tbuckley/cabot-search huggingface dataset:
Impact of low-income public insurance on survival for children and young adults with bone and soft tissue sarcomas.
Authors: Neela Lakshmi Penumarthy, Robert Goldsby, Lena Penumarthy
Journal: Journal of Clinical Oncology (2019)

10037 Background: Racial and ethnic survival disparities have been described for many pediatric malignancies, but the impact of income has not been extensively explored. To assess whether socioeconomic status affects outcomes, we evaluated low-income public health insurance as a proxy. We analyzed how low-income public health insurance influences overall survival in children, adolescents, and young adults diagnosed with bone and soft tissue sarcomas. Methods: The University of California San Francisco Cancer Registry was used to identify patients age 0-39 diagnosed with bone or soft tissue sarcomas between 2000-2015. Low-income patients were defined as those with Medicaid, which is only available under state law to eligible low-income individuals or families, or those with no insurance. The comparison group included all other patients with private insurance, Medicare, or Tricare. Survival curves were computed using the Kaplan-Meier method and compared using log-rank tests and Cox models. Logistic regression was used to investigate the association of low-income public insurance and presence of metastatic disease at diagnosis. Results: A total of 1,106 patients were included in the analysis. 444 (40%) were considered low-income; of these, 428 (39%) had public insurance and 16 (1%) had no insurance. Low-income patients were more likely to both be racial/ethnic minorities and present with metastatic disease on multivariable analysis. Low-income patients had significantly worse 5-year OS (61% vs 71%, p = 0.0003). When stratified by localized, regional, or metastatic disease, low-income patients consistently had significantly worse 5-year OS (localized: 78% vs 84%, regional: 64% vs 73%, metastatic: 23% vs 30% respectively, p &lt; 0.0001). Age and race/ethnicity did not significantly impact OS in this study population. Conclusions: Low-income patients with bone and soft tissue sarcomas had decreased overall survival. While these patients were more likely to have metastatic disease, disparities in survival were noted even within the localized and regional disease groups. The means by which insurance status impacts survival requires additional investigation, but may be through reduced access to care.
Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma
Authors: Shigeki Sekine, Tohru Kiyono, Eijitsu Ryo, Reiko Ogawa, Susumu Wakai, Hitoshi Ichikawa, Koyu Suzuki, Satoru Arai, Koji Tsuta, Mitsuaki Ishida, Yuko Sasajima, Naoki Goshima, Naoya Yamazaki, Taisuke Mori
Journal: Journal of Clinical Investigation (2019)

Poroma is a benign skin tumor exhibiting terminal sweat gland duct differentiation. The present study aimed to explore the potential role of gene fusions in the tumorigenesis of poromas. RNA sequencing and reverse transcription PCR identified highly recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poromas (92/104 lesions, 88.5%) and their rare malignant counterpart, porocarcinomas (7/11 lesions, 63.6%). A WWTR1-NUTM1 fusion was identified in a single lesion of poroma. Fluorescence in situ hybridization confirmed genomic rearrangements involving these genetic loci. Immunohistochemical staining could readily identify the YAP1 fusion products as nuclear expression of the N-terminal portion of YAP1 with a lack of the C-terminal portion. YAP1 and WWTR1, also known as YAP and TAZ, respectively, encode paralogous transcriptional activators of TEAD, which are negatively regulated by the Hippo signaling pathway. The YAP1 and WWTR1 fusions strongly transactivated a TEAD reporter and promoted anchorage-independent growth, confirming their tumorigenic roles. Our results demonstrate the frequent presence of transforming YAP1 fusions in poromas and porocarcinomas and suggest YAP1/TEAD-dependent transcription as a candidate therapeutic target against porocarcinoma.
Copy number instability (CNI) combined with CA19-9 as a biomarker for postoperative prognostic prediction of pancreatic cancer.
Authors: Qian Zhan, Dandan Ren, Beibei Mao, Xue Song, Yanna Ma, Henghui Zhang, Baiyong Shen
Journal: Journal of Clinical Oncology (2019)

e15730 Background: Pancreatic cancer is one of the most aggressive human malignancies and has a poor prognosis. Large-scale studies have reported on its initiation, progression, diagnosis and prognosis. However, over the past several decades, the overall 5-year survival rate of pancreatic cancer has remained at less than 5%. Thus, the current major challenge in the postoperative management of pancreatic cancer is to identify high-risk recurrent patients. We retrospectively investigated the clinical, pathological and outcome data for 48 pancreatic cancer patients to clarify the associations of molecular mechanisms and prognosis. Methods: Eligible pancreatic cancer patients were included, and formalin-fixed paraffin-embedded (FFPE) tumor specimens and matched blood samples were collected at Ruijin Hospital, Shanghai Jiao tong University School of Medicine. Genome profiles were analyzed by using a designed 1408-gene panel based on next-generation sequencing (NGS). The copy number instability (CNI) score in primary tumor tissue was calculated to investigate the relationship between molecular features of the primary tumor and prognosis. Results: The CNI score in primary tumor tissue was positively correlated with lymph node metastasis, TP53 mutation, and early recurrence. Moreover, preoperative Carbohydrate antigen 19-9 (CA19-9) levels and CNI scores in primary tumor tissue were significant independent predictors associated with PFS in pancreatic ductal adenocarcinoma (PDAC). Finally, we performed an independent signature that includes CNI score and Carbohydrate antigen 19-9 (CA19-9) level to predict prognosis of pancreatic cancer. Conclusions: These results suggest that CNI score in primary tumor tissue is an independent predictive prognostic biomarker for PDAC. CNI combined with CA19-9 is a better predictor for postoperative prognostic prediction of pancreatic cancer.
Factors associated with non-completion of radiation therapy (RT) or radiochemotherapy (RTCT) in head and neck squamous cell carcinoma (HNSCC): A prospective study.
Authors: Florian Clatot, Lucie Lebret, Olivier Rigal, Laureline Lefebvre, Simon Dandoy, Marine Cabourg, Cristian Moldovan, Ovidiu Veresezan, Jean Christophe Thery, Camille Petrau, Mathilde Lebreton, Fanny Guérault, Mélanie Ebran, Céline Gouley-Toutain, Nicolas Bon-Mardion, Vianney Bastit, Frédéric Di Fiore, Bernard M. Dubray, Justine Lequesne, Sébastien Thureau
Journal: Journal of Clinical Oncology (2019)

e17568 Background: Although numerous factors have been reported to increase RT/RTCT toxicity, identification of patients with high risk of toxicities is lacking. Methods: The monocentric NutriNeck study (NCT02900963) recruited all HNSCC patients between 2014 and 2018 treated by RT or RTCT. Patients fed by enteral nutrition before RT initiation were excluded. All clinical and biological, planned RT or RTCT parameters were collected at baseline. A daily monitoring of the weight and a weekly evaluation of clinical, biological and food intake during RT/RTCT were performed. A nutritional intervention by enteral feeding was systematically proposed in case of 2 kg weight loss under treatment. Complete treatment was defined as full planned RT doses without more than 3 days interruption, and full planned doses of cisplatin and cetuximab if indicated. Primary endpoint assessed factors associated with non-completion of the planned treatment. Secondary endpoint assessed factors associated with use of enteral nutrition during treatment. A p value &lt; 0.01 was considered significant. Results: Among the 249 HNSCC patients included, 118 (47%) were treated by RT and 131 (53%) by RTCT. 63 patients (25%) did not complete treatment: 3/118 (2.5%) in the RT group compared to 60/131 (45.8%) the RTCT group, p &lt; 0.0001. Median weight lost during treatment (7 vs 3.8 kg, p &lt; 0.0001) and grade 3 toxicities (53 vs 33%, p = 0.006) were more frequent in patients with incomplete RT/RTCT. Nutritional intervention was performed in 111 patients: 28 (23.7%) with RT and 83 (62.6%) with RTCT (p &lt; 0.0001). Week 4 was associated with the higher rate of enteral nutrition initiation in both RT and RTCT groups. Among RTCT group, weight loss during treatment (OR 1.2 for each kg, p &lt; 0.0001) and use of enteral feeding (OR 2.7, p = 0.005) were associated with incomplete treatment in multivariate analysis. Of note, 48 patients refused enteral nutrition while indicated, they had comparable grade 3 toxicities and weight loss during treatment compared to the 111 patients who accepted enteral nutrition. Conclusions: Incomplete treatment is overwhelmingly associated with RTCT rather than RT. Baseline clinical, biological features or treatment volume/dose are not associated with incomplete treatment. Enteral nutrition initiated during treatment is poorly efficient.
Oncologists’ perceived confidence in managing pre-existing chronic comorbidities during patients’ active cancer treatment.
Authors: Dudith Pierre-Victor, Iman K. Martin, Brenda Adjei, Mary Shaw-Ridley, Bruce D. Rapkin, Marge Good, Diane C. St. Germain, Bernard W. Parker, Worta J. McCaskill-Stevens
Journal: Journal of Clinical Oncology (2019)

e18036 Background: Cancer frequently occurs with other chronic diseases, and this poses serious care coordination challenges during patients’ active cancer treatment (ACT). There is limited research addressing chronic comorbidity (CC) management during ACT. This study aimed to examine practicing oncologists’ perceived confidence in independently managing CC during ACT. Methods: Oncologists in the National Cancer Institute’s Community Oncology Research Program (NCORP) were surveyed about their perceived confidence in managing CC. The Likert scale survey was piloted-tested, IRB-approved, and administered to oncologists. In December 2018, NCORP network oncologists were sent an email invitation to complete the online survey. Pearson chi-square test was used to identify oncologists’ differences in perceived confidence in managing CC. Results: Among the 201 respondents of the ongoing survey, 48% were medical oncologists, 21.2% radiation or surgical oncologists, and 30.8% were of other specialties. Overall, 69% agreed (agree or strongly agree), 17.3% were neutral, and 13.4% disagreed (strongly disagree or disagree) that they were confident in managing all CC independently. While 69% of oncologists were confident when managing any CC, only 49% and 19.8% remained confident when managing CC previously managed by a primary care physician (PCP) and by a non-oncology subspecialist, respectively. Across oncologic subspecialties, 47.6%, 77.9% and 72.1% of radiation/surgical oncologists, medical oncologists, and those of other specialties, respectively, agreed that they were confident in independently managing CC (p = 0.003). Conclusions: Most oncologists are confident in managing all CC during patients’ ACT. However, they were less confident with CC previously managed by PCPs, and even less confident for CC previously managed by non-oncology subspecialists. These results indicate opportunities for greater collaboration between oncology and non-oncology specialists to ensure complete and coordinated care for cancer patients with comorbidities.
RNA interference mediated silencing of SPINK reduces invasion and proliferation of prostate cancer cells
Authors: Jas Singh, Dania Y. Azari, Qihan Dong
Journal: Cancer Research (2006)

3507  Serine protease inhibitors (SPI) regulate the activity of proteases that are known to promote tumor invasion and metastasis. The expression of protease inhibitors has been generally considered to be an anti-malignant phenotype. However, recent studies indicate that certain SPI are linked to a worse prognosis for cancer patients, thus adding a new dimension to their functions in Tumor Biology. Recently, a SPI belonging to the Kazal type family, known as Serine Protease Inhibitor Kazal type 1 (SPINK) has been shown to be overexpressed in various malignancies (1-4). In prostate cancer, SPINK is overexpressed by more than 100-fold compared to normal prostate according to Serial Analysis of Gene Expression.. We aimed to investigate the biological significance of the increase in SPINK and its mode of action in prostate cancers based on the hypothesis that downregulation of SPINK mRNA levels could affect cell proliferation and invasion. We transfected human prostate cancer cell lines (LNCaP, PC3 and DU145) with short interfering RNA (siRNA) against SPINK and verified the gene knockdown effect (68%) with real-time RT-PCR. Using Matrigel invasion and colorimetric cell viability (MTS) assays, we found that the knockdown of SPINK caused >34% decrease (*P
Relationship between body composition and hormone sensitivity for androgen deprivation therapy in metastatic prostate cancer patients.
Authors: Eiji Kashiwagi, Masaki Shiota, Kenjiro Imada, Keisuke Monji, Ario Takeuchi, Junichi Inokuchi, Katsunori Tatsugami, Masatoshi Eto
Journal: Journal of Clinical Oncology (2019)

e16500 Background: Obesity has been reported to have an influence on prostate cancer incidence and its aggressive phenotype but this remains controversial. Body mass index (BMI) is useful marker of obesity but it does not represent body fat percentage precisely. The relationship between body composition and the efficacy of androgen deprivation therapy (ADT) has not well been studied. Here, we investigated whether body composition features including the psoas muscle may be predictive factors of ADT. Methods: This study enrolled hormone-sensitive metastatic prostate cancer patients who were treated with primary ADT from April 2006 to August 2009 in Kyushu University Hospital, and who underwent a CT scan prior to primary ADT for calculating body fat percentage, psoas muscle ratio (psoas muscle, cm 3 /height, cm 2 ), and BMI. Results: Of the 178 patients enrolled, 60 patients died during follow-up. Median follow-up was 32 months, and progression-free survival (PFS) and overall survival (OS) were 28 and 80 months, respectively. Multivariate analysis revealed that the psoas muscle ratio was correlated with OS (hazard ratio [HR]: 0.448; 95% CI = 0.206–0.922; P= 0.028). Conclusions: This study demonstrated that higher psoas muscle ratio predicts longer OS among non-localized prostate cancer patients treated with primary ADT. [Table: see text]
Anthracycline and Peripartum Cardiomyopathies
Authors: Joshua A. Cowgill, Sanjeev A. Francis, Douglas B. Sawyer
Journal: Circulation Research (2019)

Anthracycline-associated cardiomyopathy and peripartum cardiomyopathy are nonischemic cardiomyopathies that often afflict previously healthy young patients; both diseases have been well described since at least the 1970s and both occur in the settings of predictable stressors (ie, cancer treatment and pregnancy). Despite this, the precise mechanisms and the ability to reliably predict who exactly will go on to develop cardiomyopathy and heart failure in the face of anthracycline exposure or childbirth have proven elusive. For both cardiomyopathies, recent advances in basic and molecular sciences have illuminated the complex balance between cardiomyocyte and endothelial homeostasis via 3 broad pathways: reactive oxidative stress, interference in apoptosis/growth/metabolism, and angiogenic imbalance. These advances have already shown potential for specific, disease-altering therapies, and as our mechanistic knowledge continues to evolve, further clinical successes are expected to follow.
A novel RAS internal tandem duplication involving the switch II domain disrupts GAP-binding and activates oncogenic signaling.
Authors: Emil Lou, Thomas Turbyville, Dhirendra Simanshu, Rendong Yang, John Columbus, Bob Stephens, Drew Sciacca, Anne Sarver, Subbaya Subramanian, Dwight Nissley, Andrew Nelson
Journal: Journal of Clinical Oncology (2019)

e15069 Background: Recent clinical guidelines for expansion of molecular testing of oncogenic RAS mutations in colorectal carcinoma have led to increased identification of mutations in this patient population. The clinical characteristics of NRAS-mutated colorectal carcinoma have not been well established because of the lower prevalence of these mutations (&lt; 6%) as compared to oncogenic KRAS mutations. Here, we report the discovery of a novel internal tandem duplication (ITD) mutation of NRAS, which disrupts the Switch II domain in an index case of a patient with widely disseminated colorectal cancer. Methods: Hotspot next generation sequencing of a brain metastasis using a clinical solid tumor panel identified this novel NRAS ITD and a TP53 missense mutation (p.P275F). Whole exome sequencing of the primary tumor and two metastatic lesions (lung and brain) was performed to identify other genetic factors potentially driving the disease. Results: The above approach confirmed that the NRAS ITD and TP53 mutation were conserved between the primary tumor and both metastatic tumors and identified an additional pathogenic mutation in CSMD1 (a tumor suppressor gene). No other clearly pathogenic driver mutations were identified. Structural biology and biochemical analyses demonstrated that the inserted 15 amino acids prevented binding to GAP protein, leading to sustained RAS activation and increased interaction with RAF to stimulate downstream MAPK activation. Conclusions: These genomic and biochemical studies indicate that a novel NRAS ITD was the primary driver mutation of this aggressive colorectal carcinoma. Identical or similar ITDs in NRAS and KRAS may also drive other forms of colorectal cancer and other aggressive malignancies and represent a new subset of RAS-driven drug-resistant cancers.
Feasibility of a platform trial based on molecular analysis in rare gynecologic cancers.
Authors: Jubilee Brown, John H. Farley, Thomas J. Herzog, Erin Crane, Al Covens, David Arguello, Pilar Ramos, Wangjuh Chen, Adam ElNaggar
Journal: Journal of Clinical Oncology (2019)

e14585 Background: Challenges in patient accrual limit successful conduct of clinical trials in rare gynecologic malignancies. A platform trial using molecular analysis to guide therapy choice would optimize enrollment but would require actionable mutations (AM) to be feasible. Therefore, we sought to determine if enough AMs exist in rare gynecologic cancers (CA) to justify the design of a platform trial. Methods: We compiled all molecular profiling data performed at Caris Life Sciences through February 2019. Non-epithelial ovarian cancer (OC), rare epithelial OC, non-endometrioid uterine, neuroendocrine gynecologic, and vulvar CA were compiled. AMs were identified. Results: Among 280 cases of non-epithelial OC, 228 malignant stromal tumors and 52 germ cell tumors were identified. AMs in stromal tumors included KMT2D (9.8%), PIK3CA (7.8%), and 16 other AMs ( &lt; 1% each). AMs in germ cell tumors included PIK3CA (20%), KIT (10%), PTEN (10%), TMB (8.2%), CDKN2A (8%), ARID1A (6%), and 16 other AMs ( &lt; 6% each). Among 702 rare epithelial OCs, 132 mucinous CAs, 91 low-grade serous/endometrioid, 367 clear cell, and 112 carcinosarcoma (CS) cases were identified. AMs in mucinous CAs included KRAS (61.8%), CDKN2A (15.3%), PIK3CA (12.7%), ARID1A (9.9%), GNAS (6.9%), and 20 other AMs ( &lt; 5% each). AMs in low-grade serous/endometrioid included KRAS (28.9%), ARID1A (13.3%), PTEN (8.9%), PIK3CA (7.8%), MSI (6.2%), and 15 other AMs ( &lt; 6% each). AMs in clear cell OCs included ARID1A (53.4%), PIK3CA (47.5%), KRAS (11.6%), PTEN (6.8%), and 36 other AMs ( &lt; 6% each). AMs in ovarian CSs included PIK3CA (7.2%), ARID1A (6.2%), and 22 other AMs ( &lt; 5% each). Among 4864 rare uterine CA, 4670 sarcomas, 173 serous CAs, and 21 clear cell CAs were identified. AMs in uterine sarcomas included PTEN (40.1%), PIK3CA (37.1%), ARID1A (31.6%), MSI (20.7%), KRAS (16.8%), TMB (14%), PIK3R1 (10%), and 41 other AMs ( &lt; 10% each). Among 102 gynecologic neuroendocrine tumors, AMs included ARID1A (29.2%), PIK3CA (18%), PTEN (18%), MSI (6.5%), TMB (6%), and 4 other AMs ( &lt; 6% each). Among 59 vulvar CAs, AMs included CDKN2A (28.7%), PIK3CA (17.8%), NOTCH1 (9.6%), TMB (6.8%), and 24 other AMs ( &lt; 5% each). Conclusions: A variety of actionable mutations are present in every type of rare gynecologic cancer evaluated, but mutations specific to individual histologies are not reliably present. This supports the use of molecular profiling to identify potential targets and supports a platform trial strategy to study rare gynecologic cancers.
AB1024 USE,EFFICACY AND LONG TERM SAFETY OF RITUXIMAB IN PEDIATRIC RHEUMATIC DISEASES: SINGLE CENTER EXPERIENCE FROM NORTH INDIA
Authors: sumidha mittal, Manjari Agarwal, Sujata Sawhney
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Rituximab(RTX) is used in pediatric rheumatic diseases as an off label indication.There is paucity of data on safety and long term efficacy in countries with high burden of infectious diseases. <h3>Objectives</h3> 1. To study the use and safety of RTX in pediatric rheumatic diseases 2. To assess the long term efficacy of RTX in pediatric systemic lupus erythematosus(pSLE). <h3>Methods</h3> Data of all children who received RTX was collected on standardized collection forms.This data set was reviewed.Children with pSLE who were given RTX were included for efficacy analysis.Screening, use and safety were evaluated for all patients. <h3>Results</h3> USE: Rituximab was given to 4 children with polyarticular juvenile idiopathic arthritis(PJIA)(4/145=2.7%) and 17 children with pSLE(17/225=7.5%).In children with PJIA, RTX was used as third line treatment, who failed methotrexate and TNF inhibitor therapy. In pSLE, lupus nephritis was the primary indication for RTX(56%), vasculitis(17%), neuropsychiatric SLE and refractory cytopenias(12% each) and aggressive polyarthritis with steroid dependence( 5%). SAFETY: Pre-biologic screen for HIV, Hepatitis B and C and tuberculosis was negative. Total immunoglobulinG level was assayed prior to RTX for all children. CMV PCR was done in 11/17 pSLE patients. No immediate or delayed anaphylaxis was noted. No child had reactivation of herpes zoster.There was no mortality in this cohort. EFFICACY: Studied in 17 children with pSLE over 21 episodes of RTX(2 received 3 cycles of RTX over 5 years).Median age at RTX use was 13.66 years(range 6.58-21.66 years).Median duration of follow up was 48 months(range 3-120 months).During long term follow up 14 patients didnot have any disease flare. Three(17.6%) flared and required cyclophosphamide/second cycle of RTX. Mean dose of prednisolone prior to RTX was 0.7mg/kg/day while that at 1 year post RTX was 0.065mg/kg/day(p value 0.001) and at 2 years was 0.05mg/kg/day(p value 0.003). Mean SLE disease activity index 2K(SLEDAI-2K) prior to RTX was 16.25 while that at 1 year post RTX was 1.25(p value 0.004), at 2 years was 2( p value 0.004) and at 3 years was 0.85(p value 0.028). <h3>Conclusion</h3> We conclude that RTX is efficacious for use in severe spectrum of pSLE and is relatively safe to use even in a developing country like ours with huge infectious disease burden. <h3>References</h3> [1] Gladman DD, Ibanez D, Urowitz MB (2002) Systemic lupus erythematosus disease activity index 2000. J Rheumatol 29:288–291 <h3>Disclosure of Interests</h3> None declared