tbuckley/cabot-search huggingface dataset:
Rising thyroid cancer incidence in Kerala: Is it real or over diagnosis?
Authors: Saadvik Raghuram, Bharadwaj Ponnada, Pavithran Keechilat
Journal: Journal of Clinical Oncology (2019)

e17589 Background: There has been an increase in the incidence of thyroid cancer in India and in high income countries. One of the reasons for this has been attributed to the large number of screening programs. Kerala state ranks second highest in the incidence of thyroid cancer in India. Screening provides the advantage of early detection of cancer and successful treatment but also tends to over diagnose. Methods: To study the trend of incidence of primary thyroid cancer among newly diagnosed cancer patients and its association with the mode of detection, we retrospectively reviewed hospital based cancer registry data of patients with thyroid cancer who were treated at AIMS (Amrita Institute of Medical Sciences), Kochi between 2004-2014. All patients who were newly diagnosed with primary thyroid cancer at our center or referred to us after initial surgery were included in this analysis. Patients with recurrent cancer/metastases were excluded. Results: We analyzed the records of 2,315 newly diagnosed thyroid cancer patients. Median age was 44.1yrs (range 13-90yrs). There were 619 males and 1696 females. Papillary type was the most common 85.8% followed by follicular type 7.4%. 1235 cases were operated at AIMS. 74 cases (3.2%) were diagnosed incidentally by Ultrasonography/PET scan/CT scan. All others (97% n = 2,245) presented with neck swelling. It was seen that the proportion of new cases of thyroid cancer among all new cancer cases was increasing serially from 4.6 % (n = 106, 95% 2004) to 7.4% (n = 195) to13.7% (n = 317, 2014). There was a significant increase in the number of cases of T1a and T1b at the time of diagnosis during the study period (n = 1235, p value &lt; 0.001 and p value for trend &lt; 0.001 respectively) which indicates that there was early diagnosis. 97% of the cases presented with thyroid related symptoms indicating that clinical presentation has still been the main mode of detection in our series. Conclusions: Our data shows that there may be a true increase in the number of cases of thyroid cancer as majority presented with clinical symptoms, except few detected incidentally. As it is a single institution based data we need further studies to see if over use of USG based imaging for any thyroid swelling is responsible for an apparent increase in the number of thyroid cancer cases.
Characteristics of the course of squamous cell carcinoma of the oral cavity depending on the HPV status.
Authors: Pavel V. Svetitskiy, Tatiana A. Zykova, Viktoriya L. Volkova, Irina V. Aedinova
Journal: Journal of Clinical Oncology (2019)

e17579 Background: HPV infection has a positive prognostic value in the treatment of patients with oropharyngeal squamous cell carcinoma. The purpose of the study was to evaluate the effect of HPV status on the course of oral cavity cancer. Methods: Formalin-fixed paraffin-embedded tumor tissues were studied in 34 patients with cancer of the floor of the mouth aged 47-85 years, 3 (8.8%) women and 31 (91.2%) men. All patients had histologically verified squamous cell carcinoma: stage (st) I in 1 (2.9%), II st - 8 (23.5%), III st - 12 (35.3%), IV st - 13 (38.3%); G1 in 15 (44.1%), G2 - 19 (55.9%). HPV DNAs were detected by Real-time PCR. Results: HPV DNAs were found in 12 (35.3%) samples of tumor tissues, including type 6 in 1 (2.9%), 11 in 3 (8.8%), 16 in 6 (17.6%), 35 in 1 (2.9%), 16+35 in 1 (2.9%). HPV+ tumors were more often in women (66.7% vs 32.3% in men), but high-risk HPV types were detected in men only - 8 (25.8%). Among patients aged 47-55 years, HPV+ tumor status was detected in 4 (33.3%), 56-65 years in 7 (53.8%), 66 years and older - in 1 (11.1%). In st I, no HPV+ tumors were observed; st II - 3 (37.5%) HPV+ tumors, low-risk in all; st III - 3 (25%) HPV+ patients, including high-risk in 2 (16.7%); st IV - 6 (46.2%) HPV+ samples, high-risk in all. G1 tumors: HPV+ in 7 (46.7%), HPV- in 8 (53.3%) patients; G2 tumors: HPV+ in 5 (26.3%), HPV- in 14 (73.7%) patients. Among patients with HPV+ tumors, metastases were observed in 5 (41.7%), no metastases - in 7 (58.3%); for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. 4 (33.3%) patients with HPV+ tumors died, while 8 (66.7%) survived; for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. Conclusions: The development of squamous cell carcinoma of the oral cavity was multidirectional and depended on the HPV status. HPV+ tumors, especially high-risk ones, were more often registered in stages III and IV. HPV+ tumors were more often lower-grade ones and less often metastasized; the mortality rate among patients with HPV+ tumors was lower than with HPV- ones.
Randomized phase II trial of a DNA vaccine encoding prostatic acid phosphatase (pTVG-HP) versus GM-CSF adjuvant in patients with PSA-recurrent prostate cancer.
Authors: Glenn Liu, Lawrence Fong, Emmanuel S. Antonarakis, Jens C. Eickhoff, Ellen G. Wargowski, Laura E. Johnson, Robert Jeraj, Douglas G. McNeel
Journal: Journal of Clinical Oncology (2019)

5037 Background: Phase I/II studies of pTVG-HP showed safety and increases in prostatic acid phosphatase (PAP)-specific T cells. Based on these, we conducted a multi-center, randomized phase II trial using pTVG-HP with GM-CSF adjuvant vs GM-CSF alone in patients with PSA-recurrent, non-metastatic, non-castrate, prostate cancer (stage M0). Methods: 99 patients with M0 prostate cancer (negative CT and bone scan) with PSA doubling time (DT) of &lt; 12m were randomly assigned to pTVG-HP + GM-CSF vs GM-CSF. Treatments were every 2 wk x 6, and then quarterly for up to 24m. Primary endpoint was 2-year MFS. Secondary endpoints included median MFS, changes in PSA DT, and immune response to PAP antigen. Additional analysis included quantitative changes in bone lesion activity by NaF PET/CT. Results: Few grade 3/4 events were observed and were not statistically different between arms. 2-year MFS between control and pTVG-HP was 42.3% and 41.8% (p = 0.97). Median MFS was not different (18.3m control versus 18.9m pTVG-HP, HR = 1.6, p = 0.13). Changes in PSA DT, and immunity to the PAP target, were not different between study arms. A pre-planned subset analysis showed median MFS was significantly longer in patients with rapid PSA DT ( &lt; 3m) treated with pTVG-HP (6.1m versus 12.0m, n = 21, HR = 4.4, p = 0.03). In patients with baseline metastases detected on NaF PET/CT, total activity (SUVtotal) increased 17% with GM-CSF alone, but decreased 29% with pTVG-HP from baseline to month 6 (n = 27, p = 0.07). Conclusions: This trial did not demonstrate an overall increase in 2-year MFS following treatment with pTVG-HP, but suggested a modest effect in patients with rapidly progressive disease. NaF PET/CT imaging suggests that pTVG-HP has a detectable effect on decreasing metastatic activity in bone. A separate trial suggests that pTVG-HP is an immune activating agent that improves activity of PD-1 blockade. A trial using pTVG-HP in combination with nivolumab in patients with M0 prostate cancer is currently underway. Clinical trial information: NCT01341652.
FOxTROT: an international randomised controlled trial in 1052 patients (pts) evaluating neoadjuvant chemotherapy (NAC) for colon cancer.
Authors: Matthew T. Seymour, Dion Morton
Journal: Journal of Clinical Oncology (2019)

3504 Background: NAC is well established in many solid tumours but has not undergone large-scale evaluation in colon cancer. Methods: Pts had operable, non-obstructed colon cancer; CT-predicted stage T3-4, N0-2, M0, and were fit for FOLFOX and surgery. They were randomised 2:1 to the novel sequence (6 wk FOLFOX NAC, then surgery, then 18 wk FOLFOX) or control (surgery then 24 wk FOLFOX). RAS-wt pts allocated to the novel arm could optionally be sub-randomized 1:1 to ± panitumumab (pan) during the NAC phase. Two "dealer’s choices" allowed total chemo duration 12 wk instead of 24 (in older/low-risk pts) and OxCap in place of FOLFOX (except in pts randomized ± pan). Primary endpoint is freedom from recurrent or persistent disease after 2 yrs, by ITT. Secondary endpoints include safety, histological stage, completeness of resection, OS. Results: 1052 pts were randomised, Jun 2008-Dec 2016, at 85 centres in UK, Denmark and Sweden. Conclusions: NAC was well tolerated and safe, with no increase in perioperative morbidity and a trend toward fewer serious postoperative complications. Evidence of histological regression was seen in 59% pts after NAC, including some pCRs. This resulted in marked histological downstaging and a halving of the rate of incomplete resections. We observed an improvement in 2-yr failure rate (HR=0.77), but this fell short of statistical significance (p=0.11). NAC for colon cancer improves surgical outcomes and can now be considered as a treatment option; longer follow-up and further trials are required to confirm the long-term benefits, refine its use and optimise case selection. Clinical trial information: 87163246. [Table: see text]
Predictors of adjuvant chemotherapy for breast cancer patients with an intermediate Oncotype-DX score: A SEER-based population study.
Authors: Sowmya Goranta, Tarek Haykal, Areeg Bala, Ragheed Al-Dulaimi, Ghassan Bachuwa, Trailokya Nath Pandit, Rizwan Danish
Journal: Journal of Clinical Oncology (2019)

e12014 Background: Oncotype-DX Assay is a 21-gene based recurrence score (RS) that helps stratify breast cancer patients based on their risk of recurrence. It is often used to help identify patients that may benefit from adjuvant chemotherapy (AC). Prior to the TAILORx Trial results, there were no guidelines for AC in patients with an intermediate score (18-30). Management of these patients was often at the clinical judgement of the provider. We sought to determine predictors of AC among these patients, and measure treatment effect on survival. Methods: We queried the Surveillance, Epidemiology, and End-Results database for breast cancer patients newly diagnosed between 2010-2015. We included patients with T1-T3, hormone receptor positive, HER2-negative, and lymph node-negative breast cancer with an intermediate RS. Male patients, those younger than 40 years, tumors 5 mm or less, and incomplete records were excluded. Univariate and multivariate analysis was performed to derive independent predictors of AC. Cox Proportional-Hazards Model was done to examine the effect of AC on survival. Results: We included 14,710 patients of whom 4,508 (30.6%) received AC. Patients that received AC were younger (55.4 years [8.8] vs 60.0 [9.7], p &lt; 0.001), grade III or higher (29.8% vs 16.4%, p &lt; 0.001), and had a higher RS (23.9 [3.6] vs 21.5 [3.1], p &lt; 0.001). Higher T stage was associated with a higher rate of patients receiving AC (p &lt; 0.001). Marital status was also associated with AC; a higher proportion of patients who received AC were married (67.9% vs 64.4%, p &lt; 0.001). There was no significant association between race/ethnicity or insurance type with AC. Multivariate analysis showed that RS (OR: 1.24 [1.23-1.26], p &lt; 0.001), T stage (OR: 1.67 [1.21-2.30], p &lt; 0.001), and a grade III tumor (OR: 1.85 [1.64-2.09], p &lt; 0.001) were the strongest predictors of AC. The age decile 80-89 years (OR: 0.05 [0.02-0.10], p &lt; 0.001) was the most negative predictor of AC. AC did not have an effect on 5 year overall survival (97.6% vs 96.0%, p = 0.28). Conclusions: Between 2010-2015, our study shows 30.6% of breast cancers patients with an intermediate Oncotype-DX score were given AC. The decision to treat was largely based on tumor size, grade and age. AC had no effect on overall survival.
Evaluation of next generation sequencing for detecting HER2 copy number in breast and gastric cancers.
Authors: Dongmei Lin, Jiafu Ji, Dongfeng Niu, Lei Li, Yang Yu, Yun Gao, Wanchun Zhang, Zhongwu Li, Guanhua Rao, Lianju Gao, Gang Cheng
Journal: Journal of Clinical Oncology (2019)

e13004 Background: Amplicon-based next generation sequencing (NGS) approaches have been preferentially adopted by the clinical laboratories on the basis of a short turnaround time (TAT) and small DNA input needs. However, little work has been done to assess the amplicon-based NGS methods for copy number variation (CNV) detection in comparison with current standard methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). The correlation between NGS based CNV detection and the later standard methods has remained unexplored. Methods: We developed an amplicon-based panel to detect human epidermal receptor growth factor (HER2) amplification in formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 280 breast cancer and 50 gastric cancer patients. Assessment by IHC and FISH was conducted in parallel, and descriptive statistics were used to assess the concordance. Results: The copy number detected by NGS was correlated with either the average HER2 copy number (signals/cell) (r = 0.844; p &lt; 0.001) or the HER2/CEP17 ratio (r = 0.815; p &lt; 0.001). We determined a cut-off value for NGS to categorize HER2 amplification status by using 131 HER2 non-amplified FFPE samples. In breast cancer patients, the cut-off value was 2.910, with 95.28%, 99.23% and 97.29% sensitivity, specificity and concordance, respectively. However, this cut-off value displayed low sensitivity in gastric cancer patients (64.71%), and the following macro-dissection procedure was not effective for increasing sensitivity (57.14%). Thus indicated that HER2 copy number correlation between NGS and FISH in gastric cancer was different from breast cancer. Conclusions: Evaluation of HER2 copy number with NGS in our study was comparable with IHC and FISH in breast cancer patients, but concordance in gastric cancer was only moderate. NGS-based HER2 assessment may decrease the equivocal HER2 determinations in breast cancer patients assessed by FISH/IHC. The greater discordance in gastric cancer may reflect the underlying biological mechanisms, and further study is warranted.
Effect of MALAT1 in the crosstalk between nucleus and mitochondria on mitochondrial reprogramming in hepatocellular carcinoma cells.
Authors: Yijing Zhao, Jiuwei Cui, Jifan Hu, Andrew R Hoffman
Journal: Journal of Clinical Oncology (2019)

e14711 Background: Mitochondria-nuclear crosstalk is a bidirectional pathway of communication between mitochondria and nucleus that influences many cellular and organismal activities. This crosstalk can regulate several oncogenic pathways involved in tumorigenesis. MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), a nucleus-encoded lncRNA, dysregulated in multiple human malignancies is recently found to drive mitochondria dysfunction in Mitochondria-nuclear crosstalk. Methods: RNA sequencing, “RNA reverse transcription-associated trap sequencing” (RAT-seq), RNA immunoprecipitation(RIP), fluorescence in situ hybridization (FISH), were performed to detect the position of the MALAT1, and its interaction protein and DNAs in HepG2 cell line. After silencing MALAT1 by shRNAs, Seahorse, ATP production, lysotracker staining, Western blot, and electronic microscope were used to measure metabolism, ROS amount, mitophagy, apoptosis and mitochondrial morphology of the silencing cell lines. Results: By combining mitochondrial RNA-Seq with FISH, it is surprised to discover that MALAT1 was enriched in the mitochondria of HepG2 cells. Using RAT-seq approach, MALAT1 was found to utilized it 3’-fragment to interact with multiple loci of mitochondrial DNA( D-loop, COX2, ND3, and CYTB ). The RIP and affinity RNA pulldown assays suggested that the RNA-binding protein HuR mediated the transportation of MALAT1 to the mitochondria. Also, mitochondria transmembrane protein mitochondrial carrier 2(MTCH2) is found to interacted MALAT1, suggesting that MALAT1 may through the MTCH2 to get into the inside of the mitochondria. Knockdown of MALAT1 induced multiple abnormalities in mitochondrial functions, including low OXPHOS, low ATP production, reduced mitophagy, declined mtDNA copy number, and activation of the mitochondrial apoptosis pathway. Conclusions: Together, this study greatly expands our knowledge of the nucleus-encoded lncRNA MALAT1 driving the mitochondria dysfunction. Our study establishes MALAT1 as a regulator through interacting with MT-DNA, HuR, MTCH2 protein, revealing a new regulatory mechanism of mitochondria. Many novel nucleus-encoded RNAs existing in mitochondria were identified at the first time, suggesting novel biological functions of lncRNAs, laying the foundation for further clarifying their roles.
AB1406-HPR DIET AND LUPUS: WHAT DO THE PATIENTS THINK?
Authors: George Robinson, Thomas Mcdonnell, Chris Wincup, Lucia Martin-Gutierrez, James Wilton, Anastasia Kalea, Coziana Ciurtin, Ines Pineda Torra, Elizabeth Jury, Jury Lab, Jury Lab, Jury Lab
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cardiovascular disease (CVD) is the leading cause of mortality in patients with systemic lupus erythematosus (lupus). Therefore, using diet to control blood lipid levels and modify CVD risk could be a promising therapeutic strategy to control disease symptoms. <h3>Objectives</h3> The primary objective of this study was to learn about lupus patient experiences with diet including their opinion on considering diet as a therapeutic option. The secondary objective was to obtain this information in a cost and time effective manner. <h3>Methods</h3> A lay summary and a 15 question diet-based online survey was publicly available for 3 weeks. Social media was used to promote the survey through relevant charities, hospitals and research groups. <h3>Results</h3> 300 responses were received, 284 of whom had lupus. Patients reported that there was a lack of clinical counselling regarding diet with only 24% of patients stating that their doctor had spoken to them about diet. Despite this, 100% of patients stated that they would change their diet if they knew it would help their symptoms and 83% would take part in a future diet-based clinical trial. Text analysis of patient research suggestions identified a particular interest in using diet to treat fatigue and manage disease flares. <h3>Conclusion</h3> This project successfully gathered patient information regarding diet and lupus over a short timeframe using an anonymous social media platform. The survey provided evidence that patients support further research and potential diet intervention studies investigating the effect of diet on the symptoms of lupus. <h3>References</h3> [1] Bernatsky S, Boivin JF, Joseph L, Manzi S, Ginzler E, Gladman DD, et al. Mortality in systemic lupus erythematosus. Arthritis &amp; Rheumatism. 2006;54(8):2550-7. [2] McDonnell TCR, Wincup C, Rahman A, Giles I. Going viral in rheumatology: a rapid, cost-effective method of obtaining patient opinion about mechanistic research in SLE and APSA. Rheumatology. 2018;57:1. <h3>Acknowledgement</h3> Lupus UK, Rosetrees Trust, Versus Arthritis, Survey Monkey <h3>Disclosure of Interests</h3> None declared
Association between baseline disease characteristics and relapse-free survival (RFS) in patients (pts) with <i>BRAF</i> V600-mutant resected stage III melanoma treated with adjuvant dabrafenib (D) + trametinib (T) or placebo (PBO).
Authors: Dirk Schadendorf, Reinhard Dummer, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, James M.G. Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Mark Haydon, Laurent Mortier, Caroline Robert, Jacob Schachter, Christine-Elke Ortmann, Egbert De Jong, Eduard Gasal, Richard Kefford, John M. Kirkwood, Georgina V. Long
Journal: Journal of Clinical Oncology (2019)

9582 Background: In the COMBI-AD trial (NCT01682083), 12 mo of adjuvant D+T led to significant improvement of RFS vs PBO (hazard ratio [HR], 0.47; P &lt; .001) in pts with resected BRAF V600–mutant stage III melanoma; 3- and 4-year RFS rates were 59% and 54%, respectively. Previous results demonstrated consistent treatment benefit across baseline disease stage according to AJCC edition 7 or 8. Here, we further explored the association between baseline disease characteristics and RFS to identify pt subgroups likely to benefit from adjuvant treatment. Methods: Randomized pts with completely resected BRAF V600E/K–mutant stage III melanoma received 12 mo of adjuvant D (150 mg BID) + T (2 mg QD) or PBO. Within each subgroup, predictive value was explored using Kaplan-Meier analysis, and HRs were calculated using a Pike estimator. Results: Minimum follow-up was 40 mo for 870 enrolled pts (D+T, 438; PBO, 432). Kaplan-Meier analysis demonstrated treatment benefit across all subgroups analyzed. Assessment of RFS by extent of primary tumor (T stage) showed consistent benefit favoring D+T vs PBO (HR [95% CI]; T1, 0.42 [0.25-0.70]; T2, 0.51 [0.34-0.76]; T3, 0.55 [0.39-0.77]; T4, 0.42 [0.29-0.60]). HRs by nodal burden (N stage) also showed consistent treatment benefit (N1, 0.52 [95% CI, 0.37-0.72]; N2, 0.38 [95% CI, 0.28-0.53]; N3, 0.58 [95% CI, 0.41-0.83]). Substantial treatment benefit was observed in pts with baseline in-transit metastases (HR, 0.45 [95% CI, 0.24-0.82]) and those with no in-transit metastases detected at baseline (HR, 0.49 [95% CI, 0.40-0.60]). When RFS was assessed according to melanoma presentation, treatment benefit favoring D+T vs PBO was observed in pts with superficial spreading melanoma (HR, 0.48 [95% CI, 0.35-0.66]) and those with nodular melanoma (HR, 0.53 [95% CI, 0.37-0.75]). Conclusions: These results confirm earlier findings showing that treatment benefit with adjuvant D+T vs PBO is independent of baseline factors. Clinical trial information: NCT01682083.