miller, Philip B. McGlave, Bruce R. Blazar, John E. Wagner
Journal: Blood (2008)
Correlation between peripheral blood and bone marrow regarding FLT3 ITD and NPM1 mutational status in patients with AML.
Authors: Weigang Tong, Brent L. Wood, Vicky Sandhu, Paul Hendrie, Pamela S. Becker, Roland B. Walter, John M. Pagel, Elihu Estey
Journal: Journal of Clinical Oncology (2014)

7077 Background: Internal tandem duplications (ITD) of the FLT3 gene and mutations in the NPM1 gene are among the most common genetic aberrations in AML. Patients with these abnormalities frequently present with high circulating blast counts. Hence we hypothesized that the diagnosis of FLT3 ITD, or NPM1, positive AML can be made using peripheral blood (PB) without need for a bone marrow (BM), as has been shown to generally be the case with routine cytogenetic studies (Weinkauff et al Am J Clin Pathol 1999;111:733-740). Here we examined whether the same is true for NPM and FLT3. Methods: We reviewed 1016 AML (≥ 20% blasts) patients that were treated at SCCA/FHCRC from January 2008 to December 2013. We identified 30 patients in whom FLT3 ITD and 18 patients in whom NPM1 mutation status was performed in both PB and BM within 3 days of each other. We compared the clinical characteristics of these patients, as well as the correlation for FLT3 ITD allelic ratio in both PB and BM using Spearman correlation analysis. Results: For the patients with FLT3 ITD data, the median WBC count was 13,090 (range 170-117,470) and median absolute blood blasts were 1,535 (range 0-113,060) while these values were 21,000 (range 1,190-97,000) and 5,200 (range 230-62,000) respectively for the patients with NPM data. Eight of the 30 FLT 3 patients were positive in both PB and BM, 21 were negative in both, only one patient (WBC 19,800) was negative in PB and positive in marrow (low level, < 0.01). There were two patients with very low WBC counts (0.4 and 0.17) and no circulating blasts, but FLT3 ITD was detected in both PB and BM. Allelic ratios were highly correlated in PB and BM correlation coefficient 0.92 (95% CI 0.82 to 0.96; p < 0.0001). While there was complete concordance between PB and BM with respect to NPM1 mutational status, only 4 of 18 patients were positive for NPM1 mutation as detected in both PB and BM. Conclusions: Within the limits of our patient numbers, these data suggest that in patients with AML, peripheral blood can often serve as a substitute for bone marrow in evaluating FLT3 ITD and NPM1 mutational status, perhaps even in patients with lower white cell counts and blast percentage.
Pharmacodynamic (PD) evaluation of soluble proteins from a phase I trial of lapatinib (L) in combination with sorafenib (S).
Authors: Matteo Simonelli, Paolo Andrea Zucali, Elena Lorenzi, Luca Rubino, Fabio De Vincenzo, Matteo Perrino, Lorenza Rimassa, Laura Giordano, Armando Santoro
Journal: Journal of Clinical Oncology (2012)

e21139 Background: At ASCO 2011 we presented safety and efficacy results from a phase I study of L in combination with S in patients with solid tumors refractory to standard therapy (NCT00984425). To investigate potential biomarkers of biological activity of this combination, we analyzed serum levels of a panel of soluble proteins characterizing the oncogenic signalling pathways targeted by L and S (VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu), and others mediators of angiogenesis such as sPDGFR, IL-8, IL-6, bFGF, PIGF, TGF-α e β, HGF. Methods: Serum samples from 22/30 patients enrolled in this trial were prospectively collected at baseline and then every two months until treatment discontinuation. Serum levels of VEGF, sVEGFR-2, EGF, sEGFR, sHER2/neu and sPDGFR were measured via enzyme-linked immunoadsorbent assays analysis (ELISA). Possible correlations between serum proteins levels and disease-control rate (SCR), PFS or OS were assessed by logistic and Cox regression model, respectively. Results: Analysis of baseline biomarkers as a function of demographic variables indicated that VEGF levels were inversely correlated with age (P= .018) and VEGFR-2 was significantly associated with tumor burden (P= .037). Risk of progression increased with high baseline sEGFR levels (HR 1.10; p= .0498). Overall, PD changes suggest that treatment with L and S increased VEGF and sHER2/neu levels, while decreased EGF, sEGFR, VEGFR-2 and sPDGFR. Mainly, sEGFR levels decreased by at least 75% at the first radiological assessment in half of patients, whereas at the end of treatment a reduction ≥80% was observed in 18 patients; a greater reduction of sEGFR levels was significantly associated with a higher risk of progression (HR 8.3; P &lt;.01) and death (HR 3.6; P= .023). An increase of VEGF levels during treatment seemed to be associated with better SCR (OR: 6.33; P= .085). Conclusions: In this small subset of patients treated with L and S a significant modulation of serum biomarkers was observed. The clinical significance of these changes as potential surrogate markers requires further evaluation. Data concerning other angiogenic markers along with tissue analysis (IHC, FISH and mutation) will be presented at the meeting.
Impact of extra-nodal metastasis on survival in gastric cancer patients with lymph node involvement.
Authors: Noriyuki Nishiwaki, Masanori Tokunaga, Kenichiro Furukawa, Keiichi Fujiya, Hayato Omori, Wataru Takagi, Fumiko Hirata, Sanae Kaji, Makoto Hikage, Rie Makuuchi, Yutaka Tanizawa, Tomoyuki Irino, Etsuro Bando, Taiichi Kawamura, Yusuke Kinugasa, Teiichi Sugiura, Katsuhiko Uesaka, Masanori Terashima
Journal: Journal of Clinical Oncology (2017)

57 Background: Extra-nodal metastasis (ENM) is defined as a tumor nodule without lymph node structure, and distinguished from lymph node metastasis by histological findings. Despite the possible difference in metastatic mechanism, both are counted as metastasized lymph nodes according to the 3rd English edition of Japanese Classification of Gastric Carcinoma, and thus the prognostic value of ENM remains unclear. The aim of this study was to clarify the clinicopathogical characteristics and prognostic impact of ENM in gastric cancer patients with lymph node involvement. Methods: This study included 388 patients who underwent curative gastrectomy for primary gastric cancer between January 2009 and August 2013. A total of 2093 pathologically positive tumor nodules, including both metastatic lymph nodes and ENM, were examined. Clinicopathological characteristics and survival outcomes were compared between an ENM positive (ENMP) group (95 patients) and an ENM negative (ENMN) group (293 patients). In addition, multivariable analysis was performed to clarify the independent prognostic factors. Results: ENM was found in 269 of 2093 tumor nodules (12.9 percent). The incidence of ENM was significantly higher in patients with large tumor size, high pathological T stage (pT), high pathological N stage (pN) and in those with macroscopic infiltrative tumors, vascular and lymphatic invasion. Three-year relapse free survival was significantly worse in the ENMP group (56.5%) than in the ENMN group (82.4%, p &lt; 0.001). Multivariable analysis revealed that ENM as well as age, pT and histological type was an independent prognostic factor. Conclusions: ENM is an independent prognostic factor in gastric cancer patients with lymph node involvement. A new N classification stratified by the presence of ENM might be considered.
From helplessness to self help: Breast cancer surviorship in India.
Authors: Rebecca DeSouza, Shona Milon Nag, Rama Sivaram, Anupama Dutt Mane
Journal: Journal of Clinical Oncology (2017)

208 Background: In The Indian Scenario, a diagnosis of cancer is accompanied with social stigma and emotional upheavals, especially in breast cancer patients. They are typically thinking: “I would be less of a woman,” “I don’t know if people understand me,” “I feel isolated from myself, my family and my friends,” “Would I be normal again?” “Do I know how to help myself?” or “What will happen in the future, to my kids, to my husband?” Methods: All of these concerns are not always addressed by the medical professions. To address these issues, the Indian Breast Cancer Survivors Conference was organized as an annual conference with an attendance of 200-250 breast cancer survivors from the state of Maharashtra, India. The conference would address the psychological, emotional and social distress experienced by the patients with an aim from living a longer life to living a better and fulfilled life. Results: The emphasis of the sessions were educational (with recent updates on the surgical, medical and radiation therapy aspects of breast cancer treatment), practical (emphasized important issues like side-effects of treatment, patient advocacy, complementary therapies, spirituality, lifestyle changes, etc.), and entertaining. The summary and outcomes of the last 5 annual survivorship conferences will be described and enumerated. Results of questionnaires administered during the last 2 conferences and addressing health behavior patterns of survivors will be presented. Conclusions: We can evaluate through post conference support group discussions and conference feedback, qualify patient psychological and social health as 1) Physical:There are side effects but I choose to go on; 2) Mental: There are times that I am low, depressed, anxious, scared, guilty, but this is my new normal; 3) Emotional:Little things upset me, angry quickly but I am dealing with it; 4)Spiritual:Moved away from bargaining with God to accepting, from rituals to spiritual; 5) Social:don’t hesitate to reach out for support and to support; and 5) Intellectual:Knowledge is power, so I have learned to ask, to question, and then to decide. Achieving psychological and social health is the effort of the patient, the treating team and the support group.
The use of tumor growth rate (TGR) in evaluating sorafenib and everolimus treatment in mRCC patients: An integrated analysis of the TARGET and RECORD phase III trials data.
Authors: Charles Ferte, Laurence Albiges, Jean-Charles Soria, Yohann Loriot, Karim Fizazi, Bernard J. Escudier
Journal: Journal of Clinical Oncology (2012)

4540 Background: RECIST criteria may not be sufficient to evaluate targeted therapies in mRCC. TGR includes the time between each evaluation and is expected to overcome some of the RECIST pitfalls. How TGR is modified under targeted therapies and how it correlates with outcome in mRCC remains unknown. Methods: Medical records from all patients (pts) prospectively treated at Institut Gustave Roussy (IGR) in the TARGET (n=84) and in the RECORD (n= 52) phase III trials were extracted. Results were subsequently validated in the entire TARGET cohort (TARGET) (n=902). TGR was computed by dividing tumor shrinkage by the time between the two related evaluations (% RECIST x 100 / days). Typical treatment periods were assessed: BEFORE treatment (wash-out), UNDER treatment (first cycle), at PROGRESSION (pts still receiving the drug) and AFTER treatment interruption (wash-out). Results: As compared to placebo, TGR UNDER was significantly decreased following sorafenib (-23.6 vs. 20 (IGR) and -19 vs. 22 (TARGET)) and everolimus (-5.2 vs. 30 (IGR)). The great majority of pts (IGR) had a decrease in the TGR UNDER vs. BEFORE, regardless of the RECIST evaluation, both with sorafenib (28/29) or everolimus (36/37). TGR AFTER sorafenib or everolimus interruption was significantly higher than TGR at PROGRESSION in both settings (IGR) (14.6 vs. 31 and 17.9 vs. 32.1 respectively). No significant difference was observed between TGR AFTER vs. BEFORE either in sorafenib or in everolimus pts (IGR). High TGR UNDER is associated with poor progression free survival (HR= 2.6) and overall survival (HR= 2.3) in sorafenib-treated pts (multivariate analysis, trained in IGR and validated in TARGET cohorts) and with poor overall survival in everolimus-treated pts (IGR)(HR= 1.2). Conclusions: Adding TGR assessment in mRCC unravels interesting traits that make it potentially adaptable for clinical practice: (i) better evaluation of the tumor response, regardless of RECIST criteria, (ii) independent prognosis value, (iii) it suggests that maintaining sorafenib or everolimus after disease progression might benefit to patients and should be prospectively evaluated.
Effect of concomitant medication use on outcomes of treatment and placebo arms of the COU-AA-301 and COU-AA-302 studies of abiraterone acetate (AA) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Robert James Hamilton, Jinhui Li, Vahid Naini, Thian San Kheoh, Peter De Porre, Arturo Molina, Raya Leibowitz-Amit, Johann Sebastian De Bono, Howard I. Scher, Charles J. Ryan, Kim N. Chi, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2014)

e16045 Background: There is increasing interest in drug repurposing in cancer therapeutics based on preclinical and epidemiological data. We conducted an exploratory analysis of the COU-AA-301 (COU301) and COU-AA-302 (COU302) studies of patients with mCRPC to determine whether 14 commonly prescribed medications with putative anticancer properties affected clinically relevant outcomes. Methods: COU301 and COU302 are randomized phase 3 trials of patients randomized 2:1 and 1:1, respectively, to abiraterone acetate (AA) (1 g) + prednisone (P) (5 mg BID) or placebo + P in post-docetaxel and chemotherapy-naïve mCRPC settings, respectively. Concomitant medications of interest (metformin, digoxin, verapamil, proton pump inhibitors, nitrates, statins, COX-2 inhibitors, warfarin, heparins, ascorbic acid, selenium, tocopherol, antidepressants, and erythropoietin) were analyzed for association with overall survival (OS). No adjustment for multiple testing was made for these analyses. Results: Initial assessments revealed improved OS for concomitant use of statins (COU301, p = 0.004; COU302, p = 0.0195) and metformin (COU301, p = 0.0263; COU302, p = 0.084) only. Analysis by treatment arm revealed 13-32% relative improvements in overall survival for statins and metformin, but only with statin use were the improvements statistically significant (Table). Multivariate analysis was not performed due to low n and imbalance between groups. Conclusions: Of all commonly prescribed concomitant medications analyzed, statins and metformin may be associated with beneficial outcomes in the COU301 and COU302 studies, although confounders cannot be ruled out given limitations of the statistical analyses. Clinical trial information: NCT00638690, NCT00887198. Statins COU301 COU302 AA P AA P n (+/-) 236/561 103/295 229/317 207/335 HR 95% CI p value 0.76 (0.63-0.93) 0.0078 0.81 (0.62-1.07) 0.1335 0.87 (0.63-1.21) 0.4105 0.70 (0.52-0.96) 0.0241 Metformin COU301 COU302 AA P AA P n (+/-) 73/724 31/367 66/480 68/474 HR 95% CI p value 0.76 (0.55-1.05) 0.0984 0.85 (0.54-1.32) 0.4683 0.81 (0.48-1.36) 0.4268 0.68 (0.42-1.11) 0.1236
A multi-institutional phase II trial of pazopanib monotherapy in advanced anaplastic thyroid cancer.
Authors: Keith Christopher Bible, VeraJean Suman, Michael E. Menefee, Robert C. Smallridge, Julian R. Molina, William James Maples, Nina J. Karlin, Anne M. Traynor, Priya Kumar, Boon C. Goh, Wan-Teck Lim, Ayoko R Bossou, Crescent R Isham, Kevin P. Webster, Andrea K. Kukla, Carolyn Bieber, Jill K. Burton, Pamela Jo Harris, Charles Erlichman
Journal: Journal of Clinical Oncology (2012)

5544 Background: Pazopanib, an orally bioavailable multitargeted inhibitor of kinases including VEGF-R, demonstrated impressive activity in metastatic differentiated thyroid cancer (49% durable RECIST PRs) and promising preclinical activity in anaplastic thyroid cancer (ATC) models, prompting its evaluation also as a candidate therapeutic in advanced ATC. Methods: A multicenter single arm phase II trial of 800 mg pazopanib daily was undertaken with the primary endpoint of RECIST response rate. The trial was designed such that there would be a 90% chance of detecting a response rate of &gt;20% at the 0.10 significance level when the true tumor response rate is &gt;5%. A pre-specified stopping rule designated that enrollment would cease unless 1 or more RECIST PRs+CRs were observed in the first 14 of 33 potential patients. Eligibility required informed consent, &gt;18 years of age, performance status ECOG 0-2, systolic blood pressure (BP) &lt;140 mm Hg and diastolic BP &lt;90 mm Hg at entry, QTc interval &lt;480 msecs, and measurable disease by RECIST criteria. Anatomical imaging and toxicity evaluations were required every 4 weeks. Results: Sixteen patients were enrolled. One patient withdrew prior to therapy, leaving 15 evaluable patients – 33.3% were male, with a median age of 66 years (range 45-77); 11 of 15 patients had progressed through prior systemic therapy. Four patients required 1-2 dose reductions, with the most common severe toxicities (CTC-AE version 3.0 grades 3-5) hypertension (13%) and pharyngolaryngeal pain (13%). Reasons for treatment discontinuation included: disease progression (12 pts), death on study due to a vascular event possibly related to treatment (1 pt.), and intolerability (radiation recall tracheitis – 1 pt, and uncontrolled hypertension – 1 pt). Although transient disease regression was observed in several patients, there were no confirmed RECIST tumor responses, triggering study closure at time of interim analysis. Two patients are alive with disease 9.9 months and 2.9 years post-registration; the remaining 13 died of disease. The median time to progression was 62 days and the median survival time was 111 days. Conclusions: Pazopanib has poor single agent activity in advanced anaplastic thyroid cancer.
Cancer patients and their information needs for prediction of symptom burden during and after treatment: Implications for symptom management.
Authors: Luke Joseph Peppone, Michelle Christine Janelsins, Marie Anne Flannery, Mohamedtaki Abdulaziz Tejani, Anita Roselyn Peoples, Charles Stewart Kamen, James Norman Atkins, Jeffrey K. Giguere, Rakesh Gaur, Bart Frizzell, Karen Michelle Mustian
Journal: Journal of Clinical Oncology (2014)

9650 Background: Throughout and after treatment, cancer patients often face a high symptom burden (e.g. fatigue, pain, cognitive difficulties, etc.). A high symptom burden can reduce QOL and treatment adherence, potentially reducing survival. However, predicting the symptom burden in cancer patients remains challenging. Methods: Cancer patients scheduled to receive chemotherapy and/or radiation therapy were prospectively surveyed at pre-treatment (n=972), during treatment (n=748), and 6-month follow-up (n=652). At pre-treatment, patients indicated symptom concern (Low, Moderate, or High) and the desire for additional information (Yes, No) on relieving symptoms. During treatment and at 6-month follow-up, patients reported on the severity (an 11-point scale: 0 “None” to 10 = “Worst”) of 12 symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain, concentration, hot flashes, weight loss, skin problems, and dyspnea). Total Symptom Score (TSS) is the sum of all 12 symptoms. Mean symptom severity by symptom concern and additional information desire were determined by ANCOVA analysis. Results: Symptom concern at pre-treatment predicted symptom severity during treatment (Table). Patients who wanted more information on symptoms management before also had a significantly greater TSS (Yes = 46.7 vs No = 39.4; p=0.02) during treatment. Patients with high concern at pre-treatment also had a significantly higher TSS 6 months after treatment (High = 24.5 vs Low = 21.1; p<0.05). Conclusions: Pre-treatment patient symptom concern and wanting more symptom management information predicted symptom burden during treatment and 6 months after treatment. Clinicians should consider using these questions as indicator to which patients may require additional symptom management care. Low Moderate High P Total symptom score (TSS) 37.9 39.7 44.9 <0.001 Fatigue 5.5 5.8 6.1 0.044 Pain 3.4 3.2 3.9 0.030 Concentration 2.8 3.0 3.6 0.014 Memory 2.7 2.9 3.4 0.021 Depression 3.2 3.5 3.9 0.028 Nausea 2.3 3.2 3.7 <0.001 *Adjusted for severity of the respective symptom at pre-treatment.