tbuckley/cabot-search huggingface dataset:
Randomized phase II study of sapanisertib (SAP) + paclitaxel (PAC) versus PAC alone in patients (pts) with advanced, recurrent, or persistent endometrial cancer.
Authors: Giovanni Scambia, Sileny N. Han, Amit M. Oza, Nicoletta Colombo, Ana Oaknin, Francesco Raspagliesi, Robert Michael Wenham, Elena Ioana Braicu, Andrea Jewell, Vicky Makker, Eva M. Guerra, Katherine M. Moxley, Jean-Francois Baurain, Zhenqiang Su, Rachel Neuwirth, Sylvie Vincent, Farhad Sedarati, Douglas V. Faller, Jonathan Krell
Journal: Journal of Clinical Oncology (2020)

6087 Background: SAP (TAK-228, MLN0128) is a selective dual inhibitor of mammalian target of rapamycin complexes 1 and 2. In endometrial tumor xenograft models, SAP+PAC exhibited stronger antitumor efficacy than PAC alone. Methods: Female pts with histologic/cytologic diagnosis of endometrial cancer were randomized to receive SAP 4 mg by mouth (days [d] 2–4, 9–11, 16–18, 23–25) plus PAC 80 mg/m 2 intravenously (d 1, 8, 15), or PAC alone, in 28-day cycles until unacceptable toxicity or disease progression. Randomization was stratified by histologic subtype, lines of prior chemotherapy (1 vs. 2), and prior taxane therapy. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR; ORR + stable disease), and safety. Additional treatment arms of SAP alone (weekly dosing) and SAP+TAK-117 were closed after futility analyses. Results: 180 pts were randomized to SAP+PAC (n=90) or PAC (n=90); 86 and 87 pts received SAP+PAC and PAC, respectively; 3 pts from each arm were ongoing on treatment at data cut (30 July 2019). Baseline characteristics were balanced between arms. After a median follow-up of 17.2 vs. 14.4 mos with SAP+PAC vs. PAC, median PFS was 5.6 mos vs. 3.7 mos (hazard ratio [HR] 0.82; 95% CI 0.58–1.15). In pts with endometrioid histology (n=116), median PFS was 5.7 mos with SAP+PAC vs 3.3 mos with PAC (HR 0.66; 95% CI 0.43–1.03). In pts with nonendometrioid histology (n=64), median PFS was 3.6 mos with SAP+PAC vs. 5.4 mos with PAC (HR 1.09; 95% CI 0.62–1.90). Median OS was 13.7 mos with SAP+PAC vs. 14.6 mos with PAC (HR 1.01; 95% CI 0.67–1.53). Confirmed ORR was 24% with SAP+PAC vs. 18% with PAC (endometrioid, 23% vs. 16%; nonendometrioid, 28% vs. 22%); CBR was 80% vs. 58% (endometrioid, 84% vs. 55%; nonendometrioid, 72% vs. 63%). Median number of cycles received was 5 (range 1–23) with SAP+PAC and 4 (range 1–37) with PAC. Rates of grade ≥3 treatment-emergent adverse events (TEAEs) were 90% with SAP+PAC vs. 54% with PAC; the most common included anemia (21% vs.12%), neutropenia (12% vs. 3%), fatigue (12% vs. 5%), hypophosphatemia (12% vs. 1%), and pulmonary embolism (11% vs. 3%). Conclusions: Median PFS was longer with SAP+PAC vs. PAC in pts with endometrial cancer but did not reach statistical significance. PFS was particularly longer in the endometrioid subtype but again was not significant, and further studies are warranted. Incidence of grade ≥3 TEAEs was higher with SAP+PAC vs. PAC, but SAP+PAC toxicity was manageable, with no new safety signals. Clinical trial information: NCT02725268.
NK cell receptor NKG2D enforces proinflammatory features and pathogenicity of Th1 and Th17 cells
Authors: Marina Babic, Christoforos Dimitropoulos, Quirin Hammer, Christina Stehle, Frederik Heinrich, Assel Sarsenbayeva, Almut Eisele, Pawel Durek, Mir-Farzin Mashreghi, Berislav Lisnic, Jacques Van Snick, Max Löhning, Simon Fillatreau, David R. Withers, Nicola Gagliani, Samuel Huber, Richard A. Flavell, Bojan Polic, Chiara Romagnani
Journal: The Journal of Experimental Medicine (2020)

NKG2D is a danger sensor expressed on different subsets of innate and adaptive lymphocytes. Despite its established role as a potent activator of the immune system, NKG2D-driven regulation of CD4+ T helper (Th) cell–mediated immunity remains unclear. In this study, we demonstrate that NKG2D modulates Th1 and proinflammatory T-bet+ Th17 cell effector functions in vitro and in vivo. In particular, NKG2D promotes higher production of proinflammatory cytokines by Th1 and T-bet+ Th17 cells and reinforces their transcription of type 1 signature genes, including Tbx21. Conditional deletion of NKG2D in T cells impairs the ability of antigen-specific CD4+ T cells to promote inflammation in vivo during antigen-induced arthritis and experimental autoimmune encephalomyelitis, indicating that NKG2D is an important target for the amelioration of Th1- and Th17-mediated chronic inflammatory diseases.
A real-world comparative analysis of pomalidomide (POM) and other antimyeloma treatments following lenalidomide (LEN) discontinuation among patients with multiple myeloma.
Authors: Robert M. Rifkin, Zoe Clancy, Ronda Copher, Kathleen M. Aguilar, Yiqiong Xie, Marley Boyd, Chuck Wentworth
Journal: Journal of Clinical Oncology (2020)

e19337 Background: In clinical trials, POM has demonstrated favorable clinical outcomes in patients with multiple myeloma (MM) who received prior LEN. Few studies, however, have examined POM treatment for MM in the community oncology setting. This retrospective cohort study compared treatment patterns and outcomes between patients who received a post-LEN treatment, either POM or another antimyeloma regimen. Methods: Adult patients with MM in the US Oncology Network (USON) who initiated a post-LEN treatment within 60 days of LEN discontinuation between Jan 1, 2016 and May 1, 2018, were not clinical trial participants, and had ≥ 2 subsequent clinic visits, were eligible. Data were sourced from USON’s iKnowMed electronic health records. Among patients observed to have discontinued treatment, time to treatment discontinuation (TTTD) was estimated from date of initiation of post-LEN treatment (index treatment) to date of discontinuation. Among patients who started a new treatment after the index treatment, time to next treatment (TTNT) was estimated from date of initiation of index treatment until date of initiation of the next treatment. TTTD and TTNT were analyzed using the Kaplan–Meier (KM) method across the whole study sample; patients who did not discontinue or start a next treatment were censored. Results: Of 547 eligible patients, 155 (28.3%) initiated POM and 392 (71.7%) initiated another antimyeloma regimen. Demographic characteristics were similar between the groups (for all patients, median age was 68 years, 54.5% patients were male and 71.7% were white). In total, 74.2% and 83.7% of patients discontinued the index treatment in the POM and other-treatment groups, respectively. Among the entire study population, KM estimates of median TTTD were 3.5 months (95% CI 2.8–4.6) and 1.9 months (95% CI 1.6–2.4) in the POM and other-treatment group, respectively (log-rank P &lt; 0.001). In total, 65.2% and 71.2% of patients initiated subsequent treatment in the POM and other-treatment groups, respectively. KM estimates of median TTNT were 6.2 months (95% CI 4.5–7.8) and 4.5 months (95% CI 3.9–5.3) in the POM and other-treatment groups, respectively (log-rank P = 0.38). Conclusions: For patients with MM the use of POM following LEN treatment resulted in longer TTNT and TTTD compared with those who received other antimyeloma therapy. These findings support the use of POM treatment after LEN as an option for patients with relapsed/refractory MM.
Launch prices and price developments of cancer drugs in the United States and Europe.
Authors: Kerstin Noëlle Vokinger, Paola Daniore, ChangWon C Lee, Aaron S Kesselheim, Thomas J Hwang
Journal: Journal of Clinical Oncology (2020)

2006 Background: Cancer drug costs are rising in the US and Europe. While drug manufacturers set prices without restriction in the US, European countries have regulations that allow national authorities to directly negotiate drug prices at launch and over time. We analyzed and compared the launch prices and price developments of cancer drugs in the US, Germany, Switzerland and England. Methods: We identified new drugs indicated to treat solid tumors in adults that were FDA-approved between 2009 and 2019 and had also been approved by the EMA and Swissmedic by 31 December 2019. Launch prices and post-launch price changes as of 1 January 2020 were extracted and adjusted to average sales prices for monthly treatment costs in the US and compared to comparable currency-adjusted ex-factory monthly treatment costs in Germany, Switzerland, and England. A cross-sectional analysis was conducted to infer yearly trends in launch prices and post-launch price changes across the countries. Results: The study cohort included 42 drugs for solid tumors, of which 40 (95%) drugs were first approved in the US compared to Germany and England, and 41 (98%) to Switzerland. Average launch prices for monthly treatment costs per patient were $15,178 in the US vs $7,049 in Germany, $7,421 in Switzerland and $8,176 in England, i.e., 215% (interquartile range [IQR] 263%-187%), 205% (IQR 202%-185%) and 186% (IQR 166%-189%) higher in the US compared to Germany, Switzerland and England respectively. Post-launch prices of 36 (86%), 40 (95%), and 38 (90%) drugs decreased over time with total savings of monthly treatment costs for all drugs in the study cohort of $86,744, $44,936, and $1744 in Germany, Switzerland, and England respectively. By contrast, prices of 8 (19%) drugs decreased, while 34 (81%) increased post-launch in the US with total additional expenses of $128,192 for monthly treatment costs. Conclusions: Launch prices for cancer drugs are far higher in the US than in Germany, Switzerland, or England. These price disparities continue to increase substantially after market entry since cancer drug prices, in general, decrease over time in Europe and increase in the US. Spending on cancer drugs could be reduced in the US if it adopted the principles used to more effectively negotiate drug prices in Europe.
Screening for hearing loss and deafness-related genes in newborns
Authors: Hong Yu, Jingqun Yang, Dan Liu, Zhiqiang Wu
Journal: BMJ (2018)

To screen the hearing loss and deafness-related genes in newborns, the screenings for hearing loss and the mutations of common deafness-related genes were performed among 8 187 infants born in Shaoxing Maternal and Child Health Care Hospital from August 2013 to November 2014.Twenty mutation spots in deafness-related genes GJB2, GJB3, 12SrRNA and SLC26A4 were detected with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Of 8 187 newborns, hearing loss was confirmed in 10 cases, and mutations in deafness-related genes were detected in 441 cases with a detection rate of 5.39%.Among 441 cases with positive gene mutations, there were 243 cases with GJB2 mutations (2.97%).147 cases with SCL26A4 mutations (1.80%), 43 cases with GJB3 mutations (0.53%)and 15 cases with mutations of mitochondrial gene 12SrRNA (0.18%). The spot of highest detection frequency was GJB2 235delC (2.31%), followed by SCL26A4 IVS72A>G (1.31%). The deafness gene detection rate for newborns who did not pass the hearing tests (8.16%, 79/968) was higher than these who passed (5.01%, 362/7 219; χ2=10.978, P<0.05). Five of 10 newborns with hearing loss were detected carrying deafness genes. The detection rate of the common deafness genes among the newborns is relatively high in this region.Screening for hearing loss and deafness gene may contribute to early diagnosis and intervention, and also to long-term precaution for those carrying heterozygosity deafness genes.


Key words: 
Newborns; Deafness; Gene; Hearing disorder
Effects of initiating in-office germline testing in safety net clinic patients with epithelial ovarian cancer.
Authors: Scott Jordan, Samantha Spring, Matthew Schlumbrecht, Marilyn Huang
Journal: Journal of Clinical Oncology (2020)

1588 Background: Germline genetic mutations occur in approximately 25% of women with epithelial ovarian cancers. Recent advances in frontline maintenance therapy for patients with hereditary breast and ovarian cancer syndrome make timely germline testing critical. Adherence to genetic testing remains low (approximately 30% nationally), including at our safety net hospital where germline testing by a genetic counselor was performed in only 38% of patients. After initiating in-office genetic testing, our aim was to compare current patients with historical controls to determine whether this intervention shortened the time to testing and results. Methods: IRB approval was obtained. Patients seen for a diagnosis of epithelial ovarian cancer between 4/1/2018 and 12/31/2019 were identified. Patients with only one visit or those who received testing elsewhere were excluded. Patient and visit data were abstracted for each visit during the study period. Comparison was made between patients treated before (control cohort) and after in-office testing was initiated (intervention cohort) on 5/21/2019. Categorical variables were compared using Chi Squared and Fisher’s Exact test. Mann Whitney U test was used to compare time from first clinic visit to the date of genetic testing and to the reporting of test results in the chart. All tests were two-sided and significance was set at p = 0.05. Results: 74 patients were identified and 504 clinic visits were analyzed. 57 (77%) patients were White Hispanic, 15 (20.3%) were Black, and 2 (2.7%) were White non-Hispanic. 56 (75.7%) underwent germline testing. Overall median time to testing from the first clinic visit was 21.2 weeks, and median time to reporting of results was 37 weeks. Though there was no significant difference in testing rate between the cohorts, the time to the date of genetic testing in the intervention group was approximately one-third as long as in the control group (9.6 vs 32.1 weeks, p &lt; 0.001). Among the 52 patients with reported genetic results, results were recorded in a clinic note at 4.1 weeks from first visit in the intervention group, compared with 28.8 weeks in the control group (p &lt; 0.001). In the intervention group, during clinic visits without genetics performed to date, testing was performed at that visit 25% of the time. Conclusions: By initiating in-office testing, time to testing and receipt of results were meaningfully shortened. Removing delays to test results will greatly improve the ability of our patients to receive potentially life-saving maintenance therapy following front line treatment.
The effect of hapten on the clinical efficacy and survival of patients with liver cancer treated by UMIPIC.
Authors: Feng Gao, Peng Jing, Jian Liu, Wei Han, Xingyou Xu, Wei Shang, Jianbin Feng, Peicheng Zhang, Xiaomin Zhang, Guangyong He, Yanfei Wu, Baofa Yu
Journal: Journal of Clinical Oncology (2020)

e16130 Background: To observe the effect of adjuvant on the clinical efficacy and survival period of patients with liver cancer treated by UMIPIC (Ultra-minimum Incision personalized intratumoral chemoimmunotherapy). Methods: 156 liver cancer patients who were treated with UMIPIC with hapten or without hapten from January 2011 to December 2015 were selected for the study objects, including 124 cases with hapten as studying group and 32 cases without hapten as comparing group. All patients signed the treatment consent, treated according to the treatment guidelines of UMIPIC, followed up for the efficacy and the survival period of all patients more than 3 months, and observed whether there was effect on the clinical efficacy, adverse reactions, survival period and survival rate of patients with liver cancer patients treated with UMIPIC. Results: The common side effects of hapten group were fever 45.16%, pain 27.42%, hemoglobin reduction 14.78%, leucopenia 11.97%, thrombocytopenia 10.26%, liver function damage 5.26%, nausea 4.03%, renal dysfunction 2.61%. No rash, neurotoxicity and hair loss were found; The common adverse reactions in the non hapten group were fever 40.63%, pain 25.00%, hemoglobin reduction 17.24%, leucopenia 13.79%, thrombocytopenia 10.34%, nausea 6.25%. No other adverse reactions were found; there was no difference between the two groups (P &gt; 0.05). The benefit rate of hapten group was 89.06% lower than that of non hapten group (94.74%) (P &gt; 0.05). According to the follow-up results, the mean and median survival time of hapten group was 26.421 and 9.930 months, significantly higher than that of non hapten (16.473 and 7.230 months) (P &lt; 0.05).The 1-year, 2-year, 3-year and 5-year survival rates of adjuvant group respectively were 45.69%, 33.33%, 25.68% and 20.83%,The 1-year, 2-year, 3-year and 5-year survival rates in the adjuvant free group respectively were 27.50%, 20.59%, 14.81% and 14.29%, The 1-year survival rate of hapten group was significantly higher than that of non hapten group (P &lt; 0.05). Conclusions: There is no significant difference in the adverse reactions and clinical efficacy of UMIPIC in the treatment of liver cancer patients with and without hapten. Adding hapten can significantly prolong the survival time and improve the survival rate of patients with liver cancer patients treated with UMIPIC.
Financial toxicity and its associated patient and cancer factors among women with breast cancer in China.
Authors: Jingfeng Jing, Ran Feng, Xiaojun Zhang, Ming Li, Jinnan Gao
Journal: Journal of Clinical Oncology (2020)

e19402 Background: The term “Financial toxicity(FT)” is widely used to describe the distress or hardship patients suffering from the financial burden of cancer treatment[1]. Increased evidences have showed that cancer-associated FT is common and has a negative impact on patients’ mental health, quality and length of life[1,2]. The scale of COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) was used to assess the FT of cancer patients, which has been validated and widely used internationally [3] and China [4]. To our knowledge, little is known about the FT of breast cancer patients in China. The aim of this study is to assess the FT and to investigate patients and cancer characteristic that associated with it in patients in central China. Methods: This was a cross-sectional study among 188 patients with stage 0-III women breast cancer admitted in Bethune hospital in Taiyuan, Shanxi province during January - May 2019. FT was self-reported using the COST-FACIT. Patients’ socio-demographic factors, clinical examination, and cancer treatment were collected from questionnaire and hospital record. The financial concern and coping strategy was self-reported. Factors associated with FT was identified using linear regression analysis. Results: One hundred and sixty-six (88.2%) completed the questionnaire. The COST score ranged 0-40 with a mean of 21.2 (median 22.5, standard deviation 8.1). On multivariate linear regression analysis, older age (β coefficient: 0.19, 95% CI: 0.10-0.29, p&lt;0.001), higher household income (β coefficient: 3000-5000 Yuan: 6.48, 95% CI: 2.78-10.17, p =0.001; ≥ 5000 Yuan: 11.17, 95% CI: 7.25-15.09, p&lt;0.001) were positively associated with COST scores. Advanced cancer stage was the strongest predictor of FT among the cancer characteristics (β coefficient: -1.81, 95% CI: -3.17, -0.46, p=0.009). To cope with the FT, 131 (78.8%) patients decreased non-medical expenses, and 56 (33.7%) reduced or quit treatment. Conclusions: FT was significantly associated with patient’s age, income, and cancer stage. Women having financial concerns after diagnosis were more likely to reduce their non-medical expenses and even quit treatments. Clinicians should take into account the FT levels in all patients and work out appropriate treatment strategies for optimal clinical outcome.
65岁以上多器官功能障碍综合征89例临床分析
Authors: 王仁萍, 彭小菊, 李堃, 杨慧英
Journal: BMJ (2007)

近年来,医学界对多器官功能障碍综合征(MODS)越来越重视,尤其65岁以上患者临床表现复杂且不典型,病死率高[1].因此探讨老年人MODS发病原因、死亡高危因素及临床特点,对提高抢救成功率具有重要的意义。
Blood glucose abnormality in elderly patients with cardiocerebral vascular diseases
Authors: Xian Zhang, Yi-rui Li, Li-hua Zou, Han-ju Huang, Yan Lu, Yun Zhang, Yue Zhou
Journal: BMJ (2009)

One hundred and four patients aged of 65 years or above with cardiocerebral vascular diseases admitted from March to September 2008 were enrolled in the study. The fast plasma glucose (FPG) and 2 hours postprandial blood glucose (2 hPG) were tested. For patients with undiagnosed diabetes, if FPG≥7.0 mmol/L, 2 hPG≥11.1 mmol/L, their blood sugar index was checked again; if 2hPG was 7.8 mmol/L to 11.1 mmol/L, FPG from 6.1 mmol/L to 7.0 mmol/L, Oral glucose tolerance test (OGTT) was performed. Among the 104 patients, 30 cases of diabetes were diagnosed previously accounting for 28.8 %; 7 cases were newly diagnosed accounting for 6.8%; 21 cases were diagnosed as impaired glucose regulation accounting for 20.2%, with a total rate of sugar metabolism abnormality of 55.8%. The results indicate that blood glucose index should be regularly checked for elderly patients with cardiocerebral vascular diseases.

Key words: 
Aged;  Glucose metabolism disorders
Effect of idronoxil combined with cisplatin on refractory immune responses in nasopharyngeal carcinoma.
Authors: Ngar-Woon Kam, Victor Ho-Fun Lee, Tae Yang Desmond Hung, Man Kim Yim, George Tsao, Olivier Laczka, Frederic Delebecque, John Wilkinson, Dora LW Kwong
Journal: Journal of Clinical Oncology (2020)

e15186 Background: Nasopharyngeal carcinoma (NPC) is endemic in Southern China. Although it is both radio-and chemo-sensitive, resistance to these treatments remains a major problem for successful management of NPC. The main characteristic of a cancer cell is its resistance to undergo apoptosis; therefore, reversing this resistance may represent the best approach for the treatment of cancer. Additionally, NPC is well-known to be heavily infiltrated by lymphocytes and constitute a unique but poorly defined tumor microenvironment (TME). We aimed at delineating and defining the contribution of idronoxil (IDX) in restoring sensitivity to apoptosis and potentially modulating the immune microenvironment of NPC. Methods: The IC 50 of cisplatin (Cis) and IDX from 2D and 3D spheroid cultures of four NPC cancer cell lines (C666, C17, and the paired NPC43 EBV-positive and EBV-negative cell lines) were evaluated. The migration and proliferation of cells treated with IDX and/or Cis were investigated by Transwell and XTT, respectively. Cell phenotype and migratory analyses were measured by flow cytometry on Cis/IDX-pretreated NPC cell lines cocultured with HLA-matched PBMC. Results: IDX and Cis inhibited NPC migration and cell proliferation (IC 50 for IDX in 2D and 3D was 2µM; IC 50 for Cis in 2D and 3D: was 0.6µM and 1.4µM, respectively). A dose-dependent induction of apoptosis in NPC cell lines by IDX was observed [early apoptotic cells (Annexin V+/PI- at 1µM); late apoptotic cells (Annexin V+/PI+ at 2µM), and necrotic cells (Annexin V-/PI+, at 4µM) were distinguished]. Intriguingly, IDX increased the migratory potential of PBMC towards tumor cells in both 2D and 3D spheroid cultures. Finally, IDX, but not Cis, facilitated the migration of CD8+ T cells toward tumor cells by 3.5-fold (p &lt; 0.05) as well as promoted the expansion of proliferative CD8+ T cells (increased by ~2.8-fold) with degranulation activities (~1.3-fold and 3-fold increase in surface CD107a and intracellular granzyme B expression, respectively) in the cocultures. Conclusions: IDX was shown to induce apoptosis in NPC cells while inhibiting their migration and proliferation. Moreover, the ability of IDX to modulate T cell populations indicates the drug’s potential to enhance the efficacy of current chemotherapy treatments in NPC by upregulating cellular trafficking to the cancer cell.
良性前列腺增生症的药物治疗
Authors: 宋健
Journal: BMJ (2010)

良性前列腺增生(BPH)是一种缓慢进展的前列腺良性疾病,发病率随着年龄的增长而增加[1].BPH临床进展包括:下尿路症状(LUTS)加重而导致患者生存质量下降、最大尿流率进行性下降、急性尿潴留、反复血尿、复发性尿路感染和肾功能损害等~([2-3])。