tbuckley/cabot-search huggingface dataset:
Pulmonary sequestration: a literature review of 2625 cases
Authors: Yong Wei, Fan Li
Journal: BMJ (2010)

Total 2625 cases of pulmonary sequestration were collected from literatures of Chinese National Knowledge Infrastructure from 1998 to 2008. The age, gender, clinical symptoms, chest CT scan,chest X-ray findings, lesion location, supplying artery, venous reflux, and preoperative misdiagnosis of 2625 cases were retrospectively reviewed. The male: female ratio of all cases was 1.58: 1. The main clinical symptoms of pulmonary sequestration were cough, sputum, fever, hemoptysis and chest pain, but 13.36% patients were asymptomatic. Chest CT scan showed pulmonary massive lesions (49.00%), pulmonary cystic lesions (28.57%), pulmonary cystic-solid lesions ( 11.57% ), and flaky shadows (7.96%). Pulmonary sequestration mainly located in the lower lobe; 66. 43% located in the left posterior basal segments, and 20. 16% located in the right posterior basal segments. Pulmonary sequestrations were divided into three types, intralobar sequestration (83. 84% ), extralobar sequestration ( 16.03% ), and mixed sequestration (0.13% ). The arterial supply was mainly from branches of thoracic aorta (76. 55% ) and abdominal aorta (18.47%). The clinical manifestations of pulmonary sequestration were various, so the preoperative misdiagnosis rate was as high as (59 ± 20) %. We should take full advantage of clinical symptoms, imaging findings and location characteristics to improve the preoperative diagnosis rate.

Key words: 
Bronchpulmonary sequestration;  Review literature
The long and winding road in drug development: Learnings from on-going development of IEPA for chemotherapy-induced myelosuppression.
Authors: Dirk Pleimes, Michael Meyer, Maciej Czajkowski
Journal: Journal of Clinical Oncology (2020)

e24134 Background: An orally bioavailable small molecule IEPA (Imidazolyl Ethanamide Pentandioic Acid) is under development as treatment for chemotherapy-induced myelosuppression (CIM) since 2013. A clinical phase 2a study in epirubicin and cyclophosphamide (CP) treated breast cancer patients demonstrated efficacy of prophylactic (5d pre-CTX) IEPA (100 mg ≈ 1.7 mg/kg/d) in the first but not the second batch of the drug product. After causality due to manufacturing was systematically excluded, the R&amp;D team reassessed the development path and reinitiated non-clinical in vivo studies for efficacy optimization investigating a) the mode of action under different challenge (chemotherapy (CTX); radiation (RX)) b) treatment starting point c) dose d) frequency and e) route of administration to improve reproducibility of efficacy. Methods: The first study assessed hematological recovery over 19 days in mice receiving CTX and treated prophylactically (5 d pre-CTX) or therapeutically (1 h pre-CTX or 24 h post-CTX) with oral IEPA (100 mg/kg, Human Equivalent Dose (HED): 8 mg/kg) either once or twice daily. The second study investigated survival (LD25/30 and 50/30) and hematology in mice exposed to RX in prophylactically (3 d pre-RX) or therapeutically (24 h post-RX) IEPA (50 mg/kg/d) once vs. twice daily, oral vs. intraperitoneal (IP). Results: In mice exposed to CTX (200 mg/kg CP), both prophylactic and therapeutic IEPA treatment accelerated recovery of neutrophils, lymphocytes, and thrombocytes. The time to recovery of white blood cells to the baseline was reduced from 16.8 days to 5.5 days after therapeutic use of IEPA. Dose, treatment start and frequency showed comparable efficacy. In mice exposed to RX (6 Gy, LD50/30), therapeutic IEPA treatment improved survival by 30% (86% IEPA vs. 56% in control). Additionally, accelerated recovery of bone marrow cellularity and reduced body weight loss was observed. Higher doses increased efficacy, while frequency and route of administration of IEPA had limited impact. Conclusions: Two in vivo studies in mice reconfirmed IEPA’s safety and efficacy against both RX-induced mortality and CTX- and RX-induced myelosuppression. While once vs. twice daily and oral vs. IP produced no or only minor improvements, higher doses and therapeutics treatment starting 24 h post-exposure demonstrated reproducible efficacy. Results indicate that increasing the dose to up to 8 mg/kg (based on HED conversion) and starting treatment 24 h post-CTX may improve efficacy in future clinical trials.
大肠癌的早期诊断和干预治疗
Authors: 李世荣, 姜民慧
Journal: BMJ (2009)

不要轻易相信你所看到的,这是一句老生常谈,尤其是对于在网络上看到的健康信息资料. 如今,当你想了解某个疾病或健康问题时,上网搜索就能查到丰富的相关资料.但众多的信息中,许多看似真的,其实并不真实可靠。
A phase II trial of durvalumab (MEDI4736) and tremelimumab with chemotherapy in metastatic EGFR mutant non-squamous non-small cell lung cancer (NSCLC) following progression on EGFR tyrosine kinase inhibitors (TKIs) (ILLUMINATE).
Authors: Chee Khoon Lee, Shalini Subramaniam, Antony Mersiades, Jenna Mitchell, Hannora Jurkovic, Mariya Walker, Loc Le, Chris Brown, Benjamin J. Solomon, Tom John, Martin R. Stockler, Bin-Chi Liao, James Chih-Hsin Yang, Chao-Hua Chiu
Journal: Journal of Clinical Oncology (2020)

TPS9631 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven remarkably effective in the treatment of advanced EGFR mutant non-small cell lung cancer (NSCLC). However, drug resistance is inevitable and outcomes with subsequent platinum-pemetrexed chemotherapy are poor. The role of immune-checkpoint inhibitor monotherapy in EGFR mutant NSCLC remains uncertain with trials demonstrating inferior survival outcomes compared to chemotherapy. However, a recent randomised study with combination checkpoint inhibitor-chemotherapy demonstrated improved survival over chemotherapy alone in this patient population. This study aims to evaluate the efficacy and tolerability of combination dual immune-checkpoint blockade, durvalumab and tremelimumab, with platinum-pemetrexed chemotherapy in metastatic EGFR mutant NSCLC following progression on EGFR-TKIs. Methods: This international phase II cohort study will recruit 100 participants from Australia and Taiwan with advanced EGFR mutant NSCLC following disease progression with EGFR-TKIs [Cohort 1 (n=50): T790M mutation negative on tissue and plasma; Cohort 2 (n=50): T790M mutation positive on tissue and/or plasma, and progression on3 rd generation TKIs]. Participants will receive 4 cycles of induction durvalumab 1500mg and tremelimumab 75mg with platinum-pemetrexed chemotherapy every 3 weeks, followed by maintenance durvalumab 1500mg and pemetrexed 500mg/m2 every 4 weeks until disease progression. Response will be assessed at 6 and 12 weeks, then 8-weekly during the first year, and 12-weekly thereafter. Major endpoints include objective tumour response rate (OTRR; RECIST1.1; primary), disease control rate, OTRR (iRECIST), progression-free survival, overall survival, and adverse events. Correlative studies include biomarker assessment as potential predictive/prognostic factors. ILLUMINATE is a collaboration between the Australasian Lung Cancer Trials Group, National Health Research Institutes (Taiwan) and the NHMRC Clinical Trials Centre, University of Sydney. As of 6/2/2020, 11 of planned 100 participants have been recruited. Clinical trial information: NCT03994393 .
Concordance between independent and investigator assessment of disease-free survival (DFS) in the APACT trial.
Authors: Michele Reni, Hanno Riess, Eileen Mary O'Reilly, James Andrew Reeves, Elena Chiorean, Thomas J. George, Werner Scheithauer, Artru Pascal, Markus Lerch, Warren S. Brenner, Yoo-Joung Ko, Josep Tabernero, Eric Van Cutsem, Philip Agop Philip, David Goldstein, Jordan Berlin, Andrew Biankin, Margaret A. Tempero
Journal: Journal of Clinical Oncology (2020)

4618 Background: APACT was a phase III trial of adjuvant nab-paclitaxel + gemcitabine ( nab-P + Gem) vs Gem alone in patients with resected pancreatic cancer (PC) and the first adjuvant PC trial to use independently assessed DFS as the primary endpoint (DFS by investigator review was a prespecified sensitivity analysis). We examined concordance between independent and investigator DFS review. Methods: For the independent assessment, reviewers determined recurrence by computed tomography or magnetic resonance imaging but were blinded to treatment and clinical data. Investigator-assessed DFS was based on all available data. Concordance was summarized by κ statistics. Patients who did not have recurrence or were alive were censored at the last tumor assessment date with disease-free status or the randomization date if the last tumor assessment with disease-free status was missing. Patients who received new anticancer therapy or cancer-related surgery prior to recurrence or death were censored at the date of last tumor assessment with disease-free status prior to the start of new anticancer therapy or cancer-related surgery or the randomization date if the last tumor assessment date with disease-free status prior to the start of subsequent new anticancer therapy or cancer-related surgery was missing. All censoring rules were the same for analysis of DFS by independent and investigator review. Results: Median DFS by independent review was 19.4 ( nab-P + Gem) vs 18.8 (Gem) months (hazard ratio [HR] 0.88; 95% CI, 0.73 - 1.06; P = 0.18); median investigator-assessed DFS was 16.6 ( nab-P + Gem) vs 13.7 (Gem) months (HR 0.82; 95% CI, 0.69 - 0.97; nominal P = 0.017). Moderate concordance was found between independent- and investigator-assessed DFS (Table); similar results were observed in the nab-P + Gem (concordance, 78%; κ coefficient, 0.56) and Gem alone (concordance, 76%; κ coefficient, 0.53) arms. Conclusions: The results reflect the complexities of defining the recurrence timepoint accurately and suggest that radiological review in the absence of clinical context is suboptimal for recurrence detection in resected PC. These findings may inform future clinical trial design. Registration: EudraCT (2013-003398-91); ClinicalTrials.gov (NCT01964430). Clinical trial information: NCT01964430 . [Table: see text]
アジュバント! オンラインは乳癌集学的チーム(MDT)の補助化学療法に著しい影響は無い | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: A Balakrishnan, S A Haysom, D Ravichandran
Journal: Annals of Oncology (2011)
Incidence of diabetes and prediabetes unmasked by dexamethasone in women undergoing (neo) adjuvant taxane therapy.
Authors: Dana Mahinbakht, Sayeh Moazami Lavasani, Wai (Kim) Yu, Raynald Samoa, Nora Ruel, Joanne E. Mortimer
Journal: Journal of Clinical Oncology (2020)

e12526 Background: Women with early stage breast cancer receive premedication with dexamethasone prior to administration of paclitaxel and docetaxel. We undertook a retrospective chart review to determine the frequency of steroid-induced hyperglycemia in women receiving steroid premedication with paclitaxel and docetaxel. Methods: Women who were receiving paclitaxel or taxotere chemotherapy as (neo)adjuvant therapy were identified from pharmacy records. Patients were excluded if they were currently receiving insulin or hypoglycemic agents for diabetes. A Comprehensive Metabolic Panel (CMP) was performed prior to chemotherapy and the random glucose level was recorded. The highest random glucose level recorded during all cycles of treatment was used in the analysis. The threshold for diabetes is a random glucose of 200 mg/dL and levels &gt; 150 mg/dL, but less than 200 mg/dL is considered prediabetes. Between August 2017 to December 2019, 131 patients were identified and 100 met the criteria for inclusion. The study was approved by the Institutional Review Board. A single individual abstracted the data which included demographic data, BMI, comorbidities, random glucose levels prior to therapy and whether they received treatment for the elevations in blood glucose. Results: A total of 131 charts were reviewed, but 31 were excluded because 2 were male, 13 had type 2 diabetes at diagnosis, and 16 had metastatic disease. The median age of the 100 patients was 53 years (range 31 to 82 years); 45% were White/Non-Hispanic, 28% Hispanic, 18% Asian, 5% African American, 1% were Native Hawaiian or other Pacific Islander, 2% were unknown, and 1% were of mixed race. Prediabetic random glucose levels were recorded in 30% of patients and 23% had levels consistent with a diagnosis of diabetes. Out of the patients who exhibited a blood glucose above 200, 16 out of the 23 patients were White, 6 of them were Hispanic and 1 was Asian. The average BMI was 27.7. The average BMI of patients who exhibited a blood glucose of over 200 mg/dL was 28.85 and the average of those who had a blood glucose of over 150 mg/dL was 27.56. Conclusions: Diabetes and prediabetes were unmasked by taking the premedication with dexamethasone in 53% of women undergoing (neo)adjuvant docetaxel or paclitaxel. Current guidelines do not recommend additional blood work after completion of active treatment. Given our results, it is important that medical oncologist ensure that patients with elevations in random glucose be referred for appropriate endocrine workup and therapy, including lifestyle modifications.
Radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC): A prospective, observational study.
Authors: Janna Berg, May-Bente Bengtson, Ann Rita Halvorsen, Jon Olav Haugstvedt, Odd Terje Brustugun, Aslaug Helland
Journal: Journal of Clinical Oncology (2020)

e21065 Background: RP is a clinically challenging side effect following SBRT. The reported incidence of RP varies from 2.2% to 46.8%, depending on study design and different grading systems. We evaluated the grading systems for RP and identified possible predictive tests for RP. Furthermore, we estimated the correlation between RP and dosimetric measurements from the radiation therapy. Methods: Medically inoperable patients, n = 44, with peripherally located NSCLC stage I-II, were treated with SBRT, with a total dose of 45–56 Gy in 3–8 fractions. Median age was 75 years, 43.2% were female and 60% had moderate to very severe COPD. Follow up included physical examination by pulmonologist, spirometry and single-breath lung diffusing capacity (DLCO) and CT evaluation at baseline and 1.5, 3, 6, 9 and 12 months after SBRT. Results: We constructed three groups for grading RP based on CTCAE version 5.0 and imaging changes according to EORTC (LENT-SOMA) Non-RP (asymptomatic or mild symptoms and slight imaging changes, n = 19, 43%), Asymptomatic, radiology-only RP (asymptomatic or mild symptoms, increased density imaging changes, n = 17, 39%) and Symptomatic and radiology-detected RP (moderate and severe symptoms and increased density imaging changes, n = 8, 18%). Active smokers and patients with emphysema were overrepresented in non-RP group. In the symptomatic RP group, DLCO and FEV1 dropped almost 5% 4-6 weeks after SBRT, before symptoms and imaging changes, and DLCO, FVC and FEV1 dropped significantly at 3 months (table). Development of RP was associated with critical dose-volume parameter 1000ccm and 1500ccm. Several dosimetric parameters significantly negative correlate with FVC-drop at 1 and 3 months only in symptomatic RP. Conclusions: Active smokers and patients with emphysema have less propensity of RP. Symptomatic RP is seen with a presymptomatic drop in FEV1 and DLCO occurring 4-6 weeks after SBRT. Critical dose-volume parameter is important parameters for RP. Correlation between dosimetric parameters and FVC-drop in symptomatic RP. Clinical trial information: NCT02428049 . [Table: see text]
Population pharmacokinetic (PK) and exposure-response analyses from the pivotal ALTA-1L study: Model-based analyses supporting the brigatinib dose in patients with anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC).
Authors: Neeraj Gupta, Karen L. Reckamp, D. Ross Camidge, Huub Jan Kleijn, Aziz Ouerdani, Francesco Bellanti, John Maringwa, Michael J. Hanley, Shining Wang, Pingkuan Zhang, Karthik Venkatakrishnan
Journal: Journal of Clinical Oncology (2020)

e21725 Background: Brigatinib is a next-generation ALK tyrosine kinase inhibitor (TKI) with differential activity by dose (90 mg vs 180 mg [with a 7-day lead-in at 90 mg] qd) in the phase 2 post-crizotinib ALTA trial (NCT02094573). Herein, we describe results from population PK and exposure-response analyses of the efficacy and safety of brigatinib 180 mg qd (with a 7-day lead-in at 90 mg) from data in the first-line phase 3 ALTA-1L study (NCT02737501). Methods: Brigatinib plasma concentration-time data were described by a 3-compartment model with transit compartment absorption. Post hoc individual apparent clearance estimates for brigatinib were obtained using Bayesian re-estimation and used to calculate time-averaged area under the concentration-time curve (AUC) values for logistic regression analyses of relationships to response endpoints (confirmed objective response rate [ORR], intracranial ORR) and time-varying AUC values for parametric time-to-event models of relationships to progression-free survival (PFS). Population PK modeling, covariate analysis, and simulations were performed using NONMEM (version 7.3 or higher), running under PsN (Perl-speaks-NONMEM, version 4.6 or higher), while exposure–efficacy and safety analyses were performed using R (version 3.5.2 or higher). Results: Brigatinib PK parameters and estimated systemic exposures for patients in ALTA-1L (ALK TKI–naive setting) were similar to those in the 180 mg qd arm of ALTA. Patient covariates including weight, sex, age, race, and renal function (CrCL ≥30 mL/min) were not found to impact brigatinib exposure, suggesting no dose adjustment based on these covariates. In the exposure-response analyses, brigatinib exposure was not a significant predictor of response (≥partial response) or PFS. This suggests that the efficacy benefit was consistent across the range of exposures achieved with the 180 mg dosing regimen including after dose modifications. There was a significant relationship ( P&lt; 0.05) between exposure and certain laboratory abnormalities (increased amylase and lipase). There was no relationship between exposure and CPK elevation, and brigatinib exposure had no effect on time to first dose reduction. Conclusions: These results support a favorable benefit/risk profile of the proposed 180 mg qd brigatinib dose (with a 7-day lead-in at 90 mg) for the front-line treatment of patients with ALK+ NSCLC. Clinical trial information: NCT02737501.
Timing of response to venetoclax combination treatment in older patients with acute myeloid leukemia.
Authors: Brian Andrew Jonas, Courtney Denton Dinardo, Keith Pratz, Andrew Wei, Wan-Jen Hong, Brenda Chyla, Yinghui Duan, Jalaja Potluri, Michael Werner, Daniel Aaron Pollyea
Journal: Journal of Clinical Oncology (2020)

7531 Background: Venetoclax (Ven) has synergistic activity with hypomethylating agents (eg, azacitidine [Aza] or decitabine [Dec]) or low-dose cytarabine (LDAC). These Ven-based combinations have demonstrated rapid median response times. This analysis describes the rapidity and likelihood of response to Ven treatments, and its associated characteristics, in older patients with newly diagnosed acute myeloid leukemia (AML). Methods: Included are data from two open-label trials of Ven, at label recommended doses, in combination with Aza, Dec (NCT02203773; phase 1b), or low-dose cytarabine (NCT02287233; phase 1/2) in newly diagnosed patients with AML. Patients were classified based on CR/CRi timing: within 2 cycles of therapy, after 2 cycles, or never achieving CR/CRi. Within each group, baseline and post-baseline characteristics were evaluated to determine impact on response timing. The percentage of patients in each category and duration of response (DOR) in each category were also evaluated. Results: Data cutoff was August 2018. Of 197 patients, 42% (n = 83) had CR/CRi in ≤2 cycles, 22% (n = 44) had CR/CRi in &gt; 2 cycles, and 36% (n = 70) did not achieve CR/CRi. Median DOR was 21.2 mos. (95% CI 14.1-NR) for ≤2 cycle responders and 8.1 mos. (95% CI 5.3-14.9) for &gt; 2 cycle responders. Baseline characteristics are shown in the Table. Patients with baseline IDH1/2 mutation were more likely to have CR/CRi in ≤2 cycles, while those with secondary AML and no response by the end of cycle 2 were more likely to never achieve CR/CRi. Of the patients who achieved CR/CRi after 2 cycles of therapy, 43% (19/44) achieved MLFS within the first two cycles. Of those who never achieved CR/CRi, 17% (12/70) of patients achieved MLFS within 2 cycles. In depth regression analyses of factors predictive of response, including analysis of biomarkers, will be available upon presentation. Conclusions: Over 1/3 rd of patients that achieved CR/CRi on Ven combination therapy within these two studies required more than 2 cycles of treatment. Therefore, prior to discontinuing therapy for nonresponders, it is critical to assess key predictive patient characteristics. Clinical trial information: NCT02203773 and NCT02287233 . [Table: see text]
A phase Ib/III randomized, double-blind, placebo-controlled study of tazemetostat plus doxorubicin as frontline therapy for patients with advanced epithelioid sarcoma.
Authors: Shiraj Sen, Meredith Ann McKean, Laura Sierra, Jessica Ainscough, Jay Yang, Anthony Hamlett, Tom Zimmerman, Melinda Merchant, Sant P. Chawla
Journal: Journal of Clinical Oncology (2020)

TPS11573 Background: Epithelioid sarcoma (ES) is characterized by loss of inhibitor of integrase 1 (INI1), allowing enhancer of zeste homologue 2 (EZH2) to repress cell differentiation and promote tumorigenesis. Tazemetostat (TAZ) is an EZH2 inhibitor approved by the FDA as monotherapy for the treatment of patients (pts) aged ≥16 years with metastatic or locally advanced ES ineligible for complete resection. The most common ( &gt; 20%) adverse events include pain, fatigue, nausea, decreased appetite, vomiting, and constipation. TAZ demonstrated anti-cancer activity in ES pts who previously received doxorubicin (dox), a commonly used front line FDA approved therapy for soft tissue sarcomas (STS), including ES. Preclinical studies have demonstrated synergy between TAZ and dox. This phase 1b/3 study (NCT04204941) is assessing the safety and efficacy of TAZ + dox in pts with advanced ES. Methods: This study is enrolling treatment-naïve adult pts with histologically confirmed STS (phase 1b) or INI1-deficient ES pts (phase 3) with ECOG performance status of 0-2 and life expectancy of ≥3 months. The open-label phase 1b portion is currently enrolling up to 24 patients with STS. The primary objectives are to evaluate the safety and tolerability of TAZ + dox, and to identify the recommended phase 3 dose (RP3D). Using a standard 3 + 3 design, TAZ will be evaluated at 3 dose levels (400 mg, 600 mg, and 800 mg orally BID) with standard fixed dose of dox (75 mg/m 2 on day 1 of 21-day cycles for up to 6 cycles). After completion of dox, pts will continue to receive TAZ monotherapy until disease progression or intolerable toxicity. Up to 12 additional pts will be enrolled at the maximum tolerated dose for collection of additional safety and pharmacokinetic (PK) data. The double-blind phase 3 study will randomize (1:1) up to 140 pts to receive either TAZ (RP3D) + dox (75 mg/m 2 ) or placebo + dox. The adaptive study design will allow sample size re-estimation (at interim analysis) to up to 200 pts. Pts may continue TAZ or placebo monotherapy after completing 6 cycles of TAZ + dox. Tumor assessments will be performed at screening and every 6 weeks from the start of dosing. The primary objective of phase 3 will be to evaluate the progression-free survival (PFS) by independent review committee. Secondary objectives will include assessment of PFS by investigators, overall survival, safety, disease control rate, overall response rate, duration of response, time to subsequent anticancer therapy, PFS on next treatment, quality of life, and PK. Clinical trial information: NCT04204941 .