tbuckley/cabot-search huggingface dataset:
Consensus molecular subtypes (CMS) as a marker for treatment and disease biology in metastatic colorectal cancer (CRC).
Authors: Michael Lam, Preeti Kanikarla Marie, Amir Mehrvarz Sarshekeh, Van K. Morris, Dzifa Yawa Duose, BaiLi Zhang, Huiqin Chen, Jeffrey Morris, Trupti R. Mehta, Riham Katkhuda, Scott Kopetz
Journal: Journal of Clinical Oncology (2020)

4089 Background: Consensus molecular subtypes (CMS) categorize colorectal cancer (CRC) into groups based on gene transcription and are prognostic in early-stage and first-line metastatic settings. Their impact on treatment history is unknown. We hypothesized that the best prognosis CMS2 would have higher utilization of liver-directed therapies and maintenance chemotherapy over the worst prognosis CMS4. Methods: Primary surgical resection specimens were annotated for CMS on a translational protocol in a 5FU-refractory metastatic CRC population. Specimens that had neoadjuvant chemotherapy or radiation were excluded. CMS1, CMS3 and indeterminate CMS were also excluded. Liver-directed therapies were defined as any surgery, direct injection of cytotoxics or microspheres, radiation or radiofrequency ablation. Multiple occurrences of liver-directed therapies or maintenance chemotherapy in the same patient were recorded once for statistical tests of association. Results: CMS1 (7.4%), CMS3 (8.2%) and indeterminate calls (4.1%) accounted for 20% of all samples tested. There were 43 (44%) CMS2 and 55 (56%) CMS4 patients eligible. Age, stage at diagnosis, mismatch repair and RAS mutational status were similar in both groups. Left-sided tumors were more common in CMS2 (79%) than CMS4 (42%), p = .001. The median overall survival (OS) from stage IV diagnosis was 40 [34 - 51] versus (vs) 28 [21 – 33] months (p &lt; .0001) for CMS2 vs CMS4 respectively. Liver-directed therapy was greater in CMS2 (53%) vs CMS4 (31%), p = .024. The number further increased when multiple treatments in a single patient were taken into account. Microsphere injection, radiation and liver surgery combined with RFA were the most skewed towards CMS2 over CMS4. No difference in median OS was seen from first liver-directed therapy in CMS2 vs CMS4 (29 vs 27 months, p = .31). There was a trend towards greater maintenance chemotherapy in CMS2 (47%) vs CMS4 (29%), p = .076. Conclusions: Better prognosis with CMS2 is consistent with other studies. Significantly increased liver-directed therapy was observed in CMS2. Selection criteria for liver-directed therapy such as slowly progressing, oligometastatic and hepatic-confined disease may be enriching for CMS2 and gives insight into the natural history of this subtype.
Implementing a tumor program strengthening initiative in western Sydney.
Authors: Lynleigh Evans, Yiren Liu, Terence Kwan, Brendan Donovan, Karen Byth, Paul R. Harnett
Journal: Journal of Clinical Oncology (2020)

e19223 Background: While multidisciplinary teams (MDTs) are well-established in many healthcare institutions, both how they function and their role in decision making vary widely. This study assessed the effectiveness of a multipronged approach to strengthening multidisciplinary team performance for a cancer service over three years. Methods: The study comprised the introduction of a structured quality improvement program, the Tumour Program Strengthening Initiative (TPSI), to improve MDT performance, and an annual survey to evaluate MDT members’ perceptions of their teams’ performance. Three iterations of the survey have been completed. Results: 12 teams participated in TPSI with 129, 118, and 146 members completing the MDT member survey in 2017, 2018, and 2019 respectively. Of the 18 questions that were asked throughout the study, nine showed significant improvement, and of these, seven were highly significant. Questions related to patient wellbeing and to audits and quality improvement showed no significant change. Conclusions: The Tumour Program Strengthening Initiative resulted in sustained and significant improvement in MDT performance over three years. The MDT survey proved to be useful not only for cancer care teams to identify their strengths and weaknesses and monitoring performance but also for management to flag priority areas for improvement and further support. The significance of this initiative is that overall program improvement reflects the strengthening of the weakest teams as well as further improvement in highly performing MDTs. [Table: see text]
Effectiveness of a Guided Web-Based Self-help Intervention to Prevent Depression in Patients With Persistent Back Pain
Authors: Lasse B. Sander, Sarah Paganini, Yannik Terhorst, Sandra Schlicker, Jiaxi Lin, Kerstin Spanhel, Claudia Buntrock, David D. Ebert, Harald Baumeister
Journal: JAMA Psychiatry (2020)

Depression is a frequent comorbid condition in patients with persistent back pain and is associated with substantial adverse consequences, including the risk of developing opioid use disorders. Shifting the focus from depression treatment to preventing depression might be a viable way to reduce the disease burden.To evaluate the effectiveness of a web-based self-help intervention to reduce the incidence of major depressive episode (MDE) in patients with persistent back pain.Prevention of Depression in Back Pain Patients (PROD-BP) was a pragmatic, observer-blinded randomized clinical trial with a parallel design conducted in Germany. Eligible adults with a diagnosis of persistent back pain and subclinical depressive symptoms, but who were depression free, were recruited either on-site or after discharge from 82 orthopedic clinics between October 1, 2015, and July 31, 2017. All analyses were conducted according to the intention-to-treat principle from October 31, 2018, to April 30, 2019.The intervention group received an e-coach-guided, web-based self-help intervention that was based on cognitive behavioral therapy and tailored to the needs of patients with persistent back pain. The intervention included 6 obligatory modules and 3 optional modules to be completed by participants as well as feedback from e-coaches. Both the intervention and control groups had unrestricted access to treatment as usual.Primary outcome was time to onset of an MDE over a 12-month period as assessed by blinded diagnostic raters using the Structured Clinical Interview for DSM-5. Secondary outcomes included depression severity, quality of life, pain intensity, pain-related disability, pain self-efficacy, work capacity, and user satisfaction assessed with a variety of instruments.A total of 295 participants (mean [SD] age, 52.8 [7.7] years; 184 women [62.4%]) were recruited and randomized to either the intervention group (n = 149) or control group (n = 146). The intervention reduced the risk of MDE onset by 52% (hazard ratio, 0.48; 95% CI, 0.28-0.81; P < .001). Twenty-one participants (14.1%) in the intervention group and 41 participants (28.1%) in the control group experienced an MDE over the 12-month period. The number needed to treat to prevent 1 new case of MDE was 2.84 (95% CI, 1.79-9.44).Results of this trial showed that among patients with persistent back pain, depression can be prevented by a guided web-based self-help intervention in addition to treatment as usual. This finding suggests that using a scalable digital approach to integrate psychological treatment into routine pain management is feasible.German Clinical Trials Register Identifier: DRKS00007960.
Transoral robotic surgical resection followed by randomization to low- or standard-dose IMRT in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN Cancer Research Group (E3311).
Authors: Robert L. Ferris, Yael Flamand, Gregory S. Weinstein, Shuli Li, Harry Quon, Ranee Mehra, Joaquin J. Garcia, Christine H. Chung, Maura L. Gillison, Umamaheswar Duvvuri, Bert W. O'malley, Enver Ozer, Giovana R. Thomas, Wayne Koch, Michael Elliot Kupferman, Richard Bryan Bell, Nabil F. Saba, Miriam Lango, Eduardo Mendez, Barbara Burtness
Journal: Journal of Clinical Oncology (2020)

6500 Background: ECOG-ACRIN 3311 examines reduced postoperative therapy in patients with “intermediate risk” p16+ oropharynx cancer (OPC) undergoing primary transoral surgical management. We report the primary endpoint of 2-year progression free survival (PFS) for patients randomized to 50Gy vs 60Gy without chemotherapy. Methods: Between December 2013 and July 2017, 82 credentialed surgeons performed transoral resection (TOS) for 519 OPC patients (cT1-2 stage III/IV AJCC7 without matted neck nodes); post-operative management was determined by pathologically assessed risk. Among 353 eligible and treated patients, Arm A enrolled 10% (N=37) for clear margins, 0-1 nodes, no extranodal extension (ENE)), Arms B (50Gy, N=102) or C (60Gy, N=104) randomized 58%, for clear/close margins, 2-4 + nodes, or ENE ≤1mm, while Arm D (N=110, 60-66Gy plus weekly cisplatin, 40 mg/m2, positive margin with any T stage, &gt;4 + nodes, or &gt;1mm ENE) enrolled 31%. Arm D assignment was based on &gt;1mm ENE (76%), &gt; 4 nodes (27%), and/or positive margins (11%). Intermediate-risk patients were stratified by smoking history (&gt;10 pk-yr). Of the 80 pts (15%) deemed ineligible, 28 had scans/labs not done per protocol, however treatment arm distribution for all patients mirrored that for the 353 pts eligible and treated. Results: Median follow-up was 31.8 months. 2 yr PFS for Arms A, B and C were 93.9% (90% CI=87.3%, 100%), 95.0% (90% CI=91.4%, 98.6%) and 95.9% (90% CI=92.6%, 99.3%) respectively, while Arm D was 90.5% (90% CI=85.9%, 95.3%). The regimen of TOS + low-dose radiation is considered worthy of further study, since the primary endpoint of the upper bound of the 90% CI (in the intermediate risk group) exceeding 85% was met. Of 17 progression events, 7 were locoregional. There were 10 distant recurrences: Arm A=1, Arm B=2, Arm C=4, Arm D=3. Grade III/IV treatment-related AE rates were 15%/2% during surgery, 13%/2% for Arm B and 25%/0% for Arm C. There were 2 treatment-related deaths (one surgical and one Arm D). Conclusions: Transoral resection of p16+ OPC is safe and results in good oncologic outcome, presenting a promising deintensification approach. For patients with low-risk disease, 2-yr PFS is favorable without post-operative therapy. For those with uninvolved surgical margins, &lt;5 involved nodes, and minimal (&lt;1mm) ENE, reduced dose postoperative RT without chemotherapy appears sufficient. Transoral surgery plus 50Gy should be compared to optimal non-surgical therapy in a phase III trial. Clinical trial information: NCT01898494 .
Awareness and knowledge of Helicobacter pylori infection among medical staff in Shanghai
Authors: Lika Yang, Qincong Pan, Qiang Shen, Min Liu, Lixia Zhang, Nuo Cheng
Journal: BMJ (2017)

Objective
To survey the awareness and knowledge of Helicobacter pylori (Hp) infection among medical staff in Shanghai.


Methods
A questionnaire survey was conducted among 316 medical staff in Shanghai, including 74 gastroenterologists(GI), 158 general practitioners(GP), and 68 gastroenterology nurses(GN), from October 2014 to September 2015. The questionnaire was designed according to the Fourth Helicobacter Pylori Infection Treatment Consensus Report of China (the Consensus) . There were 4 parts and 29 questions in the questionnaire, including the knowledge and performance of the Consensus(8 questions), the indications of Hp eradication(8 questions), detection methods of Hp infection(7 questions)and the therapy of Hp eradication(6 questions).


Results
Total 300 valid questionnaires were received with a response rate of 94.9%(300/316). The awareness rate of the Consensus in GI, GP and GN groups was 81.1%(60/74), 57.6%(91/158)and 26.4%(18/68), respectively(χ2=43.67, P=0.001). GI had higher awareness rate than GP and GN in indications of Hp eradications (for peptic ulcer, mucosa-associated lymphoid malignancies, post-resection patients of early gastric cancer, and family history of gastric cancer, the χ2 values were 16.68, 35.60, 33.46 and 39.22, respectively; all P<0.05). In part of Hp infection detection methods, the responses of GI, GP and GN groups in C14 or C13 urea breathing test were 97.3% (72/74), 47.5% (75/158)and 82.1%(55/68), respectively (χ2=72.38, P=0.001); in gastric mucosa tissue rapid urease test were 70.3% (52/74), 13.9% (22/158)and 25.4%(17/68), respectively (χ2=78.22, P=0.001); in serological test were 58.1% (43/74), 20.9% (33/158)and 44.8%(30/68), respectively (χ2=40.30, P=0.001); in gastric mucosa tissue section staining were 56.8% (42/74), 13.3% (21/158)and 22.4%(15/68), respectively (χ2=50.35, P=0.00). In part of Hp eradication therapy the responses of GI, GP and GN groups in recommended bismuth quadruple therapy were 71.6% (53/74), 47.5%(75/158) and 40.3% (25/62), respectively (χ2=15.93, P=0.001); in triple therapy were 27.0% (20/74), 51.6%(81/158)and 42.0%(26/62), respectively(χ2=12.42, P=0.002); in 10 or 14 d for treatment duration were 78.4%(58/74), 78.5%(124/158)and 67.6% (46/68), respectively (χ2=3.36, P=0.186).


Conclusion
Gastroenterologists are more likely to adhere with the Consensus than general practitioners and gastroenterological nurses in the management of Hp infection. The survey suggests that more attention should be paid for popularization and implementation of Hp infection guidelines and consensus among Shanghai medical staff, especially for GP and nurses.


Key words: 
Helicobacter pylori; Diagnosis; Therapy; Cognition
Outcomes of patients with metastatic renal cell carcinoma (mRCC) treated with first-line Immuno-oncology (IO) agents who do not meet eligibility criteria for clinical trials.
Authors: Chun Loo Gan, Shaan Dudani, Connor Wells, Ziad Bakouny, Nazli Dizman, Sumanta K. Pal, Bernadett Szabados, Lori Wood, Christian K. Kollmannsberger, Neeraj Agarwal, Frede Donskov, Naveen S. Basappa, Georg A. Bjarnason, Francis Parnis, Camillo Porta, Ian D. Davis, Ulka N. Vaishampayan, Ravindran Kanesvaran, Toni K. Choueiri, Daniel Yick Chin Heng
Journal: Journal of Clinical Oncology (2020)

5070 Background: IO combination therapies [including IOIO and IO/vascular endothelial growth factor inhibitor (IOVE) combinations] in mRCC have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of trial ineligible patients who are treated with first-line IOIO or IOVE combinations are unknown. Methods: Metastatic RCC patients treated with first-line IOIO or IOVE were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria in IO trials) if they had a Karnofsky performance status (KPS) &lt; 70%, no clear-cell component, brain metastases, hemoglobin (Hb) &lt; 9 g/dL, eGFR &lt; 40 mL/min, platelet count of &lt; 100,000/mm 3 , and/or neutrophil count &lt; 1500/mm 3 . Time to treatment failure (TTF) and overall survival (OS) were calculated from time of starting first-line IO therapy. Results: Overall, 26% (155/592) of patients in the International mRCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Baseline characteristics are listed in Table. The reasons for ineligibility were: no clear-cell component (34%, 53/155), Hb &lt; 9g/dL (28%, 44/155), eGFR &lt; 40 mL/min (19%, 30/155), brain metastases (19%, 29/155), KPS &lt; 70% (14%, 21/155), platelet &lt; 100,000/mm 3 (3%, 4/155) and neutrophil count &lt; 1500/mm 3 (0%, 0/155). Between ineligible versus eligible patients, the response rate, median TTF and median OS of first-line IOIO or IOVE was 34% vs 46% (p = 0.02), 4.2 vs 9.7 months (p &lt; 0.01), and 25.3 vs 44.4 months (p &lt; 0.01), respectively. When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.50 (95% CI 1.05-2.14). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. These data may guide patient counselling and specific trials addressing the unmet needs of protocol ineligible patients are warranted. [Table: see text]
Patient-reported global health predicts adverse health outcomes in a cohort of patients with advanced sarcoma.
Authors: Marium Husain, Audra Phillips, Gabriel Tinoco, James Lin Chen, David A. Liebner
Journal: Journal of Clinical Oncology (2020)

e23547 Background: Given the rare nature of sarcoma cancers and the sometimes severe treatment-related effects of chemotherapy, many patients with sarcoma face quality of life issues during treatment. Unplanned hospital admission and emergency room (ER) visits can occur from uncontrolled symptoms and ultimately delay treatment regimens and negatively impact quality of life. The PROMIS Global Health v1.2 (PROMIS-10) surveys are validated tools to assess patients’ physical and mental well-being at the time of the survey. We sought to evaluate the correlation between PROMIS-10 scores and adverse outcomes of interest, including unplanned admissions/ED visits and patient mortality. Methods: All patients currently seen in the Sarcoma Clinics at Ohio State University routinely complete the PROMIS-10 survey at each clinic visit. For this pilot study, we collected the raw and normalized t-scores for PROMIS-10 surveys for all patients consented to The Ohio State University Sarcoma Registry (OSU-14242) from 6/1/2018 to 11/20/2019. We also collected data on unplanned hospital admission/ED visits and mortality data for each patient. Results: A total of 864 surveys for 112 patients were collected for the study period. The median number of surveys answered per patient was 6. Mean global physical t-scores (43.7 ± 8.5) and mental t-scores (47.9 ± 9.2) were lower than reference scores for the general US population (p &lt; 0.001). 109 of 112 patients experienced an unplanned admission or ED visit during the study, with a total of 270 such encounters during the study period. PROMIS-10 scores were slightly but significantly lower for patients experiencing an admission or ED visit within 30 days of taking the survey (physical: 41.9 vs 44.1, p = 0.006; mental: 46.4 vs 48.2, p = 0.035). A total of 26 patients died during the study period; surveys completed prior to death were consistent with a greater level of physical and mental distress, with the median physical t-score = 34.9 (range: 23.5 – 50.8) and mental t-score = 43.5 (range: 33.8 – 67.6). Conclusions: We showed that we are able to obtain worthwhile data to objectively evaluate patients’ physical and mental well-being through survey data during cancer treatment. We are currently performing additional confirmatory analysis of the predictive value of the PROMIS-10 survey for adverse events and for treatment-related complications.
全胸腔镜下食管平滑肌瘤切除12例临床分析
Authors: 史宏灿, 束余声, 石维平, 陆世春, 王康, 孙超
Journal: BMJ (2010)

食管平滑肌瘤是最常见的食管良性肿瘤,发病率约占食管良性肿瘤与囊肿的50%～80%[1],其中食管下段平滑肌瘤的发生率最高[1].手术切除是其惟一有效的治疗手段,是胸外科典型的大切口、小手术。
Evaluation of circulating miRNAs for earlier cancer detection through machine-learning expression profiling.
Authors: Jason Chia-Hsun Hsieh, Chun-Ta Liao, Hung-Ming Wang, Ming-Yu Lien, Yung-Chang Lin, Shih-Che Shen, Shih-Ting Kang, Wei-Ming Chen, Yi-Shan Hsieh, Ya-Chun Fan, Eric Pok Eric Yang
Journal: Journal of Clinical Oncology (2020)

1559 Background: Earlier cancer diagnosis leads to higher patient survival rate and reduces financial burdens for patients and their families. Over the past five years, liquid biopsy has demonstrated tremendous promise in the early detection of tumor presence. In addition to circulating tumor cells and circulating tumor DNAs, extracellular microRNAs (miRNAs) have also been shown to be promising diagnostic biomarkers. Through machine-learning profiling, we sought to determine whether or not we could use individuals’ miRNA expression to distinguish between healthy subjects and cancer patients. Methods: Blood samples were collected from healthy donors and from patients of various cancer types. Plasma samples were purified within two hours of sample collection, followed by miRNA extraction. After performing reverse transcription of miRNAs into cDNAs, expression analysis of miRNAs was done using a novel multi-gene, amplification-based detection system that simultaneously analyzes over 160 miRNAs. For subsequent data processing, miRNAs without amplification signals across all profiles were first removed, resulting in 135 miRNAs. These 135 resulting miRNAs were then used as features in Support Vector Machine (SVM) to build OncoSweep classifier, a proprietary prediction algorithm for classification of the samples. Ten-fold cross validation was used to evaluate the performance of OncoSweep. Results: 344 healthy donor samples and 417 cancer patient samples were collected for the study. The prediction algorithm, OncoSweep, was derived based on the miRNA expression patterns of the healthy and the patient samples. The algorithm scored an overall accuracy for cancer prediction of 86.47%, with a sensitivity of 91.4%, a specificity of 85%, a PPV of 85% and an NPV of 88.5%. Conclusions: Utilizing machine-learning method of analyzing circulating miRNA expression profiles, the derived algorithm OncoSweep shows significant promise in cancer prediction. Validation is currently being performed in a larger study. We believe circulating miRNAs, through stringent sample processing and machine-learning methodology, are powerful biomarkers for earlier cancer detection.
PrE0505: Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (MPM)—A PrECOG LLC study.
Authors: Patrick M. Forde, Zhuoxin Sun, Valsamo Anagnostou, Hedy L. Kindler, William T. Purcell, Bernardo H. L. Goulart, Arkadiusz Z. Dudek, Hossein Borghaei, Julie R. Brahmer, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2020)

9003 Background: First-line CP was FDA-approved in 2004 for unresectable MPM. Given the role of inflammation in MPM and promising responses to PD-1 pathway blockade in pretreated MPM, we conducted a phase 2 single arm study of the anti-PD-L1 antibody, durvalumab (durva), combined with CP for patients (pts) with untreated MPM of any subtype. Methods: Eligible pts were treatment-naïve with surgically unresectable MPM. Primary endpoint was overall survival (OS); pts received up to 6 cycles of durva-CP, followed by maintenance durva up to 1 year. Carboplatin was permitted for pts with baseline hearing or renal impairment. The first 15 pts were monitored for dose-limiting toxicities (DLTs). Secondary endpoints included toxicity, objective response by modified RECIST, progression-free survival (PFS), and correlative analyses. With a sample size of 55 patients and 32 events, the study had 90% power to detect a 58% improvement in median OS from 12 months (m) (historical control) to 19 m with durva-CP. Results: PrE0505 enrolled 55 patients at 15 US-based sites between 06/2017 and 06/2018. Histologic subtypes were epithelioid (75%), biphasic (11%), sarcomatoid (13%), and desmoplastic (2%). There were no DLTs during the run-in period. As of January 2020 the median follow up is 20.6 m and 29 deaths have occurred. The median OS at the time of report is 21.1 m. The 12 m OS rate was 70% with a 2 sided 95% confidence interval (56%, 81%) and two-sided 80% CI (62%, 78%). Analyses for the secondary endpoints were ongoing at abstract submission. Exome sequencing, TCR sequencing and dual PD-L1/CD8 staining have been completed on baseline tumors from at least 45 of the 55 patients enrolled as well as RNA sequencing for those with adequate tissue. Initial results show that tumors harbored an average tumor mutation burden of 22 somatic sequence alterations and varying levels of aneuploidy were detected. Conclusions: The combination of chemotherapy with durvalumab delivered a promising median OS for previously untreated pts with unresectable MPM. Full results from the study along with the extensive correlative analyses performed will be reported. The phase 3 PrE0506/DREAM3R trial evaluating CP-durvalumab versus CP alone will commence enrollment in the United States and Australia in 2020. Clinical trial information: NCT02899195.