tbuckley/cabot-search huggingface dataset:
New concepts in the diagnosis and management of choroidal metastases
Authors: Thibaud Mathis, Pauline Jardel, Olivier Loria, Benoit Delaunay, Anh-minh Nguyen, Francesco Lanza, Carlo Mosci, Jean-Pierre Caujolle, Laurent Kodjikian, Juliette Thariat
Journal: Progress in Retinal and Eye Research (2018)

The most frequent site of ocular metastasis is the choroid. The occurrence of choroidal metastases has increased steadily due to the longer survival of metastatic patients and the improvement of diagnostic tools. Fundoscopy, ultrasonography, and fluorescein angiography are now complemented by indocyanine green angiography and optical coherence tomography. Choroidal tumor biopsy may also confirm the metastatic nature of the tumor and help to determine the site of the primary malignancy. There is currently no consensus on the treatment strategy. Most patients have a limited life expectancy and for these complex treatments are generally not recommended. However, recent advances in systemic therapy have significantly improved survival of certain patients who may benefit from an aggressive ocular approach that could preserve vision. Although external beam radiation therapy is the most widely used treatment, more advanced forms of radiotherapy that are associated with fewer side effects can be proposed in select cases. In patients with a shorter life expectancy, systemic therapies such as those targeting oncogenic drivers, or immunotherapy can induce a regression of the choroidal metastases, and may be sufficient to temporarily decrease visual symptoms. However, they often acquire resistance to systemic treatment and ocular relapse usually requires radiotherapy for durable control. Less invasive office-based treatments, such as photodynamic therapy and intravitreal injection of anti-VEGF, may also help to preserve vision while reducing time spent in medical settings for patients in palliative care. The aim of this review is to summarize the current knowledge on choroidal metastases, with emphasis on the most recent findings in epidemiology, pathogenesis, diagnosis and treatment.
From <i>Muridae</i> to <i>Homo</i>: Patient-researcher engagement in the research translation continuum.
Authors: Stephanie Michaud, Louise Binder, John C. Bell, Kathy Brodeur-Robb, Patrick Sullivan, Marcus O. Butler
Journal: Journal of Clinical Oncology (2018)

e23000 Background: Patient-researcher partnership, achieved through the BioCanRx-Cancer Stakeholder Learning Institute model, will ultimately improve trial design and implementation, and improve research in general. Methods: Inspired by a similar successful patient-researcher engagement initiative in the field of HIV, the BioCanRx-CSA Learning Institute brings cancer patients and researchers together at the annual Summit for Cancer Immunotherapy. Researchers are exposed to the realities of the cancer patient experience and patients are familiarized with research concepts in immuno-oncology. Results: Researchers and patients build partnerships and skills in knowledge exchange and translation, and nurture a growing culture in patient engagement in research. Conclusions: These patient-researcher partnerships will attract more participants to clinical trials and retain their interest longer. It helps trials better align with health care policies and navigate through government approval systems. It also builds capacity for scientific discourse and knowledge translation between patients and researchers that ultimately result in improved trial design. Learn why representatives from the immuno-oncology researcher and patient communities in Canada partnered with BioCanRx, a Canadian immuno-oncology research network, to develop and pilot the BioCanRx-Cancer Stakeholder Alliance Learning Institute.
External validation of prognostic indices for aggressive adult T-cell leukemia/lymphoma (ATL-PI/JCOG-PI) in Okinawa.
Authors: Keita Tamaki, Satoko Morishima, Shogo Nomura, Takeaki Tomoyose, Sawako Nakachi, Yukiko Nishi, Naoya Taira, Takashi Miyagi, Kaori Karimata, Masayo Ohama, Atsushi Yamanoha, Kazumitsu Tamaki, Masaki Hayashi, Jun-nosuke Uchihara, Kazuiku Ohshiro, Yoshitaka Asakura, Megumi Kuba-Miyara, Kennosuke Karube, Takuya Fukushima, Hiroaki Masuzaki
Journal: Journal of Clinical Oncology (2017)

e19036 Background: Aggressive adult T-cell leukemia/lymphoma (aATL) has an extremely poor prognosis (median OS, 8-10 months). Okinawa, Japan’s only subtropical region, is hyperendemic for aATL. Recently, we demonstrated poorer outcomes among aATL patients in Okinawa compared with patients elsewhere in Japan, and a possible association of strongyloidiasis with ATL-related death. Two prognostic indices (PIs)—ATL-PI and JCOG-PI—have been developed using a database of national surveys and clinical trials. However, aATL patients in Okinawa were not included. This study aimed to validate these PIs using an Okinawa database. We also investigated the impact of strongyloidiasis on aATL patient survival. Methods: We constructed a clinical database of aATL patients from 7 institutions in Okinawa diagnosed between January 2002 and December 2011. The study endpoint was OS. Standard survival analysis methods (Kaplan-Meier method, log-rank test, and Cox proportional-hazards model) were used. Results: The study involved 433 evaluable patients (median OS, 6 months). Risks according to the two PIs in each patient were not always consistent (Table), but both PIs stratified aATL patients by risk. Three-year OS rates for ATL-PI were 35.9% (low-risk, n=66), 10.4% (intermediate-risk, n=256), and 1.6% (high-risk, n=111); rates for JCOG-PI were 22.4% (moderate-risk, n=176) and 5.3% (high-risk, n=257). Strongyloidiasis had little impact on OS (HR and 95% CI from univariate Cox analysis, 1.22 and 0.90-1.66, respectively). Multivariable Cox analysis returned almost the same factors as had been screened out in the previous studies to construct the two PIs. Conclusions: ATL-PI and JCOG-PI were well reproducible in Okinawa database. Strongyloidiasis did not affect prognosis in aATL patients. ATL-PI identifies low-risk aATL patients more clearly than JCOG-PI, and both identify high-risk patients with extremely poor prognosis. These will be useful to devise novel treatment strategies based on risk stratification of all Japan/world aATL patients. [Table: see text]
Molecular testing, frequency of molecular alterations and targeted 1st-line treatment of patients with non-small cell lung carcinoma in Germany: First results from the prospective German Registry CRISP (AIO-TRK-0315).
Authors: Frank Griesinger, Wilfried Ernst Erich Eberhardt, Arnd Nusch, Marcel Reiser, Mark-Oliver Zahn, Norbert Walter Marschner, Martina Jänicke, Annette Fleitz, Lisa Spring, Joerg Sahlmann, Aysun Karatas, Annette Hipper, Wilko Weichert, Achim Rittmeyer, Martin Metzenmacher, Cornelius F. Waller, Martin Sebastian, Michael Thomas
Journal: Journal of Clinical Oncology (2018)

e21236 Background: Treatment in non-small cell lung cancer is quickly evolving and new agents make it to the routine practice at a rapid pace. It is of high interest to patients (pts), physicians and reimbursement institutions to investigate how outcomes from clinical trials translate into routine practice. Methods: The prospective, national clinical research platform CRISP recruits pts in currently 144 representative cancer centres in all therapeutic sectors in Germany. More than 8000 pts will be recruited and followed until death or up to a maximum of 3 years, respectively. Data from 823 pts recruited by 89 centers by June 30th, 2017 was analysed regarding molecular testing and 1st-line targeted treatment regimens. Results: Median age was 67 years, 61% of pts were male. 12% of pts were never smokers. 79% of pts had non-squamous carcinoma (nsqc), 21% squamous carcinoma (sqc). In pts with nsqc (n = 653) molecular test rates for EGFR, ALK, and ROS-1 were 73%, 70%, and 53% respectively. In pts with sqc (n = 170) molecular test rates for EGFR, ALK, and ROS-1 were 23%, 21%, and 15%, respectively. Test rates for PD-L1 increased from 23% in 2016 to 48% in the first half of 2017. For pts with nsqc for whom test results were available at time of analysis, an EGFR alteration was detected in 15% (n = 71), an ALK alteration in 8% (n = 37), and a ROS-1 alteration in 3% (n = 10) of pts. 37% (n = 65) of pts for whom PD-L1 tumour proportion score (TPS) results were available had a TPS ≥50%. 71% of pts with any EGFR alteration (n = 72) were treated with a protein kinase inhibitor (most frequently afatinib) in 1st-line, 43% of pts with any ALK alteration (n = 38) with crizotinib. These rates also include treatment of some pts with uncommon and non-druggable EGFR or ALK alterations. Further details will be presented. In 2017, 73% of pts with a PD-L1 TPS ≥50% were treated with pembrolizumab in 1st-line. Conclusions: For the first time, CRISP presents real life data from all treatment sectors in Germany. Pts are frequently tested for molecular alterations, however a proportion of pts with molecular alterations does not start 1st-line treatment with a targeted therapy. Clinical trial information: NCT02622581.
The clinical significance of increase in SUVmax at delayed phase on 18F-FDG PET/CT scan in patients with early stage breast cancer.
Authors: Atsushi Kagimoto, Hideo Shigematsu, Takayuki Kadoya, Norio Masumoto, Akiko Emi, Yoshie Kobayashi, Morihito Okada
Journal: Journal of Clinical Oncology (2016)

11551 Background: The maximum standardized uptake values (SUVmax) on 18F-FDG PET/CT scan is useful to predict malignancy grades and the prognosis of patients with breast cancer, however the clinical significance of increase in SUVmax of delayed phase has not been determined. The aim of this study was to evaluate the association between the increase of SUVmax and, biological malignancy and prognosis in patients with early stage breast cancer. Methods: Of 817 consecutive cases with clinical stages I–III breast cancer, who underwent 18F-FDG PET/CT scan at early (PET-1) and delayed (PET-2) phase before surgery or induction therapy between January 2008 and August 2015, the association between the increase of SUVmax and, biological malignancy and prognosis was evaluated. The difference of SUVmax (ΔSUVmax) between both examination was calculated Results: The median follow up was 3 years. There were 39 (5%) cases diagnosed to have recurrent breast cancer at excision. Receiver operating characteristics curve analysis showed the cutoff value of the ΔSUVmax to predict breast cancer recurrence was 1.3 (AUC = 0.694, 95%CI: 0.605-0.784, p < 0.001). ΔSUVmax ≥ 1.3 was significantly associated with a higher T stage, node-positivity, higher nuclear grade, negative for estrogen and progesterone receptors, positive for HER2, and high Ki 67 index. The 3 year recurrence free survival was 97% for patients with ΔSUVmax ≥ 1.3 and 79% for patients withΔSUVmax < 1.3. In multivariate analysis, ΔSUVmax ≥ 1.3 was significantly associated with poor prognosis (hazard ratio, 3.1; 95% confidence interval, 1.6-6.6; P < .001). Conclusions: The increase of SUVmax was associated with high biological malignancy and poor prognosis in patients with early stage breast cancer.
Universal screening for mismatch repair deficiency in pancreatic cancer.
Authors: Aser Abrha, Rachel Koff, Teri A. Longacre, Navika Shukla, George A. Fisher, Sigurdis Haraldsdottir
Journal: Journal of Clinical Oncology (2018)

e16254 Background: Microsatellite instability (MSI) and mismatch repair deficiency (dMMR) are observed infrequently in pancreatic cancer (PC). Nevertheless, given the recent approval of anti-PD1/PDL1 checkpoint therapy for PC, it is important to screen and identify PC patients (pts) with dMMR. At Stanford Comprehensive Cancer Institute, all GI cancer pts have been universally screened for dMMR via immunohistochemistry since 01/2016. Here, we describe the clinical characteristics and outcomes of PC pts diagnosed with dMMR following implementation of a universal screening program. Methods: We conducted a retrospective review of all PC pts that were screened for dMMR from 01/2016 to 12/2017 at Stanford. Clinical and pathologic characteristics, treatment regimens and outcomes were recorded. Median with quartiles was used to calculate time to recurrence and follow up. Results: We identified 184 PC pts that were tested for dMMR. Of these, 15 (8%) pts (8 male, 7 female; median age 64 yrs) were found to have loss of expression or equivocal staining of one or more MMR proteins. Four of 15 (27%) pts had MSH2/MSH6 missing, 3/15 (20%) had MSH6 missing, and 1/15 (7 %) had MLH1/PMS2 missing. Seven of 15 (47%) pts were equivocal and after repeat staining, 1/7 (14%) was conclusive for dMMR and 6/7 (86%) were inconclusive due to lack of an internal positive control. Two pts (21%) were found to have Lynch syndrome on germline testing. Nine of 12 pts (75%) who underwent germline testing had no pathogenic variants. Seven of 15 (47%) pts had resectable disease and underwent a Whipple surgery. Of these, 3 /7 pts recurred with median time to recurrence of 14 months (Q1 11, Q3 19). Five of 8 (63%) pts with metastatic disease received pembrolizumab for in the 2nd line (3/5, 60%) or 3rd line and beyond (2/5, 40%). Three pts remain on treatment and 4/5 pts are alive with a median follow-up time of 14 months (Q1 8, Q3 27). Conclusions: A total of 8% of all screened PC pts had abnormal/equivocal MMR stains. Given that 75% of pts with germline testing had no pathogenic variants, it is possible that somatic mutations are a driver for dMMR phenotype in PC pts. Tumor testing may help clarify these unexplained dMMR cases.
Impact of central nervous system (CNS) involvement in advanced non-small cell lung cancer (NSCLC) patients (pts) treated with immune checkpoint inhibitors (ICI).
Authors: Lizza Hendriks, Clemence Henon, Laura Mezquita, Edouard Auclin, Roberto Ferrara, Clarisse Audigier-Valette, Cecile Le Pechoux, Angela Botticella, Samy Ammari, Anas Gazzah, Caroline Caramella, Julien Adam, David Planchard, Anne-Marie C. Dingemans, Benjamin Besse
Journal: Journal of Clinical Oncology (2018)

9066 Background: CNS metastases (CNS+) are frequent in NSCLC. Unfortunately, pts with (untreated) CNS+ are often excluded from ICI clinical trials so that their outcome on ICI is largely unknown. Methods: Retrospective data collection of all consecutive advanced ICI treated NSCLC pts in 2 French centers (nov 2012 – jan 2018). Progression free survival (PFS), overall survival (OS), intracranial objective response rate (iORR) and site of progression (PD) (CNS, extracranial or both) on ICI was collected. Active brain metastases (BM) were defined as non-irradiated new and/or growing lesions on brain imaging < 6 weeks before ICI start. Results: 483 pts were included, 65% male, 84% WHO PS 0-1, median age 64 years, 75% nonsquamous, 10% targetable driver mutations, 37% known PD-L1 (66% ≥1% expression). ICI treatment was median 2nd line (range 1-12), 95% had monotherapy PD(L)-1 inhibition. 137 pts (28%) had CNS+ at start ICI, 93% had only BM, the others had BM +/- leptomeningeal metastases. 42% had active CNS+. CNS+ pts had significantly more often a smoking history compared to CNS- pts (97 vs 91% p = 0.02), were younger (61 vs 64 years, p = 0.002), had more often adenocarcinoma (73 vs 62%, p = 0.04), and had a higher number of organs with metastases (3.3 vs 2.4, p < 0.001). Baseline characteristics did not differ for active vs non-active CNS+. With a median follow-up of 16 mo (95% CI 14-21 mo), median iORR, PFS and OS were not significantly different for those with CNS+ vs CNS- and active CNS+ vs non-active CNS+ (table). CNS failure was significantly more often in CNS+ pts vs CNS- pts (CNS only PD: 12% vs 5%, CNS and extracranial PD: 19% vs 6%: p < 0.001). The proportion of CNS failure did not differ significantly for active and non-active CNS+ (p = 0.12). Conclusions: (Active) CNS involvement does not negatively impact outcome on ICI although CNS failure is more common in CNS+ compared to CNS- pts. Pts, nr iORR in evaluable pts (%) Median PFS (95% CI), months p-value Median OS (95% CI), months p-value Total 483 2 (1-2) 10 (8-13) CNS status CNS-346 2 (1-2) 0.17 11 (8-16) 0.28 CNS+137 29 2 (1-3) 9 (6-13) Active CNS+57 29 2 (1-6) 0.71 8 (4-NR) 0.81 Non-active CNS+ 76 (4 no recent imaging) 29 1 (1-4) 10 (7-17)
Association of postoperative carcinoembryonic antigen (CEA) levels with survival in stage III colon cancer (CC): Post hoc analysis of the MOSAIC and PETACC-8 studies.
Authors: Edouard Auclin, Julien Taieb, Come Lepage, Thomas Aparicio, Roger Faroux, Enrico Mini, Gunnar Folprecht, Ramon Salazar, Maria Banzi, Christophe Louvet, Jean-Luc Van Laethem, Josep Tabernero, Tamas Hickish, Aimery De Gramont, Thierry Andre, Dewi Vernerey
Journal: Journal of Clinical Oncology (2018)

3568 Background: CEA is a CC biological marker that correlates with tumor stage. Its measurement is recommended for follow up after surgery. CEA above 5 ng/mL is of poor prognosis, however this cutoff is debated. Thus, we explored the prognostic value of postoperative CEA, in its continuous form. Methods: Eligible patients (pts) in MOSAIC and PETACC-8 studies had postoperative CEA available. The association between CEA and overall (OS) and disease free survival (DFS) was explored in the MOSAIC discovery cohort. It was assessed in 3 groups of pts (group 1: 0 to 1.30 ng/ml, n = 630; group 2: 1.30 to 5 ng/ml, n = 613; group 3: > 5 ng/ml, n = 49) by the Kaplan Meier method. Then relation of CEA and outcomes was continuously modelled with the restricting cubic splines (RCS) and multiple polynomial fractional (MFP) methods. Cox uni- and multivariate models were constructed. Findings were confirmed in a PETACC-8 validation cohort. Results: CEA was available in 1292 (96%) and 2477 (97%) pts in the discovery and validation cohorts, respectively with 96.2% and 95.9% of pts having a CEA below 5 ng/ml. In the discovery cohort, 5y OS were 79% (95%CI: 76-82), 70% (95%CI: 66-74) and 47% (95% CI: 35-64) in groups 1, 2 and 3, p < 0.001. Five-year DFS rate were 68% (95%CI: 65-72), 58% (95%CI: 54-62) and 42% (95%CI: 31-61), in groups 1, 2 and 3, p < 0.001. RCS and MFP showed that relation between CEA and survival was following a square root function, suggesting that values over 1.3 ng/ml were associated with prognosis. CEA over 1.3 ng/ml was an independent prognostic factor for OS and DFS (Table 1). All those results were confirmed in the validation cohort (Table 1). Conclusions: In 2 cohorts from large phase III trials, we showed that postoperative CEA was highly prognostic for OS and DFS. This was true for CEA levels above and below 5 ng/ml, suggesting that this single cutoff is not sufficient and that CEA should be used more precisely as stratification factors in future adjuvant trials. Hr (95%ci) from multivariate cox models. Discovery Validation OS DFS OS DFS Group 1 1 1 1 1 2 1.7 (1.3-2.3) 1.7 (1.3-2.2) 1.5 (1.2-1.8) 1.4 (1.2-1.7) 3 2.3 (1.3-4.4) 2.7 (1.5-4.7) 2.6 (1.7-3.8) 2.7 (1.9-3.8) All p-values < 0.001
TCT-569 Lower mortality after clinically significant bleeding in patients treated with reversible P2Y12 agent Ticagrelor: A comparative, all-comers, prospective, 2-year follow up study in patients treated with invasive strategy after acute coronary syndrome
Authors: Girish Viswanathan, James Russel, Nadia Dullaghan, Sotirios Dardas, Amit Taneja, Shabnam Venkat
Journal: Journal of the American College of Cardiology (2018)
Use and usefulness of the “know yourself” tool in outpatient cancer care.
Authors: Zackary Berger, Pooja Yesantharao, Alice Zhou, Amanda Blackford, Thomas J. Smith, Claire Frances Snyder
Journal: Journal of Clinical Oncology (2017)

e21558 Background: Patient-physician communication is important to cancer care. The National Coalition for Cancer Survivorship developed the Know Yourself Tool, a 2-page form, to improve patients’ understanding of goals of care and clinicians’ understanding of patients’ priorities/expectations. We assessed the Tool’s use and usefulness. Methods: This mixed-methods study at an academic cancer center recruited 1 medical, 1 radiation, and 1 surgical oncologist for each of 5 cancer types: breast, lung, gastrointestinal, genitourinary, head &amp; neck. For each clinician (n = 15), we recruited 2 control patients to observe usual care (n = 30) and then 4 intervention patients who were provided the Tool (n = 60); eligible patients were at a decision point in their care. Data were collected for the decision making visit via patient and physician post-visit surveys analyzed descriptively and visit recordings/transcripts to analyze: 1) option presentation 2) patient preference assessment 3) shared decision making elements 4) patient question asking opportunities. Results: Of 90 patients, 39 (43%) were female and 75 (83%) were white. Of the 60 intervention patients, 42 (70%) completed a post-visit survey: 15 (36% of respondents) reported using the Tool and 13 (31%) discussing the Tool. Nearly half (49%) reported the Tool helped them prepare for follow-up visits and know the importance of their perspective in decision making. Patients reported the Tool was easy to use (76%) and would recommend the Tool to others (52%). Clinicians reported on Tool use for 24 visits, finding it most helpful in identifying areas of concern (74%). Based on visit transcripts, physicians were more likely to describe certain options as more appropriate than others with intervention vs control patients. However, physicians were less likely to assess patient preference, engage in shared decision making behaviors, and provide opportunities for patients to ask questions with intervention vs control patients. Conclusions: Use and usefulness of the Know Yourself Tool was limited. Further work should identify barriers to Tool use, determine if there are specific subgroups for whom the Tool would be more useful, and further elucidate how the Tool affects patient-clinician interactions.
A retrospective analysis of the correlation between anti-CENP-F titres and malignant tumors.
Authors: Sandra Falagan, Alex Vlagea, Juan Moreno-Rubio, Enrique Casado, Maria Sereno
Journal: Journal of Clinical Oncology (2018)

e13565 Background: In last years, the relationship among antinuclear antibodies (ANAs) and cancer has been widely studied. Anti-centromere protein –F (Anti-CENP-F), a subtype of ANAs targeted to nuclear centromere proteins, is one of the most important ANAs related to several cancer subtypes. Different authors found that around 50% of individuals with high serum titre of anti-CENP-F developed a neoplasia and these tumours had an overexpression in immunohistochemical analysis. Methods: In this study, we have carried out a retrospective analysis in a cohort of individuals from six hospitals in Madrid tested for ANAs titres because autoimmune diseases was suspected from November 2015 to October 2016. We focused in anti-CENP-F analysis and the possible association to cancer in those cases with a high titre of these ANAs subtypes Results: In our retrospective serie, ANAs were tested in 750 individuals and in 43/750 (5.7%) (11 men and 32 women) presented elevated levels of anti-CENP-F titres. In these cases, during the period of inclusion, only 5/43 (11,6%) developed different malignant cancers in different stages and locations (breast, gastric, bladder, prostate and Hodgkin lymphoma). Further follow-up is need in these individuals with high levels of anti-CENP-F with a potential higher risk to develop different tumours Conclusions: In this study, we have observed the association among high titres of anti-CENP-F and the development of different cancers. A further prospective analysis as well as a longer follow up is need to confirm this potential relationship.
O2 LOSS OF AUTOPHAGY IN DENDRITIC CELLS PROMOTES CD4+ TREG EXPANSION AND LIMITS THE DEVELOPMENT OF ATHEROSCLEROSIS IN MICE
Authors: M Clément, F Lareyre, J Raffort, S Saveljeva, L Masters, S Newland, A Finigan, J Harrison, A Kaser, Z Mallat
Journal: Cardiovascular Research (2018)