tbuckley/cabot-search huggingface dataset:
Real-life results from the prospective QoliXane trial of the platform for outcome, quality of life, and translational research on pancreatic cancer (PARAGON) registry.
Authors: Salah-Eddin Al-Batran, Ralf Dieter Hofheinz, Alexander Reichart, Claudia Pauligk, Rudolf Schlag, Gabriele Margareta Siegler, Heinz-Gert Hoeffkes, Wolfgang Blau, Nils Homann, Jorg Trojan, Oliver Waidmann, Daniel Pink, Helmut Messmann, Volker Kunzmann, Arndt Vogel, Thomas Jens Ettrich, Caroline Schoenherr, Marina Schaaf, Gerrit zur Hausen, Thorsten Oliver Goetze
Journal: Journal of Clinical Oncology (2020)

4625 Background: Gemcitabine and nab-paclitaxel (NPG) is standard first-line therapy for metastatic pancreatic cancer (mPC), but the pivotal study did not include quality of life (QoL) analyses. Methods: The QOLIXANE-PARAGON study started as a prospective, non-interventional, multicenter study conducted in Germany and transitioned into a permanent registry for pancreatic cancer patients (pts) considering all types of treatments. This report focuses on the pts enrolled into the QOLIXANE portion of the study. Pts were recruited from 95 German centers. QoL was prospectively measured via EORTC-C30 questionnaires (prior to and every month thereafter): therapy and efficacy parameters were prospectively collected. QoL and efficacy endpoints were analyzed in the intention-to-treat population (ITT). The primary endpoint was the rate of pts without deterioration of QoL/Global Health Score (QoL/GHS) at 3 months. Results: 600 pts were enrolled. Mean GHS/QoL score at baseline was low and was 46.2 (SD 22.8). Median progression-free survival was 5.85 months (95% CI, 5.23 to 6.25). Median overall survival (OS) was 8.91 months (95% CI, 7.89 to 10.19). The KM-analysis showed that 61% and 41% of pts had maintained QoL/GHS after 3 and 6 months, respectively. Median time to deterioration of QoL/GHS was 4.68 months (95% CI, 4.04 to 5.59). Mean QoL/GHS improved from 46.1 (SD 22.7) at baseline to 52.8 (SD 21.3) after 6 months. In the QoL response analysis, 34.6%, 37.4% and 28% of evaluable pts had improved, stable and worse QoL/GHS after 3 months, respectively. In the Cox regression analysis, GHS/QoL scores strongly predicted survival with a HR of 0.86 (p &lt; 0.0001). Conclusions: QoliXane the largest study on QoL of mPC. It shows that time to deterioration of QoL is short but that a relevant group of mPC in first line have improved or maintained QoL after 3 and 6 months and that QoL is a predictor of pts outcome. Clinical trial information: NCT02691052 .
A phase I trial a FR alpha targeted thymidylate synthase inhibitor CT900 exploring four schedules of treatment in expansion cohorts of patients with high-grade serous ovarian cancer.
Authors: Susana N. Banerjee, Alvaro Ingles Russo, Andrea Biondo, Ionut-Gabriel Funingana, Martin Little, Toby Prout, Mona Parmar, Bora Gurel, Ruth Riisnaes, Ben Jenkins, Emma Hall, Ed Ainscow, Stuart McIntosh, Nina Tunariu, Anna Rachel Minchom, Juanita Suzanne Lopez, Johann S. De Bono, Natalie Cook, Bristi Basu, Udai Banerji
Journal: Journal of Clinical Oncology (2020)

6043 Background: CT900 (BTG945/ONX-0801) is a novel small molecule that binds to folate receptor alpha (FRα), is internalized and causes cytotoxicity by thymidylate synthase inhibition. Methods: The aims of the expansion cohorts were to determine toxicity, response rates and correlation of the response to FRα expression in patients with HGSOC (NCT02360345). Four expansion cohorts were studied which included: schedule A (6 mg/m 2 /q every 2 weeks), schedule B (12 mg/m 2 /q every 2 weeks), schedule C (12 mg/m 2 /q every 2 weeks with 12 mg dexamethasone IV and 8 mg of dexamethasone for 2 days) and schedule D (12 mg/m 2 /q every 3 weeks). Response rates were assessed by RECIST V1.1 and GCIG CA125 response criteria. Patients who were withdrawn for reasons other than toxicity within 8 weeks (cohorts A, B, C) and 12 weeks (cohort D) were not assessable for efficacy. FRα expression was quantified using immunohistochemistry. Results: A total of 67 patients were treated in the 4 cohorts (14, 25, 15 and 13 for cohorts A, B, C and D). The median age was 62 (IQR 57 - 68) and the median lines of previous treatment was 5 (range 1 to 13). A majority of patients were platinum resistant. The most common toxicities across all expansion cohorts were: fatigue (51%), nausea (36%), anemia (27%), fever (25%), AST elevation (21%), most of which were grade 1 - 2. Toxicity of special interest included radiological changes of pneumonitis and was 15% in all cohorts (7%, 16%, 27% and 8% in cohorts A, B, C and D, respectively). These changes were grade 1 - 2 in all but one case. RECIST response rates in evaluable patients across the different cohorts were: A 1/8 (13%), B 6/21 (29%), C 5/12 (42%) and D 2/12 (17%). FRα expression in archival tumor tissue was measured in 59/67 patients. Expression was found to be high/medium in 43/59 (73%), low in 7/59 (12%) and negative/very low in 9/59 (15%). In patients with high/medium FRα expression, the RECIST response rates in different cohorts were: A 0/9 (0%), B 6/16 (38%), C 4/12 (33%) and D 1/6 (17%). The CA125 response rate in all patients within cohort B was 13/25 (52%) and 10/16 (63%) in patients with high/medium FRα expression. Conclusions: CT900 has shown clinical activity in patients with heavily pre-treated platinum-resistant, high/medium FRα expressing HGSOC. Based on toxicity and efficacy, the schedule of 12 mg/m 2 /q2 weekly (schedule B) is the recommended phase II dose for further evaluation in patients with relapsed high/medium FRα expressing HGSOC. Clinical trial information: NCT02360345.
Assessment of Overall and Specific Cancer Risks in Patients With Hidradenitis Suppurativa
Authors: Joon Min Jung, Keon Hee Lee, Ye-Jee Kim, Sung Eun Chang, Mi Woo Lee, Jee Ho Choi, Chong Hyun Won, Woo Jin Lee
Journal: JAMA Dermatology (2020)

Large population-based studies investigating the risks of overall and specific cancers among patients with hidradenitis suppurativa (HS) are limited.To assess the overall and specific cancer risks in patients with HS compared with the risks in patients without HS in the Republic of Korea.A nationwide population-based cohort study, using the Korean Health Insurance Review and Assessment Service database was conducted over a 2-year period from January 1, 2007, to December 31, 2008. Individuals in the control group who were never diagnosed with HS or cancer during the washout period were randomly extracted and matched by age, sex, index year, and insurance type at a case-control ratio of 1:8, and patients with newly diagnosed HS between January 1, 2009, and December 31, 2017, were included. Follow-up data on incident cancer from January 1, 2009, to December 31, 2018, were included.The overall and specific cancer incidence rates were calculated per 100 000 person-years in patients with HS and in the matched control cohort. The risk for cancers was assessed by multivariable Cox regression models in patients with HS compared with the matched control cohort.In total, 22 468 patients with HS and 179 734 matched controls were included in the study. The mean (SD) age was 33.63 (17.61) years and 63.7% of the participants in both groups were male. The adjusted hazard ratio (aHR) of overall cancer in patients with HS was 1.28 (95% CI, 1.15-1.42). Patients with HS had significantly higher risk for Hodgkin lymphoma (aHR, 5.08; 95% CI, 1.21-21.36), oral cavity and pharyngeal cancer (aHR, 3.10; 95% CI, 1.60-6.02), central nervous system cancer (aHR, 2.40; 95% CI, 1.22-4.70), nonmelanoma skin cancer (HR, 2.06; 95% CI, 1.12-3.79), prostate cancer (aHR, 2.05; 95% CI, 1.30-3.24), and colorectal cancer (aHR, 1.45; 95% CI, 1.09-1.93).In this study, HS appeared to be associated with a significantly increased risk of overall cancer as well as several specific cancers.
Nationwide incidence of sarcomas and tumors of intermediate malignancy in the NETSARC network with central pathology review: Correlation with published clinical research.
Authors: Gonzague De Pinieux, Marie Karanian, Francois Le Loarer, Sophie Le Guellec, Philippe Terrier, Corinne Bouvier, Maxime Battistella, Yves Marie Robin, Jean-François Emile, Anne Moreau, Frederique Larousserie, Agnès Leroux, Nathalie Stock, Marick Laé, Françoise Collin, Antoine Italiano, Axel Le Cesne, Nicolas Penel, Jean Michel Coindre, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2020)

11560 Background: Since 2010, presentation to a designated sarcoma tumor board and pathological review by an expert network are mandatory for sarcoma patients in France. NETSARC+ (merging the 3 initial RREPS, RESOS &amp; NETSARC) collected prospectively all cases of reviewed sarcomas and tumors of intermediate malignancy (TIM) nationwide. We report on the incidence of subtypes according to WHO classification from 2013 to 2016. Methods: Sarcoma expert pathologists reviewed samples were all prospectively integrated in the database; the results using the latest WHO classification are presented for the years 2013 to 2016, including yearly variations. Correlation of the incidence of each histotype with dedicated published clinical trials was conducted. Results: 139 different histological subtypes are reported among the 25172 patients with sarcomas (n = 18710, 64%) or TIM (n = 6460, 36%), respectively n = 5838, n = 6153, n = 6654, and n = 6527 yearly from 2013 to 2016. Over these 4 years, the observed yearly incidence of sarcomas, TIM, and all was therefore 79.7, 24.9 and 95.1/10e6/year, above that previously reported. GIST, liposarcoma, leiomyosarcomas, undifferentiated sarcomas represented 13%, 13%, 11% and 11% of all sarcomas. Only GIST, as a single entity exceeded a yearly incidence above 10/million per year. There were respectively 30, 63 and 66 different histological subtypes of sarcomas or TIM (single entities or lumped together, e.g. MPNST, or vascular sarcomas...) with an incidence ranging from 10 to 1/10e6/year, 1-0.1/10e6 per year, or &lt; 0.1/10e6/year respectively. The 2 later “incidence groups” included 21% of the patients. The incidence of 8 histotypes varied significantly over this 4 years. Patients with tumors with an incidence above 1/10e6 per year have significantly higher numbers of dedicated published phase III and phase II clinical trials (p &lt; 10e-6). Conclusions: This nationwide registry of sarcoma patients with an histology reviewed by sarcoma experts shows that the incidence of sarcoma and TIM is higher than previously reported, may vary over years for some histotypes, and that tumors with an incidence &lt; 10e6 have a much lower access to clinical trials.
Qualitative patient interviews on symptoms and impacts in metastatic synovial sarcoma (mSS).
Authors: Brandon Becker, Laurie Eliason, Kenneth W. Culver, Rob Arbuckle, Anya Francis, Shibani Pokras
Journal: Journal of Clinical Oncology (2020)

e23576 Background: Synovial sarcoma (SS), a soft tissue sarcoma, is a rare and aggressive malignancy, with significant morbidity and mortality associated with mSS. There are currently no patient-reported outcome (PRO) instruments specific to mSS patients and little qualitative research to understand impacts on mSS patients’ health-related quality of life (QoL). The objective of this study was to characterize the symptoms and impacts experienced by mSS patients to inform the selection of content-valid PRO instruments for use in investigational trials in mSS patients. Methods: This was a non-interventional, qualitative interview study of adult participants in the United States (US) with physician-confirmed mSS. Participants were consented from a large private practice in the US. Six semistructured concept elicitation interviews (60–90m by telephone) were conducted by trained interviewers. Participants were asked to describe their mSS symptoms and their impact on functioning in an open-ended fashion with follow-up probes. Verbatim transcripts were analyzed using thematic analysis methods and Atlas.Ti software. Socio-demographics and clinical characteristics were collected by the site. The study received Institutional Review Board (IRB) approval from Western IRB. Results: Among the 6 participants, average age was 45y (range 21–61y) and 2 were female. All 6 participants had pulmonary metastasis, 1 participant had a liver metastasis, and 1 participant had a mediastinal mass. The most common symptoms participants spontaneously identified were pain (n = 6), fatigue (n = 6), coughing (n = 5, with 2 upon probing), shortness of breath (n = 4), phlegm/mucus in the lungs (n = 3), coughing up blood (n = 2), and gastrointestinal complications (n = 2). Nerve/shooting/burning pain (n = 5) was mentioned upon probing. Participants also reported impacts of their disease on sleep (quantity and quality) (n = 6), physical activity (n = 6), social life (n = 6), daily activities (n = 5), emotions (n = 5), loss of appetite (n = 3), and finances (n = 1). Although not spontaneously reported, global ratings of overall health and QoL were considered relevant by all participants. Conclusions: This is the first study to identify patient-relevant symptoms and impacts associated with mSS. Further interviews with additional participants are ongoing, and we will analyze these data to identify appropriate PRO instruments for use in investigational trials in mSS patients. Funding: GlaxoSmithKline (209386).
Risk factors of atherosclerosis in elderly senile obstructive sleep apnea hypopnea syndrome patients with hypertension and type 2 diabetes
Authors: Gaisheng Tian
Journal: BMJ (2015)

Objective
To explore the related factors of atherosclerosis in senile obstructive sleep apnea hypopnea syndrome (OSAHS) patients.


Methods
From May 2012 to January 2014, 129 elderly hypertension and type 2 diabetes patients were recruited. According to the presence or absence of OSAHS, they were divided into OSAHS (n=60) and non-OSAHS (n=69) groups. And 30 physical examination subjects were selected as control group. The parameters of age, gender, height, weight, high sensitivity C-reactive protein (Hs-CRP), homocysteine (Hcy), triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and intimate-media thickness of carotid artery (CIMT) were measured with ultrasonography. And their levels were compared among OSAHS, non-OSAHS and normal control groups. And the correlations were analyzed between CIMT and Hs-CRP, Hcy, TG, TC, HDL-C, LDL-C, age and body mass index (BMI).


Results
The levels of Hs-CRP[(3.40±0.91) mg/L, (2.57±1.01) mg/L], Hcy[(16.50±2.89) μmol/L, (11.20±2.32) μmol/L], CIMT[(1.06±0.14) mm, (0.93±0.13) mm], TG[(2.52±1.40) mmol/L, (2.51±2.02) mmol/L], TC[(5.74±1.16) mmol/L, (5.49±1.09) mmol/L]and LDL-C[(3.15±0.47) mmol/L, (3.05±0.70) mmol/L]in both OSAHS and non-OSAHS groups were higher than those in normal control group [Hs-CRP: (2.06±1.22) mg/L, Hcy: (6.04±1.85) μmol/L, CIMT: (0.65±0.07) mm, TG: (0.99±0.24) mmol/L, TC: (3.63±0.71) mmol/L and LDL-C: (2.47±0.27) mmol/L] (OSHAS group vs. control group, t=5.88, 18.15, 15.62, 5.91, 9.17, 7.47, non-OSAHS group vs. control group, t=2.20, 10.73, 11.51, 4.09, 8.56, 4.45, all P<0.05). The levels of Hs-CRP, Hcy, CIMT and plaque score were higher in OSAHS group than those in non-OSAHS group[(1.92±1.03) vs. (1.35±0.97) points] (OSHAS group vs. non-OSAHS group, t=4.84, 11.72, 5.54, 3.91, all P<0.05). CIMT or carotid artery plaque were related with age, BMI, TG, TC, LDL-C, Hs-CRP and Hcy in OSAHS group.


Conclusions
OSAHS may elevate the level of inflammatory factors and cause atherosclerosis. And the changes of CIMT, Hs-CRP and Hcy are parallel. Hcy also has important clinical significance in the progression of atherosclerosis.


Key words: 
Sleep apnea, obstructive; C reactive protein; Homocysteine
Research progress in thyroid associated ophthalmopathy
Authors: 林雪, 郭雪松, 张明欣, 毕淑娟, 王志荣, 孙丰源
Journal: BMJ (2007)

甲状腺相关性眼病(thyroid associated ophthalmopathy,TAO)又名Graves眼病、内分泌突眼、浸润性突眼、甲状腺眼病、免疫性眼眶病、免疫相关性眼病、甲状腺眼眶病等,各文献报道不一,近年来发病率较高,尤其在我国有增高趋势,占眼眶病的20%,成为主要致盲原因之一。
Acceptance status of internet+ health management among hypertensive patients in Xuzhou city and its influencing factors
Authors: Lihe Nie, Lizhen Zhao, Xin Zhang, Xiuyin Gao
Journal: BMJ (2019)

Objective
To investigate the acceptance status of internet+health management among hypertensive patients in Xuzhou city and the related influencing factors.


Methods
An interviewing questionnaire survey on the acceptance of internet+health management was conducted among 1,200 hypertensive patients from Xuzhou community health service centers selected by randomized cluster sampling and stratified sampling methods from February tp August 2018, 1 116 valid questionnaires were finally obtained with a response rate of 93.0%. The respondents were divided into two groups according to whether they would accept the internet+health management, and the general conditions and health management status of the two groups were compared.


Results
The acceptance rate of internet+health management was 71.9% (802/1 116). The univariate analysis showed that age, education level, occupation, and monthly income of hypertensive patients were associated with the acceptance of internet+health management (P<0.05); patients with family history of hypertension, cardiovascular and cerebrovascular complications and high health literacy had higher acceptance rate of internet+health management (P<0.05). Multivariate analysis showed that educational levels of junior high school and above (OR=0.426, 0.318, 0.089), good sleep (OR=0.453) were protective factors for acceptance of internet+health management; while not knowing the diagnostic criteria for hypertension (OR=1.494), not knowing the blood pressure monitoring (OR=2.668), not knowing ECG monitoring (OR=2.247), quitting smoking (OR=2.444), no complications (OR=2.247), and not participating in community health management (OR=1.758) were the risk factors of acceptance of internet+health management for patients with hypertension.


Conclusion
The acceptance rate of internet+health management among hypertensive patients in Xuzhou city is relatively high. A variety of factors have impact on the acceptance of internet + health management.


Key words: 
Hypertension; Community health management; Internet plus; Influencing factors
Safety of <sup>177</sup>Lu-DOTATATE in patients with advanced neuroendocrine tumors: Data from a U.S. expanded access program.
Authors: Martin S. Auerbach, Edward M. Wolin, Val Nassiri, Per Broberg, Ghassan El-Haddad
Journal: Journal of Clinical Oncology (2020)

4604 Background: The NETTER-1 clinical trial showed that peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE increased progression-free survival in patients with somatostatin-receptor-positive advanced midgut neuroendocrine tumors (NETs) compared with high-dose octreotide long-acting repeatable, and was associated with few serious adverse events (AEs). To assess the safety profile of 177 Lu-DOTATATE in a real-world population, we analyzed safety data from a US expanded access program (NCT02705313). Methods: Patients had inoperable, histologically proven, somatostatin-receptor-positive, locally advanced or metastatic GEPNETs (Ki-67 index ≤ 20%) that progressed after somatostatin analog therapy. Exclusion criteria were: surgery, radiotherapy or chemotherapy in the last 12 weeks; treatment with an interferon, mTOR inhibitor, or other systemic therapy in the last 4 weeks; or ongoing octreotide therapy that could not be interrupted for PRRT. Patients with impaired renal function (serum creatinine &gt; 1.7 mg/dL or creatinine clearance &lt; 50 mL/min) or serious coexisting conditions were excluded. The analysis included patients who received ≥ 1 cycle of 177 Lu-DOTATATE between July 5, 2016 and December 21, 2018. Data were collected from the first cycle to the latest data collection point (up to October 7, 2019). Results: 299 patients received a mean 177 Lu-DOTATATE cumulative dose of 552 mCi (20.4 GBq) (standard deviation [SD]: 220 mCi [8.1 GBq]) over a mean of 2.8 cycles (SD: 1.1). Mean age was 60.8 years (SD: 11.7); 38.5% of patients were men. Over a mean follow-up of 131 days (SD: 87), 48.8% of patients reported treatment-related AEs (TRAEs), with a maximum severity of grade 1, 2 and 3 for 26.8% (n = 80), 18.1% (n = 54) and 4.0% (n = 12) of patients, respectively; there were no grade 4–5 TRAEs. The most common TRAEs of any grade (≥ 5.0% of patients) were nausea (31.1%), vomiting (13.7%), fatigue (9.4%) and thrombocytopenia (6.0%). The most prevalent grade 3 TRAEs were lymphocyte count decrease (1.0%) and thrombocytopenia (0.7%). Serious TRAEs occurred in 1.0% of patients (carcinoid crisis, dehydration, syncope and vomiting). AEs led to dose modification in 1.7% of patients, dose delay in 6.4% (most commonly due to nausea [2.0%] or thrombocytopenia [2.0%]) and discontinuation in 1.3% (due to thrombocytopenia [1.0%] and extravasation [0.3%]). Conclusions: In a real-world population of US patients with advanced GEPNETs, 177 Lu-DOTATATE treatment was well tolerated with few TRAEs, consistent with the safety profile in the NETTER-1 trial. Clinical trial information: NCT02705313 .
Marvelous objective response of low dose radiotherapy plus ICIs for extended stage small cell lung cancer.
Authors: Lin Zhou, Min Yu, Lin Chen, Yan Zhang, Zhu Jiang, Yongmei Liu, Youling Gong, Yong Xu, Jianxin Xue, Yanying Li, Meijuan Huang, You Lu
Journal: Journal of Clinical Oncology (2020)

e21097 Background: Immune checkpoint inhibitors (ICIs) has limited efficacy with unsatisfactory objective response for extensive stage small cell lung cancer (ES-SCLC). In this respective study, efficacy and toxicities of low dose radiotherapy (LDRT) plus ICIs for pretreated failure ES-SCLC has been evaluated, and marvelous objective response has been observed. Methods: From March 2018 to Dec 2019, ten pretreated failure ES-SCLC patients received LDRT (8-20Gy/2-10f, BED 10 9.5-24Gy) for lesions located in lung or other sites plus ICIs (Nivolumab, Pembrolizumab, Ipilimumab, Durvalumab, and Sintilimab) were enrolled. Two patients received concurrent chemotherapy of etoposide plus cisplatin or albumin-bound paclitaxel monotherapy. ICIs were given within 7 days after LDRT. Efficacy, toxicities, and lung cancer symptom scale (LCSS) scores were evaluated. Results: Thirteen lesions (ten located in lungs, and the others located in adrenal gland, axillary lymph node, and abdomen) received LDRT. The gross tumor volume and planning target volume were 32.56 cc-430.19cc and 73.74 cc-771.41 cc, respectively. Eleven lesions did not receive radiotherapy. The objective response rate (ORR) of whole patients was 90% (9/10). The ORR and disease control rate (DCR) of radiated lesions were 92.3% (12/13) and 100% (13/13), compared to 9.1% (1/11) and 18.2% (2/11) for no radiated lesions. Volume shrinkage rates (VSRs) of radiated lesions were 35.16% to 95.91% (13.75cc-277.02cc), and 61.5% (8/13) of radiated lesions reduced more than 80%. VSRs for radiated lesions with volume &gt; 100cc were 63.07% to 95.91% (122.38cc-277.02cc). LCSS improved significantly after treatment (465±13.02 vs. 380±17.8, p= 0.0013). Lymphocyte declined initially and then recovered in patients with disease not progressed, on the contrary, it declined continuously in patients with disease progressed. The most popular toxicities were lymphopenia (70%) and anemia (60%). Grade 3-4 toxicities included lymphopenia (40%), thrombocytopenia (20%), anemia (20%), and granulocytopenia (10%). Conclusions: LDRT might enhance the effectiveness of ICIs greatly for tumor lesions, and radiotherapy should be considered to be given initially for ES-SCLC received ICIs treatment.