tbuckley/cabot-search huggingface dataset:
Prognostic value of B cells in cutaneous melanoma
Authors: Sara R. Selitsky, Lisle E. Mose, Christof C. Smith, Shengjie Chai, Katherine A. Hoadley, Dirk P. Dittmer, Stergios J. Moschos, Joel S. Parker, Benjamin G. Vincent
Journal: Genome Medicine (2019)

Measures of the adaptive immune response have prognostic and predictive associations in melanoma and other cancer types. Specifically, intratumoral T cell density and function have considerable prognostic and predictive value in skin cutaneous melanoma (SKCM). Less is known about the significance of tumor-infiltrating B cells in SKCM. Our goal was to understand the prognostic and predictive value of B cell phenotypic subsets in SKCM using RNA sequencing. We used our previously published algorithm, V'DJer, to assemble B cell receptor (BCR) repertoires and estimate diversity from short-read RNA sequencing (RNA-seq). We applied machine learning-based cellular phenotype classifiers to measure relative similarity of bulk tumor sample gene expression profiles and different B cell phenotypes. We assessed these aspects of B cell biology in 473 SKCM from the Cancer Genome Atlas Project (TCGA) as well as in RNA-seq data corresponding to tumor samples procured from patients who received CTLA-4 and PD-1 inhibitors for metastatic SKCM. We found that the BCR repertoire was associated with different clinical factors, such as tumor tissue site and sex. However, increased clonality of the BCR repertoire was favorably prognostic in SKCM and was prognostic even after first conditioning on various clinical factors. Mutation burden was not correlated with any BCR measurement, and no specific mutation had an altered BCR repertoire. Lack of an assembled BCR in pre-treatment tumor tissues was associated with a lack of anti-tumor response to a CTLA-4 inhibitor in metastatic SKCM. These findings suggest an important prognostic and predictive role for B cell characteristics in SKCM. This has implications for melanoma immunobiology and potential development of immunogenomics features to predict survival and response to immunotherapy.
At the forefront of the sequencing revolution—notes from the RNGS19 conference
Authors: Sander Wuyts, Nicola Segata
Journal: Genome biology (2019)

Herein we present a meeting report on the third edition of the ‘Revolutionizing Next-Generation Sequencing’ conference, organized by the Flemish life-science research institute VIB and held at Antwerp, Belgium, 25–26 March 2019.
Prospective Registry of Multiplex Testing (PROMPT): Follow-up.
Authors: Jamie Brower, Heather Symecko, Jada G. Hamilton, Tricia Harstad, Margaret Merrill, Judith Balmaña, Michael Francis Walsh, Judy Ellen Garber, Kenneth Offit, Susan M. Domchek, Mark E. Robson
Journal: Journal of Clinical Oncology (2019)

1527 Background: Prospective Registry of Multiplex Testing (PROMPT) is an online registry for individuals who have had multiplex panel testing for cancer susceptibility. The main objective of this registry is to ascertain families to allow penetrance calculations for mutations in less well characterized genes. Methods: Since September 2014, health care providers and commercial laboratories have given PROMPT information with the test results to eligible individuals. Participants with pathogenic mutations or variants of unknown significance in cancer susceptibility genes have self-enrolled in PROMPT. We have sent annual follow-up surveys to participants to capture updated personal and family histories, additional genetic testing in the family, and changes in cancer screening patterns. Results: To date, 5800 participants have enrolled in PROMPT and 2321 follow-up surveys are completed. Of those eligible for follow-up, 1980 (44%) have completed at least one survey. 134 (5.8%) reported a new cancer diagnosis since baseline. Breast cancer (37, 27.6%) and non-Melanoma skin cancer (35, 26.2%) were the most commonly reported new diagnoses. 5.7% of participants with an ATM variant, 5.2% of those with a BRCA2 variant, and 4.3% of those with a CHEK2 variant and at least one follow-up survey have reported a new primary cancer diagnosis (excluding non-Melanoma skin cancer). In addition, 70 (3%) participants reported a cancer recurrence since time of last follow-up. Bone (9, 12.9%) and liver (8, 11.4%) were the most common recurrence sites. 12.7% of those with a TP53 variant, 7.1% of those with a BARD1 variant, and 3.3% of those with an ATM variant and at least one follow-up survey have reported a recurrence. 59 (2.5%) participants had additional clinical genetic testing, and 555 (24%) participants reported clinical genetic testing of family members. Conclusions: PROMPT collects updated health information from participants to achieve the primary goal of determining cancer incidence among carriers of different mutations. Moreover, PROMPT has increased participant contacts through use of annual follow-up surveys and gene-specific surveys with subsets of participants. Ongoing efforts include obtaining pathology reports of new and recurrent cancer diagnoses on study.
AB0884 CLINICAL AND DEMOGRAPHIC CHARACTERISTICS OF PATIENTS WITH OCHRONOTIC ARTHROPATHY
Authors: Tuba Yüce İnel, Pelin Teke Kısa, Ali Balcı, Sadettin Uslu, Zümrüt Arslan, Burcu Ozturk Hismi, Nur Arslan, Fatos Onen, İsmail Sari
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Alkaptonuria (AKU) is a metabolic disorder that causes accumulation of oxidized homogentisic acid (HGA) in the connective tissues. The excessive deposition of HGA and its metabolites can cause joint destruction and skeletal abnormalities which the entity is clinically referred as ochronotic arthropathy (OA) [1]. <h3>Objectives</h3> To assess clinical, demographic features and radiographic findings in patients with OA. <h3>Methods</h3> Adult AKU patients registered in the database were included in the study. All patients investigated for the presence of OA and inflammatory symptoms. Patients with musculoskeletal symptoms (MSK) underwent conventional X-rays and routine laboratory evaluation. In cases suggestive of inflammatory disease additional work-up such as autoantibodies, HLA-B27 and MRI with inflammatory protocol were performed. <h3>Results</h3> Six out of 15 patients had symptoms compatible with OA (40%; 4 male [M], 2 female [F], median age 56 [51-62] years). The median duration of MSK symptoms were 7 (2-19) years. None of the patients had family history of rheumatologic disease. Baseline CRP were normal in all patients. The HLA-B27 test was negative in all cases. One patient had high titers of rheumatoid factor along with positive anti-CCP that were accompanying erosive arthritis on MCP joints by X-rays. Two patient had positive ANA. All patients had chronic back pain and had changes compatible with OA in their spines (narrowing of the intervertebral spaces, vacuum phenomenon and intervertebral disc calcification). Two patient had inflammatory type of pain character (IBP). Radiographic sacroiliitis according to modified New York criteria was present in 2 cases. Inflammatory spine and SIJ lesions were detected by MRI in 1 patient. Extra-articular involvement including enthesitis (1 patient), interstitial lung disease (1 patient) and scleritis (1 patient) was also noted. The clinical and demographic characteristics of the OA are given in Table 1. <h3>Conclusion</h3> There was a high prevalence of inflammatory arthritis (2 axSpA; 1 RA) in OA (50%) which contradicts with the common concept that OA is a degenerative disorder. According to our results, inflammatory disease should be carefully screened in OA patients as accumulated metabolic products may trigger inflammatory pathways. <h3>References</h3> [1] Phornphutkul, C., et al., Natural history of alkaptonuria. New England journal of medicine, 2002. 347(26): p.2111-2121. <h3>Disclosure of Interests</h3> None declared
Clinical significance of peritoneal molecular markers in patients with locally advanced gastric cancer (LAGC) without macroscopic peritoneal implants treated with perioperative chemotherapy (ChT).
Authors: Luis Paul Del Carpio Huerta, Mariona Calvo, Olbia Serra, Mar Varela, Gloria Hormigo, Nuria Baixeras, Valentín Navarro-Perez, Humberto Aranda, Mònica Miró, Natalia Romero, MaCarmen Galan
Journal: Journal of Clinical Oncology (2019)

e15583 Background: Presence of malignant cells in the peritoneal lavage (Cyt+) of patients with LAGC in absence of macroscopic peritoneal implants reflects bad prognosis and is a surrogate of metastatic disease. The presence of molecular markers (Mol+), such as CEA and CK20 mRNA, had also been suggested to carry the same bad prognosis as Cyt+ after upfront curative gastrectomy. There is no recommendation about the management of Mol+ patients (pts) within the current perioperative ChT. Methods: We retrospectively analyzed all pts treated in our high volume multidisciplinary team between 2011 – 2015, with LAGC amenable to surgical resection, without macroscopic peritoneal implants in laparoscopy staging and treated with perioperative ChT. Pre-treatment peritoneal Cyt and Mol analysis (CEA and CK20 mRNA detected by RT-PCR), as well other clinical factors were analyzed. Results: From a total a 310 pts, 60 were included. Median follow up was 72.9 months (m). Mean age was 60y, 37% had PS0, 37% had diffuse histology, 85% wereT4(a-b), 93% N+ stage and 50% were located in gastric body. Accordig Cyt and Mol markers: 3% were Cyt+ and 18% were Mol+, 63% were Cyt-/Mol-, 15% Cyt-/Mol+, 3% Cyt+/Mol+, 0% Cyt+/Mol-, and 18% were Cyt or Mol unknown (uk). 83% underwent gastric surgery, of them, 93% achieved R0. Median PFS (mPFS) was 61.9m. mPFS for Mol+ was 11.0m (95%CI 2.6-19.4) vs the rest (Mol-/uk and Cyt +/-/uk) 69.9m (95%CI 45.0-94.8), p &lt; 0.001. HR = 3.8. mOS was 68.3m. mOS for Mol+ vs the rest was 20.7m (95%CI 4.5-36.8) and not reached, respectively, p = 0.002. HR = 3.4. Mol+ pts who underwent surgery had longer mOS than Mol+ pts which did not (not-reached vs 7.8m (95CI% 3.4-12.9), p = 0.03). In the multivariate adjusted analysis PS (0 vs 1-2) and Mol (- vs +) were significant both for mPFS and mOS. Mol+: HR = 4.0 (95%CI 2.0-11.0),p &lt; 0.001 for mPFS and HR = 5.4 (95%CI 1.9-14.9),p = 0.001 for mOS. Conclusions: Molecular peritoneal analysis may identify a subset of LAGC patients with bad prognosis despite negative cytology and absence of peritoneal macroscopic implants (Cyt-Mol+). Gastric surgery and perioperative chemotherapy may improve prognosis in some Mol+ patients
Mutational landscape of early-stage non-small cell lung cancer patients using a 451 gene panel.
Authors: Guanxian Mao, Peng Xuxing, Wu Hao, Wang Junbing, Liu Suyue, Wu Qiang, Liu Ying, Qiang Ren, Jixian Liu, Charles E. Melançon
Journal: Journal of Clinical Oncology (2019)

e20048 Background: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Methods: Many studies have reported mutation landscapes of non-small cell lung cancer (NSCLC), but most of the data were from advanced-stage patients. This study reports the mutation landscape of early-stage NSCLC patients. Results: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0%)0/39) for BRAF,5.7% (2/35) and 0%)0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53. Conclusions: In all, 74 tDNA and ctDNA samples were analyzed. A total of 285 mutations were identified, including 174 in tDNA and 111 in plasma ctDNA. Genes with the highest -frequencies of mutations in tDNA were EGFR, TP53, KMT2B, BRAF, PIK3CA, CDKN2A, and KRAS,while TP53, EGFR, NOTCH3, PIK3CA, andATM were the genes with the highest frequencies of mutations in ctDNA. The detection rate of driver mutations in tDNA and ctDNA, respectively, were: 42.9% (15/35) and 12.8% (5/39) for EGFR, 5.7% (2/35) and 2.6% (1/39) for ALK, 5.7% (2/35) and 2.6% (1/39) for ERBB2, 11.4% (4/35) and 0% )0/39) for BRAF,5.7% (2/35) and 0% )0/39) for RET, 37% (13/35) and 23.1% (9/39) for TP53.
Case 26-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Louis Burke, Debra A. Bell
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 34-year-old woman was admitted to the hospital because of vulvar cellulitis.There was an 11-year history of Crohn's disease, with rectal involvement and perirectal abscesses, for which a colectomy and ileostomy were performed elsewhere 8 years before entry. A long-standing chronic fistula near the right buttock drained fecal material before the colectomy and was dry thereafter. Five years before admission a distal pancreatectomy with splenectomy and cholecystectomy was performed because of repeated bouts of pancreatitis, with the demonstration of calculi in the pancreatic ducts on endoscopic retrograde cholangiopancreatographic (ERCP) examination. Diabetes mellitus developed postoperatively, and insulin . . .
The diagnosis and outcomes when the outpatients receiving chemotherapy visited the emergency room: A tertiary referral center retrospective study of 734 cases.
Authors: Takatsugu Ogata, Hironaga Satake, Misato Ogata, Hisateru Yasui
Journal: Journal of Clinical Oncology (2019)

6552 Background: Today, the chemotherapy is performed in outpatient, but there is no research on the safety. This study aimed to determine the safety of outpatients receiving chemotherapy and the points to note when they visit the emergency room. Methods: We retrospectively collected data from July 2011 to October 2018 in tertiary referral center of outpatients receiving chemotherapy when they visited the ER within 3 months from the administration of chemotherapy. Results: Seven hundred and thirty-four cases (345 patients) were enrolled (median age, 71 years; male 410, female 324). The median days of the patients visiting the ER was 16 days after the administration of chemotherapy. The tumor types were gastrointestinal (226 cases), urological (199 cases), respiratory (112 cases), and the other (197 cases). The cytotoxic agents, antibody, or hormonal agents were 530 cases, 150 cases, or 173 cases, respectively. The median body temperature and systolic blood pressure were 36.8 °C and 130 mmHg, respectively. The median estimated glomerular filtration rate was 68. The cases of emergent admission were 256 cases. The tumor-associated disease was 184 cases and the chemotherapy-associated disease was 105 cases. The most frequent chemotherapy-associated disease was febrile neutropenia (FN) (35 cases). The admission of tumor-associated disease or chemotherapy-associated were 94 cases or 41 cases, respectively (p = 0.273). Conclusions: The outpatients receiving chemotherapy visited the emergency room because of the tumor-associated symptoms rather than chemotherapy-associated symptoms. It was safe that the chemotherapy is performed in outpatient. FN was the most frequent chemotherapy-associated disease. It is important to be careful that not only chemotherapy-associated symptoms but also tumor-associated symptoms when the outpatients receiving chemotherapy visited the ER.
Efficacy of aspirin for stage III colorectal cancer: A randomized double-blind placebo-controlled trial (JCOG1503C, EPISODE-III trial).
Authors: Atsuo Takashima, Kenichi Miyamoto, Yuya Sato, Natsuko Okita, Manabu Shiozawa, Shigeki Yamaguchi, Ryo Inada, Yusuke Nishizawa, Masayuki Ohue, Nobuhiro Takiguchi, Junki Mizusawa, Hiroshi Katayama, Kenichi Nakamura, Taro Shibata, Haruhiko Fukuda, Yasuhiro Shimada, Yukihide Kanemitsu, Tetsuya Hamaguchi
Journal: Journal of Clinical Oncology (2019)

TPS3623 Background: Adjuvant chemotherapy is the current standard treatment for stage III colorectal cancer after curative resection. However, the prognosis of stage III colorectal cancer is still poor even after curative resection and adjuvant chemotherapy. Recently, several observational studies suggested the anti-tumor effect of aspirin for advanced colorectal cancer. The main mechanism of the anti-tumor effect by aspirin may be to suppress cyclooxygenase activity in the arachidonic acid cascade and to inhibit the production of prostaglandins involved in tumor growth. So far, aspirin showed a prolongation of survival for colorectal cancer in several retrospective studies. However, in these studies, aspirin was given not to be evaluated the effect on prognosis of colorectal cancer in adjuvant setting but to prevent cardiovascular event. In addition, baseline patient characteristics were imbalanced between aspirin group and non-aspirin group and both dosage amount and dosing period of aspirin were different among patients. Methods: We planned a randomized double-blind placebo-controlled phase III trial commenced in Japan in March 2018 to confirm the superiority of aspirin in terms of disease-free survival (DFS) over placebo for stage III colorectal cancer patients after curative resection. Patients receive aspirin (100 mg/day) or placebo for 3 years with the standard adjuvant chemotherapy of mFOLFOX6, CAPOX or capecitabine until relapse or unacceptable toxicities. The primary endpoint is DFS and the secondary endpoints are overall survival, relapse-free survival, relative dose intensity, adverse events, and serious adverse events. We assumed the 3-year DFS of aspirin arm as 74% based on two previous trials conducted by JCOG and expected a 6% increase in the 3-year DFS with aspirin adding to standard adjuvant chemotherapy after curative surgery. A total of 880 patients will be accrued from 20 Japanese institutions within 3 years, and 47 patients were enrolled as of Jan 31, 2019. Both aspirin and placebo are provided by Bayer Yakuhin Ltd. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031180009 (https://jrct.niph.go.jp/detail/589). Clinical trial information: jRCTs031180009.
Abstract 17897: Does Prescriptive Exercise With Mobile Health Tracking Improve Self-efficacy and Health Status in Individuals With Metabolic Syndrome?
Authors: Melanie I Stuckey, Dawn P Gill, Sheree Shapiro, Kristin J Sabourin, Robert J Petrella
Journal: Circulation (2013)

Individuals [n=127, mean age 57.4 (SD 9.1) y, 74% female] with metabolic syndrome were randomized to a prescriptive exercise plus mobile health (mHealth) tracking group (intervention group) or a pr...
Gene mutations of SWI/SNF complex and molecular profile in colorectal cancer.
Authors: Ryuma Tokunaga, Joanne Xiu, Richard M. Goldberg, Philip Agop Philip, Andreas Seeber, Francesca Battaglin, Hiroyuki Arai, Jae Ho Lo, Alberto Puccini, Madiha Naseem, Martin D. Berger, Shivani Soni, Wu Zhang, Wangjuh Sting Chen, Jimmy J. Hwang, Anthony Frank Shields, John Marshall, Hideo Baba, W. Michael Korn, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2019)

3600 Background: The SWI/SNF complex includes proteins produced by 29 genes that regulate chromatin structure remodeling through effects upon transcription, replication, and repair. Understanding how SWI/SNF gene mutations interact to affect cancer progression could lead to new treatment strategies. Methods: We analyzed 7,370 colorectal cancer (CRC) samples with immunohistochemical stains (IHC) and Next-Generation Sequencing (NGS) using a 592-gene panel to examine the association between gene mutations of the SWI/SNF complex ( ARID1A, ARID2, PBRM1, SMARCA4, SMARCB1, SMARCE1, BCL11A, BCL11B, BCL7A, SS18, and SS18L1) and molecular features. Results: The overall mutation rate of the SWI/SNF complex genes was 11.3% ( ARID1A: 7.7% , ARID2: 1.7% , SMARCA4: 1.3% , PBRM1: 1.2% , BCL11A: 1.0% , SMARCB1: 0.5% , BCL11B: 0.5% , SMARCE1: 0.3% , SS18: 0.3% , BCL7A: 0.1% , SS18L1: 0.1%). When compared to tumors with SWI/SNF wild-type genes, those tumors with SWI/SNF gene mutations showed significantly higher rates of microsatellite instability (MSI)-high (40.9% vs 2.4%, P &lt; 0.001), tumor mutational burden (TMB)-high (&gt;= 10mut/MB) (56.8% vs 21.6%, P &lt; 0.001) and PD-L1 positivity (17.9% vs 5.5%, P &lt; 0.001). Tumors with each gene mutant also had strong association with the immune profile (MSI-high, TMB-high, and PD-L1 positivity) (Table). Furthermore, even SWI/SNF gene mutant samples with microsatellite stable status were significantly associated with TMB-high (28.2%, P &lt; 0.001) and PD-L1 positivity (10.0%, P &lt; 0.001). Conclusions: Gene mutations of the SWI/SNF complex exhibit findings that suggest that this subgroup of CRCs may have a higher likelihood of response to PD-1 and PD-L1 targeting monoclonal antibodies. If validated in other data sets, these findings can be used to justify clinical trials with eligibility based upon the presence of mutations within the SWI/SNF complex. [Table: see text]
Revised FIGO staging shows dramatic survival differences in cervical cancer patients with positive lymph nodes in Louisiana.
Authors: Navya Nair, Lu Zhang, Anna Kuan-Celarier, Xiao-cheng Wu, Amelia Jernigan
Journal: Journal of Clinical Oncology (2019)

e17010 Background: With revisions to FIGO cervical cancer staging system in 2018, patients with positive pelvic or para-aortic lymph nodes (LN) are now classified as stage IIIC. Rationale for this change is based on data published in 1990. Methods for work up and treatment of cervical cancer have advanced since then. We aim to determine if updated FIGO staging reflects contemporary survival differences in women with cervical cancer in Louisiana. Methods: Women with FIGO stage I-III cervical cancer diagnosed between 2010 and 2016 were identified from the Louisiana Tumor Registry. Those with &lt; 30 days follow up were excluded. Patients were classified into 3 groups: true stage I &amp; II (LN negative), revised stage IIIC (old stage I or II but positive LN), previous stage III (old FIGO stage IIIA or IIIB). Cox proportional hazards were used to estimate differences in overall and (OS) cause-specific survival (CSS). Covariates of age, race, insurance, census-tract poverty level, and marital status were controlled. Results: 740 patients were included with a median follow up of 40.6 months. Patients in revised stage IIIC group were younger than the others (45.9 yrs vs 47.9 yrs in true stage I&amp;II vs 55yrs in previous stage III, p &lt; 0.0001). True stage I&amp;II patients were more likely to be privately insured (48.9% vs 32.1% revised stage IIIC vs 27.7% previous stage III, p &lt; 0.0001). The groups did not differ by race, poverty level, or marital status. Revised stage IIIC and previous stage III patients had significantly worse survival outcomes compared to true stage I &amp; II in both OS [revised stage IIIC HR 1.93 (1.20-3.11); previous stage III 5.92 (4.27, 8.22)] and CSS [revised stage IIIC HR 2.54 (1.45-4.44); previous stage III HR 7.95 (5.29, 11.94)]. Kaplan-Meier survival curves demonstrate significant differences in both OS and CSS (p &lt; 0.0001) with best outcomes in true stage I&amp;II and worst in previous stage III patients. Conclusions: LN status is an important prognostic indicator for contemporary cervical cancer patients in Louisiana. This analysis provides recent data to support the revised FIGO staging system in upstaging patients with positive LN to stage IIIC as they have significantly worse survival than the true stage I &amp; II patients. Importantly, revised stage IIIC patients who would have previously been stage I &amp; II have strikingly better survival outcomes than women with stage IIIA and IIIB disease. If staging is to be intuitive, the stage III subcategories may need to be redefined.