tbuckley/cabot-search huggingface dataset:
Outcomes in patients with head and neck squamous cell carcinoma (HNSCC) requiring salvage resection after definitive therapy.
Authors: Sulsal Haque, Muhammad Kashif Riaz, Sarah Hassan, Vidhya Karivedu, Jun Ying, Vinita Takiar, Trisha Michel Wise-Draper
Journal: Journal of Clinical Oncology (2017)

e17572 Background: Salvage surgical resection is often offered in HNSCC patients who develop locally recurrent disease after definitive therapy. However, survival outcomes are often poor and subsequent recurrence is frequently fatal. Patients with adverse pathological features (extracapsular extension (ECE) of lymph nodes (LN), positive margins, peri-neural spread, lympovascular invasion, multiple LN metastases) after primary surgical resection have been shown to have poor outcomes. It is unclear if these same features affect outcomes in surgical salvage patients. Therefore we conducted a retrospective analysis to analyze outcomes and potential risk factors in these patients. Methods: We analyzed forty-five patients at the University of Cincinnati from 2008-2014 that underwent salvage surgery after definitive radiation with or without chemotherapy. Independent categorical variables analyzed were age, gender, alcohol, smoking, time to relapse after definitive therapy and adverse pathological features. Dependent variables were relapse free survival (RFS) and overall survival (OS) censored at time of event or last follow-up visit. Kaplan-Meier curves were used to estimate RFS and OS and Cox Proportional Hazard models were used to assess hazard ratios between groups. Results: Median age was 57 (range 41 to 86). 75.6% of patients were male. 68.9% patients had adverse pathological features. Median OS was 59 months and median RFS was 38 months from surgery. Demographics and adverse pathological features did not affect survival. However, patients who relapsed after definitive therapy within 6 months vs. after 6 months had worse OS (See Table 1). Conclusions: Although adverse pathological features correlate with poor outcome in primary surgery, these features did not impact outcomes after salvage surgery in our population. However, patients who relapsed within 6 months of definitive therapy and underwent salvage resection had significantly worse outcomes than those who developed recurrence after 6 months. [Table: see text]
PD-1+CD8+ T cells are clonally expanding effectors in human chronic inflammation
Authors: Alessandra Petrelli, Gerdien Mijnheer, David P. Hoytema van Konijnenburg, Maria M. van der Wal, Barbara Giovannone, Enric Mocholi, Nadia Vazirpanah, Jasper C. Broen, Dirkjan Hijnen, Bas Oldenburg, Paul J. Coffer, Sebastian J. Vastert, Berent J. Prakken, Eric Spierings, Aridaman Pandit, Michal Mokry, Femke van Wijk
Journal: Journal of Clinical Investigation (2018)

Chronic inflammatory diseases are characterized by recurrent inflammatory attacks in the tissues mediated by autoreactive T cells. Identity and functional programming of CD8+ T cells at the target site of inflammation still remain elusive. One key question is whether, in these antigen-rich environments, chronic stimulation leads to CD8+ T cell exhaustion comparable to what is observed in infectious disease contexts. In the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients, a model of chronic inflammation, an overrepresentation of PD-1+CD8+ T cells was found. Gene expression profiling, gene set enrichment analysis, functional studies, and extracellular flux analysis identified PD-1+CD8+ T cells as metabolically active effectors, with no sign of exhaustion. Furthermore, PD-1+CD8+ T cells were enriched for a tissue-resident memory (Trm) cell transcriptional profile and demonstrated increased clonal expansion compared with the PD-1– counterpart, suggesting antigen-driven expansion of locally adapted cells. Interestingly, this subset was also found increased in target tissues in other human chronic inflammatory diseases. These data indicate that local chronic inflammation drives the induction and expansion of CD8+ T cells endowed with potential detrimental properties. Together, these findings lay the basis for investigation of PD-1–expressing CD8+ T cell targeting strategies in human chronic inflammatory diseases.
Efficacy of an educational program for patients with pancreatic and biliary cancers, and their caregivers.
Authors: Reiko Makihara Ando, Chikako Doutani, Sayaka Kanehira, Mariko Nishizawa, Kyoko Hirata, Hitomi Miura, Moe Nishio, Tomoko Suzuki, Yumiko Fujimaki, Naoko Goto, Rieko Shimizu, Hironobu Inoguchi, Satoshi Shiba, Yasunari Sakamoto, Shunsuke Kondo, Chigusa Morizane, Hideki Ueno, Ken Shimizu, Takuji Okusaka
Journal: Journal of Clinical Oncology (2017)

e18221 Background: We first introduced an educational program delivered in a classroom environment for patients with pancreatic and biliary cancers and their caregivers in 2007. Physicians, pharmacists, nurses, clinical psychotherapists, dietitians, and medical social workers attended and talked about their specialties. We conducted a prospective observational study from Jan. 2016 through Dec. 2016 to assess the efficacy of this educational program. Methods: This study was approved by our institutional review board and informed consent was obtained from all the participants. The 2-hour program included an overview of disease and information about treatment and management. The participants completed a questionnaire assessing their knowledge and including the Distress Thermometer both before and after the program. In addition, the participants completed a questionnaire regarding their satisfaction with the program to assess their informational needs. Results: Thirty-three patients and 50 caregivers were enrolled. Although no significant differences were seen in the mean baseline knowledge levels of the patients and caregivers, the mean baseline distress level was greater for the caregiver than for the patients. After attending the program, both the knowledge and distress levels were significantly improved for both the two groups. Regarding the satisfaction questionnaire, more than 90% of the participants reported being satisfied with the contents of the program and responded that the program was useful for their life. However, the percentage of respondents who reported being satisfied with hearing other participants’ stories was less than 40%. Conclusions: This study suggests that an educational program can improve knowledge and distress levels in patients and caregivers. We are planning to improve our program to further satisfy the needs of patients and caregivers, such as providing an opportunity to communicate with other participants, and to perform further evaluations.
When Is Milk Really Milk?
Authors: Rebecca Voelker
Journal: JAMA (2018)

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
Clonal evolution in acute myeloid leukemia (AML): Relapse after a long remission period.
Authors: Musa Yilmaz, Feng Wang, Sanam Loghavi, Carlos E. Bueso-Ramos, Curtis Gumbs, Latasha Little, Xingzhi Song, Jianhua Zhang, Tapan M. Kadia, Gautam Borthakur, Elias Jabbour, Guillermo Garcia-Manero, Zeev Estrov, Hagop M. Kantarjian, Phillip Andrew Futreal, Koichi Takahashi, Farhad Ravandi, Nicholas James Short
Journal: Journal of Clinical Oncology (2018)

7022 Background: Late relapse in AML occurring more than 5 years after achieving remission is uncommon and underlying biological events are poorly understood. We aim to determine the clonal events resulting in late relapse of AML. Methods: We identified patients (pts) with AML who received intensive induction chemotherapy between 1990 and 2010, achieved complete remission (CR), and remained in CR for at least 5 years. A total 349 pts were identified, and 15 (4%) relapsed beyond 5 years. Whole exome-sequencing was performed in diagnosis (dx) and 1st relapse bone marrow samples (available in 10 pts). Results: A total of 43 driver mutations were identified in 10 pts, of which 12 were primary tumor specific, 18 relapse-specific, and 13 were shared between primary and relapsed tumor (Table). Twenty-seven of 43 driver mutations (63%) were nonsynonymous SNV and 16 (37%) were indels. At relapse, 3 clonal evolution patterns were identified: pattern 1, the founding clone in the primary tumor gained additional mutations and evolved into the relapse clone and a subset of primary tumor mutations were not detected at relapse (UPN 1, 5, 6, and 7); pattern 2, the founding clone in the primary tumor gained additional mutations at relapse (UPN 9, 10, 12, and 14); pattern 3, relapsing clone harbored none of the primary tumor mutations, thus it represented a new clone (UPN 3 and 15). Conclusions: Relapse after a long remission in pts with AML is associated with persistence of the founding clone and acquisition of new relapse-specific mutations in the majority. Understanding the mechanisms of such quiescence may assist in increasing CR duration in pts with AML. Driver mutations identified in 10 primary-relapse pairs. UPN Age at Dx CR Duration (year) Primary Specific Shared Relapse Specific 1 17 24 NRAS DNMT3A ASXL1, RUNX1 3* 34 12 NF1, FANCM, ZRSR2¥ none XPO1 5 44 8 NF1 DNMT3A, TET2 TET2† 6 38 8 NRAS, MYO1A IDH1, PRRG1 FLT3, GNAI2, RAD21, RNF128 7 57 8 CHD2 IDH2, SRSF2 AR, TRAPPC8, ASXL1, RUNX1 9 75 7 none ASXL1 NF1 10 37 6 FLT3, RELN DNM2 none§ 12 67 6 none IDH2, SRSF2 NPM1 14 63 6 none IDH2, SRSF2 FLT3, TET2, GATA2 15 60 6 KRAS none IRF1 UPN: unified pt number, †Different TET2 mut., ¥ 2 different ZRSR2 mut.,*allo-SCT in CR1, § at relapse karyotype showed newl del 7q and persistent del 5q
Association between HPV-related cancers and inflammatory bowel disease.
Authors: Ryan Suk, Kalyani Sonawane, Elizabeth Chiao, Jagpreet Chhatwal, Andrew G. Sikora, Keith Sigel, Ashish A Deshmukh
Journal: Journal of Clinical Oncology (2018)

e13576 Background: Patients with inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are likely to be at high risk of human papillomavirus (HPV) infection due to therapeutic immunosuppression and alterations in mucosal immunity; however, the association of IBD and HPV-related cancers has not been well established. Methods: We performed a retrospective analysis of 2003-2014 National Inpatient Sample (NIS) database. We compared patients with CD and UCwith a control group of patients with diverticulitis. Groups were matched by age, sex, race, and comorbidity (Elixhauser score) using propensity score matching. We then performed multivariate analysis to assess the odds of concurrently having HPV-related cancers among individuals with IBD. Results: Individuals with IBD were more likely to have HPV-related cancers when compared with individuals with diverticulitis; odds ratio, OR = 2.5; 95% CI, 2.1 to 2.8. Odds for the IBD group were highest for vulvar cancer (OR = 6.0) followed by anal cancer (OR = 4.0) and were lowest (1.4) for cervical cancer. Conclusions: The association for HPV-related cancer is significantly greater among individuals with IBD. Table 1. ORs, IBD vs Diverticulitis OR (95% CI) (IBD vs Diverticulitis) OR (95% CI) (UC vs Diverticulitis) OR (95% CI) (CD vs Diverticulitis) HPV-related Cancers 2.5 (2.1-2.8) 2.5 (2.1-3.0) 2.5 (2.1-2.9) Anal 4.0 (3.0-5.4) 3.6 (2.6-5.1) 4.3 (3.1-5.9) Female 3.7 (2.5-5.6) 3.8 (2.4-6.1) 3.7 (2.4-5.7) Male 4.2 (2.8-6.4) 3.3 (2.0-5.4) 4.9 (3.1-7.6) Oropharyngeal 2.2 (1.7-2.8) 2.0 (1.5-2.7) 2.4 (1.8-3.2) Female 2.7 (1.8-3.8) 3.0 (1.8-4.9) 2.5 (1.7-3.7) Male 1.9 (1.4-2.7) 1.5 (1.0-2.1) 2.3 (1.6-3.3) Cervical 1.4 (1.1-1.8) 2.2 (1.6-2.9) 1.0 (0.7-1.3) Vaginal 3.3 (1.6-6.6) 2.1 (0.9-5.0) 3.9 (1.9-8.2) Vulvar 6.0 (3.4-10.6) 4.8 (2.5-9.0) 7.2 (4.0-13.0) Penile 2.0 (0.7-5.4) 2.9 (1.0-9.0) 1.1 (0.3-4.1) Non-HPV Cancers 1.1 (1.0-1.1) 1.3 (1.2-1.4) 0.9 (0.9-1.0) Colon 0.9 (0.9-1.0) 1.2 (1.1-1.3) 0.8 (0.7-0.8) Ovarian 1.1 (0.9-1.2) 1.2 (1.0-1.4) 1.0 (0.9-1.2) Prostate 1.3 (1.2-1.4) 1.5 (1.3-1.6) 1.2 (1.1-1.3) Esophageal 1.3 (1.0-1.6) 1.6 (1.2-2.0) 1.0 (0.8-1.4)
Determinants of severe chronic fatigue among epithelial ovarian cancer survivors: A GINECO VIVROVAIRE study.
Authors: Florence Joly, Elsa Kalbacher, Dominique Berton-Rigaud, Olivier Tredan, Michel Fabbro, Natacha Heutte, Aude-Marie Savoye, jean Emmanuel Kurtz, Jerome Alexandre, Philippe Follana, Valérie Delecroix, Nadine Dohollou, Celia Roemer-Becuwe, Gaetan De Rauglaudre, Alain Lortholary, Karinne Prulhiere, Anne Gompel, Catherine Lhommé, Djihane Ahmed-Lecheheb, Anne Floquet
Journal: Journal of Clinical Oncology (2018)

5573 Background: Vivrovaire was a large case-control study comparing patients reported outcomes (PROs) between 318 Epithelial Ovarian Cancer Survivors (EOCS) without relapse ≥3 years after 1st line treatment and age matched controls. Severe chronic fatigue (SCF), the main end point, (26% of EOCS) was one of the most frequent reported late side effects (Joly et al, abstr 940PD, ESMO 2017). The aim of this exploratory study was to assess determinants of SCF among EOCS. Methods: EOCS were recruited in 27 centers. Patients filled-in PROs questionnaires: quality of life, neurotoxicity and fatigue (FACT-G, FACT-O, FACT/GOG-Ntx, FACT-F), anxiety/depression (HADS), sleep disturbance (ISI) and physical activity (IPAQ). SCF was defined as FACT-F score < 37. Variables associated with SCF (p < 0.01) were included in a multivariate logistic regression. Results: EOCS were: Median age 65[20-86] years, high level of education (52%), FIGO stage I/II (50%), III/IV (48%). Histologic subtypes were: serous 49%, endometrioid 15%, clear-cell 8%, mucinous 4%. BRCA1/2 mutations: n = 23 (15%). 98% of EOCS had surgery and 99% received platinum and taxane chemotherapy, associated with antiangiogenic agent (13%). Median follow-up was 5[2-24] years. Current treatments included psychotropic (12%) and pain medications (3%). 26% of EOCS reported SCF, 63% poor quality of sleep, 53% and 22% anxiety/depression, and 27% neurotoxicity. Only 18% of EOCS had high physical activity. Results of univariate and multivariate analysis appear in table. Conclusions: Depression, persistence of neurotoxicity, and sleep disturbance are the main determinants of SCF among EOCS. These symptoms should be early detected and treated. Univariate associations with SCF Multivariate logistic regression OR 95% CI P value OR 95% CI P value Comorbidities*a 2.6 1.4-5 .003 Psychotropic and pain medicationsa 7.4 3.5-16 < .0001 Physical activity (vs High) Low 3.8 1.6-8.7 .001 Moderate 1.3 0.6-3.2 .517 Anxietya 5.9 3-11 < .0001 Depressiona 20.7 10-42 < .0001 17.5 7.8-39 < 0.0001 Neurotoxicitya 0.8 0.8-0.9 < .0001 6.4 3-13.6 < 0.0001 Sleep disturbancea 6.6 3-14 < .0001 3.5 1.4-8.3 0.005 *= Diabetes, Thyroid and heart diseases, Depressive syndrome, Obesity a : yes vs no
OS6.3 Radiomics and machine learning on [18F]FET PET and T1ce MRI discriminate between low-grade and high-grade glioma
Authors: S Bonte, S Donche, M Henrotte, R van Holen, I Goethals
Journal: Neuro-Oncology (2018)

Gliomas are the most frequent malignant primary brain tumours in adults, accounting for about 70% of adult malignant primary brain tumours. They can be categorised into low-grade gliomas (LGG, WHO grade I-II) or high-grade gliomas (HGG, WHO grade III-IV). Accurate and early diagnosis of these tumours, for which histopathological analysis is the gold standard, is key to determine the optimal treatment procedure. Because biopsy and tumour resection are invasive procedures, there has been a growing interest in automated classification of brain tumours based on medical imaging. This retrospective study intends to evaluate automatic tumour segmentation and radiomics features from [18F]FET PET and contrast-enhanced T1-weighted (T1ce) MRI images for discrimination between LGG and HGG. A pretreatment [18F]FET PET scan and anatomical MRI were performed in 30 patients. Histopathological analysis led to the diagnosis of 14 LGG and 16 HGG patients. An in-house developed and previously validated segmentation algorithm was used to automatically delineate the tumour simultaneously on T1ce and FLAIR MRI. This resulted in the identification of four tumour-related tissues: necrosis, oedema, non-enhancing tumour and contrast-enhancing tumour. These different tumour masks were used to extract 2913 quantitative radiomics features per patient from the T1ce and PET images. For each feature, a two sample t-test was performed between LGG and HGG patients as an initial feature selection. The 150 features with the lowest p-values were retained. Next, forward sequential selection and five-fold cross-validation was implemented to identify up to 15 features that are able to make the optimal distinction between LGG and HGG using a Random Forests classification model. The accuracy was assessed using leave-one-out validation. This procedure was performed three times: using only T1ce features, only PET features, and both T1ce and [18F]FET features. We achieve accuracies of 86.6%, 83.3% and 96.7% for the classification tasks using MRI-based, PET-based and combined features, respectively. The best result is obtained when combining one texture feature calculated on T1ce in the oedema and non-enhancing tumour region with two histogram and five texture features calculated on [18F]FET PET, both in the oedematous and total abnormal regions. This model achieves an excellent discrimination between LGG and HGG (accuracy 96.7%, AUC=0.951), using a minimal amount of features. We further observe that many predictive features are based on infiltrating rather than tumour core regions. This study illustrates that automatic tumour segmentation and extraction of radiomics features from combined [18F]FET PET and T1ce MRI scans are able to discriminate between LGG and HGG. Further evaluation on larger datasets is however necessary to validate this result.
Analysis of changes in the markers of DNA methylation in the process of complex treatment in acute myeloid leukemia in children
Authors: V.V. Rudenko, S.A. Kazakova, A.S. Tanas, V.S. Nemirovchenko, A.V. Popa, V.V. Strelnikov
Journal: Annals of Oncology (2018)

Background: Acute myeloid leukemia (AML) is an "epigenetic" disease in the sense that the most common mutations in AML are somatic mutations in genes that regulate DNA methylation and demethylation. An aberrant DNA methylation distribution is a functional event in the process of leukemogenesis and a target of epigenetic therapy. Although epigenetic drugs (demethylating agents, histone deacetylase inhibitors) have been already used in the clinic for AML treatment, they do not provide point activation of the target region. Epigenetic variants of AML typical for children are particularly poorly understood. Methods: To identify DNA methylation markers most common for any molecular subtype of pediatric acute myeloid leukemia (AML) we have applied a method of unbiased differential methylation screening of the genomes and designed multiplex methyl sensitive PCR system of DNA methylation markers belonging to the promoter regions of the genes CLDN7, CXCL14, GSG1L, EGFLAM, SOX8, and TMEM176A/176B. Results: The system has a sensitivity of 90% for determining the malignant process. We have studied bone marrow samples from 43 children with AML. All patients were treated by decitabine and all-trans retinoic acid in complex with standard chemotherapy (CT). Methylation index (MI) was 0.197 ± 0.181 for patients with a myeloblasts content less than 40%, and 0.514 ± 0.222 for patients with myeloblasts content more than 40% (p = 0.000736). Methylation of the CLDN7, GSGL1 and EGFLAM genes is absent in the group with low MI. Patients with the initial content of myeloblasts less than 40% demonstrate absence of methylation on the 15th day after the start of the CT. The average MI decreases in the group with the initially high content of myeloblasts due to decrease in the frequencies of methylation of the genes CXCL14, TMEM176A/176B, GSGL1 and SOX8. The 5-day course of demethylation therapy with decitabine is accompanied by an increase in the content of blast cells and an equalization of the methylation profile. Conclusions: With the marker system developed it is possible to evaluate the malignant progression of blast cells, which are considered morphologically normal after CT, demonstrating at the same time the abnormal methylation profile of tumor cells. Legal entity responsible for the study: Research Centre for Medical Genetics. Funding: Council on grants of the President of the Russian Federation for state support of young Russian scientists and on state support of the leading scientific schools of the Russian Federation. Disclosure: All authors have declared no conflicts of interest.
Screening for new primary cancers in patients with metastatic breast cancer: A provincial analysis of the Choosing Wisely Canada recommendations.
Authors: Megan E. Tesch, Kara E. Laing
Journal: Journal of Clinical Oncology (2018)

e18817 Background: As part of the broader Choosing Wisely Canada campaign, a list was published in May 2015 of practices in oncology that are commonly performed despite evidence showing negligible benefit and the potential to cause harm. One of these recommendations is for physicians to avoid routine cancer screening or surveillance for a new primary malignancy in patients with metastatic disease. The objective of our study was to assess whether local practice is in keeping with these recommendations. Methods: A retrospective review of screening for new primary cancers was conducted in metastatic breast cancer patients seen at the Dr. H. Bliss Murphy Cancer Centre in St. John’s, Newfoundland and Labrador (NL) during the three-year period of January 1, 2014 to December 31, 2016. Specific screening investigations included screening mammography, Papanicolaou test, fecal immunochemical test, and screening colonoscopy or flexible sigmoidoscopy. Results: A total of 305 patient medical records were reviewed. Overall, 114 patients (37.4%) underwent at least one screening investigation (mean, 2.92 investigations per screened patient). 70% of screening investigations were ordered by primary care providers, in comparison to 14% by oncologists and 12% by other specialists. The median overall survival of breast cancer patients after diagnosis of metastatic disease was 42 months, with a 5-year overall survival of 35.9%. Conclusions: A significant proportion of patients with metastatic breast cancer in NL and are still undergoing screening for new primary cancers, in discordance with Choosing Wisely guidelines. Increased educational strategies are needed if recommendations are to be implemented into routine clinical practice.