tbuckley/cabot-search huggingface dataset:
Circulating tumor DNA analysis to reveal genomic profiles for epithelial ovarian cancer.
Authors: Yang Xiang, Shan Zhu, Weiran Wang, Dongyan Cao, Xi-Run Wan, Junjun Yang, Jiaxin Yang, Mei Yu, Yuhua Gong, Yanfang Guan, Jing Wang, Peiling Li, Ying Yue, Guo-Nan Zhang, Ping Wang, Yongjun Wang, Xuefeng Xia, Ling Yang, Xin Yi
Journal: Journal of Clinical Oncology (2019)

5543 Background: Circulating tumor DNA (ctDNA) analysis in epithelial ovarian cancer (EOC) was previously reported, however with limited samples or limited genes. Here, we reported an analysis of ctDNA in EOC cohort using targeted sequencing with a 1021-gene panel. Methods: Patients with EOC were enrolled, and treatment-naïve tumor tissues and blood samples were collected. We utilized a 1021-gene NGS panel in matched tissue DNA and ctDNA to identify somatic mutations with white blood cell DNA as a germline control. Results: Mutations were identified in all of the 65 tissues and in 53 (81.5%) ctDNA. The median ctDNA mutation allelic frequency was 2.5%, ranging from 0.1% to 36.2%. A median of 66.7% (12.5%-100.0%) of tissue derived mutations were observed in ctDNA. Besides, there were 91 ctDNA private mutations, including TP53 gene mutations. The most frequently mutated genes were TP53 (55.4%), PIK3CA (13.8%) and ARID1A (12.3%) in ctDNA analysis, which were consistent with tissue analysis (60.0%, 26.2% and 20.0% of tissues with TP53, PIK3CA and ARID1A mutations, respectively). Mutations of TP53 (37/42) in high-grade serous ovarian carcinoma (HGSOC), PIK3CA (10/11) and ARID1A (8/11) in ovarian clear cell carcinoma, BRAF (4/5) in low-grade serous ovarian carcinoma and PIK3CA (3/5), ARID1A (2/5) and PTEN (2/5) in endometrioid carcinoma were observed as the most commonly genetic aberrations in ctDNA in different sub-types of EOC, which located in different signal pathways and suggested different pathogenesis. In total, 90.5% (38/42) of HGSOC were ctDNA positive, comparing with 65.2% (15/23) of other EOC subtypes (p = 0.012). In addition, 56.5% (13/23) of stage I~II EOC were ctDNA positive, comparing with 94.7% (36/38) of stage III (p = 0.002). No association between ctDNA positivity and other clinic characteristics was observed, including pathological differentiation, CA125, lesion density (solid vs. cystic-solid and cystic). Multivariable analysis suggested FIGO stage III (p = 0.008) as an independent predictor of ctDNA detection. Conclusions: In summary, genomic characterization of EOC may offer insights into tumorigenesis and identify potential therapeutic targets in this disease.
Cost-effectiveness of tyrosine kinase inhibition in first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer.
Authors: Jiaqi Han, Huabin Hu, Mengting Liao, Longjiang She, Linli Yao, Dong Ding, Shan Zeng, Shen Liang-Fang, Jin Huang
Journal: Journal of Clinical Oncology (2019)

e20504 Background: Patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR) mutation have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the economic efficiency of this application is unclear, especially in limited health resource settings. To inform policy makers about the value of these medications, we developed a Markov model to compare the cost-effectiveness of these strategies. Methods: A Markov model was developed to compare the cost-effectiveness of chemotherapy, gefitinib, erlotinib, afatinib and osimertinib treatments from a public payers’ perspective in the U.S and China. Health states consisted of progression-free survival, progressive disease, and death. Model transition, adverse event probabilities, disease progression, and death were obtained from randomized clinical trials and network meta-analysis. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) over a 10-year lifetime horizon were calculated. One-way and probabilistic sensitivity analyses were performed by multiple potentially modifiable parameters. Results: The tyrosine kinase inhibitors were more cost-effective than chemotherapy treatment in both the U.S and China. In the U.S, compared with erlotinib, afatinib had an ICER of $241,420/QALY while osimertinib had an ICER of $351,315/QALY. In China, the incremental utility for osimertinib versus gefitinib was 0.68QALYs, and the ICER was $25,622/QALY. The probability sensitivity analyses also illustrated that the erlotinib was the optimal treatment at a willingness-to-pay (WTP) threshold of $150,000/QALY in the U.S and osimertinib was the most cost-effective treatment at a WTP of $26,508/QALY in China. Conclusions: Based on our current analysis, erlotinib appears to be the preferred first-line treatment for advanced EGFR mutation-positive NSCLC patients in the US at a WTP of $150,000/QALY. However, because of the price reduction and more health benefits, osimertinib was considered to be most cost-effective at a WTP of $26,508/QALY in China.
Case 14-1976
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Lewis B. Holmes, Robert E. Scully
Journal: New England Journal of Medicine (1976)

Presentation of CaseA 17-year-old woman was admitted to the hospital because of a pelvic mass.She was born of a normal pregnancy and delivery, the eighth pregnancy of a mother 31 years of age. Her birth weight was 3.18 kg. No abnormality was noted on examination, and she was discharged home with her mother. Her early development appeared normal. A routine examination at the age of three months disclosed a large head. Four months later she was admitted to this hospital, where examination again disclosed a large skull; no other abnormality was found, and neurologic examination was negative. X-ray . . .
Health-related quality of life (HRQoL) and pain progression with enzalutamide (ENZ) in metastatic hormone-sensitive prostate cancer (mHSPC) from the ARCHES study.
Authors: Arnulf Stenzl, Curtis Dunshee, Ugo De Giorgi, Boris Alekseev, Taro Iguchi, Russell Zelig Szmulewitz, Thomas W. Flaig, Bertrand F. Tombal, Robert Morlock, Cristina Ivanescu, Krishnan Ramaswamy, Fred Saad, Andrew J. Armstrong
Journal: Journal of Clinical Oncology (2019)

5044 Background: The Phase 3 ARCHES trial (NCT02677896) evaluated the efficacy and safety of ENZ + androgen deprivation therapy (ADT) vs placebo (PBO) + ADT in 1150 men with mHSPC. Here we report patient-reported outcome (PRO) data using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory Short Form (BPI-SF). Methods: FACT-P and BPI-SF were assessed at baseline (BL), week (wk) 13, and then every 12 wks until disease progression. Longitudinal changes were assessed using mean scores and mixed-model repeated measures; lower BPI-SF scores represent less pain/interference; higher FACT-P scores represent better HRQoL. Time from BL to first deterioration in PRO score was assessed by Kaplan-Meier estimates and Cox proportional hazards models. Clinically meaningful difference was defined by change from baseline ≥10 for FACT-P total and ≥2 for worst pain/severity. Results: PRO instrument completion rates were high (88−96%) up to wk 73. At BL, men in both arms were generally asymptomatic and reported good HRQoL (FACT-P total: ENZ + ADT, 113.9; PBO + ADT, 112.7) and low pain (worst pain [item 3]: ENZ + ADT, 1.80; PBO + ADT, 1.77). HRQoL and pain scores remained stable over time and there were no clinically meaningful differences between groups in change from BL to wk 73. The proportion of men with no change or improvement in PRO scores (67–88%) was similar in both groups at all time points up to wk 73. There was no significant difference between arms for time to deterioration in FACT-P total (HR 0.90 [95% CI] (0.74, 1.09); p = 0.2998). ENZ + ADT significantly delayed time to pain progression for worst pain (HR 0.82 [0.69, 0.98]; p = 0.0322) and pain severity (HR 0.79 [0.65, 0.97]; p = 0.0209) vs PBO + ADT. Conclusions: Men with mHSPC were generally asymptomatic and had high levels of HRQoL and low levels of pain at BL, likely due to most men initiating ADT several months prior to study entry. No clinically meaningful differences in HRQoL were observed between ENZ and PBO. The prolongation in radiographic progression-free survival observed with ENZ + ADT was accompanied by a significantly prolonged time to progression of worst pain and pain severity vs PBO + ADT. Clinical trial information: NCT02677896.
Combination therapy of dendritic cell vaccination plus chemotherapy in pancreatic cancer.
Authors: Maurizio Chiriva-Internati, Leonardo Mirandola, Robert Bresalier, Scott Dahlbeck, Jose A. Figueroa, Diane Duyen Thuy Nguyen
Journal: Journal of Clinical Oncology (2019)

e15748 Background: Pancreatic cancer is one of the world’s deadliest malignancies with an average 5-year survival rate of only 9%. Fortunately, immunotherapy is providing encouraging results for treatment of this historically resistant malignancy. Kiromic Biopharma is performing a phase I/II dendritic cell vaccine trial for progressive solid malignancies. We present here a notable response to metastatic pancreatic cancer. Methods: The patient is a 73-year-old male with the history of a locally advanced pancreatic cancer treated initially with gemcitabine, concurrent 5FU and radiation therapy, and consolidation 5FU, followed by surgical resection in 2009 . Although the patient did well exceeding typical survival curves, the patient’s cancer became metastatic, requiring multiple lines of chemotherapy including FOLFIRINOX, gemzar and abraxane, and most recently Onivyde and leucovorin/5FU in February - August, 2017 for progressive liver and lung metastases. The patient was then enrolled onto Kiromic Biopharma’s DC vaccination trial in March, 2018. Results: He subsequently received 6 ID autologous dendritic cell vaccinations over 12 weeks, demonstrating a tumor antigen specific immunogenic response by IFN-gamma immunoassay. Total tumor burden (TTB) prior to clinical trial enrollment at the sites of metastatic disease was 2,221mm2, and after completion of the DC vaccination protocol in May, 2018, the TTB increased to 4,466mm2 in June, 2018 (not considered to be pseudo-progression due to a corresponding increase in tumor biomarkers). The patient then received a repeat course of Onivyde and leucovorin/5FU on 8-3-18, completing that course of therapy on 9-14-18, with subsequent TTB decreasing to 2,986 mm2. Conclusions: The sequential combination of dendritic cell vaccine and chemotherapy resulted in a substantial response with a recession in metastatic tumor burden. A CT scan was obtained just 6 days after the 5 week course of Onivyde was completed, and given the optimal immunotherapy window after the DC vaccination, and the repeat of the same chemotherapy regimen, it is unlikely that chemotherapy alone led to such a rapid decrease in the TTB. Metastatic sites were likely populated by chemo resistant clones that survived the August 2017 administration of the Onivyde regimen. Thus, chemo alone would be unlikely to act so quickly. We hypothesize that there was synergistic activity between the DC immunotherapy and the Onivyde/5FU regimen, accounting for the decrease in TTB between May and September, 2018. Clinical trial information: NCT02705703.
Association of Ras-Raf-MEK-Erk/JNK pathway mutations with overall survival for lung squamous cell carcinoma patients.
Authors: Long Xu, Ming Liu, Tanxiao Huang, Suo Peisu, Lele Song, Yuanyuan Liu, Mimi Fu, Chunmei Zhang, Jeremy Edwards, Shifu Chen
Journal: Journal of Clinical Oncology (2019)

e14754 Background: Genomic alterations often lead to aberrant signaling pathways which play an important role in tumorigenesis and development. Here we report the mutational status of genes associated with the Ras-Raf-MEK-Erk/JNK signaling pathway as a biomarker for predicting overall survival (OS) for Lung squamous cell carcinoma (SQCC) patients. Methods: We used the cBioPortal platform to analyze a cohort of 494 SQCC samples from TCGA data. The general Ras-Raf-MEK-Erk/JNK signaling pathway includes 26 genes (KRAS, HRAS, BRAF, RAF1, MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPK12, MAPK14, DAB2, RASSF1, RAB25). We analyzed the number of samples with/without mutations in the Ras-Raf-MEK-Erk/JNK pathway and found is 214 and 284 that had, or didn’t have, mutations in this pathway, respectively. The overall survival of these two groups was analyzed using the Kaplan-Meier Estimate, and the statistical difference between these groups was calculated using the log-rank test afterwards. Results: The log-rank test p-value is 2.086e-3, which indicates a significant difference in the overall survival between the two groups. It shows that the group with alterations in the Ras-Raf-MEK-Erk/JNK signaling pathway had a longer overall survival than the group without those alterations. The details are as follows: Conclusions: Ras-Raf-MEK-Erk/JNK pathway mutations are significantly associated with longer OS for lung SQCC patients. Mutations in this pathway can be a potential indicator for SQCC patients, but the biological reasons behind this relationship remain to be explored.[Table: see text]
PrE0807 phase Ib feasibility trial of neoadjuvant nivolumab (N)/lirilumab (L) in cisplatin-ineligible muscle-invasive bladder cancer (BC).
Authors: Petros Grivas, Maneka Puligandla, Suzanne Cole, Kevin Dale Courtney, Robert Dreicer, Benjamin Adam Gartrell, Jeremy Paul Cetnar, Marc Dall'era, Matt D. Galsky, Rohit K. Jain, Benjamin Louis Maughan, Neeraj Agarwal, Vadim S Koshkin, Noah M. Hahn, Michael Anthony Carducci
Journal: Journal of Clinical Oncology (2019)

TPS4594 Background: Neoadjuvant cisplatin-based chemotherapy before radical cystectomy (RC) improves outcomes but ~50% of patients (pts) are cisplatin-unfit. Anti-PD(L)1 agents can prolong overall survival (OS) in platinum-resistant advanced BC and have shown high pathologic complete response rate (pCR) and safety as single agent in phase II trials in the neoadjuvant setting. The combination of anti-PD-1 and anti-KIR agents is feasible and very attractive based on complementary and non-overlapping roles in regulating adaptive and innate immune response as well as impacting the function CD8+ T and NK-cells. Higher CD8+ T cell density (TCD) at RC tissue correlates with longer OS. We hypothesize, that combining anti-PD1 (N) with anti-KIR (L) is safe and feasible as neoadjuvant therapy in cisplatin-unfit pts and results in high CD8+ TCD at RC. Methods: Phase Ib multi-institutional trial evaluating 2 doses (4 weeks apart) of N alone or N+L in 2 cohorts; pts will be assigned sequentially to N (Cohort 1), and if there is no negative safety signal after the first 12 pts, subsequent pts will be assigned to N+L (Cohort 2). Key eligibility: cT2-4aN0-1M0 stage, ≥20% tumor at TURBT, adequate organ function, no autoimmune disease within 2 years, no concurrent invasive upper urinary tract carcinoma or other active cancer. Primary endpoint: safety based on CTCAE v5.0 measured as the rate of ≥G3 treatment related adverse events (AE). Key secondary endpoints: CD8+ TCD absolute and % change between TURBT and RC, % of pts who do not get RC within 6 weeks after neoadjuvant treatment due to treatment-related AE, % pCR, recurrence-free survival, and evaluation of biomarkers in tumor tissue, blood, urine. Rates of ≥Grade 3 AE with neoadjuvant treatment will be reported along with 90% exact binomial CI. In Cohort 1, maximum CI width is 0.51; in Cohort 2, it is 0.36. Our hypothesis is that the change in CD8+ TCD between TURBT and RC will be about 3 CD8+ T cells / 100 tumor cells within HPF. Up to 43 pts will be enrolled for 36 eligible, treated pts (12:N, 24:N+L). Cohort 1 and 2 have 81% and 98% power, respectively, to detect the hypothesized difference with 1-sided type I error rate of 0.05. Trial is open to accrual in US. Clinical trial information: NCT03532451.
Implementation of the Quality Training Program in Spain.
Authors: Rafael Lopez, Antonio Anton, Enrique Aranda, Alfredo Carrato, Manuel Constenla, Juan Jesús Cruz, Eduardo Díaz-Rubio, Margarita Feyjoo, Jesús García Foncillas, Pedro Gascon, Vicente Guillem, Ilse Lugo, Carlos Camps
Journal: Journal of Clinical Oncology (2019)

e18296 Background: The ECO Foundation is a collaboration of experts representing the major Spanish hospitals in the pursuit of excellence in cancer treatment. Since 2015, ECO has been collaborating with ASCO (American Society of Clinical Oncology) in quality initiatives in cancer care, like the QOPI (Quality Oncology Practice Initiative) program and the QOPI Certification Program (QCP). The Quality Training Program (QTP) is a 6-month program with 3 in-person learning sessions that prepares oncology teams to design implement and lead successful quality improvement activities in their practices. In 2018, ECO reached a new agreement with ASCO to implement this program in Spain. Methods: The QTP was developed in Spain by the ECO Foundation in collaboration with ASCO, following the same methodology and contents of ASCO’s program. The first session was carried out on October 2018, with 12 Spanish teams participating with diverse quality improvement projects. The program counted with ASCO and ECO faculty, constituted by experts in the quality and oncology field. Results: The QTP Spanish teams counted with 2-3 representatives from their hospitals. Each team develop an improvement project, following the methodology of the course, including a problem statement, process map, cause and effect diagram, diagnostic data, aim statement, measures, baseline data, priority/pay-off matrix of possible changes/interventions, change data, next steps/plan for sustainability, among others. The projects were mainly focused on the waiting time reduction in the Emergency Area, the waiting time reduction for cancer patients from the visit to the oncologist until treatment administration, burnout reduction on oncology professionals, improvement of the identification and management of complications for cancer patients receiving immunotherapy, improvement of the uniformity in the medical records registry, among others. QTP participants will present the results of their projects on the third and last session of the program, on April 2019. Conclusions: The quality improvement approach followed in the QTP allows Spanish teams and the ECO Foundation to enhance the goal of a quality-oriented health care system. ECO will continue pursuing excellence and quality with further initiatives like the QOPI program, the QCP and the QTP.
Medicare Advantage Expands Telehealth Services
Authors: Rita Rubin
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Case 8-1984
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely, Z. Myron Falchuk, Nancy L. Harris
Journal: New England Journal of Medicine (1984)

Presentation of CaseA 70-year-old woman was admitted to the hospital because of dyspnea.She was well until 46 years earlier, when bilateral thrombophlebitis developed, and ligation of the inferior vena cava was performed. Persistent peripheral edema developed. Thirteen years before admission she began to experience postprandial abdominal pain and vomiting. Eleven years before entry she was first seen at this hospital, where examination showed that she was thin, with + + + + peripheral edema. The protein was 3.4 g (the albumin 2.1 g and the globulin 1.3 g) per 100 ml. A d-xylose absorption test revealed 1.3 g . . .
A Change of Heart
Authors: Zekun Feng
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Real-world economic burden of rapid disease progression (RDP) in patients (pts) with advanced/metastatic non-small cell lung cancer (aNSCLC).
Authors: Stacey DaCosta Byfield, Cliff Molife, Marta Batus, Katherine B. Winfree, John C White, Zhanglin Lin Cui, Lincy S. Lal, Victoria Jennifer Stefaniak, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2019)

e20716 Background: RDP on initial therapy imposes significant clinical burden among pts with aNSCLC. This retrospective claims study provides estimates of the economic burden associated with RDP during subsequent therapy following RDP v non-RDP on platinum-based (Pt) therapy. Methods: Adult Medicare Advantage or commercially insured aNSCLC pts receiving a subsequent line of therapy (LOT) from 03/2015 to 08/2017 after initial Pt therapy were identified in the Optum Research Database and assigned to unmatched RDP &amp; non-RDP cohorts based on Pt treatment duration (≤ 12 and &gt; 12 weeks, respectively) as a surrogate. All-cause healthcare costs were inflation adjusted to 2017 US$ and computed as per patient per month (PPPM) during the subsequent LOT. Total costs were the sum of medical (inpatient, ambulatory, ER, and other costs) and outpatient pharmacy costs. Results: Patient characteristics were similar between RDP (n = 751) and non-RDP (n = 1,304) cohorts, with mean age of 68 years for the total study sample (n = 2,055). Overall, nivolumab was the most common subsequent regimen post Pt; 40% of the total study sample. While duration of subsequent LOTs was shorter for RDP pts (Kaplan-Meier median, 167 v 192 days and log rank test P = 0.03), mean systemic therapy drug costs were similar ($10,516 v $9,642, P = 0.14) during the LOT and PPPM total costs for RDP pts were $4,103 higher than those for non-RDP pts, driven by higher PPPM costs for inpatient stays and ambulatory visits (Table). Conclusions: This study sheds light on the significant economic burden of aNSCLC that rapidly progresses, and may inform management strategies to improve outcomes and lower downstream costs for RDP pts. Future research should continue to explore unmet needs for RDP pts, including underlying cost drivers, to provide context for the rapidly changing aNSCLC treatment landscape.[Table: see text]