tbuckley/cabot-search huggingface dataset:
Tumor associated carbohydrate antigens in prostatic adenocarcinoma (PAC): Correlation of sialyl-Tn with malignant phenotype.
Authors: Silva Kristo, Zuzana Brnakova, Radoslav Goldman, Renhuizi Wei, Joeffrey J Chahine, Kyungmin Ko, Jillian M Prendergast, Daniel T Dransfield, Bhaskar Kallakury
Journal: Journal of Clinical Oncology (2018)

e24279 Background: Epithelial cancers express various tumor-associated carbohydrate antigens. Diagnostic and prognostic utility of expression of these antigens has been studied in cancers of thyroid, breast and colorectal origin. We investigated the expression of sialyl-Tn (STn, Sia01 antibody) and T (3C9 antibody) carbohydrate antigens in PAC because of the increased expression of ST6GalNAc1 enzyme in this malignancy. Methods: Immunohistochemical staining for STn (164 cases) and T (subset of 100 cases) antigens was performed on formalin-fixed paraffin-embedded sections of prostatic resections and biopsies from patients with PAC. Staining intensity and percentage positivity was semiquantitatively scored in both benign and malignant glands and correlated with tumor grade. Results: Expression of STn significantly increased in the tumor glands while T decreased in the tumor compared to benign glands (p < 0.01). Using a cut off of 10% positivity, STn expression correlated with lower Gleason score ( < 7, p = 0.01) with loss of staining in 21% of high grade tumors. Foci of prostatic intraepithelial neoplasia showed expression of STn and luminal secretions were strongly positive for this antigen. At a threshold of 10% expression, STn positivity distinguishes malignant from adjacent benign glands with 48% sensitivity and 95% specificity. In the subset of 100 cases tested, there was inverse correlation between STn and T expression (STn positive/T negative) in the tumor glands. Conclusions: Majority of the malignant glands express STn with a distribution greater than in the benign glands. This is accompanied by lower expression of T-antigen likely due to increased activity of the ST6GalNAc1 sialyltransferase in prostate tumors. Despite the low sensitivity and negativity in some grade 4 and 5 tumors, the ligand may be a potential therapeutic target as it seems to initiate carcinogenesis. Similar to racemase/AMACR, STn staining may be of diagnostic use in distinguishing malignant from benign glands in prostate tissue evaluation. Positive prostatic secretions suggest a potential for non-invasive monitoring of early stage tumors.
Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1
Authors: Andrew L Mammen, Arun Rajan, Katherine Pak, Tanya Lehky, Livia Casciola-Rosen, Renee N Donahue, Lauren M Lepone, Anastasia Zekeridou, Sean J Pittock, Raffit Hassan, Jeffrey Schlom, James L Gulley
Journal: Annals of the Rheumatic Diseases (2018)

Immune checkpoint inhibitors enhance the immune response against tumours but may also trigger immune-related adverse events (IRAEs). Myositis is a rare IRAE. For example, creatine kinase (CK) elevations occurred in just 0.3% of those treated with avelumab, an antiprogrammed death-ligand 1 antibody.1 

Thymomas are the most common anterior mediastinal masses in adults. Since effective systemic therapies for thymic epithelial tumours are lacking, we included seven patients with recurrent thymoma and one patient with recurrent thymic carcinoma in a phase I trial of avelumab (NCT01772004). Details regarding this trial have been published separately.2 

Myasthenia gravis and myositis occur in up to 30% and 5% of patients with thymoma, respectively.3 Although no patient had a history of autoimmunity or weakness and each had normal baseline CK levels, four patients developed weakness and elevated CK levels, ranging from 762 IU/L to 16 037 IU/L, within 5 weeks of avelumab administration (see online supplementary text and table 1). CK levels normalised in patients within weeks of stopping avelumab and starting immunosuppressive therapy. Of note, …
Prognostic implication of minimal residual disease in AML.
Authors: Aisha Al-Khinji, Carole Shaw, Roland B. Walter, Pamela Sue Becker, Paul Hendrie, Kathleen Kay Shannon Dorcy, Elihu H Estey
Journal: Journal of Clinical Oncology (2016)

7016 Background: Patients with AML who, although in complete remission (CR) by conventional criteria after receipt of “intensive therapy” have measurable residual disease, (MRD) are at increased risk of relapse and subsequent death. The same is true for patients who achieve only CR with incomplete count recovery (CRi). Thus, there is increasing sentiment that the goal of initial therapy should be CR without MRD (CR, MRD-). Here, we were interested in whether the proportion of responses that are CR, MRD– changed with increasing number of induction courses in patients with newly-diagnosed (ND) or relapsed/refractory (R/R) AML given induction therapy containing cytarabine at doses ≥ 1g/m2. Methods: We review here 434 patients (328 newly diagnosed (ND), 106 relapsed or refractory (R/R) who achieved CR +/- MRD or CRi (+/- MRD as their best response. MRD was assessed using multiparameter flow cytometry. Results: For ND patients the relation between best response and courses to best response i is shown in the table. Conclusions: Hence if a response occurs among ND patients the probability that it will be CR without MRD decreases if more than one course is needed to see the response (p < 0.0001). The percent of all responses occurring on courses after a first was similar in ND and R/R patients (33% vs. 36% respectively). However there was more tendency for responses occurring on courses after a first to be CR without MRD in R/R patients (p = 0.09) than in ND patients. These data suggest there should be more hesitancy in administering a second course of identical therapy to ND patients than to R/R patients if the goal of therapy is to produce CR without MRD. Courses to best response Number of Responses CR, MRD- CR MRD+ CRi MRD- CRi MRD+ ND patients 1 219 162 (74%) 30(14%) 15 (7%) 12 (5%) 2 79 40(51%) 23(29%) 8 (10%) 8 (10%) > 2 30 12 (40%) 10(33%) 5(17%) 3(10%) R/R patients 1 71 33(46.5%) 11(15.5%) 16(23%) 11(15%) 2 19 6(31%) 2(11%) 5(26%) 6(32%) > 2 16 6(38%) 3(19%) 3(19%) 4 (25%)
Real-world data (RWD) on tumor response (rwTR) in advanced non-small cell lung cancer (aNSCLC) patients receiving cancer immunotherapy and targeted therapies.
Authors: Michael Lu, Natalia Sadetsky, Peter Lambert, Sam Whipple, Michael Dennis Taylor, Todd Riehl, Gregory J. Riely
Journal: Journal of Clinical Oncology (2018)

6578 Background: Overall response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) is an established early efficacy endpoint used in clinical trials. Comparison of real world tumor response (rwTR) and ORR can provide important insights for health professionals, regulators, and researchers. Methods: We retrospectively analyzed electronic health records (EHRs) of patients with metastatic or recurrent NSCLC treated with epidermal growth factor receptor (EGFR)-targeted therapy (afatinib or erlotinib) and a programmed cell death 1 (PD-1) inhibitor (nivolumab), as well as a subset of BRAF mutation (BRAFmut)–positive patients in the Flatiron (FIH) EHR and FIH-Foundation Medicine (FMI) Clinico-Genomics database (CGDB) from 2011 to 2017. Structured and unstructured data elements from FIH EHRs were processed via technology-enabled abstraction. RwTR was based on abstraction of clinician’s assessment of radiographic evidence. Results: All patients with rwTR (CGDB, n=595; BRAFmut, n=30) were evaluated. Observed rwTR rates for the relevant patient populations are described in the Table. Conclusions: This analysis demonstrates the potential of leveraging routinely captured EHRs to provide RWD on treatment effectiveness in patients with NSCLC. These results show that rwTR for targeted and immunotherapies appear to correlate well with RECIST ORR rates in pivotal clinical studies matched by EGFR mutation status, treatment, and line of treatment. Future work includes expanding similar rwTR evaluation to more treatment contexts. ORR by line of therapy. rwTR Reference clinical study/ population/ RECIST response EGFR mut EGFR wt Afatinib 1L, n = 29 56% (14/25) 25% (1/4) LUX-Lung 3/ EGFR mut/ 56% 2L, n = 23 30% (6/20) NA Erlotinib 1L, n = 106 69% (60/86) 35% (7/20) EURTAC/ EGFR mut/ 65% ENSURE / EGFR mut/ 63% 2L, n = 34 53% (8/15) 15% (3/19) BR21/ EGFR (any)/ 9% Nivolumab All comers 1L, n = 63 33% (21/63) - Checkmate 026/ 1L/ 26% 2L, n = 131 28% (37/131) - Checkmate- 017/ 2L+ squamous/ 20% Checkmate- 057/ 2L+ nonsquamous/ 19% 3L, n = 55 15% (8/55) - Checkmate- 017/ 2L+ squamous/ 20% Checkmate- 057/ 2L+ nonsquamous/ 19%
Understanding melanoma patients’ needs in the new era of treatment: A mixed-methods approach.
Authors: Ling Na, Elisabeth Croft Richards, Jessy Gao, Brandon Bosch, Dale Hample
Journal: Journal of Clinical Oncology (2018)

e22132 Background: Advances in cancer immunotherapy and targeted therapy have improved clinical outcomes for patients with advanced melanoma. However, there is a lack of understanding of patients’ emerging needs in this new treatment landscape. The purpose of this study was to explore melanoma patients’ medical and psychosocial needs and perceived barriers to care based on their online postings. Methods: A large online support forum for melanoma patients was chosen for analysis (https://www.melanoma.org). A random week from each month between June and November, 2017 was selected (6 weeks total). Within the sampling frame, a total of 1272 messages were collected, with 201 unique IDs, excluding the anonymous IDs. Patient sociodemographic and clinical characteristics were analyzed. Researchers conducted a content analysis to identify emerging themes, analyzed the frequency distribution of these themes, and created a thematic map. Inter-coder reliability was established on coding of > 10% of sample data, and each message was coded by two coders to maintain agreement. Results: Emerging themes related to medical and psychosocial needs were identified as treatment, side-effect management, diagnosis, exposure, stress management, work management, disclosure, insurance and costs, patient empowerment, and emotional support. Perceived barriers to care included financial barriers, transportation barriers, limited treatment options, long wait time, and provider-related barriers. Subthemes were also explored. Immunotherapy was the most discussed therapy related to treatment and side-effect management. Emotional support, treatment, side-effect management, and diagnosis were the most prevalent themes. Perceived overall barriers to care were associated with negative emotion, patient empowerment, and treatment. Negative emotion was associated with barriers and diagnosis. Conclusions: Unobtrusive observation of online patient forums offers an opportunity to understand melanoma patients’ care needs in real-time. These forums can be used as a meaningful approach to inform real-world interventions, such as physician and patient education and support programs that ameliorate barriers to care.
The clinical outcome of second generation anti-hormonal therapy in patients with metastatic castrate-resistant prostate cancer following CHAARTED regimen.
Authors: Jaspreet Chahal, Thomas Paul Bradley, Cristina Sison, Xinhua Zhu
Journal: Journal of Clinical Oncology (2018)

e17044 Background: Prostate cancer (PC) is the most common malignancy in men. Treatment for metastatic PC historically had been androgen-deprivation therapy (ADT) alone. Docetaxel and ADT became standard of care for treating metastatic hormone sensitive prostate cancer (mHSPC) after CHAARTED trial was reported in 2014. Progression-free survival (PFS) and overall survival (OS) were significantly longer with combination of docetaxel and ADT. Treatment for metastatic castrate-resistant prostate cancer (mCRPC) after docetaxel in hormone sensitive setting is not established. Second generation antihormonal drugs, enzalutamide and abiraterone, were established in treatment of mCRPC before CHAARTED, but the clinical outcome of mCRPC patients after chemo-hormonal therapy has yet to be reported. Methods: We are conducting a single institution, retrospective study of patients who developed mCRPC after docetaxel-ADT and then treated with abiraterone or enzalutamide, based on clinician’s choice, from 2016 to 2018. Primary endpoint is OS. Secondary endpoints are radiographic PFS, time to prostate-specific antigen (PSA) progression, and PSA response rate. Results: Of the 17 patients identified, 13 got abiraterone and 4 got enzalutamide. Four of thirteen patients progressed on abiraterone with median PFS of 8.5 months (mos). Median time to PSA progression was 7 mos. The longest PFS was 16 mos on abiraterone. No patient on enzalutamide progressed to date. PSA response rate was 69% for abiraterone and 75% for enzalutamide. OS has not been reached. Conclusions: Our results show increased radiographic PFS of 3 mos on abiraterone as first line treatment for mCRPC after CHAARTED protocol as compared to results of trial COU-AA-301 in which mCRPC patients received abiraterone second line after docetaxel. Time to PSA progression was 7 mos here and 10 mos in COU-AA-301, however our study has limited patients. Our results indicate the potential benefit of giving abiraterone in mCRPC after docetaxel-ADT. Chemo-hormonal therapy is standardized initial treatment for mHSPC, therefore, the use of second generation antihormonal drugs to treat mCRPC requires further exploration.
Investigating hospice utilization for oncology patients using a claims database.
Authors: Margaret C. Horvath, Rebecca Wurtz, Beth A. Virnig, Nicole Engel-Nitz, Lincy S. Lal, Caitlin Elliott, Stacey DaCosta Byfield
Journal: Journal of Clinical Oncology (2018)

6570 Background: Cancer is the second leading cause of death in the United States and also one of the most expensive diseases to treat. End of life care is often low in quality despite the availability of palliative care, advanced care planning, and hospice. Research studying Medicare beneficiaries has found most patients receive hospice, but with short length of stays (LOS). Limited studies exist on hospice use among non-elderly (18-64 year old) cancer patients with commercial insurance. Methods: Retrospective review of claims databases of Optum (Eden Prairie, MN) affiliated insurers identified patients, aged 18-64, who died of cancer between September 1, 2011 and August 31, 2016. Mortality information was sourced from the Social Security Administration Death Master File. Patients were identified as receiving 6 months of continuous insurance enrollment (CE) and 12 months CE prior to death date. Patients were described by cancer diagnosis and hospice LOS at the end of life. This project was considered exempt by the IRB at the University of Minnesota. Results: Among 15,330 cancer patients who died during this study period, we identified 3,730 patients aged 18-64 at time of death with 6 months of CE and a subset of 3,263 patients with 12 months CE. Our study included 99.5% of the target population. In the 6 month CE cohort, 2,263 (60.67%) patients received hospice with a median hospice LOS of 13 days, and 38.93% of patients received hospice received ≤7 days. We observed variation in hospice use by cancer type ranging from 49.11% (prostate cancer) to 66.84% (pancreatic cancer) p < 0.001. Median LOS ranged from 8 days (liver cancer) to 16 days (colorectal cancer). Similar results were found for the 12 month CE cohort. Conclusions: In our database, a majority of the non-elderly oncology patients received some hospice. We observed that over a third of the patients that received hospice had short LOS (≤7 days), representing an opportunity for quality improvement. More studies are needed to improve the quality of EOL care for non-Medicare oncology patients in the U.S.
Phone call for chemotherapy validation in outpatient unit as a way to optimize health care without compromising patients' satisfaction and quality of life.
Authors: Patricia Marino, Rajae Touzani, Myriam Palomares, Maria-Antonietta Cappiello, Anne Deborah Bouhnik, Najoua Guelmani, Magali Provansal, Martine Vittot, Slimane Dermeche, Farida Braham, Simon Launay, Anthony Goncalves, Pauline Ries, Jean-Marc Extra, Marine Gilabert, Jean Francois Moulin, Gwenaelle Gravis
Journal: Journal of Clinical Oncology (2017)

6588 Background: Patients’ satisfaction is known to be closely linked to the time spent with the physician. However, longer waiting times may be a source of dissatisfaction as well as organizational dysfunctions of the outpatient unit. Is a validation of chemotherapy by phone call instead of a medical consultation with a senior physician before chemotherapy (CT) is feasible without compromising patients’ satisfaction and quality of life? Methods: Pts with OMS &lt; 1, able to respond to phone call, &lt; 76 years, receiving day 8 and or d15 of CT were included. We enrolled 343 pts in a before/after study between 2013 and 2016. In the “before” step (control arm), 168 pts had a systematic physician consultation the same day before CT administration. In the intervention arm 175 pts received a phone call by a junior physician the day preceding CT administration. A specific questionnaire for CT -related toxicity of the previous cycle was recorded and CT was validated or not by physician. The day after, pts received prepared CT without appointment with the oncologist and delay in administration for already prepared CT. At the end of CT protocol, socio demographics, patients’ satisfaction (In-PatSat32) and health status (EQ-5D) questionnaires were completed by patients. Results: Questionnaires were completed by 83% and 74% in before and after step respectively, 241 questionnaires were analyzed. Satisfaction with care showed similar In-PatSat32 scores between arms, for satisfaction with: physician, nurse, organization and services. No differences of perceived health status and toxicity were observed between both groups, but patients’ time spent in hospital was lower in the intervention group versus the control group, (p = 0.007). Conclusions: An alternative care pathway implementing phone calls before CT administration if feasible without compromising pts’ satisfaction, quality of life and toxicity. We believe that saving time of pts, physicians and pharmacists is a way to optimize the model of care in outpatient unit, particularly in the immunotherapy area with more pts received intra venous treatment, probably for a long time.
P04.07 Mild-thermic intracranial drug delivery using biodegradable wireless electronics for glioblastoma treatment
Authors: H Cho, C Park, J Kim, D Kim, S Choi
Journal: Neuro-Oncology (2018)

Treatment of glioblastoma (GBM) is extremely challenging because the efficacy of conventional chemotherapy to tumor cells is limited by the blood-brain barrier (BBB). Implantation of biodegradable polymeric wafers containing anti-cancer drugs near the tumor cells was proposed as an alternative chemotherapy route, since it bypasses the BBB. However, more dramatic improvement of the therapeutic efficacy is needed. We developed a mild-thermic intracranial drug delivery device using the biodegradable wireless electronics integrated with a flexible polymeric drug reservoir. The oxidized-starch-based patch-type bioresorbable electronic implant is used in association with wireless mild-thermic actuation. Therapeutic effects of the device were tested in mouse and canine GBM models in vivo. It significantly enhances the drug penetration depth and the drug release duration while minimizing the unintended drug delivery to the cerebrospinal fluid. The improved survival rate and tumor suppression are confirmed with the mouse human xenograft GBM model in vivo. Successful mild-thermic actuation in a canine GBM model presents the potential for human GBM therapy. We believe that the mild-thermic intracranial drug delivery strategy using the BEP based on novel materials and device designs and with the customized therapeutic guidelines provides a new innovative approach to the effective treatment of GBM. The current study will be of significant interest to researchers involved in a number of fields, including those focusing on controlled drug delivery, biodegradable materials, brain tumor treatment, implantable medical devices, and soft bioelectronics.
A retrospective observational study of intraductal breast papilloma and its coexisting lesions: A real-world experience.
Authors: Mao Xiaoyun, Zhe Sun, Chuifeng Fan, Feng Jin
Journal: Journal of Clinical Oncology (2018)

e13558 Background: Breast intraductal papilloma comprises a wide spectrum of lesions, ranging from benign intraductal papilloma to papilloma with foci of atypia or papillary carcinoma, it can harbor occult malignancy also. The management of papilloma remains controversial. Methods: The current study is a retrospective analysis to investigate the intraductal breast papilloma and its coexisting lesions in the real-world practice. We identified 4450 intraductal breast papilloma patients with surgical excision from November 1999 through July 2017 at the First Affiliated Hospital of China Medical University. Results: 18.36% (817/4450) intraductal breast papilloma coexisting with malignant lesions of breast, 37.33% (1660/4450) coexisting with atypia hyperplasia, 25.24% (1123/4450) coexisting with benign lesions, only 19.10% (850/4450) without concomitant. 36.80% intraductal breast papilloma had nipple discharge, 51.46% had palpable breast mass. 16.45%had nipple discharge and palpable breast mass meanwhile. 28.18% experienced discomfort or asymptomatic. 98.99% had ultrasonic abnormality and 53.06% had intraductal hypoechoic by ultrasonic. 31.89% had mammographic distortion and 14.45% had microcalcification in mammography. The intraductal breast papilloma with malignancy had significantly relations with clinical manifestations such as palpable breast mass (p < 0.01), the concurrent nipple discharge and palpable mass (p < 0.01). The coexisting malignancy also related with ultrasonic abnormality (BIRADS 4C and 5) (p < 0.01), mammographic distortion and microcalcification in mammography, not related with the intraductal hypoechoic by ultrasonic. Conclusions: Although the sonography and mammography has been proven crucial in identifying the papilloma and its coexisting lesions, more than half of intraductal papilloma coexisting with malignancy or atypia hyperplasia, and the clinical information for papilloma and its coexist lesions are nonspecificity, we recommend a more aggressive approach including surgical excision of all benign intraductal papillary lesions.
Half of all European clinical trials break rules on reporting results within a year
Authors: Jacqui Wise
Journal: BMJ (2018)

Half of all clinical trials fail to report results within a year of completion as required under European Union rules.

Research published in The BMJ shows that pharmaceutical companies are far better at complying with the reporting rules than non-commercial sponsors such as universities.1

In 2012, the European Medicines Agency said that results of trials must be posted on the EU Clinical Trials Register within a year of the end of the trial and within six months of completion for trials involving children. The final deadline for compliance was 21 December 2016.

Researchers from the DataLab at the University of Oxford found that of 7274 trials on the EU clinical trials database which were completed and where results were due only 49.5% had reported results. The study shows that 68.1% of …