tbuckley/cabot-search huggingface dataset:
Is neratinib following trastuzumab in early-stage HER2-positive breast cancer cost-effective?
Authors: Naomi RM Schwartz, Meghan Rose Flanagan, Joseph B Babigumira, Lotte Maria Gertruda Steuten, Joshua A. Roth
Journal: Journal of Clinical Oncology (2019)

6625 Background: Neratinib after adjuvant trastuzumab significantly improves disease-free survival (DFS) in human epidermal growth factor receptor 2-postiive (HER2+) breast cancer, but the median absolute DFS gain is only 1.3 months. There has been much controversy in the clinical and lay media as to whether the substantial cost of neratinib is justified by its effects, including a prominent ASCO Post article from Dr. Vogl about a year ago. We performed a cost-utility analysis to formally assess the value of adding neratinib based on Phase III ExteNET trial results. Methods: We developed a Markov state-transition model to assess the value of neratinib in Stage I-III HER2+ breast cancer. Five-year recurrence rates were derived from ExteNet. Mortality and recurrence rates after 5 years were derived from the HERceptin Adjuvant (HERA) trial. Costs were derived from wholesale acquisition costs and peer-reviewed literature. Health state utilities were derived from ExteNET and prior publications. Outcomes included life years (LY), quality-adjusted life years (QALYs), direct medical expenditures, and cost per QALY gained. The analysis took a payer perspective over a lifetime horizon and results were discounted at 3% per year. One-way and probabilistic analyses were conducted to evaluate uncertainty. As neratinib conferred more clinical benefit in hormone receptor-positive (HR+) disease, we also assessed value in that specific subgroup. Results: Base case results are presented in Table. At typical U.S. willingness to pay thresholds of $100,000 and $150,000 per QALY gained, neratinib had 16.7% and 27.2%, probabilities of cost-effectiveness, respectively. In the HR+ subgroup, neratinib had a cost of $275,311 per QALY gained (19.9% &amp; 31.2% probability of cost-effectiveness at $100,000 &amp; $150,000 per QALY). Conclusions: In the first independent assessment of the value of neratinib after adjuvant trastuzumab, neratinib is not projected to be cost-effective, even among patients who derived the most clinical benefit. Future analyses should reassess the cost-effectiveness of neratinib treatment as trial data mature. Base case results. [Table: see text]
The use of noninvasive ventilation after weaning of acute respiratory failure prevent reintubation and decrease hospital mortality
Authors: S. R. P. O. R. Rosinha, S. M. A. Lobo, H. S. Sanches, M. Deraldini, A. M. A. Vidal, L. T. Tofoli, G. P. P. Schetino, Carlos Roberto Ribeiro de Carvalho, M. B. P. Amato, C. S. V. Barbas
Journal: American Journal of Respiratory and Critical Care Medicine (2002)
Comparison of mortality trends in patients with non-salivary gland and salivary gland adenoid cystic carcinoma in the United States population.
Authors: Girindra Ghanshyam Raval, Germame Hailegiorgis Ajebo, Locke Johnson Bryan, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2019)

e17584 Background: Adenoid cystic carcinoma is the most common histological subtype of malignancy seen in major and minor salivary glands. Although indolent they tend to recur and progress. Adenoid cystic carcinoma also arises from other structures such as lacrimal glands and trachea. This study compares the incidence-based mortality between patients who have salivary and no-salivary origin adenoid cystic carcinomas of the head and neck region over the period of 2000 to 2014. Methods: A nation-wide analysis was conducted utilizing the Surveillance, Epidemiology, and End Results (SEER) Database from the years 2000 to 2014. Incidence-based mortality for all stages of adenoid cystic carcinoma was queried and the results were grouped by race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander) and gender. All stages were included in the analysis. T-test was used to determine statistically significance difference between various subgroups. Linearized trend lines were used to visualize the mortality trends of all sub groups. Results: Incidence-based mortality for salivary gland adenoid cystic carcinomas in African American/Black patients is comparable to Caucasian/White patients despite a higher incidence in Caucasian/White patients (no statistically significant difference was noted). Also, the incidence-based mortality for non-salivary gland adenoid cystic carcinomas of the head and neck region in African American/Black patients was similar to Caucasian/White patients. Essentially no racial difference in mortality was noted between salivary and non-salivary gland tumors. Comparison of mortality between genders in both races in salivary and non-salivary gland tumors also did not show any statistically significant difference. Conclusions: This study showed that adenoid cystic carcinoma of non-salivary gland origin have the same mortality trends as that from salivary gland origin in both Caucasian/White and American/Black patients and in both genders. Given such uniformity, genetic and environmental factors may not play significant role in the progression and outcomes of this disease. Hence, adenoid cystic carcinoma may be treated with similar therapeutic approaches regardless of the origin, gender and race of the patient.
Analysis of nationwide lung, breast, and prostate cancer incidence in relation to provider availability and training programs in oncology.
Authors: Smit Mehta, Armand A Krikorian
Journal: Journal of Clinical Oncology (2019)

e13116 Background: Lung, Breast, and Prostate cancer are the leading causes of cancer incidences and mortality across all ages, races, and genders. These accumulate to 1.2 million deaths from 2011-2015. We hypothesize that the regional provider availability should match the local patterns of cancer incidences due to resource scarcity. This analysis examines the nationwide incidence of the most common cancers in relation to provider availability and conducts a further analysis of the location of training programs in relation to cancer incidence. Methods: Lung, Breast, and Prostate cancer incidences in the U.S. between ages 19-85 was assessed using data from the CDC and NCI. Oncology fellowships were found through the ERAS portal and the databases of the AMA. Oncologists’ practicing locations were found using Doximity data. These datasets were mapped using Google Maps software and a gap analysis was conducted. Results: In 2015, approximately 6.2% of the population were diagnosed with lung cancer, 12.4% of women with breast cancer, and 11.2% of men with prostate cancer. The highest incidences were seen in Kentucky, Connecticut, and New Jersey. Above average incidences were seen in New Hampshire, West Virginia, Mississippi, Louisiana, and Massachusetts. Roughly 25% of the 16,215 registered oncologists were concentrated in Florida, Texas, and California. A total of 132 oncology fellowships were identified, with only eight located within a 50-mile radius of the areas of most need. Conclusions: We found a significant disparity in the distribution of cancer incidences versus location in oncologists and fellowship programs. This data, along with data from the 2018 National Oncologists Workforce suggests that Florida, California, Michigan, Illinois, and New York have the highest percentage of oncologists near or above retirement age; indicating that the gap is likely to widen. It also showed a 12-fold variation in oncologist retention compared to where they completed their fellowship, with metropolitan areas in California rounding out the top 10 highest percentages of trained oncologists 1 . This highlights the need to match the workforce with areas of highest need, such as the Appalachian states; which have some of the highest cancer incidences and largest discrepancies of training programs and oncologists.
Suspected and confirmed germline variants from tumor-only somatic sequencing of 864 gastrointestinal malignancies.
Authors: Shivani Khanna, Steven Brad Maron, Leah Chase, Samantha Lomnicki, Sonia Kupfer, Daniel V.T. Catenacci
Journal: Journal of Clinical Oncology (2019)

e13131 Background: Targeted tumor-only somatic sequencing informs therapies and is becoming a routine part of cancer care. It also identifies patients with possible germline variants who require confirmatory genetic testing. The aim was to identify patients with suspected and confirmed germline variants whose GI tumors underwent somatic sequencing. Methods: 864 patients with GI tumors who had Foundation One (FO) somatic sequencing from 4/2003-3/2018 were evaluated. Inclusion criteria for suspected germline variants were: a) allele frequency ≥ 35% in hereditary cancer genes and b) pathogenic variants by FO and/or ClinVar. Variants in commonly mutated somatic genes ( TP53, KRAS, CDKN2A) were excluded in patients over age 40. Recommendation of genetic evaluation and germline test results were recorded. Patient, family, and tumor characteristics were compared using univariate analysis. Results: 199 of 864 patients had suspected germline pathogenic variants. 50 patients were recommended genetic evaluation, and 26 patients underwent genetic testing. A germline pathogenic variant was confirmed in 15 patients. Among all patients suspected to have germline variants, 8% were confirmed by genetic testing. Patients under age 40 and those with family cancer history were more often referred for testing (Table). Patients with variants in BRCA1, MLH1, MSH2, PMS2, POLE and TP53 were more often referred for testing. Conclusions: A quarter of patients carried a somatic pathogenic variant with allele frequency ≥35% in a hereditary cancer gene. 25% of these patients were recommended for genetic evaluation. Younger patients and those with family history were more often referred. 8% of patients with suspected germline variants were confirmed by genetic testing. These results provide “real world” experience in using somatic only tumor testing to identify patients with germline pathogenic variants who then might benefit from future cancer screening and genetic testing in family members. Comparison of characteristics by recommendation to undergo genetic testing based on somatic tumor sequencing results. [Table: see text]
SP0108 LSFM AND CATCHING UP IN JOINT IMAGING
Authors: Anika Grueneboom
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Bone tissue differs from other organs by its hardness and high optical density. These physical characteristics are challenging in the context of fluorescence based imaging studies addressing bone anatomy and physiology. The development of novel imaging technologies, such as light-sheet fluorescence microscopy and X-ray microscopy, and tissue-specific preparation procedures like optical clearing allowed us to reveal a so far overseen network of blood vessels in the cortical bone. These trans-cortical vessels (TCVs) directly connect the bone marrow vascularization with the periosteum and make the major contribution to total blood flow in long bones. Furthermore, we could show that immune cells are recruited to the peripheral circulation via TCVs and that TCVs are highly remodeled und inflammatory conditions. In case of chronic arthritis we observed a massive increase in TCV numbers, especially at the metaphysis of long bones. This increase in bone vascularization confirms observations of previous studies describing increasing numbers of microcanals in the bare area of metacarpal heads in the hands of rheumatoid arthritis patients. These alterations in bone anatomy might hint to an alternative mechanism by which immune cells are recruited into inflamed joint tissue. While current concepts describe the recruitment of immune cells from the systemic circulation, immune cells can potentially infiltrate the arthritic joints directly from the underlying bone marrow. <h3>Objectives:</h3> Clarifying the anatomical routes of cell recruitment as well as exploring the regulatory mechanism guiding immune cells from the bone marrow to the site of inflammation might bear novel therapeutic strategies to resolve inflammation and tissue injury in rheumatoid arthritis. <h3>Methods:</h3> 3D optical imaging approaches like Light-sheet fluorescence microscopy and 2-Photon laser-scanning microscopy enable the visualization of entire bones and joints. In combination with tissue-specific preparation procedures and labeling strategies inflammatory mediated changes in vascularization and cell recruitment can be analyzed. <h3>Results:</h3> The joint tissue architecture is massively affected by inflammatory arthritic processes leading to changes in vascularization, permeability and cellular tissue composition. These processes are directly connected to the onset as well as the resolution of inflammatory arthritis. <h3>Conclusion:</h3> Newly available imaging techniques as light-sheet fluorescence microscopy facilitate new insights into bone and joint tissue architecture, function and inflammatory processes. These findings might guide the identification of novel proresolving mediators to develop therapeutic strategies for managing tissue-damage-induced inflammation. <h3>Reference:</h3> [1] Grüneboom, A. et al., A network of trans-cortical capillaries as mainstay for blood circulation in long bones. Nature Metabolism 1, 236-250, doi:10.1038/s42255-018-0016-5 (2019) <h3>Disclosure of Interests:</h3> None declared
Publisher Correction: The long tail of oncogenic drivers in prostate cancer
Authors: Joshua Armenia, Stephanie A. M. Wankowicz, David Liu, Jianjiong Gao, Ritika Kundra, Ed Reznik, Walid K. Chatila, Debyani Chakravarty, G. Celine Han, Ilsa Coleman, Bruce Montgomery, Colin Pritchard, Colm Morrissey, Christopher E. Barbieri, Himisha Beltran, Andrea Sboner, Zafeiris Zafeiriou, Susana Miranda, Craig M. Bielski, Alexander V. Penson, Charlotte Tolonen, Franklin W. Huang, Dan Robinson, Yi Mi Wu, Robert Lonigro, Levi A. Garraway, Francesca Demichelis, Philip W. Kantoff, Mary-Ellen Taplin, Wassim Abida, Barry S. Taylor, Howard I. Scher, Peter S. Nelson, Johann S. de Bono, Mark A. Rubin, Charles L. Sawyers, Arul M. Chinnaiyan, Nikolaus Schultz, Eliezer M. Van Allen
Journal: Nature Genetics (2019)
A pretreatment CT model predicts survival following chemolipiodolization in patients with hepatocellular carcinoma.
Authors: Dong Wu, Hengwei Fan, Shuping Qu
Journal: Journal of Clinical Oncology (2019)

e14509 Background: This study aimed to establish a computed tomography-based prognostic model for patients with hepatocellular carcinoma treated with transarterial chemoembolization. Methods: Using prospectively collected data from 195 consecutive patients with hepatocellular carcinoma who underwent chemolipiodolization at the Eastern Hepatobiliary Surgery Hospital between 2013 and 2016, we established a prognostic model based on hepatocellular carcinoma enhancement patterns on computed tomography scans to predict the outcome of transarterial chemoembolization. Furthermore, a histopathology analysis was performed on 108 different patients undergoing resection between 2014 and 2016 to identify whether there was a correlation between enhancement pattern and microvessel density. Results: The prognostic model classified hepatocellular carcinoma into 3 types: Type I, which reached peak enhancement during the arterial phase and had a high mean microvessel density (101.5 vessels/0.74 mm 2 ); Type II, which reached peak enhancement during the portal venous or delayed phase and had an intermediate microvessel density (53.6 vessels/0.74 mm 2 ); and Type III, in which the tumor was insignificantly enhanced and had a low microvessel density (21.1 vessels/0.74 mm 2 ). For type I, II, and III hepatocellular carcinoma, the post-transarterial chemoembolization 1-year tumor complete necrosis rates were 13.7%, 36.5%, and 0%, respectively (p &lt; 0.001) and the 3-year overall survival rates were 14.1%, 38.6%, and 0%, respectively (p &lt; 0 .001). Conclusions: Our results indicate that hepatocellular carcinoma type is an independent predictor of complete necrosis and overall survival.
A plasma-only integrated genomic and epigenomic circulating tumor DNA (ctDNA) assay to inform recurrence risk in colorectal cancer (CRC).
Authors: Aparna Raj Parikh, Emily E. Van Seventer, Genevieve Marie Boland, Anna Hartwig, Ariel Jaimovich, Victoria M. Raymond, AmirAli Talasaz, Ryan Bruce Corcoran
Journal: Journal of Clinical Oncology (2019)

3602 Background: ctDNA identifies patients (pts) at high risk for disease recurrence post CRC resection (post-op). Current ctDNA residual disease detection approaches assess only genomic alterations (alts) and rely on tissue sequencing to identify tumor-derived alts. We evaluated a plasma-only ctDNA assay to identify high risk pts. Methods: 72 CRC pts (surgery only = 42; adjuvant therapy (adj) = 30) had post-op and/or post-adj plasma samples (3-4mL). Extracted cfDNA (median 27 ng) was analyzed using a single-sample NGS test validated in early stage CRC that integrates assessment of genomic alts with epigenomic cancer signature (Guardant Health, CA). A variant classifier was applied to differentiate tumor-derived from non-tumor derived alts in a tumor tissue-uninformed approach. Results: In the surgery cohort, samples were collected a median of 31 days (d) post-op. 7/8 pts with post-op ctDNA detected (ctDNA+) recurred (PPV 88%; median time to recurrence (mTTR) 248d). The recurrence-free pt has &lt; 180d follow-up. 7/34 pts without ctDNA detected (ctDNA-) recurred (NPV 79%; mTTR 333d). 1/1 Stage 0-II ctDNA+ pt recurred (PPV 100%; TTR 440d) while 1/20 ctDNA- recurred (NPV 95%; TTR 440d). 27 pts in the adj cohort had samples collected a median of 37d post-adj. 6/6 ctDNA+ pts recurred (PPV 100%, mTTR 239d). 4/21 ctDNA- pts recurred (NPV 81%, mTTR 466d). 2/2 ctDNA+ and 0/11 ctDNA- Stage III pts recurred (PPV, NPV 100%, mTTR 420d). All 3 post-op ctDNA+/post-adj ctDNA+ (ctDNA persistence) pts recurred. 1/2 post-op ctDNA+/post-adj ctDNA- (ctDNA clearance) pts is recurrence free (306d). 2 post-op ctDNA-/post-adj ctDNA+ pts recurred. In the entire cohort, ctDNA+ after standard therapy completion had a recurrence PPV 93%, NPV 80%, HR 11.29 (p &lt; 0.0001). Conclusions: In post-op CRC, ctDNA detection utilizing a tumor-uninformed integrated genomic and epigenomic assay has high recurrence PPV and NPV following standard therapy completion. ctDNA identifies pts who may benefit from post-op adj therapy or additional/modified post-adj therapy. These findings demonstrate that ctDNA detection from a single post-op/post-adj plasma sample stratifies high/low risk pts and informs therapy decision making.
Utilizing social media for cancer prevention.
Authors: Ana Maria Lopez, Jennyffer Morales, Garrett Harding, Donna Branson
Journal: Journal of Clinical Oncology (2019)

e13076 Background: Cancer prevention and cancer screening behaviors are challenging to support. A myriad of variables including improved knowledge, language access, and health care access serve as facilitators for cancer screening behaviors. Utah is a vast state that is remarkably sparsely populated with more than 96% of the state defined as either rural (&lt; 100 persons per square mile) or frontier (&lt; 7 persons per square mile). Huntsman Cancer Institute is the only academic health center in the Mountain West and serves as the only NCI Comprehensive Cancer Center in the region. Methods: Access to the internet and to social media helps to bridge geography and support engagement. Facebook Live and Twitter Chats were used to deliver content. Language, Spanish, access was considered. Social media was also utilized to connect interested populations with in-person cancer prevention education events. Results: We will present our outreach results by intervention. Conclusions: Our work has successfully engaged rural and Latino populations in cancer prevention activities through social media.
Mutations of H3.3 and H3.1 in a large cohort of glioma tumors.
Authors: Ashley Love Sumrall, Joanne Xiu, Jennifer M Eschbacher, Sandeep Mittal, Zoran Gatalica, Manjari K Pandey, Surasak Phuphanich, Wolfgang Michael Korn, Gregory N. Fuller, Amy B. Heimberger
Journal: Journal of Clinical Oncology (2019)

e13540 Background: Mutations in the histone genes H3.3 and H3.1 are driver events in pediatric and adult gliomas and carry diagnostic and prognostic importance for tumors originating from midline structures. Patients with tumors affected by these mutations are notoriously difficult to treat, and the prevalence and molecular correlates of H3 mutations in a large glioma population have not been systematically reported. We aim to survey a large cohort of gliomas for H3-mutations. Methods: Consecutive gliomas submitted for tumor profiling at Caris Life Sciences from 2015- 2018 were analyzed. NextGen sequencing was done on 592 genes (NextSEQ Illumina); MGMT promoter methylation was tested by pyrosequencing; and EGFRvIII and gene fusions were tested by RNA-sequencing (ArcherDx FusionPlex). Results: Of the 1763 tumors analyzed, 41 harbored H3F3A alterations, including 33 with the K27M mutation (4 arose from the spinal cord, 1 from cerebellum, 1 from brain stem, 4 from thalamus, and 23 from brain, NOS). Eight G34R mutations were identified. A HIST1H3B-K27M was detected in a tumor from the brain stem. Overall, H3 mutations were more prevalent in pediatric tumors (8 of 26, 31%) than adult tumors (34 of 1737, 2%). All H3 mutations seen in pediatric tumors were from grade IV tumors. Among the 34 H3-mutated adult tumors, histology differed. There were 2 grade II tumors (diffuse astrocytoma), 1 low grade glioma from the spinal cord, 1 anaplastic ganglioglioma and 2 anaplastic astrocytomas. In the investigated cohort, H3-mutations were mutually exclusive of IDH1/2 mutations and EGFR alterations. Significantly higher mutation rates were seen in H3-mutated tumors for TP53 (69%. Vs. 37%), ATRX (46% vs. 24%), NF1 (23% vs. 12%) , PDGFRA (17% vs. 1%), FGFR1 (12% vs. 1%), FBXW7 (5% vs. 0), BLM (3% vs. 0) and TSC2 (2% vs.0) compared with H3-WT (p &lt; 0.05). The H3-WT tumors were more enriched for MGMT-methylation (53% vs. 26%) and PTEN mutation (22% vs. 7%) (p &lt; 0.05). In H3-mutated tumors that were MGMT-methylated (n = 10), most H3-mutations seen were G34R (n = 8) while K27M (n = 2) was largely exclusive. Conclusions: This survey of a large cohort of gliomas revealed a heterogeneous distribution of H3 mutations. The co-occurring molecular alterations seen in H3-mutated tumors further support the hypothesis that these tumors are a distinct molecular entity. By better characterizing these associations, we are closer to developing more insight into novel treatment strategies for a class of tumors with historically dismal prognosis.