tbuckley/cabot-search huggingface dataset:
Intra-patient heterogeneity in urothelial cancer (UC) circulating tumor cells (CTC) and PDL1 expression to identify biomarkers of response and new therapeutic targets: A pilot study.
Authors: Waddah Arafat, Charlotte Stahlfeld, Jamie M Sperger, Erika Heninger, Dharmesh Gopalakrishnan, Pedro C. Barata, Marcelo Lamenza, Sarah Devonshire, Nita Hoxha, Pam Profusek, Brian I. Rini, Moshe Chaim Ornstein, Jorge A. Garcia, Christos Kyriakopoulos, Joshua Michael Lang, Petros Grivas
Journal: Journal of Clinical Oncology (2017)

4537 Background: Recent use of immune checkpoint inhibitors (CI) has improved overall survival (OS) in a subset of patients (pts) with metastatic UC. Intra-patient tumoral heterogeneity and epithelial-to-mesenchymal transition has been hypothesized as a driver of treatment resistance to both chemotherapy and CI in UC. There is a critical need to evaluate heterogeneity in UC for biomarkers of treatment response and new therapeutic targets. Trop2 is hypothesized to play a role in UC progression and is the target of a new antibody-drug conjugate, IMMU-132 that is being tested in UC trials. We report the phenotypic comparison of PDL1 expression among CTC subpopulations in UC pts. Methods: Peripheral blood samples were collected from pts with UC treated at Cleveland Clinic and U. of Wisconsin. Immunomagnetic capture and CTC enumeration using both EpCAM and Trop2 from matched blood samples was performed in the VERSA platform. Protein expression for PDL1 in these CTC populations was quantified. Longitudinal analysis of UC pts treated with chemotherapy or CI is ongoing. Results: CTC were captured using EpCAM and Trop2 in all 10 pts in our initial cohort. The frequency of Trop2 CTC was higher than EpCAM CTC with a mean of 248 Trop2 CTC (range 2-1885) compared to 76 EpCAM CTC (range 1-632). PDL1 expression was more frequent in Trop2 CTC than EpCAM CTC. In two pts progressing on Atezolizumab, Trop2 CTC had a higher frequency of PDL1 expression compared to EpCAM CTC (85% vs 2% in pt 1 and 2% vs 0% in pt 2). In pts followed longitudinally, Trop2 CTC dropped from 1885 to 1 in a pt with response to Atezolizumab and PDL1+ CTC declined from 4 to 0. After 1 cycle of Carbo/Gem in another pt, EpCAM CTC declined from 46 to 3 while Trop2 CTC from 116 to 47. Conclusions: This is the first report of CTC heterogeneity in pts with UC identifying high frequency of Trop2 CTCs with variable expression of PDL1 across different pts. Early results from longitudinal analysis suggest CTC as potential predictive / pharmacodynamic biomarkers of treatment response. Prospective data validation in larger cohort is ongoing, while IMMU-132 clinical trials in UC may provide context for future validation.
The course of vulvar cancer: The utility of multistate models in the AGO-CaRE-1 study.
Authors: Christine zu Eulenburg, Linn Lena Woelber, Klaus H. Baumann, Petra Neuser, Falk Thiel, Alexander Mustea, Werner Meier, Philipp Harter, Pauline Wimberger, Lars Christian Hanker, Barbara Schmalfeldt, Ulrich Canzler, Tanja N. Fehm, Alexander Luyten, Martin Hellriegel, Alexander Reuss, Anna Suling, Sven Mahner
Journal: Journal of Clinical Oncology (2016)

5596 Background: Analysis of multiple endpoints in cancer is complex. Different types of events during the course of disease (e.g. recurrence at different localisations) can have divergent associations with prognostic factors and also later endpoints such as death. Therefore combined endpoints as progression-free survival may conceal important information. Methods: The AGO CaRE-1 study is a retrospective observational study of patients with primary squamous-cell vulvar cancer. Overall, 1,618 patients, treated at 29 gynecologic cancer centers in Germany between 1998 and 2008 were included. The current sub-analysis focuses on patients with surgical groin staging and known nodal status. A multistate Cox model was adapted considering primary disease recurrence at five different sites and death. Results: A total of 1249 patients were analyzed. Disease recurrence was observed in 360 (28.8%) patients. Median disease-free survival was 69.3 months. Localization of recurrence was restricted to the vulva in 193/360 (53.6%) patients and restricted to the groins in 41/360 (11.4%) patients. 28/360 (7.8%) developed recurrence at the vulva and the groins only, and 90/360 (25.0%) at the pelvis or distant sites. Localization of recurrence was unknown in 8/360 (2.2%) patients. Recurrence probabilities differed significantly in these five groups: Cumulative incidences after 2 years were 12.6% (vulva), 3.8% (groins), 2.2% (vulva and groins), 7.8% (pelvis or distant) and 0.4% (unknown site). Further, the five types of disease recurrence changed the prognosis for overall survival with a different magnitude: HR 5.9, 95%CI (4.3-8.2) for vulvar recurrence; HR 6.0, 95%CI (3.5-10.2) for recurrence at the groins, HR 14.1, 95%CI (7.5-26.4) for vulva and groin recurrence, HR 21.2, 95%CI (15.3-29.4) for pelvic recurrence or distant metastases; and HR 15.7, 95%CI [3.5-70.2] for unknown site of recurrence. Conclusions: With this multistate model the significance of different recurrence sites for prognosis in vulvar cancer can be investigated. This type of analysis can help to counsel patients regarding individual prognosis although it does not account for treatment of disease recurrence.
A widely used sampling device in colorectal cancer screening programmes allows for large-scale microbiome studies
Authors: Dita Gudra, Saeed Shoaie, Davids Fridmanis, Janis Klovins, Hugo Wefer, Ivars Silamikelis, Raitis Peculis, Ineta Kalnina, Ilze Elbere, Ilze Radovica-Spalvina, Rolf Hultcrantz, Ģirts Šķenders, Marcis Leja, Lars Engstrand
Journal: Gut (2018)

We read with interest the article by Passamonti et al ,1 reporting the performance of two different faecal immunochemical tests (FITs) highlighting the importance of standardisation and validation of screening methodologies. Conventionally, laboratory-based FIT is the preferred approach in testing for occult blood in faeces, which includes colorectal cancer screening programmes.2–4 The potential of preserving stable faecal samples in a widely used FIT buffer for microbiome research would enable prospective microbiome studies in generally healthy subjects undergoing colorectal cancer screening.

For this purpose, we evaluated faecal sample stability in the commonly used OC-Sensor (Eiken Chemical, Tokyo, Japan) under various storage conditions. Faecal samples from five healthy adult individuals were used for the analysis and exposed to 16 different conditions: immediately frozen at −86°C (with FIT (wFIT)/without FIT (woFIT)); immediately frozen at −20°C (wFIT/woFIT); wFIT stored at 4°C for 1, 2, 7, 14 days; stored at 20°C for 1, 2, 7, 14 days; stored at 30°C for 1, 2, 7 days and lastly stored at 4°C for 2 days and at 20°C for additional 2 days. Shotgun metagenomic analysis was performed by Illumina 2500, while taxonomic compositions were determined by 16S rRNA analysis employing Illumina MiSeq and Ion Torrent PGM.

Our first attempt to extract DNA from wFIT samples failed due to low amount of DNA obtained. Thus, lyophilisation for all of the wFIT samples, except for woFIT samples, was applied, increasing the yield of DNA up to 30 times.

As shown by the figure 1, the Shannon index in both platforms displayed a clear pattern of …
Patterns of patient-reported chemotherapy toxicities across twenty-eight ambulatory oncology settings.
Authors: Christopher Ryan Friese, Minal R Patel, Kari Mendelsohn-Victor, Alex J Fauer, Bidisha Ghosh, Arthi Ramakrishnan, Louise Bedard, Jennifer J. Griggs, Milisa Manojlovich
Journal: Journal of Clinical Oncology (2018)

e18721 Background: The National Cancer Institute and other key stakeholders endorse soliciting patient-reported outcomes to understand cancer treatment experiences outside of clinical trials. We examined the patterns of patient-reported chemotherapy toxicities in a statewide oncology quality improvement collaborative. Methods: We surveyed adult patients who recently completed at least one cycle of systemic chemotherapy. Patients reported their severity of nausea, vomiting, constipation, neuropathy, and pain in the past week using the Patient-Reported Outcomes version of the CTCAE (PRO-CTCAE), which evaluates toxicities on a 5-point scale. We calculated the number of patients who rated at least one toxicity in the past week as severe/very severe in addition to level of severity based on a combined score across symptoms (1 = none rated as severe, 25 = all rated as very severe). We used linear regression models (with robust standard errors to account for clustering) to examine differences in toxicity severity by race, gender, and ethnicity, after adjusting for county-level self-reported health status. Results: Out of 3,532 eligible patients across 28 practices, 2,209 (63%) completed the survey. 7% of patients (range across practices 0-50%) reported ≥ 1 toxicity as severe/very severe, the mean(SD) severity score was 8.4(2.9) (range across practices 1.0-23.0). In an adjusted model, white patients rated toxicities as less severe than non-white patients (β = -0.7, 95% CI -1.3,-0.2, p = .01). No differences were observed by gender or Hispanic ethnicity. Conclusions: Patient completion of the PRO-CTCAE is feasible in routine practice and provides actionable data to implement supportive care protocols. In a large survey of patients receiving chemotherapy in routine settings, toxicities are more burdensome in non-white patients. Future studies should investigate tumor, treatment intensity, and underlying severity of illness differences to confirm and explain observed disparities in treatment experiences.
Abstract 14934: Adjunct Vasopressin in Cardiogenic Shock is Associated With Increased Mortality
Authors: Jonathan R Hootman, Michael L Bentley, David C Sane
Journal: Circulation (2017)

Background: Cardiogenic shock (CS) is a state of systemic hypoperfusion due to cardiac dysfunction, with high rates of mortality. Vasopressin has emerged as an adjunct to catecholamines in stabiliz...
The predictive value of uncommon <i>EGFR</i> mutation in patients with non-small-cell lung cancer.
Authors: Haiyan Tu, Ee Ke, Yue-Li Sun, Ming-Ying Zheng, Jin-Ji Yang, Zhen Wang, Si-Pei Wu, Jian Su, Xuchao Zhang, Xiao-Yan Bai, Xue-Ning Yang, Wenzhao Zhong, Hong-Hong Yan, Qing Zhou, Yi-Long Wu
Journal: Journal of Clinical Oncology (2017)

9028 Background: Non-small-cell lung cancers with uncommon epidermal growth factor receptor ( EGFR) mutations are regarded as a heterogeneous group with variable responses to EGFR-targeted drugs. Here we designed this retrospective study to describe the epidemiology and clinical outcomes of uncommon EGFR mutations in a Chinese cohort of lung cancer patients. Methods: Between June 2007 and June 2014, 5363 lung cancer patients whose EGFR genotyping was performed successfully at Guangdong Lung Cancer Institute (GLCI, Guangzhou, China) were screened. 1837 patients were included in the epidemiological analysis. The clinical outcome was analyzed in 97 advanced-stage patients harboring uncommon EGFR mutations with follow-up data. Results: 218 patients harbored uncommon EGFR mutations, making up 11.9% of all cancers with documented EGFR mutations. Compared with common mutants, those with uncommon mutations were more commonly found in smokers and male patients. The most frequently detected uncommon mutations were exon 20 insertions, G719X mutations and L858R complex mutations, occurring in 30.7%, 21.1% and 17.0% of all EGFR-uncommon-mutation cases. G719X and L858R complex mutations were associated with similar benefit from EGFR-TKI; median PFS was 15.2 (95% CI 8.7-21.7) and 11.6 (95% CI 3.6-19.6) months, respectively. T790M or 20INS was associated with a poorer EGFR-TKI response; median PFS was 1.0 (95% CI 0.0-2.2) and 3.0 (95% CI 1.3-4.7) months, respectively. Of note, two patients with 23% and 65% tumor shrinkages had N771_P772insN and H773_V774insQ, with PFS of 5.7 and 6.1 months respectively. Conclusions: Favorable responses were observed in specific subtypes including complex L858R and G719X, and our results suggested first-line EGFR-TKI should be preferable in such patients.
Broad safety impact of high-dose ascorbic acid and induction chemotherapy for high-risk pancreatic cancer.
Authors: Howard Bruckner, Azriel Hirschfeld, Daniel Gurell, King Lee
Journal: Journal of Clinical Oncology (2017)

e15711 Background: High dose ascorbic acid inhibits many tumors in vitro. It may reduce chemotherapy's adverse hematologic events and improve quality of life. Moderate dose gemcitabine, fluorouracil, leucovorin, irinotecan, oxaliplatin (GFLIP) is an effective regimen for patients with many cancers (Anticancer Research 17). High dose ascorbic acid may reverse half the preexisting and largely eliminate the predicted cumulative toxicity of GFLIP (ASCO 15). Methods: High dose ascorbic acid AA 75-100 grams IV was given 1-2 times per week with GFLIP every 2 weeks until progression with serial wkly and Q2wk blood tests and 3 month imaging. Eligibility: Unresectable, III, recurrent and metastatic, mod and high grade typical pancreatic ca; ECOG 0-2; +/- prior chemo; adults of any age with consent. Results: A prescheduled 2 yr analysis found 26 patients; 16 ≥ 65, (9 ≥ 70 years of age). 25 stage IV; Nine had failed at least one prior standard chemo (35%), 3 were PS 2, 9 had severe weight loss. Safety: Five had uncomplicated 3 (19%) and none had 4 neutropenia or neutropenic infection, one (4%) had a 3 anemia and thrombocytopenia without bleeding. Prophylactic growth factors were not used and limited to 1-2 as needed low doses used infrequently. There was no limiting diarrhea, enteritis, stomatitis, weight loss or coagulopathy due to GFLIP. GFLIP is on track to reproduce/retain prior response and survival benefit (ASCO 08). Conclusions: Ascorbic Acid-GFLIP can be exceptionally safe and well tolerated. It may avoid standard 20-40% rates of severe toxicities. It can be, otherwise unavailable, safe reduced cost, treatment for many elderly and prior resistant tumor patients. Given the broad multi-disease role of the GFLIP drugs, and available personalized medicine tests (Cancer Letters), further development is very attractive and feasible. Potential outcome can spare all, and especially high risk pancreatic ca patients, 20k severe toxicities every year toxicities as much as $100 million cost and make some ineligibility criteria unnecessary. Development of safe AA regimens may benefit quality of life and improve survival for many with a broad spectrum of cancers that otherwise go untreated. Clinical trial information: NCT01905150.
Zebrafish blastomere screen identifies retinoic acid suppression of <i>MYB</i> in adenoid cystic carcinoma
Authors: Joseph Mandelbaum, Ilya A. Shestopalov, Rachel E. Henderson, Nicole G. Chau, Birgit Knoechel, Michael J. Wick, Leonard I. Zon
Journal: The Journal of Experimental Medicine (2018)

Pluripotent cells have been used to probe developmental pathways that are involved in genetic diseases and oncogenic events. To find new therapies that would target
PTU-021 Variation in diathermy use for colonic polypectomy – results from a national survey
Authors: AM Verma, A Chilton
Journal: Gut (2017)

Introduction  The transition from trainee to consultant and subsequent accredited bowel cancer screening colonoscopist reveals variability in diathermy practice for colonic polypectomy. There is no standardised teaching with a paucity of guidelines. We therefore designed a survey to evaluate current practice.  Method  This national survey was hosted on www.surveymonkey.co.uk, it has been approved by the endoscopy committees of the BSG and Association of Coloproctology of Great Britain and Ireland (ACPGBI) and was circulated to their memberships.  The questions  1. Which region do you work in?  2. Endoscopy grade and role  3. Endoscopy lists provided in a typical working month  4. What level of polypectomy do you undertake in a typical working month?  5. What diathermy modes do you use for polypectomy in the LEFT side of colon?  6. What diathermy modes do you use for polypectomy in the RIGHT side of colon?  7. Do you use lower diathermy current settings for right side polypectomy vs left side?  8. Do you feel confident in your knowledge and use of diathermy for polypectomy?  Results  The survey was open in 2016. Analysis shows:  • 250/348 (71.8%) completed the full survey from across the United Kingdom.  • 159 Gastroenterologists (63.6%), 36 Surgeons (14.4%), 34 Gastroenterology Trainees (13.6%), 21 others (8.4%).  • Predominant use of coagulation current or coagulation and cutting combination for small and large pedunculated polypectomy.  • Wide variance in diathermy modes for polypectomy of large sessile and very large polyps.  • High use of cold snare polypectomy for small sessile polyps (right 43.2% > left 34.4%).  • Low use of endocut mode irrespective of size/location of polyp (17.2%–32.0%)%).  • 204/250 (81.6%) use reduced current settings for right colonic polypectomy.  • 208/250 (83.2%) confident on knowledge and use of diathermy.  Conclusion  When designing a survey the challenge is to capture the information required and balance this with a high completion rate. We have achieved this with a large number of complete responses.  The guidance for the management of large non-pedunculated colorectal polyps advises that prolonged pure coagulation current be avoided due to risks of delayed bleeding and thermal injury. 1 Many complications are as direct result of thermal injury and polypectomy is the most frequent therapeutic intervention, appropriate training and BSG formal guidance is lacking.  This national survey has exposed wide variations in diathermy use for colonic polypectomy, further analysis is ongoing prior to publication of a paper and we will make representations to the BSG and ACPGBI endoscopy committees to provide a platform to develop training and guidance to improve patient safety.  Reference  . Rutter MD, et al. The guidance for the management of large non-pedunculated colorectal polyps. Gut2015;64:1847–1873. doi:10.1136/gutjnl-2015-30957  Disclosure of Interest  None Declared
LuCaS (Lung Cancer Surveillance) study: Surveillance models for advanced lung cancer patients.
Authors: Sarah Anne Fraser
Journal: Journal of Clinical Oncology (2017)

e20546 I hope to present the trial protocol as a poster at ASCO with co design work commencing 2017. Background: Lung cancer is the leading cause of cancer death in NZ. 1 85% of registrations annually are stage four at diagnosis, presenting a significant burden on resources. Despite novel therapies, survival is poor and quality of life is a key consideration in patient management . 2,3 Currently the aim of surveillance is to detect for disease progression and follows a three monthly pattern. There is little literature around benefits of surveillance on survival, and quality of life in these patients. 4-6 Alternative approaches to surveillance should be evaluated to ensure safe, convenient, economical care. Lung cancer outcomes for Maori patients sit significantly lower than those for New Zealand Europeans. Maori patients are twice as likely to present with locally advanced disease and four times less likely to receive curative treatment (multivariate analysis). There are significant barriers for Maori patients to attending health care including time off work, health literacy, costs, child care, language barriers, and transport. 19 Ministry of Health data describes poor outcomes for Maori lung cancer patients with rate of death sitting at 3.4 times that of non-Maori. Co-Primary End Points To determine if there is a reduction in health services utilisation (ED visits, hospital visits, unplanned clinic visits, GP visits, and Nurse Specialist contact) with the end point identified at progression, lost to follow up, or death. To compare the impact of a novel virtual surveillance model (VSM) versus usual follow-up care on patient anxiety measured using the HADS-A tool. Methods: LuCaS is a Randomised Controlled trial in patients with advanced lung cancer randomised to virtual model or standard care. Results: recruitment begins this year. Conclusions: Hypothesis:A virtual follow up model for advanced stage non-small cell lung cancer patients, extensive stage small cell lung cancer patients, and mesothelioma patients will reduce health care utilisation and patient experienced anxiety defined by reduction in Hospital Anxiety and Depression Scale (HADS-A) score, while maintaining effectiveness detecting recurrence and survival.
Understanding treatment patterns and outcomes in patients with metastatic NSCLC treated in a US community oncology network.
Authors: Eric S. Nadler, Janet L. Espirito, Melissa Pavilack, Marley Boyd, Andrea Leninka Vergara-Silva, Ancilla Fernandes
Journal: Journal of Clinical Oncology (2017)

e20643 Background: Multiple therapeutic options exist for metastatic non-small cell lung cancer (mNSCLC), including chemotherapy (CH), targeted therapy (T), and immunotherapy (IT). The first IT for mNSCLC was FDA approved in 2015 for use after progression on platinum-based CH and T in patients (pts) with EGFR or ALK mutations. The current study evaluates treatment (tx) patterns and outcomes in mNSCLC pts receiving first- (1L), 2nd- (2L), and 3rd-line (3L) therapy. Methods: This is a retrospective, observational cohort study of mNSCLC pts receiving initial tx from 1/2012–4/2016, with follow-up to 6/2016. Data were obtained from The US Oncology Network/McKesson Specialty Health electronic health records database. Demographics, clinical characteristics, and tx patterns were characterized. Overall survival (OS) was assessed using the Kaplan-Meier method. Results: 10,689 1L pts were identified during the study period. Median age was 68 y, and 54% were male. Most pts (59%) had an ECOG performance status of 1, 77% had nonsquamous histology, and 85% were former or current smokers. Initial tx was CH in 93% of pts. Among pts receiving initial T therapy, most were never smokers (48%) vs initial CH pts (12%; P&lt; 0.0001). Median OS (mOS) for all pts at 1L was 12.3 mo (95% CI, 11.9–12.7), and mOS was significantly longer in pts who received T (24.3 vs 11.7 mo for T vs CH, p&lt; 0.0001). Among pts who received 2L therapy in the study period (n = 4235), 66%, 17%, and 17% received CH, T, and IT respectively. Pemetrexed or docetaxel monotherapy was most commonly used for 2L CH, erlotinib was most used as 2L T, and nivolumab for 2L IT. mOS from start of 2L for CH, T, and IT was 9.2, 11.2, and 9.7 mo, respectively (log rank P= 0.01). In 3L pts (n = 1580), nivolumab was most frequently used (17%), and mOS from 3L for CH, T, and IT was 8.0, 7.4, and 11.3 mo, respectively ( P= 0.0187). Conclusions: These data demonstrate integration of novel therapies for mNSCLC in the community. Longer survival was observed in 2L and 3L patients treated with T and IT as compared with CH. This warrants additional randomized studies to investigate optimal sequencing of these agents.