tbuckley/cabot-search huggingface dataset:
Nanomechanical profiling of human breast tumors as prognostic marker for breast cancer.
Authors: Rosemarie Anne Burian, Tobias Appenzeller, Philipp Oertle, Christian Raez, Roderick Y.H. Lim, Serafino Forte, Sophie Dellas, Ellen Obermann, Marija Plodinec
Journal: Journal of Clinical Oncology (2017)

11618 Background: Assessment of tumor aggressiveness is crucial when making treatment decisions. Established prognostic markers may be insufficient to stratify cancer patients into treatment relevant risk groups. Emerging evidence indicates mechanical properties of cancer cells and their microenvironment play a vital role in cancer invasion and metastases. Detecting and measuring these nanomechanical changes could be a marker of cancer aggressiveness. Methods: We developed an atomic force microscope (AFM) based method: ARTIDIS (Automated and Reliable Tissue Diagnostics) for measuring nanomechanical properties of human tissue biopsies. These were performed on fresh, non-fixed tissue under physiological conditions. This novel method uses a micro-fabricated 20nm tip indenting and measuring stiffness of thousands of locations within 60-180minutes. This quantitative, biopsy-wide, nanomechanical profile strongly correlates to the tissue's biological composition. Post-AFM this biopsy is analyzed by pathology. We sought to differentiate benign from cancerous lesions based on nanomechanical properties; then link the cancerous nanomechanical profiles prospectively to the clinical outcomes. Results: Our results demonstrate the first AFM based nanomechanical profiling to detect aggressive breast cancer subtypes using fresh tissue in a clinical setting. We have shown that nanomechanical profiles of human breast cancer biopsies display stiffness profiles distinct from surrounding normal tissue. Breast cancer subtypes were distinguishable by their nanomechanical properties only. We have discovered specific nanomechanical profiles of tumor subtypes likely to metastasize. When the primary tumor displayed the same soft nanomechanical profile as adjacent tissue, this was associated with positive nodal status. Conclusions: Our results demontrate nanomechanical profiling is a fast and sensitive method to stratify malignant biopsies into relevant subgroups in a clinical setting. Relative stiffness and distribution values provide a nanomechanical profile indicating cancer aggressiveness. This will help optimize specific cancer diagnosis, orientate therapy choice and support patient follow up.
Ongoing phase 1/2 study of INCB050465 for relapsed/refractory (R/R) B-cell malignancies (CITADEL-101).
Authors: Rod Ramchandren, Tycel Jovelle Phillips, Michael Wertheim, Martin Gutierrez, William Jeffery Edenfield, Luke Paul Akard, Paolo Fabrizio Caimi, Justin Call, Daniel Oscar Persky, Douglas James DeMarini, Li Zhou, Swamy Yeleswaram, Andres Forero-Torres
Journal: Journal of Clinical Oncology (2017)

7530 Background: INCB050465 is a selective PI3Kδ inhibitor with no preclinical hepatotoxicity at clinically relevant doses. We report emerging safety and efficacy data from a phase 1/2 study of INCB050465 in patients (pts) with r/r B-cell malignancies (NCT02018861). Methods: The protocol was initiated with a single patient cohort, treated with INCB050465 5 mg QD PO. Subsequent cohorts used a 3+3 design and evaluated doses of 10–45 mg QD. Based on PK/PD, the 20 and 30 mg QD cohorts were expanded. Responses were assessed Q9W by the Lugano Classification or International Working Group on Chronic Lymphocytic Lymphoma (CLL) criteria. Results: As of the data cutoff (Nov 1, 2016), 52 pts were treated (median age, 65 y [range, 30–88]; baseline tumors: diffuse large B-cell lymphoma [DLBCL], n=14; follicular lymphoma [FL], n=10; Hodgkin lymphoma [HL], n=9; marginal zone lymphoma [MZL], n=8; CLL, n=6; mantle cell lymphoma [MCL], n=5; 62% had &gt;3 prior systemic regimens). Median duration of therapy was 3.3 mo (range, 0.6–13.4); no DLTs were identified. 67% of pts discontinued therapy (disease progression, 31%; AEs, 25%); 33% had dose interruption; 4% had reduction. Most common nonhematologic AEs (all grade [Gr]; Gr ≥3): nausea (38%; 0%), diarrhea (31%; 6%), vomiting (25%; 0%); Gr ≥3 hematologic AEs: neutropenia (21%), lymphopenia (17%), thrombocytopenia (10%), anemia (4%). 40% of pts had serious AEs, most frequently colitis, diarrhea, hypotension (all n=3). 1 pt had Gr 3 pneumonitis; none had Pneumocystis jirovecii pneumonia (PJP) or Gr ≥2 elevated transaminase. Objective responses (ORs) occurred at all doses (Table), except 5 mg QD; 90% were observed at first assessment. Conclusions: INCB050465 demonstrated manageable toxicities with no clinically meaningful transaminitis/PJP. OR rates were generally high, with 90% observed at first assessment. Different dosing regimens/schedules, long-term safety, and disease-specific cohorts are being evaluated. Clinical trial information: NCT02018861. [Table: see text]
Diabetes risk in childhood cancer survivors: A population-based study.
Authors: Iliana Carolina Lega, Jason D Pole, Peter Austin, Cindy Lau, Paul C. Nathan, Nancy N. Baxter
Journal: Journal of Clinical Oncology (2017)

10558 Background: Cure rates for childhood cancer have improved significantly over the last three decades. Diabetes has emerged as a delayed side-effect of treatment for childhood cancer. Methodologic limitations may have led to underestimation of the risk for diabetes in previous studies. Understanding the extent of diabetes risk and identifying risk factors for diabetes is imperative for improving screening and prevention strategies in this population. Methods: We used the Ontario population-based cancer registry and administrative health databases to evaluate the risk of diabetes in adult survivors of childhood cancer. Diabetes was measured using a validated algorithm. Survivors were compared to age and sex-matched controls from the general population using a multivariable, cause-specific hazard regression model where death and development of another cancer was treated as a competing risk. Results: We identified 10,438 1-year survivors of childhood cancer diagnosed prior to age 21 years between January 1 st , 1990 and December 31 st , 2010. Mean age at cancer diagnosis was 10.7 years (standard deviation [SD] 6.8) and the mean follow up was 11.2 years (SD 6.9). In multivariable models adjusted for rurality and income status, cancer survivors had a 55% increased rate of developing diabetes compared to matched controls (HR 1.55, 95% CI 1.31-1.83). Individuals treated for cancer between age 6-10 years (HR 4.01, 2.33-6.91) had the highest increased rate for diabetes among age categories. Leukemia (HR 2.39, 1.74-3.27) and lymphoma (HR 1.61, 1.12-2.31) was also associated with an increased risk for diabetes compared to the general population. Conclusions: Our study provides evidence of an increased risk for diabetes in adult survivors of childhood cancer. The increased risk is highest among those treated at younger ages, and after treatment for leukemia and lymphoma. Future research is warranted to identify optimal ways for diabetes screening and prevention in this population. Given the burden of cardiovascular disease in survivors, identifying and treating diabetes early may help improve overall morbidity and mortality.
Prognostic value of intratumoral carbonic anhydrase IX (CA IX) expression in testicular germ cell tumors.
Authors: Michal Mego, Katarina Kalavska, Zuzana Cierna, Michal Chovanec, Martina Takacova, Daniela Svetlovska, Vera Miskovska, Jana Obertova, Patrik Palacka, Zuzana Sycova-Mila, Katarina Machalekova, Karol Kajo, Stanislav Spanik, Pavel Babal, Silvia Pastorekova, Jozef Mardiak
Journal: Journal of Clinical Oncology (2016)

e16060 Background: Testicular germ cell tumors (TGCTs) represent highly curable malignancy, however small proportion of patients fails to be cured with cisplatin-based chemotherapy. Carbonic anhydrase IX (CA IX) is up-regulated by hypoxia in several cancer types and correlates with poor prognosis. This translational study evaluated expression and prognostic value of CA IX in TGCTs. Methods: Surgical specimens from 228 patients with TGCTs were processed by the tissue microarray method and subjected to immunohistochemistry with the M75 monoclonal antibody. CA IX expression was evaluated in tumors versus adjacent normal testicular tissues and correlated with clinicopathological characteristics and clinical outcome. Results: CA IX expression was detected in 62 (30.2%) of TGCTs compared to 0 (0%) of normal tissue adjacent to testicular tumor (p < 0.001). The highest frequency of the CA IX expression was detected in teratoma (39.0%), followed by seminoma (22.7%), yolk sac tumor (22.2%), embryonal carcinoma (11.9%) and choriocarcinoma (7.7%). None of germ cell neoplasia in situ exhibited the CA IX expression. Patients without the CA IX tumor expression showed significantly better progression-free survival, but not overall survival, compared to patients with the CAIX expression (hazard ratio [HR] = 0.57, 95% CI 0.32 – 1.02, p = 0.037 and HR = 0.58, 95% CI 0.29 – 1.16, p = 0.088, respectively). There was no significant correlation between the CA IX expression and clinicopathological variables. Conclusions: The intratumoral CA IX expression can serve as a prognostic marker in the TGCT patients. This finding suggests that activation of the hypoxia-induced pathways could play important role in the treatment failure in TGCTs patients.
Impact of body mass index (BMI) and weight change after treatment in patients (pts) with HER2-positive (HER2+) early breast cancer (EBC): Secondary analysis of the ALTTO BIG 2-06 trial.
Authors: Samuel Martel, Matteo Lambertini, Dominique Agbor-Tarh, Noam Falbel Ponde, Andrea Gombos, Vicki Paterson, Florentine Hilbers, Larissa Korde, Anna Manukyants, Amylou C. Dueck, Christian Maurer, Martine J. Piccart-Gebhart, Alvaro Moreno-Aspitia, Christine Desmedt, Serena Di Cosimo, Evandro De Azambuja
Journal: Journal of Clinical Oncology (2018)

10067 Background: Obesity is associated with worse outcomes in hormone receptor-positive (HR+) EBC. However, the association between obesity and prognosis in HER2+ EBC remains unclear. We aimed to determine the impact of BMI at diagnosis and weight change after treatment on the outcomes of HER2+ EBC pts. Methods: ALTTO was a phase 3 trial of HER2+ EBC pts. BMI was collected at baseline and at the 2-year visit. WHO BMI categories were used: underweight < 18.5 kg/m2, normal weight 18.5-24.9 kg/m2, overweight 25-29.9 kg/m2, and obese ≥30 kg/m2. A change in weight from baseline of ≥5.0% and ≤5.0% was categorised as weight gain and weight loss, respectively. The impact of baseline BMI and weight change at the 2-year visit on disease-free survival (DFS), distant DFS (DDFS) and overall survival (OS) were investigated. Multivariate analyses adjusting for baseline pts and tumor characteristics were performed. The impact of weight change was assessed using a landmark analysis. Results: A total of 8,381 pts were included: 187 (2.2%), 3,797 (45.3%), 2,690 (32.1%), 1,707 (20.4%) were underweight, normal weight, overweight and obese at baseline, respectively. Compared to normal weight pts, being obese at diagnosis was associated with a significant worse DDFS (adjusted hazard ratio [aHR] 1.25; 95% CI 1.04-1.50) and OS (aHR 1.27; 95% CI 1.01-1.60), and a trend towards worse DFS (aHR 1.14; 95% confidence interval [CI] 0.97-1.32). Weight loss ≥5.0% at the 2-year visit was associated with poorer outcomes: DFS (aHR 1.34; 95% CI 1.05-1.71), DDFS (aHR 1.46; 95% CI 1.07-1.98) and OS (aHR 1.83; 95% CI 1.18-2.84). A similar trend, although not significant, was observed for weight gain ≥5.0%. Results were affected by hormone receptor status and menopausal status but not by anti-HER2 treatment. Grade 3-4 toxicities, pts with ≥1 serious adverse event and treatment discontinuation were more frequent in obese patients. Conclusions: In HER2+ EBC pts, obesity at baseline is a poor prognostic factor. Weight changes during treatment and follow-up impacts clinical outcomes: this calls for the need of dietary counselling and physical exercise in the context of survivorship programs. Clinical trial information: NCT00490139.
Prognosis of resectable pancreatic cancer based on systemic therapy sequence and regimen: An NCDB analysis.
Authors: Aileen Deng, Chun Wang, Steven J. Cohen, Jordan Michael Winter, Atrayee Basu Mallick
Journal: Journal of Clinical Oncology (2018)

4120 Background: While surgical resection can cure pancreatic cancer (PC), the majority of patients who undergo resection recur. As newer multi-agent chemotherapy regimens have evolved for metastatic PC, there has been increased interest in its use in the neoadjuvant (NAT) setting. However, U.S. clinical practice patterns vary widely. We evaluated the effect of systemic therapy sequence and regimen on prognosis in resected PC. Methods: Adult patients with resected, clinical stage I or II PC were identified in the NCDB from 2010-2015. Patients who received NAT followed by resection were matched by a minimum distance approach with those who underwent upfront resection (UR) with or without adjuvant therapy (AT) based upon demographics and disease-specific variables. OS was compared with Kaplan-Meier curves in matched cohorts. The effects of single-agent (SA) versus multi-agent (MA) chemotherapy (CT) on OS was evaluated using multivariate Cox proportional hazards regression model. Results: We identified 23,576 patients with clinical stage I or II resected PC. 3,446 patients who received NAT were matched with 3,446 patients who underwent UR. Those who received NAT had improved OS compared to those who underwent UR with or without AT (median survival time [MST] 27.9 versus 23.3 months, respectively; log-rank p < 0.0001). Among different treatment sequences, patients who received both NAT and AT had the longest OS compared to those who received either NAT or AT alone (MST 31.3 versus 26.2 versus 26.5 months, respectively; log-rank p < 0.0001). In patients treated with NAT alone, those who received MA CT had an improved OS compared to those who received SA CT (adjusted HR 0.72, 95% CI 0.64-0.81). In patients who received MA chemotherapy, MA NAT was associated with an 18% reduction in risk of death compared to those treated with MA AT (adjusted HR 0.82, 95% CI 0.73-0.93). Conclusions: In resectable PC, patients who received both NAT and AT had improved survival compared to those who receive NAT or AT alone. This supports future evaluation of maintenance therapy in the adjuvant setting. MA NAT was associated with improved survival compared to SA NAT. This supports current clinical practice and ongoing clinical trials.
TCT-408 Bifurcation and Ostial Optical Coherence Tomography Mapping (BOOM) – Analysis of a Novel Co-Registration Based Technique
Authors: Evan Shlofmitz, Alec Goldberg, Fernando Sosa, Jeffrey W. Moses, Kiran Reddy, None Thomas Pappas, Paul Lee, Akiko Maehara, Ziad Ali, Gary Mintz, Gregg Stone, Richard Shlofmitz, Allen Jeremias
Journal: Journal of the American College of Cardiology (2018)
Concomitant use of glucocorticoids in patients with metastatic castration resistant prostate cancer (mCRPC) treated with oral therapies.
Authors: Yongling Xiao, Ajay S. Behl, Lorie Ellis, Dominic Pilon, Patrick Lefebvre
Journal: Journal of Clinical Oncology (2016)

e16577 Background: This study aims to assess whether there was an association of concomitant GC usage with dose reduction in patients treated with abiraterone acetate (AA) or enzalutamide (ENZ). Methods: The MarketScan databases were used to conduct a retrospective analysis, in which mCRPC patients initiated on AA or ENZ (index date) between 10/2012 and 12/2014 with ≥ 6 months of continuous eligibility prior to index date and ≥ 1 PC diagnosis during the period of continuous eligibility were included. Patients were followed until either 12 months of follow-up, loss to follow-up, or end of data. Multivariate Cox proportional hazards models were used to assess whether there was an association between concomitant GC use and the risk of dose reduction in oral PC therapies – AA and ENZ. Relative dose intensity (RDI) was used to measure dose reduction, calculated as the ratio of the delivered dose intensity (i.e., dose per unit of time, calculated by dividing the total delivered dose by the time period over which the total dose was measured) to the standard dose intensity as recommended in the package insert for AA or ENZ. Results: Respectively, 2,591 and 807 patients initiated on AA or ENZ and formed the study population. During follow-up, GCs were used in 91% of AA patients and 32% of ENZ patients.. Cox models showed that use of GC was associated with a lower risk of dose reduction (hazard ratio [HR] = 0.49, and 0.44 [RDI ≤ 0.85, ≤ 0.80], respectively [all p < 0.01]). Similar results were obtained using Cox models stratified by AA or ENZ (HR = 0.39, 0.33, 0.50 and 0.54 for AA [RDI ≤ 0.85, 0.80] and ENZ [RDI ≤ 0.85, 0.80], respectively). Conclusions: GC usage was associated with a lower risk of dose reduction in oral mCRPC therapies for patients initiated on AA or ENZ. Additional research is needed to understand the protective effect of GC usage on dose reduction in patients receiving the oral mCRPC therapies in this study.
Mammography use in breast cancer survivors: An administrative claims study.
Authors: Kathryn Jean Ruddy, Lindsey R. Sangaralingham, Heather B. Neuman, Caprice Christian Greenberg, Rachel A. Freedman, Ahmedin Jemal, Sarah Schellhorn Mougalian, Katie N. Hunt, Tufia C. Haddad, Valerie Lemaine, Karthik Ghosh, Tina J. Hieken, Celine Vachon, Cary Philip Gross, Nilay D. Shah
Journal: Journal of Clinical Oncology (2017)

6531 Background: Annual mammography is recommended to screen residual breast tissue for new cancers and recurrent disease after treatment for early stage breast cancer. This study aimed to assess mammography rates over time in breast cancer survivors. Methods: We used administrative claims data from a large U.S. commercial insurance database, OptumLabs, to retrospectively identify privately- and Medicare Advantage-insured women with operable breast cancer who had residual breast tissue after definitive breast surgery between 2006 and 2015. We required coverage for at least 13 months following surgery. For each subsequent 13-month time period, we only included women without a loss of coverage, bilateral mastectomy, metastatic breast cancer diagnosis, or non-breast cancer diagnosis. We calculated the proportion of patients who had a mammogram during each 13-month period following breast surgery. We used multivariable logistic regression to test for factors associated with mammography in the first 13 months. Results: The cohort included 26,011 women followed for a median of 2.9 years (IQR 1.9-4.6) after surgery; 63.1% were less than 65 years of age, and 74.4% were white. In their first year of follow-up, 86% underwent mammography, but by year 7, this decreased to 73%. Fewer than 1% underwent MRI instead of mammography. In multivariable analysis, mammograms were less likely during the first year after surgery among women aged &lt; 50 years (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.6 to 0.8), African Americans (OR, 0.7; 95% CI, 0.7 to 0.8), patients who underwent mastectomy (OR, 0.7; 95% CI, 0.6 to 0.7), and patients residing in the Western part of the country (OR, 0.9; 95% CI, 0.7 to 0.9). Those with 1-2 comorbidities were more likely (OR, 1.1; 95% CI 1.1-1.2) than those with none to have a mammogram during that period. Mammography use did not differ significantly by year of diagnosis (2006-2015). Conclusions: Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance mammography. Mammography use falls as the time from the early stage breast cancer diagnosis increases. Understanding factors associated with lack of mammographic screening may help improve survivorship care.
TCT-54 The distribution of high-risk plaques with respect to artery stenosis in non-culprit non-ischemic native coronary lesions of diabetic patients – data from COMBINE OCT-FFR study
Authors: Tomasz Roleder, Balazs Berta, Alexander Ijsselmuiden, Fernando Alfonso, Floris Kauer, Rik Hermanides, Wojtek Wojakowski, Elvin Kedhi
Journal: Journal of the American College of Cardiology (2018)
Recurrence of eyelid tumor after Mohs vs. frozen sections.
Authors: Alice Song, Julia Song, Trisa maria Palmares, Harold Song, Eric Hong, Michael Song
Journal: Journal of Clinical Oncology (2018)

e21594 Background: Malignant eyelid tumors are common, as the eyelids are exposed to environmental factors. The three most common malignant tumors are basal cell, squamous cell, and melanoma. The standard treatment is resection. However, if there are positive margins, Mohs surgery or frozen sections are methods to remove the tumor in its entirety. Both techniques are very similar. Frozen section techniques examine the edges of the specimen. This study investigates the prevalence of malignant eyelid tumors in a referral practice, the location, the type of tumor, the treatment and the long-term results, including recurrence function and function of the eyelid. Methods: This is a 10-year retrospective study of patients with biopsy-proven adnexal malignant from a single surgeon in a referral practice. The patients underwent frozen section removal of tumor with reconstruction or reconstruction following Mohs resection by a dermatologist. Pathology results were reviewed from 1 of 3 hospitals with in-house pathologists. Results: There was a total of 57 patients. 40 were male. 17 had Mohs removal with eyelid reconstruction, and 36 had frozen sections. 50 were Caucasian, 4 were Latino, and 2 were Asian. A majority (48) had squamous cell carcinoma; 4 had basal cell, and 2 had melanoma, one had mucinous carcinoma, 2 had sebaceous cell carcinoma, and 2 had lymphoma. The recurrence rates for frozen section patients was 22% ?HIGH) with an average time to recurrence at 2 years. The recurrence rate for Mohs resection patients was 19%. This was not statistically significant (p=0.23). It was noted that the recurrence rate was highest at one of the major medical centers (p<0.05). Conclusions: Both Mohs resection and frozen sections successfully remove tumors. The recurrence of tumor may be higher in frozen section patients, but this was not significant. However, the recurrence was higher depending on the medical center, indicating that pathologic analysis may be a factor. Further studies are warranted.
Preemptive rituximab prevents long-term relapses in immune-mediated thrombotic thrombocytopenic purpura
Authors: Matthieu Jestin, Ygal Benhamou, An-Sofie Schelpe, Elien Roose, François Provôt, Lionel Galicier, Miguel Hié, Claire Presne, Pascale Poullin, Alain Wynckel, Samir Saheb, Christophe Deligny, Aude Servais, Stéphane Girault, Yahsou Delmas, Tarik Kanouni, Alexandre Lautrette, Dominique Chauveau, Christiane Mousson, Pierre Perez, Jean-Michel Halimi, Anne Charvet-Rumpler, Mohamed Hamidou, Pascal Cathébras, Karen Vanhoorelbeke, Agnès Veyradier, Paul Coppo
Journal: Blood (2018)